Department of Neurosurgery, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland.
Department of Neurosurgery, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland.
Eur J Cancer. 2022 Nov;175:158-168. doi: 10.1016/j.ejca.2022.08.020. Epub 2022 Sep 17.
Recent therapeutic advances in metastatic melanoma have led to improved overall survival (OS) rates, with consequently an increased incidence of brain metastases (BM). The role of BM resection in the era of targeted and immunotherapy should be reassessed. In the current study we analysed the role of residual intracranial tumour load in a cohort of melanoma BM patients.
Retrospective single-centre analysis of a prospective registry of resected melanoma BM from 2013 to 2021. Correlations of residual tumour volume and outcome were determined with respect to patient, tumour and treatment regimens characteristics.
121 individual patients (66% male, mean age 59.9 years) were identified and included in the study. Pre- and postoperative systemic treatments included BRAF/MEK inhibitors, as well as combination or monotherapy of immune-checkpoint inhibitors (ICIs). Median OS of the entire cohort was 20 months. Cox proportional-hazard analysis revealed postoperative anti-CTLA4+anti-PD-1 therapy (HR 0.07, p = .01) and postoperative residual intracranial tumour burden (HR 1.4, p = .027) as significant predictors for OS. Further analysis revealed that ICI-naïve patients with residual tumour volume ≤3.5 cm and postoperative ICI showed significantly prolonged OS compared to patients with residual volume >3.5 cm (p < .0001). Subgroup analysis of ICI-naïve patients showed steroid intake postoperatively to be negatively associated with OS, however residual tumour volume ≤3.5 cm remained independently correlated with superior OS (HR 0.14, p < .001).
Besides known predictive factors like postoperative ICI, a maximal intracranial tumour burden reduction seems to be beneficial, especially in ICI-naïve patients. This highlights the importance of local CNS control and the need to further investigating the role of initial surgical tumour load reduction in randomised clinical trials.
转移性黑色素瘤的最近治疗进展提高了总体生存率（OS），导致脑转移瘤（BM）的发生率增加。在靶向和免疫治疗时代，BM 切除术的作用应重新评估。在本研究中，我们分析了一组黑色素瘤 BM 患者的残留颅内肿瘤负荷的作用。
对 2013 年至 2021 年切除的黑色素瘤 BM 的前瞻性登记进行回顾性单中心分析。根据患者、肿瘤和治疗方案的特点，确定残余肿瘤体积与结局的相关性。
确定并纳入了 121 名个体患者（66%为男性，平均年龄为 59.9 岁）。术前和术后的系统治疗包括 BRAF/MEK 抑制剂，以及免疫检查点抑制剂（ICIs）的联合或单药治疗。整个队列的中位 OS 为 20 个月。Cox 比例风险分析显示术后抗 CTLA4+抗 PD-1 治疗（HR 0.07，p =.01）和术后颅内残余肿瘤负担（HR 1.4，p =.027）是 OS 的显著预测因素。进一步分析显示，残留肿瘤体积≤3.5cm 且术后接受 ICI 的 ICI 初治患者与残留体积>3.5cm 的患者相比，OS 显著延长（p<.0001）。ICI 初治患者的亚组分析显示，术后使用类固醇与 OS 呈负相关，但残留肿瘤体积≤3.5cm 与更好的 OS 仍呈独立相关（HR 0.14，p<.001）。
除了已知的预测因素如术后 ICI 外，最大限度地减少颅内肿瘤负担似乎有益，尤其是在 ICI 初治患者中。这凸显了局部中枢神经系统控制的重要性，并需要进一步研究在随机临床试验中初始手术肿瘤负荷降低的作用。
