John C. Hunting

Nearly half of patients with cancer are diagnosed at 70 years or older, which presents challenges in cancer care due to their high comorbidity burden and the underrepresentation of this age group in clinical trials. This retrospective study evaluated the association between comorbidity burden and immune checkpoint inhibitors (ICIs) treatment outcomes among older adults. Data were collected from patients aged 70 years or older at the time of diagnosis who were treated with ICIs from 2011 to 2022. Key clinical outcomes include changes in performance status, overall survival (OS), progression-free survival (PFS), and immune-related adverse events (irAEs) and were compared between low baseline Charlson Comorbidity Index (CCI) and high CCI (n = 300) had a significantly shorter OS (11.4 vs. 13.6 months, p = 0.0461) but similar PFS (8.0 vs. 7.7 months, p = 0.258) compared to patients with CCI scores p = 0.14) or in the irAE prevalence between the two groups (39.3% vs. 38.3%, p = 0.786). Our study suggests that ICIs are safe in patients with high comorbidity burden but that the presence of pre-treatment comorbidities decreases overall survival.

Prior research indicates a connection between immune-related adverse events (irAEs) and improved progression-free survival (PFS) and overall survival (OS) in non-small cell lung cancer. However, limited data exists for extensive stage small cell lung cancer (ES-SCLC). This study included all ES-SCLC patients who received at least one dose of an immune checkpoint inhibitor between 2 January 2011 and 4 July 2022 using a large retrospective registry from a single institution. PFS and OS were right-censored at the date of last follow-up and were estimated using the Kaplan-Meier method. Differences in PFS and OS between irAE groups were assessed using Cox proportional hazards models. Among 245 patients with ES-SCLC; 56 (23%) experienced irAEs, 24 (42.9%) of which were high-grade (3-4). High-grade irAEs occurred at a median of 1.2 months (interquartile range [IQR] 0.45-2.5), while low-grade irAE occurred at 2.8 months (1.3-5.2). PFS was significantly longer among any irAE vs none (HR = 0.49; [95%CI 0.32-0.77]) as was OS (HR = 0.49; [95%CI 0.34-0.72]). In ES-SCLC patients treated with immunotherapy, those who experienced any irAE demonstrated a two-fold increase in both PFS and OS compared to those without an irAE. This is consistent with other tumor primaries.

Background: Immune checkpoint inhibitors (ICIs) have become common lines of therapy for genitourinary cancers (GUcs). Given their widespread use, understanding the risk factors, comparative profiles, and timing of immune-related adverse events (irAEs) is essential. Methods: We created an IRB-approved retrospective registry of all patients who received at least one dose of an ICI for any indication between 1 February 2011 and 7 April 2022 at a comprehensive cancer center and its outreach clinics. Dichotomous outcomes were modeled using multivariable logistic regression. Survival outcomes were compared using multivariable Cox regression. Results: Among 3101 patients, 196 had renal cell carcinoma (RCC) and 170 had urothelial tumors. RCC patients were more likely to experience irAEs (OR 1.78; 95% CI 1.32–2.39), whereas urothelial carcinoma patients were not (OR 1.22; 95% CI 0.88–1.67). RCC patients were more prone to dermatitis, thyroiditis, acute kidney injury, and myocarditis, compared to other tumors, while urothelial carcinoma patients were not. The impact of irAEs on survival was not significantly different for GUcs compared to other tumors. Conclusions: RCC primaries have a significantly different irAE profile than most tumors, as opposed to urothelial primaries. Further, RCC was more likely to experience any irAEs. Heterogeneity of survival benefits by irAEs was not seen.

Aim: Neurological adverse events (NAEs) are infrequent immune checkpoint inhibitor (ICI) outcomes poorly characterized in extant research, complicating their clinical management. Methods: This stud... Plain language summary Immune checkpoint inhibitors are new drugs for cancer. They boost your body's defenses to fight cancer cells. These drugs can be used alone or with other cancer treatments. M...

Background: Clinical biomarkers for brain metastases remain elusive. Increased availability of genomic profiling has brought discovery of these biomarkers to the forefront of research interests.Method: In this single institution retrospective series, 130 patients presenting with brain metastasis secondary to Non-Small Cell Lung Cancer (NSCLC) underwent comprehensive genomic profiling conducted using next generation circulating tumor deoxyribonucleic acid (DNA) (Guardant Health, Redwood City, CA). A total of 77 genetic mutation identified and correlated with nine clinical outcomes using appropriate statistical tests (general linear models, Mantel-Haenzel Chi Square test, and Cox proportional hazard regression models). For each outcome, a genetic signature composite score was created by summing the total genes wherein genes predictive of a clinically unfavorable outcome assigned a positive score, and genes with favorable clinical outcome assigned negative score.Results: Seventy-two genes appeared in at least one gene signature including: 14 genes had only unfavorable associations, 36 genes had only favorable associations, and 22 genes had mixed effects. Statistically significant associated signatures were found for the clinical endpoints of brain metastasis velocity, time to distant brain failure, lowest radiosurgery dose, extent of extracranial metastatic disease, concurrent diagnosis of brain metastasis and NSCLC, number of brain metastases at diagnosis as well as distant brain failure. Some genes were solely associated with multiple favorable or unfavorable outcomes.Conclusion: Genetic signatures were derived that showed strong associations with different clinical outcomes in NSCLC brain metastases patients. While these data remain to be validated, they may have prognostic and/or therapeutic impact in the future.Statement of translation relevance: Using Liquid biopsy in NSCLC brain metastases patients, the genetic signatures identified in this series are associated with multiple clinical outcomes particularly these ones that lead to early or more numerous metastases. These findings can be reverse-translated in laboratory studies to determine if they are part of the genetic pathway leading to brain metastasis formation.