A deep learning-based system for survival benefit prediction of tyrosine kinase inhibitors and immune checkpoint inhibitors in stage IV non-small cell lung cancer patients: A multicenter, prognostic study

Background For clinical decision making, it is crucial to identify patients with stage IV non-small cell lung cancer (NSCLC) who may benefit from tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). In this study, a deep learning-based system was designed and validated using pre-therapy computed tomography (CT) images to predict the survival benefits of EGFR-TKIs and ICIs in stage IV NSCLC patients. Methods This retrospective study collected data from 570 patients with stage IV EGFR-mutant NSCLC treated with EGFR-TKIs at five institutions between 2010 and 2021 (data of 314 patients were from a previously registered study), and 129 patients with stage IV NSCLC treated with ICIs at three institutions between 2017 and 2021 to build the ICI test dataset. Five-fold cross-validation was applied to divide the EGFR-TKI-treated patients from four institutions into training and internal validation datasets randomly in a ratio of 80%:20%, and the data from another institution was used as an external test dataset. An EfficientNetV2-based survival benefit prognosis (ESBP) system was developed with pre-therapy CT images as the input and the probability score as the output to identify which patients would receive additional survival benefit longer than the median PFS. Its prognostic performance was validated on the ICI test dataset. For diagnosing which patient would receive additional survival benefit, the accuracy of ESBP was compared with the estimations of three radiologists and three oncologists with varying degrees of expertise (two, five, and ten years). Improvements in the clinicians' diagnostic accuracy with ESBP assistance were then quantified. Findings ESBP achieved positive predictive values of 80.40%, 75.40%, and 77.43% for additional EGFR-TKI survival benefit prediction using the probability score of 0.2 as the threshold on the training, internal validation, and external test datasets, respectively. The higher ESBP score (>0.2) indicated a better prognosis for progression-free survival (hazard ratio: 0.36, 95% CI: 0.19-0.68, p<0.0001) in patients on the external test dataset. Patients with scores >0. 2 in the ICI test dataset also showed better survival benefit (hazard ratio: 0. 33, 95% CI: 0.18-0. 55, p<0. 0001). This suggests the potential of ESBP to identify the two subgroups of benefiting patients by decoding the commonalities from pre-therapy CT images (stage IV EGFR-mutant NSCLC patients receiving additional survival benefit from EGFR-TKIs and stage IV NSCLC patients receiving additional survival benefit from ICIs). ESBP assistance improved the diagnostic accuracy of the clinicians with two years of experience from 47.91% to 66.32%, and the clinicians with five years of experience from 53.12% to 61.41%. Interpretation This study developed and externally validated a preoperative CT image-based deep learning model to predict the survival benefits of EGFR-TKI and ICI therapies in stage IV NSCLC patients, which will facilitate optimized and individualized treatment strategies. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Automated summary

A deep learning-based system was developed and validated to predict the survival benefits of EGFR-TKIs and ICIs in stage IV NSCLC patients using pre-therapy CT images, facilitating optimized and individualized treatment strategies.