Impact of New Systemic Treatment and Radiotherapy in Melanoma Patients with Leptomeningeal Metastases.
Impact of New Systemic Treatment and Radiotherapy in Melanoma Patients with Leptomeningeal Metastases.
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DOI：
10.3390/cancers12092635
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发表时间：
2020-09-16
期刊：
影响因子：
5.2
通讯作者：
Lebbé C
中科院分区：
文献类型：
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作者：
Tétu P;Sirven-Villaros L;Cuzzubbo S;Ursu R;Baroudjian B;Delyon J;Nataf F;De Margerie-Mellon C;Allayous C;Lefevre W;Carpentier AF;Lebbé C
尽管近年来在治疗晚期黑色素瘤（包括脑转移）方面取得了令人难以置信的进展，但患有轻脑膜病（LM）的黑色素瘤患者的生存率仍然很低。目前只有少数报道表明BRAF和MEK抑制剂，或免疫检查点抑制剂，可能诱导晚期黑色素瘤LM患者的生存获益。本研究的目的是在新的全身治疗和放射外科时代，更好地了解LM黑色素瘤患者、疾病特征和治疗干预措施。这项研究表明，新的治疗方式似乎是黑色素瘤LM的新治疗选择，需要在更大的前瞻性研究中进行测试。一部分患者是长期存活的，与生存率提高相关的因素如低血清LDH水平可能被确定。重要性：很少有数据表明黑色素瘤患者的腰膜病（LM）接受了新的全身治疗。目的：在新的全身治疗时代，更好地了解黑色素瘤合并LM患者的患者、疾病特征和治疗干预措施。设计：收集诊断为LM的黑色素瘤患者的临床特征、治疗方法和生存率，这些患者分离或伴有脑转移。Cox回归模型评估患者和黑色素瘤特征对生存率的影响。背景：单中心、回顾性、真实的黑色素瘤LM患者队列研究。参与者：纳入2013年12月至2020年2月期间在圣路易斯大学医院随访并诊断为LM的所有患者。对于每一位确诊的患者，由皮肤肿瘤学家和神经肿瘤学家专家进行中心检查，以确认LM的诊断。暴露：新的全身疗法和放疗的影响。结果：在2013年至2020年期间在圣路易斯医院随访的452例晚期黑色素瘤患者中，有41例黑色素瘤LM患者被确定。其中29例经中枢神经肿瘤学家复查后诊断为“确诊”或“可能”的LM患者纳入研究。19例患者在LM诊断时已知黑色素瘤脑转移。27例接受全身治疗的患者中，免疫治疗17例，靶向治疗5例，化疗1例，抗pd -1联合BRAF抑制剂4例。中位总生存期（OS）为5.1个月。接受全身治疗联合放疗的9例患者中位OS为7.1个月，未接受联合放疗的20例患者中位OS为3.2个月。血清乳酸脱氢酶（LDH）升高（HR 1.44, 95% CI 1.09-1.90, p < 0.01）和LM诊断时出现神经症状（HR 2.96, 95% CI 1.25-6.99, p = 0.01）与生存不良相关。在数据分析时，5例患者仍然存活，中位随访时间为47.4个月，并且持续完全缓解。结论：靶向治疗和免疫治疗是黑色素瘤LM的新治疗选择，可以提高总生存率，并可能在一些患者中引起持久的缓解。
Although the recent years have seen incredible progress in the treatment of advanced melanoma including brain metastases, the survival of melanoma patients with leptomeningeal disease (LM) is still poor. There are currently only a handful of reports suggesting that BRAF and MEK inhibitors, or immune checkpoint inhibitors, may induce survival benefit in advanced melanoma patients with LM. The objective of this study was to gain a better understanding of patients, disease characteristics, and therapeutics interventions in LM melanoma patients in the era of new systemic treatment and radiosurgery. This study demonstrated that new treatment modalities appear to be promising new treatment options for melanoma LM, and need to be tested in larger prospective studies. A subset of patients are long-term survivors, and factors associated with improved survival such as low serum LDH level may be identified. Importance: Few data are available on patients with leptomeningeal disease (LM) from melanoma treated with new systemic therapies. Objective: To gain a better understanding of patients, disease characteristics, and therapeutic interventions in melanoma patients with LM in the era of new systemic treatment. Design: Clinical characteristics, treatments, and survival of melanoma patients diagnosed with LM, isolated or associated with brain metastases, were collected. The Cox regression model assessed the influence of patient and melanoma characteristics on survival. Setting: Monocentric, retrospective, real-life cohort of patients with LM from melanoma. Participants: All patients followed up at Saint-Louis University Hospital and diagnosed with LM between December 2013 and February 2020 were included. For each patient identified, a central review by dermato-oncologist and neuro-oncologist experts was performed to confirm the diagnosis of LM. Exposure: Impact of new systemic therapies and radiotherapy. Results: Among the 452 advanced melanoma patients followed at St Louis Hospital between 2013 and 2020, 41 patients with LM from melanoma were identified. Among them, 29 patients with a diagnosis of LM “confirmed” or “probable” after central neuro-oncologists reviewing were included. Nineteen patients had known melanoma brain metastases at LM diagnosis. Among the 27 patients treated with systemic therapy, 17 patients were treated with immunotherapy, 5 patients received targeted therapy, 1 was treated with chemotherapy, and 4 patients were treated with anti-PD-1 in combination with BRAF inhibitor. The median overall survival (OS) from LM diagnosis was 5.1 months. Median OS was 7.1 months for the 9 patients receiving systemic therapy combined with radiotherapy, and 3.2 months for the 20 patients not receiving combined radiotherapy. Elevated serum lactate dehydrogenase (LDH) (HR 1.44, 95% CI 1.09–1.90, p < 0.01) and presence of neurological symptoms at LM diagnosis (HR 2.96, 95% CI 1.25–6.99, p = 0.01) were associated with poor survival. At the time of data analysis, five patients were still alive with a median follow-up of 47.4 months and had persistent complete response. Conclusion: Targeted therapy and immunotherapy are promising new treatment options in LM from melanoma that can increase overall survival, and may induce long lasting remission in some patients.
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影响因子：
--
作者：
Le Rhun E;Taillibert S;Chamberlain MC
通讯作者：
Chamberlain MC
DOI：
10.1016/s1470-2045(16)30053-5
发表时间：
2016-07
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Goldberg SB;Gettinger SN;Mahajan A;Chiang AC;Herbst RS;Sznol M;Tsiouris AJ;Cohen J;Vortmeyer A;Jilaveanu L;Yu J;Hegde U;Speaker S;Madura M;Ralabate A;Rivera A;Rowen E;Gerrish H;Yao X;Chiang V;Kluger HM
通讯作者：
Kluger HM
影响因子：
50.5
作者：
Foppen, M. H. Geukes;Brandsma, D.;Boogerd, W.
通讯作者：
Boogerd, W.
DOI：
10.1016/s1470-2045(17)30429-1
发表时间：
2017-07
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Davies MA;Saiag P;Robert C;Grob JJ;Flaherty KT;Arance A;Chiarion-Sileni V;Thomas L;Lesimple T;Mortier L;Moschos SJ;Hogg D;Márquez-Rodas I;Del Vecchio M;Lebbé C;Meyer N;Zhang Y;Huang Y;Mookerjee B;Long GV
通讯作者：
Long GV
影响因子：
51.1
作者：
Margolin, Kim;Ernstoff, Marc S.;Hodi, F. Stephen
通讯作者：
Hodi, F. Stephen