Adding Chemotherapy to Radiotherapy Does Not Appear to Affect Cognitive Function in Patients With Low-Grade Glioma


Key Points

  • Mini-Mental State Examination (MMSE) scores significantly increased in both groups over time, with no significant difference between groups.
  • Few patients in either group experienced significant decreases in MMSE score.

The addition of PCV (procarbazine [Matulane], lomustine [CeeNu], vincristine) chemotherapy to radiotherapy improves progression-free survival in patients with grade 2 glioma, but the potential effect of treatment intensification on cognitive function is a concern in this group of patients with good long-term survival. In a study reported in the Journal of Clinical Oncology, Prabhu et al found that the addition of PCV to radiotherapy had no apparent effect on cognitive function, with few patients in either group experiencing marked declines and function improving overall in both groups over 5-year follow-up.

Study Details

The study involved the Mini-Mental State Examination (MMSE) assessment of cognitive function in patients with grade 2 glioma aged ≥ 40 years with any extent of resection or aged < 40 years with subtotal resection/biopsy who had been randomly assigned to radiation therapy (54 Gy) with (n = 125) or without (n = 126) PCV in the Radiation Therapy Oncology Group study 98-02. An additional 111 patients aged < 40 years with gross total resection served as an observation group; these patients had more favorable prognostic characteristics in association with their low-risk status. MMSE assessment was performed at baseline and at years 1, 2, 3, and 5. Significant MMSE score decline was defined as a decrease of > 3 points, and significant gain was defined as an increase of > 3 points.

Improvement Over Time

On multivariate analysis, both the PCV/radiotherapy group and the radiotherapy group showed significant increases in average MMSE score over time (P < .001), with no difference in score change over time observed between the two groups (P = .57). Patients with good neurologic function score at baseline (P = .01) and right tumor lateralization (P = .04) had significant improvement in MMSE scores over time vs those without these characteristics.

Categorical Changes

With regard to categorical changes in MMSE score, few patients experienced significant decline. Significant decline and gain were observed in 0% and 3% of the observation group, 7% and 4% of the radiotherapy group, and 4% and 10% of the PCV/radiotherapy group at 1 year (P = .99 overall); 0% and 0%, 2% and 2%, and 0% and 14% at 2 years (P = .5 overall); 0% and 0%, 2% and 4%, and 0% and 12% at 3 years (P = .5 overall); and 0% and 0%, 0% and 5%, and 8% and 12% at 5 years (P = .98 overall).

The investigators concluded: “The MMSE is a relatively insensitive tool, and subtle changes in [cognitive function] may have been missed. However, the addition of PCV to [radiotherapy] did not result in significantly higher rates of MMSE score decline than [radiotherapy] alone through 5 years of follow-up. Patients in both randomly assigned arms experienced a statistically significant average MMSE score increase over time, with no difference between arms. The addition of PCV chemotherapy to [radiotherapy] improves [progression-free survival] without excessive [cognitive function] detriment over [radiotherapy] alone for patients with low-grade glioma.”

Roshan S. Prabhu, MD, MS, of Southeast Radiation Oncology Group, Charlotte, North Carolina, is the corresponding author for the Journal of Clinical Oncology article.

The study was supported by grants from the National Center for Advancing Translational Sciences of the National Institutes of Health, Radiation Therapy Oncology Group, and Community Clinical Oncology Program of the National Cancer Institute. For full disclosures of the study authors, visit

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