Tang Hiu Kwan Carolyn, Rao Ankit, Peters Christina, Ambulkar Tanvi, Ho Michael Fx, Wang Bo, Patel Poulam
Department of Oncology, Nottingham City Hospital, Hucknall Road, Nottingham, NG5 1PB, United Kingdom.
Trinity Hall, University of Cambridge, Cambridge, CB2 1TJ, United Kingdom.
J Cancer. 2024 May 5;15(11):3495-3509. doi: 10.7150/jca.93306. eCollection 2024.
Immune-activating anti-CTLA4 and anti-PD1 monoclonal antibodies (alone or in combination) are being used to treat advanced melanoma patients and can lead to durable remissions, and long-term overall survival may be achieved in between 50-60% of patients. Although intracranial metastases are very common in melanoma (about 50-75% of all patients with advanced disease), most of the pivotal prospective clinical trials exclude patients with intra-cranial metastases, certainly if their lesions are symptomatic and steroid-requiring and the degree of sensitivity of intra-cranial melanoma to immunotherapy remains uncertain, and requires further investigation especially in view of the demonstrable activity of RAF-MEK inhibitors in this clinical setting and the emergence of stereotactic radiotherapy. Our study aimed to evaluate the efficacy and toxicity of immunotherapy against advanced melanoma patients with brain metastases. In terms of comparative studies, only retrospective analyses could be identified. Based on 3 retrospective studies, treatment of patients with melanoma brain metastases with immunotherapeutic approaches improves overall survival substantially compared with supportive measures alone (no active anticancer treatment). The efficacy of targeted therapy appeared to be comparable to that of immune therapy in terms of overall survival, based on a small number of patients. The combination of concurrent radiation therapy to the brain and systemic immunotherapy led to improved overall survival compared to radiotherapy alone, suggesting potential synergism between the approaches, and combination treatment could be delivered safely. Our review supports the use of immunotherapeutic strategies for these patients although treatment efficacy appears to be lower for symptomatic lesions. In view of the extremely high efficacy of stereotactic radiotherapy approaches in the brain, understanding the interaction between radiotherapy and immunotherapy is vital and should be an area of active investigation.
免疫激活型抗CTLA4和抗PD1单克隆抗体（单独使用或联合使用）正用于治疗晚期黑色素瘤患者，并可带来持久缓解，约50 - 60%的患者可能实现长期总生存。尽管颅内转移在黑色素瘤中非常常见（约占所有晚期疾病患者的50 - 75%），但大多数关键的前瞻性临床试验都排除了有颅内转移的患者，尤其是当他们的病灶有症状且需要使用类固醇药物时，并且颅内黑色素瘤对免疫治疗的敏感程度仍不确定，需要进一步研究，特别是考虑到RAF - MEK抑制剂在这种临床情况下已证实的活性以及立体定向放射治疗的出现。我们的研究旨在评估免疫治疗对伴有脑转移的晚期黑色素瘤患者的疗效和毒性。在比较研究方面，仅能找到回顾性分析。基于3项回顾性研究，与单纯支持治疗（无积极抗癌治疗）相比，采用免疫治疗方法治疗黑色素瘤脑转移患者可显著提高总生存率。基于少数患者，在总生存方面，靶向治疗的疗效似乎与免疫治疗相当。与单纯放疗相比，脑同步放疗与全身免疫治疗联合可提高总生存率，提示两种方法之间可能存在协同作用，且联合治疗可安全实施。我们的综述支持对这些患者使用免疫治疗策略，尽管有症状的病灶治疗效果似乎较低。鉴于立体定向放射治疗方法在脑部的极高疗效，了解放疗与免疫治疗之间的相互作用至关重要，且应成为积极研究的领域。
