Cranial Spinal Spreading of Canine Brain Gliomas after Hypofractionated Volumetric-Modulated Arc Radiotherapy and Concomitant Temozolomide Chemotherapy: A Four-Case Report

Abstract

Gliomas are the second-most-common primary brain tumors in dogs. Surgery and radiotherapy are established treatment approaches with similar median survival time, whereas conventional chemotherapy is burdened by severe adverse effects. Spinal and leptomeningeal spread of gliomas have been described following radiotherapy treatment alone. The purpose of this study was to evaluate the outcome for four dogs with primary high-grade gliomas in the forebrain without evidence, at diagnosis, of neoplastic invasion along the spinal cord, that were treated with concomitant chemotherapy (temozolomide) and hypofractionated volumetric-modulated arc radiotherapy (VMAT-RT). Temozolomide was selected for its radiosensitive properties, and radiotherapy dose protocols of 37 Gy in 7 fractions or 42 Gy in 10 fractions were used. After an initial complete or partial response, tumors recurred across the cranial-spinal pathway. Post-mortem macroscopic examinations confirmed swollen spinal cord and hyperemic meningeal sleeve, with nodular lesions on the meningeal surface. Microscopically, infiltration of the spinal cord and meninges by neoplastic cells (with features of oligodendrogliomas) were observed. This work seems to suggest that the entire central nervous system should be investigated in diagnostic examinations of canine gliomas. Dose-escalation trials and/or spinal cord prophylaxis treatment could also be evaluated to prevent tumor progression.

Keywords: dog gliomas; spinal-spreading; temozolomide; volumetric-modulated radiotherapy.

Figure 1

Case 3, grade IV glioma (a) T1-W image with contrast enhancement showing a well-demarcated tumor at the temporal-paraventricular region (dark-yellow arrow). (b) Two months post RT near-complete regression was observed (dark-yellow arrow). (c) Six months post RT, hypointense lesion consistent with a gliotic scar at the temporal-paraventricular region (dark-yellow arrow). (d) Case 4, grade IV glioma; cervical and thoracic involvement of the spinal cord on T2-W image by the hyperintensity signal (dark-yellow arrow). and with concomitant enlargement of the fourth ventricle (blue arrow).

Figure 2

Case 3, histological and immunohistochemistry findings of the dissected neoplastic tissue in the spinal cord. H&E stained slides (a–d) show neoplastic cells (*) at the meningeal area and at the ependymal canal (E), multifocally forming glomeruloid bodies (G). By immunohistochemistry, neoplastic cells (*) were negative for GFAP (e) and Iba1 (f), while positive for Olig2 (g,h).