e14138 Background: Immune checkpoint inhibitors have become breakthrough therapy for various types of cancers. However, regarding their total response rate around 20% based on clinical trials, predicting accurate aPD-1 response for individual patient is unestablished. The presence of PD-L1 expression or tumor infiltrating lymphocyte may be used as indicators of response but are limited. We developed models using machine learning methods to predict the aPD-1 response. Methods: A total of 126 advanced NSCLC patients treated with the aPD-1 were enrolled. Their clinical characteristics, treatment outcomes, and adverse events were collected. Total clinical data (n = 126) consist of 15 variables were divided into two subsets, discovery set (n = 63) and test set (n = 63). Thirteen supervised learning algorithms including support vector machine and regularized regression (lasso, ridge, elastic net) were applied on discovery set for model development and on test set for validation. Each model were evaluated according to the ROC curve and cross-validation method. Same methods were used to the subset which had additional flow cytometry data (n = 40). Results: The median age was 64 and 69.8% were male. Adenocarcinoma was predominant (69.8%) and twenty patients (15.1%) were driver mutation positive. Clinical data set (n = 126) demonstrated that the Ridge regression (AUC: 0.79) was the best model for prediction. Of 15 clinical variables, tumor burden, age, ECOG PS and PD-L1, were most important based on the random forest algorithm. When we merged the clinical and flow cytometry data, the Ridge regression model (AUC:0.82) showed better performance compared to using clinical data only. Among 52 variables of merged set, the top most important immune markers were as follows: CD3+CD8+CD25+/Teff-CD28, CD3+CD8+CD25-/Teff-Ki-67, and CD3+CD8+CD25+/Teff-NY-ESO/Teff-PD-1, which indicate activated tumor specific T cell subset. Conclusions: Our machine learning based model has benefit for predicting aPD-1 responses. After further validation in independent patient cohort, the supervised learning based non-invasive predictive score can be established to predict aPD-1 response.
Resolving complex hierarchies in chemical mixtures: how chemometrics may serve in understanding the immune system
