Functional Lung Avoidance for Individualized Radiation Therapy (FLAIR): Results of a Randomized, Double-Blind Clinical Trial

Abstract

To determine if functional lung avoidance based on 3-He MRI improves quality of life (QoL) outcomes for patients with advanced non-small cell lung cancer (NSCLC) undergoing concurrent chemoradiotherapy (CRT). Patients with stage III NSCLC (or stage IV oligometastatic disease treated with curative intent) undergoing CRT who had at least a 10 pack-year smoking history were eligible for this randomized trial (NCT02002052). All patients underwent a pre-treatment 3-He MRI to measure lung ventilation and had two radiotherapy (RT) plans created and approved before randomization: a standard plan, which did not make use of the 3-He MRI, and an avoidance plan, which preferentially spared well-ventilated lung. All participants were blinded to the allocated treatment arm except the physicist responsible for exporting the selected plan. The primary endpoint was patient-reported QoL measured at 3 months post-RT by the FACT-L lung cancer subscale (LCS); secondary QoL endpoints were the FACT-L trial outcome index (TOI), and the FACT-L total score. Additional pre-specified secondary endpoints included toxicity and survival outcomes. Between July 2014 and August 2016, 27 patients were randomized. The trial was closed before reaching the target of 64 patients due to slower-than-expected accrual. Baseline patient characteristics were well-matched between arms (Table 1). Sixteen patients were randomized to the avoidance arm while the remaining 11 received standard RT. At 3 months post-RT, the FACT-L LCS scores (mean ± SD) were 17.4 ± 2.8 and 17.3 ± 6.1 for the standard and avoidance arms (P=0.48) based on 20 patients alive and with complete data. Similarly, the TOI and total scores were 55.2 ± 12.0 / 53.5 ± 13.2 (P=1.00) and 98.0 ± 18.6 / 94.7 ± 17.2 (P=0.85) respectively. A clinically relevant, pre-specified, decline of ≥ 3 points in the FACT-L LCS score was observed in 50% of patients in the standard arm and 33% in the avoidance arm (P=0.65). Median follow-up was 22 months. Two patients in each arm developed grade ≥ 2 pneumonitis while no grade ≥ 4 toxicity of any kind was observed. No statistically significant difference in progression-free or overall survival was observed between the two arms. In this double-blind trial, functional lung avoidance RT was safely delivered, though without any significant improvement in QoL compared to standard RT. Due to the scarcity of 3-He MRI, other, more commonly-available methods to measure functional lung, such as 4D-CT ventilation mapping, may be considered in the assessment of functional lung avoidance RT in the broader multicenter trial setting.Abstract 3201; Table 1Baseline characteristics and questionnaire scoresVariableStandard Arm (n=11)Avoidance Arm (n=16)Age (years) – mean ± SD67 ± 865 ± 8Male – n (%)7 (64)6 (38)Pack-Years – mean ± SD45 ± 1244 ± 26Stage (AJCC version 8) – n (%) IIIA IIIB IVB7 (64)3 (27)1 (9)10 (63)5 (31)1 (6)FACT-L LCS – mean ± SD18 ± 418 ± 5FACT-L TOI – mean ± SD61 ± 1256 ± 15FACT-L total – mean ± SD106 ± 1799 ± 21 Open table in a new tab