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

• Autor(a) principal: Wildemberg, Luiz Eduardo
• Data de Publicação: 2021
• Outros Autores: 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, Portes, Evandro, Ribeiro-Oliveira, Antonio, Vilar, Lucio, Boguszewski, Cesar Luiz, Winter Tavares, Ana Beatriz, Nunes-Nogueira, Vania S [UNESP], Mazzuco, Tânia Longo, Rech, Carolina Garcia Soares Leães, Marques, Nelma Veronica, Chimelli, Leila, Czepielewski, Mauro, Bronstein, Marcello D, Abucham, Julio, De Castro, Margaret, Kasuki, Leandro, Gadelha, Mônica
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://dx.doi.org/10.1210/clinem/dgab125; http://hdl.handle.net/11449/229017
• topic: acromegaly; biomarker; machine learning; precision medicine; prediction model; somatostatin receptor; somatostatin receptor ligands

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.