Machine learning-based prediction model for treatment of acromegaly with first-generation somatostatin receptor ligands.

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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.To develop a prediction model of therapeutic response of acromegaly to fg-SRL.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 GH < 1.0 ng/mL and normal age-adjusted 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).A total of 153 patients were analyzed. Controlled patients were older (p = 0.002), had lower GH at diagnosis (p = 0.01), had lower pretreatment GH and IGF-I (p < 0.001), and more frequently harbored tumors that were densely granulated (p = 0.014) or highly expressed SST2 (p < 0.001).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%.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.

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Authors: Luiz Eduardo Wildemberg, Aline Helen da Silva Camacho, Renan Lyra Miranda, Paula C L Elias, Nina R de Castro Musolino, Debora Nazato, Raquel Jallad, Martha K P Huayllas, Jose Italo Mota, Tobias Almeida, Evandro Portes, Antonio Ribeiro-Oliveira, Lucio Vilar, Cesar Luiz Boguszewski, Ana Beatriz Winter Tavares, Vania S Nunes-Nogueira, Tânia Longo Mazzuco, Carolina Garcia Soares Leães Rech, Nelma Veronica Marques, Leila Chimelli, Mauro Czepielewski, Marcello D Bronstein, Julio Abucham, Margaret de Castro, Leandro Kasuki, Mônica Gadelha