From
Dr. Amr Moursi
Essential Evidence for Glioblastoma: A Must-Know for Neurosurgery Exams
With Dr. Amr Moursi
Chapter 2 of 8 · Evidence & Research
Stupp protocol
Stupp Protocol: Standard of Care
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What the experts said
Awake craniotomy offers significant advantages over general anesthesia for glioblastoma near eloquent brain by allowing real-time patient interaction to map and preserve critical functions like speech and movement.
Awake craniotomy helps maximize tumor resection while minimizing postoperative neurological deficits.
Drawbacks of awake craniotomy include need for careful patient selection, potential discomfort and anxiety during surgery, and longer operative times in some cases.
Intraoperative MRI is not available in all hospitals and requires strong infrastructure and investment to install in neurosurgical theater.
The Stupp protocol was published in 2005 as a landmark paper combining radiotherapy and chemotherapy with maximal surgical resection as the gold standard.
The Stupp protocol radiotherapy consists of 60 Gy over 6 weeks with 2 Gy daily Monday to Friday (30 fractions total).
Concurrent phase temozolomide in the Stupp protocol is 75 mg daily for six weeks.
Adjuvant temozolomide monotherapy is 150-200 mg per meter squared on days 1-5 of each 28-day cycle for a total of 6 cycles.
RANO (Response Assessment in Neuro-Oncology) criteria classify resections based on residual contrast-enhancing tumor on T1 and non-contrast-enhancing hyperintense tissue on FLAIR, believed to represent glioblastoma infiltrative tissue.
RANO Class 1 (supramaximal contrast-enhancing resection) leaves 0 cubic centimeters of contrast-enhancing and less than 5 cubic centimeters of non-contrast-enhancing tissue, with median overall survival of 24 months.
RANO Class 2A (maximal surgical resection) leaves 0 cubic centimeters of contrast-enhancing and more than 5 cubic centimeters of non-contrast-enhancing tissue.
RANO Class 2B (maximal surgical resection) leaves less than 1 cubic centimeter of contrast-enhancing tissue, with median overall survival of 19 months.
RANO Class 3 (submaximal contrast-enhancing resection) leaves less than 5 or more than 5 cubic centimeters of contrast-enhancing tissue on T1 postoperatively, with median overall survival of 15 months.
RANO Class 4 (biopsy) has no reduction of tumor volume and gives 10 months median overall survival if the patient had chemoradiotherapy.
5-ALA crosses the blood-brain barrier and enters mitochondria where it becomes protoporphyrinogen IX and protoporphyrin IX. In glioblastoma, ferrochelatase enzyme is less effective, leading to accumulation of protoporphyrin IX.
Protoporphyrin IX emits bright pink fluorescence when exposed to blue light microscope with wavelength 405 to 633 nanometers, allowing tumor visualization during surgery.
5-ALA is administered as 1.5 g powder reconstituted in 50 mL drinking water (30 mg/mL oral solution) at a dosage of 20 mg per kg, given 2 to 4 hours before surgery.
A randomized controlled trial of fluorescence-guided surgery with 5-ALA showed complete contrast-enhancing resection in 65% of patients using 5-ALA compared to 36% using white light.
5-ALA fluorescence guidance allowed higher 6-month progression-free survival compared to white light surgery.
Intraoperative MRI allows real-time imaging during surgery, enhancing the surgeon's ability to achieve maximum resections and increasing the rate of complete resections.
Senft 2011 study on intraoperative MRI showed more patients had complete tumor resection than the control group, and postoperative rate of neurological deficits did not differ between groups.
VEGF (vascular endothelial growth factor) is responsible for stimulating endothelial cell proliferation and migration in glioblastoma microenvironment.
Bevacizumab reduces regression of existing microvessels and inhibits growth of new blood vessels, acting like dexamethasone but with more potent effect.
Bevacizumab increases overall survival by only a few months.
Bevacizumab is FDA-approved in the United States.
The European Medicines Agency and UK NICE guidance have not proven bevacizumab as a cost-effective treatment.
Tumor treating fields is a non-invasive modality applying mild electric fields that disturb cancer cell division.
Tumor treating fields combined with temozolomide shows significant improvement in progression-free survival.
There is currently a trial in the UK running to see the effectiveness of tumor treating fields and to prove it for inclusion in NICE guidelines.
Tumor treating fields plus temozolomide versus temozolomide alone increased progression-free survival by 2.7 months.
Tumor treating fields plus temozolomide versus temozolomide alone improved overall survival by 4.9 months.