# Development of a Machine Learning-Based Prognostic Model Using Systemic Inflammation Markers in Patients Receiving Nivolumab Immunotherapy: A Real-World Cohort Study

## TL;DR

This study develops a machine learning model to predict how patients will respond to nivolumab immunotherapy using inflammation markers like CRP and LDH.

## Contribution

The novel contribution is the development and evaluation of a multi-algorithmic ML model using systemic inflammation markers to predict nivolumab response in a real-world cohort.

## Key findings

- Gradient Boosting achieved the highest AUC (0.816) for predicting nivolumab response.
- CRP and LDH were the most common predictors across models, with high levels indicating non-response.
- Support Vector Machine showed the best overall predictive performance with high accuracy and F1-score.

## Abstract

Background: Systemic inflammation is an essential factor in the formation of the tumor microenvironment and has an impact on patient response to immune checkpoint inhibitors. Although there is a growing interest in biomarkers of inflammation, there is a gap in understanding their predictive value for response to nivolumab in clinical practice. The objective of this research was to design and assess a multi-algorithmic machine learning (ML) model based on regular systemic inflammation measurements to forecast the response of treatment to nivolumab. Methods: An analysis of a retrospective real-world cohort of 177 nivolumab-treated patients was performed. Baseline inflammatory biomarkers, such as neutrophils, lymphocytes, platelets, CRP, LDH, albumin, and derived indices (NLR, PLR, SII), were derived. After preprocessing, 5 ML models (Logistic Regression, Random Forest, Gradient Boosting, Support Vector Machine, and Neural Network) were trained and tested on a 70/30 stratified split. Accuracy, AUC, precision, recall, F1-score, and Brier score were used to evaluate predictive performance. The interpretability of the model was analyzed based on feature-importance ranking and SHAP. Results: Gradient Boosting performed best in terms of discriminative (AUC = 0.816), whereas Support Vector Machine performed best on overall predictive profile (accuracy = 0.833; F1 = 0.909; recall = 1.00; and Brier Score = 0.134) performance. CRP and LDH became the most common predictors of all models, and then neutrophils and platelets. SHAP analysis has verified that high CRP and LDH were strong predictors that forced the prediction to non-response, whereas higher lymphocyte levels were weak predictors that increased the response probability prediction. Conclusions: Machine learning models based on common inflammatory systemic markers give useful predictive information about nivolumab response. Their discriminative ability is moderate, but the high performance of SVM and Gradient Boosting pays attention to the opportunities of inflammation-based ML tools in making personalized decisions regarding immunotherapy. A combination of clinical, radiomic, and molecular biomarkers in the future can increase predictive capabilities and clinical use.