Joeky Senders

11 General introduction and thesis outline GENERAL INTRODUCTION Neurosurgical oncology Pathophysiology and epidemiology Malignant brain tumors are fast-growing neoplasms in the brain and can broadly be classified into primary and secondary (i.e., metastatic) brain tumors. 1 Primary brain tumors arise fromwithin the brain, whereas secondary tumors originate elsewhere and spread to the brain as a result of hematogenous dissemination. 2,3 In the Netherlands, roughly 1,300 new patients are diagnosed with a primary malignant brain tumor each year. 4,5 Gliomas account for the majority (80-85%) and encompass a heterogenous group of brain tumors that originally evolve from astrocytes, oligodendrocytes, or ependymal cells. 2 These non-neural cell lines facilitate a wide range of supportive functions in the brain in addition to their structural support. 6 Due to the heterogenous nature and behavior of the disease, overall survival ranges between several months or years after diagnosis, yet all subtypes remain non-curative to date. 7–9 Glioblastoma constitutes the most common (~60%) and malignant glioma subtype with a median survival of 15 months after diagnosis despite improved surgical and adjuvant treatment strategies. 10,11 Brain metastases occur in approximately 6-17% of all cancer patients, and the incidence may be increasing as control of the systemic disease improves. 3,12 The most common primary tumors to metastasize to the brain are lung cancer, breast cancer, and melanoma accounting for 67-80% of all brain metastases. 3 The median survival in patients with brain metastases is typically in the order of months after diagnosis. Individual patient survival, however, varies widely depending on the age and functional status of the patient, the histological subtype and control of the primary tumor, and the number and intracerebral spread of brain metastases present. 13 Clinical management The aggressive growth within healthy and functional brain tissue poses significant challenges with regards to the surgical and medical management of patients with a malignant brain tumor. Surgery is considered as the first line of treatment; however, the benefit of surgery should always be balanced against the risk of neurological deficits and mortality. 7,14 Adjuvant treatment largely depends on the histological and molecular subtype of the tumor. Histopathological examination of the resected tissue is therefore required to tailor clinical management to the needs of the individual patient. Standard of care for patients with a glioblastoma includes maximal safe resection followed by chemoradiation (i.e., radiotherapy with concomitant and adjuvant chemotherapy using temozolomide). 7 In the context of brain metastases, surgical resection should be considered in patients with a reasonable functional status and prognosis, a limited