skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: WE-EF-BRA-10: Prophylactic Cranial Irradiation Reduces the Incidence of Brain Metastasis in a Mouse Model of Metastatic Breast Cancerr

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 threemore » 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.« less

Authors:
; ; ; ;  [1]
  1. MD Anderson Cancer Center, Houston, TX (United States)
Publication Date:
OSTI Identifier:
22572209
Resource Type:
Journal Article
Journal Name:
Medical Physics
Additional Journal Information:
Journal Volume: 42; Journal Issue: 6; Other Information: (c) 2015 American Association of Physicists in Medicine; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0094-2405
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 61 RADIATION PROTECTION AND DOSIMETRY; BRAIN; FLUORESCENCE; HAZARDS; INJECTION; IRRADIATION; LEUKEMIA; LUNGS; MAMMARY GLANDS; METASTASES; MICE; PATIENTS; PROTEINS; RADIATION DOSES; RADIOTHERAPY; VEINS

Citation Formats

Smith, D, Debeb, B, Larson, R, Diagaradjane, P, and Woodward, W. WE-EF-BRA-10: Prophylactic Cranial Irradiation Reduces the Incidence of Brain Metastasis in a Mouse Model of Metastatic Breast Cancerr. United States: N. p., 2015. Web. doi:10.1118/1.4925989.
Smith, D, Debeb, B, Larson, R, Diagaradjane, P, & Woodward, W. WE-EF-BRA-10: Prophylactic Cranial Irradiation Reduces the Incidence of Brain Metastasis in a Mouse Model of Metastatic Breast Cancerr. United States. doi:10.1118/1.4925989.
Smith, D, Debeb, B, Larson, R, Diagaradjane, P, and Woodward, W. Mon . "WE-EF-BRA-10: Prophylactic Cranial Irradiation Reduces the Incidence of Brain Metastasis in a Mouse Model of Metastatic Breast Cancerr". United States. doi:10.1118/1.4925989.
@article{osti_22572209,
title = {WE-EF-BRA-10: Prophylactic Cranial Irradiation Reduces the Incidence of Brain Metastasis in a Mouse Model of Metastatic Breast Cancerr},
author = {Smith, D and Debeb, B and Larson, R and Diagaradjane, P and Woodward, W},
abstractNote = {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.},
doi = {10.1118/1.4925989},
journal = {Medical Physics},
issn = {0094-2405},
number = 6,
volume = 42,
place = {United States},
year = {2015},
month = {6}
}