A Phase II Study of Accelerated Hypofractionated 3-Dimensional Conformal Radiotherapy for Inoperable T1-3 N0 M0 Non-Small Cell Lung Cancer: NCIC CTG BR.25

Radiation therapy is a curative treatment option for early stage non-small cell lung cancer (NSCLC). Based on promising retrospective data using accelerated hypofractionated schedules, a prospective multi-institutional phase II trial was performed. This was done in an era when the majority of centers did not have stereotactic body radiation therapy capability. From 2006-2008, 80 patients with peripherally located T1-3 N0 M0 NSCLC were enrolled from 17 institutions across Canada. All patients had biopsy confirmation of NSCLC. Maximum allowable tumor size was 5 cm. Eligible patients received a dose of 60 Gy in 15 fractions using a 3-dimensional conformal technique without inhomogeneity correction. The gross tumor volume (GTV) was the primary tumor only, with no expansion for the clinical target volume (CTV). The planning target volume (PTV) margin was 1.5 cm in all directions. The PTV margin could be decreased to 1.0 cm in the transverse plane to spare critical structures. An assessment for breathing induced tumor motion (fluoroscopy or 4D CT) was required to ensure that the tumor was adequately covered by the PTV. Daily image guidance was not mandated during treatment. All radiation therapy plans were centrally reviewed. Patients were evaluated weekly during treatment and every 4 months afterwards until 2 years. From years 2 to 5, the follow-up decreased to every 6 months. The primary endpoint was the 2 year local control rate of the primary tumor using a modified RECIST criteria. Toxicities were measured using the CTCAE v3.0. Five patients were found to be ineligible and 2 had major protocol violations. Median follow-up of the patients was 49 months (range 21-63 months). Median age of the patients was 75.9 years. 80% of patients were ECOG 0-1 at baseline. The actuarial rate of local control at 2 years was 88%. Overall survival was 69% at 2 years. The actuarial rates of developing regional and distant relapse at 2 years were 9% and 24%, respectively. Distant relapse included the development of a solitary tumor anywhere in the lung separate from the treated primary tumor. Tumor size >3 cm was associated with a statistically significant increase in distant relapse (p = 0.03). The most common grade > = 3 toxicities were fatigue (6.3%), cough (7.5%), dyspnea (13.8%), and pneumonitis (10%). One patient died of massive hemoptysis over 2 years after radiation therapy that was scored as possibly related to the protocol treatment. Conformal radiation therapy to a dose of 60 Gy in 15 fractions resulted in favorable local control and overall survival rates in patients with medically inoperable T1-3 N0 M0 NSCLC. Severe toxicities were uncommon in this prospective study of a relatively simple treatment technique.