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, we calculate the relative biological effectiveness (RBE) of carbon ions compared with X-rays in an autochthonous mouse model of soft tissue sarcoma. We used Cre/loxP technology to generate primary sarcomas in mice. Primary tumors were irradiated with a single fraction of carbon ions (10 Gy), X-rays (20 Gy, 25 Gy, or 30 Gy), or observed as controls. The RBE was calculated by determining the dose of X-rays that resulted in similar time to posttreatment tumor volume quintupling and exponential growth rate as 10 Gy carbon ions. The median tumor volume quintupling time and exponential growth rate of sarcomas treated with 10 Gy carbon ions and 30 Gy X-rays were similar: 27.3 and 28.1 days and 0.060 and 0.059 mm/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. .

Charged Particle and Conventional Radiotherapy: Current Implications as Partner for Immunotherapy

“…This is the first comprehensive study comparing CIRT and photon RT in combination with immune checkpoint inhibitors. However, the authors used the same physical dose of carbon ions and X-rays, despite the fact that RBE values of 1.5–2 based on clonogenic assay and an RBE of 3 based on growth delay assay for this cancer cell line have been reported, which makes the interpretation of the data biased [ 247 ]. To date, results on the efficacy of protons in combination with IO have not been reported.…”

Modeling Radioimmune Response—Current Status and Perspectives

“…One may suspect about a more efficient activation of the cGAS/STING pathway or an enhanced release of DAMPs ( 74 , 75 ). Considering the temporal pattern of the immune response, the time scales between irradiation and radiation effects are expected to be modified after high LET radiation, accounting for the more severe inflicted damage ( 76 , 77 ). A faster manifestation of cell inactivation as compared to low-LET radiation suggests a more rapid immune activation and T cell recruitment, while at the same time providing a stronger delay in tumor growth.…”

State-of-the-Art and Future Prospects of Ion Beam Therapy: Physical and Radiobiological Aspects

“…Sørensen [24] compare tumor control, acute skin reactions and late radiation induced fibrosis in a mouse model. Brownstein et al [25] analyze the response of primary sarcomas in a mouse model after carbon ion irradiation. Systematic studies using different sublines of a syngeneic prostate carcinoma model have been reported in [26] [27][28] [29].…”