2532 - Assessing the Impact of Targeted Therapy and Immunotherapy on Clinical Outcomes in Intact Brain Metastases Treated with Stereotactic Radiosurgery - A Single Institution Experience

A. K. Ibrahimi¹, A. Alzibdeh¹, A. Almousa¹, M. Al-Hussaini², M. Y. Alsmairat¹, H. Asfour¹, T. Alrawajih¹, and T. Abu hejleh¹; ¹King Hussein Cancer Center, Amman, Jordan, ²King Hussein Cancer Center, AMMAN, Jordan

Purpose/Objective(s): Brain metastases (BM) are known to carry poor prognosis with survival of less than two years. Stereotactic radiosurgery (SRS) has been shown to provide excellent local control. Recently, targeted therapy (TT) and immunotherapy (IT) have transformed metastatic disease treatment, significantly enhancing survival. Nevertheless, there is limited literature on their specific impact on the clinical course of brain metastases in the setting of SRS. This study aims to elucidate the potential influence of TT and IT on SRS outcomes for intact BM. Materials/

Methods: A retrospective study was conducted at a single institution from September 2018 to August 2023 of patients who underwent SRS or fractionated SRS in 3 or 5 treatments for intact BM. Postoperative cavity SRS and re-irradiated lesions were excluded. Patients who previously received WBRT were excluded. Concurrent TT or IT was defined as administration within 3 months following or preceding SRS. Data were analyzed to assess overall survival (OS), regional brain control (RBC), and local control (LC); using Kaplan-Meier survival curves at 1 year, employing Cox proportional hazards model and log-rank test to assess the impact of treatment regimens and reporting hazard ratios with 95% confidence intervals.
Results: The study included 217 patients, treated with SRS for 465 intact BM. Patients aged 19 to 81 years (median 56) and were evenly split by gender. Primary sites per patient included lung (n=100), breast (n=70), kidney (n=8), melanoma (n=6), and others (n=33). Ninety -six patients (44%) received TT, seventy-six (79%) of which were concurrent. Thirty-one patients (14%) received IT, twenty-two (71%) of them were concurrent. Median follow-up was 21 months. For the entire cohort, median OS was 15 months, median regional brain control time was 9 months, median LC time was not reached. One-year post-SRS OS, RBC and LC were (58.3%), (44.7%), and (92.1%) respectively. On multivariate analysis adjusted to primary site, IT (regardless if concurrent or not) was associated with worse LC (HR of 6.0, CI 2.24 to 15.59), while TT (regardless if concurrent or not) conferred better LC (HR of 0.50, CT 0.23 to 0.95). When comparing patients who received concurrent TT versus concurrent IT versus no concurrent treatment, no difference in OS, RBC or LC was found. No difference was found in OS, RBC or LC when comparing concurrent versus non-concurrent TT. When comparing concurrent versus non-concurrent IT, no difference was found in OS or RBC, nonetheless better LC was demonstrated in the non-concurrent group (HR of 5.0, 95% CI 1.265 to 19.70).
Conclusion: Our findings suggest no significant differences in OS, RBC, or LC between patients with intact BM receiving SRS with concurrent or non-concurrent TT or IT. Interestingly, non-concurrent IT exhibited improved LC. These findings highlight the intricate relationship between TT/IT timing and SRS outcomes in brain metastases treatment, necessitating further prospective research on optimal treatment sequencing.