Medicine and Health Sciences Commons^™

Upfront Treatment Of Flt3-Mutated Aml: A Look Back At The Ratify Trial And Beyond., Gina Keiffer, Kimberly L Aderhold, Neil D Palmisiano

Department of Medical Oncology Faculty Papers

In April 2017, following the results of the RATIFY trial (1), midostaurin, a multikinase FLT3 inhibitor, became the first FDA approved targeted agent for the treatment of acute myeloid leukemia (AML) (2). The addition of midostaurin to standard induction therapy with anthracycline and cytarabine (7 + 3) rapidly became the new standard of care for treatment-naïve, fit patients with FLT3-mutated (FLTmut+) AML (3). More recently, gilteritinib, a selective FLT3 inhibitor, showed superiority to chemotherapy in the treatment of relapsed or refractory FLTmut+ AML (4). With two FLT3 inhibitors now approved by the FDA—that is, the more selective gilteritinib and the …

Dimensions Of Misinformation About The Hpv Vaccine On Instagram: Content And Network Analysis Of Social Media Characteristics., Philip M. Massey, Matthew D. Kearney, Michael K. Hauer, Preethi Selvan, Emmanuel Koku, Amy Leader

Department of Medical Oncology Faculty Papers

BACKGROUND: The human papillomavirus (HPV) vaccine is a major advancement in cancer prevention and this primary prevention tool has the potential to reduce and eliminate HPV-associated cancers; however, the safety and efficacy of vaccines in general and the HPV vaccine specifically have come under attack, particularly through the spread of misinformation on social media. The popular social media platform Instagram represents a significant source of exposure to health (mis)information; 1 in 3 US adults use Instagram.

OBJECTIVE: The objective of this analysis was to characterize pro- and anti-HPV vaccine networks on Instagram, and to describe misinformation within the anti-HPV vaccine …

Discordant Responses Between Primary Head And Neck Tumors And Nodal Metastases Treated With Neoadjuvant Nivolumab: Correlation Of Radiographic And Pathologic Treatment Effect., Dante J. Merlino, Jennifer M. Johnson, Madalina Tuluc, Stacey Gargano, Robert Stapp, Larry Harshyne, Benjamin E. Leiby, Adam Flanders, Ralph Zinner, Rita Axelrod, Joseph Curry, David M. Cognetti, Kyle Mannion, Young J. Kim, Ulrich Rodeck, Athanassios Argiris, Adam J. Luginbuhl

Department of Medical Oncology Faculty Papers

PD-1 blockade represents a promising treatment in patients with head and neck squamous cell carcinoma (HNSCC). We analyzed results of a neoadjuvant randomized window-of-opportunity trial of nivolumab plus/minus tadalafil to investigate whether immunotherapy-mediated treatment effects vary by site of involvement (primary tumor, lymph nodes) and determine how radiographic tumor shrinkage correlates with pathologic treatment effect.

Patients and Methods: Forty-four patients enrolled in trial NCT03238365 were treated with nivolumab 240 mg intravenously on days 1 and 15 with or without oral tadalafil, as determined by random assignment, followed by surgery on day 31. Radiographic volumetric response (RVR) was defined as percent …

A Phase Ii Study Of The Insulin-Like Growth Factor Type I Receptor Inhibitor Imc-A12 In Patients With Metastatic Uveal Melanoma., Jane Mattei, Alexej Ballhausen, Roland Bassett, Michael Shephard, Chandrani Chattopadhyay, Courtney Hudgens, Michael Tetzlaff, Scott Woodman, Takami Sato, Sapna P Patel

Department of Medical Oncology Faculty Papers

Uveal melanoma is a rare and aggressive malignancy and up to half of all patients will develop metastatic disease despite the effective treatment of the primary tumor. Insulin-like growth factors I/II play a fundamental role in the cell migration, proliferation, and apoptosis. IMC-A12, a mAb specifically targets insulin-like growth factor type I receptor, has shown promise in preclinical studies. We performed a multicenter phase II study for patients with metastatic uveal melanoma administered IMC-A12 10 mg/kg IV every two weeks until disease progression or unacceptable toxicity. The primary endpoint was objective response (proportion of patients with complete or partial response), …

Molecular Landscape And Actionable Alterations In A Genomically Guided Cancer Clinical Trial: National Cancer Institute Molecular Analysis For Therapy Choice (Nci-Match)., Keith T Flaherty, Robert J Gray, Alice P Chen, Shuli Li, Lisa M Mcshane, David Patton, Stanley R Hamilton, P Mickey Williams, A John Iafrate, Jeffrey Sklar, Edith P Mitchell, Lyndsay N Harris, Naoko Takebe, David J Sims, Brent Coffey, Tony Fu, Mark Routbort, James A Zwiebel, Larry V Rubinstein, Richard F Little, Carlos L Arteaga, Robert Comis, Jeffrey S Abrams, Peter J O'Dwyer, Barbara A Conley

Department of Medical Oncology Faculty Papers

PURPOSE: Therapeutically actionable molecular alterations are widely distributed across cancer types. The National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial was designed to evaluate targeted therapy antitumor activity in underexplored cancer types. Tumor biopsy specimens were analyzed centrally with next-generation sequencing (NGS) in a master screening protocol. Patients with a tumor molecular alteration addressed by a targeted treatment lacking established efficacy in that tumor type were assigned to 1 of 30 treatments in parallel, single-arm, phase II subprotocols.

PATIENTS AND METHODS: Tumor biopsy specimens from 5,954 patients with refractory malignancies at 1,117 accrual sites were analyzed centrally with …

Combating Acquired Resistance To Mapk Inhibitors In Melanoma By Targeting Abl1/2-Mediated Reactivation Of Mek/Erk/Myc Signaling., Rakshamani Tripathi, Zulong Liu, Aditi Jain,, Anastasia Lyon, Christina Meeks, Dana Richards, Jinpeng Liu, Daheng He, Chi Wang, Marika Nespi, Andrey Rymar, Peng Wang, Melissa Wilson, Rina Plattner

Department of Medical Oncology Faculty Papers

Metastatic melanoma remains an incurable disease for many patients due to the limited success of targeted and immunotherapies. BRAF and MEK inhibitors reduce metastatic burden for patients with melanomas harboring BRAF mutations; however, most eventually relapse due to acquired resistance. Here, we demonstrate that ABL1/2 kinase activities and/or expression are potentiated in cell lines and patient samples following resistance, and ABL1/2 drive BRAF and BRAF/MEK inhibitor resistance by inducing reactivation of MEK/ERK/MYC signaling. Silencing/inhibiting ABL1/2 blocks pathway reactivation, and resensitizes resistant cells to BRAF/MEK inhibitors, whereas expression of constitutively active ABL1/2 is sufficient to promote resistance. Significantly, nilotinib (2^{nd …}

Early Evidence Of Dose-Dependent Pharmacodynamic Activity Following Treatment With Sy-5609, A Highly Selective And Potent Oral Cdk7 Inhibitor, In Patients With Advanced Solid Tumors, Kyriakos P. Papadopoulos, Manish R. Sharma, Erika Hamilton, Debra Richardson, Babar Bashir, Graeme Hodgson, Nan Ke, Qing Kang-Fortner, Li Zhou, William Zamboni, Hina A. Jolin, Catherine Madigan, Michael J. Kelly, David A. Roth

Department of Medical Oncology Faculty Papers

No abstract provided.

Measurable Residual Disease-Guided Treatment To Prevent Relapse In Acute Myeloid Leukemia And Myelodysplastic Syndrome., Jonathan Pan, Daniel Altman, Lindsay Wilde

Department of Medical Oncology Faculty Papers

No abstract provided.

Comparison Of Outcomes Of Hct In Blast Phase Of Bcr-Abl1- Mpn With De Novo Aml And With Aml Following Mds, Vikas Gupta, Soyoung Kim, Zhen-Huan Hu, Ying Liu, Mahmoud Aljurf, Ulrike Bacher, Amer Beitinjaneh, Jean-Yves Cahn, Jan Cerny, Edward Copelan, Shahinaz M Gadalla, Robert Peter Gale, Siddhartha Ganguly, Biju George, Aaron T Gerds, Usama Gergis, Betty K Hamilton, Shahrukh Hashmi, Gerhard C Hildebrandt, Rammurti T Kamble, Tamila Kindwall-Keller, Hillard M Lazarus, Jane L Liesveld, Mark Litzow, Richard T Maziarz, Taiga Nishihori, Richard F Olsson, David Rizzieri, Bipin N Savani, Sachiko Seo, Melhem Solh, Jeff Szer, Leo F Verdonck, Baldeep Wirk, Ann Woolfrey, Jean A Yared, Edwin P Alyea, Uday R Popat, Ronald M Sobecks, Bart L Scott, Ryotaro Nakamura, Wael Saber

Department of Medical Oncology Faculty Papers

Comparative outcomes of allogeneic hematopoietic cell transplantation (HCT) for BCR-ABL1- myeloproliferative neoplasms (MPNs) in blast phase (MPN-BP) vs de novo acute myeloid leukemia (AML), and AML with prior myelodysplastic syndromes (MDSs; post-MDS AML), are unknown. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we compared HCT outcomes in 177 MPN-BP patients with 4749 patients with de novo AML, and 1104 patients with post-MDS AML, using multivariate regression analysis in 2 separate comparisons. In a multivariate Cox model, no difference in overall survival (OS) or relapse was observed in patients with MPN-BP vs de novo AML with …

Knowledge And Practice Regarding Prostate Cancer Germline Testing Among Urologists: Gaps To Address For Optimal Implementation, Stacy Loeb, Nataliya Byrne, Dawn Walter, Danil V Makarov, David R Wise, Daniel Becker, Veda N Giri

Department of Medical Oncology Faculty Papers

BACKGROUND: Germline testing is recommended for all men with metastatic prostate cancer (PCa), and for some with localized PCa meeting specific histologic or family history criteria. Germline genetic evaluation has important implications for PCa prognosis and management, as well as implications for family members and cancer screening. Despite the importance of germline evaluation, its utilization in urologic practice is unknown.

MATERIALS AND METHODS: We conducted a 32-item survey of U.S. urologists to examine knowledge of germline testing guidelines and practice patterns. It was shared through email to 6 American Urological Association sections, the Veterans Affairs Urology Mailgroup, and social media. …

Soluble Glycoprotein Vi Is A Predictor Of Major Bleeding In Patients With Suspected Heparin-Induced Thrombocytopenia, Allyson M Pishko, Robert K Andrews, Elizabeth E Gardiner, Daniel S Lefler, Adam Cuker

Department of Medical Oncology Faculty Papers

We have shown that patients with suspected heparin-induced thrombocytopenia (HIT) have a high incidence of major bleeding. Recent studies have implicated elevated soluble glycoprotein VI (sGPVI) levels as a potential risk factor for bleeding. We sought to determine if elevated sGPVI plasma levels are associated with major bleeding events in patients with suspected HIT. We used a cohort of 310 hospitalized adult patients with suspected HIT who had a blood sample collected at the time HIT was suspected. Plasma sGPVI levels were measured by using enzyme-linked immunosorbent assay. Patients were excluded who had received a platelet transfusion within 1 day …

Translocase Of The Outer Mitochondrial Membrane Complex Subunit 20 (Tomm20) Facilitates Cancer Aggressiveness And Therapeutic Resistance In Chondrosarcoma., Megan E Roche, Zhao Lin, Diana Whitaker-Menezes, Tingting Zhan, Karoly Szuhai, Judith V M G Bovee, John A Abraham, Wei Jiang, Ubaldo Martinez-Outschoorn, Atrayee Basu-Mallick

Department of Medical Oncology Faculty Papers

Chondrosarcoma is the second most common primary bone malignancy, representing one fourth of all primary bone sarcomas. It is typically resistant to radiation and chemotherapy treatments. However, the molecular mechanisms that contribute to cancer aggressiveness in chondrosarcomas remain poorly characterized. Here, we studied the role of mitochondrial transporters in chondrosarcoma aggressiveness including chemotherapy resistance. Histological grade along with stage are the most important prognostic biomarkers in chondrosarcoma. We found that high-grade human chondrosarcoma tumors have higher expression of the mitochondrial protein, translocase of the outer mitochondrial membrane complex subunit 20 (TOMM20), compared to low-grade tumors. TOMM20 overexpression in human chondrosarcoma …

Caring For Aml Patients During The Covid-19 Crisis: An American And Italian Experience., Lindsay Wilde, Md, Alessandro Isidori, Gina Keiffer, Md, Neil D. Palmisiano, Md, Margaret Kasner

Department of Medical Oncology Faculty Papers

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the subsequent pandemic have impacted every aspect of oncology care worldwide. Healthcare systems have been forced to rapidly change practices in order to maximize the safety of patients and healthcare providers and preserve scare resources. Patients with acute myeloid leukemia are at increased risk of complications from SARS-CoV-2 not only due to immune compromise related to the malignancy but also due to the acuity of the disease and intensity of treatment. These issues have created unique challenges during this difficult time. In this article, we present the approaches taken …

The Effect Of Neighborhood Social Environment On Prostate Cancer Development In Black And White Men At High Risk For Prostate Cancer, Shannon M Lynch, Elizabeth Handorf, Kristen A Sorice, Elizabeth Blackman, Lisa Bealin, Veda N. Giri, Elias Obeid, Camille Ragin, Mary Daly

Department of Medical Oncology Faculty Papers

INTRODUCTION: Neighborhood socioeconomic (nSES) factors have been implicated in prostate cancer (PCa) disparities. In line with the Precision Medicine Initiative that suggests clinical and socioenvironmental factors can impact PCa outcomes, we determined whether nSES variables are associated with time to PCa diagnosis and could inform PCa clinical risk assessment.

MATERIALS AND METHODS: The study sample included 358 high risk men (PCa family history and/or Black race), aged 35-69 years, enrolled in an early detection program. Patient variables were linked to 78 nSES variables (employment, income, etc.) from previous literature via geocoding. Patient-level models, including baseline age, prostate specific antigen (PSA), …

Improving Nutrition And Immunity With Dry Chain And Integrated Pest Management Food Technologies In Lmics., Peetambar Dahal, Meghnath Dhimal, Krishna Belbase, Sundar Tiwari, John Groopman, Keith West, Bradley Pollock, Subodh Pyakurel, Ganga Acharya, Sunil Aryal, Yug Nath Ghimire, Manish Neupane, Rosina Poudel, Johan Van Ashbrouck, Keshavulu Kunusoth, Sarah De Saeger, Marthe De Boevre, Gokarna Gharti-Chhetri, Tek Bahadur Gurung, Kent J Bradford

Department of Medical Oncology Faculty Papers

No abstract provided.

Associations Between Aquaglyceroporin Gene Polymorphisms And Risk Of Stroke Among Patients With Hypertension, Qingyun Tu, Li Yan, Chun Wang, Aohan Han, Yu Qin, Lan Cui, Quanyong Xiang

Department of Medical Oncology Faculty Papers

Background: Dysregulations ofAQP7andAQP9were found to be related to lipid metabolism abnormality, which had been provento be one of the mechanisms of stroke. However, limited epidemiological studies explore the associations betweenAQP7andAQP9and the risk of stroke among patients with hypertension in China.

Aims: We aimed to investigate the associations between genetic variants in AQP7andAQP9and the risk of stroke among patients with hypertension, as well as to explore gene-gene andgene-environment interactions.

Methods: Baseline blood samples were drawn from 211 cases with stroke and 633 matched controls. Genomic DNA was extracted by a commercially available kit. Genotyping of 5 single nucleotide polymorphisms (SNPs) in …

A New Regulatory Mechanism Of Protein Phosphatase 2a Activity Via Set In Acute Myeloid Leukemia., Elena Arriazu, Carmen Vicente, Raffaella Pippa, Irene Peris, Elena Martínez-Balsalobre, Patricia García-Ramírez, Nerea Marcotegui, Ana Igea, Diego Alignani, José Rifón, María C. Mateos, María L. Cayuela, Angel R. Nebreda, María D. Odero

Department of Medical Oncology Faculty Papers

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy. Although novel emerging drugs are available, the overall prognosis remains poor and new therapeutic approaches are required. PP2A phosphatase is a key regulator of cell homeostasis and is recurrently inactivated in AML. The anticancer activity of several PP2A-activating drugs (e.g., FTY720) depends on their interaction with the SET oncoprotein, an endogenous PP2A inhibitor that is overexpressed in 30% of AML cases. Elucidation of SET regulatory mechanisms may therefore provide novel targeted therapies for SET-overexpressing AMLs. Here, we show that upregulation of protein kinase p38β is a common event in AML. We …

Individual And Joint Effects Of Metformin And Statins On Mortality Among Patients With High-Risk Prostate Cancer., Xiang-Lin Tan, Jian-Yu E, Yong Lin, Timothy R Rebbeck, Shou-En Lu, Mingyi Shang, William K Kelly, Anthony D'Amico, Mark N Stein, Lanjing Zhang, Thomas L Jang, Isaac Yi Kim, Kitaw Demissie, Anna Ferrari, Grace Lu-Yao

Department of Medical Oncology Faculty Papers

BACKGROUND: Pre-clinical studies suggest that metformin and statins may delay prostate cancer (PCa) metastases; however, data in humans are limited. To the best of our knowledge, this is the first human study aimed to quantify the individual and joint effects of statin and metformin use among patients with high-risk PCa.

METHODS: This population-based retrospective cohort study identified patients from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Exposure to metformin and statins was ascertained from Medicare Prescription Drug Event files. The association with all-cause and PCa mortality were evaluated using Cox proportional hazard model with competing causes of death, …

An Outcome Assessment Of A Single Institution's Longitudinal Experience With Uveal Melanoma Patients With Liver Metastasis., Rino S. Seedor, David J. Eschelman, Carin F. Gonsalves, Robert D. Adamo, Marlana Orloff, Anjum Amjad, Erin Sharpe-Mills, Inna Chervoneva, Carol L. Shields, Jerry A. Shields, Michael Mastrangelo, Takami Sato

Department of Medical Oncology Faculty Papers

There is no FDA-approved treatment for metastatic uveal melanoma (UM) and overall outcomes are generally poor for those who develop liver metastasis. We performed a retrospective single-institution chart review on consecutive series of UM patients with liver metastasis who were treated at Thomas Jefferson University Hospital between 1971–1993 (Cohort 1, n = 80), 1998–2007 (Cohort 2, n = 198), and 2008–2017 (Cohort 3, n = 452). In total, 70% of patients in Cohort 1 received only systemic therapies as their treatment modality for liver metastasis, while 98% of patients in Cohort 2 and Cohort 3 received liver-directed treatment either alone …

Treating Hematologic Malignancies During A Pandemic: Utilizing Telehealth And Digital Technology To Optimize Care., Adam F Binder, Nathan R Handley, Lindsay Wilde, Neil Palmisiano, Ana Maria Lopez

Department of Medical Oncology Faculty Papers

In late January 2020, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2) was reported as an outbreak in Wuhan, China. Within 2 months it became a global pandemic. Patients with cancer are at highest risk for both contracting and suffering complications of its resultant disease, Coronavirus 19 (COVID-19). Healthcare systems across the world had to adapt quickly to mitigate this risk, while continuing to provide potentially lifesaving treatment to patients. Bringing care to the home through the use of telehealth, home based chemotherapy, and remote patient monitoring technologies can help minimize risk to the patient and healthcare workers without sacrificing quality …

Management Of Patients With Hematologic Malignancies During The Covid-19 Pandemic: Practical Considerations And Lessons To Be Learned, Alessandro Isidori, Laurence De Leval, Usama Gergis, Pellegrino Musto, Pierluigi Porcu

Department of Medical Oncology Faculty Papers

The COVID-19 pandemic has created unprecedented hurdles to the delivery of care to patients with cancer. Patients with hematologic malignancies appear to have a greater risk of SARS-CoV-2 infection and severe disease due to myelosuppression and lymphopenia. The first challenge, therefore, is how to continue to deliver effective, curative therapy to vulnerable patients and at the same time avoid exposing them, and their health care teams (HCT), to SARS-CoV-2. An additional challenge is the timely completion of the diagnostic and staging studies required to formulate appropriate treatment plans. Deferred procedures and avoidance of multiple trips to the surgical, diagnostic, and …