Impact of baseline quantitative parameters of 18F-FDG-PET/CT on prediction of brain metastases in melanoma patients

Introduction: Malignant melanoma is an aggressive malignancy with high propensity of brain metastases. Identification of cases who are at higher risk for brain metastases is crucial for subsequent surveillance and even prophylactic treatment options. The aim of this study was to investigate predictability of baseline metabolic parameters of 18F-FDG PET/CT for brain metastases free survival (BMFS) in malignant melanoma. In addition, we performed a quantitative organ-specific analysis, since brain metastases may be related to unique features of melanoma and precursor mutations of various prometastatic subclones.

Methods: Overall, the data of 159 patients (men age: 71 ± 14 years, 45.3% female and 54.7% male), who underwent baseline 18F-FDG-PET/CT and had available clinical and imaging follow-ups were included for the analysis. Initial staging of the disease performed based on histopathology, brain MRI and 18F-FDG-PET/CT from 2008 to 2021. Exclusion criteria was undefined stage of the disease, infection and atypical tumors in the primary pathology and those who represented with brain metastases at the time of first diagnosis as well as second primary malignancy during follow up time. Organ-specific quantitative PET parameters of the primary tumor, lymph node, bone, liver and lung were measured for the analyses [maximum standardized uptake value (SUVmax), SUVmean, (Lean body mass corrected SUV) SUL max, SUL peak, Metabolic Tumor Volume (MTV), Total Lesion Glycolysis (TLG) and number of lesions]. Clinical variables (Gender, age, primary stage, BRAF mutation and Breslow thickness) were also collected for the assessment of their impact on BMFS.

Results: The median follow-up time was 6.3 years (range: 1-23 years). Fifty-nine patients (37%) showed brain metastases with median BMFS of 60.58 months (range of 2 to 221 months). Negative 18F-FDG PET/CT at initial staging was significantly correlated with BMFS, regardless of initial stage, gender and BRAF mutation (P value 0.002, Hazard ratio 0.43, CI 0.25-0.74). However, no significant correlation was seen between the metabolic tumor burden on 18F-FDG-PET/CTand BMFS. In addition, significant correlation was found between SULpeak and SULmax of the prominent lymph node metastasis (P value 0.026, Hazard ratio 1.05, CI 1.00-1.11) and SULpeak of the primary tumor with BMFS (P value 0.009, Hazard ratio 1.06, CI 1.01-1.11). Initial SULpeak value of higher than 25 indicates probability of brain metastasis is more than 80% in the next 36 months. Tumor thickness and primary stage of the disease were significant clinical predictors of BMFS.

Conclusions: To our best knowledge, this is the first study that represents the predictive value of quantitative, organ-specific, parameters of 18-FDG-PET/CT for BMFS in melanoma patients. Negative baseline metabolic PET burden was significant independent predictor of brain metastases, regardless of clinical stage and variables of the disease. Baseline 18F-FDG-PET metabolic parameters of the lymph node (i.e. SULpeak and SUVmax) and primary tumor (i.e. SULpeak) seem to be important factors for prediction of brain metastases which could be implemented in clinical prognostic models for accurate stratification of the high-risk patients, who may benefit from further imaging surveillance and prophylactic treatment.