A Phase II Trial of Individualized Stereotactic Ablative Radiotherapy for Lung Tumors (iSABR). International journal of radiation oncology, biology, physics Gensheimer, M. F., Gee, H. E., Von Eyben, R., Shirato, H., Taguchi, H., Wong, S., Brown, E., Nguyen, N., Liang, R., Maxim, P. G., Wakelee, H. A., Neal, J. W., Das, M., Loo, B. W., Diehn, M. 2021; 111 (3S): S89-S90


PURPOSE/OBJECTIVE(S): Stereotactic ablative radiotherapy (SABR) is an effective treatment for lung tumors, but can result in toxicity such as chest wall pain and life-threatening damage to central lung structures. We hypothesized that while larger tumors require higher dose, small tumors up to 10cc in volume can be controlled with biologically effective dose < 100Gy. In this phase II single-arm trial, we tested the hypothesis that individualizing lung SABR dose and fractionation to tumor size, location, and histology would result in excellent local control with acceptable toxicity. The trial was conducted at two centers in the United States and Japan (NCT# redacted for blinded review).MATERIALS/METHODS: Patients in three groups were enrolled: initial diagnosis of non-small cell lung cancer (NSCLC), AJCC 7th edition stage T1-3 N0 M0 (group 1); new primary NSCLC with history of NSCLC, or multiple synchronously diagnosed NSCLCs (group 2); and lung metastases from NSCLC or another primary site (group 3). Up to four tumors could be treated with once-daily SABR. There were six dose/fractionation schedules used, depending on gross tumor volume (=10cc, 10-30cc, > 30cc) and location (peripheral vs. central). Larger tumors received higher dose and central tumors generally received lower dose per fraction. Dose ranged from 25Gy in one fraction for 0-10cc peripheral tumors to 60Gy in 8 fractions for > 30cc central tumors. Colorectal cancer metastases were treated to higher dose, at least 50Gy in 4 fractions. The primary endpoint was per-group cumulative incidence of local recurrence at 1 year (recurrence of treated tumor within same lobe), with distant recurrence and death as competing risks. Treated tumor recurrence (recurrence with epicenter within 1cm of PTV) and toxicity were also analyzed.RESULTS: A total of 217 patients were enrolled from 2011-2018 (some patients were enrolled multiple times). Median age was 72, 59% were male, and 69% were current/former smokers. There were 240 treatment courses and 285 tumors treated (range 1-3 tumors per course). 211 tumors were peripheral and 74 were central. Tumor size distribution was: =10cc, 74%; 10-30cc, 19%; > 30cc, 7%. The most common dose was 25Gy in one fraction (158 tumors). Median follow-up was 30 months (range 2-95). Median overall survival was 57 months. Local recurrence data are currently being updated and will be presented at the meeting. The rate of grade 2 or higher pneumonitis was 16/217 (7%) and grade 3 or higher pneumonitis was 3/217 (1%). The rate of grade 2 or higher chest wall pain was 13/217 (6%). One patient had a grade 5 adverse event, developing pulmonary hemorrhage that was possibly related to radiotherapy, 17 months after treatment of a large central NSCLC.CONCLUSION: Individualized SABR to lung cancers resulted in excellent local control and favorable toxicity profile.

View details for DOI 10.1016/j.ijrobp.2021.07.212

View details for PubMedID 34700657