Radiomics, Tumor Volume, and Blood Biomarkers for Early Prediction of Pseudoprogression in Patients with Metastatic Melanoma Treated with Immune Checkpoint Inhibition.

We assessed the predictive potential of positron emission tomography (PET)/CT-based radiomics, lesion volume, and routine blood markers for early differentiation of pseudoprogression from true progression at 3 months. 112 patients with metastatic melanoma treated with immune checkpoint inhibition were included in our study. Median follow-up duration was 22 months. 716 metastases were segmented individually on CT and 2[18F]fluoro-2-deoxy-D-glucose (FDG)-PET imaging at three timepoints: baseline (TP0), 3 months (TP1), and 6 months (TP2). Response was defined on a lesion-individual level (RECIST 1.1) and retrospectively correlated with FDG-PET/CT radiomic features and the blood markers LDH/S100. Seven multivariate prediction model classes were generated. Two-year (median) overall survival, progression-free survival, and immune progression-free survival were 69% (not reached), 24% (6 months), and 42% (16 months), respectively. At 3 months, 106 (16%) lesions had progressed, of which 30 (5%) were identified as pseudoprogression at 6 months. Patients with pseudoprogressive lesions and without true progressive lesions had a similar outcome to responding patients and a significantly better 2-year overall survival of 100% (30 months), compared with 15% (10 months) in patients with true progressions/without pseudoprogression ( Noninvasive PET/CT-based radiomics, especially in combination with blood parameters, are promising biomarkers for early differentiation of pseudoprogression, potentially avoiding added toxicity or delayed treatment switch.

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©2020 American Association for Cancer Research.