Ladbury Colton, Germino Elizabeth, Novak Jennifer, Liu Jason, Horne Zachary, Dyer Brandon, Glaser Scott
Department of Radiation Oncology, City of Hope National Cancer Center, Duarte, CA, USA.
Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, PA, USA.
Transl Cancer Res. 2021 May;10(5):2609-2619. doi: 10.21037/tcr-20-3019.
Definitive and adjuvant radiation and chemoradiation have been mainstays in the management of multiple gynecologic malignancies for decades. However, despite these treatments, the prognosis of patients with locally advanced, recurrent, refractory, and metastatic disease continues to be poor. Over the last decade, immune checkpoint inhibitors have emerged as a promising therapeutic modality, but response rates to monotherapy are low. Mounting basic science and translational research suggests that immunotherapy and radiation may act synergistically with the potential to improve clinical outcomes across multiple disease sites relative to monotherapy with either radiation or immunotherapy alone. Results from early clinical trials in other disease sites, and burgeoning trials within the gynecologic malignancies space hold promise for combined modality treatment. With increasing clinical data supporting combined modality therapy, there is interest in reevaluating treatment paradigms in gynecologic malignancies to improve the current standards of care. In this review, current proposed mechanisms, rationale, and evidence for treatment of gynecologic malignancies with combined radiation and immunotherapy, specifically immune checkpoint inhibitors, will be discussed. Additionally, although currently early and limited, existing clinical data will be summarized as it applies to cervical, endometrial, ovarian, and vulvar cancers. The status of current clinical trials investigating the sequencing, dosing, and fractionation of combined radiation and immunotherapy in these disease sites will also be reviewed.
几十年来，根治性放疗和辅助放疗以及放化疗一直是多种妇科恶性肿瘤治疗的主要手段。然而，尽管有这些治疗方法，局部晚期、复发、难治性和转移性疾病患者的预后仍然很差。在过去十年中，免疫检查点抑制剂已成为一种有前景的治疗方式，但单药治疗的有效率较低。越来越多的基础科学和转化研究表明，免疫疗法和放疗可能具有协同作用，相对于单独使用放疗或免疫疗法的单药治疗，有可能改善多个疾病部位的临床结果。其他疾病部位早期临床试验的结果以及妇科恶性肿瘤领域正在兴起的试验为联合治疗带来了希望。随着越来越多的临床数据支持联合治疗，人们有兴趣重新评估妇科恶性肿瘤的治疗模式，以提高当前的护理标准。在这篇综述中，将讨论目前提出的联合放疗和免疫疗法（特别是免疫检查点抑制剂）治疗妇科恶性肿瘤的机制、原理和证据。此外，尽管目前尚处于早期且有限，但将总结适用于宫颈癌、子宫内膜癌、卵巢癌和外阴癌的现有临床数据。还将综述目前在这些疾病部位研究联合放疗和免疫疗法的顺序、剂量和分割的临床试验状况。
