Sherman, Wendy Joyce

OBJECTIVE The authors’ goal was to use a multicenter, observational cohort study to determine whether supramarginal resection (SMR) of FLAIR-hyperintense tumor beyond the contrast-enhanced (CE) area influences the overall survival (OS) of patients with isocitrate dehydrogenase–wild-type (IDH-wt) glioblastoma after gross-total resection (GTR). METHODS The medical records of 888 patients aged ≥ 18 years who underwent resection of GBM between January 2011 and December 2017 were reviewed. Volumetric measurements of the CE tumor and surrounding FLAIR-hyperintense tumor were performed, clinical variables were obtained, and associations with OS were analyzed. RESULTS In total, 101 patients with newly diagnosed IDH-wt GBM who underwent GTR of the CE tumor met the inclusion criteria. In multivariate analysis, age ≥ 65 years (HR 1.97; 95% CI 1.01–2.56; p < 0.001) and contact with the lateral ventricles (HR 1.59; 95% CI 1.13–1.78; p = 0.025) were associated with shorter OS, but preoperative Karnofsky Performance Status ≥ 70 (HR 0.47; 95% CI 0.27–0.89; p = 0.006), MGMT promotor methylation (HR 0.63; 95% CI 0.52–0.99; p = 0.044), and increased percentage of SMR (HR 0.99; 95% CI 0.98–0.99; p = 0.02) were associated with longer OS. Finally, 20% SMR was the minimum percentage associated with beneficial OS (HR 0.56; 95% CI 0.35–0.89; p = 0.01), but > 60% SMR had no significant influence (HR 0.74; 95% CI 0.45–1.21; p = 0.234). CONCLUSIONS SMR is associated with improved OS in patients with IDH-wt GBM who undergo GTR of CE tumor. At least 20% SMR of the CE tumor was associated with beneficial OS, but greater than 60% SMR had no significant influence on OS.

Lynch syndrome is an autosomal dominant disorder leading to cancer predisposition caused by mutations in mismatch repair genes. There is minimal published experience treating glioblastoma in patients with Lynch syndrome. We report a patient with Lynch syndrome who was initially diagnosed with a left occipital isocitrate dehydrogenase (IDH) wild-type glioblastoma. After resection, she was treated with chemoradiation, followed by tumour treating fields. Three years after diagnosis, recurrence was resected. After refusing cytotoxic chemotherapy, decision was made to treat with off-label nivolumab concurrently with radiation. She has been maintained on nivolumab without recurrence of her glioblastoma now over 5 years out from her initial diagnosis. This case provides the first report of glioblastoma in a patient with Lynch syndrome responding to nivolumab and concurrent radiation. In patients with Lynch syndrome and glioblastoma, immunotherapy in the form of nivolumab may be an alternative option to standard cytotoxic chemotherapy.