Performance status

Surrogate endpoint

Proportional hazards model

Response Evaluation Criteria in Solid Tumors

Clinical trial

Lung cancer

Biochemistry

Phases of clinical research

Radiology

Biomarker

Retrospective cohort study

Imaging biomarker

Internal medicine

Oncology

Medicine

Chemistry

Immunotherapy

Immunohistochemistry

Cancer

Magnetic resonance imaging

Journal for ImmunoTherapy of Cancer

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.18F-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.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.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.

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