Prognostic studies can provide important information about disease biology and improve the use of biomarkers to optimize treatment decisions. Methods: A total of 199 patients with advanced melanoma treated with BRAF + MEK inhibitors were included in our single-center retrospective study. We analyzed the risk of progression and death using multivariate Cox proportional hazard models. The predictive effect of prognostic factors on progression-free survival (PFS) was evaluated in ROC analysis. Results: We found that primary tumor localization, Clark level, pT category, baseline M stage and baseline serum S100B are independent and significant prognostic factors for PFS. The discriminative power of the combination of these factors was excellent for predicting 18 month PFS (AUC 0.822 [95% CI 0.727; 0.916],p< 0.001). Primary tumor localization on the extremities, Clark level V, baseline M1c stage or M1d stage, and elevated baseline serum S100B and LDH levels were independently and significantly associated with unfavorable overall survival (OS). Conclusion: Baseline M stage and serum S100B appear to be independent prognostic factors for both PFS and OS in melanoma patients treated with BRAF + MEK inhibitors. We newly identified significant and independent prognostic effects of primary tumor localization and Clark level on survival that warrant further investigation.
预后研究能够提供关于疾病生物学的重要信息，并有助于优化生物标志物的应用以指导治疗决策。方法：本研究为单中心回顾性分析，共纳入199例接受BRAF+MEK抑制剂治疗的晚期黑色素瘤患者。采用多变量Cox比例风险模型分析疾病进展及死亡风险，并通过ROC曲线评估预后因素对无进展生存期（PFS）的预测效能。结果：研究发现原发肿瘤部位、Clark分级、pT分期、基线M分期及基线血清S100B水平是PFS的独立显著预后因素。这些因素联合预测18个月PFS的区分效能优异（AUC 0.822 [95% CI 0.727; 0.916], p<0.001）。四肢原发灶、Clark V级、基线M1c或M1d分期、以及基线血清S100B和LDH水平升高均与不良总生存期（OS）独立显著相关。结论：在接受BRAF+MEK抑制剂治疗的黑色素瘤患者中，基线M分期和血清S100B水平似乎是PFS和OS的共同独立预后因素。本研究首次发现原发肿瘤部位和Clark分级对生存期具有显著独立的预后价值，值得进一步深入研究。
肿瘤(癌症)患者之家