Saad A. Khan, MD

All Publications

• Phase I/IIa clinical trial of a small molecule EBNA1 inhibitor, VK-2019, in patients with Epstein Barr virus-positive nasopharyngeal cancer with pharmacokinetic and pharmacodynamic correlative studies. Colevas, A., Rudek, M. A., Even, C., Lee, V., Gillison, M. L., Khan, S. A., Lu, R., Winters, E., Biedermann, S., Lai, S., Messick, T. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001053772003156

• Opioid prescribing patterns for head and neck cancer radiation patients, with a comparison to breast cancer radiation patients Lasonde, B., Lu, R., Hawa, S., Biedermann, S., Lai, S., Winters, E., Khan, S. A. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001053772004056

• Radiotherapy and paclitaxel plus pazopanib or placebo in anaplastic thyroid cancer (NRG/RTOG 0912): a randomised, double-blind, placebo-controlled, multicentre, phase 2 trial. The Lancet. Oncology Sherman, E. J., Harris, J., Bible, K. C., Xia, P., Ghossein, R. A., Chung, C. H., Riaz, N., Gunn, G. B., Foote, R. L., Yom, S. S., Wong, S. J., Koyfman, S. A., Dzeda, M. F., Clump, D. A., Khan, S. A., Shah, M. H., Redmond, K., Torres-Saavedra, P. A., Le, Q., Lee, N. Y. 2023

  Abstract

  BACKGROUND: Anaplastic thyroid cancer is a rare and aggressive cancer with no standard radiotherapy-based local treatment. Based on data suggesting synergy between pazopanib and paclitaxel in anaplastic thyroid cancer, NRG Oncology did a double-blind, placebo-controlled, randomised phase 2 clinical trial comparing concurrent paclitaxel and intensity-modulated radiotherapy (IMRT) with the addition of pazopanib or placebo with the aim of improving overall survival in this patient population.METHODS: Eligible patients were aged 18 years or older with a pathological diagnosis of anaplastic thyroid cancer, any TNM stage, Zubrod performance status of 0-2, no recent haemoptysis or bleeding, and no brain metastases. Patients were enrolled from 34 centres in the USA. Initially, a run-in was done to establish safety. In the randomised phase 2 trial, patients in the experimental group (pazopanib) received 2-3 weeks of weekly paclitaxel (80 mg/m2) intravenously and daily pazopanib suspension 400 mg orally followed by concurrent weekly paclitaxel (50 mg/m2), daily pazopanib (300 mg), and IMRT 66 Gy given in 33 daily fractions (2 Gy fractions). In the control group (placebo), pazopanib was replaced by matching placebo. Patients were randomly assigned (1:1) to the two treatment groups by permuted block randomisation by NRG Oncology with stratification by metastatic disease. All investigators, patients, and funders of the study were masked to group allocation. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This trial is registered with Clinicaltrials.gov, NCT01236547, and is complete.FINDINGS: The safety run-showed the final dosing regimen to be safe based on two out of nine participants having adverse events of predefined concern. Between June 23, 2014, and Dec 30, 2016, 89 patients were enrolled to the phase 2 trial, of whom 71 were eligible (36 in the pazopanib group and 35 in the placebo group; 34 [48%] males and 37 [52%] females). At the final analysis (data cutoff March 9, 2020), with a median follow-up of 2·9 years (IQR 0·002-4·0), 61 patients had died. Overall survival was not significantly improved with pazopanib versus placebo, with a median overall survival of 5·7 months (95% CI 4·0-12·8) in the pazopanib group versus 7·3 months (4·3-10·6) in the placebo group (hazard ratio 0·86, 95% CI 0·52-1·43; one-sided log-rank p=0·28). 1-year overall survival was 37·1% (95% CI 21·1-53·2) in the pazopanib group and 29·0% (13·2-44·8) in the placebo group. The incidence of grade 3-5 adverse events did not differ significantly between the treatment groups (pazopanib 88·9% [32 of 36 patients] and placebo 85·3% [29 of 34 patients]; p=0·73). The most common clinically significant grade 3-4 adverse events in the 70 eligible treated patients (36 in the pazopanib group and 34 in the placebo group) were dysphagia (13 [36%] vs 10 [29%]), radiation dermatitis (8 [22%] vs 13 [38%]), increased alanine aminotransferase (12 [33%] vs none), increased aspartate aminotransferase (eight [22%] vs none), and oral mucositis (five [14%] vs eight [24%]). Treatment-related serious adverse events were reported for 16 (44%) patients on pazopanib and 12 (35%) patients on placebo. The most common serious adverse events were dehydration and thromboembolic event (three [8%] each) in patients on pazopanib and oral mucositis (three [8%]) in those on placebo. There was one treatment-related death in each group (sepsis in the pazopanib group and pneumonitis in the placebo group).INTERPRETATION: To our knowledge, this study is the largest randomised anaplastic thyroid cancer study that has completed accrual showing feasibility in a multicenter NCI National Clinical Trials Network setting. Although no significant improvement in overall survival was recorded in the pazopanib group, the treatment combination was shown to be feasible and safe, and hypothesis-generating data that might warrant further investigation were generated.FUNDING: National Cancer Institute and Novartis.

  View details for DOI 10.1016/S1470-2045(22)00763-X

  View details for PubMedID 36681089

• AMADEUS TRIAL: TUMOR AGNOSTIC PRE- AND ONTREATMENT BIOMARKERS OF RESPONSE TO NIVOLUMAB PLUS IPILIMUMAB CORRELATE WITH ONTREATMENT TUMORAL T CELL INFILTRATION Alayli, F., Okrah, K., Tsimberidou, A., Drakaki, A., Khalil, D., Khan, S., Hodi, S., Oh, D., Amouzgar, M., Guatam, S., Kageyama, R., Pfeiffer, S., Meier, S., Cabanski, C., Da Silva, D., Kumar, D., Santulli-Marotto, S., Tetzlaff, M., Foo, W., Hollman, T., Li, Y., Adamow, M., Wong, P., Spasic, M., Chen, R., Bucktrout, S., Fairchild, J., Butterfield, L., LaVallee, T., Padron, L., Salvador, L., O'Donnell-Tormey, J., Dugan, U., Sharma, P. BMJ PUBLISHING GROUP. 2022: A614

  View details for DOI 10.1136/jitc-2022-SITC2022.0587

  View details for Web of Science ID 000919423400550

• Abemaciclib in metastatic or locally advanced anaplastic thyroid cancer. Khanna, V., Miles, C., Sundaram, V., Sheth, S., Steffen, M., Biedermann, S., Jun, D., Winters, E., Khan, S. A. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for Web of Science ID 000863680305043

• A phase II study of tarloxotinib (a hypoxia activated prodrug of a pan-erb tyrosine kinase inhibitor) in patients with recurrent or metastatic squamous cell carcinoma of the head and neck or skin. Investigational new drugs McLean, L. S., Morris, T. A., Gramza, A., Liu, S., Khan, S. A., Colevas, A. D., Pearce, T., Rischin, D. 2022

  Abstract

  BACKGROUND: Tarloxotinib, a hypoxia-activated prodrug of an irreversible pan-ErbB tyrosine kinase inhibitor, represents a novel therapeutic which exploits the tumor-specific hypoxic environment as a mechanism for tumor-specific targeting. This study evaluated the safety and activity of tarloxotinib in recurrent or metastatic (R/M) cutaneous (CSCC) or head and neck squamous cell carcinoma (HNSCC).METHODS: This was a phase II two-stage multi-centre study for patients with R/M HNSCC or CSCC. All patients received tarloxotinib 150mg/m2 on days 1,8,15 and 22 in a 28-day cycle. Stage 1 enrolled patients in three cohorts: p16-negative HNSCC, p16-positive oropharyngeal SCC, and CSCC. In order for a cohort to proceed to stage 2 a minimum response rate of 5% was required.RESULTS: 30 patients were enrolled: 23% were female with median age of 63.3 years. The median duration of follow-up was 20 weeks. The median progression-free survival was 2.0 months (95%CI 1.8-3.4) and median overall survival 5.7 months (95%CI 3.6-8.0). Treatment was well tolerated. The objective response rate was 3% with one patient with CSCC having a partial response.CONCLUSIONS: Hypoxia-activated prodrugs represent a novel approach to cancer treatment, however, no clinically meaningful benefit for tarloxotinib in R/M HNSCC or CSCC was identified in this study.TRIAL REGISTRATION NUMBER: NCT02449681 (May 20, 2015).

  View details for DOI 10.1007/s10637-022-01230-w

  View details for PubMedID 35435625

• Clinical Role of Positron Emission Tomography/Computed Tomography Imaging in Head and Neck Squamous Cell Carcinoma. PET clinics Abdalla, A. S., Sheybani, N. D., Khan, S. A. 2022

  Abstract

  Head and neck squamous cell carcinoma (HNSCC) imaging is nearly synonymous with positron emission tomography (PET) scans. Many of the nearly 60,000 newly diagnosed patients with HNSCC in the US-and 900,000 worldwide-will undergo a PET scan, if not multiple, throughout the course of their care. In this review, we describe the clinical utility of PET scans in HNSCC, emphasizing whereby their input is most impactful in improving patient outcomes as well as scenarios whereby PET/CT scans should be avoided. We also describe important considerations for capturing and processing PET scans with a special focus on the important role of tumor volume segmentation, scan timing relative to therapy, and concurrent conditions (eg, COVID-19). In addition, we will illustrate the latest innovations in the management of HNSCC. This article also will delve to exhibit novel potential biomarkers in the management of HNSCC. Finally, we describe future directions for PET imaging, including the advent of novel PET radiotracers as an alternative to 18F-fluorodeoxyglucose (18F-FDG).

  View details for DOI 10.1016/j.cpet.2021.12.008

  View details for PubMedID 35256298

• Risk factors for ED visits and admissions during outpatient chemotherapy in head and neck cancer Shukla, N., Saraswathula, A., Khan, S. A., Divi, V. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2020.39.28_suppl.223

  View details for Web of Science ID 000707130200219

• Extracapsular extension, pathologic node status, and adjuvant treatment in primary surgery patients with human papillomavirus-mediated oropharyngeal cancer: A national hospital-based retrospective cohort analysis. Head & neck Day, A. T., Yang, A. M., Tanamal, P., Blackwell, J., Wang, E., Sumer, B. D., Bishop, J. A., Hughes, R. S., Khan, S. A., Sher, D. J. 2021

  Abstract

  BACKGROUND: The significance of extracapsular extension (ECE) and adjuvant treatment paradigm in patients with surgically managed human papillomavirus-positive (HPV+) oropharyngeal cancer (OPC) is debated.METHODS: National, hospital-based, retrospective cohort study of 2663 patients pN+ HPV+ OPC who underwent primary surgery.RESULTS: Patients with ECE had a 1.74-times risk of death (95% confidence interval [CI]: 1.26-2.40, p=0.001) compared to patients without ECE. Among patients with pN1, ECE-positive disease, risk of overall mortality was similar across treatment paradigms (surgery alone: ref; adjuvant radiation therapy [RT]: aHR: 0.81; 95% CI: 0.36-1.85; p=0.62; adjuvant CRT: aHR: 0.66; 95% CI: 0.34-1.32; p=0.24). Patients with pN2 ECE-positive disease treated with adjuvant RT alone exhibited similar risk of all-cause mortality (hazard ratio: 1.04, 95% CI: 0.24-4.47, p=0.96) compared to adjuvant chemoradiation (CRT). In patients with advanced, ECE-positive disease (e.g., pT3-T4pN2), adjuvant CRT did not reduce the risk of overall mortality relative to adjuvant RT.CONCLUSION: Although pathologic ECE negatively predicts for survival in patients with HPV+ OPC, our analyses support expansion of postoperative de-intensification clinical trial eligibility criteria in patients with ECE-positive disease.

  View details for DOI 10.1002/hed.26825

  View details for PubMedID 34331477

• NRG Oncology HN006: Randomized phase II/III trial of sentinel lymph node biopsy versus elective neck dissection for early-stage oral cavity cancer. Lai, S., Torres-Saavedra, P. A., Dunlap, N. E., Beadle, B., Chang, S. S., Subramaniam, R. M., Yu, J., Lowe, V. J., Khan, S. A., Truong, M., Bell, D., Liu, C. Z., Kovalchuk, N., Rong, Y., Abazeed, M. E., Kappadath, S., Harris, J., Le, Q. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2021.39.15_suppl.TPS6093

  View details for Web of Science ID 000708120307003

• Genomic Analysis of Salivary Gland Cancer and Treatment of Salivary Gland Cancers. Surgical pathology clinics Palsgrove, D., Allahabadi, S., Khan, S. A. 2021; 14 (1): 151–63

  Abstract

  Salivary gland cancer is a heterogenous group of tumors that presents challenges with both diagnosis and therapy. Recent advances in the classification of salivary gland cancers have led to distinct histologic and genomic criteria that successfully differentiate between cancers with similar clinical behavior and appearance. Genomic abnormalities have led to the emergence of targeted therapies being used in their therapy with drastic improvements in outcomes as well as reductions in treatment-related toxicity. Dramatic results seen with molecular targets, such as HER2, TRK, and others, indicate that this approach has the potential to yield even better treatments for the future.

  View details for DOI 10.1016/j.path.2020.10.001

  View details for PubMedID 33526219

• Efficacy and Safety of Glembatumumab Vedotin in Patients With Advanced or Metastatic Squamous Cell Carcinoma of the Lung (PrECOG 0504) Khan, S., Sun, Z., Pillai, R., Dahlberg, S., Malhotra, J., Keresztes, R., Ikpeazu, C., Ma, P., Ramalingam, S. ELSEVIER SCIENCE INC. 2021: S131-S132

  Abstract

  Glycoprotein NMB is a transmembrane protein linked with poor prognosis and is expressed in most squamous lung cancer. Glembatumumab vedotin is an antibody-drug conjugate targeting glycoprotein NMB, administered intravenously every 3 weeks in this phase 1 study to determine the safety, tolerability, and maximum tolerated dose in patients who had progressed on any number of previous therapies.A total of 13 patients were enrolled; adverse events (of any grade) including dyspnea, neutropenia, respiratory failure, anemia, increased aspartate transaminase/alanine transaminase, diarrhea, and hypophosphatemia were seen in 15% of patients. Grade 5 events included two cases of respiratory failure, either completely or partially attributed to cancer progression. The only other grade 5 event was "disease progression." The most common adverse events (23%) were decreased appetite, fatigue, rash, and weight loss.The median overall and progression-free survivals were 5.7 months (90% confidence interval: 2.5-16.8) and 2.5 months (90% confidence interval: 1.6-5.8) respectively.Glembatumumab vedotin exhibited no serious or unexpected toxicity in this heavily pretreated population, except those caused by disease progression. Modest anticancer activity was observed with a recommendation for a phase 2 dose of 1.9 mg/kg. This portion of the study was not undertaken owing to the company's decision to discontinue drug development.

  View details for Web of Science ID 000631349600122

  View details for PubMedID 34590018

  View details for PubMedCentralID PMC8474292

• Association between body mass index, dosing strategy, and efficacy of immune checkpoint inhibitors JOURNAL FOR IMMUNOTHERAPY OF CANCER Ahmed, M., von Itzstein, M. S., Sheffield, T., Khan, S., Fattah, F., Park, J. Y., Popat, V., Saltarski, J. M., Gloria-McCutchen, Y., Hsiehchen, D., Ostmeyer, J., Khan, S. A., Sultana, N., Xie, Y., Li, Q., Wakeland, E. K., Gerber, D. E. 2021; 9 (6)

  Abstract

  Increased body mass index (BMI) has been associated with improved response to immune checkpoint inhibitors (ICIs) in multiple cancer types. We evaluated associations between BMI, ICI dosing strategy, and clinical outcomes.We abstracted clinical data on patients with cancer treated with ICI, including age, sex, cancer type, BMI, ICI type, dosing strategy (weight-based or fixed), radiographic response, overall survival (OS), and progression-free survival (PFS). We compared clinical outcomes between low-BMI and high-BMI populations using Kaplan-Meier curves, Cox regressions, and Pearson product-moment correlation coefficients.A total of 297 patients were enrolled, of whom 40% were women and 59% were overweight (BMI≥25). Of these, 204 (69%) received fixed and 93 (31%) received weight-based ICI dosing. In the overall cohort, overweight BMI was associated with improved PFS (HR 0.69; 95% CI 0.51 to 0.94; p=0.02) and had a trend toward improved OS (HR 0.77; 95% CI 0.57 to 1.04; p=0.08). For both endpoints, improved outcomes in the overweight population were limited to patients who received weight-based ICI dosing (PFS HR 0.53; p=0.04 for weight-based; vs HR 0.79; p=0.2 for fixed dosing) (OS HR 0.56; p=0.03 for weight-based; vs HR 0.89; p=0.54 for fixed dosing). In multivariable analysis, BMI was not associated with PFS or OS. However, the interaction of BMI≥25 and weight-based dosing had a trend toward association with PFS (HR 0.53; 95% CI 0.26 to 1.10; p=0.09) and was associated with OS (HR 0.50; 95% CI 0.25 to 0.99; p=0.05). Patients with BMI<25 tended to have better outcomes with fixed-dose compared with weight-based ICI, while patients with BMI≥25 tended to have better outcomes with weight-based ICI, although these differences did not achieve statistical significance. There was no association between radiographic response and BMI with fixed-dose ICI (p=0.97), but a near-significant trend with weight-based ICI (p=0.1). In subset analyses, the association between BMI, ICI dosing strategy, and clinical outcomes appeared limited to men.The clinical benefit of ICI in high-BMI populations appears limited to individuals receiving weight-based ICI dosing. Further research into optimal ICI dosing strategies may be warranted.

  View details for DOI 10.1136/jitc-2021-002349

  View details for Web of Science ID 000691842800004

  View details for PubMedID 34127546

  View details for PubMedCentralID PMC8237749

• Survivin expression and impact on head and neck cancer outcomes. Oral oncology Khan, S. A., Burke, M., Zhu, F., Yang, D., Dubyk, C., Mehra, R., Lango, M. J., Ridge, J. A., Sher, D. J., Burtness, B. 2020; 112: 105049

  Abstract

  INTRODUCTION: Survivin is an inhibitor of apoptosis that is proposed as a target for anti-cancer therapy because of its high expression in cancer cells. It has potential as a prognostic and predictive biomarker of response to radiation and systemic therapies. We report its expression in head and neck squamous cell carcinoma (HNSCC) and its correlation with treatment response and survival.METHODS: We measured survivin protein expression in tumor specimens from 96 patients with HNSCC treated at Fox Chase Cancer Center, of whom 21 were p16+. Quantitative automated immunofluorescence was employed to score nuclear and cytoplasmic survivin in 5 tissue microarrays (TMAs) consisting of 316 H&N tumor cores and 107 control tissue cores. Survivin levels were then correlated to therapy response and survival outcomes.RESULTS: Using the median score as the cutoff, overall survival (OS) was significantly shorter for the group expressing higher survivin in nuclear (p=0.013), cytoplasmic (p=0.018) and total compartments (p=0.006). No correlation was seen between survivin expression and patient sex or grade of tumor, T or N stage, or p16 status. Survivin expression in metastases did not significantly differ from that in primary tumors. Levels of p53 expression showed a significant positive correlation with higher survivin expression in the cytoplasm (p=0.0264) and total compartments (p=0.0264), but not in the nucleus (p=0.0729).CONCLUSIONS: Survivin expression above the median is associated with shorter overall survival in HNSCC, including for patients treated with chemotherapy or radiation. p16 expression did not correlate with survivin levels.

  View details for DOI 10.1016/j.oraloncology.2020.105049

  View details for PubMedID 33221541

• Head and neck oncology during the COVID-19 pandemic: Reconsidering traditional treatment paradigms in light of new surgical and other multilevel risks ORAL ONCOLOGY Day, A. T., Sher, D. J., Lee, R. C., Truelson, J. M., Myers, L. L., Sumer, B. D., Stankova, L., Tillman, B. N., Hughes, R. S., Khan, S. A., Gordin, E. A. 2020; 105: 104684

  Abstract

  The COVID-19 pandemic demands reassessment of head and neck oncology treatment paradigms. Head and neck cancer (HNC) patients are generally at high-risk for COVID-19 infection and severe adverse outcomes. Further, there are new, multilevel COVID-19-specific risks to patients, surgeons, health care workers (HCWs), institutions and society. Urgent guidance in the delivery of safe, quality head and neck oncologic care is needed. Novel barriers to safe HNC surgery include: (1) imperfect presurgical screening for COVID-19; (2) prolonged SARS-CoV-2 aerosolization; (3) occurrence of multiple, potentially lengthy, aerosol generating procedures (AGPs) within a single surgery; (4) potential incompatibility of enhanced personal protective equipment (PPE) with routine operative equipment; (5) existential or anticipated PPE shortages. Additionally, novel, COVID-19-specific multilevel risks to HNC patients, HCWs and institutions, and society include: use of immunosuppressive therapy, nosocomial COVID-19 transmission, institutional COVID-19 outbreaks, and, at some locations, societal resource deficiencies requiring health care rationing. Traditional head and neck oncology doctrines require reassessment given the extraordinary COVID-19-specific risks of surgery. Emergent, comprehensive management of these novel, multilevel surgical risks are needed. Until these risks are managed, we temporarily favor nonsurgical therapy over surgery for most mucosal squamous cell carcinomas, wherein surgery and nonsurgical therapy are both first-line options. Where surgery is traditionally preferred, we recommend multidisciplinary evaluation of multilevel surgical-risks, discussion of possible alternative nonsurgical therapies and shared-decision-making with the patient. Where surgery remains indicated, we recommend judicious preoperative planning and development of COVID-19-specific perioperative protocols to maximize the safety and quality of surgical and oncologic care.

  View details for DOI 10.1016/j.oraloncology.2020.104684

  View details for Web of Science ID 000533567700021

  View details for PubMedID 32330858

  View details for PubMedCentralID PMC7136871

• Late-Onset Immunotherapy Toxicity and Delayed Autoantibody Changes: Checkpoint Inhibitor-Induced Raynaud's-Like Phenomenon ONCOLOGIST Khan, S., von Itzstein, M. S., Lu, R., Bermas, B. L., Karp, D. R., Khan, S. A., Fattah, F. J., Park, J. Y., Saltarski, J. M., Gloria-McCutchen, Y., Xie, Y., Li, Q., Wakeland, E. K., Gerber, D. E. 2020; 25 (5): E753-E757

  Abstract

  Immune checkpoint inhibitor (ICI)-induced immune-related adverse events (irAEs) may affect almost any organ system and occur at any point during therapy. Autoantibody analysis may provide insight into the mechanism, nature, and timing of these events. We report a case of ICI-induced late-onset Raynaud's-like phenomenon in a patient receiving combination immunotherapy. A 53-year-old woman with advanced non-small lung cancer received combination anti-cytotoxic T-lymphocyte antigen 4 and anti-programmed death 1 ICI therapy. She developed early (hypophysitis at 4 months) and late (Raynaud's at >20 months) irAEs. Longitudinal assessment of 124 autoantibodies was correlated with toxicity. Although autoantibody levels were generally stable for the first 18 months of therapy, shortly before the development of Raynaud's, a marked increase in multiple autoantibodies was observed. This case highlights the potential for delayed autoimmune toxicities and provides potential biologic insights into the dynamic nature of these events. KEY POINTS: A patient treated with dual anti-PD1 and anti-CTLA4 therapy developed Raynaud's-like signs and symptoms more than 18 months after starting therapy. In this case, autoantibody changes became apparent shortly before onset of clinical toxicity. This case highlights the potential for late-onset immune-related adverse events checkpoint inhibitors, requiring continuous clinical vigilance. The optimal duration of checkpoint inhibitor therapy in patients with profound and prolonged responses remains unclear.

  View details for DOI 10.1634/theoncologist.2019-0666

  View details for Web of Science ID 000534394900002

  View details for PubMedID 32167195

  View details for PubMedCentralID PMC7216445

• Unique Patterns of Distant Metastases in HPV-Positive Head and Neck Cancer ONCOLOGY Sacks, R., Law, J. Y., Zhu, H., Beg, M. S., Gerber, D. E., Sumer, B. D., Myers, L. L., Truelson, J. M., Nedzi, L., Sher, D., Hughes, R. S., Khan, S. A. 2020; 98 (3): 179-185

  Abstract

  HPV-positive head and neck squamous cell carcinoma (HPV+ HNSCC) demonstrates favorable outcomes compared to HPV-negative SCC, but distant metastases (DM) still occur. The pattern of DM in HPV+ HNSCC is unclear.1,494 HNSCC patients were treated from 2006 to 2012. Recurrence time and metastatic sites in HPV+ HNSCC (Group 1) were compared to patients with HPV-negative/unknown cancers arising in the hypopharynx, larynx, or glottis (Group 2) as well as to patients with HPV-negative/unknown cancers in theoral cavity, oropharynx, hard palate, or tonsil (Group 3).7/109 (6.4%) patients with HPV+ HNSCC developed DM. The median time to metastases was 11 months. At a median follow-up of 18-25 months, there was no difference in the overall rate of DM for the HPV+ HNSCC group compared to Group 2 (HPV-/unknown) (p = 0.21) and Group 3 (HPV-/unknown) (p = 0.13). There was a significant difference in the rate of DM to the lung in the HPV+ HNSCC group compared to Group 2 (HPV-/unknown) (p = 0.012) and Group 3 (HPV-/unknown) (p = 0.002).There was no observed difference in the time to development of DM between the HPV-/unknown and HPV+ HNSCC groups. However, the HPV+ HNSCC group showed a higher rate of DM to the lung compared to the HPV-/unknown -HNSCC group (p = 0.002).

  View details for DOI 10.1159/000504651

  View details for Web of Science ID 000519117200008

  View details for PubMedID 31846962

• Safety and Efficacy of Andecaliximab (GS-5745) Plus Gemcitabine and Nab-Paclitaxel in Patients with Advanced Pancreatic Adenocarcinoma: Results from a Phase I Study. The oncologist Bendell, J. n., Sharma, S. n., Patel, M. R., Windsor, K. S., Wainberg, Z. A., Gordon, M. n., Chaves, J. n., Berlin, J. n., Brachmann, C. B., Zavodovskaya, M. n., Liu, J. n., Thai, D. n., Bhargava, P. n., Shah, M. A., Khan, S. A., Starodub, A. n. 2020

  Abstract

  Matrix metalloproteinase 9 (MMP9) expression in the tumor microenvironment is implicated in multiple protumorigenic processes. Andecaliximab (GS-5745), a monoclonal antibody targeting MMP9 with high affinity and selectivity, was evaluated in combination with gemcitabine and nab-paclitaxel in patients with advanced pancreatic adenocarcinoma.This phase I study was completed in two parts: part A was a dose-finding, monotherapy phase that enrolled patients with advanced solid tumors, and part B examined andecaliximab in combination with chemotherapy in specific patient cohorts. In the cohort of patients with pancreatic adenocarcinoma (n = 36), andecaliximab 800 mg every 2 weeks was administered in combination with gemcitabine and nab-paclitaxel. Patients were treated until unacceptable toxicity, withdrawal of consent, disease progression, or death. Efficacy, safety, and biomarker assessments were performed.Andecaliximab combined with gemcitabine and nab-paclitaxel appeared to be well tolerated and did not demonstrate any unusual toxicities in patients with pancreatic adenocarcinoma. The most common treatment-emergent adverse events were fatigue (75.0%), alopecia (55.6%), peripheral edema (55.6%), and nausea (50.0%). Median progression-free survival was 7.8 months (90% confidence interval, 6.9-11.0) with an objective response rate of 44.4% and median duration of response of 7.6 months. Maximal andecaliximab target binding, defined as undetectable, andecaliximab-free MMP9 in plasma, was observed.Andecaliximab in combination with gemcitabine and nab-paclitaxel demonstrates a favorable safety profile and clinical activity in patients with advanced pancreatic adenocarcinoma.The combination of andecaliximab, a novel, first-in-class inhibitor of matrix metalloproteinase 9, with gemcitabine and nab-paclitaxel in patients with advanced pancreatic adenocarcinoma provided a median progression-free survival of 7.8 months and objective response rate of 44.4%. The majority of systemic biomarkers related to matrix metalloproteinase 9 activity and immune suppression increased at 2 months, whereas biomarkers related to tumor burden decreased. Although this study demonstrates promising results with andecaliximab plus chemotherapy in patients with advanced pancreatic adenocarcinoma, andecaliximab was not associated with a survival benefit in a phase III study in patients with advanced gastric/gastroesophageal junction carcinoma.

  View details for DOI 10.1634/theoncologist.2020-0474

  View details for PubMedID 32812320

• Novel anti-EGFR antibody-drug conjugate AVID100: A phase 2a trial in patients with EGFR-overexpressing advanced solid tumors Melear, J., Lakhani, N., O'Shaughnessy, J. A., Wilks, S. T., Khan, S., Chandana, S. R., Tolcher, A. W., Papadopoulos, K. P., Cole, Y., Rivas, K., Ghosh, R., Sinclair, S., Lutz, R., Nadler, P. I., Wood, D. L., Burtness, B. AMER ASSOC CANCER RESEARCH. 2019

  View details for DOI 10.1158/1535-7163.TARG-19-A088

  View details for Web of Science ID 000510047200076

• Therapy with tyrosine kinase inhibitor lenvatinib in radioactive iodine-naive advanced differentiated thyroid cancer INTERNATIONAL JOURNAL OF ENDOCRINE ONCOLOGY Sukumar, J., Moore, W., Khan, S. A. 2019; 6 (4)

  View details for DOI 10.2217/ije-2019-0007

  View details for Web of Science ID 000512669200002

• Head and neck neuroendocrine tumors at a single institution over 15 years CLINICAL CASE REPORTS Bacalao, M., Beg, M. S., Cavuoti, D., Zhu, H., Sumer, B., Myers, L., Truelson, J., Nedzi, L., Sher, D., Hughes, R., Khan, S. A. 2019; 7 (12): 2508-2512

  Abstract

  Head and neck cancer is a diverse group of rare diseases such as neuroendocrine tumors which can be thought of as extrapulmonary small-cell cancer. Surgery, chemotherapy, and radiation can frequently cure this disease, possibly due to early detection.

  View details for DOI 10.1002/ccr3.2545

  View details for Web of Science ID 000496753400001

  View details for PubMedID 31893090

  View details for PubMedCentralID PMC6935626

• Association of electronic medical record (EMR) QTc alerts with higher mortality within 10 days for patients with blood, lung, GI, and soft tissue cancer. Bleiberg, B., Xie, D., Lightfoot, T., Reisch, J., Khan, S. A. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for DOI 10.1200/JCO.2019.37.27_suppl.235

  View details for Web of Science ID 000518223100232

• Confluent tracheal recurrences of head and neck squamous cell carcinoma CLINICAL CASE REPORTS Bleiberg, B., Abu-Hijleh, M., Moore, W., Khan, S. A. 2019; 7 (10): 1849-1853

  Abstract

  Tracheal head and neck squamous cell cancer recurrence without metastases may be related to physical displacement of cancer cells.

  View details for DOI 10.1002/ccr3.2371

  View details for Web of Science ID 000481390100001

  View details for PubMedID 31624596

  View details for PubMedCentralID PMC6787807

• Unique mutation patterns in anaplastic thyroid cancer identified by comprehensive genomic profiling HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Khan, S. A., Ci, B., Xie, Y., Gerber, D. E., Beg, M. S., Sherman, S. I., Cabanillas, M. E., Busaidy, N. L., Burtness, B. A., Heilmann, A. M., Bailey, M., Ross, J. S., Sher, D. J., Ali, S. M. 2019; 41 (6): 1928-1934

  Abstract

  Anaplastic thyroid cancer (ATC) is a highly aggressive thyroid cancer. Those ATC with genomic alterations (GAs) in TSC2, ALK, and BRAF may respond to targeted therapies.Comprehensive genomic profiling on 90 ATC specimens identified base substitutions, short insertions and deletions, amplifications, copy number alterations, and genomic rearrangements in up to 315 cancer-related genes and 28 genes commonly rearranged in cancer.Median patient age was 65 (range, 33-86) years, 50 patients were male. There was a mean of 4.2 GA per case, range 1-11. The most common GA were TP53 (66%), BRAF (34%), TERT (32%), CDKN2A (32%), and NRAS (26%). BRAF V600E and NRAS/HRAS/KRAS alteration were mutually exclusive. BRAF, CDKN2A, PIK3CA, and JAK2 were more frequent in patients >70 years of age; while myc, PTEN, and NRAS were more common in those ≤50 years.ATC shows many GA with potential therapeutic significance and suggesting different molecular pathways can lead to ATC.

  View details for DOI 10.1002/hed.25634

  View details for Web of Science ID 000468629500048

  View details for PubMedID 30758123

• Evaluating sociodemographic, behavioral and psychologic disparities in 918 head and neck cancer survivors. Day, A. T., Vasudevan, A., Wynings, E., Balachandra, S., Khan, S. A., Sumer, B. D., Murphy, C. C. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for DOI 10.1200/JCO.2019.37.15_suppl.e17541

  View details for Web of Science ID 000487345801760

• Risk of Unplanned Hospital Encounters in Patients Treated With Radiotherapy for Head and Neck Squamous Cell Carcinoma JOURNAL OF PAIN AND SYMPTOM MANAGEMENT Moore, Z. R., Nhat-Long Pham, Shah, J., Nedzi, L., Sumer, B. D., Day, A. T., Khan, S. A., Sher, D. J. 2019; 57 (4): 738-+

  Abstract

  Radiotherapy is highly effective for treating squamous cell carcinoma of the head and neck but is often associated with significant toxicities and severe morbidity. Unplanned emergency department (ED) visits and hospitalizations are common during treatment and come with a substantial financial and health burden as well as the potential for impaired long-term outcomes due to treatment disruption.The objective of this study was to identify patient, disease, and treatment characteristics that were associated with ED encounters and admissions.A cohort of 462 patients with cancer of the head and neck treated with radiotherapy at UT Southwestern between 2010 and 2015 was retrospectively analyzed. The risks of ED visits, admissions, multiple admissions, and extended admissions were determined. Risk factors for an unplanned hospital encounter were analyzed using univariate and multivariate logistic regression.Overall, 36% of patients had an unplanned hospital encounter during the treatment window. Patients with advanced disease, those with high comorbidity score, and those treated with concurrent chemotherapy were more likely to have unplanned admissions/ED visits. Social factors such as marital status, smoking status, and registration in the public hospital system were also strongly associated with admissions and multiple encounters.The high rate of admissions and ED visits emphasizes the importance of anticipating and managing toxicities during treatment. Social factors have a strong association with unplanned encounters and may present opportunities for targeted interventions to reduce admissions for patients at highest risk.

  View details for DOI 10.1016/j.jpainsymman.2018.12.337

  View details for Web of Science ID 000462027900006

  View details for PubMedID 30610892

• Association between treatment delays and oncologic outcome in patients treated with surgery and radiotherapy for head and neck cancer HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Tumati, V., Hoang, L., Sumer, B. D., Truelson, J. M., Myers, L. L., Khan, S., Hughes, R. S., Nedzi, L., Sher, D. J. 2019; 41 (2): 315-321

  Abstract

  This study sought to determine the oncologic impact of delays to surgery, radiotherapy, and completion of therapy in patients with head and neck squamous cell carcinoma.The impact of biopsy to surgery (BTS) time, surgery to start of radiation time (STSR), and radiation treatment time (RTT) on locoregional recurrence (LRR), distant metastases (DMs), and cancer-specific mortality (CSM) was examined. The cumulative incidences (CI) of LRR, DMs, and CSM were examined using Fine-Gray testing.A total of 277 patients treated with surgery and adjuvant radiotherapy were analyzed. On multivariable testing, BTS >50 days was associated with DM (P = .03), whereas RTT and STSR were not. RTT >43 days was associated with LRR (P = .02) in patients with non-p16-positive-oropharynx cancer.An increase in DM appears to be the mechanism by which prolonged time to treatment initiation leads to worse overall survival. Prolonged RTT has the greatest impact on patients with non-p16 positive oropharynx cancers.

  View details for DOI 10.1002/hed.25457

  View details for Web of Science ID 000457416500010

  View details for PubMedID 30548892

• Blocking Monocytic Myeloid-Derived Suppressor Cell Function via Anti-DC-HIL/GPNMB Antibody Restores the In Vitro Integrity of T Cells from Cancer Patients CLINICAL CANCER RESEARCH Kobayashi, M., Chung, J., Beg, M., Arriaga, Y., Verma, U., Courtney, K., Mansour, J., Haley, B., Khan, S., Horiuchi, Y., Romani, V., Harker, D., Gopal, P., Araghizadeh, F., Cruz, P. D., Ariizumi, K. 2019; 25 (2): 828-838

  Abstract

  Blocking the function of myeloid-derived suppressor cells (MDSC) is an attractive approach for cancer immunotherapy. Having shown DC-HIL/GPNMB to be the T-cell-inhibitory receptor mediating the suppressor function of MDSCs, we evaluated the potential of anti-DC-HIL mAb as an MDSC-targeting cancer treatment.Patients with metastatic cancer (n = 198) were analyzed by flow cytometry for DC-HIL or PDL1 expression on blood CD14+HLA-DRno/lo MDSCs. Their suppressor function was assessed by in vitro coculture with autologous T cells, and the ability of anti-DC-HIL or anti-PDL1 mAb to reverse such function was determined. Tumor expression of these receptors was examined histologically, and the antitumor activity of the mAb was evaluated by attenuated growth of colon cancers in mice.Patients with metastatic cancer had high blood levels of DC-HIL+ MDSCs compared with healthy controls. Anti-DC-HIL mAb reversed the in vitro function in ∼80% of cancer patients tested, particularly for colon cancer. Despite very low expression on blood MDSCs, anti-PDL1 mAb was as effective as anti-DC-HIL mAb in reversing MDSC function, a paradoxical phenomenon we found to be due to upregulated expression of PDL1 by T-cell-derived IFNγ in cocultures. DC-HIL is not expressed by colorectal cancer cells but by CD14+ cells infiltrating the tumor. Finally, anti-DC-HIL mAb attenuated growth of preestablished colon tumors by reducing MDSCs and increasing IFNγ-secreting T cells in the tumor microenvironment, with similar outcomes to anti-PDL1 mAb.Blocking DC-HIL function is a potentially useful treatment for at least colorectal cancer with high blood levels of DC-HIL+ MDSCs.See related commentary by Colombo, p. 453.

  View details for DOI 10.1158/1078-0432.CCR-18-0330

  View details for Web of Science ID 000456143100039

  View details for PubMedID 30049749

• Immune dysregulation in cancer patients developing immune-related adverse events BRITISH JOURNAL OF CANCER Khan, S., Khan, S. A., Luo, X., Fattah, F. J., Saltarski, J., Gloria-McCutchen, Y., Lu, R., Xie, Y., Li, Q., Wakeland, E., Gerber, D. E. 2019; 120 (1): 63-68

  Abstract

  Up to 40% of cancer patients on immune checkpoint inhibitors develop clinically significant immune-related adverse events (irAEs). The role of host immune status and function in predisposing patients to the development of irAEs remains unknown.Sera from 65 patients receiving immune checkpoint inhibitors and 13 healthy controls were evaluated for 40 cytokines at pre-treatment, after 2-3 weeks and after 6 weeks and analysed for correlation with the development of irAEs.Of the 65 cancer patients enrolled, 55% were women; the mean age was 65 years and 98% received anti-PD1/PDL1 therapy. irAEs occurred in 35% of cases. Among healthy controls, cytokine levels were stable over time and lower than those in cancer patients at baseline. Significant increases in CXCL9, CXCL10, CXCL11 and CXCL13 occurred 2 weeks post treatment, and in CXCL9, CXCL10, CXCL11, CXCL13, IL-10 and CCL26 at 6 weeks post treatment. Patients who developed irAEs had lower levels of CXCL9, CXCL10, CXCL11 and CXCL19 at baseline and exhibited greater increases in CXCL9 and CXCL10 levels at post treatment compared to patients without irAEs.Patients who developed irAEs have lower baseline levels and greater post-treatment increases in multiple cytokine levels, suggesting that underlying immune dysregulation may be associated with heightened risk for irAEs.

  View details for DOI 10.1038/s41416-018-0155-1

  View details for Web of Science ID 000455095200010

  View details for PubMedID 30377338

• Activity and pharmacology of homemade silver nanoparticles in refractory metastatic head and neck squamous cell cancer HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Singh, J., Moore, W., Fattah, F., Jiang, X., Zheng, J., Kurian, P., Beg, M. S., Khan, S. A. 2019; 41 (1): E11-E15

  Abstract

  Silver nanoparticles (AgNP) show efficacy in cancer cell lines. We present the first in-human outcome of AgNP in a cancer patient.Homemade AgNP solution is manufactured using online instructions by a 78-year old male. He started consuming AgNP while on hospice after he developed nasal cavity squamous cell cancer metastatic to liver and lung.Electron microscopy of AgNP solution revealed bimodal nanoparticle size distribution: 3 and 12 nm. Inductively coupled plasma mass spectrometry showed basal silver ion concentrations of 32 ng/g, rising to 46 ng/g 1 hour after ingesting 60 mL of AgNP solution. Urine showed no AgNP. No toxicities were observed and he had complete radiographic resolution of his cancer. He remains without evidence of cancer 18 months later.AgNP ingestion was associated with sustained radiographic resolution of cancer. Further testing of AgNP should be done to confirm its efficacy in head and neck cancer.

  View details for DOI 10.1002/hed.25492

  View details for Web of Science ID 000456174700003

  View details for PubMedID 30537286

• Comparative effectiveness of primary radiotherapy versus surgery in elderly patients with locally advanced oropharyngeal squamous cell carcinoma ORAL ONCOLOGY Sher, D. J., Yan, J., Day, A., Sumer, B. D., Nhat-Long Pham, Khan, S., Zhu, H. 2019; 88: 18-26

  Abstract

  To determine the comparative effectiveness of primary radiotherapy (RT) and primary surgery (PS) for locally advanced oropharyngeal squamous cell carcinoma (OPSCC).Eligible individuals were patients in the SEER-Medicare registry diagnosed with locally advanced OPSCC between 2000 and 2011. Patients were categorized as receiving either primary RT ± chemotherapy, or PS ± adjuvant RT or chemoradiotherapy (CRT). Overall survival (OS) was analyzed using Cox multivariable analysis (MVA). Risks of gastrostomy dependence (GD), esophageal stricture (ES), and osteoradionecrosis (ORN) were analyzed using logistic regression.A total of 2754 patients (69% RT, 31% PS) were included in this cohort, with a median age of 72 years. Patients treated with RT, CRT and PS experienced 3-year OS outcomes of 36.1%, 52.8%, and 54.9%, respectively (p < 0.001). Increasing age, unmarried status, increasing comorbidity, lower income, base of tongue (BOT) site, higher stage, no prior PET, and RT alone (but not CRT) were associated with inferior OS. Independent predictors of GD at 6 months included black race, BOT site, advanced stage, and CRT. The risks of ORN and stricture were not associated with treatment modality. Concurrent chemotherapy improved OS with definitive RT but had no impact in adjuvant RT. Only cisplatin- and taxane-containing regimens improved OS, but all concurrent agents, including cetuximab, significantly worsened GD.Local therapy decisions for locally advanced OPSCC must be individualized, with CRT increasing acute and chronic GD. The differential survival impact of concurrent chemotherapy in the definitive and adjuvant setting may be a consideration in decision-making.

  View details for DOI 10.1016/j.oraloncology.2018.11.004

  View details for Web of Science ID 000454890700004

  View details for PubMedID 30616791

• Prevalence and usage patterns of opiates in patients with lung, breast, and head and neck cancer. Westbrook, K., Ahn, C., Khan, S. A. AMER SOC CLINICAL ONCOLOGY. 2018

  View details for DOI 10.1200/JCO.2018.36.34_suppl.120

  View details for Web of Science ID 000464876100116

• Pan-squamous genomic profiling stratified by anatomic tumor site and viral association Montesion, M., Chung, C. H., Sokol, E. S., Khan, S. A., Kang, H., Albacker, L. A., Johnson, J. M., Frampton, G. M., Miller, V. A., Ross, J. S., Ali, S. M. OXFORD UNIV PRESS. 2018

  View details for Web of Science ID 000459277300068

• Impact of Concurrent Medication Use on Pancreatic Cancer Survival-SEER-Medicare Analysis AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS Beg, M. S., Gupta, A., Sher, D., Ali, S., Khan, S., Gao, A., Stewart, T., Ahn, C., Berry, J., Mortensen, E. M. 2018; 41 (8): 766-771

  Abstract

  Preclinical studies have suggested that non-antineoplastic medication use may impact pancreatic cancer biology. We examined the association of several medication classes on pancreatic cancer survival in a large medical claims database.Histologically confirmed pancreatic adenocarcinoma diagnosed between 2006 and 2009 were analyzed from the Surveillance, Epidemiology, and End Results-Medicare database with available part D data. Drug use was defined as having 2 prescriptions filled within 12 months of pancreatic cancer diagnosis. The following medication classes/combinations were analyzed: β-blocker, statin, insulin, metformin, thiazolidinedione, warfarin, heparin, β-blocker/statin, metformin/statin, and β-blocker/metformin. Multivariable Cox proportional hazard models adjusting for age, sex, race, stage at diagnosis, site of cancer, and Charlson comorbidity index were constructed to test the association between medication classes and overall survival.A total of 13,702 patients were included in the study; median age 76 years, 42.5% males, 77.1% white. The most common anatomic site and stage at diagnosis were head of the pancreas (49.9%) and stage 4 (49.6%), respectively. Ninety-four percent of patients died in the follow-up period (median overall survival 5.3 mo). Multivariable Cox regression analysis showed that use of β-blockers, heparin, insulin, and warfarin were significantly associated with improved survival (P<0.05 for each one), whereas metformin, thiazolidinedione, statin, and combination therapies were not.In this study, use of β-blockers, heparin, insulin, and warfarin were associated with improved survival in patients with pancreatic cancer. Additional studies are needed to validate these findings in the clinical setting.

  View details for DOI 10.1097/COC.0000000000000359

  View details for Web of Science ID 000453919800007

  View details for PubMedID 28079594

  View details for PubMedCentralID PMC5503814

• Comprehensive genomic profiling of anaplastic thyroid carcinoma Bowles, D. W., Ross, J. S., Gay, L. M., Agrawal, V., Ali, S., Khan, S. A. AMER SOC CLINICAL ONCOLOGY. 2018

  View details for DOI 10.1200/JCO.2018.36.15_suppl.6089

  View details for Web of Science ID 000442916002379

• Relationship of anaplastic thyroid cancer high tumor mutation burden and MSI-H status with response to anti-PD1 monotherapy Khan, S. A., Kurian, P., Mobley, B., Burks, T., Beg, M., Ross, J. S., Ali, S., Bowles, D. W. AMER SOC CLINICAL ONCOLOGY. 2018

  View details for DOI 10.1200/JCO.2018.36.15_suppl.e18114

  View details for Web of Science ID 000442916005665

• Underlying host immune dysregulation in cancer patients developing immune-related adverse events. Gerber, D. E., Khan, S., Luo, X., Khan, S. A., Fattah, F., Saltarski, J., Gloria-McCutchen, Y., Park, J., Xie, Y., Li, Q., Wakeland, E. AMER SOC CLINICAL ONCOLOGY. 2018

  View details for DOI 10.1200/JCO.2018.36.15_suppl.3030

  View details for Web of Science ID 000442916001403

• Safety and efficacy of concurrent immune checkpoint inhibitors and hypofractionated body radiotherapy ONCOIMMUNOLOGY Mohamad, O., de Leon, A., Schroeder, S., Leiker, A., Christie, A., Zhang-Velten, E., Trivedi, L., Khan, S., Desai, N. B., Laine, A., Albuquerque, K., Iyengar, P., Arriaga, Y., Courtney, K., Gerber, D. E., Hammers, H., Choy, H., Timmerman, R., Brugarolas, J., Hannan, R. 2018; 7 (7): e1440168

  Abstract

  Integration of hypofractionated body radiotherapy (H-RT) into immune checkpoint inhibitor (ICI) therapy may be a promising strategy to improve the outcomes of ICIs, although sufficient data is lacking regarding the safety and efficacy of this regimen. We, hereby, reviewed the safety and efficacy of this combination in 59 patients treated with H-RT during or within 8 weeks of ICI infusion and compared results with historical reports of ICI treatment alone. Most patients had RCC or melanoma. Median follow-up was 11 months. Most patients received either Nivolumab alone or with Ipilimumab; 83% received stereotactic RT and 17% received conformal H-RT. Any grade adverse events (AEs) were reported in 46 patients, and grade 3-4 in 12 patients without any treatment-related grade 5 toxicity. The most common grade 3 AEs were fatigue and pneumonitis. Grade 3-4 toxicities were higher with ICI combination and with simultaneous ICIs. Overall, most any-grade or grade ≥3 AE rates did not differ significantly from historically reported rates with single-agent or multi-agent ICIs. Toxicity did not correlate with H-RT site, dose, fraction number, tumor type, or ICI and H-RT sequencing. Median progression-free survival was 6.5 months. Objective response rate (ORR) was 26%; 10% had complete response (CR). Median duration of response was 9.4 ± 4.6 months. H-RT of lung lesions was more likely to achieve CR than other sites. H-RT of bone lesions had a lower ORR than non-bone H-RT. In conclusion, combining body H-RT with ICIs is safe and promising. Prospective validation is warranted.

  View details for DOI 10.1080/2162402X.2018.1440168

  View details for Web of Science ID 000433549100007

  View details for PubMedID 29900043

  View details for PubMedCentralID PMC5993514

• How does autoimmune disease impact treatment and outcomes among patients with lung cancer? A national SEER-Medicare analysis LUNG CANCER Khan, S. A., Pruitt, S. L., Xuan, L., Makris, U., Gerber, D. E. 2018; 115: 97-102

  Abstract

  The advent of cancer immunotherapy has made autoimmune disease in oncology populations clinically important. We analyzed the association of autoimmune disease with treatment and outcomes among lung cancer patients.Using linked Surveillance Epidemiology and End Results (SEER)-Medicare data, we identified lung cancer patients diagnosed between 1992 and 2009 with autoimmune diseases. We recorded number and timing of autoimmune disease diagnoses, lung cancer treatment, and markers of healthcare utilization including emergency department visits, hospitalizations, and outpatient visits. To account for potential lead-time bias, we used a matched case-control analysis wherein living and deceased patients were matched on survival time. We performed unadjusted and multivariable adjusted logistic regressions separately by cancer stage for all-cause and lung cancer-specific mortality.Among 172,285 lung cancer patients, 23,084 (13.4%) had ≥1 autoimmune disease at any time. Overall, 10,927 patients (6.3%) had one autoimmune disease before cancer diagnosis; 9338 (5.4%) had two or more before cancer diagnosis; and 2819 (1.6%) had one or more after cancer diagnosis. Healthcare utilization was higher in the autoimmune disease population. Lung cancer treatment patterns were similar among patients with and without autoimmune disease and there was no significant association with mortality.Among patients with lung cancer, autoimmune disease does not influence treatment patterns and is not associated with mortality.

  View details for DOI 10.1016/j.lungcan.2017.11.024

  View details for Web of Science ID 000424181800015

  View details for PubMedID 29290269

  View details for PubMedCentralID PMC5751945

• Risk of contralateral nodal failure following ipsilateral IMRT for node-positive tonsillar cancer ORAL ONCOLOGY Gottumukkala, S., Nhat-Long Pham, Sumer, B., Myers, L., Truelson, J., Nedzi, L., Khan, S., Hughes, R., Sher, D. J. 2017; 75: 35-38

  Abstract

  To determine the risk of contralateral nodal failure following ipsilateral radiotherapy in a series of patients with node-positive tonsillar squamous cell carcinoma.Retrospective review was used to identify 34 patients with well-lateralized node-positive tonsillar squamous cell carcinoma treated with definitive or adjuvant radiation to the primary site and ipsilateral neck between 2005 and 2015. Contralateral nodal failure, locoregional recurrence, distant metastasis, and overall survival were calculated using actuarial and/or cumulative incidence statistics.At last follow-up, contralateral nodal failure was only observed in 1 patient (3%) with N1 disease. At median follow-up of 34 months for surviving patients, the 3-year overall survival probability was 87%, and the 3 year cumulative incidences of locoregional failure and distant metastasis were 6.5% and 7.2%, respectively. No disease-free patient was permanently gastrostomy-dependent.Ipsilateral radiation treatment with IMRT is effective in node-positive patients with well-lateralized tonsillar cancer, resulting in a low risk of contralateral regional recurrence, even in patients with N2b disease.

  View details for DOI 10.1016/j.oraloncology.2017.10.010

  View details for Web of Science ID 000417555400007

  View details for PubMedID 29224820

• Exploring the association between KRAS mutations and depression in non-small cell lung cancer (NSCLC) patients Li, J., Harper, J., Bhulani, N., Gerber, D. E., Khan, S. A., Madrigales, A., Gates, S., Toups, M., Beg, M. AMER SOC CLINICAL ONCOLOGY. 2017

  View details for DOI 10.1200/JCO.2017.35.31_suppl.114

  View details for Web of Science ID 000443263300107

• Race- and Sex-Based Disparities in the Therapy and Outcomes of Squamous Cell Carcinoma of the Anus JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Arora, N., Gupta, A., Zhu, H., Christie, A., Meyer, J. J., Khan, S. A., Beg, M. S. 2017; 15 (8): 998-1004

  Abstract

  Background: Squamous cell carcinoma of the anus (SCCA) is one of the few cancers with an increasing incidence in the United States. We aimed to characterize race- and sex-based disparities in receipt of therapy and overall survival (OS) of SCCA using the SEER database. Methods: Cases of locoregional SCCA (T2-T4 any N M0) diagnosed between 2000 and 2012 in the SEER database were included. Demographics, tumor characteristics, type of therapy, and outcomes were extracted. Univariable and multivariable Cox proportional hazard models were constructed to test factors associated with OS. Data were reported as hazard ratios (HRs) and 95% CIs. Results: A total of 7,882 cases of locoregional SCCA were identified, with a median age of 58 years, 61.2% of whom were women, and 86.3% were white. Most patients (82.3%) received radiation therapy (RT), with the lowest rate in black men (76.7%) and the highest in white women (86.1%). The median OS was 135 months; OS was lower in elderly patients (age ≥65 years; 68 months), men (108 months), blacks (109 months), and those who did not receive RT (121 months). In multivariable analysis, age (HR, 1.19; 95% CI, 1.17-1.21 per 5 years increase), sex (HR, 1.59; 95% CI, 1.47-1.73, men vs women), race (HR, 1.51; 95% CI, 1.34-1.71, black vs white), and RT (HR, 0.90; 95% CI, 0.82-0.99) were independently associated with OS (P<.05). Conclusions: Significant race- and sex-based disparities exist in survival of patients with locoregional SCCA. Further investigation into the causes of these disparities and methods for elimination are warranted.

  View details for DOI 10.6004/jnccn.2017.0135

  View details for Web of Science ID 000407058700007

  View details for PubMedID 28784861

• Clinical Practice in PET/CT for the Management of Head and Neck Squamous Cell Cancer AMERICAN JOURNAL OF ROENTGENOLOGY Goel, R., Moore, W., Sumer, B., Khan, S., Sher, D., Subramaniam, R. M. 2017; 209 (2): 289-303

  Abstract

  The purpose of this article is to summarize the evidence for the value of PET/CT for the management of patients with head and neck squamous cell cancer and suggest best clinical practices.FDG PET/CT is a valuable imaging tool for identifying unknown primary tumors in patients with known cervical node metastases leading to management change and is the standard of care for the initial staging of stage III and IV head and neck squamous cell carcinomas (HNSCCs), for assessing therapy response when performed at least 12 weeks after chemoradiation therapy, and for avoiding unnecessary planned neck dissection. Neck dissection is avoided if PET/CT findings are negative-regardless of the size of the residual neck nodes-because survival outcomes are not compromised. FDG PET/CT is valuable in detecting recurrences and metastases during follow-up when suspected because of clinical symptoms and serves as a prognostic marker for patient survival outcomes, for 5 years. Using FDG PET/CT for routine surveillance of HNSCC after 6 months of treatment without any clinical suspicion should be discouraged.

  View details for DOI 10.2214/AJR.17.18301

  View details for Web of Science ID 000406042300022

  View details for PubMedID 28731808

• Blocking the DC-HIL receptor reverses the T-cell suppression induced by proliferating myeloid-derived suppressor cells in common cancer types Kobayashi, M., Chung, J., Beg, M., Arriaga, Y., Verma, U., Courtney, K., Mansour, J., Haley, B., Khan, S., Horiuchi, Y., Harker, D., Gopal, P., Cruz, P. D., Ariizumi, K. AMER ASSOC CANCER RESEARCH. 2017

  View details for DOI 10.1158/1538-7445.AM2017-3660

  View details for Web of Science ID 000442513301416

• Genomic profiling of squamous malignancies across anatomic sites. Chung, C. H., Frampton, G., Chalmers, Z., Chung, J., Khan, S. A., Schrock, A., Gay, L. M., Sharma, N., Elvin, J., Fabrizio, D., Connelly, C. F., Kang, H., Stephens, P. J., Miller, V. A., Johnson, J., Ross, J. S., Ali, S., Ganesan, S. AMER SOC CLINICAL ONCOLOGY. 2017

  View details for DOI 10.1200/JCO.2017.35.15_suppl.11512

  View details for Web of Science ID 000411932207090

• Phase II trial of ribociclib and everolimus in p16 low anaplastic thyroid cancer (ATC). Tawfik, B., Gerber, D. E., Burtness, B., Hughes, R. S., Myers, L. L., Sumer, B. D., Truelson, J., Strom, T., Kurian, P., Saleem, S., Pearson, J., Zhu, H., Khan, S. A. AMER SOC CLINICAL ONCOLOGY. 2017

  View details for DOI 10.1200/JCO.2017.35.15_suppl.TPS6098

  View details for Web of Science ID 000411931705094

• In-human activity and pharmacology of homemade silver nanoparticles in highly refractory metastatic head and neck squamous cell cancer. Singh, J., Fattah, F., Burks, T., Zheng, J., Jiang, X., Kurian, P., Saleem, S., Pearson, J., Khan, S. A. AMER SOC CLINICAL ONCOLOGY. 2017

  View details for DOI 10.1200/JCO.2017.35.15_suppl.e17533

  View details for Web of Science ID 000411931705126

• Comparative effectiveness of primary radiotherapy versus surgery in oropharyngeal squamous cell carcinoma in elderly patients: A SEER-Medicare analysis. Sher, D., Yan, J., Strom, T., Khan, S. A., Zhu, H. AMER SOC CLINICAL ONCOLOGY. 2017

  View details for DOI 10.1200/JCO.2017.35.15_suppl.e18124

  View details for Web of Science ID 000411931707031

• Impact of prior radiation on survival in metastatic lung cancer ECOG-ACRIN trials. Khan, S. A., Puligandla, M., Dahlberg, S., Masters, G. A., Langer, C. J., Brahmer, J. R., Hanna, N. H., Bonomi, P., Gerber, D. E., Johnson, D. H., Schiller, J. H., Ramalingam, S. S. AMER SOC CLINICAL ONCOLOGY. 2017

  View details for DOI 10.1200/JCO.2017.35.15_suppl.9051

  View details for Web of Science ID 000411932202113

• Cutaneous adnexal adenocarcinoma with exquisite sensitivity to trastuzumab HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Brown, T. J., Sher, D. J., Nedzi, L. A., Hughes, R. S., Beg, M. S., Mull, J., Sarode, V. R., Khan, S. A. 2017; 39 (5): E69-E71

  Abstract

  Cutaneous adnexal adenocarcinoma is a rare cancer that is occasionally human epidermal growth factor receptor-2 (HER-2)-positive, and demonstrates variable response to HER-2 inhibitors.We report a case of adnexal adenocarcinoma of the scalp in a 56-year-old man. He underwent wide local excision with cervical node dissection followed by radiation, but had extensive local recurrence.Pathology demonstrated a poorly differentiated adnexal adenocarcinoma with HER-2 overexpression by immunohistochemistry (IHC) and high HER-2 gene amplification by fluorescence in situ hybridization. The patient was treated with trastuzumab-based therapy with dramatic response and clinical resolution of the tumor. Upon pausing trastuzumab, he developed local relapse, but had an excellent response to restarting trastuzumab monotherapy. He lacks visible disease 43 months after the initial diagnosis.We believe the exquisite sensitivity of the primary carcinoma and subsequent recurrence to trastuzumab therapy was due to strong HER-2 expression both at the protein and gene level. © 2017 Wiley Periodicals, Inc. Head Neck 39: E69-E71, 2017.

  View details for DOI 10.1002/hed.24682

  View details for Web of Science ID 000399646800001

  View details for PubMedID 28225558

• Pediatric, Adolescent, and Young Adult Thyroid Carcinoma Harbors Frequent and Diverse Targetable Genomic Alterations, Including Kinase Fusions ONCOLOGIST Vanden Borre, P., Schrock, A. B., Anderson, P. M., Morris, J. C., Heilmann, A. M., Holmes, O., Wang, K., Johnson, A., Waguespack, S. G., Ou, S., Khan, S., Fung, K., Stephens, P. J., Erlich, R. L., Miller, V. A., Ross, J. S., Ali, S. M. 2017; 22 (3): 255-263

  Abstract

  Thyroid carcinoma, which is rare in pediatric patients (age 0-18 years) but more common in adolescent and young adult (AYA) patients (age 15-39 years), carries the potential for morbidity and mortality.Hybrid-capture-based comprehensive genomic profiling (CGP) was performed prospectively on 512 consecutively submitted thyroid carcinomas, including 58 from pediatric and AYA (PAYA) patients, to identify genomic alterations (GAs), including base substitutions, insertions/deletions, copy number alterations, and rearrangements. This PAYA data series includes 41 patients with papillary thyroid carcinoma (PTC), 3 with anaplastic thyroid carcinoma (ATC), and 14 with medullary thyroid carcinoma (MTC).GAs were detected in 93% (54/58) of PAYA cases, with a mean of 1.4 GAs per case. In addition to BRAF V600E mutations, detected in 46% (19/41) of PAYA PTC cases and in 1 of 3 AYA ATC cases, oncogenic fusions involving RET, NTRK1, NTRK3, and ALK were detected in 37% (15/41) of PAYA PTC and 33% (1/3) of AYA ATC cases. Ninety-three percent (13/14) of MTC patients harbored RET alterations, including 3 novel insertions/deletions in exons 6 and 11. Two of these MTC patients with novel alterations in RET experienced clinical benefit from vandetanib treatment.CGP identified diverse clinically relevant GAs in PAYA patients with thyroid carcinoma, including 83% (34/41) of PTC cases harboring activating kinase mutations or activating kinase rearrangements. These genomic observations and index cases exhibiting clinical benefit from targeted therapy suggest that young patients with advanced thyroid carcinoma can benefit from CGP and rationally matched targeted therapy. The Oncologist 2017;22:255-263 IMPLICATIONS FOR PRACTICE: The detection of diverse clinically relevant genomic alterations in the majority of pediatric, adolescent, and young adult patients with thyroid carcinoma in this study suggests that comprehensive genomic profiling may be beneficial for young patients with papillary, anaplastic, or medullary thyroid carcinoma, particularly for advanced or refractory cases for which clinical trials involving molecularly targeted therapies may be appropriate.

  View details for DOI 10.1634/theoncologist.2016-0279

  View details for Web of Science ID 000395996600004

  View details for PubMedID 28209747

  View details for PubMedCentralID PMC5344643

• Racial and gender disparities in therapy and outcomes of squamous cell cancer of the anus Gupta, A., Arora, N., Zhu, H., Christie, A., Meyer, J., Khan, S. A., Beg, M. S. AMER SOC CLINICAL ONCOLOGY. 2017

  View details for DOI 10.1200/JCO.2017.35.4_suppl.691

  View details for Web of Science ID 000443281700672

• National Patterns of Care and Predictors of Neoadjuvant and Concurrent Chemotherapy Use With Definitive Radiotherapy in the Treatment of Patients With Oropharyngeal Squamous Cell Carcinoma CANCER Sher, D. J., Rusthoven, C. G., Khan, S. A., Fidler, M., Zhu, H., Koshy, M. 2017; 123 (2): 273-282

  Abstract

  To the authors' knowledge, the patterns of care for the radiotherapy-based treatment of patients with stage III to IVB oropharyngeal squamous cell carcinoma (OPSCC) are poorly defined. The objective of the current study was to characterize the use and predictors of chemotherapy with radiotherapy for this population using the National Cancer Database.Patients in the National Cancer Database with AJCC (American Joint Committee on Cancer) stage III to IV OPSCC who were treated with radiotherapy between 2003 and 2012 were eligible for analysis. Treatment was defined as radiotherapy alone, concurrent chemoradiotherapy, or induction chemotherapy (IC). Multivariable regression with multilevel modeling was used to determine predictors of any chemotherapy use and, among patients receiving chemotherapy, the predictors of IC.The majority (90%) of the 30,875 eligible patients received chemotherapy, the majority of whom (71% of the total) were treated with definitive chemoradiotherapy; a sizeable percentage of patients received IC (19% of total). On multivariable regression, younger age, favorable comorbidity status, and more advanced tumor and lymph node disease were found to be independent predictors of any chemotherapy and IC use. Nonwhite patients (odds ratio [OR], 0.71; P<.0001), women (OR, 0.74; P<.0001), and individuals without private insurance were found to be significantly less likely to receive chemotherapy. Patients treated at higher-volume institutions were significantly less likely to receive IC (OR, 0.69; P = .0006). Human papillomavirus status did not appear to independently influence treatment choice.The vast majority of patients with stage III to IVB OPSCC who were treated with definitive radiotherapy received chemotherapy, which is consistent with high-level data and national recommendations. However, disparities with regard to race, sex, and insurance status emerged thereby requiring additional investigation. The frequent use of IC despite limited supportive evidence warrants research on physician and patient decision making and presents an opportunity to improve evidence-based treatment delivery. Cancer 2017;123:273-282. © 2016 American Cancer Society.

  View details for DOI 10.1002/cncr.30255

  View details for Web of Science ID 000394719200014

  View details for PubMedID 27649421

• A Phase I/II Study of Nab-Paclitaxel, Cisplatin, and Cetuximab With Concurrent Radiation Therapy for Locally Advanced Squamous Cell Cancer of the Head and Neck CANCER INVESTIGATION Chun, S. G., Hughes, R., Sumer, B. D., Myers, L. L., Truelson, J. M., Khan, S. A., Ma, T., Xie, Y., Yordy, J. S., Cooley, S., Wu, J., Choy, H., Nedzi, L. A. 2017; 35 (1): 23-31

  Abstract

  Nab-paclitaxel might impact efficacy of radiation for head and neck (H&N) cancer. Nab-paclitaxel, cisplatin, cetuximab, and radiation were evaluated in patients with locally advanced head and neck cancer in this phase I/II trial. Median follow-up was 24 months for 34 patients. The maximum tolerated dose of nab-paclitaxel was 20 mg/m2 with 20 mg/m2 cisplatin and 250 mg/m2 cetuximab. The 2-year progression-free survival (PFS) was 60% (95% confidence interval (CI) 0.42, 0.78), local control 71% (95% CI 0.55, 0.87), and overall survival 68% (95% CI 0.50, 0.86). This is the first study evaluating these agents with radiation in humans, with similar 2-year PFS as historic control.

  View details for DOI 10.1080/07357907.2016.1213275

  View details for Web of Science ID 000393906100002

  View details for PubMedID 27892728

• Prevalence of Autoimmune Disease Among Patients With Lung Cancer: Implications for Immunotherapy Treatment Options JAMA ONCOLOGY Khan, S. A., Pruitt, S. L., Xuan, L., Gerber, D. E. 2016; 2 (11): 1507-1508

  View details for DOI 10.1001/jamaoncol.2016.2238

  View details for Web of Science ID 000388235300024

  View details for PubMedID 27262099

  View details for PubMedCentralID PMC5656433

• Molecular diagnostics and anaplastic thyroid carcinoma: the time has come to harvest the high hanging fruit INTERNATIONAL JOURNAL OF ENDOCRINE ONCOLOGY Cabanillas, M. E., Busaidy, N. L., Khan, S. A., Gunn, G., Dadu, R., Rao, S. N., Waguespack, S. G. 2016; 3 (3): 221-233

  View details for DOI 10.2217/ije-2016-0007

  View details for Web of Science ID 000387501100004

• Patterns of Care and Comparative Effectiveness of Intensified Adjuvant Therapy for Resected Oropharyngeal Squamous Cell Carcinoma in the Human Papillomavirus Era JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY Sher, D. J., Nedzi, L., Khan, S., Hughes, R., Sumer, B. D., Myers, L. L., Truelson, J. M., Koshy, M. 2016; 142 (8): 777-788

  Abstract

  There is a growing debate on the relative benefits of adjuvant chemoradiotherapy (CRT) and boost doses of postoperative radiotherapy (B-PORT) in oropharyngeal squamous cell carcinoma (OPSCC) treated with primary surgery, especially for patients with human papillomavirus (HPV)-driven disease.To characterize the recent patterns of care in and overall survival (OS) outcomes following the use of adjuvant CRT and B-PORT after primary surgery for OPSCC.Retrospective analysis of patients in the National Cancer Database with stage III to IVA-B OPSCC treated with surgery and adjuvant radiotherapy between 2010 and 2012 at Commission on Cancer-accredited facilities. The data analysis was performed between June 15, 2015, and May 4, 2016.The primary outcomes were prevalence of CRT and B-PORT, and OS. The primary predictors were HPV positivity and high-risk pathologic features (HRPFs) (extracapsular extension and positive surgical margins).Of the 1409 patients (1153 [82%] male; median age, 57 [interquartile range {IQR}, 51-63] years), 873 (62%) and 789 (56%) patients received CRT and B-PORT, respectively; most patients (n = 583 [79%]) with HRPFs received CRT, and many patients (n = 227 [40%]) without HRPFs received CRT. Multivariable predictors of CRT included adverse pathologic features (extracapsular extension [OR, 6.99; 95% CI, 5.22-9.35], positive surgical margins [OR, 2.07; 95% CI, 1.50-2.87], ≥6 involved nodes [OR, 2.34; 95% CI, 1.39-3.92], or low-neck disease [OR, 1.52; 95% CI, 1.01-2.28]), and treatment at a nonacademic institution (OR, 1.59 [95% CI, 1.21-2.10] for comprehensive community cancer center vs academic program). Patients with HPV-positive disease (OR, 0.47; 95% CI, 0.33-0.68) were less likely to receive CRT; this decrease was limited to absent HRPF treated at academic institutions (n = 173, 44 [25%] received CRT). With a median follow-up of surviving patients of 27 (IQR, 21-33) months, the 2-year OS probability was 92% (95% CI, 90%-94%). Multivariable analysis including age, sex, pathologic T stage, 6 or more positive nodes, and educational status confirmed the prognostic impact of HPV positivity (hazard ratio [HR], 0.41; 95% CI, 0.21-0.80) and HRPFs (positive surgical margins [HR, 2.15; 95% CI, 1.27-3.66] and ≥6 involved nodes [HR, 2.11; 95% CI, 1.13-3.93]), but neither CRT (HR, 1.27; 95% CI, 0.70-2.30) nor B-PORT (HR, 1.04; 95% CI, 0.63-1.73) was associated with improved OS.Postoperative CRT and B-PORT following resection of OPSCC were dependent on factors beyond HRPFs, including HPV status and treatment at an academic institution. No benefit was seen with intensified adjuvant therapy, supporting enrollment of the HPV-positive population into deintensification trials.

  View details for DOI 10.1001/jamaoto.2016.1162

  View details for Web of Science ID 000383774000010

  View details for PubMedID 27368076

• A phase 2 study of tarloxotinib bromide (TRLX) in patients (Pts) with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) or skin (SCCS). Rischin, D., Boyer, M. J., Brzezniak, C. E., Colevas, A., Doebele, R., Gilbert, J., Gitlitz, B., Khan, S. A., Mehra, R., Seiwert, T. Y., Kroll, S., Pearce, T. E., Liu, S. V. AMER SOC CLINICAL ONCOLOGY. 2016

  View details for DOI 10.1200/JCO.2016.34.15_suppl.TPS6105

  View details for Web of Science ID 000404711502231

• Comprehensive genomic sequencing (CGS) of 90 patient samples of anaplastic thyroid cancer (ATC). Khan, S. A., Ci, B., Gerber, D. E., McFadden, D. G., Beg, M., Xie, Y., Kurian, P., Cabanillas, M. E., Busaidy, N., Sherman, S. I., Heilmann, A., Ross, J. S., Bailey, M., Burtness, B., Ali, S. AMER SOC CLINICAL ONCOLOGY. 2016

  View details for DOI 10.1200/JCO.2016.34.15_suppl.6014

  View details for Web of Science ID 000404711502142

• Phase II trial of carboplatin/paclitaxel and cetuximab, followed by carboplatin/paclitaxel/cetuximab and erlotinib, in metastatic or recurrent squamous cell carcinoma of the head and neck. Bhatia, A. K., Mehra, R., Khan, S. A., Egleston, B. L., Alpaugh, R., Lango, M., Ridge, J. A., Burtness, B. AMER SOC CLINICAL ONCOLOGY. 2016

  View details for DOI 10.1200/JCO.2016.34.15_suppl.6027

  View details for Web of Science ID 000404711502154

• Prevalence of autoimmune conditions among patients with lung cancer: Implications for immunotherapy treatment options. Khan, S. A., Xuan, L., Pruitt, S., Gerber, D. E. AMER SOC CLINICAL ONCOLOGY. 2016

  View details for DOI 10.1200/JCO.2016.34.15_suppl.9039

  View details for Web of Science ID 000404711506187

• Toxic Effects of Sorafenib in Patients With Differentiated Thyroid Carcinoma Compared With Other Cancers JAMA ONCOLOGY Jean, G. W., Mani, R. M., Jaffry, A., Khan, S. A. 2016; 2 (4): 529-534

  Abstract

  Sorafenib is approved by the US Food and Drug Administration for metastatic, radioactive iodine-refractory differentiated thyroid cancer. However, adverse effects common to the tyrosine kinase inhibitor class occur at a noticeably higher rate with sorafenib use in thyroid cancer patients. The mechanism for this increase in toxic effects is unknown.To provide an overview of the adverse effect profile of sorafenib in differentiated thyroid cancer and summarizes the literature regarding the frequency and etiology of selected adverse effects, with particular emphasis on the hand-foot skin reaction.A PubMed database search for relevant literature on this topic published within the last 15 years was conducted. Publications dealing with sorafenib and any of its common adverse effects were considered; this included randomized trials, observational studies, case reports or case series, and pertinent review articles. Given the lack of widespread literature on the topic, articles were generally not excluded from consideration unless there were serious flaws in study design.The DECISION trial of sorafenib in patients with differentiated thyroid cancer demonstrated significantly higher rates of common adverse effects, most notably hand-foot skin reaction, diarrhea, and hypertension, compared with sorafenib experience in renal or hepatocellular cancer. Other phase 2 and 3 trials have also consistently shown these differences. This review details the putative mechanisms behind the increase in toxic effects, but further work is needed to fully explain the toxic effects differential seen when using the same drug in different cancers.There is a distinct increase in the rate of occurrence of adverse effects of sorafenib when used in differentiated thyroid cancer compared with renal and hepatocellular cancer. While many theoretical explanations have been proposed, the exact mechanism for this differential in toxic effects remains unclear.

  View details for DOI 10.1001/jamaoncol.2015.5927

  View details for Web of Science ID 000383683200024

  View details for PubMedID 26847808

• Comparative effectiveness of induction chemotherapy for oropharyngeal squamous cell carcinoma: A population-based analysis ORAL ONCOLOGY Sher, D. J., Schwartz, D. L., Nedzi, L., Khan, S., Hughes, R., Fidler, M., Koshy, M. 2016; 54: 58-67

  Abstract

  Despite several randomized trials, the optimal chemotherapy paradigm for locally advanced oropharyngeal carcinoma (OPSCC) is controversial. This population-based analysis assessed the overall survival (OS) benefit of induction chemotherapy (IC) for patients with stage III-IVB OPSCC.Patients in the National Cancer Database with stage III-IVA-B OPSCC treated with curative-dose radiotherapy and IC or concurrent chemotherapy (CRT) between 2003 and 2011 were eligible. The primary outcome was OS, and secondary endpoints included OS for high-risk (T4 and/or N3 disease) and human papillomavirus (HPV) subsets.Of the 14,856 analyzed patients, 78% and 22% received CRT and IC, respectively. With a median follow-up for surviving patients of 44 months, the 5-year OS probability for the entire cohort was 66% (66% CRT vs. 64% IC, p=0.022). Multivariable survival analysis showed no significant difference between CRT and IC (hazard ratio, HR, 0.95 for IC, p=0.255), and sensitivity analyses to adjust for immortal time bias brought the HR to 1.0 (p=0.859). There was also no OS difference for high-risk patients. There was a trend in favor of CRT for HPV-positive OPSCC (HR 1.63 with IC, p=0.064), with a significant OS benefit for HPV-negative, high-risk OPSCC (HR 0.63, p=0.048).For the vast majority of patients, including HPV-positive individuals, there was no difference in OS with IC, arguing for CRT to remain as the standard therapy. Subset analysis revealed a small cohort of aggressive cancer (T4/N3 HPV-negative) which may benefit from from IC, although selection bias could not be ruled out.

  View details for DOI 10.1016/j.oraloncology.2015.12.008

  View details for Web of Science ID 000370005900019

  View details for PubMedID 26794877

• Racial and sex disparities in changing trends of squamous cell cancer of the anus (SSCA). Gupta, A., Zhu, H., Christie, A., Meyer, J., Khan, S. A., Beg, M. AMER SOC CLINICAL ONCOLOGY. 2016

  View details for DOI 10.1200/jco.2016.34.4_suppl.520

  View details for Web of Science ID 000378109600500

• ESMO / ASCO Recommendations for a Global Curriculum in Medical Oncology Edition 2016. ESMO open Dittrich, C. n., Kosty, M. n., Jezdic, S. n., Pyle, D. n., Berardi, R. n., Bergh, J. n., El-Saghir, N. n., Lotz, J. P., Österlund, P. n., Pavlidis, N. n., Purkalne, G. n., Awada, A. n., Banerjee, S. n., Bhatia, S. n., Bogaerts, J. n., Buckner, J. n., Cardoso, F. n., Casali, P. n., Chu, E. n., Close, J. L., Coiffier, B. n., Connolly, R. n., Coupland, S. n., De Petris, L. n., De Santis, M. n., de Vries, E. G., Dizon, D. S., Duff, J. n., Duska, L. R., Eniu, A. n., Ernstoff, M. n., Felip, E. n., Fey, M. F., Gilbert, J. n., Girard, N. n., Glaudemans, A. W., Gopalan, P. K., Grothey, A. n., Hahn, S. M., Hanna, D. n., Herold, C. n., Herrstedt, J. n., Homicsko, K. n., Jones, D. V., Jost, L. n., Keilholz, U. n., Khan, S. n., Kiss, A. n., Köhne, C. H., Kunstfeld, R. n., Lenz, H. J., Lichtman, S. n., Licitra, L. n., Lion, T. n., Litière, S. n., Liu, L. n., Loehrer, P. J., Markham, M. J., Markman, B. n., Mayerhoefer, M. n., Meran, J. G., Michielin, O. n., Moser, E. C., Mountzios, G. n., Moynihan, T. n., Nielsen, T. n., Ohe, Y. n., Öberg, K. n., Palumbo, A. n., Peccatori, F. A., Pfeilstöcker, M. n., Raut, C. n., Remick, S. C., Robson, M. n., Rutkowski, P. n., Salgado, R. n., Schapira, L. n., Schernhammer, E. n., Schlumberger, M. n., Schmoll, H. J., Schnipper, L. n., Sessa, C. n., Shapiro, C. L., Steele, J. n., Sternberg, C. N., Stiefel, F. n., Strasser, F. n., Stupp, R. n., Sullivan, R. n., Tabernero, J. n., Travado, L. n., Verheij, M. n., Voest, E. n., Vokes, E. n., Von Roenn, J. n., Weber, J. S., Wildiers, H. n., Yarden, Y. n. 2016; 1 (5): e000097

  Abstract

  The European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) are publishing a new edition of the ESMO/ASCO Global Curriculum (GC) thanks to contribution of 64 ESMO-appointed and 32 ASCO-appointed authors. First published in 2004 and updated in 2010, the GC edition 2016 answers to the need for updated recommendations for the training of physicians in medical oncology by defining the standard to be fulfilled to qualify as medical oncologists. At times of internationalisation of healthcare and increased mobility of patients and physicians, the GC aims to provide state-of-the-art cancer care to all patients wherever they live. Recent progress in the field of cancer research has indeed resulted in diagnostic and therapeutic innovations such as targeted therapies as a standard therapeutic approach or personalised cancer medicine apart from the revival of immunotherapy, requiring specialised training for medical oncology trainees. Thus, several new chapters on technical contents such as molecular pathology, translational research or molecular imaging and on conceptual attitudes towards human principles like genetic counselling or survivorship have been integrated in the GC. The GC edition 2016 consists of 12 sections with 17 subsections, 44 chapters and 35 subchapters, respectively. Besides renewal in its contents, the GC underwent a principal formal change taking into consideration modern didactic principles. It is presented in a template-based format that subcategorises the detailed outcome requirements into learning objectives, awareness, knowledge and skills. Consecutive steps will be those of harmonising and implementing teaching and assessment strategies.

  View details for DOI 10.1136/esmoopen-2016-000097

  View details for PubMedID 27843641

  View details for PubMedCentralID PMC5070299

• Comprehensive genomic profiling of clinically advanced medullary thyroid carcinoma Heilmann, A., Subbiah, V., Wang, K., Elvin, J., Chmielecki, J., Yelensky, R., Vergilio, J. A., Erlich, R., Lipson, D., Ross, J., Miller, V., Ali, S., Stephens, P. ELSEVIER SCI LTD. 2015: S562

  View details for DOI 10.1016/S0959-8049(16)31556-8

  View details for Web of Science ID 000361887402445

• A phase 1 safety study of veliparib combined with cisplatin and etoposide in extensive stage small cell lung cancer: A trial of the ECOG-ACRIN Cancer Research Group (E2511) LUNG CANCER Owonikoko, T. K., Dahlberg, S. E., Khan, S. A., Gerber, D. E., Dowell, J., Moss, R. A., Belani, C. P., Hann, C. L., Aggarwal, C., Ramalingam, S. S. 2015; 89 (1): 66-70

  Abstract

  Veliparib (V) potentiated therapeutic efficacy of cisplatin (C) and etoposide (E) in preclinical models of SCLC. We conducted this phase 1 study to establish the safety of the combination in human subjects.The study employed the 3+3 dose escalation design to establish the safety and recommended phase 2 dose (RP2D) of V when combined with fixed doses of C (75 mg/m(2) on day 1) and E (100mg/m(2) on days 1-3) in a 21-day cycle. The starting dose of V was 60 mg (bid days 1-7) with plan to escalate to 100mg (days 1-7) or de-escalate to 40 mg (days 1-7) depending on the dose limiting toxicity (DLT) experience during cycle 1. Patients with treatment-naïve, extensive stage SCLC were included.The study enrolled 9 patients: M/F (4/5); median age (60); White/African American (8/1). V was tolerated at the 60 mg (DLT in 0 of 3 patients) and 100mg dose (DLT in 1 of 6 patients; grade 5 cardiac failure). Veliparib at 100mg in combination with standard doses of C and E was established as the RP2D. Grades 3-5 adverse events irrespective of attribution during cycle 1 included: dehydration (1), diarrhea (1), fatigue (1), febrile neutropenia (1), heart failure (1), leukopenia (6), lymphopenia (1), nausea (2), neutropenia (8), respiratory failure (1), and thrombocytopenia (2). Investigator-assessed efficacy outcome in 7 evaluable patients were stable disease in 2/7 (28.6%), partial response in 4/7 (57.1%), and complete response in 1/7 (14.3%) patients.This study demonstrated the safety of combining veliparib with cisplatin and etoposide in previously untreated SCLC patients.

  View details for DOI 10.1016/j.lungcan.2015.04.015

  View details for Web of Science ID 000356546300013

  View details for PubMedID 25985977

  View details for PubMedCentralID PMC4539011

• Ceritinib in anaplastic thyroid cancer (ATC) with ALK abnormalities. Khan, S. A., Bauman, J. E., Burtness, B., Frankel, A. E., Harper, J., Hughes, R. S., Kurian, P., Myers, L. L., Nedzi, L., Schwartz, D. L., Sumer, B. D., Truelson, J., Zhu, H. AMER SOC CLINICAL ONCOLOGY. 2015

  View details for DOI 10.1200/jco.2015.33.15_suppl.tps6085

  View details for Web of Science ID 000358036904811

• Neuroendocrine tumors of the head and neck: SEER analysis of survival and incidence. Khan, S. A., Zhu, H., Bacalao, M. AMER SOC CLINICAL ONCOLOGY. 2015

  View details for DOI 10.1200/jco.2015.33.15_suppl.e17051

  View details for Web of Science ID 000358036903430

• Use of 18-FDG PET in Determination of Disease Extent in HPV/p16-Positive Oropharyngeal Squamous Cell Carcinoma Gannavarapu, B., Sumer, B. D., Prabhu, R. S., Yordy, J. S., Nedzi, L. A., Khan, S. A., Schwartz, D., Chen, S. A. ELSEVIER SCIENCE INC. 2014: S519-S520

  View details for DOI 10.1016/j.ijrobp.2014.05.1589

  View details for Web of Science ID 000342331401681

• Patterns of distant metastases in HPV-positive head and neck squamous cell carcinoma. Law, J., Chen, S., Gerber, D. E., Hughes, R. S., Madrigales, A., Myers, L. L., Nedzi, L., Sumer, B. D., Truelson, J., Yordy, J., Zhu, H., Khan, S. A. LIPPINCOTT WILLIAMS & WILKINS. 2014

  View details for DOI 10.1200/jco.2014.32.15_suppl.6071

  View details for Web of Science ID 000358613203663