General Introduction 1

With an estimated worldwide age-standardised incidence rate (ASIR) of 3.4 per 100,000 person years
(PY), which corresponds with a global incidence of over 250,000 newly identified cases annually,
malignant primary brain tumours are per definition rare neoplasms and make up about only 1.8 % of
newly diagnosed cancers [1], and 3 % of all existing cancers, worldwide [2,3]. However, despite their
rarity, they make an important contribution to worldwide cancer mortality and morbidity [4]. The
extremely aggressive character of most malignant primary brain tumours (and even the incapacitating
properties of some of their non-malignant counterparts due to eloquent brain area involvement [1])—
with poor prognoses—makes them the lead cause (over 25 %) of child mortality due to malignant
neoplasms [1,3,5,6]. These ideas and considerations reinforce the need for extensive research within
the domain of neuro-oncology.

1.1 Aims of the thesis

Adequate and accurate assessment of tumour type and grade is of paramount importance to deter-
mine further management policies. The main goal of this thesis is to validate two forms of non-
invasive preoperative molecular-biological imaging modalities in primary brain tumours (namely pos-
itron emission tomography and magnetic resonance spectroscopy) by correlating them with postop-
eratively acquired histopathological diagnoses. Subsequently, this thesis aims to determine the po-
tential role of these non-invasive, minimal-risk imaging modalities in definite preoperative diagnosis
of primary brain tumours. After all, proper management of a neoplasm primarily relies on its adequate
and correct diagnosis and staging. However, histopathological tumour evaluation of still forms the
gold standard for definite determination of the tumour type and grade [7–16].
The greatest disadvantage of this gold standard is the need for neurosurgical interventions (biopsy or
(sub)total tumour resection) for tissue sampling, which remains invasive and has its own non-negligi-
ble risks. For example, it is well known that in patients with glioma, early surgical tumour resection
may positively influence prognosis. However, as per the gold standard, the definite diagnosis of tu-
mour type and grade (whether it be a glioma or not) must rely on histopathological evaluation fol-
lowing neurosurgical intervention. Therefore, per definition, the advantageous character of early re-
section of a medical imaging-based suspected glioma can only be ascertained after biopsy or resec-
tion. This means that, to date, a proportion of patients with suspected glioma, turning out not to be
glioma after surgery and subsequent histopathological validation, will unnecessarily have been ex-
posed to the risks that surgery bears [17].
Wijnenga et al. showed that in the total group of patients with any kind of (primary or secondary)
brain tumour, those who underwent a surgical biopsy of the tumour showed significantly lower over-
all survival rates than those subjected to either an early (sub)total tumour resection or to a wait-and-
scan policy, with a hazard ratio of over 2.50. In contrast, no significant difference was found between
those undergoing (sub)total resection and those subjected to a wait-and-scan policy [17]. Though
difficult to explain, one may imagine that when a group of patients consists of patients with glioma
and patients with a non-glioma tumour, biopsy may lead to definite diagnosis, but will unnecessarily
expose non-glioma patients (likely also patients with small non-malignant tumours) to the risks of