The Prognostic Value of MTV Is Retained in New Proposed SUV 4 Threshold: An International Comparison of Follicular and Hodgkin Patient Survival
Authors: Chauvie Stephane , Guerra Luca , Fallanca Federico , Gregianin Michele , Versari Annibale , Durmo Rexhep , Bergesio Fabrizio , De Maggi Adriano , Bergalla Enrica , Rambaldi Alessandro , Ferrero Simone , Patti Caterina , Federico Massimo , Gallamini Andrea , Luminari Stefano 
Published: December 2024

Lymphoma encompasses a diverse group of malignancies necessitating precise staging and response assessment for optimal management. 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT) is pivotal in lymphoma management, offering significant prognostic insights through pre-treatment total metabolic tumor volume (TMTV) measurements. Despite its validation across various lymphoma subtypes, TMTV cut-offs for risk stratification vary due to differences in segmentation methods. This study aims to compare the prognostic value of three common segmentation methods: SUV4 SUV41% and SUV2.5, across different lymphoma patient populations.
Two large multi-center phase 3 clinical trials were analyzed: 330 Hodgkin Lymphoma (HL) patients from the HD0607 trial (NCT00795613) and 296 Follicular Lymphoma (FL) patients from the FOLL12 trial (NCT02063685). Only PET-negative HL patients receiving six cycles of ABVD were included. Baseline FDG PET/CT scans were segmented using a percentage threshold of 41% and two fixed thresholds at SUV=4 and 2.5. Only metabolic tumor volumes (MTV) larger than 3 ml were analyzed. TMTV cut-offs were obtained using maximally selected log-rank statistics, and progression-free survival (PFS) analyses were conducted using Kaplan-Meier curves.
In the FOLL12 trial, 296 patients (132 male) with a median follow-up of 48 months and a median age of 60 years were analyzed. Ann Arbor stages were 36 stage II, 63 stage III, and 197 stage IV, with 182 patients having a FLIPI2 score of 1. In the HD0607 trial, 330 patients (152 male) with a median follow-up of 38 months and a median age of 31 years were analyzed. Ann Arbor stages were 116 stage II, 116 stage III, and 98 stage IV, with 130, 159, and 41 patients having high, intermediate, and low IPS, respectively.
The median TMTV in FOLL12 were 127 ml, 136 ml, and 221 ml with SUV4, SUV41%, and SUV2.5 thresholds, respectively. The cut-offs were 602 ml, 708 ml, and 802 ml, discriminating low and high-risk populations with log-rank p-values of 0.00035, 0.00033, and &lt;0.0001, respectively. The 3-year PFS for low and high TMTV were 0.86 and 0.69 with SUV4.
In HD0607, the median TMTV were 165 ml, 226 ml, and 303 ml with SUV4, SUV41%, and SUV2.5 thresholds, respectively. The cut-offs were 140 ml, 409 ml, and 333 ml, discriminating low and high-risk populations with log-rank p-values of 0.049, 0.0099, and 0.0056, respectively. The 3-year PFS for low and high TMTV were 0.88 and 0.81 with SUV4.
The SUV4 method has recently been proposed as a standard for lesion segmentation in lymphoma due to its high reproducibility and ease of use, making it suitable for clinical practice. Our findings confirm that the SUV4 segmentation method provides similar prognostic value as the SUV41% and SUV2.5 methods, supporting the adoption of TMTV as a reproducible biomarker in lymphoma.