February 06, 2020
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Maximal resection of certain tumors extends survival in glioblastoma

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Annette M. Molinaro, PhD
Annette M. Molinaro

Maximal resection of the contrast-enhanced tumor appeared associated with longer OS among all subgroups of patients with glioblastoma, according to results of a retrospective study published in JAMA Oncology.

Additionally, researchers observed an association between maximal resection of the noncontrast-enhanced tumor and longer OS among younger patients with glioblastoma regardless of IDH mutation status, as well as among patients with IDH wild-type glioblastoma regardless of promoter-region methylation status of the DNA repair enzyme 06-methylguanine-DNA methyltransferase.

The findings may indicate a need to reevaluate surgical strategies for these patients, according to researchers.

“Current standard of care for newly diagnosed [patients with glioblastoma] is temozolomide, radiation and surgery to remove the enhancing portion of the tumor on MRI,” Annette M. Molinaro, PhD, associate professor in the department of neurological surgery and division of epidemiology and biostatistics at University of California, San Francisco, told Healio. “Temozolomide became standard of care in 2005, increasing median OS from 12 months to 14 months. Currently, median OS is around 16 months.”

Maximum resection of the contrast-enhanced (CE) tumor on T1-weighted MRI has been associated with longer survival for patients with glioblastoma, about 91% of whom have tumors with IDH wild-type mutations, researchers wrote. However, the association of maximal resection with survival among glioblastoma subgroups and the potential importance of resection of noncontrast-enhanced (NCE) disease had not been established.

Molinaro and colleagues conducted a multicohort study to assess the association between resection of CE and NCE tumors and molecular and clinical information in order to formulate a new strategy for cytoreductive surgery.

The researchers retrospectively analyzed a development cohort of 761 patients newly diagnosed with glioblastoma between 1997 and 2017 (median follow-up, 9.6 years), and two validation cohorts of 107 patients diagnosed between 2004 and 2014 (median follow-up, 5.7 years) and 99 patients diagnosed between 2008 and 2011 (median follow-up, 10.9 months).

OS served as the study’s primary endpoint.

Results showed that, among the 761 patients (median age, 60 years; 61.5% men) in the development cohort, younger patients with IDH-wild-type tumors and aggressive resection of CE and NCE tumors had median OS of 37.3 months (95% CI, 31.6-70.7), which appeared similar to that of patients with IDH-mutant tumors.

Younger patients with IDH wild-type tumors who had reduction of CE tumors and residual NCE tumors had median OS of 16.5 months (95% CI, 14.7-18.3).

Older patients with IDH wild-type tumors benefited from a reduction of the CE tumor, demonstrating median OS of 12.4 months (95% CI, 11.4-14).

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Results among the external cohorts validated those of the development cohort, researchers wrote.

The association between aggressive CE and NCE among patients with IDH wild-type tumors was not weakened by the methylation status of the promoter region of the DNA repair enzyme O6-methylguanine-DNA methyltransferase.

The study’s retrospective nature served as a limitation.

“We believe that this study will lead to a different surgical roadmap for these patients,” Molinaro said. “Instead of removing the enhancing tumor, when safely feasible and preferably using mapping, the surgeons will remove nonenhancing portions.”

Evidence suggests maximal but safe tumor resection is the best treatment option for younger patients with glioblastoma, William T. Curry Jr., MD, director of neurosurgical oncology at Massachusetts General Hospital, and colleagues wrote in an accompanying editorial.

“Despite the added complexity associated with the molecular era, the role of surgery for glioblastoma certainly deserves continued consideration,” Curry and colleagues wrote. “Greater extent of resection in contrast-enhanced disease improves survival despite age and molecular classification. [For patients aged 65 years and younger], aggressive resection that includes noncontrast-enhanced disease also provides benefit. For now, the best available evidence supports maximal, but safe, tumor resection for glioblastoma.” – by John DeRosier

For more information:

Annette Molinaro, PhD, can be reached at annette.molinaro@ucsf.edu.

Disclosures: Molinaro reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures. The editorial authors report no relevant financial disclosures.