NeoPred: dual-phase CT AI forecasts pathologic response to neoadjuvant chemo-immunotherapy in NSCLC

Accurate preoperative prediction of major pathological response or pathological complete response after neoadjuvant chemo-immunotherapy remains a critical unmet need in resectable non-small-cell lung cancer (NSCLC). Conventional size-based imaging criteria offer limited reliability, while biopsy confirmation is available only post-surgery.

We retrospectively assembled 509 consecutive NSCLC cases from four Chinese thoracic-oncology centers (March 2018 to March 2023) and prospectively enrolled 50 additional patients. Three 3-dimensional convolutional neural networks (pre-treatment CT, pre-surgical CT, dual-phase CT) were developed; the best-performing dual-phase model (NeoPred) optionally integrated clinical variables. Model performance was measured by area under the receiver-operating-characteristic curve (AUC) and compared with nine board-certified radiologists.

In an external validation set (n=59), NeoPred achieved an AUC of 0.772 (95% CI: 0.650 to 0.895), sensitivity 0.591, specificity 0.733, and accuracy 0.627; incorporating clinical data increased the AUC to 0.787. In a prospective cohort (n=50), NeoPred reached an AUC of 0.760 (95% CI: 0.628 to 0.891), surpassing the experts' mean AUC of 0.720 (95% CI: 0.574 to 0.865). Model assistance raised the pooled expert AUC to 0.829 (95% CI: 0.707 to 0.951) and accuracy to 0.820. Marked performance persisted within radiological stable-disease subgroups (external AUC 0.742, 95% CI: 0.468 to 1.000; prospective AUC 0.833, 95% CI: 0.497 to 1.000).

Combining dual-phase CT and clinical variables, NeoPred reliably and non-invasively predicts pathological response to neoadjuvant chemo-immunotherapy in NSCLC, outperforms unaided expert assessment, and significantly enhances radiologist performance. Further multinational trials are needed to confirm generalizability and support surgical decision-making.