Medicine and Health Sciences Commons^™

Multiple Sclerosis Outcomes After Cancer Immunotherapy, Catherine R. Garcia, Rani Jayswal, Val R. Adams, Lowell B. Anthony, John L. Villano

Markey Cancer Center Faculty Publications

INTRODUCTION: Neurological immune-related adverse events are a rare but potentially deadly complication after immune checkpoint inhibitor (ICI) treatment. As multiple sclerosis (MS) is an immune-mediated disease, it is unknown how ICI treatment may affect outcomes.

METHODS: We analyzed the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database for pembrolizumab, atezolizumab, nivolumab, ipilimumab, avelumab, and durvalumab 2 years prior their FDA approval until December 31, 2017, to include all cases with confirmed diagnosis/relapse of MS. We also included cases reported in the literature and a patient from our institution.

RESULTS: We identified 14 cases of MS …

Tumor Heterogeneity As A Predictor Of Response To Neoadjuvant Chemotherapy In Locally Advanced Rectal Cancer, Alissa Greenbaum, David R. Martin, Therese J. Bocklage, Ji-Hyun Lee, Scott A. Ness, Ashwani Rajput

Pathology and Laboratory Medicine Faculty Publications

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) is the standard of care for locally advanced adenocarcinoma of the rectum, but it is currently unknown which patients have disease that will respond. This study tested the correlation between response to nCRT and intratumoral heterogeneity using next-generation sequencing assays.

PATIENTS AND METHODS: DNA was extracted from formalin-fixed, paraffin-embedded biopsy samples from a cohort of patients with locally advanced rectal adenocarcinoma (T3/4 or N1/2 disease) who received nCRT. High read-depth sequencing of > 400 cancer-relevant genes was performed. Tumor mutations and variant allele frequencies were used to calculate mutant-allele tumor heterogeneity (MATH) scores as measures of intratumoral …

Demographic, Presentation, And Treatment Factors And Racial Disparities In Ovarian Cancer Hospitalization Outcomes, Tomi F. Akinyemiju, Gurudatta Naik, Kemi Ogunsina, Daniel T. Dibaba, Neomi Vin-Raviv

Epidemiology and Environmental Health Faculty Publications

BACKGROUND: This study examines whether racial disparities in hospitalization outcomes persist between African-American and White women with ovarian cancer after matching on demographic, presentation, and treatment factors.

METHODS: Using data from the Nationwide Inpatient Sample database, 5,164 African-American ovarian cancer patients were sequentially matched with White patients on demographic (e.g., age, income), presentation (e.g., stage, comorbidities), and treatment (e.g., surgery, radiation) factors. Racial differences in-hospital length of stay, post-operative complications, and in-hospital mortality were evaluated using conditional logistic regression models.

RESULTS: White ovarian cancer patients had relatively higher odds of post-operative complications when matched on demographics (OR 1.35, 95% CI …

Cetuximab Plus Carboplatin And Paclitaxel With Or Without Bevacizumab Versus Carboplatin And Paclitaxel With Or Without Bevacizumab In Advanced Nsclc (Swog S0819): A Randomised, Phase 3 Study, Roy S. Herbst, Mary W. Redman, Edward S. Kim, Thomas J. Semrad, Lyudmila Bazhenova, Gregory Masters, Kurt Oettel, Perry Guaglianone, Christopher Reynolds, Anand Karnad, Susanne M. Arnold, Marileila Varella-Garcia, James Moon, Philip C. Mack, Charles D. Blanke, Fred R. Hirsch, Karen Kelly, David R. Gandara

Markey Cancer Center Faculty Publications

Background

EGFR antibodies have shown promise in patients with advanced non-small-cell lung cancer (NSCLC), particularly with squamous cell histology. We hypothesised that EGFR copy number by fluorescence in-situ hybridisation (FISH) can identify patients most likely to benefit from these drugs combined with chemotherapy and we aimed to explore the activity of cetuximab with chemotherapy in patients with advanced NSCLC who are EGFR FISH-positive.

Methods

We did this open-label, phase 3 study (SWOG S0819) at 277 sites in the USA and Mexico. We randomly assigned (1:1) eligible patients with treatment-naive stage IV NSCLC to receive paclitaxel (200 mg/m ²; every …

Common Tdp1 Polymorphisms In Relation To Survival Among Small Cell Lung Cancer Patients: A Multicenter Study From The International Lung Cancer Consortium, Pawadee Lohavanichbutr, Lori C. Sakoda, Christopher I. Amos, Susanne M. Arnold, David C. Christiani, Michael P. A. Davies, John K. Field, Eric B. Haura, Rayjean J Hung, Takashi Kohno, Maria Teresa Landi, Geoffrey Liu, Yi Liu, Michael W. Marcus, Grainne M. O'Kane, Matthew B. Schabath, Kouya Shiraishi, Stacey A. Slone, Adonina Tardón, Ping Yang, Kazushi Yoshida, Ruyang Zhang, Xuchen Zong, Gary E. Goodman, Noel S. Weiss, Chu Chen

Internal Medicine Faculty Publications

Background—DNA topoisomerase inhibitors are commonly used for treating small-cell lung cancer (SCLC). Tyrosyl-DNA phosphodiesterase (TDP1) repairs DNA damage caused by this class of drugs and may therefore influence treatment outcome. In this study, we investigated whether common TDP1 single-nucleotide polymorphisms (SNP) are associated with overall survival among SCLC patients.

Methods—Two TDP1 SNPs (rs942190 and rs2401863) were analyzed in 890 patients from 10 studies in the International Lung Cancer Consortium (ILCCO). The Kaplan–Meier method and Cox regression analyses were used to evaluate genotype associations with overall mortality at 36 months postdiagnosis, adjusting for age, sex, race, and tumor stage. …

Ecog-Acrin (E4805) Randomized Phase Ii Study To Determine The Effect Of 2 Different Doses Of Aflibercept In Patients With Metastatic Renal Cell Carcinoma, Roberto Pili, Opeyemi Jegede, Michael A. Carducci, Judith Manola, David L. Groteluschen, Leonard L. Appleman, Glenn Liu, James C. Shanks, Shaker R. Dakhil, Janice Dutcher, Robert S. Dipaola

Internal Medicine Faculty Publications

Background—Aflibercept is a recombinantly-produced fusion protein that has potent anti-VEGF activity. We tested whether aflibercept has clinical activity in clear cell renal cell carcinoma (ccRCC). The recommended Phase 2 dose was 4 mg/kg but several patients treated at 1 mg/kg demonstrated prolonged progression-free survival (PFS). We therefore tested both doses in a parallel group randomized trial.

Methods—Eligible patients (pts) had histologically confirmed advanced or metastatic ccRCC and previous treatments including prior exposure to a VEGF RTKI. Patients received aflibercept (either 1 mg/kg or 4 mg/kg) day 1 of a 14-day cycle until progression. Patients randomized to 1 mg/kg …

Understanding The Patient Experience With Carcinoid Syndrome: Exit Interviews From A Randomized, Placebo-Controlled Study Of Telotristat Ethyl, Lowell B. Anthony, Claire Ervin, Pablo Lapuerta, Matthew H. Kulke, Pamela Kunz, Emily Bergsland, Dieter Hörsch, David C. Metz, Janice Pasieka, Nick Pavlakis, Marianne Pavel, Martyn Caplin, Kjell Öberg, John Ramage, Emily Evans, Qi Melissa Yang, Shanna Jackson, Karie Arnold, Linda Law, Dana B. Dibenedetti

Markey Cancer Center Faculty Publications

Purpose: Telotristat ethyl, an oral tryptophan hydroxylase inhibitor, is intended to treat carcinoid syndrome by reducing serotonin production. Telotristat ethyl was evaluated in TELESTAR, a Phase III study for patients who had carcinoid syndrome with at least 4 bowel movements (BMs) per day and who were receiving somatostatin analogue therapy. This interview substudy was conducted to provide insight into the patient experience in TELESTAR and to help understand whether reductions in BM frequency (the primary end point) and other symptoms were clinically meaningful.

Methods: Participating sites were asked to invite (before randomization) all eligible patients to telephone interviews scheduled at …

Lisinopril Or Coreg Cr In Reducing Cardiotoxicity In Women With Breast Cancer Receiving Trastuzumab: A Rationale And Design Of A Randomized Clinical Trial, Maya Guglin, Pamela Munster, Angelina Fink, Jeffrey Krischer

Internal Medicine Faculty Publications

Background—Trastuzumab (TZB) is an established therapy for HER2 positive breast cancer. The use of TZB is commonly associated with cardiotoxicity manifesting as asymptomatic decrease in left ventricular ejection fraction (LVEF) or overt heart failure. Several studies demonstrated favorable effects of angiotensin converting enzyme (ACE) inhibitors and beta blockers (BB) in the prevention of chemotherapy-induced cardiotoxicity. We hypothesize that patients, randomized to receive an ACE inhibitor or a beta-blocker during trastuzumab therapy for breast cancer, will maintain a higher LVEF than patients randomized to placebo.

Methods and Results—We designed a prospective, multicenter, randomized, phase II placebo-controlled clinical trial to …

Targeting Wnt/Β-Catenin Pathway In Hepatocellular Carcinoma Treatment, Valery Vilchez, Lilia M. Turcios, Francesc Marti, Roberto Gedaly

Surgery Faculty Publications

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Liver cancer is generally related to hepatitis B or C infection and cirrhosis. Usually, patients with HCC are asymptomatic and are diagnosed at late stages when surgical treatment is no longer suitable. Limited treatment options for patients with advanced HCC are a major concern. Therefore, there is an urge for finding novel therapies to treat HCC. Liver cancer is highly heterogeneous and involved deregulation of several signaling pathways. Wnt/β-catenin pathway is frequently upregulated in HCC and it is implicated in maintenance of tumor initiating cells, drug …

G9a Is Essential For Emt-Mediated Metastasis And Maintenance Of Cancer Stem Cell-Like Characters In Head And Neck Squamous Cell Carcinoma, Shuli Liu, Dongxia Ye, Wenzheng Guo, Wenwen Yu, Yue He, Jingzhou Hu, Yanan Wang, Ling Zhang, Yueling Liao, Hongyong Song, Shuangshuang Zhong, Dongliang Xu, Huijing Yin, Beibei Sun, Xiaofei Wang, Jingyi Liu, Yadi Wu, Binhua P. Zhou, Zhiyuan Zhang, Jiong Deng

Markey Cancer Center Faculty Publications

Head and neck squamous cell carcinoma (HNSCC) is a particularly aggressive cancer with poor prognosis, largely due to lymph node metastasis and local recurrence. Emerging evidence suggests that epithelial-to-mesenchymal transition (EMT) is important for cancer metastasis, and correlated with increased cancer stem cells (CSCs) characteristics. However, the mechanisms underlying metastasis to lymph nodes in HNSCC is poorly defined. In this study, we show that E-cadherin repression correlates with cancer metastasis and poor prognosis in HNSCC. We found that G9a, a histone methyltransferase, interacts with Snail and mediates Snail-induced transcriptional repression of E-cadherin and EMT, through methylation of histone H3 lysine-9 …