Angiogenesis and Lymphangiogenesis in Medulloblastoma Development

Abstract

Medulloblastoma (MB) is the most prevalent brain tumor in children. Although the current cure rate stands at approximately 70%, the existing treatments that involve a combination of radio- and chemotherapy are highly detrimental to the patients’ quality of life. These aggressive therapies often result in a significant reduction in the overall well-being of the patients. Moreover, the most aggressive forms of MB frequently relapse, leading to a fatal outcome in a majority of cases. However, MB is highly vascularized, and both angiogenesis and lymphangiogenesis are believed to play crucial roles in tumor development and spread. In this context, our objective is to provide a comprehensive overview of the current research progress in elucidating the functions of these two pathways.

Clinico-Radiological Outcomes in WNT-Subgroup Medulloblastoma

“…MB has a high propensity to spread throughout the craniospinal axis via cerebrospinal fluid (CSF) pathways, with metastatic disease being identified on neuraxial staging in nearly one-third of patients at initial diagnosis [2,3] necessitating treatment of the entire brain and spinal cord, including its covering meninges for disease control. Recently, the existence of circulating tumour cells (CTCs) in the peripheral blood of patients with MB has been demonstrated [6] and explains the rare phenomenon of extraneural metastases (ENM) via the hematogenous route seen in <1% of patients at initial diagnosis. Occasionally, these CTCs can migrate towards the leptomeninges, leading to neuraxial dissemination [6].…”

“…Recently, the existence of circulating tumour cells (CTCs) in the peripheral blood of patients with MB has been demonstrated [6] and explains the rare phenomenon of extraneural metastases (ENM) via the hematogenous route seen in <1% of patients at initial diagnosis. Occasionally, these CTCs can migrate towards the leptomeninges, leading to neuraxial dissemination [6]. A lymphatic network has also been described in the CNS, particularly in the meninges (within the dura mater), which facilitates CSF drainage, part of which is in the subarachnoid space and drains into the cervical lymph nodes that connect with the lymphatic circulation, thereby incriminating CNS lymphatics as a potential pathway of spread [6].…”

“…Occasionally, these CTCs can migrate towards the leptomeninges, leading to neuraxial dissemination [6]. A lymphatic network has also been described in the CNS, particularly in the meninges (within the dura mater), which facilitates CSF drainage, part of which is in the subarachnoid space and drains into the cervical lymph nodes that connect with the lymphatic circulation, thereby incriminating CNS lymphatics as a potential pathway of spread [6]. Contemporary management for noninfantile MB [2,3,7] comprises maximal safe resection followed by postoperative risk-stratified adjuvant craniospinal irradiation (CSI) to a dose of 23.4-36 Gy/13-20 fractions plus boost irradiation of the tumour-bed to a dose of 18-30.6 Gy/10-17 fractions, resulting in a total primary site radiotherapy (RT) dose of 54 Gy/30 fractions.…”