Breen William G, Leventakos Konstantinos, Dong Haidong, Merrell Kenneth W
Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.
Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA.
J Thorac Dis. 2020 Nov;12(11):7011-7023. doi: 10.21037/jtd-2019-cptn-07.
Immunotherapy (IO) has become a standard treatment in patients with metastatic and locally advanced non-small cell lung cancer (NSCLC), and is now being tested in patients with early stage disease. IO agents currently in use for lung cancer target PD-1, PD-L1, and CTLA-4. While survival and tumor control have improved with IO, many patients have limited or short responses to IO. Therefore, methods to improve the systemic response to IO are needed. Radiation therapy (RT) is an integral component of lung cancer treatment, and may improve systemic response to IO by increasing antigen presentation, increasing co-stimulatory signaling, increasing T-cells recruitment, upregulating PD-L1, increasing tumor stromal lymphocyte infiltration, and altering the microenvironment. IO after definitive chemoradiation is now standard treatment in unresectable stage III NSCLC following publication of the PACIFIC clinical trial. For early stage NSCLC, IO is being investigated in conjunction with stereotactic body radiotherapy (SBRT). The benefit of adding RT to IO in patients with metastatic disease may be especially pronounced in patients with low baseline PD-L1 expression, potentially when delivered as a short course of SBRT, as supported by the PEMBRO-RT clinical trial. Current and ongoing clinical trials are evaluating the optimal radiation dose, timing, and sequencing of RT with IO.
免疫疗法（IO）已成为转移性和局部晚期非小细胞肺癌（NSCLC）患者的标准治疗方法，目前正在早期疾病患者中进行测试。目前用于肺癌的IO药物靶向PD-1、PD-L1和CTLA-4。虽然IO改善了生存率和肿瘤控制，但许多患者对IO的反应有限或短暂。因此，需要提高对IO的全身反应的方法。放射治疗（RT）是肺癌治疗的一个组成部分，可能通过增加抗原呈递、增加共刺激信号、增加T细胞募集、上调PD-L1、增加肿瘤基质淋巴细胞浸润以及改变微环境来改善对IO的全身反应。在PACIFIC临床试验发表后，确定性放化疗后的IO现在是不可切除的III期NSCLC的标准治疗方法。对于早期NSCLC，正在研究IO与立体定向体部放疗（SBRT）联合使用。在转移性疾病患者中，将RT添加到IO中的益处可能在基线PD-L1表达低的患者中尤其明显，可能是在作为短疗程SBRT进行时，这得到了PEMBRO-RT临床试验的支持。当前和正在进行的临床试验正在评估RT与IO的最佳放射剂量、时机和顺序。
