title: Estimated risk of perihippocampal disease progression after hippocampal avoidance during whole-brain radiotherapy: safety profile for RTOG 0933.
abstract: OBJECTIVE
  RTOG 0933 is a phase II clinical trial of hippocampal avoidance during whole-brain radiotherapy (HA-WBRT) to prevent radiation-induced neurocognitive decline. By quantifying baseline incidence of perihippocampal or hippocampal metastasis, we sought to estimate the risk of developing metastases in the hippocampal avoidance region (the hippocampus plus 5mm margin).
  
  
  METHODS
  Patients with < or = 10 brain metastases treated at two separate institutions were reviewed. Axial images from pre-treatment, post-contrast MRIs were used to contour each metastasis and hippocampus according to a published protocol. Clinical and radiographic variables were correlated with perihippocampal metastasis using a binary logistical regression analysis, with two-sided p<0.05 for statistical significance.
  
  
  RESULTS
  1133 metastases were identified in 371 patients. Metastases within 5mm of the hippocampus were observed in 8.6% of patients (95% CI 5.7-11.5%) and 3.0% of brain metastases. None of the metastases lay within the hippocampus. A 1-cm(3) increase in the aggregate volume of intra-cranial metastatic disease was associated with an odds ratio of 1.02 (95% CI 1.006-1.034, p=0.003) for the presence of perihippocampal metastasis.
  
  
  CONCLUSIONS
  With an estimated perihippocampal metastasis risk of 8.6%, we deem HA-WBRT safe for clinical testing in patients with brain metastases as part of RTOG 0933.
authors.affiliation: Department of Human Oncology, University of Wisconsin Comprehensive Cancer Center, Madison, WI 53792, USA. gondi@humonc.wisc.edu
authors.forename: Vinai
authors.initials: V
authors.lastname: Gondi
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Tome
authors.forename: James
authors.initials: J
authors.lastname: Marsh
authors.forename: Aaron
authors.initials: A
authors.lastname: Struck
authors.forename: Amol
authors.initials: A
authors.lastname: Ghia
authors.forename: Julius V
authors.initials: JV
authors.lastname: Turian
authors.forename: Søren M
authors.initials: SM
authors.lastname: Bentzen
authors.forename: John S
authors.initials: JS
authors.lastname: Kuo
authors.forename: Deepak
authors.initials: D
authors.lastname: Khuntia
authors.forename: Minesh P
authors.initials: MP
authors.lastname: Mehta
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000473:pathology / Q000556:secondary*; D003071:Cognition / Q000528:radiation effects*; D016371:Cranial Irradiation / Q000009:adverse effects*; D005260:Female; D006624:Hippocampus / Q000473:pathology / Q000528:radiation effects*; D006801:Humans; D008297:Male; D008875:Middle Aged
references.citation: J Clin Oncol. 2002 Aug 15;20(16):3445-53
references.pmid: 12177105
references.citation: J Clin Oncol. 2006 Mar 10;24(8):1295-304
references.pmid: 16525185
references.citation: Int J Radiat Oncol Biol Phys. 1997 Mar 1;37(4):745-51
references.pmid: 9128946
references.citation: Int J Radiat Oncol Biol Phys. 2010 Nov 15;78(4):1244-52
references.pmid: 20598457
references.citation: Int J Radiat Oncol Biol Phys. 2007 Jul 15;68(4):971-7
references.pmid: 17446005
references.citation: Int J Radiat Oncol Biol Phys. 2007 Oct 1;69(2):589-97
references.pmid: 17869672
references.citation: J Clin Oncol. 2003 Jul 1;21(13):2529-36
references.pmid: 12829672