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

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Wildemberg, Luiz Eduardo
Da Silva Camacho, Aline Helen
Miranda, Renan Lyra
Elias, Paula C. L
De Castro Musolino, Nina R
Nazato, Debora
Jallad, Raquel
Huayllas, Martha K. P
Mota, Jose Italo S
Almeida, Tobias

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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.



acromegaly, biomarker, machine learning, precision medicine, prediction model, somatostatin receptor, somatostatin receptor ligands

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Journal of Clinical Endocrinology and Metabolism, v. 106, n. 7, p. 2047-2056, 2021.