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用于评估因骨转移而行放疗的转移性肺癌患者生存情况的列线图的开发与验证。

Development and Validation of a Nomogram for Assessing Survival in Patients With Metastatic Lung Cancer Referred for Radiotherapy for Bone Metastases.

机构信息

Department of Radiation Oncology, Linkou Chang Gung Memorial Hospital Medical Center, Taoyuan City, Taiwan.

Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.

出版信息

JAMA Netw Open. 2018 Oct 5;1(6):e183242. doi: 10.1001/jamanetworkopen.2018.3242.

Abstract

IMPORTANCE

A survival prediction model for patients with bone metastases arising from lung cancer would be highly valuable.

OBJECTIVE

To develop and validate a nomogram for assessing the survival probability of patients with metastatic lung cancer receiving radiotherapy for osseous metastases.

DESIGN, SETTING, PARTICIPANTS: In this prognostic study, the putative prognostic indicators for constructing the nomogram were identified using multivariable Cox regression analysis with backward elimination and model selection based on the Akaike information criterion. The nomogram was subjected to internal (bootstrap) and external validation; its calibration and discriminative ability were evaluated with calibration plots and the Uno C statistic, respectively. The training and validation set cohorts were from a tertiary medical center in northern Taiwan and a tertiary institution in southern Taiwan, respectively. The training set comprised 477 patients with metastatic lung cancer who received radiotherapy for osseous metastases between January 2000 and December 2013. The validation set comprised 235 similar patients treated between January 2011 and December 2017. Data analysis was conducted May 2018 to July 2018.

MAIN OUTCOMES AND MEASURES

The nomogram end points were death within 3, 6, and 12 months.

RESULTS

Of 477 patients in the training set, 292 patients (61.2%) were male, and the mean (SD) age was 62.86 (11.66) years. Of 235 patients in the validating set, 113 patients (48.1%) were male, and the mean (SD) age was 62.65 (11.49) years. In the training set, 186 (39%), 291 (61%), and 359 (75%) patients died within 3, 6, and 12 months, respectively, and the median overall survival was 4.21 (95% CI, 3.68-4.90) months. In the validating set, 84 (36%), 120 (51%), and 144 (61%) patients died within 3, 6, and 12 months, respectively, and the median overall survival was 5.20 (95% CI, 4.07-7.17) months. Body mass index (18.5 to <25 vs ≥25: hazard ratio [HR], 1.42; 95% CI, 1.14-1.78 and <18.5 vs ≥25: HR, 2.31; 95% CI, 1.56-3.44), histology (non-small cell vs small cell lung cancer: HR, 0.59; 95% CI, 0.41-0.86), epidermal growth factor receptor mutation (positive vs unknown: HR, 0.66; 95% CI, 0.46-0.93 and negative vs unknown: HR, 0.98; 95% CI, 0.66-1.45), smoking status (ever smoker vs never smoker: HR, 1.50; 95% CI, 1.24-1.83), age, and neutrophil to lymphocyte ratio were incorporated. The HRs of age and neutrophil to lymphocyte ratio were modeled nonlinearly with restricted cubic splines (both P < .001). The nomogram's discriminative ability was good in the training set (C statistic, ≥0.77; P < .001) and was validated using both an internal bootstrap method (C statistic, ≥0.76; P < .001) and an external validating set (C statistic, ≥0.75; P < .001). The calibration plots for the end points showed optimal agreement between the nomogram's assessment and actual observations.

CONCLUSIONS AND RELEVANCE

The nomogram (with web-based tool) can be useful for assessing the probability of survival at 3, 6, and 12 months in patients with metastatic lung cancer referred for radiotherapy to treat bone metastases, and it may guide radiation oncologists in treatment decision making and engaging patients in end-of-life discussions and/or hospice referrals at appropriate times.

摘要

重要性

对于肺癌骨转移患者的生存预测模型,将具有重要价值。

目的

开发并验证用于评估接受放射性治疗骨转移的转移性肺癌患者生存概率的列线图。

设计、地点、参与者:在这项预后研究中,使用多变量 Cox 回归分析进行候选预后指标的识别,并采用向后消除和基于赤池信息量准则的模型选择进行模型选择。对列线图进行内部(自举)和外部验证;通过校准图和 Uno C 统计量评估其校准和判别能力。训练集和验证集队列分别来自中国台湾北部的一家三级医疗中心和中国台湾南部的一家三级机构。训练集包括 477 名接受放射性治疗骨转移的转移性肺癌患者,他们在 2000 年 1 月至 2013 年 12 月期间接受治疗。验证集包括 235 名在 2011 年 1 月至 2017 年 12 月期间接受治疗的类似患者。数据分析于 2018 年 5 月至 7 月进行。

主要结果和措施

列线图终点为 3、6 和 12 个月内死亡。

结果

在训练集中,477 名患者中 292 名(61.2%)为男性,平均(SD)年龄为 62.86(11.66)岁。在验证集中,235 名患者中有 113 名(48.1%)为男性,平均(SD)年龄为 62.65(11.49)岁。在训练集中,186 名(39%)、291 名(61%)和 359 名(75%)患者分别在 3、6 和 12 个月内死亡,中位总生存期为 4.21(95%CI,3.68-4.90)个月。在验证集中,84 名(36%)、120 名(51%)和 144 名(61%)患者分别在 3、6 和 12 个月内死亡,中位总生存期为 5.20(95%CI,4.07-7.17)个月。体质指数(18.5 至<25 与≥25:风险比[HR],1.42;95%CI,1.14-1.78 和<18.5 与≥25:HR,2.31;95%CI,1.56-3.44)、组织学(非小细胞与小细胞肺癌:HR,0.59;95%CI,0.41-0.86)、表皮生长因子受体突变(阳性与未知:HR,0.66;95%CI,0.46-0.93 和阴性与未知:HR,0.98;95%CI,0.66-1.45)、吸烟状态(曾吸烟者与从不吸烟者:HR,1.50;95%CI,1.24-1.83)、年龄和中性粒细胞与淋巴细胞比值被纳入。年龄和中性粒细胞与淋巴细胞比值的 HR 采用受限立方样条进行非线性建模(均 P<0.001)。列线图的判别能力在训练集(C 统计量,≥0.77;P<0.001)和内部自举法(C 统计量,≥0.76;P<0.001)以及外部验证集(C 统计量,≥0.75;P<0.001)中均得到验证。终点的校准图显示,列线图的评估与实际观察之间具有最佳一致性。

结论和相关性

该列线图(带有网络工具)可用于评估接受放射性治疗骨转移的转移性肺癌患者在 3、6 和 12 个月时的生存概率,并可帮助放射肿瘤学家在适当的时间进行治疗决策和让患者参与临终讨论和/或临终关怀。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a7a/6324455/b317d71e1529/jamanetwopen-1-e183242-g001.jpg

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