Chapter 

General Introduction: Aims of the Thesis 

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 counter-
parts 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 con-
siderations 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
determine 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 positron emission tomography and magnetic resonance spectroscopy) by correlating
them with postoperatively acquired histopathological diagnoses. Subsequently, this thesis aims
to determine the potential role of these non-invasive, minimal-risk imaging modalities in defi-
nite preoperative diagnosis of primary brain tumours. After all, proper management of a neo-
plasm primarily relies on its adequate and correct diagnosis and staging. However, histopatho-
logical tumour evaluation of still forms the gold standard for definite determination of the tu-
mour type and grade [7–16].
The greatest disadvantage of this gold standard is the need for neurosurgical interventions (bi-
opsy or (sub)total tumour resection) for tissue sampling, which remains invasive and has its
own non-negligible risks. For example, it is well known that in patients with glioma, early sur-
gical tumour resection may positively influence prognosis. However, as per the gold standard,
the definite diagnosis of tumour type and grade (whether it be a glioma or not) must rely on
histopathological evaluation following neurosurgical intervention. Therefore, per definition,
the advantageous character of early resection of a medical imaging-based suspected glioma can
only be ascertained after biopsy or resection. This means that, to date, a proportion of patients
with suspected glioma, turning out not to be glioma after surgery and subsequent histopatho-
logical validation, will unnecessarily have been exposed to the risks that surgery bears [17].
Wijnenga et al. showed that in the total group of patients with any kind of (primary or second-
ary) brain tumour, those who underwent a surgical biopsy of the tumour showed significantly
lower overall survival rates than those subjected to either an early (sub)total tumour resection