AI Serial Image Prediction of Progression-Free Survival (PFS) for Locally Advanced Non-Small Cell Lung Cancer (LA-NSCLC) Patients Treated with Chemoradiation (CRT) and Durvalumab Consolidation

Abstract

Patient outcomes with definitive CRT for LA-NSCLC remain poor, with no imaging biomarkers to predict benefit. Hence, we developed a serial image AI model using paired planning CT (pCT) and first week cone-beam CT (CBCT) to predict PFS and measured AI model fairness defined as the bias in the classification with respect to gender as a protected attribute. Sixty-four consecutive patients with LA-NSCLC treated with concurrent CRT to 60 Gy in 30 fractions and durvalumab consolidation were analyzed. Three prediction models were created. A previously developed AI image foundation model [1] was pre-trained with unlabeled 6,402 3D CT scans sourced from institutional and the Cancer Imaging Archive and modified to predict PFS as a binarized outcome (high PFS > 6 months and low PFS < 6 months) using pCT scans. Serial image AI model was created by adding the first week CBCT scan. The third model measured tumor growth rate (TGR) as relative change in tumor and nodal volume from pCT to CBCT derived using a different published AI model [2]. Association with PFS using univariable and multivariable Cox regression after adjusting for age, gender, planning tumor volume, and smoking status were measured using TGR and the two AI model predictions using a cutoff of > 50% probability for low PFS. AI model fairness metrics area under receiver operating curve (AUROC), precision, sensitivity, and specificity were computed. TGR was not associated with PFS on univariate (Hazard ratio [HR] of 1.515, 95% confidence interval [CI] of 0.32 to 7.26, p = 0.60) or multivariate analysis (HR: 1.58, 95% CI: 0.32 to 7.80, p = 0.58) and resulted in a Harrell's C-index of 54.7%. The serial image AI model prediction was associated with PFS in both univariable (HR: 2.12, 95% CI: 1.02 to 4.40, p = 0.045) and multivariable analysis (HR 2.39, 95% CI of 1.09 to 5.25, p = 0.029), and a C-index of 62.5%. The pCT AI model was associated with PFS in univariate (HR 2.06, 95% CI of 1.06 to 4.01, p = 0.034) but not in multivariable analysis (HR 1.89, 95% CI of 0.93 to 3.87, p = 0.08), and a C-index of 59.9%. The serial image AI model reduced the parity in classification compared to pCT AI model indicating higher fairness (Table I). The multi-image AI model predicted PFS with slightly higher accuracy and resulted in higher fairness than the pCT AI model. These results underscore the potential for incorporating multi-imaging biomarkers to predict treatment response.