Integrating Novel and Classical Prognostic Factors in Locally Advanced Cervical Cancer: A Machine Learning-Based Predictive Model (ESTHER Study)

<b>Background/Objective</b>: This study aimed to assess the prognostic significance of pretreatment nutritional and systemic inflammatory indices (IIs), and body composition parameters in patients with locally advanced cervical cancer (LACC) treated with chemoradiation and brachytherapy. The goal was to identify key predictors of clinical outcomes, such as local control (LC), metastasis-free survival (MFS), disease-free survival (DFS), and overall survival (OS), using machine learning techniques. <b>Materials and methods</b>: A retrospective analysis of 173 patients with LACC treated between 2007 and 2021 was conducted. The study utilized machine learning techniques, including LASSO regression and Classification and Regression Tree (CART) analysis, to identify significant predictors of outcomes. Clinical data, tumor-related parameters, and treatment factors, along with IIs and body composition metrics (e.g., sarcopenic obesity), were incorporated into the models. Model performance was evaluated using ROC curves and AUC values. <b>Results</b>: Among 173 patients, hemoglobin (Hb) levels, ECOG performance status, and total protein emerged as primary prognostic indicators across multiple endpoints. For 2-year LC, patients with Hb > 11.9 g/dL had a rate of 95.1% compared to 73.6% in those with lower levels, with further stratification by ECOG status, ANRI, and total protein refining predictions. For 5-year LC, rates were 83.1% for Hb > 11.5 g/dL and 43.3% for lower levels. For 2-year MFS, ECOG 0 patients had an 88.1% rate compared to 73.8% for ECOG ≥ 1. In 2-year OS, Hb > 11.9 g/dL predicted a 95.1% rate, while ≤11.9 g/dL correlated with 74.0%. IIs (ANRI, SIRI, MLR) demonstrated predictive value only within specific patient subgroups defined by the primary prognostic indicators. The model showed strong predictive accuracy, with AUCs ranging from 0.656 for 2-year MFS to 0.851 for 2-year OS. <b>Conclusions</b>: These findings underscore the value of integrating traditional prognostic factors with emerging markers to enhance risk stratification in LACC. The use of machine learning techniques like LASSO and CART demonstrated strong predictive capabilities, highlighting their potential to refine individualized treatment strategies. Prospective validation of these models is warranted to confirm their utility in clinical practice.