Search

e21151 Background: Although predictive of chemotherapy toxicity, geriatric assessment measures are not systematically collected in clinical practice and may or may not be predictive for immune-related adverse events. Furthermore, hospitalization during immune checkpoint inhibitor (ICI) treatment for advanced lung cancer has variable prognostic significance. This study aimed to evaluate whether age and documented patient characteristics mapped to geriatric assessment domains (frailty markers, FM) predict survival in this setting. Methods: A single-center retrospective cohort of advanced stage lung cancer patients who received >1 dose of an ICI from 6/1/18 to 2/1/20, were later hospitalized, and received ≥ 1 dose of systemic corticosteroids (n=97) was analyzed. Chart review ascertained documentation of any of the following FMs prior to ICI initiation: inability to walk one block, unintentional weight loss, decreased social activities, recent falls, need for assistance with medications, visual or hearing impairments, living alone, and concern regarding social support. Patients were stratified according to age and three FM categories (0 FM [low risk], ≥1 FMs [at risk], and ≥2 FMs [high risk]). Overall survival (OS) analysis was calculated from first dose of ICI to date of death or last follow-up. Cox’s proportional hazards models were used to assess the relationship between FMs and age on OS; hazard ratios (HR) and 95% confidence intervals (CI) were calculated. Results: Analysis of < 75 and ≥ 75 yo revealed a median OS of 15.1 and 5.4 months respectively (HR 2.76, CI 1.62-4.72). Controlled for performance status (PS), older age (≥75 yo) was associated with a higher risk of death (HR 2.39, CI 1.32-4.31). FMs were associated with higher mortality, adjusted for PS and age (at risk patients HR 1.81, CI 1.03-3.16; high risk patients HR 2.02, CI 1.07-3.78). PS prior to starting ICI was not associated with OS. Conclusions: Age ≥ 75 yo is associated with short survival among lung cancer patients hospitalized while receiving ICI. Pre-treatment FMs documented as part of usual care were associated with worse OS, even after controlling for PS and age. This study shows promise for use of machine learning algorithms to stratify risk in hospitalized patients undergoing treatment for lung cancer with ICIs. These data would allow providers to better target serious illness conversations and end-of-life resources.[Table: see text]

e18016 Background: Next generation sequencing (NGS) has introduced the opportunity for targeted therapies and guidance regarding disease course and prognosis. The mutational landscape of squamous cell cancers of the head and neck (HNSCC) remains incompletely described. DNA repair gene (DRG) mutations are targeted by PARP inhibitors. This study presents the prevalence of DRG mutations in tumor and blood samples of patients with HNSCC and their outcome data. Methods: In this retrospective study, demographic and outcome data were collected and analyzed with regard to the presence or absence of mutated DRG (BRCA1, BRCA2, ATM, BRIP1, BARD1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, RAD51L, APC, ARID1A and MLL3). Mutated DRG were detected in tumor tissue (tDNA) by Foundation Medicine and/or in blood (ctDNA) by Guardant 360. All 18 genes were analyzed by FM, but only six are included in the G360 panel (BRCA1, BRCA2, ATM, APC, ARID1A and CDK12). Results: Our analysis included 170 HNSCC patients. Of these, 138 underwent NGS via ctDNA, 146 via tDNA and 114 via both methods. Sixty-five patients (47%) had at least one tDNA DRG mutation, 54 patients (37%) had at least one ctDNA DRG mutation and 96 patients (56%) had at least one DRG mutation detected by either method. No significant association was found between DRG mutations and age, gender, race, HPV status, tobacco/alcohol use or stage at diagnosis. Subsite analyses revealed that laryngeal primaries were associated with higher prevalence of DRG mutations detected via tDNA (p = 0.05), ctDNA (p = 0.03) or either method (p = 0.01). Oropharyngeal primaries correlated with a lower prevalence of DRG mutations detected via tDNA (p = 0.03) or via either method (p = 0.02) but were less significant when mutations were detected via ctDNA alone (p = 0.08). Mutated DRG detected via ctDNA correlated significantly with stage at time of ctDNA collection (p = 0.03), presence/absence of cancer at last visit (p = 0.05) and with stage at last visit (p = 0.05). Two-year survival and overall survival (OS) measured from the time of ctDNA collection correlated significantly with mutated ctDNA DRG. The relationship between ctDNA DRG mutations and OS remained statistically significant in a Cox proportional hazards regression model when adjusted for age, tobacco use, tumor site, nodal stage at diagnosis, and previous treatment with chemotherapy, radiation or combined chemoradiation therapy in a multivariate analysis model (p = 0.05). No similar correlation was found between tDNA mutations in DRG and prognosis. Conclusions: A significant proportion of patients with HNSCC were found to have mutations in DRG. Patients with laryngeal disease were most likely to have DRG mutations, whereas those with oropharyngeal disease were less likely. Patients with DRG mutations in ctDNA, but not tDNA, had significantly worse prognoses with a lower likelihood of overall survival and higher disease burden at last visit.