Cell:斯坦福科学家建立癌症患者长期预后的预测模型,1-5年内癌症进展预测精准率超八成,还可指导用药

2019-07-17 奇点糕 奇点网

最近,斯坦福大学科学家开发了这样一个水晶球,叫“连续个体化风险指标”模型,这个模型能根据一些实时的检测指标,准确预测癌症病人12-60个月内的进展风险。并且还能指导病人采取最合适的治疗方法。

最近,斯坦福大学科学家开发了这样一个水晶球,叫“连续个体化风险指标”模型,这个模型能根据一些实时的检测指标,准确预测癌症病人12-60个月内的进展风险。并且还能指导病人采取最合适的治疗方法。

目前,该模型已在弥漫性大B细胞淋巴瘤、慢性淋巴细胞白血病以及乳腺癌中取得了良好的效果,相信它能极大地推动精准医疗的发展。相关研究发表在顶级学术期刊《细胞》上,论文的第一作者的是David M. Kurtz博士,通讯作者是Ash A. Alizadeh教授。


Alizadeh教授(右)(图片来自斯坦福大学官网)

对于很多身患重病的人来说,准确预测长期可能出现的结果,是一件生死攸关的大事。

因为这关系到什么时候治,怎么治的问题。

此外,由于癌症异质性的存在,不同患者或同一患者不同的时期,疾病状态都会不同,长期结果也会有差异,需要不同的应对措施[2]。

因此,只有准确判断不同患者在不同时刻的预后,才能进行精确的治疗,以使患者获益最大化,这才是精准医疗的意义所在。

不过,要对每个患者都做到个性化治疗,可不是一件简单的事。一方面,要对每个患者都能准确判断其预后;另一方面,还需有一个适用于大多数患者的通用预测工具,不然成本将无比高昂。

要同时满足这两个条件,才能达到精准医疗时代的要求。


精准医疗(图片来自reverserett.org)

目前,科学家们已经发现了很多风险因子,能对患者的预后做出一定的预测,例如可以对患者进行危险分级,以及预测药物的治疗效果等等[3]。

不过,这些风险因子预测的准确性、适用范围以及长期效果,都有很大的局限,离精准医疗的要求,还相去甚远。

怎么办呢?既然单个风险因子不行,那就把它们联合起来使用。

Alizadeh团队的研究人员收集之前11个研究中2500名弥漫性大B细胞淋巴瘤患者的数据,选取了几个之前预测效果不错的风险因子,包括国际预后指数(IPI)、分子标志、影像组学特征、ctDNA、微小残留病变(MDR),分别在患者治疗前、治疗中和治疗结束后的不同时期获得这些数据,通过贝叶斯公式,建立了一个“连续个体化风险指标”模型。


模型构建流程

研究人员用这个模型来预测患者的预后,并用已知的预后结果,对模型进行反馈和修正,最后得到一个修正好的模型。

他们用一个队列对这个模型进行了检验,让其预测患者24个月的无事件生存率(EFS)情况,发现曲线下面积达到0.81。用该模型预测患者24个月的总生存率时,效果更好,曲线下面积达到了0.86。

这个模型不只是对24个月内的预测有效,分别让其预测患者12-18-24-30-36个月的EFS,发现曲线下面积都稳定在0.8以上,可见这个模型对弥漫性大B细胞淋巴瘤患者长期风险的预测,具有相当的稳定性。

随后,研究人员又在其他癌种里测试了该“水晶球”的预言能力。

他们用慢性淋巴细胞白血病患者的参数调整了该模型,用其预测患者36个月内无进展生存率和总生存率,发现曲线下面积也在0.8左右。

这个预言球在乳腺癌中的表现更加惊人。对接受新辅助治疗的乳腺癌患者12-60个月内,临床终点的预测,曲线下面积都在0.80以上。并且,还能分辨出哪些患者的远端复发风险更高!这有助于患者及时发现和预防


预测癌症患者的转移风险

此外,“水晶球”的能力不止在于预测患者的风险,还能指导用药。

在调整了模型后,研究人员发现,该模型还能分辨出哪些慢性淋巴细胞白血病患者,更能够从FCR(氟达拉滨+环磷酰胺+利妥昔单抗)疗法中获益;哪些乳腺癌患者,更适合新辅助化疗或HER2双靶向(曲妥珠单抗+帕妥珠单抗)治疗。

从这些结果看,这个模型的预测能力可以说是相当强大。

而这个强大的基于贝叶斯公式的模型还很好建立,相比机器学习算法,一方面,它不需要用海量的数据进行训练,只需用已经发现的几个风险因子便可建立;另一方面它相对简单,更易于升级。

当然,也必须承认,目前该模型预测的准确率还有提升的空间,这是需要继续改进的地方。

不过,无论如何,这个简单而强大的模型,对于癌症精准医疗的发展具有重要的推动意义。

原始出处:David M. Kurtz, Mohammad S. Esfahani, Florian Scherer, et al. Dynamic Risk Profiling Using Serial Tumor Biomarkers for Personalized Outcome Prediction. Cell. July 04, 2019

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    2020-02-22 维他命
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    2019-09-18 zhaojie88
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    2019-07-18 CHANGE

    梅斯里提供了很多疾病的模型计算公式,赞一个!

    0

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