Frontiers in Oncology (Jan 2023)

Real-world data to build explainable trustworthy artificial intelligence models for prediction of immunotherapy efficacy in NSCLC patients

  • Arsela Prelaj,
  • Arsela Prelaj,
  • Edoardo Gregorio Galli,
  • Edoardo Gregorio Galli,
  • Edoardo Gregorio Galli,
  • Vanja Miskovic,
  • Mattia Pesenti,
  • Giuseppe Viscardi,
  • Giuseppe Viscardi,
  • Benedetta Pedica,
  • Laura Mazzeo,
  • Laura Mazzeo,
  • Laura Mazzeo,
  • Achille Bottiglieri,
  • Achille Bottiglieri,
  • Leonardo Provenzano,
  • Leonardo Provenzano,
  • Andrea Spagnoletti,
  • Andrea Spagnoletti,
  • Roberto Marinacci,
  • Alessandro De Toma,
  • Claudia Proto,
  • Roberto Ferrara,
  • Marta Brambilla,
  • Mario Occhipinti,
  • Sara Manglaviti,
  • Giulia Galli,
  • Diego Signorelli,
  • Diego Signorelli,
  • Claudia Giani,
  • Claudia Giani,
  • Teresa Beninato,
  • Teresa Beninato,
  • Chiara Carlotta Pircher,
  • Chiara Carlotta Pircher,
  • Alessandro Rametta,
  • Alessandro Rametta,
  • Sokol Kosta,
  • Michele Zanitti,
  • Maria Rosa Di Mauro,
  • Arturo Rinaldi,
  • Settimio Di Gregorio,
  • Martinetti Antonia,
  • Marina Chiara Garassino,
  • Marina Chiara Garassino,
  • Filippo G. M. de Braud,
  • Filippo G. M. de Braud,
  • Marcello Restelli,
  • Giuseppe Lo Russo,
  • Monica Ganzinelli,
  • Francesco Trovò,
  • Alessandra Laura Giulia Pedrocchi

DOI
https://doi.org/10.3389/fonc.2022.1078822
Journal volume & issue
Vol. 12

Abstract

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IntroductionArtificial Intelligence (AI) methods are being increasingly investigated as a means to generate predictive models applicable in the clinical practice. In this study, we developed a model to predict the efficacy of immunotherapy (IO) in patients with advanced non-small cell lung cancer (NSCLC) using eXplainable AI (XAI) Machine Learning (ML) methods.MethodsWe prospectively collected real-world data from patients with an advanced NSCLC condition receiving immune-checkpoint inhibitors (ICIs) either as a single agent or in combination with chemotherapy. With regards to six different outcomes - Disease Control Rate (DCR), Objective Response Rate (ORR), 6 and 24-month Overall Survival (OS6 and OS24), 3-months Progression-Free Survival (PFS3) and Time to Treatment Failure (TTF3) - we evaluated five different classification ML models: CatBoost (CB), Logistic Regression (LR), Neural Network (NN), Random Forest (RF) and Support Vector Machine (SVM). We used the Shapley Additive Explanation (SHAP) values to explain model predictions.ResultsOf 480 patients included in the study 407 received immunotherapy and 73 chemo- and immunotherapy. From all the ML models, CB performed the best for OS6 and TTF3, (accuracy 0.83 and 0.81, respectively). CB and LR reached accuracy of 0.75 and 0.73 for the outcome DCR. SHAP for CB demonstrated that the feature that strongly influences models’ prediction for all three outcomes was Neutrophil to Lymphocyte Ratio (NLR). Performance Status (ECOG-PS) was an important feature for the outcomes OS6 and TTF3, while PD-L1, Line of IO and chemo-immunotherapy appeared to be more important in predicting DCR.ConclusionsIn this study we developed a ML algorithm based on real-world data, explained by SHAP techniques, and able to accurately predict the efficacy of immunotherapy in sets of NSCLC patients.

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