Stereotactic body radiation therapy conferred primary tumor control with low treatment-related morbidity among patients with operable early-stage lung cancer, study data showed.
A research letter written by the same authors noted that despite significant rates of recurrence, the treatment also appeared useful over the long term among patients with inoperable disease.
Robert D. Timmerman, MD, professor of radiation oncology and neurosurgery at University of Texas Southwestern Medical Center, and colleagues sought to evaluate whether SBRT delivered in an outpatient setting could cure patients with early-stage operable lung cancer, eliminating the need for surgery. In a second trial, the researchers evaluated SBRT for patients with inoperable disease.
“The NRG Oncology Radiation Therapy Oncology Group 0236 trial, as well as several other international cooperative group trials, has shown that SBRT affords high rates of tumor control while avoiding severe toxic effects in the majority of patients with early-stage lung cancer unable to tolerate surgical resection,” Timmerman and colleagues wrote. “[Although] surgery has long been the standard treatment [among] patients with operable disease, the convenience, noninvasiveness and favorable outcomes experienced by patients with medically inoperable disease have logically led to interest in using SBRT for all patients with stage I lung cancer.”
The NRG Oncology Radiation Therapy Oncology Group 0618 trial — a single-arm, phase 2 study — included 33 patients with operable, early-stage non-small cell lung cancer who underwent SBRT at a dose of 54 Gy delivered in three fractions.
Primary tumor control served as the primary endpoint. Secondary endpoints included with survival, adverse events, and the incidence and outcome of surgical salvage.
Twenty-six patients (58% men; median age 72.5 years) were evaluable, of whom 23 had T1 disease and three had T2 disease.
At enrollment, patients had a median forced expiratory volume in 1 second of 72.5% of predicted value, and a median diffusing capacity of the lung for carbon monoxide of 68% of predicted value.
Median follow-up was 48.1 months.
One patient experienced primary tumor recurrence, and no patients experienced involved lobe failure. This patient received salvage lobectomy 1.2 years after therapy, which was complicated by grade 4 cardiac arrhythmia.
Both the estimated 4-year primary tumor control rate and local control rate were 96% (95% CI, 83-100).
Researchers reported a 4-year estimated DFS rate of 57% (95% CI, 36-74) and 4-year OS rate of 56% (95% CI, 35-73).
Median OS was 55.2 months (95% CI, 37.7 months to not reached).
Two patients (8%; 95% CI, 0.1-25) experienced treatment-related grade 3 adverse events, whereas no patients experienced grade 4 or grade 5 adverse events.
“SBRT for this operable population may be a viable alternative to surgical resection, which would ideally be compared in a phase 3, randomized clinical trial,” the researchers wrote.
In a research letter, Timmerman and colleagues reported 5-year results from the single-arm, phase 2 NRG Oncology Radiation Therapy Oncology Group 0236 trial, which indicated SBRT benefitted patients with inoperable stage I lung cancer.
Fifty-five of 59 patients with early-stage lung cancer were evaluable. These patients received the same SBRT dosage as those in the 0168 trial.
Five-year recurrence rates were 7.3% (95% CI, 2.3-16.3) for primary tumor, 20% (95% CI, 10.6-31.6) for primary tumor and involved lobe, 10.9% (95% CI, 4.3-20.9) for regional disease, 25.5% (95% CI, 14.7-37.6) for local-regional disease and 23.6% (95% CI, 13.3-35.6) for disseminated disease.
At 5 years, 25.5% (95% CI, 14.7-37.6) of patients achieved DFS and 40% (95% CI, 27.1-52.5) achieved OS.
Overall median DFS was 3 years (95% CI, 2.1-3.8), and median OS was 4 years (95% CI, 2.5-5.3).
No grade 5 treatment-related adverse events occurred in the 5-year follow-up. Fifteen patients (27.3%) experienced grade 3 events, and two (3.6%) experienced grade 4 events. Two additional patients had grade 3 or higher adverse events in the 5-year report compared with an earlier 3-year report, most of which fell into the pulmonary or musculoskeletal categories.
“[Although] patients continue to experience recurrence and need better therapies, long-term follow-up demonstrates SBRT’s useful performance in at-risk populations and showed that even late toxic effects can be managed by careful application of advanced technology,” Timmerman and colleagues wrote. – by Andy Polhamus
Disclosures: Timmerman reports research grants from Accuray, Inc., Elekta Oncology and Varian Medical systems. Please see the study for a complete list of all other authors’ relevant financial disclosures. The research letter authors report no relevant financial disclosures.