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

Int J Radiat Oncol Biol Phys. 2025 Jul 2:S0360-3016(25)04519-5. doi: 10.1016/j.ijrobp.2025.06.3884. Online ahead of print.

Abstract

Purpose: xxxxx 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 xxxxx 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 & 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 (PRO) measures, the EORTC 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 > 0.05) between the two 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 (rho=0.27, p<0.0001) as well as between change in pathways score and QLQ-C30 global health status (rho=0.16, p=0.022).

Conclusions: It is feasible to study hopefulness in the context of prospective trials conducted within the National Clinical Trials Network (NCTN). 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.

Keywords: Hope. Hippocampus. Quality of Life. Small cell lung cancer.