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This is truly an exciting time in the field of neuro-oncology, particularly in the area of highgrade
gliomas. The management of patients with high-grade gliomas has historically been one
of the most challenging and disheartening fields in medicine, where failure is the rule and
longevity is the exception. The jaded often state that despite purported advances in surgical
and radiotherapeutic techniques and a myriad of clinical trials of medical therapies, the survival
statistics for glioblastoma have not changed in the last three decades. The nihilism
associated with these tumors is such that some practitioners still advise against treatment or
even biopsy, recommending palliative care with the diagnosis based only on history and an
MRI scan. If the current state-of-the-art in the diagnosis and management of high-grade
gliomas was truly so bleak, there would be no reason to compile and publish a monograph on
the subject. The fact is that we have recently entered an era where real progress is being made
in our understanding and treatment of high-grade gliomas that is directly benefiting some
patients.
We are slowly but surely chipping away at this problem. One approach has exploited
correlations between particular molecular markers and therapeutic response. The first such
“breakthrough” in high-grade glioma was the observation that loss of chromosomes 1p and
19q uniformly predict chemosensitivity in anaplastic oligodendrogliomas (1). Subsequent
work has refined this relationship using additional markers to forecast longevity in patients
with these tumors (2). More recently we have seen similar observations in glioblastoma where
methylation of the methyl-guanine-methyl transferase (MGMT) gene promoter is associated
with better response to temozolomide (TMZ) (3). Similarly, co-expression of the vIII mutation
of epidermal growth factor receptor (EGFR) and the PTEN tumor suppressor gene predicts
response to EGFR inhibitors (4).
Another approach has been large multi-center clinical trials using conventional and unconventional
agents. Stupp et al have shown that radiotherapy with concurrent low dose temozolomide
and subsequent high dose TMZ leads to longer survival than radiotherapy alone for
newly diagnosed glioblastoma (5). Presently a large multicenter trial is comparing the use of
an immuotoxin (IL13-PE39QQR) delivered by convection enhanced delivery against
carmustine-impregnated biodegradable wafers in patients with operable glioblastoma at first
recurrence. Yet another avenue of investigation is to use preclinical animal testing to improve
response by refining traditional therapeutic delivery schedules, combining agents and investigating
various modes of delivery and concentrations of agents achieved in tumor, brain and
CSF.
So in this volume we present the spectrum of issues pertaining to high-grade gliomas from
the basics of clinical characteristics and management to the state-of-the-art in diagnosis and
therapeutics, as well as current areas of investigation that may lead to the treatments of
tomorrow. We explore whether molecular diagnosis complements histology or is likely to
supercede it, the most current information in imaging techniques to assist us in diagnosing and
monitoring treatment, and the latest in “conventional” treatments such as surgery, radiation,
and cytotoxic chemotherapy. |
