预估免疫细胞受照剂量对周围型早期NSCLC患者预后的影响

Impact of radiation dose to the immune system on prognosis for peripheral early-stage NSCLC treated with stereotactic body radiation therapy

目的研究放疗过程中机体免疫系统的受照射剂量对接受立体定向放疗(SBRT)的周围型早期非小细胞肺癌(ES-NSCLC)患者疾病进展和生存的影响。方法回顾性分析2007年1月至2020年12月在天津医科大学肿瘤医院经病理确诊为周围型ES-NSCLC且接受SBRT治疗患者的资料。引用并验证放疗过程中“估计机体免疫细胞所受的辐射剂量”(EDRIC)对接受SBRT治疗的ES-NSCLC患者预后的影响。EDRIC的计算公式采用孔凤鸣教授团队首先提出并由Ladbury等改进的公式。采用Kaplan-Meier法和Cox比例风险回归估计肿瘤特异性生存(CSS)、无进展生存(PFS)、无局部进展生存(LPFS)和无远处转移生存(DMFS)。采用Pearson相关分析评估各变量之间的相关性。结果179例患者SBRT的中位处方剂量为60(范围为48~60)Gy,中位分割次数为5(范围为3~10)次,中位随访时间为52.17(范围为1.17~154.77)个月。中位大体肿瘤体积(GTV)和中位EDRIC分别是10.98(范围为0.91~120.34)cm3和2.064(范围为0.426~6.015)Gy。Person相关分析显示,GTV和EDRIC呈正相关(r=0.712,P<0.001)。多因素分析显示,EDRIC是CSS和DMFS重要的预后变量,较高的EDRIC与较差的CSS(HR=1.763,P=0.004)和DMFS(HR=1.902,P=0.004)显著相关。依据EDRIC的四分位数进行分组的组间比较:与EDRIC≤1.56 Gy的患者相比,EDRIC>2.64 Gy(P<0.001)和EDRIC为<2.06~2.64 Gy(P=0.049)患者的CSS明显降低。DMFS在EDRIC按照四分位数分组之间的差异有统计学意义(与EDRIC≤1.56 Gy相比,P值分别是<0.001、0.004、0.022)。结论EDRIC是接受SBRT治疗的周围型ES-NSCLC患者CSS和DMFS的重要预测因素,提示在放疗过程中免疫系统所受辐射剂量对预后的影响不容忽视,EDRIC有助于量化SBRT对机体免疫系统的影响。

Objective To investigate the effects of radiation dose to the host immune system during radiotherapy on disease progression and survival in patients with peripheral early-stage non-small cell lung cancer(ES-NSCLC)receiving stereotactic body radiation therapy(SBRT).Methods Clinical data of pathologically confirmed ES-NSCLC patients who were treated with SBRT at Tianjin Medical University Cancer Institute and Hospital between January 2007 and December 2020 were retrospectively analyzed.The prognostic significance of the estimated dose of radiation to immune cells(EDRIC)in ES-NSCLC patients undergoing SBRT was cited and validated.EDRIC was calculated using the model developed by Kong et al.and improved by Ladbury et al.Kaplan-Meier method and Cox proportional hazards regression were adopted to estimate cancer-specific survival(CSS),progression-free survival(PFS),local progression-free survival(LPFS),and distant metastasis-free survival(DMFS).Pearson's correlation was used to assess the correlation between variables.Results The median prescription dose/fraction was 60 Gy/5 fractions(range:48-60 Gy in 3-10 fractions).The median follow-up time was 52.17(1.17-154.77)months.The median gross tumor volume(GTV)and EDRIC were 10.98(0.91-120.34)cm3 and 2.064(0.426-6.015)Gy,respectively.Person's correlation analysis showed that GTV was positively correlated with EDRIC(r=0.712,P<0.001).In multivariate analysis,EDRIC was an important prognostic variable of CSS and DMFS.Higher EDRIC was significantly associated with worse CSS(HR=1.763,P=0.004)and DMFS(HR=1.902,P=0.004).Compared to patients with EDRIC≤1.56 Gy,those with EDRIC>2.64 Gy and EDRIC between<2.06-2.64 Gy exhibited significantly lower CSS(P<0.001,P=0.049).There were significant differences in DMFS among the groups divided by quartiles of EDRIC(compared to EDRIC≤1.56 Gy,the P values were<0.001,0.004,and 0.022 respectively).Conclusions EDRIC is an important predictor of CSS and DMFS in ES-NSCLC patients treated with SBRT,suggesting that radiation dose to the immune system is a critical determinant of treatment outcomes.EDRIC can be used to quantify the effects of radiation therapy on the host immune system.