Loco-Regional Control and Survival Outcomes After Combined Stereotactic Radiation Therapy and Immune Checkpoint Inhibitors for Brain Metastases From Non-Small Cell Lung Cancer

Abstract

Over the past decade, improvements in the management of advanced non-small-cell lung cancer (NSCLC) through immunotherapy (IT) with PD-1 pathway inhibitors have been significant, with a major improvement in progression-free survival (PFS) and overall survival (OS). Nevertheless, brain metastases (BM) remain frequent at the time of diagnosis (10%) or during the disease (40%). Stereotactic radiation therapy (SRT) has demonstrated its interest in patients with BM from NSCLC, allowing a clear decrease in neurological toxicity compared to that induced by whole brain RT, without loss of OS. The purpose of this study was to analyze locoregional control (LRC), OS, and neurological toxicity in patients with BM from NSCLC treated with IT and SRT and propose the best possible therapeutic sequence between these two treatments.We retrospectively analyzed NSCLC patients' data with BM treated with IT and SRT within six months between 2015 and 2019. The treated lesions were categorized into the following three groups: "SRT before IT,'' "concurrent SRT and IT," and "SRT after IT.'' "Concurrent" was defined as IT within one month of SRT. Regional progression was defined as the progression or apparition of a BM outside an irradiated area. Regional progression-free interval (R-PFI), OS, and local progression-free interval (L-PFI) were estimated using Kaplan-Meier method and compared using the log-rank test.Fifty-one patients with 84 BM received SRT and IT. The patients were mostly men (60.8%) and WHO 1 (56.9%). For SRT, most lesions were treated with either 15 to 21 Gy in a single fraction (56.0%); or with 18 to 27 Gy in three fractions (41.8%). For IT, patients were treated with Nivolumab (47.1%), Pembrolizumab (33.3%), Durvalumab (15.7%), or Atezolizumab (3.9%) for a median duration of 4.9 months. Among lesions, 76 (90.5%) were intact, and eight (9.5%) were previously resected. The median follow-up from SRT was 22.5 months (2.7-47.3). Six- months and 1-year R-PFI in "SRT before IT" group, "concurrent SRT and IT" group, and "SRT after IT" group were 24.1% and 24.1% vs 56.3% and 49.6% vs 41.0% and 34,2% respectively, (P = 0.094). Although no significant difference has been observed in R-PFI, there was a trend in better regional control of BM from NSCLC in the ''concurrent SRT and IT" group. One-year OS was 67.5% vs 70.2% vs 69.2%, respectively (P = 0.44). One- year L-PFI was 70.1% vs 78.9% vs 77.8%, respectively (P = 0.79). There was no difference in toxicity between the three groups regarding radionecrosis or acute neurological toxicity.Regional control of BM from NSCLC seems to be better in the ''concurrent SRT and IT" group without an increase in acute neurological toxicity or radionecrosis rate. These results may lead to prospective studies on larger cohorts.J. Porte: None. C. Saint Martin: None. T. Frederic Moreau: None. M. Massiani: None. E. Jadaud: None. J. Otz: None. P. Verrelle: None. N. Girard: None. G. Crehange: None. A. Beddok: None.