Estimated risk of perihippocampal disease progression after hippocampal avoidance during whole-brain radiotherapy: safety profile for RTOG 0933.
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.
Gondi
Vinai
V
Department of Human Oncology, University of Wisconsin Comprehensive Cancer Center, Madison, WI 53792, USA. gondi@humonc.wisc.edu
Tome
Wolfgang A
WA
Marsh
James
J
Struck
Aaron
A
Ghia
Amol
A
Turian
Julius V
JV
Bentzen
Søren M
SM
Kuo
John S
JS
Khuntia
Deepak
D
Mehta
Minesh P
MP
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
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