The predictive value of interim FDG-PET in early-stage Hodgkin lymphoma is not well established.

A recent study by Zaucha et al. [1] included 106 patients with early-stage Hodgkin lymphoma. These patients were treated with 2–4 cycles of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by radiation therapy (RT) or with six cycles of ABVD. These patients underwent interim FDG-PET scans after one cycle of ABVD in all 106 cases, whereas 57 (53.8%) underwent FDG-PET imaging both after one and two cycles of ABVD. After one cycle of ABVD, FDG-PET scans of 87/106 (82%) patients were scored negative (i.e. Deauville score 1–3), whereas 19/106 (18%) were scored positive (i.e. Deauville score 4–5), of whom four were excluded from further analysis because of progression and treatment escalation. Of the patients with negative interim FDG-PET results, 4/87 had an event (one progression, three relapses), whereas in the group of patients with positive interim FDG-PET results, 5/15 experienced an event (three progressions, two relapses), resulting in a negative predictive value (NPV) and positive predictive value (PPV) of 95% and 33%, respective. Of the 56 patients with FDG-PET scans performed after two cycles of ABVD, 50 (89.3%) had negative and 6 (10.7%) had positive results. Three of these latter six patients were excluded because of progression and treatment escalation. Consequently, only three patients with positive results at interim FDG-PET after two cycles were evaluable. Each of these three patients (100%) experienced an event (one progression, two relapses), whereas only 2/50 patients with negative interim FDG-PET results (4%) experienced an event (two progressions). Zaucha et al. [1] concluded FDGPET after two cycles of ABVD to be the optimal tool that can distinguish very well between responders and non-responders. However, we disagree with their conclusion that is based on their very small number of FDG-PET-positive patients, since several important and larger studies evaluating the value of interim FDG-PET after two or more cycles of ABVD that reported contrasting results remained unreported in their discussion (Table 1). Note that results on the predictive value of interim FDG-PET in early-stage Hodgkin lymphoma are heterogeneous (relapse rates ranging from 0% to 100%), with several large-scale studies showing a very low PPV of positive interim FDG-PET results, contradicting the results of Zaucha et al. [1]. In particular, the large-scale EORTC/LYSA/FIL H10 trial [2] is important. This study included 1925 patients with early-stage Hodgkin lymphoma and FDG-PET after two cycles of ABVD. Of 1925 patients, 361 (18.8%) patients had positive FDG-PET results of whom 192 (53.2%) were randomized to standard ABVD with RT. Remarkably, these patients had a very good prognosis, with only 36/192 (18.8%) of these patients developing disease relapse after therapy. Even more striking are the results of Radford et al. [3] who included 565 early-stage Hodgkin lymphoma who had an FDG-PET scan after three cycles of ABVD, of whom 145 (25.7%) had positive results. Of these 145 patients who were resistant to three cycles of ABVD according to FDG-PET, only 15 (10.3%) developed disease relapse after being additionally treated with only one cycle of ABVD and RT, resulting in a low PPV of only 10.3%. In conclusion, several large-scale studies have shown earlystage Hodgkin lymphoma patients with positive interim FDGPET results after two or more cycles of ABVD to have a good prognosis, contradicting the results and conclusion of Zaucha et al. [1]. Consequently, interim FDG-PET may not be an adequate tool to distinguish responders from non-responders.