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Title: Characterizing the potency and impact of carbon ion therapy in a primary mouse model of soft tissue sarcoma

Abstract

Carbon ion therapy (CIT) offers several potential advantages for treating cancers compared with X-ray and proton radiotherapy, including increased biological efficacy and more conformal dosimetry. However, CIT potency has not been characterized in primary tumor animal models. Here in this paper, we calculate the relative biological effectiveness (RBE) of carbon ions compared to X-rays in an autochthonous mouse model of soft tissue sarcoma. We used Cre/loxP technology to generate primary sarcomas in KrasLSL-G12D/+; p53fl/fl mice. Primary tumors were irradiated with a single fraction of carbon ions (10 Gy), X-rays (20, 25, or 30 Gy), or observed as controls. The RBE was calculated by determining the dose of X-rays that resulted in similar time to post-treatment tumor volume quintupling and growth rate as 10 Gy carbon ions. The median tumor volume quintupling time and growth rate of sarcomas treated with 10 Gy carbon ions and 30 Gy X-rays were similar: 27.3 days and 28.1 days, and 0.060 mm3/day and 0.059 mm3/day, respectively. Tumors treated with lower doses of X-rays had faster regrowth. Thus, the RBE of carbon ions in this primary tumor model is 3. When isoeffective treatments of carbon ions and X-rays were compared, we observed significant differences in tumormore » growth kinetics, proliferative indices, and immune infiltrates. We found that carbon ions were three times as potent as X-rays in this aggressive tumor model and identified unanticipated differences in radiation response that may have clinical implications.« less

Authors:
 [1]; ORCiD logo [2];  [2];  [1];  [3];  [1];  [4];  [4];  [5];  [6];  [1];  [1];  [1];  [1];  [6];  [5];  [1]
  1. Duke Univ., Durham, NC (United States). Radiation Oncology
  2. Duke Univ., Durham, NC (United States). Dept. of Pharmacology & Cancer Biology
  3. Brookhaven National Lab. (BNL), Upton, NY (United States)
  4. Univ. of Trento (Italy). Dept. of Physics
  5. Trento Inst. for Fundamental Physics and Applications (TIFPA), Povo (Italy)
  6. Duke Univ., Durham, NC (United States). Biostatistics and Bioinformatics
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Org.:
National Aeronautics and Space Administration (NASA)
OSTI Identifier:
1425188
Report Number(s):
BNL-200003-2018-JAAM
Journal ID: ISSN 1535-7163
Grant/Contract Number:
SC0012704
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Molecular Cancer Therapeutics
Additional Journal Information:
Journal Volume: 17; Journal Issue: 4; Journal ID: ISSN 1535-7163
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Brownstein, Jeremy Michael, Wisdom, Amy Jordan, Castle, Katherine D., Mowery, Yvonne M., Guida, Peter M., Lee, Chang-Lung, Tommasino, Francesco, La Tessa, Chiara, Scifoni, Emanuele, Gao, Junheng, Luo, Lixia, Da Silva Campos, Lorraine, Ma, Yan, Williams, Nerissa, Jung, Sin-Ho, Durante, Marco, and Kirsch, David G. Characterizing the potency and impact of carbon ion therapy in a primary mouse model of soft tissue sarcoma. United States: N. p., 2018. Web. doi:10.1158/1535-7163.MCT-17-0965.
Brownstein, Jeremy Michael, Wisdom, Amy Jordan, Castle, Katherine D., Mowery, Yvonne M., Guida, Peter M., Lee, Chang-Lung, Tommasino, Francesco, La Tessa, Chiara, Scifoni, Emanuele, Gao, Junheng, Luo, Lixia, Da Silva Campos, Lorraine, Ma, Yan, Williams, Nerissa, Jung, Sin-Ho, Durante, Marco, & Kirsch, David G. Characterizing the potency and impact of carbon ion therapy in a primary mouse model of soft tissue sarcoma. United States. doi:10.1158/1535-7163.MCT-17-0965.
Brownstein, Jeremy Michael, Wisdom, Amy Jordan, Castle, Katherine D., Mowery, Yvonne M., Guida, Peter M., Lee, Chang-Lung, Tommasino, Francesco, La Tessa, Chiara, Scifoni, Emanuele, Gao, Junheng, Luo, Lixia, Da Silva Campos, Lorraine, Ma, Yan, Williams, Nerissa, Jung, Sin-Ho, Durante, Marco, and Kirsch, David G. Wed . "Characterizing the potency and impact of carbon ion therapy in a primary mouse model of soft tissue sarcoma". United States. doi:10.1158/1535-7163.MCT-17-0965.
@article{osti_1425188,
title = {Characterizing the potency and impact of carbon ion therapy in a primary mouse model of soft tissue sarcoma},
author = {Brownstein, Jeremy Michael and Wisdom, Amy Jordan and Castle, Katherine D. and Mowery, Yvonne M. and Guida, Peter M. and Lee, Chang-Lung and Tommasino, Francesco and La Tessa, Chiara and Scifoni, Emanuele and Gao, Junheng and Luo, Lixia and Da Silva Campos, Lorraine and Ma, Yan and Williams, Nerissa and Jung, Sin-Ho and Durante, Marco and Kirsch, David G.},
abstractNote = {Carbon ion therapy (CIT) offers several potential advantages for treating cancers compared with X-ray and proton radiotherapy, including increased biological efficacy and more conformal dosimetry. However, CIT potency has not been characterized in primary tumor animal models. Here in this paper, we calculate the relative biological effectiveness (RBE) of carbon ions compared to X-rays in an autochthonous mouse model of soft tissue sarcoma. We used Cre/loxP technology to generate primary sarcomas in KrasLSL-G12D/+; p53fl/fl mice. Primary tumors were irradiated with a single fraction of carbon ions (10 Gy), X-rays (20, 25, or 30 Gy), or observed as controls. The RBE was calculated by determining the dose of X-rays that resulted in similar time to post-treatment tumor volume quintupling and growth rate as 10 Gy carbon ions. The median tumor volume quintupling time and growth rate of sarcomas treated with 10 Gy carbon ions and 30 Gy X-rays were similar: 27.3 days and 28.1 days, and 0.060 mm3/day and 0.059 mm3/day, respectively. Tumors treated with lower doses of X-rays had faster regrowth. Thus, the RBE of carbon ions in this primary tumor model is 3. When isoeffective treatments of carbon ions and X-rays were compared, we observed significant differences in tumor growth kinetics, proliferative indices, and immune infiltrates. We found that carbon ions were three times as potent as X-rays in this aggressive tumor model and identified unanticipated differences in radiation response that may have clinical implications.},
doi = {10.1158/1535-7163.MCT-17-0965},
journal = {Molecular Cancer Therapeutics},
number = 4,
volume = 17,
place = {United States},
year = {Wed Feb 07 00:00:00 EST 2018},
month = {Wed Feb 07 00:00:00 EST 2018}
}

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