Baseline dual-energy CT iodine uptake predicts systemic but not lesion-level progression in immunotherapy-treated...

Immune checkpoint inhibitors (ICI) have transformed melanoma treatment, but reliable prognostic biomarkers are lacking. Dual-energy CT (DECT)-derived iodine concentration is a non-invasive quantitative measure of tumor vascularity. We investigated whether spatially resolved baseline iodine concentration predicts ICI outcomes in metastatic melanoma.

We retrospectively analyzed 73 patients with metastatic melanoma (614 baseline lesions) treated with ICI who underwent baseline abdominal DECT. Each lesion was partitioned into three concentric shells (core, transition zone, and rim) and iodine concentration was normalized to portal vein uptake (mNIC). Cox proportional hazards regression adjusting for lesion count and tumor volume was used to assess associations with progression-free survival (PFS). Poisson regression models were used to model new metastasis development.

Associations between baseline mNIC and shorter PFS increased from core to periphery. After adjustment, the peripheral rim remained independently associated with shorter PFS, while the transition zone showed borderline significance. Kaplan-Meier analysis confirmed significant survival separation for peripheral rim mNIC. Organ-specific analyses demonstrated heterogeneous effects, with splenic, soft tissue, and hepatic metastases showing significant positive associations, and lymph node metastases showing a significant inverse association. Higher peripheral mNIC also predicted greater new-lesion burden through the first two follow-up examinations. Baseline mNIC was not significantly associated with progressive disease of individual baseline lesions at second follow-up.

Peripheral tumor iodine concentration on dual-energy computed tomography independently predicts both shorter progression-free survival and greater new-lesion burden in immune checkpoint inhibitor-treated metastatic melanoma.