Oncology Commons^™

Efficacy And Safety Of Tepotinib In Asian Patients With Advanced Nsclc With Met Exon 14 Skipping Enrolled In Vision, Terufumi Kato, James Chih-Hsin Yang, Myung-Ju Ahn, Hiroshi Sakai, Masahiro Morise, Yuh-Min Chen, Ji-Youn Han, Jin-Ji Yang, Jun Zhao, Te-Chun Hsia, Karin Berghoff, Rolf Bruns, Helene Vioix, Simone Lang, Andreas Johne, Xiuning Le, Paul K Paik

Journal Articles

BACKGROUND: Tepotinib, a MET inhibitor approved for the treatment of MET exon 14 (METex14) skipping NSCLC, demonstrated durable clinical activity in VISION (Cohort A + C; N = 313): objective response rate (ORR) 51.4% (95% CI: 45.8, 57.1); median duration of response (mDOR) 18.0 months (95% CI: 12.4, 46.4). We report outcomes in Asian patients from VISION (Cohort A + C) (cut-off: November 20, 2022).

METHODS: Patients with advanced METex14 skipping NSCLC, detected by liquid or tissue biopsy, received tepotinib 500 mg (450 mg active moiety) once daily.

PRIMARY ENDPOINT: objective response (RECIST 1.1) by independent review. Secondary endpoints included: …

Prognostic Impact Of Cooccurring Mutations In Flt3-Itd Pediatric Acute Myeloid Leukemia., Katherine Tarlock, Robert B. Gerbing, Rhonda E. Ries, Jenny L. Smith, Amanda Leonti, Benjamin J. Huang, Danielle Kirkey, Leila Robinson, Jack H. Peplinksi, Beverly Lange, Todd M. Cooper, Alan S. Gamis, E Anders Kolb, Richard Aplenc, Jessica A. Pollard, Todd A. Alonzo, Soheil Meshinchi

Manuscripts, Articles, Book Chapters and Other Papers

We sought to define the cooccurring mutational profile of FLT3-ITD-positive (ITDpos) acute myeloid leukemia (AML) in pediatric and young adult patients and to define the prognostic impact of cooperating mutations. We identified 464 patients with FLT3-ITD mutations treated on Children's Oncology Group trials with available sequencing and outcome data. Overall survival, event-free survival (EFS), and relapse risk were determined according to the presence of cooccurring risk stratifying mutations. Among the cohort, 79% of patients had cooccurring alterations across 239 different genes that were altered through mutations or fusions. Evaluation of the prognostic impact of the cooccurring mutations demonstrated that patients …

Master Transcription Factor Reprogramming Unleashes Selective Translation Promoting Castration Resistance And Immune Evasion In Lethal Prostate Cancer, Sandra Santasusagna, Shijia Zhu, Vijayakumar Jawalagatti, Marc Carceles-Cordon, Adam Ertel, Saioa Garcia-Longarte, Won-Min Song, Naoto Fujiwara, Peiyao Li, Isabel Mendizabal, Daniel P. Petrylak, William Kevin Kelly, E. Premkumar Reddy, Liguo Wang, Matthew J. Schiewer, Amaia Lujambio, Jeffrey Karnes, Karen E. Knudsen, Carlos Cordon-Cardo, Haidong Dong, Haojie Huang, Arkaitz Carracedo, Yujin Hoshida, Veronica Rodriguez-Bravo, Josep Domingo-Domenech

Department of Medical Oncology Faculty Papers

Signaling rewiring allows tumors to survive therapy. Here we show that the decrease of the master regulator microphthalmia transcription factor (MITF) in lethal prostate cancer unleashes eukaryotic initiation factor 3B (eIF3B)-dependent translation reprogramming of key mRNAs conferring resistance to androgen deprivation therapy (ADT) and promoting immune evasion. Mechanistically, MITF represses through direct promoter binding eIF3B, which in turn regulates the translation of specific mRNAs. Genome-wide eIF3B enhanced cross-linking immunoprecipitation sequencing (eCLIP-seq) showed specialized binding to a UC-rich motif present in subsets of 5' untranslated regions. Indeed, translation of the androgen receptor and major histocompatibility complex I (MHC-I) through this motif …

Targeting The Αvβ3/Ngr2 Pathway In Neuroendocrine Prostate Cancer, Anna Testa, Fabio Quaglia, Nicole M. Naranjo, Cecilia E. Verrillo, Christopher D. Shields, Stephen Lin, Maxwell W. Pickles, Drini F. Hamza, Tami Von Schalscha, David A. Cheresh, Benjamin E Leiby, Qin Liu, Jianyi Ding, William K. Kelly, D. Craig Hooper, Eva Corey, Edward F. Plow, Dario C. Altieri, Lucia R. Languino

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Highly aggressive, metastatic, neuroendocrine prostate cancer, which typically develops from prostate cancer cells acquiring resistance to androgen deprivation therapy, is associated with limited treatment options and hence poor prognosis. We have previously demonstrated that the αVβ3 integrin is over-expressed in neuroendocrine prostate cancer. We now show that LM609, a monoclonal antibody that specifically targets the human αVβ3 integrin, hinders the growth of neuroendocrine prostate cancer patient-derived xenografts in vivo. Our group has recently identified a novel αVβ3 integrin binding partner, NgR2, responsible for regulating the expression of neuroendocrine markers and for inducing neuroendocrine differentiation in prostate cancer cells. Through in …

Xaluritamig, A Steap1 × Cd3 Xmab 2+1 Immune Therapy For Metastatic Castration-Resistant Prostate Cancer: Results From Dose Exploration In A First-In-Human Study, William K. Kelly, Daniel C. Danila, Chia-Chi Lin, Jae-Lyun Lee, Nobuaki Matsubara, Patrick J. Ward, Andrew J. Armstrong, David Pook, Miso Kim, Tanya B. Dorff, Stefanie Fischer, Yung-Chang Lin, Lisa G. Horvath, Christopher Sumey, Zhao Yang, Gabor Jurida, Kristen M. Smith, Jamie N. Connarn, Hweixian L. Penny, Julia Stieglmaier, Leonard J. Appleman

Kimmel Cancer Center Faculty Papers

ABSTRACT : Xaluritamig (AMG 509) is a six-transmembrane epithelial antigen of the prostate 1 (STEAP1)-targeted T-cell engager designed to facilitate lysis of STEAP1-expressing cancer cells, such as those in advanced prostate cancer. This first-in-human study reports monotherapy dose exploration for patients with metastatic castration-resistant prostate cancer (mCRPC), primarily taxane pretreated. Ninety-seven patients received ≥1 intravenous dose ranging from 0.001 to 2.0 mg weekly or every 2 weeks. MTD was identified as 1.5 mg i.v. weekly via a 3-step dose. The most common treatment-related adverse events were cytokine release syndrome (CRS; 72%), fatigue (45%), and myalgia (34%). CRS occurred primarily during …

Conditional Risks Of Biochemical Failure And Prostate Cancer-Specific Death In Patients Undergoing External Beam Radiotherapy: A Secondary Analysis Of 2 Randomized Clinical Trials, Gregory S. Alexander, Rebecca F Krc, James W Assif, Kai Sun, Jason K Molitoris, Phuoc Tran, Zaker Rana, Søren M Bentzen, Mark V Mishra

Department of Radiation Oncology Faculty Papers

IMPORTANCE: As patients achieve years of survival after treatment for prostate cancer, the risk of biochemical failure (BF) or prostate cancer-specific death (PCSD) may evolve over time, with clinical relevance to both patients and clinicians.

OBJECTIVE: To determine conditional BF-free survival, PSCD, and overall survival estimates for patients with low- or intermediate-risk prostate cancer enrolled in the Radiation Therapy Oncology Group (RTOG) 0126 and RTOG 0415 clinical trials. A secondary objective was to determine whether prognostic factors at diagnosis remain relevant at later points in follow-up.

DESIGN, SETTING, AND PARTICIPANTS: A pooled secondary analysis of patients treated with external-beam radiotherapy …

Relative Burden Of Cancer And Noncancer Mortality Among Long-Term Survivors Of Breast, Prostate, And Colorectal Cancer In The Us, Madhav Kc, Jane Fan, Terry Hyslop, Sirad Hassan, Michael Cecchini, Shi-Yi Wang, Andrea Silber, Michael S. Leapman, Ira Leeds, Stephanie B. Wheeler, Lisa P. Spees, Cary P. Gross, Maryam Lustberg, Rachel A. Greenup, Amy C. Justice, Kevin C. Oeffinger, Michaela A. Dinan

Kimmel Cancer Center Faculty Papers

IMPORTANCE: Improvements in cancer outcomes have led to a need to better understand long-term oncologic and nononcologic outcomes and quantify cancer-specific vs noncancer-specific mortality risks among long-term survivors.

OBJECTIVE: To assess absolute and relative cancer-specific vs noncancer-specific mortality rates among long-term survivors of cancer, as well as associated risk factors.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included 627 702 patients in the Surveillance, Epidemiology, and End Results cancer registry with breast, prostate, or colorectal cancer who received a diagnosis between January 1, 2003, and December 31, 2014, who received definitive treatment for localized disease and who were alive 5 …

African American Males Have More Distress During Cancer Treatment Than White Males, Stephanie Kjelstrom, Charis Wynn, Sharon Larson

College of Population Health Faculty Papers

African American (AA) males have a higher incidence and mortality rate for some cancers than other races and sexes, which could be associated with distress during treatment, medical mistrust, and health disparities. We hypothesize distress in AA males during treatment is higher than in other races and sexes. We assessed effect modification of moderate to severe (≥ 4) distress scores during cancer treatment by race and sex, age, and socioeconomic status (SES). National Comprehensive Cancer Network's distress thermometer (scale 0-10) and characteristics for 770 cancer patients were collected from a Philadelphia hospital. Variables included age, sex, race, smoking status, marital …

Long-Term Outcomes Of Bevacizumab And Chemoradiation For Locoregionally Advanced Nasopharyngeal Carcinoma: A Nonrandomized Controlled Trial, Nancy Y. Lee, Jonathan Harris, John Kim, Adam Garden, James Mechalakos, David G. Pfister, Anthony T.C. Chan, Kenneth Hu, A. Dimitrios Colevas, Steven Frank, George Shenouda, Voichita Bar-Ad, John N. Waldron, Paul M. Harari, Adam Raben, Pedro Torres-Saavedra, Quynh-Thu Le

Department of Radiation Oncology Faculty Papers

IMPORTANCE: The long-term outcomes associated with adding bevacizumab, a vascular endothelial growth factor inhibitor, to standard chemoradiation have continued to be favorable for a group of patients with locoregionally advanced nasopharyngeal carcinoma (NPC).

OBJECTIVE: To assess long-term toxic effects and clinical outcomes associated with chemotherapy, radiation therapy (RT), and bevacizumab for NPC.

DESIGN, SETTING, AND PARTICIPANTS: This single-arm phase II nonrandomized controlled trial was conducted by the National Cancer Trials Network group and NRG Oncology (formerly Radiation Therapy Oncology Group), with accrual from December 13, 2006, to February 5, 2009, and data analysis from June 26 to July 1, 2019. …

Impact Of An Expanded Definition Of Family History On Outcomes Of Active Surveillance For Prostate Cancer, Adam C. Schneider, Thenappan Chandrasekar, Nicholas Bowler, Ryan Fogg, Joon Yau Leong, Andrew Gusev, Linda H. Rodgers, Shelley R. Mccormick, Douglas M. Dahl, Jason A. Efstathiou, Michael L. Blute, Anthony L. Zietman, Chin-Lee Wu, Matthew R. Smith, Eliezer M. Van Allen, Adam S. Feldman, Keyan Salari

Department of Urology Faculty Papers

PURPOSE: Despite family history being an established risk factor for prostate cancer, the role of a broader definition of family history inclusive of not just prostate cancer but other genetically related malignancies has not been investigated in the active surveillance population. Here, we evaluate the impact of an expanded definition of family history on active surveillance outcomes.

MATERIALS AND METHODS: Patients undergoing active surveillance for prostate cancer at Massachusetts General Hospital from 1997-2019 with detailed data available on family cancer history were identified. Primary outcome was biopsy progression-free survival, and secondary outcomes were treatment-free survival, adverse pathological features at prostatectomy, …

Association Of Radiotherapy Duration With Clinical Outcomes In Patients With Esophageal Cancer Treated In Nrg Oncology Trials: A Secondary Analysis Of Nrg Oncology Randomized Clinical Trials, Christopher L. Hallemeier, Jennifer Moughan, Michael G. Haddock, Arnold M. Herskovic, Bruce D. Minsky, Mohan Suntharalingam, Kenneth L. Zeitzer, Madhur K. Garg, Bruce D. Greenwald, Ritsuko U. Komaki, Lindsay L. Puckett, Hyun Kim, Shane Lloyd, David A. Bush, Harold E. Kim, Thomas E. Lad, Joshua E. Meyer, Gordon S. Okawara, Adam Raben, Tracey E. Schefter, Jerry L. Barker, Carla I. Falkson, Gregory M.M. Videtic, Rojymon Jacob, Kathryn A. Winter, Christopher H. Crane

Einstein Health Papers

IMPORTANCE: For many types of epithelial malignant neoplasms that are treated with definitive radiotherapy (RT), treatment prolongation and interruptions have an adverse effect on outcomes.

OBJECTIVE: To analyze the association between RT duration and outcomes in patients with esophageal cancer who were treated with definitive chemoradiotherapy (CRT).

DESIGN, SETTING, AND PARTICIPANTS: This study was an unplanned, post hoc secondary analysis of 3 prospective, multi-institutional phase 3 randomized clinical trials (Radiation Therapy Oncology Group [RTOG] 8501, RTOG 9405, and RTOG 0436) of the National Cancer Institute-sponsored NRG Oncology (formerly the National Surgical Adjuvant Breast and Bowel Project, RTOG, and Gynecologic Oncology …

A Rare Metastatic Mesenteric Malignant Pecoma With Tsc2 Mutation Treated With Palliative Surgical Resection And Nab-Sirolimus: A Case Report, Luke Meredith, Timothy Chao, Avinoam Nevler, Atrayee Basu Mallick, Rajan Singla, Peter Mccue, Wilbur Bowne, Wei Jiang, Md, Phd

Kimmel Cancer Center Faculty Papers

BACKGROUND: Malignant perivascular epithelioid cell tumors (PEComas) are exceedingly rare malignant mesenchymal neoplasms with characteristic morphological and immunohistochemical (IHC) patterns. However, some malignant PEComas are poorly differentiated with atypical histopathological features, making a definitive diagnosis difficult. PEComas are most commonly found in females and often show either TSC1 or TSC2 alterations, which result in the activation of the mTOR pathway, or TFE3 fusions. Given these molecular characteristics, mTOR inhibitors have recently been approved by the FDA in the treatment of malignant PEComas, particularly in those with TSC1/2 alterations. Therefore, molecular analyses may be helpful for both the diagnostic workup of …

An Unusual Case Of Hemophagocytic Lymphohistiocytosis Associated With Mycobacterium Chimaera Or Large-Cell Neuroendocrine Carcinoma, Tejaswi Venigalla, Sheila Kalathil, Meena Bansal, Mark Morginstin, Vinicius Jorge, Patricia Perosio

Einstein Health Papers

Hemophagocytic lymphohistiocytosis (HLH) is a rare and very dangerous condition characterized by abnormal activation of the immune system, causing hemophagocytosis, inflammation, and potentially widespread organ damage. The primary (genetic) form, caused by mutations affecting lymphocyte cytotoxicity, is most commonly seen in children. Secondary HLH is commonly associated with infections, malignancies, and rheumatologic disorders. Most current information on diagnosis and treatment is based on pediatric populations. HLH is a disease that should be diagnosed and treated promptly, otherwise it is fatal. Treatment is directed at treating the triggering disorder, along with symptomatic treatment with dexamethasone and etoposide. We present a 56-year-old …

Hemangioblastoma With Late Leptomeningeal Metastasis: A Case Report, Spencer J. Poiset, Aneesh Reddy, Catherine M. Tucker, Lawrence C. Kenyon, Kevin D. Judy, Wenyin Shi

Department of Radiation Oncology Faculty Papers

BACKGROUND: Hemangioblastoma of the central nervous system is an uncommon benign neoplasm, with about 25% of cases in patients with von Hippel-Lindau disease. The incidence of metastasis is rare, particularly in patients without von Hippel-Lindau disease. We report a case of hemangioblastoma with leptomeningeal dissemination as a late recurrence.

CASE PRESENTATION: A 65-year-old Caucasian man with a history of World Health Organization grade I hemangioblastoma of the cerebellar vermis underwent gross total resection in 1997. In early 2018, he developed intracranial recurrences with diffuse leptomeningeal disease of the entire spine. The patient underwent resection of intracranial recurrence, followed by palliative …

Arrhythmogenic Cardiotoxicity Associated With Contemporary Treatments Of Lymphoproliferative Disorders, Saadia Sherazi, Susan Schleede, Scott Mcnitt, Carla Casulo, Jeremiah E. Moore, Eugene Storozynsky, Arpan Patel, Neelima Vidula, Mehmet K. Aktas, Clive S. Zent, Ilan Goldenberg

Division of Cardiology Faculty Papers

Background

Methods and Results

State Variation In Squamous Cell Carcinoma Of The Anus Incidence And Mortality, And Association With Hiv/Aids And Smoking In The United States, Haluk Damgacioglu, Yueh-Yun Lin, Ana Patricia Ortiz, Chi-Fang Wu, Zahed Shahmoradi, Shiang Shiuan Shyu, Ruosha Li, Alan G Nyitray, Keith Sigel, Gary M Clifford, Naomi Jay, Vivian Colon Lopez, Gregory M Barnell, Elizabeth Y Chiao, Elizabeth A Stier, Karen J Ortiz-Ortiz, Jeslie M Ramos-Cartagena, Kalyani Sonawane, Ashish A Deshmukh

Journal Articles

PURPOSE: Squamous cell carcinoma of the anus (SCCA) incidence and mortality rates are rising in the United States. Understanding state-level incidence and mortality patterns and associations with smoking and AIDS prevalence (key risk factors) could help unravel disparities and provide etiologic clues.

METHODS: Using the US Cancer Statistics and the National Center for Health Statistics data sets, we estimated state-level SCCA incidence and mortality rates. Rate ratios (RRs) were calculated to compare incidence and mortality in 2014-2018 versus 2001-2005. The correlations between SCCA incidence with current smoking (from the Behavioral Risk Factor Surveillance System) and AIDS (from the HIV Surveillance …

Harnessing Transcriptionally Driven Chromosomal Instability Adaptation To Target Therapy-Refractory Lethal Prostate Cancer., Brittiny Dhital, Sandra Santasusagna, Perumalraja Kirthika, Michael Xu, Peiyao Li, Marc Carceles-Cordon, Rajesh K. Soni, Zhuoning Li, Ronald C. Hendrickson, Matthew J. Schiewer, William K. Kelly, Cora N. Sternberg, Jun Luo, Amaia Lujambio, Carlos Cordon-Cardo, Monica Alvarez-Fernandez, Marcos Malumbres, Haojie Huang, Adam Ertel, Josep Domingo-Domenech, Veronica Rodriguez-Bravo

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

Metastatic prostate cancer (PCa) inevitably acquires resistance to standard therapy preceding lethality. Here, we unveil a chromosomal instability (CIN) tolerance mechanism as a therapeutic vulnerability of therapy-refractory lethal PCa. Through genomic and transcriptomic analysis of patient datasets, we find that castration and chemotherapy-resistant tumors display the highest CIN and mitotic kinase levels. Functional genomics screening coupled with quantitative phosphoproteomics identify MASTL kinase as a survival vulnerability specific of chemotherapy-resistant PCa cells. Mechanistically, MASTL upregulation is driven by transcriptional rewiring mechanisms involving the non-canonical transcription factors androgen receptor splice variant 7 and E2F7 in a circuitry that restrains deleterious CIN and …

Effect Of A Muc5ac Antibody (Npc-1c) Administered With Second-Line Gemcitabine And Nab-Paclitaxel On The Survival Of Patients With Advanced Pancreatic Ductal Adenocarcinoma: A Randomized Clinical Trial, Brandon M Huffman, Atrayee Basu Mallick, Nora K Horick, Andrea Wang-Gillam, Peter Joel Hosein, Michael A Morse, Muhammad Shaalan Beg, Janet E Murphy, Sharon Mavroukakis, Anjum Zaki, Benjamin L Schlechter, Hanna Sanoff, Christopher Manz, Brian M Wolpin, Philip Arlen, Jill Lacy, James M Cleary

Department of Medical Oncology Faculty Papers

Importance: Treatment options are limited for patients with advanced pancreatic ductal adenocarcinoma (PDAC) beyond first-line 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX), with such individuals commonly being treated with gemcitabine and nab-paclitaxel.

Objective: To determine whether NPC-1C, an antibody directed against MUC5AC, might increase the efficacy of second-line gemcitabine and nab-paclitaxel in patients with advanced PDAC.

Design, setting, and participants: This multicenter, randomized phase II clinical trial enrolled patients with advanced PDAC between April 2014 and March 2017 whose disease had progressed on first-line FOLFIRINOX. Eligible patients had tumors with at least 20 MUC5AC staining by centralized immunohistochemistry review. Statistical analysis …

High Local Control And Low Ocular Toxicity Using Ultra-Low-Dose “Boom-Boom” Radiotherapy For Indolent Orbital Lymphoma, Sanjna Shelukar, Christian Fernandez, Zeynep Bas, Lydia Komarnicky, Sara E. Lally, Carol L Shields, Adam Binder, Pierluigi Porcu, Onder Alpdogan, Ubaldo Martinez-Outschoorn, Wenyin Shi

Department of Medical Oncology Faculty Papers

Background: The first line definitive treatment for early-stage indolent B-cell lymphoma is radiation therapy (RT). Due to the sensitivity of orbital structures to radiation, ultra-low-dose RT (4 Gy in 2 fractions, "boom-boom") has and been utilized as an attractive option for orbital lymphoma. In this retrospective study, we evaluated the outcome and toxicity of "boom-boom" RT for indolent orbital lymphoma with an emphasis on ophthalmologic toxicity.

Methods: This is a retrospective case series with 17 patients with orbital lymphoma who received boom-boom RT at a single tertiary referral center between January 2017 and June 2022. Medical records, imaging and radiation …

The Nogo Receptor Ngr2, A Novel Αvβ3 Integrin Effector, Induces Neuroendocrine Differentiation In Prostate Cancer, Fabio Quaglia, Shiv Ram Krishn, Khalid Sossey-Alaoui, Priyanka Shailendra Rana, Elzbieta Pluskota, Pyung Hun Park, Christopher D. Shields, Stephen Lin, Peter Mccue, Andrew V. Kossenkov, Yanqing Wang, David W. Goodrich, Sheng-Yu Ku, Himisha Beltran, William K. Kelly, Eva Corey, Maja Klose, Christine Bandtlow, Qin Liu, Dario C. Altieri, Edward F. Plow, Lucia R. Languino

Department of Cancer Biology Faculty Papers

Androgen deprivation therapies aimed to target prostate cancer (PrCa) are only partially successful given the occurrence of neuroendocrine PrCa (NEPrCa), a highly aggressive and highly metastatic form of PrCa, for which there is no effective therapeutic approach. Our group has demonstrated that while absent in prostate adenocarcinoma, the αVβ3 integrin expression is increased during PrCa progression toward NEPrCa. Here, we show a novel pathway activated by αVβ3 that promotes NE differentiation (NED). This novel pathway requires the expression of a GPI-linked surface molecule, NgR2, also known as Nogo-66 receptor homolog 1. We show here that NgR2 is upregulated by αVβ3, …

Genomic Testing In Localized Prostate Cancer Can Identify Subsets Of African Americans With Aggressive Disease, Shivanshu Awasthi, G. Daniel Grass, Javier Torres-Roca, Peter A. S. Johnstone, Julio Pow-Sang, Jasreman Dhillon, Jong Park, Robert J. Rounbehler, Elai Davicioni, Alex Hakansson, Yang Liu, Angelina K. Fink, Amanda Derenzis, Jordan H. Creed, Michael Poch, Roger Li, Brandon Manley, Daniel Fernandez, Arash Naghavi, Kenneth Gage, Grace Lu-Yao, Evangelia Katsoulakis, Ryan J. Burri, Andrew Leone, Cesar E. Ercole, Joshua D. Palmer, Neha Vapiwala, Curtiland Deville, Timothy R. Rebbeck, Adam P. Dicker, William Kelly, Kosj Yamoah

Department of Medical Oncology Faculty Papers

BACKGROUND: Personalized genomic classifiers have transformed the management of prostate cancer (PCa) by identifying the most aggressive subsets of PCa. Nevertheless, the performance of genomic classifiers to risk classify African American men is thus far lacking in a prospective setting.

METHODS: This is a prospective study of the Decipher genomic classifier for National Comprehensive Cancer Network low- and intermediate-risk PCa. Study-eligible non-African American men were matched to African American men. Diagnostic biopsy specimens were processed to estimate Decipher scores. Samples accrued in NCT02723734, a prospective study, were interrogated to determine the genomic risk of reclassification (GrR) between conventional clinical risk …

A Scoping Review Protocol To Elucidate Outcomes Following Abiraterone Versus Enzalutamide For Prostate Cancer, Yash B Shah, Amy L Shaver, William Kevin Kelly, Grace Lu-Yao

Department of Medical Oncology Faculty Papers

INTRODUCTION: Abiraterone acetate and enzalutamide are commonly employed in prostate cancer therapy in an interchangeable manner. These drugs are highly efficacious in androgen antagonism to improve patient outcomes, but they also carry noteworthy risk of adverse effects. Common toxicities vary amongst the two drugs and may have differential interactions with patient co-morbidities, but these patterns are unclear as co-morbidities typically serve as exclusion criteria in clinical trials. Hence, there is no existing guidance on how clinicians may tailor treatment based on patient-specific factors. Analysis of differential patient outcomes between these two drugs can inform future systematic reviews, new clinical studies, …

Understanding The Role Of Sex On Outcomes For The Cancer Patient Undergoing Treatment With Immune Checkpoint Inhibitors: A Scoping Review Protocol, Amy L Shaver, Nikita Nikita, Swapnil Sharma, Daniel S Lefler, Atrayee Basu-Mallick, Jennifer M Johnson, Meghan L Butryn, Grace Lu-Yao

Department of Medical Oncology Faculty Papers

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have changed the treatment landscape for multiple cancer types. Sex plays an important role in both the development of cancer as well as the functioning of the immune system. Though a difference in response to immune therapy is emerging between men and women it is unclear how this difference affects cancer outcomes and what the potential underlying mechanisms are for those effects. The objective of this study is to describe the influence that sex has on the outcomes experienced by cancer patients on ICI therapy and to identify and analyse any knowledge gaps in the …

Effect Of Musculature On Mortality, A Retrospective Cohort Study, Amy L Shaver, Mary E Platek, Anurag K Singh, Sung Jun Ma, Mark Farrugia, Gregory Wilding, Andrew D Ray, Heather M Ochs-Balcom, Katia Noyes

Department of Medical Oncology Faculty Papers

Background: While often life-saving, treatment for head and neck cancer (HNC) can be debilitating resulting in unplanned hospitalization. Hospitalizations in cancer patients may disrupt treatment and result in poor outcomes. Pre-treatment muscle quality and quantity ascertained through diagnostic imaging may help identify patients at high risk of poor outcomes early. The primary objective of this study was to determine if pre-treatment musculature was associated with all-cause mortality.

Methods: Patient demographic and clinical characteristics were abstracted from the cancer center electronic database (n = 403). Musculature was ascertained from pre-treatment CT scans. Propensity score matching was utilized to adjust for confounding …

The Impact Of Racial Disparities And Outcomes On Urinary Anastomotic Leak In Radical Prostatectomy, Young Son, Benjamin A. Fink, Lance Earnshaw, Brian Thomas, Fred Okoye, Ryan Moriarty, Kathryn Goettle, Thomas Mueller

Rowan-Virtua Research Day

Prostate cancer is the leading malignancy and third most common cause of cancer death among men. In the United States, racial disparities exist in prostate cancer incidence and mortality rates. According to the National Cancer Institute, African American (AA) men have a significantly increased incidence of prostate cancer compared to Caucasians or Asians. Urinary leak at the urethrovesical anastomosis has been cited as a complication of radical prostatectomy (RP), with incidence rates as high as 23%. Urinary anastomotic leak is associated with increased rates of ileus, prolonged hospitalization rates, and longer time to achieve continence. The etiology of risk factors …

Genetic Evaluation For Hereditary Cancer Syndromes Among African Americans: A Critical Review, Ambreen Khan, Charles R Rogers, Carson D Kennedy, Ana Maria Lopez, Joanne Jeter

Department of Medical Oncology Faculty Papers

While hereditary cancer syndromes have been described and studied for centuries, the completion of the human genome project fueled accelerated progress in precision medicine due to the introduction of genetic testing in the 1990s, creating avenues for tailored treatments and medical management options. However, genetic testing has not benefited everyone equitably, with nearly all of the published work based on individuals of non-Hispanic White/European ancestry. There remains a gap in knowledge regarding the prevalence, penetrance, and manifestations of common hereditary cancer syndromes in the African-American population due to significant disparities in access and uptake of genetic testing. This review summarizes …

When Eating Becomes Torturous: Understanding Nutrition-Related Cancer Treatment Side Effects Among Individuals With Cancer And Their Caregivers, Brandy-Joe Milliron, Lora Packel, Dan Dychtwald, Cynthia Klobodu, Laura Pontiggia, Ochi Ogbogu, Byron Barksdale, Jonathan Deutsch

Institute of Emerging Health Professions Faculty Papers

Individuals living with cancer often experience multiple nutrition-related side effects from cancer treatment, including changes in taste and smell, nausea, diarrhea, loss of appetite, and pain during eating. These side effects can profoundly impact nutritional status and quality of life. The purpose of this study was to explore experiences with nutrition-related cancer treatment side effects among cancer patients and their family caregivers, the way they manage such side effects, and the resulting changes in food preferences and behaviors. Structured surveys and in-depth interviews were conducted. Interviews focused on the presence and management of treatment side effects, how those changes influenced …

Assessment Of Regional Variability In Covid-19 Outcomes Among Patients With Cancer In The United States., Jessica E Hawley, Tianyi Sun, David D Chism, Narjust Duma, Julie C Fu, Na Tosha N Gatson, Sanjay Mishra, Ryan H Nguyen, Sonya A Reid, Oscar K Serrano, Sunny R K Singh, Neeta K Venepalli, Ziad Bakouny, Babar Bashir, Mehmet A Bilen, Paolo F Caimi, Toni K Choueiri, Scott J Dawsey, Leslie A Fecher, Daniel B Flora, Christopher R Friese, Michael J Glover, Cyndi J Gonzalez, Sharad Goyal, Thorvardur R Halfdanarson, Dawn L Hershman, Hina Khan, Chris Labaki, Mark A Lewis, Rana R Mckay, Ian Messing, Nathan A Pennell, Matthew Puc, Deepak Ravindranathan, Terence D Rhodes, Andrea V Rivera, John Roller, Gary K Schwartz, Sumit A Shah, Justin A Shaya, Mitrianna Streckfuss, Michael A Thompson, Elizabeth M Wulff-Burchfield, Zhuoer Xie, Peter Paul Yu, Jeremy L Warner, Dimpy P Shah, Benjamin French, Clara Hwang

Kimmel Cancer Center Faculty Papers

Importance: The COVID-19 pandemic has had a distinct spatiotemporal pattern in the United States. Patients with cancer are at higher risk of severe complications from COVID-19, but it is not well known whether COVID-19 outcomes in this patient population were associated with geography.

Objective: To quantify spatiotemporal variation in COVID-19 outcomes among patients with cancer.

Design, Setting, and Participants: This registry-based retrospective cohort study included patients with a historical diagnosis of invasive malignant neoplasm and laboratory-confirmed SARS-CoV-2 infection between March and November 2020. Data were collected from cancer care delivery centers in the United States.

Exposures: Patient residence was categorized …

Machine Learning Analyses Of Highly-Multiplexed Immunofluorescence Identifies Distinct Tumor And Stromal Cell Populations In Primary Pancreatic Tumors, Krysten Vance, Alphan Alitinok, Seth Winfree, Heather Jensen Smith, Benjamin Swanson Md, Phd, Paul M. Grandgenett, Kelsey Klute, Daniel J Crichton, Michael A. Hollingsworth

Journal Articles: Eppley Institute

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a formidable challenge for patients and clinicians.

OBJECTIVE: To analyze the distribution of 31 different markers in tumor and stromal portions of the tumor microenvironment (TME) and identify immune cell populations to better understand how neoplastic, non-malignant structural, and immune cells, diversify the TME and influence PDAC progression.

METHODS: Whole slide imaging (WSI) and cyclic multiplexed-immunofluorescence (MxIF) was used to collect 31 different markers over the course of nine distinctive imaging series of human PDAC samples. Image registration and machine learning algorithms were developed to largely automate an imaging analysis pipeline identifying distinct cell …

Risk Of Developing Alzheimer's Disease And Related Dementias In Association With Cardiovascular Disease, Stroke, Hypertension, And Diabetes In A Large Cohort Of Women With Breast Cancer And With Up To 26 Years Of Follow-Up, Xianglin L Du, Lulu Song, Paul E Schulz, Hua Xu, Wenyaw Chan

Journal Articles

BACKGROUND: No study on the long-term incidence of Alzheimer's disease (AD) and related dementias (ADRD) has been reported in women with breast cancer by vascular diseases.

OBJECTIVE: to determine the risk of ADRD in association with cardiovascular diseases (CVD), stroke, hypertension, and diabetes in women with breast cancer.

METHODS: Study identified 246,686 women diagnosed with breast cancer at age≥65 years in 1991-2015 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Women were free of ADRD at the time of cancer diagnosis and followed from 1991 to 2016.

RESULTS: Cumulative incidence of AD over 26 years of follow-up varied …