Fluorine-18-fluorodeoxyglucose positron emission tomography in response assessment before high-dose chemotherapy for lymphoma: a systematic review and meta-analysis

Abstract

Background: We conducted a systematic review and meta-analysis to better define the prognostic ability of fluorine-18-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) following salvage chemotherapy for relapsed or refractory Hodgkin's lymphoma (HL) and aggressive non-Hodgkin's lymphoma.

Methods: We searched PubMed (from inception to January 31, 2010), bibliographies, and review articles without language restriction. Two assessors independently assessed study characteristics, quality, and results. We performed a meta-analysis to determine prognostic accuracy.

Results: Twelve studies including 630 patients were eligible. The most commonly evaluated histologies were diffuse large B-cell lymphoma (n = 313) and HL (n = 187), which were typically treated with various salvage and high-dose chemotherapy regimens. Studies typically employed nonstandardized protocols and diagnostic criteria. The prognostic accuracy was heterogeneous across the included studies. (18)F-FDG PET had a summary sensitivity of 0.69 (95% confidence interval [CI], 0.56-0.81) and specificity of 0.81 (95% CI, 0.73-0.87). The summary estimates were stable in sensitivity analyses. In four studies that performed direct comparisons between PET and conventional restaging modalities, PET had a superior accuracy for predicting treatment outcomes. Subgroup and metaregression analyses did not identify any particular factor to explain the observed heterogeneity.

Conclusion: (18)F-FDG PET performed after salvage therapy appears to be an appropriate test to predict treatment failure in patients with refractory or relapsed lymphoma who receive high-dose chemotherapy. Some evidence suggests PET is superior to conventional restaging for this purpose. Given the methodological limitations in the primary studies, prospective studies with standardized methodologies are needed to confirm and refine these promising results.

Figure 1.

Study flow diagram. Abbreviation: PET, positron emission tomography.

Figure 2.

Sensitivity and specificity of pre–high-dose therapy ¹⁸F-FDG PET for lymphoma. The size of the square plotting symbol is proportional to the sample size (the number of patients who progressed or relapsed for sensitivity and in remission for specificity) for each study. Horizontal lines are the 95% confidence intervals. Dashed vertical lines are the summary sensitivity and specificity. Abbreviations: ¹⁸F-FDG PET, fluorine-18-fluorodeoxyglucose positron emission tomography.

Figure 3.

ROC plotting and summary ROC curve of pre–high-dose therapy ¹⁸F-FDG PET for lymphoma. Individual study estimates of sensitivity and 1 − specificity are shown. The size of each circle is proportional to the sample size for each study (all study participants). The dashed crescent boundary represents the 95% confidence region for the summary sensitivity and specificity (shown as the square symbol). Abbreviations: ¹⁸F-FDG PET, fluorine-18-fluorodeoxyglucose positron emission tomography; ROC, receiver operating characteristic.

Figure 4.

Comparison between pre–high-dose therapy ¹⁸F-FDG PET and conventional restaging. Individual study estimates of sensitivity and 1 − specificity are shown with a circular (PET) or square (conventional restaging) symbol. A solid (PET) or dashed (conventional restaging) line represents the summary receiver operating characteristic curve. Abbreviation: ¹⁸F-FDG PET, fluorine-18-fluorodeoxyglucose positron emission tomography.

Figure 5.

Subgroup and sensitivity analyses. Squares represent the summary sensitivity or specificity estimates for each analysis. Horizontal lines represent 95% confidence intervals. Dashed vertical lines indicate the summary sensitivity and specificity for the main analysis (top row). Abbreviations: DLBCL, diffuse large B-cell lymphoma; HL, Hodgkin's lymphoma; MRU, minimal residual uptake; NHL, non-Hodgkin's lymphoma.