Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China.
Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China.
Clin Lung Cancer. 2018 Jul;19(4):e399-e404. doi: 10.1016/j.cllc.2017.12.012. Epub 2018 Jan 4.
Stereotactic ablative body radiotherapy (SABR) represents an exciting, tolerable, and highly effective form of radiotherapy. Ongoing investigations into the interactions between radiotherapy and the immune system have uncovered new mechanisms that can be exploited to improve efficacy. We determined whether baseline or posttreatment immune parameters could predict disease control and toxicity in stage I non-small-cell lung cancer (NSCLC) patients treated with SABR.
Peripheral blood samples were collected from 62 patients 24 hours before treatment and within 4 weeks after treatment for lymphocyte subset count analysis. All peripheral blood samples were analyzed by flow cytometry. Associated parameters were evaluated to determine their association with progression-free survival (PFS) and symptomatic radiation pneumonitis (grade 2 or higher). The survival rates were estimated with Kaplan-Meier and multivariable analyses using binary logistic regression analysis or a Cox proportional hazards model.
At a median follow-up time of 36.0 months, the PFS rates for years 1, 2, and 3 were 91.0%, 82.5%, and 48.9%, respectively. The multivariable logistic regression analysis showed that only proportion of lung receiving 20 Gy of radiotherapy (odds ratio = 1.41; 95% confidence interval, 1.05-1.87; P = .023) and mean lung dose (odds ratio = 2.02; 95% confidence interval, 1.16-3.53; P = .016) were associated with symptomatic radiation pneumonitis (grade 2 or higher). Moreover, the immune parameters had no predictive value. In the multivariable Cox regression analysis, an elevated posttreatment cytotoxic CD8 T-cell level was an independent prognostic factor for longer PFS in stage I NSCLC (hazard ratio, 1.16; 95% confidence interval, 1.01-1.28; P = .01).
A higher posttreatment cytotoxic CD8 T-cell level was predictive of better PFS in stage I NSCLC patients receiving SABR. Thus, enhancing tumor antigen-specific cellular immunity by combining radiotherapy and immunotherapy might be a crucial strategy for improving survival in these patients.
立体定向消融体放射治疗(SABR)是一种令人兴奋、耐受良好且非常有效的放射治疗形式。对放射治疗与免疫系统相互作用的持续研究揭示了新的机制,可以利用这些机制来提高疗效。我们确定了在接受 SABR 治疗的 I 期非小细胞肺癌(NSCLC)患者中,基线或治疗后免疫参数是否可以预测疾病控制和毒性。
在治疗前 24 小时和治疗后 4 周内,从 62 名患者中采集外周血样本,用于淋巴细胞亚群计数分析。所有外周血样本均通过流式细胞术进行分析。评估相关参数,以确定它们与无进展生存期(PFS)和有症状的放射性肺炎(2 级或更高)的相关性。使用 Kaplan-Meier 法和多变量分析,使用二元逻辑回归分析或 Cox 比例风险模型估计生存率。
在中位随访时间为 36.0 个月时,第 1、2 和 3 年的 PFS 率分别为 91.0%、82.5%和 48.9%。多变量逻辑回归分析显示,仅肺接受 20Gy 放射治疗的比例(比值比=1.41;95%置信区间,1.05-1.87;P=0.023)和平均肺剂量(比值比=2.02;95%置信区间,1.16-3.53;P=0.016)与有症状的放射性肺炎(2 级或更高)相关。此外,免疫参数没有预测价值。在多变量 Cox 回归分析中,治疗后细胞毒性 CD8 T 细胞水平升高是 I 期 NSCLC 患者更长 PFS 的独立预后因素(风险比,1.16;95%置信区间,1.01-1.28;P=0.01)。
在接受 SABR 治疗的 I 期 NSCLC 患者中,治疗后细胞毒性 CD8 T 细胞水平升高与更好的 PFS 相关。因此,通过将放射治疗与免疫治疗相结合来增强肿瘤抗原特异性细胞免疫可能是提高这些患者生存率的关键策略。