A. Deviers

Presence of neural progenitors in spontaneous canine gliomas: A histopathological and immunohistochemical study of 20 cases.

Gliomas are the most common primary brain tumours in humans and are associated with a poor prognosis. An accurate animal model of human glioma tumorigenesis is needed to test new treatment strategies. Dogs represent a promising model because they develop spontaneous diffusely-infiltrating gliomas. This study investigated whether spontaneous canine gliomas contain cancer stem cells previously identified in all grades of human gliomas. Twenty spontaneous cases of canine gliomas were graded according to the human WHO classification. The expression of different markers of lineage differentiation was evaluated with immunohistochemistry as follows: nestin and CD133 for neural stem cells, doublecortin for neuronal progenitor cells, Olig2 for glial progenitor cells, glial fibrillary acidic protein, vimentin and S-100 for mature glial cells, and NeuN and βIII-tubulin for mature neurons. Gliomas were characterised as follows: five grade II (oligodendrogliomas); nine grade III (seven anaplastic oligodendrogliomas, one anaplastic astrocytoma, one anaplastic oligoastrocytoma); six grade IV (glioblastomas). Immunohistochemical evaluation revealed that (1) nestin and CD133 were expressed in all grades of gliomas with a higher proportion of positive cells in high-grade gliomas; (2) the expression of S-100 protein and Olig2 did not differ substantially between astrocytic and oligodendroglial tumours, and (3) all gliomas were negative for mature neuron markers. The results demonstrated the presence of undifferentiated neural progenitors in all grades of spontaneous canine gliomas, confirming the relevance of this animal model for further studies on cancer stem cells.

Blood Flows in Tributaries of the Portal Vein: Anatomical and Angiographic Studies in Normal Beagle Dogs

Liver anatomy, particularly its vascularization, has been investigated in many studies in dogs. Knowledge of blood flow from the main tributaries of the portal vein (PV) is necessary to explain the preferential sites of secondary lesions within the liver based on the site of the initial malignant lesion. How these flows come together was established in an earlier ex vivo study. Here, we highlight in vivo the blood flows from the main PV tributaries and their distribution in the liver of normal dogs. Portographs of the main PV tributaries were obtained in seven dogs after injection of an angiographic contrast medium. After euthanasia, the livers and their portal vascularization (PV and tributaries) were extracted for a comparative corrosion cast study. Flows were demonstrated in the cranial mesenteric vein, caudal mesenteric vein and splenic vein. However, no proper flow could be distinguished for the gastroduodenal and ileocolic veins. All these tributaries primarily supply the lateral liver lobes (right or left). Most of our observations indicate that the cranial mesenteric, caudal mesenteric and splenic veins primarily supply the right lateral lobe and the caudate process of the caudate lobe and secondarily the left lateral lobe, left medial lobe and the quadrate lobe. The two other tributaries (gastroduodenal and ileocolic veins) primarily supply the right lateral lobe and the caudate process of the caudate lobe.

Anatomy, histology, and ultrasonography of the normal adrenal gland in brown lemur: Eulemur fulvus

The medical care currently to brown lemurs (Eulemur fulvus) is limited by a lack of knowledge of their anatomy. The aim of this study was to describe the anatomy and histology and obtain ultrasonographic measurements of normal adrenal glands in these animals.

SP-0363: Predictive value of MR spectroscopic imaging for relapse site in GBM and integration in a dose-painting trial

Purpose: To review the current status of hypoxia PET imaging for delineating hypoxic volumes (HVs) inside the gross target volume (GTV) and for radiotherapy (RT) outcome prediction. Methods: Hypoxia PET tracers currently used in clinical trials are mainly [F]-FMISO, [F]-FAZA and [F]-HX4. Different image acquisition protocols and methods for delineating HVs will be presented in this talk. Furthermore, results of recent clinical trials will be reviewed where the prognostic value of hypoxia PET imaging before and during RT with respect to outcome as investigated. In our institution, a clinical phase II trial is currently carried out where to date n=33 head and neck cancer patients were included. Patients were examined using dynamic FMISO PET imaging plus conventional FDG PET imaging in addition to planning CT and eventually MRI before the start of RT. HVs were segmented based on parameters derived from the pharmaco-kinetic analysis of the dynamic FMISO PET data. Patients were randomized into two treatment arms. Patients in the experimental arm were treated with a 10% dose escalation to the HV whereas patients in the control arm received standard IMRT treatment with 70 Gy in 35 fractions. Results: Different manual and (semi-)automatic methods for HV delineation based on hypoxia PET data have been used in clinical studies, such as thresholding, tumour-to-background ratio (TBR) based methods, advanced automatic methods or delineations based on dynamic PET imaging. Different contouring techniques for HV definition may result in strongly varying volumes. Recently published clinical trials confirm the prognostic character of hypoxia PET imaging. However, no consensus was found yet with regard to the timing of the hypoxia PET examination. Some studies found that pretreatment hypoxia PET information was correlated to outcome whereas others stated that hypoxia PET data acquired two weeks into RT had prognostic value. For our hypoxia dose painting trial, a planned interim analysis was carried out after recruiting n=20 patients. Median followup time for this group was 36 (11 52) months. 5 patients did not show any tumour hypoxia (HV = 0 mL). The mean HV of the hypoxic tumours was 8.6 mL (0.3 – 49.2 mL). Furthermore, data acquired in this study could confirm a prognostic model relating TCP to a measure derived from dynamic FMISO PET imaging acquired before the start of RT. Conclusion: Hypoxia PET imaging is a very promising tool for the stratification of patients into different risk groups and thus a potentially very interesting molecular marker in the advent of biologically adapted, personalized RT. However, a comparison of results from different clinical trials is difficult due to large discrepancies in terms of imaging protocols and data analysis strategies.

OC-0615: Voxel-based perfusion normalisation in GBM patients included in a phase I-II trial of RT/Tipifarnib combination

2.7%, p= 0.041). In the Capox-RT group, 85.7% (191/223) patients received radiotherapy on schedule and 74.9% (166/223) with concurrent chemotherapy on schedule, as did 94.1% (238/253) and 92.1% (233/353) in the Cap-RT group, respectively. Grade 3-4 acute toxicity was observed in 38.1% of patients in the Capox-RT group and in 29.2% in the Cap-RT group (p = 0.041). Grade 3–4 tenesmus was more common in the Capox-RT group than in the Cap-RT group (5.4% vs. 2.0%), as were grade 3–4 nausea (2.2% vs. 0%), grade 3–4 vomiting (1.8% vs. 0%), and grade 3–4 fatigue (3.1% vs. 0.4%). Conclusions: The interim analysis revealed that inclusion of oxaliplatin into capecitabine based postoperative chemoradiotherapy was feasible and could decrease cumulative locoregional recurrence rate for patients with locally advanced rectal cancer.