# Baseline Radiomics as a Prognostic Tool for Clinical Benefit from Immune Checkpoint Inhibition in Inoperable NSCLC Without Activating Mutations

## TL;DR

This study uses machine learning on CT scans to better predict which lung cancer patients will benefit from immunotherapy, improving treatment decisions.

## Contribution

A novel radiomics ensemble model outperforms existing methods in predicting long-term survival from immunotherapy in NSCLC patients.

## Key findings

- An ensemble radiomics model achieved an AUC of 0.863 for predicting 24-month survival in NSCLC patients.
- Combined clinical and radiomics features outperformed models using only clinical or radiomics data.
- The model could help avoid unnecessary immunotherapy for non-responders, improving cost-effectiveness and reducing toxicity.

## Abstract

This study introduces a powerful machine learning-based radiomics approach to help improve predictions of immunotherapy outcomes in patients with non-small cell lung cancer (NSCLC). We believed that the full potential of CT scan-based tumor analysis had not been achieved, partly due to limited use of model integrations (ensembles) in previous research. To address this, we tested 1680 combinations of data processing and machine learning methods, selecting the best-performing ones to create an integrated (ensemble) model. Using clinical and imaging data, our final model achieved an AUC of 0.86 for predicting 24-month patient survival, which, to our knowledge, exceeds previously published results for this diagnosis and disease outcomes. This approach reduces the weaknesses of relying on a single model and offers a more reliable and accurate tool for predicting immunotherapy outcomes.

Background/Objectives: Checkpoint inhibitors (ICIs) are key therapies for NSCLC, but current selection criteria, such as excluding mutation carriers and assessing PD-L1, lack sensitivity. As a result, many patients receive costly treatments with limited benefit. Therefore, this study aimed to predict which NSCLC patients would achieve durable survival (≥24 months) with immunotherapy. Methods: A comprehensive ensemble radiomics approach was applied to pretreatment CT scans to prognosticate overall survival (OS) and predict progression-free survival (PFS) in a cohort of 220 consecutive patients with inoperable NSCLC treated with first-line ICIs (pembrolizumab or atezolizumab, nivolumab or prolgolimab) as monotherapy or in combination. The radiomics pipeline evaluated four normalization methods (none, min-max, Z-score, mean), four feature selection techniques (ANOVA, RFE, Kruskal–Wallis, Relief), and ten classifiers (e.g., SVM, random forest). Using two to eight radiomics features, 1680 models were built in the Feature Explorer (FAE) Python package. Results: Three feature sets were evaluated: clinicopathological (CP) only, radiomics only, and a combined set, using 6- and 12-month PFS and 24-month OS endpoints. The top 15 models were ensembled by averaging their probability scores. The best performance was achieved at 24-month OS with the combined CP and radiomics ensemble (AUC = 0.863, accuracy = 85%), followed by radiomics-only (AUC = 0.796, accuracy = 82%) and CP-only (AUC = 0.671, accuracy = 76%). Predictive performance was lower for 6-month (AUC = 0.719) and 12-month PFS (AUC = 0.739) endpoints. Conclusions: Our radiomics pipeline improved selection of NSCLC patients for immunotherapy and could spare non-responders unnecessary toxicity while enhancing cost-effectiveness.