Medicine and Health Sciences Commons^™

Cyclophosphamide Induces Durable Molecular And Clinical Responses In Patients With Relapsed T-Lgl Leukemia., Zachary Braunstein, Eric Mclaughlin, Anjali Mishra, Jonathan E Brammer

Department of Medical Oncology Faculty Papers

No abstract provided.

Engaging Patients With Late-Stage Non-Small Cell Lung Cancer In Shared Decision Making About Treatment., Ronald E. Myers, Phd, Dsw, Shailesh M Advani, Pamela Myers, Preethi Selvan Mph Student, Gregory Garber, Msw, Lcsw, Brooke Worster, Md, Neal Flomenberg, Md, Andrew Chapman, Do, Ralph Zinner

Department of Medical Oncology Faculty Papers

Few treatment decision support interventions (DSIs) are available to engage patients diagnosed with late-stage non-small cell lung cancer (NSCLC) in treatment shared decision making (SDM). We designed a novel DSI that includes care plan cards and a companion patient preference clarification tool to assist in shared decision making. The cards answer common patient questions about treatment options (chemotherapy, chemotherapy plus immunotherapy, targeted therapy, immunotherapy, clinical trial participation, and supportive care). The form elicits patient treatment preference. We then conducted interviews with clinicians and patients to obtain feedback on the DSI. We also trained oncology nurse educators to implement the prototype. …

A Retrospective Cohort Study Of Myosteatosis And Quality Of Life In Head And Neck Cancer Patients., Amy L Shaver, Katia Noyes, Heather M Ochs-Balcom, Gregory Wilding, Andrew D Ray, Sung Jun Ma, Mark Farrugia, Anurag K Singh, Mary E Platek

Department of Medical Oncology Faculty Papers

Head and neck cancer (HNC) treatment-related morbidity can be detrimental to quality of life (QOL). Myosteatosis is associated with poor QOL in multiple cancers. If predictive of poor QOL trajectories, myosteatosis would be a tool for clinicians to determine which patients may require additional support during treatment. The purpose of this study was to determine if pretreatment myosteatosis is associated with a poor QOL trajectory following treatment completion.

METHODS: In a retrospective cohort design, myosteatosis was determined from pretreatment CT scans. Both physical and global QOL score was assessed through patient interview on follow-up appointment. Demographic, cancer-specific, and social covariates …

Integration Of Circulating Tumor Cell And Neutrophil-Lymphocyte Ratio To Identify High-Risk Metastatic Castration-Resistant Prostate Cancer Patients., Weelic Chong, Zhenchao Zhang, Rui Luo, Jian Gu, Jianqing Lin, Qiang Wei, Bingshan Li, Ronald E. Myers, Phd, Dsw, Grace Lu-Yao, William Kevin Kelly, Chun Wang, Hushan Yang

Department of Medical Oncology Faculty Papers

BACKGROUND: The neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and circulating tumor cells (CTCs) have been associated with survival in castration-resistant prostate cancer (CRPC). However, no study has examined the prognostic value of NLR and PLR in the context of CTCs.

METHODS: Baseline CTCs from mCRPC patients were enumerated using the CellSearch System. Baseline NLR and PLR values were calculated using the data from routine complete blood counts. The associations of CTC, NLR, and PLR values, individually and jointly, with progression-free survival (PFS) and overall survival (OS), were evaluated using Kaplan-Meier analysis, as well as univariate and multivariate Cox models.

RESULTS: …

A Phase I Trial Of The Met/Alk/Ros1 Inhibitor Crizotinib Combined With The Vegf Inhibitor Pazopanib In Patients With Advanced Solid Malignancies, Sarina A Piha-Paul, Ecaterina E Dumbrava, Binoj C Nair, Wendy Xiong, Li Xu, Rosa Mostorino, Vivek Subbiah, Nizar Tannir, Siqing Fu, Aung Naing, Filip Janku, Daniel D Karp, Shreyaskumar Patel, Najat C Daw, David Hong, Funda Meric-Bernstam, Ralph G. Zinner

Department of Medical Oncology Faculty Papers

Background: Crizotinib inhibits ALK, MET and ROS1 tyrosine kinases but the development of resistance to monotherapy is an issue. The anti-angiogenic properties of pazopanib could overcome crizotinib drug resistance. Additionally, the anti-angiogenic properties of crizotinib could augment the clinical efficacy of pazopanib.

Methods: We evaluated the safety and responses in patients with advanced solid tumors treated with crizotinib and pazopanib.

Results: Eighty-two patients (median age 53 years, range 18-78 years) were enrolled. The median number of prior systemic therapies was 3 (range, 0-8). We were able to dose escalate to dose level 8 (crizotinib 250 mg twice daily and pazopanib …

Approaching Neoadjuvant Therapy In The Management Of Early-Stage Breast Cancer., Tara Hyder, Saveri Bhattacharya, Kristine Gade, Azadeh Nasrazadani, Adam M Brufsky

Department of Medical Oncology Faculty Papers

Neoadjuvant therapy is integral to the treatment of early-stage breast cancer. Goals of treatment include surgical downstaging of the tumor, rendering inoperable tumors resectable, and de-escalating axillary surgery in those with clinically positive nodes. Additionally, response to treatment provides important prognostic information regarding risk of recurrence and guides future adjuvant treatment. Although chemotherapy serves as the backbone of neoadjuvant treatment, an increased understanding of the tumor's clinical course as well as its molecular and genetic make-up aids in individualizing treatment and developing novel agents. This review summarizes current clinical approaches and the future direction to the management of breast cancer …

Dual Targeting Of Cdk4/6 And Cmet In Metastatic Uveal Melanoma., Masahiro Ohara, Kengo Saito, Ken Kageyama, Mizue Terai, Hanyin Cheng, A E Aplin, Takami Sato

Department of Medical Oncology Faculty Papers

Uveal melanoma (UM) is the most common cancer of the eye in adults. Up to 50% of UM patients subsequently develop metastases, especially in the liver. It has been reported that the retinoblastoma (RB) pathway is deregulated in more than 90% of UM despite the rarity of mutations in the RB1 gene itself. CDK4/6 inhibition (CDK4/6i) is a rational strategy for treatment of UM. In this report, we investigated the antiproliferative activity of a selective CDK4/6 inhibitor on metastatic UM. A CDK4/6 inhibitor suppressed UM cell lines growth in in vitro and in vivo experiments. Hepatocyte growth factor (HGF) decreased …

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

Department of Medical Oncology Faculty Papers

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

Laryngeal Preservation Strategies In Locally Advanced Laryngeal And Hypopharyngeal Cancers., Athanassios Argiris, Jean Louis Lefebvre

Department of Medical Oncology Faculty Papers

For long, the treatment of locoregionally advanced laryngeal and hypopharyngeal squamous cell cancers (SCC) consisted of either total laryngectomy (TL) or definitive radiotherapy (RT). The development of induction cisplatin plus 5-fluorouracil (PF) and the correlation between chemosensitivity and radiosensitivity in previously untreated patients opened a new era of treatment aiming at laryngeal preservation (LP). The fundamental concept was to employ induction PF in order to select patients for subsequent treatment with either TL or RT according to tumor response to PF. The first two trials (VALGSG for laryngeal SCC and EORTC 24891 for hypopharyngeal SCC) concluded that such an approach …

New Interleukin-15 Superagonist (Il-15sa) Significantly Enhances Graft-Versus-Tumor Activity., Cavan P Bailey, Tulin Budak-Alpdogan, Christopher T Sauter, Michelle M Panis, Cihangir Buyukgoz, Emily K Jeng, Hing C Wong, Neal Flomenberg, Md, Onder Alpdogan

Department of Medical Oncology Faculty Papers

Interleukin-15 (IL-15) is a potent cytokine that increases CD8+ T and NK cell numbers and function in experimental models. However, obstacles remain in using IL-15 therapeutically, specifically its low potency and short in vivo half-life. To help overcome this, a new IL-15 superagonist complex comprised of an IL-15N72D mutation and IL-15RαSu/Fc fusion (IL-15SA, also known as ALT-803) was developed. IL-15SA exhibits a significantly longer serum half-life and increased in vivo activity against various tumors. Herein, we evaluated the effects of IL-15SA in recipients of allogeneic hematopoietic stem cell transplantation. Weekly administration of IL-15SA to transplant recipients significantly increased the number …

Depression Among Asian-American Adults In The Community: Systematic Review And Meta-Analysis., Hee Jun Kim, Eunmi Park, Carla L Storr, Katherine Tran, Hee-Soon Juon

Department of Medical Oncology Faculty Papers

OBJECTIVES: In this systematic review, we provide an overview of the literature on depression among Asian-Americans and explore the possible variations in depression prevalence estimates by methodological and demographic factors.

METHODS: Six databases were used to identify studies reporting a prevalence estimate for depression in Asian-American adults in non-clinical settings. Meta-analysis was used to calculate pooled estimates of rates of depression by assessment type. Statistical heterogeneity was assessed for subgroup analyses by gender, age, ethnicity, and other participant characteristics.

RESULTS: A total of 58 studies met the review criteria (n = 21.731 Asian-American adults). Heterogeneity across the studies was considerably …

Polymorphisms In Genes Of Tricarboxylic Acid Cycle Key Enzymes Are Associated With Early Recurrence Of Hepatocellular Carcinoma., Shaogui Wan, Yousheng Wu, Xingchun Zhou, Yibing Chen, Jiaze An, Xiaohe Yu, Huiqing Zhang, Hushan Yang, Jinliang Xing

Department of Medical Oncology Faculty Papers

Alterations of activity and expression in tricarboxylic acid (TCA) cycle key enzymes have been indicated in several malignancies, including hepatocellular carcinoma (HCC). They play an important role in the progression of cancer. However, the impact of single nucleotide polymorphisms (SNPs) in genes encoding these key enzymes on the recurrence of HCC has not been investigated. In this study, we genotyped 17 SNPs in genes encoding TCA cycle key enzymes and analyzed their association with recurrence-free survival (RFS) in a cohort of 492 Chinese HCC patients by Cox proportional hazard model and survival tree analysis. We identified 7 SNPs in SDHC, …

Complementary And Alternative Medicine In Cancer Prevention And Therapy., Peng Cao, Senthamil R Selvan, Esra Küpeli Akkol, Ning Wang, Hongjun Yang, Xiaolan Cheng

Department of Medical Oncology Faculty Papers

No abstract provided.

Prognostic Indications Of Elevated Mct4 And Cd147 Across Cancer Types: A Meta-Analysis, Cory D Bovenzi, James Hamilton, Md, Patrick Tassone, Md, Pgy-3, Jennifer Johnson, David Cognetti, Adam J. Luginbuhl, William M. Keane, Tingting Zhan, Madalina Tuluc, Voichita Bar-Ad, Ubaldo E. Martinez-Outshoorn, Md, Joseph M. Curry

Department of Medical Oncology Faculty Papers

No abstract provided.

Tp53 Mutations Detected In Circulating Tumor Cells Present In The Blood Of Metastatic Triple Negative Breast Cancer Patients., Sandra V Fernandez, Catherine Bingham, Patricia Fittipaldi, Laura Austin, Juan P. Palazzo, Gary Palmer, Katherine Alpaugh, Massimo Cristofanilli

Department of Medical Oncology Faculty Papers

INTRODUCTION: Circulating tumor cells (CTCs) are tumor cells shed from either primary tumors or its metastases that circulate in the peripheral blood of patients with metastatic cancers. The molecular characterization of the CTCs is critical to identifying the key drivers of cancer metastasis and devising therapeutic approaches. However, the molecular characterization of CTCs is difficult to achieve because their isolation is a major technological challenge.

METHODS: CTCs from two triple negative breast cancer patients were enriched using CellSearch and single cells selected by DEPArray™. A TP53 R110 fs*13 mutation identified by next generation sequencing in the breast and chest skin …

Azd8931, An Equipotent, Reversible Inhibitor Of Signaling By Epidermal Growth Factor Receptor (Egfr), Her2, And Her3: Preclinical Activity In Her2 Non-Amplified Inflammatory Breast Cancer Models., Zhaomei Mu, Teresa Klinowska, Xiaoshen Dong, Emily Foster, Chris Womack, Sandra V Fernandez, Massimo Cristofanilli

Department of Medical Oncology Faculty Papers

INTRODUCTION: Epidermal growth factor receptor (EGFR) overexpression has been associated with prognostic and predictive value in inflammatory breast cancer (IBC). Epidermal growth factor receptor 2 (HER2) overexpression is observed at a higher rate in IBC compared with noninflammatory breast cancer. Current clinically available anti-HER2 therapies are effective only in patients with HER2 amplified breast cancer, including IBC. AZD8931 is a novel small-molecule equipotent inhibitor of EGFR, HER2, and HER3 signaling. In this study, we investigated the antitumor activity of AZD8931 alone or in combination with paclitaxel using preclinical models of EGFR-overexpressed and HER2 non-amplified IBC cells.

METHODS: Two IBC cell …

Cell-Mediated Immunity And Vaccines, Jaya Kumari, Senthamil R. Selvan, Stéphane Bécart, Subhasis Chattopadhyay, Roy Ambli Dalmo

Department of Medical Oncology Faculty Papers

No abstract provided.

Phase I Evaluation Of Intravenous Ascorbic Acid In Combination With Gemcitabine And Erlotinib In Patients With Metastatic Pancreatic Cancer., Daniel A. Monti, Md, Edith Mitchell, Anthony J Bazzan, Susan Littman, George Zabrecky, Charles J Yeo, Madhaven V Pillai, Andrew B Newberg, Sandeep Deshmukh, Mark Levine

Department of Medical Oncology Faculty Papers

BACKGROUND: Preclinical data support further investigation of ascorbic acid in pancreatic cancer. There are currently insufficient safety data in human subjects, particularly when ascorbic acid is combined with chemotherapy.

METHODS AND FINDINGS: 14 subjects with metastatic stage IV pancreatic cancer were recruited to receive an eight week cycle of intravenous ascorbic acid (three infusions per week), using a dose escalation design, along with standard treatment of gemcitabine and erlotinib. Of 14 recruited subjects enrolled, nine completed the study (three in each dosage tier). There were fifteen non-serious adverse events and eight serious adverse events, all likely related to progression of …

Ceacam1 Separates Graft-Versus-Host-Disease From Graft-Versus-Tumor Activity After Experimental Allogeneic Bone Marrow Transplantation., Sydney X Lu, Lucy W Kappel, Anne-Marie Charbonneau-Allard, Renée Atallah, Amanda M Holland, Claire Turbide, Vanessa M Hubbard, Jimmy A Rotolo, Marsinay Smith, David Suh, Christopher King, Uttam K Rao, Nury Yim, Johanne L Bautista, Robert R Jenq, Olaf Penack, Il-Kang Na, Chen Liu, George Murphy, Onder Alpdogan, Richard S Blumberg, Fernando Macian, Kathryn V Holmes, Nicole Beauchemin, Marcel R M Van Den Brink

Department of Medical Oncology Faculty Papers

BACKGROUND: Allogeneic bone marrow transplantation (allo-BMT) is a potentially curative therapy for a variety of hematologic diseases, but benefits, including graft-versus-tumor (GVT) activity are limited by graft-versus-host-disease (GVHD). Carcinoembryonic antigen related cell adhesion molecule 1 (Ceacam1) is a transmembrane glycoprotein found on epithelium, T cells, and many tumors. It regulates a variety of physiologic and pathological processes such as tumor biology, leukocyte activation, and energy homeostasis. Previous studies suggest that Ceacam1 negatively regulates inflammation in inflammatory bowel disease models.

METHODS: We studied Ceacam1 as a regulator of GVHD and GVT after allogeneic bone marrow transplantation (allo-BMT) in mouse models. In …

In Vitro Migration Of Cytotoxic T Lymphocyte Derived From A Colon Carcinoma Patient Is Dependent On Ccl2 And Ccr2., Klara Berencsi, Pyapalli Rani, Tianqian Zhang, Laura Gross, Michael Mastrangelo, Neal J Meropol, Dorothee Herlyn, Rajasekharan Somasundaram

Department of Medical Oncology Faculty Papers

BACKGROUND: Infiltration of colorectal carcinomas (CRC) with T-cells has been associated with good prognosis. There are some indications that chemokines could be involved in T-cell infiltration of tumors. Selective modulation of chemokine activity at the tumor site could attract immune cells resulting in tumor growth inhibition. In mouse tumor model systems, gene therapy with chemokines or administration of antibody (Ab)-chemokine fusion proteins have provided potent immune mediated tumor rejection which was mediated by infiltrating T cells at the tumor site. To develop such immunotherapeutic strategies for cancer patients, one must identify chemokines and their receptors involved in T-cell migration toward …

Gitr Activation Induces An Opposite Effect On Alloreactive Cd4(+) And Cd8(+) T Cells In Graft-Versus-Host Disease., Stephanie J Muriglan, Teresa Ramirez-Montagut, Onder Alpdogan, Thomas W Van Huystee, Jeffrey M Eng, Vanessa M Hubbard, Adam A Kochman, Kartono H Tjoe, Carlo Riccardi, Pier Paolo Pandolfi, Shimon Sakaguchi, Alan N Houghton, Marcel R M Van Den Brink

Department of Medical Oncology Faculty Papers

Glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR) is a member of the tumor necrosis factor receptor (TNFR) family that is expressed at low levels on unstimulated T cells, B cells, and macrophages. Upon activation, CD4(+) and CD8(+) T cells up-regulate GITR expression, whereas immunoregulatory T cells constitutively express high levels of GITR. Here, we show that GITR may regulate alloreactive responses during graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT). Using a BMT model with major histocompatibility complex class I and class II disparity, we demonstrate that GITR stimulation in vitro and in vivo enhances alloreactive CD8(+)CD25(-) T …

Il-7 Enhances Peripheral T Cell Reconstitution After Allogeneic Hematopoietic Stem Cell Transplantation., Onder Alpdogan, Stephanie J Muriglan, Jeffrey M Eng, Lucy M Willis, Andrew S Greenberg, Barry J Kappel, Marcel R M Van Den Brink

Department of Medical Oncology Faculty Papers

We used clinically relevant murine allogeneic bone marrow transplantation (BMT) models to study the mechanisms by which IL-7 administration can improve posttransplant peripheral T cell reconstitution. After transplant we could distinguish two populations of mature donor T cells: (a) alloreactive T cells with decreased expression of CD127 (IL-7 receptor alpha chain) and (b) nonalloreactive T cells, which express CD127 and undergo homeostatic proliferation. IL-7 administration increased the homeostatic proliferation of nonalloreactive T cells, but had no effect on alloreactive T cells and the development of graft-versus-host disease. Allogeneic transplant of purified hematopoietic stem cells and adoptive transfer of thymocytes into …