The role of radiation therapy in treatment of adults with newly diagnosed glioblastoma multiforme: a systematic review and evidence-based clinical practice guideline update

Target population: These recommendations apply to adult patients diagnosed with newly diagnosed glioblastoma. Question 1: In adult patients (aged 65 and under) with newly diagnosed glioblastoma, is the addition of radiation therapy (RT) more beneficial than management without RT in improving survival? Recommendations: Level I: Radiation therapy (RT) is recommended for the treatment of newly diagnosed malignant glioblastoma in adults. Question 2: In adult patients (aged 65 and under) with newly diagnosed glioblastoma, is the RT regimen of 60 Gy given in 2 Gy daily fractions more beneficial than alternative regimens in providing survival benefit while minimizing toxicity? Recommendations: Level I: Treatment schemes should include dosage of up to 60 Gy given in 2 Gy daily fractions that includes the enhancing area. Question 3: In adult patients (aged 65 and under) with newly diagnosed glioblastoma, is a tailored target volume superior to regional RT for reduction of radiation-induced toxicity while maintaining efficacy? Recommendation: Level II: It is recommended that radiation therapy planning include 1–2 cm margin around the radiographically T1 weighted contrast-enhancing tumor volume or the T2 weighted abnormality on MRI. Level III: Recalculation of the radiation volume during RT treatment may be necessary to reduce the radiated volume of normal brain since the volume of surgical defect will change during the long period of RT. Question 4: In adult patients (aged 65 and under) with newly diagnosed glioblastoma, does the addition of RT of the subventricular zone to standard tumor volume treatment improve tumor control and overall survival? Recommendation: No recommendation can be formulated as there is contradictory evidence in favor of and against intentional radiation of the subventricular zone (SVZ) Question 5: In elderly (age > 65 years) and/or frail patients with newly diagnosed glioblastoma, does the addition of RT to surgical intervention improve disease control and overall survival? Recommendation: Level I: Radiation therapy is recommended for treatment of elderly and frail patients with newly diagnosed glioblastoma to improve overall survival. Question 6: In elderly (age > 65 years) and/or frail patients with newly diagnosed glioblastoma, does modification of RT dose and fractionation scheme from standard regimens decrease toxicity and improve disease control and survival? Recommendation: Level II: Short RT treatment schemes are recommended in frail and elderly patients as compared to conventional 60 Gy given in 2 daily fractions because overall survival is not different while RT risk profile is better for the short RT scheme. Level II: The 40.05 Gy dose given in 15 fractions or 25 Gy dose given in 5 fractions or 34 Gy dose given in 10 fractions should be considered as appropriate doses for Short RT treatments in elderly and/or frail patients. Question 7: In adult patients with newly diagnosed glioblastoma is there advantage to delaying the initiation of RT instead of starting it 2 weeks after surgical intervention in decreasing radiation-induced toxicity and improving disease control and survival? Recommendation: Level III: It is suggested that RT for patients with newly diagnosed GBM starts within 6 weeks of surgical intervention as compared to later times. There is insufficient evidence to recommend the optimal specific post-operative day within the 6 weeks interval to start RT for adult patients with newly diagnosed glioblastoma that have undergone surgical resection. Question 8: In adult patients with newly diagnosed supratentorial glioblastoma is Image-Modulated RT (IMRT) or similar techniques as effective as standard regional RT in providing tumor control and improve survival? Recommendation: Level III: There is no evidence that IMRT is a better RT delivering modality when compared to conventional RT in improving overall survival in adult patients with newly diagnosed glioblastoma. Hence, IMRT should not be preferred over the Conventional RT delivery modality. Question 9: In adult patients with newly diagnosed glioblastoma does the use of radiosensitizers with RT improve the efficacy of RT as determined by disease control and overall survival? Recommendation: Level III: Iododeoxyuridine is not recommended to be used as radiosensitizer during RT treatment for patients with newly diagnosed GBM Question 10: In adult patients with newly diagnosed glioblastoma is the use of Ultrafractionated RT superior to standard fractionation regimens in improving disease control and survival? Recommendation: There is insufficient evidence to formulate a recommendation regarding the use of ultrafractionated RT schemes and patient population that could benefit from it. Question 11: In patients with poor prognosis with newly diagnosed glioblastoma is hypofractionated RT indicated instead of a standard fractionation regimen as measured by extent of toxicity, disease control and survival? Recommendation: Level I: Hypofractionated RT schemes may be used for patients with poor prognosis and limited survival without compromising response. There is insufficient evidence in the literature for us to be able to recommend the optimal hypofractionated RT scheme that will confer longest overall survival and/or confer the same overall survival with less toxicities and shorter treatment time. Question 12: In adult patients with newly diagnosed glioblastoma is the addition of brachytherapy to standard fractionated RT indicated to improve disease control and survival? Recommendation: Level I: Brachytherapy as a boost to external beam RT has not been shown to be beneficial and is not recommended in the routine management of patients with newly diagnosed GBM. Question 13: In elderly patients (> 65 year old) with newly diagnosed glioblastoma under what circumstances is accelerated hyperfractionated RT indicated instead of a standard fractionation regimen as measured by extent of toxicity, disease control and survival? Recommendation: Level III: Accelerated Hyperfractionated RT with a total RT dose of 45 Gy or 48 Gy has been shown to shorten the treatment time without detriment in survival when compared to conventional external beam RT and should be considered as an option for treatment of elderly patients with newly diagnosed GBM. Question 14: In adult patients with newly diagnosed glioblastoma is the addition of Stereotactic Radiosurgery (SRS) boost to conventional standard fractionated RT indicated to improve disease control and survival? Recommendation: Level I: Stereotactic Radiosurgery boost to external beam RT has not been shown to be beneficial and is not recommended in patients undergoing routine management of newly diagnosed malignant glioma.