Department of Medical Physics and Biomedical Engineering, University College London, London, UK.
Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Belfast, UK.
Br J Radiol. 2019 Jan;92(1093):20180004. doi: 10.1259/bjr.20180004. Epub 2018 Jul 26.
Proton radiotherapy is undergoing rapid expansion both within the UK and internationally, but significant challenges still need to be overcome if maximum benefit is to be realised from this technique. One major limitation is the persistent uncertainty in proton relative biological effectiveness (RBE). While RBE values are needed to link proton radiotherapy to our existing experience with photon radiotherapy, RBE remains poorly understood and is typically incorporated as a constant dose scaling factor of 1.1 in clinical plans. This is in contrast to extensive experimental evidence indicating that RBE is a function of dose, tissue type, and proton linear energy transfer, among other parameters. In this article, we discuss the challenges associated with obtaining clinically relevant values for proton RBE through commonly-used assays, and highlight the wide range of other experimental end points which can inform our understanding of RBE. We propose that accurate and robust optimization of proton radiotherapy ultimately requires a multiscale understanding of RBE, integrating subcellular, cellular, and patient-level processes.
质子放射治疗在英国和国际上都在迅速发展，但如果要从这项技术中获得最大的效益，仍需要克服重大挑战。一个主要的限制是质子相对生物效应（RBE）持续存在的不确定性。虽然需要 RBE 值将质子放射治疗与我们现有的光子放射治疗经验联系起来，但 RBE 仍未被充分理解，并且在临床计划中通常作为常数剂量缩放因子 1.1 进行合并。这与广泛的实验证据形成对比，这些证据表明 RBE 是剂量、组织类型和质子线性能量传递等参数的函数。在本文中，我们讨论了通过常用测定法获得与临床相关的质子 RBE 值所面临的挑战，并强调了其他许多可以帮助我们了解 RBE 的实验终点。我们提出，准确和稳健的质子放射治疗优化最终需要对 RBE 进行多尺度理解，整合亚细胞、细胞和患者水平的过程。
