Andrew T. Faucheux

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.

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.

Background Despite being a groundbreaking cancer therapy, immune checkpoint inhibitors (ICI) can lead to potentially life-threatening toxicity with checkpoint inhibitor pneumonitis (CIP). While treatable, it is easy for clinicians to miss the symptoms of CIP, which can lead to a delay in diagnosis and worsening respiratory function. There is no consensus approach to systematically identifying patients at risk of developing CIP. Thus, we sought to create a workflow that could inform patient selection for ICI therapy based on previously reported risk factors for CIP development. Materials and methods We retrospectively identified 250 patients with lung cancer treated with at least one dose of an ICI over 20 months. Data were collected on comorbidities, cancer type and stage, performance status, ICI cycles, biomarkers, prior curative treatment, diagnostic evaluation, antibiotics, steroids, progression, and survival. A single-blinded radiologist characterized radiographic patterns of suspected CIP cases. Results Among 97 patients who received steroids while admitted to the hospital, 12 (6%) had at least one sign or symptom suggestive of CIP. Chronic obstructive pulmonary disease and non-small cell lung cancer subtypes correlated with suspicion of having CIP. CIP was confirmed in five patients (42%) and ruled out (mimics) in seven (58%). Median times until symptoms were 17 months and one month for confirmed and mimic cases, respectively. The median time to confirm or exclude CIP was 5 ± 4 days. Most suspected cases underwent thoracic imaging, blood cultures, and empiric antibiotics. Radiographic patterns in suspected cases included ground glass opacities, organizing pneumonia, acute interstitial pneumonia/acute respiratory distress syndrome, bronchiolitis, radiation recall pneumonitis, hypersensitivity pneumonitis, and post-radiation fibrotic changes. Conclusions CIP mimics are common in clinical practice; therefore, it is reasonable to empirically treat suspected cases with shorter courses of steroids until diagnostic clarity is achieved. This proof-of-concept study demonstrates that this novel workflow can identify the true incidence of CIP, inform treatment decisions, and lead to the development of implementation studies to improve patient care directly.

Failure to predict response to immunotherapy (IO) limited its benefit in the treatment of head and neck squamous cell cancer (HNSCC) to 20% of patients or less. Biomarkers including tumor mutational burden (TMB) and programmed death ligand-1 (PD-L1) were evaluated as predictors of response to IO, but the results are inconsistent and with a lack of standardization of their methods. In this retrospective study, TMB and PD-L1 were measured by commercially available methodologies and were correlated to demographics, outcome, and response to PD-1 inhibitors. No correlation was found between TMB and PD-L1 levels. High TMB was associated with smoking and laryngeal primaries. PD-L1 was significantly higher in African Americans, patients with earlier stage tumors, nonsmokers, and nonethanol drinkers. Patients with high TMB fared better in univariate and multivariate survival analysis. No correlation was found between PD-L1 expression and prognosis. There was a statistically significant association between PFS and response to IO and TMB. There was no association between response to ICI and PD-L1 in this study, possibly affected by variations in the reporting method. Further studies are needed to characterize the biomarkers for IO in HNSCC, and this study supports further research into the advancement of TMB in prospective studies.

PARP inhibitors are currently approved for a limited number of cancers and targetable mutations in DNA damage repair (DDR) genes. In this single-institution retrospective study, the profiles of 170 patients with head and neck squamous cell cancer (HNSCC) and available tumor tissue DNA (tDNA) and circulating tumor DNA (ctDNA) results were analyzed for mutations in a set of 18 DDR genes as well as in gene subsets defined by technical and clinical significance. Mutations were correlated with demographic and outcome data. The addition of ctDNA to the standard tDNA analysis contributed to identification of a significantly increased incidence of patients with mutations in one or more genes in each of the study subsets of DDR genes in groups of patients older than 60 years, patients with laryngeal primaries, patients with advanced stage at diagnosis and patients previously treated with chemotherapy and/or radiotherapy. Patients with DDR gene mutations were found to be significantly less likely to have primary tumors within the in oropharynx or HPV-positive disease. Patients with ctDNA mutations in all subsets of DDR genes analyzed had significantly worse overall survival in univariate and adjusted multivariate analysis. This study underscores the utility of ctDNA analysis, alone, and in combination with tDNA, for defining the prevalence and the role of DDR gene mutations in HNSCC. Furthermore, this study fosters research promoting the utilization of PARP inhibitors in HNSCC precision oncology treatments.