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. Conclusion: 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.
背景：胰腺癌是最具侵袭性和致死性的癌症之一，亟需新的治疗策略。基于其生物学和物理特性，粒子放射治疗可能为克服胰腺癌的放射抵抗性提供途径。在各类粒子中，氦离子疗法因其能在实现最佳适形性的同时保护周围正常组织而成为一种极具吸引力的治疗选择。本研究旨在评估氦离子照射对胰腺癌的体外细胞毒性效应。 方法：采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，并联合吉西他滨处理。光子照射使用生物舱X射线辐照仪完成，氦离子照射则在海德堡离子束治疗中心（HIT）采用扫描束流技术通过展宽布拉格峰实现。通过克隆形成实验测定对胰腺癌细胞的细胞毒性效应，并将生存曲线与通过修正微剂量动力学模型（mMKM）计算的理论预测曲线进行比较。 结果：氦离子照射的实验相对生物学效应（RBE）范围为1.0至1.7。通过mMKM计算获得的预测生存曲线与实验生存曲线吻合。在AsPC-1、BxPC-3和Panc-1细胞系中主要观察到叠加的细胞毒性效应。 结论：本研究结果证实了氦离子放射治疗对胰腺癌的体外细胞毒性效力，同时验证了mMKM计算在氦离子治疗胰腺癌中的生物学计划优化能力与应用价值。氦离子照射联合吉西他滨化疗在胰腺癌细胞系中主要产生叠加的细胞毒性效应。本研究数据可为未来氦离子放射治疗胰腺癌的实验与临床研究提供放射生物学基础。
Evaluation of Helium Ion Radiotherapy in Combination with Gemcitabine in Pancreatic Cancer In Vitro
肿瘤(癌症)患者之家