Local Control Outcomes Following Three- Versus Five-Fraction Stereotactic Radiosurgery for Brain Metastases

Summary: Stereotactic radiosurgery (SRS) is a well-established and effective treatment for brain metastases. Fractionated stereotactic radiosurgery (FSRS) is an alternative to single-fraction SRS that is often utilized when treating large lesions or those bordering sensitive organs at risk. However, there remains variation in practice and uncertainty regarding the optimal dose-fractionation schedule to maximize disease control. Therefore, we performed a comparison of treatment outcomes following three- v. five-fraction SRS to help inform clinical decision making. A retrospective study was conducted within an integrated health care system from June 2017 to December 2022 of 43 patients who underwent FSRS to a total of 61 intact brain metastases to a dose of 24-30 Gy in three fractions (n=49) (median dose: 27 Gy) or 30 Gy in five fractions (n=12). Lesions previously irradiated or resected prior to FSRS were excluded, as were those patients who received whole brain radiotherapy. Overall survival (OS) and local control (LC) were estimated by the Kaplan-Meier method. Univariate and multivariate analyses were performed using Cox proportional hazards models to identify prognostic factors for LC. Median follow up was 11.3 months (range: 0.5 – 41.2). Median patient age was 67 years (range: 25-87), and 31 (50.8%) patients were male. Primary tumors included lung (n=28), cutaneous melanoma (n=14), colorectal (n=6), breast (n=4), and other (n=9). Median gross tumor volume was larger in lesions treated with five-fraction SRS compared to the three-fraction group (10.8cc v. 4.1cc, p27 Gy. Median survival after LR was 2.9 months (range: 1.1 – 4.2). Radiation necrosis (RN) was observed in five (10.2%) and zero (0.0%) of treated lesions in the three- and five-fraction groups, respectively (p=0.57). In patients who undergo FSRS for brain metastases, three-fraction treatment was associated with superior LC compared to five-fraction treatment. Although no cases of RN were observed in patients treated over 5 fractions, poor LC rates in this group suggest the need to escalate dose beyond 30 Gy. For patients treated with 3 fractions, dose escalation to 27 Gy was not associated with superior LC. Prospective evaluation is warranted to better understand the optimal dose-fractionation schedule for FSRS. Adam Beighley (he/him/his), MD (Presenting Author) - Kaiser Permanente Southern California; Michael Cohen, MSc (Co-Author) - Kaiser Permanente; Arthur Wong, MD (Co-Author) - Kaiser Permanente; Fernando Torres, MD (Co-Author) - Kaiser Permanente; Anandh Rajamohan, MD (Co-Author) - Kaiser Permanente; Justin Vinci, MSc (Co-Author) - Kaiser Permanente; Javad Rahimian, PhD (Co-Author) - Kaiser Permanente; Kenneth Lodin, MD (Co-Author) - Kaiser Permanente; Michael Girvigian, MD (Co-Author) - Kaiser Permanente; Onita Bhattasali, MD, MPH (Co-Author) - Kaiser Permanente