Immune Assessment Today: Optimizing and Standardizing Efforts to Monitor Immune Responses in Cancer and Beyond.

As part of a symposium, current and former directors of Immune Monitoring cores and investigative oncologists presented insights into the past, present and future of immune assessment. Dr. Gnjatic presented a classification of immune monitoring technologies ranging from universally applicable to experimental protocols, while emphasizing the need for assay harmonization. Dr. Obeng discussed physiologic differences among CD8 T cells that align with anti-tumor responses. Dr. Lyerly presented the Soldano Ferrone lecture, commemorating the passionate tumor immunologist who inspired many, and covered a timeline of monitoring technology development and its importance to immuno-oncology. Dr. Sonabend presented recent achievements in glioblastoma treatment, accentuating the range of monitoring techniques that allowed him to refine patient selection for clinical trials. Dr. Guevara-Patiño focused on hypoxia within the tumor environment and stressed that T cell viability is not to be confused with functionality. Dr. Butterfield accentuated monitoring of dendritic cell metabolic (dys)function as a determinant for tumor vaccine success. Lectures were interspersed with select abstract presentations. To summarize the concepts, Dr. Maecker from Stanford led an informative forum discussion, pointing towards the future of immune monitoring. Immune monitoring continues to be a guiding light towards effective immunotherapeutic strategies.

Epidemiology of geographic disparities in heart failure among US older adults: a Medicare-based analysis.

BACKGROUND: There are prominent geographic disparities in the life expectancy (LE) of older US adults between the states with the highest (leading states) and lowest (lagging states) LE and their causes remain poorly understood. Heart failure (HF) has been proposed as a major contributor to these disparities. This study aims to investigate geographic disparities in HF outcomes between the leading and lagging states. METHODS: The study was a secondary data analysis of HF outcomes in older US adults aged 65+, using Center for Disease Control and Prevention sponsored Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database and a nationally representative 5% sample of Medicare beneficiaries over 2000-2017. Empiric estimates of death certificate-based mortality from HF as underlying cause of death (CBM-UCD)/multiple cause of death (CBM-MCD); HF incidence-based mortality (IBM); HF incidence, prevalence, and survival were compared between the leading and lagging states. Cox regression was used to investigate the effect of residence in the lagging states on HF incidence and survival. RESULTS: Between 2000 and 2017, HF mortality rates (per 100,000) were higher in the lagging states (CBM-UCD: 188.5-248.6; CBM-MCD: 749.4-965.9; IBM: 2656.0-2978.4) than that in the leading states (CBM-UCD: 79.4-95.6; CBM-MCD: 441.4-574.1; IBM: 1839.5-2138.1). Compared to their leading counterparts, lagging states had higher HF incidence (2.9-3.9% vs. 2.2-2.9%), prevalence (15.6-17.2% vs. 11.3-13.0%), and pre-existing prevalence at age 65 (5.3-7.3% vs. 2.8-4.1%). The most recent rates of one- (77.1% vs. 80.4%), three- (59.0% vs. 60.7%) and five-year (45.8% vs. 49.8%) survival were lower in the lagging states. A greater risk of HF incidence (Adjusted Hazards Ratio, AHR [95%CI]: 1.29 [1.29-1.30]) and death after HF diagnosis (AHR: 1.12 [1.11-1.13]) was observed for populations in the lagging states. The study also observed recent increases in CBMs and HF incidence, and declines in HF prevalence, prevalence at age 65 and survival with a decade-long plateau stage in IBM in both leading and lagging states. CONCLUSION: There are substantial geographic disparities in HF mortality, incidence, prevalence, and survival across the U.S.: HF incidence, prevalence at age 65 (age of Medicare enrollment), and survival of patients with HF contributed most to these disparities. The geographic disparities and the recent increase in incidence and decline in survival underscore the importance of HF prevention strategies.

A Grant-Based Experiment to Train Clinical Investigators: The AACR/ASCO Methods in Clinical Cancer Research Workshop.

To address the need for clinical investigators in oncology, American Association for Cancer Research (AACR) and American Society for Clinical Oncology (ASCO) established the Methods in Clinical Cancer Research Workshop (MCCRW). The workshop's objectives were to: (i) provide training in the methods, design, and conduct of clinical trials; (ii) ensure that clinical trials met federal and international ethical guidelines; (iii) evaluate the effectiveness of the workshop; and (iv) create networking opportunities for young investigators with mentoring senior faculty. Educational methods included: (i) didactic lectures, (ii) Small Group Discussion Sessions, (iii) Protocol Development Groups, and (iv) one-on-one mentoring. Learning focused on the development of an Institutional Review Board (IRB)-ready protocol, which was submitted on the last day of the workshop. Evaluation methods included: (i) pre- and postworkshop tests, (ii) students' workshop evaluations, (iii) faculty's ratings of protocol development, (iv) students' productivity in clinical research after the workshop, and (v) an independent assessment of the workshop. From 1996 to 2014, 1,932 students from diverse backgrounds attended the workshop. There was a significant improvement in the students' level of knowledge from the pre- to the postworkshop exams (P < 0.001). Across the classes, student evaluations were very favorable. At the end of the workshop, faculty rated 92% to 100% of the students' protocols as ready for IRB submission. Intermediate and long-term follow-ups indicated that more than 92% of students were actively involved in patient-related research, and 66% had implemented five or more protocols. This NCI-sponsored MCCRW has had a major impact on the training of clinicians in their ability to design and implement clinical trials in cancer research.

Cardiovascular comorbidities and survival of lung cancer patients: Medicare data based analysis.

OBJECTIVES: To evaluate the role of cardiovascular disease (CVD) comorbidity in survival of patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The impact of seven CVDs (at the time of NSCLC diagnosis and during subsequent follow-up) on overall survival was studied for NSCLC patients aged 65+ years using the Surveillance, Epidemiology, and End Results data linked to the U.S. Medicare data, cancer stage- and treatment-specific. Cox regression was applied to evaluate death hazard ratios of CVDs in univariable and multivariable analyses (controlling by age, TNM statuses, and 78 non-CVD comorbidities) and to investigate the effects of 128 different combinations of CVDs on patients' survival. RESULTS: Overall, 95,167 patients with stage I (n=29,836, 31.4%), II (n=5133, 5.4%), IIIA (n=11,884, 12.5%), IIIB (n=18,020, 18.9%), and IV (n=30,294, 31.8%) NSCLC were selected. Most CVDs increased the risk of death for stages I-IIIB patients, but did not significantly impact survival of stage IV patients. The worse survival of patients was associated with comorbid heart failure, myocardial infarction, and cardiac arrhythmias that occurred during a period of follow-up: HRs up to 1.85 (p<0.001), 1.96 (p<0.05), and 1.67 (p<0.001), respectively, varying by stage and treatment. The presence of hyperlipidemia at baseline (HR down to 0.71, p<0.05) was associated with better prognosis. Having multiple co-existing CVDs significantly increased mortality for all treatments, especially for stages I and II patients treated with surgery (HRs up to 2.89, p<0.05) and stages I-IIIB patients treated with chemotherapy (HRs up to 2.59, p<0.001) and chemotherapy and radiotherapy (HRs up to 2.20, p<0.001). CONCLUSION: CVDs impact the survival of NSCLC patients, particularly when multiple co-existing CVDs are present; the impacts vary by stage and treatment. This data should be considered in improving cancer treatment selection process for such potentially challenging patients as the elderly NSCLC patients with CVD comorbidities.

Translational Research Working Group developmental pathway for immune response modifiers.

The Translational Research Working Group (TRWG) was created as a national initiative to evaluate the current status of the investment of National Cancer Institute in translational research and envision its future. The Translational Research Working Group conceptualized translational research as a set of six developmental processes or pathways focused on various clinical goals. One of those pathways describes the development of immune response modifiers such as vaccines and cytokines. A hallmark of the Immune Response Modifier Developmental Pathway is the coordinated development of multiple components. The Immune Response Modifier Pathway was conceived not as a comprehensive description of the corresponding real-world processes but rather as a tool designed to facilitate movement of a candidate assay through the translational process to the point where it can be handed off for definitive clinical testing. This paper discusses key challenges associated with the immune response modifier agent development process in light of the pathway.