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  • A Modified Disease-Specific Graded Prognostic Assessment (ds-GPA) Scale for Melanoma Consisting of Age, Karnofsky Perfomance Score (KPS), Cumulative Intracranial Tumor Volume (CITV), and BRAF Mutation

    Final Number:

    Manmeet Ahluwalia; Mir Ali; Rushikesh Joshi; Ian McCutcheon; Veronica Chiang; Georges Sinclair; Jiri Bartek; Clark Chen

    Study Design:

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2018 Annual Meeting

    Introduction: Survival prognostication is an important aspect of personalizing oncologic care for patients with melanoma brain metastasis (BM). We previously demonstrated the utility of a cumulative intracranial tumor volume modified diagnosis-specific graded prognostic assessment scale (CITV-dsGPA) for SRS-treated melanoma BM patients. Pertinent prognostic variables in this model included age, Karnofsky performance status (KPS), and CITV. Here we determined whether the incorporation of BRAF mutation status into this CITV-modified scale further enhanced its prognostic accuracy.

    Methods: We collated the survival pattern of 331 melanoma BM patients with known BRAF mutation status treated with stereotactic radiosurgery (SRS) and validated our findings in an independent cohort of 174 patients. All patients with BRAF mutation were treated with BRAF inhibitors. The prognostic utility of the model with and without BRAF mutation information was compared using the net reclassification index (NRI > 0) and integrated discrimination improvement (IDI) metric.

    Results: BRAF mutation status is an important determinant of clinical survival in both univariate analysis (Hazard Ratio for death for BRAF mutated melanomas (HR) = 0.74, p<0.001 as well as a multivariate Cox proportional hazard model that included age, KPS, and CITV (HR for BRAF mutated melanoma = 0.72, p < 0.001). Addition of BRAF mutation status to the CITV-ds-GPA model for melanoma significantly improved its prognostic value, with NRI > 0 of 0.294 (p=0.01) and IDI of 0.017 (p=0.02). We validated these the prognostic utility of this model in an independent cohort of 174 melanoma patients.

    Conclusions: Optimal survival prognostication for SRS-treated patients with melanoma BM requires an integrated assessment of age, KPS, CITV, and BRAF mutation status.

    Patient Care: This research will help improve patient care because successful disease management requires that physicians tailor their treatment strategies based on the clinical status of the patient, and the projected survival expectations. Creating a more robust prognostic model with the inclusion of BRAF mutation status will help establish more granular and sensitive prognoses that can be used to guide treatment management.

    Learning Objectives: 1) • Understand the importance of BRAF mutation status as a prognostic factor for patients afflicted with Melanoma brain metastases (BM) 2) • Understand how best to determine survival expectation for patients afflicted with Melanoma BM, who underwent stereotactic radiosurgery (SRS) for treatment 3) • Create a more robust, synthesized prognostic tool to help guide clinical decision making for patients suffering from Melanoma BM, who were treated by SRS


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