Association of Maximal Extent of Resection of Contrast-Enhanced and Non–Contrast-Enhanced Tumor With Survival Within Molecular Subgroups of Patients With Newly Diagnosed Glioblastoma

Importance

Per the World Health Organization 2016 integrative classification, newly diagnosed glioblastomas are separated into isocitrate dehydrogenase gene 1 or 2 (IDH)–wild-type andIDH-mutant subtypes, with median patient survival of 1.2 and 3.6 years, respectively. Although maximal resection of contrast-enhanced (CE) tumor is associated with longer survival, the prognostic importance of maximal resection within molecular subgroups and the potential importance of resection of non–contrast-enhanced (NCE) disease is poorly understood.

Objective

To assess the association of resection of CE and NCE tumors in conjunction with molecular and clinical information to develop a new road map for cytoreductive surgery.

Design, Setting, and Participants

This retrospective, multicenter cohort study included a development cohort from the University of California, San Francisco (761 patients diagnosed from January 1, 1997, through December 31, 2017, with 9.6 years of follow-up) and validation cohorts from the Mayo Clinic (107 patients diagnosed from January 1, 2004, through December 31, 2014, with 5.7 years of follow-up) and the Ohio Brain Tumor Study (99 patients with data collected from January 1, 2008, through December 31, 2011, with a median follow-up of 10.9 months). Image accessors were blinded to patient groupings. Eligible patients underwent surgical resection for newly diagnosed glioblastoma and had available survival, molecular, and clinical data and preoperative and postoperative magnetic resonance images. Data were analyzed from November 15, 2018, to March 15, 2019.

Main Outcomes and Measures

Overall survival.

Results

Among the 761 patients included in the development cohort (468 [61.5%] men; median age, 60 [interquartile range, 51.6-67.7] years), younger patients withIDH–wild-type tumors and aggressive resection of CE and NCE tumors had survival similar to that of patients withIDH-mutant tumors (median overall survival [OS], 37.3 [95% CI, 31.6-70.7] months). Younger patients withIDH–wild-type tumors and reduction of CE tumor but residual NCE tumors fared worse (median OS, 16.5 [95% CI, 14.7-18.3] months). Older patients withIDH–wild-type tumors benefited from reduction of CE tumor (median OS, 12.4 [95% CI, 11.4-14.0] months). The results were validated in the 2 external cohorts. The association between aggressive CE and NCE in patients withIDH–wild-type tumors was not attenuated by the methylation status of the promoter region of the DNA repair enzyme O6-methylguanine-DNA methyltransferase.

Conclusions and Relevance

This study confirms an association between maximal resection of CE tumor and OS in patients with glioblastoma across all subgroups. In addition, maximal resection of NCE tumor was associated with longer OS in younger patients, regardless ofIDHstatus, and among patients withIDH–wild-type glioblastoma regardless of the methylation status of the promoter region of the DNA repair enzyme O6-methylguanine-DNA methyltransferase. These conclusions may help reassess surgical strategies for individual patients with newly diagnosed glioblastoma.