Efficacy and safety of online adaptive magnetic resonance-guided fractionated stereotactic radiotherapy for brain metastases in non-small cell lung cancer (GASTO-1075): a single-arm, phase 2 trial.

BACKGROUND

Brain metastases (BMs) in non-small cell lung cancer (NSCLC) are associated with poor prognosis and quality of life (QoL). This study aimed to evaluate the efficacy and safety of online adaptive MR-guided fractionated stereotactic radiotherapy (FSRT) using a 1.5 T MR-Linac in this subgroup of patients.

METHODS

This single-arm phase 2 trial was conducted at Sun Yat-sen University Cancer Centre. Patients aged 18-75 years with NSCLC, 1-10 BMs, and an ECOG status of 0-1 were included. Key exclusion criteria included inability to undergo contrast-enhanced MRI and contraindications to bevacizumab. Patients received 30 Gy adaptive FSRT in 5 daily fractions under real-time MR guidance, with bevacizumab before (day 1) and after (day 21) FSRT. The primary endpoint was 1-year intracranial progression-free survival (IPFS); secondary endpoints included objective response rate (ORR), 1-year progression-free survival (PFS), 1-year overall survival (OS), treatment-related toxicities, and QoL. All enrolled patients were included in primary and safety analyses. This trial is registered with Clinicaltrials.gov, NCT04946019.

FINDINGS

Between June 10th, 2021 and June 29th, 2023, 70 patients were assessed for eligibility and 55 patients were enrolled (median follow-up: 22.3 months). The median age was 58 years (IQR: 51-65), with 33% (18/55) female patients, and 82% (45/55) presenting with adenocarcinoma. The 1-year IPFS rate was 78.7% (95% CI, 68.2%-90.7%), with a median IPFS of 21.9 months (95% CI, 13.8-30.1 months). The 1-year PFS rate was 63.5% (95% CI: 51.8%-78.2%), and OS was 82.4% (95% CI: 72.6%-93.6%). The ORR reached 78% (95% CI: 65.0%-88.2%). Treatment-related toxicity was minimal, with only one case (2%) of grade 1 radiation necrosis. QoL improved steadily, with the Global Health Status score increasing from 65.67 ± 16.97 to 79.33 ± 8.79 at 6 months post FSRT (p < 0.0001).

INTERPRETATION

Online adaptive FSRT using a 1.5 T MR-Linac has demonstrated effectiveness and good tolerability for BMs in patients with NSCLC. However, the relatively small sample size and short follow-up may affect result generalizability. Further randomised studies are warranted to confirm these findings and establish optimal treatment protocols.

FUNDING

The National Natural Science Foundation of China (Grant Number 82073328).