Results of a Multi-Institutional Phase II Clinical Trial for 4DCT-Ventilation Functiona Avoidance Thoracic Radiotherapy.
International Journal of Radiation Oncology, Biology, Physics
Purpose/Objective(s)Pulmonary toxicity, and in particular radiation pneumonitis, remains a major limitation in the radiotherapy treatment of lung cancer patients. Functional avoidance radiotherapy proposes to use functional imaging to reduce pulmonary toxicity by designing radiotherapy treatment plans that reduce doses to functional regions of the lung. A novel form of lung functional imaging has been proposed that uses 4DCT imaging to calculating 4DCT-based lung ventilation (4DCT-ventilation) maps. A phase II, multi-center, prospective study was initiated to evaluate 4DCT-ventilaiton 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% ≥ grade 2 historical pneumonitis rate. Based on a binomial, one-sided 95% confidence interval (CI), the trial would be positive if ≤ 11 of 67 patients (16.4%) experienced ≥ grade 2 radiation pneumonitis.
Materials/MethodsLung cancer patients receiving curative intent radiotherapy (prescription doses of 45-75 Gy) and planned curative intent chemotherapy were accrued from 2 institutions. Patient 4DCTs along with image processing techniques 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 and respecting tolerances of organs-at-risk. Functional doses were reduced by selecting favorable arc geometry and employing optimization techniques. Patients were evaluated for pneumonitis at 3, 6, and 12 months after completing radiotherapy.
ResultsSixty-seven evaluable patients were accrued between April 2015 and December 2019. Median Karnofsky performance status was 90 and 76% of patient's had stage III disease. The median prescription dose was 60 Gy (range 45–66 Gy) delivered in 30 fractions (range 15–33 fractions). Eleven patients (16%) underwent surgery as part of their treatment, 88% of patients received concurrent chemotherapy, and 25% of patients were treated with immunotherapy while they were on study. Median follow-up was 312 days. The crude rate of ≥ grade 2 radiation pneumonitis was 14.9% (10/67 patients, upper 95% CI of 24.0%), meeting the phase II criteria.
ConclusionBecause 4DCTs are a standard part of the treatment planning process for lung cancer patients, 4DCT-ventilation offers an imaging modality that is convenient and provides functional imaging without an extra imaging procedure necessary. Our study reports on the first multi-center, prospective study of 4DCT-ventilation functional avoidance radiotherapy. The study met phase II criteria demonstrating reduced pneumonitis rates and provides favorable evidence for 4DCT-ventilation functional avoidance to be investigated in a phase III study. Future work will report on secondary objective including pulmonary function, patient-reported outcomes, and imaging-based end-points.
Vinogradskiy Y, Castillo R, Castillo E, Schubert LK, Jones BL, Faught AM, Gaspar LE, Kwak J, Bowles DW, Waxweiler TV, Dougherty M, Gao D, Stevens CW, Miften M, Kavanagh BD, Grills IS, Rusthoven, Jr. CG, Guerrero TM. Results of a multi-institutional phase II clinical trial for 4DCT-ventilation functional avoidance thoracic radiotherapy. Int J Radiat Oncol Biol Phys. 2021; 111(3 suppl.):S8-S9.