Predictive Value of Interim [¹⁸F]Fluorodeoxyglucose–Positron Emission Tomography in Advanced-Stage Hodgkin Lymphoma Is Not Well Established

Abstract

1 that included 331 patients with stage III or IV Hodgkin lymphoma (HL) who underwent interim [18 F]fluorodeoxyglucose (FDG) -positron emission tomography (PET) after two cycles (PET2) of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine). PET2-negative patients received four additional cycles of ABVD, whereas PET2-positive patients were switched to escalated BEA-COPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) for six cycles. Importantly, no control arm was used to determine the additional value of this treatment strategy compared with continuation of standard ABVD treatment in terms of progression-free (PFS) and overall survival (OS). After two cycles of ABVD, 271 (82%) of 331 patients acquired FDG-PET-negative status, whereas PET2 was positive in 60 (18%) of 331 patients. The 2-year estimate of PFS for 271 PET2-negative patients was 82%, with 58 patients experiencing treatment failure, and the 2-year estimate of PFS for the 60 PET2-positive patients was 64%, with 20 patients experiencing treatment failure. During follow-up, 17 deaths were reported, including six resulting from HL. Press et al concluded interim FDG-PET responseadapted therapy to be promising, considering the 2-year PFS of 64% for PET2-positive patients, which was described to be much higher than the historically observed 2-year PFS of 15% to 30%.However, we disagree with the conclusion of Press et al. 1 Their claim that a positive interim FDG-PETresults in a dismal prognosis in case of continuation of standard treatment was not supported by a recent meta-analysis on this topic.2 This meta-analysis showed mixed results among studies, including the subgroup of patients with advanced-stage HL.2 In particular, studies reporting that a positive interim FDG-PET in advanced-stage HL resulted in low PFS were methodologically flawed, because these studies did not use histopathology or did not report whether histopathology was used to confirm residual disease and instead determined disease relapse by means of follow-up imaging studies.3,4 Considering the high false-positive rate of follow-up FDG-PET, 5,6 the prognostic value of a positive interim FDG-PET result was likely thoroughly overestimated. Indeed, results of the large-scale HD15 trial 7 that included 191 patients with advanced-stage HL whose FDG-PET scans indicated persistent disease after six to eight cycles of BEACOPP showed that these patients had a good 4-year PFS of 86.2% after being additionally treated with radiation therapy. These findings imply one of the following: HL that even persists after the entire BEACOPP regimen does not require treatment intensification beyond radiation therapy, or FDG-PET during or after antilymphoma treatment is prone to a high false-positive rate (the latter has already been demonstrated by studies in non-HL showing an unacceptably high biopsy-proven false-positive proportion among FDG-avid residual lesions 8,9 ). Furthermore, administering a more intensified treatment is only justified when FDG-P...

Unproven value of end-of-treatment FDG-PET in Hodgkin lymphoma

“…However, we strongly disagree with their conclusions. First, we believe there is no place for interim FDG-PET in routine clinical care, because the results on its value are too heterogeneous [9]. Note that a recently published, prospective large-scale study including 1100 patients with advanced-stage Hodgkin lymphoma reported interim FDG-PET to have no value at all in predicting prognosis [10].…”

Response to Drs Von Hoff and Renschler

“…Additionally, the results from our experience with the modified biweekly gemcitabine and nab-paclitaxel regimen appear to be similar to the results of the weekly regimen, as shown in more recent studies. 11 …”

Reply: Interim PET in Hodgkin Lymphoma: Is It So Useless?

“…In addition, comparisons with historical studies that suffered from inadequate methodology and heterogeneous results are futile (21). We individually criticized all 3 of these studies for these issues (27)(28)(29). On the other hand, multiple, recently published, large-scale studies (14,(24)(25)(26) unambiguously showed that (in contrast to the studies by Gallamini et al (12,13)) a high proportion of the large group of patients with negative interim 18 F-FDG PET/CT results develops disease relapse during follow-up and that, therefore, a negative interim 18 F-FDG PET/CT result cannot exclude residual disease.…”