Abstract P016

FENIX Score: A Novel PET-Derived Signature Predicting Neurotoxicity in Advanced Hodgkin Lymphoma Treated with A+AVD

Background: Brentuximab vedotin plus AVD (A+AVD) is a standard treatment for advanced-stage Hodgkin lymphoma (HL), but peripheral neuropathy (PN) remains a frequent and clinically relevant toxicity. Reliable predictors are lacking. While PET-derived parameters are established prognostic biomarkers, their role in predicting treatment-related toxicity is largely unexplored.

Methods: We retrospectively analyzed 21 patients with stage IV HL treated with frontline A+AVD. Baseline PET/CT parameters included SUVmax, total metabolic tumor volume (TMTV4), and total lesion glycolysis (TLG4). The FENIX score (FDG-based Extraction of Neurotoxicity Imaging indeX) was defined as a composite PET-derived index integrating focal metabolic activity and global tumor burden, calculated as (SUVmax/TMTV4 + SUVmax/TLG4) ×100, reflecting the relative metabolic intensity of the disease. The primary endpoint was grade ≥2 PN. Continuous variables were compared using the Mann–Whitney test, while categorical variables were analyzed using Fisher’s exact test. Receiver operating characteristic (ROC) analysis was performed to assess the discriminative performance and identify an optimal cut-off.

Results: Baseline PET showed heterogeneous tumor burden. Grade ≥2 PN occurred in 9/21 patients (42.9%). FENIX score was significantly higher in patients developing PN (p=0.017). ROC analysis demonstrated good discrimination (AUC 0.81). Using an optimal cut-off of 8.7, FENIX identified patients at higher risk with 77.8% sensitivity and 83.3% specificity. PN incidence was higher in patients with high FENIX score (75.0% vs 23.1%, p=0.032). Among baseline clinical variables, only hemoglobin was associated with PN, while no significant associations were observed for other baseline characteristics.

Conclusion: The FENIX score, a PET-derived index integrating metabolic activity and tumor burden, predicts clinically relevant PN using baseline PET alone. The FENIX score reflects the relative metabolic intensity of the disease, integrating peak metabolic activity with both tumor mass and overall metabolic burden. These findings support the role of PET-based biomarkers in identifying patients at increased risk of neurotoxicity and guiding personalized therapeutic strategies. The association with hemoglobin should be interpreted with caution given the small sample size. Prospective validation is warranted.