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Randomized Controlled Trial
. 2025 Nov 1;123(3):642-652.
doi: 10.1016/j.ijrobp.2025.06.3884. Epub 2025 Jul 2.

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

Benjamin W Corn  1 , Rebecca Paulus  2 , Vinai Gondi  3 , Minesh P Mehta  4 , Shannon Fogh  5 , Jeffrey S Wefel  6 , Gregory M Videtic  7 , Alexander Sun  8 , Harold Yoon  9 , John H Heinzerling  10 , Ronald C McGarry  11 , Vijayananda Kundapur  12 , Kiran Devisetty  13 , Abraham Wu  14 , Edward C McCarron  15 , Jondavid Pollock  16 , Andrew A Kanner  17 , David B Feldman  18 , Stephanie L Pugh  2 , Lisa A Kachnic  19 , Benjamin Movsas  20
Affiliations
Randomized Controlled Trial

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

Benjamin W Corn et al. Int J Radiat Oncol Biol Phys. .

Abstract

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.

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Conflict of interest statement

Conflicts of Interest:

Drs Devisetty, Feldman, Fogh, Gondi, Heinzerling, Kanner, Kundapur, McCarron, Movsas, Pollock, Sun, Videtic, Yoon and Ms. Paulus have nothing to disclose.

Dr Corn declares in the last 36 months payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing or educational events from I received honoraria for lectures that I delivered at UCLA, Cedars-Sinai Medical Center, and Moffitt Cancer Center with Specifications/Comments of Payments were made to me. The lectures were all academic in nature, Support for attending meetings and/or travel from I received support from NRG oncology to attend (and make presentations) at their semi-annual meetings with Specifications/Comments of Payments were made directly to me, Participation on a Data Safety Monitoring Board or Advisory Board from I participated in a DSMB for Lutris Pharma with Specifications/Comments of Payments were made directly to me.

Dr Kachnic declares in the last 36 months support for attending meetings and/or travel for NRG Oncology as I am the associate PI for their NCORP program, Leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid from NRG Oncology Associate NCORP PI; unpaid.

Dr McCarry declares in the last 36 months Participation on a Data Safety Monitoring Board or Advisory Board for Veterans’ Administration VALOR, DSMC member.

Dr Mehta declares in the last 36 months consulting fees received from AIQ, Telix, Kazia, Novocure, Zap, Xoft, Mevion with Specifications/Comments of Self, Patents planned, issued, or pending of Baptist Health South Florida, Pulsed reduced Dose Rate Proton Therapy with Specifications/Comments of No payments, Leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid of NRG Oncology Train Tumor Committee Chair, National Association of Proton Therapy Board with Specifications/Comments of No payments, Stock or stock options received from Chimerix stock with Specifications/Comments of Self.

Dr Pugh declares in the last 36 months since the initial planning of the work all support for the present manuscript from NCI.

Dr Wefel declares in the last 36 months consulting fees received from Astellas, Bayer, GT Medical Technologies, Intra-Cellular Therapeutics, Juno, Novocure with Specifications/Comments of consulting payments, institutional payments.

Dr Wu declares in the last 36 months payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing or educational events from CardinalHealth with CardinalHealth of Honorarium for attending educational event, one-time payment to myself, Participation on a Data Safety Monitoring Board or Advisory Board from Simphotek, Inc. with Specifications/Comments of Scientific advisory board member, compensated with stock options, Stock or stock options received from Simphotek, Inc..

Figures

Figure 1.
Figure 1.
CONSORT Diagram. HA=Hippocampal Avoidance; PCI=Prophylactic Cranial Irradiation; AHS=Adult Hope Scale
Figure 2.
Figure 2.
Whisker plot showing “pathways score” and “agency score” within the Adult Hope Scale (AHS) at baseline and at 6-months as a function of treatment arm (PCI alone or PCI with hippocampal avoidance).
See this image and copyright information in PMC

References

    1. NRG-CC003 at ClinicalTrials.gov NCT #02635009. Accessed on January 4, 2024..
    1. Gondi V, Pugh SL, Tome WA, et al. Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): a phase II multi-institutional trial. J Clin Oncol 2014. Dec 1;32(34):3810–6. doi: 10.1200/JCO.2014.57.2909. - DOI - PMC - PubMed
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