Pazopanib therapy for cerebellar hemangioblastomas in von Hippel-Lindau disease: case report

Abstract

von Hippel-Lindau (VHL) disease is a genetically acquired multisystem tumor syndrome of the viscera and central nervous system (CNS). The most common tumors associated with this disease are histologically benign, slow-growing CNS hemangioblastomas affecting the retina, cerebellum, brainstem, spinal cord or nerve roots. With mean age at diagnosis of 30 years, CNS hemangioblastomas are usually the first manifestation of the disease. Ongoing clinical and radiological surveillance is required, with symptomatic lesions necessitating treatment. As tumor growth is inevitable during the lifetime of most VHL patients, and the multiplicity of tumors may preclude surgical cure, the search for effective therapies is ongoing. Here we provide the first report demonstrating clinical and radiological anti-tumor response using pazopanib, a small molecule multi-receptor tyrosine kinase inhibitor, in a patient with treatment-refractory VHL-associated CNS hemangioblastoma. Treatment initiation with daily oral pazopanib (800 mg/day) resulted in significant neurologic improvement and radiologic tumor volume reduction.

Fig. 1

Representative magnetic resonance images from a patient with VHL disease on pazopanib therapy. Axial, coronal, sagittal T1-weighted images (post-contrast) and T2-weighted images with fluid-attenuated inversion recovery sequence (FLAIR) 3 weeks before treatment (a–d) and 19 months after starting pazopanib (e–h). These demonstrate decreasing tumor volume, contrast enhancement and vasogenic edema over time. All images are displayed per standard radiographic convention

Fig. 2

Evaluation of radiologic responsiveness of von Hippel–Lindau (VHL)-associated CNS hemangioblastomas to pazopanib therapy. Five hemangioblastomas (a–e) were assessed in a VHL patient on pazopanib therapy. Tumor volume reduction shows moderate responsiveness to pazopanib with the largest symptomatic lesion (a) decreasing in volume by 54% (left graph). This reduction in tumor volume correlated directly with improved bulbar and cerebellar functions. Corresponding absolute tumor volumes pre- and post- pazopanib treatment are also shown (right table). Tumor volumetric assessment was conducted using Vitrea2 software (version 2.2; Vital images, Plymouth, MN). MR image area corresponding to the hemangioblastoma showing contrast enhancement was manually segmented to delineate tumor-specific pixels across all sections