Non-invasive measurement of PD-L1 status and prediction of immunotherapy response using deep learning of PET/CT images

Background Currently, only a fraction of patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) experience a durable clinical benefit (DCB). According to NCCN guidelines, Programmed death-ligand 1 (PD-L1) expression status determined by immunohistochemistry (IHC) of biopsies is the only clinically approved companion biomarker to trigger the use of ICI therapy. Based on prior work showing a relationship between quantitative imaging and gene expression, we hypothesize that quantitative imaging (radiomics) can provide an alternative surrogate for PD-L1 expression status in clinical decision support. Methods 18 F-FDG-PET/CT images and clinical data were curated from 697 patients with NSCLC from three institutions and these were analyzed using a small-residual-convolutional-network (SResCNN) to develop a deeply learned score (DLS) to predict the PD-L1 expression status. This developed model was further used to predict DCB, progression-free survival (PFS), and overall survival (OS) in two retrospective and one prospective test cohorts of ICI-treated patients with advanced stage NSCLC. Results The PD-L1 DLS significantly discriminated between PD-L1 positive and negative patients (area under receiver operating characteristics curve ≥0.82 in the training, validation, and two external test cohorts). Importantly, the DLS was indistinguishable from IHC-derived PD-L1 status in predicting PFS and OS, suggesting the utility of DLS as a surrogate for IHC. A score generated by combining the DLS with clinical characteristics was able to accurately (C-indexes of 0.70-0.87) predict DCB, PFS, and OS in retrospective training, prospective testing and external validation cohorts. Conclusion Hence, we propose DLS as a surrogate or substitute for IHC-determined PD-L1 measurement to guide individual pretherapy decisions pending in larger prospective trials.