Extended supercooled storage of red blood cells.

Red blood cell (RBC) transfusions facilitate many life-saving acute and chronic interventions. Transfusions are enabled through the gold-standard hypothermic storage of RBCs. Today, the demand for RBC units is unfulfilled, partially due to the limited storage time, 6 weeks, in hypothermic storage.

Raising the Bar for Real-World Data in Oncology: Approaches to Quality Across Multiple Dimensions.

Purpose: Electronic health record (EHR)-based real-world data (RWD) are integral to oncology research, and understanding fitness for use is critical for data users. Complexity of data sources and curation methods necessitate transparency into how quality is approached. We describe the application of data quality dimensions in curating EHR-derived oncology RWD.

Emulating Randomized Controlled Trials with Hybrid Control Arms in Oncology: A Case Study.

This proof-of-concept study retrospectively assessed the feasibility of applying a hybrid control arm design to a completed phase III randomized controlled trial (RCT; CheckMate-057) in advanced non-small cell lung cancer using a real-world data (RWD) source. The emulated trial consists of an experimental arm (patients from the RCT experimental cohort) and a hybrid control arm (patients from the RCT and RWD control cohorts). For the RWD control cohort, this study used a nationwide electronic health record-derived de-identified database.

Quantifying the Value of Multigene Testing in Resected Early Stage Lung Adenocarcinoma.

Introduction: Tyrosine kinase inhibitors and immune checkpoint inhibitors (ICIs), each requiring testing for precision biomarkers, have recently been approved in the adjuvant setting. We assessed the potential value of multigene testing in early lung adenocarcinoma (LUAD).

Methods: Using a real-world clinicogenomic database linking deidentified electronic health record-derived clinical data to genomic data, we selected patients with LUAD who underwent tissue comprehensive genomic profiling (CGP).

Sex Differences in Acute Neuroendocrine Responses to Stressors in Rodents and Humans.

Sex differences in the neuroendocrine response to acute stress occur in both animals and humans. In rodents, stressors such as restraint and novelty induce a greater activation of the hypothalamic-pituitary-adrenal axis (HPA) in females compared to males. The nature of this difference arises from steroid actions during development (organizational effects) and adulthood (activational effects).

Natural History of Human Epidermal Growth Factor Receptor 2-Amplified and Human Epidermal Growth Factor Receptor 2 Wild-Type Refractory Metastatic Colorectal Cancer in US Clinical Practice.

Purpose: The molecular heterogeneity of metastatic colorectal cancer (mCRC) presents a therapeutic challenge, with few trials focused on patients with human epidermal growth factor receptor 2 amplification (HER2-Amp). Our limited understanding of real-world patterns and outcomes by HER2 status of treatment-refractory patients leaves treatment decisions with little contextual information. We conducted a retrospective cohort study to describe the natural disease history of patients with refractory mCRC using an electronic health record-derived database with oncogenomic information.

Copy Number as a Quantitative Biomarker for Real-World Outcomes to Anti-Human Epidermal Growth Factor Receptor 2 Therapy in Advanced Gastroesophageal Adenocarcinoma.

Purpose: Human epidermal growth factor receptor 2 (HER2) overexpression or amplification (amp) are biomarkers for approved anti-HER2 therapies. amp may better predict response compared with immunohistochemistry or in situ hybridization, and quantitative copy number (CN) may further stratify patients. We characterized amp in advanced gastroesophageal adenocarcinomas (GEA) and hypothesized that increased CN was associated with better outcome to trastuzumab.

Accounting for Delayed Entry in Analyses of Overall Survival in Clinico-Genomic Databases.

Background: Clinico-genomic databases favor inclusion of long-term survivors, leading to potentially biased overall survival (OS) analyses. Risk set adjustments relying on the independent delayed entry assumption may mitigate this bias. We aimed to determine whether this assumption is satisfied in a dataset of patients with advanced non-small cell lung cancer (aNSCLC), and to give guidance for clinico-genomic OS analyses when the assumption is not satisfied.

Real-world association of HER2/ concordance with trastuzumab clinical benefit in advanced esophagogastric cancer.

To assess concordance between HER2 status measured by traditional methods and amplification measured by next-generation sequencing and its association with first-line trastuzumab clinical benefit in patients with advanced esophagogastric cancer. Retrospective analysis of HER2/ concordance using a deidentified USA-based clinicogenomic database. Clinical outcomes were assessed for patients with HER2 advanced esophagogastric cancer who received first-line trastuzumab.

TRK Fusion Cancer: Patient Characteristics and Survival Analysis in the Real-World Setting.

Background: Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are oncogenic drivers in various tumor types. While NTRK gene fusions are predictive of benefit from tropomyosin receptor kinase inhibitors regardless of tumor type, the prognostic significance of NTRK gene fusions in a pan-tumor setting remains unclear.

Objective: This study evaluated the characteristics and prognosis of tropomyosin receptor kinase fusion cancer in the real-world setting.

RAS Amplification as a Negative Predictor of Benefit from Anti-EGFR-Containing Therapy Regimens in Metastatic Colorectal Cancer.

Background: RAS short variant (SV) mutations in colorectal cancer (CRC) are associated with lack of benefit from epidermal growth factor receptor (EGFR) monoclonal antibody (EGFRmAb). However, the clinical implications for RAS amplification (RASa) as a biomarker for anti-EGFR therapy in CRC remain ill defined.

Methods: Genomic analysis was performed using the Foundation Medicine (FM) comprehensive genomic profiling database of 37,233 CRC cases.

Prevalence of High Tumor Mutational Burden and Association With Survival in Patients With Less Common Solid Tumors.

Importance: Tumor mutational burden (TMB) is a potential biomarker associated with response to immune checkpoint inhibitor therapies. The prognostic value associated with TMB in the absence of immunotherapy is uncertain.

Objective: To assess the prevalence of high TMB (TMB-H) and its association with overall survival (OS) among patients not treated with immunotherapy with the same 10 tumor types from the KEYNOTE-158 study.

Retrospective analysis of real-world data to determine clinical outcomes of patients with advanced non-small cell lung cancer following cell-free circulating tumor DNA genomic profiling.

Objectives: Liquid biopsy and comprehensive genomic profiling (CGP) of circulating tumor DNA (ctDNA) are increasingly used for detection of targetable genomic alterations (GA) in non-small cell lung cancer (NSCLC). To examine the clinical outcomes for patients following CGP using liquid biopsy versus tissue biopsy, receipt of matched targeted therapy post-CGP and associated outcomes were evaluated in the real-world setting.

Methods: 6491 patients with NSCLC and liquid biopsy (N = 937 tests) and/or tissue (N = 5582 tests) CGP were included in a de-identified commercial clinico-genomic database.

Evaluating the Impact of Oncology Care Model Reporting Requirements on Biomarker Testing and Treatment.

Purpose: The Oncology Care Model (OCM) is Medicare's first alternative payment model program for patients with cancer. As of October 2017, participating practices were required to report biomarker testing of patients with advanced non-small-cell lung cancer (aNSCLC). Our objective was to evaluate the effect of this OCM reporting requirement on quality of care.

Letting the GENIE Out of Its Bottle: Examining the Potential of Real-World Clinicogenomic Data.

In this issue, Smyth and colleagues investigate the natural history of -mutant metastatic breast cancer using the AACR Project GENIE, a novel research platform comprised of real-world, clinicogenomic data. A rare subset of tumors, -mutant breast cancers demonstrated similar clinical and demographic characteristics and overall survival as -wild-type tumors, but a longer duration of therapy on mTOR inhibitors..

Impact of patient symptoms and caregiving tasks on psychological distress in caregivers for head and neck cancer (HNC).

Objective: To determine the association of caregiving task burden and patient symptom burden with psychological distress among caregivers of head and neck cancer (HNC) patients.

Methods: Adults with HNC and their primary caregivers were included. Patient symptom burden was assessed with the Vanderbilt Head and Neck Symptom Survey-2.

Tumor-specific MHC-II expression drives a unique pattern of resistance to immunotherapy via LAG-3/FCRL6 engagement.

Immunotherapies targeting the PD-1 pathway produce durable responses in many cancers, but the tumor-intrinsic factors governing response and resistance are largely unknown. MHC-II expression on tumor cells can predict response to anti-PD-1 therapy. We therefore sought to determine how MHC-II expression by tumor cells promotes PD-1 dependency.

Taxonomic status of Paraguay's only endemic bird, the Chaco Nothura Nothura chacoensis (Aves: Tinamidae).

The Chaco Nothura Nothura chacoensis Conover is endemic to the Chaco of western Paraguay. Originally described as a subspecies of the Spotted Nothura N. maculosa (Temminck), it has been regarded by many authorities as a distinct species based on alleged sympatry with N.

Patient Protection and Affordable Care Act Medicaid expansion and gains in health insurance coverage and access among cancer survivors.

Background: The Patient Protection and Affordable Care Act extends Medicaid coverage to millions of low-income adults, including many survivors of cancer who were unable to purchase affordable health insurance coverage in the individual health insurance market.

Methods: Using data from the 2011 to 2015 Behavioral Risk Factor Surveillance System, the authors compared changes in coverage and health care access measures for low-income cancer survivors in states that did and did not expand Medicaid.

Results: The study population of 17,381 individuals included adults aged 18 to 64 years, and was predominantly female, white, and unmarried.

Financial and socio-economic factors influencing pre- and post-cancer therapy oral care.

Purpose: The primary objective of this study is to evaluate how attendance at dental visits may change as cancer patients move through pre-diagnosis, diagnosis, and into survivorship.

Methods: The Health and Retirement Study consists of longitudinal survey data collected biannually detailing financial and health information in subjects over 51 years old. We assessed a subset of 4195 patients who received a new cancer diagnosis during the study period.

Driven by Mutations: The Predictive Value of Mutation Subtype in EGFR-Mutated Non-Small Cell Lung Cancer.

EGFR-mutated NSCLC is a genetically heterogeneous disease that includes more than 200 distinct mutations. The implications of mutational subtype for both prognostic and predictive value are being increasingly understood. Although the most common EGFR mutations-exon 19 deletions or L858R mutations-predict sensitivity to EGFR tyrosine kinase inhibitors (TKIs), it is now being recognized that outcomes may be improved in patients with exon 19 deletions.

Immunotherapy in Lung Cancer.

Lung cancer has not traditionally been viewed as an immune-responsive tumor. However, it is becoming evident that tumor-induced immune suppression is vital to malignant progression. Immunotherapies act by enhancing the patient's innate immune response and hold promise for inducing long-term responses in select patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC).

Re-Evaluating Progression in an Era of Progress: A Review of First- and Second-Line Treatment Options in Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer.

Unlabelled: : The advent of crizotinib, the first small molecule inhibitor against anaplastic lymphoma kinase (ALK), has led to impressive advances in the care of patients with advanced ALK-rearranged non-small cell lung cancer. The development of second-generation ALK inhibitors, starting with the recent U.S.

Making the Grade: The Impact of Low-Grade Toxicities on Patient Preference for Treatment With Novel Agents.

Background: Targeted therapies have shown clinical benefit in the treatment of solid tumors. The toxicity profiles and treatment duration and schedule of these agents differ considerably from those of traditional chemotherapy. Many studies of targeted therapies report sizeable numbers of grade 1 or 2 toxicities.