Public Health 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: …

Mainehealth Cancer Care Network Ticket Intake Process, Lauren Couture, Brett Cropp, Gavin Carr, Ashok Kunche, Heather Boulier, Evelyn Taylor

Operations Transformation

The MaineHealth Cancer Care Network informatics team is manually submitting most reporting tickets for oncology customers. The current intake ticket process includes various communication channels to the business intelligence developers [BID] when a reporting need is identified resulting in workflow deficiencies and redundancies. As of FY23, MaineHealth has moved to a new ticket reporting system called ServiceHub which includes new customer self-service tools that have not yet been utilized.

Transition To Adult Care For Bleeding Disorders: Building A Multidisciplinary Tool, Leslie Larson, Ekaterina Funk, Dana Grass, Felicia Munster, Eric Larsen, Louise Baca, Glen Roy, Sara Artinyan

Operations Transformation

Youth with chronic illnesses often have poorer health outcomes after transitioning to adult care. Maine Health Bleeding Disorders is a Health Resources and Services Administration (HRSA) grant funded Hemophilia Treatment Center (HTC) that serves patients with congenital bleeding disorders. We provide multidisciplinary specialty care throughout the lifespan which includes pediatric and adult hematologists, family nurse practitioners, nurses, physical therapists, social worker, dietitian, genetic counselor, and research coordinator. In 2022, HRSA mandated all federally funded HTCs increase by 25 percent from baseline the number of individuals ages 12 to 26 years seen in a comprehensive clinic that have a health care …

C-Terminal Binding Protein 2 Is A Novel Tumor Suppressor Targeting The Myc-Irf4 Axis In Multiple Myeloma, Coty Hing Yau Cheung, Chi Keung Cheng, Kam Tong Leung, Chi Zhang, Chi Yan Ho, Xi Luo, Angel Yuet Fong Kam, Tian Xia, Thomas Shek Kong Wan, Herbert Augustus Pitts, Natalie Pui Ha Chan, Joyce Sin Cheung, Raymond Siu Ming Wong, Xiao-Bing Zhang, Margaret Heung Ling Ng

Journal Articles

Multiple myeloma (MM) cells are addicted to MYC and its direct transactivation targets IRF4 for proliferation and survival. MYC and IRF4 are still considered "undruggable," as most small-molecule inhibitors suffer from low potency, suboptimal pharmacokinetic properties, and undesirable off-target effects. Indirect inhibition of MYC/IRF4 emerges as a therapeutic vulnerability in MM. Here, we uncovered an unappreciated tumor-suppressive role of C-terminal binding protein 2 (CTBP2) in MM via strong inhibition of the MYC-IRF4 axis. In contrast to epithelial cancers, CTBP2 is frequently downregulated in MM, in association with shortened survival, hyperproliferative features, and adverse clinical outcomes. Restoration of CTBP2 exhibited potent …

Phase Ib/Ii Study Of Lacnotuzumab In Combination With Spartalizumab In Patients With Advanced Malignancies, Jibran Ahmed, Bettzy Stephen, Yali Yang, Evan Kwiatkowski, Chinenye Lynette Ejezie, Shubham Pant

Journal Articles

INTRODUCTION: Blocking the colony-stimulating factor 1 (CSF-1) signal on tumor-associated macrophages can lead to an upregulation of checkpoint molecules, such as programmed cell death ligand 1 (PD-L1), thus causing resistance to this blockade. Combining spartalizumab (PDR001), a high-affinity, ligand-blocking, humanized anti-PD-1 immunoglobulin G4 antibody, with lacnotuzumab (MCS110), a high-affinity, humanized monoclonal antibody directed against human CSF-1 can potentially overcome this resistance.

METHODS: This was a multicenter, phase Ib/II trial using a combination of spartalizumab with lacnotuzumab in patients with advanced cancers, including anti-PD-1/PD-L1 treatment-resistant melanoma, and anti-PD-1/PD-L1 treatment-naïve triple-negative breast cancer, pancreatic cancer, and endometrial cancer (ClinicalTrials.gov identifier: NCT02807844). The …

Evidenced-Based Strategies To Increase Cervical Cancer Screening Rates, Tuong Cat Vo Bsn-Rn, Nada Salloukh Bsn-Rn, Tatiana Elena Swanson Bsn-Rn, Xiao Mie Cindy Zhu Bsn-Rn, Laura Taylor Reed Dnp, Aprn, Fnp-Bc

Doctor of Nursing Practice Projects

Purpose/Background

Cervical cancer is the fourth leading cause of cancer affecting women worldwide (Staley et al., 2021). With cervical cancer being a preventable disease, an effective method of reducing healthcare costs and mortality is primary prevention, such as screenings. Financial burdens and barriers to accessing medical care may result due to the lack of proper cervical cancer screenings. Detecting cervical cancer includes screening women 21 to 65 years old with a Papanicolaou (PAP) test every three years. Women aged 30 to 65 years old can extend the screening of cervical cancer by having a Human Papillomavirus (HPV) test along with …

Medical Home Implementation And Follow-Up Of Cancer-Related Abnormal Test Results In The Veterans Health Administration, Suja S Rajan, Shashank Sarvepalli, Li Wei, Ashley N D Meyer, Daniel R Murphy, Debra T Choi, Hardeep Singh

Journal Articles

IMPORTANCE: Lack of timely follow-up of cancer-related abnormal test results can lead to delayed or missed diagnoses, adverse cancer outcomes, and substantial cost burden for patients. Care delivery models, such as the Veterans Affairs' (VA) Patient-Aligned Care Team (PACT), which aim to improve patient-centered care coordination, could potentially also improve timely follow-up of abnormal test results. PACT was implemented nationally in the VA between 2010 and 2012.

OBJECTIVE: To evaluate the long-term association between PACT implementation and timely follow-up of abnormal test results related to the diagnosis of 5 different cancers.

DESIGN, SETTING, AND PARTICIPANTS: This multiyear retrospective cohort study …

Single-Cell Transcriptomics Reveals Pre-Existing Covid-19 Vulnerability Factors In Lung Cancer Patients, Wendao Liu, Wenbo Li, Zhongming Zhao

Journal Articles

UNLABELLED: Coronavirus disease 2019 (COVID-19) and cancer are major health threats, and individuals may develop both simultaneously. Recent studies have indicated that patients with cancer are particularly vulnerable to COVID-19, but the molecular mechanisms underlying the associations remain poorly understood. To address this knowledge gap, we collected single-cell RNA-sequencing data from COVID-19, lung adenocarcinoma, small cell lung carcinoma patients, and normal lungs to perform an integrated analysis. We characterized altered cell populations, gene expression, and dysregulated intercellular communication in diseases. Our analysis identified pathologic conditions shared by COVID-19 and lung cancer, including upregulated TMPRSS2 expression in epithelial cells, stronger inflammatory …

Response To The Letter To The Editor: Surgical Delay Of Thoracodorsal Artery Perforator Flaps For Bilateral Autologous Breast Reconstruction, Robert J. Allen, Mark A. Maier

School of Medicine Faculty Publications

No abstract provided.

Most Deprived Louisiana Census Tracts Have Higher Hepatocellular Carcinoma Incidence And Worse Survival, Kendra L. Ratnapradipa, Tingting Li, Mei Chin Hsieh, Laura Tenner, Edward S. Peters

School of Public Health Faculty Publications

Background: Liver cancer incidence increased in the US from 1975 through 2015 with heterogeneous rates across subpopulations. Upstream or distal area-level factors impact liver cancer risks. Objective: The aim of this study was to examine the association between area-level deprivation and hepatocellular carcinoma (HCC) incidence and survival. We also explored the association between area deprivation and treatment modalities. Methods: Louisiana Tumor Registry identified 4,151 adult patients diagnosed with malignant HCC from 2011 to 2020 and linked residential address to census tract (CT)-level Area Deprivation Index (ADI) categorized into quartiles (Q1 = least deprived). ANOVA examined the association between ADI quartile …

Gut Microbiome Of Patients With Breast Cancer In Vietnam, Sang M Nguyen, Huong T T Tran, Jirong Long, Martha J Shrubsole, Hui Cai, Yaohua Yang, Lan M Nguyen, Giang H Nguyen, Chu V Nguyen, To V Ta, Jie Wu, Qiuyin Cai, Wei Zheng, Thuan V Tran, Xiao-Ou Shu

Journal Articles

PURPOSE: Gut microbiota play an important role in human health, including cancer. Cancer and its treatment, in turn, may alter the gut microbiome. To understand this complex relationship, we profiled the gut microbiome of 356 Vietnamese patients with breast cancer.

MATERIALS AND METHODS: Stool samples were collected before chemotherapy, with 162 pre- and 194 postsurgery. The gut microbiome was measured by shotgun metagenomic sequencing. Associations of gut microbial diversity, taxa abundance, and gut microbiome health index (GMHI) with sociodemographic, clinical factors, and tumor characteristics were evaluated.

RESULTS: Postsurgery samples were associated with significantly lower α- and β-diversities (

CONCLUSION: Our …

Quality Of Life Among Cancer Survivors: Comparison Of Multiple Cancers Using Icare2, Shinobu Watanabe-Galloway, Rachael L. Schmidt, Kendra Ratnapradipa, Kristin Dickinson, Abbey Fingeret, Whitney Goldner

Manuscripts: Epidemiology

Background: The number of cancer survivors continues to increase due to dramatic improvements in cancer treatment, accounting for approximately 5% of the entire population. As cancer survivors continue to live longer, it is important to understand their quality of life (QoL) in order to maximize supportive care efforts.

Objectives: In this study, the quality of life (QoL) among patients with different types of cancer was examined. The objectives were to: 1) compare patient-reported outcome measures of QoL using the Short-Form (SF-36) Health Survey scores among patients of different cancer types and 2) identify demographic, oncologic, and clinical factors that are …

Developing A National Implementation Strategy To Accelerate Uptake Of Evidence-Based Family Caregiver Support In Us Cancer Centers, J Nicholas Odom, Heather M Young, Katherine Sterba, Timothy S Sannes, Susan Reinhard, Chandylen L Nightingale, Diane Meier, Tamryn F Gray, Betty Ferrell, Maria E Fernandez, Heidi Donovan, Kayleigh Curry, Erin R Currie, Tara Bryant, Marie A Bakitas, Allison J Applebaum

Journal Articles

OBJECTIVE: Characterize key factors and training needs of U.S. cancer centers in implementing family caregiver support services.

METHODS: Sequential explanatory mixed methods design consisting of: (1) a national survey of clinicians and administrators from Commission-on-Cancer-accredited cancer centers (N = 238) on factors and training needed for establishing new caregiver programs and (2) qualitative interviews with a subsample of survey respondents (N = 30) to elicit feedback on survey findings and the outline of an implementation strategy to facilitate implementation of evidence-based family caregiver support (the Caregiver Support Accelerator). Survey data was tabulated using descriptive statistics and transcribed interviews were analyzed …

Unraveling The Prognostic Significance Of Rgs Gene Family In Gastric Cancer And The Potential Implication Of Rgs4 In Regulating Tumor-Infiltrating Fibroblast, Yalan Yang, Siyuan Xing, Xi Luo, Lulu Guan, Yao Lu, Yiting Wang, Feng Wang

Journal Articles

Regulator of G-protein signaling (RGS) proteins are regulators of signal transduction mediated by G protein-coupled receptors (GPCRs). Current studies have shown that some molecules in the RGS gene family are related to the occurrence, development and poor prognosis of malignant tumors. However, the RGS gene family has been rarely studied in gastric cancer. In this study, we explored the mutation and expression profile of RGS gene family in gastric cancer, and evaluated the prognostic value of RGS expression. Then we established a prognostic model based on RGS gene family and performed functional analysis. Further studies showed that RGS4, as an …

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. …

Breast Multiparametric Mri For Prediction Of Neoadjuvant Chemotherapy Response In Breast Cancer: The Bmmr2 Challenge, Wen Li, Savannah C Partridge, David C Newitt, Jon Steingrimsson, Helga S Marques, Patrick J Bolan, Michael Hirano, Benjamin Aaron Bearce, Jayashree Kalpathy-Cramer, Michael A Boss, Xinzhi Teng, Jiang Zhang, Jing Cai, Despina Kontos, Eric A Cohen, Walter C Mankowski, Michael Liu, Richard Ha, Oscar J Pellicer-Valero, Klaus Maier-Hein, Simona Rabinovici-Cohen, Tal Tlusty, Michal Ozery-Flato, Vishwa S Parekh, Michael A Jacobs, Ran Yan, Kyunghyun Sung, Anum S Kazerouni, Julie C Dicarlo, Thomas E Yankeelov, Thomas L Chenevert, Nola M Hylton

Journal Articles

Purpose To describe the design, conduct, and results of the Breast Multiparametric MRI for prediction of neoadjuvant chemotherapy Response (BMMR2) challenge. Materials and Methods The BMMR2 computational challenge opened on May 28, 2021, and closed on December 21, 2021. The goal of the challenge was to identify image-based markers derived from multiparametric breast MRI, including diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) MRI, along with clinical data for predicting pathologic complete response (pCR) following neoadjuvant treatment. Data included 573 breast MRI studies from 191 women (mean age [±SD], 48.9 years ± 10.56) in the I-SPY 2/American College of Radiology Imaging …

Activation Of Piezo1 Increases The Sensitivity Of Breast Cancer To Hyperthermia Therapy, Shao-Kang Wang, Xiao-Ting Zhang, Xuan-Yao Jiang, Bi-Jiang Geng, Tao-Lin Qing, Lei Li, Yun Chen, Jin-Feng Li, Xiao-Fang Zhang, Shuo-Gui Xu, Jiang-Bo Zhu, Yu-Ping Zhu, Mei-Tang Wang, Ji-Kuai Chen

Journal Articles

Photothermal therapy (PTT) of nanomaterials is an emerging novel therapeutic strategy for breast cancer. However, there exists an urgent need for appropriate strategies to enhance the antitumor efficacy of PTT and minimize damage to surrounding normal tissues. Piezo1 might be a promising novel photothermal therapeutic target for breast cancer. This study aims to explore the potential role of Piezo1 activation in the hyperthermia therapy of breast cancer cells and investigate the underlying mechanisms. Results showed that the specific agonist of Piezo1 ion channel (Yoda1) aggravated the cell death of breast cancer cells triggered by heat stress

The Dose-Response Effect Of Aerobic Exercise On Inflammation In Colon Cancer Survivors, Justin C. Brown, Stephanie L.E. Compton, Jeffrey A. Meyerhardt, Guillaume Spielmann, Shengping Yang

School of Medicine Faculty Publications

Background; Physical activity after surgical resection for colon cancer is associated with significantly longer disease-free survival. Inflammation is hypothesized to mediate the association between physical activity and disease-free survival in colon cancer. Methods; In this exploratory analysis of a randomized dose-response trial, 39 colon cancer survivors who completed standard therapy were stratified by cancer stage and randomized in a 1;1;1 ratio to one of three treatment groups for 24 weeks of usual-care control, 150 min/wk of moderate-intensity aerobic exercise (low-dose), or 300 min/wk of moderate-intensity aerobic exercise (high-dose). Inflammation outcomes included high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL6), and soluble tumor …

Cancer Disparities In Southeast Asia: Intersectionality And A Call To Action, Erin Jay G. Feliciano, Frances Dominique V. Ho, Kaisin Yee, Joseph A. Paguio, Michelle Ann B. Eala, Janine Patricia G. Robredo, Kenrick Ng, Jasmine Lim, Khin Thuzar Pyone, Catherine A. Peralta, Jerickson Abbie Flores, J. Seth Yao, Patricia Mae G. Santos, Christian Daniel U. Ang, Gideon Lasco, Jeffrey Shi Kai Chan, Gary Tse, Enrico D. Tangco, T. Peter Kingham, Imjai Chitapanarux, Nirmala Bhoo-Pathy, Gerardo D. Legaspi, Edward Christopher Dee

Ateneo School of Medicine and Public Health Publications

No abstract provided.

Morphological And Metabolic Criteria Of Covid-19 Vaccine Associated Axillary Nodes On 18-Fluorodeouxyglucose Pet/Ct Imaging In Breast Cancer Patients, Nosheen Fatima, Unaiza Zaman, Areeba Zaman, Sidra Zaman, Rabia Tehseen, Maseeh Uz Zaman

Department of Radiology

Background: In the current era vaccine-associated lymphadenopathy (VAL) is not an uncommon presentation on 18F-FDG PET/CT examinations in patients inoculated with Coronavirus disease 2019 (COVID-19) vaccination. In this study, we are presenting data of VAL on 18F-FDG PET/CT regarding its prevalence, temporal response to vaccination and imaging characteristics of VAL.
Methods: Seventy-eight (78) consecutive vaccinated breast cancer (BC) patients who had 18FDG PET/CT were retrospectively analyzed. All patients had COVID-19 vaccine shots in contralateral arms and none in breast cancer site axilla (BSA). In 35 patients 18FDG avid nodes were found in vaccine site axilla (VSA). In 25 patients 18FDG …

Editorial: Resilience, Quality Of Life And Psychosocial Outcomes Of Cancer Patients And Their Caregivers, Nida Zahid, Nargis Asad, Ashraf El-Metwally

Department of Surgery

No abstract provided.

Leveraging National And Global Political Determinants Of Health To Promote Equity In Cancer Care, Edward Christopher Dee, Michelle Ann B. Eala, Janine Patricia G. Robredo, Duvern Ramiah, Anne Hubbard, Frances Dominique V. Ho, Richard Sullivan, Ajay Aggarwal, Christopher M. Booth, Gerardo D. Legaspi, Paul L. Nguyen, C. S. Pramesh, Surbhi Grover

Ateneo School of Medicine and Public Health Publications

Health and politics are deeply intertwined. In the context of national and global cancer care delivery, political forces-the political determinants of health-influence every level of the cancer care continuum. We explore the "3-I" framework, which structures the upstream political forces that affect policy choices in the context of actors' interests, ideas, and institutions, to examine how political determinants of health underlie cancer disparities. Borrowing from the work of PA Hall, M-P Pomey, CJ Ho, and other thinkers, interests are the agendas of individuals and groups in power. Ideas represent beliefs or knowledge about what is or what should be. Institutions …

Tmem27 Suppresses Tumor Development By Promoting Ret Ubiquitination, Positioning, And Degradation, Qianjin Guo, Zi-Ming Cheng, Hector Gonzalez-Cantú, Matthew Rotondi, Gabriela Huelgas-Morales, Purushoth Ethiraj, Zhijun Qiu, Jonathan Lefkowitz, Wan Song, Bethany N Landry, Hector Lopez, Cynthia M Estrada-Zuniga, Shivi Goyal, Mohammad Aasif Khan, Timothy J Walker, Exing Wang, Faqian Li, Yanli Ding, Lois M Mulligan, Ricardo C T Aguiar, Patricia L M Dahia

Journal Articles

The TMEM127 gene encodes a transmembrane protein of poorly known function that is mutated in pheochromocytomas, neural crest-derived tumors of adrenomedullary cells. Here, we report that, at single-nucleus resolution, TMEM127-mutant tumors share precursor cells and transcription regulatory elements with pheochromocytomas carrying mutations of the tyrosine kinase receptor RET. Additionally, TMEM127-mutant pheochromocytomas, human cells, and mouse knockout models of TMEM127 accumulate RET and increase its signaling. TMEM127 contributes to RET cellular positioning, trafficking, and lysosome-mediated degradation. Mechanistically, TMEM127 binds to RET and recruits the NEDD4 E3 ubiquitin ligase for RET ubiquitination and degradation via TMEM127 C-terminal PxxY motifs. Lastly, increased cell …

The Philadelphia Lung Cancer Learning Community: A Multi-Health-System, Citywide Approach To Lung Cancer Screening, Julie A. Barta, Cherie P. Erkmen, Christine S. Shusted, Ronald E. Myers, Chelsea Saia, Sarah Cohen, Jocelyn Wainwright, Charnita Zeigler-Johnson, Farouk Dako, Richard Wender, Gregory C. Kane, Anil Vachani, Katharine A. Rendle

Division of Pulmonary and Critical Care Medicine Faculty Papers

Background

Lung cancer screening uptake for individuals at high risk is generally low across the United States, and reporting of lung cancer screening practices and outcomes is often limited to single hospitals or institutions. We describe a citywide, multicenter analysis of individuals receiving lung cancer screening integrated with geospatial analyses of neighborhood-level lung cancer risk factors. Methods

The Philadelphia Lung Cancer Learning Community consists of lung cancer screening clinicians and researchers at the 3 largest health systems in the city. This multidisciplinary, multi-institutional team identified a Philadelphia Lung Cancer Learning Community study cohort that included 11 222 Philadelphia residents who …

Perceptions Of Facilitators And Barriers To Smoking Cessation Among Patients And Providers In A Cancer Center: A Single Institution Qualitative Exploratory Study, Luke M. Shenton, Udara Perera, Amy Leader, Ann C. Klassen

College of Population Health Faculty Papers

PURPOSE: Cancer patients who remain tobacco users have poorer outcomes, including increased mortality and decreased treatment tolerance; however, cessation post-diagnosis is challenging. Our formative research explored cessation-related perspectives among patients and staff at one National Cancer Institute-designated cancer center, to inform improving cessation services within oncology care.

METHODS: Using a descriptive phenomenological approach, a purposive sample of current cancer patients (n = 13) and cancer center physicians and cessation program staff (n = 9) were recruited to complete one-on-one audio-recorded in-depth qualitative interviews, to explore experiences providing or receiving cessation support, and perspectives on patients' readiness and needs regarding cessation. …

Targeting Breast Cancer: The Familiar, The Emerging, And The Uncharted Territories, Hamidreza Montazeri Aliabadi, Arthur Manda, Riya Sidgal, Co Chung

Pharmacy Faculty Articles and Research

Breast cancer became the most diagnosed cancer in the world in 2020. Chemotherapy is still the leading clinical strategy in breast cancer treatment, followed by hormone therapy (mostly used in hormone receptor-positive types). However, with our ever-expanding knowledge of signaling pathways in cancer biology, new molecular targets are identified for potential novel molecularly targeted drugs in breast cancer treatment. While this has resulted in the approval of a few molecularly targeted drugs by the FDA (including drugs targeting immune checkpoints), a wide array of signaling pathways seem to be still underexplored. Also, while combinatorial treatments have become common practice in …

Surgical Delay Of Thoracodorsal Artery Perforator Flaps For Bilateral Autologous Breast Reconstruction, Ryan D. Hoffman, Mark A. Maier, Hugo St. Hilaire, Robert J. Allen

School of Medicine Faculty Publications

Summary; Autologous reconstruction accounts for nearly one-quarter of all breast reconstruction cases in the United States, with the abdomen functioning as the most popular donor site. This case describes a 62-year-old woman who presented to our clinic with a remote history of estrogen receptor+/progesterone+ breast cancer and bilateral implant-based reconstruction. After grade IV capsular contracture of her left breast, she presented for autologous reconstruction. Due to her body habitus and prior belt lipectomy, deep inferior epigastric perforator flap reconstruction was contra-indicated. The thoracodorsal artery perforator (TDAP) flap is well described in the literature, and was chosen as an alternative salvage …

T-Cell Receptor Beta Variable Gene Polymorphism Predicts Immune-Related Adverse Events During Checkpoint Blockade Immunotherapy, Bettzy Stephen, Joud Hajjar, Shrutii Sarda, Dzifa Yawa Duose, Jeffrey M Conroy, Carl Morrison, Anas Alshawa, Mingxuan Xu, Abdulrazzak Zarifa, Sapna P Patel, Ying Yuan, Evan Kwiatkowski, Linghua Wang, Jordi Rodon Ahnert, Siqing Fu, Funda Meric-Bernstam, Geoffrey M Lowman, Timothy Looney, Aung Naing

Journal Articles

BACKGROUND: Immune checkpoint inhibitors have revolutionized cancer treatment. However, they are associated with a unique spectrum of side effects, called immune-related adverse events (irAEs), which can cause significant morbidity and quickly progress to severe or life-threatening events if not treated promptly. Identifying predictive biomarkers for irAEs before immunotherapy initiation is therefore a critical area of research. Polymorphisms within the T-cell receptor beta (TCRB) variable (TRBV) gene have been implicated in autoimmune disease and may be mechanistically linked to irAEs. However, the repetitive nature of the TCRB locus and incomplete genome assembly has hampered the evaluation of TRBV polymorphisms in the …

African American Males Have More Distress During Cancer Treatment Than White Males, Stephanie Kjelstrom, Charis Wynn, Sharon Larson

College of Population Health Faculty Papers

African American (AA) males have a higher incidence and mortality rate for some cancers than other races and sexes, which could be associated with distress during treatment, medical mistrust, and health disparities. We hypothesize distress in AA males during treatment is higher than in other races and sexes. We assessed effect modification of moderate to severe (≥ 4) distress scores during cancer treatment by race and sex, age, and socioeconomic status (SES). National Comprehensive Cancer Network's distress thermometer (scale 0-10) and characteristics for 770 cancer patients were collected from a Philadelphia hospital. Variables included age, sex, race, smoking status, marital …

Blm Overexpression As A Predictive Biomarker For Chk1 Inhibitor Response In Parp Inhibitor–Resistant Brca-Mutant Ovarian Cancer, Nitasha Gupta, Tzu-Ting Huang, Jayakumar R Nair, Daniel An, Grant Zurcher, Erika J Lampert, Ann Mccoy, Ashley Cimino-Mathews, Elizabeth M Swisher, Marc R Radke, Christina M Lockwood, Jonathan B Reichel, Chih-Yuan Chiang, Kelli M Wilson, Ken Chih-Chien Cheng, Darryl Nousome, Jung-Min Lee

Journal Articles

Poly(ADP-ribose) polymerase inhibitors (PARPis) have changed the treatment paradigm in breast cancer gene (BRCA)–mutant high-grade serous ovarian carcinoma (HGSC). However, most patients eventually develop resistance to PARPis, highlighting an unmet need for improved therapeutic strategies. Using high-throughput drug screens, we identified ataxia telangiectasia and rad3-related protein/checkpoint kinase 1 (CHK1) pathway inhibitors as cytotoxic and further validated the activity of the CHK1 inhibitor (CHK1i) prexasertib in PARPi-sensitive and -resistant BRCA-mutant HGSC cells and xenograft mouse models. CHK1i monotherapy induced DNA damage, apoptosis, and tumor size reduction. We then conducted a phase 2 study (NCT02203513) of prexasertib …