Results of a Multi-Institutional Phase 2 Clinical Trial for 4DCT-Ventilation Functional Avoidance Thoracic Radiation Therapy

• Authors: Yevgeniy Vinogradskiy, University of Colorado, Aurora; Richard Castillo, Emory University; Edward Castillo, Beaumont Health System; Leah Schubert, University of Colorado, Aurora; Bernard L Jones, University of Colorado, Aurora; Austin Faught, St Jude Childrens Research Hospital; Laurie E Gaspar, University of Colorado, Aurora; Jennifer Kwak, University of Colorado, Aurora; DW Bowles, University of Colorado, Aurora; Timothy Waxweiler, University of Colorado, Aurora; Jing M Dougherty, Mayo Clinic, Jacksonville; Dexiang Gao, University of Colorado; Craig Stevens, Beaumont Health System; Moyed Miften, University of Colorado, Aurora; Brian Kavanagh, University of Colorado, Aurora; Inga Grills, Beaumont Health System; Chad G Rusthoven, University of Colorado, Aurora; Thomas Guerrero, Beaumont Health System
• Journal Title: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
• Volume: Volume 112, Number 4
• Publisher: ELSEVIER SCIENCE INC | 2022-02-18, Pages 986-995
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.ijrobp.2021.10.147
• Subjects: Health Sciences, Oncology; Biology, Biostatistics
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; Radiology, Nuclear Medicine & Medical Imaging; CELL LUNG-CANCER; IMAGE-GUIDED RADIOTHERAPY; INTENSITY-MODULATED RADIOTHERAPY; COMPUTED-TOMOGRAPHY VENTILATION; PULMONARY VENTILATION; REGIONAL VENTILATION; PNEUMONITIS; CONCURRENT; CHEMORADIOTHERAPY; CHEMORADIATION

Abstract

Purpose: Radiation pneumonitis remains a major limitation in the radiation therapy treatment of patients with lung cancer. Functional avoidance radiation therapy uses functional imaging to reduce pulmonary toxic effects by designing radiation therapy plans that reduce doses to functional regions of the lung. Lung functional imaging has been developed that uses 4-dimensional computed tomography (4DCT) imaging to calculate 4DCT-based lung ventilation (4DCT-ventilation). A phase 2 multicenter study was initiated to evaluate 4DCT-ventilation functional avoidance radiation therapy. The study hypothesis was that functional avoidance radiation therapy could reduce the rate of grade ≥2 radiation pneumonitis to 12% compared with a 25% historical rate, with the trial being positive if ≤16.4% of patients experienced grade ≥2 pneumonitis. Methods and Materials: Lung cancer patients receiving curative-intent radiation therapy (prescription doses of 45-75 Gy) and chemotherapy were accrued. Patient 4DCT scans 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 after radiation therapy. 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 the functional volume of lung receiving ≥20 Gy with functional avoidance was 3.5% (range, 0%-12.8%). The median follow-up was 312 days. The rate of grade ≥2 radiation pneumonitis was 10 of 67 patients (14.9%; 95% upper CI, 24.0%), meeting the phase 2 criteria. Conclusions: 4DCT-ventilation offers an imaging modality that is convenient and provides functional imaging without an extra procedure necessary. This first report of a multicenter study of 4DCT-ventilation functional avoidance radiation therapy provided data showing that the trial met phase 2 criteria and that evaluation in a phase 3 study is warranted.