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Author Smith, D. ♦ Debeb, B. ♦ Larson, R. ♦ Diagaradjane, P. ♦ Woodward, W.
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ RADIATION PROTECTION AND DOSIMETRY ♦ BRAIN ♦ FLUORESCENCE ♦ HAZARDS ♦ INJECTION ♦ IRRADIATION ♦ LEUKEMIA ♦ LUNGS ♦ MAMMARY GLANDS ♦ METASTASES ♦ MICE ♦ PATIENTS ♦ PROTEINS ♦ RADIATION DOSES ♦ RADIOTHERAPY ♦ VEINS
Abstract Purpose: Prophylactic cranial irradiation (PCI) is a clinical technique used to reduce the incidence of brain metastasis and improve overall survival in select patients with acute lymphoblastic leukemia and small-cell lung cancer. We examined whether PCI could benefit breast cancer patients at high risk of developing brain metastases. Methods: We utilized our mouse model in which 500k green fluorescent protein (GFP)-labeled breast cancer cells injected into the tail vein of SCID/Beige mice resulted in brain metastases in approximately two-thirds of untreated mice. To test the efficacy of PCI, one set of mice was irradiated five days after cell injection with a single fraction of 4-Gy (two 2-Gy opposing fields) whole-brain irradiation on the XRAD 225Cx small-animal irradiator. Four controls were included: a non-irradiated group, a group irradiated two days prior to cell injection, and two groups irradiated 3 or 6 weeks after cell injection. Mice were sacrificed four and eight weeks post-injection and were evaluated for the presence of brain metastases on a fluorescent stereomicroscope. Results: The incidence of brain metastasis in the non-irradiated group was 77% and 90% at four and eight weeks, respectively. The PCI group had a significantly lower incidence, 20% and 30%, whereas the other three control groups had incidence rates similar to the non-treated control (70% to 100%). Further, the number of metastases and the metastatic burden were also significantly lower in the PCI group compared to all other groups. Conclusion: The timing of irradiation to treat subclinical disease is critical, as a small dose of whole-brain irradiation given five days after cell injection abrogated tumor burden by greater than 90%, but had no effect when administered twenty-one days after cell injection. PCI is likely to benefit breast cancer patients at high risk of developing brain metastases and should be strongly considered in the clinic.
ISSN 00942405
Educational Use Research
Learning Resource Type Article
Publisher Date 2015-06-15
Publisher Place United States
Journal Medical Physics
Volume Number 42
Issue Number 6


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