Swamy Kumara
Aster CMI, Bangalore, India.
Front Oncol. 2022 Jan 26;12:729250. doi: 10.3389/fonc.2022.729250. eCollection 2022.
In the stereotactic body radiotherapy (SBRT) and immunotherapy era, we are moving toward an "immunological radiation plan", i.e., radiation scheduling with abscopal effect as a vital endpoint as well. The literature review of part A enumerates the advantages of the intermediate dose of SBRT 6-10 Gy per fraction, appropriate use of dose painting, proper timing with immunotherapy, and the potential of immunoadjuvants to maximize cell kill in the irradiated lesions, found to have improved the abscopal effects. Part B summarizes part A, primarily the findings of animal trials, forming the basis of the tenets of the proposed model given in part C to realize the true abscopal potential of the SBRT tumor cell kill of the index lesions. Part C proposes a theoretical model highlighting tumor vasculature integrity as the central theme for converting "abscopal effect by chance" to "abscopal effect by design" using a harmonized combinatorial approach. The proposed model principally deals with the use of SBRT in strategizing increased cell kill in irradiated index tumors along with immunomodulators as a basis for improving the consistency of the abscopal effect. Included is the possible role of integrating immunotherapy just after SBRT, "cyclical" antiangiogenics, and immunoadjuvants/immune metabolites as abscopal effect enhancers of SBRT tumor cell kill. The proposed model suggests convergence research in adopting existing numerous SBRT abscopal enhancing strategies around the central point of sustained vascular integrity to develop decisive clinical trial protocols in the future.
在立体定向体部放射治疗(SBRT)和免疫治疗时代,我们正朝着“免疫放疗计划”迈进,即把具有远隔效应作为重要终点的放疗方案安排。A部分的文献综述列举了SBRT每次分割剂量为6 - 10 Gy的中等剂量的优势、剂量递增的合理应用、与免疫治疗的恰当时间配合以及免疫佐剂在最大化照射病灶内细胞杀伤方面的潜力,发现这些措施可改善远隔效应。B部分总结了A部分内容,主要是动物试验的结果,为C部分提出的模型原则奠定了基础,以实现SBRT对靶病灶肿瘤细胞杀伤的真正远隔效应潜力。C部分提出了一个理论模型,强调肿瘤血管系统完整性是核心主题,通过协调组合方法将“偶然的远隔效应”转化为“设计的远隔效应”。所提出的模型主要涉及利用SBRT来规划增加照射靶肿瘤内的细胞杀伤,并结合免疫调节剂作为改善远隔效应一致性的基础。其中包括在SBRT后立即整合免疫治疗、“周期性”抗血管生成药物以及免疫佐剂/免疫代谢产物作为SBRT肿瘤细胞杀伤远隔效应增强剂的可能作用。所提出的模型建议围绕持续血管完整性这一中心点,对现有的众多SBRT远隔效应增强策略进行整合研究,以制定未来决定性的临床试验方案。