title: Decline in tested and self-reported cognitive functioning after prophylactic cranial irradiation for lung cancer: pooled secondary analysis of Radiation Therapy Oncology Group randomized trials 0212 and 0214.
abstract: OBJECTIVE
  To assess the impact of prophylactic cranial irradiation (PCI) on self-reported cognitive functioning (SRCF), a functional scale on the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30).
  
  
  METHODS
  Radiation Therapy Oncology Group (RTOG) protocol 0214 randomized patients with locally advanced non-small cell lung cancer to PCI or observation; RTOG 0212 randomized patients with limited-disease small cell lung cancer to high- or standard-dose PCI. In both trials, Hopkins Verbal Learning Test (HVLT)-Recall and -Delayed Recall and SRCF were assessed at baseline (after locoregional therapy but before PCI or observation) and at 6 and 12 months. Patients developing brain relapse before follow-up evaluation were excluded. Decline was defined using the reliable change index method and correlated with receipt of PCI versus observation using logistic regression modeling. Fisher's exact test correlated decline in SRCF with HVLT decline.
  
  
  RESULTS
  Of the eligible patients pooled from RTOG 0212 and RTOG 0214, 410 (93%) receiving PCI and 173 (96%) undergoing observation completed baseline HVLT or EORTC QLQ-C30 testing and were included in this analysis. Prophylactic cranial irradiation was associated with a higher risk of decline in SRCF at 6 months (odds ratio 3.60, 95% confidence interval 2.34-6.37, P<.0001) and 12 months (odds ratio 3.44, 95% confidence interval 1.84-6.44, P<.0001). Decline on HVLT-Recall at 6 and 12 months was also associated with PCI (P=.002 and P=.002, respectively) but was not closely correlated with decline in SRCF at the same time points (P=.05 and P=.86, respectively).
  
  
  CONCLUSIONS
  In lung cancer patients who do not develop brain relapse, PCI is associated with decline in HVLT-tested and self-reported cognitive functioning. Decline in HVLT and decline in SRCF are not closely correlated, suggesting that they may represent distinct elements of the cognitive spectrum.
authors.affiliation: Central Dupage Hospital Cancer Center, Warrenville, Illinois 60555, USA. vgondi@chicagocancer.org
authors.forename: Vinai
authors.initials: V
authors.lastname: Gondi
authors.forename: Rebecca
authors.initials: R
authors.lastname: Paulus
authors.forename: Deborah W
authors.initials: DW
authors.lastname: Bruner
authors.forename: Christina A
authors.initials: CA
authors.lastname: Meyers
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Gore
authors.forename: Aaron
authors.initials: A
authors.lastname: Wolfson
authors.forename: Maria
authors.initials: M
authors.lastname: Werner-Wasik
authors.forename: Alexander Y
authors.initials: AY
authors.lastname: Sun
authors.forename: Hak
authors.initials: H
authors.lastname: Choy
authors.forename: Benjamin
authors.initials: B
authors.lastname: Movsas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000528:radiation effects; D001932:Brain Neoplasms / Q000517:prevention & control* / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000517:prevention & control* / Q000556:secondary; D003071:Cognition / Q000528:radiation effects*; D003072:Cognition Disorders / Q000209:etiology; D016001:Confidence Intervals; D016371:Cranial Irradiation / Q000009:adverse effects* / Q000379:methods; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology; D008297:Male; D008570:Memory, Short-Term / Q000528:radiation effects*; D008875:Middle Aged; D016017:Odds Ratio; D011788:Quality of Life; D057566:Self Report; D011795:Surveys and Questionnaires; D013997:Time Factors