title: Effect of the addition of chemotherapy to radiotherapy on cognitive function in patients with low-grade glioma: secondary analysis of RTOG 98-02.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Roshan S. Prabhu, Southeast Radiation Oncology Group; Levine Cancer Institute, Charlotte; Edward G. Shaw, Wake Forest University School of Medicine, Winston-Salem, NC; Minhee Won and Chen Hu, Radiation Therapy Oncology Group, Philadelphia, PA; David G. Brachman, Arizona Oncology Services Foundation and Barrows Neurologic Institute, Phoenix, AZ; Jan C. Buckner, Mayo Clinic, Rochester, MN; Keith J. Stelzer, Mid-Columbia Medical Center, Celilo Cancer Center, The Dalles, OR; Geoffrey R. Barger, Wayne State University School of Medicine, Detroit, MI; Paul D. Brown and Mark R. Gilbert, MD Anderson Cancer Center, Houston, TX; and Minesh P. Mehta, University of Maryland School of Medicine, Baltimore, MD.
authors.forename: Roshan S
authors.initials: RS
authors.lastname: Prabhu
authors.forename: Minhee
authors.initials: M
authors.lastname: Won
authors.forename: Edward G
authors.initials: EG
authors.lastname: Shaw
authors.forename: Chen
authors.initials: C
authors.lastname: Hu
authors.forename: David G
authors.initials: DG
authors.lastname: Brachman
authors.forename: Jan C
authors.initials: JC
authors.lastname: Buckner
authors.forename: Keith J
authors.initials: KJ
authors.lastname: Stelzer
authors.forename: Geoffrey R
authors.initials: GR
authors.lastname: Barger
authors.forename: Paul D
authors.initials: PD
authors.lastname: Brown
authors.forename: Mark R
authors.initials: MR
authors.lastname: Gilbert
authors.forename: Minesh P
authors.initials: MP
authors.lastname: Mehta
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology / Q000532:radiotherapy*; D059186:Chemoradiotherapy, Adjuvant; D003071:Cognition / Q000187:drug effects* / Q000528:radiation effects*; D003072:Cognition Disorders / Q000139:chemically induced / Q000209:etiology; D018572:Disease-Free Survival; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology / Q000532:radiotherapy*; D006801:Humans; D008130:Lomustine / Q000008:administration & dosage; D008297:Male; D060787:Neoplasm Grading; D011344:Procarbazine / Q000008:administration & dosage; D011446:Prospective Studies; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D011344:Procarbazine; D014750:Vincristine; D008130:Lomustine