Targeted treatment and immunotherapy in leptomeningeal metastases from melanoma
Targeted treatment and immunotherapy in leptomeningeal metastases from melanoma
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DOI：
10.1093/annonc/mdw134
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发表时间：
2016-06-01
影响因子：
50.5
通讯作者：
Boogerd, W.
中科院分区：
文献类型：
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作者：
Foppen, M. H. Geukes;Brandsma, D.;Boogerd, W.
背景资料：历史上，黑色素瘤的软脑膜转移（LM）预后不良，尽管接受治疗，中位生存期仅为2个月。靶向治疗和免疫检查点抑制剂是晚期黑色素瘤有希望的新治疗选择。我们试图确定靶向治疗和免疫治疗对LM黑色素瘤患者预后的影响，并评估预后因素的影响。我们分析了2010年5月至2015年3月期间在荷兰癌症研究所治疗的39例连续诊断为LM的黑色素瘤患者。其中34例患者还患有脑转移瘤（BM）。统计分析评估了临床和生物学特征对生存的影响，整个队列的中位总生存期为6.9周（95%置信区间0.9-12.8）。由于体能状态不佳或疾病进展迅速，14例患者未接受治疗。诊断为LM后未治疗患者的中位总生存期为2.9周，治疗患者为16.9周（P < 0.001）。21例接受全身靶向治疗和/或免疫治疗（有或无RT）的患者的中位生存期为21.7周（范围2-235周）。5例患者有LM，无BM。这些患者中有3例在给予任何治疗前3周内死亡，而2例患者持续缓解26周（达拉菲尼治疗后）和235周（WBRT和伊匹单抗治疗后）。诊断为LM时血清乳酸脱氢酶和S100 B水平升高与生存期缩短相关。正如在颅外转移性疾病中观察到的那样，新的治疗方式，如全身靶向治疗和免疫检查点抑制剂似乎可以增加LM的总生存期，并可能导致长期缓解。LM患者应考虑这些新的治疗选择。
Background: Historically leptomeningeal metastases (LM) from melanoma have a poor prognosis, with a median survival of only 2 months despite treatment. Targeted therapy and immune checkpoint inhibitors are promising new treatment options in advanced melanoma. We sought to determine the impact of targeted therapy and immunotherapy on the outcome of melanoma patients with LM and to evaluate the influence of prognostic factors.We analyzed a series of 39 consecutive patients diagnosed with LM from melanoma between May 2010 and March 2015 treated at the Netherlands Cancer Institute. Thirty-four of these patients also had brain metastases (BM). Statistical analyses assessed the influence of clinical and biological characteristics on survival.Median overall survival of the entire cohort was 6.9 weeks (95% confidence interval 0.9-12.8). Due to a poor performance status or rapidly progressive disease, 14 patients received no treatment. Median overall survival of untreated patients after the diagnosis of LM was 2.9 versus 16.9 weeks for treated patients (P < 0.001). The median survival of 21 patients treated with systemic targeted therapy and/or immunotherapy, with or without RT was 21.7 weeks (range 2-235 weeks). Five patients had LM without BM. Three of these patients died within 3 weeks before any treatment was given, whereas 2 patients are in ongoing remission for 26 weeks (following dabrafenib) and 235 weeks (following WBRT and ipilimumab). Elevated serum lactate dehydrogenase and S100B at diagnosis of LM were associated with shorter survival.LM from melanoma still has an extremely poor prognosis. As observed in extracranial metastatic disease, new treatment modalities such as systemic targeted therapy and immune checkpoint inhibitors seem to increase overall survival in LM, and may result in long-term remission. These new treatment options should be considered in patients with LM.