Dr. Bui is a Clinical Assistant Professor of Medicine at the Stanford Cancer Institute and a specialist in Sarcoma. Dr. Bui earned an undergraduate degree in Computer Science at Stanford University and went on to earn his medical degree from the University of Texas Southwestern Medical Center. He completed Internal Medicine residency at Stanford Hospital and Hematology/Oncology fellowship at the University of California San Diego, where he performed extensive research in bioinformatics to analyze tumor sequencing data.

His research background and interests are in the field of bioinformatics as applied to large data sets and the study of novel compounds in rare malignancies. He is involved in numerous sarcoma clinical trials, leading efforts to take new therapeutics from the lab to clinical practice. He also is involved in education at the Stanford University School of Medicine, serving as a lecturer and mentor to students and trainees. Dr. Bui is the founding Editor-in-Chief of the journal “Current Problems in Cancer: Case Reports”, an international, peer-reviewed journal that publishes groundbreaking cases that give insight into redefining concepts in cancer.

Clinical Focus

  • Medical Oncology
  • Soft Tissue Sarcoma
  • Bone Sarcoma
  • Gastrointestinal Stromal Tumors (GIST)

Academic Appointments

Boards, Advisory Committees, Professional Organizations

  • Member, American Society of Clinical Oncology (ASCO) (2014 - Present)
  • Associate Member, Stanford Cancer Institute (2018 - Present)
  • Member, Connective Tissue Oncology Society (CTOS) (2017 - Present)

Professional Education

  • Residency: Stanford University Internal Medicine Residency (2014) CA
  • Board Certification: American Board of Internal Medicine, Medical Oncology (2017)
  • Fellowship: UCSD Hematology and Oncology Training (2017) CA
  • Board Certification: American Board of Internal Medicine, Hematology (2017)
  • Medical Education: University of Texas Southwestern Medical School Registrar (2011) TX
  • Board Certification: American Board of Internal Medicine, Internal Medicine (2014)
  • B.S., Stanford University, Computer Science (2007)

Clinical Trials

  • A Study of AL102 in Patients With Progressing Desmoid Tumors Recruiting

    The current study is designed to evaluate the efficacy and safety of AL102 in patients with progressive desmoid tumors.

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  • Phase 1/2a Study of SQ3370 in Patients With Advanced Solid Tumors Recruiting

    The purpose of this study is to evaluate the safety, tolerability, and preliminary activity of SQ3370 in patients with advanced solid tumors.

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  • Study of Cryoablation and Nirogacestat for Desmoid Tumor Recruiting

    The primary purpose of this protocol is Systemic therapy with oral study agent, nirogacestat, followed by a single cryoablation procedure.

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  • A Phase II Clinical Trial Evaluating the Combination of Olaparib and Temozolomide for the Treatment of Advanced Uterine Leiomyosarcoma Not Recruiting

    This phase II trial studies olaparib and temozolomide in treating patients with uterine leiomyosarcoma (LMS) that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced), that has spread from where it first started to other places in the body (metastatic) or cannot be removed by surgery (unresectable). PARPs are proteins that help repair DNA mutations. PARP inhibitors, such as olaparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. Chemotherapy drugs, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving olaparib and temozolomide may work better than giving either drug alone in treating patients with LMS.

    Stanford is currently not accepting patients for this trial. For more information, please contact Site Public Contact, 650-498-7061.

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  • A Study to Test the Safety of the Investigational Drug Selitrectinib in Children and Adults That May Treat Cancer Not Recruiting

    This research study is done to test the safety of the new drug selitrectinib in children and adults with cancer having a change in a particular gene (NTRK1, NTRK2 or NTRK3). The drug may treat cancer by interfering with the effect of the NTRK genes on cancer growth. The study also investigates how the drug is absorbed and processed in the human body, and how well and for how long the cancer responds to the drug. This is the first study to test selitrectinib in humans with cancer, for whom no other effective therapy exists.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • A Study Using [18F]F AraG PET to Evaluate Response to Checkpoint Inhibitor Therapy(CkIT) in Patients With Solid Tumors Not Recruiting

    In this study, patients with advanced solid tumors will undergo [18F]F AraG PET/CT imaging to assess for changes in tracer uptake following treatment with CkIT.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maria Isabel Galvez Leonio, 650-723-0371.

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  • ADI-PEG 20 in Combination With Gemcitabine and Docetaxel for the Treatment of Soft Tissue Sarcoma, Osteosarcoma, Ewing's Sarcoma, and Small Cell Lung Cancer Not Recruiting

    The investigators have recently demonstrated that argininosuccinate synthase 1 (ASS1) expression is silenced in 88% of all sarcomas (n=708), and that this loss is associated with a decreased overall survival. Using the extracellular arginine depleting enzyme PEGylated arginine deiminase (ADI-PEG20), an extracellular arginine depleting enzyme, the investigators demonstrated ADI-PEG20 induces a prosurvival metabolic reprogramming in ASS1-deficient sarcomas that redirects glucose into the serine/folate pathway directing the carbons from glucose into pyrimidine biosynthesis, thus sensitizing cells to death by the pyrimidine antimetabolite gemcitabine by using metabolomics. The synthetic lethality was increased by the addition of docetaxel. Therefore a phase II clinical trial of ADI with gemcitabine and docetaxel, a standard second line therapy for soft tissue sarcoma will be conducted to determine if the clinical benefit rate of gemcitabine and docetaxel is improved by the metabolic changes induced by ADI-PEG20. Recently published data shows that priming ASS1-deficient tumors with ADI-PEG 20 and docetaxel improves the effect of gemcitabine. Therefore, a cohort of patients consisting of ten patients diagnosed with either osteosarcoma or Ewing's sarcoma (ideally five of each), and five patients diagnosed with small cell lung cancer will be included as an exploratory cohort. Enrollment to Cohort 2 will occur concurrently with Cohort 1.

    Stanford is currently not accepting patients for this trial. For more information, please contact Nam Bui, M.D., 713-412-8721.

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  • Nirogacestat for Adults With Desmoid Tumor/Aggressive Fibromatosis (DT/AF) Not Recruiting

    This study evaluates nirogacestat (PF-03084014) in the treatment of desmoid tumor/aggressive fibromatosis (DT/AF). In the double-blind phase, half of the participants will receive nirogacestat while the other half will receive placebo. Once participants are eligible to roll into the open-label phase, they will receive nirogacestat.

    Stanford is currently not accepting patients for this trial.

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  • Olaparib in Treating Patients With Advanced Glioma, Cholangiocarcinoma, or Solid Tumors With IDH1 or IDH2 Mutations Not Recruiting

    This phase II trial studies how well olaparib works in treating patients with glioma, cholangiocarcinoma, or solid tumors with IDH1 or IDH2 mutations that has spread from where it first started (primary site) to other places in the body (metastatic) and that does not respond to treatment (refractory). Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • Phase III Trial of Anlotinib, Catequentinib in Advanced Alveolar Soft Part Sarcoma, Leiomyosarcoma, Synovial Sarcoma (APROMISS) Not Recruiting

    THIS STUDY IS CURRENTLY RECRUITING PATIENTS WITH ALVEOLAR SOFT PART SARCOMA ONLY AND IS NO LONGER RECRUITING PATIENTS WITH SYNOVIAL SARCOMA OR LEIOMYOSARCOMA. This study evaluates the safety and efficacy of AL3818 (anlotinib) hydrochloride in the treatment of metastatic or advanced alveolar soft part sarcoma (ASPS), leiomyosarcoma (LMS), and synovial sarcoma (SS). All participants with ASPS will receive open-label AL3818. In participants with LMS or SS, AL3818 will be compared to IV dacarbazine. Two-thirds of the participants will receive AL3818, one-third of the participants will receive IV dacarbazine.

    Stanford is currently not accepting patients for this trial.

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  • Treatment of Milademetan Versus Trabectedin in Patient With Dedifferentiated Liposarcoma Not Recruiting

    Randomized, multicenter, open-label, Phase 3 registration study designed to evaluate the safety and efficacy of milademetan compared to trabectedin in patients with unresectable (i.e., where resection is deemed to cause unacceptable morbidity or mortality) or metastatic DD liposarcoma that progressed on 1 or more prior systemic therapies, including at least 1 anthracycline-based therapy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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All Publications

  • Sarcoma microenvironment cell states and ecosystems are associated with prognosis and predict response to immunotherapy. Nature cancer Subramanian, A., Nemat-Gorgani, N., Ellis-Caleo, T. J., van IJzendoorn, D. G., Sears, T. J., Somani, A., Luca, B. A., Zhou, M. Y., Bradic, M., Torres, I. A., Oladipo, E., New, C., Kenney, D. E., Avedian, R. S., Steffner, R. J., Binkley, M. S., Mohler, D. G., Tap, W. D., D'Angelo, S. P., van de Rijn, M., Ganjoo, K. N., Bui, N. Q., Charville, G. W., Newman, A. M., Moding, E. J. 2024


    Characterization of the diverse malignant and stromal cell states that make up soft tissue sarcomas and their correlation with patient outcomes has proven difficult using fixed clinical specimens. Here, we employed EcoTyper, a machine-learning framework, to identify the fundamental cell states and cellular ecosystems that make up sarcomas on a large scale using bulk transcriptomes with clinical annotations. We identified and validated 23 sarcoma-specific, transcriptionally defined cell states, many of which were highly prognostic of patient outcomes across independent datasets. We discovered three conserved cellular communities or ecotypes associated with underlying genomic alterations and distinct clinical outcomes. We show that one ecotype defined by tumor-associated macrophages and epithelial-like malignant cells predicts response to immune-checkpoint inhibition but not chemotherapy and validate our findings in an independent cohort. Our results may enable identification of patients with soft tissue sarcomas who could benefit from immunotherapy and help develop new therapeutic strategies.

    View details for DOI 10.1038/s43018-024-00743-y

    View details for PubMedID 38429415

    View details for PubMedCentralID 4486342

  • 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


    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

  • 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


    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

  • Phase II Study of Olaparib and Temozolomide for Advanced Uterine Leiomyosarcoma (NCI Protocol 10250). Journal of clinical oncology : official journal of the American Society of Clinical Oncology Ingham, M., Allred, J. B., Chen, L., Das, B., Kochupurakkal, B., Gano, K., George, S., Attia, S., Burgess, M. A., Seetharam, M., Boikos, S. A., Bui, N., Chen, J. L., Close, J. L., Cote, G. M., Thaker, P. H., Ivy, S. P., Bose, S., D'Andrea, A., Marino-Enriquez, A., Shapiro, G. I., Schwartz, G. K. 2023: JCO2300402


    Uterine leiomyosarcoma (uLMS) is an aggressive subtype of soft-tissue sarcoma with frequent metastatic relapse after curative surgery. Chemotherapy provides limited benefit for advanced disease. Multiomics profiling studies have identified homologous recombination deficiency in uLMS. In preclinical studies where olaparib and temozolomide provided modest activity, the combination was highly effective for inhibiting uLMS tumor growth.NCI Protocol 10250 is a single-arm, open-label, multicenter, phase II study evaluating olaparib and temozolomide in advanced uLMS. Patients with progression on ≥1 prior line received temozolomide 75 mg/m2 orally once daily with olaparib 200 mg orally twice a day both on days 1-7 in 21-day cycles. The primary end point was the best objective response rate (ORR) within 6 months. A one-stage binomial design was used. If ≥5 of 22 responded, the treatment would be considered promising (93% power; α = .06). All patients underwent paired biopsies that were evaluated with whole-exome sequencing (WES)/RNAseq and a RAD51 foci formation assay.Twenty-two patients were evaluable. The median age was 55 years, and 59% had received three or more prior lines. Best ORR within 6 months was 23% (5 of 22). The overall ORR was 27% (6 of 22). The median progression-free survival (mPFS) was 6.9 months (95% CI, 5.4 months to not estimable). Hematologic toxicity was common (grade 3/4 neutropenia: 75%; thrombocytopenia: 32%) but manageable with dose modification. Five of 16 (31%) of tumors contained a deleterious homologous recombination gene alteration by WES, and 9 of 18 (50%) were homologous recombination-deficient by the RAD51 assay. In an exploratory analysis, mPFS was prolonged for patients with homologous recombination-deficient versus homologous recombination-proficient tumors (11.2 v 5.4 months, P = .05) by RAD51.Olaparib and temozolomide met the prespecified primary end point and provided meaningful clinical benefit in patients with advanced, pretreated uLMS.

    View details for DOI 10.1200/JCO.23.00402

    View details for PubMedID 37467452

  • 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


    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

  • LBA11504 Randomized phase II trial of cabozantinib combined with PD-1 and CTLA-4 inhibition versus cabozantinib in metastatic soft tissue sarcoma. JOURNAL OF CLINICAL ONCOLOGY Eulo, V., Toeniskoetter, J., Ruff, T., Luo, J., Kemp, L., Moreno 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. 2023; 41 (17_SUPPL): LBA11504
  • 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
  • Impact of nirogacestat on pain, a key symptom in patients with desmoid tumors (DT): Results from the phase 3 DeFi study Van der Graaf, W. A., Gounder, M. M., Ratan, R., Ivanescu, C., Marcus, J., Bell, T., Lim, A., Smith, L., Oton, A., Alcindor, T., Schoffski, P., Wilky, B. A., Riedel, R. F., Benson, C., Bui, N., Chugh, R., Kummar, S., Kasper, B. LIPPINCOTT WILLIAMS & WILKINS. 2023
  • 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)


    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)


    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


    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

  • Nirogacestat, a gamma-Secretase Inhibitor for Desmoid Tumors. The New England journal of medicine Gounder, M., Ratan, R., Alcindor, T., Schoffski, P., van der Graaf, W. T., Wilky, B. A., Riedel, R. F., Lim, A., Smith, L. M., Moody, S., Attia, S., Chawla, S., D'Amato, G., Federman, N., Merriam, P., Van Tine, B. A., Vincenzi, B., Benson, C., Bui, N. Q., Chugh, R., Tinoco, G., Charlson, J., Dileo, P., Hartner, L., Lapeire, L., Mazzeo, F., Palmerini, E., Reichardt, P., Stacchiotti, S., Bailey, H. H., Burgess, M. A., Cote, G. M., Davis, L. E., Deshpande, H., Gelderblom, H., Grignani, G., Loggers, E., Philip, T., Pressey, J. G., Kummar, S., Kasper, B. 2023; 388 (10): 898-912


    BACKGROUND: Desmoid tumors are rare, locally aggressive, highly recurrent soft-tissue tumors without approved treatments.METHODS: We conducted a phase 3, international, double-blind, randomized, placebo-controlled trial of nirogacestat in adults with progressing desmoid tumors according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Patients were assigned in a 1:1 ratio to receive the oral gamma-secretase inhibitor nirogacestat (150 mg) or placebo twice daily. The primary end point was progression-free survival.RESULTS: From May 2019 through August 2020, a total of 70 patients were assigned to receive nirogacestat and 72 to receive placebo. Nirogacestat had a significant progression-free survival benefit over placebo (hazard ratio for disease progression or death, 0.29; 95% confidence interval, 0.15 to 0.55; P<0.001); the likelihood of being event-free at 2 years was 76% with nirogacestat and 44% with placebo. Between-group differences in progression-free survival were consistent across prespecified subgroups. The percentage of patients who had an objective response was significantly higher with nirogacestat than with placebo (41% vs. 8%; P<0.001), with a median time to response of 5.6 months and 11.1 months, respectively; the percentage of patients with a complete response was 7% and 0%, respectively. Significant between-group differences in secondary patient-reported outcomes, including pain, symptom burden, physical or role functioning, and health-related quality of life, were observed (P≤0.01). Frequent adverse events with nirogacestat included diarrhea (in 84% of the patients), nausea (in 54%), fatigue (in 51%), hypophosphatemia (in 42%), and maculopapular rash (in 32%); 95% of adverse events were of grade 1 or 2. Among women of childbearing potential receiving nirogacestat, 27 of 36 (75%) had adverse events consistent with ovarian dysfunction, which resolved in 20 women (74%).CONCLUSIONS: Nirogacestat was associated with significant benefits with respect to progression-free survival, objective response, pain, symptom burden, physical functioning, role functioning, and health-related quality of life in adults with progressing desmoid tumors. Adverse events with nirogacestat were frequent but mostly low grade. (Funded by SpringWorks Therapeutics; DeFi number, NCT03785964.).

    View details for DOI 10.1056/NEJMoa2210140

    View details for PubMedID 36884323

  • The Next Frontier in Sarcoma: Molecular Pathways and Associated Targeted Therapies. Cancers Kim, T., Bui, N. Q. 2023; 15 (6)


    Soft tissue sarcomas (STS) are a rare, complex, heterogeneous group of mesenchymal neoplasms with over 150 different histological subtypes. Treatments for this malignancy have been especially challenging due to the heterogeneity of the disease and the modest efficacy of conventional chemotherapy. The next frontier lies in discerning the molecular pathways in which these mesenchymal neoplasms arise, metastasize, and develop drug-resistance, thereby helping guide new therapeutic targets for the treatment of STS. This comprehensive review will discuss the current understanding of tumorigenesis of specific STS subtypes, including oncogenic pathway alterations involved in cell cycle regulation, angiogenesis, NOTCH signaling, and aberrant genetic rearrangements. It will then review current therapies that have been recently developed to target these pathways, including a review of ongoing clinical studies for targeted sarcoma treatment, as well as discuss new potential avenues for therapies against known molecular pathways of sarcomagenesis.

    View details for DOI 10.3390/cancers15061692

    View details for PubMedID 36980578

  • 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)


    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

  • 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


    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

  • The Impact of TSC-1 and -2 Mutations on Response to Therapy in Malignant PEComa: A Multicenter Retrospective Analysis. Genes Liu, L., Dehner, C., Grandhi, N., Lyu, Y., Borcherding, D. C., Chrisinger, J. S., Zhang, X., Luo, J., Tao, Y., Parkes, A., Bui, N. Q., Davis, E. J., Milhem, M. M., Monga, V., Weiss, M., Tine, B. V., Hirbe, A. C. 2022; 13 (11)


    BACKGROUND: Perivascular epithelioid cell neoplasms (PEComas) are a diverse family of mesenchymal tumors with myomelanocytic differentiation that disproportionately affect women and can be associated with tuberous sclerosis (TS). Although mTOR inhibition is widely used as first-line treatment, it is unclear what genomic alterations exist in these tumors and how they influence the response to therapy.METHODS: This was a multicenter study conducted at five sites within the US. The data were collected from 1 January 2004 to 31 January 2021. We conducted a retrospective analysis to identify PEComa patients with next-generation sequencing (NGS) data and compared outcomes based on mutations.RESULTS: No significant differences in survival were identified between TSC-1 and TSC-2 mutated PEComa or TSC-1/-2 versus other mutations. No significant difference was seen in progression-free survival (PFS) after first-line therapy between mTOR inhibition versus other systemic therapies.CONCLUSIONS: We were unable to detect differences in survival based on genomic alterations or PFS between mTOR inhibition versus other systemic therapies. Future studies should seek to identify other drivers of TSC-1/-2 silencing that could predict response to mTOR inhibition.

    View details for DOI 10.3390/genes13111932

    View details for PubMedID 36360169

  • 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


    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

  • 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)


    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

  • 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)


    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

  • The interaction of SWI/SNF with the ribosome regulates translation and confers sensitivity to translation pathway inhibitors in cancers with complex perturbations. Cancer research Ulicna, L., Kimmey, S. C., Weber, C. M., Allard, G. M., Wang, A., Bui, N. Q., Bendall, S. C., Crabtree, G. R., Bean, G. R., Van Rechem, C. 2022


    Subunits from the chromatin remodelers mammalian SWItch/Sucrose Non-Fermentable (mSWI/SNF) are mutated, deleted or amplified in more than 40% of cancers. Understanding their functions in normal cells and the consequences of cancerous alterations will provide insight into developing new targeted therapies. Here we examined whether mSWI/SNF mutations increase cellular sensitivity to specific drugs. Taking advantage of the DepMap studies, we demonstrate that cancer cells harboring mutations of specific mSWI/SNF subunits exhibit a genetic dependency on translation factors and are sensitive to translation pathway inhibitors. Furthermore, mSWI/SNF subunits were present in the cytoplasm and interacted with the translation initiation machinery, and short-term inhibition and depletion of specific subunits decreased global translation, implicating a direct role for these factors in translation. Depletion of specific mSWI/SNF subunits also increased sensitivity to mTOR-PI3K inhibitors. In patient-derived breast cancer samples, mSWI/SNF subunits expression in both the nucleus and the cytoplasm was substantially altered. In conclusion, an unexpected cytoplasmic role for mSWI/SNF complexes in translation suggests potential new therapeutic opportunities for patients afflicted by cancers demonstrating alterations in their subunits.

    View details for DOI 10.1158/0008-5472.CAN-21-1360

    View details for PubMedID 35749589

  • SQ3370 in advanced solid tumors: Interim phase 1 results. Chawla, S. P., Batty, K., Bhadri, V., Bui, N., Guminski, A. D., Oneto, J., Srinivasan, S., Strauss, J. F., Subbiah, V., Weiss, M. C., Wilson, R., Yee, N. A., Zacharian, M., Kwatra, V. AMER ASSOC CANCER RESEARCH. 2022
  • Interim phase 1 results for SQ3370 in advanced solid tumors. Chawla, S. P., Batty, K., Aleckovic, M., Bhadri, V., Bui, N., Guminski, A., Oneto, J., Srinivasan, S., Strauss, J., Subbiah, V., Weiss, M. C., Wilson, R., Yee, N. A., Zakharian, M., Kwatra, V. LIPPINCOTT WILLIAMS & WILKINS. 2022
  • Correlative results from NCI protocol 10250: A phase II study of temozolomide and olaparib for the treatment of advanced uterine leiomyosarcoma. Bose, S., Ingham, M., Chen, L., Kochupurakkal, B., Marino-Enriquez, A., Allred, J. B., George, S., Attia, S., Burgess, M., Seetharam, M., Boikos, S., Bui, N., Chen, J., Close, J., Cote, G., Ivy, S., Das, B., Shapiro, G., Schwartz, G. K. LIPPINCOTT WILLIAMS & WILKINS. 2022
  • 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


    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

  • WEE1 kinase is a therapeutic vulnerability in CIC-DUX4 undifferentiated sarcoma. JCI insight Ponce, R. K., Thomas, N. J., Bui, N. Q., Kondo, T., Okimoto, R. A. 2022; 7 (6)


    CIC-DUX4 rearrangements define an aggressive and chemotherapy-insensitive subset of undifferentiated sarcomas. The CIC-DUX4 fusion drives oncogenesis through direct transcriptional upregulation of cell cycle and DNA replication genes. Notably, CIC-DUX4-mediated CCNE1 upregulation compromises the G1/S transition to confer a dependence on the G2/M cell cycle checkpoint. Through an integrative transcriptional and kinase activity screen using patient-derived specimens, we now show that CIC-DUX4 sarcomas depend on the G2/M checkpoint regulator WEE1 as part of an adaptive survival mechanism. Specifically, CIC-DUX4 sarcomas depended on WEE1 activity to limit DNA damage and unscheduled mitotic entry. Consequently, genetic or pharmacologic WEE1 inhibition in vitro and in vivo led to rapid DNA damage-associated apoptotic induction of patient-derived CIC-DUX4 sarcomas. Thus, we identified WEE1 as a vulnerability targetable by therapeutic intervention in CIC-DUX4 sarcomas.

    View details for DOI 10.1172/jci.insight.152293

    View details for PubMedID 35315355

  • 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


    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

  • 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)


    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

  • Isolated Leptomeningeal Progression in a Patient with NTRK Fusion+ Uterine Sarcoma: A Case Report. Case reports in oncology Lanman, T., Hayden Gephart, M., Bui, N., Toland, A., Nagpal, S. 2021; 14 (3): 1841-1846


    While neurotrophic tropomyosin receptor kinase (NTRK) fusions represent rare oncogenic drivers (<1% of solid cancers), the recent approval of NTRK inhibitors (larotrectinib and entrectinib) led to dramatic responses in patients with NTRK fusion+ tumors. Both drugs have phase I data, demonstrating efficacy in the central nervous system (CNS), including both primary brain tumors and brain metastases. We present a 29-year-old woman who was diagnosed with NTRK3-SPECC1L fusion+ undifferentiated uterine sarcoma and underwent resection, chemotherapy, and radiotherapy. Two years later, lung metastases were discovered. She was started on larotrectinib with complete response. She remained stable on larotrectinib until she presented with altered mental status and seizures. MRI demonstrated leptomeningeal enhancement, but because leptomeningeal progression from sarcoma is exceedingly rare and her symptoms improved dramatically with antiepileptics, these findings were initially attributed to seizures. After 2 unrevealing lumbar punctures and stable systemic imaging, a brain biopsy demonstrated metastatic sarcoma, still showing NTRK positivity. She underwent whole brain radiotherapy and was switched to entrectinib, but had clinical progression 1 month later and transitioned to hospice. This case demonstrates the efficacy of NTRK inhibitors in rare and aggressive cancer but highlights that these patients can develop isolated CNS progression even in the setting of CNS-penetrant drugs. CNS progression can occur if there is incomplete CNS drug penetration, discordance in molecular profiles between CNS and systemic disease, or acquired NTRK inhibitor resistance. In this case, CNS disease maintained the NTRK fusion status, but either inadequate CNS penetration or development of a resistance gene may explain the isolated CNS progression.

    View details for DOI 10.1159/000521158

    View details for PubMedID 35111018

  • 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
  • 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


    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

  • Phase 1 trial of SQ3370 in solid tumors. Guminski, A., Wang, D., Bui, N., Bhadri, V., De Silva, M., Steffner, R., Yee, N. A., Srinivasan, S., Oneto, J., Saville, M., Subbiah, V. AMER ASSOC CANCER RESEARCH. 2021
  • 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
  • NCI protocol 10250: A phase II study of temozolomide and olaparib for the treatment of advanced uterine leiomyosarcoma. Ingham, M., Allred, J. B., Gano, K., George, S., Attia, S., Burgess, M., Seetharam, M., Boikos, S., Bui, N., Chen, J., Close, J., Cote, G., Thaker, P. H., Ivy, S., Das, B., Shapiro, G., Kochupurakkal, B., Trepel, J. B., Pommier, Y., Schwartz, G. K. LIPPINCOTT WILLIAMS & WILKINS. 2021
  • Prognostic relevance of the hexosamine biosynthesis pathway activation in leiomyosarcoma. NPJ genomic medicine Tolwani, A., Matusiak, M., Bui, N., Forgo, E., Varma, S., Baratto, L., Iagaru, A., Lazar, A. J., van de Rijn, M., Przybyl, J. 2021; 6 (1): 30


    Metabolic reprogramming of tumor cells and the increase of glucose uptake is one of the hallmarks of cancer. In order to identify metabolic pathways activated in leiomyosarcoma (LMS), we analyzed transcriptomic profiles of distinct subtypes of LMS in several datasets. Primary, recurrent and metastatic tumors in the subtype 2 of LMS showed consistent enrichment of genes involved in hexosamine biosynthesis pathway (HBP). We demonstrated that glutamine-fructose-6-phosphate transaminase 2 (GFPT2), the rate-limiting enzyme in HBP, is expressed on protein level in a subset of LMS and the expression of this enzyme is frequently retained in patient-matched primary and metastatic tumors. In a new independent cohort of 327 patients, we showed that GFPT2 is associated with poor outcome of uterine LMS but not extra-uterine LMS. Based on the analysis of a small group of patients studied by 18F-FDG-PET imaging, we propose that strong expression of GFPT2 in primary LMS may be associated with high metabolic activity. Our data suggest that HBP is a potential new therapeutic target in one of the subtypes of LMS.

    View details for DOI 10.1038/s41525-021-00193-w

    View details for PubMedID 33941787

  • Uterine Leiomyosarcoma with FN1-Anaplastic Lymphoma Kinase Fusion Responsive to Alectinib and Lorlatinib. Case reports in oncology Testa, S., Million, L., Longacre, T., Bui, N. 2021; 14 (2): 812-819


    Uterine leiomyosarcoma (LMS) is a rare malignant neoplasm of the female genital tract poorly responsive to conventional chemotherapy and radiotherapy, with an overall poor prognosis. Pazopanib is at the moment the only FDA-approved targeted molecular therapy for uterine LMS, given the exceedingly rare occurrence of actionable genetic mutations in this type of cancer. Here, we describe the first reported case of metastatic uterine LMS with an FN1-anaplastic lymphoma kinase (ALK) fusion mutation occurring in a 63-year-old woman with a history of uterine leiomyomas. The patient progressed on several lines of therapy, including conventional chemotherapy, pazopanib, and the first-generation ALK inhibitor crizotinib. Interestingly, the patient showed a remarkable 16-month response to second generation ALK inhibitors alectinib and lorlatinib. This case demonstrates that ALK inhibitors can be an effective therapeutic strategy for patients with ALK fusion-positive uterine LMS that has progressed on conventional chemotherapy.

    View details for DOI 10.1159/000516758

    View details for PubMedID 34248545

  • Evolving role of entrectinib in treatment of NTRK-positive tumors. Future oncology (London, England) Chawla, N., Bui, N. Q., Seetharam, M. 2021


    Targeted therapy has shown to be a very effective treatment in tumors with specific genomic drivers. Trkhas proven to be one such target. Efforts to target the Trk fusion with specific inhibitors have shown remarkable responses in a tumor agnostic fashion, with responses seen even in patients with intracranial metastasis. Entrectinib is a first-generation Trk inhibitor with impressive activity in early phase trials performed in patients with NTRK fusion positive solid tumors and ROS1 positive non-small-cell lung cancers with subsequent approval for those indications. Entrectinib was also found to be effective in treatment of brain metastasis and generally well tolerated.

    View details for DOI 10.2217/fon-2020-0936

    View details for PubMedID 33896226

  • A Case of Isolated Leptomeningeal Progression in a Patient with NTRK Fusion plus Uterine Sarcoma Lanman, T., Hayden, M., Bui, N., Nagpal, S. LIPPINCOTT WILLIAMS & WILKINS. 2021
  • 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


    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

  • 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


    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

  • 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


    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


    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

  • 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


    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

  • 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
  • SQ3370-001 IS A MULTI-CENTER OPEN-LABEL PHASE I DOSE-ESCALATION STUDY TO TEST A NOVEL INTRATUMORAL AND SYSTEMIC APPROACH TO TREAT ADVANCED SOLID TUMORS Bhadri, V., Bui, N., Guminski, A., Oneto, J., Murthy, R., Sankhala, K., Saville, M., Srinivasan, S., Steffner, R., Subbiah, V., Wang, D., Yee, N. BMJ PUBLISHING GROUP. 2020: A253–A254
  • NCI protocol 10250: A phase II study of temozolomide and olaparib for the treatment of advanced uterine leiomyosarcoma. Ingham, M., Allred, J. B., Gano, K., George, S., Attia, S., Burgess, M., Boikos, S., Bui, N., Chen, J., Close, J., Seetharam, M., Thaker, P. H., Schwartz, G. K. LIPPINCOTT WILLIAMS & WILKINS. 2020
  • Increasing Clinical Trial Accrual via Automated Matching of Biomarker Criteria. Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing Chen, J. W., Kunder, C. A., Bui, N. n., Zehnder, J. L., Costa, H. A., Stehr, H. n. 2020; 25: 31–42


    Successful implementation of precision oncology requires both the deployment of nucleic acid sequencing panels to identify clinically actionable biomarkers, and the efficient screening of patient biomarker eligibility to on-going clinical trials and therapies. This process is typically performed manually by biocurators, geneticists, pathologists, and oncologists; however, this is a time-intensive, and inconsistent process amongst healthcare providers. We present the development of a feature matching algorithmic pipeline that identifies patients who meet eligibility criteria of precision medicine clinical trials via genetic biomarkers and apply it to patients undergoing treatment at the Stanford Cancer Center. This study demonstrates, through our patient eligibility screening algorithm that leverages clinical sequencing derived biomarkers with precision medicine clinical trials, the successful use of an automated algorithmic pipeline as a feasible, accurate and effective alternative to the traditional manual clinical trial curation.

    View details for PubMedID 31797584

  • Increasing Clinical Trial Accrual via Automated Matching of Biomarker Criteria Chen, J. W., Kunder, C. A., Bui, N., Zehnder, J. L., Costa, H. A., Stehr, H., Altman, R. B., Dunker, A. K., Hunter, L., Ritchie, M. D., Murray, T., Klein, T. E. WORLD SCIENTIFIC PUBL CO PTE LTD. 2020: 31-42
  • Successful treatment of HIV-negative Kaposi sarcoma with ipilimumab and nivolumab and concurrent management of baseline psoriasis and bullous pemphigoid. JAAD case reports Tabata, M. M., Novoa, R. A., Bui, N. Q., Zaba, L. C. 2020; 6 (5): 447–49

    View details for DOI 10.1016/j.jdcr.2020.03.001

    View details for PubMedID 32382643

    View details for PubMedCentralID PMC7200441

  • 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


    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

  • Dose escalation of tinostamustine in patients with advanced solid tumors Mita, A., Loeffler, M., Bui, N., Mehrling, T., Rimmel, B. J., Natale, R. B., Kummar, S. AMER ASSOC CANCER RESEARCH. 2019
  • 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
  • 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
  • Chromatin dysregulation and DNA methylation at transcription start sites associated with transcriptional repression in cancers NATURE COMMUNICATIONS Ando, M., Saito, Y., Xu, G., Bui, N. Q., Medetgul-Ernar, K., Pu, M., Fisch, K., Ren, S., Sakai, A., Fukusumi, T., Liu, C., Haft, S., Pang, J., Mark, A., Gaykalova, D. A., Guo, T., Favorov, A., Yegnasubramanian, S., Fertig, E. J., Ha, P., Tamayo, P., Yamasoba, T., Ideker, T., Messer, K., Califano, J. A. 2019; 10
  • Next-Generation Sequencing of Tissue and Circulating Tumor DNA: The UC San Diego Moores Center for Personalized Cancer Therapy Experience with Breast Malignancies MOLECULAR CANCER THERAPEUTICS Shatsky, R., Parker, B. A., Bui, N. Q., Heisten, T., Schwab, R. B., Boles, S. G., Kurzrock, R. 2019; 18 (5): 1001–11
  • 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


    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

  • Editorial. Current problems in cancer Bui, N. n. 2019; 43 (4): 249
  • Contemporary management of metastatic soft tissue sarcoma. Current problems in cancer Bui, N. Q., Wang, D. S., Hiniker, S. M. 2019


    Soft tissue sarcoma (STS) is a rare, heterogeneous cancer that can have high rates of distant metastases. Optimal treatment planning requires detailed knowledge of distinct sarcoma histologies as well as the wide array of therapeutic options through surgical, medical, radiation, and interventional oncology. In this review article, we discuss the contemporary management of metastatic STS and the underlying data behind these recommendations. All patients with metastatic STS should be discussed in a multidisciplinary tumor board at an experienced sarcoma center. For patients with oligometastatic disease, there should be strong consideration for definitive local therapy such as surgical resection, stereotactic body radiation therapy, or ablative procedures. In cases with widespread metastases, cytotoxic chemotherapy represents the standard treatment for STS patients with traditional chemotherapies, such as anthracyclines, gemcitabine/docetaxel, ifosfamide, and dacarbazine, still being the most commonly used drugs today. The recent approvals of trabectedin, eribulin, and pazopanib have expanded the therapeutic armamentarium for metastatic STS. Histology-directed treatment is crucial for certain subtypes of STS which are highly sensitive to targeted therapy and relatively insensitive to chemotherapy. Despite the significant progress that has been made in metastatic STS in the past decade, overall prognosis is poor and there is a critical need for novel therapeutics.

    View details for DOI 10.1016/j.currproblcancer.2019.06.005

    View details for PubMedID 31248634

  • Reviewing the role of healthy volunteer studies in drug development. Journal of translational medicine Karakunnel, J. J., Bui, N., Palaniappan, L., Schmidt, K. T., Mahaffey, K. W., Morrison, B., Figg, W. D., Kummar, S. 2018; 16 (1): 336


    BACKGROUND: With the exception of genotoxic oncology drugs, first-in-human, Phase 1 clinical studies of investigational drugs have traditionally been conducted in healthy volunteers (HVs). The primary goal of these studies is to investigate the pharmacokinetics and pharmacodynamics of a novel drug candidate, determine appropriate dosing, and document safety and tolerability.MAIN BODY: When tailored to specific study objectives, HV studies are beneficial to manufacturers and patients alike and can be applied to both non-oncology and oncology drug development. Enrollment of HVs not only increases study accrual rates for dose-escalation studies but also alleviates the ethical concern of enrolling patients with disease in a short-term study at subtherapeutic doses when other studies (e.g. Phase 2 or Phase 3 studies) may be more appropriate for the patient. The use of HVs in non-oncology Phase 1 clinical trials is relatively safe but nonetheless poses ethical challenges because of the potential risks to which HVs are exposed. In general, most adverse events associated with non-oncology drugs are mild in severity, and serious adverse events are rare, but examples of severe toxicity have been reported. The use of HVs in the clinical development of oncology drugs is more limited but is nonetheless useful for evaluating clinical pharmacology and establishing an appropriate starting dose for studies in cancer patients. During the development of oncology drugs, clinical pharmacology studies in HVs have been used to assess pharmacokinetics, drug metabolism, food effects, potential drug-drug interactions, effects of hepatic and renal impairment, and other pharmacologic parameters vital for clinical decision-making in oncology. Studies in HVs are also being used to evaluate biosimilars versus established anticancer biologic agents.CONCLUSION: A thorough assessment of toxicity and pharmacology throughout the drug development process is critical to ensure the safety of HVs. With the appropriate safeguards, HVs will continue to play an important role in future drug development.

    View details for PubMedID 30509294

  • Disruption of NSD1 in head and neck cancer promotes favorable chemotherapeutic responses linked to hypomethylation. Molecular cancer therapeutics Bui, N., Huang, J. K., Bojorquez-Gomez, A., Licon, K., Sanchez, K. S., Tang, S. N., Beckett, A. N., Wang, T., Zhang, W., Shen, J. P., Kreisberg, J. F., Ideker, T. 2018


    Human papillomavirus (HPV) negative head and neck squamous cell carcinoma (HNSCC) represents a distinct classification of cancer with poor expected outcomes. Of the 11 genes recurrently mutated in HNSCC, we identify a singular and substantial survival advantage for mutations in the gene encoding Nuclear Set Domain Containing Protein 1 (NSD1), a histone methyltransferase altered in approximately 10% of patients. This effect, a 55% decrease in risk of death in NSD1-mutated versus non-mutated patients, can be validated in an independent cohort. NSD1 alterations are strongly associated with widespread genome hypomethylation in the same tumors, to a degree not observed for any other mutated gene. To address whether NSD1 plays a causal role in these associations, we use CRISPR-Cas9 to disrupt NSD1 in HNSCC cell lines and find that this leads to substantial CpG hypomethylation and sensitivity to cisplatin, a standard chemotherapy in head and neck cancer, with a 40 - 50% decrease in IC50. Such results are reinforced by a survey of 1,001 cancer cell lines, in which loss-of-function NSD1 mutations have an average 23% decrease in cisplatin IC50 compared to cell lines with wild type NSD1. This study identifies a favorable subtype of head and neck cancer linked to NSD1 mutation, hypomethylation and cisplatin sensitivity.

    View details for DOI 10.1158/1535-7163.MCT-17-0937

    View details for PubMedID 29636367

  • 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


    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

  • Cell-Free DNA from Ascites and Pleural Effusions: Molecular Insights into Genomic Aberrations and Disease Biology MOLECULAR CANCER THERAPEUTICS Husain, H., Nykin, D., Nam Bui, N., Quan, D., Gomez, G., Woodward, B., Venkatapathy, S., Duttagupta, R., Fung, E., Lippman, S. M., Kurzrock, R. 2017; 16 (5): 948-955


    Collection of cell-free DNA (cfDNA) from the blood of individuals with cancer has permitted noninvasive tumor genome analysis. Detection and characterization of cfDNA in ascites and pleural effusions have not yet been reported. Herein, we analyzed cfDNA in the ascites and pleural effusions from six individuals with metastatic cancer. In all cases, cfDNA copy number variations (CNV) were discovered within the effusate. One individual had a relevant alteration with a high copy amplification in EGFR in a never smoker with lung cancer, who showed only MDM2 and CDK4 amplification in a prior tissue biopsy. Another subject with metastatic breast cancer had cytology-positive ascites and an activating PIK3CA mutation identified in the tissue, blood, and ascites collectively. This individual had tumor regression after the administration of the mTOR inhibitor everolimus and had evidence of chromotripsis from chromosomal rearrangements noted in the cell-free ascitic fluid. These results indicate that cfDNA from ascites and pleural effusions may provide additional information not detected with tumor and plasma cell-free DNA molecular characterization, and a context for important insights into tumor biology and clonal dynamic change within primary tumor and metastatic deposits. Mol Cancer Ther; 16(5); 948-55. ©2017 AACR.

    View details for DOI 10.1158/1535-7163.MCT-16-0436

    View details for Web of Science ID 000400713500017

    View details for PubMedID 28468865

  • Chart review versus an automated bioinformatic approach to assess real-world crizotinib effectiveness in ALK-positive NSCLC. JCO clinical cancer informatics Bui, N., Henry, S., Wood, D., Wakelee, H. A., Neal, J. W. 2017; 2017

    View details for DOI 10.1200/CCI.16.00055

    View details for PubMedID 28868517

  • Strategies to Overcome Bypass Mechanisms Mediating Clinical Resistance to EGFR Tyrosine Kinase Inhibition in Lung Cancer MOLECULAR CANCER THERAPEUTICS Husain, H., Scur, M., Murtuza, A., Bui, N., Woodward, B., Kurzrock, R. 2017; 16 (2): 265-272


    The vast majority of patients with metastatic lung cancers who initially benefit from EGFR-targeted therapies eventually develop resistance. An increasing understanding of the number and complexity of resistance mechanisms highlights the challenge of treating tumors resistant to EGFR inhibitors. Resistance mechanisms include new, second-site mutations within EGFR (e.g., T790M and C797S), upregulation of MET kinase, upregulation of insulin growth factor receptor (IGFR), HER2 amplification, increased expression of AXL, BIM modulation, NF-κB activation, histologic switch to small-cell cancer, epithelial-to-mesenchymal transition, PDL1 expression with subsequent immune tolerance, and release of cytokines such as TGFβ and IL6. Herein, we review the growing body of knowledge regarding EGFR bypass pathways, and the development of new drugs and combination treatment strategies to overcome resistance. Mol Cancer Ther; 16(2); 265-72. ©2017 AACR.

    View details for DOI 10.1158/1535-7163.MCT-16-0105

    View details for Web of Science ID 000395563700002

    View details for PubMedID 28159915

  • Molecular insights into desmoid tumors. Oncotarget Bui, N. n., Kummar, S. n. 2017; 8 (53): 90608–9

    View details for DOI 10.18632/oncotarget.21293

    View details for PubMedID 29207578

    View details for PubMedCentralID PMC5710859

  • Evolution of early phase clinical trials in oncology. Journal of molecular medicine (Berlin, Germany) Bui, N. Q., Kummar, S. n. 2017


    The therapeutic armamentarium for the treatment of cancer has rapidly evolved with the advent of molecularly targeted and immuno-oncology agents. Dramatic and prolonged responses observed in patients with advanced cancers have created excitement and promise for expedited development of effective new treatments. However, this has also necessitated a rethinking of our early phase clinical trial designs and the process of optimally developing a novel agent. In this review, we discuss the current state and future directions of phase I clinical trials in oncology. Firstly, we cover the statistical methodologies behind rules and model-based dose escalation designs, and what the future holds for optimal dose selection beyond targeting the maximum tolerated dose. Next, we discuss the recent adoption of seamless expansion strategies to expedite drug development timelines, highlighted by the pembrolizumab KEYNOTE-001 trial, and potential pitfalls with this approach. Finally, we delve into the concepts behind genomic matching trials, including early success stories and the challenges that lie ahead.

    View details for PubMedID 29177698

  • Novel Treatment Strategies for Brain Metastases in Non-small-cell Lung Cancer CURRENT TREATMENT OPTIONS IN ONCOLOGY Bui, N., Woodward, B., Johnson, A., Husain, H. 2016; 17 (5)


    Brain metastases are common in patients with non-small cell lung cancer (NSCLC), and due to associated poor prognosis, this field is an important area of need for the development of innovative medical therapies. Therapies including local approaches through surgical intervention and/or radiation and evolving systemic therapies have led to improvements in the treatment of brain metastases in patients with lung cancer. Strategies that consider applying advanced radiation techniques to minimize toxicity, intervening early with effective systemic therapies to spare radiation/surgery, testing radiosensitization combinations, and developing drug penetrant molecules have and will continue to define new practice patterns. We believe that in carefully considered asymptomatic patients, first-line systemic therapy may be considered before radiation therapy and small-molecule targeted therapy may provide an opportunity to defer radiation therapy for recurrence or progression of disease. The next several years in oncology drug development will see the reporting on of brain penetrant molecules in oncogene-defined non-small cell lung cancer. Ongoing studies will evaluate immunotherapies in patients with brain metastases with associated endpoints. We hope that continued drug development and carefully designed clinical trials may afford an opportunity to improve the lives of patients with brain metastases.

    View details for DOI 10.1007/s11864-016-0400-x

    View details for Web of Science ID 000374565200002

    View details for PubMedID 27085533

  • Reactivation of hepatitis B virus after withdrawal of erlotinib CURRENT ONCOLOGY Bui, N., Wong-Sefidan, I. 2015; 22 (6): 430-432


    Reactivation of hepatitis B virus (hbv) is a reported complication for patients undergoing chemotherapy, particularly immunochemotherapy with anti-CD20 agents such as rituximab. However, as the use of molecularly targeted agents increases, the risk of viral reactivation is less clearly defined. Here, we present the case of a 62-year-old woman with newly diagnosed EGFR mutation-positive metastatic non-small-cell lung cancer (nsclc). Per interview, our patient had a remote history of hbv infection. She was started on erlotinib and developed profound diarrhea leading to renal failure that required hospital admission and temporary discontinuation of erlotinib. At 8 days after erlotinib cessation, she had a marked spike in her liver function tests, with viral serologies that were consistent with hbv reactivation. Although erlotinib and other tyrosine kinase inhibitors (tkis) are not classically associated with hbv reactivation, hbv reactivation can occur even in the setting of tki withdrawal. Before tki initiation, careful patient screening in those at risk for hbv should be performed to attenuate preventable hepatotoxicity and to differentiate between other causes of hepatotoxicity (for example, drug-induced toxicity).

    View details for DOI 10.3747/co.22.2665

    View details for Web of Science ID 000366983500022

    View details for PubMedID 26715877

    View details for PubMedCentralID PMC4687665

  • Dorsal aesthetic lines in rhinoplasty: a quantitative outcome-based assessment of the component dorsal reduction technique. Plastic and reconstructive surgery Mojallal, A., Ouyang, D., Saint-Cyr, M., Bui, N., Brown, S. A., Rohrich, R. J. 2011; 128 (1): 280-288


    Preservation or reconstruction of the middle nasal vault structure and internal nasal valve after dorsal reduction is challenging. The purpose of this study was to retrospectively analyze a series of 100 consecutive rhinoplasty cases with respect to preservation or restoration of the dorsal nasal lines following component dorsal reduction. A new quantitative mathematical application for subject digital images was performed.Medical information and digital images were obtained from 100 consecutive primary rhinoplasty patients from one author (R.J.R.) with University of Texas Southwestern Medical Center Institutional Review Board consent. All postoperative subject digital images were taken at more than 1-year follow-up. Preoperative and postoperative digital images of the dorsal nasal aesthetic lines were analyzed using a software application that quantitated various facial anatomical features compared with landmark measurements unique for each subject (pupil-to-pupil distance). Dorsal line symmetry, nose width, and variation of deformities on each side of the face were determined.Mean subject dorsal line symmetry was 68 percent preoperatively and 94 percent postoperatively. Only 32.5 percent of dorsal lines were harmonious preoperatively, whereas 97 percent of dorsal lines were harmonious postoperatively. Identification of dorsal lines postoperatively versus preoperatively was similar in 74.6 percent, improved in 15.7 percent, and decreased in 9.7 percent. Nasal width lines were similar in 36 subjects, 21 subjects had wider nasal width lines, and 43 subjects had narrower width lines after surgery.Component dorsal hump reduction procedures result in reliable and reproducible clinical outcomes. Quantitative assessments provide evidence that improved and harmonious curves of dorsal aesthetic lines are achievable.Therapeutic, IV.(Figure is included in full-text article.).

    View details for DOI 10.1097/PRS.0b013e318218fc2d

    View details for PubMedID 21701345