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基于机器学习的第一代生长抑素受体配体治疗肢端肥大症的预测模型。

Machine Learning-based Prediction Model for Treatment of Acromegaly With First-generation Somatostatin Receptor Ligands.

机构信息

Endocrine Unit and Neuroendocrinology Research Center, Medical School and Hospital Universitário Clementino Fraga Filho-Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.

Neuroendocrine Unit-Instituto Estadual do Cérebro Paulo Niemeyer, Secretaria Estadual de Saúde , Rio de Janeiro, RJ, Brazil.

出版信息

J Clin Endocrinol Metab. 2021 Jun 16;106(7):2047-2056. doi: 10.1210/clinem/dgab125.

Abstract

CONTEXT

Artificial intelligence (AI), in particular machine learning (ML), may be used to deeply analyze biomarkers of response to first-generation somatostatin receptor ligands (fg-SRLs) in the treatment of acromegaly.

OBJECTIVE

To develop a prediction model of therapeutic response of acromegaly to fg-SRL.

METHODS

Patients with acromegaly not cured by primary surgical treatment and who had adjuvant therapy with fg-SRL for at least 6 months after surgery were included. Patients were considered controlled if they presented growth hormone (GH) <1.0 ng/mL and normal age-adjusted insulin-like growth factor (IGF)-I levels. Six AI models were evaluated: logistic regression, k-nearest neighbor classifier, support vector machine, gradient-boosted classifier, random forest, and multilayer perceptron. The features included in the analysis were age at diagnosis, sex, GH, and IGF-I levels at diagnosis and at pretreatment, somatostatin receptor subtype 2 and 5 (SST2 and SST5) protein expression and cytokeratin granulation pattern (GP).

RESULTS

A total of 153 patients were analyzed. Controlled patients were older (P = .002), had lower GH at diagnosis (P = .01), had lower pretreatment GH and IGF-I (P < .001), and more frequently harbored tumors that were densely granulated (P = .014) or highly expressed SST2 (P < .001). The model that performed best was the support vector machine with the features SST2, SST5, GP, sex, age, and pretreatment GH and IGF-I levels. It had an accuracy of 86.3%, positive predictive value of 83.3% and negative predictive value of 87.5%.

CONCLUSION

We developed a ML-based prediction model with high accuracy that has the potential to improve medical management of acromegaly, optimize biochemical control, decrease long-term morbidities and mortality, and reduce health services costs.

摘要

背景

人工智能(AI),尤其是机器学习(ML),可用于深入分析第一代生长抑素受体配体(fg-SRL)治疗肢端肥大症时的反应生物标志物。

目的

建立肢端肥大症患者对 fg-SRL 治疗反应的预测模型。

方法

纳入经初次手术治疗未能治愈且术后接受 fg-SRL 辅助治疗至少 6 个月的肢端肥大症患者。如果患者的生长激素(GH)<1.0ng/ml 且年龄校正的胰岛素样生长因子(IGF)-I 水平正常,则认为患者得到控制。评估了 6 种 AI 模型:逻辑回归、k 最近邻分类器、支持向量机、梯度提升分类器、随机森林和多层感知器。分析中包含的特征包括诊断时的年龄、性别、诊断时和治疗前的 GH 和 IGF-I 水平、生长抑素受体亚型 2 和 5(SST2 和 SST5)蛋白表达以及角蛋白颗粒模式(GP)。

结果

共分析了 153 例患者。得到控制的患者年龄更大(P=0.002)、诊断时 GH 水平更低(P=0.01)、治疗前 GH 和 IGF-I 水平更低(P<0.001),且更常存在颗粒密集(P=0.014)或高度表达 SST2(P<0.001)的肿瘤。表现最佳的模型是支持向量机,其特征包括 SST2、SST5、GP、性别、年龄以及治疗前 GH 和 IGF-I 水平。该模型的准确率为 86.3%,阳性预测值为 83.3%,阴性预测值为 87.5%。

结论

我们开发了一种基于 ML 的预测模型,其具有较高的准确率,有可能改善肢端肥大症的医疗管理,优化生化控制,降低长期发病率和死亡率,并降低医疗服务成本。

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