Multifactorial risk factors for mortality after chemotherapy and radiotherapy for non-small cell lung cancer
Multifactorial risk factors for mortality after chemotherapy and radiotherapy for non-small cell lung cancer
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DOI：
10.1016/j.radonc.2019.09.005
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发表时间：
2020-11-01
影响因子：
5.7
通讯作者：
De Ruysscher, Dirk
中科院分区：
文献类型：
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作者：
Defraene, Gilles;Dankers, Frank J. W. M.;De Ruysscher, Dirk
背景和目的：非小细胞肺癌(NSCLC)患者心脏辐射剂量越高，死亡率越高。然而，当其他死亡危险因素也被考虑在内时，心脏剂量的贡献是未知的。材料和方法：我们构建了明确的非小细胞肺癌放化疗后死亡率的外部验证预测模型。对145例I-IIIB期非小细胞肺癌患者建立模型。临床(表现状态、年龄、合并原发肿瘤和受累淋巴结的大体肿瘤体积(GTV)、当前吸烟者)和剂量学(平均肺(MLD)和心脏(MHD)剂量)变量被考虑在内。采用5次交叉验证建立预测12个月和24个月死亡率的多变量Logistic回归模型。结果：结合GTV、吸烟者和/或MHD的最佳判别预测模型：12个月和24个月的自举AUC(95%CI)分别为0.74(0.66~0.78)和0.69(0.55~0.74)。在外部验证时，24个月死亡率GTV-Smoker-MHD模型稳健地显示出中等分辨率(模型更新前AUC=0.61-0.64，模型更新后AUC=0.64-0.65)，与仅GTV模型相比，改善有限0.01-0.07，校正斜率(0.64-0.65)。该模型可以识别哪些患者可能需要减少MHD(例如PPV=77%，NPV=52%(60%截断值))。结论：肿瘤体积与非小细胞肺癌放化疗后头两年的死亡风险密切相关。模型表明，减少心脏剂量的努力可能与小肿瘤有关，吸烟与生存有重要的负相关。(C)2019爱思唯尔B.V.保留所有权利。
Background and purpose: A higher radiation dose to the heart is known to be associated with increased mortality in non-small cell lung cancer (NSCLC) patients. It is however unknown what the contribution of the heart dose is when other risk factors for mortality are also accounted for.Materials and methods: We constructed and externally validated prediction models of mortality after definitive chemoradiotherapy for NSCLC. Models were developed in 145 stage I-IIIB NSCLC patients. Clinical (performance status, age, gross tumour volume (GTV) combining primary tumour and involved lymph nodes, current smoker) and dosimetric (mean lung (MLD) and heart (MHD) dose) variables were considered. Multivariable logistic regression models predicting 12 and 24 month mortality were built in 5-fold cross-validation. Discrimination and calibration was assessed in 3 external validation datasets containing 878 (via distributed learning), 127 and 96 NSCLC patients.Results: The best discriminating prediction models combined GTV, smoker and/or MHD: bootstrapping AUC (95% CI) of 0.74 (0.66-0.78) and 0.69 (0.55-0.74) at 12 and 24 months. At external validation, the 24 month mortality GTV-smoker-MHD model robustly showed moderate discrimination (AUC = 0.61- 0.64 before and 0.64-0.65 after model update) with limited 0.01-0.07 improvement over a GTV-only model, and calibration slope (0.64-0.65). This model can identify patients for whom a MHD reduction may be useful (e.g. PPV = 77%, NPV = 52% (60% cut-off)).Conclusions: Tumour volume is strongly related to mortality risk in the first 2 years after chemoradiotherapy for NSCLC. Modelling indicates that efforts to reduce cardiac dose may be relevant for small tumours and that smoking has an important negative association with survival. (C) 2019 Elsevier B.V. All rights reserved.