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Hippocampal avoidance in whole brain radiotherapy and prophylactic cranial irradiation: a systematic review and meta-analysis

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Abstract

Purpose

We systematically reviewed the current landscape of hippocampal-avoidance radiotherapy, focusing specifically on rates of hippocampal tumor recurrence and changes in neurocognitive function.

Methods

PubMed was queried for studies involving hippocampal-avoidance radiation therapy and results were screened using PRISMA guidelines. Results were analyzed for median overall survival, progression-free survival, hippocampal relapse rates, and neurocognitive function testing.

Results

Of 3709 search results, 19 articles were included and a total of 1611 patients analyzed. Of these studies, 7 were randomized controlled trials, 4 prospective cohort studies, and 8 retrospective cohort studies. All studies evaluated hippocampal-avoidance whole brain radiation treatment (WBRT) and/or prophylactic cranial irradiation (PCI) in patients with brain metastases. Hippocampal relapse rates were low (overall effect size = 0.04; 95% confidence interval [0.03, 0.05]) and there was no significant difference in risk of relapse between the five studies that compared HA-WBRT/HA-PCI and WBRT/PCI groups (risk difference = 0.01; 95% confidence interval [− 0.02, 0.03]; p = 0.63). 11 out of 19 studies included neurocognitive function testing. Significant differences were reported in overall cognitive function and memory and verbal learning 3–24 months post-RT. Differences in executive function were reported by one study, Brown et al., at 4 months. No studies reported differences in verbal fluency, visual learning, concentration, processing speed, and psychomotor speed at any timepoint.

Conclusion

Current studies in HA-WBRT/HA-PCI showed low hippocampal relapse or metastasis rates. Significant differences in neurocognitive testing were most prominent in overall cognitive function, memory, and verbal learning. Studies were hampered by loss to follow-up.

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Acknowledgements

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The authors declare that no financial support was received during the preparation of this manuscript.

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Authors and Affiliations

  1. State University of New York Downstate Medical Center, Brooklyn, NY, USA

    Sandra Leskinen

  2. Zucker School of Medicine at Hofstra/Northwell, New York, NY, USA

    Harshal A. Shah

  3. Department of Neurology, Zucker School of Medicine at Hofstra/Northwell, Lenox Hill Hospital, New York, NY, USA

    Beril Yaffe & Shonna J. Schneider

  4. Department of Neurological Surgery, Zucker School of Medicine at Hofstra/Northwell, Lenox Hill Hospital, New York, NY, USA

    Netanel Ben-Shalom, John A. Boockvar & Randy S. D’Amico

  5. Department of Radiation Oncology, Zucker School of Medicine at Hofstra/Northwell, Lenox Hill Hospital, New York, NY, USA

    A. Gabriella Wernicke

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All authors contributed to the study conception and design. Data collection, analysis, and the first draft were prepared by SL and HS. All authors commented on subsequent versions of the draft. All authors read and approved the final manuscript.

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Correspondence to A. Gabriella Wernicke.

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Leskinen, S., Shah, H.A., Yaffe, B. et al. Hippocampal avoidance in whole brain radiotherapy and prophylactic cranial irradiation: a systematic review and meta-analysis. J Neurooncol 163, 515–527 (2023). https://doi.org/10.1007/s11060-023-04384-6

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