This review assessed diagnostic performance of computed tomography (CT), 18F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET), FDG-PET/CT fusion and whole-body magnetic resonance imaging (WB-MRI) in the staging of malignant lymphoma. The conclusions that FDG-PET may have a role in re-staging and FDG-PET/CT fusion appears more accurate than either modality alone are supported by the data presented and are likely to be reliable.

To assess the diagnostic performance of computed tomography (CT), ¹⁸F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET), FDG-PET/CT fusion and whole -body magnetic resonance imaging (WB-MRI) in the staging of malignant lymphoma.

MEDLINE and EMBASE were searched to July 2007; the search strategy was reported in full. Only studies published in English, German or French were considered for inclusion. Bibliographies of included studies were screened for additional articles.

Studies that investigated the diagnostic performance of CT, FDG-PET, FDG-PET/CT or WB-MRI in staging or re-staging of 11 or more patients with histologically proven malignant lymphoma were eligible for inclusion. Included studies were required to image the area from neck to pelvis, as a minimum. Included studies were required to employ a clinicoradiological follow-up period of at least six months as the reference standard in all patients and to report sufficient data to calculate estimates of diagnostic performance with confidence intervals (CIs). Studies that did not distinguish between initial staging and re-staging were excluded. Studies of older generation CT scanners (incremental, single-section and dual-section CT), FDG-PET with a gamma camera in coincidence mode or low-field strength (<1.0T) MRI were also excluded.

Imaging criteria for positivity varied across studies of the same imaging modality.

Two reviewers independently assessed studies for inclusion and disagreements were resolved by consensus.

The internal and external validity of included studies were separately assessed. Internal validity was assigned a score out of 7 based on the following criteria: prospective study, avoidance of incorporation bias, avoidance of diagnostic review bias, avoidance of test review bias, avoidance of comparator review bias, minimum of withdrawal bias and avoidance of study examination bias. External validity was assigned a score out of 5 based on the following criteria: avoidance of patient filtering bias, avoidance of spectrum bias, avoidance of selection bias, standard execution of the index test and avoidance of observer variability bias. Scores were expressed as a percentage of the total.

Two reviewers independently assigned scores. Disagreements were resolved by consensus.

Data were extracted on criteria for positivity and to calculate sensitivity and specificity, with 95% CIs.

The authors stated neither how data were extracted for the review nor how many reviewers performed the data extraction.

Studies were combined in a narrative synthesis, grouped by imaging modality. Where possible, data were presented separately for staging and re-staging and for Hodgkin disease and non-Hodgkin lymphoma.

Nineteen studies were included in the review. Three studies (n=94) investigated CT, 17 studies (n=832) investigated FDG-PET and four studies (n=234) investigated FDG-PET/CT fusion. No studies of WB-MRI were identified. Two of the three studies of CT scored 3 for internal and external validity and the remaining study scored 4 for internal validity and 3 for external validity. Both internal and external validity scores for FDG-PET studies ranged from 2 to 4. Internal validity scores for FDG-PET/CT fusion studies ranged from 2 to 3 and external validity scores ranged from 3 to 5.

Accuracy of CT: One study assessed the performance of CT for initial staging by region of Hodgkin disease and reported a sensitivity of 87.5% (95% CI 75.3 to 94.1) and a specificity of 85.6% (95% CI 78.0 to 91.2). All three CT studies reported performance for re-staging. For the study that reported results by region for Hodgkin disease, performance was similar to that for initial staging. The remaining two studies were in mixed populations and reported per-patient sensitivities of 100% (95% CI 51.0 to 100) and 25 (95% CI 4.6 to 70) and corresponding specificities of 58.8% (95% CI 36.0 to 78.4) and 41.7 (95% CI 24.5 to 61.2).

Accuracy of FDG-PET: One study reported per-lesion data for initial staging of Hodgkin disease with sensitivity of 87.5% (95% CI 52.9 to 97.8) and specificity 100% (95% CI 34.2 to 100). Per-patient sensitivity for re-staging of Hodgkin disease ranged from 86.2% (95% CI 69.4 to 94.5) to 100% (95% CI 87.1 to 100) and specificity ranged from 57.1% (95% CI 36.6 to 75.5) to 100% (95% CI 89.0 to 100) based on data from eight studies. One study reported per-lesion data for initial staging of non-Hodgkin lymphoma with sensitivity of 83.3% (95% CI 43.7 to 97.0) and specificity of 100% (95% CI 20.7 to 100). Per-patient sensitivity for re-staging of non-Hodgkin lymphoma ranged from 60.0% (95% CI 35.8 to 80.2) to 87.0% (95% CI 74.3 to 93.9) and specificity ranged from 80.0% (95% CI 64.1 to 90.0) to 100% (95% CI 88.7 to 100) based on data from four studies. Seven studies of mixed populations reported similar performance characteristics.

Accuracy of FDG-PET/CT fusion: Performance characteristics of FDG-PET/CT fusion in mixed populations were similar across studies for initial staging and re-staging and using by-region and by-patient analysis. Overall, sensitivities ranged from 91.3% (95% CI 73.2 to 97.6) to 100% (95% CI 87.5 to 100) and specificities ranged from 90.6% (95% CI 85.3 to 94.1) to 100% (95% CI 97.8 to 100). One study assessed the accuracy of FDG-PET/CT fusion for re-staging Hodgkin disease on a per patient basis with sensitivity of 100% (95% CI 85.7 to 100) and specificity of 90.7% (95% CI 78.4 to 96.3).

Included studies were of moderate methodological quality and used different staging systems. CT remains the standard imaging modality for initial staging of malignant lymphoma. FDG-PET had an essential role in re-staging. Initial data suggested that FDG-PET/CT fusion outperformed either modality used alone. Data on the diagnostic performance of WB-MRI were lacking.

The review addressed a clearly stated research question and appropriate inclusion criteria were defined. A range of sources were searched for relevant studies, but the restriction to English, German and French studies left open the possibility of language bias. No attempt to identify unpublished studies was reported, which raised the possibility of publication bias. Inclusion screening and assessment of methodological quality incorporated measures to reduce error and bias, but it was unclear whether similar measures were applied to the data extraction process. The use of a narrative synthesis seemed appropriate given the heterogeneity in criteria for positivity between studies of the same imaging modality. The authors' conclusions on the potential role of FDG-PET and FDG-PET/CT fusion are a reasonable interpretation of the data presented and are likely to be reliable. However, the conclusion that CT remains the standard imaging modality for initial staging of malignant lymphoma did not seem to be supported by data included in the review.

Practice: The authors did not specify any implications for practice.

Research: The authors stated that well-designed studies that expressed results according to the Ann Arbor staging system were needed to determine the most accurate and cost-effective imaging modality in staging malignant lymphoma.

Not reported.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.