Rationale

To assess 18F-labeled 2-fluoro-2-deoxy-D-glucose (18F-FDG) uptake in children with a newly diagnosed diffuse intrinsic brainstem glioma (BSG) and to investigate associations with progression-free survival (PFS), overall survival (OS) and MRI indices.

Methods

Two Pediatric Brain Tumor Consortium (PBTC) therapeutic trials in children with newly diagnosed BSG were designed to test radiation therapy combined with molecularly targeted agents (PBTC-007: Phase I/II study of gefitinib; PBTC-014: Phase I/II study of tipifarnib). Baseline brain 18F-FDG PET scans were obtained in 40 children in these trials. Images were evaluated by consensus of two PET experts for intensity and uniformity of tracer uptake. Associations of 18F-FDG uptake intensity and uniformity with both PFS and OS were evaluated as well as associations with tumor MRI indices at baseline (tumor volume on FLAIR, baseline intratumoral enhancement, diffusion and perfusion values.

Results

In the majority of children, BSG 18F-FDG uptake was less than gray matter uptake. Survival was poor irrespective of intensity of 18F-FDG uptake, with no association between intensity of 18F-FDG uptake and PFS or OS. However, hyperintense 18F-FDG uptake in tumor compared to gray matter suggested poorer survival rates. Patients with 18F-FDG uptake in ≥ 50% of the tumor had shorter PFS and OS compared to patients with 18F-FDG uptake in < 50% of tumor. There was some evidence that tumors with higher 18F-FDG uptake were more likely to show enhancement; and when the diffusion ratio was lower the uniformity of 18F- FDG uptake appeared higher.

Conclusion

Children with BSG where 18F-FDG uptake involves at least half the tumor appear to have inferior survival compared to children with uptake in <50% of tumor. A larger independent study is needed to verify this hypothesis. Intense tracer uptake in the tumors compared to gray matter suggests decreased survival. Higher 18F-FDG uptake within the tumor was associated with enhancement on MRI. Increased tumor cellularity as reflected by restricted MR diffusion may be associated with increased 18F-FDG uniformity throughout the tumor.

Purpose

To determine the response rate to oral capsular fenretinide in children with recurrent or biopsy proven refractory high-risk neuroblastoma.

Experimental Design

Patients received 7 days of fenretinide: 2475 mg/m2/day divided TID (<18 years) or 1800 mg/m2/day divided BID (≥18 years) every 21 days for a maximum of 30 courses. Patients with stable or responding disease after course 30 could request additional compassionate courses. Best response by course 8 was evaluated in Stratum 1 (measurable disease on CT/MRI +/− bone marrow and/or MIBG avid sites) and Stratum 2 (bone marrow and/or MIBG avid sites only).

Results

Sixty-two eligible patients, median age 5 years (range 0.6–19.9), were treated in Stratum 1 (n=38) and Stratum 2 (n=24). One partial response (PR) was seen in Stratum 2 (n=24 evaluable). No responses were seen in Stratum 1 (n=35 evaluable). Prolonged stable disease (SD) was seen in 7 patients in Stratum 1 and 6 patients in Stratum 2 for 4–45+ (median 15) courses. Median time to progression was 40 days (range 17–506) for Stratum 1 and 48 days (range 17–892) for Stratum 2. Mean 4-HPR steady state trough plasma concentrations were 7.25 µM (coefficient of variation 40–56%) at day 7 course 1. Toxicities were mild and reversible.

Conclusions

Although neither stratum met protocol criteria for efficacy, 1 PR + 13 prolonged SD occurred in 14/59 (24%) of evaluable patients. Low bioavailability may have limited fenretinide activity. Novel fenretinide formulations with improved bioavailability are currently in pediatric Phase I studies.

The purpose of this study is to evaluate the accuracy of registration positron emission tomography (PET) head images to the MRI-based brain atlas. The [18F]fluoro-2-deoxyglucose PET images were normalized to the MRI-based brain atlas using nine registration algorithms including objective functions of ratio image uniformity (RIU), normalized mutual information (NMI), and normalized cross correlation (CC) and transformation models of rigid-body, linear, affine, and nonlinear transformations. The accuracy of normalization was evaluated by visual inspection and quantified by the gray matter (GM) concordance between normalized PET images and the brain atlas. The linear and affine registration based on the RIU provided the best GM concordance (average similarity index of 0.71 for both). We also observed that the GM concordances of linear and affine registration were higher than those of the rigid and nonlinear registration among the methods evaluated.

Background

Positron-emission tomography (PET) imaging using [18F]fluorodeoxyglucose (FDG) is useful for detection, staging, and monitoring a variety of malignancies, including lymphoma, in adults, but its utility in sarcomas, especially soft tissue sarcomas (STS), in children and young adults is not clear.

Procedure

To evaluate the potential utility of FDG PET in the care of STS in children and young adults, we analyzed 46 PET scans in 25 patients acquired over 12 years. Scans were interpreted by two imaging physicians blinded to findings from other imaging studies and clinical information. Results were compared with computed tomography and magnetic resonance imaging, biopsy results, where available, and clinical follow-up of at least 12 months.

Results

For a total of 46 scans in 25 patients, there were 25 true positive scans, 3 false positive scans, 12 true negative scans, and 6 false negative scans. The sensitivity of the PET scan was 86%, specificity was 80%, positive predictive value was 89%, and negative predictive value was 67%.

Conclusion

FDG PET may be a useful imaging modality in the management of children and young adults with STS, although prospective studies are needed to establish its true utility.