Abstract 3663: Allostatic load, tumor genomics, and outcomes in NSCLC

Abstract Introduction: Allostatic load (AL) is a multi-system measure of chronic stress shown to be an emerging framework for understanding disparities in cancer outcomes, but there have been no AL studies in lung cancer. Methods: We conducted a retrospective review of patients diagnosed with stage IV lung adenocarcinoma from 2016 - 2020 at the University of Illinois Hospital and Health System. An AL index included 9 biomarkers (systolic blood pressure, diastolic blood pressure, resting heart rate, BMI, albumin, eGFR, creatinine, glucose, and use of medications for hypertension, diabetes, or hypocholesteremia) with 1 point assigned for each biomarker meeting a pre-determined cutoff. AL was dichotomized between AL-high (5-9) and AL-low (0-4) with median progression-free survival of first-line therapy (mPFS1) and median overall survival (mOS) estimated for both groups with Kaplan-Meier curves. Rates of clinically actionable driver mutations (driver-POS), including EGFR, ALK, ROS1, BRAF V600e, RET, MET, NTRK, and KRAS G12C, were compared for both groups using chi-squared test. Mean AL was compared between those who were driver-POS and those who did not have a clinically actionable driver mutation (driver-NEG) using independent samples t-test. Results: A total of 61 patients were identified with 56% female and 74% former or current tobacco users. The cohort was 49% Black, 21% White, and 13% Hispanic or Latino. Mean AL at diagnosis was 3.3 (+/- 1.4). AL-high patients comprised 20% (12) of the cohort compared with 80% (49) AL-low. Between AL-high and AL-low cohorts, there was no statistically significant difference in mPFS1 (15 vs. 13 months, P = 0.98) and mOS (34 vs. 18 months, P = 0.33). Rates of driver-POS were lower in AL-high compared with AL-low (25% vs 69%, P <0.01). Mean AL was higher in the driver-NEG population compared with driver-POS population (3.79 vs 3.03, P = 0.04). Conclusions: Patients whose tumors did not have a clinically actionable driver mutation were associated with a higher AL, suggestive of higher chronic stress playing a role in more aggressive tumor biology. No statistically significant survival difference was observed in AL-high versus AL-low populations for mPFS1 and mOS. Larger, prospective trials are planned to correlate AL at diagnosis with clinical and biomarker data. AL, which serves as a measure of physiological dysfunction due to chronic stress associated with social disadvantage, may have implications for tumor biology and clinical outcomes in lung cancer. Citation Format: Ryan H. Nguyen, Michael Weinfeld, Mary Pasquinelli, Frank Weinberg, Natalie Reizine, Lawrence Feldman, Vijayakrishna K. Gadi. Allostatic load, tumor genomics, and outcomes in NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3663.