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Abstract：
BACKGROUND: Pancreatic cancer is one of the most aggressive and lethal cancers. New treatment strategies are highly warranted. Particle radiotherapy could offer a way to overcome the radioresistant nature of pancreatic cancer because of its biological and physical characteristics. Within particles, helium ions represent an attractive therapy option to achieve the highest possible conformity while at the same time protecting the surrounding normal tissue. The aim of this study was to evaluate the cytotoxic efficacy of helium ion irradiation in pancreatic cancer in vitro.
METHODS: Human pancreatic cancer cell lines AsPC-1, BxPC-3 and Panc-1 were irradiated with photons and helium ions at various doses and treated with gemcitabine. Photon irradiation was performed with a biological cabin X-ray irradiator, and helium ion irradiation was performed with a spread-out Bragg peak using the raster scanning technique at the Heidelberg Ion Beam Therapy Center (HIT). The cytotoxic effect on pancreatic cancer cells was measured with clonogenic survival. The survival curves were compared to the predicted curves that were calculated via the modified microdosimetric kinetic model (mMKM).
RESULTS: The experimental relative biological effectiveness (RBE) of helium ion irradiation ranged from 1.0 to 1.7. The predicted survival curves obtained via mMKM calculations matched the experimental survival curves. Mainly additive cytotoxic effects were observed for the cell lines AsPC-1, BxPC-3 and Panc-1.
CONCLUSIONS: Our results demonstrate the cytotoxic efficacy of helium ion radiotherapy in pancreatic cancer in vitro as well as the capability of mMKM calculation and its value for biological plan optimization in helium ion therapy for pancreatic cancer. A combined treatment of helium irradiation and chemotherapy with gemcitabine leads to mainly additive cytotoxic effects in pancreatic cancer cell lines. The data generated in this study may serve as the radiobiological basis for future experimental and clinical works using helium ion radiotherapy in pancreatic cancer treatment.
METHODS: Human pancreatic cancer cell lines AsPC-1, BxPC-3 and Panc-1 were irradiated with photons and helium ions at various doses and treated with gemcitabine. Photon irradiation was performed with a biological cabin X-ray irradiator, and helium ion irradiation was performed with a spread-out Bragg peak using the raster scanning technique at the Heidelberg Ion Beam Therapy Center (HIT). The cytotoxic effect on pancreatic cancer cells was measured with clonogenic survival. The survival curves were compared to the predicted curves that were calculated via the modified microdosimetric kinetic model (mMKM).
RESULTS: The experimental relative biological effectiveness (RBE) of helium ion irradiation ranged from 1.0 to 1.7. The predicted survival curves obtained via mMKM calculations matched the experimental survival curves. Mainly additive cytotoxic effects were observed for the cell lines AsPC-1, BxPC-3 and Panc-1.
CONCLUSIONS: Our results demonstrate the cytotoxic efficacy of helium ion radiotherapy in pancreatic cancer in vitro as well as the capability of mMKM calculation and its value for biological plan optimization in helium ion therapy for pancreatic cancer. A combined treatment of helium irradiation and chemotherapy with gemcitabine leads to mainly additive cytotoxic effects in pancreatic cancer cell lines. The data generated in this study may serve as the radiobiological basis for future experimental and clinical works using helium ion radiotherapy in pancreatic cancer treatment.
摘要：
背景：胰腺癌是最具侵袭性和致死性的癌症之一。新的治疗策略是非常必要的。由于其生物学和物理特性，粒子放射疗法可以为克服胰腺癌的放射抗性提供一种方法。在粒子内，氦离子代表了一种有吸引力的治疗选择，以实现尽可能高的一致性，同时保护周围的正常组织。这项研究的目的是评估氦离子照射在体外胰腺癌中的细胞毒性功效。
方法：用不同剂量的光子和氦离子照射人胰腺癌细胞系AsPC-1，BxPC-3和Panc-1，并用吉西他滨处理。用生物舱X射线辐射器进行光子辐照，在海德堡离子束治疗中心（HIT）使用光栅扫描技术，以扩展的布拉格峰进行氦离子辐照。对胰腺癌细胞的细胞毒性作用用克隆性存活来测量。将存活曲线与通过改进的微剂量动力学模型(mMKM)计算的预测曲线进行比较。
结果：氦离子辐照的实验相对生物有效性（RBE）范围为1.0至1.7。通过mMKM计算获得的预测存活曲线与实验存活曲线相匹配。对于细胞系AsPC-1、BxPC-3和Panc-1观察到主要的加性细胞毒性作用。
结论：我们的结果证明了氦离子放疗对胰腺癌的体外细胞毒性功效，以及mMKM计算的能力及其在氦离子治疗胰腺癌的生物学计划优化中的价值。吉西他滨对氦气照射和化学疗法的联合治疗在胰腺癌细胞系中主要导致累加的细胞毒性作用。本研究中产生的数据可作为未来在胰腺癌治疗中使用氦离子放射治疗的实验和临床工作的放射生物学基础。
方法：用不同剂量的光子和氦离子照射人胰腺癌细胞系AsPC-1，BxPC-3和Panc-1，并用吉西他滨处理。用生物舱X射线辐射器进行光子辐照，在海德堡离子束治疗中心（HIT）使用光栅扫描技术，以扩展的布拉格峰进行氦离子辐照。对胰腺癌细胞的细胞毒性作用用克隆性存活来测量。将存活曲线与通过改进的微剂量动力学模型(mMKM)计算的预测曲线进行比较。
结果：氦离子辐照的实验相对生物有效性（RBE）范围为1.0至1.7。通过mMKM计算获得的预测存活曲线与实验存活曲线相匹配。对于细胞系AsPC-1、BxPC-3和Panc-1观察到主要的加性细胞毒性作用。
结论：我们的结果证明了氦离子放疗对胰腺癌的体外细胞毒性功效，以及mMKM计算的能力及其在氦离子治疗胰腺癌的生物学计划优化中的价值。吉西他滨对氦气照射和化学疗法的联合治疗在胰腺癌细胞系中主要导致累加的细胞毒性作用。本研究中产生的数据可作为未来在胰腺癌治疗中使用氦离子放射治疗的实验和临床工作的放射生物学基础。
