氦离子放射治疗联合吉西他滨治疗胰腺癌的体外评估

Evaluation of Helium Ion Radiotherapy in Combination with Gemcitabine in Pancreatic Cancer In Vitro.

作者信息

Cepni Bahar, Tessonnier Thomas, Dokic Ivana, Brons Stephan, Tawk Bouchra, Mairani Andrea, Abdollahi Amir, Debus Jürgen, Herfarth Klaus, Liermann Jakob

机构信息

Heidelberg University School of Medicine, 69120 Heidelberg, Germany.

Heidelberg Ion-Beam Therapy Center (HIT), Department of Radiation Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany.

出版信息

Cancers (Basel). 2024 Apr 14;16(8):1497. doi: 10.3390/cancers16081497.

DOI:10.3390/cancers16081497

PMID:38672579

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11049166/

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.

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.

摘要

背景

胰腺癌是最具侵袭性和致命性的癌症之一。非常有必要采用新的治疗策略。粒子放疗因其生物学和物理特性，可能为克服胰腺癌的放射抗性提供一种方法。在粒子中，氦离子是一种有吸引力的治疗选择，可在实现尽可能高的适形性的同时保护周围正常组织。本研究的目的是评估氦离子照射对体外胰腺癌细胞的细胞毒性作用。

方法

将人胰腺癌细胞系AsPC-1、BxPC-3和Panc-1用不同剂量的光子和氦离子进行照射，并给予吉西他滨处理。光子照射使用生物舱X射线辐照仪进行，氦离子照射在海德堡离子束治疗中心（HIT）采用光栅扫描技术的扩展布拉格峰进行。用克隆形成存活率来测量对胰腺癌细胞的细胞毒性作用。将存活曲线与通过改进的微剂量动力学模型（mMKM）计算得到的预测曲线进行比较。