Annals of Oncology 13:157-160, 2002
© 2002 European Society for Medical Oncology
FDGPET for detection of recurrences from malignant primary bone tumors: comparison with conventional imaging

Departments of 1Nuclear Medicine, 2Clinical Radiology and 3Pediatric Hematology and Oncology, University Hospital, Münster, Germany
Received 27 April 2001; revised 28 June 2001; accepted 27 July 2001.
| Abstract |
|---|
|
|
|---|
Background
The aim of this study was to assess the diagnostic ability of positron emission tomography using 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDGPET) in the detection of recurrences from malignant primary bone tumors compared with conventional imaging.
Patients and methods
In 27 patients (6 osteosarcomas, 21 Ewings sarcomas), 41 FDGPET examinations performed for diagnosis or exclusion of recurrent disease were evaluated. Conventional imaging techniques consisted of magnetic resonance imaging of the primary tumor site, thoracic computed tomography, and Tc-99m methylene diphosphonate bone scintigraphy. The reference methods were the histopathological analysis and/or the clinical and imaging follow-up.
Results
In 25 examinations reference methods revealed 52 sites of recurrent disease (local n = 7; distant: osseous n = 22, pulmonary n = 13, soft tissue n = 10). On an examination-based analysis FDGPET had a sensitivity of 0.96, a specificity of 0.81 and an accuracy of 0.90. Corresponding values for conventional imaging were 1.0, 0.56 and 0.82.
Conclusions
The sensitivity, specificity and accuracy of FDGPET in the detection of recurrences from osseous sarcomas are high. On an examination-based analysis, FDGPET had a not significantly lower sensitivity in comparison with conventional imaging. However, FDGPET showed a small advantage in the detection of osseous and soft-tissue recurrences compared with conventional imaging.
Key words: bone scintigraphy, CT, FDGPET, malignant primary bone tumors, MRI, recurrences
| Introduction |
|---|
|
|
|---|
The current diagnostic tools for the detection or exclusion of recurrences from primary osseous sarcomas are clinical examination, magnetic resonance imaging (MRI) [or computed tomography (CT) or X-ray] of the primary tumor site, chest X-ray (or thoracic CT) and bone scintigraphy [1, 2]. Positron emission tomography using 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDGPET) has been used for the grading and therapy monitoring of malignant primary osseous tumors [35]. However, a systematic evaluation of the ability of FDGPET to detect local and distant recurrences from malignant primary bone tumors has not been published before now.
| Patients and methods |
|---|
|
|
|---|
Patient population
In this retrospective analysis, we included all 27 patients (aged between 8 and 35 years, median 17 years; nine female, 18 male; six osteosarcomas, 21 Ewings sarcomas) with a histologically proven malignant primary osseous tumor who underwent one (n = 19) or more (n = 8) FDGPET examinations (total n = 41) within a 5.5-year period, and who had a documented complete remission of their disease before the examination(s). FDGPET examinations and conventional imaging had been performed as routine follow-up (n = 33) or because of suspicious recurrence due to pain (n = 8).
Imaging techniques
FDGPET. FDGPET scans (15 emission, 26 emission/transmission scanning) were acquired as described previously [6]. Blood glucose levels at the time of injection were <6.66 mmol/l in all studies. All patients/parents gave their informed consent to all FDGPET examinations.
Conventional imaging. The conventional imaging methods, performed within 1 month of the FDGPET, either before or after, were Tc-99m methylene diphosphonate bone scintigraphy (n = 41), thoracic computed tomography (n = 38; thoracic X-ray in three examinations), and MRI of the primary tumor site (n = 39; CT in one examination and X-ray in one examination).
Planar bone scintigraphy and spiral thoracic CT examination were performed as described previously [6, 7]. MRI of the primary tumor site was performed using a 1.5 Tesla system (Magnetom SP or Magnetom Vision, Siemens, Erlangen, Germany) with the smallest available surface coil. Pulse sequences comprised pre-contrast T1- and T2-weighted spinecho (SE) images as well as post-contrast T1-weighted SE images with and without fat suppression after injection of gadolinium diethylenetriamine penta-acid (0.1 mmol/kg body weight). Pulse sequence parameters and slice orientation varied with the examined anatomic site.
Imaging analysis
All images were evaluated qualitatively by two experienced observers (consensus readings) blinded to any results of other imaging studies and to pathological data. On FDGPET scans (emission scans, and attenuation-corrected scans if available) any focal uptake above background level was considered to be recurrent disease, unless explained by other conditions, i.e. adequate trauma. FDG activity ratios between the visually detectable lesions and homologous normal tissue were calculated using regions of interest (maximum count rates).
Reference methods
Recurrent disease was confirmed by histological examination and/or by an obvious progression in the number and/or size of the lesions on follow-up examinations. A lesion was determined as being benign by a stable clinical and imaging follow-up for at least 5 months (534 months, median 15 months) and/or a histological examination.
| Results |
|---|
|
|
|---|
Reference methods
Reference methods (follow-up n = 24, histology n = 28) revealed 52 sites of recurrent disease [local n = 7 (13%); distant: osseous n = 22 (42%), pulmonary/pleural n = 13 (25%), soft tissue n = 10 (19%)] in 25 of 41 (61%) examinations (routine follow-up n = 7, symptoms n = 18; 16 patients). Follow-up and histological analyses (n = 4) revealed no recurrent disease in the remaining 16 examinations (11 patients).
Imaging
Results are shown in Tables 1 and 2. There were no significant differences between the tumor types, osteosarcoma and Ewings sarcoma.
|
|
The FDG activity ratios of foci ranged from 1.3 to 4.0. A differentiation between malignant and benign lesions was not possible using this semi-quantitative analysis.
| Discussion |
|---|
|
|
|---|
In the present analysis, FDGPET demonstrated a high accuracy in the detection of recurrent disease of osseous sarcomas in both local and distant sites.
Local recurrences
All local recurrences (n = 7) were identified by FDGPET and conventional imaging in our patient group. This is in agreement with previous investigations performed in patients with soft-tissue sarcomas [810]. In the present study, the number of false-positive results showed a superiority of FDGPET. Despite advances in MRI, differentiating viable tumors from scarring after treatment can be difficult [2, 10]. Furthermore, scar tissue may co-exist with tumor tissue. In addition, tracer enhancement in skeletal scintigraphy could also be a result of trauma or infection [11]. By characterizing metabolic behavior, FDGPET has potential in distinguishing recurrent lesions from metabolically inactive tissue and in providing unique information about the distribution of active tumor. This may help in finding appropriate regions for biopsy [9].
Pulmonary/pleural recurrences
The inferiority of FDGPET in the detection of pulmonary recurrences is in agreement with data from soft-tissue sarcoma patients [10]. Furthermore, the superiority of thoracic CT in the diagnosis of pulmonary/pleural metastases from osseous sarcomas has been shown [6]. Reasons for the poor FDGPET results might be the small size of pulmonary lesions resulting in partial volume effects and the blurring of the lesions in the FDGPET images caused by breathing [6]. However, sensitivity of FDGPET in the detection of pulmonary recurrences in this study (0.85) is higher compared with the overall detection of pulmonary involvement, either at the time of the first tumor manifestation or of the recurrent disease (0.50) [6]. Data from grading studies suggest that the higher sensitivity may indicate a more aggressive biological behavior [3].
Osseous recurrences
Pathological tracer uptake in skeletal scintigraphy is unspecific, resulting in a high number of false-positive findings [1]. In the present analysis, there is a superiority of FDGPET in sensitivity and specificity (false-positive findings), although the number of false-positive lesions seems to be a problem with FDGPET as well. In a previous study, the few skeletal metastases deriving from osteosarcoma (five metastases in two patients) were false negative using FDGPET [7]. In the present study, all sites of osseous recurrent disease (n = 6) deriving from osteosarcoma were true positive by FDGPET, possibly because of a higher metabolic activity compared with primary metastases.
Soft-tissue recurrences
Using conventional imaging, asymptomatic soft-tissue recurrences could only be detected in cases where they were located in the field of view of local MRI or thoracic CT, or if they produced osseous matrix (osteosarcoma) resulting in phosphonate uptake in skeletal scintigraphy. The advantage of FDGPET is that all organ systems, including soft tissue, can be visualized in a single whole-body examination [47, 10].
Conclusion
In the detection of recurrences of osseous sarcoma, sensitivity, specificity and accuracy of FDGPET are high. Compared with conventional imaging, FDGPET shows only a small advantage in the detection of osseous and soft-tissue recurrences. The results of the present study warrant a systematic, prospective and multi-centric evaluation of the clinical value of FDGPET in the diagnosis of bone sarcoma recurrences, including assessment of the convenience for the patients, the influence on outcome and costbenefit analysis. In particular, the detection of bone and soft-tissue recurrences in comparison with bone scintigraphy and, furthermore, with whole-body MRI [12] should be addressed. In future, FDGPET might replace bone scintigraphy within the imaging follow-up.
| Acknowledgements |
|---|
The authors gratefully acknowledge S. Bielack and S. Flege (Department of Pediatric Hematology and Oncology) for many helpful suggestions and their friendly ongoing cooperation, and A. Heinecke (Department of Medical Computer Science and Biomathematics) for his expert assistance with the statistical analysis. They would also like to thank all involved physicians, nurses, technicians and members of supporting services of the Departments of Pediatric Hematology and Oncology, Clinical Radiology and Nuclear Medicine at the University Hospital, Münster.
| Footnotes |
|---|
+ Correspondence to: Department of Nuclear Medicine, Münster University, Albert-Schweitzer-Strasse 33, 48149 Münster, Germany. Tel: +49-251-83-47362; Fax: +49-251-83-47383; E-mail: franziu@uni-muenster.de
Present address: Department of Radiology, Technical University, München, Germany. ![]()
| References |
|---|
|
|
|---|
1. Körholz D, Verheyen J, Engelbrecht V et al. Follow-up of patients with osteosarcoma and Ewings sarcoma: a retrospective costbenefit analysis. Klin Pädiatr 2000; 212: 220223.[Web of Science][Medline]
2. Reuther G, Mutschler W. Detection of local recurrent disease in muskuloskeletal tumors: magnetic resonance imaging versus computed tomography. Skeletal Radiol 1990; 19: 8590.[Web of Science][Medline]
3.
Schulte M, Brecht-Krauss D, Heymer B et al. Grading of tumors and tumorlike lesions of bone: evaluation by 2-(fluorine-18)-fluoro-2deoxy-D-glucose positron emission tomography. J Nucl Med 2000; 41: 16951701.
4.
Schulte M, Brecht-Krauss D, Werner M et al. Evaluation of neoadjuvant therapy response of osteogenic sarcoma using FDGPET. J Nucl Med 1999; 40: 16371643.
5. Franzius C, Sciuk J, Brinkschmidt C et al. Evaluation of chemotherapy response in primary bone tumors with F-18 FDG positron emission tomography compared with histologically assessed tumor necrosis. Clin Nucl Med 2000; 25: 874881.[Web of Science][Medline]
6.
Franzius C, Daldrup-Link HE, Sciuk J et al. FDGPET for detection of pulmonary metastases from malignant primary bone tumors: comparison with spiral CT. Ann Oncol 2001; 12: 479486.
7. Franzius C, Sciuk J, Daldrup-Link HE et al. FDGPET for detection of osseous metastases from malignant primary bone tumors: comparison with bone scintigraphy. Eur J Nucl Med 2000; 27: 13051311.[Web of Science][Medline]
8. Hain SF, ODoherty MJ, Lucas JD, Smith MA. Fluorodeoxyglucose PET in the evaluation of amputations for soft tissue sarcoma. Nucl Med Commun 1999; 20: 845848.[Web of Science][Medline]
9. Schwarzbach MHM, Dimitrakopoulou-Strauss A, Willeke F et al. Clinical value of [18-F]fluorodeoxyglucose positron emission tomography imaging in soft tissue sarcomas. Ann Surg 2000; 231: 380386.[Web of Science][Medline]
10. Lucas JD, ODoherty MJ, Wong JCH et al. Evaluation of fluorodeoxyglucose positron emission tomography in the management of soft-tissue sarcomas. J Bone Joint Surg Br 1998; 80: 441447.
11. Körholz D, Verheyen J, Kemperdick HF, Göbel U. Evaluation of follow-up investigations in osteosarcoma patients: suggestion for an effective follow-up program. Med Pediatr Oncol 1998; 30: 5258.[Web of Science][Medline]
12.
Daldrup-Link HE, Franzius C, Rummeney EJ et al. Whole body MRI for detection of bone marrow metastases in pediatric patients: comparison with skeletal scintigraphy and FDGPET. Am J Roentgenol 2001; 177: 229236.
![]()
CiteULike
Connotea
Del.icio.us What's this?
This article has been cited by other articles:
![]() |
G. J. Cheon, M. S. Kim, J. A. Lee, S.-Y. Lee, W. H. Cho, W. S. Song, J.-S. Koh, J. Y. Yoo, D. H. Oh, D. S. Shin, et al. Prediction Model of Chemotherapy Response in Osteosarcoma by 18F-FDG PET and MRI J. Nucl. Med., September 1, 2009; 50(9): 1435 - 1440. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. M. Bestic, J. J. Peterson, and L. W. Bancroft Use of FDG PET in Staging, Restaging, and Assessment of Therapy Response in Ewing Sarcoma RadioGraphics, September 1, 2009; 29(5): 1487 - 1500. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. J. Renouf, L. Wilson, and C. D. Blanke Successes and Challenges in Translational Research: The Development of Targeted Therapy for Gastrointestinal Stromal Tumours Clin. Cancer Res., June 15, 2009; 15(12): 3908 - 3911. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. C. Toner and R. J. Hicks PET for Sarcomas Other Than Gastrointestinal Stromal Tumors Oncologist, April 1, 2008; 13(suppl_2): 22 - 26. [Abstract] [Full Text] [PDF] |
||||
![]() |
U. Tateishi, U. Yamaguchi, K. Seki, T. Terauchi, Y. Arai, and E. E. Kim Bone and Soft-Tissue Sarcoma: Preoperative Staging with Fluorine 18 Fluorodeoxyglucose PET/CT and Conventional Imaging Radiology, December 1, 2007; 245(3): 839 - 847. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. U. Gerth, K. U. Juergens, U. Dirksen, J. Gerss, O. Schober, and C. Franzius Significant Benefit of Multimodal Imaging: PET/CT Compared with PET Alone in Staging and Follow-up of Patients with Ewing Tumors J. Nucl. Med., December 1, 2007; 48(12): 1932 - 1939. [Abstract] [Full Text] [PDF] |
||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||




