Recurrent extraneural sonic hedgehog medulloblastoma exhibiting sustained response to vismodegib and temozolomide monotherapies and inter-metastatic molecular heterogeneity at progression.

BACKGROUND: Response to targeting and non-targeting agents is variable and molecular information remains poorly described in patients with recurrent sonic-hedgehog-driven medulloblastoma (SHH-MB). MATERIALS AND METHODS: Clinical and PET/CT findings during treatment with successive hedgehog antagonists and temozolomide monotherapies are described in a heavily pre-treated patient with recurrent extraneural metastases from PTCH1 mutated/ wild type smoothened (SMO) CNS SHH-MB. Molecular tests were prospectively performed in tissue from two extraneural sites at progression. RESULTS: Sustained clinical/metabolic response was obtained to vismodegib. At progression, itraconazole was ineffective, but salvage temozolomide treatment results in a response similar to vismodegib. At further progression, acquired SMO and PIK3CA mutations were identified in bone (G477L and H1047A, respectively) and epidural (L412P and H1065L, respectively) metastases. No response was observed with subsequent sonidegib treatment. CONCLUSIONS: This is the first clinical report of recurrent extraneural PTCH1 mutated SHH-MB exhibiting: 1) a sustained response to vismodegib and temozolomide, and 2) inter-metastatic molecular heterogeneity and acquired SMO-G477L, SMO-L412P, and PIK3CA-H1065L mutations at progression, highlighting the need for a multitarget treatment approach.

An Alternate, Egg-Free Radiolabeled Meal Formulation for Gastric-Emptying Scintigraphy.

Tc-radiolabeled scrambled eggs (SEs) are most often used as the ingested solid phase for gastric-emptying scintigraphy, leading egg-reluctant patients to avoid the examination. We formulated and validated 2 egg-free alternate meals, in the absence of any commercialized formulation: chocolate mug cake (MC) and scrambled tofu (ST). Six healthy volunteers underwent gastric-emptying scintigraphy after ingesting Tc-radiolabeled MC, ST, or SE. Gastric retention indexes did not change significantly between formulations (% of overtime variation to SE: MC 7.75% ± 7.1%, ST 7.17% ± 5.8%; P = 0.6618, not statistically significant), suggesting MC and ST as interesting egg-free alternatives.

18F-DOPA, a clinically available PET tracer to study brain inflammation?

We report 2 cases of suspected low-grade glioma with positive 18F-fluorodihydroxyphenylalanine (18F-FDOPA) PET scan, and histological diagnosis of brain inflammation corresponding to an acute disseminated encephalomyelitis (ADEM) and to a neurosarcoidosis. It has been shown that this amino-acid PET radiotracer serves to evaluate tumoral proliferation related to the metabolism of L-amino-acid transporters, and that inflammation may also contribute to the tumoral uptake. This report suggests it may serve to study brain inflammation.

Value of diagnosis imaging in the evaluation of the severity of histological lesions in duplex systems.

OBJECTIVE: In order to determine the effectiveness of imagery in the assessment of the severity of histological lesions in duplex systems in children we compared histology results from heminephrectomies with diagnosis imaging findings [renal ultrasound (US), scintigraphy, unenhanced and contrast-enhanced magnetic resonance imagery (MRI)]. MATERIALS AND METHODS: Between 2007 and 2013, 34 children with duplex system underwent surgery. The results from US (n = 34), dimer captosuccinic acid scintigraphy (n = 23) and MRI (n = 16) were compared with histological data. Five histological lesions were found (chronic interstitial inflammation, interstitial fibrosis, tubular atrophy, glomerulosclerosis and dysplasia) and categorized as severe (>25%) or moderate (≤ 25%). RESULTS: Severe histological lesions were found in 76.5% and moderate lesions in 23.5%. Radiological features were compared with histological results. In US, severe parenchymal thinning was associated with chronic interstitial inflammatory. The absence of parenchymal enhancement and/or severe cortical thinning in MR urography (MRU) was significantly associated with interstitial fibrosis. All poorly functioning poles were associated with severe histological lesions (p = 0.091), but not to a specific category of lesions. CONCLUSIONS: MRI sensibility was excellent (90%) in the diagnosis of poorly functioning pole. Severe thinning on US and minimal pole function on MRU can be used to predict the severity of histological lesions.