Central Nervous System

SS 40 - CNS 3 - CNS Metastasis

291 - Preoperative Radiosurgery For Resected Brain Metastases: Updated Analysis of Efficacy and Toxicity Of A Novel Treatment Paradigm

Wednesday, October 24
1:50 PM - 2:00 PM
Location: Room 004

Preoperative Radiosurgery For Resected Brain Metastases: Updated Analysis of Efficacy and Toxicity Of A Novel Treatment Paradigm
R. S. Prabhu1, K. R. Miller2, A. Asher3, J. H. Heinzerling4, B. J. Moeller1, K. Patel5, and S. H. Burri4; 1Southeast Radiation Oncology Group, Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC, 2Levine Cancer Institute, Charlotte, NC, 3Carolina Neurosurgery and Spine Associates, Charlotte, NC, 4Levine Cancer Institute, Atrium Health and Southeast Radiation Oncology Group, Charlotte, NC, 5Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT

Purpose/Objective(s): Postoperative (post-op) radiosurgery (SRS) has been proposed as a standard of care for brain metastases (BM) to minimize risk of local recurrence (LR) based on 2 phase III trials. We have previously demonstrated that preoperative (pre-op) SRS is a feasible alternative to post-op SRS and has potential advantages in risk of radiation necrosis (RN) and leptomeningeal disease (LMD) recurrence. The goal of this study was to determine the efficacy and toxicity of pre-op SRS in an expanded patient (pt) cohort with longer follow-up period.

Materials/Methods: The records for pts with BM treated with pre-op SRS and planned surgical resection were reviewed. Pts with classically radiosensitive tumors, planned adjuvant whole brain radiation therapy (WBRT), or no cranial imaging at least 1 month after surgery were excluded. Pre-op SRS dose was based on lesion size and approximately 20% reduced from standard. Surgery generally followed within 48 hours. Overall survival (OS) was estimated using the Kaplan-Meier method. Intracranial event rates were estimated using cumulative incidence with competing risk of death.

Results: The study cohort consisted of 117 pts with 125 lesions treated with single fraction pre-op SRS and planned surgical resection, of which 24 pts were enrolled on an initial prospective trial and an additional 93 consecutive pts were retrospectively reviewed. Most pts had a single BM (70.1%), underwent gross total resection (95.2%), and had non-small cell lung cancer (42.7%), followed by breast (18.8%), melanoma (15.4%), and renal cell (11.1%). Median time from SRS to surgery was 2 days, median SRS dose was 15 Gy, and median gross tumor volume was 8.3 cm3 (approximately equivalent to 2.5 cm diameter lesion). Median cranial imaging follow-up period was 10.5 months for all pts and 18.7 months for alive pts. The median, 1 and 2-year OS rate was 17.2 months, 60.6% and 36.7%, respectively. The 1 and 2-year rate of cavity LR was 19.9% and 25.1%, distant brain failure (DBF): 45.3% and 60.2%, and LMD: 4.3% and 4.3%, respectively. The 1 and 2-year rate of any RN and symptomatic RN was 5.1% and 8.5%, and 2.6% and 4.8%, respectively. The 1 and 2-year rate of the composite endpoint of cavity LR, symptomatic RN, or LMD was 24.5% and 30.7%, respectively. Three pts (2.6%) experienced grade 3 toxicity: RN requiring surgery (n=1), postoperative wound complications (n=1), and cavity hematoma requiring evacuation (n=1).

Conclusion: This expanded and updated analysis confirms that single fraction pre-op SRS confers excellent cavity local control with very low risk of RN or LMD. Pre-op SRS has several potential advantages compared to post-op SRS including reduced risk of RN due to smaller irradiated volume without need for cavity margin expansion and reduced risk of LMD due to sterilizing tumor cells prior to spillage at the time of surgery. These data will be compared to published post-op SRS results. Based on these results, a randomized trial of pre-op vs. post-op SRS is being designed at this time.

Author Disclosure: R.S. Prabhu: None. A. Asher: None. J.H. Heinzerling: None. B.J. Moeller: Independent Contractor; Novant Health. S.H. Burri: Partner; Southeast Radiation Oncology. Chairman of Radiaiton Oncology; Levine Cancer Institute.

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