Harrabi Semi B, Adeberg Sebastian, Winter Marcus, Haberer Thomas, Debus Jürgen, Weber Klaus-Josef
Department of Radiation Oncology, University Hospital of Heidelberg, Im Neuenheimer Feld 400, Heidelberg 69120, Germany Heidelberg Ion Therapy Center (HIT), Im Neuenheimer Feld 450, Heidelberg 69120, Germany
Department of Radiation Oncology, University Hospital of Heidelberg, Im Neuenheimer Feld 400, Heidelberg 69120, Germany.
J Radiat Res. 2016 Mar;57(2):110-4. doi: 10.1093/jrr/rrv097. Epub 2016 Jan 7.
Densely ionizing charged particle irradiation offers physical as well as biological advantages compared with photon irradiation. Radiobiological data for the combination of such particle irradiation (i.e. therapeutic carbon ions) with commonly used chemotherapeutics are still limited. Recent in vitro results indicate a general prevalence of additive cytotoxic effects in combined treatments, but an extension of established multimodal treatment regimens with photons to the inclusion of particle therapy needs to evaluate possible peculiarities of using high linear energy transfer (LET) radiation. The present study investigates the effect of combined radiochemotherapy using gemcitabine and high-LET irradiation with therapeutic carbon ions. In particular, the earlier observation of S-phase specific radiosensitization with photon irradiation should be evaluated with carbon ions. In the absence of the drug gemcitabine, carbon ion irradiation produced the typical survival behavior seen with X-rays-increased relative biological efficiency, and depletion of the survival curve's shoulder. By means of serum deprivation and subsequent replenishment, ∼70% S-phase content of the cell population was achieved, and such preparations showed radioresistance in both treatment arms-,photon and carbon ion irradiation. Combined modality treatment with gemcitabine caused significant reduction of clonogenic survival especially for the S-phase cells. WIDR cells exhibited S-phase-specific radioresistance with high-LET irradiation, although this was less pronounced than for X-ray exposure. The combined treatment with therapeutic carbon ions and gemcitabine caused the resistance phenomenon to disappear phenotypically.
与光子辐射相比，密集电离带电粒子辐射具有物理和生物学优势。此类粒子辐射（即治疗用碳离子）与常用化疗药物联合使用的放射生物学数据仍然有限。最近的体外研究结果表明，联合治疗中细胞毒性作用通常具有相加性，但将已确立的光子多模式治疗方案扩展到包含粒子治疗，需要评估使用高线性能量传递（LET）辐射可能存在的特殊性。本研究调查了吉西他滨与治疗用碳离子高LET辐射联合放化疗的效果。特别是，应该用碳离子评估早期观察到的光子辐射S期特异性放射增敏作用。在没有吉西他滨药物的情况下，碳离子辐射产生了与X射线相同的典型存活行为——相对生物效应增加，存活曲线的肩部消失。通过血清剥夺和随后的补充，细胞群体的S期含量达到了约70%，并且这种制剂在光子和碳离子辐射两个治疗组中均显示出放射抗性。吉西他滨联合治疗显著降低了克隆形成存活率，尤其是对S期细胞。WIDR细胞在高LET辐射下表现出S期特异性放射抗性，尽管这种抗性不如X射线照射时明显。治疗用碳离子与吉西他滨联合治疗使抗性现象在表型上消失。
