The Complementary Prognostic Role of Baseline and Interim PET in Predicting Treatment Outcome in Advanced-Stage Hodgkin Lymphoma

INTRODUCTION: We retrospectively evaluated the contribution of the positron emission tomography (PET) combined with computed tomography (PET/CT) and contrast enhanced computed tomography (ceCT) in the staging and in the prognostication of untreated advanced Hodgkin’s lymphoma (HL).

METHODS: One-hundred-sixty-two HL patients from Italian, Poland and Danish centers entered this study. Treatment consisted on ABVD with or without radiotherapy. All patients were staged at baseline with ceCT and PET/CT (PET-0) and after 2 ABVD with PET/CT (PET-2). All the ceCT and FDG/PET scans were centrally reviewed. PET-2 was reported according to the 5-point Deauville scale: score 1 to 3 considered negative and score 4-5 positive.

RESULTS: Patients breakdown into (a) stage I-II; (b) III or (c) IV for CeCT and PET/CT-staged patients was as follows: 49.1%, 31.0%, 19.9% and 46.6%, 21.7%, 31.7%, respectively. ceCT and PET-0 were concordant or discordant in 117 (72.2%) and 45 (27.8%) patients, respectively. Combining the PET-0 and ceCT data we demonstrated an extra-nodal sites (ENS) in 57 (35.2%) of the 162 patients. Most (27/57) extra-nodal sites (ENS) were detected by PET-0 alone while ENS were concordantly detected by ceCT and PET-0 in other 25 cases and by ceCT alone in the remaining 5 patients. These latter three patient groups showed similar 2-y EFS rates of 62%, 83% and 56%, respectively.

In patients with PET/CT-documented ENS, a pathological metabolic uptake was documented, respectively, in the BM (18 cases), lung (7 cases) and in two other parenchymal sites (2 cases). Overall, the 2 and 5-year OS and EFS for the entire patient cohort were 97.4%, 97.4% and 86.6% and 82.6%, respectively. PET-2 was positive in 40 cases (25.1%) and negative in 119 (74.84%). At univariate and multivariate analyses ENS disease and a positive PET-2 were the only variables significantly affecting the EFS rates, with a HR of 3.9 (95% CI:1.62-9.36; P=.002) and 2.9 (95% CI:1.82-4.52; P<.00001), respectively. Combining these two variables we stratified the patients in 4 risk groups with significantly different EFS rates (P<.00001). Group 1 (i.e. nodal disease and a negative PET-2) identified patients with a very favorable 3-y EFS (98%), whereas group 4 (i.e. presence of ENS disease and a positive PET-2) had a very dismal prognosis, with a 3-y EFS of 0%. Group 2 (i.e. presence of ENS and a negative PET-2) and group 3 (nodal disease and a positive PET-2) identified patients at intermediate risk.

CONCLUSION: Present findings indicate that (1) PET/CT is mandatory for baseline HL staging while CeCT is of limited value. (2) The combination of ENS and PET-2 in a integrated prognostic model was even more predictive than PET-2 alone on treatment outcome in ABVD-treated HL patients.