For patients with centrally located lung cancers in a multicenter phase 1/2 trial, a specific five-fraction radiotherapy schedule was well tolerated and linked to fairly low rates of treatment-related toxicity, investigators say.
The 12-Gy/fraction schedule of stereotactic body radiotherapy (SBRT) had a 7.2% rate of dose-limiting toxicities and a high tumor-control rate in the NRG Oncology/RTOG 0813 trial, which enrolled 120 patients with medically inoperable stage T1/2 N0M0 non–small cell lung cancers at 43 centers in the United States and Canada.
This is an important study that has implications for clinical practice, according to the investigators, led by Andrea Bezjak, MD, of Princess Margaret Cancer Centre in Toronto.
“The ability to treat patients with centrally located node-negative tumors in multiple institutions across the United States and Canada while maintaining plan qualities and achieving good patient outcomes and relatively modest rates of toxicity is an important achievement,” Dr. Bezjak and coinvestigators said in the Journal of Clinical Oncology.
These patients are frequently at increased risk from surgery, because of advanced age and the comorbidities that come with it, they added.
The 12-Gy/fraction dose level was the highest of nine dose levels included in the study protocol. Doses were delivered in five fractions over the course of 1.5-2 weeks. Investigators sought to determine the maximum tolerated dose of SRBT, defined as the level at which the probability of dose-limiting toxicities (grade 3 or greater) within the first year was as close to 20% as possible, without going over.
Thus, the 7.2% rate of dose-limiting toxicities at this highest-allowed dose level was “well below” that protocol-specified threshold, investigators said, commenting on results of the study.
The rate of local control at 2 years was 89.4% for the 12-Gy/fraction dose level. The 2-year overall survival was 70%, which compared favorably to what has been seen previously with use of SBRT in similar patients with peripheral tumors, according to Dr. Bezjak and colleagues.
Most deaths in the study were attributable to causes other than lung cancer, according to investigators, who noted that all accrued patients were deemed medically inoperable by an experienced thoracic surgeon.
“Thus, this study provides robust data about the safety and efficacy of a five-fraction SBRT schedule that is well tolerated and associated with relatively low rates of serious treatment-related toxicity,” they concluded.
Dr. Bezjak reported disclosures related to AstraZeneca and Abbvie. Coauthors provided disclosures related to Varian Medical Systems, Elekta, Accuray, Seattle Genetics, Celgene, Exelixis, Gilead Sciences, Illumina, Ions Pharmaceuticals, and EMD Serono, among others.
SOURCE: Bezjak A et al. J Clin Oncol. 2019 Apr 3. doi: 10.1200/JCO.18.00622.
