Safety and Effectiveness of Definitive Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer Among Older Patients: Does Frailty Matter?

Abstract

Older patients with inoperable early-stage non-small cell lung cancer (NSCLC) are mainly treated with definitive stereotactic body radiation therapy (SBRT) and represent an especially frail patient subset with unique challenges that may impact treatment tolerability and survival outcomes. The Electronic Rapid Fitness Assessment (eRFA) is a validated web-based comprehensive geriatrics assessment used for measuring frailty. We report our initial experience prospectively applying the eRFA to inoperable NSCLC patients treated with SBRT.We collected baseline pretreatment eRFAs from early-stage (cT1a-T3N0) NSCLC patients aged 60 years and older receiving definitive SBRT (48-60 Gy in 3-8 fractions) from June 2019 to December 2020. Patient demographics and Charlson comorbidity index (CCI) were assessed. Geriatric assessment domains measured by the eRFA include functional status, social and emotional wellbeing, cognitive function, fall risk, nutritional status and polypharmacy. Our primary endpoint was the association between pretreatment eRFA scores and physician-assessed SBRT toxicity per CTCAE v5.0. Secondary outcomes included overall survival (OS), local control (LC) and distant metastasis-free survival (DMFS). Survivals were assessed using the Kaplan-Meier method. Univariate and multivariate logistic regression and Cox proportional hazards modeling were performed.We enrolled 80 patients (median age: 78) with 88 primary tumors. We observed high baseline rates of geriatric vulnerabilities with a median of four eRFA impairments (IQR: 2-6). More than 50% of patients reported limited social activity, poor social support, depression, and dependency for activities of daily living, and more than 40% reported significant distress. Karnofsky Performance Status was ≤80 in 38% of patients. Cumulative toxicity rates after SBRT were 13% and 1% for Grade II and III toxicities, respectively. After a median follow-up of 12.9 months, 1-year OS, LC and DMFS rates were 96%, 92% and 97%, respectively. Comprehensive eRFA scores were significantly associated with increased likelihood of developing posttreatment toxicities on univariate analysis (LR: 2.20, P < 0.001), as were CCI scores (LR: 1.47, P = 0.025). Due to co-correlation of CCI and eRFA multivariate analysis was not performed. eRFA scores did not predict overall survival.In this cohort, definitive SBRT was well-tolerated with excellent oncologic outcomes despite high observed rates of baseline geriatric vulnerabilities. Frailty assessed by the eRFA score was associated with higher cumulative toxicity rate. Future studies should further explore such relationships and assess interventions aimed at minimizing toxicity for patients with higher degree of geriatric frailty.