Medicine and Health Sciences Commons^™

Efficacy And Safety Of Tepotinib In Asian Patients With Advanced Nsclc With Met Exon 14 Skipping Enrolled In Vision, Terufumi Kato, James Chih-Hsin Yang, Myung-Ju Ahn, Hiroshi Sakai, Masahiro Morise, Yuh-Min Chen, Ji-Youn Han, Jin-Ji Yang, Jun Zhao, Te-Chun Hsia, Karin Berghoff, Rolf Bruns, Helene Vioix, Simone Lang, Andreas Johne, Xiuning Le, Paul K Paik

Journal Articles

BACKGROUND: Tepotinib, a MET inhibitor approved for the treatment of MET exon 14 (METex14) skipping NSCLC, demonstrated durable clinical activity in VISION (Cohort A + C; N = 313): objective response rate (ORR) 51.4% (95% CI: 45.8, 57.1); median duration of response (mDOR) 18.0 months (95% CI: 12.4, 46.4). We report outcomes in Asian patients from VISION (Cohort A + C) (cut-off: November 20, 2022).

METHODS: Patients with advanced METex14 skipping NSCLC, detected by liquid or tissue biopsy, received tepotinib 500 mg (450 mg active moiety) once daily.

PRIMARY ENDPOINT: objective response (RECIST 1.1) by independent review. Secondary endpoints included: …

Association Of Cancer Diagnosis With Disability Status Among Older Survivors Of Colorectal Cancer: A Population-Based Retrospective Cohort Study, Shiming Zhang, Lin-Na Chou, Michael D Swartz, Hemalkumar B Mehta, James S Goodwin, Yong-Fang Kuo, Sharon Hermes Giordano, Carole A Tucker, Karen M Basen-Engquist, Elizabeth J Lyons, Brian Downer, Susan K Peterson, Tru Cao, Maria C Swartz

Journal Articles

BACKGROUND: Older cancer survivors likely experience physical function limitations due to cancer and its treatments, leading to disability and early mortality. Existing studies have focused on factors associated with surgical complications and mortality risk rather than factors associated with the development of poor disability status (DS), a proxy measure of poor performance status, in cancer survivors. We aimed to identify factors associated with the development of poor DS among older survivors of colorectal cancer (CRC) and compare poor DS rates to an age-sex-matched, non-cancer cohort.

METHODS: This retrospective cohort study utilized administrative data from the Texas Cancer Registry Medicare-linked database. …

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 …

Barriers To Colorectal Cancer Screening For Low-Income Hispanic Men In Urban Areas Between 50-75, Alex Vega

Rowan-Virtua Research Day

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States. Although CRC screening rates have improved in non-Hispanic whites (NHW), Hispanic adult males (HAM) aged 50-75 in urban areas continue to experience low screening rates and higher CRC morbidity and mortality. This review aims to identify the barriers to CRC screening among HAM and propose targeted interventions to increase screening rates. A comprehensive literature review was conducted using databases such as PubMed, Scopus, and Google Scholar. Key search terms included "colorectal cancer", "screening", "Hispanic adult males", "urban", "barriers", and "interventions". Factors identified include poverty, language …

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 …

Impact Of Timing To Initiate Adjuvant Therapy On Survival Of Elderly Glioblastoma Patients Using The Seer-Medicare And National Cancer Databases, Ping Zhu, Xianglin L Du, Lu-Yu Hwang, David Lairson, Ruosha Li, Yoshua Esquenazi, Jay-Jiguang Zhu

Journal Articles

The optimal time to initiate adjuvant therapy (AT) in elderly patients with glioblastoma (GBM) remains unclear. We investigated the impact of timing to start AT on overall survival (OS) using two national-scale datasets covering elderly GBM populations in the United States. A total of 3159 and 8161 eligible elderly GBM patients were derived from the Surveillance, Epidemiology and End Results (SEER)-Medicare linked dataset (2004-2013) and the National Cancer Database (NCDB) (2004-2014), respectively. The intervals in days from the diagnosis to the initiation of AT were categorized based on two scenarios: Scenario I (quartiles), ≤ 15, 16-26, 27-37, and ≥ 38 …

State Variation In Squamous Cell Carcinoma Of The Anus Incidence And Mortality, And Association With Hiv/Aids And Smoking In The United States, Haluk Damgacioglu, Yueh-Yun Lin, Ana Patricia Ortiz, Chi-Fang Wu, Zahed Shahmoradi, Shiang Shiuan Shyu, Ruosha Li, Alan G Nyitray, Keith Sigel, Gary M Clifford, Naomi Jay, Vivian Colon Lopez, Gregory M Barnell, Elizabeth Y Chiao, Elizabeth A Stier, Karen J Ortiz-Ortiz, Jeslie M Ramos-Cartagena, Kalyani Sonawane, Ashish A Deshmukh

Journal Articles

PURPOSE: Squamous cell carcinoma of the anus (SCCA) incidence and mortality rates are rising in the United States. Understanding state-level incidence and mortality patterns and associations with smoking and AIDS prevalence (key risk factors) could help unravel disparities and provide etiologic clues.

METHODS: Using the US Cancer Statistics and the National Center for Health Statistics data sets, we estimated state-level SCCA incidence and mortality rates. Rate ratios (RRs) were calculated to compare incidence and mortality in 2014-2018 versus 2001-2005. The correlations between SCCA incidence with current smoking (from the Behavioral Risk Factor Surveillance System) and AIDS (from the HIV Surveillance …

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 …

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 …

Do Breast Cancer Survivors With A Recent History Of Clinical Depression Report Worse Experiences With Care? A Retrospective Cohort Study Using Seer-Cahps Data, Mariana Arevalo, Trevor A Pickering, Sally W Vernon, Kayo Fujimoto, Melissa F Peskin, Albert J Farias

Journal Articles

PURPOSE: We examined whether breast cancer survivors' experiences with care differed by a recent history of clinical depression, and whether associations differed by race/ethnicity.

METHODS: Using the Epidemiology and End Results-Consumer Assessment of Healthcare Providers and Systems (SEER-CAHPS) dataset, we analyzed records of breast cancer survivors who completed a survey at least 12 months after their cancer diagnosis. We assessed clinical depression 12 months prior to survey completion using Medicare claims. We used separate multivariable logistic regressions to examine the associations between depression and excellent (vs. less than excellent) ratings of experiences with care (i.e., doctor communication, getting needed care, …

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 …

Machine Learning Analyses Of Highly-Multiplexed Immunofluorescence Identifies Distinct Tumor And Stromal Cell Populations In Primary Pancreatic Tumors, Krysten Vance, Alphan Alitinok, Seth Winfree, Heather Jensen Smith, Benjamin Swanson Md, Phd, Paul M. Grandgenett, Kelsey Klute, Daniel J Crichton, Michael A. Hollingsworth

Journal Articles: Eppley Institute

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a formidable challenge for patients and clinicians.

OBJECTIVE: To analyze the distribution of 31 different markers in tumor and stromal portions of the tumor microenvironment (TME) and identify immune cell populations to better understand how neoplastic, non-malignant structural, and immune cells, diversify the TME and influence PDAC progression.

METHODS: Whole slide imaging (WSI) and cyclic multiplexed-immunofluorescence (MxIF) was used to collect 31 different markers over the course of nine distinctive imaging series of human PDAC samples. Image registration and machine learning algorithms were developed to largely automate an imaging analysis pipeline identifying distinct cell …

Risk Of Developing Alzheimer's Disease And Related Dementias In Association With Cardiovascular Disease, Stroke, Hypertension, And Diabetes In A Large Cohort Of Women With Breast Cancer And With Up To 26 Years Of Follow-Up, Xianglin L Du, Lulu Song, Paul E Schulz, Hua Xu, Wenyaw Chan

Journal Articles

BACKGROUND: No study on the long-term incidence of Alzheimer's disease (AD) and related dementias (ADRD) has been reported in women with breast cancer by vascular diseases.

OBJECTIVE: to determine the risk of ADRD in association with cardiovascular diseases (CVD), stroke, hypertension, and diabetes in women with breast cancer.

METHODS: Study identified 246,686 women diagnosed with breast cancer at age≥65 years in 1991-2015 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Women were free of ADRD at the time of cancer diagnosis and followed from 1991 to 2016.

RESULTS: Cumulative incidence of AD over 26 years of follow-up varied …

Racial Disparities In Treatments And Mortality Among A Large Population-Based Cohort Of Older Men And Women With Colorectal Cancer, Xianglin L Du, Lulu Song

Journal Articles

BACKGROUND: There were racial disparities in treatment and mortality among patients with colorectal cancer, but few studies incorporated information on hypertension and diabetes and their treatment status.

PATIENTS AND METHODS: The study identified 101,250 patients from Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database in the United States who were diagnosed with colorectal cancer at age ≥65 years between 2007 and 2015 with follow-up to December 2016.

RESULTS: There were substantial racial and ethnic disparities in the prevalence of hypertension and diabetes in patients with colorectal cancer, in receiving chemotherapy and radiation therapy, and in receiving antihypertensive and antidiabetic treatment. …

Clinical Outcomes Of Patients With Newly Diagnosed Acute Lymphoblastic Leukemia In A County Hospital System, Effrosyni Apostolidou, Curtis Lachowiez, Harinder S Juneja, Wei Qiao, Onyebuchi Ononogbu, Courtney Nicole Miller-Chism, Mark Udden, Hilary Ma, Martha Pritchett Mims

Journal Articles

BACKGROUND: Major advances in the treatment of acute lymphoblastic leukemia (ALL) over the past decade have resulted in 5-year overall survival (OS) rates of 80% in mature B cell ALL, 50% in precursor B cell ALL, 50% to 60% in T cell ALL, and 60% to 70% in Philadelphia chromosome-positive (Ph+) ALL, as reported in studies from large, specialized centers. However, many patients treated in the community have limited access to novel therapies and stem cell transplantation (HSCT).

PATIENTS AND METHODS: The purpose of this retrospective cohort analysis was to evaluate the clinical outcomes of patients ≥ 16 years with …

Ovarian Cancer Epidemiology, Healthcare Access And Disparities (Orchid): Methodology For A Population-Based Study Of Black, Hispanic And White Patients With Ovarian Cancer, Tomi Akinyemiju, April Deveaux, Lauren Wilson, Anjali Gupta, Ashwini Joshi, Malcolm Bevel, Chioma Omeogu, Onyinye Ohamadike, Bin Huang, Maria Pisu, Margaret Liang, Molly Mcfatrich, Erin Daniell, Laura Jane Fish, Kevin Ward, Maria Schymura, Andrew Berchuck, Arnold L. Potosky

Biostatistics Faculty Publications

INTRODUCTION: Less than 40% of patients with ovarian cancer (OC) in the USA receive stage-appropriate guideline-adherent surgery and chemotherapy. Black patients with cancer report greater depression, pain and fatigue than white patients. Lack of access to healthcare likely contributes to low treatment rates and racial differences in outcomes. The Ovarian Cancer Epidemiology, Healthcare Access and Disparities study aims to characterise healthcare access (HCA) across five specific dimensions-Availability, Affordability, Accessibility, Accommodation and Acceptability-among black, Hispanic and white patients with OC, evaluate the impact of HCA on quality of treatment, supportive care and survival, and explore biological mechanisms that may contribute to …

Dietary Patterns And Hepatocellular Carcinoma Risk Among Us Adults, Iman Moussa, Rena S Day, Ruosha Li, Xianglin L Du, Ahmed O Kaseb, Prasun K Jalal, Carrie Daniel-Macdougall, Rikita I Hatia, Ahmed Abdelhakeem, Asif Rashid, Yun Shin Chun, Donghui Li, Manal M Hassan

Journal Articles

The objective of this study was to assess the association between dietary patterns and risk of hepatocellular carcinoma (HCC) among US adults in a hospital-based case-control study. We analyzed data from 641 cases and 1002 controls recruited at The University of Texas MD Anderson Cancer Center during 2001-2018. Cases were patients with a pathologically or radiologically confirmed new diagnosis of HCC; controls were cancer-free spouses of patients with cancers other than gastrointestinal, lung, liver, or head and neck cancer. Cases and controls were frequency-matched by age and sex. Dietary patterns were identified by principal component analysis. Odds ratios (ORs) and …

Mir-9-1 Suppresses Cell Proliferation And Promotes Apoptosis By Targeting Uhrf1 In Lung Cancer, Cheng-You Jia, Wei Xiang, Ji-Bin Liu, Geng-Xi Jiang, Feng Sun, Jian-Jun Wu, Xiao-Li Yang, Rui Xin, Yi Shi, Dan-Dan Zhang, Wen Li, Zavuga Zuberi, Jie Zhang, Gai-Xia Lu, Hui-Min Wang, Pei-Yao Wang, Fei Yu, Zhong-Wei Lv, Yu-Shui Ma, Da Fu

Journal Articles

Lung cancer is listed as the most common reason for cancer-related death all over the world despite diagnostic improvements and the development of chemotherapy and targeted therapies. MicroRNAs control both physiological and pathological processes including development and cancer. A microRNA-9 to 1 (miR-9 to 1) overexpression model in lung cancer cell lines was established and miR-9 to 1 was found to significantly suppress the proliferation rate in lung cancer cell lines, colony formation in vitro, and tumorigenicity in nude mice of A549 cells. Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) was then identified to direct target of miR-9 …

Pomalidomide, Dexamethasone, And Daratumumab In Relapsed Refractory Multiple Myeloma After Lenalidomide Treatment., David S Siegel, Gary J Schiller, Christy Samaras, Michael Sebag, Jesus Berdeja, Siddhartha Ganguly, Jeffrey Matous, Kevin Song, Christopher S Seet, Giampaolo Talamo, Mirelis Acosta-Rivera, Michael Bar, Donald Quick, Bertrand Anz, Gustavo Fonseca, Donna Reece, William E Pierceall, Weiyuan Chung, Faiza Zafar, Amit Agarwal, Nizar J Bahlis

Articles, Abstracts, and Reports

Patients with multiple myeloma who have relapsed after or become refractory to lenalidomide in early treatment lines represent a clinically important population in need of effective therapies. The safety and efficacy of pomalidomide, low-dose dexamethasone, and daratumumab was evaluated in lenalidomide-pretreated patients with relapsed or refractory multiple myeloma (RRMM) after one to two prior treatment lines in the phase 2 MM-014 study. Patients received pomalidomide 4 mg daily from days 1-21 and dexamethasone 40 mg weekly (28-day cycles). Daratumumab 16 mg/kg was administered per label. Primary endpoint was overall response rate (ORR); secondary endpoints included progression-free survival (PFS) and safety. …

Long Term Survival And Local Control Outcomes From Single Dose Targeted Intraoperative Radiotherapy During Lumpectomy (Targit-Iort) For Early Breast Cancer: Targit-A Randomised Clinical Trial., Jayant S Vaidya, Max Bulsara, Michael Baum, Frederik Wenz, Samuele Massarut, Steffi Pigorsch, Michael Alvarado, Michael Douek, Christobel Saunders, Henrik L Flyger, Wolfgang Eiermann, Chris Brew-Graves, Norman R Williams, Ingrid Potyka, Nicholas Roberts, Marcelle Bernstein, Douglas Brown, Elena Sperk, Siobhan Laws, Marc Sütterlin, Tammy Corica, Steinar Lundgren, Dennis R Holmes, Lorenzo Vinante, Fernando Bozza, Montserrat Pazos, Magali Le Blanc-Onfroy, Günther Gruber, Wojciech Polkowski, Konstantin J Dedes, Marcus Niewald, Jens Blohmer, David Mccready, Richard Hoefer, Pond Kelemen, Gloria Petralia, Mary Falzon, David J Joseph, Jeffrey S Tobias

Articles, Abstracts, and Reports

OBJECTIVE: To determine whether risk adapted intraoperative radiotherapy, delivered as a single dose during lumpectomy, can effectively replace postoperative whole breast external beam radiotherapy for early breast cancer.

DESIGN: Prospective, open label, randomised controlled clinical trial.

SETTING: 32 centres in 10 countries in the United Kingdom, Europe, Australia, the United States, and Canada.

PARTICIPANTS: 2298 women aged 45 years and older with invasive ductal carcinoma up to 3.5 cm in size, cN0-N1, eligible for breast conservation and randomised before lumpectomy (1:1 ratio, blocks stratified by centre) to either risk adapted targeted intraoperative radiotherapy (TARGIT-IORT) or external beam radiotherapy (EBRT).

INTERVENTIONS: …

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), …

Beyond An Updated Graded Prognostic Assessment (Breast Gpa): A Prognostic Index And Trends In Treatment And Survival In Breast Cancer Brain Metastases From 1985 To Today, Paul W Sperduto, Shane Mesko, Jing Li, Daniel Cagney, Ayal Aizer, Nancy U Lin, Eric Nesbit, Tim J Kruser, Jason Chan, Steve Braunstein, Jessica Lee, John P Kirkpatrick, Will Breen, Paul D Brown, Diana Shi, Helen A Shih, Hany Soliman, Arjun Sahgal, Ryan Shanley, William Sperduto, Emil Lou, Ashlyn Everett, Drexell Hunter Boggs, Laura Masucci, David Roberge, Jill Remick, Kristin Plichta, John M Buatti, Supriya Jain, Laurie E Gaspar, Cheng-Chia Wu, Tony J C Wang, John Bryant, Michael Chuong, James Yu, Veronica Chiang, Toshimichi Nakano, Hidefumi Aoyama, Minesh P Mehta

Journal Articles

PURPOSE: Brain metastases are a common sequelae of breast cancer. Survival varies widely based on diagnosis-specific prognostic factors (PF). We previously published a prognostic index (Graded Prognostic Assessment [GPA]) for patients with breast cancer with brain metastases (BCBM), based on cohort A (1985-2007, n = 642), then updated it, reporting the effect of tumor subtype in cohort B (1993-2010, n = 400). The purpose of this study is to update the Breast GPA with a larger contemporary cohort (C) and compare treatment and survival across the 3 cohorts.

METHODS AND MATERIALS: A multi-institutional (19), multinational (3), retrospective database of 2473 …

Protein-Altering Germline Mutations Implicate Novel Genes Related To Lung Cancer Development., Xuemei Ji, Semanti Mukherjee, Maria Teresa Landi, Yohan Bosse, Philippe Joubert, Dakai Zhu, Ivan Gorlov, Xiangjun Xiao, Younghun Han, Olga Gorlova, Rayjean J Hung, Yonathan Brhane, Robert Carreras-Torres, David C Christiani, Neil Caporaso, Mattias Johansson, Geoffrey Liu, Stig E Bojesen, Loic Le Marchand, Demetrios Albanes, Heike Bickeböller, Melinda C Aldrich, William S Bush, Adonina Tardon, Gad Rennert, Chu Chen, Jinyoung Byun, Konstantin H Dragnev, John K Field, Lambertus Fa Kiemeney, Philip Lazarus, Shan Zienolddiny, Stephen Lam, Matthew B Schabath, Angeline S Andrew, Pier A Bertazzi, Angela C Pesatori, Nancy Diao, Li Su, Lei Song, Ruyang Zhang, Natasha Leighl, Jakob S Johansen, Anders Mellemgaard, Walid Saliba, Christopher Haiman, Lynne Wilkens, Ana Fernandez-Somoano, Guillermo Fernandez-Tardon, Erik H F M Van Der Heijden, Jin Hee Kim, Michael P A Davies, Michael W Marcus, Hans Brunnström, Jonas Manjer, Olle Melander, David C Muller, Kim Overvad, Antonia Trichopoulou, Rosario Tumino, Gary E Goodman, Angela Cox, Fiona Taylor, Penella Woll, Erich Wichmann, Thomas Muley, Angela Risch, Albert Rosenberger, Kjell Grankvist, Mikael Johansson, Frances Shepherd, Ming-Sound Tsao, Susanne M Arnold, Eric B Haura, Ciprian Bolca, Ivana Holcatova, Vladimir Janout, Milica Kontic, Jolanta Lissowska, Anush Mukeria, Simona Ognjanovic, Tadeusz M Orlowski, Ghislaine Scelo, Beata Swiatkowska, David Zaridze, Per Bakke, Vidar Skaug, Lesley M Butler, Kenneth Offit, Preethi Srinivasan, Chaitanya Bandlamudi, Matthew D Hellmann, David B Solit, Mark E Robson, Charles M Rudin, Zsofia K Stadler, Barry S Taylor, Michael F Berger, Richard Houlston, John Mclaughlin, Victoria Stevens, David C Nickle, Ma'en Obeidat, Wim Timens, María Soler Artigas, Sanjay Shete, Hermann Brenner, Stephen Chanock, Paul Brennan, James D Mckay, Christopher I Amos

Articles, Abstracts, and Reports

Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio = 8.82, P = 1.18 × 10-15) and replication (adjusted OR = 2.93, P = 2.22 × 10-3) that is more pronounced in females (adjusted OR = 6.81 and 3.19 and for discovery and replication). We observe an excess loss of heterozygosity in lung tumors among ATM L2307F allele carriers. L2307F is …

Randomized Phase Ii Study Of Stereotactic Body Radiotherapy And Interleukin-2 Versus Interleukin-2 In Patients With Metastatic Melanoma., Brendan Curti, Marka R Crittenden, Steven K Seung, Christopher B Fountain, Roxanne Payne, Shuching Chang, Jessica Fleser, Kimberly Phillips, Ian Malkasian, Lyn B Dobrunick, Walter Urba

Articles, Abstracts, and Reports

BACKGROUND: A pilot study of stereotactic body radiation therapy (SBRT) followed by high-dose interleukin-2 (IL-2) showed a higher than anticipated objective response rate (ORR) among patients with metastatic melanoma (MM). We performed a prospective randomized study to determine if the ORR of SBRT + IL-2 was greater than IL-2 monotherapy in patients with advanced melanoma.

METHODS: Patients with MM who had adequate physiological reserve for IL-2 and at least one site suitable for SBRT were eligible. There was a 1:1 randomization to SBRT + IL-2 or IL-2 monotherapy. Patients received one or two doses of SBRT (20 Gy per fraction) …

Prospective Molecular Profiling Of Circulating Tumor Cells From Patients With Melanoma Receiving Combinatorial Immunotherapy., Selena Y Lin, Shu-Ching Chang, Stella Lam, Romela Irene Ramos, Kevin Tran, Shuichi Ohe, Matthew P Salomon, Ali Asgar S Bhagat, Chwee Teck Lim, Trevan D Fischer, Leland J Foshag, Christine L Boley, Steven J O'Day, Dave Hoon

Articles, Abstracts, and Reports

BACKGROUND: Blood molecular profiling of circulating tumor cells (CTCs) can enable monitoring of patients with metastatic melanoma during checkpoint inhibitor immunotherapy (CII) and in combination with targeted therapies. We developed a microfluidics-based CTC platform to explore CTC profiling utility in CII-treated patients with melanoma using a melanoma messenger RNA (mRNA)/DNA biomarker panel.

METHODS: Blood samples (n = 213) were collected prospectively from 75 American Joint Committee on Cancer-staged III/IV melanoma patients during CII treatment and those enriched for CTCs. CTC profiling was performed using 5 known melanoma mRNA biomarkers and BRAF V600E DNA mutation. CTC biomarker status associations with clinical …

Transcriptional And Immunohistological Assessment Of Immune Infiltration In Pancreatic Cancer., Brady Bernard, Venkatesh Rajamanickam, Christopher Dubay, Brian D. Piening, Emilio Alonso, Zeljka Jutric, Ephraim Tang, Pippa Newell, Paul D Hansen, Terry R Medler, Andrew J Gunderson, Kristina H Young, Carlo Bifulco, Joanna Pucilowska, Marka R Crittenden, Michael J. Gough

Articles, Abstracts, and Reports

Pancreatic adenocarcinoma is characterized by a complex tumor environment with a wide diversity of infiltrating stromal and immune cell types that impact the tumor response to conventional treatments. However, even in this poorly responsive tumor the extent of T cell infiltration as determined by quantitative immunohistology is a candidate prognostic factor for patient outcome. As such, even more comprehensive immunophenotyping of the tumor environment, such as immune cell type deconvolution via inference models based on gene expression profiling, holds significant promise. We hypothesized that RNA-Seq can provide a comprehensive alternative to quantitative immunohistology for immunophenotyping pancreatic cancer. We performed RNA-Seq …