International journal of radiation oncology, biology, physics 2015-11-15
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: NRG Oncology RTOG 0915 (NCCTG N0927).
Abstract
Purpose
To compare 2 stereotactic body radiation therapy (SBRT) schedules for medically inoperable early-stage lung cancer to determine which produces the lowest rate of grade ≥3 protocol-specified adverse events (psAEs) at 1 year.
Methods and materials
Patients with biopsy-proven peripheral (≥2 cm from the central bronchial tree) T1 or T2, N0 (clinically node negative by positron emission tomography), M0 tumors were eligible. Patients were randomized to receive either 34 Gy in 1 fraction (arm 1) or 48 Gy in 4 consecutive daily fractions (arm 2). Rigorous central accreditation and quality assurance confirmed treatment per protocol guidelines. This study was designed to detect a psAEs rate >17% at a 10% significance level (1-sided) and 90% power. Secondary endpoints included rates of primary tumor control (PC), overall survival (OS), and disease-free survival (DFS) at 1 year. Designating the better of the 2 regimens was based on prespecified rules of psAEs and PC for each arm.
Results
Ninety-four patients were accrued between September 2009 and March 2011. The median follow-up time was 30.2 months. Of 84 analyzable patients, 39 were in arm 1 and 45 in arm 2. Patient and tumor characteristics were balanced between arms. Four (10.3%) patients on arm 1 (95% confidence interval [CI] 2.9%-24.2%) and 6 (13.3%) patients on arm 2 (95% CI 5.1%-26.8%) experienced psAEs. The 2-year OS rate was 61.3% (95% CI 44.2%-74.6%) for arm 1 patients and 77.7% (95% CI 62.5%-87.3%) for arm 2. The 2-year DFS was 56.4% (95% CI 39.6%-70.2%) for arm 1 and 71.1% (95% CI 55.5%-82.1%) for arm 2. The 1-year PC rate was 97.0% (95% CI 84.2%-99.9%) for arm 1 and 92.7% (95% CI 80.1%-98.5%) for arm 2.
Conclusions
34 Gy in 1 fraction met the prespecified criteria and, of the 2 schedules, warrants further clinical research.
Related Questions
What dose do you use for single fraction SBRT when treating a small, peripheral early stage NSCLC?
There have been two randomized phase II studies of single fraction versus multi-fraction lung SBRT for medically inoperable early stage lung cancer patients. In RTOG 0915, 82% of patients were T1. In the Roswell Park Cancer Institute study, 86% of patients were stage IA. With that in mind, the curre...
Will you offer single fraction SBRT for pulmonary oligometastases?
We use single fraction radiation frequently for most peripheral lung metastasis. In addition to TROG 13.01/SAFRON-II (randomized to 48 Gy/4 fx versus 28 Gy/1 fx, with the important footnote that dose was prescribed for 99% PTV coverage rather than the typical 95%), two other randomized trials - RTOG...
Is 10 Gy x 5 an acceptable dose to use for lung SBRT in tumors with favorable location (eg. not central and not encroaching on the chest wall?)
The paper cited, which my colleague Kevin Stephans authored, used our large institutional data base with long term follow up to carry out a retrospective review of BED adjusted SBRT schedules and showed no difference in overall survival, but slightly improved local control, with higher BED schedules...
Is SBRT appropriate for a small endobronchial tumor distal to the proximal bronchial tree?
In my opinion, you can approach them like any other peripheral NSCLC. There are challenges with small tumors in terms of finding them on CBCT sometimes and getting the dose in if they are very small. The 0236 protocol mandated a minimum aperture of 3.5 cm, which made it not very useful to treat tumo...
When should single fraction SBRT be offered for peripheral NSCLC?
Based on the updated results of RTOG 0915 single fraction radiation to 34 Gy in 1 fraction is reasonable to offer to any patient with a peripheral stage I NSCLC < 5cm (limited single institution data from Germany and Japan shows safety and efficacy even for large lesions). While RTOG 0915 does inclu...
Should lung SBRT fractions be delivered on consecutive days, every other day, or perhaps an even more prolonged schedule?
For North Ameridcan Radiaton Oncologists whose experience with lung SBRT began when they participated in one or both of the RTOG lung SBRT protocols (0236, 0813), they would have quickly learned that their patients would be classified as having either "peripheral" or "central" tumors based on the de...