Long-Term Follow-Up on NRG Oncology RTOG 0915 (NCCTG n0927): A Randomized Phase 2 study Comparing 2 Stereotactic Body Radiation Therapy Schedules for Medically Inoperable Patients with Stage I Peripheral Non-Small Cell Lung Cancer
Videtic GM, Paulus R, Singh AK, Chang JY, Parker W, Olivier K, Timmerman RD, Komaki RU, Urbanic JJ, Stephans KL, Yom SS, Robinson CG, Belani C, Iyengar P, Ajlouni M, Gopaul DD, Lele S, McGarry RC, Choy H, and Bradley JD. Long-term follow-up on NRG oncology RTOG 0915 (NCCTG n0927): A randomized phase 2 study comparing 2 stereotactic body radiation therapy schedules for medically inoperable patients with stage i peripheral non-small cell lung cancer. Int J Radiat Oncol Biol Phys 2017; 99(2):S6.
Int J Radiat Oncol Biol Phys
Purpose/Objective(s): NRG Oncology RTOG 0915/NCCTG N0927 was a randomized lung stereotactic body radiotherapy (SBRT) trial of 34 Gy in 1 fraction (arm 1) versus 48 Gy in 4 fractions (arm 2) designed to select the better of the 2 regimens by comparing them at 1 year (yr): first by rates of pre-specified protocol-specified adverse events (psAEs), then by primary tumor control for each arm. Thirty-four Gy emerged as the least toxic yet equally efficacious regimen. Herein, we update those results with long-term follow-up. Purpose/Objective(s): This phase II North American multicenter study of patients aged 18 yrs or older with medically inoperable non-small cell lung cancer with biopsy-proven peripheral (≥2 cm from the central bronchial tree) T1 or T2, N0 (clinically node negative by positron emission tomography), M0 tumors was designed to detect 1-yr psAEs rates >17% as primary endpoint. Primary tumor failure (PTF) (either infield or marginal failure) and local failure (either infield, marginal, or involved lobe failure) [with death without failure considered as a competing event]; overall survival (OS); disease-free survival (DFS) and progression-free survival (PFS) were secondary endpoints, but the study was not designed for statistical comparisons of these outcomes. The study opened in September 2009 and closed in March 2011. Updated data were analyzed through November 14, 2016. Results: Ninety-four patients were accrued, with 86 eligible for analysis: 41 in arm 1 and 45 in arm 2, after 8 cases were excluded. Median follow-up time was 3.8 yrs for all patients, and 5.1 yrs for those alive at analysis. The grade 3 and higher treatment-related toxicity profile was unchanged since previous report, with specifically no new high grade chest wall or grade 5 events. Four of 48 Gy patients had subsequent grade 3 changes in spirometry since meeting the primary endpoint. Medians (in yrs) for 34 Gy and 48 Gy were: 4.1 vs. 4.0 for OS, and 2.6 vs. 2.8 for DFS, respectively. Five-yr outcomes as % (95% CI) for 34 Gy and 48 Gy were: PTF rate of 7.9 (2.0, 19.5) vs. 6.8 (1.7, 16.9); OS of 28.8 (15.4, 43.8) vs. 40.2 (24.9, 55.0); PFS of 19.1 (8.5, 33.0) vs. 31.8 (18.6, 45.9); and second primary rate of 15.5 (6.1, 28.9) vs. 13.3 (5.3, 25.1), respectively. Distant failure as the sole failure or a component of first failure was numerically higher in the 34 Gy arm (7 (46.7%)), but in the 48 Gy arm, rate of second primary development was higher (7 (43.8%)). Approximately 1/3 of patients' causes of death were unknown, and another 1/3 was related to causes other than cancer or treatment. Conclusion: No excess in late-appearing toxicity was seen in either arm. Primary tumor control rates at 5 yrs were similar by arm. Median survivals of 4 yrs for each arm suggest similar efficacy pending any larger studies appropriately powered to detect survival differences.