Combined radiotherapy and immunotherapy in urothelial bladder cancer: harnessing the full potential of the anti-tumor immune response
Combined radiotherapy and immunotherapy in urothelial bladder cancer: harnessing the full potential of the anti-tumor immune response
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DOI：
10.1007/s00345-020-03440-4
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发表时间：
2020-09-11
影响因子：
3.4
通讯作者：
Sargos, Paul
中科院分区：
文献类型：
--
作者：
Daro-Faye, Mame;Kassouf, Wassim;Sargos, Paul
目的放射治疗(RT)作为三联疗法的一部分，是治疗尿路上皮肌浸润性膀胱癌(MIBC)的一种有吸引力的替代疗法。越来越多的证据表明，RT的免疫调节作用及其与免疫治疗的潜在协同作用。本综述的目的是报告这一联合治疗的最新进展，包括RT免疫调节的机制，RT和免疫治疗相结合的实用方法，以及正在进行的膀胱癌临床试验。方法利用PubMed数据库检索2004年3月至2020年4月发表的关于放射治疗与免疫治疗相结合治疗局部或转移性MIBC的文章。搜索ClinicalTrials.gov和Clinicaltrialsregister.eu/也检索到关于这个主题的正在进行的临床试验。结果RT联合免疫治疗可导致免疫原性细胞死亡和免疫标志物增加，从而改善肿瘤控制。对于局限性MIBC，同时使用免疫治疗和低分割RT治疗存在安全性问题，因此首选新辅助或辅助免疫治疗。在转移的情况下，多点放射治疗与SBRT类剂量(=6GY/次)和同时免疫治疗的组合似乎在利用非局部性效应方面最有效。在MIBC中，至少有25项结合免疫疗法和RT的临床试验目前正在进行中，并将回答有关安全性、有效性和关于RT时间表、分割和靶区容量的实际考虑的悬而未决的问题。结论RT与免疫治疗有协同作用，可改善局部或转移性MIBC患者的肿瘤预后。临床试验结果令人翘首以待。
Purpose Radiotherapy (RT), as part of trimodal therapy, is an attractive alternative treatment in patients with urothelial muscle-invasive bladder cancer (MIBC). There is accumulating evidence suggesting the immunomodulatory effects of RT and its potential synergy when combined with immunotherapy. The aim of this review was to report on the most recent advances on this combination, including the mechanisms of RT immunomodulation, practical approach to combining RT and immunotherapy, and ongoing clinical trials in bladder cancer. Methods Using the PubMed database, we identified articles published between March 2004 and April 2020 on the combination of RT with immunotherapy in localized or metastatic MIBC. A search of the Clinicaltrials.gov and Clinicaltrialsregister.eu/ retrieved ongoing clinical trials on the topic as well. Results Combination of RT with immunotherapy leads to immunogenic cell death and an increase in immune markers thus leading to improved tumor control. For localized MIBC, there are safety concerns related to the use of concurrent immunotherapy with hypofractionated RT, thus neoadjuvant or adjuvant immunotherapy is preferred. In the metastatic setting, the combination of multi-site RT with SBRT-like doses (>= 6 Gy per fraction) and concurrent immunotherapy seems most efficacious at harnessing the abscopal effect. At least 25 clinical trials combining immunotherapy and RT in MIBC are currently ongoing and will answer pending questions on safety, efficacy, and practical considerations on RT scheduling, fractionation, and targets volumes. Conclusion RT has the potential to synergize with immunotherapy to improve oncological outcomes in patient with localized or metastatic MIBC. Clinical trials results are eagerly awaited.