M. U. Karim, C. Martinez, V. Panet-Raymond, C. Tsien, N. Kopek, and B. S. Abdulkarim; Department of Radiation Oncology, McGill University Health Centre, Montreal, QC, Canada
Purpose/Objective(s): Lung cancer (LC) is the leading cause of brain metastases (BM), accounting for 50% of all BM. Local treatment such as surgery and stereotactic radiosurgery (SRS), whole brain radiotherapy (WBRT) have shown promise in improving local control and overall survival (OS). With use of Next generation sequencing (NGS), KRAS mutation (KRAS+) is estimated up to 25% of LC. In this study, we aimed to investigate incidence, recurrence, and OS in KRAS+ LC with BM treated with SRS in our institution. Materials/
Methods: A retrospective review of 473 patients with stage IV NSCLC with available NGS results, treated between 2018-2023 in our tertiary care institution, was conducted and we selected 161 patients based on KRAS mutation status. Demographic and clinical information was collected, including number of BM, local treatment, SRS fractions, recurrence, and salvage treatment. Statistical analyses—both univariate and multivariate were performed to gain insights from the data using statistical software. Results: Among 473 patients, 81 (17.12%) were KRAS+ and 80 (16.91%) were KRAS-wild type (KRAS-) tumors were selected based on NGS available data. At presentation, 39% had single BM, and 61% had more than one BM. Initial surgery was performed in 51.5% of patients. The majority of patients (69.5%) received single fraction of SRS. The recurrence rate at 12 months was equally distributed in both group (64% in KRAS+, 72.4% in KRAS-, P=0.5). The overall recurrence rate was comparable between KRAS+ and KRAS- (30.9% vs 36.3%, P= 0.4). In the KRAS+ group, patients with a single BM showed similar rate of recurrence (local and distant) compared to the KRAS- (60% vs. 41.4%, P=0.1). Interestingly, the CNS recurrence rate remains consistent across both groups, regardless of SRS fractionation (P=0.8). At first progression, 16% of patients in the KRAS+ group received salvage WBRT compared to 24.1% of the KRAS- (P=0.1). There was no significant difference in extracranial (EC) disease control between the two groups (KRAS+ 34.6% and KRAS- 31.1%, P=0.6). The CNS progression free survival (PFS) and OS were not significantly different between the two groups. Multivariable logistic regression analysis showed that ECOG 0/1 [(P<0.001) HR CI 95% 2.4 (1.61-3.69)], Age<60 [(P=0.07) HR CI 95% 1.5 (0.95-2.42)], salvage local treatment (SRS or WBRT) [(P=0.02) HR CI 95% 0.5 (0.37-0.91)] and progression in systemic disease [(P= <0.001) HR CI 95% 2.9 (1.86-4.77)] were independent prognostic factors associated with improved OS. Conclusion: This is the first report suggesting that KRAS+ LC with BM have similar CNS recurrence rate compared to KRAS- with trend of having lower risk of salvage treatment with WBRT. With increased utilization of KRAS inhibitor in stage IV LC KRAS+, further studies are warranted to investigate the response of KRAS+ to SRS and its influence on BM outcomes in LC.
