Resting energy expenditure in children newly diagnosed with stage IV neuroblastoma.

Children with stage IV neuroblastoma (NBIV) are often malnourished at time of diagnosis, observed as high as 50%. The emphasis of this study was to determine whether an increased resting energy expenditure (REE) is a causative factor. Our hypothesis was that children diagnosed with NBIV have an increased REE, which normalizes with cancer treatment. Changes in nutritional status from time of diagnosis in response to nutritional support were examined. REE and nutritional evaluation were obtained three times: at diagnosis before starting treatment, where tumor burden is expected to be highest; after two courses of chemotherapy, where some response to treatment is expected; and after surgical excision of the primary tumor, where there was presumably minimal residual disease. Ten subjects completed the study. Results showed that REE was not increased, and there was no significant difference between phases (p = 0.29). Fifty percent of our subjects were malnourished at diagnosis. Because REE is not increased in NBIV, it is concluded that malnutrition seen in NBIV is not due to increased energy needs, but is likely due to decreased intake because of the intra-abdominal mass and malignant malaise.

Assessment of proliferation in vivo using 2-[(11)C]thymidine positron emission tomography in advanced intra-abdominal malignancies.

The purpose of this study was to determine the relationship between 2-[(11)C]thymidine positron emission tomography (PET) in vivo-derived parameters and the ex vivo Ki-67 index of proliferation in human tumors. The study comprised 17 treatment-naïve patients with advanced intra-abdominal malignancies. Tumor thymidine kinetics were measured using 2-[(11)C]thymidine PET. Tissue data were analyzed to give the standardized uptake value, the area under the time activity curve, and the fractional retention of thymidine (FRT) obtained by kinetic modeling. For the latter, the contribution of labeled metabolites was accounted for by measuring thymidine metabolites in arterial plasma. To examine the influence of tumor blood flow on the thymidine PET data, a perfusion scan using inhaled [(15)O]CO(2) was carried out in a subset of 11 patients. Biopsies were stained with a MIB1 antibody to obtain a Ki-67 index, and correlations with the PET-derived parameters were investigated. There was no relationship between tumor blood flow and the thymidine PET data, showing that the retention of 2-[(11)C]thymidine in tumors was independent of tumor perfusion. There was no correlation between the Ki-67 index and either standard uptake value or area under the curve. There was a correlation between the Ki-67 index and FRT (r = 0.58; P = 0.01). The correlation between the Ki-67 index and FRT in this dataset was not influenced by the interval between biopsy and imaging (0.1-126 weeks), the origin of the biopsy for Ki-67 staining (primary tumor or metastasis), or whether the biopsy was from an imaged or a nonimaged tumor. This is the first report in human tumors showing that 2-[(11)C]thymidine PET-derived parameters correlate with the level of tumor proliferation measured using Ki-67 immunohistochemistry. The study shows that the in vivo measurement of 2-[(11)C]thymidine in tumors using PET can provide a surrogate marker of proliferation and supports the potential use of the technique in the early assessment of response to antiproliferative cancer treatment.