Interim-Positron Emission Tomography with [18F]Fluorodeoxyglucose (interim-PET) Evaluation In Mediastinal Lymphoma Including Hodgkin Lymphoma (HL) and Primary Mediastinal Large B-Cell Lymphoma (PMBL)

Histological lymphoma diagnosis of adult patients with bulky mediastinal mass is either HL or PMBL, two distinct diseases with a specific outcome. PET interpretation is often difficult for mediastinal lymphoma because of the volume of the tumor and the presence of blood pool. No specific criteria for interpretation of interim-PET have yet been defined in this clinical entity. The purpose of this study was to investigate the prognostic value of qualitative and semiquantitative evaluations of interim-PET in mediastinal lymphoma.

We retrospectively included 72 patients with either HL (n=48) or PMBL (n=24), previously untreated, aged under 60 at diagnosis and who underwent at least one interim-PET evaluation. Patients with sub-diaphragmatic or medullar localisations of lymphoma were excluded. All PET scans were reviewed. Qualitative evaluation included global visual evaluation (GVE) (positive or negative) and 5 points-scale (5PS). Semiquantitative evaluation consisted in maximum standardized uptake value (SUV_max) and SUV_max reduction between the baseline PET (PET₀) and the evaluation performed after two (PET₂) or four (PET₄) cycles of chemotherapy. Prognostic impact was evaluated on the event-free survival (EFS), defined as disease progression/first relapse (n=18) or death (n=2). ROC (Receiver Operating Characteristic) curve was used to assess the value of SUV_max reduction in discriminating future deaths or relapses, based on area under the curve (AUC). The “best“ cut-off that provides both the lowest false positive and the lowest false negative rates was computed.

Median age was 29 (24 - 35), 60% male. Tumoral mass was more than 7.5 cm in 70% of the patients, and M/T ratio>= 0.35 in 79%. Median SUV_max at baseline, PET₂ and PET₄ were 12.8 (4.1;33.2), 1.9 (1.7;3.1), and 2.4 (1.7;3.1), respectively. With a median follow-up at 24 months, 2-year event-free survival (EFS) was 67%, without significant difference between HL and PMBL (p=0.98). Except for ECOG performance status in PMBL, neither clinical nor biological feature was predictive for EFS. Using GVE, a negative PET₂ (n=36/59) and PET₄ (n=24/34), were achieved in 61% and 71%, respectively. GVE and 5PS have a significant negative predictive value (NPV) at PET₂ (HR=3.2, 95%CI: 1.2–8.2; p=0.012, and HR=1.9, 95%CI: 1.1–3.3, p=0.01) and at PET₄ (HR=13.9, 95%CI: 3.5–55; p=0.0001, and 2.6, 95%CI: 1.5–4.7, p=0.001 respectively), with a 2-year estimated EFS of 69% for PET₂-negative patients versus 51% for PET₂-positive patients (p=0.012), and of 86% for PET₄-negative patients versus 20% for PET₄-positive patients (p=0.001). An optimal cut-off of 81% SUV_max reduction from PET₀ to PET₂ or PET₄ yielded a 2-year estimated EFS of 70% in patients with reduction of more than 81%, versus 47% in those with reduction of 81% or less (p=0.004). In the HL subgroup, GVE and SUV_max reduction higher than 81% at PET₂ (p=0.0001, p=0.015, respectively) and PET₄ (p=0.004, p=0.015, respectively) showed significant prognostic values for EFS. In the PMBL subgroup, neither qualitative nor semiquantitative evaluation at PET₂ was predictive for EFS. At PET₄, GVE and 5PS were strongly predictive for EFS (p=0.005, p=0.0001). Patients with SUV_max reduction higher than 81% between PET₀ and PET₄ reached a 67% 2-year EFS, while patients with lower SUV_max reduction had only a 33% 2-year EFS (p=0.13).

The cut-off value of SUV_max reduction estimated for predicting EFS with best accuracy in mediastinal lymphoma was 81%. Although the SUV semiquantification helps to reduce the number of false positives, visual global analysis had a significant negative predictive value in interim-PET in mediastinal lymphoma, with a possible very early prediction, as early as PET₂ in HL, and a better prediction at PET₄ than PET₂ in PMBL.

No relevant conflicts of interest to declare.