A prospective evaluation of whole brain volume loss and neurocognitive decline following hippocampal-sparing prophylactic cranial irradiation for limited-stage small-cell lung cancer

  • Chengcheng Gui
  • Namrata Chintalapati
  • Russell Kenneth Hales
  • Khinh Ranh Voong
  • Haris Iqbal Sair
  • Jimm Grimm
  • Mario Duhon
  • Lawrence Richard Kleinberg
  • Tracy Dawn Vannorsdall
  • Kristin Janson RedmondEmail author
Clinical Study



This study evaluated an association between whole brain volume loss and neurocognitive decline following prophylactic cranial irradiation (PCI) for limited-stage small-cell lung cancer (SCLC).


This was a secondary analysis of a prospective clinical trial that accrued patients at a single institution from 2013 to 2016. Patients with limited-stage SCLC treated with standard chemo-radiation received PCI 25 Gy/10 fractions, with mean hippocampal dose limited to < 8 Gy. Whole brain volumes were measured using MR imaging obtained before and at 6, 12, 18, and 24 months after PCI. Verbal memory was measured by the Hopkins Verbal Learning Test-Revised (HVLT-R) before and at 6 and 12 months after PCI. Univariate and multivariate linear regression evaluated associations between changes in whole brain volume and verbal memory.


Twenty-two patients enrolled. The median whole brain volume before PCI was 1301 mL. Subsequent reduction in whole brain volume was greatest at 18 months after PCI (median change − 23 mL, range − 142 to 20, p = 0.03). At 6 months after PCI, reduction in volume was independently associated with decline in verbal memory, measured by two components of the HVLT-R (Delayed Recall: 0.06/mL volume change, p = 0.046; Percent Retained: 0.66/mL volume change, p = 0.030), when controlling for education and global cognitive function at baseline.


This is the first study to correlate reduction in whole brain volume and decline in neurocognitive function following whole brain radiation therapy (WBRT). This suggests that loss of brain volume after WBRT may be clinically significant and subsequently impact cognition and quality of life.


Small-cell lung cancer Whole brain radiation therapy Cognitive toxicity Radiographic volume loss Verbal memory 



The study was internally funded by the Department of Radiation Oncology and Molecular Radiation Sciences at the Johns Hopkins Hospital.

Compliance with ethical standards

Conflict of interest

Dr. Kleinberg reports grants and personal fees from Accuray, grants from Arbor, personal fees and an advisory board position from Novocure, outside the submitted work. Dr. Redmond reports grants from Elekta AB, personal fees from AstraZeneca, personal fees from Medtronic, grants and personal fees from Accuray, outside the submitted work. Dr. Sair reports grant support from ImmunArray, outside the submitted work. The other authors have nothing to disclose.

Research involving human participants

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Johns Hopkins Medicine Institutional Review Boards (NA_00078659) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Statement on the welfare of animals

This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

11060_2019_3235_MOESM1_ESM.docx (18 kb)
Supplementary file1 (DOCX 19 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Chengcheng Gui
    • 1
  • Namrata Chintalapati
    • 1
  • Russell Kenneth Hales
    • 1
  • Khinh Ranh Voong
    • 1
  • Haris Iqbal Sair
    • 2
    • 4
  • Jimm Grimm
    • 1
  • Mario Duhon
    • 1
  • Lawrence Richard Kleinberg
    • 1
  • Tracy Dawn Vannorsdall
    • 3
  • Kristin Janson Redmond
    • 1
    Email author
  1. 1.Department of Radiation Oncology and Molecular Radiation SciencesJohns Hopkins University, Johns Hopkins Sidney Kimmel Comprehensive Cancer CenterBaltimoreUSA
  2. 2.Department of Radiology and Radiological ScienceJohns Hopkins UniversityBaltimoreUSA
  3. 3.Department of Psychiatry and Behavioral SciencesJohns Hopkins UniversityBaltimoreUSA
  4. 4.Malone Center for Engineering in Healthcare, Whiting School of EngineeringJohns Hopkins UniversityBaltimoreUSA

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