Central Nervous System

PV QA 2 - Poster Viewing Q&A 2

MO_9_2707 - Clinical, Dosimetric, and Radiographic Predictors of Local Failure Following Stereotactic Radiosurgery for Melanoma Brain Metastases

Monday, October 22
10:45 AM - 12:15 PM
Location: Innovation Hub, Exhibit Hall 3

Clinical, Dosimetric, and Radiographic Predictors of Local Failure Following Stereotactic Radiosurgery for Melanoma Brain Metastases
A. H. Masters1, E. McTyre1, M. C. LeCompte1, C. Okoukoni2, R. Barcus3, P. Triozzi4, M. D. Chan1, and C. T. Whitlow5; 1Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC, 2Wake Forest Baptist Medical Center, Winston-Salem, NC, 3Department of Diagnostic Radiology, Wake Forest Medical Center, Winston-Salem, NC, 4Department of Medicine (Hematology & Oncology), Wake Forest School of Medicine, Winston-Salem, NC, 5Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC

Purpose/Objective(s): The treatment of melanoma brain metastases with stereotactic radiosurgery (SRS) remains a challenge, in part due to the relative radioresistance of melanoma, which recent evidence suggests may be related at least in part to BRAF status. In this study we attempt to discern the clinical, dosimetric, and radiographic factors predictive of relative radioresistance in melanoma brain metastases.

Materials/Methods: From January 2000 to December 2015, a total of 107 patients with 540 melanoma brain metastases were treated with SRS. Patient characteristics were stratified by BRAF mutation status. Time-to-event outcomes were summarized using the Kaplan-Meier estimator. Probability of local failure was estimated with the cumulative incidence method. For spatial analysis, each patient’s magnetic resonance imaging (MRI) DICOM files were converted to NIfTI format and then registered to MNI-152 template space using ANTs affine registration. The transformations used for this registration were then applied to each segmented lesion. Lesions were categorized by local failure status, after which Fisher exact tests were performed for each voxel to determine regions with higher likelihood of local failure. For dosimetric analysis, dose-volume data was analyzed for all lesions, and logistic regressions for local failure were performed at discrete intervals for both dose received by a given volume (VD(Gy)) and volume receiving a given dose (DV(%)).

Results: Median overall survival (OS) for all patients was 7.7 mo (CI: 5.3-11.0 mo). OS at 6,12, and 24 months for all patients was 56.3%, 35.8%, and 21.6%, respectively. The cumulative incidence of local failure at one and two years for all patients was 2.3% and 3.3%. The cumulative incidence of local failure at 1 and 2 years was 5.8% and 8.6% for BRAF wildtype (WT) vs. 1.5% and 1.5% for BRAF mutated (Gray’s p-value = 0.002). Tumor volume (cm3; continuous) was also predictive of local failure (HR: 1.13, 95% CI: 1.08-1.19, p <0.001). Voxelwise spatial analysis revealed that lesions in the superior frontal gyrus had a significantly higher likelihood of experiencing local failure (p = 0.001). There was also a higher likelihood of metastasis from BRAF WT versus BRAF mutated in the right superior frontal gyrus (p = 0.03). Dosimetric analysis revealed the most statistically significant predictors of local failure to be the V23.1Gy for BRAF mutated (p=0.001) and the V25.1Gy for BRAF WT(p = 0.004). Fitted logistic regression models were created to determine the probability of local failure associated with several representative discrete doses (Gy) and relative volumes (%) based on BRAF status.

Conclusion: Tumor volume, BRAF status, and lesion location predict for local control in melanoma brain metastases. BRAF WT requires higher SRS doses for comparable local control compared to BRAF mutated. Additionally, it appears there may be a spatial component contributing to local failure patterns which would benefit from further investigation.

Author Disclosure: A.H. Masters: None. E. McTyre: Employee; Wake Forest University Baptist Medical Center. M.C. LeCompte: None. C. Okoukoni: None. R. Barcus: None. P. Triozzi: None. M.D. Chan: Honoraria; Elekta. Advisory Board; Novocure.

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