Radiation treatment (RT) is a mainstay treatment for many types of cancer. Recommendations for RT and the radiation plan are individualized to each patient, taking into consideration the patient’s tumor pathology, staging, anatomy, and other clinical characteristics. Information on germline mutations and somatic tumor mutations is at present rarely used to guide specific clinical decisions in RT. Many genes, such asATM,andBRCA1/2, have been identified in the laboratory to confer radiation sensitivity. However, our understanding of the clinical significance of mutations in these genes remains limited and, as individual mutations in such genes can be rare, their impact on tumor response and toxicity remains unclear. Current guidelines, including those from the National Comprehensive Cancer Network (NCCN), provide limited guidance on how genetic results should be integrated into RT recommendations. With an increasing understanding of the molecular underpinning of radiation response, genomically-guided RT can inform decisions surrounding RT dose, volume, concurrent therapies, and even omission to further improve oncologic outcomes and reduce risks of toxicities. Here, we review existing evidence from laboratory, pre-clinical, and clinical studies with regard to how genetic alterations may affect radiosensitivity. We also summarize recent data from clinical trials and explore potential future directions to utilize genetic data to support clinical decision-making in developing a pathway toward personalized RT.
放射治疗（RT）是多种癌症的主要治疗手段。针对放射治疗的建议和放疗方案需根据每位患者的具体情况进行个体化制定，需综合考虑患者的肿瘤病理学特征、分期、解剖结构及其他临床特点。目前，生殖细胞突变和体细胞肿瘤突变信息在指导放射治疗具体临床决策中应用较少。实验室研究发现，许多基因（如ATM、BRCA1/2等）可影响放射敏感性。然而，我们对这些基因突变临床意义的认识仍然有限，且由于此类基因的个体突变较为罕见，其对肿瘤反应和毒副作用的实际影响尚不明确。现行指南（包括美国国家综合癌症网络NCCN指南）关于如何将基因检测结果纳入放疗决策的指导较为有限。随着对放射反应分子机制的深入理解，基因组指导的放射治疗可为放疗剂量、照射范围、联合治疗方案乃至是否豁免放疗等决策提供依据，从而进一步提高肿瘤治疗效果并降低毒性风险。本文综述了来自实验室研究、临床前研究及临床研究的现有证据，探讨基因变异如何影响放射敏感性。同时，我们总结了近期临床试验数据，并探索未来利用基因数据支持临床决策的潜在发展方向，以推动个性化放射治疗路径的建立。
Moving the Needle Forward in Genomically-Guided Precision Radiation Treatment
肿瘤(癌症)患者之家