18F-FDG PET radiomic analysis to predict outcomes in metastatic melanoma treated with immune checkpoint inhibitors

Front Immunol. 2026 Feb 25:17:1642620. doi: 10.3389/fimmu.2026.1642620. eCollection 2026.

Abstract

Purpose: Cutaneous melanoma (CM) incidence is rising, and despite advances in immune checkpoint inhibitors (ICI), many metastatic patients do not respond or develop resistance. This study aimed to evaluate the prognostic value of a pre-treatment FDG-PET/CT-based radiomic model (MEL-RAD) for predicting 1-year progression-free survival (1y-PFS) in metastatic CM patients treated with first-line ICI.

Methods: We retrospectively included 154 metastatic CM patients from two centers who underwent pre-treatment FDG-PET/CT before ICI initiation. Patients were split into a development cohort (n=95) and an independent testing cohort (n=59). Radiomic features were extracted and harmonized to reduce inter-cohort variability. A two-step feature selection identified three key wavelet-transformed texture features used to build the MEL-RAD predictive model. The model's performance was assessed by receiver operating characteristic (ROC) analysis, sensitivity, specificity, and predictive values. Survival analyses (progression-free (PFS) and overall survival (OS)) were performed with Cox regression and Kaplan-Meier methods.

Results: In the development cohort, MEL-RAD achieved an AUC of 0.74 (p<0.0001) for predicting 1y-PFS. Using a 55% probability threshold, sensitivity was 93.8%, specificity 31.9%, with positive and negative predictive values of 58.4% and 83.4%, respectively. Patients with MEL-RAD >55% had significantly worse PFS (HR = 2.73, p=0.0009) and OS (HR = 3.20, p=0.0003). These results were externally validated: in the testing cohort, MEL-RAD positivity remained significantly associated with poorer PFS (HR = 2.73, p=0.047), and showed non-significant for OS.

Conclusion: The MEL-RAD radiomic model based on pre-treatment FDG-PET/CT offers a non-invasive biomarker to stratify metastatic CM patients treated with immunotherapy.

Keywords: BRAF; FDG-PET; NRAS; immune checkpoint inhibition; melanoma; radiomic.

MeSH terms

  • Aged
  • Female
  • Fluorodeoxyglucose F18*
  • Humans
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Male
  • Melanoma* / diagnostic imaging
  • Melanoma* / drug therapy
  • Melanoma* / mortality
  • Middle Aged
  • Neoplasm Metastasis
  • Positron Emission Tomography Computed Tomography* / methods
  • Prognosis
  • Radiomics
  • Radiopharmaceuticals
  • Retrospective Studies
  • Skin Neoplasms* / diagnostic imaging
  • Skin Neoplasms* / drug therapy
  • Skin Neoplasms* / mortality
  • Treatment Outcome

Substances

  • Immune Checkpoint Inhibitors
  • Fluorodeoxyglucose F18
  • Radiopharmaceuticals