Results of a Multi-Institutional Phase II Clinical Trial for 4DCT-Ventilation Functional Avoidance Thoracic Radiotherapy.

Abstract Purpose Radiation pneumonitis remains a major limitation in the radiotherapy treatment of lung cancer patients. Functional avoidance radiotherapy uses functional imaging to reduce pulmonary toxicity by designing radiotherapy plans that reduce doses to functional regions of the lung. Lung functional imaging has been developed that uses 4DCT imaging to calculating 4DCT-based lung ventilation (4DCT-ventilation). A phase II, multi-center, study was initiated to evaluate 4DCT-ventilation functional avoidance radiotherapy. The study hypothesis was that functional avoidance radiotherapy could reduce the rate of ≥ grade 2 radiation pneumonitis to 12% compared to a 25% historical rate; with the trial being positive if ≤ 16.4% of patients experienced ≥ grade 2 pneumonitis. Materials and Methods Lung cancer patients receiving curative-intent radiotherapy (prescription doses of 45-75 Gy) and chemotherapy were accrued. Patient 4DCTs were used to generate 4DCT-ventilation images. The 4DCT-ventilation images were used to generate functional avoidance plans that reduced doses to functional portions of the lung while delivering the prescribed tumor dose. Pneumonitis was evaluated by a clinician at 3, 6, and 12 months post radiotherapy. Results Sixty-seven evaluable patients were accrued between April, 2015 and December, 2019. The median prescription dose was 60 Gy (range 45–66 Gy) delivered in 30 fractions (range 15–33 fractions). The average reduction in functional volume of lung receiving ≥20 Gy with functional avoidance was 3.5% (range 0 to 12.8%). Median follow-up was 312 days. The rate of ≥ grade 2 radiation pneumonitis was 14.9% (10/67 patients, 95% CI 24.0%), meeting the phase II criteria. Conclusion 4DCT-ventilation offers an imaging modality that is convenient and provides functional imaging without an extra procedure necessary. Our study reports on the first multi-center study of 4DCT-ventilation functional avoidance radiotherapy with data showing that the trial met phase II criteria and that evaluation in a phase III study is warranted.