Five-Fraction SBRT for Centrally Located, Inoperable NSCLC
In the phase I/II NRG Oncology/RTOG 0813 study reported in the Journal of Clinical Oncology, Bezjak et al found that five-fraction stereotactic body radiotherapy (SBRT) was associated with relatively low rates of serious treatment-related toxicity and good outcomes in patients with centrally located, medically inoperable non–small cell lung cancer (NSCLC).
The study included 100 eligible and evaluable patients from sites in the United States and Canada with T1 to 2 (≤ 5 cm), N0, M0 centrally located NSCLC. Patients underwent a dose-escalated, 5-fraction SBRT schedule ranging from 10 to 12 Gy/fraction delivered over 1.5 to 2 weeks.
Dose-limiting toxicity (DLT) was defined as any treatment-related grade ≥ 3 predefined toxicity that occurred within the first year. Maximum tolerated dose (MTD) was defined as the SBRT dose at which the probability of DLT was closest to 20% without exceeding it. Patients had a median age of 72 years, and most cancers were T1 (65%); among patients with a specified histology, 45% had squamous cell carcinoma and 39% had adenocarcinoma. The organs closest to planning target volume or most at risk were the main bronchus and large vessels.
MTD and Outcomes
Median follow-up was 37.1 months for all patients and 54.7 months for surviving patients.
DLTs within the first year of follow-up were experienced by five patients, with DLTs consisting of death–not otherwise specified, sinus bradycardia, hypoxia, pneumonitis, and pleural effusion. The MTD was 12.0 Gy/fraction, which was associated with a DLT probability of 7.2%. Among the 71 patients in the 2 highest dose cohorts, 4 patients (12.1%) each in the 11.5 Gy/fraction and 12 Gy/fraction groups had a grade 3 adverse event during the first year of follow-up.
Two-year rates in the 11.5 Gy/fraction and 12.0 Gy/fraction cohorts were 89.4% and 87.9% for local control, 52.2% and 54.5% for progression-free survival, and 67.9% and 72.7% for overall survival. Most deaths were attributed to causes other than lung cancer.
The investigators concluded, “The MTD for this study was 12.0 Gy/[fraction]; it was associated with 7.2% DLTs and high rates of tumor control. Outcomes in this medically inoperable group of mostly elderly patients with comorbidities were comparable with that of patients with peripheral early-stage tumors.”
Andrea Bezjak, MD, of the Princess Margaret Cancer Centre, Toronto, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants from the National Cancer Institute. The study authors’ full disclosures can be found at jco.ascopubs.org.
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