Despite its rarity, glioblastoma casts a long shadow, accounting for nearly half of all malignant brain tumors and presenting a median survival of just 15 months despite aggressive treatment.
Key Takeaways
- The age-adjusted incidence rate of glioblastoma in the United States from 2015-2019 was 3.19 per 100,000 person-years
- Glioblastoma accounts for 14.3% of all primary brain tumors and 48.6% of all malignant primary brain tumors in the US (CBTRUS 2021)
- The median age at diagnosis for glioblastoma is 65 years, with 75% of cases occurring in individuals over 55 years old
- Headache is the most common initial symptom in 50-60% of glioblastoma patients
- Seizures occur at presentation in 30-50% of glioblastoma cases
- Cognitive impairment is reported in 40% of newly diagnosed glioblastoma patients
- Glioblastoma is characterized by pseudopalisading necrosis in 90% of cases
- IDH1/2 wild-type status is present in 90-95% of primary glioblastomas
- EGFR amplification occurs in 40-60% of glioblastoma tumors
- Maximal safe resection is achieved in 30-40% of glioblastoma cases
- Standard treatment includes temozolomide (TMZ) with radiotherapy yielding median OS of 14.6 months (Stupp protocol)
- Gross total resection improves survival by 3-5 months compared to biopsy only
- Median OS with standard therapy is 15 months, dropping to 9 months with age >60
- 5-year survival rate for glioblastoma is 6.9% overall (SEER 2015-2019)
- IDH-mutant glioblastomas have 27-month median OS vs 14 months wild-type
Glioblastoma is a rare but aggressive brain cancer diagnosed primarily in older adults.
Clinical Presentation
- Headache is the most common initial symptom in 50-60% of glioblastoma patients
- Seizures occur at presentation in 30-50% of glioblastoma cases
- Cognitive impairment is reported in 40% of newly diagnosed glioblastoma patients
- Hemiparesis develops in 25-35% of patients prior to diagnosis
- Nausea and vomiting due to increased intracranial pressure in 25% of cases
- Aphasia presents in 20-30% of left temporal lobe glioblastomas
- Visual field defects occur in 15% of glioblastoma patients at onset
- Personality changes noted in 10-20% of frontal lobe glioblastomas
- Ataxia is a symptom in 10% of cerebellar-infiltrating glioblastomas
- Cranial nerve palsies appear in 5-10% of brainstem-proximal glioblastomas
- Mean symptom duration before diagnosis is 3-6 months
- 70% of glioblastomas are supratentorial, leading to focal deficits
- Memory loss affects 25% of temporal lobe glioblastoma patients
- Dysphasia incidence is 35% in dominant hemisphere tumors
- Fatigue is reported by 60% of glioblastoma patients at presentation
- Sensory disturbances in 15% of parietal lobe glioblastomas
- Hydrocephalus symptoms in 20% due to ventricular obstruction
- Diplopia from sixth nerve palsy in 8% of cases
- Behavioral changes in 15% of non-eloquent area glioblastomas
- Gait instability in 12% of infratentorial glioblastomas
- Anosmia rare but occurs in 2% of anterior frontal glioblastomas
- Urinary incontinence as a late symptom in 5% due to frontal involvement
- 40% of patients experience progressive neurological deterioration
- Mass effect symptoms like papilledema in 30% on exam
- Psychosis-like symptoms in <1% of glioblastoma cases
- Hearing loss in 3% of temporal glioblastomas invading auditory pathways
- Facial weakness in 7% of pontine glioblastomas
- Vertigo reported in 5% of CPA angle glioblastomas
Clinical Presentation Interpretation
This statistical portrait of glioblastoma, dominated by headaches and seizures, is a chilling reminder that this tumor's first language is neurological sabotage, speaking in deficits long before it shouts its name on a scan.
Epidemiology
- The age-adjusted incidence rate of glioblastoma in the United States from 2015-2019 was 3.19 per 100,000 person-years
- Glioblastoma accounts for 14.3% of all primary brain tumors and 48.6% of all malignant primary brain tumors in the US (CBTRUS 2021)
- The median age at diagnosis for glioblastoma is 65 years, with 75% of cases occurring in individuals over 55 years old
- Males have a 1.6 times higher incidence rate of glioblastoma compared to females (3.93 vs 2.49 per 100,000)
- In Europe, the incidence of glioblastoma is approximately 3-4 per 100,000 population annually
- Glioblastoma represents 49% of all gliomas diagnosed in adults
- The incidence of glioblastoma has remained stable over the past decade at around 3.2 per 100,000 in high-income countries
- African Americans have a slightly lower incidence of glioblastoma (2.91 per 100,000) compared to Whites (3.26 per 100,000)
- Ionizing radiation exposure increases glioblastoma risk by 2-5 fold
- No strong association exists between cell phone use and glioblastoma incidence (pooled RR 0.98)
- Pediatric glioblastoma incidence is 0.1-0.2 per 100,000 children under 15
- In Asia, glioblastoma incidence is lower at 0.59 per 100,000 compared to Western countries
- Glioblastoma prevalence in the US is estimated at 124,000 cases in 2022
- Occupational exposure to pesticides is linked to a 1.4-fold increased risk of glioblastoma
- Familial aggregation occurs in less than 5% of glioblastoma cases
- The highest incidence of glioblastoma is in Denmark at 5.52 per 100,000
- Glioblastoma incidence peaks in the 65-74 age group at 12.5 per 100,000
- HIV patients have a 1.5 times higher risk of glioblastoma
- Annual glioblastoma diagnoses in the US: approximately 13,000 new cases
- Women have a better survival rate post-glioblastoma diagnosis (HR 0.87)
- Glioblastoma is rare before age 40, comprising only 10% of cases
- Southeast Asian populations show glioblastoma incidence of 0.3 per 100,000
- Smoking is not a significant risk factor for glioblastoma (OR 1.05)
- Glioblastoma mortality rate mirrors incidence at 3.15 per 100,000 in the US
- Cowden syndrome increases glioblastoma lifetime risk to 3-6%
- Urban residence is associated with 10% higher glioblastoma incidence
- Glioblastoma accounts for 15% of brain cancers in adults over 45
- Incidence in Hispanics is 2.8 per 100,000 vs 3.4 in non-Hispanics
- Turcot syndrome type 1 raises glioblastoma risk by 30-fold
- Global glioblastoma burden: 34,000 new cases annually (2018 GLOBOCAN)
Epidemiology Interpretation
Glioblastoma may be statistically 'rare' at about 3 per 100,000, but it asserts a grim dominance, accounting for nearly half of all malignant brain tumors and showing a particular, unyielding fondness for men over 65.
Pathology and Molecular Features
- Glioblastoma is characterized by pseudopalisading necrosis in 90% of cases
- IDH1/2 wild-type status is present in 90-95% of primary glioblastomas
- EGFR amplification occurs in 40-60% of glioblastoma tumors
- PTEN mutations are found in 25-40% of glioblastomas
- MGMT promoter methylation frequency is 35-45% in glioblastoma
- TERT promoter mutations in 80-90% of IDH-wildtype glioblastomas
- Ki-67 proliferation index averages 15-20% in glioblastoma
- Chromosome 7 polysomy in 70% and 10q loss in 70% of cases
- PDGFRA amplification in 10-15% of glioblastomas
- NF1 mutations occur in 20-25% of glioblastoma samples
- Giant cell variant comprises 1-3% of glioblastomas with TP53 mutations
- Sarcomatous features in gliosarcoma subtype (2% of GBMs)
- Microvascular proliferation is a hallmark in 85% of high-grade gliomas like GBM
- ATRX loss rare in primary GBM (5%) but common in IDH-mutant
- H3F3A K27M mutations in <1% of adult glioblastomas
- CDKN2A/B homozygous deletion in 50-55% of GBMs
- BRAF V600E mutation in 1-2% of glioblastomas
- Tumor mutational burden averages 2.5 mut/Mb in glioblastoma
- Hypermutation phenotype in 2-5% due to POLE mutations
- Mesenchymal subtype (29%) shows NF-κB pathway activation
- Proneural subtype (28%) associated with IDH mutation (low in primary)
- Classical subtype (31%) defined by EGFR amp and Chr7 gain
- Neural subtype (6%) expresses neuron markers
- G-CIMP phenotype in 15% linked to better prognosis
- PI3K pathway alterations in 80-90% of glioblastomas
- TP53 mutations in 28% of primary glioblastomas
- MET amplification in 4-7% of GBM cases
- IDH1 R132H mutation defines secondary GBM (5-10% of all)
- Average tumor diameter at diagnosis is 4-6 cm
Pathology and Molecular Features Interpretation
Glioblastoma is a molecularly crowded and grimly efficient party where nearly every tumor brings its own signature genetic dish, yet the guest list is so chaotic that finding a common weakness feels like trying to organize the chaos itself.
Prognosis and Survival
- Median OS with standard therapy is 15 months, dropping to 9 months with age >60
- 5-year survival rate for glioblastoma is 6.9% overall (SEER 2015-2019)
- IDH-mutant glioblastomas have 27-month median OS vs 14 months wild-type
- MGMT methylation improves OS to 21.7 vs 12.7 months non-methylated
- Gross total resection (GTR) OS 16.3 months vs 11.6 months STR
- Young age (<50) median OS 22 months vs 12 months >70 years
- Karnofsky performance status (KPS) >=70 predicts OS >12 months (HR 0.6)
- Recursive partitioning analysis (RPA) class III: 17.1 months OS, class V: 5.7 months
- Gliosarcoma subtype OS similar to GBM at 13 months
- Long-term survivors (>5 years) comprise 5-10%, often with MGMT meth
- Post-recurrence survival averages 6-9 months
- 1-year survival rate 37%, 2-year 17% (CBTRUS data)
- Female sex confers 10-15% better OS (HR 0.85)
- Multifocal GBM at diagnosis OS 8 months vs unifocal 15 months
- Ventricular involvement reduces OS by 4 months
- Proneural subtype OS 15.2 months vs mesenchymal 11.8 months
- High Ki-67 (>15%) halves OS to 10 months
- Secondary GBM from low-grade has OS 6-7 years vs primary 1 year
- TTFields + TMZ/RT OS 20.9 months (EF-14 trial)
- Elderly hypoRT + TMZ OS 9.3 months vs RT alone 7.6 months
- Tumor volume >50 cc predicts OS <10 months
- 30-day postoperative mortality 2-5% in GBM resections
- G-CIMP+ tumors OS 26.4 months median
- KPS <60 OS 3-4 months regardless of treatment
- EGFRvIII expression associated with poorer OS (HR 1.3)
- Leptomeningeal spread at recurrence halves survival to 2 months
- Pediatric GBM 5-year OS 20% vs 5% adults
- Pretreatment neutrophil-lymphocyte ratio >4 predicts worse OS
- Corpus callosum involvement OS 10 months median
- Hypermutated GBM OS 22 months despite recurrence
Prognosis and Survival Interpretation
Glioblastoma numbers ruthlessly illustrate a clinical truth: while factors like youth, a methylated MGMT promoter, and a clean surgical resection can buy precious time, the disease remains a master of brutal arithmetic where even the most favorable variables rarely rewrite the terminal equation.
Treatment
- Maximal safe resection is achieved in 30-40% of glioblastoma cases
- Standard treatment includes temozolomide (TMZ) with radiotherapy yielding median OS of 14.6 months (Stupp protocol)
- Gross total resection improves survival by 3-5 months compared to biopsy only
- Bevacizumab extends PFS by 4 months (median 10.7 vs 6.4 months) but not OS
- MGMT-methylated tumors respond better to TMZ (HR 0.53 for OS)
- Hypofractionated RT (40 Gy/15 fx) equivalent to standard 60 Gy/30 fx in elderly
- Tumor-treating fields (TTFields) add 5 months OS (20.9 vs 16.0 months)
- Dose-dense TMZ schedules improve PFS in 25% recurrence cases
- Laser interstitial thermal therapy (LITT) used in 10% inoperable cases
- Carmustine wafers implanted in 5-10% of resected cavities
- Proton beam therapy reduces neurocognitive decline by 20% vs photon RT
- Immunotherapy checkpoint inhibitors (nivolumab) show 10% ORR in GBM
- DCVax-L vaccine extends OS to 23.1 months in phase III
- Stereotactic radiosurgery (SRS) for small recurrences (<3cm) PFS 6 months
- Lomustine + TMZ rechallenge ORR 22% at recurrence
- Fluorescence-guided surgery with 5-ALA increases GTR by 20%
- Elderly (>70) short-course TMZ monotherapy OS 8.3 months
- Regorafenib phase II OS 7.4 months at recurrence
- Intra-arterial chemotherapy trials show 30% tumor reduction
- CAR-T therapy targeting EGFRvIII in early trials PFS 3 months
- Whole brain RT avoided; focal RT volumes average 200-300 cc
- Neoadjuvant immunotherapy increases TILs by 50% in resected GBM
- RTOG 0525 trial: dose-intensified TMZ no OS benefit
- Oncolytic HSV (DNX-2401) 20% response in injected tumors
- Pazopanib monotherapy PFS 3.2 months
- Awake craniotomy enables 75% resection in eloquent areas
- PCV chemotherapy inferior to TMZ in anaplastic gliomas but tested in GBM
- Nano-particle albumin-bound paclitaxel in trials ORR 10%
- Metabolic therapy (keto diet) adjunct PFS benefit in 20% retrospective
Treatment Interpretation
While the sobering reality of glioblastoma remains a relentless foe, our incremental, hard-won gains—from adding precious months with surgical precision and targeted therapies to sparking glimmers of long-term hope with novel vaccines—paint a portrait of a field doggedly chipping away at a mountain.
Sources & References
- Reference 1NEURO-ONCOLOGYneuro-oncology.oxfordjournals.orgVisit source
- Reference 2NCBIncbi.nlm.nih.govVisit source
- Reference 3CANCERcancer.govVisit source
- Reference 4CANCERcancer.orgVisit source
- Reference 5PUBMEDpubmed.ncbi.nlm.nih.govVisit source
- Reference 6PUBMEDpubmed.ncbi.nih.govVisit source
- Reference 7MAYOCLINICmayoclinic.orgVisit source
- Reference 8NEJMnejm.orgVisit source