“Hope” Drives Quality of Life in Patients With Brain Metastases, But, the “Hope Center” Remains Elusive: An Analysis of NRG-CC003

Purpose: NRG-CC003 randomized 393 patients with small cell lung cancer to prophylactic cranial irradiation (PCI) with or without hippocampal avoidance (HA). “Hopefulness” is a cognitive construct with 3 components: goals, pathways, and agency. Hope is measurable with validated instruments. Since hope is cognitive in nature, the existence of a “hope center” in the brain—most likely in the hippocampus—has been hypothesized. One exploratory objective of NRG-CC003 posited that if hope levels were better maintained in patients randomized to PCI + HA, then the hippocampus would be implicated in the mechanism of hopefulness. Methods and Materials: PCI consisted of 10 fractions of 2.5 Gy. The Adult Hope Scale (AHS) was administered at time-zero and at 6 months. Regarding patient-reported outcome measures, the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 was administered at baseline and at 3, 6-, 12-, 18- and 24-month intervals. Comparisons of AHS scores by arm were made using Wilcoxon–Mann–Whitney tests, and correlation of AHS with EORTC QLQ-C30 by Pearson correlation coefficients. Results: Approximately 95% completed the AHS at baseline and 67% filled out the questionnaire at 6 months paralleling the completion rates of the conventional tools for QOL and neurocognition. When comparing hope levels (change from baseline to 6 months) there was no significant difference (P > .05) between the 2 arms of the trial. There was a correlation for the components of hopefulness with QOL; specifically, between change in agency score and QLQ-C30 global health status (ρ = 0.27, P < .0001) as well as between change in pathways score and QLQ-C30 global health status (ρ = 0.16, P = .022). Conclusions: It is feasible to study hopefulness in the context of prospective trials conducted within the National Clinical Trials Network. The hippocampus could not be implicated as a critical structure in a central pathway that coordinates hopefulness. For the first time, validated tools established a relationship between hope and quality of life among cancer patients.