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

Journal Article · Wed Feb 07 00:00:00 EST 2018 · Molecular Cancer Therapeutics

DOI:https://doi.org/10.1158/1535-7163.MCT-17-0965· OSTI ID:1425188

Brownstein, Jeremy Michael ^[1]; Wisdom, Amy Jordan  ^[2]; Castle, Katherine D. ^[2]; Mowery, Yvonne M. ^[1]; Guida, Peter M. ^[3]; Lee, Chang-Lung ^[1]; Tommasino, Francesco ^[4]; La Tessa, Chiara ^[4]; Scifoni, Emanuele ^[5]; Gao, Junheng ^[6]; Luo, Lixia ^[1]; Da Silva Campos, Lorraine ^[1]; Ma, Yan ^[1]; Williams, Nerissa ^[1]; Jung, Sin-Ho ^[6]; Durante, Marco ^[5]; Kirsch, David G. ^[1]

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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

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.

• Research Organization: Brookhaven National Lab. (BNL), Upton, NY (United States)
• Sponsoring Organization: National Aeronautics and Space Administration (NASA)
• Grant/Contract Number: SC0012704
• OSTI ID: 1425188
• Report Number(s): BNL-200003-2018-JAAM
• Journal Information: Molecular Cancer Therapeutics, Vol. 17, Issue 4; ISSN 1535-7163
• Publisher: American Association for Cancer Research (AACR)
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES