Focal skeletal FDG uptake indicates poor prognosis in cHL regardless of extent and first‐line chemotherapy

Abstract

18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) is used for staging classical Hodgkin lymphoma (cHL) with high sensitivity for skeletal involvement. However, it is unclear whether a single bone lesion carries the same adverse prognosis as multifocal lesions and if this is affected by type of chemotherapy [ABVD (adriamycin, bleomycin, vincristine, dacarbazine) versus BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone)]. We reviewed the clinico-pathological and outcome data from 209 patients with newly diagnosed cHL staged by FDG-PET/CT. Patterns of skeletal/bone marrow uptake (BMU) were divided into 'low' and 'high' diffuse BMU (i.e. without focal lesions), and unifocal or multifocal lesions. Additional separate survival analysis was performed, taking type of chemotherapy into account. Forty patients (19Á2%) had skeletal lesions (20 unifocal, 20 multifocal). The 3-year progression-free-survival (PFS) was 80% for patients with 'low BMU', 87% for 'high BMU', 69% for 'unifocal' and 51% for 'multifocal' lesions; median follow-up was 38 months. The presence of bone lesions, both uni-and multifocal, was associated with significantly inferior PFS (log rank P = 0Á0001), independent of chemotherapy type. Thus, increased diffuse BMU should not be considered as a risk factor in cHL, whereas unifocal or multifocal bone lesions should be regarded as important predictors of adverse outcome, irrespective of the chemotherapy regimen used.

Value of detecting bone marrow involvement in Hodgkin lymphoma

“…Tumour stage is the most important prognostic factor in Hodgkin lymphoma and a high tumour stage may be assigned on other grounds than bone marrow involvement alone, which may also carry prognostic information. As a result, the prognostic value of bone marrow involvement at FDG‐PET as reported by Pedersen et al () will probably be biased. This is reflected by the finding that stage IV patients without focal bone marrow involvement had an equal prognosis to stage IV patients with focal bone marrow involvement (Pedersen, et al , ).…”

“…As a result, the prognostic value of bone marrow involvement at FDG‐PET as reported by Pedersen et al () will probably be biased. This is reflected by the finding that stage IV patients without focal bone marrow involvement had an equal prognosis to stage IV patients with focal bone marrow involvement (Pedersen, et al , ). Note that the failure of bone marrow status to predict prognosis in stage IV patients has also previously been demonstrated when bone marrow biopsy (BMB, which is highly specific for the determination of bone marrow involvement) was used for this purpose (Munker, et al , ; Ferme, et al , ; Hasenclever & Diehl, ).…”

“…Diffusely increased bone FDG uptake was not prognostic, but was associated with low haemoglobin levels, low albumin levels, lymphocyte count as well as increased total leucocyte count and erythrocyte sedimentation rate. The authors postulated their results emphasize the importance of detecting bone lesions in Hodgkin lymphoma, because they are significantly associated with poor outcome (Pedersen et al , ). Furthermore, they claim diffusely increased bone marrow FDG uptake to be have an inflammatory/reactive aetiology.…”

“…A recent study by Pedersen et al () aimed to determine the prognostic value of increased (focal or diffuse) bone marrow fluorodeoxyglucose (FDG) uptake at pre‐treatment positron emission tomography (PET) in patients with Hodgkin lymphoma treated with various first‐line therapy regimens. The study included 209 patients with Hodgkin lymphoma, of whom 19 (9·1%) had stage I, 98 (46·9%) had stage II, 38 (18·2%0 had stage III, and 54 (25·9%) had stage IV disease.…”

“…Therefore, the Cotswolds report on the evaluation and staging of Hodgkin lymphoma (Lister, et al , ), which was published before FDG‐PET became clinically available, recommended that BMB should be restricted to patients with extramedullary, computed tomography‐based stage IIB, III and IV disease and only if a positive finding would change treatment planning. It would therefore have been valuable if Pedersen et al () had reported in how many cases bone marrow involvement as detected by FDG‐PET upstaged patients with presumed/extramedullary early‐stage disease to advanced‐stage disease, but unfortunately, this was not done. Furthermore, several benign conditions – which not infrequently occur in Hodgkin lymphoma (Sovani, et al , ) ‐ may mimic bone marrow involvement (Kwee, et al , ), and it remains questionable whether upstaging early‐stage Hodgkin lymphoma patients solely on the basis of increased uni‐ or multifocal increased FDG uptake is justified.…”