In patients with newly diagnosed glioblastoma, maximal extent of surgical resection of non–contrast enhanced (NCE) tumor as well as contrast-enhanced (CE) tumor is associated with increased survival regardless of tumor subtype, according to a study recently published in JAMA Oncology.
Glioblastoma subtypes are known to impact disease outcome: while the 91% of patients with glioblastoma whose tumors display isocitrate dehydrogenase gene 1 or 2 (IDH) wild-type mutations have a median survival of 1.2 years, the remaining 9% of patients, who have IDH-mutant tumors, have a median survival of 3.6 years. Methylation status of the DNA repair enzyme 06-methylguanine-DNA methyltransferase (MGMT) is also associated with longer survival. This study is the first to examine the association between maximal resection of CE and NCE tumor with survival by IDH–wild-type and IDH-mutant subtypes and by MGMT methylation status.
"For both [IDH–wild-type and IDH-mutant] glioblastoma, the standard of care for patients with newly diagnosed disease is surgical resection followed by radiotherapy given in combination with the DNA-alkylating agent temozolomide," write Annette Molinaro, PhD, Associate Professor of Neurological Surgery and of Epidemiology and Biostatistics at the University of California, San Francisco (UCSF), and colleagues. "Maximum resection of CE tumor on T1-weighted magnetic resonance imaging has been consistently associated with longer survival. However, the association of maximal resection of the CE tumor with survival within glioblastoma subgroups and the potential importance of resection of NCE disease remain poorly understood."
The retrospective, multicenter cohort study included a development cohort from UCSF consisting of 761 patients, diagnosed with glioblastoma between 1997 and 2017 with a median of 9.6 years of follow-up, and two validation cohorts, one comprising 107 patients from Mayo Clinic, diagnosed between 2004 and 2014 with 5.7 years of follow-up, and the other consisting of 99 patients in the Cleveland Clinic's Ohio Brain Tumor Study, for whom data was collected between 2008 and 2011, with a median follow-up of 10.9 months.
Younger patients (under age 65) with IDH–wild-type glioblastoma and aggressive resection of CE and NCE tumors had a median overall survival of 37.3 months. This duration of survival was similar to that of patients with IDH-mutant glioblastoma, although after three years, the patients with IDH–wild-type glioblastoma declined at a faster rate compared with those who had IDH-mutant tumors. In contrast, younger patients with IDH–wild-type glioblastoma who had reduction of CE tumor but residual NCE tumor had a median overall survival of only 16.5 months. Older patients with IDH–wild-type glioblastoma benefited from CE tumor reduction, with a median overall survival of 12.4 months. These results were confirmed by data from the two external cohorts.
The associations between aggressive resection of CE and NCE tumor and overall survival were not significantly impacted by MGMT methylation status in patients with IDH–wild-type glioblastoma, while the impact of MGMT status on associations for patients with IDH-mutant glioblastoma could not be assessed because MGMT methylation was measured for too few tumors in this subgroup (7 of 36).
"Traditionally, the goal of neurosurgeons has been to achieve total resection, the complete removal of contrast-enhancing tumor," stated the study's senior author, Mitchel Berger, MD, Director of the UCSF Brain Tumor Center. "This study shows that we have to recalibrate the way we have been doing things, and, when safe, include non–contrast-enhancing tumor to achieve maximal resection."
"Although these data show a survival benefit associated with maximal resection, it remains critically important that we do our best to remove tumor in a manner that will not harm the patient," noted co-author Shawn Hervey-Jumper, MD, PhD, a neurosurgeon at the UCSF Brain Tumor Center and the Weill Institute for Neurosciences.
For More Information
Molinaro AM, Hervey-Jumper S, Morshed RA, et al (2020). 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. JAMA Oncol. [Epub ahead of print] DOI:10.1001/jamaoncol.2019.6143
Image credit: Christaras A. Licensed under CC BY-SA 3.0