What Is Glioblastoma and Why Is It So Difficult?
Glioblastoma arises from the astrocytes, the brain's support cells; it divides rapidly and develops a rich vascular network. Its central difficulty is that its border is not clear-cut: beyond the mass seen on MRI, microscopic tumor cells extend into apparently healthy tissue. For this reason even the most successful surgery leaves microscopic cells behind, and additional treatment is essential. Today a diagnosis of glioblastoma is made not by microscope appearance alone but with molecular markers such as IDH gene status; in current classification glioblastoma is defined as an 'IDH-wildtype' tumor. This molecular distinction is more decisive than the classic microscopic view in predicting the tumor's behaviour and response to treatment.
Symptoms and the Diagnostic Process
Because glioblastoma grows quickly, symptoms usually appear and progress over weeks: an increasing headache that becomes prominent towards morning, a first-ever epileptic seizure, and — depending on tumor location — limb weakness, speech disturbance, visual field loss, and changes in personality or memory are common. Contrast-enhanced brain MRI is the basic tool in diagnosis; glioblastoma typically appears as an irregular ring-enhancing mass with central necrosis (dead tissue) and wide surrounding oedema. Perfusion MRI, MR spectroscopy and, where needed, PET contribute to the differential diagnosis. However, definitive diagnosis is made only by pathological and molecular examination of tissue taken at surgery or biopsy; imaging alone is not enough.
Standard Treatment: Surgery + Concurrent Radiotherapy-Chemotherapy
The accepted approach in glioblastoma is the multi-stage treatment known as the 'Stupp protocol'. The first step is the widest possible surgical removal while preserving function; because the volume of tumor removed directly affects survival, awake surgery, neuronavigation and fluorescence-guided (5-ALA) techniques may be used for tumors near functional areas. Within 3–6 weeks after surgery, about 6 weeks of radiotherapy is given with concurrent temozolomide (oral chemotherapy); several maintenance cycles of temozolomide then follow. In selected patients additional options such as tumor-treating electric fields (TTFields) may come into consideration. For deep-seated tumors not suited to surgery, treatment is radiotherapy and chemotherapy following a diagnostic biopsy. The whole plan is decided in a multidisciplinary board.
Why Do MGMT and Other Markers Matter?
Molecular markers are now part of the standard in glioblastoma treatment. Silencing (methylation) of a DNA-repair gene called MGMT is a favourable sign indicating greater benefit from temozolomide chemotherapy. IDH gene status determines the tumor's true type and overall course; rare IDH-mutant tumors belong to a different group and usually run a slower course. These markers are studied from the tissue taken at surgery and clarify both the choice of treatment and realistic expectation. The aim of surgery is therefore not only to reduce the tumor but also to obtain enough quality tissue for a correct molecular diagnosis; the treatment plan is personalised according to these results.
Realistic Expectations and Quality of Life
We must be honest about glioblastoma: despite all advances, this tumor is not at present a disease that ends in definitive cure, and no one can guarantee otherwise. The aim of treatment is to prolong survival by keeping the disease under control and to spend that time with as good a quality of life as possible. Survival varies markedly from person to person according to factors such as the patient's age and general condition, the proportion of tumor removed at surgery, MGMT status and adherence to treatment. The likelihood of recurrence is high, and at recurrence a second surgery, re-irradiation, different chemotherapies or clinical trials may be considered. Open communication with the family, control of pain and seizures, nutrition and psychological support are inseparable parts of treatment; realistic and compassionate planning is preferred to misleading hopes.