不可手术的 III 期非小细胞肺癌患者同步放化疗联合或不联合免疫检查点抑制的首站转移模式：一项回顾性分析。
First-site-metastasis pattern in patients with inoperable stage III NSCLC treated with concurrent chemoradiotherapy with or without immune check-point inhibition: a retrospective analysis.
机构信息
Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany.
Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany.
出版信息
Strahlenther Onkol. 2024 Jul;200(7):614-623. doi: 10.1007/s00066-023-02175-6. Epub 2023 Nov 17.
PURPOSE
The aim of this study was to investigate a first-site-metastasis pattern (FSMP) in unresectable stage III NSCLC after concurrent chemoradiotherapy (cCRT) with or without immune checkpoint inhibition (ICI).
METHODS
We defined three patient subgroups according to the year of initial multimodal treatment: A (2011-2014), B (2015-2017) and C (2018-2020). Different treatment-related parameters were analyzed. Observed outcome parameters were brain metastasis-free survival (BMFS), extracranial distant metastasis-free survival (ecDMFS) and distant metastasis-free survival (DMFS).
RESULTS
136 patients treated between 2011 and 2020 were included with ≥ 60.0 Gy total dose and concurrent chemotherapy (cCRT); thirty-six (26%) received ICI. Median follow-up was 49.7 (range:0.7-126.1), median OS 31.2 (95% CI:16.4-30.3) months (23.4 for non-ICI vs not reached for ICI patients, p = 0.001). Median BMFS/ecDMFS/DMFS in subgroups A, B and C was 14.9/16.3/14.7 months, 20.6/12.9/12.7 months and not reached (NR)/NR/36.4 months (p = 0.004/0.001/0.016). For cCRT+ICI median BMFS was 53.1 vs. 19.1 months for cCRT alone (p = 0.005). Median ecDMFS achieved 55.2 vs. 17.9 (p = 0.003) and median DMFS 29.5 (95% CI: 1.4-57.6) vs 14.93 (95% CI:10.8-19.0) months (p = 0.031), respectively. Multivariate analysis showed that age over 65 (HR:1.629; p = 0.036), GTV ≥ 78 cc (HR: 2.100; p = 0.002) and V20 ≥ 30 (HR: 2.400; p = 0.002) were negative prognosticators for BMFS and GTV ≥ 78 cc for ecDMFS (HR: 1.739; p = 0.027). After onset of brain metastasis (BM), patients survived 13.3 (95% CI: 6.4-20.2) months and 8.6 months (95% CI: 1.6-15.5) after extracranial-distant-metastasis (ecDM). Patients with ecDM as FSMP reached significantly worse overall survival of 22.1 (range:14.4-29.8) vs. 40.1 (range:18.7-61.3) months (p = 0.034) in the rest of cohort. In contrast, BM as FSMP had no impact on OS.
CONCLUSION
This retrospective analysis of inoperable stage III NSCLC patients revealed that age over 65, V20 ≥ 30 and GTV ≥ 78 cc were prognosticators for BMFS and GTV ≥ 78 cc for ecDMFS. ICI treatment led to a significant improvement of BMFS, ecDMFS and DMFS. ecDM as FSMP was associated with significant deterioration of OS, whereas BM as FSMP was not.
目的
本研究旨在探讨同步放化疗（cCRT）联合或不联合免疫检查点抑制（ICI）治疗不可切除的 III 期非小细胞肺癌（NSCLC）后的首发转移模式（FSMP）。
方法
我们根据初始多模式治疗的年份将患者分为三个亚组：A（2011-2014 年）、B（2015-2017 年）和 C（2018-2020 年）。分析了不同的治疗相关参数。观察的结局参数为脑转移无进展生存期（BMFS）、颅外远处转移无进展生存期（ecDMFS）和远处转移无进展生存期（DMFS）。
结果
纳入了 2011 年至 2020 年间接受≥60.0Gy 总剂量和同步化疗（cCRT）的 136 例患者；其中 36 例（26%）接受了 ICI 治疗。中位随访时间为 49.7（范围：0.7-126.1）个月，中位总生存期（OS）为 31.2（95%CI：16.4-30.3）个月（非 ICI 组为 23.4，ICI 组未达到，p=0.001）。亚组 A、B 和 C 的中位 BMFS/ecDMFS/DMFS 分别为 14.9/16.3/14.7 个月、20.6/12.9/12.7 个月和未达到（NR）/NR/36.4 个月（p=0.004/0.001/0.016）。对于 cCRT+ICI，中位 BMFS 为 53.1 个月，而 cCRT 单独治疗为 19.1 个月（p=0.005）。中位 ecDMFS 达到 55.2 个月，而 17.9 个月（p=0.003），中位 DMFS 为 29.5（95%CI：1.4-57.6）和 14.93（95%CI：10.8-19.0）个月（p=0.031）。多变量分析显示，年龄超过 65 岁（HR：1.629；p=0.036）、GTV≥78cc（HR：2.100；p=0.002）和 V20≥30（HR：2.400；p=0.002）是 BMFS 的负预后因素，而 GTV≥78cc 是 ecDMFS 的负预后因素（HR：1.739；p=0.027）。发生脑转移（BM）后，患者存活 13.3（95%CI：6.4-20.2）和颅外远处转移（ecDM）后存活 8.6 个月（95%CI：1.6-15.5）。作为首发转移模式的 ecDM 的患者的总生存期明显较差，为 22.1（范围：14.4-29.8）个月，而其余队列的患者为 40.1（范围：18.7-61.3）个月（p=0.034）。相反，BM 作为首发转移模式对 OS 没有影响。
结论
本回顾性分析不可切除的 III 期 NSCLC 患者显示，年龄超过 65 岁、V20≥30 和 GTV≥78cc 是 BMFS 的预后因素，GTV≥78cc 是 ecDMFS 的预后因素。ICI 治疗显著改善了 BMFS、ecDMFS 和 DMFS。作为首发转移模式的 ecDM 与 OS 显著恶化相关，而 BM 作为首发转移模式则没有。
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