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用于预测鼻咽癌患者预后及诱导化疗疗效的生化标志物的构建与验证

Construction and validation of a biochemical signature to predict the prognosis and the benefit of induction chemotherapy in patients with nasopharyngeal carcinoma.

作者信息

Sun Xue-Song, Liu Sai-Lan, Xie Si-Yi, Sun Rui, Luo Dong-Hua, Chen Qiu-Yan, Mai Hai-Qiang

机构信息

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy Guangzhou, Guangdong 510060, P. R. China.

Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center 651 Dongfeng Road East, Guangzhou, Guangdong 510060, P. R. China.

出版信息

Am J Cancer Res. 2022 Apr 15;12(4):1635-1647. eCollection 2022.

Abstract

This study aimed to develop and validate a biochemical signature for predicting the prognosis of patients with nasopharyngeal carcinoma (NPC) and explore roles of the constructed signature for screening optimal candidates for induction chemotherapy (IC). The biochemical signature was constructed based on a retrospective cohort of 3742 patients from January 2008 to December 2010; 2078 patients from prospective studies from January 2011 to December 2012 and 2153 patients from January 2013 to December 2016 served as validation cohort A and validation cohort B. Overall survival (OS) was the primary endpoint. The least absolute shrinkage and selection operator coefficients on the Cox regression model were calculated to construct the prediction model with the data of 33 biochemical indicators. A total of six prognostic indicators, including sodium, alkaline phosphatase, lactate dehydrogenase, albumin, indirect bilirubin, and cystatin-C, were screened for constructing the biochemical signature. The patients were divided into low-risk and high-risk groups using an optimal cut-off value of 0.823. The patients in high-risk group had significantly lower OS and distant metastasis-free survival (DMFS) compared with patients in low-risk group in three cohorts (P < 0.05). Furthermore, among patients with high-risk scores in the combined cohort, the addition of IC to CCRT further improved their OS and DMFS, whereas patients with low-risk scores did not benefit from IC. Our study developed and validated a clinically useful biochemical signature that could predict the survival outcomes in NPC patients. This signature can help clinicians design personalized treatment strategies.

摘要

本研究旨在开发并验证一种用于预测鼻咽癌(NPC)患者预后的生化标志物,并探讨所构建标志物在筛选诱导化疗(IC)最佳候选患者中的作用。基于2008年1月至2010年12月的3742例患者的回顾性队列构建生化标志物;2011年1月至2012年12月前瞻性研究中的2078例患者以及2013年1月至2016年12月的2153例患者作为验证队列A和验证队列B。总生存期(OS)是主要终点。计算Cox回归模型上的最小绝对收缩和选择算子系数,以利用33种生化指标的数据构建预测模型。共筛选出包括钠、碱性磷酸酶、乳酸脱氢酶、白蛋白、间接胆红素和胱抑素-C在内的6个预后指标用于构建生化标志物。使用最佳临界值0.823将患者分为低风险组和高风险组。在三个队列中,高风险组患者的OS和无远处转移生存期(DMFS)显著低于低风险组患者(P<0.05)。此外,在联合队列中高风险评分的患者中,IC联合同步放化疗(CCRT)进一步改善了他们的OS和DMFS,而低风险评分的患者未从IC中获益。我们的研究开发并验证了一种临床上有用的生化标志物,其可预测NPC患者的生存结局。该标志物可帮助临床医生设计个性化治疗策略。

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Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma.吉西他滨和顺铂诱导化疗治疗鼻咽癌。
N Engl J Med. 2019 Sep 19;381(12):1124-1135. doi: 10.1056/NEJMoa1905287. Epub 2019 May 31.

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