Kristen N Ganjoo

All Publications

• Feasibility of Longitudinal ctDNA Assessment in Patients with Uterine and Extra-Uterine Leiomyosarcoma. Cancers Zhou, M., Bui, N., Rathore, R., Sudhaman, S., George, G. V., Malashevich, A. K., Malhotra, M., Liu, M. C., Aleshin, A., Ganjoo, K. N. 2022; 15 (1)

  Abstract

  Background: Leiomyosarcomas (LMS) are aggressive malignancies with a propensity for early relapse. Current surveillance modalities include physical exam and imaging; however, radiological response to therapy may only manifest after 4-6 cycles of treatment. Herein, we evaluated the feasibility of longitudinal circulating tumor DNA (ctDNA) assessment in LMS patients to identify disease progression. Methods: We performed a retrospective review of patients with LMS who underwent treatment at Stanford Cancer Center between September 2019 and May 2022. ctDNA detection was performed using a personalized, tumor-informed ctDNA assay. Genomic analysis was conducted to characterize tumor mutation burden (TMB) and known driver mutations. Results: A total of 148 plasma samples were obtained from 34 patients with uterine (N = 21) and extrauterine (N = 13) LMS (median follow-up: 67.2 (19-346.3) weeks] and analyzed for ctDNA presence. Nineteen patients had metastatic disease. The most frequently mutated driver genes across sub-cohorts were TP53, RB1, and PTEN. Patients were stratified into four sub-cohorts (A-D) based on ctDNA kinetics. ctDNA levels tracked longitudinally with progression of disease and response to therapy. Conclusion: Our results indicate that while undetectable ctDNA may suggest a lower likelihood of relapse, ctDNA positivity may indicate progressive disease, enabling closer monitoring of patients for early clinical intervention.

  View details for DOI 10.3390/cancers15010157

  View details for PubMedID 36612153

• Management of Patients with Newly Diagnosed Desmoid Tumors in a First-Line Setting. Cancers Testa, S., Bui, N. Q., Charville, G. W., Avedian, R. S., Steffner, R., Ghanouni, P., Mohler, D. G., Ganjoo, K. N. 2022; 14 (16)

  Abstract

  The initial management of desmoid tumors (DTs) is shifting from surgery towards active surveillance, with systemic and locally ablative treatments reserved for enlarging and/or symptomatic disease. However, it remains unclear which patients would benefit most from an initial conservative rather than interventional approach. To answer this question, we retrospectively analyzed adult and pediatric patients with DTs treated at a tertiary academic cancer center between 1992 and 2022. Outcomes measured were progression-free survival (PFS) and time to next treatment (TTNT) after first-line therapy. A total of 262 treatment-naïve patients were eligible for analysis with a median age of 36.5 years (range, 0-87 years). The 5-year PFS and the median TTNT (months) after first-line treatment were, respectively: 50.6% and 69.1 mo for surgery; 64.9% and 149.5 mo for surgery plus adjuvant radiotherapy; 57.1% and 44.7 mo for surgery plus adjuvant systemic therapy; 24.9% and 4.4 mo for chemotherapy; 26.7% and 5.3 mo for hormonal therapy; 41.3% and 29.6 mo for tyrosine kinase inhibitors (TKIs); 44.4% and 8.9 mo for cryoablation and high intensity focused ultrasound; and 43.1% and 32.7 mo for active surveillance. Age ≤ 40 years (p < 0.001), DTs involving the extremities (p < 0.001), a maximum tumor diameter > 60 mm (p = 0.04), and hormonal therapy (p = 0.03) predicted a higher risk of progression. Overall, our results suggest that active surveillance should be considered initially for patients with smaller asymptomatic DTs, while upfront TKIs, local ablation, and surgery achieve similar outcomes in those with more aggressive disease.

  View details for DOI 10.3390/cancers14163907

  View details for PubMedID 36010900

• Fourteen-Day Gemcitabine-Docetaxel Chemotherapy Is Effective and Safer Compared to 21-Day Regimen in Patients with Advanced Soft Tissue and Bone Sarcoma CANCERS Pan, M., Trieu, M. K., Sidhu, M., Yu, J., Seto, T., Ganjoo, K. 2021; 13 (8)

  Abstract

  Gemcitabine-docetaxel (G-D) combination is an effective chemotherapy for patients with advanced soft tissue and bone sarcoma, first developed with G administered on days 1 and 8, and D on day 8 every 21 days and later modified to be administered every 14 days in 2012. The 14-day regimen has become increasingly adopted. However, its efficacy and toxicities have not been compared. We identified 161 patients with metastatic or locally advanced soft tissue and bone sarcoma treated with either a 14-day or 21-day regimen within Northern California Kaiser Permanente from 1 January 2017 to 30 July 2020 and compared the outcomes and toxicity profiles of patients treated with the either regimen. Seventy-nine (49%) and 82 (51%) patients received the 14-day and the 21-day regimen, respectively, with similar response rate (22.8% and 15.8%, p = 0.26), median progression-free survival (PFS, 4.0 and 3.2 months, p = 0.15), and median overall survival (OS, 12.6 and 14.7 months, p = 0.55). Subset analysis of the untreated patients (approximately 60% of the entire cohort) as well as the patients with leiomyosarcoma only (approximately 50% of the entire cohort) showed that OS was not significantly different between the two regimens. Febrile neutropenia requiring hospitalization occurred in 10 and one patients (p = 0.006) and intolerance leading to discontinuation of chemotherapy occurred in 12 and two patients (p = 0.006) treated with the 21-day and the 14-day regimens, respectively. CDKN2A deletion/mutation or CDK4 amplification was associated with worse median OS (p = 0.06), while a RB1 deletion/mutation was associated with better median PFS (p = 0.05), and these two genomic alterations were mutually exclusive. Our data demonstrate that, compared to the traditional 21-day G-D regimen, the 14-day G-D regimen is equally effective but safer. In addition, CDKN2A and RB1 pathways play significant role on the outcomes of the patients.

  View details for DOI 10.3390/cancers13081983

  View details for Web of Science ID 000644016300001

  View details for PubMedID 33924080

• Nivolumab plus ipilimumab for soft tissue sarcoma: a single institution retrospective review IMMUNOTHERAPY Zhou, M., Bui, N., Bolleddu, S., Lohman, M., Becker, H., Ganjoo, K. 2020; 12 (18): 1303–12

  View details for DOI 10.2211/imt-2020-0155

  View details for Web of Science ID 000598571200001

• NCCN Guidelines Insights: Soft Tissue Sarcoma, Version 1.2021. Journal of the National Comprehensive Cancer Network : JNCCN von Mehren, M., Kane, J. M., Bui, M. M., Choy, E., Connelly, M., Dry, S., Ganjoo, K. N., George, S., Gonzalez, R. J., Heslin, M. J., Homsi, J., Keedy, V., Kelly, C. M., Kim, E., Liebner, D., McCarter, M., McGarry, S. V., Meyer, C., Pappo, A. S., Parkes, A. M., Paz, I. B., Petersen, I. A., Poppe, M., Riedel, R. F., Rubin, B., Schuetze, S., Shabason, J., Sicklick, J. K., Spraker, M. B., Zimel, M., Bergman, M. A., George, G. V. 2020; 18 (12): 1604–12

  Abstract

  The NCCN Guidelines for Soft Tissue Sarcoma provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with soft tissue sarcomas. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including the development of a separate and distinct guideline for gastrointestinal stromal tumors (GISTs); reconception of the management of desmoid tumors; inclusion of further recommendations for the diagnosis and management of extremity/body wall, head/neck sarcomas, and retroperitoneal sarcomas; modification and addition of systemic therapy regimens for sarcoma subtypes; and revision of the principles of radiation therapy for soft tissue sarcomas.

  View details for DOI 10.6004/jnccn.2020.0058

  View details for PubMedID 33285515

• Detection of Circulating Tumor DNA in Patients With Uterine Leiomyomas JCO PRECISION ONCOLOGY Przybyl, J., Spans, L., Lum, D. A., Zhu, S., Vennam, S., Forgo, E., Varma, S., Ganjoo, K., Hastie, T., Bowen, R., Debiec-Rychter, M., van de Rijn, M. 2019; 3

  View details for DOI 10.1200/PO.18.00409

  View details for Web of Science ID 000491150900001

• Combination Approach for Detecting Different Types of Alterations in Circulating Tumor DNA in Leiomyosarcoma CLINICAL CANCER RESEARCH Przybyl, J., Chabon, J. J., Spans, L., Ganjoo, K. N., Vennam, S., Newman, A. M., Forgo, E., Varma, S., Zhu, S., Debiec-Rychter, M., Alizadeh, A. A., Diehn, M., van de Rijn, M. 2018; 24 (11): 2688–99

  View details for DOI 10.1158/1078-0432.CCR-17-3704

  View details for Web of Science ID 000433971400023

• Phase II Study of the Safety and Antitumor Activity of the Hypoxia-Activated Prodrug TH-302 in Combination With Doxorubicin in Patients With Advanced Soft Tissue Sarcoma JOURNAL OF CLINICAL ONCOLOGY Chawla, S. P., Cranmer, L. D., Van Tine, B. A., Reed, D. R., Okuno, S. H., Butrynski, J. E., Adkins, D. R., Hendifar, A. E., Kroll, S., Ganjoo, K. N. 2014; 32 (29): 3299-?

  Abstract

  TH-302, a prodrug of the cytotoxic alkylating agent bromo-isophosphoramide mustard, is preferentially activated in hypoxic conditions. This phase II study investigated TH-302 in combination with doxorubicin, followed by single-agent TH-302 maintenance therapy in patients with first-line advanced soft tissue sarcoma (STS) to assess progression-free survival (PFS), response rate, overall survival, safety, and tolerability.In this open-label phase II study, TH-302 300 mg/m(2) was administered intravenously on days 1 and 8 with doxorubicin 75 mg/m(2) on day 1 of each 21-day cycle. After six cycles, patients with stable and/or responding disease could receive maintenance monotherapy with TH-302.Ninety-one patients initiated TH-302 plus doxorubicin induction treatment. The PFS rate at 6 months (primary efficacy measure) was 58% (95% CI, 46% to 68%). Median PFS was 6.5 months (95% CI, 5.8 to 7.7 months); median overall survival was 21.5 months (95% CI, 16.0 to 26.2 months). Best tumor responses were complete response (n = 2 [2%]) and partial response (n = 30 [34%]). During TH-302 maintenance (n = 48), five patients improved from stable disease to partial response, and one patient improved from partial to complete response. The most common adverse events during induction were fatigue, nausea, and skin and/or mucosal toxicities as well as anemia, thrombocytopenia, and neutropenia. These were less severe and less frequent during maintenance. There was no evidence of TH-302-related hepatic, renal, or cardiac toxicity.PFS, overall survival, and tumor response compared favorably with historical outcomes achieved with other first-line chemotherapies for advanced STS. A phase III study of TH-302 is ongoing (NCT01440088).

  View details for DOI 10.1200/JCO.2013.54.3660

  View details for Web of Science ID 000342988000015

• A Phase 2 Trial of R1507, a Monoclonal Antibody to the Insulin-Like Growth Factor-1 Receptor (IGF-1R), in Patients With Recurrent or Refractory Rhabdomyosarcoma, Osteosarcoma, Synovial Sarcoma, and Other Soft Tissue Sarcomas Results of a Sarcoma Alliance for Research Through Collaboration Study CANCER Pappo, A. S., Vassal, G., Crowley, J. J., Bolejack, V., Hogendoorn, P. C., Chugh, R., Ladanyi, M., Grippo, J. F., Dall, G., Staddon, A. P., Chawla, S. P., Maki, R. G., Araujo, D. M., Geoerger, B., Ganjoo, K., Marina, N., Blay, J., Schuetze, S. M., Chow, W. A., Helman, L. J. 2014; 120 (16): 2448-2456

  Abstract

  Insulin-like growth factor-1 receptor (IGF-1R) is implicated in the pathogenesis of rhabdomyosarcoma (RMS), osteosarcoma (OS), and synovial sarcoma (SS). The authors conducted a multi-institutional phase 2 trial of the monoclonal antibody R1507 in patients with various subtypes of recurrent or refractory sarcomas.Eligibility criteria included age ≥ 2 years and a diagnosis of recurrent or refractory RMS, OS, SS, and other soft tissue sarcomas. Patients received a weekly dose of 9 mg/kg R1507 intravenously. The primary endpoint was the best objective response rate using World Health Organization criteria. Tumor imaging was performed every 6 weeks × 4 and every 12 weeks thereafter.From December 2007 through August 2009, 163 eligible patients from 33 institutions were enrolled. The median patient age was 31 years (range, 7-85 years). Histologic diagnoses included OS (n = 38), RMS (n = 36), SS (n = 23), and other sarcomas (n = 66). The overall objective response rate was 2.5% (95% confidence interval, 0.7%-6.2%). Partial responses were observed in 4 patients, including 2 patients with OS, 1 patient with RMS, and 1 patient with alveolar soft part sarcoma. Four additional patients (3 with RMS and 1 with myxoid liposarcoma) had a ≥ 50% decrease in tumor size that lasted for <4 weeks. The median progression-free survival was 5.7 weeks, and the median overall survival was 11 months. The most common grade 3/4 toxicities were metabolic (12%), hematologic (6%), gastrointestinal (4%), and general constitutional symptoms (8%).R1507 is safe and well tolerated but has limited activity in patients with recurrent or refractory bone and soft tissue sarcomas. Additional studies to help identify the predictive factors associated with clinical benefit in selected histologies such as RMS appear to be warranted.

  View details for DOI 10.1002/cncr.28728

  View details for Web of Science ID 000340464100011

  View details for PubMedID 24797726

• Gastrointestinal stromal tumors, version 2.2014. Journal of the National Comprehensive Cancer Network von Mehren, M., Randall, R. L., Benjamin, R. S., Boles, S., Bui, M. M., Casper, E. S., Conrad, E. U., DeLaney, T. F., Ganjoo, K. N., George, S., Gonzalez, R. J., Heslin, M. J., Kane, J. M., Mayerson, J., McGarry, S. V., Meyer, C., O'Donnell, R. J., Pappo, A. S., Paz, I. B., Pfeifer, J. D., Riedel, R. F., Schuetze, S., Schupak, K. D., Schwartz, H. S., Van Tine, B. A., Wayne, J. D., Bergman, M. A., Sundar, H. 2014; 12 (6): 853-862

  Abstract

  Gastrointestinal stromal tumors (GIST) are the most common soft tissue sarcoma of the gastrointestinal tract, resulting most commonly from KIT or platelet-derived growth factor receptor α (PDGFRα)-activating mutations. These NCCN Guideline Insights highlight the important updates to the NCCN Guidelines for Soft Tissue Sarcoma specific to the management of patients with GIST experiencing disease progression while on imatinib and/or sunitinib.

  View details for PubMedID 24925196

• Soft Tissue Sarcoma, Version 2.2014 Featured Updates to the NCCN Guidelines JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK von Mehren, M., Randall, R. L., Benjamin, R. S., Boles, S., Bui, M. M., Casper, E. S., Conrad, E. U., DeLaney, T. F., Ganjoo, K. N., George, S., Gonzalez, R. J., Heslin, M. J., Kane, J. M., Mayerson, J., McGarry, S. V., Meyer, C., O'Donnell, R. J., Pappo, A. S., Paz, I. B., Pfeifer, J. D., Riedel, R. F., Schuetze, S., Schupak, K. D., Schwartz, H. S., Van Tine, B. A., Wayne, J. D., Bergman, M. A., Sundar, H. 2014; 12 (4): 473-483

  Abstract

  These NCCN Guidelines Insights highlight the important updates to the NCCN Guidelines for Soft Tissue Sarcoma (STS) specific to the role of radiation therapy in the management of patients with retroperitoneal/intra-abdominal STS. The guidelines have also included recommendations for genetic testing and counseling for patients with a clinical and/or family history of genetic cancer syndromes associated with a predisposition for the development of STS.

  View details for Web of Science ID 000334014900006

• A multicenter phase II study of pazopanib in patients with advanced gastrointestinal stromal tumors (GIST) following failure of at least imatinib and sunitinib. Annals of oncology Ganjoo, K. N., Villalobos, V. M., Kamaya, A., Fisher, G. A., Butrynski, J. E., Morgan, J. A., Wagner, A. J., D'adamo, D., McMillan, A., Demetri, G. D., George, S. 2014; 25 (1): 236-240

  Abstract

  Advanced GISTs are incurable, but often treatable for years with tyrosine kinase inhibitors (TKIs). The majority of GISTs harbor an oncogenic activating mutation in KIT or PDGFRA. Inhibition of this activating mutation with TKIs most often leads to durable disease control for many patients. However, almost all patients develop resistance to these TKIs, typically due to the development of secondary mutations, heralding the need for new therapeutic options. We conducted a phase II study evaluating the efficacy and toxicity of pazopanib, a broad spectrum TKI inhibiting KIT, VEGFRs (-1, -2, and -3), and PDGFR (-α and-β) in patients with advanced GIST following failure of at least imatinib and sunitinib.Patients received pazopanib 800 mg orally once daily. All patients were assessed for efficacy with CT scans every 8 weeks (two cycles). Patients continued pazopanib until progression or unacceptable toxicity. The primary end point was the 24-week nonprogression [complete response+partial response+stable disease (SD)] rate (NPR) per RECIST 1.1. Secondary end points included PFS, OS, and toxicity.Between August 2011 and September 2012, a total of 25 patients were treated at two institutions. Median number of prior therapy was 3 (range 2-7). A total of 90 cycles of pazopanib were administered, with a median of two cycles (range 1 to 17+) per patient. Best response of SD at any time was observed in 12 (48%) patients. The NPR was 17% [95% confidence interval (CI) 4.5-37]. All but one patient discontinued protocol either due to PD (n = 19) or intolerance (n = 4). One patient with succinate dehydrogenase (SDH)-deficient GIST exhibited continuing disease control after 17 cycles. The median PFS for the entire cohort was 1.9 months (95% CI 1.6-5.2), and the median OS was 10.7 months (95% CI 3.9-NR).Pazopanib was reasonably well tolerated with no unexpected toxicities. Pazopanib as a single agent has marginal activity in unselected heavily pretreated patients with advanced GIST.

  View details for DOI 10.1093/annonc/mdt484

  View details for PubMedID 24356634

• R1507, a Monoclonal Antibody to the Insulin-Like Growth Factor 1 Receptor, in Patients With Recurrent or Refractory Ewing Sarcoma Family of Tumors: Results of a Phase II Sarcoma Alliance for Research Through Collaboration Study JOURNAL OF CLINICAL ONCOLOGY Pappo, A. S., Patel, S. R., Crowley, J., Reinke, D. K., Kuenkele, K., Chawla, S. P., Toner, G. C., Maki, R. G., Meyers, P. A., Chugh, R., Ganjoo, K. N., Schuetze, S. M., Juergens, H., Leahy, M. G., Geoerger, B., Benjamin, R. S., Helman, L. J., Baker, L. H. 2011; 29 (34): 4541-4547

  Abstract

  The type 1 insulin-like growth factor 1 receptor (IGF-1R) has been implicated in the pathogenesis of the Ewing sarcoma family of tumors (ESFT). We conducted a multicenter phase II study of the fully human IGF-1R monoclonal antibody R1507 in patients with recurrent or refractory ESFT.Patients ≥ 2 years of age with refractory or recurrent ESFT received R1507 at doses of 9 mg/kg intravenously one a week or 27 mg/kg intravenously every three weeks. Response was measured by using WHO criteria. Tumor imaging was performed every 6 weeks for 24 weeks and then every 12 weeks.From December 2007 through April 2010, 115 eligible patients from 31 different institutions were enrolled. The median age was 25 years (range, 8 to 78 years). The location of the primary tumor was bone in 57% of patients and extraskeletal in 43% of patients. A total of 109 patients were treated with R1507 9 mg/kg/wk, and six patients were treated with 27 mg/kg/3 wk. The overall complete response/partial response rate was 10% (95% CI, 4.9% to 16.5%). The median duration of response was 29 weeks (range, 12 to 94 weeks), and the median overall survival was 7.6 months (95% CI, 6 to 9.7 months). Ten of 11 responses were observed in patients who presented with primary bone tumors (P = .016). The most common adverse events of grades 3 to 4 were pain (15%), anemia (8%), thrombocytopenia (7%), and asthenia (5%).R1507 was a well-tolerated agent that had meaningful and durable benefit in a subgroup of patients with ESFT. The identification of markers that are predictive of a benefit is necessary to fully capitalize on this approach.

  View details for DOI 10.1200/JCO.2010.34.0000

  View details for Web of Science ID 000298136500021

  View details for PubMedID 22025149

• Current and Emerging Pharmacological Treatments for Gastrointestinal Stromal Tumour DRUGS Ganjoo, K. N., Patel, S. 2011; 71 (3): 321-330

  Abstract

  Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumours of the gastrointestinal tract, previously classified as leiomyosarcomas. Most GIST express KIT and the majority have mutations in the KIT gene. The most common KIT mutation occurs in the juxtamembrane domain of exon 11. These mutations lead to cellular proliferation and survival. GIST with exon 11 mutations respond better to tyrosine kinase inhibitors (TKIs) than those with exon 9 mutations. Most KIT-negative GIST express platelet-derived growth factor receptor (PDGFR)-α; however, a small percentage of GIST are negative for both KIT and PDGFRα. Imatinib and other TKIs have dramatically improved the outcome of patients with metastatic GIST. Newer and more advanced TKIs are under intense investigation as eventually all GIST patients develop resistant tumours. In addition, these drugs can be utilized in the preoperative setting for patients with unresectable localized tumours or those at high risk for surgical morbidity. TKIs have been given in the adjuvant setting for patients with resected tumours at high risk for recurrence. The duration of adjuvant therapy is currently under evaluation; however, it is possible that these patients would need to continue therapy indefinitely.

  View details for Web of Science ID 000288311600006

  View details for PubMedID 21319869

• A Phase I Study of the Safety and Pharmacokinetics of the Hypoxia-Activated Prodrug TH-302 in Combination with Doxorubicin in Patients with Advanced Soft Tissue Sarcoma ONCOLOGY Ganjoo, K. N., Cranmer, L. D., Butrynski, J. E., Rushing, D., Adkins, D., Okuno, S. H., Lorente, G., Kroll, S., Langmuir, V. K., Chawla, S. P. 2011; 80 (1-2): 50-56

  Abstract

  The purpose of this study was to determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), safety, pharmacokinetics and preliminary activity of TH-302, a hypoxia-activated prodrug, in combination with doxorubicin in patients with advanced soft tissue sarcoma. Patients andTH-302 was administered intravenously on days 1 and 8 and doxorubicin 75 mg/m² on day 1 (2 h after TH-302) of every 3-week cycle. TH-302 starting dose was 240 mg/m² with a classic 3 + 3 dose escalation. Pharmacokinetics were assessed on days 1 and 8 of cycle 1. Tumor assessments were performed after every second cycle.Sixteen patients enrolled. Prophylactic growth factor support was added due to grade 4 neutropenia. The MTD was 300 mg/m². DLTs at 340 mg/m² were neutropenia-associated infection and grade 4 thrombocytopenia. Common adverse events included fatigue, nausea and skin rash. There was no evidence of pharmacokinetic interaction between TH-302 and doxorubicin. Five of 15 (33%) evaluable patients had a partial response by RECIST (Response Evaluation Criteria in Solid Tumors) criteria.The hematologic toxicity of doxorubicin is increased when combined with TH-302. This can be mitigated by prophylactic growth factor support. Toxicities were manageable and there was evidence of antitumor activity.

  View details for DOI 10.1159/000327739

  View details for Web of Science ID 000291753800007

  View details for PubMedID 21625179

• New Developments in Targeted Therapy for Soft Tissue Sarcoma CURRENT ONCOLOGY REPORTS Ganjoo, K. N. 2010; 12 (4): 261-265

  Abstract

  Soft tissue sarcomas (STS) are rare diseases, with an estimated 10,390 new cases in the United States in 2008. Unfortunately, only 50% are cured with surgical resection. The standard cytotoxic chemotherapeutic agents have not been successful in the treatment of metastatic disease. The standard single-agent chemotherapy for metastatic disease is doxorubicin, with only 20% to 25% response rates. The combination of doxorubicin with other agents, such as ifosfamide, has improved response rates, without any improvement in overall survival. New targeted therapies have shown some activity in STS; however, disease stabilization is seen more often than a true radiographic response. The combination of cytotoxic chemotherapy with more targeted and novel agents may be appropriate to improve outcome in these patients. The agents of interest in sarcomas at this time are multi-tyrosine kinase inhibitors, antiangiogenesis agents, inhibitors of mammalian target of rapamycin, hypoxia-activating prodrugs, insulin growth factor monoclonal antibodies, and tumor necrosis factor-related apoptosis-inducing ligand agonists.

  View details for DOI 10.1007/s11912-010-0107-2

  View details for Web of Science ID 000287500300007

  View details for PubMedID 20464642

• Soft Tissue Sarcoma JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Demetri, G. D., Antonia, S., Benjamin, R. S., Bui, M. M., Casper, E. S., Conrad, E. U., DeLaney, T. F., Ganjoo, K. N., Heslin, M. J., Hutchinson, R. J., Kane, J. M., Letson, G. D., McGarry, S. V., O'Donnell, R. J., Paz, I. B., Pfeifer, J. D., Pollock, R. E., Randall, R. L., Riedel, R. F., Schupak, K. D., Schwartz, H. S., Thornton, K., von Mehren, M., Wayne, J. 2010; 8 (6): 630-674

  View details for Web of Science ID 000279929100002

  View details for PubMedID 20581298

• NCCN Task Force Report: Update on the Management of Patients with Gastrointestinal Stromal Tumors JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Demetri, G. D., von Mehren, M., Antonescu, C. R., DeMatteo, R. P., Ganjoo, K. N., Maki, R. G., Pisters, P. W., Raut, C. P., Riedel, R. F., Schuetze, S., Sundar, H. M., Trent, J. C., Wayne, J. D. 2010; 8: S1-S43

  Abstract

  The standard of care for managing patients with gastrointestinal stromal tumors (GISTs) rapidly changed after the introduction of effective molecularly targeted therapies involving tyrosine kinase inhibitors (TKIs), such as imatinib mesylate and sunitinib malate. A better understanding of the molecular characteristics of GISTs have improved the diagnostic accuracy and led to the discovery of novel immunomarkers and new mechanisms of resistance to TKI therapy, which in turn have resulted in the development of novel treatment strategies. To address these issues, the NCCN organized a task force consisting of a multidisciplinary panel of experts in the fields of medical oncology, surgical oncology, molecular diagnostics, and pathology to discuss the recent advances, identify areas of future research, and recommend an optimal approach to care for patients with GIST at all stages of disease. The task force met for the first time in October 2003 and again in December 2006 and October 2009. This supplement describes the recent developments in the field of GIST as discussed at the October 2009 meeting.

  View details for Web of Science ID 000279177400001

  View details for PubMedID 20457867

• Antiangiogenesis Agents in the Treatment of Soft Tissue Sarcomas CANCER Ganjoo, K., Jacobs, C. 2010; 116 (5): 1177-1183

  Abstract

  Soft tissue sarcomas (STSs) are a heterogeneous group of malignancies that includes >50 different subtypes, each with unique clinical and pathologic qualities. In general, there is a 50% cure rate, and most cures are achieved with complete surgical resection with or without radiation therapy. The results from chemotherapeutic agents for unresectable or metastatic disease have been disappointing with minimal long-term benefit. New targeted and novel agents are needed to improve response and survival. Tumor angiogenesis has been an intense focus in cancer therapy over the past decade. Several of numerous antiangiogenesis agents have been developed, and many already have been approved for the treatment of both solid and liquid tumors. Certain STSs are highly vascular tumors that often demonstrate angiogenesis markers. The objective of this review was to evaluate these angiogenesis markers in defining the role of angiogenesis in the treatment of patients with STS. In addition, the authors conducted an in-depth review of the results from using key antiangiogenesis agents in the treatment of STS.

  View details for DOI 10.1002/cncr.24859

  View details for Web of Science ID 000274772300006

  View details for PubMedID 20052715

• Trabectedin: an anticancer drug from the sea EXPERT OPINION ON PHARMACOTHERAPY Ganjoo, K. N., Patel, S. R. 2009; 10 (16): 2735-2743

  Abstract

  Trabectedin (ET-743) is an anticancer agent originally isolated from Ecteinascidia turbinata, a marine organism.The goal of this review is to describe the chemical characteristics, mechanism of action and the results of clinical trials with this compound. The toxicities are described, as well as the pharmacokinetics. The regulatory affairs and marketing strategies for this compound are also discussed.Medline and meeting proceedings were searched to accomplish our objectives.Trabectedin is a unique alkylating agent. It affects a variety of transcription factors, cell proliferation, and nucleotide excision repair mechanism. In addition, it inhibits the MDR-1 gene, which is responsible for the resistance of cancer cells to chemotherapeutic agents. The main toxicities of this agent are transaminitis and myelosuppression, both reversible and noncumulative. At present, trabectedin is approved in Europe for the treatment of sarcoma. The combination of this compound with other chemotherapeutics has been tested in Phase I studies in sarcomas and is feasible. This drug in combination with doxil has shown to improve outcome in relapsed ovarian cancer, compared with doxil alone. The results of this study may lead to an FDA approval of the combination in the USA, for the treatment of relapsed ovarian cancer.

  View details for DOI 10.1517/14656560903277236

  View details for Web of Science ID 000271971500014

  View details for PubMedID 19743937

• Acute myeloid leukemia in patients with gastrointestinal stromal tumors treated with Gleevec LEUKEMIA & LYMPHOMA Ganjoo, K. N., Demetri, G. D., Jacobs, C., Patel, S. 2009; 50 (11): 1882-1884

  View details for DOI 10.3109/10428190903242610

  View details for Web of Science ID 000272145000031

  View details for PubMedID 19883316

• Surgery and stereotactic radiosurgery for spinal leiomyosarcoma: a single-institution retrospective series and systematic review. Journal of neurosurgery. Spine Zamarud, A., Marianayagam, N. J., Sekar, V., Testa, S., Park, D. J., Yener, U., McCleary, T. L., Yoo, K. H., Emrich, S., Tayag, A., Ustrzynski, L., Pollom, E., Soltys, S., Wang, L., Charville, G., Ganjoo, K., Chang, S. D., Meola, A. 2023: 1-13

  Abstract

  Leiomyosarcoma (LMS) is a rare, aggressive soft-tissue sarcoma that seldom spreads to the bone. The spine can be either the site of LMS osseous metastases or the primary tumor site. The optimal treatment option for spinal LMS is still unclear. The authors present a cohort of patients with spinal LMS treated with either upfront surgery or upfront CyberKnife stereotactic radiosurgery (SRS).The authors retrospectively studied the clinical and radiological outcomes of 17 patients with spinal LMS treated at their institution between 2004 and 2020. Either surgery or SRS was used as the upfront treatment. The clinical and radiological outcomes were assessed. A systematic review of the literature was also conducted.Of the 17 patients (20 spinal lesions), 12 (70.6%) were female. The median patient age was 61 years (range 41-80 years). Ten patients had upfront surgery for their spinal lesions, and 7 had upfront CyberKnife radiosurgery. The median follow-up was 11 months (range 0.3-130 months). The median overall survival (OS) for the entire cohort was 13 months (range 0.3-97 months). In subgroup analysis, the median OS was lower for the surgical group (13 months, range 0.3-50 months), while the median OS for the SRS group was 15 months (range 5-97 months) (p = 0.5). Forty percent (n = 4) of those treated with surgery presented with local recurrence at a median of 6.7 months (range 0.3-36 months), while only 14% (n = 1) of those treated with CyberKnife radiosurgery had local recurrence after 5 months. Local tumor control (LTC) rates at the 6-, 12-, and 18-month follow-ups were 72%, 58%, and 43%, respectively, for the SRS group and 40%, 30%, and 20%, respectively, for the surgery group (p < 0.05). The literature review included 35 papers with 70 patients harboring spinal LMS; only 2 patients were treated with SRS. The literature review confirms the clinical and radiological outcomes of the surgical group, while data on SRS are anecdotal.The authors present the largest series in the literature of spinal LMS and the first on SRS for spinal LMS. This study shows that LTC is statistically significantly better in patients receiving upfront SRS instead of surgery. The OS does not appear different between the two groups.

  View details for DOI 10.3171/2023.10.SPINE23666

  View details for PubMedID 38157539

• Sex-Dependent Prognosis of Patients with Advanced Soft Tissue Sarcoma. Clinical cancer research : an official journal of the American Association for Cancer Research Pan, M., Zhou, M. Y., Jiang, C., Zhang, Z., Bui, N. Q., Bien, J., Siy, A., Achacoso, N., Solorzano, A. V., Tse, P., Chung, E., Thomas, S., Habel, L. A., Ganjoo, K. N. 2023

  Abstract

  To examine whether overall survival (OS) differs for male and female patients with advanced soft tissue sarcoma (STS).The study included patients from Kaiser Permanente Northern California and Stanford Cancer Center with grade 2 and 3 locally advanced or metastatic STS whose tumor underwent next-generation sequencing. We used Cox regression modeling to examine association of sex and OS adjusting for other important factors.Among 388 eligible patients, 174 had leiomyosarcoma (LMS), 136 had undifferentiated pleomorphic sarcoma (UPS), and 78 had LPS (Liposarcoma). OS for male versus female patients appeared to be slightly better among the full cohort (HR =0.89, [95% CI 0.66-1.20]); this association appeared to be stronger among the subsets of patients with LMS (HR = 0.76, [95% CI 0.39-1.49]) or LPS (HR = 0.74, [95% CI 0.32-1.70]). Better OS for male versus female patients was also observed among all molecular subgroups except mutRB1 and mutATRX, especially among patients whose tumor retained wtTP53 (HR = 0.73, [95% CI 0.44-1.18]), wtCDKN2A (HR = 0.85, [95% CI 0.59-1.23]), wtRB1 (HR = 0.73, [95% CI .51-1.04]) and among patients whose tumor had mutPTEN (HR = 0.37, [95% CI 0.09-1.62]). OS also appeared to be better for males in the MSK-IMPACT and TCGA datasets.A fairly consistent pattern of apparent better OS for males across histologic and molecular subgroups of STS was observed. If confirmed, our results could have implications for clinical practice for prognostic stratification and possibly treatment tailoring as well as for future clinical trials design.

  View details for DOI 10.1158/1078-0432.CCR-23-1990

  View details for PubMedID 37831066

• Epstein Barr Virus-Positive Lymphoproliferative Disorder Following Lymphodepletion for MAGE A4 Adoptive Cellular Therapy in a Patient with Synovial Sarcoma: A Case Report. Case reports in oncology Zhou, M., Jawed, G., Ganjoo, K. N. 2023; 16 (1): 886-892

  Abstract

  Lymphoproliferative disorder (LPD) associated with viral reactivation is a known risk of immunocompromised patients. With development of novel cellular therapies utilizing lymphodepletion regimens in advanced cancer, the risk of LPDs should be a consideration. Here, we report a case of a 61-year-old treated male with history of metastatic synovial sarcoma and multiple treatment lines treated with cell therapy (lymphodepleting chemotherapy and afami-cel, formerly ADP-A2M4, T-cell treatment) on clinical study that developed Epstein Barr virus-positive LPD. Patient was treated with rituximab and achieved a complete response. New cellular therapies present promising treatment options for patients and adverse events should be monitored carefully.

  View details for DOI 10.1159/000533129

  View details for PubMedID 37900845

  View details for PubMedCentralID PMC10601716

• Phase 2, multicenter, open-label basket trial of nab-sirolimus for patients with malignant solid tumors harboring pathogenic inactivating alterations in TSC1 or TSC2 genes (PRECISION I) Lee, E., Rodon, J., Demeure, M., Deming, D., Federman, N., McKean, M., Spira, A., Kwiatkowski, D., Hussein, M., Gordon, E., Crockett, D., Ganjoo, K., Schulte, B., Cranmer, L., Schmid, A., Navarro, W., Itri, L., Iyer, G. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2023: S185

  View details for DOI 10.1016/j.ygyno.2023.06.204

  View details for Web of Science ID 001079556100293

• Response to treatment with nab-sirolimus among patients with primary uterine PEComa: A sub analysis from AMPECT Palma, N., Navarro, W., Ravi, V., Dickson, M., Ganjoo, K., Ding, L., Schmid, A., Wagner, A. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2023: S180-S181

  View details for DOI 10.1016/j.ygyno.2023.06.195

  View details for Web of Science ID 001079556100284

• MR-guided focused ultrasound therapy of extra-abdominal desmoid tumors: a multicenter retrospective study of 105 patients. European radiology Düx, D. M., Baal, J. D., Bitton, R., Chen, J., Brunsing, R. L., Sheth, V. R., Rosenberg, J., Kim, K., Ozhinsky, E., Avedian, R., Ganjoo, K., Bucknor, M., Dobrotwir, A., Ghanouni, P. 2023

  Abstract

  To assess the safety and efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment extra-abdominal desmoids.A total of 105 patients with desmoid fibromatosis (79 females, 26 males; 35 ± 14 years) were treated with MRgFUS between 2011 and 2021 in three centers. Total and viable tumors were evaluated per patient at last follow-up after treatment. Response and progression-free survival (PFS) were assessed with (modified) response evaluation criteria in solid tumors (RECIST v.1.1 and mRECIST). Change in Numerical Rating Scale (NRS) pain and 36-item Short Form Health Survey (SF-36) scores were compared. Treatment-related adverse events were recorded.The median initial tumor volume was 114 mL (IQR 314 mL). After MRgFUS, median total and viable tumor volume decreased to 51 mL (95% CI: 30-71 mL, n = 101, p < 0.0001) and 29 mL (95% CI: 17-57 mL, n = 88, p < 0.0001), respectively, at last follow-up (median: 15 months, 95% CI: 11-20 months). Based on total tumor measurements (RECIST), 86% (95% CI: 75-93%) had at least stable disease or better at last follow-up, but 50% (95% CI: 38-62%) of remaining viable nodules (mRECIST) progressed within the tumor. Median PFS was reached at 17 and 13 months for total and viable tumors, respectively. NRS decreased from 6 (IQR 3) to 3 (IQR 4) (p < 0.001). SF-36 scores improved (physical health (41 (IQR 15) to 46 (IQR 12); p = 0.05, and mental health (49 (IQR 17) to 53 (IQR 9); p = 0.02)). Complications occurred in 36%, most commonly 1st/2nd degree skin burns.MRgFUS reduced tumor volume, reduced pain, and improved quality of life in this series of 105 patients with extra-abdominal desmoid fibromatosis.Imaging-guided ablation is being increasingly used as an alternative to surgery, radiation, and medical therapy for the treatment of desmoid fibromatosis. MR-guided high-intensity focused ultrasound is an incisionless ablation technique that can be used to reduce tumor burden effectively and safely.• Desmoid fibromatosis was treated with MR-guided high-intensity focused ultrasound in 105 patients. • MR-guided focused ultrasound ablation reduced tumor volume and pain and improved quality of life. • MR-guided focused ultrasound is a treatment option for patients with extra-abdominal desmoid tumors.

  View details for DOI 10.1007/s00330-023-10073-9

  View details for PubMedID 37615768

• Management Strategies and Outcomes in Primary Liver Angiosarcoma. American journal of clinical oncology Ramakrishnan, N., Mokhtari, R., Charville, G. W., Bui, N., Ganjoo, K. 2023

  Abstract

  Primary hepatic angiosarcoma is a rare tumor of the liver that originates from endothelial and fibroblastic tissue, with poor prognosis and lack of standardized treatment. We retrospectively analyzed the clinical characteristics and treatment outcomes of 23 patients with primary liver angiosarcoma treated at an academic sarcoma center.We screened all patients with primary liver angiosarcoma treated at Stanford between 2000 and 2022. Data was collected from EPIC electronic medical records and included patient demographics, tumor characteristics, treatment modalities, and patient outcomes. Statistical analysis was completed using Python 3.0, while survival curves were generated using the Kaplan-Meier method and Lifelines Packages.There were nearly equal numbers of males (11) and females (12) in our study, with most patients aged 70 to 79 at diagnosis. The median overall survival (OS) was 6 months (range 0.07 to 222.6 mo). The 2- and 5-year OS were both 38.6%. 71% of patients received systemic treatment with chemotherapy, while 29% received immunotherapy. Local treatment with surgery or radioembolization was performed in 14% of patients. Three patients in our study displayed particularly improved OS and received various treatments, which ranged from hepatic resection to ipilimumab/nivolumab.Our study demonstrated that primary liver angiosarcoma has poor outcomes despite treatment. Surgical resection with negative margins is the only curative modality. However, most patients present with advanced disease and are not surgical candidates. Further research is needed to identify more effective systemic therapy options for this devastating disease.

  View details for DOI 10.1097/COC.0000000000001032

  View details for PubMedID 37580871

• Systemic Treatments and Molecular Biomarkers for Perivascular Epithelioid Cell Tumors: A Single-institution Retrospective Analysis. Cancer research communications Testa, S., Bui, N. Q., Ganjoo, K. N. 2023; 3 (7): 1212-1223

  Abstract

  Perivascular epithelioid cell tumors (PEComa) are a large family of mesenchymal neoplasms, with variable clinical course. Evidence regarding treatment of advanced PEComas is scarce, with only one FDA-approved treatment available. The goals of this study were to provide data regarding systemic treatments for advanced PEComas and to identify biomarkers of prognostic relevance. This is a single-institution retrospective study of patients with advanced PEComas requiring systemic treatment, including malignant PEComa, angiomyolipoma (including the epithelioid variant), and lymphangioleiomyomatosis. Outcomes measured were overall survival (OS), first-line and combined progression-free survival (PFS), and tumor response. Kaplan-Meier, univariable, and multivariable Cox proportional hazards analysis were performed. A total of 29 patients were included, most with malignant PEComa (n = 17). Median OS was 204.9 months, while median PFS was 92.4 months from first-line, and 15.8 months for all lines combined. TFE3 overexpression correlated with higher risk of death (HR: 11.8, P = 0.04), and shorter median OS (P = 0.001). Chemotherapy and mTOR inhibitors showed similar OS (P = 0.84), and first-line PFS (P = 0.67). Combined PFS was similar between individual mTOR inhibitors, chemotherapy, immune checkpoint inhibitors and other treatments (P = 0.19). Different mTOR inhibitors demonstrated similar efficacy, making cost and availability important considerations when choosing a specific agent. mTOR inhibitors showed similar outcomes as chemotherapy, suggesting that these should be preferred whenever possible for patients with PEComas given the morbidity associated with chemotherapy. TFE3 overexpression highlighted a subgroup of PEComas with worse prognosis and more aggressive behavior.Significance: This study examines systemic treatments for advanced PEComas, a rare group of sarcomas, and identifies molecular biomarkers of prognosis. Our results show that mTOR inhibitors have similar efficacy as chemotherapy, and that TFE3 overexpression, on IHC or FISH, correlates with a more aggressive disease course.

  View details for DOI 10.1158/2767-9764.CRC-23-0139

  View details for PubMedID 37448552

• Randomized phase II trial of cabozantinib combined with PD-1 and CTLA-4 inhibition versus cabozantinib in metastatic soft tissue sarcoma Van Tine, B., Eulo, V., Toeniskoetter, J., Ruff, T., Luo, J., Kemp, L., Tellez, C., Weiss, M. C., Hirbe, A. C., Meyer, C., Elias, A. D., Diamond, M., Hartner, L. P., Bui, N., Ganjoo, K. N., Maki, R. G., Wilky, B. A. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001043181100045

• The SPEARHEAD-1 trial of afamitresgene autoleucel (afami-cel [formerly ADP-A2M4]): Analysis of overall survival in advanced synovial sarcoma Van Tine, B., Ganjoo, K. N., Blay, J., Valverde, C., Araujo, D. M., Razak, A., Le Cesne, A., Schuetze, S., Wagner, M. J., Attia, S., Forcade, E., Druta, M., Pollack, S., Bai, J., Bayer, P., Van Winkle, E., Norry, E., McAlpine, C., Williams, D., D'Angelo, S. P. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001053772002866

• Phase 2, multicenter, open-label basket trial of nab-sirolimus for patients with malignant solid tumors harboring pathogenic inactivating alterations in TSC1 or TSC2 genes (PRECISION I) Iyer, G., Deming, D. A., Demeure, M. J., Federman, N., McKean, M., Lee, E., Spira, A. I., Kwiatkowski, D. J., Hussein, M. A., Gordon, E., Crockett, D. G., Ganjoo, K. N., Schulte, B., Cranmer, L. D., Ding, L., Schmid, A. N., Navarro, W. H., Ahnert, J. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001053772005605

• The SPEARHEAD-1 trial of afamitresgene autoleucel (afami-cel [formerly ADP-A2M4]): Pooled analysis of cytokine release syndrome across cohorts in patients with advanced synovial sarcoma. D'Angelo, S. P., Ganjoo, K. N., Blay, J., Valverde, C., Araujo, D. M., Razak, A., Le Cesne, A., Schuetze, S., Wagner, M. J., Attia, S., Forcade, E., Druta, M., Pollack, S., Bai, J., Lunt, C., Sun, A., Yule, M., McAlpine, C., Williams, D., Van Tine, B. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001053772001647

• Treatment of De-Differentiated Liposarcoma in the Era of Immunotherapy. International journal of molecular sciences Zhou, M. Y., Bui, N. Q., Charville, G. W., Ganjoo, K. N., Pan, M. 2023; 24 (11)

  Abstract

  Well-differentiated/de-differentiated liposarcoma (WDLPS/DDLPS) is one of the most common histologic subtypes of soft tissue sarcoma (STS); however, treatment options remain limited. WDLPS and DDLPS both exhibit the characteristic amplification of chromosome region 12q13-15, which contains the genes CDK4 and MDM2. DDLPS exhibits higher amplification ratios of these two and carries additional genomic lesions, including the amplification of chromosome region 1p32 and chromosome region 6q23, which may explain the more aggressive biology of DDLPS. WDLPS does not respond to systemic chemotherapy and is primarily managed with local therapy, including multiple resections and debulking procedures whenever clinically feasible. In contrast, DDLPS can respond to chemotherapy drugs and drug combinations, including doxorubicin (or doxorubicin in combination with ifosfamide), gemcitabine (or gemcitabine in combination with docetaxel), trabectedin, eribulin, and pazopanib. However, the response rate is generally low, and the response duration is usually short. This review highlights the clinical trials with developmental therapeutics that have been completed or are ongoing, including CDK4/6 inhibitors, MDM2 inhibitors, and immune checkpoint inhibitors. This review will also discuss the current landscape in assessing biomarkers for identifying tumors sensitive to immune checkpoint inhibitors.

  View details for DOI 10.3390/ijms24119571

  View details for PubMedID 37298520

• A Retrospective Multi-Institutional Cohort Analysis of Clinical Characteristics and Outcomes in Dedifferentiated Chondrosarcoma. Cancers Bui, N., Dietz, H., Farag, S., Hirbe, A. C., Wagner, M. J., Van Tine, B. A., Ganjoo, K., Jones, R. L., Keedy, V. L., Davis, E. J. 2023; 15 (9)

  Abstract

  BACKGROUND: Dedifferentiated chondrosarcoma (DDCS) is a rare subset of chondrosarcoma. It is an aggressive neoplasm characterized by a high rate of recurrent and metastatic disease with overall poor outcomes. Systemic therapy is often used to treat DDCS; however, the optimal regimen and timing are not well defined, with current guidelines recommending following osteosarcoma protocols.METHODS: We conducted a multi-institutional retrospective analysis of clinical characteristics and outcomes of patients with DDCS. Between 1 January 2004 and 1 January 2022, the databases from five academic sarcoma centers were reviewed. Patient and tumor factors, including age, sex, tumor size, site, location, the treatments rendered, and survival outcomes, were collected.RESULTS: Seventy-four patients were identified and included in the analysis. Most patients presented with localized disease. Surgical resection was the mainstay of therapy. Chemotherapy was used predominantly in the metastatic setting. Partial responses were low (n = 4; 9%) and occurred upon treatment with doxorubicin with cisplatin or ifosfamide and single-agent pembrolizumab. For all other regimens, stable disease was the best response. Prolonged stable disease occurred with the use of pazopanib and immune checkpoint inhibitors.CONCLUSIONS: DDCS has poor outcomes and conventional chemotherapy has limited benefit. Future studies should focus on defining the possible role of molecularly targeted therapies and immunotherapy in the treatment of DDCS.

  View details for DOI 10.3390/cancers15092617

  View details for PubMedID 37174084

• Monitoring sarcoma response to immune checkpoint inhibition and local cryotherapy with circulating tumor DNA analysis. Clinical cancer research : an official journal of the American Association for Cancer Research Bui, N. Q., Nemat-Gorgani, N., Subramanian, A., Torres, I. A., Lohman, M., Sears, T. J., van de Rijn, M., Charville, G. W., Becker, H. C., Wang, D. S., Hwang, G. L., Ganjoo, K. N., Moding, E. J. 2023

  Abstract

  Immune checkpoint inhibition has led to promising responses in soft tissue sarcomas (STSs), but the majority of patients do not respond and biomarkers of response will be crucial. Local ablative therapies may augment systemic responses to immunotherapy. We evaluated circulating tumor DNA (ctDNA) as a biomarker of response in patients treated on a trial combining immunotherapy with local cryotherapy for advanced STSs.We enrolled 30 patients with unresectable or metastatic STS to a phase 2 clinical trial. Patients received ipilimumab and nivolumab for 4 doses followed by nivolumab alone with cryoablation performed between cycles 1 and 2. The primary endpoint was objective response rate (ORR) by 14 weeks. Personalized ctDNA analysis using bespoke panels was performed on blood samples collected prior to each immunotherapy cycle.ctDNA was detected in at least one sample for 96% of patients. Pre-treatment ctDNA allele fraction was negatively associated with treatment response, progression-free survival (PFS), and overall survival (OS). ctDNA increased in 90% of patients from pre-treatment to post-cryotherapy, and patients with a subsequent decrease in ctDNA or undetectable ctDNA after cryotherapy had significantly better PFS. Of the 27 evaluable patients, the ORR was 4% by RECIST and 11% by irRECIST. Median PFS and OS were 2.7 and 12.0 months, respectively. No new safety signals were observed.ctDNA represents a promising biomarker for monitoring response to treatment in advanced STS, warranting future prospective studies. Combining cryotherapy and immune checkpoint inhibitors did not increase the response rate of STSs to immunotherapy.

  View details for DOI 10.1158/1078-0432.CCR-23-0250

  View details for PubMedID 37130154

• Phase 2, multicenter, open-label basket trial of nab-sirolimus for patients with malignant solid tumors harboring pathogenic inactivating alterations in TSC1 or TSC2 genes (PRECISION I). Iyer, G., Demeure, M. J., Deming, D. A., Federman, N., McKean, M., Lee, E., Spira, A. I., Kwiatkowski, D. J., Hussein, M. A., Gordon, E., Crockett, D. G., Ganjoo, K. N., Schulte, B., Cranmer, L. D., Schmid, A. N., Navarro, W. H., Itri, L. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001098050200075

• Phase 2, multicenter, open-label basket trial of nab-sirolimus for patients with malignant solid tumors harboring pathogenic inactivating alterations in TSC1 or TSC2 genes (PRECISION I). Deming, D. A., Ahnert, J., Demeure, M. J., Federman, N., McKean, M., Lee, E., Spira, A. I., Kwiatkowski, D. J., Hussein, M. A., Gordon, E., Crockett, D. G., Ganjoo, K. N., Schulte, B., Cranmer, L. D., Schmid, A. N., Navarro, W. H., Itri, L., Iyer, G. LIPPINCOTT WILLIAMS & WILKINS. 2023: TPS818

  View details for Web of Science ID 001093994600106

• PHASE 2, MULTICENTER, OPEN-LABEL BASKET TRIAL OF NAB-SIROLIMUS FOR PATIENTS WITH MALIGNANT SOLID TUMORS HARBORING PATHOGENIC INACTIVATING ALTERATIONS IN TSC1 OR TSC2 GENES (PRECISION I) Rodon, J., Demeure, M., Deming, D., Federman, N., Mckean, M., Lee, E., Spira, A., Kwiatkowski, D., Hussein, M., Gordon, E., Crockett, D., Ganjoo, K., Schulte, B., Cranmer, L., Schmid, A., Navarro, W., Itri, L., Iyer, G. BMJ PUBLISHING GROUP. 2022: A231-A232

  View details for DOI 10.1136/ijgc-2022-igcs.527

  View details for Web of Science ID 000899252300483

• Long-term Outcomes of Diffuse or Recurrent Tenosynovial Giant Cell Tumor Treated with Postoperative External Beam Radiation Therapy. Practical radiation oncology Baniel, C., Yoo, C. H., Jiang, A., von Eyben, R., Mohler, D. G., Ganjoo, K., Bui, N., Donaldson, S. S., Million, L., Rijn, M. v., Moon Oh, J., Hiniker, S. M. 2022

  Abstract

  PURPOSE: Tenosynovial giant cell tumor (TGCT) is a rare proliferative disorder of synovial membrane that previously was known as pigmented villonodular synovitis (PVNS). Primary treatment involves surgical resection, however, complete removal of all disease involvement is difficult to achieve. Radiation may be useful to reduce the risk of recurrence. We report and update our institutional experience treating diffuse and recurrent TGCT with postsurgical external beam radiation therapy.METHODS AND MATERIALS: We performed a retrospective chart review of 30 patients with TGCT from 2003-2019 treated with radiation therapy. Each patient was evaluated for demographics, radiation treatment parameters, surgical management, complications, and outcome.RESULTS: With mean follow-up of 82 months (range 3-211), 24 patients (80%) who underwent surgery followed by radiation therapy did not experience any further relapse, and all 30 patients achieved local control (100%) with additional salvage therapy following radiotherapy. The most common site of disease was the knee (n=22, 73%), followed by the ankle (n=5, 16%) and the hand (n=3, 10%). Seven patients (24%) presented at time of initial diagnosis while 23 (76%) presented with recurrent disease following surgical resection, with an average of 2.6 surgical procedures prior to radiotherapy. Following resection, 18/30 patients (67%) demonstrated residual TGCT by imaging. The median radiotherapy dose delivered was 36 Gy (range, 34-36 Gy) in 1.8-2.5 Gy/fractions over 4 weeks. In the assessment of post-treatment joint function, 26 sites (86%) exhibited excellent or good function, 2 (7%) fair, and 2 poor (7%) as determined by our scoring system. There were no cases of radiation-associated malignancy.CONCLUSIONS: Among patients with diffuse or recurrent TGCT, postsurgical external beam radiation therapy provided excellent local control and good functional status, with minimal treatment-related complications. Post-surgical radiation therapy is a well-tolerated noninvasive treatment that should be considered following maximal cytoreductive resection to prevent disease progression and recurrence.

  View details for DOI 10.1016/j.prro.2022.11.004

  View details for PubMedID 36460182

• Enrollment of pediatric and adolescent patients with MAGE-A4+advanced synovial sarcoma into cohort 2 of SPEARHEAD-1: a phase 2 trial of afamitresgene autoleucel ("afami-cel" [formerly ADP-A2M4]) Lunt, C., D'Angelo, S. P., Razak, A., Wagner, M. J., Van Tine, B. A., Ganjoo, K., Blay, J., Araujo, D. M., Agulnik, M., Glod, J. W., Van Winkle, E., Elefant, E., Biswas, S., Williams, D., Le Cesne, A. AMER ASSOC CANCER RESEARCH. 2022: 3-4

  View details for Web of Science ID 000860580000005

• Enrollment of pediatric and adolescent patients with MAGE-A4+advanced synovial sarcoma into cohort 2 of SPEARHEAD-1: a phase 2 trial of afamitresgene autoleucel ("afami-cel" [formerly ADP-A2M4]) Lunt, C., D'Angelo, S. P., Razak, A., Wagner, M. J., Van Tine, B. A., Ganjoo, K., Blay, J., Araujo, D. M., Agulnik, M., Glod, J. W., Van Winkle, E., Elefant, E., Biswas, S., Williams, D., Le Cesne, A. AMER ASSOC CANCER RESEARCH. 2022

  View details for Web of Science ID 001053847900094

• Interactions in CSF1-driven Tenosynovial Giant Cell Tumors. Clinical cancer research : an official journal of the American Association for Cancer Research van IJzendoorn, D. G., Matusiak, M., Charville, G. W., Spierenburg, G., Varma, S., Colburg, D. R., van de Sande, M. A., van Langevelde, K., Mohler, D. G., Ganjoo, K. N., Bui, N. Q., Avedian, R. S., Bovee, J. V., Steffner, R., West, R. B., van de Rijn, M. 2022

  Abstract

  A major component of cells in Tenosynovial Giant Cell Tumor (TGCT) consists of bystander macrophages responding to CSF1 that is overproduced by a small number of neoplastic cells with a chromosomal translocation involving the CSF1 gene. An autocrine loop was postulated where the neoplastic cells would be stimulated through CSF1R expressed on their surface. Here we use single cell RNA sequencing to investigate cellular interactions in TGCT.A total of 18,788 single cells from three TGCT and two Giant Cell Tumor of Bone (GCTB) samples underwent singe cell RNAseq. The three TGCTs were additionally analyzed using long read RNA sequencing. Immunofluorescence and immunohistochemistry for a range of markers was used to validate and extend the scRNAseq findings.Two recurrent neoplastic cell populations were identified in TGCT that are highly similar to non-neoplastic synoviocytes. We identified GFPT2 as a marker that highlights the neoplastic cells in TCGT. We show that the neoplastic cells themselves do not express CSF1R. We identified overlapping features between the giant cells in TGCT and GCTB.The neoplastic cells in TGCT are highly similar non-neoplastic synoviocytes. The lack of CSF1R on the neoplastic cells indicates they may be unaffected by current therapies. High expression of GFPT2 in the neoplastic cells is associated with activation of the YAP1/TAZ pathway. In addition, we identified expression of the PDGF receptor in the neoplastic cells. These findings suggest two additional pathways to target in this tumor.

  View details for DOI 10.1158/1078-0432.CCR-22-1898

  View details for PubMedID 36007098

• Pexidartinib Provides Modest Pain Relief in Patients With Tenosynovial Giant Cell Tumor: Results From ENLIVEN. Clinical orthopaedics and related research Healey, J. H., Tap, W. D., Gelhorn, H. L., Ye, X., Speck, R. M., Palmerini, E., Stacchiotti, S., Desai, J., Wagner, A. J., Alcindor, T., Ganjoo, K., Martin-Broto, J., Wang, Q., Shuster, D., Gelderblom, H., van de Sande, M. 2022

  Abstract

  BACKGROUND: The double-blind, randomized, placebo-controlled phase 3 study of orally administered PLX3397 in patients with pigmented villonodular synovitis or giant cell tumor of the tendon sheath (ENLIVEN) showed that pexidartinib provides a robust objective tumor response in adults with tenosynovial giant cell tumors (TGCT) not amenable to improvement with surgery. Based on these results, in 2019, pexidartinib received accelerated approval in the United States in this population as a breakthrough therapy under an orphan drug designation. However, the ability of pexidartinib to relieve pain in ENLIVEN was not fully detailed, and the relationship between pain relief and objective tumor response was not described.QUESTIONS/PURPOSES: (1) What level of pain relief was achieved by pexidartinib treatment in ENLIVEN? (2) How was pain relief related to objective tumor responses? (3) How durable was pain relief?METHODS: The current study included planned primary and exploratory assessments of patient-assessed worst pain at the site of the tumor in the ENLIVEN trial. ENLIVEN was a phase 3 randomized, placebo-controlled clinical trial in which adults with TGCT not amenable to improvement with surgery received pexidartinib or placebo for 24 weeks, after which eligible patients could receive open-label pexidartinib. Of 174 patients assessed for eligibility, 121 were randomized (50% [60] to placebo, 50% [61] to pexidartinib), and 120 were given either placebo or pexidartinib (59 received placebo and 61 received pexidartinib) and were included in an intent-to-treat analysis. Fifty-nine percent (71 of 120) of the overall treated population was female, and 88% (106 of 120) were White. Mean age was 45 ± 13 years. Tumors were mostly in the lower extremities (92% [110 of 120]), most commonly in the knee (61% [73 of 120]) and ankle (18% [21 of 120]). As a secondary outcome, patients scored worst pain at the site of the tumor in the past 24 hours on an 11-point numeric rating scale (NRS). The primary definition of a pain response was a decrease of at least 30% in the weekly mean worst-pain NRS score and increase of less than 30% in narcotic analgesic use between baseline and week 25. Planned exploratory assessments of pain included the frequency of a pain response using alternative thresholds, including a decrease in worst-pain NRS score of 50% or more and a decrease of at least 2 points (minimum clinically important difference [MCID]), the magnitude of pain reduction between baseline and week 25, correlation between worst-pain NRS score and tumor shrinkage by RECIST 1.1 criteria, and the durability of the pain response during the open-label extension. Pain responses during the randomized portion of the trial were compared according to intention-to-treat analysis, with a one-sided threshold of p < 0.025 to reduce the risk of false-positive results. Pain assessment was complete for 59% (35 of 59) of patients in the placebo group and 54% (33 of 61) of patients in the pexidartinib group. Demographic and disease characteristics did not differ between the two treatment groups.RESULTS: A difference in the primary assessment of a pain response was not detected between pexidartinib and placebo (response percentage 31% [19 of 61] [95% CI 21% to 44%] versus 15% [9 of 59] [95% CI 8% to 27%]; one-sided p = 0.03). In the exploratory analyses, pexidartinib provided a modest improvement in pain (response percentage 26% [16 of 61] [95% CI 17% to 38%] versus 10% [6 of 59] [95% CI 5% to 20%]; one-sided p = 0.02 using the 50% threshold and 31% [19 of 61] [95% CI 21% to 44%] versus 14% [8 of 59] [95% CI 7% to 25%]; one-sided p = 0.02 using the MCID threshold). The least-squares mean change in the weekly mean worst-pain NRS score between baseline and week 25 was larger in patients treated with pexidartinib than placebo (-2.5 [95% CI -3.0 to -1.9] versus -0.3 [95% CI -0.9 to 0.3]; p < 0.001), although the mean difference between the two groups (-2.2 [95% CI -3.0 to -1.4]) was just over the MCID. Improvement in the weekly mean worst-pain NRS score correlated with the reduction in tumor size (r = 0.44; p < 0.001) and tumor volume score (r = 0.61; p < 0.001). For patients in the open-label extension, the change in the worst-pain NRS score from baseline was similar to the change at the end of the randomized portion and just above the MCID (mean -2.7 ± 2.2 after 25 weeks and -3.3 ± 1.7 after 50 weeks of receiving pexidartinib).CONCLUSION: Based on the current study, a modest reduction in pain, just larger than the MCID, may be an added benefit of pexidartinib in these patients, although the findings are insufficient to justify the routine use of pexidartinib for pain relief.LEVEL OF EVIDENCE: Level II, therapeutic study.

  View details for DOI 10.1097/CORR.0000000000002335

  View details for PubMedID 36001000

• A phase II trial of regorafenib in patients with advanced Ewing sarcoma and related tumors of soft tissue and bone: SARC024 trial results. Cancer medicine Attia, S., Bolejack, V., Ganjoo, K. N., George, S., Agulnik, M., Rushing, D., Loggers, E. T., Livingston, M. B., Wright, J., Chawla, S. P., Okuno, S. H., Reinke, D. K., Riedel, R. F., Davis, L. E., Ryan, C. W., Maki, R. G. 2022

  Abstract

  BACKGROUND: Regorafenib is one of several FDA-approved cancer therapies targeting multiple tyrosine kinases. However, there are few subtype-specific data regarding kinase inhibitor activity in sarcomas. We report results of a single arm, phase II trial of regorafenib in advanced Ewing family sarcomas.METHODS: Patients with metastatic Ewing family sarcomas (age≥18, ECOG 0-2, good organ function) who had received at least one line of therapy and experienced progression within 6months of registration were eligible. Prior kinase inhibitors were not allowed. The initial dose of regorafenib was 160mg oral days 1-21 of a 28-day cycle. The primary endpoint was estimating progression-free rate (PFR) at 8weeks employing RECIST 1.1.RESULTS: Thirty patients (median age, 32years; 33% women [10 patients]; bone primary, 40%; extraskeletal primary, 60%) enrolled at 14 sites. The most common grade 3 or higher toxicities were hypophosphatemia (5 grade 3, 1 grade 4), hypertension (2 grade 3), elevated ALT (2 grade 3). Sixteen patients required dose reductions, most often for hypophosphatemia (n=7 reductions in 6 patients); two stopped regorafenib for toxicity. There was one death unrelated to treatment in the 30-day post-study period. Median progression-free survival (PFS) was 14.8weeks (95% CI 7.3-15.9); PFR at 8weeks by Kaplan-Meier analysis was 63% (95% CI 46-81%). The RECIST 1.1 response rate was 10%. Median OS was 53weeks (95% CI 37-106weeks).CONCLUSIONS: Regorafenib has modest activity in the Ewing family sarcomas. Toxicity was similar to that seen in approval studies.

  View details for DOI 10.1002/cam4.5044

  View details for PubMedID 35950293

• Cutaneous Angiosarcoma of the Head and Neck-A Retrospective Analysis of 47 Patients. Cancers Ramakrishnan, N., Mokhtari, R., Charville, G. W., Bui, N., Ganjoo, K. 2022; 14 (15)

  Abstract

  Cutaneous angiosarcoma (CAS) is a rare and aggressive malignant tumor with blood vessel or lymphatic-type endothelial differentiation. It has a poor prognosis with lack of standardized treatment options. This study retrospectively evaluated the clinical characteristics and treatment outcomes of 47 patients with CAS of the head and neck treated at an academic sarcoma center. Patient data were collected from the electronic medical records. 62% of patients were male with the scalp being the most commonly affected area (64%). The majority of patients presented with localized disease (53%). Median overall survival (OS) was 3.4 years with an OS of 36% at 5 years. There was a statistically significant increase in OS for patients who underwent surgery compared to those who did not (5.4 vs. 2.8 years). In contrast, radiotherapy (RT) or chemotherapy did not significantly increase OS. 45% of patients had recurrence of disease during their treatment course with a median time to recurrence of 22.8 months. There was not a significant difference in OS for patients who underwent immunotherapy compared to those who underwent chemotherapy, although only a few patients received immunotherapy. We found that surgery was an effective treatment modality in patients with easily resectable disease, while RT, chemotherapy, and immunotherapy did not significantly improve OS.

  View details for DOI 10.3390/cancers14153841

  View details for PubMedID 35954504

• First Recurrence of Synovial Sarcoma Presenting With Solitary Pancreatic Mass CUREUS JOURNAL OF MEDICAL SCIENCE Narayan, R. R., Charville, G. W., Delitto, D., Ganjoo, K. N. 2022; 14 (6)

  View details for DOI 10.7759/cureus.26356

  View details for Web of Science ID 000818961000017

• nab-Sirolimus for patients with advanced malignant PEComa with or without prior mTOR inhibitors: Biomarker results from AMPECT and an expanded access program. Dickson, M., Ravi, V., Riedel, R. F., Ganjoo, K. N., Van Tine, B., Chugh, R., Cranmer, L. D., Gordon, E., Chen, J., Murphy, M., Schmid, A. N., Desai, N., Palma, N., Kwiatkowski, D. J., Wagner, A. J. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for Web of Science ID 000863680300415

• First Recurrence of Synovial Sarcoma Presenting With Solitary Pancreatic Mass. Cureus Narayan, R. R., Charville, G. W., Delitto, D., Ganjoo, K. N. 2022; 14 (6): e26356

  Abstract

  Synovial sarcoma usually presents in the lower extremities and metastasizes to the lungs; however, unusual patterns of recurrence can occur. For patients with recurrent synovial sarcoma to a proximal peripancreatic lymph node, a pancreaticoduodenectomy or Whipple procedure is the best option for a cure. Lymph node metastasis from synovial sarcoma is exceptionally rare, and data guiding the use of the Whipple procedure for curative resection of metastatic synovial sarcoma are even more sparse. In this report, we describe the management of a patient with metastatic synovial sarcoma to a proximal peripancreatic lymph node with a pancreaticoduodenectomy.

  View details for DOI 10.7759/cureus.26356

  View details for PubMedID 35903565

  View details for PubMedCentralID PMC9326242

• Local control outcomes using stereotactic body radiotherapy or surgical resection for metastatic sarcoma. International journal of radiation oncology, biology, physics Gutkin, P. M., von Eyben, R., Chin, A., Donaldson, S. S., Oh, J., Jiang, A., Ganjoo, K. N., Avedian, R. S., Bruzoni, M., Steffner, R. J., Moding, E. J., Hiniker, S. M. 2022

  Abstract

  Traditional management of metastatic sarcoma primarily relies on systemic therapy, with surgery often used for tumor control. We analyzed the rates of recurrence, overall survival, and treatment complications in patients undergoing either surgical resection or stereotactic body radiotherapy (SBRT) for metastatic sarcoma of the bone and/or soft tissue.The records of patients with metastatic sarcoma between 2009-2020 were reviewed. Local recurrence (LR) was defined as tumor growth or recurrence at the tumor site. Cumulative local recurrence incidence was analyzed accounting for the competing risk of death, and groups were compared using the Gray test. Overall survival (OS) was assessed using the Kaplan Meier method and log-rank test. Hazard ratios were determined using Cox proportional test.A total of 525 metastatic lesions in 217 patients were analyzed. Mean age was 57 years (range 4-88). The lung was the predominant site treated (50%), followed by intra-abdominal (13%), and soft-tissue (11%). Two-year cumulative incidences of LR for surgery and SBRT were 14.8% (95% confidence interval [CI], 11.6-18.5) and 1.7% (95% CI, 0.1-8.2), respectively (p=0.003). LR occurred in 72/437 (16.5%) tumors treated with surgery and 2/88 (2.3%) tumors treated with SBRT. Adjusted hazard ratio for LR of lesions treated surgically was 11.5 (p=0.026) when controlled for tumor size and tumor site. Median OS was 29.8 months (95% CI, 25.6-40.9). There were 47 surgical complications of a total of 275 procedures (18%). Of 58 radiation treatment courses, radiation-related toxicity was reported during the treatment of 7 lesions (12%), and none were higher than grade 2.We observed excellent local control among patients selected for treatment with SBRT for metastatic sarcoma, with no evidence of increase in LR following SBRT when compared to surgical management. Further investigation is necessary to better define the most appropriate local control strategies for metastatic sarcoma.

  View details for DOI 10.1016/j.ijrobp.2022.05.017

  View details for PubMedID 35643255

• Current management and recent progress in desmoid tumors. Cancer treatment and research communications Zhou, M. Y., Bui, N. Q., Charville, G. W., Ghanouni, P., Ganjoo, K. N. 2022; 31: 100562

  Abstract

  Desmoid tumors are rare soft tissue tumors that can have aggressive infiltrative growth and relapse locally. Desmoid tumors can impact functionality and cause treatment-related morbidity and mortality. Here, the authors review current management strategies and avenues for further investigation. As part of the evolution of therapy away from primary surgical approaches to less invasive options, image-guided ablation has been accepted as less morbid and include cryoablation and high-intensity focused ultrasound. Systemic therapy options currently include hormonal agents, nonsteroidal anti-inflammatory drugs, tyrosine kinase inhibitors, and anthracycline-based regimens. Hormonal agents and nonsteroidal anti-inflammatory drugs have benign side effect profiles but generally limited efficacy. Anthracycline-based therapies are limited by the risk of secondary malignancies and cardiomyopathy. Tyrosine kinase inhibitors are well studied, and sorafenib is now one of the most utilized therapies, though limited by its side effect profile. Nirogacestat (PF-0308401) is an investigational small molecule gamma-secretase (GS) inhibitor that has demonstrated efficacy in phase 1 and II trials. A phase III trial investigating patients with desmoid tumors or aggressive fibromatosis is estimated to be completed December 2021 (NCT03785964). In addition to nirogacestat, the gamma-secretase inhibitor AL102 is being investigated for the treatment of patients with progressing desmoid tumors in the phase II/III RINGSIDE trial. Finally, the beta-catenin inhibitor Tegavivint (BC2059) is being investigated in a phase 1 open-label trial in patients with a proven primary or recurrent desmoid tumor that is unresectable and symptomatic or progressive.

  View details for DOI 10.1016/j.ctarc.2022.100562

  View details for PubMedID 35460976

• Selinexor in Advanced, Metastatic Dedifferentiated Liposarcoma: A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Gounder, M. M., Razak, A. A., Somaiah, N., Chawla, S., Martin-Broto, J., Grignani, G., Schuetze, S. M., Vincenzi, B., Wagner, A. J., Chmielowski, B., Jones, R. L., Riedel, R. F., Stacchiotti, S., Loggers, E. T., Ganjoo, K. N., Le Cesne, A., Italiano, A., Garcia Del Muro, X., Burgess, M., Piperno-Neumann, S., Ryan, C., Mulcahy, M. F., Forscher, C., Penel, N., Okuno, S., Elias, A., Hartner, L., Philip, T., Alcindor, T., Kasper, B., Reichardt, P., Lapeire, L., Blay, J., Chevreau, C., Valverde Morales, C. M., Schwartz, G. K., Chen, J. L., Deshpande, H., Davis, E. J., Nicholas, G., Groschel, S., Hatcher, H., Duffaud, F., Herraez, A. C., Beveridge, R. D., Badalamenti, G., Eriksson, M., Meyer, C., von Mehren, M., Van Tine, B. A., Gotze, K., Mazzeo, F., Yakobson, A., Zick, A., Lee, A., Gonzalez, A. E., Napolitano, A., Dickson, M. A., Michel, D., Meng, C., Li, L., Liu, J., Ben-Shahar, O., Van Domelen, D. R., Walker, C. J., Chang, H., Landesman, Y., Shah, J. J., Shacham, S., Kauffman, M. G., Attia, S. 2022: JCO2101829

  Abstract

  PURPOSE: Antitumor activity in preclinical models and a phase I study of patients with dedifferentiated liposarcoma (DD-LPS) was observed with selinexor. We evaluated the clinical benefit of selinexor in patients with previously treated DD-LPS whose sarcoma progressed on approved agents.METHODS: SEAL was a phase II-III, multicenter, randomized, double-blind, placebo-controlled study. Patients age 12 years or older with advanced DD-LPS who had received two-five lines of therapy were randomly assigned (2:1) to selinexor (60 mg) or placebo twice weekly in 6-week cycles (crossover permitted). The primary end point was progression-free survival (PFS). Patients who received at least one dose of study treatment were included for safety analysis. (Registration: ClinicalTrials.gov identifier: NCT02606461.).RESULTS: Two hundred eighty-five patients were enrolled (selinexor, n = 188; placebo, n = 97). PFS was significantly longer with selinexor versus placebo: hazard ratio (HR) 0.70 (95% CI, 0.52 to 0.95; one-sided P = .011; medians 2.8 v 2.1 months), as was time to next treatment: HR 0.50 (95% CI, 0.37 to 0.66; one-sided P < .0001; medians 5.8 v 3.2 months). With crossover, no difference was observed in overall survival. The most common treatment-emergent adverse events of any grade versus grade 3 or 4 with selinexor were nausea (151 [80.7%] v 11 [5.9]), decreased appetite (113 [60.4%] v 14 [7.5%]), and fatigue (96 [51.3%] v 12 [6.4%]). Four (2.1%) and three (3.1%) patients died in the selinexor and placebo arms, respectively. Exploratory RNA sequencing analysis identified that the absence of CALB1 expression was associated with longer PFS with selinexor compared with placebo (median 6.9 v 2.2 months; HR, 0.19; P = .001).CONCLUSION: Patients with advanced, refractory DD-LPS showed improved PFS and time to next treatment with selinexor compared with placebo. Supportive care and dose reductions mitigated side effects of selinexor. Prospective validation of CALB1 expression as a predictive biomarker for selinexor in DD-LPS is warranted.

  View details for DOI 10.1200/JCO.21.01829

  View details for PubMedID 35394800

• Efficacy and Safety of TRC105 Plus Pazopanib vs Pazopanib Alone for Treatment of Patients With Advanced Angiosarcoma: A Randomized Clinical Trial. JAMA oncology Jones, R. L., Ravi, V., Brohl, A. S., Chawla, S., Ganjoo, K. N., Italiano, A., Attia, S., Burgess, M. A., Thornton, K., Cranmer, L. D., Cheang, M. C., Liu, L., Robertson, L., Adams, B., Theuer, C., Maki, R. G. 2022

  Abstract

  Importance: Angiosarcoma is a rare sarcoma subtype with a poor outcome. Carotuximab plus pazopanib produced a median progression-free survival (PFS) of 7.8 months in pazopanib-naive patients with chemotherapy-refractory angiosarcoma in a phase 1/2 trial.Objective: To determine whether carotuximab plus pazopanib improves PFS compared with pazopanib alone in patients with advanced angiosarcoma.Design, Setting, and Participants: The TAPPAS Trial: An Adaptive Enrichment Phase 3 Trial of TRC105 and Pazopanib vs Pazopanib Alone in Patients With Advanced Angiosarcoma was a multinational, multicenter, open-label, parallel-group, phase 3 randomized clinical trial of 123 patients 18 years or older with advanced angiosarcoma that was conducted between February 16, 2017, and April 12, 2019, at 31 sites in the US and the European Union. Patients were randomized 1:1 to receive pazopanib alone or carotuximab plus pazopanib. The trial incorporated an adaptive enrichment design. Inclusion criteria were no more than 2 prior lines of systemic therapy and an Eastern Cooperative Oncology Group performance status of 0 or 1. The efficacy analysis used the intent-to-treat population; the safety analysis included all patients who received a dose of either study drug.Exposures: Oral pazopanib, 800 mg/d, or intravenous carotuximab, 10 mg/kg, administered weekly, plus oral pazopanib, 800 mg/d, with dose modification allowed per patient tolerance or until disease progression.Main Outcomes and Measures: The primary end point was PFS, assessed by blinded independent radiographic and cutaneous photographic review per Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, version 1.1. Secondary end points included the objective response rate and overall survival. An interim analysis to determine the final sample size was conducted after enrollment of 123 patients. PFS in the group receiving pazopanib alone was compared with PFS in the group receiving carotuximab plus pazopanib using the log rank test.Results: Of 114 patients with evaluable data (53 in the pazopanib arm and 61 in the carotuximab plus pazopanib arm), 69 (61%) were female and the median age was 68 years (range, 24-82 years); 57 (50%) had cutaneous disease and 32 (28%) had had no prior treatment. The primary end point (PFS) was not reached (hazard ratio [HR], 0.98; 95% CI, 0.52-1.84; P=.95), with a median of 4.3 months (95% CI, 2.9 months to not reached) for pazopanib and 4.2 months (95% CI, 2.8-8.3 months) for the combination arm. The most common all-grade adverse events in the single-agent pazopanib arm vs the combination arm were fatigue (29 patients [55%] vs 37 [61%]), headache (12 patients [23%] vs 39 [64%]), diarrhea (27 patients [51%] vs 35 [57%]), nausea (26 patients [49%] vs 29 [48%]), vomiting (12 patients [23%] vs 23 [38%]), anemia (5 patients [9%] vs 27 [44%]), epistaxis (2 patients [4%] vs 34 [56%]), and hypertension (29 patients [55%] vs 22 [36%]).Conclusions and Relevance: In this phase 3 randomized clinical trial, carotuximab plus pazopanib did not improve PFS compared with pazopanib alone in patients with advanced angiosarcoma.Trial Registration: ClinicalTrials.gov Identifier: NCT02979899.

  View details for DOI 10.1001/jamaoncol.2021.3547

  View details for PubMedID 35357396

• Post-operative Stereotactic Radiosurgery of Malignant Melanotic Schwannoma. Cureus Hall, J. C., Chang, S. D., Wilson, T. J., Ganjoo, K. N., Toland, A., Vogel, H., Pollom, E. L., Rahimy, E. 2022; 14 (3): e22849

  Abstract

  Melanotic schwannoma is an extremely rare schwannoma variant with malignant potential, demonstrating high local and distant recurrence. Given the paucity of data, recommended treatment with localized disease is radical resection, with the unclear benefit of adjuvant therapy.We present a case of an 18-year-old female with no past medical history or genetic syndromeswho underwent margin-positive resection of an S1 nerve root melanotic schwannoma followed by adjuvant stereotactic radiosurgery (SRS). SRS was delivered without acute or late toxicity by 2.5 years post-treatment. She remains without evidence of recurrent disease, although longer follow-up is needed given the risk of late recurrence. Our case adds to the limited literature documenting the efficacy of adjuvant radiotherapy in melanotic schwannoma and is the first to describe the successful use of SRS for this rare disease.

  View details for DOI 10.7759/cureus.22849

  View details for PubMedID 35399431

• Detection of MDM2 amplification by shallow whole genome sequencing of cell-free DNA of patients with dedifferentiated liposarcoma. PloS one Przybyl, J., Spans, L., Ganjoo, K., Bui, N., Mohler, D., Norton, J., Poultsides, G., Debiec-Rychter, M., van de Rijn, M. 2022; 17 (1): e0262272

  Abstract

  High-level amplification of MDM2 and other genes in the 12q13-15 locus is a hallmark genetic feature of well-differentiated and dedifferentiated liposarcomas (WDLPS and DDLPS, respectively). Detection of this genomic aberration in plasma cell-free DNA may be a clinically useful assay for non-invasive distinction between these liposarcomas and other retroperitoneal tumors in differential diagnosis, and might be useful for the early detection of disease recurrence. In this study, we performed shallow whole genome sequencing of cell-free DNA extracted from 10 plasma samples from 3 patients with DDLPS and 1 patient with WDLPS. In addition, we studied 31 plasma samples from 11 patients with other types of soft tissue tumors. We detected MDM2 amplification in cell-free DNA of 2 of 3 patients with DDLPS. By applying a genome-wide approach to the analysis of cell-free DNA, we also detected amplification of other genes that are known to be recurrently affected in DDLPS. Based on the analysis of one patient with DDLPS with longitudinal plasma samples available, we show that tracking MDM2 amplification in cell-free DNA may be potentially useful for evaluation of response to treatment. The patient with WDLPS and patients with other soft tissue tumors in differential diagnosis were negative for the MDM2 amplification in cell-free DNA. In summary, we demonstrate the feasibility of detecting amplification of MDM2 and other DDLPS-associated genes in plasma cell-free DNA using technology that is already routinely applied for other clinical indications. Our results may have clinical implications for improved diagnosis and surveillance of patients with retroperitoneal tumors.

  View details for DOI 10.1371/journal.pone.0262272

  View details for PubMedID 34986184

• NCCN Guidelines Insights: Gastrointestinal Stromal Tumors, Version 2.2022. Journal of the National Comprehensive Cancer Network : JNCCN von Mehren, M., Kane, J. M., Riedel, R. F., Sicklick, J. K., Pollack, S. M., Agulnik, M., Bui, M. M., Carr-Ascher, J., Choy, E., Connelly, M., Dry, S., Ganjoo, K. N., Gonzalez, R. J., Holder, A., Homsi, J., Keedy, V., Kelly, C. M., Kim, E., Liebner, D., McCarter, M., McGarry, S. V., Mesko, N. W., Meyer, C., Pappo, A. S., Parkes, A. M., Petersen, I. A., Poppe, M., Schuetze, S., Shabason, J., Spraker, M. B., Zimel, M., Bergman, M. A., Sundar, H., Hang, L. E. 2022; 20 (11): 1204-1214

  Abstract

  Gastrointestinal stromal tumors (GIST) are the most common type of soft tissue sarcoma that occur throughout the gastrointestinal tract. Most of these tumors are caused by oncogenic activating mutations in the KIT or PDGFRA genes. The NCCN Guidelines for GIST provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with these tumors. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including revised systemic therapy options for unresectable, progressive, or metastatic GIST based on mutational status, and updated recommendations for the management of GIST that develop resistance to specific tyrosine kinase inhibitors.

  View details for DOI 10.6004/jnccn.2022.0058

  View details for PubMedID 36351335

• Soft Tissue Sarcoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network : JNCCN von Mehren, M., Kane, J. M., Agulnik, M., Bui, M. M., Carr-Ascher, J., Choy, E., Connelly, M., Dry, S., Ganjoo, K. N., Gonzalez, R. J., Holder, A., Homsi, J., Keedy, V., Kelly, C. M., Kim, E., Liebner, D., McCarter, M., McGarry, S. V., Mesko, N. W., Meyer, C., Pappo, A. S., Parkes, A. M., Petersen, I. A., Pollack, S. M., Poppe, M., Riedel, R. F., Schuetze, S., Shabason, J., Sicklick, J. K., Spraker, M. B., Zimel, M., Hang, L. E., Sundar, H., Bergman, M. A. 2022; 20 (7): 815-833

  Abstract

  Soft tissue sarcomas (STS) are rare malignancies of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Soft Tissue Sarcoma provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as retroperitoneal/intra-abdominal STS, desmoid tumors, and rhabdomyosarcoma. This portion of the NCCN Guidelines discusses general principles for the diagnosis and treatment of retroperitoneal/intra-abdominal STS, outlines treatment recommendations, and reviews the evidence to support the guidelines recommendations.

  View details for DOI 10.6004/jnccn.2022.0035

  View details for PubMedID 35830886

• Efficacy and Safety of Trans-Arterial Yttrium-90 Radioembolization in Patients with Unresectable Liver-Dominant Metastatic or Primary Hepatic Soft Tissue Sarcomas. Cancers Testa, S., Bui, N. Q., Wang, D. S., Louie, J. D., Sze, D. Y., Ganjoo, K. N. 2022; 14 (2)

  Abstract

  Patients with liver-dominant metastatic or primary hepatic soft tissue sarcomas (STS) have poor prognosis. Surgery can prolong survival, but most patients are not surgical candidates, and treatment response is limited with systemic chemotherapy. Liver-directed therapies have been increasingly employed in this setting, and Yttrium-90 trans-arterial radioembolization (TARE) is an understudied yet promising treatment option. This is a retrospective analysis of 35 patients with metastatic or primary hepatic STS who underwent TARE at a single institution between 2006 and 2020. The primary outcomes that were measured were overall survival (OS), liver progression-free survival (LPFS), and radiologic tumor response. Clinical and biochemical toxicities were assessed 3 months after the procedure. Median OS was 20 months (95% CI: 13.9-26.1 months), while median LPFS was 9 months (95% CI: 6.2-11.8 months). The objective response rate was 56.7%, and the disease control rate was 80.0% by mRECIST at 3 months. The following correlated with better OS post-TARE: liver disease control (DC) at 6 months (median OS: 40 vs. 17 months, p = 0.007); LPFS ≥ 9 months (median OS: 50 vs. 8 months, p < 0.0001); ECOG status 0-1 vs. 2 (median OS: 22 vs. 6 months, p = 0.042); CTP class A vs. B (median OS: 22 vs. 6 months, p = 0.018); and TACE post-progression (median OS: 99 vs. 16 months, p = 0.003). The absence of metastases at diagnosis was correlated with higher median LPFS (7 vs. 1 months, p = 0.036). Two grade 4 (5.7%) and ten grade 3 (28.6%) laboratory toxicities were identified at 3 months. There was one case of radioembolization-induced liver disease and two cases of radiation-induced peptic ulcer disease. We concluded that TARE could be an effective and safe treatment option for patients with metastatic or primary hepatic STS with good tumor response rates, low incidence of severe toxicity, and longer survival in patients with liver disease control post-TARE.

  View details for DOI 10.3390/cancers14020324

  View details for PubMedID 35053486

• Genomic Predictors of Recurrence Patterns in Localized Soft Tissue Sarcoma Treated With Radiation Therapy. International journal of radiation oncology, biology, physics Devine, M., Chin, A. L., Million, L., Ganjoo, K. N., Bui, N. Q., Moding, E. J. 2021; 111 (3S): e316

  Abstract

  PURPOSE/OBJECTIVE(S): Soft tissue sarcomas (STSs) are diverse mesenchymal tumors that are primarily managed with surgery. Radiation therapy (RT) is frequently added pre- or post-operatively for localized disease but uncommonly used as definitive treatment because the majority of unresected tumors progress with RT alone. Advances in next-generation sequencing have led to the widespread use of clinical genomic profiling, but the genetic determinants of radiation response in STSs are unknown. We hypothesized that integrating patient outcome data and clinical tumor mutation profiling could identify genomic predictors of recurrence patterns after RT for localized STS.MATERIALS/METHODS: We retrospectively identified 31 patients treated at our institution with definitive RT with or without surgery for localized STS who underwent tumor genomic profiling using a sequencing platform. For genes altered in at least 10% of patients, the associations between genetic alterations and local failure or distant metastasis were analyzed with univariable and multivariable competing risk regression adjusted for the competing risk of death. Age, maximum tumor diameter, tumor grade, and extent of resection were included as co-variables, and P values were adjusted for multiple hypothesis testing.RESULTS: Median follow up was 24 months, and the median RT dose was 50.4 Gy in 28 fractions. The most common histologies were leiomyosarcoma (n = 4) and myxofibrosarcoma (n = 4). The majority of tumors were located in the trunk and extremities (68%) with the remaining tumors originating in the head and neck (16%) or abdomen and pelvis (16%). 48% of patients underwent margin-negative resection, 36% had microscopically positive margins, and 16% were unresected or had gross residual disease following surgery. Median age was 58, median tumor size was 7.5 cm, and 65% of tumors were high grade. On univariable analysis, younger age (P = 0.02) and extent of resection (P = 0.0002) were significantly associated with local recurrence, and there was a trend towards association between higher grade and distant metastasis (P = 0.09). On univariable analysis, amplification of FRS2 in isolation or in combination with MDM2 and CDK4 was associated with a significantly increased risk of local recurrence (n = 4, HR 4.3), and genetic alterations in FBXO11 were associated with a significantly increased risk of distant metastasis (n = 4, HR 3.9). On multivariable analysis, FBXO11 alterations continued to predict for distant metastasis (HR 5.7, P = 0.0002), but there were no significant predictors of local recurrence.CONCLUSION: Our results suggest that somatic tumor mutations may contribute to the risk of local recurrence and distant metastasis in patients treated with RT for localized STS. Additional analysis and validation in larger multi-institutional cohorts will be critical to identify molecular predictors of prognosis and patterns of recurrence.

  View details for DOI 10.1016/j.ijrobp.2021.07.976

  View details for PubMedID 34701163

• Genomic Predictors of Recurrence Patterns in Localized Soft Tissue Sarcoma Treated With Radiation Therapy Devine, M., Chin, A. L., Million, L., Ganjoo, K. N., Bui, N. Q., Moding, E. J. ELSEVIER SCIENCE INC. 2021: E316

  View details for Web of Science ID 000715803800637

• Clinical activity of single-agent cabozantinib (XL184), a multi-receptor tyrosine kinase inhibitor, in patients with refractory soft tissue sarcomas. Clinical cancer research : an official journal of the American Association for Cancer Research O'Sullivan Coyne, G., Kummar, S., Hu, J., Ganjoo, K., Chow, W. A., Do, K. T., Zlott, J., Bruns, A., Rubinstein, L., Foster, J. C., Jawara, L., Meehan, R., Piekarz, R., Streicher, H., Sharon, E., Takebe, N., Regier Voth, A., Bottaro, D., Costello, R., Wright, J. J., Doroshow, J. H., Chen, A. P. 2021

  Abstract

  PURPOSE: Soft tissue sarcomas (STS) are a rare, heterogeneous group of mesenchymal tumors. For decades the mainstay of treatment for advanced, unresectable STS has been palliative chemotherapy. High levels of activated MET receptor have been reported in various sarcoma cell lines, together with elevated VEGF levels in patients with STS, suggesting that dual targeting of the VEGF and MET pathways with the multi-receptor tyrosine kinase inhibitor cabozantinib would result in clinical benefit in this population.EXPERIMENTAL DESIGN: We performed an open-label, multi-institution, single-arm phase II trial of single-agent cabozantinib in adult patients with advanced STS and progressive disease after at least 1 standard line of systemic therapy. Patients received 60 mg oral cabozantinib once daily in 28-day cycles and dual primary endpoints of overall response rate and 6-month progression free survival (PFS) were assessed. Changes in several circulating biomarkers were assessed as secondary endpoints.RESULTS: Six (11.1%, 95% CI: 4.2%-22.6%) of the 54 evaluable patients enrolled experienced objective responses (all partial responses). Six-month PFS was 49.3% (95% CI: 36.2%-67.3%), with a median time on study of 4 cycles (range, 1-99). The most common grade 3/4 adverse events were hypertension (7.4%) and neutropenia (16.7%). Patients' levels of circulating HGF, soluble MET, and VEGF-A generally increased after a cycle of therapy while soluble VEGFR2 levels decreased, regardless of clinical outcome.CONCLUSION: Cabozantinib single-agent antitumor activity was observed in patients with selected STS histologic subtypes (alveolar soft part sarcoma, undifferentiated pleomorphic sarcoma, extraskeletal myxoid chondrosarcoma, and leiomyosarcoma) highlighting the biomolecular diversity of STS.

  View details for DOI 10.1158/1078-0432.CCR-21-2480

  View details for PubMedID 34716194

• Use of a computer model and care coaches to increase advance care planning conversations for patients with metastatic cancer Gupta, D., Fardeen, T., Teuteberg, W., Seevaratnam, B., Asuncion, M., Alves, N., Rogers, B., Neal, J. W., Fan, A. C., Parikh, D., Patel, M. I., Shah, S., Srinivas, S., Huang, J. E., Reddy, S. A., Ganjoo, K. N., Bui, N., Hansen, J., Gensheimer, M. F., Ramchandran, K. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2020.39.28_suppl.8

  View details for Web of Science ID 000707130200008

• Safety and Feasibility of Cryoablation during Immunotherapy in Patients with Metastatic Soft Tissue Sarcoma. Journal of vascular and interventional radiology : JVIR Doshi, A., Zhou, M., Bui, N., Wang, D. S., Ganjoo, K., Hwang, G. L. 2021

  Abstract

  PURPOSE: Patients with metastatic soft tissue sarcoma (STS) undergo a wide array of treatments, including surgery, radiation, chemotherapy, immunotherapy, and ablative therapies, to control their disease. The combination of cryoablation and immunotherapy may lead to an enhanced anti-tumor immune response via the abscopal effect. It is hypothesized that the combination of cryoablation and immunotherapy in patients with metastatic STS is safe and feasible.MATERIALS/METHODS: A single-center retrospective analysis was performed on patients with metastatic STS who underwent cryoablation. Sixteen patients were treated with 27 cryoablation procedures while receiving ipilimumab and nivolumab from April 2017 to July 2020. RECIST 1.1 criteria was used to determine outcomes of non-target tumors. Progression-free survival (PFS) and overall survival (OS) were calculated from the date of first cryoablation after initiating immunotherapy until progression or death.RESULTS: Thirty-four tumors were cryoablated, 23 of which were intentionally subtotal. Most common tumor subtype was liposarcoma (n = 4). Thirteen patients (81%) had previously demonstrated disease progression on multiple lines of chemotherapy. All tumors cryoablated with complete intention demonstrated complete response. Seven patients had clinical benefit, including 1 complete response, 1 partial response, and 5 with stable disease. The median OS was 14.1 months, with a median PFS of 2.3 months (95% CI 1.8-14.3). Five patients had post-cryoablation pneumothoraces, two of whom required chest tube placement. Eleven patients experienced adverse events related to immunotherapy, 10 of which were grade 1 or 2.CONCLUSION: Cryoablation in patients with metastatic soft tissue sarcoma undergoing immunotherapy is feasible and safe.

  View details for DOI 10.1016/j.jvir.2021.08.017

  View details for PubMedID 34478852

• Ripretinib intrapatient dose escalation after disease progression provides clinically meaningful outcomes in advanced gastrointestinal stromal tumour. European journal of cancer (Oxford, England : 1990) George, S., Chi, P., Heinrich, M. C., von Mehren, M., Jones, R. L., Ganjoo, K., Trent, J., Gelderblom, H., Razak, A. A., Gordon, M. S., Somaiah, N., Jennings, J., Meade, J., Shi, K., Su, Y., Ruiz-Soto, R., Janku, F. 2021; 155: 236-244

  Abstract

  PURPOSE: Ripretinib is a switch-control tyrosine kinase inhibitor that broadly inhibits KIT and platelet-derived growth factor receptor alpha kinase signalling. Ripretinib showed preliminary efficacy in patients with advanced gastrointestinal stromal tumour (GIST) in a phase I study across a range of doses. Results were confirmed in the phase III INVICTUS study, and ripretinib 150mg once daily (QD) was subsequently approved as a ≥fourth-line therapy. Here, we report the phase I study results of intrapatient dose escalation (IPDE) in patients with GIST treated across second, thirdand later lines of therapy.METHODS: Patients with advanced GIST who experienced disease progression (PD) at ripretinib 150mg QD could dose escalate to 150mg twice daily (BID). Progression-free survival (PFS) 1 was calculated from the date of the first dose of ripretinib 150mg QD to PD (as per Response Evaluation Criteria in Solid Tumours 1.1); PFS2 was from the date of IPDE (150mg BID) to PD or death. Treatment-emergent adverse events (TEAEs) were summarised by dosing periods and compared descriptively.RESULTS: Of 142 patients with GIST receiving ripretinib 150mg QD, 67 underwent IPDE. IPDE provided benefit across all lines of therapy; the median PFS2 was 5.6, 3.3and 4.6 months for patients on second-, third-and ≥fourth-line therapy, respectively. A partial metabolic response after IPDE was demonstrated in 13 of 37 patients with available positron emission tomography scans. TEAEs reported at both doses were similar.CONCLUSION: Ripretinib IPDE after PD provided continued clinical benefit in advanced GIST across second, third and later lines of therapy with a similar safety profile to that observed with the QD regimen.

  View details for DOI 10.1016/j.ejca.2021.07.010

  View details for PubMedID 34391056

• Dermatopathological review of cutaneous squamous cell carcinoma events in patients with gastrointestinal stromal tumors treated with ripretinib Patel, A., George, S., Janku, F., Ganjoo, K., Young, R., Chi, P., Westwood, D., Stearns, S., Meade, J., Ruiz-Soto, R., Lacouture, M. ELSEVIER. 2021: S134-S135

  View details for DOI 10.1016/j.annonc.2021.05.162

  View details for Web of Science ID 000670004200107

• Skin angiography assisted mastectomy in secondary breast angiosarcoma: Complete clinical response after neoadjuvant immunotherapy. The breast journal Ju, T., Foster, D., Titan, A., Najjar, S., Bean, G. R., Ganjoo, K., Wapnir, I. 2021

  Abstract

  Radiation-induced breast angiosarcoma, or secondary angiosarcoma (SAS), is a rare entity with a high risk of metastatic recurrence. Herein, we describe the use of intraoperative fluorescence-based skin angiography to guide surgical resection following a novel immunotherapy-based regimen for SAS resulting in a complete pathological response.

  View details for DOI 10.1111/tbj.14270

  View details for PubMedID 34173294

• Phase II trial of pegylated arginine deiminase in combination with gemcitabine and docetaxel for the treatment of soft tissue sarcoma. Van Tine, B., Hirbe, A. C., Luo, J., Oppelt, P., Weiss, M. C., Eulo, V., Toeniskoetter, J., Haarberg, S., Abaricia, S., Ruff, T., Bomalaski, J. S., Johnston, A., Kuo, C., Shiu, C., Ingham, M., Bui, N., Chawla, S. P., Schwartz, G. K., Ganjoo, K. N. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2021.39.15_suppl.11508

  View details for Web of Science ID 000708120606045

• IGNYTE-ESO: A master protocol to assess safety and activity of letetresgene autoleucel (lete-cel; GSK3377794) in HLA-A*02+patients with synovial sarcoma or myxoid/round cell liposarcoma (Substudies 1 and 2). D'Angelo, S. P., Noujaim, J., Thistlethwaite, F., Razak, A., Stacchiotti, S., Chow, W., Haanen, J. G., Chalmers, A., Robinson, S., Van Tine, B., Ganjoo, K. N., Johnson, M. L., Chiou, V. L., Faitg, T. H., Woessner, M., Pearce, L., Shalabi, A., Blay, J., Demetri, G. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2021.39.15_suppl.TPS11582

  View details for Web of Science ID 000708120306173

• Institutional experience with nab-sirolimus in patients with malignancies harboring TSC1 or TSC2 mutations. Dickson, M., Ravi, V., Ganjoo, K. N., Iyer, G. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2021.39.15_suppl.3111

  View details for Web of Science ID 000708120601285

• P10015/SARC033: A phase 2 trial of trametinib in patients with advanced epithelioid hemangioendothelioma (EHE). Schuetze, S., Ballman, K. V., Ganjoo, K. N., Davis, E. J., Morgan, J. A., Tinoco, G., Burgess, M., Van Tine, B., Choy, E., Shepard, D., Kelly, C., Riedel, R. F., von Mehren, M., Siontis, B. L., Attia, S., Schwartz, G. K., Deshpande, H., Kozlowski, E., Chen, H. X., Rubin, B. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2021.39.15_suppl.11503

  View details for Web of Science ID 000708120606040

• Pexidartinib improves physical functioning and stiffness in patients with tenosynovial giant cell tumor: results from the ENLIVEN randomized clinical trial ACTA ORTHOPAEDICA van de Sande, M., Tap, W. D., Gelhorn, H. L., Ye, X., Speck, R. M., Palmerini, E., Stacchiotti, S., Desai, J., Wagner, A. J., Alcindor, T., Ganjoo, K., Martin-Broto, J., Wang, Q., Shuster, D., Gelderblom, H., Healey, J. H. 2021

  View details for DOI 10.1080/17453674.2021.1922161

  View details for Web of Science ID 000649692800001

• Rare and fatal complication of immune checkpoint inhibition: a case report of haemophagocytic lymphohistiocytosis with severe lichenoid dermatitis. British journal of haematology Choi, S., Zhou, M., Bahrani, E., Martin, B. A., Ganjoo, K. N., Zaba, L. C. 2021

  View details for DOI 10.1111/bjh.17442

  View details for PubMedID 33954981

• Rapid Response of a BRCA2/TP53/PTEN-Deleted Metastatic Uterine Leiomyosarcoma to Olaparib: A Case Report. The Permanente journal Pan, M., Ganjoo, K., Karam, A. 2021; 25

  Abstract

  None: Patients with metastatic uterine leiomyosarcoma (uLMS) have poor prognosis due to limited treatment options, especially when disease progresses on doxorubicin and gemcitabine-docetaxel regimens. Here we report a patient whose metastatic uLMS contains a BRCA2 deep deletion as well as TP53 and PTEN deep deletion. The patient responded rapidly to olaparib, a poly (ADP-ribose) polymerase inhibitor, after progressing on gemcitabine-docetaxel, doxorubicin, and temozolomide regimens. This case report shall be helpful to the treatment of other patients with metastatic uLMS that harbors a BRCA2 mutation or deletion.

  View details for DOI 10.7812/TPP/20.251

  View details for PubMedID 33970096

• Evaluation of Absolute Lymphocyte Count at Diagnosis and Mortality Among Patients With Localized Bone or Soft Tissue Sarcoma. JAMA network open Brewster, R., Purington, N., Henry, S., Wood, D., Ganjoo, K., Bui, N. 2021; 4 (3): e210845

  Abstract

  Importance: Host-related immune factors have been implicated in the development and progression of diverse malignant neoplasms. Identifying associations between immunologic laboratory parameters and overall survival may inform novel prognostic biomarkers and mechanisms of antitumor immunity in localized bone and soft tissue sarcoma.Objective: To assess whether lymphopenia at diagnosis is associated with overall survival among patients with localized bone and soft tissue sarcoma.Design, Setting, and Participants: This retrospective cohort study analyzed patients from the Stanford Cancer Institute with localized bone and soft tissue sarcoma between September 1, 1998, and November 1, 2018. Patients were included if laboratory values were available within 60 days of diagnosis and, if applicable, prior to the initiation of chemotherapy and/or radiotherapy. Statistical analysis was performed from January 1, 2019, to November 1, 2020.Exposures: Absolute lymphocyte count within 60 days of diagnosis and antimicrobial exposure, defined by the number of antimicrobial agent prescriptions and the cumulative duration of antimicrobial administration within 60 days of diagnosis.Main Outcomes and Measures: The association between minimum absolute lymphocyte count at diagnosis and 5-year overall survival probability was characterized with the Kaplan-Meier method and multivariate Cox proportional hazards regression models. Multivariable logistic regressions were fitted to evaluate whether patients with lymphopenia were at greater risk of increased antimicrobial exposure.Results: Among 634 patients, the median age at diagnosis was 53.7 years (interquartile range, 37.5-66.8 years), and 290 patients (45.7%) were women, with a 5-year survival probability of 67.9%. There was a significant inverse association between lymphopenia at diagnosis and overall survival (hazard ratio [HR], 1.82; 95% CI, 1.39-1.40), resulting in a 13.5% 5-year survival probability difference compared with patients who did not have lymphopenia at diagnosis (60.2% vs 73.7% for those who never had lymphopenia). In addition, poorer survival was observed with higher-grade lymphopenia (grades 3 and 4: HR, 2.44; 95% CI, 1.68-3.55; grades 1 and 2: HR, 1.60; 95% CI, 1.18-2.18). In an exploratory analysis, patients with increased antibiotic exposure were more likely to have lymphopenia (odds ratio, 1.96; 95% CI, 1.26-3.07 for total number of antimicrobial agents; odds ratio, 1.70; 95% CI, 1.10-2.57 for antimicrobial duration) than antimicrobial-naive patients.Conclusions and Relevance: This study suggests that an abnormally low absolute lymphocyte count at diagnosis is associated with higher mortality among patients with localized bone and soft tissue sarcoma; therefore, lymphopenia may serve as a reliable prognostic biomarker. Potential mechanisms associated with host immunity and overall survival include a suppressed antitumor response and increased infectious complications, which merit future investigation.

  View details for DOI 10.1001/jamanetworkopen.2021.0845

  View details for PubMedID 33666664

• Phase II Randomized Study of CMB305 and Atezolizumab Compared With Atezolizumab Alone in Soft-Tissue Sarcomas Expressing NY-ESO-1. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Chawla, S. P., Van Tine, B. A., Pollack, S. M., Ganjoo, K. N., Elias, A. D., Riedel, R. F., Attia, S., Choy, E., Okuno, S. H., Agulnik, M., von Mehren, M., Livingston, M. B., Keedy, V. L., Verschraegen, C. F., Philip, T., Bohac, G. C., Yurasov, S., Yakovich, A., Lu, H., Chen, M., Maki, R. G. 2021: JCO2003452

  Abstract

  CMB305 is a heterologous prime-boost vaccination regimen created to prime NY-ESO-1-specific CD8 T-cell populations and then activate the immune response with a potent TLR-4 agonist. This open-label randomized phase II trial was designed to investigate the efficacy and safety of adding the CMB305 regimen to atezolizumab (anti-programmed death ligand-1 therapy) in comparison with atezolizumab alone in patients with synovial sarcoma or myxoid liposarcoma.Patients with locally advanced, relapsed, or metastatic synovial sarcoma or myxoid liposarcoma (any grade) were randomly assigned to receive CMB305 with atezolizumab (experimental arm) or atezolizumab alone (control arm). The primary end points were progression-free survival (PFS) and overall survival (OS) analyzed using the Kaplan-Meier method. Safety and immune responses were assessed.A total of 89 patients were enrolled; 55.1% had received ≥ 2 prior lines of chemotherapy. Median PFS was 2.6 months and 1.6 months in the combination and control arms, respectively (hazard ratio, 0.9; 95% CI, 0.6 to 1.3). Median OS was 18 months in both treatment arms. Patients treated with combination therapy had a significantly higher rate of treatment-induced NY-ESO-1-specific T cells (P = .01) and NY-ESO-1-specific antibody responses (P < .0001). In a post hoc analysis of all dosed patients, OS was longer (36 months) in the subset who developed anti-NY-ESO-1 T-cell immune response (hazard ratio, 0.3; P = .02).Although the combination of CMB305 and atezolizumab did not result in significant increases in PFS or OS compared with atezolizumab alone, some patients demonstrated evidence of an anti-NY-ESO-1 immune response and appeared to fare better by imaging than those without such an immune response. Combining prime-boost vaccines such as CMB305 with anti-programmed death ligand-1 therapies merits further evaluation in other clinical contexts.

  View details for DOI 10.1200/JCO.20.03452

  View details for PubMedID 34260265

• Management Strategies for Patients With Epithelioid Hemangioendothelioma: Charting an Indolent Disease Course. American journal of clinical oncology Yurkiewicz, I. R., Zhou, M., Ganjoo, K. N., Charville, G. W., Bolleddu, S., Lohman, M., Bui, N. 2021

  Abstract

  Epithelioid hemangioendothelioma (EHE) is a malignant vascular neoplasm representing ∼1% of sarcomas. Due to its rarity, its clinical course is not well characterized and optimal treatment remains unknown.This was a retrospective review of patients with EHE treated at Stanford University between 1998 and 2020. Demographic characteristics, pathology results, treatment modalities, and clinical outcomes were collected from the electronic medical records.A total of 58 patients had a mean age of 50.6 years and a slight female predominance (52%). Primary disease sites were liver (33%), soft tissue (29%), lung (14%), bone (9%), and mediastinum (9%). A majority (55%) had advanced or metastatic disease. Median overall survival (OS) was 16.9 years, with OS 89% at 1 year, 68% at 5 years, and 64% at 10 years. The longest median OS was associated with soft tissue sites and shortest with lung and mediastinal disease (P=0.03). The localized disease had improved median OS compared with metastatic disease (P=0.02). There was no OS difference between tumors >3 cm and those equal or smaller (P=0.85). Surgery was a common treatment (71%), while radiation and ablation were sometimes used (28% and 9%, respectively). The median time to initiating therapy of any kind was 68 days. The median time to systemic therapy was 114 days.We report on the clinical characteristics and outcomes of patients with EHE at a large academic center. Treatment options included surgical excision, liver transplant, ablation, radiation, and systemic therapy. A subset of patients had indolent disease not requiring treatment upfront.

  View details for DOI 10.1097/COC.0000000000000827

  View details for PubMedID 34028371

• A Retrospective Comparative Analysis of Outcomes and Prognostic Factors in Adult and Pediatric Patients with Osteosarcoma. Current oncology (Toronto, Ont.) Testa, S., Hu, B. D., Saadeh, N. L., Pribnow, A., Spunt, S. L., Charville, G. W., Bui, N. Q., Ganjoo, K. N. 2021; 28 (6): 5304-5317

  Abstract

  Osteosarcoma is the most common primary bone malignancy in both children and adults. Despite introduction of intensive multimodal treatment with chemotherapy and surgery, outcomes are still poor, especially for patients with metastatic disease and adults. Hence, there is an ongoing need for better prognostic markers and outcome data to inform management decisions in both the adult and pediatric setting. Here, we retrospectively analyzed 112 patients with bone osteosarcoma treated at two large adult and pediatric tertiary academic centers between 1989 and 2019. Patients were divided into an adult (≥18 years) and pediatric (<18 years) cohort for comparison. Our aim was to evaluate predictors of outcomes in pediatric and adult patients, with a specific focus on the role of methotrexate when added to a combination of doxorubicin-cisplatin; the prognostic value of tumor necrosis after neoadjuvant chemotherapy; and outlining any differences in outcomes between adults and pediatric patients that could inform clinical management. Adult patients treated with methotrexate-doxorubicin-cisplatin and those treated with doxorubicin-cisplatin had similar 5-year PFS (26%, 95%CI: 45.5%-10% vs. 50%, 95%CI: 69.6%-26.2%, p = 0.1) and 5-year OS (63%, 95%CI: 82%-34%, vs. 78%, 95%CI: 90.6%-52.6%, p = 0.5). In the adult cohort, there was no difference between patients with ≥90% necrosis and <90% necrosis in either 5-year PFS (42%, 95%CI: 71.1%-11.3% vs. 38%, 95%CI: 57.7%-18.2%, p = 0.4) or 5-year OS (85%, 95%CI: 97.8%-33.4% vs. 56%, 95%CI: 76.8%-27.6%, p = 0.4). In the pediatric cohort, compared to patients with <90% necrosis, those with ≥90% necrosis had significantly better 5-year PFS (30%, 95%CI: 49.3%-14.1% vs. 55%, 95%CI: 73.9%-38.5%, p = 0.003) and 5-year OS (64%, 95%CI: 80.8%-41.1% vs. 78%, 95%CI: 92%-60.9%, p = 0.04). Adult and pediatric patients had similar 5-year OS (69%, 95%CI: 83.2%-49.8% vs. 73%, 95%CI: 83.2%-59.3%, p = 0.8) and 5-year PFS (37%, 95%CI: 52.4%-22.9% vs. 43%, 95%CI: 56.2%-30.4% p = 0.3) even though the proportion of patients with ≥90% necrosis after neoadjuvant chemotherapy was higher for children compared to adults (60.3% vs. 30%, OR: 3.54, 95%CI: 1.38-8.46, p = 0.006). In conclusion, in adult patients, the addition of methotrexate to doxorubicin and cisplatin did not correlate with a significant survival benefit, questioning the therapeutic value of methotrexate overall. Our study confirms the prognostic utility of percent tumor necrosis after neoadjuvant chemotherapy in pediatric patients but not in adult patients. Lastly, this is one of the few reported studies where patients with osteosarcoma younger and older than 18 years had similar PFS and OS.

  View details for DOI 10.3390/curroncol28060443

  View details for PubMedID 34940082

• Long-Term Remission with Ipilimumab/Nivolumab in Two Patients with Different Soft Tissue Sarcoma Subtypes and No PD-L1 Expression. Case reports in oncology Zhou, M., Bui, N., Lohman, M., van de Rjin, M., Hwang, G., Ganjoo, K. 2021; 14 (1): 459–65

  Abstract

  Checkpoint inhibitor therapy has been shown to improve outcomes in multiple solid malignancies; however, data are limited in soft tissue sarcoma. We present two cases of patients with advanced soft tissue sarcoma of different subtypes (dedifferentiated liposarcoma and myxofibrosarcoma) with zero percent PD-L1 expression by immunohistochemistry who were treated with ipilimumab and nivolumab followed by maintenance nivolumab. Both patients had failed multiple lines of systemic treatment and experienced long-term remission after starting ipilimumab and nivolumab. Genetic testing revealed that no genetic mutations were found in common between the two cases. One patient received concurrent cryoablation, which may have sensitized his tumor to immunotherapy. Checkpoint inhibitor therapy may improve outcomes in soft tissue sarcoma regardless of PD-L1 status, especially when combined with cryoablation. Studies are needed to evaluate whether treatment response varies by sarcoma subtype and what molecular markers can be used to guide patient selection.

  View details for DOI 10.1159/000512828

  View details for PubMedID 33790767

• Surgical resection of leiomyosarcoma of the inferior vena cava: A case series and literature review. Surgical oncology Zhou, M., Javadi, C., Charville, G. W., Bui, N. Q., Harris, E. J., Poultsides, G. A., Norton, J. A., Visser, B., Lee, B., Dua, M. M., Ganjoo, K. N. 2021; 39: 101670

  Abstract

  We review our institution's experience in treating leiomyosarcomas involving the inferior vena cava, and we offer guidance on the management.A text-based search was performed to identify all patients who underwent surgical resection between January 2002 and October 2020. Clinicopathologic data, intraoperative variables, and outcomes were extracted from chart review.Twelve of 16 patients (75%) had localized disease; the remaining had limited metastatic disease. Seven of 16 patients (44%) received neoadjuvant chemotherapy or radiation; three patients had partial responses, and four patients had stable disease using RECIST 1.1 criteria. IVC reconstruction was performed in 14 of 16 patients (88%); IVC was ligated for the remaining two patients. Half of all patients had R0 resection on final pathology; the remaining had R1 resections. Progression-free survival (PFS) and overall survival (OS) were not statistically different between patients with R0 and R1 resection. Median PFS was 1.8 years (95% CI 0.89 - not reached); median OS was 6.5 years (1.8 - not reached). Only one patient (6%) experienced local disease recurrence; 4 of 16 patients (25%) experienced disease recurrence distally without local recurrence.Resection of IVC leiomyosarcomas at a sarcoma referral center with experience in vascular reconstruction can lead to many years of recurrence-free survival. Surgical resection should be offered to patients with a low volume of metastatic disease to reduce local complications from the primary tumor, many of which exert significant mass effect on surrounding organs. For patients with metastatic disease or large, high-risk tumors, neoadjuvant chemotherapy can provide a biologic test of disease stability prior to resection.

  View details for DOI 10.1016/j.suronc.2021.101670

  View details for PubMedID 34710646

• nab-Sirolimus for Patients With Malignant Perivascular Epithelioid Cell Tumors. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Wagner, A. J., Ravi, V., Riedel, R. F., Ganjoo, K., Van Tine, B. A., Chugh, R., Cranmer, L., Gordon, E. M., Hornick, J. L., Du, H., Grigorian, B., Schmid, A. N., Hou, S., Harris, K., Kwiatkowski, D. J., Desai, N. P., Dickson, M. A. 2021: JCO2101728

  Abstract

  Malignant perivascular epithelioid cell tumor (PEComa) is a rare aggressive sarcoma, with no approved treatment. To our knowledge, this phase II, single-arm, registration trial is the first prospective clinical trial in this disease, investigating the safety and efficacy of the mammalian target of rapamycin inhibitor nab-sirolimus (AMPECT, NCT02494570).Patients with malignant PEComa were treated with nab-sirolimus 100 mg/m2 intravenously once weekly for 2 weeks in 3-week cycles. The primary end point was objective response rate evaluated by independent radiology review. Key secondary end points included duration of response, progression-free survival, and safety. A key exploratory end point was tumor biomarker analysis.Thirty-four patients were treated (safety evaluable), and 31 were evaluable for efficacy. The overall response rate was 39% (12 of 31; 95% CI, 22 to 58) with one complete and 11 partial responses, 52% (16 of 31) of patients had stable disease, and 10% (3 of 31) had progressive disease. Responses were of rapid onset (67% by week 6) and durable. Median duration of response was not reached after a median follow-up for response of 2.5 years, with 7 of 12 responders with treatment ongoing (range 5.6-47.2+ months). Twenty-five of 31 patients had tumor mutation profiling: 8 of 9 (89%) patients with a TSC2 mutation achieved a confirmed response versus 2 of 16 (13%) without TSC2 mutation (P < .001). The median progression-free survival was 10.6 months (95% CI, 5.5 months to not reached), and the median overall survival was 40.8 months (95% CI, 22.2 months to not reached). Most treatment-related adverse events were grade 1 or 2 and were manageable for long-term treatment. No grade ≥ 4 treatment-related events occurred.nab-Sirolimus is active in patients with malignant PEComa. The response rate, durability of response, disease control rate, and safety profile support that nab-sirolimus represents an important new treatment option for this disease.

  View details for DOI 10.1200/JCO.21.01728

  View details for PubMedID 34637337

• Fusion and rearrangement (RE) detection using DNA and RNA-based comprehensive genomic profiling (CGP) of sarcomas Ganjoo, K., Madison, R., Rosenzweig, M., Oxnard, G., Venstrom, J., Ward, A., Schrock, A. B. ELSEVIER. 2021: S1116-S1117

  View details for DOI 10.1016/j.annonc.2021.08.862

  View details for Web of Science ID 000700527703079

• Ripretinib intra-patient dose escalation (IPDE) following disease progression provides clinically meaningful progression-free survival (PFS) in gastrointestinal stromal tumor (GIST) in phase I Janku, F., Chi, P., Heinrich, M., von Mehren, M., Jones, R. L., Ganjoo, K., Trent, J., Gelderblom, H., Razak, A., Gordon, M., Somaiah, N., Jennings, J., Shi, K., Ruiz-Soto, R., George, S. ELSEVIER. 2020: S974–S975

  View details for DOI 10.1016/j.annonc.2020.08.1849

  View details for Web of Science ID 000573469102210

• Switch Control Inhibition of KIT and PDGFRA in Patients With Advanced Gastrointestinal Stromal Tumor: A Phase I Study of Ripretinib. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Janku, F., Abdul Razak, A. R., Chi, P., Heinrich, M. C., von Mehren, M., Jones, R. L., Ganjoo, K., Trent, J., Gelderblom, H., Somaiah, N., Hu, S., Rosen, O., Su, Y., Ruiz-Soto, R., Gordon, M., George, S. 2020: JCO2000522

  Abstract

  PURPOSE: In advanced gastrointestinal stromal tumor (GIST), there is an unmet need for therapies that target both primary and secondary mutations of pathogenic KIT/PDGFRA oncoproteins. Ripretinib is a novel switch-control kinase inhibitor designed to inhibit a wide range of KIT and PDGFRA mutations.PATIENTS AND METHODS: This first-in-human, to our knowledge, phase I study of ripretinib (ClinicalTrials.gov identifier: NCT02571036) included a dose-escalation phase and subsequent expansion phase at the recommended phase II dose (RP2D). Eligible patients included those with advanced GIST, intolerant to or experienced progression on ≥ 1 line of systemic therapy, and other advanced malignancies. Safety, dose-limiting toxicities (DLTs), maximum-tolerated dose (MTD), and preliminary antitumor activity were evaluated.RESULTS: At data cutoff (August 31, 2019), 258 patients (n = 184 GIST) were enrolled, with 68 patients in the dose-escalation phase. Three DLTs were reported: grade 3 lipase increase (n = 2; 100 mg and 200 mg twice a day) and grade 4 increased creatine phosphokinase (n = 1; 150 mg once daily). MTD was not reached (maximum dose evaluated, 200 mg twice a day); 150 mg once daily was established as the RP2D. The most frequent (> 30%) treatment-emergent adverse events in patients with GIST receiving ripretinib 150 mg once daily (n = 142) were alopecia (n = 88 [62.0%]), fatigue (n = 78 [54.9%]), myalgia (n = 69 [48.6%]), nausea (n = 65 [45.8%]), palmar-plantar erythrodysesthesia (n = 62 [43.7%]), constipation (n = 56 [39.4%]), decreased appetite (n = 48 [33.8%]), and diarrhea (n = 47 [33.1%]). Objective response rate (confirmed) of 11.3% (n = 16/142) ranging from 7.2% (n = 6/83; fourth line or greater) to 19.4% (n = 6/31; second line) and median progression-free survival ranging from 5.5 months (fourth line or greater) to 10.7 months (second line), on the basis of investigator assessment, were observed.CONCLUSION: Ripretinib is a well-tolerated, novel inhibitor of KIT and PDGFRA mutant kinases with promising activity in patients with refractory advanced GIST.

  View details for DOI 10.1200/JCO.20.00522

  View details for PubMedID 32804590

• A Randomized, Double-Blind, Placebo-Controlled, Phase II Study of Regorafenib vs. Placebo in Advanced/Metastatic, Treatment-Refractory Liposarcoma: Results from the SARC024 Study. The oncologist Riedel, R. F., Ballman, K. V., Attia, S., Loggers, E. T., Ganjoo, K. N., Livingston, M. B., Chow, W., Wright, J., Ward, J. H., Rushing, D., Okuno, S. H., Reed, D. R., Liebner, D. A., Keedy, V. L., Mascarenhas, L., Davis, L. E., Ryan, C., Reinke, D. K., Maki, R. G. 2020

  Abstract

  LESSONS LEARNED: The results from the liposarcoma cohort of SARC024 confirm previously published data and do not support the routine use of regorafenib in this patient population. Continued exploration of novel therapies, including combination approaches, is warranted for a patient population in whom limited treatment options exist.BACKGROUND: Regorafenib is a multi-targeted kinase inhibitor with a kinase profile overlapping, but distinct from pazopanib, an agent approved for recurrent/metastatic non-gastrointestinal tumors (GIST), non-adipocytic soft tissue sarcoma. We conducted a randomized, phase II study of regorafenib versus placebo in refractory liposarcoma patients.METHODS: Patients with advanced/metastatic, treatment-refractory liposarcoma were randomized 1:1 to receive regorafenib 160 mg or placebo once daily (3weeks on, 1 week off). Patients with well-differentiated liposarcoma only were excluded. Crossover for placebo was allowed upon progression. The primary endpoint was progression-free survival (PFS), according to RECIST version 1.1.RESULTS: Forty-eight subjects with liposarcoma (34 dedifferentiated, 12 myxoid/round cell, 2 pleomorphic) were enrolled. Median PFS was 1.87 (95% confidence interval [CI]: 0.92-3.67) months for regorafenib versus 2.07 (95% CI: 1.64-3.44) months for placebo; stratified hazard ratio [HR] 0.85 (95% CI: 0.46, 1.58), p value = .62. No responses were seen on regorafenib. One PR was observed on placebo. Median overall survival was 6.46 (95% CI: 4.16-23.48) months for regorafenib and 4.89 (95% CI: 3.02-9.77) months for placebo, stratified HR 0.66 (95% CI: 0.31-1.40), p value = .28). Treatment-related adverse events were similar to the known safety profile of regorafenib.CONCLUSION: Regorafenib did not appear to improve PFS in treatment-refractory liposarcoma. No new significant safety signals were observed.

  View details for DOI 10.1634/theoncologist.2020-0679

  View details for PubMedID 32701199

• Long-term follow-up for duration of response (DoR) after weekly nab-sirolimus in patients with advanced malignant perivascular epithelioid cell tumors (PEComa): Results from a registrational open-label phase II trial, AMPECT. Wagner, A. J., Ravi, V., Riedel, R. F., Ganjoo, K. N., Van Tine, B., Chugh, R., Cranmer, L. D., Gordon, E., Hornick, J. L., Kwiatkowski, D. J., Du, H., Grigorian, B., Schmid, A. N., Hou, S., Harris, K., Desai, N., Dickson, M. AMER SOC CLINICAL ONCOLOGY. 2020

  View details for Web of Science ID 000560368300377

• Angiosarcoma of the Breast: Management and Outcomes. American journal of clinical oncology Gutkin, P. M., Ganjoo, K. N., Lohman, M. n., von Eyben, R. n., Charville, G. W., Nazerali, R. S., Dirbas, F. M., Horst, K. C. 2020

  Abstract

  Angiosarcoma of the breast is rare and has a poor prognosis. We reviewed our institution's experience with this disease to characterize presentation, identify management patterns, and report outcomes.Fifty-eight patients with nonmetastatic angiosarcoma were identified from 1998 to 2019 and retrospectively reviewed. Overall survival (OS) and recurrence-free survival (RFS) were calculated using the Kaplan-Meier analysis and log-rank test.The median follow-up was 43.4 months (range: 1.8 to 203.3 mo). Twenty-four patients had primary angiosarcoma (PAS) and 34 patients had secondary angiosarcoma (SAS). Patients with PAS were significantly younger than those with SAS (P<0.0001). Mastectomy was the main surgical treatment in our cohort (n=47) and 3 underwent a lumpectomy. The multifocal disease was found in 5/23 patients with PAS and 11/35 patients with SAS. Twenty-eight patients received chemotherapy. Radiation was administered to 13 patients with PAS and 3 patients with SAS. Five-year OS was 73.7% for PAS and 63.5% for SAS. Local recurrence occurred in a greater proportion of patients with margins <5 mm than those with margins ≥5 mm. Chemotherapy did not impact RFS and was not associated with OS in PAS (P=0.35). Those with SAS treated with chemotherapy had significantly greater OS than those who did not receive chemotherapy (P=0.043). Radiation did not significantly influence RFS or OS.Five-year OS was higher than anticipated. Margins >5 mm appear important for local control. Patients with SAS, but not PAS, may achieve improved survival with chemotherapy. National trials using prespecified agents may be needed to identify an optimal chemotherapy regimen for women with SAS.

  View details for DOI 10.1097/COC.0000000000000753

  View details for PubMedID 32889893

• Sinonasal FUS-ERG-Rearranged Ewing's Sarcoma Mimicking Glomangiopericytoma. Case reports in oncology Zhou, M. n., Ko, Y. C., Charville, G. W., Ganjoo, K. N. 2020; 13 (3): 1393–96

  Abstract

  Ewing's sarcoma is a rare and aggressive tumor that typically arises in the long bones of the extremities. It belongs in the family of small round blue cell tumors and is characterized immunohistochemically by diffuse CD99 expression and molecularly by one of several oncogenic translocations, most commonly t(11;22)(q24;q12) between the EWSR1 gene and the FLI1 gene. Here we present a rare case of Ewing's sarcoma in the sinonasal tract with FUS-ERG gene arrangement that was regarded for almost a decade as a sinonasal-type hemangiopericytoma (glomangiopericytoma). This case illustrates the surprisingly prolonged natural history of Ewing's sarcoma that did not receive therapy for many years and the importance of considering alternative genetic translocations. Our experience suggests that the presence of diffuse CD99 membranous staining pattern in a small blue round cell tumor with morphology typical for Ewing's sarcoma but FISH negative for EWSR1 rearrangement should prompt consideration of FUS-ERG fusion.

  View details for DOI 10.1159/000511415

  View details for PubMedID 33442361

  View details for PubMedCentralID PMC7772862

• Tenosynovial giant cell tumor of the suboccipital region - A rare, benign neoplasm in this location. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Singh, R. n., Stienen, M. N., Ganjoo, K. n., Kolahi, K. S., Cayrol, R. n., Charville, G. W., Born, D. E., Zygourakis, C. C. 2020

  Abstract

  Tenosynovial giant cell tumors (TGCTs) are benign neoplasms that arise from the synovium of tendon sheaths, bursae, and joints. We report a rare presentation of TGCT involving the suboccipital spine.

  View details for DOI 10.1016/j.jocn.2020.05.022

  View details for PubMedID 32631721

• Nivolumab plus ipilimumab for soft tissue sarcoma: a single institution retrospective review. Immunotherapy Zhou, M. n., Bui, N. n., Bolleddu, S. n., Lohman, M. n., Becker, H. C., Ganjoo, K. n. 2020

  Abstract

  Aim: To analyze the efficacy of checkpoint inhibitors in soft tissue sarcoma. Materials & methods: We retrospectively reviewed patients with advanced soft tissue sarcoma treated with ipilimumab and nivolumab. All patients who received at least one cycle were included. Results: One patient had a complete response and five had a partial response, for an objective response rate of 15%. Clinical benefit rate was 34% with a median duration of 12.0 months (range: 4.5 to 28.9+ months [mo]). Median overall survival was 12.0 months (95% CI: 4.5-23.7+ mo). Median progression-free survival was 2.7 months (95% CI: 2.3-4.5+ mo) by Response Evaluation Criteria in Solid Tumors 1.1 and 2.9 months (2.5-6.0+ mo) by immune-related Response Evaluation Criteria in Solid Tumors. Adverse events of any grade were seen in 58% of patients, the most common being fatigue (21%) and cough (10%), 5% of patients experienced a grade 3 adverse event (AE) (hyperglycemia) or grade 4 AE (myocarditis). Conclusion: Ipilimumab/nivolumab combination showed efficacy and was well tolerated in advanced soft tissue sarcoma.

  View details for DOI 10.2217/imt-2020-0155

  View details for PubMedID 32967520

• Effect of Doxorubicin Plus Olaratumab vs Doxorubicin Plus Placebo on Survival in Patients With Advanced Soft Tissue Sarcomas: The ANNOUNCE Randomized Clinical Trial. JAMA Tap, W. D., Wagner, A. J., Schöffski, P. n., Martin-Broto, J. n., Krarup-Hansen, A. n., Ganjoo, K. N., Yen, C. C., Abdul Razak, A. R., Spira, A. n., Kawai, A. n., Le Cesne, A. n., Van Tine, B. A., Naito, Y. n., Park, S. H., Fedenko, A. n., Pápai, Z. n., Soldatenkova, V. n., Shahir, A. n., Mo, G. n., Wright, J. n., Jones, R. L. 2020; 323 (13): 1266–76

  Abstract

  Patients with advanced soft tissue sarcoma (STS) have a median overall survival of less than 2 years. In a phase 2 study, an overall survival benefit in this population was observed with the addition of olaratumab to doxorubicin over doxorubicin alone.To determine the efficacy of doxorubicin plus olaratumab in patients with advanced/metastatic STS.ANNOUNCE was a confirmatory, phase 3, double-blind, randomized trial conducted at 110 sites in 25 countries from September 2015 to December 2018; the final date of follow-up was December 5, 2018. Eligible patients were anthracycline-naive adults with unresectable locally advanced or metastatic STS, an Eastern Cooperative Oncology Group performance status of 0 to 1, and cardiac ejection fraction of 50% or greater.Patients were randomized 1:1 to receive doxorubicin, 75 mg/m2 (day 1), combined with olaratumab (n = 258), 20 mg/kg in cycle 1 and 15 mg/kg in subsequent cycles, or placebo (n = 251) on days 1 and 8 for up to 8 21-day cycles, followed by olaratumab/placebo monotherapy.Dual primary end points were overall survival with doxorubicin plus olaratumab vs doxorubicin plus placebo in total STS and leiomyosarcoma (LMS) populations.Among the 509 patients randomized (mean age, 56.9 years; 58.2% women; 46.0% with LMS), all were included in the primary analysis and had a median length of follow-up of 31 months. No statistically significant difference in overall survival was observed between the doxorubicin plus olaratumab group vs the doxorubicin plus placebo group in either population (total STS: hazard ratio, 1.05 [95% CI, 0.84-1.30], P = .69, median overall survival, 20.4 months vs 19.7 months; LMS: hazard ratio, 0.95 [95% CI, 0.69-1.31], P = .76, median overall survival, 21.6 months vs 21.9 months). Adverse events of grade 3 or greater reported in 15% or more of total patients with STS were neutropenia (46.3% vs 49.0%), leukopenia (23.3% vs 23.7%), and febrile neutropenia (17.5% vs 16.5%).In this phase 3 clinical trial of patients with advanced STS, treatment with doxorubicin plus olaratumab vs doxorubicin plus placebo resulted in no significant difference in overall survival. The findings did not confirm the overall survival benefit observed in the phase 2 trial.ClinicalTrials.gov Identifier: NCT02451943.

  View details for DOI 10.1001/jama.2020.1707

  View details for PubMedID 32259228

• Updated results of phase 1 study of ripretinib (DCC-2618), a broad-spectrum KIT and PDGFRA inhibitor, in patients with gastrointestinal stromal tumor (GIST) by line of therapy (NCT02571036) Chi, P., Janku, F., Heinrich, M., Ganjoo, K., Gelderblom, H., Gordon, M., Jones, R., Razak, A., Trent, J., von Mehren, M., Hu, S., Su, Y., Ruiz-Soto, R., George, S. AMER ASSOC CANCER RESEARCH. 2019

  View details for DOI 10.1158/1535-7163.TARG-19-C077

  View details for Web of Science ID 000510047200318

• Detection of Circulating Tumor DNA in Patients With Uterine Leiomyomas. JCO precision oncology Przybyl, J., Spans, L., Lum, D. A., Zhu, S., Vennam, S., Forgó, E., Varma, S., Ganjoo, K., Hastie, T., Bowen, R., Debiec-Rychter, M., van de Rijn, M. 2019; 3

  Abstract

  The preoperative distinction between uterine leiomyoma (LM) and leiomyosarcoma (LMS) is difficult, which may result in dissemination of an unexpected malignancy during surgery for a presumed benign lesion. An assay based on circulating tumor DNA (ctDNA) could help in the preoperative distinction between LM and LMS. This study addresses the feasibility of applying the two most frequently used approaches for detection of ctDNA: profiling of copy number alterations (CNAs) and point mutations in the plasma of patients with LM.By shallow whole-genome sequencing, we prospectively examined whether LM-derived ctDNA could be detected in plasma specimens of 12 patients. Plasma levels of lactate dehydrogenase, a marker suggested for the distinction between LM and LMS by prior studies, were also determined. We also profiled 36 LM tumor specimens by exome sequencing to develop a panel for targeted detection of point mutations in ctDNA of patients with LM.We identified tumor-derived CNAs in the plasma DNA of 50% (six of 12) of patients with LM. The lactate dehydrogenase levels did not allow for an accurate distinction between patients with LM and patients with LMS. We identified only two recurrently mutated genes in LM tumors (MED12 and ACLY).Our results show that LMs do shed DNA into the circulation, which provides an opportunity for the development of ctDNA-based testing to distinguish LM from LMS. Although we could not design an LM-specific panel for ctDNA profiling, we propose that the detection of CNAs or point mutations in selected tumor suppressor genes in ctDNA may favor a diagnosis of LMS, since these genes are not affected in LM.

  View details for DOI 10.1200/po.18.00409

  View details for PubMedID 32232185

  View details for PubMedCentralID PMC7105159

• Results of the TAPPAS trial: An adaptive enrichment phase III trial of TRC105 and pazopanib (P) versus pazopanib alone in patients with advanced angiosarcoma (AS) Jones, R. L., Ravi, V., Brohl, A. S., Chawla, S. P., Ganjoo, K., Italiano, A., Attia, S., Burgess, M., Thornton, K., Cranmer, L., Liu, L., Theuer, C., Maki, R. OXFORD UNIV PRESS. 2019: 683

  View details for Web of Science ID 000491295504327

• Ripretinib (DCC-2618) pharmacokinetics (PK) in a Phase I study in patients with gastrointestinal stromal tumors (GIST) and other advanced malignancies: A retrospective evaluation of the PK effects of proton pump inhibitors (PPIs) Janku, F., Heinrich, M., Chi, P., Razak, A., von Mehren, M., Gordon, M., Ganjoo, K., Trent, J., Jones, R. L., Gelderblom, H., Running, K., Wang, J., Ruiz-Soto, R., George, S. AMER ASSOC CANCER RESEARCH. 2019

  View details for DOI 10.1158/1538-7445.AM2019-CT058

  View details for Web of Science ID 000488129900053

• ANNOUNCE: A randomized, placebo (PBO)-controlled, double-blind, phase (Ph) III trial of doxorubicin (dox) plus olaratumab versus dox plus PBO in patients (pts) with advanced soft tissue sarcomas (STS). Tap, W. D., Wagner, A. J., Papai, Z., Ganjoo, K. N., Yen, C., Schoffski, P., Razak, A., Martin Broto, J., Spira, A. I., Kawai, A., Krarup-Hansen, A., Le Cesne, A., Van Tine, B., Naito, Y., Park, S., Soldatenkova, V., Mo, G., Shahir, A., Wright, J., Jones, R. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for DOI 10.1200/JCO.2019.37.18_suppl.LBA3

  View details for Web of Science ID 000489109800008

• Uterine sarcomas. Current problems in cancer Ganjoo, K. N. 2019

  Abstract

  Uterine sarcomas comprise a small percentage of uterine malignancies. The most common uterine sarcoma is leiomyosarcoma (LMS). Early stage uterine LMS is curable with complete hysterectomy with removal of an intact uterus. Patients with metastatic disease may achieve tumor responses with improvements in quality of life, but long-term remissions are rare. In this review article, I outline adjuvant therapies for early stage resected uterine LMS, as well as treatment of metastatic disease.

  View details for DOI 10.1016/j.currproblcancer.2019.06.001

  View details for PubMedID 31235185

• Randomized Double-Blind Phase II Study of Regorafenib in Patients With Metastatic Osteosarcoma JOURNAL OF CLINICAL ONCOLOGY Davis, L. E., Bolejack, V., Ryan, C. W., Ganjoo, K. N., Loggers, E. T., Chawla, S., Agulnik, M., Livingston, M. B., Reed, D., Keedy, V., Rushing, D., Okuno, S., Reinke, D. K., Riedel, R. F., Attia, S., Mascarenhas, L., Maki, R. G. 2019; 37 (16): 1424-+

  View details for DOI 10.1200/JCO.18.02374

  View details for Web of Science ID 000471946600008

• A phase II randomized study of CMB305 and atezolizumab versus atezolizumab in NY-ESO-1(+) soft tissue sarcoma: Analysis of immunogenicity, tumor control, and patient survival. Chawla, S. P., Van Tine, B., Pollack, S., Ganjoo, K. N., Elias, A. D., Riedel, R. F., Attia, S., Choy, E., Okuno, S. H., Agulnik, M., von Mehren, M., Livingston, M. B., Keedy, V., Verschraegen, C. F., Philip, T., Bohac, G. C., Yurasov, S., Lu, H., Chen, M., Maki, R. G. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for Web of Science ID 000487345804108

• Responder analysis of patient-reported outcomes measurement information system (PROM'S) physical function (PF) and worst stiffness among patients with tenosynovial giant cell tumors (TGCT) in the ENLIVEN study. Tap, W. D., Speck, R. M., Ye, X., Palmerini, E., Stacchiotti, S., Desai, J., Wagner, A. J., Alcindor, T., Ganjoo, K. N., Broto, J., Wang, Q., Shuster, D., Gelhorn, H., Gelderblom, H. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for DOI 10.1200/JCO.2019.37.15_suppl.e18236

  View details for Web of Science ID 000487345802191

• A phase II study of ADI-PEG 20 in combination with gemcitabine and docetaxel for the treatment of soft tissue sarcoma. Van Tine, B., Bui, N., Prudner, B., Bomalaski, J. S., Wu, B., Chawla, S. P., Ganjoo, K. N., Oppelt, P., Hirbe, A. C. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for Web of Science ID 000487345803233

• Multi-institutional analysis of outcomes in patients with dedifferentiated chondrosarcoma (DDCS). Bui, N., Dietz, H., Hirbe, A. C., Ganjoo, K. N., Van Tine, B., Keedy, V., Davis, E. J. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for Web of Science ID 000487345804124

• ABI-009 (nab-sirolimus) in advanced malignant perivascular epithelioid cell tumors (PEComa): Preliminary efficacy, safety, and mutational status from AMPECT, an open label phase II registration trial. Wagner, A. J., Ravi, V., Ganjoo, K. N., Van Tine, B., Riedel, R. F., Chugh, R., Cranmer, L. D., Gordon, E., Hornick, J. L., Kwiatkowski, D. J., Du, H., Grigorian, B., Schmid, A. N., Hou, S., Harris, K., Desai, N., Dickson, M. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for Web of Science ID 000487345804102

• Randomized Double-Blind Phase II Study of Regorafenib in Patients With Metastatic Osteosarcoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Davis, L. E., Bolejack, V., Ryan, C. W., Ganjoo, K. N., Loggers, E. T., Chawla, S., Agulnik, M., Livingston, M. B., Reed, D., Keedy, V., Rushing, D., Okuno, S., Reinke, D. K., Riedel, R. F., Attia, S., Mascarenhas, L., Maki, R. G. 2019: JCO1802374

  Abstract

  PURPOSE: SARC024 is a phase II clinical trial of the multikinase inhibitor regorafenib in specific sarcoma subtypes, including advanced osteosarcoma. We hypothesized that regorafenib would improve progression-free survival (PFS) in patients with sarcoma and report the results of the osteosarcoma cohort.PATIENTS AND METHODS: This trial enrolled patients with progressive metastatic osteosarcoma with measurable disease by RECIST who had received at least one prior line of therapy. Patients were randomly assigned at a ratio of one to one to regorafenib or placebo. Crossover was allowed at time of disease progression. PFS was the primary end point of the study, which was powered to detect a difference of at least 3 months in median PFS.RESULTS: Forty-two patients from 12 centers were enrolled between September 2014 and May 2018. Median age was 37 years (range, 18 to 76 years). Patients had received an average of 2.3 prior therapy regimens. Ten patients receiving placebo crossed over to active drug at time of progression. Study enrollment was stopped early, after a data safety monitoring committee review. Median PFS was significantly improved with regorafenib versus placebo: 3.6 months (95% CI, 2.0 to 7.6 months) versus 1.7 months (95% CI, 1.2 to 1.8 months), respectively (hazard ratio, 0.42; 95% CI, 0.21 to 0.85; P = .017). In the context of the crossover design, there was no statistically significant difference in overall survival. Fourteen (64%) of 22 patients initially randomly assigned to regorafenib experienced grade 3 to 4 events attributed to treatment, including one grade 4 colonic perforation.CONCLUSION: The study met its primary end point, demonstrating activity of regorafenib in patients with progressive metastatic osteosarcoma. No new safety signals were observed. Regorafenib should be considered a treatment option for patients with relapsed metastatic osteosarcoma.

  View details for PubMedID 31013172

• The Outcome of Patients With Localized Undifferentiated Pleomorphic Sarcoma of the Lower Extremity Treated at Stanford University AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS Kamat, N. V., Million, L., Yao, D., Donaldson, S. S., Mohler, D. G., van de Rijn, M., Avedian, R. S., Kapp, D. S., Ganjoo, K. N. 2019; 42 (2): 166–71

  View details for DOI 10.1097/COC.0000000000000496

  View details for Web of Science ID 000465420000010

• A clinico-genomic analysis of soft tissue sarcoma patients reveals CDKN2A deletion as a biomarker for poor prognosis. Clinical sarcoma research Bui, N. Q., Przybyl, J., Trabucco, S. E., Frampton, G., Hastie, T., van de Rijn, M., Ganjoo, K. N. 2019; 9: 12

  Abstract

  Background: Sarcomas are a rare, heterogeneous group of tumors with variable tendencies for aggressive behavior. Molecular markers for prognosis are needed to risk stratify patients and identify those who might benefit from more intensive therapeutic strategies.Patients and methods: We analyzed somatic tumor genomic profiles and clinical outcomes of 152 soft tissue (STS) and bone sarcoma (BS) patients sequenced at Stanford Cancer Institute as well as 206 STS patients from The Cancer Genome Atlas. Genomic profiles of 7733 STS from the Foundation Medicine database were used to assess the frequency of CDKN2A alterations in histological subtypes of sarcoma.Results: Compared to all other tumor types, sarcomas were found to carry the highest relative percentage of gene amplifications/deletions/fusions and the lowest average mutation count. The most commonly altered genes in STS were TP53 (47%), CDKN2A (22%), RB1 (22%), NF1 (11%), and ATRX (11%). When all genomic alterations were tested for prognostic significance in the specific Stanford cohort of localized STS, only CDKN2A alterations correlated significantly with prognosis, with a hazard ratio (HR) of 2.83 for overall survival (p=0.017). These findings were validated in the TCGA dataset where CDKN2A altered patients had significantly worse overall survival with a HR of 2.7 (p=0.002). Analysis of 7733 STS patients from Foundation One showed high prevalence of CDKN2A alterations in malignant peripheral nerve sheath tumors, myxofibrosarcomas, and undifferentiated pleomorphic sarcomas.Conclusion: Our clinico-genomic profiling of STS shows that CDKN2A deletion was the most prevalent DNA copy number aberration and was associated with poor prognosis.

  View details for DOI 10.1186/s13569-019-0122-5

  View details for PubMedID 31528332

• Pexidartinib versus placebo for advanced tenosynovial giant cell tumour (ENLIVEN): a randomised phase 3 trial. Lancet (London, England) Tap, W. D., Gelderblom, H. n., Palmerini, E. n., Desai, J. n., Bauer, S. n., Blay, J. Y., Alcindor, T. n., Ganjoo, K. n., Martín-Broto, J. n., Ryan, C. W., Thomas, D. M., Peterfy, C. n., Healey, J. H., van de Sande, M. n., Gelhorn, H. L., Shuster, D. E., Wang, Q. n., Yver, A. n., Hsu, H. H., Lin, P. S., Tong-Starksen, S. n., Stacchiotti, S. n., Wagner, A. J. 2019

  Abstract

  Tenosynovial giant cell tumour (TGCT), a rare, locally aggressive neoplasm, overexpresses colony-stimulating factor 1 (CSF1). Surgery is standard with no approved systemic therapy. We aimed to evaluate pexidartinib, a CSF1 receptor inhibitor, in patients with TGCT to provide them with a viable systemic treatment option, especially in cases that are not amenable to surgical resection.This phase 3 randomised trial had two parts. Part one was a double-blind study in which patients with symptomatic, advanced TGCT for whom surgery was not recommended were randomly assigned via an integrated web response system (1:1) to the pexidartinib or placebo group. Individuals in the pexidartinib group received a loading dose of 1000 mg pexidartinib per day orally (400 mg morning; 600 mg evening) for the first 2 weeks, followed by 800 mg per day (400 mg twice a day) for 22 weeks. Part two was an open-label study of pexidartinib for all patients. The primary endpoint, assessed in all intention-to-treat patients, was overall response at week 25, and was centrally reviewed by RECIST, version 1.1. Safety was analysed in all patients who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, number NCT02371369.Between May 11, 2015, and Sept 30, 2016, of 174 patients assessed for eligibility, 120 patients were randomly assigned to, and received, pexidartinib (n=61) or placebo (n=59). There were 11 dropouts in the placebo group and nine in the pexidartinib group. Emergence of mixed or cholestatic hepatotoxicity caused the data monitoring committee to stop enrolment six patients short of target. The proportion of patients who achieved overall response was higher for pexidartinib than placebo at week 25 by RECIST (24 [39%] of 61 vs none of 59; absolute difference 39% [95% CI 27-53]; p<0·0001). Serious adverse events occurred in eight (13%) of 61 patients in the pexidartinib group and one (2%) of 59 patients in the placebo group. Hair colour changes (67%), fatigue (54%), aspartate aminotransferase increase (39%), nausea (38%), alanine aminotransferase increase (28%), and dysgeusia (25%) were the most frequent pexidartinib-associated adverse events. Three patients given pexidartinib had aminotransferase elevations three or more times the upper limit of normal with total bilirubin and alkaline phosphatase two or more times the upper limit of normal indicative of mixed or cholestatic hepatotoxicity, one lasting 7 months and confirmed by biopsy.Pexidartinib is the first systemic therapy to show a robust tumour response in TGCT with improved patient symptoms and functional outcomes; mixed or cholestatic hepatotoxicity is an identified risk. Pexidartinib could be considered as a potential treatment for TGCT associated with severe morbidity or functional limitations in cases not amenable to improvement with surgery.Daiichi Sankyo.

  View details for DOI 10.1016/S0140-6736(19)30764-0

  View details for PubMedID 31229240

• The Outcome of Patients With Localized Undifferentiated Pleomorphic Sarcoma of the Lower Extremity Treated at Stanford University. American journal of clinical oncology Kamat, N. V., Million, L., Yao, D., Donaldson, S. S., Mohler, D. G., van de Rijn, M., Avedian, R. S., Kapp, D. S., Ganjoo, K. N. 2018

  Abstract

  BACKGROUND: As a diagnosis of exclusion, Undifferentiated Pleomorphic Sarcoma (UPS) has unclear clinical characteristics. The objective of this retrospective cohort study is to investigate which clinical and prognostic factors of primary lower-extremity UPS will determine failure.METHODS: We retrospectively reviewed 55 primary lower-extremity UPS cases treated at Stanford between 1998 and 2015. Overall Survival (OS) and Disease-Free Survival (DFS) curves were calculated. Univariate Fisher's Exact Tests were used to examine relationships between disease recurrence, treatment, patient factors, tumor characteristics, and surgical margins.RESULTS: 5-year DFS and OS rates were 60% (95% CI, 45%-72%) and 68% (95% CI, 53%-79%), respectively. The 5-year DFS rate for patients with positive margins was 33.3% (95% CI, 5%-68%) compared with 63% (95% CI, 47%-76%) for patients with negative margins. (Log-rank, P=0.03). The OS rate for those with disease recurrence was 42% % (95% CI, 16%-67%) compared with 76% (95% CI, 59%-87%) for patients who did not have disease recurrence (log-rank, P=0.021). Local failure occurred more frequently with omission of radiation therapy (Fisher's exact test, P=0.009).CONCLUSIONS: Positive surgical margins are an important prognostic factor for predicting relapse in UPS. Relapse of any kind led to worse OS. Radiation therapy improved local control of disease but had no statistically significant effect on DFS, highlighting the need for improved diagnostics to identify those at highest risk for hematogenous metastasis and for selection of patients for adjuvant systemic treatment.

  View details for PubMedID 30557163

• The impact of postoperative therapy on primary cardiac sarcoma. The Journal of thoracic and cardiovascular surgery Wu, Y., Million, L., Moding, E. J., Scott, G., Berry, M., Ganjoo, K. N. 2018; 156 (6): 2194-2203

  Abstract

  Primary cardiac sarcomas (PCS) are extremely rare, portend a very poor prognosis, and have limited outcomes data to direct management. This study evaluated the impact of postoperative chemotherapy and/or radiotherapy on survival for PCS.A retrospective chart review was conducted of 12 patients diagnosed with and who underwent resection for PCS at a single institution between 2000 and 2016. Data were collected on patient/tumor characteristics and analyzed with respect to treatment and outcome using Kaplan-Meier methods.Median age was 43 (range 21-73 years) with a 50:50 male-to-female ratio. The most common subtype was angiosarcoma (42%), and 25% presented with distant metastases (DMs). The initial treatment modality for all patients was surgery, with 58% having macroscopically positive (R2) margins. In total, 75% received postoperative chemotherapy and/or radiotherapy. Median progression-free survival (PFS) was 5.9 months, and median overall survival (OS) was 12.0 months. Achieving negative or microscopically positive margins (R0/R1) as compared with R2 resection significantly improved PFS (12.6 vs 2.7 months, P = .008) and OS (21.8 vs 7.2 months, P = .006). DM at presentation demonstrated a significantly shorter OS (7.0 vs 16.9 months, P = .04) and PFS (0.7 vs 7.9 months, P = .003) compared with localized disease. Patients given postoperative therapy had longer OS compared with surgery only, but this difference was not statistically significant (15.5 vs 2.6 months, P = .12).Gross total surgical resection can significantly improve PFS and OS in PCS, but DM at diagnosis is an extremely poor prognostic sign. Postoperative therapy should be considered, although this study was likely underpowered to demonstrate a statistically significant benefit.

  View details for DOI 10.1016/j.jtcvs.2018.04.127

  View details for PubMedID 30454911

• Initial results of phase I study of DCC-2618, a broad-spectrum KIT and PDGFRa inhibitor, in patients (pts) with gastrointestinal stromal tumor (GIST) by number of prior regimens George, S., Heinrich, M., Chi, P., Razak, A., von Mehren, M., Gordon, M., Ganjoo, K. N., Somaiah, N., Trent, J. C., Ahnert, J., Wolf, J., Ruiz-Soto, R., Rosen, O., Janku, F. OXFORD UNIV PRESS. 2018

  View details for Web of Science ID 000459277303372

• Initial results of phase I study of DCC-2618, a broad-spectrum KIT and PDGFRa inhibitor, in patients (pts) with gastrointestinal stromal tumor (GIST) by number of prior regimens. Annals of oncology : official journal of the European Society for Medical Oncology George, S., Heinrich, M., Chi, P., Razak, A., von Mehren, M., Gordon, M., Ganjoo, K. N., Somaiah, N., Trent, J. C., Rodon Ahnert, J., Wolf, J., Ruiz-Soto, R., Rosen, O., Janku, F. 2018; 29 Suppl 8: viii576–viii577

  View details for DOI 10.1093/annonc/mdy299.002

  View details for PubMedID 32137524

• Aldoxorubicin therapy for the treatment of patients with advanced soft tissue sarcoma FUTURE ONCOLOGY Seetharam, M., Kolla, K. R., Ganjoo, K. N. 2018; 14 (23): 2323–33

  Abstract

  Soft tissue sarcomas are a group of rare tumors of mesenchymal origin, and account for less than 1% of all cancers. The most commonly used drug for the treatment of soft tissue sarcoma is anthracycline chemotherapeutic agent, doxorubicin. The major limitation for doxorubicin is cardiotoxicity. Hence, to overcome this limitation and to increase efficacy, aldoxorubicin was developed, which has demonstrated activity in soft tissue sarcomas without much cardiotoxicity. In this review article, we discuss mechanism of action, pharmacokinetics, preclinical studies, clinical trial data and safety profile of aldoxorubicin and its potential applicability in the future of sarcoma treatment.

  View details for DOI 10.2217/fon-2018-0047

  View details for Web of Science ID 000449031200002

  View details for PubMedID 29869517

• Pharmacokinetic (PK), safety, and tolerability profile of DCC-2618 in a phase I trial supports 150mg QD selected for a pivotal phase III trial in gastrointestinal stromal tumor (GIST) Janku, F., Heinrich, M., Razak, A., Gordon, M., Chi, P., Ganjoo, K., von Mehren, M., Somaiah, N., Lee, J., Kuida, K., Soto, R., Rosen, O., George, S. AMER ASSOC CANCER RESEARCH. 2018

  View details for DOI 10.1158/1538-7445.AM2018-CT029

  View details for Web of Science ID 000468818900028

• Association of Dasatinib With Progression-Free Survival Among Patients With Advanced Gastrointestinal Stromal Tumors Resistant to Imatinib JAMA ONCOLOGY Schuetze, S. M., Bolejack, V., Thomas, D. G., von Mehren, M., Patel, S., Samuels, B., Choy, E., D'Amato, G., Staddon, A. P., Ganjoo, K. N., Chow, W. A., Rushing, D. A., Forscher, C. A., Priebat, D. A., Loeb, D. M., Chugh, R., Okuno, S., Reinke, D. K., Baker, L. H. 2018; 4 (6): 814–20

  Abstract

  Gastrointestinal stromal tumors (GISTs) are life-threatening when metastatic or not amenable to surgical removal. In a few patients with advanced GISTs refractory to imatinib mesylate, treatment with sunitinib malate followed by regorafenib provides tumor control; however, additional active treatments are needed for most patients.To evaluate the 6-month progression-free survival (PFS), tumor objective response, and overall survival rates in patients with GISTs treated with dasatinib.This single-arm clinical trial used a Bayesian design to enroll patients 13 years or older with measurable imatinib-refractory metastatic GISTs treated at 14 sarcoma referral centers from June 1, 2008, through December 31, 2009. A control group was not included. Patients were followed up for survival for a minimum of 5 years from date of enrollment. Tumor imaging using computed tomography or magnetic resonance imaging was performed every 8 weeks for the first 24 weeks and every 12 weeks thereafter. Tumor response was assessed by local site using the Choi criteria. Treatment was continued until tumor progression, unacceptable toxic effects after reduction in drug dose, or patient or physician decision. Archival tumor tissue was evaluated for expression of the proto-oncogene tyrosine-protein kinase Src (SRC), phosphorylated SRC (pSRC), and succinate dehydrogenase complex iron sulfur subunit B (SDHB) proteins and for mutation in the V-Kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) and platelet-derived growth factor receptor α (PDGFRA) genes. Data analysis was performed from May 19, 2017, through December 20, 2017.Dasatinib, 70 mg orally twice daily.The primary end point was the 6-month PFS estimate using greater than 30% as evidence of an active drug and less than 10% as evidence of inactive treatment.In this study, 50 patients were enrolled (median age, 60 years; age range, 19-78 years; 31 [62%] male and 19 [38%] female; 41 [82%] white), and 48 were evaluable for response. The estimated 6-month PFS rate was 29% in the overall population and 50% in a subset of 14 patients with pSRC in GISTs. Objective tumor response was observed in 25%, including 1 patient with an imatinib-resistant mutation in PDGFRA exon 18.Dasatinib may have activity in a subset of patients with imatinib-resistant GISTs. Further study is needed to determine whether pSRC is a prognostic biomarker.

  View details for PubMedID 29710216

• Mutation profile of drug resistant gastrointestinal stromal tumor (GIST) patients (pts) enrolled in the phase 1 study of DCC-2618. George, S., Heinrich, M. C., Razak, A., Chi, P., Gordon, M. S., Ganjoo, K. N., von Mehren, M., Somaiah, N., Trent, J. C., Su, Y., Ruiz-Soto, R., Rosen, O., Janku, F. AMER SOC CLINICAL ONCOLOGY. 2018

  View details for DOI 10.1200/JCO.2018.36.15_suppl.11511

  View details for Web of Science ID 000442916003594

• Mutational analysis and safety/efficacy in a phase 2 multi-center investigation of ABI-009 (nab-rapamycin) in patients with advanced malignant perivascular epithelioid cell tumors (PEComa). Wagner, A. J., Riedel, R. F., Van Tine, B., Chugh, R., Ganjoo, K. N., Cranmer, L. D., Pollack, S., Sankhala, K., Gordon, E., Ravi, V., Hornick, J. L., Kwiatkowski, D. J., Grigorian, B., Desai, N., Dickson, M. AMER SOC CLINICAL ONCOLOGY. 2018

  View details for DOI 10.1200/JCO.2018.36.15_suppl.TPS11589

  View details for Web of Science ID 000442916008050

• A randomized, double-blind, placebo-controlled, phase II study of regorafenib vs placebo in advanced/metastatic, treatment-refractory liposarcoma: results from the SARC024 study. Riedel, R. F., Ballman, K. V., Lu, Y., Attia, S., Loggers, E., Ganjoo, K. N., Livingston, M. B., Chow, W., Wright, J. A., Ward, J., Rushing, D. A., Okuno, S. H., Reed, D. R., Liebner, D. A., Keedy, V., Mascarenhas, L., Davis, L., Ryan, C. W., Reinke, D. K., Maki, R. G. AMER SOC CLINICAL ONCOLOGY. 2018

  View details for DOI 10.1200/JCO.2018.36.15_suppl.11505

  View details for Web of Science ID 000442916003588

• Final results of ENLIVEN: A global, double-blind, randomized, placebo-controlled, phase 3 study of pexidartinib in advanced tenosynovial giant cell tumor (TGCT). Tap, W. D., Gelderblom, H., Stacchiotti, S., Palmerini, E., Ferrari, S., Desai, J., Bauer, S., Blay, J., Alcindor, T., Ganjoo, K. N., Broto, J., Ryan, C. W., Shuster, D., Zhang, L., Wang, Q., Hsu, H., Lin, P. S., Tong, S., Wagner, A. J. AMER SOC CLINICAL ONCOLOGY. 2018

  View details for DOI 10.1200/JCO.2018.36.15_suppl.11502

  View details for Web of Science ID 000442916003585

• Decreased lymphocyte count at diagnosis as a marker for worse outcome in localized sarcoma. Bui, N., Henry, S., Ganjoo, K. N. AMER SOC CLINICAL ONCOLOGY. 2018

  View details for DOI 10.1200/JCO.2018.36.15_suppl.e23537

  View details for Web of Science ID 000442916007238

• CDKN2A deletion as a prognostic marker: A clinico-genomic analysis of sarcoma patients. Nam Bui, Przybyl, J., Million, L., Van De Rijn, M., Ganjoo, K. N. AMER SOC CLINICAL ONCOLOGY. 2018

  View details for DOI 10.1200/JCO.2018.36.15_suppl.11543

  View details for Web of Science ID 000442916003625

• Soft Tissue Sarcoma, Version 2.2018 JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK von Mehren, M., Randall, R., Benjamin, R. S., Boles, S., Bui, M. M., Ganjoo, K. N., George, S., Gonzalez, R. J., Heslin, M. J., Kane, J. M., Keedy, V., Kim, E., Koon, H., Mayerson, J., McCarter, M., McGarry, S. V., Meyer, C., Morris, Z. S., O'Donnell, R. J., Pappo, A. S., Paz, I., Petersen, I. A., Pfeifer, J. D., Riedel, R. F., Ruo, B., Schuetze, S., Tap, W. D., Wayne, J. D., Bergman, M., Scavone, J. L. 2018; 16 (5): 536–63

  Abstract

  Soft tissue sarcomas (STS) are rare solid tumors of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Guidelines for STS provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as intra-abdominal/retroperitoneal STS, gastrointestinal stromal tumors, desmoid tumors, and rhabdomyosarcoma. This portion of the NCCN Guidelines discusses general principles for the diagnosis, staging, and treatment of STS of the extremities, superficial trunk, or head and neck; outlines treatment recommendations by disease stage; and reviews the evidence to support the guidelines recommendations.

  View details for DOI 10.6004/jnccn.2018.0025

  View details for Web of Science ID 000431928700012

  View details for PubMedID 29752328

• Circulating tumor DNA levels correlate with response to treatment in LMS patients Przybyl, J., Chabon, J. J., Spans, L., Ganjoo, K., Vennam, S., Newman, A. M., Forgo, E., Varma, S., Zhu, S., Debiec-Rychter, M., Alizadeh, A., Diehn, M., van de Rijn, M. AMER ASSOC CANCER RESEARCH. 2018: 38–39

  View details for Web of Science ID 000422882000043

• The Impact of Post-Operative Therapy on Primary Cardiac Sarcoma The Journal of Thoracic and Cardiovascular Surgery Wu, Y., Million, L., Moding, E. J., Scott, G., Berry, M., Ganjoo, K. N. 2018

  View details for DOI 10.1016/j.jtcvs.2018.04.127

• Anaplastic Thyroid Cancer With Extensive Skeletal Muscle Metastases on 18F-FDG PET/CT. Clinical nuclear medicine Yurkiewicz, I. R., Ganjoo, K. N., Iagaru, A. n. 2018

  Abstract

  A 61-year-old woman with newly diagnosed anaplastic thyroid cancer and known metastases to the brain, lungs, and adrenal glands complained of groin muscle pain. F-FDG PET/CT was performed to assess for extent of disease and showed extensive hypermetabolic lesions throughout the skeletal musculature concerning for metastatic disease. As this would be a very rare presentation for anaplastic thyroid carcinoma, a biopsy of the left gluteal muscle was conducted. Pathology demonstrated anaplastic thyroid carcinoma, metastatic to skeletal muscle.

  View details for PubMedID 29356736

• Combination approach for detecting different types of alterations in circulating tumor DNA in leiomyosarcoma. Clinical cancer research : an official journal of the American Association for Cancer Research Przybyl, J. n., Chabon, J. J., Spans, L. n., Ganjoo, K. n., Vennam, S. n., Newman, A. M., Forgó, E. n., Varma, S. n., Zhu, S. n., Debiec-Rychter, M. n., Alizadeh, A. A., Diehn, M. n., van de Rijn, M. n. 2018

  Abstract

  The clinical utility of circulating tumor DNA (ctDNA) monitoring has been shown in tumors that harbor highly recurrent mutations. Leiomyosarcoma (LMS) represents a type of tumor with a wide spectrum of heterogeneous genomic abnormalities; thus, targeting hotspot mutations or a narrow genomic region for ctDNA detection may not be practical. Here we demonstrate a combinatorial approach that integrates different sequencing protocols for the orthogonal detection of single nucleotide variants (SNVs), small indels and copy number alterations (CNAs) in ctDNA.We employed Cancer Personalized Profiling by deep Sequencing (CAPP-Seq) for the analysis of SNVs and indels, together with a genome-wide interrogation of CNAs by Genome Representation Profiling (GRP). We profiled 28 longitudinal plasma samples and 25 tumor specimens from 7 patients with LMS.We detected ctDNA in 6 of 7 of these patients with >98% specificity for mutant allele fractions down to a level of 0.01%. We show that results from CAPP-Seq and GRP are highly concordant, and the combination of these methods allows for more comprehensive monitoring of ctDNA by profiling a wide spectrum of tumor-specific markers. By analyzing multiple tumor specimens in individual patients obtained from different sites and at different times during treatment, we observed clonal evolution of these tumors that was reflected by ctDNA profiles.Our strategy allows for a comprehensive monitoring of a broad spectrum of tumor-specific markers in plasma. Our approach may be clinically useful not only in LMS but also in other tumor types that lack recurrent genomic alterations.

  View details for PubMedID 29463554

• A multicenter phase II study of Q3 week or weekly paclitaxel in combination with bevacizumab for the treatment of metastatic or unresectable angiosarcoma. Rare tumors Bui, N. n., Kamat, N. n., Ravi, V. n., Chawla, S. n., Lohman, M. n., Ganjoo, K. N. 2018; 10: 2036361318771771

  Abstract

  Paclitaxel (P) and bevacizumab (B) are agents that provide clinical benefit in advanced angiosarcoma (AS). The objective of this study was to assess the efficacy and safety of P-B in two different scheduled regimens. Patients were to receive P 200mg/m2 IV with B 15mg/kg IV every 21 days (Regimen A) or P 90mg/m2 IV weekly D1, 8, 15 with B 15mg/kg IV D1 of a 28 day cycle (Regimen B) x6 cycles. Maintenance B followed at a dose of 15 mg/kg intravenously once every 21 days. The primary end point was 4 month non-progression rate (NPR). A total of 16 patients were enrolled. 4 month NPR was 62.5% with median overall survival 16 months and median progression free survival 5.06 months. 11 patients made it to cycle 3 and were evaluable for response with 1 CR (9%), 4 PR (36%), 2 SD (18%), and 6 PD (36%). There were ten grade 3 toxicities and four grade 4 toxicities. The breakdown between the two regimens revealed comparable efficacy and safety. Paclitaxel and Bevacizumab is an active regimen in angiosarcoma. Q3 week and weekly paclitaxel appear similar in efficacy and safety.

  View details for PubMedID 29760870

• Efficacy and safety of trabectedin or dacarbazine in patients with advanced uterine leiomyosarcoma after failure of anthracycline-based chemotherapy: Subgroup analysis of a phase 3, randomized clinical trial GYNECOLOGIC ONCOLOGY Hensley, M. L., Patel, S. R., von Mehren, M., Ganjoo, K., Jones, R. L., Staddon, A., Rushing, D., Milhem, M., Monk, B., Wang, G., McCarthy, S., Knoblauch, R. E., Parekh, T. V., Maki, R. G., Demetri, G. D. 2017; 146 (3): 531–37

  Abstract

  Trabectedin demonstrated significantly improved disease control in leiomyosarcoma and liposarcoma patients in a global phase 3 trial (NCT01343277). A post hoc analysis was conducted to assess the efficacy and safety of trabectedin or dacarbazine in women with uterine leiomyosarcoma (uLMS), the largest subgroup of enrolled patients (40%).Of 577 patients randomized 2:1 to receive trabectedin 1.5mg/m2 by 24-hour IV infusion or dacarbazine 1g/m2 by 20-120-minute IV infusion once every three weeks, 232 had uLMS (trabectedin: 144; dacarbazine: 88). The primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR: complete responses+partial responses+stable disease [SD] for at least 18weeks), duration of response (DOR), and safety.PFS for trabectedin was 4.0months compared with 1.5months for dacarbazine (hazard ratio [HR]=0.57; 95% CI 0.41-0.81; P=0.0012). OS was similar (trabectedin 13.4months vs. dacarbazine 12.9months, HR=0.89; 95% CI 0.65-1.24; P=0.51) between groups. ORR was 11% with trabectedin vs. 9% with dacarbazine (P=0.82). CBR for trabectedin was 31% vs. 18% with dacarbazine (P=0.05); median DOR was 6.5months for trabectedin vs. 4.1months for dacarbazine (P=0.32). Grade 3/4 treatment-emergent adverse events observed in ≥10% of patients in the trabectedin group included transient aminotransferase (aspartate/alanine) elevations, anemia, leukopenia, and thrombocytopenia.In this post hoc subset analysis of patients with uLMS who had received prior anthracycline therapy, trabectedin treatment resulted in significantly longer PFS versus dacarbazine, with an acceptable safety profile. There was no difference in OS.

  View details for PubMedID 28651804

  View details for PubMedCentralID PMC5783302

• Doxorubicin plus evofosfamide versus doxorubicin alone in locally advanced, unresectable or metastatic soft-tissue sarcoma (TH CR-406/SARC021): an international, multicentre, open-label, randomised phase 3 trial LANCET ONCOLOGY Tap, W. D., Papai, Z., Van Tine, B. A., Attia, S., Ganjoo, K. N., Jones, R. L., Schuetze, S., Reed, D., Chawla, S. P., Riedel, R. F., Krarup-Hansen, A., Toulmonde, M., Ray-Coquard, I., Hohenberger, P., Grignani, G., Cranmer, L. D., Okuno, S., Agulnik, M., Read, W., Ryan, C. W., Alcindor, T., Garcia del Muro, X. F., Budd, G., Tawbi, H., Pearce, T., Kroll, S., Reinke, D. K., Schoffski, P. 2017; 18 (8): 1089–1103

  Abstract

  Evofosfamide is a hypoxia-activated prodrug of bromo-isophosphoramide mustard. We aimed to assess the benefit of adding evofosfamide to doxorubicin as first-line therapy for advanced soft-tissue sarcomas.We did this international, open-label, randomised, phase 3, multicentre trial (TH CR-406/SARC021) at 81 academic or community investigational sites in 13 countries. Eligible patients were aged 15 years or older with a diagnosis of an advanced unresectable or metastatic soft-tissue sarcoma, of intermediate or high grade, for which no standard curative therapy was available, an Eastern Cooperative Oncology Group performance status of 0-1, and measurable disease by Response Evaluation Criteria in Solid Tumors version 1.1. Patients were randomly assigned (1:1) to receive doxorubicin alone (75 mg/m2 via bolus injection administered over 5-20 min or continuous intravenous infusion for 6-96 h on day 1 of every 21-day cycle for up to six cycles) or doxorubicin (given via the same dose procedure) plus evofosfamide (300 mg/m2 intravenously for 30-60 min on days 1 and 8 of every 21-day cycle for up to six cycles). After six cycles of treatment, patients in the single-drug doxorubicin group were followed up expectantly whereas patients with stable or responsive disease in the combination group were allowed to continue with evofosfamide monotherapy until documented disease progression. A web-based central randomisation with block sizes of two and four was stratified by extent of disease, doxorubicin administration method, and previous systemic therapy. Patients and investigators were not masked to treatment assignment. The primary endpoint was overall survival, analysed in the intention-to-treat population. Safety analyses were done in all patients who received any amount of study drug. This study was registered with ClinicalTrials.gov, number NCT01440088.Between Sept 26, 2011, and Jan 22, 2014, 640 patients were enrolled and randomly assigned to a treatment group (317 to doxorubicin plus evofosfamide and 323 to doxorubicin alone), all of whom were included in the intention-to-treat analysis. The overall survival endpoint was not reached (hazard ratio 1·06, 95% CI 0·88-1·29; p=0·527), with a median overall survival of 18·4 months (95% CI 15·6-22·1) with doxorubicin plus evofosfamide versus 19·0 months (16·2-22·4) with doxorubicin alone. The most common grade 3 or worse adverse events in both groups were haematological, including anaemia (150 [48%] of 313 patients in the doxorubicin plus evofosfamide group vs 65 [21%] of 308 in the doxorubicin group), neutropenia (47 [15%] vs 92 [30%]), febrile neutropenia (57 [18%] vs 34 [11%]), leucopenia (22 [7%] vs 17 [6%]), decreased neutrophil count (31 [10%] vs 41 [13%]), and decreased white blood cell count (39 [13%] vs 33 [11%]). Grade 3-4 thrombocytopenia was more common in the combination group (45 [14%]) than in the doxorubicin alone group (four [1%]), as was grade 3-4 stomatitis (26 [8%] vs seven [2%]). Serious adverse events were reported in 145 (46%) of 313 patients in the combination group and 99 (32%) of 308 in the doxorubicin alone group. Five (2%) patients died from treatment-related causes in the combination group (sepsis [n=2], septic shock [n=1], congestive cardiac failure [n=1], and unknown cause [n=1]) versus one (<1%) patient in the doxorubicin alone group (lactic acidosis [n=1]).The addition of evofosfamide to doxorubicin as first-line therapy did not improve overall survival compared with single-drug doxorubicin in patients with locally advanced, unresectable, or metastatic soft-tissue sarcomas and so this combination cannot be recommended in this setting.Threshold Pharmaceuticals.

  View details for PubMedID 28651927

• Long-term outcomes, secondary malignancies and stem cell collection following bendamustine in patients with previously treated non-Hodgkin lymphoma BRITISH JOURNAL OF HAEMATOLOGY Martin, P., Chen, Z., Cheson, B. D., Robinson, K. S., Williams, M., Rajguru, S. A., Friedberg, J. W., van der Jagt, R. H., LaCasce, A. S., Joyce, R., Ganjoo, K. N., Bartlett, N. L., Lemieux, B., VanderWalde, A., Herst, J., Szer, J., Bar, M. H., Cabanillas, F., Dodds, A. J., Montgomery, P. G., Pressnail, B., Ellis, T., Smith, M. R., Leonard, J. P. 2017; 178 (2): 250–56

  Abstract

  Despite the long history of bendamustine as treatment for indolent non-Hodgkin lymphoma, long-term efficacy and toxicity data are minimal. We reviewed long-term data from three clinical trials to characterize the toxicity and efficacy of patients receiving bendamustine. Data were available for 149 subjects at 21 sites. The median age was 60 years at the start of bendamustine (range 39-84), and patients had received a median of 3 prior therapies. The histologies included grades 1-2 follicular lymphoma (FL; n = 73), grade 3 FL (n = 23), small lymphocytic lymphoma (n = 20), marginal zone lymphoma (n = 15), mantle cell lymphoma (n = 9), transformed lymphomas (n = 5), lymphoplasmacytic lymphoma (n = 2) and not reported (n = 2). The median event-free survival was 14·1 months. Nine of 12 attempted stem cell collections were successful. With a median follow-up of 8·9 years, 23 patients developed 25 cancers, including 8 patients with myelodysplastic syndrome/acute myeloid leukaemia. These data provide important information regarding the long-term toxicity of bendamustine in previously treated patients. A small but meaningful number of patients achieved durable remissions following bendamustine. These rigorously collected, patient-level, long-term follow-up data provide reassurance that bendamustine or bendamustine plus rituximab is associated with efficacy and safety for patients with relapsed or refractory indolent non-Hodgkin lymphoma.

  View details for PubMedID 28419413

  View details for PubMedCentralID PMC5737737

• Phase III study of aldoxorubicin vs investigators' choice as treatment for relapsed/refractory soft tissue sarcomas Chawla, S. P., Ganjoo, K. N., Schuetze, S., Papai, Z., Van Tine, B., Choy, E., Liebner, D. A., Agulnik, M., Chawla, S., Wieland, S., Levitt, D. J. AMER SOC CLINICAL ONCOLOGY. 2017

  View details for DOI 10.1200/JCO.2017.35.15_suppl.11000

  View details for Web of Science ID 000411932206152

• A phase II trial of regorafenib (REGO) in patients (pts) with advanced Ewing sarcoma and related tumors (EWS) of soft tissue and bone: SARCO24 trial results Attia, S., Bolejack, V., Ganjoo, K. N., George, S., Agulnik, M., Rushing, D. A., Loggers, E., Livingston, M. B., Wright, J. A., Chawla, S. P., Okuno, S. H., Reinke, D. K., Riedel, R. F., Davis, L., Ryan, C. W., Maki, R. G. AMER SOC CLINICAL ONCOLOGY. 2017

  View details for DOI 10.1200/JCO.2017.35.15_suppl.11005

  View details for Web of Science ID 000411932206156

• Improving care with portfolio of physician-led cancer quality measures at an academic center Porter, J., Smith, A., Winget, M., Rosenthal, E., Seshadri, S., Vetteth, Y., Kiamanesh, E. F., Badwe, A., Advani, R. H., Buyyounouski, M. K., Coutre, S., Dorigo, O., Ganjoo, K. N., Johnston, L. J., Recht, L., Shrager, J. B., Skinner, E. C., Swetter, S. M., Visser, B. C., Blayney, D. W. AMER SOC CLINICAL ONCOLOGY. 2017

  View details for Web of Science ID 000443301600049

• Magnetic resonance-guided focused ultrasound treatment of extra-abdominal desmoid tumors: a retrospective multicenter study EUROPEAN RADIOLOGY Ghanouni, P., Dobrotwir, A., Bazzocchi, A., Bucknor, M., Bitton, R., Rosenberg, J., Telischak, K., Busacca, M., Ferrari, S., Albisinni, U., Walters, S., Gold, G., Ganjoo, K., Napoli, A., Pauly, K. B., Avedian, R. 2017; 27 (2): 732-740

  Abstract

  To assess the feasibility, safety and preliminary efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of extra-abdominal desmoid tumours.Fifteen patients with desmoid fibromatosis (six males, nine females; age range, 7-66 years) were treated with MRgFUS, with seven patients requiring multiple treatments (25 total treatments). Changes in viable and total tumour volumes were measured after treatment. Efficacy was evaluated using an exact one-sided Wilcoxon test to determine if the median reduction in viable tumour measured immediately after initial treatment exceeded a threshold of 50 % of the targeted volume. Median decrease after treatment of at least two points in numerical rating scale (NRS) worst and average pain scores was tested with an exact one-sided Wilcoxon test. Adverse events were recorded.After initial MRgFUS treatment, median viable targeted tumour volume decreased 63 %, significantly beyond our efficacy threshold (P = 0.0013). Median viable total tumour volume decreased (105 mL [interquartile range {IQR}, 217 mL] to 54 mL [IQR, 92 mL]) and pain improved (worst scores, 7.5 ± 1.9 vs 2.7 ± 2.6, P = 0.027; average scores, 6 ± 2.3 vs 1.3 ± 2, P = 0.021). Skin burn was the most common complication.MRgFUS significantly and durably reduced viable tumour volume and pain in this series of 15 patients with extra-abdominal desmoid fibromatosis.• Retrospective four-centre study shows MRgFUS safely and effectively treats extra-abdominal desmoid tumours • This non-invasive procedure can eradicate viable tumour in some cases • Alternatively, MRgFUS can provide durable control of tumour growth through repeated treatments • Compared to surgery or radiation, MRgFUS has relatively mild side effects.

  View details for DOI 10.1007/s00330-016-4376-5

  View details for Web of Science ID 000392142000034

• Improving Care With a Portfolio of Physician-Led Cancer Quality Measures at an Academic Center Improving Care With a Portfolio of Physician-Led Cancer Quality Measures at an Academic Center Porter, J. B. 2017; 13 (8): e673-e682

  Abstract

  Development and implementation of robust reporting processes to systematically provide quality data to care teams in a timely manner is challenging. National cancer quality measures are useful, but the manual data collection required is resource intensive, and reporting is delayed. We designed a largely automated measurement system with our multidisciplinary cancer care programs (CCPs) to identify, measure, and improve quality metrics that were meaningful to the care teams and their patients.Each CCP physician leader collaborated with the cancer quality team to identify metrics, abiding by established guiding principles. Financial incentive was provided to the CCPs if performance at the end of the study period met predetermined targets. Reports were developed and provided to the CCP physician leaders on a monthly or quarterly basis, for dissemination to their CCP teams.A total of 15 distinct quality measures were collected in depth for the first time at this cancer center. Metrics spanned the patient care continuum, from diagnosis through end of life or survivorship care. All metrics improved over the study period, met their targets, and earned a financial incentive for their CCP.Our quality program had three essential elements that led to its success: (1) engaging physicians in choosing the quality measures and prespecifying goals, (2) using automated extraction methods for rapid and timely feedback on improvement and progress toward achieving goals, and (3) offering a financial team-based incentive if prespecified goals were met.

  View details for DOI 10.1200/JOP.2017.021139

  View details for PubMedCentralID PMC5880618

• Phase 2 Study of Dasatinib in Patients With Alveolar Soft Part Sarcoma, Chondrosarcoma, Chordoma, Epithelioid Sarcoma, or Solitary Fibrous Tumor CANCER Schuetze, S. M., Bolejack, V., Choy, E., Ganjoo, K. N., Staddon, A. P., Chow, W. A., Tawbi, H. A., Samuels, B. L., Patel, S. R., von Mehren, M., D'Amato, G., Leu, K. M., Loeb, D. M., Forscher, C. A., Milhem, M. M., Rushing, D. A., Lucas, D. R., Chugh, R., Reinke, D. K., Baker, L. H. 2017; 123 (1): 90-97

  Abstract

  Alveolar soft part sarcoma (ASPS), chondrosarcoma (CS), chordoma, epithelioid sarcoma, and solitary fibrous tumor (SFT) are malignant tumors that are relatively resistant to chemotherapy and for which more effective drug therapy is needed.The 5 listed subtypes were enrolled into a single indolent sarcoma cohort in a phase 2 study of dasatinib using a Bayesian continuous monitoring rule for enrollment. The primary objective was to estimate the 6-month progression-free survival (PFS) rate according to the Choi criteria with a target of ≥50%. Cross-sectional imaging was performed before the start of treatment, every 2 months for 6 months, and then every 3 months during treatment. The 2- and 5-year survival rates were determined.One hundred sixteen patients were enrolled within 45 months, and 109 began treatment with dasatinib. The 6-month PFS rate and the median PFS were 48% and 5.8 months, respectively. The PFS rate at 6 months was highest with ASPS (62%) and lowest with SFT (30%). More than 10% of the patients with ASPS, CS, or chordoma had stable disease for more than 1 year. Collectively, for all 5 subtypes, the 2- and 5-year overall survival rates were 44% and 13%, respectively. An objective response was observed in 18% of the patients with CS or chordoma.Dasatinib failed to achieve control of sarcoma growth for at least 6 months in more than 50% of the patients in this trial according to the Choi tumor response criteria. An objective tumor response and prolonged stable disease was observed in >10% of patients with CS or chordoma. Cancer 2017;90-97. © 2016 American Cancer Society.

  View details for DOI 10.1002/cncr.30379

  View details for Web of Science ID 000394719100012

• Concurrent Imatinib and Radiation Therapy for Unresectable and Symptomatic Desmoid Tumors. Sarcoma Moding, E. J., Million, L., Avedian, R., Ghanouni, P., Kunder, C., Ganjoo, K. N. 2017; 2017: 2316839

  Abstract

  Desmoid tumors are locally aggressive fibroproliferative neoplasms that can lead to pain and dysfunction due to compression of nerves and surrounding structures. Desmoid tumors often progress through medical therapy, and there is frequently a delay of multiple months before radiation can provide symptomatic relief. To achieve more rapid symptomatic relief and tumor regression for unresectable desmoid tumors causing significant morbidity such as brachial plexus impingement with loss of extremity function, we have selectively utilized a combination of imatinib and radiation therapy. Here, we retrospectively review four patients treated with concurrent imatinib and radiation therapy. The treatment was typically tolerated with minimal toxicity though one patient developed avascular necrosis of the irradiated humeral head possibly related to the combined treatment. All the patients treated have had a partial response or stable disease on imaging. Improvement of symptoms was observed in all the treated patients with a median time to relief of 2.5 months after starting radiation therapy. Concurrent radiation and imatinib may represent a viable treatment option for unresectable and symptomatic desmoid tumors where rapid relief is needed to prevent permanent loss of function.

  View details for PubMedID 28761389

• Phase 2 study of dasatinib in patients with alveolar soft part sarcoma, chondrosarcoma, chordoma, epithelioid sarcoma, or solitary fibrous tumor. Cancer Schuetze, S. M., Bolejack, V., Choy, E., Ganjoo, K. N., Staddon, A. P., Chow, W. A., Tawbi, H. A., Samuels, B. L., Patel, S. R., von Mehren, M., D'Amato, G., Leu, K. M., Loeb, D. M., Forscher, C. A., Milhem, M. M., Rushing, D. A., Lucas, D. R., Chugh, R., Reinke, D. K., Baker, L. H. 2016

  Abstract

  Alveolar soft part sarcoma (ASPS), chondrosarcoma (CS), chordoma, epithelioid sarcoma, and solitary fibrous tumor (SFT) are malignant tumors that are relatively resistant to chemotherapy and for which more effective drug therapy is needed.The 5 listed subtypes were enrolled into a single indolent sarcoma cohort in a phase 2 study of dasatinib using a Bayesian continuous monitoring rule for enrollment. The primary objective was to estimate the 6-month progression-free survival (PFS) rate according to the Choi criteria with a target of ≥50%. Cross-sectional imaging was performed before the start of treatment, every 2 months for 6 months, and then every 3 months during treatment. The 2- and 5-year survival rates were determined.One hundred sixteen patients were enrolled within 45 months, and 109 began treatment with dasatinib. The 6-month PFS rate and the median PFS were 48% and 5.8 months, respectively. The PFS rate at 6 months was highest with ASPS (62%) and lowest with SFT (30%). More than 10% of the patients with ASPS, CS, or chordoma had stable disease for more than 1 year. Collectively, for all 5 subtypes, the 2- and 5-year overall survival rates were 44% and 13%, respectively. An objective response was observed in 18% of the patients with CS or chordoma.Dasatinib failed to achieve control of sarcoma growth for at least 6 months in more than 50% of the patients in this trial according to the Choi tumor response criteria. An objective tumor response and prolonged stable disease was observed in >10% of patients with CS or chordoma. Cancer 2017;90-97. © 2016 American Cancer Society.

  View details for DOI 10.1002/cncr.30379

  View details for PubMedID 27696380

• Soft Tissue Sarcoma, Version 2.2016 Clinical Practice Guidelines in Oncology JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK von Mehren, M., Randall, R. L., Benjamin, R. S., Boles, S., Bui, M. M., Conrad, E. U., Ganjoo, K. N., George, S., Gonzalez, R. J., Heslin, M. J., Kane, J. M., Koon, H., Mayerson, J., McCarter, M., McGarry, S. V., Meyer, C., O'Donnell, R. J., Pappo, A. S., Paz, I. B., Petersen, I. A., Pfeifer, J. D., Riedel, R. F., Schuetze, S., Schupak, K. D., Schwartz, H. S., Tap, W. D., Wayne, J. D., Bergman, M. A., Scavone, J. 2016; 14 (6): 758-786

  Abstract

  Soft tissue sarcomas (STS) are rare solid tumors of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Guidelines for Soft Tissue Sarcoma (available at NCCN.org) provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as intra-abdominal/retroperitoneal STS, gastrointestinal stromal tumor, desmoid tumors, and rhabdomyosarcoma. This manuscript discusses guiding principles for the diagnosis and staging of STS and evidence for treatment modalities that include surgery, radiation, chemoradiation, chemotherapy, and targeted therapy.

  View details for Web of Science ID 000377690100009

  View details for PubMedID 27283169

• Magnetic resonance-guided focused ultrasound treatment of extra-abdominal desmoid tumors: a retrospective multicenter study. European radiology Ghanouni, P., Dobrotwir, A., Bazzocchi, A., Bucknor, M., Bitton, R., Rosenberg, J., Telischak, K., Busacca, M., Ferrari, S., Albisinni, U., Walters, S., Gold, G., Ganjoo, K., Napoli, A., Pauly, K. B., Avedian, R. 2016: -?

  Abstract

  To assess the feasibility, safety and preliminary efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of extra-abdominal desmoid tumours.Fifteen patients with desmoid fibromatosis (six males, nine females; age range, 7-66 years) were treated with MRgFUS, with seven patients requiring multiple treatments (25 total treatments). Changes in viable and total tumour volumes were measured after treatment. Efficacy was evaluated using an exact one-sided Wilcoxon test to determine if the median reduction in viable tumour measured immediately after initial treatment exceeded a threshold of 50 % of the targeted volume. Median decrease after treatment of at least two points in numerical rating scale (NRS) worst and average pain scores was tested with an exact one-sided Wilcoxon test. Adverse events were recorded.After initial MRgFUS treatment, median viable targeted tumour volume decreased 63 %, significantly beyond our efficacy threshold (P = 0.0013). Median viable total tumour volume decreased (105 mL [interquartile range {IQR}, 217 mL] to 54 mL [IQR, 92 mL]) and pain improved (worst scores, 7.5 ± 1.9 vs 2.7 ± 2.6, P = 0.027; average scores, 6 ± 2.3 vs 1.3 ± 2, P = 0.021). Skin burn was the most common complication.MRgFUS significantly and durably reduced viable tumour volume and pain in this series of 15 patients with extra-abdominal desmoid fibromatosis.• Retrospective four-centre study shows MRgFUS safely and effectively treats extra-abdominal desmoid tumours • This non-invasive procedure can eradicate viable tumour in some cases • Alternatively, MRgFUS can provide durable control of tumour growth through repeated treatments • Compared to surgery or radiation, MRgFUS has relatively mild side effects.

  View details for PubMedID 27147222

• SARC009: Phase 2 study of dasatinib in patients with previously treated, high-grade, advanced sarcoma. Cancer Schuetze, S. M., Wathen, J. K., Lucas, D. R., Choy, E., Samuels, B. L., Staddon, A. P., Ganjoo, K. N., von Mehren, M., Chow, W. A., Loeb, D. M., Tawbi, H. A., Rushing, D. A., Patel, S. R., Thomas, D. G., Chugh, R., Reinke, D. K., Baker, L. H. 2016; 122 (6): 868-874

  Abstract

  Dasatinib exhibited activity in preclinical models of sarcoma. The Sarcoma Alliance for Research through Collaboration (SARC) conducted a multicenter, phase 2 trial of dasatinib in patients with advanced sarcoma.Patients received dasatinib twice daily. The primary objective was to estimate the clinical benefit rate (CBR) (complete response or partial response within 6 months or stable disease duration of ≥6 months) with a target of ≥25%. Patients were enrolled into 1 of 7 different cohorts and assessed by imaging every 8 weeks using Choi criteria tumor response and a Bayesian hierarchical design. For each subtype, enrollment was stopped after a minimum of 9 patients were treated if there was a <1% chance the CBR was ≥25%.A total of 200 patients were enrolled. Accrual was stopped early in 5 cohorts because of low CBR. The leiomyosarcoma (LMS) and undifferentiated pleomorphic sarcoma (UPS) cohorts fully accrued and 6 of 47 and 8 of 42 evaluable patients, respectively, exhibited clinical benefit. The probability that the CBR was ≥25% in the LMS and UPS cohorts was 0.008 and 0.10, respectively. The median progression-free survival ranged from 0.9 months in patients with rhabdomyosarcoma to 2.2 months in patients with LMS. The median overall survival was 8.6 months. The most frequent adverse events were constitutional, gastrointestinal, and respiratory, and 36% of patients required dose reduction for toxicity. Serious adverse events attributed to therapy occurred in 11% of patients.Dasatinib may have activity in patients with UPS but is inactive as a single agent in the other sarcoma subtypes included herein. The Bayesian design allowed for the early termination of accrual in 5 subtypes because of lack of drug activity. Cancer 2016;122:868-74. © 2015 American Cancer Society.

  View details for DOI 10.1002/cncr.29858

  View details for PubMedID 26710211

• Efficacy and Safety of Trabectedin or Dacarbazine for Metastatic Liposarcoma or Leiomyosarcoma After Failure of Conventional Chemotherapy: Results of a Phase III Randomized Multicenter Clinical Trial. Journal of clinical oncology Demetri, G. D., von Mehren, M., Jones, R. L., Hensley, M. L., Schuetze, S. M., Staddon, A., Milhem, M., Elias, A., Ganjoo, K., Tawbi, H., Van Tine, B. A., Spira, A., Dean, A., Khokhar, N. Z., Park, Y. C., Knoblauch, R. E., Parekh, T. V., Maki, R. G., Patel, S. R. 2016; 34 (8): 786-793

  Abstract

  This multicenter study, to our knowledge, is the first phase III trial to compare trabectedin versus dacarbazine in patients with advanced liposarcoma or leiomyosarcoma after prior therapy with an anthracycline and at least one additional systemic regimen.Patients were randomly assigned in a 2:1 ratio to receive trabectedin or dacarbazine intravenously every 3 weeks. The primary end point was overall survival (OS), secondary end points were disease control-progression-free survival (PFS), time to progression, objective response rate, and duration of response-as well as safety and patient-reported symptom scoring.A total of 518 patients were enrolled and randomly assigned to either trabectedin (n = 345) or dacarbazine (n = 173). In the final analysis of PFS, trabectedin administration resulted in a 45% reduction in the risk of disease progression or death compared with dacarbazine (median PFS for trabectedin v dacarbazine, 4.2 v 1.5 months; hazard ratio, 0.55; P < .001); benefits were observed across all preplanned subgroup analyses. The interim analysis of OS (64% censored) demonstrated a 13% reduction in risk of death in the trabectedin arm compared with dacarbazine (median OS for trabectedin v dacarbazine, 12.4 v 12.9 months; hazard ratio, 0.87; P = .37). The safety profiles were consistent with the well-characterized toxicities of both agents, and the most common grade 3 to 4 adverse effects were myelosuppression and transient elevation of transaminases in the trabectedin arm.Trabectedin demonstrates superior disease control versus conventional dacarbazine in patients who have advanced liposarcoma and leiomyosarcoma after they experience failure of prior chemotherapy. Because disease control in advanced sarcomas is a clinically relevant end point, this study supports the activity of trabectedin for patients with these malignancies.

  View details for DOI 10.1200/JCO.2015.62.4734

  View details for PubMedID 26371143

• First-Line Aldoxorubicin vs Doxorubicin in Metastatic or Locally Advanced Unresectable Soft-Tissue Sarcoma A Phase 2b Randomized Clinical Trial JAMA ONCOLOGY Chawla, S. P., Papai, Z., Mukhametshina, G., Sankhala, K., Vasylyev, L., Fedenko, A., Khamly, K., Ganjoo, K., Nagarkar, R., Wieland, S., Levitt, D. J. 2015; 1 (9): 1272-1280

  View details for DOI 10.1001/jamaoncol.2015.3101

  View details for Web of Science ID 000383678300015

• First-Line Aldoxorubicin vs Doxorubicin in Metastatic or Locally Advanced Unresectable Soft-Tissue Sarcoma: A Phase 2b Randomized Clinical Trial. JAMA oncology Chawla, S. P., Papai, Z., Mukhametshina, G., Sankhala, K., Vasylyev, L., Fedenko, A., Khamly, K., Ganjoo, K., Nagarkar, R., Wieland, S., Levitt, D. J. 2015; 1 (9): 1272-1280

  Abstract

  Standard therapy for advanced soft-tissue sarcoma has not changed substantially in decades, and patient prognosis remains poor. Aldoxorubicin, a novel albumin-binding prodrug of doxorubicin, showed clinical activity against advanced soft-tissue sarcoma in phase 1 studies.To evaluate efficacy and safety of aldoxorubicin vs doxorubicin in patients with advanced soft-tissue sarcoma.International, multicenter, phase 2b, open-label, randomized study at general community practices, private practices, or institutional practices. Between August 2012 and December 2013, 140 patients with previously untreated locally advanced, unresectable, or metastatic soft-tissue sarcoma were screened.Randomization (2:1) to aldoxorubicin 350 mg/m2 (dose equivalent to doxorubicin 260 mg/m2) or doxorubicin 75 mg/m2, administered once every 3 weeks for up to 6 cycles.Primary end point was progression-free survival. Secondary end points were 6-month progression-free survival, overall survival, tumor response rate, and safety. All efficacy end points were evaluated by independent and local review.A total of 126 patients were randomized, and 123 received aldoxorubicin (n = 83) or doxorubicin (n = 40). Median (range) patient age was 54.0 (21-77 years); 42 (34%) had leiomyosarcoma. By independent review, median progression-free survival was significantly improved (5.6 [95% CI, 3.0-8.1] vs 2.7 [95% CI, 1.6-4.3] months; P = .02) with aldoxorubicin compared with doxorubicin, as was the rate of 6-month progression-free survival (46% and 23%; P = .02). Median overall survival was 15.8 (95% CI, 13.0 to not available) months with aldoxorubicin and 14.3 (95% CI, 8.6-20.6) months with doxorubicin (P = .21). Overall tumor response rate (by Response Evaluation Criteria in Solid Tumors, version 1.1) by independent review was higher with aldoxorubicin than with doxorubicin (25% [20 patients, all partial response] vs 0%). Grade 3 or 4 neutropenia was more frequent with aldoxorubicin than with doxorubicin (24 [29%] vs 5 [12%]), but not grade 3 or 4 febrile neutropenia (12 [14%] vs 7 [18%]). No acute cardiotoxic effects were observed with either treatment, although left ventricular ejection fraction less than 50% occurred in 3 of 40 patients receiving doxorubicin.Single-agent aldoxorubicin therapy showed superior efficacy over doxorubicin by prolonging progression-free survival and improving rates of 6-month progression-free survival and tumor response. Aldoxorubicin therapy exhibited manageable adverse effects, without unexpected events, and without evidence of acute cardiotoxicity. Further investigation of aldoxorubicin therapy in advanced soft-tissue sarcoma is warranted.clinicaltrials.gov Identifier: NCT01514188.

  View details for DOI 10.1001/jamaoncol.2015.3101

  View details for PubMedID 26378637

• Sarcoma Resection With and Without Vascular Reconstruction: A Matched Case-control Study ANNALS OF SURGERY Poultsides, G. A., Tran, T. B., Zambrano, E., Janson, L., Mohler, D. G., Mell, M. W., Avedian, R. S., Visser, B. C., Lee, J. T., Ganjoo, K., Harris, E. J., Norton, J. A. 2015; 262 (4): 632-640

  Abstract

  To examine the impact of major vascular resection on sarcoma resection outcomes.En bloc resection and reconstruction of involved vessels is being increasingly performed during sarcoma surgery; however, the perioperative and oncologic outcomes of this strategy are not well described.Patients undergoing sarcoma resection with (VASC) and without (NO-VASC) vascular reconstruction were 1:2 matched on anatomic site, histology, grade, size, synchronous metastasis, and primary (vs. repeat) resection. R2 resections were excluded. Endpoints included perioperative morbidity, mortality, local recurrence, and survival.From 2000 to 2014, 50 sarcoma patients underwent VASC resection. These were matched with 100 NO-VASC patients having similar clinicopathologic characteristics. The rates of any complication (74% vs. 44%, P = 0.002), grade 3 or higher complication (38% vs. 18%, P = 0.024), and transfusion (66% vs. 33%, P < 0.001) were all more common in the VASC group. Thirty-day (2% vs. 0%, P = 0.30) or 90-day mortality (6% vs. 2%, P = 0.24) were not significantly higher. Local recurrence (5-year, 51% vs. 54%, P = 0.11) and overall survival after resection (5-year, 59% vs. 53%, P = 0.67) were similar between the 2 groups. Within the VASC group, overall survival was not affected by the type of vessel involved (artery vs. vein) or the presence of histology-proven vessel wall invasion.Vascular resection and reconstruction during sarcoma resection significantly increases perioperative morbidity and requires meticulous preoperative multidisciplinary planning. However, the oncologic outcome appears equivalent to cases without major vascular involvement. The anticipated need for vascular resection and reconstruction should not be a contraindication to sarcoma resection.

  View details for DOI 10.1097/SLA.0000000000001455

  View details for Web of Science ID 000367999800009

• Sarcoma Resection With and Without Vascular Reconstruction: A Matched Case-control Study. Annals of surgery Poultsides, G. A., Tran, T. B., Zambrano, E., Janson, L., Mohler, D. G., Mell, M. W., Avedian, R. S., Visser, B. C., Lee, J. T., Ganjoo, K., Harris, E. J., Norton, J. A. 2015; 262 (4): 632-40

  Abstract

  To examine the impact of major vascular resection on sarcoma resection outcomes.En bloc resection and reconstruction of involved vessels is being increasingly performed during sarcoma surgery; however, the perioperative and oncologic outcomes of this strategy are not well described.Patients undergoing sarcoma resection with (VASC) and without (NO-VASC) vascular reconstruction were 1:2 matched on anatomic site, histology, grade, size, synchronous metastasis, and primary (vs. repeat) resection. R2 resections were excluded. Endpoints included perioperative morbidity, mortality, local recurrence, and survival.From 2000 to 2014, 50 sarcoma patients underwent VASC resection. These were matched with 100 NO-VASC patients having similar clinicopathologic characteristics. The rates of any complication (74% vs. 44%, P = 0.002), grade 3 or higher complication (38% vs. 18%, P = 0.024), and transfusion (66% vs. 33%, P < 0.001) were all more common in the VASC group. Thirty-day (2% vs. 0%, P = 0.30) or 90-day mortality (6% vs. 2%, P = 0.24) were not significantly higher. Local recurrence (5-year, 51% vs. 54%, P = 0.11) and overall survival after resection (5-year, 59% vs. 53%, P = 0.67) were similar between the 2 groups. Within the VASC group, overall survival was not affected by the type of vessel involved (artery vs. vein) or the presence of histology-proven vessel wall invasion.Vascular resection and reconstruction during sarcoma resection significantly increases perioperative morbidity and requires meticulous preoperative multidisciplinary planning. However, the oncologic outcome appears equivalent to cases without major vascular involvement. The anticipated need for vascular resection and reconstruction should not be a contraindication to sarcoma resection.

  View details for DOI 10.1097/SLA.0000000000001455

  View details for PubMedID 26366542

• Combined F-18-NaF and F-18-FDG PET/CT in the Evaluation of Sarcoma Patients CLINICAL NUCLEAR MEDICINE Jackson, T., Mosci, C., von Eyben, R., Mittra, E., Ganjoo, K., Biswal, S., Gambhir, S. S., Iagaru, A. 2015; 40 (9): 720-724

  Abstract

  The combined administration of F-NaF and F-FDG in a single PET/CT scan has the potential to improve patient convenience and cancer detection. Here we report the use of this approach for patients with sarcomas.This is a retrospective review of 21 patients (12 men, 9 women; age, 19-66 years) with biopsy-proven sarcomas who had separate F-NaF PET/CT, F-FDG PET/CT, and combined F-NaF/F-FDG PET/CT scans for evaluation of malignancy. Two board-certified nuclear medicine physicians and 1 board-certified musculoskeletal radiologist were randomly assigned to review the scans. Results were analyzed for sensitivity and specificity, using linear regression and receiver operating characteristics.A total of 13 patients had metastatic disease on F-NaF PET/CT, F-FDG PET/CT, and combined F-NaF/F-FDG PET/CT. Skeletal disease was more extensive on the F-NaF PET/CT scan than on the F-FDG PET/CT in 3 patients, whereas in 1 patient, F-FDG PET/CT showed skeletal disease and the F-NaF PET/CT was negative. Extraskeletal lesions were detected on both F-FDG and combined F-NaF/F-FDG PET/CT in 20 patients, with 1 discordant finding in the lung.The combined F-NaF/F-FDG PET/CT scan allows for accurate evaluation of sarcoma patients. Further evaluation of this proposed imaging modality is warranted to identify the most suitable clinical scenarios, including initial treatment strategy and evaluation of response to therapy.

  View details for DOI 10.1097/RLU.0000000000000845

  View details for Web of Science ID 000359668600005

  View details for PubMedID 26053718

• Denosumab, a Potential Alternative to the Surgical Treatment of Distal Radius Giant Cell Tumor of Bone: Case Report. journal of hand surgery Park, M. J., Ganjoo, K. N., Ladd, A. L. 2015; 40 (8): 1620-1624

  Abstract

  Juxta-articular giant cell tumors can pose major surgical challenges. Aggressive distal radius giant cell tumors often require complex reconstructive procedures that are associated with numerous complications. We present a case of a 25-year old man with a Campanacci grade 3 giant cell tumor of the distal radius that was successfully treated with denosumab without complex reconstructive procedures. At 3.5-year follow-up and 1-year drug free period, the patient remained asymptomatic without histologic evidence of recurrent tumor. With denosumab therapy, patients can potentially avoid surgery and achieve a successful outcome.

  View details for DOI 10.1016/j.jhsa.2015.03.018

  View details for PubMedID 25935517

• Clinically Relevant Molecular Subtypes in Leiomyosarcoma. Clinical cancer research Guo, X., Jo, V. Y., Mills, A. M., Zhu, S. X., Lee, C., Espinosa, I., Nucci, M. R., Varma, S., Forgó, E., Hastie, T., Anderson, S., Ganjoo, K., Beck, A. H., West, R. B., Fletcher, C. D., van de Rijn, M. 2015; 21 (15): 3501-3511

  Abstract

  Leiomyosarcoma is a malignant neoplasm with smooth muscle differentiation. Little is known about its molecular heterogeneity and no targeted therapy currently exists for leiomyosarcoma. Recognition of different molecular subtypes is necessary to evaluate novel therapeutic options. In a previous study on 51 leiomyosarcomas, we identified three molecular subtypes in leiomyosarcoma. The current study was performed to determine whether the existence of these subtypes could be confirmed in independent cohorts.Ninety-nine cases of leiomyosarcoma were expression profiled with 3'end RNA-Sequencing (3SEQ). Consensus clustering was conducted to determine the optimal number of subtypes.We identified 3 leiomyosarcoma molecular subtypes and confirmed this finding by analyzing publically available data on 82 leiomyosarcoma from The Cancer Genome Atlas (TCGA). We identified two new formalin-fixed, paraffin-embedded tissue-compatible diagnostic immunohistochemical markers; LMOD1 for subtype I leiomyosarcoma and ARL4C for subtype II leiomyosarcoma. A leiomyosarcoma tissue microarray with known clinical outcome was used to show that subtype I leiomyosarcoma is associated with good outcome in extrauterine leiomyosarcoma while subtype II leiomyosarcoma is associated with poor prognosis in both uterine and extrauterine leiomyosarcoma. The leiomyosarcoma subtypes showed significant differences in expression levels for genes for which novel targeted therapies are being developed, suggesting that leiomyosarcoma subtypes may respond differentially to these targeted therapies.We confirm the existence of 3 molecular subtypes in leiomyosarcoma using two independent datasets and show that the different molecular subtypes are associated with distinct clinical outcomes. The findings offer an opportunity for treating leiomyosarcoma in a subtype-specific targeted approach. Clin Cancer Res; 21(15); 3501-11. ©2015 AACR.

  View details for DOI 10.1158/1078-0432.CCR-14-3141

  View details for PubMedID 25896974

• Leiomyosarcoma: One Disease or Distinct Biologic Entities Based on Site of Origin? JOURNAL OF SURGICAL ONCOLOGY Worhunsky, D. J., Gupta, M., Gholami, S., Tran, T. B., Ganjoo, K. N., van de Rijn, M., Visser, B. C., Norton, J. A., Poultsides, G. A. 2015; 111 (7): 808-812

  Abstract

  Leiomyosarcoma (LMS) can originate from the retroperitoneum, uterus, extremity, and trunk. It is unclear whether tumors of different origin represent discrete entities. We compared clinicopathologic features and outcomes following surgical resection of LMS stratified by site of origin.Patients with LMS undergoing resection at a single institution were retrospectively reviewed. Clinicopathologic variables were compared across sites. Survival was calculated using the Kaplan-Meier method and compared using log-rank and Cox regression analyses.From 1983 to 2011, 138 patients underwent surgical resection for LMS. Retroperitoneal and uterine LMS were larger, higher grade, and more commonly associated with synchronous metastases. However, disease-specific survival, recurrence-free survival, and recurrence patterns were not significantly different across the four sites. Synchronous metastases (HR 3.20, P < 0.001), but not site of origin, size, grade, or margin status, were independently associated with worse DSS. A significant number of recurrences and disease-related deaths were noted beyond 5 years.Although larger and higher grade, retroperitoneal and uterine LMS share similar survival and recurrence patterns with their trunk and extremity counterparts. LMS of various anatomic sites may not represent distinct disease processes based on clinical outcomes. The presence of metastatic disease remains the most important prognostic factor for LMS.

  View details for DOI 10.1002/jso.23904

  View details for PubMedID 25920434

• Phase 1/2 Study of Ocaratuzumab, an Fc-Engineered Humanized Anti-CD20 Monoclonal Antibody, in Low-Affinity Fc?RIIIa Patients with Previously Treated Follicular Lymphoma. Leukemia & lymphoma Ganjoo, K. N., de Vos, S., Pohlman, B. L., Flinn, I. W., Forero-Torres, A., Enas, N. H., Cronier, D. M., Dang, N. H., Foon, K. A., Carpenter, S. P., Slapak, C. A., Link, B. K., Smith, M. R., Mapara, M. Y., Wooldridge, J. E. 2015; 56 (1): 42-48

  Abstract

  Abstract This phase 2 study assessed the safety and efficacy of ocaratuzumab, a humanized anti-CD20 monoclonal antibody. Fifty patients with previously treated follicular lymphoma (FL) and a low-affinity genotype of FcγRIIIa received ocaratuzumab 375 mg/m(2) weekly for 4 weeks. Grade 3/4/5 adverse events (AEs) were reported in 11/1/1 patients, respectively. Serious AEs were reported by 11/50 patients, and three discontinued due to AEs. One patient died from aspiration pneumonia due to possibly drug-related nausea and vomiting. Investigator-assessed response rate was 30% (15/50), including four complete responses (CR), three CR unconfirmed (CRu) and eight partial responses (PR). Investigator-assessed median Progression-free survivial (PFS) was 38.3 weeks. Ocaratuzumab's pharmacokinetic profile was similar to that reported for rituximab. Lymphocyte subset analysis showed significant, selective reduction of B-cells during and after ocaratuzumab treatment. Ocaratuzumab at this dose and schedule is active and well tolerated in patients with previously treated FL with low affinity FcγRIIIa genotypes. ClinTrials registry number: NCT00354926.

  View details for DOI 10.3109/10428194.2014.911859

  View details for PubMedID 24717109

• Effects of denosumab on pain and analgesic use in giant cell tumor of bone: Interim results from a phase II study ACTA ONCOLOGICA Martin-Broto, J., Cleeland, C. S., Glare, P. A., Engellau, J., Skubitz, K. M., Blum, R. H., Ganjoo, K. N., Staddon, A., Dominkus, M., Feng, A., Qian, Y., Braun, A., Jacobs, I., Chung, K., Atchison, C. 2014; 53 (9): 1173-1179

  View details for DOI 10.3109/0284186X.2014.910313

  View details for Web of Science ID 000342282100006

• Active idiotypic vaccination versus control immunotherapy for follicular lymphoma. Journal of clinical oncology Levy, R., Ganjoo, K. N., Leonard, J. P., Vose, J. M., Flinn, I. W., Ambinder, R. F., Connors, J. M., Berinstein, N. L., Belch, A. R., Bartlett, N. L., Nichols, C., Emmanouilides, C. E., Timmerman, J. M., Gregory, S. A., Link, B. K., Inwards, D. J., Freedman, A. S., Matous, J. V., Robertson, M. J., Kunkel, L. A., Ingolia, D. E., Gentles, A. J., Liu, C. L., Tibshirani, R., Alizadeh, A. A., Denney, D. W. 2014; 32 (17): 1797-1803

  Abstract

  Idiotypes (Ids), the unique portions of tumor immunoglobulins, can serve as targets for passive and active immunotherapies for lymphoma. We performed a multicenter, randomized trial comparing a specific vaccine (MyVax), comprising Id chemically coupled to keyhole limpet hemocyanin (KLH) plus granulocyte macrophage colony-stimulating factor (GM-CSF) to a control immunotherapy with KLH plus GM-CSF.Patients with previously untreated advanced-stage follicular lymphoma (FL) received eight cycles of chemotherapy with cyclophosphamide, vincristine, and prednisone. Those achieving sustained partial or complete remission (n=287 [44%]) were randomly assigned at a ratio of 2:1 to receive one injection per month for 7 months of MyVax or control immunotherapy. Anti-Id antibody responses (humoral immune responses [IRs]) were measured before each immunization. The primary end point was progression-free survival (PFS). Secondary end points included IR and time to subsequent antilymphoma therapy.At a median follow-up of 58 months, no significant difference was observed in either PFS or time to next therapy between the two arms. In the MyVax group (n=195), anti-Id IRs were observed in 41% of patients, with a median PFS of 40 months, significantly exceeding the median PFS observed in patients without such Id-induced IRs and in those receiving control immunotherapy.This trial failed to demonstrate clinical benefit of specific immunotherapy. The subset of vaccinated patients mounting specific anti-Id responses had superior outcomes. Whether this reflects a therapeutic benefit or is a marker for more favorable underlying prognosis requires further study.

  View details for DOI 10.1200/JCO.2012.43.9273

  View details for PubMedID 24799467

• Results of SARC 022, a phase II multicenter study of linsitinib in pediatric and adult wild-type (WT) gastrointestinal stromal tumors (GIST). von Mehren, M., George, S., Heinrich, M. C., Schuetze, S., Belinsky, M. G., Janeway, K. A., Rink, L., Ganjoo, K. N., Yu, J., Yap, J. T., Wright, J., Van den Abbeele, A. D. AMER SOC CLINICAL ONCOLOGY. 2014

  View details for Web of Science ID 000358613204640

• Bevacizumab and cyclosphosphamide, doxorubicin, vincristine and prednisone in combination for patients with peripheral T-cell or natural killer cell neoplasms: an Eastern Cooperative Oncology Group study (E2404). Leukemia & lymphoma Ganjoo, K., Hong, F., Horning, S. J., Gascoyne, R. D., Natkunam, Y., Swinnen, L. J., Habermann, T. M., Kahl, B. S., Advani, R. H. 2014; 55 (4): 768-772

  Abstract

  Peripheral T-cell lymphoma (PTCL) and natural killer (NK) cell lymphoma have poor survival with conventional cytotoxic chemotherapy. Because angiogenesis plays an important role in the biology of PTCL, a fully humanized anti-vascular endothelial growth factor (VEGF) antibody, bevacizumab (A), was studied in combination with standard cyclosphosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy (ACHOP) to evaluate its potential to improve outcome in these patients. Patients were treated with 6-8 cycles of ACHOP followed by eight doses of maintenance A (15 mg/kg every 21 days). Forty-six patients were enrolled on this phase 2 study from July 2006 through March 2009. Forty-four patients were evaluable for toxicity and 39 were evaluable for response, progression and survival. A total of 324 cycles (range: 2-16, median 7) were administered to 39 evaluable patients and only nine completed all planned treatment. The overall response rate was 90% with 19 (49%) complete response/complete response unconfirmed (CR/CRu) and 16 (41%) a partial response (PR). The 1-year progression-free survival (PFS) rate was 44% at a median follow-up of 3 years. The median PFS and overall survival (OS) rates were 7.7 and 22 months, respectively. Twenty-three patients died (21 from lymphoma, two while in remission). Grade 3 or 4 toxicities included febrile neutropenia (n = 8), anemia (n = 3), thrombocytopenia (n = 5), congestive heart failure (n = 4), venous thrombosis (n = 3), gastrointestinal hemorrhage/perforation (n = 2), infection (n = 8) and fatigue (n = 6). Despite a high overall response rate, the ACHOP regimen failed to result in durable remissions and was associated with significant toxicities. Studies of novel therapeutics are needed for this patient population, whose clinical outcome remains poor.

  View details for DOI 10.3109/10428194.2013.816700

  View details for PubMedID 23786456

• Soft tissue sarcoma, version 2.2014. Journal of the National Comprehensive Cancer Network von Mehren, M., Randall, R. L., Benjamin, R. S., Boles, S., Bui, M. M., Casper, E. S., Conrad, E. U., DeLaney, T. F., Ganjoo, K. N., George, S., Gonzalez, R. J., Heslin, M. J., Kane, J. M., Mayerson, J., McGarry, S. V., Meyer, C., O'Donnell, R. J., Pappo, A. S., Paz, I. B., Pfeifer, J. D., Riedel, R. F., Schuetze, S., Schupak, K. D., Schwartz, H. S., Van Tine, B. A., Wayne, J. D., Bergman, M. A., Sundar, H. 2014; 12 (4): 473-483

  Abstract

  These NCCN Guidelines Insights highlight the important updates to the NCCN Guidelines for Soft Tissue Sarcoma (STS) specific to the role of radiation therapy in the management of patients with retroperitoneal/intra-abdominal STS. The guidelines have also included recommendations for genetic testing and counseling for patients with a clinical and/or family history of genetic cancer syndromes associated with a predisposition for the development of STS.

  View details for PubMedID 24717567

• The Treatment Outcome for Adult Patients with Ewing's Sarcoma. Current oncology reports Ganjoo, K. N., Patel, S. 2013; 15 (4): 372-377

  Abstract

  Ewing's sarcoma is the second most common bone malignancy in children, but is extremely rare in adults. The outcome of patients with localized disease has improved over the past decades due to better combination chemotherapies, and better methods of local control. Unfortunately, patients with metastatic disease have a very poor outcome with current antineoplastic therapies. In this article, we will review the primary treatment for adult patients with Ewing's sarcoma, both for localized and metastatic disease. The prognostic factors in adult patients with EWS will also be reviewed.

  View details for DOI 10.1007/s11912-013-0317-5

  View details for PubMedID 23605781

• Chest Wall Leiomyosarcoma After Breast-Conservative Therapy for Early-Stage Breast Cancer in a Young Woman With Li-Fraumeni Syndrome JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Henry, E., Villalobos, V., Million, L., Jensen, K. C., West, R., Ganjoo, K., Lebensohn, A., Ford, J. M., Telli, M. L. 2012; 10 (8): 939-942

  Abstract

  Li-Fraumeni syndrome (LFS) is one of the most penetrant forms of familial cancer susceptibility syndromes, characterized by early age at tumor onset and a wide spectrum of malignant tumors. Identifying LFS in patients with cancer is clinically imperative because they have an increased sensitivity to ionizing radiation and are more likely to develop radiation-induced secondary malignancies. This case report describes a young woman whose initial presentation of LFS was early-onset breast cancer and whose treatment of this primary malignancy with breast conservation likely resulted in a secondary malignancy arising in her radiation field. As seen in this case, most breast cancers in patients with LFS exhibit a triple-positive phenotype (estrogen receptor-positive/progesterone receptor-positive/HER2-positive). Although this patient met classic LFS criteria based on age and personal and family history of cancer, the NCCN Clinical Practice Guidelines in Oncology for Genetic/Familial High-Risk Assessment: Breast and Ovarian Cancer endorse genetic screening for TP53 mutations in a subset of patients with early-onset breast cancer, even in the absence of a suggestive family history, because of the potential for de novo TP53 mutations.

  View details for PubMedID 22878818

• Soft Tissue Sarcoma, Version 2.2012 Featured Updates to the NCCN Guidelines JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK von Mehren, M., Benjamin, R. S., Bui, M. M., Casper, E. S., Conrad, E. U., DeLaney, T. F., Ganjoo, K. N., George, S., Gonzalez, R., Heslin, M. J., Kane, J. M., Mayerson, J., McGarry, S. V., Meyer, C., O'Donnell, R. J., Paz, I. B., Pfeifer, J. D., Pollock, R. E., Randall, R. L., Riedel, R. F., Schuetze, S., Schupak, K. D., Schwartz, H. S., Shankar, S., Van Tine, B. A., Wayne, J., Sundar, H., McMillian, N. R. 2012; 10 (8): 951-960

  Abstract

  The major changes to the 2012 and 2011 NCCN Guidelines for Soft Tissue Sarcoma pertain to the management of patients with gastrointestinal stromal tumors (GISTs) and desmoid tumors (aggressive fibromatosis). Postoperative imatinib following complete resection for primary GIST with no preoperative imatinib is now included as a category 1 recommendation for patients with intermediate or high risk of recurrence. The panel also reaffirmed the recommendation for preoperative use of imatinib in patients with GISTs that are resectable with negative margins but associated with significant surgical morbidity. Observation was included as an option for patients with resectable desmoid tumors that are small and asymptomatic, not causing morbidity, pain, or functional limitation. Sorafenib is included as an option for systemic therapy for patients with desmoid tumors.

  View details for Web of Science ID 000307494000006

  View details for PubMedID 22878820

• Cardiac toxicity associated with bevacizumab (Avastin) in combination with CHOP chemotherapy for peripheral T cell lymphoma in ECOG 2404 trial LEUKEMIA & LYMPHOMA Advani, R. H., Hong, F., Horning, S. J., Kahl, B. S., Manola, J., Swinnen, L. J., Habermann, T. M., Ganjoo, K. 2012; 53 (4): 718-720

  View details for DOI 10.3109/10428194.2011.623256

  View details for Web of Science ID 000302067100030

  View details for PubMedID 21916830

• Maintenance Bevacizumab is Associated With Increased Hemoglobin in Patients With Advanced, Nonsquamous, Non-Small Cell Lung Cancer CANCER INVESTIGATION Riess, J. W., Logan, A. C., Krupitskaya, Y., Padda, S., Clement-Duchene, C., Ganjoo, K., Colevas, A. D., San Pedro-Salcedo, M., Kuo, C. J., Wakelee, H. A. 2012; 30 (3): 231-235

  Abstract

  We retrospectively analyzed hematologic parameters in 22 patients with advanced, nonsquamous, NSCLC undergoing VEGF inhibition on a phase II clinical trial of bevacizumab, carboplatin, and gemcitabine. We also examined TTP in relation to hemoglobin changes. Median hemoglobin increased significantly from a 12.9 g/dL pretreatment to 13.8 g/dL (p =.01) after the second cycle of maintenance bevacizumab until the first off cycle measurement. There was no difference in TTP in patients who achieved a rise in hemoglobin compared with patients who did not (median 238 days vs. 268 days, p =.38.) Maintenance bevacizumab is associated with increased hemoglobin in advanced, nonsquamous, NSCLC patients.

  View details for DOI 10.3109/07357907.2012.656862

  View details for PubMedID 22360362

• Results of a Phase 1 Study of AME-133v (LY2469298), an Fc-Engineered Humanized Monoclonal Anti-CD20 Antibody, in Fc gamma RIIIa-Genotyped Patients with Previously Treated Follicular Lymphoma CLINICAL CANCER RESEARCH Forero-Torres, A., de Vos, S., Pohlman, B. L., Pashkevich, M., Cronier, D. M., Dang, N. H., Carpenter, S. P., Allan, B. W., Nelson, J. G., Slapak, C. A., Smith, M. R., Link, B. K., Wooldridge, J. E., Ganjoo, K. N. 2012; 18 (5): 1395-1403

  Abstract

  AME-133v is a humanized monoclonal antibody engineered to have increased affinity to CD20 and mediate antibody-dependent cell-mediated cytotoxicity (ADCC) better than rituximab. Safety, pharmacokinetics, and efficacy were assessed in a phase 1/2 trial in patients with previously treated follicular lymphoma (FL).AME-133v was characterized in vitro by ADCC and cell binding assays. A phase 1 study was conducted in which 23 previously treated patients with FL were assigned sequentially to one of five dose-escalation cohorts of AME-133v at 2, 7.5, 30, 100, or 375 mg/m(2) weekly × 4 doses.AME-133v showed a 13- to 20-fold greater binding affinity for CD20 and was 5- to 7-fold more potent than rituximab in ADCC assays. Cell binding assays showed AME-133v and rituximab competed for an overlapping epitope on the CD20 antigen, and AME-133v inhibited binding of biotinylated rituximab to CD20 in a concentration-dependent manner. AME-133v was well tolerated by patients and common related adverse events included chills and fatigue. One patient experienced a dose-limiting toxicity of neutropenia. AME-133v showed nonlinear pharmocokinetics with properties similar to rituximab. Selective reduction of B cells during and after AME-133v treatment was shown by flow cytometry of peripheral blood. A partial or complete response was observed in 5 of 23 (22%) patients and the median progression-free survival was 25.4 weeks.AME-133v was safe and well tolerated at the doses tested. AME-133v showed encouraging results as an anti-CD20 therapy in heavily pretreated FL patients with the less favorable FcγRIIIa F-carrier genotype.

  View details for DOI 10.1158/1078-0432.CCR-11-0850

  View details for Web of Science ID 000301040700023

  View details for PubMedID 22223529

• The Prognostic Value of Tumor-Associated Macrophages in Leiomyosarcoma A Single Institution Study AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS Ganjoo, K. N., Witten, D., Patel, M., Espinosa, I., La, T., Tibshirani, R., van de Rijn, M., Jacobs, C., West, R. B. 2011; 34 (1): 82-86

  Abstract

  High numbers of tumor-associated macrophages (TAMs) have been associated with poor outcome in several solid tumors. In 2 previous studies, we showed that colony stimulating factor-1 (CSF1) is secreted by leiomyosarcoma (LMS) and that the increase in macrophages and CSF1 associated proteins are markers for poor prognosis in both gynecologic and nongynecologic LMS in a multicentered study. The purpose of this study is to evaluate the outcome of patients with LMS from a single institution according to the number of TAMs evaluated through 3 CSF1 associated proteins.Patients with LMS treated at Stanford University with adequate archived tissue and clinical data were eligible for this retrospective study. Data from chart reviews included tumor site, size, grade, stage, treatment, and disease status at the time of last follow-up. The 3 CSF1 associated proteins (CD163, CD16, and cathepsin L) were evaluated by immunohistochemistry on tissue microarrays. Kaplan-Meier survival curves and univariate Cox proportional hazards models were fit to assess the association of clinical predictors as well as CSF1 associated proteins with overall survival.A total of 52 patients diagnosed from 1983 to 2007 were evaluated. Univariate Cox proportional hazards models were fit to assess the significance of grade, size, stage, and the 3 CSF1 associated proteins in predicting OS. Grade, size, and stage were not significantly associated with survival in the full patient cohort, but grade and stage were significant predictors of survival in the gynecologic (GYN) LMS samples (P = 0.038 and P = 0.0164, respectively). Increased cathepsin L was associated with a worse outcome in GYN LMS (P = 0.049). Similar findings were seen with CD16 (P < 0.0001). In addition, CSF1 response enriched (all 3 stains positive) GYN LMS had a poor overall survival when compared with CSF1 response poor tumors (P = 0.001). These results were not seen in non-GYN LMS.Our data form an independent confirmation of the prognostic significance of TAMs and the CSF1 associated proteins in LMS. More aggressive or targeted therapies could be considered in the subset of LMS patients that highly express these markers.

  View details for DOI 10.1097/COC.0b013e3181d26d5e

  View details for PubMedID 23781555

• A Phase II First-Line Study of Gemcitabine, Carboplatin, and Bevacizumab in Advanced Stage Nonsquamous Non-small Cell Lung Cancer JOURNAL OF THORACIC ONCOLOGY Clement-Duchene, C., Krupitskaya, Y., Ganjoo, K., Lavori, P., McMillan, A., Kumar, A., Zhao, G., Padda, S., Zhou, L., San Pedro-Salcedo, M., Colevas, A. D., Wakelee, H. A. 2010; 5 (11): 1821-1825

  Abstract

  Bevacizumab improves responses and progression-free survival when added to first-line paclitaxel/carboplatin or cisplatin/gemcitabine for patients with advanced nonsquamous non-small cell lung cancer. This study was designed to evaluate toxicities and efficacy of gemcitabine/carboplatin/bevacizumab.Patients with untreated advanced nonsquamous non-small cell lung cancer, with no evidence of brain metastases and not on anticoagulation were eligible. Patients received gemcitabine 1000 mg/m on days 1 and 8; carboplatin area under the curve 5 day 1; and bevacizumab 15 mg/kg day 1 every 3 weeks for up to six cycles. Bevacizumab was then continued every 3 weeks until disease progression or unacceptable toxicity.From July 2006 to December 2008, 48 patients were enrolled: 23 (48%) men, 25 (52%) women, and 19 (40%) never smokers. One patient never received therapy and is not included in the analysis. Median cycle number was 8 (1-42) with 37 patients (78.7%) completing ≥4 cycles of three drugs. Dose reductions occurred in 34 (72.3%) patients. Grade 3/4 toxicities included neutropenia (47%/15%), thrombocytopenia (11%/15%), anemia (6%/0%), dyspnea (6%/2%), bacterial pneumonia (4%/0%), and hypertension (4%/2%). No neutropenic fevers occurred. One patient died of hemoptysis. Grade 3 bleeding occurred in three other patients. There were seven (14.9%) partial responses. Median time to first event (progression/death/toxicity requiring discontinuation) was 6.4 months (95% confidence interval: 4.8-7.9 months). The median overall survival (OS) was 12.8 months (95% confidence interval: 10.0-16.5). The OS is 57% at 1 year and 10% at 2 years.Although perhaps skewed by a high proportion of nonsmokers and women, treatment with gemcitabine/carboplatin/bevacizumab has an acceptable toxicity profile with promising median OS despite a low response rate.

  View details for DOI 10.1097/JTO.0b013e3181f1d23c

  View details for PubMedID 20881641

• TH-302, a tumor selective hypoxia activated prodrug, complements and enhances chemotherapy treatment with gemcitabine, docetaxel, pemetrexed, and doxorubicin 22nd European Organization for Research and Treatment of Cancer (EORTC)-National-Cancer-Institute(NCI)-American-Association-for-Cancer-Research(AACR) Symposium on Molecular Targets and Cancer Therapeutics Hart, C. P., Borad, M., Chawla, S. P., Infante, J. R., Ganjoo, K. N., Langmuir, V. K., KROLL, S., Curd, J. G. PERGAMON-ELSEVIER SCIENCE LTD. 2010: 124–24

  View details for Web of Science ID 000288460100384

• I-131-Tositumomab (BexxarA (R)) vs. Y-90-Ibritumomab (ZevalinA (R)) Therapy of Low-Grade Refractory/Relapsed Non-Hodgkin Lymphoma MOLECULAR IMAGING AND BIOLOGY Iagaru, A., Mittra, E. S., Ganjoo, K., Knox, S. J., Goris, M. L. 2010; 12 (2): 198-203

  Abstract

  The American Cancer Society estimated 66,120 new cases of non-Hodgkin lymphoma (NHL) in the USA in 2008. Radioimmunotherapy has been shown in clinical trials to be an effective treatment for refractory/relapsed NHL. The available agents are Bexxar, a (131)I radiolabeled murine monoclonal antibody, and Zevalin, a (90)Y radiolabeled murine antibody. Both target CD20 receptors present on the surface of lymphocytes. We present our clinical experience with Bexxar and Zevalin in the management of low-grade refractory or relapsed NHL.This is a retrospective study (Jan 2000-Jul 2006) of 67 patients with NHL, who were treated with Bexxar (31 patients, group A) or Zevalin (36 patients, group B) for refractory/relapsed disease. Group A included 16 men and 15 women, 35-81 years old (average, 59.3 +/- 13.4). Group B included 27 men and nine women, 36-85 years old (average, 55.4 +/- 13.8). Therapeutic doses ranged 40-138 mCi (average, 78.1 +/- 28.2) for Bexxar and 17-34 mCi (average, 28.8 +/- 4.37) for Zevalin.Objective responses were induced in 22 of the 31 patients (70.9%) in group A and 28 of the 36 patients (77.8%) in group B. Complete response was noted in 11 patients (35.5%), partial response in seven patients (22.6%), and mixed response in four patients (12.9%) in group A. There were five patients (16.1%) with stable disease and four patients (12.9%) with disease progression in the same group. Complete response was noted in 15 patients (41.7%), partial response in nine patients (25%), and mixed response in four patients (11.1%) in group B. There were four patients (11.1%) with stable disease and another four patients (11.1%) with disease progression in the same group. The average decreases at posttherapy nadir were 36.9% +/- 0.33 (group A) and 52.6% +/- 0.32 (group B) for platelets, 27.8% +/- 0.27 (group A) and 34.2% +/- 0.38 (group B) for leukocytes, and 4.9% +/- 0.15 (group A) and 7.6% +/- 0.11 (group B) for hemoglobin. Grades 3 and 4 hematological toxicity occurred in 14 patients (45.2%) treated with Bexxar and 22 patients (61.1%) treated with Zevalin, but was reversible.Our study suggests that clinical practice of Bexxar and Zevalin radioimmunotherapy is an effective and safe adjunctive treatment for patients with NHL refractory/relapsed to conventional treatment. However, due to the small number of subjects, it was not possible to determine whether differences in the outcomes or toxicities from the two agents were statistically significant.

  View details for DOI 10.1007/s11307-009-0245-9

  View details for Web of Science ID 000275974900010

  View details for PubMedID 19543946

• Bendamustine Is Effective Therapy in Patients With Rituximab-Refractory, Indolent B-cell Non-Hodgkin Lymphoma Results From a Multicenter Study CANCER Kahl, B. S., Bartlett, N. L., Leonard, J. P., Chen, L., Ganjoo, K., Williams, M. E., Czuczman, M. S., Robinson, K. S., Joyce, R., Van der Jagt, R. H., Cheson, B. D. 2010; 116 (1): 106-114

  Abstract

  Bendamustine hydrochloride is a novel alkylating agent. In this multicenter study, the authors evaluated the efficacy and toxicity of single-agent bendamustine in patients with rituximab-refractory, indolent B-cell lymphoma.Eligible patients (N = 100, ages 31-84 years) received bendamustine at a dose of 120 mg/m(2) by intravenous infusion on Days 1 and 2 every 21 days for 6 to 8 cycles. Histologies included follicular (62%), small lymphocytic (21%), and marginal zone (16%) lymphomas. Patients had received a median of 2 previous regimens (range, 0-6 previous regimens), and 36%were refractory to their most recent chemotherapy regimen. Primary endpoints included overall response rate (ORR) and duration of response (DOR). Secondary endpoints were safety and progression-free survival (PFS).An ORR of 75% (a 14% complete response rate, a 3% unconfirmed complete response rate, and a 58% partial response rate) was observed. The median DOR was 9.2 months, and median PFS was 9.3 months. Six deaths were considered to be possibly treatment related. Grade 3 or 4 (determined using National Cancer Institute Common Toxicity Criteria [version 3.0.19]. reversible hematologic toxicities included neutropenia (61%), thrombocytopenia (25%), and anemia (10%). The most frequent nonhematologic adverse events (any grade) included nausea (77%), infection (69%), fatigue (64%), diarrhea (42%), vomiting (40%), pyrexia (36%), constipation (31%), and anorexia (24%).Single-agent bendamustine produced a high rate of objective responses with acceptable toxicity in patients with recurrent, rituximab-refractory indolent B-cell lymphoma.

  View details for DOI 10.1002/cncr.24714

  View details for Web of Science ID 000273864600015

  View details for PubMedID 19890959

• Breast Angiosarcoma: Case Series and Expression of Vascular Endothelial Growth Factor. Case reports in oncology Brar, R., West, R., Witten, D., Raman, B., Jacobs, C., Ganjoo, K. 2009; 2 (3): 242-250

  Abstract

  PURPOSE: Angiosarcoma of the breast is a rare, malignant tumor for which little is known regarding prognostic indicators and optimal therapeutic regimens. To address this issue, we performed a retrospective analysis of breast angiosarcoma cases seen at Stanford University along with immunohistochemical analysis for markers of angiogenesis. METHODS: Breast angiosarcoma cases seen between 1980 and 2008 were examined. Viable tissue blocks were analyzed for expression of vascular endothelial growth factor and its receptors. RESULTS: A total of 16 cases were identified. Data was collected regarding epidemiology, treatment, response rates, disease-free survival, and the use of various imaging modalities. Five tissue blocks remained viable for immunohistochemical analysis. Vascular endothelial growth factor-A was positively expressed in 3 of these samples. CONCLUSION: Angiosarcoma of the breast is an aggressive malignancy with a propensity for both local recurrence and distant metastases. Angiogenesis inhibition may represent a novel therapeutic modality in this rare, vascular malignancy.

  View details for PubMedID 20737044

• Cardiac Toxicity Associated with the Anti-VEGF Monoclonal Antibody Bevacizumab (Avastin) in Combination with CROP (A-CHOP) Chemotherapy for Peripheral T Cell Lymphoma (PTCL): The ECOG 2404 Trial. Advani, R. H., Hong, F., Ganjoo, K. N., Manola, J. B., Swinnen, L. J., Habermann, T. M., Horning, S. J. AMER SOC HEMATOLOGY. 2009: 667

  View details for Web of Science ID 000272725802039

• A phase II first line study of gemcitabine, carboplatin and bevacizumab in advanced stage non-squamous non-small cell lung cancer Clement-Duchene, C., Krupitskaya, Y., Ganjoo, K., Lavori, P., Kumar, A., Zhao, G., Padda, S., San Pedro-Salcedo, M., Wakelee, H. LIPPINCOTT WILLIAMS & WILKINS. 2009: S674–S674

  View details for Web of Science ID 000269496002133

• Mid-treatment PET predicts progression in hypofractionated accelerated radiation therapy for lung tumors Chang, C. N., Fillion, E., Chapman, C., Rao, A., Wakelee, H., Ganjoo, K., Le, Q., Maxim, P., Quon, A., Graves, E. E., Loo, B. W. LIPPINCOTT WILLIAMS & WILKINS. 2009: S939–S939

  View details for Web of Science ID 000269496002721

• Coordinate Expression of Colony-Stimulating Factor-1 and Colony-Stimulating Factor-1-Related Proteins Is Associated with Poor Prognosis in Gynecological and Nongynecological Leiomyosarcoma AMERICAN JOURNAL OF PATHOLOGY Espinosa, I., Beck, A. H., Lee, C., Zhu, S., Montgomery, K. D., Marinelli, R. J., Ganjoo, K. N., Nielsen, T. O., Gilks, C. B., West, R. B., van de Rijn, M. 2009; 174 (6): 2347-2356

  Abstract

  Previously, we showed that the presence of high numbers of macrophages correlates with poor prognosis in nongynecological leiomyosarcoma (LMS). In gynecological LMS, a similar trend was noted but did not reach statistical significance. Colony-stimulating factor-1 (CSF1) is a major chemoattractant for macrophages. Here we show that in a subset of LMS cases, CSF1 is expressed by the malignant cells. Previously, we found that CSF1 is translocated and highly expressed in tenosynovial giant cell tumors (TGCTs), and this observation allowed us to identify genes that showed a coordinate expression with CSF1. Here, we evaluated the expression of CSF1 and TGCT-associated proteins in 149 cases of LMS. The coordinate expression of CSF1 and three TGCT-associated proteins (CD163, FCGR3a, and CTSL1) identified cases with poor prognosis in both gynecological LMS (P = 0.00006) and nongynecological LMS (P = 0.03). In gynecological LMS, the coordinate expression of these four markers was the only independent prognosticator in multivariate analysis (hazard ratio, 4.2; 95% CI, 1.12 to 16; P = 0.03). Our findings indicate that CSF1 may play an important role in the clinical behavior of LMS that may open a window for new therapeutic reagents.

  View details for DOI 10.2353/ajpath.2009.081037

  View details for PubMedID 19443701

• Opportunistic enteroviral meningoencephalitis: an unusual treatable complication of rituximab therapy LEUKEMIA & LYMPHOMA Ganjoo, K. N., Raman, R., Sobel, R. A., Pinto, H. A. 2009; 50 (4): 673-675

  View details for DOI 10.1080/10428190902782210

  View details for Web of Science ID 000265361500031

  View details for PubMedID 19373672

• Breast Angiosarcoma: Case Series and Expression of Vascular Endothelial Growth Factor CASE REPORTS IN ONCOLOGY Brar, R., West, R., Witten, D., Raman, B., Jacobs, C., Ganjoo, K. 2009; 2 (3): 242–50

  View details for DOI 10.1159/000264637

  View details for Web of Science ID 000216899300014

• Breast angiosarcomas: Case series and expression of vascular endothelial growth factor Case Reports in Oncology Rondeep Brar, Robert West, Daniela Witten, Bhargav Raman, Charlotte Jacobs, Kristen Ganjoo 2009; 2: 242-50
• Preliminary results of a Phase I study of AME-133v, an Fc-engineered humanized monoclonal antibody, in low-affinity Fc gamma RIIIa patients with previously-treated follicular lymphoma Forero, A., de Vos, S., Pohlman, B., Enas, N., Ganjoo, K. N., Cronier, D., Dang, N. H., Carpenter, S. P., Smith, M. R., Link, B. K., Wooldridge, J. E. AMER ASSOC CANCER RESEARCH. 2008

  View details for DOI 10.1158/1538-7445.AM2008-LB-70

  View details for Web of Science ID 000454834700006

• Results of a Phase 3 trial evaluating safety and efficacy of specific immunotherapy, recombinant idiotype (Id) conjugated to KLH (Id-KLH) with GM-CSF, compared to non-specific immunotherapy, KLH with GM-CSF, in patients with follicular non-Hodgkin's lymph Levy, R., Robertson, M. J., Ganjoo, K., Leonard, J., Vose, J., Denney, D. AMER ASSOC CANCER RESEARCH. 2008

  View details for DOI 10.1158/1538-7445.AM2008-LB-204

  View details for Web of Science ID 000454834700022

• The importance of angiogenesis markers in the outcome of patients with diffuse large B cell lymphoma: a retrospective study of 97 patients JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY Ganjoo, K. N., Moore, A. M., Orazi, A., Sen, J. A., Johnson, C. S., An, C. S. 2008; 134 (3): 381-387

  Abstract

  The role of angiogenesis has been extensively evaluated in solid tumors and more recently in hematologic malignancies. Several surrogate markers of angiogenesis including tumor VEGF, VEGF receptors, and microvessel density have correlated with outcome in some lymphoma studies. This is a single institution retrospective study evaluating the role of angiogenesis markers in the clinical outcome of patients with diffuse large B cell lymphoma (DLBCL).A total of 97 patients with DLBCL diagnosed and managed at Indiana University between 1993 and 2001 were included. Archived tumor samples were stained for VEGF-A, VEGF-C, VEGF-R1, and CD31 and graded as negative or positive (1+, 2+, 3+). The relationship between the expression of these markers and the international prognostic variables as well as the progression free survival (PFS) and the overall survival (OS) was evaluated.VEGF-A, VEGF-C, VEGF-R1 were expressed in 77, 98, and 18% of tumors, respectively. VEGF-A negative patients had an improved OS compared to VEGF-A (1+) (P = 0.0502). VEGF-C correlated with both LDH (r = 0.28, P = 0.0502) and IPI score (r = 0.25, P = 0.013). VEGF-R1 negative patients had a superior survival compared to those with VEGF-R1 (2+) (P = 0.0154).The presence of tumor associated angiogenesis may alter the outcome of patients with DLBCL and could be a prognostic factor. Further clinical studies are needed to correlate the degree of angiogenesis with response to anti-angiogenesis agents.

  View details for DOI 10.1007/s00432-007-0294-x

  View details for Web of Science ID 000252627000012

  View details for PubMedID 17694324

• Review of erlotinib in the treatement of advanced non-small cell lung cancer Biologics; Targets & Therapy Kristen N Ganjoo, Heather Wakelee 2008
• Review of erlotinib in the treatment of advanced non-small cell lung cancer. Biologics : targets & therapy Ganjoo, K. N., Wakelee, H. 2007; 1 (4): 335-346

  Abstract

  Epidermal growth factor receptor (EGFR) is a transmembrane receptor with a cytoplasmic tyrosine kinase (TK) domain present on many solid tumors including non-small cell lung cancer (NSCLC). Once stimulated by ligand, the downstream pathway is activated leading to cell growth, survival, and carcinogenesis. There are several methods of EGFR inhibition including monoclonal antibodies directed against the external region and small molecule inhibitors of TK domain. Erlotinib and gefitinib are orally available small molecule EGFR TK inhibitors, with proven efficacy in NSCLC. The most common side effects are skin toxicity and diarrhea. Erlotinib has been shown to improve survival compared to placebo in second or third-line therapy for NSCLC. However, erlotinib in combination with chemotherapy failed to show a survival advantage in two first-line studies which could be due to the timing of chemotherapy administration. In general, patients with adenocarcinoma histology, female gender, Asian ethnicity, and never smokers have a better response when treated with erlotinib. This could be related to the presence of EGFR mutations, lack of KRAS mutations, or overexpression of EGFR as measured by fluorescent in-situ hybridization (FISH) analysis. Future studies should concentrate on further development of predictors of clinical benefit with erlotinib, overcoming resistance to erlotinib that develops in initial responders, as well as more effective sequencing of erlotinib with chemotherapy and combinations of the drug with other "targeted" therapeutic agents.

  View details for PubMedID 19707304

  View details for PubMedCentralID PMC2721286

• Comparison of I-131-Tositumomab (Bexxar (R)) and Y-90-Ibritumomab (Zevalin (R)) therapy of refractory/relapsed non-Hodgkin lymphoma Iagaru, A., Zhu, H., Mari, C., Knox, S. J., Ganjoo, K., Goris, M. L. SPRINGER. 2007: S168

  View details for Web of Science ID 000253283900232

• Non-Hodgkin lymphoma of the breast CANCER Ganjoo, K., Advani, R., Mariappan, M. R., McMillan, A., Horning, S. 2007; 110 (1): 25-30

  Abstract

  Primary lymphoma of the breast has been reported to have a high local and central nervous system recurrence (CNS) rate, suggesting the need for consolidation radiotherapy and CNS prophylaxis. A retrospective study was done to evaluate the institutional experience in this patient population.In all, 37 patients with lymphoma involving the breast at initial diagnosis and managed at Stanford University from 1981-2005 were included. Diagnostic tissue biopsies were obtained either from the breast mass or an involved lymph node. Treatment and response data, patterns of recurrence, and outcomes were reviewed.Diffuse large B cell lymphoma (DLBCL) was the most common histologic subtype seen in 18 of 37 (49%) patients. Follicular and marginal zone subtypes were seen in 38%. Most patients presented with an incidental breast mass in stage I(E) or II(E). Four (11%) patients presented with bilateral breast involvement, with only 1 patient presenting with CNS disease. DLBCL patients received doxorubicin-based chemotherapy, with 70% receiving involved field radiotherapy and a single patient receiving intrathecal therapy. No recurrences occurred in the involved breast and a single parenchymal CNS recurrence was recorded. Among the DLBCL patients, the 5-year progression-free survival (PFS) was 61%, with a median follow-up of 3.8 years (range, 5 months to 19 years) and the 5-year overall survival (OS) was estimated at 82%. Patients with indolent lymphoma had an estimated 5-year PFS of 76% and an OS of 92%.DLBCL of the breast was successfully treated with doxorubicin-based chemotherapy alone or with involved field radiotherapy in an estimated 61% of patients at 5 years. A single CNS recurrence was observed in our series of patients, most of whom presented with limited disease.

  View details for DOI 10.1002/cncr.22753

  View details for PubMedID 17541937

• Antiangiogenesis: A new approach to the treatment of lymphoma LEUKEMIA & LYMPHOMA Ganjoo, K. 2007; 48 (3): 454-455

  View details for DOI 10.1080/10428190701200059

  View details for Web of Science ID 000245108100006

  View details for PubMedID 17454583

• Rituximab, Bevacizumab and CHOP (RA-CHOP) in untreated diffuse large B-cell lymphoma: Safety, biomarker and pharmacokinetic analysis LEUKEMIA & LYMPHOMA Ganjoo, K. N., An, C. S., Robertson, M. J., Gordon, L. I., Sen, J. A., Weisenbach, J., Li, S., Weller, E. A., Orazi, A., Horning, S. J. 2006; 47 (6): 998-1005

  Abstract

  Bevacizumab is a humanized monoclonal antibody directed against vascular endothelial growth factor (VEGF-A). Non-Hodgkin's lymphoma patients with high serum VEGF levels have an inferior survival compared to patients with low VEGF levels. Bevacizumab was administered through a central line at 15 mg kg(-1) IV on day 1 followed by rituximab (R) and CHOP on day 2 for cycle 1 and day 1 for cycles 2 - 8. Serum levels of bevacizumab and R were measured at specified time points to assess pharmacokinetics (PK). Plasma and urine samples were also analysed for VEGF. Tumor samples were stained for VEGF, CD31 and factor VIII by immunohistochemistry. Thirteen patients with newly-diagnosed DLBCL received a total of 88 cycles (range 2 - 8, median 7). Best response included five CR, six PR, one SD and one PD with an overall response rate of 85% and complete response rate of 38%. The 12-month PFS is 77% and a median follow-up of 16.9 months for the surviving patients. All tumor samples stained strongly positive for VEGF and there was a marginal association between baseline plasma VEGF and response (p = 0.04). Patients with higher plasma VEGF levels were generally younger and had bulky disease. Micro-vessel density did not correlate with presenting disease characteristics, VEGF expression or response. The PK of bevacizumab and rituximab were not influenced by combined treatment. In this patient population, treatment with RA-CHOP did not result in any episodes of grade 3 or 4 proteinuria, heart failure or hemorrhage. The RA-CHOP combination was generally well tolerated and safe.

  View details for DOI 10.1080/10428190600563821

  View details for Web of Science ID 000239037000007

  View details for PubMedID 16840188

• Phase II clinical studies of denileukin diftitox diphtheria toxin fusion protein in patients with previously treated chronic lymphocytic leukemia CANCER Frankel, A. E., Surendranathan, A., Black, J. H., White, A., Ganjoo, K., Cripe, L. D. 2006; 106 (10): 2158-2164

  Abstract

  The safety and efficacy of the interleukin-2 diphtheria toxin fusion protein (DAB(389)IL2; denileukin diftitox) directed against the IL-2 receptor (IL-2R) was tested in patients with recurrent or refractory chronic lymphocytic leukemia (CLL).Denileukin diftitox was administered as 60-minute intravenous infusions for 5 days every 21 days at a dose of 18 mug/kg per day for up to 8 cycles. In total, 28 patients were treated in 2 multiinstitutional studies with similar eligibility criteria and treatment protocols. Twenty-two patients receive > or = 2 cycles of denileukin diftitox and were evaluable for response.Twelve of 22 patients achieved reductions of peripheral CLL cells, with 5 of 12 patients achieving >80% reductions. Six of 22 patients achieved reductions in the size of lymph node on examination and computed tomography scans, and all 6 of those patients met the criteria for a partial or complete response that lasted > or = 2 months. Bone marrow biopsies before and after treatment confirmed a complete remission that lasted for 1 year in 1 patient. Overall, denileukin diftitox produced complete remission in 1 of 22 patients (4%) and partial remission in 5 of 22 patients (23%) for a total remission rate of 27%. Progression-free intervals in the responders were 2 months in 2 patients and 4 months, 6 months, 7 months, and 12 months in 1 patient each. Toxicities were moderate. No infections associated with immunosuppression were seen. There was no significant correlation of response or toxicities with the numbers of denileukin diftitox cycles received or with CD25 levels.Follow-up studies will be required to identify predictors of response that may improve the response rate to denileukin diftitox in patients with CLL.

  View details for DOI 10.1002/cncr.21851

  View details for Web of Science ID 000237278300010

  View details for PubMedID 16586495

• A phase II study of single agent gemcitabine in relapsed or refractory follicular or small lymphocytic non-Hodgkin lymphomas - A hoosier oncology group study AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS Ganjoo, K. N., Robertson, M. J., Fisher, W., Jung, S. H., McClean, J., Huh, S. Y., Bufill, J., Williams, S., Cripe, L. D. 2005; 28 (2): 169-172

  Abstract

  Gemcitabine is a pyrimidine analog that is active in patients with aggressive lymphomas and Hodgkin disease. This study assessed tumor response in patients with previously treated follicular or small lymphocytic non-Hodgkin lymphoma. This was a 2-stage phase II trial with the first stage requiring 2 of 13 responses to proceed to the second stage. Gemcitabine was given as a single agent to patients with previously treated follicular or small lymphocytic lymphomas. Gemcitabine was administered at 1250 mg/m2 over 30 minutes on days 1 and 8 of a 21-day cycle for a maximum of 6 cycles. Thirteen patients were treated with 1 to 6 cycles of chemotherapy. Two patients experienced grade 4 toxicity with neutropenia. No grade 4 nonhematologic toxicity was seen. There was 1 partial response and 8 patients (61%) had either minimal response or stable disease. Single-agent gemcitabine administered at this dose and schedule produced 1 partial remission and half the patients had stable disease. However, the study had to be stopped early because of lack of meaningful response.

  View details for DOI 10.1097/01.coc.0000144812.74663.d0

  View details for Web of Science ID 000228240600013

  View details for PubMedID 15803012

• Unusual locations of involvement by malignancies - Case 1. Testicular plasmacytoma JOURNAL OF CLINICAL ONCOLOGY Shafqat, A., Yum, M. N., Abanour, R., Ganjoo, K. N. 2003; 21 (17): 3368-3369

  View details for DOI 10.1200/JCO.2003.09.049

  View details for Web of Science ID 000185091300029

  View details for PubMedID 12947074

• Phase II study of gemcitabine plus docetaxel in advanced pancreatic cancer: A Hoosier Oncology Group study ONCOLOGY Schneider, B. P., Ganjoo, K. N., Seitz, D. E., Picus, J., Fata, F., Stoner, C., Calley, C., Loehrer, P. J. 2003; 65 (3): 218-223

  Abstract

  To determine the response rate, duration of response and survival with weekly gemcitabine plus docetaxel in metastatic or unresectable pancreatic cancer.Forty patients were enrolled, and 38 patients were evaluable for survival and toxicity. Thirty-seven patients were evaluable for response. Nine patients (24%) had locally advanced disease and 29 (76%) had metastatic disease at the time of enrollment. Median Eastern Cooperative Oncology Group performance status was 1. Patients received gemcitabine 750 mg/m(2) i.v. and docetaxel 35 mg/m(2) i.v. weekly for 3 out of 4 weeks for a maximum of 6 cycles.Patients received a median of 4 cycles (range 1-6) of chemotherapy. An objective response was obtained in 10 patients (27%) with a median duration of 17 weeks. Median survival was 7 months, and 1-year survival was 19.3%. Eight patients experienced at least one form of grade 4 toxicity and 27 patients experienced at least one type of grade 3 toxicity.The combination of gemcitabine and docetaxel is a well-tolerated regimen with clinical efficacy. The ultimate role of this combination versus single-agent gemcitabine can only be determined by a randomized phase III trial.

  View details for DOI 10.1159/000074474

  View details for Web of Science ID 000186975500005

  View details for PubMedID 14657595

• A phase I study of weekly gemcitabine and docetaxel in patients with advanced cancer: A Hoosier Oncology Group study ONCOLOGY Ganjoo, K. N., GORDON, M. S., Sandler, A. B., Warner, R. E., Fife, K., Poirier, S., Seshadri, R., Loehrer, P. J. 2002; 62 (4): 299-304

  Abstract

  To determine the maximum tolerated dose (MTD) of weekly gemcitabine plus docetaxel, a dose escalation trial of both drugs was developed with each administered weekly for 3 weeks out of 4.Dose levels for gemcitabine (mg/m(2)) and docetaxel (mg/m(2)) were as follows: level 1: 600/25; level 2: 600/35; level 3: 750/35; and level 4: 900/35. Sixteen patients with adequate renal, hepatic, and hematologic function and an Eastern Cooperative Oncology Group performance status of 0-2 were treated. Primary sites included pancreas (12) and others (4).Three patients were treated at each dose level from level 1 through level 4. The dose-limiting toxicity (DLT) was neutropenia, the maximum tolerated dose being 750 mg/m(2) of gemcitabine and 35 mg/m(2) of docetaxel. No grade 4 nonhematologic toxicity was seen. Three patients had grade 4 neutropenia. Of the 12 patients with pancreatic cancer, 1 had a partial remission and 7 had stable disease with a median duration of 8 weeks.Gemcitabine and docetaxel can be safely administered weekly at a dose of 750 and 35 mg/m(2), respectively. The DLT was neutropenia. Disease stabilization suggests that this may be an active regimen in patients with metastatic pancreatic cancer.

  View details for Web of Science ID 000176987000003

  View details for PubMedID 12138236

• Germ cell tumor associated primitive neuroectodermal tumors JOURNAL OF UROLOGY Ganjoo, K. N., Foster, R. S., Michael, H., Donohue, J. P., Einhorn, L. H. 2001; 165 (5): 1514-1516

  Abstract

  This retrospective review was done to assess the prognosis and response in patients presenting with primitive neuroectodermal tumor admixed with germ cell tumor.Of the 40 patients treated at our institution from 1984 to 1999, 15 had initial stage I and 25 had initial metastatic disease. Median followup after the diagnosis was 25 months (range 4 to 142).Of the 40 patients 15 presented with clinical stage I disease, including 9 treated with retroperitoneal lymph node dissection and 6 who elected surveillance. Seven of the 9 patients had normal lymph nodes and all continuously had no evidence of disease. Two of the 9 patients had lymph nodes involved with teratoma with or without primitive neuroectodermal tumor. Retroperitoneal relapse in 5 of the 6 patients on surveillance was treated with cisplatin based chemotherapy followed by post-chemotherapy retroperitoneal lymph node dissection. Residual primitive neuroectodermal tumor was noted in 4 of the 5 patients and only 3 of 6 are currently without disease at a median followup of 17 months (range 15 to 69). A total of 25 patients presented with metastatic disease, of whom 23 underwent cisplatin based chemotherapy. Only 3 patients achieved complete remission with chemotherapy alone and 2 of the 3 subsequently relapsed. Of the remaining 20 patients 16 underwent post-chemotherapy retroperitoneal lymph node dissection, including 11 with primitive neuroectodermal tumor in the resected specimen. Two of these 11 patients have continuously had no evidence of disease, while an additional 3 currently have no evidence of disease after further therapy. Teratoma was present in the resected specimen in 5 of 16 patients, of whom 2 have continuously had no evidence of disease, while an additional 2 currently have no evidence of disease after further surgical resection. Therefore, 11 of 25 patients who presented with metastatic disease currently have no evidence of disease at a median followup of 19 months (range 2 to 111).Primitive neuroectodermal tumor in the orchiectomy specimen has adverse prognostic significance. This condition in the retroperitoneum is potentially curable by retroperitoneal lymph node dissection but rarely eradicated by chemotherapy. Therefore, we recommend retroperitoneal lymph node dissection for all clinical stage I cases with primitive neuroectodermal tumor in the orchiectomy specimen. Patients who present with metastatic primitive neuroectodermal tumor should be treated aggressively with surgical resection as an integral part of the therapeutic strategy.

  View details for Web of Science ID 000168321500030

  View details for PubMedID 11342908

• Results of modern therapy for patients with mediastinal nonseminomatous germ cell tumors 35th Annual Meeting of the American-Society-of-Clinical-Oncology Ganjoo, K. N., Rieger, K. M., Kesler, K. A., Sharma, M., Heilman, D. K., Einhorn, L. H. JOHN WILEY & SONS INC. 2000: 1051–56

  Abstract

  The aim of this study was to determine the effects of independent prognostic variables, such as prechemotherapy tumor markers, the extent of disease at diagnosis, the tumor markers postchemotherapy (PC), and the pathology of the PC residual mass on the overall survival of patients with primary mediastinal nonseminomatous germ cell tumors (PMNSGCT).The authors undertook a retrospective review of 39 patients with PMNSGCT between 1983 and 1997 who received their initial chemotherapy at Indiana University and 36 additional patients referred for PC resection. All patients received chemotherapy based on the combination of cisplatin and etoposide. The median follow-up was 22 months (range, 12-144 months).The prechemotherapy tumor markers did not affect overall survival. Extent of disease (mediastinal only vs. visceral metastases) was an important prognostic factor for survival in univariate analysis (P = 0.042). Sixty-two of 75 patients underwent PC resection of residual disease. Fifteen of the 62 patients achieved a CR with chemotherapy alone, as the PC resection revealed only necrosis. Fourteen of these 15 patients continuously had no evidence of disease (NED). Forty-seven of the 62 patients had NED with chemotherapy and PC resection, including 31 with teratoma and 16 with carcinoma. However, 11 of 31 with teratoma and 11 of 16 with carcinoma subsequently relapsed. Although 18 patients had elevated tumor markers at the time of PC resection, 6 of 18 had only necrosis and 4 had teratoma. The PC tumor markers did not affect survival. The pathology of the resected specimen was the most significant predictor of survival in multivariate analysis (P < 0.001).Twenty-eight of 39 patients (71.8%) with PMNSGCT treated at Indiana University achieved NED status, but only 16 (41%) continuously had NED. Twenty of 36 (55.5%) referred for resection continuously had NED. Disease confined to the mediastinum and necrosis in the PC specimen were important prognostic factors for survival.

  View details for Web of Science ID 000085745800015

  View details for PubMedID 10699894

• Positron emission tomography scans in the evaluation of postchemotherapy residual masses in patients with seminoma 35th Annual Meeting of the American-Society-of-Clinical-Oncology Ganjoo, K. N., Chan, R. J., Sharma, M., Einhorn, L. H. AMER SOC CLINICAL ONCOLOGY. 1999: 3457–60

  Abstract

  To assess the ability of positron emission tomography (PET) scans in differentiating between necrosis and viable seminoma in postchemotherapy (PC) residual disease.We conducted a prospective study of 29 patients with seminoma at Indiana University. All patients had PC residual disease. Computed tomography and PET scans were performed for 19 patients after primary chemotherapy (group A) and for 10 patients after salvage chemotherapy (group B).In group A, the PC masses were >/= 3 cm in 14 patients, less than 3 cm in three patients, and not quantified in two patients. All of the patients in group A had negative PET scan results and have had stable or decreasing residual mass size (median follow-up duration, 11.5 months; range, 6 to 26 months). In group B, the PC masses were >/= 3 cm in four patients, less than 3 cm in five patients, and not quantified in one patient. One patient had a positive PET scan result for a posterior mediastinal mass. Pathologic diagnosis of the PET-positive mass showed only necrotic tissue. The same patient had a negative PET scan of the retroperitoneal mass but relapsed in that area. Overall, of patients in group B, five have stable or decreasing mass (median follow-up duration, 8 months; range, 7 to 22 months), and five had relapsed disease.PET scans have no apparent benefit in PC evaluation of residual masses in bulky seminoma.

  View details for Web of Science ID 000083473700014

  View details for PubMedID 10550142

• Primary mediastinal nonseminomatous germ cell tumors: The influence of postchemotherapy pathology on long-term survival after surgery 79th Annual Meeting of the American-Association-for-Thoracic-Surgery Kesler, K. A., Rieger, K. M., Ganjoo, K. N., Sharma, M., Fineberg, N. S., Einhorn, L. H., Brown, J. W. MOSBY-ELSEVIER. 1999: 692–700

  Abstract

  The treatment of nonseminomatous germ cell tumors with cisplatin-based chemotherapy followed by aggressive surgical resection of residual disease is one of the most successful models for multimodality cancer therapy. We reviewed the case histories of 91 patients treated at our institution from 1981 to 1998 with primary mediastinal nonseminomatous germ cell tumors to evaluate variables that may influence survival after surgery.Twelve of the 91 patients did not undergo postchemotherapy resection because of progressive disease. Seventy-nine of them underwent 82 thoracic surgical procedures and are the basis of this review. The majority (71/75) had elevated serum tumor markers, 75% (n = 50) of which returned to normal levels after first- or second-line chemotherapy.There were 3 operative deaths and 1 late death, attributed to pulmonary complications. Twenty-four patients died of recurrent disease and 3 of leukemia, for an overall survival of 61% after an average follow-up of 48 months. The pathologic findings of complete tumor necrosis (n = 19) and benign teratoma (n = 28) in the surgical specimen predicted excellent and good long-term survival, respectively, which was statistically better than that of patients having persistent nonseminomatous germ cell tumors (n = 24) or carcinomatous/sarcomatous degeneration (n = 8).Primary nonseminomatous germ cell tumors of the mediastinum can be cured with a multimodality therapy, particularly in the subset of patients with postchemotherapy pathologic findings of tumor necrosis and teratoma. Survival is poor but possible in patients with unfavorable pathologic findings after chemotherapy, currently justifying an aggressive surgical approach in patients with otherwise operable disease.

  View details for Web of Science ID 000083129400021

  View details for PubMedID 10504636

• Lung cancer presenting with solitary bone metastases - Case 1: Metastatic adenocarcinoma to the patella JOURNAL OF CLINICAL ONCOLOGY Ganjoo, K. N., Loyal, J. A., Cramer, H. M., Loehrer, P. J. 1999; 17 (9): 2995-2997

  View details for Web of Science ID 000082381000044

  View details for PubMedID 10561377

• Endometriosis Malignant Transformation Review: Rhabdomyosarcoma Arising From an Endometrioma. JSLS : Journal of the Society of Laparoendoscopic Surgeons Nezhat, C. n., Vu, M. n., Vang, N. n., Ganjoo, K. n., Karam, A. n., Folkins, A. n., Nezhat, A. n., Nezhat, F. n. ; 23 (4)

  Abstract

  Endometriosis is a widely known benign disease, but 0.5%-1% of cases are associated with malignancy. It has been linked with ovarian neoplasms, particularly endometrioid and clear cell adenocarcinoma histology. Rhabdomyosarcomas are rarely associated with endometriosis.A 35-year-old patient underwent surgical management of endometriomas to optimize infertility treatment. She later developed abdominal pain with rapid recurrence of ovarian masses. This prompted additional surgery with biopsies diagnosing ovarian rhabdomyosarcoma. Retroactive review of pathologic specimens from her prior surgery demonstrated the neoplasm originated from her prior endometrioma. Focal areas suggested possible underlying ovarian adenosarcoma with stromal overgrowth.The incidence of rhabdomyosarcoma arising from endometriosis is exceedingly rare. The accuracy of diagnosing endometriosis and ruling out neoplasm requires coordinated efforts of a multidisciplinary team, involving radiologists, pathologists, oncologists, and gynecologic surgeons.

  View details for DOI 10.4293/JSLS.2019.00038

  View details for PubMedID 31624455

  View details for PubMedCentralID PMC6791399