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Top Line: Glioblastoma multiforme (GBM) is almost guaranteed to recur at some point following definitive chemoradiation. So what happens to the biology of the tumor during that time?
The Study: This is an important question because almost everyone will need a subsequent treatment strategy, and that strategy is likely to be based on the original tumor’s biology. This study sequenced 300 genes from paired primary and recurrent GBM tumors from nearly 200 patients treated with radiation and temozolomide, making it the largest study of its kind. You first gotta wonder if a cohort of patients who are able to make it to (or through) a second resection would have different mutational landscapes from other GBM. Well, while the primary cohort was enriched for MGMT methylation (63%), other molecular features were in line with what would be expected from a general GBM population. Intriguingly, recurrent tumors were very similar to their primary tumors—retaining over 80% of the original tumor’s mutations. Fewer than 10% of tumors gained a hypermutated phenotype, and that didn’t seem to correlate with outcome. While the proportion of patients with MGMT methylation was fairly stable, 23% had a change in status. Contrary to hypermutation status, MGMT methylation did retain its prognostic significance at recurrence. The overall preservation rate of EGFR amplification status was roughly 80%, despite a 37% loss in the EGFRvIII mutation. Why do we care? Because we can't always safely re-profile recurrent GBM.
TBL: The mutational landscape of GBM looks to remain largely similar from initial diagnosis to recurrence. | Draaisma, J Clin Oncol 2019