Evaluating the Heterogeneity of Hippocampal Avoidant Whole Brain Radiotherapy Treatment Effect: A Secondary Analysis of NRG CC001. Article

Cherng, Hua-Ren R, Sun, Kai, Bentzen, Soren et al. (2023). Evaluating the Heterogeneity of Hippocampal Avoidant Whole Brain Radiotherapy Treatment Effect: A Secondary Analysis of NRG CC001. . NEURO-ONCOLOGY, noad226. 10.1093/neuonc/noad226

cited authors

  • Cherng, Hua-Ren R; Sun, Kai; Bentzen, Soren; Armstrong, Terri S; Gondi, Vinai; Brown, Paul D; Mehta, Minesh; Mishra, Mark V

authors

abstract

  • Background

    Hippocampal avoidant whole brain radiotherapy (HA-WBRT) is the standard of care for patients needing WBRT for brain metastases (BM). This study, using existing data from NRG Oncology CC001 including baseline tumor characteristics and patient-reported MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) scores, sought to identify subgroups of patients that demonstrate differential neuroprotective treatment response to HA-WBRT.

    Methods

    An exploratory analysis of NRG CC001, a phase III trial in which 518 patients were randomly assigned to WBRT plus memantine or HA-WBRT plus memantine, was performed. Rates of neurocognitive function failure (NCFF) were estimated between subgroups and stratified by arm. Covariate and subgroup interaction with differential treatment response were calculated.

    Results

    The benefit of HA-WBRT on decreasing NCFF was seen in patients living ≥ 4 months (HR 0.75, 95% CI: 0.58-0.97, P=0.03), whereas patients living < 4 months derived no significant neurocognitive benefit. Significant association between baseline MDASI-BT cognitive factor and treatment response (interaction P=0.03) was identified. Patients with lower MDASI-BT scores (less patient-reported cognitive impairment) derived significantly greater benefit (HR=0.64, 95% CI: 0.48-0.85, P=0.002) compared to those with highest MDASI-BT scores (HR=1.24, 95% CI: 0.76-2.04, P=0.39). Tumor histology also had significant interaction (P=0.01) with treatment response. Primary lung histology patients derived cognitive failure risk reduction (HR=0.58, 95% CI: 0.43-0.77, P=0.0007) from HA-WBRT, in contrast to non-lung primary histology patients (HR=1.15, 95% CI: 0.78-1.50, P=0.48).

    Conclusions

    Differential neuroprotective response to HA-WBRT was identified in this analysis. Patients surviving ≥ 4 months derived benefit from HA-WBRT. There is evidence of heterogeneity of treatment effect for patients with less severe patient-reported cognitive impairment at baseline and those with primary lung histology.

publication date

  • December 1, 2023

published in

Digital Object Identifier (DOI)

Medium

  • Print-Electronic

start page

  • noad226