What Is the Comparative Ability of 18F-FDG PET/CT, 99mTc-MDP Skeletal Scintigraphy, and Whole-body MRI as a Staging Investigation to Detect Skeletal Metastases in Patients with Osteosarcoma and Ewing Sarcoma?

Abstract

Background Skeletal metastases of bone sarcomas are indicators of poor prognosis. Various imaging modalities are available for their identification, which include bone scan, positron emission tomography/CT scan, MRI, and bone marrow aspiration/biopsy. However, there is considerable ambiguity regarding the best imaging modality to detect skeletal metastases. To date, we are not sure which of these investigations is best for screening of skeletal metastasis. Question/purpose Which staging investigation—18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT), whole-body MRI, or 99mTc-MDP skeletal scintigraphy—is best in terms of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in detecting skeletal metastases in patients with osteosarcoma and those with Ewing sarcoma? Methods A prospective diagnostic study was performed among 54 of a total 66 consecutive osteosarcoma and Ewing sarcoma patients who presented between March 2018 and June 2019. The institutional review board approved the use of all three imaging modalities on each patient recruited for the study. Informed consent was obtained after thoroughly explaining the study to the patient or the patient’s parent/guardian. The patients were aged between 4 and 37 years, and their diagnoses were proven by histopathology. All patients underwent 99mTc-MDP skeletal scintigraphy, 18F-FDG PET/CT, and whole-body MRI for the initial staging of skeletal metastases. The number and location of bone and bone marrow lesions diagnosed with each imaging modality were determined and compared with each other. Multidisciplinary team meetings were held to reach a consensus about the total number of metastases present in each patient, and this was considered the gold standard. The sensitivity, specificity, PPV, and NPV of each imaging modality, along with their 95% confidence intervals, were generated by the software Stata SE v 15.1. Six of 24 patients in the osteosarcoma group had skeletal metastases, as did 8 of 30 patients in the Ewing sarcoma group. The median (range) follow-up for the study was 17 months (12 to 27 months). Although seven patients died before completing the minimum follow-up, no patients who survived were lost to follow-up. Results With the number of patients available, we found no differences in terms of sensitivity, specificity, PPV, and NPV among the three staging investigations in patients with osteosarcoma and in patients with Ewing sarcoma. Sensitivities to detect bone metastases for 18F-FDG PET/CT, whole-body MRI, and 99mTc-MDP skeletal scintigraphy were 100% (6 of 6 [95% CI 54% to 100%]), 83% (5 of 6 [95% CI 36% to 100%]), and 67% (4 of 6 [95% CI 22% to 96%]) and specificities were 100% (18 of 18 [95% CI 82% to 100%]), 94% (17 of 18 [95% CI 73% to 100%]), and 78% (14 of 18 [95% CI 52% to 94%]), respectively, in patients with osteosarcoma. In patients with Ewing sarcoma, sensitivities to detect bone metastases for 18F-FDG PET/CT, whole-body MRI, and 99mTc-MDP skeletal scintigraphy were 88% (7 of 8 [95% CI 47% to 100%]), 88% (7 of 8 [95% CI 47% to 100%]), and 50% (4 of 8 [95% CI 16% to 84%]) and specificities were 100% (22 of 22 [95% CI 85% to 100%]), 95% (21 of 22 [95% CI 77% to 100%]), and 95% (21 of 22 [95% CI 77% to 100%]), respectively. Further, the PPVs for detecting bone metastases for 18F-FDG PET/CT, whole-body MRI, and 99mTc-MDP skeletal scintigraphy were 100% (6 of 6 [95% CI 54% to 100%]), 83% (5 of 6 [95% CI 36% to 100%]), and 50% (4 of 8 [95% CI 16% to 84%]) and the NPVs were 100% (18 of 18 [95% CI 82% to 100%]), 94% (17 of 18 [95% CI 73% to 100%]), and 88% (14 of 16 [95% CI 62% to 98%]), respectively, in patients with osteosarcoma. Similarly, the PPVs for detecting bone metastases for 18F-FDG PET/CT, whole-body MRI, and 99mTc-MDP skeletal scintigraphy were 100% (7 of 7 [95% CI 59% to 100%]), 88% (7 of 8 [95% CI 50% to 98%]), and 80% (4 of 5 [95% CI 28% to 100%]), and the NPVs were 96% (22 of 23 [95% CI 78% to 100%]), 95% (21 of 22 [95% CI 77% to 99%]), and 84% (21 of 25 [95% CI 64% to 96%]), respectively, in patients with Ewing sarcoma. The confidence intervals around these values overlapped with each other, thus indicating no difference between them. Conclusion Based on these results, we could not demonstrate a difference in the sensitivity, specificity, PPV, and NPV between 18F-FDG PET/CT, whole-body MRI, and 99mTc-MDP skeletal scintigraphy for detecting skeletal metastases in patients with osteosarcoma and Ewing sarcoma. For proper prognostication, a thorough metastatic workup is essential, which should include a highly sensitive investigation tool to detect skeletal metastases. However, our study findings suggest that there is no difference between these three imaging tools. Since this is a small group of patients in whom it is difficult to make broad recommendations, these findings may be confirmed by larger studies in the future. Level of Evidence Level II, diagnostic study.

Current approaches to management of bone sarcoma in adolescent and young adult patients

“…84,86 Data support the use of 18F-fluorodeoxyglucose positron emission tomography with computerized tomography (FDG-PET/CT) scanning both for accurate staging, especially of the skeleton, and for determining response to chemotherapy in selected patients. [87][88][89] Approaches to follow-up after treatment vary in visit intervals, pulmonary imaging modalities, and monitoring for late effects of treatment. 90,91 There is considerable variation in recommendations and practice, indicating a need for collaborative prospective evaluation and evidence-seeking.…”

“…[99][100][101][102][103] Wholebody magnetic resonance imaging (WB-MRI) appears comparable to FDG-PET/CT and superior to bone scintigraphy, without requiring ionizing radiation. 87,104 In centers with access to these imaging modalities, it is possible to avoid an invasive bone marrow biopsy. 105 Widespread acceptance for PET-CT or, alternatively, WB-MRI as the standard for staging bone marrow will require prospective trials that incorporate large homogeneous cohorts of patients with ES.…”

Is It Time to Call Time on Bone Marrow Biopsy for Staging Ewing Sarcoma (ES)?

“…The two imaging modalities were equally effective, revealing the same lesions in most body regions, except WB-MRI detected more spinal lesions [36]. A recent prospective diagnostic study on primary bone sarcoma including ES (n = 30) used frequency tables and multidisciplinary team consensus to compare the staging of bone metastases by WB-MRI and/or FDG-PET/CT with bone scan [37]. The sensitivity was 88, 88, 50%, specificity 95, 100, 95%, PPV, 88, 100, 80% and NNV, 95, 96, 84% for WB-MRI, FDG-PET/CT and bone scan, respectively [37].…”

Current Approaches to Management of Bone Sarcoma in Adolescent and Young Adult (AYA) Patients

“…85,87 Data to support the use of FDG-PET/CT scanning both for accurate staging, especially of the skeleton, and to determine response to chemotherapy, supports its use in selected patients. [88][89][90] Approaches to follow-up after treatment vary in visit intervals, pulmonary imaging modalities and monitoring for late effects of treatment. Access to rehabilitation, assistance in resuming progress on achieving life skills and identifying psychological impacts are all vital parts of effective follow up for AYAs but there is considerable variation in recommendations and practice, indicating a need for collaborative prospective evaluation and evidence-seeking.…”

“…[95][96][97][98][99] WB-MRI appears comparable to FDG-PET/CT and superior to bone scintigraphy, without requiring ionising radiation. 88,100 In centers with access to these imaging modalities, it is possible to avoid an invasive bone marrow biopsy. Widespread acceptance for PET-CT or alternatively, WB-MRI as the standard for staging bone marrow will require prospective trials that incorporate large homogenous cohorts of patients with ES.…”