Glioblastoma Symptoms and Treatment in Adults Over 50
Clinical Presentation
Glioblastoma presents with a constellation of neurological symptoms that reflect its aggressive nature and location within the brain, with headache, seizures, neurocognitive impairment, and focal neurological deficits being the most common manifestations.
Primary Symptoms
- Headache occurs in approximately 50% of patients and often reflects increased intracranial pressure 1
- Seizures develop in 20-50% of patients and paradoxically predict longer survival (median 11.2 months vs. 8.3 months without seizures) 2, 1
- Neurocognitive impairment affects 30-40% of patients and includes memory problems, behavioral changes, and disorientation 1
- Focal neurological deficits occur in 10-40% of patients depending on tumor location 1
Critical Prognostic Consideration
Patients presenting with cognitive impairment as the initial symptom have significantly worse outcomes, with median survival of only 6.4 months compared to those without cognitive symptoms 2. This occurs because:
- Cognitive symptoms are frequently misinterpreted in primary care settings, leading to diagnostic delays 2
- These patients typically have larger tumors at diagnosis 2
- The association with reduced survival persists even after accounting for tumor size 2
Additional Symptoms Related to Poor Prognosis
The following symptoms indicate more advanced disease 3:
- Intracranial hypertension (headache with nausea/vomiting, papilledema)
- Uncontrolled epilepsy despite antiepileptic medications
- Functional deficits affecting activities of daily living
- Low Karnofsky performance score (<70)
Standard Treatment Algorithm for Adults Over 50
Initial Diagnostic Workup
- MRI with gadolinium contrast is the mandatory imaging modality for diagnosis and treatment planning 3, 4
- Obtain tissue diagnosis through either maximal safe resection or biopsy 4
- MGMT promoter methylation testing is essential as it guides treatment decisions, particularly in older adults 4
First-Line Treatment Strategy
The standard of care consists of maximal safe surgical resection followed by radiotherapy with concurrent and adjuvant temozolomide 4, 5.
Surgical Management
- Gross total resection should be attempted whenever feasible to improve survival outcomes 4
- Biopsy alone is appropriate when resection is not safe or possible 4
- Surgery decisions require multidisciplinary consultation 3
Radiation Therapy Protocol
For patients under 70 years with good performance status:
- Standard fractionated radiotherapy: 60 Gy in 2-Gy fractions over 6 weeks 4
- Use partial-brain radiation therapy targeting the tumor bed with 2-3 cm margin, not whole-brain radiation 4, 5
For patients 70 years and older with good performance status:
- Hypofractionated radiotherapy is recommended to reduce treatment burden 4
- This approach maintains efficacy while improving tolerability in elderly patients
Chemotherapy Regimen
Concurrent Phase (during radiation):
- Temozolomide 75 mg/m² daily for 42 days during radiotherapy 5
- Pneumocystis pneumonia (PCP) prophylaxis is mandatory during this phase 5
- Continue treatment if: ANC ≥1.5 × 10⁹/L, platelets ≥100 × 10⁹/L, and non-hematologic toxicity ≤Grade 1 5
Maintenance Phase (after radiation):
- Begin 4 weeks after completing chemoradiotherapy 5
- Cycle 1: 150 mg/m² daily for 5 days, then 23 days rest 5
- Cycles 2-6: Escalate to 200 mg/m² daily for 5 days if tolerated 5
- Total of 6 maintenance cycles 5
Important Caveats for Older Adults (≥65 years)
- Patients ≥70 years have higher rates of Grade 4 neutropenia (25%) and thrombocytopenia (20%) in the first treatment cycle 5
- Weekly complete blood counts are mandatory during the concurrent phase 5
- The overall adverse reaction profile is similar between younger and older patients, but hematologic monitoring is critical 5
Treatment of Recurrent Disease
There is no standard treatment for recurrent glioblastoma; five therapeutic options exist 3:
- Surgical re-resection when feasible 4
- Systemic chemotherapy (temozolomide if not previously used, or alternative agents) 3
- Local carmustine implants 3
- Re-irradiation using stereotactic techniques in selected patients 3
- Palliative care without specific anticancer treatment 3
Bevacizumab may improve progression-free survival but does not improve overall survival 4. All decisions regarding recurrent disease treatment require multidisciplinary consultation 3.
Surveillance and Follow-Up
- Clinical and imaging follow-up every 3-6 months is recommended 4
- Initial post-operative MRI within 24-72 hours establishes baseline 6
- Use identical MRI protocols with RANO criteria for response assessment 3
- Pseudoprogression is most common in the first 3 months after chemoradiotherapy; consider repeat imaging in 4-8 weeks if progression is suspected 3
Prognostic Factors
Favorable prognostic indicators include 4:
- Younger age
- Good performance status (Karnofsky ≥70)
- Extent of resection (gross total > subtotal)
- MGMT promoter methylation
Poor prognostic factors include 3:
- Age >40 years
- Low Karnofsky score
- Large tumor size with mass effect
- Cognitive impairment as presenting symptom 2
- Tumor in functional zones or involving deep structures
Key Clinical Pitfalls to Avoid
- Do not dismiss cognitive symptoms as dementia or depression in older adults—these warrant urgent neuroimaging as they predict worse outcomes and larger tumors 2
- Do not use stereotactic radiosurgery (SRS) as initial treatment for glioblastoma—it is not established as appropriate 6
- Do not skip MGMT testing—it is essential for treatment planning, especially in elderly patients 4
- Do not forget PCP prophylaxis during concurrent chemoradiotherapy, and continue until lymphocyte recovery 5
- Monitor for pseudoprogression in the first 3 months after treatment—do not immediately escalate therapy without confirmation 3