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Purpose: The objective of this study was to evaluate positron emission tomography (PET) using (18)F-fluoro-2-deoxy-D-glucose (FDG) in comparison to volumetry and standardized magnetic resonance imaging (MRI) parameters for the assessment of histological response in paediatric bone sarcoma patients., Methods: FDG PET and local MRI were performed in 27 paediatric sarcoma patients [Ewing sarcoma family of tumours (EWS), n = 16; osteosarcoma (OS), n = 11] prior to and after neoadjuvant chemotherapy before local tumour resection. Several parameters for assessment of response of the primary tumour to therapy by FDG PET and MRI were evaluated and compared with histopathological regression of the resected tumour as defined by Salzer-Kuntschik., Results: FDG PET significantly discriminated responders from non-responders using the standardized uptake value (SUV) reduction and the absolute post-therapeutic SUV (SUV2) in the entire patient population (SUV, p = 0.005; SUV2, p = 0.011) as well as in the subgroup of OS patients (SUV, p = 0.009; SUV2, p = 0.028), but not in the EWS subgroup. The volume reduction measured by MRI/CT did not significantly discriminate responders from non-responders either in the entire population (p = 0.170) or in both subgroups (EWS, p = 0.950; OS, p = 1.000). The other MRI parameters alone or in combination were unreliable and did not improve the results. Comparing diagnostic parameters of FDG PET and local MRI, metabolic imaging showed high superiority in the subgroup of OS patients, while similar results were observed in the population of EWS., Conclusion: FDG PET appears to be a useful tool for non-invasive response assessment in the group of OS patients and is superior to MRI. In EWS patients, however, neither FDG PET nor volumetry or standardized MRI criteria enabled a reliable response assessment to be made after neoadjuvant treatment.

Unlabelled: Hybrid PET/CT was compared with PET alone in the staging and restaging of patients with Ewing tumor to assess the benefit of the combined imaging technique., Methods: A total of 163 (18)F-FDG PET/CT studies performed in 53 patients (age: range, 4-38 y; median, 16.5 y) with histopathologically confirmed Ewing tumor were evaluated retrospectively. All PET/CT studies included low-dose CT for attenuation correction; in 91 examinations, additional diagnostic chest CT was performed. PET and CT data were assessed independently by 2 nuclear medicine physicians and 2 radiologists, respectively. Finally, both datasets were fused by use of software and analyzed by all 4 reviewers (consensus reading). Each lesion was scored with a 5-point scale. Biopsy, imaging, or clinical follow-up served as a standard of reference. Receiver operating characteristic (ROC) analyses were performed to evaluate PET and PET/CT performance characteristics. To measure the abilities to detect and correctly localize tumor foci, localization ROC (L-ROC) curves were generated for PET., Results: A total of 609 lesions were detected by PET alone. The hybrid PET/CT technique resulted in a change of score in 160 of these lesions (26%): higher scores in 23 lesions (4%) and lower scores in 137 lesions (23%). In 49 lesions detected by PET (8%), the localization had to be changed after image fusion. Additionally, 124 (21%) more lesions were found by PET/CT than by PET alone, resulting in a total of 733 lesions. As determined by lesion-based analysis, the sensitivity, specificity, and accuracy of PET were 71%, 95%, and 88%, respectively; the corresponding values for the hybrid PET/CT technique were 87%, 97%, and 94% (P < 0.0001). The areas under the curve in the ROC analysis were 0.82 for PET and 0.92 for PET/CT (P < 0.0001), and that in the L-ROC analysis was 0.66 for PET., Conclusion: PET/CT is significantly more accurate than PET alone for the detection and localization of lesions and improves staging for patients with Ewing tumor. The hybrid technique is superior to PET alone in terms of sensitivity, specificity, and accuracy, mainly because of the detection of new lesions.

Purpose: The outlook for patients with osteosarcoma who present with synchronous regional bone metastases (skip metastases), either in the primary bone site or transarticular, is considered to be extremely poor. This study was conducted to further investigate the prognostic implication of skip metastases in osteosarcoma., Patients and Methods: The authors retrospectively analyzed the collected data of 1,765 consecutive patients with newly diagnosed high-grade osteosarcoma of bone who were registered in the neoadjuvant Cooperative Osteosarcoma Study Group studies and identified 24 patients (1.4%) with unequivocally proven skip metastases. All 24 patients were treated by an aggressive surgical approach coupled with polychemotherapy. Demographic, diagnostic, tumor, and treatment-related variables and response and survival data were analyzed., Results: Skip metastases were identified preoperatively in 11 of 24 patients by bone scan, eight of 22 patients by plain x-ray, 15 of 18 patients by magnetic resonance imaging, and five of 10 patients by computed tomography. A complete surgical remission (CSR) of all clinically detectable tumor sites was achieved in 22 of 24 patients during front-line therapy. With a median follow-up time of 4.4 years (8 years for survivors) from diagnosis, 12 patients were alive, all of whom were in continuous CSR. Survival did correlate with location of skip metastases and histologic response to neoadjuvant chemotherapy., Conclusion: Synchronous regional bone metastases are rare in osteosarcoma, and preoperative detection relies on appropriate diagnostic imaging. Aggressive multimodal therapy holds the promise to achieve prolonged survival, especially in patients in whom these metastases occur within the same bone as the primary lesion and whose tumors respond well to chemotherapy.

Unlabelled: The purpose of this retrospective analysis was to evaluate the prognostic significance of both initial glucose metabolism as measured by (18)F-FDG PET and osteoblastic activity as measured by (99m)Tc-methylene diphosphonate (MDP) bone scintigraphy in osteosarcoma., Methods: In 29 patients (18 male, 11 female; age range, 5-41 y) with primary osteosarcoma, (18)F-FDG uptake and (99m)Tc-MDP uptake were measured semiquantitatively (average and maximum tumor-to-nontumor ratios [T/NT(av) and T/NT(max), respectively]) using PET and bone scintigraphy at the time of diagnosis. After chemotherapy, the patients underwent surgery for their primary tumor, and the response was determined histologically. Cumulative overall survival and event-free survival were determined by clinical and imaging follow-up of 7-72 mo (median, 28 mo)., Results: Clinical and imaging follow-up revealed that the disease relapsed or failed to achieve complete remission in 9 patients and that 6 patients died of the disease. Both overall and event-free survival were significantly better in patients with a low (18)F-FDG T/NT(max) (less than the median) than in patients with a high (18)F-FDG T/NT(max) (at least the median). The negative relationship of (18)F-FDG T/NT(av), (99m)Tc-MDP T/NT(max), and (99m)Tc-MDP T/NT(av) with overall and event-free survival did not reach a level of significance. (18)F-FDG uptake values correlated moderately and positively with (99m)Tc-MDP uptake values, but a level of significance was reached only between (18)F-FDG T/NT(max) and (99m)Tc-MDP T/NT(av)., Conclusion: The initial glucose metabolism of primary osteosarcoma as measured by (18)F-FDG PET using T/NT(max) provides prognostic information. High (18)F-FDG uptake correlates with poor outcome. Thus, (18)F-FDG uptake may be complementary to other well-known factors in judging the prognosis in osteosarcoma.

The cellular transport systems and the transport kinetics of [123I]IMT uptake into non-malignant extracranial cells were characterized for the first time. Human fibroblasts were chosen as non-malignant extracranial cells as they are found ubiquitous in the body. [123I]IMT is exclusively transported into fibroblasts via the sodium independent system L. An apparent Michaelis constant K(m) = 116.2 +/- 18.9 microM and a maximum transport velocity V(max) = 191.6 +/- 13.9 pmol x (10(6) cells)(-1) x min(-1) were calculated for the sodium-independent transport. These results were compared with those determined in two malignantly transformed extracranial cell lines, the human Ewing's sarcoma cell lines VH-64 and CADO-ES-1.

Purpose: Despite highly efficacious chemotherapy, patients with osteosarcomas still have a poor prognosis if adequate surgical control cannot be obtained. These patients may benefit from therapy with radiolabeled phosphonates., Patients and Methods: Six patients (three male, three female; seven to 41 years) with unresectable primary osteosarcoma (n = 3) or unresectable recurrent sites of osteosarcomas (n = 3) were treated with high-activity of Sm-153-EDTMP (150 MBq/kg BW). In all patients autologous peripheral blood stem cells had been collected before Sm-153-EDTMP therapy., Results: No immediate adverse reactions were observed in the patients. In one patient bone pain increased during the first 48 hrs after therapy. Three patients received pain relief. Autologous peripheral blood stem cell reinfusion was performed on day +12 to +27 in all patients to overcome potentially irreversible damage to the hematopoietic stem cells. In three patient external radiotherapy of the primary tumor site was performed after Sm-153-EDTMP therapy and in two of them polychemotherapy was continued. Thirty-six months later one of these patients is still free of progression. Two further patients are still alive. However, they have developed new metastases. The three patients who had no accompanying external radiotherapy, all died of disease progression five to 20 months after therapy., Conclusion: These preliminary results show that high-dose Sm-153-EDTMP therapy is feasible and warrants further evaluation of efficacy. The combination with external radiation and polychemotherapy seems to be most promising. Although osteosarcoma is believed to be relatively radioresistant, the total focal dose achieved may delay local progression or even achieve permanent local tumor control in patients with surgically inaccessible primary or relapsing tumors.

Purpose: In the framework of the 3rd Consensus Conference "PET in Oncology" the bone and soft-tissue tumors study group evaluated the present position of PET for these tumor entities on the basis of international publications., Methods: After a systematic review of the literature, publications were evaluated according to previously defined quality criteria. For various indications the clinical usefulness of PET was assessed using a classification system., Results: Most studies had been performed with a small number of patients (n < 35). Therefore, only 8 of 46 publications were judged relevant. On the basis of these literature data, use of FDG-PET for grading was classified 1b (literature results predominantly show clinical usefulness). As before (1995/97), all other indications were categorized with 3 (assessment not yet possible, literature data inadequate)., Outlook: According to the opinion of experts, the detection of osseous metastases of Ewing's sarcoma, therapy monitoring and the diagnosis of recurrences are potentially useful clinical indications for FDG-PET. Therefore, prospective studies with large patient groups are essential to further evaluate the benefit of FDG-PET in these indications.

Objective: The purpose of this study was to compare the diagnostic accuracy of whole-body MR imaging, skeletal scintigraphy, and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for the detection of bone metastases in children., Subjects and Methods: Thirty-nine children and young adults who were 2--19 years old and who had Ewing's sarcoma, osteosarcoma, lymphoma, rhabdomyosarcoma, melanoma, and Langerhans' cell histiocytosis underwent whole-body spin-echo MR imaging, skeletal scintigraphy, and FDG PET for the initial staging of bone marrow metastases. The number and location of bone and bone marrow lesions diagnosed with each imaging modality were correlated with biopsy and clinical follow-up as the standard of reference., Results: Twenty-one patients exhibited 51 bone metastases. Sensitivities for the detection of bone metastases were 90% for FDG PET, 82% for whole-body MR imaging, and 71% for skeletal scintigraphy; these data were significantly different (p < 0.05). False-negative lesions were different for the three imaging modalities, mainly depending on lesion location. Most false-positive lesions were diagnosed using FDG PET., Conclusion: Whole-body MR imaging has a higher sensitivity than skeletal scintigraphy for the detection of bone marrow metastases but a lower sensitivity than FDG PET.

Purpose: The purpose of this study was to evaluate the potential of positron emission tomography using F-18-fluoro-2-deoxy-D-glucose (FDG PET) to assess the chemotherapy response of primary osseous tumors compared with the degree of necrosis determined histologically., Patients and Methods: Seventeen patients with primary bone tumors (11 osteosarcomas, 6 Ewing's sarcomas) were examined using FDG PET and planar bone scintigraphy before neoadjuvant chemotherapy and before surgery. Tumor response was classified histologically according to Salzer-Kuntschik (grades I-II: good response; grades IV-VI: poor response). In both imaging methods, quantification was performed using tumor to nontumor ratios (T:NT)., Results: Histologically, 15 patients were classified as having good responses (grade I, n = 1; grade II, n = 6; grade III, n = 8) and two as having poor responses (grades IV and V). FDG PET showed more than a 30% decrease in T:NT ratios in all patients who had good responses. However, three of these patients had increasing bone scintigraphy T:NT ratios, and another five had decreasing ratios of less than 30%. The patients with poor responses had increasing T:NT ratios and decreasing ratios of less than 30%, respectively, using both imaging methods., Conclusions: FDG PET seems to be a promising tool for evaluating the response of primary osseous tumors to chemotherapy. In this preliminary study, FDG PET was superior to planar bone scintigraphy.

The purpose of this study was to compare positron emission tomography using fluorine-18 fluorodeoxyglucose (FDG-PET) and technetium-99m methylene diphosphonate (MDP) bone scintigraphy in the detection of osseous metastases from malignant primary osseous tumours. In 70 patients with histologically proven malignant primary bone tumours (32 osteosarcomas, 38 Ewing's sarcomas), 118 FDG-PET examinations were evaluated. FDG-PET scans were analysed with regard to osseous metastases in comparison with bone scintigraphy. The reference methods for both imaging modalities were histopathological analysis, morphological imaging [additional conventional radiography, computed tomography (CT) or magnetic resonance imaging (MRI)] and/or clinical follow-up over 6-64 months (median 20 months). In 21 examinations (18%) reference methods revealed 54 osseous metastases (49 from Ewing's sarcomas, five from osteosarcomas). FDG-PET had a sensitivity of 0.90, a specificity of 0.96 and an accuracy of 0.95 on an examination-based analysis. Comparable values for bone scintigraphy were 0.71, 0.92 and 0.88. On a lesion-based analysis the sensitivity of FDG-PET and bone scintigraphy was 0.80 and 0.72, respectively. Analysing only Ewing's sarcoma patients, the sensitivity, specificity and accuracy of FDG-PET and bone scan were 1.00, 0.96 and 0.97 and 0.68, 0.87 and 0.82, respectively (examination-based analysis). None of the five osseous metastases from osteosarcoma were detected by FDG-PET, but all of them were true-positive using bone scintigraphy. In conclusion, the sensitivity, specificity and accuracy of FDG-PET in the detection of osseous metastases from Ewing's sarcomas are superior to those of bone scintigraphy. However, in the detection of osseous metastases from osteosarcoma, FDG-PET seems to be less sensitive than bone scintigraphy.

Despite highly efficacious chemotherapy, patients with osteosarcomas still have a poor prognosis if adequate surgical control cannot be obtained. We applied high-activity Sm-153-EDTMP therapy within a multimodal therapy concept to improve local control of an unresectable osteosarcoma with poor response to initial polychemotherapy. A 21-year-old woman with an extended, unresectable pelvic osteosarcoma and multiple pulmonary metastases was treated with high-activity of Sm-153- EDTMP (150 MBq/kg BW, total 8.1 GBq). Afterwards external radiotherapy of the primary tumor site was performed and polychemotherapy was continued, followed by autologous peripheral blood stem cell reinfusion. Within 48 h after Sm-153-EDTMP application the patient had complete pain relief. After three weeks the response was documented by 3-phase Tc-99m-MDP bone scintigraphy (primary tumor and metastases: decreased tracer uptake), whole-body F-18-FDG-PET (primary tumor and metastases: diminution of glucose metabolism) and thoracic CT (metastases: reduction of size). The present case warrants further evaluation of feasibility and efficacy of this multimodal therapy combination of high-activity Sm-153-EDTMP therapy, external radiation, polychemotherapy and stem cell support for unresectable osteosarcomas.