Neuro-Oncologic Veterinary Trial for the Clinical Transfer of Microbeam Radiation Therapy: Acute to Subacute Radiotolerance after Brain Tumor Irradiation in Pet Dogs.

Synchrotron Microbeam Radiation Therapy (MRT) has repeatedly proven its superiority compared with conventional radiotherapy for glioma control in preclinical research. The clinical transfer phase of MRT has recently gained momentum; seven dogs with suspected glioma were treated under clinical conditions to determine the feasibility and safety of MRT. We administered a single fraction of 3D-conformal, image-guided MRT. Ultra-high-dose rate synchrotron X-ray microbeams (50 µm-wide, 400 µm-spaced) were delivered through five conformal irradiation ports. The PTV received ~25 Gy peak dose (within microbeams) per port, corresponding to a minimal cumulated valley dose (diffusing between microbeams) of 2.8 Gy. The dogs underwent clinical and MRI follow-up, and owner evaluations. One dog was lost to follow-up. Clinical exams of the remaining six dogs during the first 3 months did not indicate radiotoxicity induced by MRT. Quality of life improved from 7.3/10 [±0.7] to 8.9/10 [±0.3]. Tumor-induced seizure activity decreased significantly. A significant tumor volume reduction of 69% [±6%] was reached 3 months after MRT. Our study is the first neuro-oncologic veterinary trial of 3D-conformal Synchrotron MRT and reveals that MRT does not induce acute to subacute radiotoxicity in normal brain tissues. MRT improves quality of life and leads to remarkable tumor volume reduction despite low valley dose delivery. This trial is an essential step towards the forthcoming clinical application of MRT against deep-seated human brain tumors.

Toward Neuro-Oncologic Clinical Trials of High-Dose-Rate Synchrotron Microbeam Radiation Therapy: First Treatment of a Spontaneous Canine Brain Tumor.

PURPOSE: The high potential of microbeam radiation therapy (MRT) in improving tumor control while reducing side effects has been shown by numerous preclinical studies. MRT offers a widened therapeutic window by using the periodical spatial fractionation of synchrotron generated x-rays into an array of intense parallel microbeams. MRT now enters a clinical transfer phase. As proof of principle and cornerstone for the safe clinical transfer of MRT, we conducted a "first in dog" trial under clinical conditions. In this report, we evaluated whether a 3-dimensional conformal MRT can be safely delivered as exclusive radiosurgical treatment in animal patients METHODS AND MATERIALS: We irradiated a 17.5-kg French bulldog for a spontaneous brain tumor (glioma suspected on magnetic resonance imaging) with conformal high-dose-rate microbeam arrays (50-µm-wide microbeams, replicated with a pitch of 400 µm) of synchrotron-generated x-rays. The dose prescription adjusted a minimal cumulated valley dose of 2.8 Gy to the plnning target volume (PTV) (cinical target volume (CTV)+ 1 mm). Thus, each beam delivered 20 to 25 Gy to the target as peak doses, and ∼1 Gy as valley doses RESULTS: The treatment was successfully delivered. Clinical follow-up over 3 months showed a significant improvement of the dog's quality of life: the symptoms disappeared. Magnetic resonance imaging, performed 3 months after irradiation, revealed reduction in tumor size (-87.4%) and mass effect with normalization of the left lateral ventricle. CONCLUSIONS: To our knowledge, this neuro-oncologic veterinary trial is the first 3-dimensional conformal synchrotron x-ray MRT treatment of a spontaneous intracranial tumor in a large animal. It is an essential last step toward the clinical transfer of MRT in the near future to demonstrate the feasibility and safety of treating deep-seated tumors using synchrotron-generated microbeams.

Combination of Prednisolone and Azathioprine for Steroid-Responsive Meningitis-Arteritis Treatment in Dogs.

Treatment with high corticosteroid dosages for steroid-responsive meningitis-arteritis (SRMA) is correlated with severe adverse effects and worse quality of life. In order to improve immunosuppression and decrease dosage and duration of glucocorticoid treatment, a second immunosuppressive drug is commonly used in most of the immune-mediated diseases. The objective of this retrospective study was to evaluate the efficacy, tolerability, and occurrence of relapse for the combination of prednisolone and azathioprine. All dogs received azathioprine 2 mg/kg q 24 hr for 1 mo and then 2 mg/kg every other day for 2 mo; prednisolone was started at an immunosuppressive dosage and tapered off gradually during a mean of 3 mo. Twenty-six dogs met inclusion criteria. Twenty-one dogs (81%) were in clinical remission with no relapse observed within the 2 yr follow-up period. Treatment was well tolerated in all dogs and side effects were most of the time mild and self-limiting. The relapse rate (19%) was lower than most published rates. A prednisolone and azathioprine combination appeared to be effective for primary treatment of dogs with SRMA and allows a quicker tapering in prednisolone dosage, a decrease in long-term side effects of steroids, a shorter duration of treatment, and a low relapse rate.

A rare case of malignant vagus nerve sheath tumor presenting with multiple cranial nerve dysfunction in a dog.

A 5-year-old intact male Gascon Saintongeois dog was presented with a 6-month history of coughing, laryngeal paralysis, a deglutition disorder of gradual onset, and left-sided Horner's syndrome. The dog was admitted as an emergency for acute central vestibular signs. Magnetic resonance images identified a left extra-axial brainstem lesion extending caudally from the medulla to the vagosympathetic trunk. Histological and immunohistological examination revealed a high grade epithelioid malignant peripheral nerve sheath tumor (MPNST). This case report is the first description of a MPNST of the vagus nerve compressing the brainstem and causing multiple cranial nerve dysfunction in a dog. Key clinical message: Nerve sheath tumors have been reported in many locations arising from spinal nerve roots and cranial nerves. Although the trigeminal nerve is the most commonly affected nerve, other cranial nerves such as the vagus can be affected.

Un cas rare de tumeur maligne de la gaine du nerf vague à l'origine d'une dysfonction de plusieurs nerfs crâniens chez un chien. Un chien mâle entier de cinq ans de race Gascon Saintongeois a été présenté avec un historique de 6 mois de toux, paralysie laryngée, trouble de la déglutition d'évolution progressive et un syndrome de Claude Bernard Horner à gauche. Le chien a été admis en urgence pour des signes vestibulaires centraux. Une imagerie par résonnance magnétique a mis en évidence une lésion extra-axiale gauche localisée au niveau du tronc cérébral s'étendant caudalement de la medulla vers le tronc vagosympathique. Les examens histologique et immunohistologique ont révélé une tumeur épithéliale maligne des gaines nerveuses de haut grade (TMGN). Ce rapport de cas est la première description de TMGN du nerf vague comprimant le tronc cérébral et à l'origine d'une dysfonction de plusieurs nerfs crâniens chez un chien.Message clinique clé:Les tumeurs des gaines des nerfs ont été rapportées de plusieurs localisations prenant leur origine des racines des nerfs spinaux et des nerfs crâniens. Bien que le nerf trijumeau soit le nerf le plus fréquemment affecté, d'autres nerfs crâniens, tel que le vague, peuvent être affectés.(Traduit par Dr Serge Messier).