Medical Specialties Commons^™

Treatment Response Of Gingival Squamous-Cell Carcinoma To Palliative Intent Immunotherapy, Natalia Trehan, Angelina Debbas, Mykaihla Sternick, Jennifer Johnson, James Gates

Department of Medical Oncology Faculty Papers

The use of PD-1 immune checkpoint inhibitor medications has become a common practice in the treatment of recurrent and metastatic head and neck squamous-cell carcinomas. Success in this setting has led to the investigation of their efficacy in locally advanced cases as a part of first-line therapy. In this report, we detail the treatment response to palliative intent immunotherapy of three geriatric patients with mandibular gingival squamous-cell carcinoma who decided against surgical intervention. Patient #1 was treated with pembrolizumab, a PD-1 inhibitor, and displayed complete clinical and radiologic response of the gingival mass after three months of treatment, which is …

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 …

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 …

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 …

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 …

Impact Of Homologous Recombination Status And Responses With Veliparib Combined With First-Line Chemotherapy In Ovarian Cancer In The Phase 3 Velia/Gog-3005 Study, Elizabeth M Swisher, Carol Aghajanian, David M O'Malley, Gini F Fleming, Scott H Kaufmann, Douglas A Levine, Michael J Birrer, Kathleen N Moore, Nick M Spirtos, Mark S Shahin, Thomas J Reid, Michael Friedlander, Karina Dahl Steffensen, Aikou Okamoto, Vasudha Sehgal, Peter J Ansell, Minh H Dinh, Michael A Bookman, Robert L Coleman

Kimmel Cancer Center Faculty Papers

Objective: In the Phase 3 VELIA trial (NCT02470585), PARP inhibitor (PARPi) veliparib was combined with first-line chemotherapy and continued as maintenance for patients with ovarian carcinoma enrolled regardless of chemotherapy response or biomarker status. Here, we report exploratory analyses of the impact of homologous recombination deficient (HRD) or proficient (HRP) status on progression-free survival (PFS) and objective response rates during chemotherapy.

Methods: Women with Stage III-IV ovarian carcinoma were randomized to veliparib-throughout, veliparib-combination-only, or placebo. Stratification factors included timing of surgery and germline BRCA mutation status. HRD status was dichotomized at genomic instability score 33. During combination therapy, …

Prospective Comparison Of Geriatric Assessment And Provider's Assessment Of Older Adults With Metastatic Breast Cancer In The Community, Rino S Seedor, Caitlin R Meeker, Bianca Lewis, Elizabeth A Handorf, Kelly A Filchner, Ramya Varadarajan, Jack Hensold, Aruna Padmanabhan, Benjamin Negin, Kenneth Blankstein, Neha R Chawla, Wei Frank Song, Jessica Epstein, Jennifer Winn, Lori J Goldstein, Efrat Dotan

Department of Medical Oncology Faculty Papers

Background: Geriatric assessment (GA) is recommended for evaluating fitness of an older adult with cancer. Our objective was to prospectively evaluate the gaps that exist in the assessment of older adults with metastatic breast cancer (OA-MBC) in community practices (CP).

Methods: Self-administered GA was compared to provider's assessment (PA) of patients living with MBC aged ≥65 years treated in CP Providers were blinded to the GA results until PA was completed. McNemar's test was used to detect differences between PA and GA.

Results: One hundred patients were enrolled across 9 CP (median age 73.9). Geriatric assessment detected a total of …

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 …

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), …

Gilteritinib Or Chemotherapy For Relapsed Or Refractory Flt3-Mutated Aml, Alexander E. Perl, Giovanni Martinelli, Jorge E. Cortes, Andreas Neubauer, Ellin Berman, Stefania Paolini, Pau Montesinos, Maria R. Baer, Richard A. Larson, Celalettin Ustun, Francesco Fabbiano, Harry P. Erba, Antonio Di Stasi, Robert Stuart, Rebecca Olin, Margaret Kasner, Fabio Ciceri, Wen-Chien Chou, Nikolai Podoltsev, Christian Recher, Hisayuki Yokoyama, Naoko Hosono, Sung-Soo Yoon, Je-Hwan Lee, Timothy Pardee, Amir T. Fathi, Chaofeng Liu, Nahla Hasabou, Xuan Liu, Erkut Bahceci, Mark J. Levis

Department of Medical Oncology Faculty Papers

BACKGROUND: Patients with relapsed or refractory acute myeloid leukemia (AML) with mutations in the FMS-like tyrosine kinase 3 gene (FLT3) infrequently have a response to salvage chemotherapy. Gilteritinib is an oral, potent, selective FLT3 inhibitor with single-agent activity in relapsed or refractory FLT3-mutated AML.

METHODS: In a phase 3 trial, we randomly assigned adults with relapsed or refractory FLT3-mutated AML in a 2:1 ratio to receive either gilteritinib (at a dose of 120 mg per day) or salvage chemotherapy. The two primary end points were overall survival and the percentage of patients who had complete remission …

Report Of The First Patient Treated For Pelvic Sarcoma With A Directional 103pd Brachytherapy Device., Serguei A. Castaneda, Marian Khalili, Jacqueline Emrich, Veronica M Zoghbi, Michael S Weingarten, Mark J Rivard, Wilbur B Bowne, Jaganmohan Poli

Department of Radiation Oncology Faculty Papers

No abstract provided.

Comparative Effectiveness Of Intensity Modulated Radiation Therapy To 3-Dimensional Conformal Radiation In Locally Advanced Lung Cancer: Pathological And Clinical Outcomes., Sarit Appel, Jair Bar, Alon Ben-Nun, Marina Perelman, Dror Alezra, Damien Urban, Maoz Ben-Ayun, Nir Honig, Efrat Ofek, Tamar Katzman, Amir Onn, Sumit Chatterji, Sergey Dubinski, Lev Tsvang, Shira Felder, Judith Kraitman, Ory Haisraely, Tatiana Rabin Alezra, Sivan Lieberman, Edith M. Marom, Nir Golan, David Simansky, Zvi Symon, Yaacov Richard Lawrence

Department of Radiation Oncology Faculty Papers

OBJECTIVE: Intensity-modulated radiotherapy (IMRT) has better normal-tissue sparing compared with 3-dimensional conformal radiation (3DCRT). We sought to assess the impact of radiation technique on pathological and clinical outcomes in locally advanced non-small cell lung cancer (LANSCLC) treated with a trimodality strategy.

METHODS: Retrospective review of LANSCLC patients treated from August 2012 to August 2018 at Sheba Medical Center, Israel. The trimodality strategy consisted of concomitant chemoradiation to 60 Gray (Gy) followed by completion surgery. The planning target volume (PTV) was defined by co-registered PET/CT. Here we compare the pathological regression, surgical margin status, local control rates (LC), disease free (DFS) …

First Report Of Nrg Oncology/Radiation Therapy Oncology Group 0622: A Phase 2 Trial Of Samarium-153 Followed By Salvage Prostatic Fossa Irradiation In High-Risk Clinically Nonmetastatic Prostate Cancer After Radical Prostatectomy., Richard K. Valicenti, Stephanie L. Pugh, Edouard J. Trabulsi, Oliver Sartor, Eric C. Ko, Michael R. Girvigian, Seth A. Rosenthal, Mark E. Shaves, Jean Hoffman-Censits, John Schallenkamp, Howard M. Sandler

Department of Urology Faculty Papers

PURPOSE: To investigate the utility of ¹⁵³Sm lexidronam (Quadramet) in the setting of men with prostate cancer status post radical prostatectomy who develop biochemical failure with no clinical evidence of osseous metastases.

PATIENTS AND METHODS: Trial NRG Oncology RTOG 0622 is a single-arm phase 2 trial that enrolled men with pT2-T4, N0-1, M0 prostate cancer status post radical prostatectomy, who meet at least 1 of these biochemical failure criteria: (1) prostate-specific antigen (PSA) > 1.0 ng/mL; (2) PSA > 0.2 ng/mL if Gleason score 9 to 10; or (3) PSA > 0.2 ng/mL if N1. Patients received ¹⁵³Sm (2.0 mCi/kg intravenously …

Determination Of An Optimal Response Cut-Off Able To Predict Progression-Free Survival In Patients With Well-Differentiated Advanced Pancreatic Neuroendocrine Tumours Treated With Sunitinib: An Alternative To The Current Recist-Defined Response., Angela Lamarca, Jorge Barriuso, Matthew Kulke, Ivan Borbath, Heinz-Josef Lenz, Jean Luc Raoul, Neal J. Meropol, Catherine Lombard-Bohas, James Posey, Sandrine Faivre, Eric Raymond, Juan W. Valle

Department of Medical Oncology Faculty Papers

BACKGROUND: Sunitinib prolongs progression-free survival (PFS) in patients with advanced pancreatic neuroendocrine tumours (pNET). Response Evaluation Criteria in Solid Tumors (RECIST)-defined partial responses (PR; classically defined as ⩾30% size decrease from baseline) are infrequent.

METHODS: Individual data of pNET patients from the phase II [NCT00056693] and pivotal phase III [NCT00428597] trials of sunitinib were analysed in this investigator-initiated, post hoc study. The primary objective was to determine the optimal RECIST (v.1.0) response cut-off value to identify patients who were progression-free at 11 months (median PFS in phase III trial); and the most informative time-point (highest area under the curve (AUC) …

Decoding Critical Long Non-Coding Rna In Ovarian Cancer Epithelial-To-Mesenchymal Transition., Ramkrishna Mitra, Xi Chen, Evan J. Greenawalt, Ujjwal Maulik, Wei Jiang, Zhongming Zhao, Christine M. Eischen

Department of Cancer Biology Faculty Papers

Long non-coding RNA (lncRNA) are emerging as contributors to malignancies. Little is understood about the contribution of lncRNA to epithelial-to-mesenchymal transition (EMT), which correlates with metastasis. Ovarian cancer is usually diagnosed after metastasis. Here we report an integrated analysis of >700 ovarian cancer molecular profiles, including genomic data sets, from four patient cohorts identifying lncRNA DNM3OS, MEG3, and MIAT overexpression and their reproducible gene regulation in ovarian cancer EMT. Genome-wide mapping shows 73% of MEG3-regulated EMT-linked pathway genes contain MEG3 binding sites. DNM3OS overexpression, but not MEG3 or MIAT, significantly correlates to worse overall patient survival. DNM3OS knockdown results in …

Intravesical Rad-Ifnα/Syn3 For Patients With High-Grade, Bacillus Calmette-Guerin-Refractory Or Relapsed Non-Muscle-Invasive Bladder Cancer: A Phase Ii Randomized Study., Neal D Shore, Stephen A Boorjian, Daniel J Canter, Kenneth Ogan, Lawrence I Karsh, Tracy M Downs, Leonard G Gomella, Ashish M Kamat, Yair Lotan, Robert S Svatek, Trinity J Bivalacqua, Robert L Grubb, Tracey L Krupski, Seth P Lerner, Michael E Woods, Brant A Inman, Matthew I Milowsky, Alan Boyd, F Peter Treasure, Gillian Gregory, David G Sawutz, Seppo Yla-Herttuala, Nigel R Parker, Colin P N Dinney

Department of Medicine Faculty Papers

Purpose Many patients with high-risk non-muscle-invasive bladder cancer (NMIBC) are either refractory to bacillus Calmette-Guerin (BCG) treatment or may experience disease relapse. We assessed the efficacy and safety of recombinant adenovirus interferon alfa with Syn3 (rAd-IFNα/Syn3), a replication-deficient recombinant adenovirus gene transfer vector, for patients with high-grade (HG) BCG-refractory or relapsed NMIBC. Methods In this open-label, multicenter (n = 13), parallel-arm, phase II study ( ClinicalTrials.gov identifier: NCT01687244), 43 patients with HG BCG-refractory or relapsed NMIBC received intravesical rAd-IFNα/Syn3 (randomly assigned 1:1 to 1 × 10(11) viral particles (vp)/mL or 3 × 10(11) vp/mL). Patients who responded at months 3, …

Detection Of Activating Estrogen Receptor Gene (Esr1) Mutations In Single Circulating Tumor Cells, Carmela Paolillo, Zhaomei Mu, Giovanna Rossi, Matthew J. Schiewer, Thomas Nguyen, Laura Austin, Ettore Capoluongo, Karen E. Knudsen, Massimo Cristofanilli, Paolo Fortina

Department of Cancer Biology Faculty Papers

Purpose: Early detection is essential for treatment plans before onset of metastatic disease. Our purpose was to demonstrate feasibility to detect and monitor estrogen receptor 1 (ESR1) gene mutations at the single circulating tumor cell (CTC) level in metastatic breast cancer (MBC). Experimental Design: We used a CTC molecular characterization approach to investigate heterogeneity of 14 hotspot mutations in ESR1 and their correlation with endocrine resistance. Combining the CellSearch and DEPArray technologies allowed recovery of 71 single CTCs and 12 WBC from 3 ER-positive MBC patients. Forty CTCs and 12 WBC were subjected to whole genome amplification by MALBAC and …

Mobilized Peripheral Blood Stem Cells Versus Unstimulated Bone Marrow As A Graft Source For T-Cell-Replete Haploidentical Donor Transplantation Using Post-Transplant Cyclophosphamide., Asad Bashey, Mei-Jie Zhang, Shannon R Mccurdy, Andrew St Martin, Trevor Argall, Claudio Anasetti, Stefan O Ciurea, Omotayo Fasan, Sameh Gaballa, Md, Mehdi Hamadani, Pashna Munshi, Monzr M Al Malki, Ryotaro Nakamura, Paul V O'Donnell, Miguel-Angel Perales, Kavita Raj, Rizwan Romee, Scott Rowley, Vanderson Rocha, Rachel B Salit, Melhem Solh, Robert J Soiffer, Ephraim Joseph Fuchs, Mary Eapen

Department of Medicine Faculty Papers

Purpose T-cell-replete HLA-haploidentical donor hematopoietic transplantation using post-transplant cyclophosphamide was originally described using bone marrow (BM). With increasing use of mobilized peripheral blood (PB), we compared transplant outcomes after PB and BM transplants. Patients and Methods A total of 681 patients with hematologic malignancy who underwent transplantation in the United States between 2009 and 2014 received BM (n = 481) or PB (n = 190) grafts. Cox regression models were built to examine differences in transplant outcomes by graft type, adjusting for patient, disease, and transplant characteristics. Results Hematopoietic recovery was similar after transplantation of BM and PB (28-day neutrophil …

Ibrutinib Unmasks Critical Role Of Bruton Tyrosine Kinase In Primary Cns Lymphoma., Christian Grommes, Alessandro Pastore, Nicolaos Palaskas, Sarah S. Tang, Carl Campos, Derrek Schartz, Paolo Codega, Donna Nichol, Owen Clark, Wan-Ying Hsieh, Dan Rohle, Marc Rosenblum, Agnes Viale, Viviane S. Tabar, Cameron W. Brennan, Igor T. Gavrilovic, Thomas J. Kaley, Craig P. Nolan, Antonio Omuro, Elena Pentsova, Alissa A. Thomas, Elina Tsyvkin, Ariela Noy, M. Lia Palomba, Paul Hamlin, Craig S. Sauter, Craig H. Moskowitz, Julia Wolfe, Ahmet Dogan, Minhee Won, Jon Glass, Scott Peak, Enrico C. Lallana, Vaios Hatzoglou, Anne S. Reiner, Philip H. Gutin, Jason T. Huse, Katherine S. Panageas, Thomas G. Graeber, Nikolaus Schultz, Lisa M. Deangelis, Ingo K. Mellinghoff

Department of Neurology Faculty Papers

Bruton tyrosine kinase (BTK) links the B-cell antigen receptor (BCR) and Toll-like receptors with NF-κB. The role of BTK in primary central nervous system (CNS) lymphoma (PCNSL) is unknown. We performed a phase I clinical trial with ibrutinib, the first-in-class BTK inhibitor, for patients with relapsed or refractory CNS lymphoma. Clinical responses to ibrutinib occurred in 10 of 13 (77%) patients with PCNSL, including five complete responses. The only PCNSL with complete ibrutinib resistance harbored a mutation within the coiled-coil domain of CARD11, a known ibrutinib resistance mechanism. Incomplete tumor responses were associated with mutations in the B-cell antigen receptor-associated …

Hematologic Toxicity Of Concurrent Administration Of Radium-223 And Next-Generation Antiandrogen Therapies., Tu Dan, Harriet B. Eldredge-Hindy, Jean Hoffman-Censits, Jianqing Lin, William K. Kelly, Leonard G. Gomella, Costas D. Lallas, Edouard J. Trabulsi, Mark D. Hurwitz, Adam P. Dicker, Robert B. Den

Department of Radiation Oncology Faculty Papers

PURPOSE/OBJECTIVES: Radium-223 is a first-in-class radiopharmaceutical recently approved for the treatment of castration-resistant prostate cancer in patients with symptomatic bone metastases. Initial studies investigating Radium-223 primarily used nonsteroidal first-generation antiandrogens. Since that time, newer antiandrogen therapies have demonstrated improved survival in patients with castration-resistant prostate cancer. It has been suggested that the rational combination of these newly approved agents with Radium-223 may lead to improved response rates and clinical outcomes. Currently, there is lack of information regarding the safety of concurrent administration of these agents with radiopharmaceuticals. Here, we report on hematologic toxicity findings from our institution in patients receiving …

Nrg Oncology-Radiation Therapy Oncology Group Study 1014: 1-Year Toxicity Report From A Phase 2 Study Of Repeat Breast-Preserving Surgery And 3-Dimensional Conformal Partial-Breast Reirradiation For In-Breast Recurrence., Douglas W. Arthur, Kathryn A. Winter, Henry M. Kuerer, Bruce G. Haffty, Laurie W. Cuttino, Dorin A. Todor, Nicole L. Simone, Shelly B. Hayes, Wendy A. Woodward, Beryl Mccormick, Randi J. Cohen, Walter M. Sahijdak, Daniel J. Canaday, Doris R. Brown, Adam D. Currey, Christine M. Fisher, Reshma Jagsi, Julia White

Department of Radiation Oncology Faculty Papers

PURPOSE: To determine the associated toxicity, tolerance, and safety of partial-breast reirradiation.

METHODS AND MATERIALS: Eligibility criteria included in-breast recurrence occurring >1 year after whole-breast irradiation, <3 >cm, unifocal, and resected with negative margins. Partial-breast reirradiation was targeted to the surgical cavity plus 1.5 cm; a prescription dose of 45 Gy in 1.5 Gy twice daily for 30 treatments was used. The primary objective was to evaluate the rate of grade ≥3 treatment-related skin, fibrosis, and/or breast pain adverse events (AEs), occurring ≤1 year from re-treatment completion. A rate of ≥13% for these AEs in a cohort of 55 patients was …

Phase Ib/Ii Study Of The Safety And Efficacy Of Combination Therapy With Multikinase Vegf Inhibitor Pazopanib And Mek Inhibitor Trametinib In Advanced Soft Tissue Sarcoma., Vivek Subbiah, Christian Meyer, Ralph G. Zinner, Funda Meric-Bernstam, Marianna L. Zahurak, Ashley O'Connor, Jason Roszik, Kenna Shaw, Joseph A. Ludwig, Razelle Kurzrock, Nilofe A. Azad

Department of Medical Oncology Faculty Papers

Purpose: Pazopanib, a multireceptor tyrosine kinase inhibitor targeting primarily VEGFRs1–3, is approved for advanced soft tissue sarcoma (STS) and renal cell cancer. Downstream of VEGFR, trametinib is an FDA-approved MEK inhibitor used for melanoma. We hypothesized that vertical pathway inhibition using trametinib would synergize with pazopanib in advanced STS. Experimental Design: In an open-label, multicenter, investigator-initiated National Comprehensive Cancer Network (NCCN)-sponsored trial, patients with metastatic or advanced STS received pazopanib 800 mg and 2 mg of trametinib continuously for 28-day cycles. The primary endpoint was 4-month progression-free survival (PFS). Secondary endpoints were overall survival, response rate, and disease control rate. …

Adjuvant Radiation Therapy, Androgen Deprivation, And Docetaxel For High-Risk Prostate Cancer Postprostatectomy: Results Of Nrg Oncology/Rtog Study 0621., Mark D. Hurwitz, Jonathan Harris, Oliver Sartor, Ying Xiao, Bobby Shayegan, Paul W. Sperduto, Kasra R. Badiozamani, Colleen A.F. Lawton, Eric M. Horwitz, Jeff M. Michalski, Kevin Roof, David C. Beyer, Qiang Zhang, Howard M. Sandler

Department of Radiation Oncology Faculty Papers

BACKGROUND: Phase 3 trials have demonstrated a benefit from adjuvant radiation therapy (ART) for men who have adverse factors at radical prostatectomy (RP). However, some patients have a high risk of progression despite ART. The role of systemic therapy with ART in this high-risk group remains to be defined.

METHODS: Patients who had either a post-RP prostate-specific antigen (PSA) nadir > 0.2 ng/mL and a Gleason score ≥7 or a PSA nadir ≤0.2 ng/mL, a Gleason score ≥8, and a pathologic tumor (pT) classification ≥ pT3 received 6 months of androgen-deprivation therapy (ADT) plus radiotherapy and 6 cycles of docetaxel. The …

Post-Transplant Outcomes In High-Risk Compared With Non-High-Risk Multiple Myeloma: A Cibmtr Analysis., Emma C. Scott, Parameswaran Hari, Manish Sharma, Jennifer Le-Rademacher, Jiaxing Huang, Dan Vogl, Muneer Abidi, Amer Beitinjaneh, Henry Fung, Siddhartha Ganguly, Gerhard Hildebrandt, Leona Holmberg, Matt Kalaycio, Shaji Kumar, Robert Kyle, Hillard Lazarus, Cindy Lee, Richard T. Maziarz, Kenneth Meehan, Joseph Mikhael, Taiga Nishihori, Muthalagu Ramanathan, Saad Usmani, Jason Tay, David Vesole, Baldeep Wirk, Jean Yared, Bipin N. Savani, Cristina Gasparetto, Amrita Krishnan, Tomer Mark, Yago Nieto, Anita D'Souza

Department of Medical Oncology Faculty Papers

Conventional cytogenetics and interphase fluorescence in situ hybridization (FISH) identify high-risk multiple myeloma (HRM) populations characterized by poor outcomes. We analyzed these differences among HRM versus non-HRM populations after upfront autologous hematopoietic cell transplantation (autoHCT). Between 2008 and 2012, 715 patients with multiple myeloma identified by FISH and/or cytogenetic data with upfront autoHCT were identified in the Center for International Blood and Marrow Transplant Research database. HRM was defined as del17p, t(4;14), t(14;16), hypodiploidy (-Y) or chromosome 1 p and 1q abnormalities; all others were non-HRM. Among 125 HRM patients (17.5%), induction with bortezomib and immunomodulatory agents (imids) was higher …

Polypharmacy And Potentially Inappropriate Medication Use In Geriatric Oncology., Manvi Sharma, Kah Poh Loh, Ginah Nightingale Pharmd, Bcop, Supriya G. Mohile, Holly M. Holmes

College of Pharmacy Faculty Papers

Polypharmacy is a highly prevalent problem in older persons, and is challenging to assess and improve due to variations in definitions of the problem and the heterogeneous methods of medication review and reduction. The purpose of this review is to summarize evidence regarding the prevalence and impact of polypharmacy in geriatric oncology patients and to provide recommendations for assessment and management. Polypharmacy has somewhat variably been incorporated into geriatric assessment studies in geriatric oncology, and polypharmacy has not been consistently evaluated as a predictor of negative outcomes in patients with cancer. Once screened, interventions for polypharmacy are even more uncertain. …

A Phase 3 Trial Of 2 Years Of Androgen Suppression And Radiation Therapy With Or Without Adjuvant Chemotherapy For High-Risk Prostate Cancer: Final Results Of Radiation Therapy Oncology Group Phase 3 Randomized Trial Nrg Oncology Rtog 9902., Seth A. Rosenthal, Daniel Hunt, A. Oliver Sartor, Kenneth J. Pienta, Leonard G. Gomella, David Grignon, Raghu Rajan, Kevin J. Kerlin, Christopher U. Jones, Michael Dobelbower, William U Shipley, Kenneth Zeitzer, Daniel A. Hamstra, Viroon Donavanik, Marvin Rotman, Alan C. Hartford, Jeffrey Michalski, Michael Seider, Harold Kim, Deborah A. Kuban, Jennifer Moughan, Howard Sandler

Department of Urology Faculty Papers

PURPOSE: Long-term (LT) androgen suppression (AS) with radiation therapy (RT) is a standard treatment of high-risk, localized prostate cancer (PCa). Radiation Therapy Oncology Group 9902 was a randomized trial testing the hypothesis that adjuvant combination chemotherapy (CT) with paclitaxel, estramustine, and oral etoposide plus LT AS plus RT would improve overall survival (OS).

METHODS AND MATERIALS: Patients with high-risk PCa (prostate-specific antigen 20-100 ng/mL and Gleason score [GS] ≥ 7 or clinical stage ≥ T2 and GS ≥ 8) were randomized to RT and AS (AS + RT) alone or with adjuvant CT (AS + RT + CT). CT was …

Risk Analysis Of Prostate Cancer In Practical, A Multinational Consortium, Using 25 Known Prostate Cancer Susceptibility Loci., Ali Amin Al Olama, Sara Benlloch, Antonis C Antoniou, Graham G Giles, Gianluca Severi, David E Neal, Freddie C Hamdy, Jenny L Donovan, Kenneth Muir, Johanna Schleutker, Brian E Henderson, Christopher Haiman, Fredrick R Schumacher, Nora Pashayan, Paul D P Pharoah, Elaine A Ostrander, Janet L Stanford, Jyotsna Batra, Judith A Clements, Suzanne K Chambers, Maren Weischer, Børge G Nordestgaard, Sue A Ingles, Karina D Sorensen, Torben F Orntoft, Jong Y Park, Cezary Cybulski, Christiane Maier, Thilo Doerk, Joanne L Dickinson, Lisa Cannon-Albright, Hermann Brenner, Timothy R Rebbeck, Charnita Zeigler-Johnson, Tomonori Habuchi, Stephen N Thibodeau, Kathleen A Cooney, Pierre O Chappuis, Pierre Hutter, Radka P Kaneva, William D Foulkes, Maurice P Zeegers, Yong-Jie Lu, Hong-Wei Zhang, Robert Stephenson, Angela Cox, Melissa C Southey, Amanda B Spurdle, Liesel Fitzgerald, Daniel Leongamornlert, Edward Saunders, Malgorzata Tymrakiewicz, Michelle Guy, Tokhir Dadaev, Sarah J Little, Koveela Govindasami, Emma Sawyer, Rosemary Wilkinson, Kathleen Herkommer, John L Hopper, Aritaya Lophatonanon, Antje E Rinckleb, Zsofia Kote-Jarai, Rosalind A Eeles, Douglas F Easton

Department of Medical Oncology Faculty Papers

BACKGROUND: Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer.

METHODS: We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS). We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived age-specific absolute risks of developing prostate cancer by PRS stratum and family history.

RESULTS: The prostate cancer risk for men in the top 1% of the …

Comparison Of Survival In Patients With T Cell Lymphoma After Autologous And Allogeneic Stem Cell Transplantation As A Frontline Strategy Or In Relapsed Disease., Amer Beitinjaneh, Rima M. Saliba, L. Jeffrey Medeiros, Francesco Turturro, Gabriela Rondon, Martin Korbling, Luis Fayad, Michelle A. Fanale, Amin M. Alousi, Paolo Anderlini, Oran Betul, Uday R. Popat, Barbara Pro, Issa F. Khouri

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

We studied the roles of autologous (A) and allogeneic (allo) stem cell transplantation (SCT) in the treatment of 134 patients with T cell lymphoma (TCL) at our center. For frontline SCT, 58 patients were studied. The 4-year overall survival (OS) rates for ASCT (n = 47; median age, 49 years) and alloSCT (n = 11; median age, 55 years) groups were 76% and 54%, respectively (P > .05). The 4-year OS rates for first complete remission (CR1) patients were 84% and 83%, respectively. For SCT for relapsed disease, 76 patients were studied (41 with ASCT and 35 with alloSCT). The 4-year …

A Pilot Clinical Trial Of Intravesical Mitomycin-C And External Deep Pelvic Hyperthermia For Non-Muscle-Invasive Bladder Cancer., Brant A Inman, Paul R. Stauffer, Oana A Craciunescu, Paolo F Maccarini, Mark W Dewhirst, Zeljko Vujaskovic

Department of Radiation Oncology Faculty Papers

PURPOSE: This paper aims to evaluate the safety and heating efficiency of external deep pelvic hyperthermia combined with intravesical mitomycin C (MMC) as a novel therapy for non-muscle-invasive bladder cancer (NMIBC).

MATERIALS AND METHODS: We enrolled subjects with bacillus Calmette-Guérin (BCG) refractory NMIBC to an early phase clinical trial of external deep pelvic hyperthermia (using a BSD-2000 device) combined with MMC. Bladders were heated to 42 °C for 1 h during intravesical MMC treatment. Treatments were given weekly for 6 weeks, then monthly for 4 months. Heating parameters, treatment toxicity, and clinical outcomes were systematically measured.

RESULTS: Fifteen patients were …

A Long-Term Study Of The Effects Of Antiviral Therapy On Survival Of Patients With Hbv-Associated Hepatocellular Carcinoma (Hcc) Following Local Tumor Ablation., Hie-Won Hann, Robert Coben, Daniel Brown, Laurence Needleman, Ernest Rosato, Albert Min, Richard Hann, Kyong Bin Park, Stephen Dunn, Anthony J. Dimarino

Department of Medicine Faculty Papers

The ultimate goal of antiviral therapy for chronic hepatitis B (CHB) is prevention of hepatocellular carcinoma (HCC). Earlier we reported favorable effects of antiviral therapy on survival of HCC patients following curative tumor ablation (Int J Cancer online 14 April 2010; doi: 10.1002/ijc.25382). It was the first observation made in the United States. We now report 12 year follow-up of this patient group. CHB patients with no prior antiviral therapy with a single HCC (≤ 7 cm) were studied. All patients underwent local tumor ablation as their first option. Patients diagnosed before 1999 received no antiviral treatment while those diagnosed …