A Phase 2 Randomized Clinical Trial Evaluating 4-Dimensional Computed Tomography Ventilation-Based Functional Lung Avoidance Radiation Therapy for Non-Small Cell Lung Cancer

Abstract

PurposeTo determine whether 4-dimensional computed tomography (4DCT) ventilation-based functional lung avoidance radiotherapy preserves pulmonary function compared with standard radiotherapy for non-small cell lung cancer (NSCLC). Material and MethodsThis single center, randomized, phase 2 trial enrolled patients with NSCLC receiving curative intent radiotherapy with either stereotactic body radiotherapy or conventionally fractionated radiotherapy between 2016 and 2022. Patients were randomized 1:1 to standard of care radiotherapy or functional lung avoidance radiotherapy. The primary endpoint was the change in Jacobian-based ventilation as measured on 4DCT from baseline to three months post-radiation. Secondary endpoints included changes in volume of high- and low-ventilating lung, pulmonary toxicity, and changes in pulmonary function tests (PFTs). ResultsA total of 122 patients were randomized and 116 were available for analysis. Median follow up was 29.9 months. Functional avoidance plans significantly (P<.05) reduced dose to high-functioning lung without compromising target coverage or organs at risk constraints. When analyzing all patients, there was no difference in the amount of lung showing a reduction in ventilation from baseline to 3 months between the two arms (1.91% vs 1.87%; P=.90). Overall grade ≥2 and grade ≥3 pulmonary toxicities for all patients were 24.1% and 8.6%, respectively. There was no significant difference in pulmonary toxicity or changes in PFTs between the two study arms. In the conventionally fractionated cohort, there was a lower rate of grade ≥2 pneumonitis (8.2% vs 32.3%; P=.049) and less of a decline in change in FEV1 (-3 vs -5; P=.042) and FVC (1.5 vs -6; P=.005) at 3 months, favoring the functional avoidance arm. ConclusionsThere was no difference in post-treatment ventilation as measured by 4DCT between the arms. In the cohort of patients treated with conventionally fractionated radiotherapy with functional lung avoidance, there was reduced pulmonary toxicity, and less decline in PFTs suggesting a clinical benefit in patients with locally advanced NSCLC. Trial RegistrationClinicalTrials.gov Identifier: NCTXXXX Anonymized for Review XXXX