Prediction of tumour necrosis fractions using metabolic and volumetric 18F-FDG PET/CT indices, after one course and at the completion of neoadjuvant chemotherapy, in children and young adults with osteosarcoma.
ABSTRACT The utility of combined metabolic and volumetric (18)F-FDG PET/CT indices for predicting tumour necrosis fractions following neoadjuvant chemotherapy has not been extensively studied in osteosarcoma. Furthermore, little is known of the early PET/CT responses after only one chemotherapy course.
Enrolled in the study were 20 children and young adults with resectable osteosarcoma who had undergone (18)F-FDG PET/CT scans before and after neoadjuvant chemotherapy. Maximum standardized uptake value (mSUV), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were measured. From among the 20 patients, 14 were prospectively recruited and underwent an additional PET/CT scan after one chemotherapy course. Histopathological necrosis fractions were compared with the above-mentioned PET/CT indices and their ratios.
MTV at the SUV threshold of 2 g/ml was closely correlated with the magnetic resonance image volumes before therapy (r = 0.91). In the prospective cohort, five patients were classified as good responders and nine as poor responders. All the metabolic indices (mSUV and its ratio) and combined metabolic/volumetric indices (MTV, TLG, and their ratios) except the mSUV ratio determined after therapy showed significant differences between good and poor responders (P <0.05). Differences were also noted for all of these indices determined after one chemotherapy course. Furthermore, most of these indices determined after therapy as well as after one chemotherapy course had good sensitivity, specificity, positive predictive value and negative predictive value with respect to predicting histological response to chemotherapy.
In our osteosarcoma patient population, (18)F-FDG PET/CT indices (either combined metabolic/volumetric or metabolic indices) determined after neoadjuvant chemotherapy were useful in predicting tumour responses. This held true after only one chemotherapy course.
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ABSTRACT: (18)F-FDG uptake in malignant tumors largely depends on the presence of facilitated glucose transporters, especially type 1 (Glut 1) and a rate-limiting glycolytic enzyme, hexokinase (HK) type II. Low expression of Glut 1 was reported in hepatocellular carcinoma (HCC), whereas high expression was found in cholangiocarcinoma. Immunohistochemistry and proteome analysis were performed to obtain a detailed evaluation of the mechanisms involved in glucose uptake and use in these tumors. Tumor tissues obtained from both HCC (n = 7) and mass-forming cholangiocarcinoma patients (n = 7) who showed increased (18)F-FDG uptake on PET were used. Immunohistochemistry for Glut 1 and HK I-III was performed in all tumor tissues. To identify proteins that regulate carbohydrate metabolism, a proteome analysis with matrix-assisted laser desorption ionization-time of flight and enzymatic digestion in-gel were performed using 8 available tumor samples and 3 normal liver tissues. Of the 8 tumor samples, 4 were HCCs; one was an intermediate phenotype HCC, and 3 were cholangiocarcinomas. The spot intensity of the proteins was calculated using proteome data; the tissues then were divided into 2 groups on the basis of the protein expression pattern, because the protein expression pattern of the intermediate-phenotype HCC was close to that of the cholangiocarcinomas. Group A included the HCCs and group B included the intermediate-phenotype HCC as well as the cholangiocarcinomas. Immunoreactivity for Glut 1 was positive in all cholangiocarcinomas, but was negative in all HCCs except the one intermediate phenotype. However, HK II was positive in HCCs but was negative in 6 of the 7 cholangiocarcinomas. A total of 331 protein spots with a P value of <0.05 were identified by proteome analysis. Thirteen of these proteins that regulate carbohydrate metabolism were selected. The pentose phosphate pathway was increased in both groups, but more significantly in group B. Gluconeogenesis enzymes were decreased in both groups, but the tricarboxylic acid cycle-regulating enzyme expression was variable. HCCs have different glucose-regulating mechanisms from those of cholangiocarcinomas, even though both tumors showed increased (18)F-FDG uptake on PET scans. Further studies are required with regard to energy metabolism and (18)F-FDG uptake patterns in association with various oncogenic alterations regulating multiple steps of the glycolytic pathways.Journal of Nuclear Medicine 10/2005; 46(10):1753-9. · 5.77 Impact Factor
- Der Pathologe 06/1983; 4(3):135-41. · 0.62 Impact Factor
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ABSTRACT: Around 1148 patients with non-metastatic osteosarcoma of the extremity were treated in a single institution between 1972 and 1999 with 4 different protocol of adjuvant and 7 different protocols of neoadjuvant chemotherapy. The rate of limb salvage increased from 20% to 71%. The 5-year event-free survival (EFS) and overall survival (OS) were 57% and 66%, respectively. The 10-year EFS and OS were 52% and 57%, respectively, and the results significantly correlated with serum alkaline phosphatase levels; the type of chemotherapy (adjuvant vs neoadjuvant); and with histologic response to pre-operative treatment. Aggressive chemotherapy and surgery could cure about the 60% of patients with osteosarcoma of the extremity. However, since local or systemic relapses, myocardiopathies and a second malignancy are possible even 5 or more years since the beginning of treatment, a long-term follow-up is recommended.European Journal of Cancer 01/2006; 41(18):2836-45. · 5.06 Impact Factor