The accuracy of 18F-FDG-PET/CT for the detection of metastatic rhabdomyosarcoma in newly diagnosed patients

Why is accurate staging of rhabdomyosarcoma important?

Rhabdomyosarcoma (RMS) accounts for 3% to 5% of all childhood cancers. Treatment consists of multidrug chemotherapy and surgery and/or radiotherapy. Treatment for newly diagnosed patients depends on the extent of the cancer. Five-year survival for patients with localised disease is around 75%, whereas it is below 30% for patients with disease that has spread to different part(s) of the body (metastatic disease). Survival for metastatic patients depends on the number of metastases as well as the site(s) of metastases. It is of great importance to accurately stage the extent of the disease because not recognising patients with metastatic disease would lead to undertreatment, whereas incorrectly identifying lesions as being metastatic would lead to overtreatment. 18F-FDG-PET/CT is a special imaging technique that could be helpful in visualising the extent of the disease in patients with newly diagnosed RMS. However, the accuracy (the ability to separate RMS metastases from other lesions) of 18F-FDG-PET/CT is currently unknown.

What was the aim of this review?

We wanted to find out how accurate 18F-FDG-PET/CT is for the detection of bone and lung metastases and lymph node involvement in patients with newly diagnosed RMS.

What was studied in this review?

We searched scientific literature databases for studies comparing the results of 18F-FDG-PET/CT to standard staging evaluation (histologic examinations (using a microscope to examine tissues and cells) or results of other imaging methods discussed by a multidisciplinary tumour board). The advantage of using 18F-FDG-PET/CT compared to standard staging evaluations would be the use of 18F-FDG-PET/CT as a single diagnostic test to detect metastases, thus reducing patient burden and lowering radiation exposure.

Main results

We included two studies involving a total of 36 participants with RMS. Because of the low number of participants in the included studies and the differences in quality between studies, we were not able to calculate summary values of sensitivity (the proportion of patients who have the condition and who received a positive result on the test) and specificity (the proportion of patients who do not have the condition and who received a negative result on the test), and the reported results should be viewed with caution.

The two included studies reported a sensitivity and specificity of 100% of 18F-FDG-PET/CT for the detection of bone metastases. The sensitivity for the detection of lung metastases was 50% in one study, and could not be estimated in the other study; specificity ranged from 96% to 100%. In both studies, the sensitivity for the detection of lymph node involvement was 100%, and specificity ranged from 89% to 100%.

How reliable are the results of the studies in this review?

The main limitation of this review was that the findings were based on only two studies with a total of 36 participants and due to the design of the studies we considered them to be at high risk of bias on specific domains.

In the included studies, histopathological (microscopic examination of tissue) confirmation was considered the optimal reference standard (the best available method to determine whether the condition is present or absent) to determine RMS metastases from other lesions; however, this was not done in all participants. In cases where no histopathological confirmation was done, the judgement of a multidisciplinary tumour board was considered the reference standard. Judgement of the multidisciplinary tumour boards was partly based on 18F-FDG-PET/CT imaging results, potentially resulting in overestimation of sensitivity and specificity. Furthermore, in one included study the participants all underwent the same diagnostic procedures, whereas in the other study this was not the case for all participants; this study did not clearly define what was considered a positive test result for 18F-FDG-PET/CT imaging. This might have biased the results.

What are the implications of this review?

The total number of studies and participants was too low to allow us to draw any firm conclusions. Large studies evaluating the accuracy of 18F-FDG-PET/CT in patients with RMS are needed.

How up-to-date is this review?

We searched for and used studies published from 1966 to 23 December 2020.

Authors' conclusions: 

The diagnostic accuracy of 18F-FDG-PET/CT for the detection of bone, lung, and lymph node metastases was reported in only two studies including a total of only 36 participants with newly diagnosed RMS. Because of the small number of studies (and participants), there is currently insufficient evidence to reliably determine the diagnostic accuracy of 18F-FDG-PET/CT in the detection of distant metastases. Larger series evaluating the diagnostic accuracy of 18F-FDG-PET/CT for the detection of metastases in patients with RMS are necessary.

Read the full abstract...
Background: 

Rhabdomyosarcoma (RMS) is the most common paediatric soft-tissue sarcoma and can emerge throughout the whole body. For patients with newly diagnosed RMS, prognosis for survival depends on multiple factors such as histology, tumour site, and extent of the disease. Patients with metastatic disease at diagnosis have impaired prognosis compared to those with localised disease. Appropriate staging at diagnosis therefore plays an important role in choosing the right treatment regimen for an individual patient.

Fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) is a functional molecular imaging technique that uses the increased glycolysis of cancer cells to visualise both structural information and metabolic activity. 18F-FDG-PET combined with computed tomography (CT) could help to accurately stage the extent of disease in patients with newly diagnosed RMS. In this review we aimed to evaluate whether 18F-FDG-PET could replace other imaging modalities for the staging of distant metastases in RMS.

Objectives: 

To determine the diagnostic accuracy of 18F-FDG-PET/CT imaging for the detection of bone, lung, and lymph node metastases in RMS patients at first diagnosis.

Search strategy: 

We searched MEDLINE in PubMed (from 1966 to 23 December 2020) and Embase in Ovid (from 1980 to 23 December 2020) for potentially relevant studies. We also checked the reference lists of relevant studies and review articles; scanned conference proceedings; and contacted the authors of included studies and other experts in the field of RMS for information about any ongoing or unpublished studies. We did not impose any language restrictions.

Selection criteria: 

We included cross-sectional studies involving patients with newly diagnosed proven RMS, either prospective or retrospective, if they reported the diagnostic accuracy of 18F-FDG-PET/CT in diagnosing lymph node involvement or bone metastases or lung metastases or a combination of these metastases. We included studies that compared the results of the 18F-FDG-PET/CT imaging with those of histology or with evaluation by a multidisciplinary tumour board as reference standard.

Data collection and analysis: 

Two review authors independently performed study selection, data extraction, and methodological quality assessement according to Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). We analysed data for the three outcomes (nodal involvement and lung and bone metastases) separately. We used data from the 2 × 2 tables (consisting of true positives, false positives, true negatives, and false negatives) to calculate sensitivity and specificity in each study and corresponding 95% confidence intervals. We did not consider a formal meta-analysis to be relevant because of the small number of studies and substantial heterogeneity between studies.

Main results: 

Two studies met our inclusion criteria. The diagnostic accuracy of 18F-FDG-PET/CT was reported in both studies, which included a total of 36 participants. We considered both studies to be at high risk of bias for the domain reference standard. We considered one study to be at high risk of bias for the domain index test and flow and timing. Sensitivity and specificity of 18F-FDG-PET/CT for the detection of bone metastases was 100% in both studies (95% confidence interval (CI) for sensitivity was 29% to 100% in study one and 40% to 100% in study two; 95% CI for specificity was 83% to 100% in study one and 66% to 100% in study two). The reported sensitivity of 18F-FDG-PET/CT for the detection of lung metastases was not calculated since only two participants in study two showed lung metastases, of which one was detected by 18F-FDG-PET/CT. Reported specificity was 96% in study one (95% CI 78% to 100%) and 100% (95% CI 72% to 100%) in study two. The reported sensitivity for the detection of nodal involvement was 100% (95% CI 63% to 100% in study one and 40% to 100% in study two); the reported specificity was 100% (95% CI 78% to 100%) in study one and 89% (95% CI 52% to 100%) in study two.