title: Hippocampal dosimetry correlates with the change in neurocognitive function after hippocampal sparing during whole brain radiotherapy: a prospective study.
abstract: BACKGROUND
  Whole brain radiotherapy (WBRT) has been the treatment of choice for patients with brain metastases. However, change/decline of neurocognitive functions (NCFs) resulting from impaired hippocampal neurogenesis might occur after WBRT. It is reported that conformal hippocampal sparing would provide the preservation of NCFs. Our study aims to investigate the hippocampal dosimetry and to demonstrate the correlation between hippocampal dosimetry and neurocognitive outcomes in patients receiving hippocampal sparing during WBRT (HS-WBRT).
  
  
  METHODS
  Forty prospectively recruited cancer patients underwent HS-WBRT for therapeutic or prophylactic purposes. Before receiving HS-WBRT, all participants received a battery of baseline neurocognitive assessment, including memory, executive functions and psychomotor speed. The follow-up neurocognitive assessment at 4 months after HS-WBRT was also performed. For the delivery of HS-WBRT, Volumetric Modulated Arc Therapy (VMAT) with two full arcs and two non-coplanar partial arcs was employed. For each treatment planning, dose volume histograms were generated for left hippocampus, right hippocampus, and the composite hippocampal structure respectively. Biologically equivalent doses in 2-Gy fractions (EQD2) assuming an alpha/beta ratio of 2 Gy were computed. To perform analyses addressing the correlation between hippocampal dosimetry and the change in scores of NCFs, pre- and post-HS-WBRT neurocognitive assessments were available in 24 patients in this study.
  
  
  RESULTS
  Scores of NCFs were quite stable before and after HS-WBRT in terms of hippocampus-dependent memory. Regarding verbal memory, the corresponding EQD2 values of 0, 10, 50, 80 % irradiating the composite hippocampal structure with <12.60 Gy, <8.81, <7.45 Gy and <5.83 Gy respectively were significantly associated with neurocognitive preservation indicated by the immediate recall of Word List Test of Wechsler Memory Scale-III. According to logistic regression analyses, it was noted that dosimetric parameters specific to left sided hippocampus exerted an influence on immediate recall of verbal memory (adjusted odds ratio, 4.08; p-value, 0.042, predicting patients' neurocognitive decline after receiving HS-WBRT).
  
  
  CONCLUSIONS
  Functional preservation by hippocampal sparing during WBRT is indeed achieved in our study. Providing that modern VMAT techniques can reduce the dose irradiating bilateral hippocampi below dosimetric threshold, patients should be recruited in prospective trials of hippocampal sparing during cranial irradiation to accomplish neurocognitive preservation while maintaining intracranial control.
  
  
  BACKGROUND
  Current Controlled Trials NCT02504788.
authors.affiliation: Department of Radiation Oncology, Chang Gung Memorial Hospital and Chang Gung University, #15, Wenhua 1st Rd., Kwei-Shan Hsiang, Taoyuan, Taiwan. pftsai1112@gmail.com.|Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan. pftsai1112@gmail.com.
authors.forename: Ping-Fang
authors.initials: PF
authors.lastname: Tsai
authors.affiliation: Department of Occupational Therapy, Division of Clinical Psychology, Master of Behavioral Sciences, College of Medicine, Chang Gung University, No. 259, Wen-Hwa 1st Road, Kwei-Shan Tao-Yuan, 333, Taiwan. ccyang@mail.cgu.edu.tw.
authors.forename: Chi-Cheng
authors.initials: CC
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Chang Gung Memorial Hospital and Chang Gung University, #5, Fu-Shin Street, Kwei-Shan Hsiang, Taoyuan, Taiwan. ccc2915@cgmh.org.tw.
authors.forename: Chi-Cheng
authors.initials: CC
authors.lastname: Chuang
authors.affiliation: Department of Neurosurgery, Chang Gung Memorial Hospital and Chang Gung University, #5, Fu-Shin Street, Kwei-Shan Hsiang, Taoyuan, Taiwan. hty9814233@gmail.com.
authors.forename: Ting-Yi
authors.initials: TY
authors.lastname: Huang
authors.affiliation: Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital and Chang Gung University, #5, Fu-Shin Street, Kwei-Shan Hsiang, Taoyuan, Taiwan. jimmy_cgmh@hotmail.com.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Wu
authors.affiliation: Department of Radiation Oncology, Chang Gung Memorial Hospital and Chang Gung University, #15, Wenhua 1st Rd., Kwei-Shan Hsiang, Taoyuan, Taiwan. ww0316@yahoo.com.tw.|Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan. ww0316@yahoo.com.tw.
authors.forename: Ping-Ching
authors.initials: PC
authors.lastname: Pai
authors.affiliation: Department of Radiation Oncology, Chang Gung Memorial Hospital and Chang Gung University, #15, Wenhua 1st Rd., Kwei-Shan Hsiang, Taoyuan, Taiwan. kantseng@msn.com.|Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan. kantseng@msn.com.
authors.forename: Chen-Kan
authors.initials: CK
authors.lastname: Tseng
authors.affiliation: Department of Radiation Oncology, Chang Gung Memorial Hospital and Chang Gung University, #15, Wenhua 1st Rd., Kwei-Shan Hsiang, Taoyuan, Taiwan. tungho48@yahoo.com.tw.|Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan. tungho48@yahoo.com.tw.
authors.forename: Tung-Ho
authors.initials: TH
authors.lastname: Wu
authors.affiliation: Department of Radiation Oncology, Chang Gung Memorial Hospital and Chang Gung University, #15, Wenhua 1st Rd., Kwei-Shan Hsiang, Taoyuan, Taiwan. patience.tw@gmail.com.
authors.forename: Yi-Liang
authors.initials: YL
authors.lastname: Shen
authors.affiliation: Department of Radiation Oncology, Chang Gung Memorial Hospital and Chang Gung University, #15, Wenhua 1st Rd., Kwei-Shan Hsiang, Taoyuan, Taiwan. rt3126@gmail.com.|Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan. rt3126@gmail.com.|Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan. rt3126@gmail.com.
authors.forename: Shinn-Yn
authors.initials: SY
authors.lastname: Lin
mesh_terms: D001932:Brain Neoplasms / Q000532:radiotherapy*; D003071:Cognition / Q000528:radiation effects; D016371:Cranial Irradiation / Q000009:adverse effects / Q000379:methods*; D006624:Hippocampus / Q000528:radiation effects*; D006801:Humans; D009483:Neuropsychological Tests; D011446:Prospective Studies; D011832:Radiation Injuries / Q000517:prevention & control*; D011874:Radiometry; D011880:Radiotherapy Planning, Computer-Assisted; D050397:Radiotherapy, Intensity-Modulated