Department of Orthopaedics, All India Institute of Medical Sciences, New Delhi, India.
Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India.
Clin Orthop Relat Res. 2021 Aug 1;479(8):1768-1779. doi: 10.1097/CORR.0000000000001681.
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?
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.
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.
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 II, diagnostic study.
骨肉瘤的骨骼转移是预后不良的指标。有多种影像学方法可用于识别这些转移，包括骨扫描、正电子发射断层扫描/CT 扫描、MRI 和骨髓抽吸/活检。然而，哪种影像学方法是检测骨骼转移的最佳方法尚存在较大争议。迄今为止，我们不确定这些检查中哪一种最适合筛查骨骼转移。
问题/目的：在检测骨肉瘤和尤文肉瘤患者的骨骼转移方面，18F-氟脱氧葡萄糖正电子发射断层扫描/CT（18F-FDG PET/CT）、全身 MRI 和 99mTc-MDP 骨骼闪烁显像的哪种分期检查在灵敏度、特异性、阳性预测值（PPV）和阴性预测值（NPV）方面具有优势？
对 2018 年 3 月至 2019 年 6 月期间连续就诊的 66 例骨肉瘤和尤文肉瘤患者中的 54 例进行了前瞻性诊断研究。机构审查委员会批准了对每位入组研究的患者使用这三种影像学方法。在向患者或其父母/监护人充分解释研究后，获得了知情同意。患者年龄在 4 至 37 岁之间，其诊断均经组织病理学证实。所有患者均接受 99mTc-MDP 骨骼闪烁显像、18F-FDG PET/CT 和全身 MRI 进行初始骨骼转移分期。确定并比较了每种影像学方法诊断的骨和骨髓病变的数量和位置。举行多学科团队会议，以确定每位患者的总转移病灶数，并将其作为金标准。通过 Stata SE v 15.1 生成每种影像学方法的灵敏度、特异性、PPV 和 NPV 及其 95%置信区间。24 例骨肉瘤患者中有 6 例有骨骼转移，30 例尤文肉瘤患者中有 8 例有骨骼转移。研究的中位（范围）随访时间为 17 个月（12 至 27 个月）。尽管 7 名患者在完成最低随访前死亡，但没有幸存者失访。
根据可获得的患者数量，我们发现骨肉瘤和尤文肉瘤患者的三种分期检查在灵敏度、特异性、PPV 和 NPV 方面没有差异。18F-FDG PET/CT、全身 MRI 和 99mTc-MDP 骨骼闪烁显像检测骨转移的灵敏度分别为 100%（6/6 [95%CI 54%至 100%]）、83%（5/6 [95%CI 36%至 100%]）和 67%（4/6 [95%CI 22%至 96%]），特异性分别为 100%（18/18 [95%CI 82%至 100%]）、94%（17/18 [95%CI 73%至 100%]）和 78%（14/18 [95%CI 52%至 94%]）。在骨肉瘤患者中，18F-FDG PET/CT、全身 MRI 和 99mTc-MDP 骨骼闪烁显像检测骨转移的灵敏度分别为 88%（7/8 [95%CI 47%至 100%]）、88%（7/8 [95%CI 47%至 100%]）和 50%（4/8 [95%CI 16%至 84%]），特异性分别为 100%（22/22 [95%CI 85%至 100%]）、95%（21/22 [95%CI 77%至 100%]）和 95%（21/22 [95%CI 77%至 100%]）。此外，18F-FDG PET/CT、全身 MRI 和 99mTc-MDP 骨骼闪烁显像检测骨转移的 PPV 分别为 100%（6/6 [95%CI 54%至 100%]）、83%（5/6 [95%CI 36%至 100%]）和 50%（4/8 [95%CI 16%至 84%]），NPV 分别为 100%（18/18 [95%CI 82%至 100%]）、94%（17/18 [95%CI 73%至 100%]）和 88%（14/16 [95%CI 62%至 98%]）。同样，18F-FDG PET/CT、全身 MRI 和 99mTc-MDP 骨骼闪烁显像检测骨转移的 PPV 分别为 100%（7/7 [95%CI 59%至 100%]）、88%（7/8 [95%CI 50%至 98%]）和 80%（4/5 [95%CI 28%至 100%]），NPV 分别为 96%（22/23 [95%CI 78%至 100%]）、95%（21/22 [95%CI 77%至 99%]）和 84%（21/25 [95%CI 64%至 96%]）。这些值的置信区间相互重叠，表明它们之间没有差异。
根据这些结果，我们无法证明骨肉瘤和尤文肉瘤患者的 18F-FDG PET/CT、全身 MRI 和 99mTc-MDP 骨骼闪烁显像在检测骨骼转移方面的灵敏度、特异性、PPV 和 NPV 存在差异。为了进行适当的预后评估，需要进行彻底的转移性检查，其中应包括一种高度敏感的检测骨骼转移的工具。然而，我们的研究结果表明，这三种影像学工具之间没有差异。由于这是一个患者人数较少的小组，很难提出广泛的建议，因此这些发现可能会在未来的更大研究中得到证实。
II 级，诊断研究。
