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: …

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 …

High Response Rate With Extended Dosing Of Cemiplimab In Advanced Cutaneous Squamous Cell Carcinoma, Danny Rischin, Brett G M Hughes, Nicole Basset-Séguin, Dirk Schadendorf, Samantha Bowyer, Sabiha Trabelsi Messai, Friedegund Meier, Thomas K Eigentler, Victoria Casado Echarren, Brian Stein, Marie Beylot-Barry, Sophie Dalac, Brigitte Dréno, Michael R Migden, Axel Hauschild, Chrysalyne D Schmults, Annette M Lim, Suk-Young Yoo, Anne J Paccaly, Apostolos Papachristos, Jenny-Hoa Nguyen, Emmanuel Okoye, Frank Seebach, Jocelyn Booth, Israel Lowy, Matthew G Fury, Alexander Guminski

Journal Articles

BACKGROUND: Cemiplimab (Libtayo

METHODS: In this open-label, phase II trial (ClinicalTrials.gov identifier NCT02760498), the cohort of patients ≥18 years old with advanced CSCC received cemiplimab 600 mg intravenously Q4W for up to 48 weeks. Tumor measurements were recorded every 8 weeks. The primary endpoint was objective response rate by independent central review.

RESULTS: Sixty-three patients with advanced CSCC were treated with cemiplimab. The median duration of follow-up was 22.4 months (range: 1.0-39.8). An objective response was observed in 39 patients (62%; 95% CI: 48.8% to 73.9%), with 22% of patients (n

CONCLUSIONS: Extended dosing of cemiplimab 600 mg intravenously Q4W …

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 …

Development Of A Follow-Up Measure To Ensure Complete Screening For Colorectal Cancer, Elizabeth L Ciemins, Jeff T Mohl, Carlos A Moreno, Francis Colangelo, Robert A Smith, Mary Barton

Journal Articles

IMPORTANCE: The current quality performance measure for colorectal cancer (CRC) screening is limited to initial screening. Despite low rates, there is no measure for appropriate follow-up with colonoscopy after receipt of an abnormal result of a stool-based screening test (SBT) for CRC. A quality performance measure is needed.

OBJECTIVE: To develop and test a quality performance measure for follow-up colonoscopy within 6 months of an abnormal result of an SBT for CRC.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective quality improvement study examined data from January 1, 2016, to December 31, 2020, with 2018 plus 6 months of follow-up as the …

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 …

Evaluation Of Ar, Ar-V7, And P160 Family As Biomarkers For Prostate Cancer: Insights Into The Clinical Significance And Disease Progression, Ruan Pimenta, Feres Camargo Malulf, Poliana Romão, Giovana Vilas Boas Caetano, Karina Serafim Da Silva, Vitoria Ghazarian, Gabriel A Dos Santos, Vanessa Guimarães, Iran Amorim Silva, Juliana Alves De Camargo, Saulo Recuero, Bárbara V Lima Aguiar Melão, Alberto Azoubel Antunes, Miguel Srougi, William Nahas, Katia R M Leite, Sabrina T Reis

Journal Articles

PURPOSE: To assess the role of the p160 family, AR, and AR-V7 in different initial presentations of prostate cancer and their association with clinical endpoints related to tumor progression.

METHODS: The study sample comprises 155 patients who underwent radical prostatectomy and 11 healthy peripheral zone biopsies as the control group. Gene expression was quantified by qPCR from the tissue specimens. The statistical analysis investigated correlations between gene expression levels, associations with disease presence, and clinicopathological features. Additionally, ROC curves were applied for distinct PCa presentations, and time-to-event analysis was used for clinical endpoints.

RESULTS: The AR-V7 diagnostic performance for any …

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 …

Vaccines: A Promising Therapy For Myelodysplastic Syndrome, Kriti Gera, Anjali Chauhan, Paul Castillo, Maryam Rahman, Akash Mathavan, Akshay Mathavan, Elizabeth Oganda-Rivas, Leighton Elliott, John R Wingard, Elias J Sayour

Journal Articles

Myelodysplastic neoplasms (MDS) define clonal hematopoietic malignancies characterized by heterogeneous mutational and clinical spectra typically seen in the elderly. Curative treatment entails allogeneic hematopoietic stem cell transplant, which is often not a feasible option due to older age and significant comorbidities. Immunotherapy has the cytotoxic capacity to elicit tumor-specific killing with long-term immunological memory. While a number of platforms have emerged, therapeutic vaccination presents as an appealing strategy for MDS given its promising safety profile and amenability for commercialization. Several preclinical and clinical trials have investigated the efficacy of vaccines in MDS; these include peptide vaccines targeting tumor antigens, whole …

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 …

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 …

Integrative Analysis Of Clinicopathological Features Defines Novel Prognostic Models For Mantle Cell Lymphoma In The Immunochemotherapy Era: A Report From The North American Mantle Cell Lymphoma Consortium, Julie M Vose, Kai Fu, Lu Wang, Adnan Mansoor, Douglas Stewart, Hongxia Cheng, Lynette Smith, Ji Yuan, Hina Naushad Qureishi, Brian K Link, Melissa H Cessna, Paul M Barr, Brad S Kahl, Matthew S Mckinney, Nadia Khan, Ranjana H Advani, Peter Martin, Andre H Goy, Tycel J Phillips, Amitkumar Mehta, Manali Kamdar, Michael Crump, Barbara Pro, Christopher R Flowers, Caron A Jacobson, Sonali M Smith, Deborah M Stephens, Veronika Bachanova, Zhaohui Jin, Shishou Wu, Francisco Hernandez-Ilizaliturri, Pallawi Torka, Andrea Anampa-Guzmán, Farshid Kashef, Xing Li, Sunandini Sharma, Timothy C Greiner, James O Armitage, Matthew Lunning, Dennis D Weisenburger, Robert G Bociek, Javeed Iqbal, Guohua Yu, Chengfeng Bi, North American Mantle Cell Lymphoma Consortium

Journal Articles

BACKGROUND: Patients with mantle cell lymphoma (MCL) exhibit a wide variation in clinical presentation and outcome. However, the commonly used prognostic models are outdated and inadequate to address the needs of the current multidisciplinary management of this disease. This study aims to investigate the clinical and pathological features of MCL in the immunochemotherapy era and improve the prognostic models for a more accurate prediction of patient outcomes.

METHODS: The North American Mantle Cell Lymphoma Project is a multi-institutional collaboration of 23 institutions across North America to evaluate and refine prognosticators for front-line therapy. A total of 586 MCL cases diagnosed …

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 …

Characteristics Of Patients Diagnosed With Pancreatic Cancer Who Access Palliative Care: An Observational Study, Nadia N Khan, Sue M Evans, Liane J Ioannou, Charles H C Pilgrim, Megan Blanchard, Barbara Daveson, Jennifer Philip, John R Zalcberg, Luc Te Marvelde

Journal Articles

PURPOSE: Despite the benefits of palliative care (PC) in pancreatic cancer, little is known about patients who access PC. This observational study examines the characteristics of patients with pancreatic cancer at their first episode of PC.

METHODS: First-time, specialist PC episodes captured through the Palliative Care Outcomes Collaboration (PCOC), in Victoria, Australia between 2014 and 2020, for pancreatic cancer, were identified. Multivariable logistic regression analyses examined the impact of patient- and service-level characteristics on symptom burden (measured through patient-reported outcome measures and clinician-rated scores) at first PC episode.

RESULTS: Of 2890 eligible episodes, 45% began when the patient was deteriorating …

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 …

Unique Transcriptional Profiles Underlie Osteosarcomagenesis Driven By Different P53 Mutants, Dhruv Chachad, Lalit R Patel, Carlos Vera Recio, Rasoul Pourebrahim, Elizabeth M Whitley, Wenyi Wang, Xiaoping Su, An Xu, Dung-Fang Lee, Guillermina Lozano

Journal Articles

UNLABELLED: Missense mutations in the DNA binding domain of p53 are characterized as structural or contact mutations based on their effect on the conformation of the protein. These mutations show gain-of-function (GOF) activities, such as promoting increased metastatic incidence compared with p53 loss, often mediated by the interaction of mutant p53 with a set of transcription factors. These interactions are largely context specific. To understand the mechanisms by which p53 DNA binding domain mutations drive osteosarcoma progression, we created mouse models, in which either the p53 structural mutant p53R172H or the contact mutant p53R245W are expressed specifically in osteoblasts, yielding …

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 …

Selective Immune Suppression Using Interleukin-6 Receptor Inhibitors For Management Of Immune-Related Adverse Events, Faisal Fa'ak, Maryam Buni, Adewunmi Falohun, Huifang Lu, Juhee Song, Daniel H Johnson, Chrystia M Zobniw, Van A Trinh, Muhammad Osama Awiwi, Nourel Hoda Tahon, Khaled M Elsayes, Kaysia Ludford, Emma J Montazari, Julia Chernis, Maya Dimitrova, Sabina Sandigursky, Jeffrey A Sparks, Osama Abu-Shawer, Osama Rahma, Uma Thanarajasingam, Ashley M Zeman, Rafee Talukder, Namrata Singh, Sarah H Chung, Petros Grivas, May Daher, Ala Abudayyeh, Iman Osman, Jeffrey Weber, Jean H Tayar, Maria E Suarez-Almazor, Noha Abdel-Wahab, Adi Diab

Journal Articles

BACKGROUND: Management of immune-related adverse events (irAEs) is important as they cause treatment interruption or discontinuation, more often seen with combination immune checkpoint inhibitor (ICI) therapy. Here, we retrospectively evaluated the safety and effectiveness of anti-interleukin-6 receptor (anti-IL-6R) as therapy for irAEs.

METHODS: We performed a retrospective multicenter study evaluating patients diagnosed with de novo irAEs or flare of pre-existing autoimmune disease following ICI and were treated with anti-IL-6R. Our objectives were to assess the improvement of irAEs as well as the overall tumor response rate (ORR) before and after anti-IL-6R treatment.

RESULTS: We identified a total of 92 patients …

Li-Fraumeni Syndrome-Associated Dimer-Forming Mutant P53 Promotes Transactivation-Independent Mitochondrial Cell Death, Joshua H Choe, Tatsuya Kawase, An Xu, Asja Guzman, Aleksandar Z Obradovic, Ana Maria Low-Calle, Bita Alaghebandan, Ananya Raghavan, Kaitlin Long, Paul M Hwang, Joshua D Schiffman, Yan Zhu, Ruiying Zhao, Dung-Fang Lee, Chen Katz, Carol Prives

Journal Articles

UNLABELLED: Cancer-relevant mutations in the oligomerization domain (OD) of the p53 tumor suppressor protein, unlike those in the DNA binding domain, have not been well elucidated. Here, we characterized the germline OD mutant p53(A347D), which occurs in cancer-prone Li-Fraumeni syndrome (LFS) patients. Unlike wild-type p53, mutant p53(A347D) cannot form tetramers and exists as a hyperstable dimeric protein. Further, p53(A347D) cannot bind or transactivate the majority of canonical p53 target genes. Isogenic cell lines harboring either p53(A347D) or no p53 yield comparable tumorigenic properties, yet p53(A347D) displays remarkable neomorphic activities. Cells bearing p53(A347D) possess a distinct transcriptional profile and undergo metabolic …

Cd73-Dependent Adenosine Signaling Through Adora2b Drives Immunosuppression In Ductal Pancreatic Cancer, Erika Y Faraoni, Kanchan Singh, Vidhi Chandra, Olivereen Le Roux, Yulin Dai, Ismet Sahin, Baylee J O'Brien, Lincoln N Strickland, Le Li, Emily Vucic, Amanda N Warner, Melissa Pruski, Trent Clark, George Van Buren, Nirav C Thosani, John S Bynon, Curtis J Wray, Dafna Bar-Sagi, Kyle L Poulsen, Lana A Vornik, Michelle I Savage, Shizuko Sei, Altaf Mohammed, Zhongming Zhao, Powel H Brown, Tingting Mills, Holger K Eltzschig, Florencia Mcallister, Jennifer M Bailey-Lundberg

Journal Articles

UNLABELLED: The microenvironment that surrounds pancreatic ductal adenocarcinoma (PDAC) is profoundly desmoplastic and immunosuppressive. Understanding triggers of immunosuppression during the process of pancreatic tumorigenesis would aid in establishing targets for effective prevention and therapy. Here, we interrogated differential molecular mechanisms dependent on cell of origin and subtype that promote immunosuppression during PDAC initiation and in established tumors. Transcriptomic analysis of cell-of-origin-dependent epithelial gene signatures revealed that Nt5e/CD73, a cell-surface enzyme required for extracellular adenosine generation, is one of the top 10% of genes overexpressed in murine tumors arising from the ductal pancreatic epithelium as opposed to those rising from acinar …

An Antibody-Drug Conjugate Targeting Gpr56 Demonstrates Efficacy In Preclinical Models Of Colorectal Cancer, Joan Jacob, Liezl E Francisco, Treena Chatterjee, Zhengdong Liang, Shraddha Subramanian, Qingyun J Liu, Julie H Rowe, Kendra S Carmon

Journal Articles

BACKGROUND: Long-term prognosis remains poor for colorectal cancer (CRC) patients with advanced disease due to treatment resistance. The identification of novel targets is essential for the development of new therapeutic approaches. GPR56, an adhesion GPCR, is highly expressed in CRC tumours and correlates with poor survival. Here, we describe the generation and preclinical evaluation of a novel ADC consisting of an anti-GPR56 antibody (10C7) conjugated with the DNA-damaging payload duocarmycin.

METHODS: RNA-seq dataset analysis was performed to determine GPR56 expression in CRC subtypes. The specificity of binding, epitope mapping, and internalisation of 10C7 was examined. 10C7 was conjugated to payload …

Pembrolizumab And Cabozantinib In Recurrent Metastatic Head And Neck Squamous Cell Carcinoma: A Phase 2 Trial, Nabil F Saba, Conor E Steuer, Asari Ekpenyong, Ashley Mccook-Veal, Kelly Magliocca, Mihir Patel, Nicole C Schmitt, William Stokes, James E Bates, Soumon Rudra, Jill Remick, Mark Mcdonald, Marin Abousaud, Aik Choon Tan, Muhammad Zaki Hidayatullah Fadlullah, Ritu Chaudhary, Jameel Muzaffar, Kedar Kirtane, Yuan Liu, Georgia Z Chen, Dong M Shin, Yong Teng, Christine H Chung

Journal Articles

Anti-programmed cell death protein 1 (PD-1) therapy is a standard of care in recurrent metastatic head and neck squamous cell carcinoma (RMHNSCC). Vascular endothelial growth factor inhibitors, including tyrosine kinase inhibitors, have immunomodulatory properties and have offered promising results when combined with anti-PD-1 agents. We conducted a phase 2, multicenter, single-arm trial of pembrolizumab and cabozantinib in patients with RMHNSCC who had Response Evaluation Criteria in Solid Tumors v.1.1 measurable disease and no contraindications to either agent. We assessed the primary end points of tolerability and overall response rate to the combination with secondary end points of progression-free survival and …

Geographic Variations And The Associated Factors In Adherence To And Persistence With Adjuvant Hormonal Therapy For The Privately Insured Women Aged 18-64 With Breast Cancer In Texas, Junghyun Kim, Man S Kim, Suja S Rajan, Xianglin L Du, Luisa Franzini, Tae Gi Kim, Sharon H Giordano, Robert O Morgan

Journal Articles

The purpose of this study is to examine the geographical patterns of adjuvant hormonal therapy adherence and persistence and the associated factors in insured Texan women aged 18-64 with early breast cancer. A retrospective cohort study was conducted using 5-year claims data for the population insured by the Blue Cross Blue Shield of Texas (BCBSTX). Women diagnosed with early breast cancer who were taking tamoxifen or aromatase inhibitors (AIs) for adjuvant hormonal therapy with at least one prescription claim were identified. Adherence to adjuvant hormonal therapy and persistence with adjuvant hormonal therapy were calculated as outcome measures. Women without a …

Geographic Variations And The Associated Factors In Adherence To And Persistence With Adjuvant Hormonal Therapy For The Privately Insured Women Aged 18-64 With Breast Cancer In Texas, Junghyun Kim, Man S Kim, Suja S Rajan, Xianglin L Du, Luisa Franzini, Tae Gi Kim, Sharon H Giordano, Robert O Morgan

Journal Articles

The purpose of this study is to examine the geographical patterns of adjuvant hormonal therapy adherence and persistence and the associated factors in insured Texan women aged 18-64 with early breast cancer. A retrospective cohort study was conducted using 5-year claims data for the population insured by the Blue Cross Blue Shield of Texas (BCBSTX). Women diagnosed with early breast cancer who were taking tamoxifen or aromatase inhibitors (AIs) for adjuvant hormonal therapy with at least one prescription claim were identified. Adherence to adjuvant hormonal therapy and persistence with adjuvant hormonal therapy were calculated as outcome measures. Women without a …

In Utero Exposure To Antiemetic And Risk Of Adult-Onset Colorectal Cancer, Caitlin C Murphy, Piera M Cirillo, Nickilou Y Krigbaum, Amit G Singal, Barbara A Cohn

Journal Articles

BACKGROUND: Incidence rates of colorectal cancer (CRC) are increasing among adults born in and after the 1960s, implicating pregnancy-related exposures introduced at that time as risk factors. Dicyclomine, an antispasmodic used to treat irritable bowel syndrome, was initially included in Bendectin (comprising doxylamine, pyridoxine, and dicyclomine), an antiemetic prescribed during pregnancy in the 1960s.

METHODS: We estimated the association between in utero exposure to Bendectin and risk of CRC in offspring of the Child Health and Development Studies, a multigenerational cohort that enrolled pregnant women in Oakland, CA, between 1959 and 1966 (n = 14 507 mothers and 18 751 …

Ninety-Day Mortality Following Transoral Robotic Surgery Or Radiation At Commission On Cancer-Accredited Facilities, James R Janopaul-Naylor, Manali Rupji, Rachel A Tobillo, Joshua W Lorenz, Jeffrey M Switchenko, Sibo Tian, Azeem S Kaka, David C Qian, Ashley J Schlafstein, Conor E Steuer, Jill S Remick, Soumon Rudra, Mark W Mcdonald, Nabil F Saba, William A Stokes, Mihir R Patel, James E Bates

Journal Articles

BACKGROUND: Postoperative mortality for oropharynx squamous cell carcinoma (OPSCC) with transoral robotic surgery (TORS) varies from 0.2% to 6.5% on trials; the real-world rate is unknown.

METHODS: NCDB study from 2010 to 2017 for patients with cT1-2N0-2M0 OPSCC with Charleson-Deyo score 0-1. Ninety-day mortality assessed from start and end of treatment at Commission on Cancer-accredited facilities.

RESULTS: 3639 patients were treated with TORS and 1937 with radiotherapy. TORS cohort had more women and higher income, was younger, more often treated at academic centers, and more likely to have private insurance (all p < 0.05). Ninety-day mortality was 1.3% with TORS and 0.7% or 1.4% from start or end of radiotherapy, respectively. From end of therapy, there was no significant difference on MVA between treatment modality.

CONCLUSIONS: There is minimal difference between 90-day mortality …

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 …

Disparities In The Use Of Assisted Reproductive Technologies After Breast Cancer: A Population-Based Study, Clare Meernik, Kirsten Jorgensen, Chi-Fang Wu, Caitlin C Murphy, Valerie L Baker, Paula C Brady, Roni Nitecki, Hazel B Nichols, J Alejandro Rauh-Hain

Journal Articles

PURPOSE: Equitable access to oncofertility services is a key component of cancer survivorship care, but factors affecting access and use remain understudied.

METHODS: to describe disparities in assisted reproductive technology (ART) use among women with breast cancer in California, we conducted a population-based cohort study using linked oncology, ART, and demographic data. We identified women age 18-45 years diagnosed with invasive breast cancer between 2000 and 2015. The primary outcome was ART use-including oocyte/embryo cryopreservation or embryo transfer-after cancer diagnosis. We used log-binomial regression to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) to identify factors associated with ART …

Disparities In Fertility-Sparing Treatment And Use Of Assisted Reproductive Technology After A Diagnosis Of Cervical, Ovarian, Or Endometrial Cancer, Kirsten Jorgensen, Clare Meernik, Chi-Fang Wu, Caitlin C Murphy, Valerie L Baker, Peiton Jarmon, Paula C Brady, Roni Nitecki, Hazel B Nichols, Jose Alejandro Rauh-Hain

Journal Articles

OBJECTIVE: to assess the presence of sociodemographic and clinical disparities in fertility-sparing treatment and assisted reproductive technology (ART) use among patients with a history of cervical, endometrial, or ovarian cancer.

METHODS: We conducted a population-based cohort study of patients aged 18-45 years who were diagnosed with cervical cancer (stage IA, IB), endometrial cancer (grade 1, stage IA, IB), or ovarian cancer (stage IA, IC) between January 1, 2000, and December 31, 2015, using linked data from the CCR (California Cancer Registry), the California Office of Statewide Health Planning and Development, and the Society for Assisted Reproductive Technology. The primary outcome …