Increased OS With Maximal Resection of CE Tumors in Patients With Glioblastoma

In a cohort study of patients with newly diagnosed glioblastoma, maximal resection of contrast-enhanced (CE) tumors was tied to increased overall survival (OS; JAMA Oncol. 2020 Feb 6. Epub ahead of print).

“Per the World Health Organization 2016 integrative classification, newly diagnosed glioblastomas are separated into isocitrate dehydrogenase gene 1 or 2 (IDH)–wild-type and IDH-mutant subtypes, with median patient survival of 1.2 and 3.6 years, respectively,” explained Annette M. Molinaro, PhD, Department of Neurological Surgery, University of California, San Francisco, and colleagues.

“Although maximal resection of…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,” they continued.

Thus, seeking to create a new road map for cytoreductive surgery, Dr Molinaro et al conducted a retrospective study to assess the link between resection of CE and NCE tumors in conjunction with molecular and clinical information.

A total of 761 patients (median age, 60 years) diagnosed between January 1, 1997, and December 31, 2017, were included in the development cohort of the multi-center study. This cohort was based at the University of California, San Francisco, and was followed-up with for 9.6 years.

A further 107 patients from the Mayo Clinic (diagnosed between January 1, 2004, and December 31, 2014, with 5.7 years of follow-up) and 99 from the Cleveland Clinic’s Ohio Brain Tumor Study (data collected between January 1, 2008, and December 31, 2011, with a median follow-up of 10.9 months) were included as validation cohorts.

Patients were deemed eligible if they underwent surgical resection for newly diagnosed glioblastoma and if they had available survival, molecular, and clinical data and preoperative and postoperative magnetic resonance images.

The main end point of the study was OS, and data analysis took place between November 15, 2018, and March 15, 2019.

In the development cohort, rates of survival were similar among younger patients with IDH–wild-type tumors and aggressive resection of CE and NCE tumors and patients with IDH-mutant tumors (median OS, 37.3 months; 95% CI, 31.6-70.7).

Of note, patients younger in age with IDH–wild-type tumors and reduction of CE tumor but who also had residual NCE tumors had poorer outcomes (median OS, 16.5 months; 95% CI, 14.7-18.3).

Alternatively, older patients with IDH–wild-type tumors had benefits from CE tumor reductions (median OS, 12.4 months; 95% CI, 11.4-14.0).

These findings were validated in the 2 external cohorts. Furthermore, methylation status of the promoter region of the DNA repair enzyme O6-methylguanine-DNA methyltransferase did not diminish the link between aggressive CE and NCE in patients with IDH–wild-type tumors.

“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 of IDH status, and among patients with IDH–wild-type glioblastoma regardless of the methylation status of the promoter region of the DNA repair enzyme O6-methylguanine-DNA methyltransferase,” Dr Molinaro and colleagues concluded.

“These conclusions may help reassess surgical strategies for individual patients with newly diagnosed glioblastoma,” they said.—Hina Porcelli