2576 - The Role of Radiotherapy in Resected Non-Small Cell Lung Cancer Brain Metastases Treated with CNS-Active Tyrosine Kinase Inhibitors
Presenter(s)
A. Choudhury1, F. K. Keane2,3, L. L. Zhu1, S. Waliany4, A. E. Marciscano2,3, J. F. Gainor3,4, Z. Piotrowska3,4, J. Lin3,4, K. S. Oh3,5, D. P. Cahill6, P. Brastianos3,4, H. Willers2,3, H. A. Shih3,7, and M. J. Khandekar2,3; 1Harvard Radiation Oncology Program, Boston, MA, 2Department of Radiation Oncology, Mass General Brigham/ Massachusetts General Hospital, Boston, MA, 3Harvard Medical School, Boston, MA, 4Massachusetts General Hospital Cancer Center, Boston, MA, 5Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, 6Department of Neurosurgery, Translational Neuro-Oncology Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 7Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA
Purpose/Objective(s):
For patients (pts) with non-small cell lung cancer (NSCLC) with targetable genomic alterations (TGAs), the increased CNS activity of 2nd/3rd generation tyrosine kinase inhibitors (CNS-TKIs) has transformed the treatment of intact brain metastases (BMs). For pts with resected BMs, radiation therapy (RT) reduces the risk of local recurrence (LR) in the resection bed. To our knowledge, there are no reports of the comparative benefits of adjuvant RT with TKI vs. TKI alone for pts with resected NSCLC BMs with TGAs. We hypothesized that omitting cranial RT may alter patterns of failure after craniotomy. Here we compare clinical outcomes of pts with NSCLC with TGAs and resected BMs treated with CNS-TKIs, with and without adjuvant RT.Materials/Methods:
We performed a retrospective analysis of consecutive pts with NSCLC with TGAs without prior CNS-TKI exposure who underwent craniotomy for BM at a single institution from March 2015 to October 2024. CNS-TKIs were defined as TKIs with >50% intracranial objective response rate in published studies. Data for overall survival (OS), time to intracranial recurrence (ICR), and LR were extracted by chart and imaging review. Analysis was performed using the Kaplan-Meier method, and statistical significance was calculated using the log-rank test. Group comparisons were made using Fisher’s exact test.Results:
We identified 38 pts, 21 of whom underwent RT and 17 of whom did not undergo RT with a median follow up of 25 months from craniotomy (range 10.3-83.1). The median age was 68 (range 36-81). The pts had the following TGAs: EGFR classical mutations (n=25), ALK fusion (4), ROS1 fusion (4), MET exon 14 skipping mutation (3), and RET fusion (2), without a difference in distribution of TGAs between the groups (p=0.40). More pts had a single BM in the RT arm (48% in RT+TKI vs. 12% in TKI (p=0.03)). 68% of pts had gross total resection (66.7% with RT+TKI, 70.1% with TKI). Of the pts undergoing RT after resection, 3 received stereotactic radiosurgery (SRS, defined as <5 fractions), 17 fractionated RT to the cavity (median dose 30 Gy (range: 30-42 Gy) in 10 fractions (range 10-14)), and 1 hippocampal avoidant whole brain RT (HA-WBRT). All pts received CNS-TKI. The 2-year rate of LR in the TKI group was 20% (95% CI, 0-38%) vs. 5% (0-15%) in the RT+TKI group (p=0.067). The 2-year rate of ICR was 60% (95% CI, 12-80%) vs. 31% (7-51%) without and with RT respectively (p=0.3). Median OS without and with RT was 41.9 (95% CI, 20.2-NA) and 61.5 months (34.9-NA) (p=0.3), respectively. One SRS pt developed radionecrosis. Of 5 pts with LR, 3 required repeat craniotomy and postoperative RT; 1 required HA-WBRT.Conclusion:
In this small retrospective cohort of pts with resected NSCLC BMs with TGAs, forgoing adjuvant RT for CNS-TKI alone was not associated with worse OS or ICR at 2 years but was associated with a trend towards increased LR. More data are needed to understand the risks of LR and salvage treatments when treating NSCLC pts with resected BMs with TGAs.