Congress of neurological surgeons systematic review and evidence-based guidelines update on the role of neuropathology in the management of progressive glioblastoma in adults

Abstract

Target population: These recommendations apply to adult patients with progressive or recurrent glioblastoma (GBM).

Question: For adult patients with progressive glioblastoma does testing for Isocitrate Dehydrogenase (IDH) 1 or 2 mutations provide new additional management or prognostic information beyond that derived from the tumor at initial presentation?

Recommendation: Level III: Repeat IDH mutation testing is not necessary if the tumor is histologically similar to the primary tumor and the patient's clinical course is as expected.

Question: For adult patients with progressive glioblastoma does repeat testing for MGMT promoter methylation provide new or additional management or prognostic information beyond that derived from the tumor at initial presentation and what methods of detection are optimal?

Recommendation: Level III: Repeat MGMT promoter methylation is not recommended.

Question: For adult patients with progressive glioblastoma does EGFR amplification or mutation testing provide management or prognostic information beyond that provided by histologic analysis and if performed on previous tissue samples, does it need to be repeated?

Recommendation: Level III: In cases that are difficult to classify as glioblastoma on histologic features EGFR amplification testing may help in classification. If a previous EGFR amplification was detected, repeat testing is not necessary. Repeat EGFR amplification or mutational testing may be recommended in patients in which target therapy is being considered.

Question: For adult patients with progressive glioblastoma does large panel or whole genome sequencing provide management or prognostic information beyond that derived from histologic analysis?

Recommendation: Level III: Primary or repeat large panel or whole genome sequencing may be considered in patients who are eligible or interested in molecularly guided therapy or clinical trials.

Question: For adult patients with progressive glioblastoma should immune checkpoint biomarker testing be performed to provide management and prognostic information beyond that obtained from histologic analysis?

Recommendation: Level III: The current evidence does not support making PD-L1 or mismatch repair (MMR) enzyme activity a component of standard testing.

Question: For adult patients with progressive glioblastoma are there meaningful biomarkers for bevacizumab responsiveness and does their assessment provide additional information for tumor management and prognosis beyond that learned by standard histologic analysis?

Recommendation: Level III: No established Bevacizumab biomarkers are currently available based upon the inclusion criteria of this guideline.

Keywords: Biomarker; EGFR; Immunohistochemistry; Infiltrating glioma; MGMT neuropathology; Molecular testing; Progressive glioblastoma; Recurrent glioblastoma.