Systematic Review and Meta-analysis on the Diagnostic Performance of FDG-PET/CT in Detecting Bone Marrow Involvement in Newly Diagnosed Hodgkin Lymphoma

Is Bone Marrow Biopsy Still Necessary?

H. J. A. Adams; T. C. Kwee; B. de Keizer; R. Fijnheer; J. M. H. de Klerk; A. S. Littooij; R. A. J. Nievelstein

Disclosures

Ann Oncol. 2014;25(5):921-927. 

In This Article

Abstract and Introduction

Abstract

Background. This study aimed to systematically review and meta-analyze published data on the diagnostic performance of 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) in detecting bone marrow involvement in newly diagnosed Hodgkin lymphoma, and to determine whether FDG-PET/CT can replace blind bone marrow biopsy (BMB) in these patients.

Patients and Methods. The PubMed/Medline and Embase databases were systematically searched for relevant studies. Methodological quality of each study was assessed. Sensitivities and specificities of FDG-PET/CT in individual studies were calculated and underwent meta-analysis with a random effects model. A summary receiver operating characteristic curve (sROC) was constructed with the Moses–Shapiro–Littenberg method. The weighted summary proportion of FDG-PET/CT-negative patients with a positive BMB among all cases was calculated under the fixed effects model.

Results. Nine eligible studies, comprising a total of 955 patients with newly diagnosed Hodgkin lymphoma, were included. Overall, the studies were of moderate methodological quality. The sensitivity and specificity of FDG-PET/CT for the detection of bone marrow involvement ranged from 87.5% to 100% and from 86.7% to 100%, respectively, with pooled estimates of 96.9% [95% confidence interval (CI) 93.0% to 99.0%] and 99.7% (95% CI 98.9% to 100%), respectively. The area under the sROC curve was 0.9860. The weighted summary proportion of FDG-PET/CT-negative patients with a positive BMB among all cases was 1.1% (95% CI 0.6% to 2.0%).

Conclusion. Although the methodological quality of studies that were included in this systematic review and meta-analysis was moderate, the current evidence suggests that FDG-PET/CT may be an appropriate method to replace BMB in newly diagnosed Hodgkin lymphoma.

Introduction

The crude incidence of Hodgkin lymphoma in the European Union is 2.2 and the mortality is 0.7 cases/100,000/year.[1] Diagnosis of bone marrow involvement is of importance in Hodgkin lymphoma, because its presence indicates the highest Ann Arbor stage (stage IV), and this may have prognostic and therapeutic implications.[2] The standard method for the diagnosis of bone marrow involvement is unilateral or bilateral blind bone marrow biopsy (BMB) of the iliac crest. However, BMB is an invasive procedure that can cause discomfort to the patient.[3] Besides being invasive, it is important to realize that BMB assesses only a very small portion of the entire bone marrow. Consequently, focal bone marrow involvement can be missed by BMB.[4] Meanwhile, 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET)/computed tomography (CT) has become a commonly used method for staging newly diagnosed Hodgkin lymphoma, outperforming CT alone in this setting.[5]18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) is used for both nodal and extranodal staging, including bone marrow assessment. Major advantages of FDG-PET/CT over BMB are its noninvasiveness and the absence of sampling errors because FDG-PET/CT can visualize the entire bone marrow. Given the fact that Hodgkin lymphoma is virtually always FDG-avid,[6] FDG-PET/CT may be a very useful method for bone marrow assessment in Hodgkin lymphoma and may potentially obviate the need for BMB. In the past few years, several studies have been published on the utility of FDG-PET/CT for bone marrow assessment in Hodgkin lymphoma. However, it is difficult to draw conclusions based on these individual studies, because the incidence of bone marrow involvement in Hodgkin lymphoma is relatively low (its incidence has been reported to vary between 4% and 14%[7]), study quality may vary, and differences in patient population and study design may cause heterogeneity in study results. In order to overcome the shortcomings of individual studies, a systematic review and meta-analysis are required. The purpose of this study was therefore to systematically review and meta-analyze published data on the diagnostic performance of FDG-PET/CT in detecting bone marrow involvement in newly diagnosed Hodgkin lymphoma, and to determine whether FDG-PET/CT can replace BMB in these patients.

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