无进展死亡作为描述局部晚期非小细胞肺癌心脏放射效应的一个终点。
Death without progression as an endpoint to describe cardiac radiation effects in locally advanced non-small cell lung cancer.
作者信息
Yegya-Raman Nikhil, Kegelman Timothy P, Ho Lee Sang, Kallan Michael J, Kim Kristine N, Natarajan Jyotsna, Deek Matthew P, Zou Wei, O'Reilly Shannon E, Zhang Zheng, Levin William, Cengel Keith, Kao Gary, Cohen Roger B, Sun Lova L, Langer Corey J, Aggarwal Charu, Singh Aditi P, O'Quinn Rupal, Ky Bonnie, Apte Aditya, Deasy Joseph, Xiao Ying, Berman Abigail T, Jabbour Salma K, Feigenberg Steven J
机构信息
Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
出版信息
Clin Transl Radiat Oncol. 2023 Jan 13;39:100581. doi: 10.1016/j.ctro.2023.100581. eCollection 2023 Mar.
BACKGROUND AND PURPOSE
Prior studies have examined associations of cardiovascular substructure dose with overall survival (OS) or cardiac events after chemoradiotherapy (CRT) for non-small cell lung cancer (NSCLC). Herein, we investigate an alternative endpoint, death without cancer progression (DWP), which is potentially more specific than OS and more sensitive than cardiac events for understanding CRT toxicity.
MATERIALS AND METHODS
We retrospectively reviewed records of 187 patients with locally advanced or oligometastatic NSCLC treated with definitive CRT from 2008 to 2016 at a single institution. Dosimetric parameters to the heart, lung, and ten cardiovascular substructures were extracted. Charlson Comorbidity Index (CCI), excluding NSCLC diagnosis, was used to stratify patients into CCI low (0-2; n = 66), CCI intermediate (3-4; n = 78), and CCI high (≥5; n = 43) groups. Primary endpoint was DWP, modeled with competing risk regression. Secondary endpoints included OS. An external cohort consisted of 140 patients from another institution.
RESULTS
Median follow-up was 7.3 years for survivors. Death occurred in 143 patients (76.5 %), including death after progression in 118 (63.1 %) and DWP in 25 (13.4 %). On multivariable analysis, increasing CCI stratum and mean heart dose were associated with DWP. For mean heart dose ≥ 10 Gy vs < 10 Gy, DWP was higher (5-year rate, 16.9 % vs 6.7 %, p = 0.04) and OS worse (median, 22.9 vs 34.1 months, p < 0.001). Ventricle (left, right, and bilateral) and pericardial but not atrial substructure dose were associated with DWP, whereas all three were inversely associated with OS. Cutpoint analysis identified right ventricle mean dose ≥ 5.5 Gy as a predictor of DWP. In the external cohort, we confirmed an association of ventricle, but not atrial, dose with DWP.
CONCLUSION
Cardiovascular substructure dose showed distinct associations with DWP. Future cardiotoxicity studies in NSCLC could consider DWP as an endpoint.
背景与目的
既往研究探讨了非小细胞肺癌（NSCLC）放化疗（CRT）后心血管亚结构剂量与总生存期（OS）或心脏事件的相关性。在此，我们研究了另一个终点，即无癌症进展死亡（DWP），对于理解CRT毒性而言，它可能比OS更具特异性，比心脏事件更敏感。
材料与方法
我们回顾性分析了2008年至2016年在单一机构接受根治性CRT治疗的187例局部晚期或寡转移NSCLC患者的记录。提取心脏、肺和十个心血管亚结构的剂量学参数。使用排除NSCLC诊断的Charlson合并症指数（CCI）将患者分为CCI低（0 - 2；n = 66）、CCI中等（3 - 4；n = 78）和CCI高（≥5；n = 43）组。主要终点是DWP，采用竞争风险回归建模。次要终点包括OS。一个外部队列由来自另一家机构的140例患者组成。
结果
幸存者的中位随访时间为7.3年。143例患者（76.5%）死亡，其中118例（63.1%）为疾病进展后死亡，25例（13.4%）为无癌症进展死亡。多变量分析显示，CCI分层增加和平均心脏剂量与无癌症进展死亡相关。平均心脏剂量≥10 Gy与<10 Gy相比，无癌症进展死亡发生率更高（5年发生率，16.9%对6.7%，p = 0.04），总生存期更差（中位生存期，22.9个月对34.1个月，p < 0.001）。心室（左、右和双侧）和心包亚结构剂量与无癌症进展死亡相关，而心房亚结构剂量则无关，而这三者均与总生存期呈负相关。切点分析确定右心室平均剂量≥5.5 Gy是无癌症进展死亡的预测因素。在外部队列中，我们证实了心室剂量而非心房剂量与无癌症进展死亡相关。
结论
心血管亚结构剂量与无癌症进展死亡显示出不同的相关性。未来NSCLC心脏毒性研究可将无癌症进展死亡作为一个终点。
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