Medicine and Health Sciences Commons^™

A Learning Community Approach To Identifying Interventions In Health Systems To Reduce Colorectal Cancer Screening Disparities., Lillian C. Man, Melissa Dicarlo, Emily Lambert, Randa Sifri, Martha Romney, Linda Fleisher, Ronald Myers

Department of Medical Oncology Faculty Papers

Although colorectal cancer (CRC) screening in the United States has been increasing, screening rates are not optimal, and there are persistent disparities in CRC screening and mortality, particularly among minority patients. As most CRC screening takes place in primary care, health systems are well-positioned to address this important population health problem. However, most health systems have not actively engaged in identifying and implementing effective evidence-based intervention strategies that can raise CRC screening rates and reduce disparities. Drawing on the Collective Impact Model and the Interactive Systems Framework for Dissemination and Implementation, our project team applied a learning community strategy to …

Performance Of Prostate Cancer Recurrence Nomograms By Obesity Status: A Retrospective Analysis Of A Radical Prostatectomy Cohort., Charnita Zeigler-Johnson, Aaron Hudson, Karen Glanz, Elaine Spangler, Knashawn H Morales

Department of Medical Oncology Faculty Papers

BACKGROUND: Obesity has been associated with aggressive prostate cancer and poor outcomes. It is important to understand how prognostic tools for that guide prostate cancer treatment may be impacted by obesity. The goal of this study was to evaluate the predicting abilities of two prostate cancer (PCa) nomograms by obesity status.

METHODS: We examined 1576 radical prostatectomy patients categorized into standard body mass index (BMI) groups. Patients were categorized into low, medium, and high risk groups for the Kattan and CaPSURE/CPDR scores, which are based on PSA value, Gleason score, tumor stage, and other patient data. Time to PCa recurrence …

Nci-Match Arms N & P: Phase Ii Study Of Pi3k Beta Inhibitor Gsk2636771 In Patients (Pts) With Cancers (Ca) With Pten Mutation/Deletion (Mut/Del) Or Pten Protein Loss, F. Janku, O. Jegede, S. L. Puhalla, P. Konstantinopoulos, F. Meric-Bernstam, E. P. Mitchell, J. A. Zwiebel, L. M. Mcshane, S. Li, L. V. Rubinstein, L. A. Doyle, D. Patton, B. A. Conley, P. J. O'Dwyer, L. N. Harris, C. Arteaga, P. M. Williams, S. R. Hamilton, A. P. Chen, K. T. Flaherty

Department of Medical Oncology Faculty Papers

Background: The NCI-MATCH trial is the largest national study (1173 sites) for ptswith relapsed/ refractory solid tumors, lymphomas and myeloma, which assigns tar-geted therapies based on individual tumor molecular alterations detected using theadapted Oncomine AmpliSeq panel (143 genes) and immunohistochemistry (IHC).We hypothesized that patients with PTEN-deficient cancers enrolled to Arms N and Pmay benefit from treatment with the PI3K beta-selective inhibitor GSK2636771.

Methods: Eligibility: relapsed/refractory ca, good end-organ function, and ECOG PS ≤ 1. Pts were screened for molecular alterations by centralized testing on fresh tumor biopsy and had deleterious PTEN mut/del without loss of expression (Arm N) or complete …

Larotrectinib Efficacy And Safety In Trk Fusion Cancer: An Expanded Clinical Dataset Showing Consistency In An Age And Tumor Agnostic Approach, U. N. Lassen, C. M. Albert, S. Kummar, C. M. Van Tilburg, S. G. Dubois, B. Geoerger, L. Mascarenhas, N. Federman, R. J. Schilder, F. Doz, J. D. Berlin, D. Y. Oh, S. S. Bielack, R. Mcdermott, D. S. Tan, S. Cruickshank, N. C. Ku, M. C. Cox, A. Drilon, D. S. Hong

Department of Medical Oncology Faculty Papers

Background: TRK fusion cancer results from gene fusions involving NTRK1, NTRK2 or NTRK3. Larotrectinib, the first selective TRK inhibitor, has demonstrated an overall response rate (ORR) of 75% with a favorable safety profile in the first 55 consecutively enrolled adult and pediatric patients with TRK fusion cancer (Drilon et al.,NEJM2018). Here, we report the clinical activity of larotrectinib in an additional 35 TRK fusion cancer patients and provide updated follow-up of the primary analysis set (PAS) of 55 patients as of 19^thFeb 2018.

Methods: Patients with TRK fusion cancer detected by molecular profiling from 3 larotrectinib clinical trials …

Synthetic Dna Immunotherapy In Biochemically Relapsed Prostate Cancer, N. Shore, E. I. Heath, L. T. Nordquist, H. Cheng, K. Bhatt, M. Morrow, T. Mcmullan, K. Kraynyak, J. Lee, B. Sacchetta, L. Liu, S. Rosencranz, S. T. Tagawa, L. J. Appleman, R. Tutrone, J. Garcia, Y. Whang, W. Kelly, I. Csiki, M. L. Bagarazzi

Department of Medical Oncology Faculty Papers

Background: INO-5150 (PSA and PSMA) +/- INO-9012 (IL-12), a synthetic DNA immunotherapy, was assessed for safety, immunogenicity and efficacy in biochemically recurrent prostate cancer patients (pts).

Methods: Phase I, open-label, multi-center study in the US included pts with rising PSA after surgery and/or RT, PSA doubling time (PSADT) >3 months (mos), testosterone >150 ng/dL and no concurrent ADT. Safety, immunogenicity and efficacy (PSA kinetics, PFS) were evaluated in 4 treatment arms of 15 pts each. Arms A: 2mg INO-5150, B: 8.5 mg INO-5150, C: 2mg INO-5150 + 1mg INO-9012 and D: 8.5mg INO-5150 + 1mg INO-9012. Pts received 4 IM …

Pan-Squamous Genomic Profiling Stratified By Anatomic Tumor Site And Viral Association, M. Montesion, C. H. Chung, E. S. Sokol, S. A. Khan, H. Kang, L. A. Albacker, J. M. Johnson, G. M. Frampton, V. A. Miller, J. S. Ross, S. M. Ali

Department of Medical Oncology Faculty Papers

Background: Squamous cell carcinomas (SCC) have diverse anatomic etiologies but may share common genomic biomarkers. We profiled 7,871 unique SCCs across nine anatomic sites to investigate commonality in genomic alterations (GA), tumor mutational burden (TMB), human papillomavirus (HPV) association, and mutational signatures.

Methods: Tissue from over 8,100 unique SCC samples originating from nine anatomic sites (anogenital (anus, cervix, penis, vagina, vulva), esophagus, head and neck, lung, and skin) were sequenced by hybrid capture-based comprehensive genomic profiling to evaluate GA and TMB. About 3% of non-cutaneous SCC samples had UV signatures, indicative of potential primary site misdiagnoses, and were filtered from …

Androgen Decline And Outcome In Castration Resistant Prostate Cancer(Mcrpc) Patients Treated With Docetaxel (Doc), Prednisone1/-Bevacizumab (B), C. J. Ryan, S. Dutta, W. Kelly, M. J. Morris, M-E. Taplin, S. Halabi

Department of Medical Oncology Faculty Papers

No abstract provided.

Fructose 2,6-Bisphosphate In Cancer Cell Metabolism, Ramon Bartrons, Helga Simon-Molas, Ana Rodríguez-García, Esther Castaño, Àurea Navarro-Sabaté, Anna Manzano, Ubaldo E. Martinez-Outshoorn

Department of Medical Oncology Faculty Papers

For a long time, pioneers in the field of cancer cell metabolism, such as Otto Warburg, have focused on the idea that tumor cells maintain high glycolytic rates even with adequate oxygen supply, in what is known as aerobic glycolysis or the Warburg effect. Recent studies have reported a more complex situation, where the tumor ecosystem plays a more critical role in cancer progression. Cancer cells display extraordinary plasticity in adapting to changes in their tumor microenvironment, developing strategies to survive and proliferate. The proliferation of cancer cells needs a high rate of energy and metabolic substrates for biosynthesis of …

Ferritin Level Prospectively Predicts Hepatocarcinogenesis In Patients With Chronic Hepatitis B Virus Infection, Zhenyuan Bian, Hie-Won Hann, Zhong Ye, Chun Yin, Yang Wang, Wan Fang, Shaogui Wan, Chun Wang, Kaishan Tao

Department of Medical Oncology Faculty Papers

Previous studies have detected a higher level of ferritin in patients with hepatocellular carcinoma (HCC), but a potential causal association between serum ferritin level and hepatocarcinogenesis remains to be clarified. Using a well-established prospective cohort and longitudinally collected serial blood samples, the association between baseline ferritin levels and HCC risk were evaluated in 1,152 patients infected with hepatitis B virus (HBV), a major risk factor for HCC. The association was assessed by Cox proportional hazards regression model using univariate and multivariate analyses and longitudinal analysis. It was demonstrated that HBV patients who developed HCC had a significantly higher baseline ferritin …

Metformin As A Therapeutic Target In Endometrial Cancers., Teresa Lee, Ubaldo E. Martinez-Outshoorn, Russell J. Schilder, Christine H. Kim, Scott D. Richard, Norman G. Rosenblum, Jennifer Johnson

Department of Medical Oncology Faculty Papers

Endometrial cancer is the most common gynecologic malignancy in developed countries. Its increasing incidence is thought to be related in part to the rise of metabolic syndrome, which has been shown to be a risk factor for the development of hyperestrogenic and hyperinsulinemic states. This has consequently lead to an increase in other hormone-responsive cancers as well e.g., breast and ovarian cancer. The correlation between obesity, hyperglycemia, and endometrial cancer has highlighted the important role of metabolism in cancer establishment and persistence. Tumor-mediated reprogramming of the microenvironment and macroenvironment can range from induction of cytokines and growth factors to stimulation …

Examining Relationships Between Age At Diagnosis And Health-Related Quality Of Life Outcomes In Prostate Cancer Survivors., Christine J. Kurian, Amy Leader, Melissa S.Y. Thong, Scott W. Keith, Charnita Zeigler-Johnson

Department of Medical Oncology Faculty Papers

BACKGROUND: Patient reports of health related quality of life can provide important information about the long-term impact of prostate cancer. Because patient symptoms and function can differ by age of the survivor, the aim of our study was to examine patient-reported quality of life and prostate symptoms by age at diagnosis among a registry of Dutch prostate cancer survivors.

METHODS: A population of 617 individuals from the Patient Reported Outcomes Following Initial Treatment and Long-Term Evaluation of Survivorship (PROFILES) database was surveyed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) and prostate symptom …

Obinutuzumab, A Potent Anti-B-Cell Agent, For Rituximab-Unresponsive Igm Anti-Mag Neuropathy., Goran Rakocevic, Ubaldo E. Martinez-Outshoorn, Marinos C. Dalakas

Department of Medical Oncology Faculty Papers

Anti-MAG demyelinating neuropathy is difficult to treat. All immunotherapies have failed except for rituximab, a chimeric B-cell–depleting monoclonal antibody against CD20, that helps up to 40% of patients based on 2 controlled and several uncontrolled series.^1,–,3 Because the majority of these patients are left disabled, stronger anti–B-cell agents might be promising.

We describe clinical response and autoantibody changes after treatment with obinutuzumab (Gazyva), a new generation of humanized anti-CD20 monoclonal antibodies, in 2 patients with anti-MAG neuropathy who continued to worsen despite multiple courses of rituximab. Obinutuzumab, approved for chronic lymphocytic leukemia (CLL), exerts greater peripheral and lymphoid B-cell …

Palina: A Phase Ii Safety Study Of Palbociclib In Combination With Letrozole Or Fulvestrant In African American Women With Hormone Receptor Positive Her2 Negative Advanced Breast Cancer, Filipa Lynce, Mervat Saleh, Ayesha Shajahan-Haq, Christopher Gallagher, Asma Dilawari, Olwen Hahn, Maysa Abu-Khalaf, Ling Cai, Paula Pohlmann, Mahsa Mohebtash, Lois Kamugisha, Claudine Isaacs

Department of Medical Oncology Faculty Papers

Palbociclib has been shown to be a highly effective therapy in hormone receptor positive metastatic breast cancer when used in combination with letrozole or fulvestrant. Grade 3/4 neutropenia is a common side effect although febrile neutropenia is relatively uncommon. Insufficient data exist to describe the hematological safety of palbociclib in African American women (AAW) known to have a high incidence of benign ethnic neutropenia (BEN). PALOMA 1, 2 and 3, the initial phase II/III studies that led to the U.S. Food and Drug Administration (FDA) approval of palbociclib in metastatic breast cancer, only included participants with baseline absolute neutrophil count …

First Results On Survival From A Large Phase 3 Clinical Trial Of An Autologous Dendritic Cell Vaccine In Newly Diagnosed Glioblastoma., Linda M. Liau, Keyoumars Ashkan, David D. Tran, Jian L. Campian, John E. Trusheim, Charles S. Cobbs, Jason A. Heth, Michael Salacz, Sarah Taylor, Stacy D. D'Andre, Fabio M. Iwamoto, Edward J. Dropcho, Yaron A. Moshel, Kevin A. Walter, Clement P. Pillainayagam, Robert Aiken, Rekha Chaudhary, Samuel A. Goldlust, Daniela A. Bota, Paul Duic, Jai Grewal, Heinrich Elinzano, Steven A. Toms, Kevin O. Lillehei, Tom Mikkelsen, Tobias Walbert, Steven R. Abram, Andrew J. Brenner, Steven Brem, Matthew G. Ewend, Simon Khagi, Jana Portnow, Lyndon J. Kim, William G. Loudon, Reid C. Thompson, David E Avigan, Karen L. Fink, Francois J. Geoffroy, Scott Lindhorst, Jose Lutzky, Andrew E. Sloan, Gabriele Schackert, Dietmar Krex, Hans-Jorg Meisel, Julian Wu, Raphael P Davis, Christopher Duma, Arnold B. Etame, David Mathieu, Santosh Kesari, David Piccioni, Manfred Westphal, David S. Baskin, Pamela Z. New, Michel Lacroix, Sven-Axel May, Timothy J. Pluard, Victor Tse, Richard M. Green, John L. Villano, Michael Pearlman, Kevin Petrecca, Michael Schulder, Lynne P Taylor, Anthony E. Maida, Robert M. Prins, Timothy F. Cloughesy, Paul Mulholland, Marnix L. Bosch

Department of Medical Oncology Faculty Papers

BACKGROUND: Standard therapy for glioblastoma includes surgery, radiotherapy, and temozolomide. This Phase 3 trial evaluates the addition of an autologous tumor lysate-pulsed dendritic cell vaccine (DCVax

METHODS: After surgery and chemoradiotherapy, patients were randomized (2:1) to receive temozolomide plus DCVax-L (n = 232) or temozolomide and placebo (n = 99). Following recurrence, all patients were allowed to receive DCVax-L, without unblinding. The primary endpoint was progression free survival (PFS); the secondary endpoint was overall survival (OS).

RESULTS: For the intent-to-treat (ITT) population (n = 331), median OS (mOS) was 23.1 months from surgery. Because of the cross-over trial design, nearly …

Limited Immune Surveillance In Lymphoid Tissue By Cytolytic Cd4+ T Cells During Health And Hiv Disease., Marcus Buggert, Son Nguyen, Laura M. Mclane, Maria Steblyanko, Nadia Anikeeva, Dominic Paquin-Proulx, Perla M Del Rio Estrada, Yuria Ablanedo-Terrazas, Kajsa Noyan, Morgan A. Reuter, Korey Demers, Johan K. Sandberg, Michael A. Eller, Hendrik Streeck, Marianne Jansson, Piotr Nowak, Anders Sönnerborg, David H. Canaday, Ali Naji, E. John Wherry, Merlin L. Robb, Steven G Deeks, Gustavo Reyes-Teran, Yuri Sykulev, Annika C. Karlsson, Michael R. Betts

Department of Medical Oncology Faculty Papers

CD4+ T cells subsets have a wide range of important helper and regulatory functions in the immune system. Several studies have specifically suggested that circulating effector CD4+ T cells may play a direct role in control of HIV replication through cytolytic activity or autocrine β-chemokine production. However, it remains unclear whether effector CD4+ T cells expressing cytolytic molecules and β-chemokines are present within lymph nodes (LNs), a major site of HIV replication. Here, we report that expression of β-chemokines and cytolytic molecules are enriched within a CD4+ T cell population with high levels of the T-box transcription factors T-bet and …

Plasma Inflammatory Cytokines And Survival Of Pancreatic Cancer Patients., A. Babic, N. Schnure, N. P. Neupane, M. M. Zaman, N. Rifai, M. W. Welch, L. K. Brais, D. A. Rubinson, V. Morales-Oyarvide, C. Yuan, S. Zhang, E. M. Poole, B. M. Wolpin, M. H. Kulke, D. A. Barbie, K. Wong, C. S. Fuchs, K. Ng

Department of Medical Oncology Faculty Papers

OBJECTIVES: Inflammation and inflammatory conditions have been associated with pancreatic cancer risk and progression in a number of clinical, epidemiological, and animal model studies. The goal of the present study is to identify plasma markers of inflammation associated with survival of pancreatic cancer patients, and assess their joint contribution to patient outcome.

METHODS: We measured circulating levels of four established markers of inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), soluble tumor necrosis factor receptor type II (sTNF-RII), and macrophage inhibitory cytokine-1 (MIC-1)) in 446 patients enrolled in an ongoing prospective clinic-based study. Hazard ratios (HRs) and 95% confidence intervals (CI) for …

Tnfα Induces Ca2+ Influx To Accelerate Extrinsic Apoptosis In Hepatocellular Carcinoma Cells, Jianjun Zhu, Mingpeng Jin, Jiaojiao Wang, Hui Zhang, Yousheng Wu, Deyang Li, Xiaoying Ji, Hushan Yang, Chun Yin, Tingting Ren, Jinliang Xing

Department of Medical Oncology Faculty Papers

BACKGROUND: Tumor necrosis factor-α has been proven an effective anticancer agent in preclinical studies. However, the translation of TNFα from research to clinic has been blocked by significant systemic toxicity and limited efficacy at maximal tolerated dose, which need urgently to be solved.

METHODS: The level of cytosolic Ca

RESULTS: Here, we demonstrated that TNFα induced extracellular Ca

CONCLUSIONS: Our study provides the evidence supporting a novel mechanism by which TNFα induces extracellular Ca

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) …

Acceptance And Commitment Therapy With Pancreatic Cancer: An Integrative Model Of Palliative Care-A Case Report., Catherine Virginia F O'Hayer, Kevin Mitchell O'Hayer, Ashwin Sama

Department of Medical Oncology Faculty Papers

Background: This case study examines the feasibility of application of an acceptance-based behavioral therapy, acceptance and commitment therapy (ACT), to a patient with end-stage metastatic pancreatic cancer, depression, and anxiety, as a form of integrative palliative care.

Case Presentation: ACT allowed the patient to identify her values of resuming her religious connection, improving relationships with family members and trusted friends, and organizing her affairs before death. As a result, the patient was able to remain engaged in cancer treatments despite side effects that she had previously deemed intolerable. She was able to move toward her values despite health-related and depression-related …