Radiomics, tumor volume and blood biomarkers for early prediction of pseudoprogression in metastatic melanoma patients treated with immune checkpoint inhibition

Radiomics, tumor volume and blood biomarkers for early prediction of pseudoprogression in metastatic melanoma patients treated with immune checkpoint inhibition:

Purpose: We assessed the predictive potential of PET/CT-based radiomics, lesion volume, and routine blood markers for early differentiation of pseudoprogression from true progression at 3 months. Experimental Design: 112 metastatic melanoma patients treated with immune checkpoint inhibition. Median follow-up: 22 months. All 716 metastases were segmented individually on CT and FDG-PET imaging at 3 time-points: baseline (TP0), 3 months (TP1), 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. Results: 2-year (median) overall survival, progression-free survival and immune-progression-free survival were 69% (not reached), 24% (6 months) and 42% (16 months). 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 to 15% (10 months) in patients with true progressions/without pseudoprogression (p=0.002). Patients with mixed progressive/pseudoprogressive lesions were in between at 53% (25 months). The blood prediction-model (LDH+S100) achieved an AUC=0.71. Higher LDH/S100 values indicated a low chance of pseudoprogression. Volume-based models: AUC=0.72 (TP1) and AUC=0.80 (delta-volume between TP0/TP1). Radiomics-models (including/excluding volume-related features): AUC=0.79/0.78. Combined blood/volume-model: AUC=0.79. Combined blood/radiomics-model (including volume-related features): AUC=0.78. The combined blood/radiomics-model (excluding volume-related features) performed best: AUC=0.82. Conclusions: Non-invasive 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.