Department of Oncology, Radiation Oncology, University of Torino, Italy.
Department of Medical Sciences, Dermatology/Oncology, University of Torino, Italy.
Radiother Oncol. 2016 Jul;120(1):1-12. doi: 10.1016/j.radonc.2016.06.003. Epub 2016 Jun 23.
The therapeutic landscape of metastatic melanoma drastically changed after the introduction of targeted therapies and immunotherapy, in particular immune checkpoints inhibitors (ICI). In recent years, positive effects on the immune system associated to radiotherapy (RT) were discovered, and radiation has been tested in combination with ICI in both pre-clinical and clinical studies (many of them still ongoing). We here summarize the rationale and the preliminary clinical results of this approach.
In the first part of this review article, redacted with narrative non-systematic methodology, we describe the clinical results of immune checkpoints blockade in melanoma as well as the biological basis for the combination of ICI with RT; in the second part, we systematically review scientific publications reporting on the clinical results of the combination of ICI and RT for advanced melanoma.
The biological and mechanistic rationale behind the combination of ICI and radiation is well supported by several preclinical findings. Retrospective observational series and few prospective trials support the potential synergistic effect between radiation and ICI for metastatic melanoma.
RT may potentiate anti-melanoma activity of ICI by enhancing response on both target and non-target lesions. Several prospective trials are ongoing with the aim of further exploring this combination in the clinical setting, hopefully confirming initial observations and opening a new therapeutic window for advanced melanoma patients.
在引入靶向治疗和免疫疗法，特别是免疫检查点抑制剂（ICI）后，转移性黑色素瘤的治疗格局发生了巨大变化。近年来，人们发现放疗（RT）对免疫系统有积极影响，并且已经在临床前和临床试验中对 RT 联合 ICI 进行了测试（其中许多仍在进行中）。我们在这里总结了这种方法的基本原理和初步临床结果。
在这篇综述文章的第一部分，我们采用叙述性非系统性方法描述了 ICI 在黑色素瘤中的临床结果，以及 ICI 与 RT 联合应用的生物学基础；在第二部分，我们系统地回顾了报道晚期黑色素瘤ICI 和 RT 联合应用临床结果的科学出版物。
ICI 和放疗联合应用的生物学和机制原理得到了许多临床前发现的很好支持。回顾性观察性研究和少数前瞻性试验支持 RT 和 ICI 联合治疗转移性黑色素瘤的潜在协同作用。
RT 可能通过增强靶病灶和非靶病灶的反应来增强 ICI 的抗黑色素瘤活性。目前正在进行几项前瞻性试验，旨在进一步探索这种联合治疗在临床环境中的应用，希望能证实初步观察结果，并为晚期黑色素瘤患者开辟新的治疗窗口。
