Congress of neurological surgeons systematic review and evidence-based guidelines update on the role of emerging developments in the management of newly diagnosed glioblastoma

Target population These recommendations apply to adult patients with newly diagnosed or suspected glioblastoma. Imaging Question What imaging modalities are in development that may be able to provide improvements in diagnosis, and therapeutic guidance for individuals with newly diagnosed glioblastoma? Recommendation Level III: It is suggested that techniques utilizing magnetic resonance imaging for diffusion weighted imaging, and to measure cerebral blood and magnetic spectroscopic resonance imaging of N-acetyl aspartate, choline and the choline to N-acetyl aspartate index to assist in diagnosis and treatment planning in patients with newly diagnosed or suspected glioblastoma. Surgery Question What new surgical techniques can be used to provide improved tumor definition and resectability to yield better tumor control and prognosis for individuals with newly diagnosed glioblastoma? Recommendations Level II: The use of 5-aminolevulinic acid is recommended to improve extent of tumor resection in patients with newly diagnosed glioblastoma. Level II: The use of 5-aminolevulinic acid is recommended to improve median survival and 2 year survival in newly diagnosed glioblastoma patients with clinical characteristics suggesting poor prognosis. Level III: It is suggested that, when available, patients be enrolled in properly designed clinical trials assessing the value of diffusion tensor imaging in improving the safety of patients with newly diagnosed glioblastoma undergoing surgery. Neuropathology Question What new pathology techniques and measurement of biomarkers in tumor tissue can be used to provide improved diagnostic ability, and determination of therapeutic responsiveness and prognosis for patients with newly diagnosed glioblastomas? Recommendations Level II: Assessment of tumor MGMT promoter methylation status is recommended as a significant predictor of a longer progression free survival and overall survival in patients with newly diagnosed with glioblastoma. Level II: Measurement of tumor expression of neuron-glia-2, neurofilament protein, glutamine synthetase and phosphorylated STAT3 is recommended as a predictor of overall survival in patients with newly diagnosed with glioblastoma. Level III: Assessment of tumor IDH1 mutation status is suggested as a predictor of longer progression free survival and overall survival in patients with newly diagnosed with glioblastoma. Level III: Evaluation of tumor expression of Phosphorylated Mitogen-Activated Protein Kinase protein, EGFR protein, and Insulin-like Growth Factor-Binding Protein-3 is suggested as a predictor of overall survival in patients with newly diagnosed with glioblastoma. Radiation Question What radiation therapy techniques are in development that may be used to provide improved tumor control and prognosis for individuals with newly diagnosed glioblastomas? Recommendations Level III: It is suggested that patients with newly diagnosed glioblastoma undergo pretreatment radio-labeled amino acid tracer positron emission tomography to assess areas at risk for tumor recurrence to assist in radiation treatment planning. Level III: It is suggested that, when available, patients be with newly diagnosed glioblastomas be enrolled in properly designed clinical trials of radiation dose escalation, altered fractionation, or new radiation delivery techniques. Chemotherapy Question What emerging chemotherapeutic agents or techniques are available to provide better tumor control and prognosis for patients with newly diagnosed glioblastomas? Recommendation Level III: As no emerging chemotherapeutic agents or techniques were identified in this review that improved tumor control and prognosis it is suggested that, when available, patients with newly diagnosed glioblastomas be enrolled in properly designed clinical trials of chemotherapy. Molecular and targeted therapy Question What new targeted therapy agents are available to provide better tumor control and prognosis for individuals with newly diagnosed glioblastomas? Recommendation Level III: As no new molecular and targeted therapies have clearly provided better tumor control and prognosis it is suggested that, when available, patients with newly diagnosed glioblastomas be enrolled in properly designed clinical trials of molecular and targeted therapies Immunotherapy Question What emerging immunotherapeutic agents or techniques are available to provide better tumor control and prognosis for patients with newly diagnosed glioblastomas? Recommendation Level III: As no immunotherapeutic agents have clearly provided better tumor control and prognosis it is suggested that, when available, patients with newly diagnosed glioblastomas be enrolled in properly designed clinical trials of immunologically-based therapies. Novel therapies Question What novel therapies or techniques are in development to provide better tumor control and prognosis for individuals with newly diagnosed glioblastomas? Recommendations Level II: The use of tumor-treating fields is recommended for patients with newly diagnosed glioblastoma who have undergone surgical debulking and completed concurrent chemoradiation without progression of disease at the time of tumor-treating field therapy initiation. Level II: It is suggested that, when available, enrollment in properly designed studies of vector containing herpes simplex thymidine kinase gene and prodrug therapies be considered in patients with newly diagnosed glioblastoma.