Radiation plus Procarbazine, CCNU, and Vincristine in Low-Grade Glioma

Abstract

BACKGROUND Grade 2 gliomas occur most commonly in young adults and cause progressive neurologic deterioration and premature death. Early results of this trial showed that treatment with procarbazine, lomustine (also called CCNU), and vincristine after radiation therapy at the time of initial diagnosis resulted in longer progression-free survival, but not overall survival, than radiation therapy alone. We now report the long-term results. METHODS We included patients with grade 2 astrocytoma, oligoastrocytoma, or oligodendroglioma who were younger than 40 years of age and had undergone subtotal resection or biopsy or who were 40 years of age or older and had undergone biopsy or resection of any of the tumor. Patients were stratified according to age, histologic findings, Karnofsky performance-status score, and presence or absence of contrast enhancement on preoperative images. Patients were randomly assigned to radiation therapy alone or to radiation therapy followed by six cycles of combination chemotherapy. RESULTS A total of 251 eligible patients were enrolled from 1998 through 2002. The median follow-up was 11.9 years; 55% of the patients died. Patients who received radiation therapy plus chemotherapy had longer median overall survival than did those who received radiation therapy alone (13.3 vs. 7.8 years; hazard ratio for death, 0.59; P=0.003). The rate of progression-free survival at 10 years was 51% in the group that received radiation therapy plus chemotherapy versus 21% in the group that received radiation therapy alone; the corresponding rates of overall survival at 10 years were 60% and 40%. A Cox model identified receipt of radiation therapy plus chemotherapy and histologic findings of oligodendroglioma as favorable prognostic variables for both progression-free and overall survival. CONCLUSIONS In a cohort of patients with grade 2 glioma who were younger than 40 years of age and had undergone subtotal tumor resection or who were 40 years of age or older, progression-free survival and overall survival were longer among those who received combination chemotherapy in addition to radiation therapy than among those who received radiation therapy alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00003375.)

Biomarkers in NOA-04: another piece to the puzzle

“…5,9 Pending molecular correlations for recently published studies may help to validate this conclusion in low-grade 13 and anaplastic 14 gliomas.…”

“…2 This inference is supported by the recent observation that survival after CT and RT together is unambiguously superior to survival after RT alone in low-grade oligodendrogliomas, most of which presumably harbor IDH mutation (and CIMP) and codeletion. 13 However, survival may not be the only relevant endpoint. Patients with (IDH mutant and) codeleted or CIMP codel tumors typically live long enough to experience late and permanent neurocognitive injury from RT.…”

Immunological effects of chemotherapy and radiotherapy against brain tumors

“…The combination of RT and PCV chemotherapy prolongs survival compared to radiotherapy alone in patients with 1p/19q co-deleted anaplastic gliomas and lowgrade tumors (17)(18)(19). TMZ is orally administered and better tolerated than PCV.…”

Relationship Between Radiation Dose and Microbleed Formation in Patients With Malignant Glioma

“…Combined adjuvant chemoradiotherapy (CRT) constitutes the standard of care after maximal safe resection in malignant glioma [1], and is gaining acceptance as adjuvant treatment for high-risk, low-grade gliomas [2]. Due to pathologic studies demonstrating microscopic spread beyond tumor visible on imaging [3][4][5], radiotherapy targets generally constitute a margin of approximately 2 cm around gross visible disease and surgical resection cavities.…”

“…Given the amount of normal irradiated brain tissue, late toxicity from radiotherapy for gliomas is of significant concern, particularly for patients with lower-grade gliomas for whom survival can extend well over 10 years [2]. Cognitive testing of long-term glioma survivors has shown significant decline across multiple cognitive domains [7], although evidence exists for tumor progression as a driver of cognitive decline in glioma patients [8].…”