Canadian Recommendations for the Treatment of Glioblastoma Multiforme

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Abstract
Recommendation 1: Management of patients with glioblastoma multiforme (GBM) should be highly individualized and should take a multidisciplinary approach involving neuro-oncology, neurosurgery, radiation oncology, and pathology, to optimize treatment outcomes. Patients and caregivers should be kept informed of the progress of treatment at every stage. Recommendation 2: Sufficient tissue should be obtained during surgery for cytogenetic analysis and, whenever feasible, for tumour banking. Recommendation 3: Surgery is an integral part of the treatment plan, to establish a histopathologic diagnosis and to achieve safe, maximal, and feasible tumour resection, which may improve clinical signs and symptoms. Recommendation 4: The preoperative imaging modality of choice is magnetic resonance imaging (MRI) with gadolinium as the contrast agent. Other imaging modalities, such as positron emission tomography with [18F]-fluoro-deoxy-D-glucose, may also be considered in selected cases. Postoperative imaging (MRI or computed tomography) is recommended within 72 hours of surgery to evaluate the extent of resection. Recommendation 5: Postoperative external-beam radiotherapy is recommended as standard therapy for patients with GBM. The recommended dose is 60 Gy in 2-Gy fractions. The recommended clinical target volume should be identified with gadolinium-enhanced T1-weighted MRI, with a margin in the order of 2–3 cm. Target volumes should be determined based on a postsurgical planning MRI. A shorter course of radiation may be considered for older patients with poor performance status. Recommendation 6: During rt, temozolomide 75 mg/m2 should be administered concurrently for the full duration of radio-therapy, typically 42 days. Temozolomide should be given approximately 1 hour before radiation therapy, and at the same time on the days that no radiotherapy is scheduled. Recommendation 7: Adjuvant temozolomide 150 mg/m2, in a 5/28-day schedule, is recommended for cycle 1, followed by 5 cycles if well tolerated. Additional cycles may be considered in partial responders. The dose should be increased to 200 mg/m2 at cycle 2 if well tolerated. Weekly monitoring of blood count is advised during chemoradiation therapy in patients with a low white blood cell count. Pneumocystis carinii pneumonia has been reported, and prophylaxis should be considered. Recommendation 8: For patients with stable clinical symptoms during combined radiotherapy and temozolomide, completion of 3 cycles of adjuvant therapy is generally advised before a decision is made about whether to continue treatment, because pseudo-progression is a common phenomenon during this time. The recommended duration of therapy is 6 months. A longer duration may be considered in patients who show continuous improvement on therapy. Recommendation 9: Selected patients with recurrent GBM may be candidates for repeat resection when the situation appears favourable based on an assessment of individual patient factors such as medical history, functional status, and location of the tumour. Entry into a clinical trial is recommended for patients with recurrent disease. Recommendation 10: The optimal chemotherapeutic strategy for patients who progress following concurrent chemoradiation has not been determined. Therapeutic and clinical–molecular studies with quality of life outcomes are needed.