deAndrés-Galiana E J, Fernández-Martínez J L, Luaces O, Del Coz J J, Fernández R, Solano J, Nogués E A, Zanabilli Y, Alonso J M, Payer A R, Vicente J M, Medina J, Taboada F, Vargas M, Alarcón C, Morán M, González-Ordóñez A, Palicio M A, Ortiz S, Chamorro C, Gonzalez S, González-Rodríguez A P
Department of Mathematics, University of Oviedo, Oviedo, Spain.
Clin Transl Oncol. 2015 Aug;17(8):612-9. doi: 10.1007/s12094-015-1285-z. Epub 2015 Apr 21.
The cure rate in Hodgkin lymphoma is high, but the response along with treatment is still unpredictable and highly variable among patients. Detecting those patients who do not respond to treatment at early stages could bring improvements in their treatment. This research tries to identify the main biological prognostic variables currently gathered at diagnosis and design a simple machine learning methodology to help physicians improve the treatment response assessment.
We carried out a retrospective analysis of the response to treatment of a cohort of 263 Caucasians who were diagnosed with Hodgkin lymphoma in Asturias (Spain). For that purpose, we used a list of 35 clinical and biological variables that are currently measured at diagnosis before any treatment begins. To establish the list of most discriminatory prognostic variables for treatment response, we designed a machine learning approach based on two different feature selection methods (Fisher's ratio and maximum percentile distance) and backwards recursive feature elimination using a nearest-neighbor classifier (k-NN). The weights of the k-NN classifier were optimized using different terms of the confusion matrix (true- and false-positive rates) to minimize risk in the decisions.
We found that the optimum strategy to predict treatment response in Hodgkin lymphoma consists in solving two different binary classification problems, discriminating first if the patient is in progressive disease; if not, then discerning among complete and partial remission. Serum ferritin turned to be the most discriminatory variable in predicting treatment response, followed by alanine aminotransferase and alkaline phosphatase. The importance of these prognostic variables suggests a close relationship between inflammation, iron overload, liver damage and the extension of the disease.
霍奇金淋巴瘤的治愈率很高,但患者对治疗的反应仍不可预测且差异很大。在早期阶段检测出那些对治疗无反应的患者可能会改善他们的治疗效果。本研究试图确定目前在诊断时收集的主要生物学预后变量,并设计一种简单的机器学习方法来帮助医生改善治疗反应评估。
我们对在西班牙阿斯图里亚斯被诊断为霍奇金淋巴瘤的263名白种人队列的治疗反应进行了回顾性分析。为此,我们使用了一份在任何治疗开始前诊断时测量的35个临床和生物学变量的清单。为了确定治疗反应最具区分性的预后变量清单,我们基于两种不同的特征选择方法(费舍尔比率和最大百分位数距离)以及使用最近邻分类器(k-NN)的反向递归特征消除设计了一种机器学习方法。使用混淆矩阵的不同项(真阳性率和假阳性率)对k-NN分类器的权重进行了优化,以最小化决策风险。
我们发现预测霍奇金淋巴瘤治疗反应的最佳策略在于解决两个不同的二元分类问题,首先区分患者是否处于疾病进展期;如果不是,则区分完全缓解和部分缓解。血清铁蛋白成为预测治疗反应最具区分性的变量,其次是丙氨酸转氨酶和碱性磷酸酶。这些预后变量的重要性表明炎症、铁过载、肝损伤与疾病范围之间存在密切关系。