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度伐利尤单抗用于局部晚期非小细胞肺癌放化疗后的临床实践结果显示,其显著延长了无远处转移生存期、无进展生存期和总生存期。

Durvalumab after chemoradiotherapy for locally advanced non-small cell lung cancer prolonged distant metastasis-free survival, progression-free survival and overall survival in clinical practice.

机构信息

Department of Radiation Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.

出版信息

BMC Cancer. 2022 Apr 4;22(1):364. doi: 10.1186/s12885-022-09354-1.

Abstract

BACKGROUND

In clinical practice, the effect of durvalumab and radiation pneumonitis (RP) on survival after intensity-modulated radiotherapy (IMRT) is not fully understood. The purpose of this retrospective study was to investigate factors related to distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS) after IMRT for locally advanced non-small cell lung cancer (LA-NSCLC).

METHODS

All patients who were treated with conventional fractionated IMRT for LA-NSCLC between April 2016 and March 2021 were eligible. Time-to-event data were assessed by using the Kaplan-Meier estimator, and the Cox proportional hazards model was used for prognostic factor analyses. Factors that emerged after the start of IMRT, such as durvalumab administration or the development of RP, were analysed as time-dependent covariates.

RESULTS

A total of 68 consecutive patients treated with conventional fractionated IMRT for LA-NSCLC were analysed. Sixty-six patients completed radiotherapy, 50 patients received concurrent chemotherapy, and 36 patients received adjuvant durvalumab. During the median follow-up period of 14.3 months, 23 patients died, and tumour progression occurred in 37 patients, including 28 patients with distant metastases. The 1-year DMFS rate, PFS rate and OS rate were 59.9%, 48.7% and 84.2%, respectively. Grade 2 RP occurred in 16 patients, grade 3 in 6 patients and grade 5 in 1 patient. The 1-year cumulative incidences of grade 2 or higher RP and grade 3 or higher RP were 33.8% and 10.3%, respectively. The results of multivariate analyses showed that durvalumab had a significantly lower hazard ratio (HR) for DMFS, PFS and OS (HR 0.31, p < 0.01; HR 0.33, p < 0.01 and HR 0.32, p = 0.02), respectively. Grade 2 or higher RP showed significance for DMFS and a nonsignificant trend for OS (HR 2.28, p = 0.04 and HR 2.12, p = 0.13), respectively, whereas a higher percentage of lung volume receiving 20 Gy or higher was significant for PFS (HR 2.25, p = 0.01).

CONCLUSIONS

In clinical practice, durvalumab administration following IMRT with concomitant chemotherapy showed a significant survival benefit. Reducing the risk of grade 2 or higher RP would also be beneficial.

摘要

背景

在临床实践中,度伐利尤单抗和放射性肺炎(RP)对调强放疗(IMRT)后生存的影响尚不完全清楚。本回顾性研究的目的是探讨与局部晚期非小细胞肺癌(LA-NSCLC)接受 IMRT 后无远处转移生存(DMFS)、无进展生存(PFS)和总生存(OS)相关的因素。

方法

所有在 2016 年 4 月至 2021 年 3 月期间接受常规分割 IMRT 治疗的 LA-NSCLC 患者均符合条件。使用 Kaplan-Meier 估计法评估时间事件数据,并使用 Cox 比例风险模型进行预后因素分析。在 IMRT 开始后出现的因素,如度伐利尤单抗的使用或 RP 的发生,被分析为时间依赖性协变量。

结果

共分析了 68 例接受常规分割 IMRT 治疗的 LA-NSCLC 患者。66 例患者完成了放疗,50 例患者接受了同步化疗,36 例患者接受了辅助度伐利尤单抗治疗。在中位随访 14.3 个月期间,23 例患者死亡,37 例患者出现肿瘤进展,包括 28 例远处转移。1 年 DMFS 率、PFS 率和 OS 率分别为 59.9%、48.7%和 84.2%。16 例患者发生 2 级 RP,6 例患者发生 3 级 RP,1 例患者发生 5 级 RP。1 年 2 级或以上 RP 和 3 级或以上 RP 的累积发生率分别为 33.8%和 10.3%。多变量分析结果表明,度伐利尤单抗对 DMFS、PFS 和 OS 的风险比(HR)显著降低(HR 0.31,p<0.01;HR 0.33,p<0.01 和 HR 0.32,p=0.02)。2 级或以上 RP 对 DMFS 有显著意义,对 OS 有非显著趋势(HR 2.28,p=0.04 和 HR 2.12,p=0.13),而肺 20Gy 及以上体积接受剂量越高对 PFS 有显著意义(HR 2.25,p=0.01)。

结论

在临床实践中,IMRT 联合化疗后使用度伐利尤单抗治疗具有显著的生存获益。降低 2 级或以上 RP 的风险也将是有益的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad47/8981776/b85930f97957/12885_2022_9354_Fig1_HTML.jpg

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