Glioblastoma is among the most aggressive tumors of the central nervous system—a disease that causes around 250,000 deaths worldwide each year and newly affects approximately 4,800 people in Germany. Despite its severity, modern neuro-oncology has made tremendous progress in recent years: more precise diagnostics, innovative therapeutic concepts, and high-performance interdisciplinary medicine now offer better prospects than ever before.
The editorial team of Leading Medicine Guide spoke with neuro-oncology specialist Priv.-Doz. Dr. med. Sied Kebir to learn which treatment options are effective and how they are applied.
“Glioblastoma arises from glial cells. These are supporting cells in the brain that normally supply and protect nerve cells. At some point, one of these cells begins to divide uncontrollably—why this happens remains unknown in the vast majority of cases. The tumor predominantly occurs in the cerebral hemispheres, especially in the frontal and temporal lobes.
In about 90 percent of cases, it appears without any recognizable precursor. In the remaining 10 percent, a slower-growing precursor tumor has transformed over months to years. From the onset of initial symptoms to diagnosis, usually only three to six weeks pass. Common early signs include a first-time epileptic seizure, sudden speech disturbances, unusual headaches, or weakness on one side of the body.
MRI imaging typically shows a mass with a bright rim and a dark center. The only confirmed risk factor is previous radiation to the head. Despite decades of research, mobile phone radiation, diet, stress, and environmental toxins have not been confirmed as triggers. A glioblastoma is not the result of incorrect behavior,” notes PD Dr. Kebir at the beginning of our conversation.
It is characteristic that glioblastoma does not grow as a clearly defined tumor but spreads in finger-like projections into the surrounding brain tissue. This allows it to infiltrate functionally critical areas and makes complete surgical removal nearly impossible. It most commonly develops in the cerebral hemispheres, particularly in frontal and temporal regions, but can in principle occur in any part of the brain.
A glioblastoma therefore arises from a complex interplay of genetic changes, biological properties of glial cells, and the unique environment of the brain. This combination makes the tumor so aggressive, elusive, and therapeutically challenging—and also explains why modern neuro-oncology relies on highly specialized, interdisciplinary approaches.
The success of glioblastoma treatment depends on a range of biological, clinical, and therapeutic factors which together determine how well a patient responds to therapy. Although glioblastoma is one of the most aggressive tumors of the central nervous system, there are clear variables that positively or negatively influence its course.
“Three factors carry more weight than all others. The first is the extent of surgical resection. If it is possible to remove all visible tumor tissue, this measurably prolongs survival. This is not always feasible, for example when the tumor is located near critical brain regions responsible for speech or movement.
The second factor is the patient’s overall physical condition. It is measured using the Karnofsky Performance Scale, which ranges from 0 to 100. Patients who are largely able to care for themselves tolerate therapy better and, on average, live longer—regardless of age. The third factor is the molecular characteristics of the tumor, particularly MGMT methylation.
More on this below. Data also show that treatment at specialized high-volume centers leads to better outcomes,” explains PD Dr. Kebir.
Some glioblastomas develop resistance early, limiting the effectiveness of standard therapy. Tumor biology also plays a role: tumors with high vascularization, pronounced hypoxia, or strong infiltration tendencies often respond less well to treatment. The patient’s general health condition also influences therapeutic success.
Younger patients with good neurological status benefit more from intensive treatment strategies. Comorbidities, neurological impairments, or reduced overall condition can limit treatment options.
Treatment of glioblastoma today lies between established standard procedures and a dynamic research landscape in which new experimental approaches are being tested. These two areas differ significantly in their objectives, level of evidence, and therapeutic potential.
PD Dr. Kebir explains: “Standard therapy consists of three consecutive steps. First, the neurosurgeon removes as much of the tumor as possible. This is aided by a fluorescent dye that makes tumor cells visible under special light, as well as electrical monitoring of critical brain functions during surgery.
This is followed by six weeks of radiation therapy combined with daily administration of the chemotherapy drug temozolomide. Each radiation session lasts only a few minutes. Afterward, temozolomide is continued for another six months in cycles: five days of tablets followed by 23 days off. In addition, tumor treating fields may be used—a portable device with electrodes on the scalp that must be worn for at least 18 hours a day.
The survival benefit amounts to a few months on average. Whether this outweighs the impact on daily life is an individual decision. Experimental approaches target tumor biology specifically rather than acting broadly. These include laboratory-engineered immune cells (CAR-T cells), individualized tumor vaccines, and drugs targeting specific genetic mutations in the tumor.
None of these approaches has yet replaced the standard. They are accessible through clinical trials and specialized neuro-oncology centers.”
Innovative and experimental approaches aim to overcome the limitations of current therapies. These include various forms of immunotherapy, such as checkpoint inhibitors, personalized tumor vaccines, or CAR-T cell therapies, all designed to activate the immune system specifically against tumor cells.
Oncolytic viruses, which are intended to infect and destroy tumor cells, are also being investigated in clinical trials. Additional experimental strategies include targeted therapies against specific molecular alterations, such as EGFR or IDH mutations, as well as novel combination therapies linking radiation, chemotherapy, and immunotherapy. Local approaches are also being explored, including intratumoral drug delivery, nanotechnology-based transport mechanisms, and new methods to overcome the blood-brain barrier.
MGMT promoter methylation is essentially a functional marker of a tumor cell’s ability to repair alkylating DNA damage. The MGMT protein removes alkyl groups from the O6 position of the guanine base—precisely where temozolomide and other alkylating agents exert their cytotoxic effect.
If the MGMT promoter is methylated, the gene is epigenetically silenced, repair capacity decreases, and tumor cells become significantly more susceptible to the DNA damage induced by temozolomide. Clinically, this results in a markedly better response to standard chemotherapy, longer progression-free intervals, and extended overall survival.
“MGMT is a repair enzyme in tumor cells. It reverses exactly the damage caused by temozolomide. If the gene for this enzyme is switched off—what specialists call ‘methylated’—temozolomide works much more effectively. Patients with methylated MGMT live longer after diagnosis.
In older patients with unmethylated MGMT and reduced general condition, radiation therapy without chemotherapy may be the more appropriate option, as the additional benefit of temozolomide is then limited. IDH is a metabolic enzyme. Tumors with an IDH mutation grow more slowly and respond better to treatment.
Since 2021, they are no longer classified as glioblastoma but as a distinct disease entity. For this group, the drug vorasidenib represents the first targeted therapy, showing a significant delay in progression in the INDIGO trial. The vast majority of glioblastomas are IDH wild-type, meaning they lack this mutation and therefore have a less favorable prognosis. Standard therapy is tailored to this group,” explains PD Dr. Kebir.
Overall, both markers complement each other remarkably: MGMT methylation provides predictive information—it indicates how well a tumor responds to a specific therapy. IDH status provides prognostic and biological information—it defines the type of tumor in question.
In clinical practice, this information informs nearly every therapeutic decision: from how aggressively to treat, to the choice of chemotherapy, to assessing suitable clinical trial options. It helps physicians counsel patients more realistically about risks and benefits and enables increasingly precise, personalized treatment planning that goes far beyond a purely histological diagnosis.
The close integration of neuro-oncology, neurosurgery, and radiation therapy in glioblastoma is not merely an organizational advantage but a true biological lever: it determines how completely a tumor can be removed, how precisely radiation therapy is planned, how effectively systemic therapies work, and how quickly complications are addressed.
A glioblastoma is a highly complex, infiltrative tumor—and that is precisely why it requires a team that contributes its perspectives simultaneously rather than sequentially.
“No single specialty can optimally treat a glioblastoma. Neurosurgery performs the operation, radiation oncology delivers radiation, and neuro-oncology manages chemotherapy and coordinates the overall plan. In addition, neuroradiologists, nuclear medicine specialists for MRI and PET evaluation, and neuropathologists for tissue analysis are involved. Collaboration is organized through tumor boards.
There, all disciplines sit together and jointly determine the next treatment step—after surgery, at every follow-up, and in the event of recurrence. The primary point of contact in daily care is usually the neuro-oncologist. Seeking a second opinion at a specialized center is always possible and is not a sign of distrust toward the treating physicians,” emphasizes PD Dr. Kebir.
An often underestimated advantage of this collaboration is speed. Glioblastomas leave little time for delays. When all disciplines work closely together, the intervals between surgery, radiation, and chemotherapy are significantly shortened.
Many modern treatment approaches—immunotherapies, vaccines, targeted therapies, tumor treating fields—can only be effectively implemented when surgery, radiation therapy, and systemic therapy are closely coordinated. Clinical trials require precise inclusion criteria, molecular characterization, and clearly defined postoperative workflows. Without a well-coordinated team, these options would not be accessible to many patients.
Interdisciplinary collaboration transforms a purely sequential treatment into a strategic overall therapy. It ensures that each decision is made in the context of the others, that biological markers are used effectively, and that patients receive not just treatment but a coherent, well-designed therapeutic concept.
When looking at what is currently considered “promising” in glioblastoma, it is less about individual miracle drugs and more about comprehensive strategies aimed at overcoming the tumor’s immunological barriers and targeting multiple pathways simultaneously.
“In CAR-T cell therapy, the patient’s own immune cells are genetically modified in the laboratory so that they can recognize and destroy tumor cells. In some patients, advanced tumors have temporarily regressed completely. The challenge is that the tumor continuously changes its surface, causing immune cells to lose their target.
Newer approaches therefore target multiple structures simultaneously. In personalized tumor vaccines, the tumor’s genetic material is decoded to identify individual vulnerabilities. This results in a customized vaccine. Early studies show measurable immune responses, but whether this extends survival remains unclear.
Checkpoint inhibitors, which have shown sometimes spectacular effects in melanoma and lung cancer, have failed as monotherapy in glioblastoma. The tumor suppresses the immune system in its environment too strongly. They are still being tested in combination with other immunotherapies. Vorasidenib has demonstrated clear benefits for IDH-mutated brain tumors in the INDIGO trial.
This does not apply to classical glioblastoma, but it indicates the direction: away from one-size-fits-all therapy and toward molecularly tailored treatment,” concludes PD Dr. Kebir.
Three particularly promising directions are emerging: specialized immunotherapies such as CAR-T cells and tumor vaccines, oncolytic viruses, and intelligent combination therapies that integrate radiation therapy, immune modulation, and targeted agents. The key factor is not a single drug but the ability to specifically modify the complex, immunosuppressive environment of glioblastoma and tailor therapies precisely to the biology of each tumor.
The quality of life of people with glioblastoma can, in fact, be influenced far more during intensive treatment phases than might initially be expected.
Quality of life is shaped by many small adjustments: recognizing symptoms early, treating them in a targeted manner, strengthening cognitive and emotional stability, incorporating moderate physical activity, and relieving the burden on caregivers. When medical, therapeutic, and social support are well coordinated and clearly communicated, patients noticeably regain orientation, energy, and autonomy.
“The most common and often most distressing problem is tumor-related fatigue. It differs fundamentally from normal tiredness and does not improve with sleep. What has been proven to help is 20 to 30 minutes of moderate physical activity daily and a structured daily routine with scheduled breaks. Concentration and memory impairments affect the majority of patients. A neuropsychological assessment can determine which areas are affected. Targeted training significantly improves daily functioning. Anxiety and low mood are not signs of weakness but expected reactions to this diagnosis.
Psycho-oncologists specialize in supporting patients in exactly this situation. This also applies to family members. Palliative care is often misunderstood. Early palliative involvement does not mean that hope is lost. It means better pain management, improved symptom control, and professional support in difficult decision-making.
Studies show that patients receiving early palliative care feel better and sometimes even live longer. Applications for rehabilitation, disability status, care level, and household assistance can be organized early through hospital social services. Physical therapy, occupational therapy, and speech therapy should be part of the treatment plan from the outset,” explains PD Dr. Kebir, bringing our conversation to a close.
Thank you very much, PD Dr. Kebir, for this encouraging and informative discussion on the treatment of this challenging disease, glioblastoma.
- Head of Clinical Neuro-Oncology at University Hospital Essen; recognized expert in CNS tumors
- Broad spectrum: including gliomas, glioblastomas, meningiomas, pituitary tumors, CNS lymphomas, brain metastases
- Close integration with neurosurgery and the West German Tumor Center (WTZ) for highly specialized interdisciplinary therapies
- Access to state-of-the-art neurosurgical technologies (fluorescence microscopy, neuronavigation, intraoperative imaging)
- Additional qualifications in intensive care medicine and pharmacological tumor therapy; extensive expertise in systemic treatments
- Strong focus on personalized, evidence-based treatment and empathetic, patient-centered care
