Moderately hypofractionated regimens have emerged as an alternative to stereotactic body radiotherapy for patients with central/ultracentral non-small cell lung cancer (NSCLC) who are medically inoperable due to age, poor performance status (PS) or associated comorbidity and who may be at a higher risk of severe toxicity. In the present study, we utilize a modified frailty index (mFI) to identify frail patients and hypothesize that frailty could better stratify clinical outcomes in these patients.
We retrospectively analyzed 32 consecutive patients with stage I-IIB NSCLC treated with 8-10 fraction hypofractionated radiation therapy (RT) in our multi-site practice. Patients who received prior thoracic RT were excluded. An 11 factor mFI score was calculated based on the following variables: ECOG score ≥ 2, impaired sensorium, diabetes, chronic lung disease, myocardial infarction within 6 months, hospitalization within 6 months for heart failure, coronary/cardiac disease, HTN on medication, history of transient ischemic attack, stroke with deficits, and peripheral vascular disease. Kaplan-Meier (KM) method was used to estimate 1-year overall-survival (OS), local control (LC), freedom from progression (FFP) and severe toxicity (≥ grade 3) with patients stratified by mFI score (0-3 vs ≥ 4), median age (< 78 vs ≥ 78) and ECOG PS (0-1 vs ≥ 2).
The patient population was predominantly elderly (median 78 years; range 58-94), 84% Caucasian, with squamous cell carcinoma (50%). Eleven pts (34.3%) had clinical stage II disease; the rest had stage I. Patients were treated with 8-10 fractions with a dose range of 50-70 Gy. The most common regimen was 70 Gy in 10 fractions. At a median follow-up of 16 months, KM estimated 1-year OS for the whole cohort was 86%. When stratified by mFI score (0-3 vs ≥ 4), there was no significant difference in 1-year LC (78% vs 100%), FFP (73% vs 80%), or OS (81% vs 91%), respectively. When stratified by median age (< 78 vs ≥ 78), there was no significant difference in 1-year LC (76% vs 91%), FFP (71% vs 81%), or OS (93% vs 81%), respectively. When stratified by ECOG PS (0-1 vs ≥ 2), there was no significant difference in 1-year LC (84.7% vs 92.3%), FFP (79.4% vs 72.2%), or OS (87.4% vs 85.6%), respectively. Treatment was well-tolerated with only 3 instances of severe grade 3 toxicity (2 pts developed or had worsening of left ventricular systolic function, 1 developed a pneumonia requiring hospitalization), all in the frailer group (mFI score ≥ 4, P = 0.053). Stratification by median age and PS was not significant.
Hypofractionated RT for early-stage NSCLC yields similar tumor control and survival whether stratified by frailty, age or PS. Higher frailty score showed a trend towards worse toxicity that was not detected by age and PS alone. Further analyses in larger datasets could evaluate significance of frailty index in this population.

Copyright © 2021. Published by Elsevier Inc.