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一种用于评估结直肠癌脑转移患者生存率的新列线图。

A new nomogram for estimating survival in patients with brain metastases secondary to colorectal cancer.

作者信息

Pietrantonio Filippo, Aprile Giuseppe, Rimassa Lorenza, Franco Pierfrancesco, Lonardi Sara, Cremolini Chiara, Biondani Pamela, Sbicego Elena Lara, Pasqualetti Francesco, Tomasello Gianluca, Niger Monica, Casagrande Mariaelena, Ghidini Michele, Muni Roberta, Montrone Sabrina, Bergamo Francesca, Berenato Rosa, Fontanella Caterina, Bozzarelli Silvia, Moretto Roberto, Battaglin Francesca, Di Bartolomeo Maria, de Braud Filippo, Miceli Rosalba

机构信息

Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Department of Oncology, University and General Hospital, Udine, Italy.

出版信息

Radiother Oncol. 2015 Nov;117(2):315-21. doi: 10.1016/j.radonc.2015.08.023. Epub 2015 Sep 4.

Abstract

BACKGROUND

The prognosis of brain metastases (BM) in colorectal cancer (CRC) is extremely poor, but the incidence is increasing. The performance of existing prognostic classifications such as recursive partitioning analysis (RPA) and graded prognostic assessment (GPA) has never been evaluated in this specific setting. Moreover, the development of nomograms for estimating survival in such patients could be extremely helpful for treating physicians.

PATIENTS AND METHODS

Between 2000 and 2013, data from 227 patients with BM from CRC were collected at 8 Italian institutions. Overall survival (OS) was estimated with the Kaplan-Meier method and statistical comparison between curves was performed using the log-rank test. The discriminative ability for OS of RPA and GPA was assessed by the Harrell C-index from univariable Cox models. Putative prognostic factors for OS were also studied by multivariable Cox analysis, using the Harrell C index to evaluate the model discriminative ability. After a backward variable selection, a nomogram was developed to predict median survival time from individual patient- and tumor-related characteristics. The nomogram was externally validated on an independent series.

RESULTS

After a median follow-up of 59 months, fifty percent of patients were still at risk at 5 months. The C index was 0.594 and 0.607 for the RPA and GPA classifications, respectively. The C-index associated with the final multivariable Cox model used for developing the nomogram was 0.643; the favorable prognostic factors for survival were lower age (p=0.061), better Karnofsky performance status (p<0.001), supratentorial site of BM (p<0.001), and lower number of BM (p=0.035). The C index evaluated on the validation series was 0.733, even better than in the development series; also, the calibration of nomogram predictions was good.

CONCLUSION

The C-index associated to the nomogram model was slightly higher than that obtained for the RPA and GPA classifications. Most importantly, the very satisfactory results of nomogram validation on the external series, make us confident that our instrument may assist in prognostic assessment, treatment decision making, and enrollment into clinical trials.

摘要

背景

结直肠癌(CRC)脑转移(BM)的预后极差,但发病率却在上升。现有预后分类方法,如递归划分分析(RPA)和分级预后评估(GPA),在这种特定情况下的表现从未得到评估。此外,为此类患者制定生存预测列线图对治疗医生可能极为有用。

患者与方法

2000年至2013年间,意大利8家机构收集了227例CRC脑转移患者的数据。采用Kaplan-Meier法估计总生存期(OS),并使用对数秩检验对曲线进行统计学比较。通过单变量Cox模型的Harrell C指数评估RPA和GPA对OS的判别能力。还通过多变量Cox分析研究OS的潜在预后因素,使用Harrell C指数评估模型判别能力。经过反向变量选择,制定了一个列线图,根据个体患者和肿瘤相关特征预测中位生存时间。该列线图在一个独立队列中进行了外部验证。

结果

中位随访59个月后,50%的患者在5个月时仍处于风险中。RPA和GPA分类的C指数分别为0.594和0.607。用于制定列线图的最终多变量Cox模型的C指数为0.643;生存的有利预后因素为年龄较小(p = 0.061)、卡诺夫斯基功能状态较好(p < 0.001)、BM位于幕上部位(p < 0.001)以及BM数量较少(p = 0.035)。在验证队列中评估的C指数为0.733,甚至优于开发队列;此外,列线图预测的校准良好。

结论

列线图模型的C指数略高于RPA和GPA分类的C指数。最重要的是,列线图在外部队列验证中取得了非常令人满意的结果,这让我们相信我们的工具可能有助于预后评估、治疗决策以及临床试验入组。

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