What is the recommended treatment for a newly diagnosed WHO grade IV glioblastoma in the right parietal lobe?

Treatment Recommendation for WHO Grade IV Glioblastoma in the Right Parietal Lobe

The standard treatment is maximal safe surgical resection followed by concurrent radiotherapy (60 Gy in 30 fractions) with daily temozolomide (75 mg/m² for up to 49 days), then 6 cycles of adjuvant temozolomide (150-200 mg/m² for 5 days every 28 days). 1, 2, 3

Initial Surgical Management

• Pursue maximal safe surgical resection as the first therapeutic step, provided neurological function is not compromised by the extent of resection 1, 4
• Gross total resection improves survival outcomes compared to subtotal resection or biopsy alone 4
• Obtain MRI within 24-48 hours post-operatively to assess extent of resection and distinguish residual tumor from post-operative changes 5, 4
• The right parietal location allows for potentially aggressive resection while monitoring for dominant hemisphere language function and sensory/motor deficits 1

Standard Chemoradiotherapy Protocol (The Stupp Regimen)

Concurrent Phase

• Begin fractionated focal radiotherapy at 60 Gy delivered as 2 Gy daily fractions, 5 days per week for 6 weeks (30-33 total fractions) 1, 2, 3
• Administer temozolomide 75 mg/m² daily starting on the first day of radiotherapy and continuing through the last day (maximum 49 days) 1, 2, 3
• This regimen demonstrated a hazard ratio of 0.63 for death (95% CI 0.52-0.75, P<0.001), increasing median survival from 12.1 to 14.6 months 3

Adjuvant Phase

• Start adjuvant temozolomide 4 weeks after completing radiotherapy 2, 3
• Administer temozolomide 150-200 mg/m² on days 1-5 of each 28-day cycle for 6 cycles 1, 2, 3
• Dose escalation from 150 to 200 mg/m² occurs after cycle 1 if absolute neutrophil count ≥1.5 × 10⁹/L and platelet count ≥100 × 10⁹/L 2
• Two-year survival improved from 10.4% to 26.5% with this combined approach 3

Critical Molecular Testing

• Test for MGMT promoter methylation status before or during treatment, as this predicts benefit from temozolomide therapy 1, 4
• MGMT methylation is the strongest predictive marker for response to alkylating chemotherapy 6
• Also obtain IDH mutation status, 1p/19q codeletion, TERT promoter mutations, and EGFR amplification for prognostic information and potential future targeted therapies 4

Supportive Care During Treatment

Corticosteroids

• Use dexamethasone 8-16 mg/day only if tumor-associated edema or neurological deficits are present 1
• Do not use prolonged steroids prophylactically after tumor resection or during radiotherapy 1
• Taper steroids as rapidly as possible to minimize myopathy, hyperglycemia, opportunistic infections, and psychiatric complications 5
• Monitor glucose levels closely 1

Seizure Management

• Initiate antiepileptic therapy only if the patient has experienced seizures 1
• Do not use prophylactic antiepileptics in asymptomatic patients 1
• Prefer third-generation agents (levetiracetam, lamotrigine, pregabalin) over first-generation drugs (phenytoin, carbamazepine, phenobarbital) because first-generation agents induce hepatic metabolism and interfere with chemotherapy 1
• Temozolomide does not interact with enzyme-inducing antiepileptics, but other chemotherapy agents may 1

Pneumocystis Prophylaxis

• Require PCP prophylaxis during concurrent temozolomide/radiotherapy regardless of lymphocyte count 2
• Continue prophylaxis until lymphocyte count recovers to ≤Grade 1 2

Age-Specific Modifications

Patients ≤70 Years

• Use the full standard protocol described above 1

Patients >70 Years

• Consider shorter hypofractionated radiotherapy regimens (40 Gy in 15 fractions or 50 Gy in 28 fractions of 1.8 Gy) 1
• Radiotherapy alone was superior to best supportive care in patients >70 years 1
• No randomized data exist for temozolomide in elderly patients with good performance status, but exclusive temozolomide chemotherapy has been proposed 1

Follow-Up Surveillance

• Perform cranial MRI every 3-4 months as standard practice 5
• Beware of pseudoprogression occurring 4-8 weeks after radiotherapy completion, which represents blood-brain barrier permeability changes rather than true progression 5
• Confirm suspected progression with repeat MRI 4 weeks later before changing therapy 5
• Monitor for venous thrombotic events, which occur frequently with residual or recurrent tumor 5

Common Pitfalls to Avoid

• Do not escalate radiotherapy beyond 60 Gy, as this has not shown benefit 1
• Do not use PCV chemotherapy (procarbazine, lomustine, vincristine) as it failed to improve survival in randomized trials for glioblastoma 1
• Carmustine wafer implantation shows only marginal benefit and has no comparison data against standard temozolomide/radiotherapy 1
• Do not change treatment based on imaging obtained 4-8 weeks post-radiotherapy without confirming true progression versus pseudoprogression 5

Treatment at Recurrence

• No established standard chemotherapy exists for recurrent glioblastoma after temozolomide failure 1
• Consider re-exposure to temozolomide if MGMT-methylated 4
• Enrollment in clinical trials is preferred for recurrent disease 1, 7
• Re-surgery or re-irradiation may be evaluated in highly selected cases 7