本立场文件由 NRG 肿瘤粒子治疗工作组牵头，重点关注临床质子治疗 (PT) 中的相对生物效应 (RBE) 概念，旨在为下一代 PT 临床试验提供建议。研究和使用 RBE 的最佳实践，这可能会偏离当前相对于光子的标准质子 RBE 值 1.1。第 1 部分回顾了当前的临床应用和实践，给出了 RBE 的背景和历史。 RBE 变化的证据与线性能量转移 (LET) 的概念一起提出。然后回顾肿瘤放射生物学、正常组织限制以及考虑 LET 和 RBE 的治疗计划的相互交织的性质。第 2 部分总结了当前和过去的临床数据，然后建议下一步探索和使用改进 RBE 动态模型的工具。第 3 部分探讨了下一代前瞻性临床试验的途径和方法，目标是优化 RBE，使其更能反映临床现实，并可在试验中部署以进行临床验证和患者间比较。这些概念为第 4 部分中回顾的个性化生物治疗奠定了基础。最后，我们进行了总结，包括临床 PT 的短期和长期科学焦点。根据现有的更多生物学数据，审查和考虑了在治疗计划中使用 RBE 的实用性和能力。 LET 优化的中间步骤被总结并提出作为通向特定案例 RBE 规划最终目标的潜在桥梁，该目标可以作为近期质子试验中的假设生成工具来实现。由 Elsevier Inc. 出版。

This position paper, led by the NRG Oncology Particle Therapy Work Group, focuses on the concept of relative biologic effect (RBE) in clinical proton therapy (PT), with the goal of providing recommendations for the next-generation clinical trials with PT on the best practice of investigating and using RBE, which could deviate from the current standard proton RBE value of 1.1 relative to photons. In part 1, current clinical utilization and practice are reviewed, giving the context and history of RBE. Evidence for variation in RBE is presented along with the concept of linear energy transfer (LET). The intertwined nature of tumor radiobiology, normal tissue constraints, and treatment planning with LET and RBE considerations is then reviewed. Part 2 summarizes current and past clinical data and then suggests the next steps to explore and employ tools for improved dynamic models for RBE. In part 3, approaches and methods for the next generation of prospective clinical trials are explored, with the goal of optimizing RBE to be both more reflective of clinical reality and also deployable in trials to allow clinical validation and interpatient comparisons. These concepts provide the foundation for personalized biologic treatments reviewed in part 4. Finally, we conclude with a summary including short- and long-term scientific focus points for clinical PT. The practicalities and capacity to use RBE in treatment planning are reviewed and considered with more biological data in hand. The intermediate step of LET optimization is summarized and proposed as a potential bridge to the ultimate goal of case-specific RBE planning that can be achieved as a hypothesis-generating tool in near-term proton trials.Published by Elsevier Inc.