Bevacizumab for the treatment of surgically unresectable cervical cord hemangioblastoma: a case report

Abstract

IntroductionHemangioblastomas are highly vascular tumors that can arise within the central nervous system as well as other organ systems within the body. They can arise sporadically or as part of von Hippel-Lindau syndrome. Those arising in critical locations within the central nervous system can be difficult to resect surgically and therefore pose a significant challenge and result in morbidity and even mortality. Hemangioblastomas express high levels of vascular endothelial growth factor that drives angiogenesis and tumor progression. We hypothesized that bevacizumab through its inhibitory effect on vascular endothelial growth factor will result in hemangioblastoma tumor regression as well as a meaningful clinical response.Case presentationWe present the case of a 51-year-old Caucasian man with surgically unresectable cervical cord hemangioblastoma presenting with progressive weakness leading to quadriparesis. He was treated with bevacizumab and his follow up magnetic resonance imaging scans showed marked tumor regression. After only six cycles of intravenous bevacizumab (10mg/kg every two weeks), he started ambulating after being wheelchair bound. He is currently still receiving treatment almost two years after initiation of bevacizumab.ConclusionsWe have shown for the first time that bevacizumab can result in significant tumor regression and a sustained clinical improvement in a patient with an otherwise unresectable spinal cord hemangioblastoma. This novel approach can be immensely useful for patients with difficult to resect hemangioblastomas or those with multiple lesions such as in von Hippel-Lindau syndrome.

Somatostatin receptor expression on von Hippel-Lindau-associated hemangioblastomas offers novel therapeutic target

“…In this study, we also demonstrate that the canonical VHL pathway252627 is not affected by SSTR activation. This suggests that agents targeting the canonical VHL pathway that have shown partial efficacy810 may potentiate SSTR agonist therapy, and may be reserved for instances of tachyphylaxis with somatostatin analogues154445.…”

“…In some cases, surgical resection of symptomatic VHL-HBs is not an option due to unresectable locations or due to extensive co-morbidities. Development of chemotherapy and anti-angiogenic therapy for such patients remains underdeveloped due to the indolent nature of VHL disease678910. Due to relatively long life expectancy of VHL patients11, treatment with toxic chemotherapeutic agents is not feasible for extended periods of time.…”

Neuropathological Characteristics of Progression after Prolonged Response to Bevacizumab in Multifocal Hemangioblastoma

“…Recently, VEGF-based antiangiogenic therapy has entered clinical practice in selected cases of hemangioblastoma [6,7,8]. However, these studies mainly show disease stabilization, while radiologic response has been described in only 1 case of bevacizumab-treated hemangioblastoma [7].…”

“…Since VEGF and VEGF receptors (VEGFRs) are expressed in hemangioblastoma [4,5], antiangiogenic therapy is now being considered as a therapeutic option beyond surgery and radiotherapy. To date, few cases of progressive hemangioblastoma treated successfully with the VEGF antibody bevacizumab have been published [6,7]. In a single-arm phase II study with the VEGFR inhibitor sunitinib in patients with VHL disease, stable disease was reported in 9/11 patients with hemangioblastoma while 6/18 patients with other VHL-related lesions showed a partial response [8].…”

Cystic Transformation of the Pancreas Due to Von Hippel–lindau Syndrome

“…Например, применение мультитирозинкиназных ингибиторов, таких как сунитиниб и пазопаниб, показало выраженный ответ на терапию у пациентов со светлоклеточным почечно-клеточным раком, ассоциированным с синдромом ФХЛ [18][19][20], феохромоцитомой [21], гемангиобластомами ЦНС [18,22]. Описано успешное применение бевацизумаба у пациентов с гемангиобластомами ЦНС и сетчатки [23,24], темсиролимусаспеци фического ингибитора mTOR-киназу пациентов с метастатическим светлоклеточным почечно-клеточным раком с неблагоприятным прогнозом [25].…”