Ahluwalia Manmeet, Ali Mir A, Joshi Rushikesh S, Park Eun Suk, Taha Birra, McCutcheon Ian, Chiang Veronica, Hong Angela, Sinclair Georges, Bartek Jiri, Chen Clark C
Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, Ohio, USA.
Department of Neurosurgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Neurooncol Adv. 2020 Nov 12;3(1):vdaa152. doi: 10.1093/noajnl/vdaa152. eCollection 2021 Jan-Dec.
Stereotactic radiosurgery (SRS) remains a mainstay therapy in the treatment of melanoma brain metastases (BM). While prognostic scales have been developed for melanoma patients who underwent SRS treatment for BM, the pertinence of these scales in the context of molecularly targeted therapies remains unclear.
Through a multi-institutional collaboration, we collated the survival patterns of 331 melanoma BM patients with known BRAF mutation status treated with SRS. We established a prognostic scale that was validated in an independent cohort of 174 patients. All patients with BRAF mutations in this series were treated with BRAF inhibitors. Prognostic utility was assessed using Net Reclassification Index (NRI > 0) and integrated discrimination improvement (IDI) metrics.
In a multivariate Cox proportional hazards model, BRAF mutation status, KPS, number of metastases, and cumulative intracranial tumor volume (CITV) independently contributed to survival prognostication for melanoma patients with SRS-treated BM ( < .05 for all variables). These variables were incorporated into a prognostic scale using the disease-specific graded prognostic assessment (ds-GPA) framework. This integrated melanoma ds-GPA scale was validated in 2 independent cohorts collated through a multi-institutional collaboration. In terms of order of prognostic importance, BRAF mutation status exerted the greatest influence on survival, while KPS, the number of metastases, and CITV exhibited comparable, lesser impacts.
Optimal survival prognostication for SRS-treated patients with melanoma BM requires an integrated assessment of patient characteristics (KPS), tumor characteristics (CITV and number of metastases), and the mutational profile of the melanoma (BRAF mutation status).
立体定向放射外科（SRS）仍然是治疗黑色素瘤脑转移（BM）的主要治疗方法。虽然已经为接受SRS治疗BM的黑色素瘤患者制定了预后量表，但这些量表在分子靶向治疗背景下的相关性仍不明确。
通过多机构合作，我们整理了331例已知BRAF突变状态且接受SRS治疗的黑色素瘤BM患者的生存模式。我们建立了一个预后量表，并在174例患者的独立队列中进行了验证。本系列中所有BRAF突变患者均接受BRAF抑制剂治疗。使用净重新分类指数（NRI>0）和综合鉴别改善（IDI）指标评估预后效用。
在多变量Cox比例风险模型中，BRAF突变状态、KPS、转移灶数量和累积颅内肿瘤体积（CITV）独立影响接受SRS治疗的黑色素瘤BM患者的生存预后（所有变量P<0.05）。这些变量使用疾病特异性分级预后评估（ds-GPA）框架纳入预后量表。这种综合黑色素瘤ds-GPA量表在通过多机构合作整理的2个独立队列中得到了验证。就预后重要性顺序而言，BRAF突变状态对生存影响最大，而KPS、转移灶数量和CITV的影响相当但较小。
对于接受SRS治疗的黑色素瘤BM患者，最佳生存预后需要综合评估患者特征（KPS）、肿瘤特征（CITV和转移灶数量）以及黑色素瘤的突变谱（BRAF突变状态）。
