Chemotherapy and Radiotherapy Combination Prolongs Survival in Low-grade Glial Brain Cancer

The addition of chemotherapy to radiation therapy (RT) prolonged survival in adults with grade 2 glial brain tumors (gliomas). Grade 2 gliomas comprise 5% to 10% of all brain tumors, but nearly all patients with grade 2 gliomas experience progressive neurologic symptoms and premature death.1

This study, published in the New England Journal of Medicine, enrolled 251 patients with grade 2 glioma diagnosed between 1998 and 2002. Their gliomas were histologically confirmed grade 2 astrocytoma, oligodendroglioma, or oligoastrocytoma. These reported results were from a long-term, randomized clinical trial.

Patients who received RT in addition to a chemotherapy regime that included procarbazine, lomustine (CCNU), and vincristine (PCV) experienced longer overall survival (OS) and progression-free survival (PFS) than patients who only received RT. Patients were randomly assigned to RT or to RT followed by 6 cycles of chemotherapy and were stratified based on age, histologic findings, Karnofsky performance-status score, and presence or absence of contrast enhancement on preoperative images.

Participants were younger than 40 years and had undergone subtotal resection or biopsy or were 40 years or older and had undergone biopsy or resection of any of the tumor. Median follow-up was 11.9 years, and 55% of the patients died.

Median OS of patients who received RT plus chemotherapy was 7.8 years, and median OS of patients who received RT alone was 13.3 years (hazard ratio (HR) for death, 0.59; P = .003). At 10 years, PFS was 51% in the group that received RT and chemotherapy and 21% in the group that received only RT. Correspondingly, OS at 10 years was 60% and 40%.

"This is the first phase III trial to demonstrate conclusively a treatment-related survival benefit for patients with grade 2 glioma," said Jan Buckner, MD, professor of oncology at the Mayo Clinic College of Medicine and Deputy Director for Practice at the Mayo Clinic Cancer Center in Rochester, Minnesota, and first author of the study.

Receipt of RT and chemotherapy and histologic findings of oligodendroglioma were favorable prognostic variables for both PFS and OS.

"Our results indicate that initial therapy of RT followed by PCV is necessary to achieve longer survival in patients with grade 2 glioma and that salvage therapy at relapse after RT alone is less effective," said Buckner.

"It has also been hypothesized that other genetic alterations may be responsible for a small subset of patients whose glial brain tumors are chemotherapy-resistant. However, radiation therapy plus PCV appears to represent the most effective treatment identified to date for the majority of patients with grade 2 glioma."


1. Buckner JC, Shaw EG, Pugh SL, et al. Radiation plus procarbazine, CCNU, and vincristine in low-grade glioma [published online ahead of print April 7, 2016]. N Engl J Med. doi:10.1056/NEJMoa1500925.

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