Pan-cancer Landscape of Programmed Death Ligand-1 and Programmed Death Ligand-2 Structural Variations.

PURPOSE: Programmed cell death protein-1 (PD-1) receptor and ligand interactions are the target of immunotherapies for more than 20 cancer types. Biomarkers that predict response to immunotherapy are microsatellite instability, tumor mutational burden, and programmed death ligand-1 (PD-L1) immunohistochemistry. Structural variations (SVs) in PD-L1 (CD274) and PD-L2 (PDCD1LG2) have been observed in cancer, but the comprehensive landscape is unknown. Here, we describe the genomic landscape of PD-L1 and PD-L2 SVs, their potential impact on the tumor microenvironment, and evidence that patients with these alterations can benefit from immunotherapy. METHODS: We analyzed sequencing data from cancer cases with PD-L1 and PD-L2 SVs across 22 publications and four data sets, including Foundation Medicine Inc, The Cancer Genome Atlas, International Cancer Genome Consortium, and the Oncology Research Information Exchange Network. We leveraged RNA sequencing to evaluate immune signatures. We curated literature reporting clinical outcomes of patients harboring PD-L1 or PD-L2 SVs. RESULTS: Using data sets encompassing 300,000 tumors, we curated 486 cases with SVs in PD-L1 and PD-L2 and observed consistent breakpoint patterns, or hotspots. Leveraging The Cancer Genome Atlas, we observed significant upregulation in PD-L1 expression and signatures for interferon signaling, macrophages, T cells, and immune cell proliferation in samples harboring PD-L1 or PD-L2 SVs. Retrospective review of 12 studies that identified patients with SVs in PD-L1 or PD-L2 revealed > 50% (52/71) response rate to PD-1 immunotherapy with durable responses. CONCLUSION: Our findings show that the 3'-UTR is frequently affected, and that SVs are associated with increased expression of ligands and immune signatures. Retrospective evidence from curated studies suggests this genomic alteration could help identify candidates for PD-1/PD-L1 immunotherapy. We expect these findings will better define PD-L1 and PD-L2 SVs in cancer and lend support for prospective clinical trials to target these alterations.

A Comprehensive Program for the Enhancement of Accrual to Clinical Trials.

BACKGROUND: The Ohio State University Comprehensive Cancer Center (OSUCCC) embarked on a single institution campaign over 2 years to enhance the enrollment of cancer patients into therapeutic clinical trials. The goal of this campaign was to achieve a 40 % increase in accrual over a 2-year period. METHODS: The entire process of accruing patients to clinical trials at the OSUCCC was carefully evaluated and broken down into several interlocking components. The four key areas of emphasis were as follows: (i) tasking of OSUCCC leadership with increased oversight of the entire process; (ii) education of all stakeholders [patients, their families, nurses and staff, physicians (both internal and external), Disease-Specific Committees (DSCs), and the OSUCCC leadership] as to the purpose, advantages, and availability of clinical trials, with an emphasis on accrual to cancer clinical trials (CCTs) being a critical function of all OSUCCC employees; (iii) increased oversight of the portfolio of clinical trials by DSCs; and (iv) optimization of accrual operations and infrastructure center-wide. RESULTS: The accrual goal was achieved a full 4 months ahead of schedule. In total, 2327 patients were accrued to therapeutic clinical trials over the course of this 2-year campaign. Prior to implementation of the accrual program, the accrual rate was consistently below 15 %. From 2009 onwards, the therapeutic accrual rate was always greater than 25 %. CONCLUSIONS: A campaign to educate key stakeholders in the clinical trials accrual process was successful in its goal of increasing accrual to therapeutic trials.

Key informants' perspectives prior to beginning a cervical cancer study in Ohio Appalachia.

Higher-than-average cervical cancer incidence and mortality rates occur in Ohio Appalachia. Little is known, however, about societal norms and social determinants that affect these rates. To examine county-level sociocultural environments to plan a cervical cancer prevention program, the authors interviewed key informants from 17 of 29 Ohio Appalachia counties. Findings include the perceived offensiveness of the term Appalachia, the importance of long-standing family ties, urban and rural areas within counties, use and acceptability of tobacco, the view that cancer is a death sentence, and the stigmatization of people with cancer. Barriers to screening included cost, lack of insurance, transportation problems, fear, embarrassment, and privacy issues. These findings highlight the important role of geography, social environment, and culture on health behaviors and health outcomes. The interviews provided information about the unique characteristics of this population that are important when developing effective strategies to address cancer-related health behaviors in this medically underserved population.