Medicine and Health Sciences Commons^™

Integrative Analysis Of Clinicopathological Features Defines Novel Prognostic Models For Mantle Cell Lymphoma In The Immunochemotherapy Era: A Report From The North American Mantle Cell Lymphoma Consortium, Julie M Vose, Kai Fu, Lu Wang, Adnan Mansoor, Douglas Stewart, Hongxia Cheng, Lynette Smith, Ji Yuan, Hina Naushad Qureishi, Brian K Link, Melissa H Cessna, Paul M Barr, Brad S Kahl, Matthew S Mckinney, Nadia Khan, Ranjana H Advani, Peter Martin, Andre H Goy, Tycel J Phillips, Amitkumar Mehta, Manali Kamdar, Michael Crump, Barbara Pro, Christopher R Flowers, Caron A Jacobson, Sonali M Smith, Deborah M Stephens, Veronika Bachanova, Zhaohui Jin, Shishou Wu, Francisco Hernandez-Ilizaliturri, Pallawi Torka, Andrea Anampa-Guzmán, Farshid Kashef, Xing Li, Sunandini Sharma, Timothy C Greiner, James O Armitage, Matthew Lunning, Dennis D Weisenburger, Robert G Bociek, Javeed Iqbal, Guohua Yu, Chengfeng Bi, North American Mantle Cell Lymphoma Consortium

Journal Articles

BACKGROUND: Patients with mantle cell lymphoma (MCL) exhibit a wide variation in clinical presentation and outcome. However, the commonly used prognostic models are outdated and inadequate to address the needs of the current multidisciplinary management of this disease. This study aims to investigate the clinical and pathological features of MCL in the immunochemotherapy era and improve the prognostic models for a more accurate prediction of patient outcomes.

METHODS: The North American Mantle Cell Lymphoma Project is a multi-institutional collaboration of 23 institutions across North America to evaluate and refine prognosticators for front-line therapy. A total of 586 MCL cases diagnosed …

Single-Cell Analysis Reveals Diversity Of Tumor-Associated Macrophages And Their Interactions With T Lymphocytes In Glioblastoma., Sai Batchu, Khalid A Hanafy, Navid Redjal, Saniya S Godil, Ajith J Thomas

Cooper Medical School of Rowan University Faculty Scholarship

Glioblastoma (GBM) is an aggressive primary CNS malignancy and clinical outcomes have remained stagnant despite introduction of new treatments. Understanding the tumor microenvironment (TME) in which tumor associated macrophages (TAMs) interact with T cells has been of great interest. Although previous studies examining TAMs in GBM have shown that certain TAMs are associated with specific clinical and/or pathologic features, these studies used an outdated M1/M2 paradigm of macrophage polarization and failed to include the continuum of TAM states in GBM. Perhaps most significantly, the interactions of TAMs with T cells have yet to be fully explored. Our study uses single-cell …

Clinical And Dosimetric Impact Of 2d Kv Motion Monitoring And Intervention In Liver Stereotactic Body Radiation Therapy., Andrew Santoso, Yevgeniy Vinogradskiy, Tyler Robin, Karyn Goodman, Tracey Schefter, Moyed Miften, Bernard Jones

Department of Radiation Oncology Faculty Papers

PURPOSE: Positional errors resulting from motion are a principal challenge across all disease sites in radiation therapy. This is particularly pertinent when treating lesions in the liver with stereotactic body radiation therapy (SBRT). To achieve dose escalation and margin reduction for liver SBRT, kV real-time imaging interventions may serve as a potential solution. In this study, we report results of a retrospective cohort of liver patients treated using real-time 2D kV-image guidance SBRT with emphasis on the impact of (1) clinical workflow, (2) treatment accuracy, and (3) tumor dose.

METHODS AND MATERIALS: Data from 33 patients treated with 41 courses …

Targeted Therapy With Nanatinostat And Valganciclovir In Recurrent Ebv-Positive Lymphoid Malignancies: A Phase 1b/2 Study, Bradley Haverkos, Onder Alpdogan, Robert Baiocchi, Jonathan E. Brammer, Tatyana A. Feldman, Marcelo Capra, Elizabeth A. Brem, Santosh Nair, Phillip Scheinberg, Juliana Pereira, Leyla Shune, Erel Joffe, Patricia Young, Susan Spruill, Afton Katkov, Robert Mcrae, Ivor Royston, Douglas V. Faller, Lisa Rojkjaer, Pierluigi Porcu

Department of Medical Oncology Faculty Papers

Lymphomas are not infrequently associated with the Epstein-Barr virus (EBV), and EBV positivity is linked to worse outcomes in several subtypes. Nanatinostat is a class-I selective oral histone deacetylase inhibitor that induces the expression of lytic EBV BGLF4 protein kinase in EBV+ tumor cells, activating ganciclovir via phosphorylation, resulting in tumor cell apoptosis. This phase 1b/2 study investigated the combination of nanatinostat with valganciclovir in patients aged ≥18 years with EBV+ lymphomas relapsed/refractory to ≥1 prior systemic therapy with no viable curative treatment options. In the phase 1b part, 25 patients were enrolled into 5 dose escalation cohorts to determine …

Identification Of Dual Strn-Ntrk2 Rearrangements In A High Grade Sarcoma, With Good Clinical Response To First-Line Larotrectinib Therapy, Ruihe Lin, Atrayee Basu Mallick, Zi-Xuan Wang, Phd, Scot Andrew Brown, Bo Lu, Md, Wei Jiang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Among the three NTRK genes, NTRK2 possesses a tremendous structural complexity and involves tumorigenesis of several types of tumors. To date, only STRN and RBPMS are identified in the fusion with NTRK2 in adult soft tissue tumors. More recently, the highly selective Trk tyrosine kinases inhibitors, including larotrectinib and entrectinib, have shown significant efficacy for treating tumors harboring NTRK fusions and were approved by FDA.

CASE PRESENTATION: We report a case of sarcoma in a 35-year-old female harboring two STRN-NTRK2 gene fusions, with a good clinical response to first-line larotrectinib treatment. Core biopsy of the 16.5 cm gluteal mass …

A Proof-Of-Concept Pilot Test Of A Behavioral Intervention To Improve Adherence To Dietary Recommendations For Cancer Prevention, Meghan Butryn, Charlotte Hagerman, Nicole Crane, Marny Ehmann, Evan Forman, Brandy-Joe Milliron, Nicole L. Simone

Department of Radiation Oncology Faculty Papers

OBJECTIVES: Prevention programs that can help adults improve the quality of their diets to reduce cancer risk are needed. This Phase IIa study prospectively tested a mHealth intervention designed to improve adherence to dietary quality guidelines for cancer prevention.

METHODS: All participants (N = 62) received nutrition education and a self-regulation skills curriculum, with a primary target of changing grocery shopping behavior. Using a randomized, factorial design, the study varied whether each of the following 4 components were added to the 20-week intervention: (1) location-triggered app messaging, delivered when individuals arrived at grocery stores, (2) reflections on benefits of change, …

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 …

Impact Of Second Primary Malignancy Post–Autologous Transplantation On Outcomes Of Multiple Myeloma: A Cibmtr Analysis, Brittany Knick Ragon, Mithun Vinod Shah, Anita D'Souza, Noel Estrada-Merly, Lohith Gowda, Gemlyn George, Marcos De Lima, Shahrukh Hashmi, Mohamed A. Kharfan-Dabaja, Navneet S. Majhail, Rahul Banerjee, Ayman Saad, Gerhard C. Hildebrandt, Hira Mian, Muhammad Bilal Abid, Minoo Battiwalla, Lazaros J. Lekakis, Sagar S. Patel, Hemant S. Murthy, Yago Nieto, Christopher Strouse, Sherif M. Badawy, Samer Al Hadidi, Bhagirathbhai Dholaria, Mahmoud Aljurf, David H. Vesole, Cindy H. Lee, Attaphol Pawarode, Usama Gergis, Kevin C. Miller, Leona A. Holmberg, Aimaz Afrough, Melhem Solh, Pashna N. Munshi, Taiga Nishihori, Larry D. Anderson, Baldeep Wirk, Gurbakhash Kaur, Muzaffar H. Qazilbash, Nina Shah, Shaji K. Kumar, Saad Z. Usmani

Department of Medical Oncology Faculty Papers

The overall survival (OS) has improved significantly in multiple myeloma (MM) over the last decade with the use of proteasome inhibitor and immunomodulatory drug-based combinations, followed by high-dose melphalan and autologous hematopoietic stem cell transplantation (auto-HSCT) and subsequent maintenance therapies in eligible newly diagnosed patients. However, clinical trials using auto-HSCT followed by lenalidomide maintenance have shown an increased risk of second primary malignancies (SPM), including second hematological malignancies (SHM). We evaluated the impact of SPM and SHM on progression-free survival (PFS) and OS in patients with MM after auto-HSCT using CIBMTR registry data. Adult patients with MM who underwent first …

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. …

Protocol And Biomarker Strategy For A Multi-Site Randomized Controlled Trial Examining Biological Mechanisms And Dosing Of Active Music Engagement In Children With Acute Lymphoblastic Leukemia And Lymphoma And Parents., Sheri L. Robb, Kristen A. Russ, Steven J. Holochwost, Kristin Stegenga, Susan M. Perkins, Seethal A. Jacob, Amanda K. Henley, Jessica A. Maclean

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Music therapy is a standard palliative care service in many pediatric and adult hospitals; however, most research has focused on the use of music to improve psychosocial dimensions of health, without considering biological dimensions. This study builds on prior work examining psychosocial mechanisms of action underlying an Active Music Engagement (AME) intervention, designed to help manage emotional distress and improve positive health outcomes in young children with cancer and parents (caregivers), by examining its effects on biomarkers of stress and immune function.

METHODS: This two-group randomized controlled trial (R01NR019190) is designed to examine biological mechanisms of effect and dose-response …

Juvenile Granulosa Cell Tumor In An Adult Woman During Pregnancy: A Case Report And Review Of The Literature, Mackenzie Cummings, Pamela Edmonds, Mark S. Shahin, Joe I. Sorosky

Abington Jefferson Health Papers

Objective

To report a case of stage IIIB juvenile granulosa cell tumor (JGCT) complicating pregnancy in a 33 year-old (y.o.) woman.

Methods

Retrospective review of the clinical data, imaging studies, and pathology reports of a case of JGCT diagnosed during pregnancy. Patient consent was obtained for review and presentation of the case. A literature review was conducted.

Results

A 33 y.o., gravida 3, para 1 was incidentally found to have an 8 cm left ovarian mass on an anatomy scan at 22 weeks gestation. Four days later, she presented to labor and delivery triage with abdominal pain. An ultrasound revealed …

In Utero Exposure To Antiemetic And Risk Of Adult-Onset Colorectal Cancer, Caitlin C Murphy, Piera M Cirillo, Nickilou Y Krigbaum, Amit G Singal, Barbara A Cohn

Journal Articles

BACKGROUND: Incidence rates of colorectal cancer (CRC) are increasing among adults born in and after the 1960s, implicating pregnancy-related exposures introduced at that time as risk factors. Dicyclomine, an antispasmodic used to treat irritable bowel syndrome, was initially included in Bendectin (comprising doxylamine, pyridoxine, and dicyclomine), an antiemetic prescribed during pregnancy in the 1960s.

METHODS: We estimated the association between in utero exposure to Bendectin and risk of CRC in offspring of the Child Health and Development Studies, a multigenerational cohort that enrolled pregnant women in Oakland, CA, between 1959 and 1966 (n = 14 507 mothers and 18 751 …

Higher Doses Of Tisagenlecleucel Are Associated With Improved Outcomes: A Report From The Pediatric Real-World Car Consortium., Heather E. Stefanski, Anne Eaton, Christina Baggott, Jenna Rossoff, Michael R. Verneris, Snehit Prabhu, Holly L. Pacenta, Christine L. Phillips, Julie-An Talano, Amy Moskop, Steven P. Margossian, Douglas Myers, Nicole A. Karras, Patrick A. Brown, Muna Qayed, Michelle Hermiston, Prakash Satwani, M Christa Krupski, Amy K. Keating, Rachel Wilcox, Cara A. Rabik, Vanessa A. Fabrizio, Vasant Chinnabhandar, A Yasemin Goksenin, Kevin J. Curran, Crystal L. Mackall, Theodore W. Laetsch, Liora M. Schultz

Manuscripts, Articles, Book Chapters and Other Papers

Remarkable complete response rates have been shown with tisagenlecleucel, a chimeric antigen receptor (CAR) T-cell therapy targeting CD19, in patients up to age 26 years with refractory/relapsed B-cell acute lymphoblastic leukemia; it is US Food and Drug Administration approved for this indication. Currently, patients receive a single dose of tisagenlecleucel across a wide dose range of 0.2 to 5.0 × 106 and 0.1 to 2.5 × 108 CAR T cells per kg for patients ≤50 and >50 kg, respectively. The effect of cell dose on survival and remission is not yet well established. Our primary goal was to determine if …

Antibody Therapies For The Treatment Of Acute Myeloid Leukemia: Exploring Current And Emerging Therapeutic Targets, Joshua W Morse, Margarita Rios, John Ye, Adan Rios, Cheng Cheng Zhang, Naval G Daver, Courtney D Dinardo, Ningyan Zhang, Zhiqiang An

Journal Articles

INTRODUCTION: Acute myeloid leukemia (AML) is the most common and deadly type of leukemia affecting adults. It is typically managed with rounds of non-targeted chemotherapy followed by hematopoietic stem cell transplants, but this is only possible in patients who can tolerate these harsh treatments and many are elderly and frail. With the identification of novel tumor-specific cell surface receptors, there is great conviction that targeted antibody therapies will soon become available for these patients.

AREAS COVERED: In this review, we describe the current landscape of known target receptors for monospecific and bispecific antibody-based therapeutics for AML. Here, we characterize each …

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 …

Integrative Analysis Of Clinicopathological Features Defines Novel Prognostic Models For Mantle Cell Lymphoma In The Immunochemotherapy Era: A Report From The North American Mantle Cell Lymphoma Consortium, Julie M. Vose, Kai Fu, Lu Wang, Adnan Mansoor, Douglas Stewart, Hongxia Cheng, Lynette M. Smith, Ji Yuan, Hina Naushad Qureishi, Brian K. Link, Melissa H. Cessna, Paul M. Barr, Brad S. Kahl, Matthew S. Mckinney, Nadia Khan, Ranjana H. Advani, Peter Martin, Andre H. Goy, Tycel J. Phillips, Amitkumar Mehta, Manali Kamdar, Michael Crump, Barbara Pro, Christopher R. Flowers, Caron A. Jacobson, Sonali M. Smith, Deborah M. Stephens, Veronika Bachanova, Zhaohui Jin, Shishou Wu, Francisco Hernandez-Ilizaliturri, Pallawi Torka, Andrea Anampa-Guzmán, Farshid Kashef, Xing Li, Sunandini Sharma, Timothy Greiner, James O. Armitage, Matthew A. Lunning, Dennis D. Weisenburger, Gregory Bociek, Javeed Iqbal, Guohua Yu, Chengfeng Bi, North American Mantle Cell Lymphoma Consortium

Journal Articles: Oncology and Hematology

BACKGROUND: Patients with mantle cell lymphoma (MCL) exhibit a wide variation in clinical presentation and outcome. However, the commonly used prognostic models are outdated and inadequate to address the needs of the current multidisciplinary management of this disease. This study aims to investigate the clinical and pathological features of MCL in the immunochemotherapy era and improve the prognostic models for a more accurate prediction of patient outcomes.

METHODS: The North American Mantle Cell Lymphoma Project is a multi-institutional collaboration of 23 institutions across North America to evaluate and refine prognosticators for front-line therapy. A total of 586 MCL cases diagnosed …

The Mutational Landscape In Chronic Myelomonocytic Leukemia And Its Impact On Allogeneic Hematopoietic Cell Transplantation Outcomes: A Center For Blood And Marrow Transplantation Research (Cibmtr) Analysis, Matthew Mei, Raju Pillai, Soyoung Kim, Noel Estrada-Merly, Michelle Afkhami, Lixin Yang, Zhuo Meng, Muhammad Bilal Abid, Mahmoud Aljurf, Ulrike Bacher, Amer Beitinjaneh, Christopher Bredeson, Jean-Yves Cahn, Jan Cerny, Edward Copelan, Corey Cutler, Zachariah Defilipp, Miguel Angel Diaz Perez, Nosha Farhadfar, César O Freytes, Shahinaz M Gadalla, Siddhartha Ganguly, Robert Peter Gale, Usama Gergis, Michael R Grunwald, Betty K Hamilton, Shahrukh Hashmi, Gerhard C Hildebrandt, Hillard M Lazarus, Mark Litzow, Reinhold Munker, Hemant S Murthy, Sunita Nathan, Taiga Nishihori, Sagar S Patel, David Rizzieri, Sachiko Seo, Mithun Vinod Shah, Melhem Solh, Leo F Verdonck, Ravi Vij, Ronald M Sobecks, Betul Oran, Bart L Scott, Wael Saber, Ryotaro Nakamura

Department of Medical Oncology Faculty Papers

Somatic mutations are recognized as an important prognostic factor in chronic myelomonocytic leukemia (CMML). However, limited data are available regarding their impact on outcomes after allogeneic hematopoietic cell transplantation (HCT). In this registry analysis conducted in collaboration with the Center for International Blood and Marrow Transplantation Registry database/sample repository, we identified 313 adult patients with CMML (median age: 64 years, range, 28- 77) who underwent allogeneic HCT during 2001-2017 and had an available biospecimen in the form of a peripheral blood sample obtained prior to the start of conditioning. In multivariate analysis, a CMML-specific prognostic scoring system (CPSS) score of …