Effect of the addition of chemotherapy to radiotherapy on cognitive function in patients with low-grade glioma: secondary analysis of RTOG 98-02

J Clin Oncol. 2014 Feb 20;32(6):535-41. doi: 10.1200/JCO.2013.53.1830. Epub 2014 Jan 13.


Purpose: The addition of PCV (procarbazine, lomustine, and vincristine) chemotherapy to radiotherapy (RT) for patients with WHO grade 2 glioma improves progression-free survival (PFS). The effect of therapy intensification on cognitive function (CF) remains a concern in this population with substantial long-term survival.

Patients and methods: A total of 251 patients with WHO grade 2 glioma age ≥ 40 years with any extent of resection or age < 40 years with subtotal resection/biopsy were randomly assigned to RT (54 Gy) or RT plus PCV. We observed 111 patients age < 40 years with gross total resection. CF was assessed by Mini-Mental State Examination (MMSE) at baseline and years 1, 2, 3, and 5.

Results: Overall, few patients experienced significant decline in MMSE score. There were no significant differences in the proportion of patients experiencing MMSE score decline between the randomized study arms at any time point. Both study arms experienced a significant gain in average MMSE score longitudinally over time, with no difference between arms.

Conclusion: The MMSE is a relatively insensitive tool, and subtle changes in CF may have been missed. However, the addition of PCV to RT did not result in significantly higher rates of MMSE score decline than RT 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 RT improves PFS without excessive CF detriment over RT alone for patients with low-grade glioma.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / psychology
  • Brain Neoplasms / radiotherapy*
  • Chemoradiotherapy, Adjuvant
  • Cognition / drug effects*
  • Cognition / radiation effects*
  • Cognition Disorders / chemically induced
  • Cognition Disorders / etiology
  • Disease-Free Survival
  • Female
  • Glioma / drug therapy*
  • Glioma / pathology
  • Glioma / psychology
  • Glioma / radiotherapy*
  • Humans
  • Lomustine / administration & dosage
  • Male
  • Neoplasm Grading
  • Procarbazine / administration & dosage
  • Prospective Studies
  • Survival Rate
  • Vincristine / administration & dosage


  • Procarbazine
  • Vincristine
  • Lomustine