Amsterdam UMC location AMC, Radiation Oncology, Amsterdam, The Netherlands.
RadboudUMC, Cardiothoracic surgery, Nijmegen, The Netherlands; Dutch Institute for Clinical Auditing, Leiden, The Netherlands.
Clin Lung Cancer. 2023 Mar;24(2):130-136. doi: 10.1016/j.cllc.2022.11.008. Epub 2022 Nov 25.
INTRODUCTION: Chemoradiotherapy (CRT) is the standard of care in inoperable non-small-cell lung cancer (NSCLC) patients, favoring concurrent (cCRT) over sequential CRT (seqCRT), with adjuvant immunotherapy in responders. Elderly and frail NSCLC patients have generally been excluded from trials in the past. In elderly patients however, the higher treatment related morbidity of cCRT, may outweigh the possible lower tumor control of seqCRT. For elderly patients with locally advanced NSCLC real-world data is essential to be able to balance treatment toxicity and treatment outcome. The aim of this study is to analyze acute toxicity and 3-month mortality of curative chemoradiation (CRT) in patients with stage III NSCLC and to analyze whether cCRT for elderly stage III NSCLC patients is safe. METHODS: The Dutch Lung Cancer Audit-Radiotherapy (DLCA-R) is a national lung cancer audit that started in 2013 for patients treated with curative intent radiotherapy. All Dutch patients treated for stage III NSCLC between 2015 and 2018 with seqCRT or cCRT for (primary or recurrent) stage III lung cancer are included in this population-based study. Information was collected on patient, tumor- and treatment characteristics and the incidence and severity of acute non-hematological toxicity (CTCAE-4 version 4.03) and mortality within 3 months after the end of radiotherapy. To evaluate the association between prognostic factors and outcome (acute toxicity and mortality within 3 months), an univariable and multivariable analysis was performed. The definition of cCRT was:radiotherapy started within 30 days after the start of chemotherapy. RESULTS: Out of all 20 Dutch departments of radiation oncology, 19 centers participated in the registry. A total of 2942 NSCLC stage III patients were treated with CRT. Of these 67.2% (n = 1977) were treated with cCRT (median age 66 years) and 32.8% (n = 965) were treated with seqCRT (median age 69 years). Good performance status (WHO 0-1) was scored in 88.6% for patients treated with cCRT and in 71.0% in the patients treated with seqCRT. Acute nonhematological 3-month toxicity (CTCAE grade ≥3 or radiation pneumonitis grade ≥2) was scored in 21.9% of the patients treated with cCRT and in 17.7% of the patients treated with seqCRT. The univariable analysis for acute toxicity showed significantly increased toxicity for cCRT (P = .008), WHO ≥2 (P = .006), and TNM IIIC (P = .031). The multivariable analysis for acute toxicity was significant for cCRT (P = .015), WHO ≥2 (P = .001) and TNM IIIC (P = .016). The univariable analysis for 3-month mortality showed significance for seqCRT (P = .025), WHO ≥2 (P < .001), higher cumulative radiotherapy dose (P < .001), higher gross tumor volume total (P = .020) and male patients (p < .001). None of these variables reached significance in the multivariable analysis for 3-month mortality. CONCLUSION: In this national lung cancer audit of inoperable NSCLC patients, 3-month toxicity was significantly higher in patients treated with cCRT (21.9% vs. 17.7% for seqCRT) higher TNM stage IIIC, and poor performance (WHO≥2) patients.The 3-months mortality was not significantly different for tested parameters. Age was not a risk factor for acute toxicity, nor 3 months mortality.
简介：在不可手术的非小细胞肺癌（NSCLC）患者中，放化疗（CRT）是标准治疗方法，同期放化疗（cCRT）优于序贯放化疗（seqCRT），且应答者辅助免疫治疗。过去，老年和体弱的 NSCLC 患者通常被排除在试验之外。然而，在老年患者中，cCRT 的治疗相关发病率较高，可能超过 seqCRT 较低的肿瘤控制率。对于局部晚期 NSCLC 的老年患者，真实世界的数据对于平衡治疗毒性和治疗结果至关重要。本研究旨在分析 III 期 NSCLC 患者接受根治性 CRT 的急性毒性和 3 个月死亡率，并分析 cCRT 治疗老年 III 期 NSCLC 患者是否安全。
方法：荷兰肺癌放疗登记处（DLCA-R）是一项始于 2013 年的全国性肺癌放疗登记处，旨在治疗有根治性放疗意愿的患者。本研究纳入了 2015 年至 2018 年期间接受 seqCRT 或 cCRT（原发性或复发性）治疗的 III 期 NSCLC 患者。本研究纳入了患者、肿瘤和治疗特征，以及急性非血液学毒性（CTCAE-4 版本 4.03）的发生率和严重程度，以及放疗结束后 3 个月内的死亡率。为了评估预后因素与结局（急性毒性和 3 个月内死亡率）之间的关联，进行了单变量和多变量分析。cCRT 的定义为：化疗开始后 30 天内开始放疗。
结果：在所有 20 个荷兰放射肿瘤学部门中，有 19 个中心参与了该登记处。共有 2942 例 III 期 NSCLC 患者接受 CRT 治疗。其中 67.2%（n=1977）接受 cCRT 治疗（中位年龄 66 岁），32.8%（n=965）接受 seqCRT 治疗（中位年龄 69 岁）。cCRT 治疗患者的良好表现状态（WHO 0-1）评分占 88.6%，seqCRT 治疗患者的评分占 71.0%。cCRT 治疗患者的急性非血液学 3 个月毒性（CTCAE 分级≥3 或放射性肺炎分级≥2）发生率为 21.9%，seqCRT 治疗患者为 17.7%。单变量分析显示，cCRT 治疗（P=0.008）、WHO≥2（P=0.006）和 TNM IIIC（P=0.031）与毒性显著相关。多变量分析显示，cCRT 治疗（P=0.015）、WHO≥2（P=0.001）和 TNM IIIC（P=0.016）与毒性显著相关。3 个月死亡率的单变量分析显示，seqCRT（P=0.025）、WHO≥2（P<0.001）、累积放疗剂量较高（P<0.001）、总肿瘤体积较大（P=0.020）和男性患者（P<0.001）与 3 个月死亡率显著相关。这些变量在多变量分析中均未达到 3 个月死亡率的显著水平。
结论：在这项不可手术的 NSCLC 患者的全国性肺癌放疗登记处研究中，cCRT 治疗患者的 3 个月毒性显著更高（cCRT 为 21.9%，seqCRT 为 17.7%），更高的 TNM 分期 IIIIC 期和较差的表现状态（WHO≥2）患者。测试参数的 3 个月死亡率没有显著差异。年龄不是急性毒性的危险因素，也不是 3 个月死亡率的危险因素。
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