Functional Lung Avoidance for Individualized Radiation Therapy: Results of a Double-Masked, Randomized Controlled Trial

Purpose: To determine whether functional lung avoidance based on He-3 magnetic resonance imaging (MRI) improves quality of life (QOL) for patients undergoing concurrent chemoradiotherapy (CCRT) for advanced non-small cell lung cancer. Methods and Materials: Patients with stage III non-small cell lung cancer (or oligometastatic disease treated with curative intent) undergoing CCRT with at least a 10 pack-year smoking history were eligible. Patients underwent pretreatment He-3 MRI to measure lung ventilation and had 2 radiation therapy (RT) plans created before randomization: a standard plan, which did not make use of the He-3 MRI, and an avoidance plan, preferentially sparing well-ventilated lung. All participants were masked to assignment except the physicist responsible for exporting the selected plan. The primary end point was patient-reported QOL measured at 3-months post-RT by the FACT-L lung cancer subscale (LCS); secondary end points included other QOL metrics, toxicity, and survival outcomes. Target accrual was 64. Results: Twenty-seven patients were randomized before the trial was closed due to slower-than-expected accrual, with 11 randomized to the standard arm and 16 to the avoidance arm. Baseline patient characteristics were well-balanced. At 3 months post-RT, the mean +/- SD LCS scores were 17.4 +/- 2.8 versus 17.3 +/- 6.1 for the standard and avoidance arms, respectively (P = .485). A clinically meaningful, prespecified decline of >= 3 points in the LCS score was observed in 50% (4/8) in the standard arm and 33% (4/12) in the avoidance arm (P = .648). Two patients in each arm developed grade >= 2 radiation pneumonitis, with no grade >= 4 toxicities. Conclusions: Although this trial did not reach full accrual, QOL scores were very similar between arms. Due to the scarcity of He-3 MRI, other, more commonly available methods to measure functional lung, such as 4-dimensional computed tomography ventilation mapping, may be considered in the assessment of functional lung avoidance RT, and a larger, multicenter approach would be needed to accrue sufficient patients to test such approaches. (C) 2022 Published by Elsevier Inc.