The findings further validate the initial 2015 findings that a five-fraction SBRT schedule is appropriate for patients with centrally located NSCLC.
Patients with centrally located non–small-cell lung cancer (NSCLC) tolerated the maximum dose of a five-fraction stereotactic body radiotherapy (SBRT) schedule and had low rates of severe toxicity, according to long-term data from the phase I/II NRG Oncology/RTOG 0813 trial. The findings were recently published in the Journal of Clinical Oncology and further validate the initial 2015 findings that a five-fraction SBRT schedule is appropriate for centrally located NSCLC.
“It’s good to have this long-term follow-up,” Nicholas Sanfilippo, MD, radiation oncologist at Weill Cornell Medicine and NewYork-Presbyterian, told Cancer Network. “What this [study] does is give us some prospective evidence to substantiate what we have thought over the last several years.”
The trial included 120 patients with medically inoperable, centrally located NSCLC. Most (84%) had a performance status of 0 or 1 and tended to be older, with a median age of 72 years. Accrual occurred between 2009 and 2013 from 43 sites in the United States and Canada. Patients were assigned to receive one of five doses for their five-fraction schedule delivered over 1.5 to 2 weeks: 10.0 Gy/fraction (fx), 10.5 Gy/fx, 11.0 Gy/fx, 11.5 Gy/fx, or 12.0 Gy/fx.
Patients who had any treatment-related grade 3 or worse toxicity within the first year were considered to have had a dose-limiting toxicity (DLT). The study investigators defined the maximum tolerated dose (MTD) as the “SBRT dose at which the probability of DLT was closest to 20% without exceeding it.”
A total of 100 patients were included in the analysis, of which 71 received the two highest doses of radiation (11.5 Gy/fx or 12.0 Gy/fx). A total of 5 patients had DLTs: 1 in the 10.5 Gy/fx arm, 1 in the 11.0 Gy/fx arm, 2 in the 11.5 Gy/fx arm, and 1 in the 12.0 Gy/fx arm. The MTD was determined to be the highest dose (12.0 Gy/fx), for which the probability of DLT was 7.25% (95% CI, 2.8%–14.5%)-within the probability threshold of 20% established by the protocol.
Among the 71 patients who received the highest doses, the 2-year local control rate was 89.4% (90% CI, 81.6%–97.4%) for the 11.5 Gy/fx arm and 87.9% (90% CI, 78.8%–97.0%) for the 12.0 Gy/fx arm. The 3-year local control rate was 86.7% (90% CI, 78.5%–94.7%) for the 11.5 Gy/fx arm and 84.7% (90% CI, 72.7%–93.9%) for the 12.0 Gy/fx arm.
At a median follow-up of 37.9 months, median overall survival was 38.1 months (95% CI, 24.8–65.0 months) for the 11.5 Gy/fx arm and 39.7 months (95% CI, 28.4–not reached months) for the 12.0 Gy/fx arm. Median progression-free survival was 24.8 months (95% CI, 12.2–38.1 months) for the 11.5 Gy/fx arm and 26.8 months (95% CI, 13.8–34.0 months) for the 12.0 Gy/fx arm.
Sanfilippo agreed with the investigators’ conclusion that 12.0 Gy/fx was the MTD. “They’ve managed to reach a very effective dose with very low rates of complications in this population that have tumors which are located more central in the chest,” he said.