Kanematsu Nobuyuki, Inaniwa Taku
Medical Physics Section, National Institute of Radiological Sciences Hospital, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan. Department of Accelerator and Medical Physics, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
Phys Med Biol. 2017 Feb 7;62(3):1062-1075. doi: 10.1088/1361-6560/62/3/1062. Epub 2017 Jan 12.
In carbon-ion radiotherapy, single-beam delivery each day in alternate directions has been common practice for efficient operation, taking advantage of the Bragg peak and the relative biological effectiveness (RBE) for uniform dose conformation to a tumor. Treatments are usually fractionated and treatment plans are evaluated with the total RBE-weighted dose; however, this is of limited relevance to the biological effect. In this study, we reformulate the biologically effective dose (BED) to normalize the dose-fractionation and cell-repopulation effects as well as the RBE of treating radiation, based on inactivation of a reference cell line by a reference carbon-ion radiation. The BED distribution virtually represents the biological effect of a treatment regardless of radiation modality or fractionation scheme. We applied the BED formulation to simplistic model treatments and to a preclinical survey for hypofractionation based on an actual prostate cancer treatment with carbon ions. The proposed formulation was demonstrated to be practical and to give theoretical implications. For a prostate cancer treatment in 12 fractions, the distributions of BED and of RBE-weighted dose were very similar. With hypofractionation, while the RBE-weighted dose distribution varied significantly, the BED distribution was nearly invariant, implying that carbon-ion radiotherapy would be effectively insensitive to fractionation. However, treatment evaluation with such a simplistic biological dose is intrinsically limited and must be complemented in practice by clinical experience and biological experiments.
在碳离子放射治疗中，为实现高效操作，每天沿交替方向进行单束照射是常见做法，利用布拉格峰和相对生物效应（RBE）使剂量均匀适形于肿瘤。治疗通常采用分次照射，治疗计划通过总RBE加权剂量进行评估；然而，这与生物效应的相关性有限。在本研究中，我们重新制定了生物有效剂量（BED），以基于参考碳离子辐射对参考细胞系的灭活作用，对剂量分割、细胞再增殖效应以及治疗性辐射的RBE进行归一化。无论辐射方式或分割方案如何，BED分布实际上都代表了一种治疗的生物效应。我们将BED公式应用于简单的模型治疗以及基于实际前列腺癌碳离子治疗的低分割临床前研究。结果表明，所提出的公式具有实用性并具有理论意义。对于12次分割的前列腺癌治疗，BED分布和RBE加权剂量分布非常相似。在低分割情况下，虽然RBE加权剂量分布变化显著，但BED分布几乎不变，这意味着碳离子放射治疗对分割的敏感性较低。然而，用这种简单的生物剂量进行治疗评估本质上是有限的，在实际应用中必须辅以临床经验和生物学实验。
