AUTHOR=Prelaj Arsela , Galli Edoardo Gregorio , Miskovic Vanja , Pesenti Mattia , Viscardi Giuseppe , Pedica Benedetta , Mazzeo Laura , Bottiglieri Achille , Provenzano Leonardo , Spagnoletti Andrea , Marinacci Roberto , De Toma Alessandro , Proto Claudia , Ferrara Roberto , Brambilla Marta , Occhipinti Mario , Manglaviti Sara , Galli Giulia , Signorelli Diego , Giani Claudia , Beninato Teresa , Pircher Chiara Carlotta , Rametta Alessandro , Kosta Sokol , Zanitti Michele , Di Mauro Maria Rosa , Rinaldi Arturo , Di Gregorio Settimio , Antonia Martinetti , Garassino Marina Chiara , de Braud Filippo G. M. , Restelli Marcello , Lo Russo Giuseppe , Ganzinelli Monica , Trovò Francesco , Pedrocchi Alessandra Laura Giulia TITLE=Real-world data to build explainable trustworthy artificial intelligence models for prediction of immunotherapy efficacy in NSCLC patients JOURNAL=Frontiers in Oncology VOLUME=12 YEAR=2023 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.1078822 DOI=10.3389/fonc.2022.1078822 ISSN=2234-943X ABSTRACT=Introduction

Artificial 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.

Methods

We 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.

Results

Of 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.

Conclusions

In 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.