Gated 18F-FDG PET/CT of the Lung Using a Respiratory Spirometric Gating Device: A Feasibility Study.

Spirometric gating devices (SGDs) can measure the respiratory signal with high temporal resolution and accuracy. The primary objective of this study was to assess the feasibility and tolerance of a gated lung PET/CT acquisition using an SGD. The secondary objective was to compare the technical quality, accuracy, and interoperability of the SGD with that of a standard respiratory gating device, Real-Time Position Management (RPM), based on measurement of vertical thoracoabdominal displacement. Methods: A prospective phase I monocentric clinical study was performed on patients undergoing 18F-FDG PET/CT for assessment of a solitary lung nodule, staging of lung malignancy, or planning of radiotherapy. After whole-body PET/CT, a centered gated acquisition of both PET and CT was simultaneously obtained with the SGD and RPM during normal breathing. Results: Of the 46 patients who were included, 6 were prematurely excluded (1 because of hyperglycemia and 5 because of distant metastases revealed by whole-body PET/CT, leading to an unjustified extra gated acquisition). No serious adverse events were observed. Of the 40 remaining patients, the gated acquisition was prematurely stopped in 1 patient because of mask discomfort (2.5%; confidence interval [CI], 0.1%-13.2%). This event was considered patient tolerance failure. The SGD generated accurately gated PET/CT images, with more than 95% of the breathing cycle detected and high temporal resolution, in 34 of the 39 patients (87.2%; 95% CI, 60.0%-100.0%) and failed to generate a biologic tumor volume in 1 of 21 patients with increased 18F-FDG uptake (4.8%; 95% CI, 0.1%-26.5%). The quality and accuracy of respiratory signal detection and synchronization were significantly better than those obtained with RPM (P < 0.05). Conclusion: This trial supports the use of an SGD for gated lung PET/CT because of its high patient tolerance and accuracy. Although this technique seems to technically outperform RPM for gated PET/CT, further assessment of its superiority and the clinical benefit is warranted. We believe that this technique could be used as a gold standard to develop innovative approaches to eliminate respiration-induced blurring artifacts.

A new subtype of high-grade mandibular osteosarcoma with RASAL1/MDM2 amplification.

In contrast to long bone osteosarcoma, mandibular osteosarcoma is highly heterogeneous and morphologically overlaps with benign tumors, obscuring diagnosis and treatment selection. Molecular characterization is difficult due to the paucity of available specimens of this rare disease. We aimed to characterize the spectrum of mandibular osteosarcoma using immunohistochemistry and molecular techniques (quantitative polymerase chain reaction and sequencing) and compare them with benign fibro-osseous lesions. Forty-nine paraffin-embedded mandible osteosarcoma tissue samples were collected retrospectively and compared with 10 fibrous dysplasia and 15 ossifying fibroma cases. These were analyzed for molecular markers thought to differ between the different diseases and subtypes: MDM2 (murine double-minute type 2) overexpression, GNAS (guanine nucleotide-binding protein/α subunit) mutations, and amplification of MDM2 and/or RASAL1 (RAS protein activator like 1). Five fibroblastic high-grade osteosarcoma subtypes showed MDM2 amplification, including 2 with a microscopic appearance of high-grade osteosarcoma with part low-grade osteosarcoma (differentiated/dedifferentiated osteosarcoma) and MDM2 overexpression. The other 3 contained a coamplification of MDM2 and RASAL1, a signature also described for juvenile ossifying fibroma, with no overexpression of MDM2. These were of the giant cell-rich high-grade osteosarcoma, with areas mimicking juvenile ossifying fibroma (ossifying fibroma-like osteosarcoma). Our results show that some diagnosed high-grade osteosarcomas are differentiated/dedifferentiated osteosarcomas and harbor an overexpression and amplification of MDM2. In addition, juvenile ossifying fibromas can potentially evolve into giant cell-rich high-grade osteosarcomas and are characterized by a RASAL1 amplification (osteosarcoma with juvenile ossifying fibroma-like genotype). Thus, the presence of a RASAL1 amplification in ossifying fibroma may indicate a requirement for closer follow-up and more aggressive management.