Treatment Paradigm

Question 1

Primary treatment of GBM?

Answer 1

Primary treatment is maximal safe surgical resection with neurologic preservation. For technically unresectable tumors, a biopsy is warranted to obtain tissue

Question 2

Why does a contrast-enhanced MRI need to be done within 72 hours of surgery?

Answer 2

To evaluate the extent of resection, obtain a contrast-enhanced MRI within 72 hours of surgery (ideally 24–48 hours) to avoid confounding with subacute blood products.

Question 3

What chemotherapy is used for GBM? Which trial set standard?

Answer 3

Daily use of temozolomide (TMZ) 75 mg/m2 daily concurrently during radiation course, including weekends. This is followed by the use of adjuvant TMZ for d1-5 of 28d cycle for 6 to 12 mos, starting at 150 mg/m2 and escalated as tolerated to 200 mg/m2. Established in the Stupp trial

Question 4

What are major side effects of TMZ?

Answer 4

Major side effects of TMZ are constipation, thrombocytopenia, and neutropenia

Question 5

Patients recieving TMZ require prophyalxis against what? What drug is given?

Answer 5

Pts treated with TMZ require prophylaxis against pneumocystis pneumonia and can be given daily DS trimethoprim/sulfamethoxazole or alternatively, two pentamidine inhalation treatments during the RT course.

Question 6

What is the mechanism of action of TMZ?

Answer 6

TMZ is a prodrug converted to MTIC, which alkylates DNA. Only 5% to 10% of methylation events yield the O-6-methylguanine, but if the methyl group is not removed prior to cell division, the adducts are highly cytotoxic

Question 7

What are the indications of RT for GBM?

Answer 7

Adjuvant RT improves OS versus observation or CHT alone after surgery and is indicated in all pts of sufficient functional status to tolerate treatment

Question 8

What dose of RT is used for GBM?

Answer 8

60 Gy/30 fx is standard. For elderly or frail individuals, various hypofractionated schemes have been investigated. 46 Gy to T2/FLAIR edema, then additional 14 Gy boost to resection cavity and T1 contrast enhancement

Question 9

What are acute toxicities of RT for GBM?

Answer 9

Fatigue, headache, exacerbation of presenting neurologic deficits, alopecia, nausea, cerebral edema, side effects related to temozolomide (constipation, thrombocytopenia, neutropenia)

Question 10

What are the late toxicities of RT for GBM?

Answer 10

Cognitive changes, radiation necrosis, hypopituitarism, cataracts, vision loss (rare and location dependent)