Department of Radiation Oncology, Duke University Health System, Durham, North Carolina.
Department of Pharmacology & Cancer Biology, Duke University, Durham, North Carolina.
Mol Cancer Ther. 2018 Apr;17(4):858-868. doi: 10.1158/1535-7163.MCT-17-0965. Epub 2018 Feb 7.
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. .
碳离子治疗 (CIT) 相比于 X 射线和质子放疗，在治疗癌症方面具有多种潜在优势，包括提高生物学疗效和更适形的剂量分布。然而，CIT 的疗效尚未在原发性肿瘤动物模型中得到证实。在这里，我们在一种软组织肉瘤的自发小鼠模型中计算了碳离子相对于 X 射线的相对生物学效应 (RBE)。我们使用 Cre/loxP 技术在小鼠中产生原发性肉瘤。原发性肿瘤接受单次碳离子照射 (10 Gy)、X 射线 (20 Gy、25 Gy 或 30 Gy) 或作为对照进行观察。通过确定导致与 10 Gy 碳离子相同的肿瘤体积五倍倍增时间和指数生长率的 X 射线剂量来计算 RBE。接受 10 Gy 碳离子和 30 Gy X 射线治疗的肉瘤的中位数肿瘤体积五倍倍增时间和指数生长率相似：分别为 27.3 天和 28.1 天，0.060 和 0.059 mm/天。接受较低剂量 X 射线治疗的肿瘤生长更快。因此，在这个原发性肿瘤模型中，碳离子的 RBE 为 3。当比较碳离子和 X 射线的等效治疗时，我们观察到肿瘤生长动力学、增殖指数和免疫浸润存在显著差异。我们发现，在这种侵袭性肿瘤模型中，碳离子比 X 射线有效 3 倍，并发现了意料之外的辐射反应差异，这可能具有临床意义。
