Decline in Tested and Patient-reported Cognitive Functioning Following Prophylactic Cranial Irradiation for Lung Cancer: Secondary Analysis of RTOG 0212 and 0214

Abstract

To assess the impact of prophylactic cranial irradiation (PCI) on cognitive functioning, tested using the Hopkins Verbal Learning Test (HVLT) and patient-reported on the EORTC QLQ-C30 questionnaire, following curative-intent treatment for limited-disease small cell lung cancer (LD-SCLC) and locally advanced Non-small cell lung cancer (LA-NSCLC). Patients with LD-SCLC and LA-NSCLC were enrolled on RTOG trials 0212 and 0214, respectively. Recall (R) and delayed recall (DR) from HVLT and patient-reported cognitive functioning (PRCF) from EORTC QLQ-C30 were assessed as secondary endpoints at baseline (following locoregional therapy but before PCI or observation) and at 6 and 12 months follow-up. After pooling data from all enrolled patients, patients who developed brain relapse prior to follow-up evaluation were excluded. Deterioration in HVLT-R, HVLT-DR, and PRCF was defined compared to baseline using the reliable change index method and correlated with receipt of PCI using multivariate logistic regression at a significance level of p < 0.05 for HVLT-R and HVLT-DR correlations and p < 0.001 for PRCF correlations due to multiple testing of EORTC QLQ-C30. Covariates included age, gender, partner status, education level, Zubrod performance score, and PCI dose. Deterioration in HVLT-R and HVLT-DR was also correlated with deterioration in PRCF using Fisher's exact test at a significance level of p < 0.001. Five hundred fifty-two (91%) and 562 (93%) of the 604 eligible patients accrued to RTOG 0212 and RTOG 0214 had baseline EORTC QLQ-C30 and HVLT assessments, respectfully, and were included in this pooled analysis. Compliance was 59% at 6 months and 48% at 12 months for HVLT and 66% at 6 months and 54% at 12 months for EORTC QLQ-C30 and did not differ between RTOG 0212 and 0214. After adjusting for covariates, deterioration in HVLT-R, HVLT-DR and PRCF at 6 and 12 months follow-up was associated with receipt of PCI (Table). At 6 or 12 months, deterioration in PRCF was not correlated with deterioration in HVLT-R (p = 0.05 and p = 0.86, respectively) or HVLT-DR (p = 0.02 and p = 0.54, respectively). In lung cancer patients who do not develop brain relapse, receipt of PCI is associated with deterioration in HVLT-tested and patient-reported cognitive functioning. Decline in HVLT and decline in patient-reported cognitive functioning are not closely correlated.TableImpact of PCI (Referent Group: No PCI)Time to deterioration from baselineHVLT-recallHVLT-delayed recallPatient-reported cognitive functioning6 Months12 Months6 Months12 Months6 Months12 MonthsAdjusted odds ratio4.905.272.072.793.603.4495% Confidence interval1.87-12.871.98-14.021.04-4.121.08-7.162.34-6.371.84-6.44p value0.0010.00090.040.03<0.0001<0.0001 Open table in a new tab