Glowa Christin, Karger Christian P, Brons Stephan, Zhao Dawen, Mason Ralph P, Huber Peter E, Debus Jürgen, Peschke Peter
Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany; Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany; National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg, Germany.
Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany; National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg, Germany.
Cancer Lett. 2016 Aug 10;378(2):97-103. doi: 10.1016/j.canlet.2016.05.013. Epub 2016 May 17.
To quantitatively study the impact of intrinsic tumor characteristics and microenvironmental factors on local tumor control after irradiation with carbon ((12)C-) ions and photons in an experimental prostate tumor model.
Three sublines of a syngeneic rat prostate tumor (R3327) differing in grading (highly (-H) moderately (-HI) or anaplastic (-AT1)) were irradiated with increasing single doses of either (12)C-ions or 6 MV photons in Copenhagen rats. Primary endpoint was local tumor control within 300 days. The relative biological effectiveness (RBE) of (12)C-ions was calculated from the dose at 50% tumor control probability (TCD50) of photons and (12)C-ions and was correlated with histological, physiological and genetic tumor parameters.
Experimental findings demonstrated that (i) TCD50-values between the three tumor sublines differed less for (12)C-ions (23.6-32.9 Gy) than for photons (38.2-75.7 Gy), (ii) the slope of the dose-response curve for each tumor line was steeper for (12)C-ions than for photons, and (iii) the RBE increased with tumor grading from 1.62 ± 0.11 (H) to 2.08 ± 0.13 (HI) to 2.30 ± 0.08 (AT1).
The response to (12)C-ions is less dependent on resistance factors as well as on heterogeneity between and within tumor sublines as compared to photons. A clear correlation between decreasing differentiation status and increasing RBE was found. (12)C-ions may therefore be a therapeutic option especially in patients with undifferentiated prostate tumors, expressing high resistance against photons.
在实验性前列腺肿瘤模型中，定量研究肿瘤内在特征和微环境因素对碳（¹²C -）离子和光子照射后局部肿瘤控制的影响。
在哥本哈根大鼠中，用递增的单剂量¹²C -离子或6 MV光子照射同基因大鼠前列腺肿瘤（R3327）的三个亚系，其分级不同（高分化（-H）、中分化（-HI）或间变（-AT1））。主要终点是300天内的局部肿瘤控制。根据光子和¹²C -离子在50%肿瘤控制概率（TCD50）时的剂量计算¹²C -离子的相对生物效应（RBE），并将其与肿瘤的组织学、生理学和遗传学参数相关联。
实验结果表明，（i）¹²C -离子照射下三个肿瘤亚系之间的TCD50值差异（23.6 - 32.9 Gy）小于光子照射下的差异（38.2 - 75.7 Gy）；（ii）每个肿瘤系的¹²C -离子剂量反应曲线斜率比光子的更陡；（iii）RBE随肿瘤分级从1.62±0.11（H）增加到2.08±0.13（HI）再增加到2.30±0.08（AT1）。
与光子相比，¹²C -离子的反应对耐药因素以及肿瘤亚系之间和内部的异质性依赖性较小。发现分化状态降低与RBE增加之间存在明显相关性。因此，¹²C -离子可能是一种治疗选择，特别是对于那些对光子具有高抗性的未分化前列腺肿瘤患者。
