Guo Tiantian, Chu Li, Chu Xiao, Yang Xi, Li Yida, Zhou Yue, Xu Dayu, Zhang Jinmeng, Wang Shengping, Hu Jie, Chu Qian, Moran Teresa, Cho William Chi-Shing, Merrell Kenneth W, Rizzo Stefania, Liu Yanfei, Ni Jianjiao, Zhu Zhengfei
Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Transl Lung Cancer Res. 2022 Feb;11(2):173-187. doi: 10.21037/tlcr-22-54.
Despite the emergence of programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors in the treatment of non-small cell lung cancer (NSCLC) patients with brain metastases (BMs), knowledge gaps remain regarding the impact and timing of cranial radiotherapy for patients receiving anti-PD-1/PD-L1 therapy.
Data were collected from 461 consecutive patients who received anti-PD-1/PD-L1 therapy for metastatic NSCLC at three institutions between June 2017 and September 2020. Intracranial progressive disease (PD) at the original disease sites, new sites, or both sites were classified as original-site PD (OPD), new-site PD (NPD), and original-and-new-site PD (ONPD), respectively. Patients with baseline BMs were categorized based on whether they received upfront cranial radiotherapy (uCRT) at any time point between the introduction of anti-PD-1/PD-L1 therapy and the first subsequent progression.
Of the 461 patients enrolled, 110 (23.9%) had BMs at baseline. The presence of BMs did not show independent prognostic value for progression-free survival (PFS) or overall survival (OS). During a median follow-up of 13.2 months, 96 patients with BMs developed PD, of whom 53 (55.2%) experienced intracranial PD. OPD, NPD, and ONPD were observed in 50.9%, 18.9%, and 30.2% of patients, respectively. Patients who received uCRT exhibited a longer median OS than those with BMs who did not receive uCRT (25.4 14.6 months, HR: 0.52, 95% CI: 0.29-0.91, P=0.041); this survival advantage was more prominent in patients with 1-4 BMs (median OS, 25.4 17.0 months, HR: 0.42, 95% CI: 0.22-0.81, P=0.024), and uCRT was independently associated with OS among these patients.
The presence of BMs at baseline was not associated with poorer OS in patients with metastatic NSCLC treated with anti-PD-1/PD-L1 therapy. Intracranial progression on PD-l/PD-L1 inhibitors predominately occurred at the original BM sites. The use of uCRT may improve OS, especially in NSCLC patients with 1-4 BMs.
尽管程序性死亡1/程序性死亡配体1（PD-1/PD-L1）抑制剂已出现用于治疗伴有脑转移（BMs）的非小细胞肺癌（NSCLC）患者，但对于接受抗PD-1/PD-L1治疗的患者，关于颅脑放疗的影响和时机仍存在知识空白。
收集了2017年6月至2020年9月期间在三家机构接受抗PD-1/PD-L1治疗的461例转移性NSCLC连续患者的数据。原发疾病部位、新部位或两个部位的颅内进展性疾病（PD）分别被分类为原发部位PD（OPD）、新部位PD（NPD）和原发及新部位PD（ONPD）。基线时有BMs的患者根据在引入抗PD-1/PD-L1治疗至首次后续进展之间的任何时间点是否接受了 upfront 颅脑放疗（uCRT）进行分类。
在纳入的461例患者中，110例（23.9%）基线时有BMs存在。BMs的存在对无进展生存期（PFS）或总生存期（OS）未显示出独立的预后价值。在中位随访13.2个月期间，110例有BMs的患者发生了PD，其中53例（55.2%）经历了颅内PD。OPD、NPD和ONPD分别在50.9%、18.9%和30.2%的患者中观察到。接受uCRT的患者的中位OS长于未接受uCRT的有BMs的患者（25.4对14.6个月，HR：0.52，95%CI：0.29 - 0.91，P = 0.041）；这种生存优势在有1 - 4个BMs的患者中更显著（中位OS，25.4对17.0个月，HR：0.42，95%CI：0. – 0.81，P = 0.024），并且在这些患者中uCRT与OS独立相关。
在接受抗PD-1/PD-L1治疗的转移性NSCLC患者中，基线时BMs的存在与较差的OS无关。PD-1/PD-L1抑制剂的颅内进展主要发生在原发BM部位。uCRT的使用可能改善OS，尤其是在有1 - 4个BMs的NSCLC患者中。
