The new biological interaction cross-section-based repairable–homologically repairable (RHR) damage formulation for radiation-induced cellular inactivation, repair, misrepair, and apoptosis was applied to optimize radiation therapy. This new formulation implies renewed thinking about biologically optimized radiation therapy, suggesting that most TP53 intact normal tissues are low-dose hypersensitive (LDHS) and low-dose apoptotic (LDA). This generates a fractionation window in LDHS normal tissues, indicating that the maximum dose to organs at risk should be ≤2.3 Gy/Fr, preferably of low LET. This calls for biologically optimized treatments using a few high tumor dose-intensity-modulated light ion beams, thereby avoiding secondary cancer risks and generating a real tumor cure without a caspase-3-induced accelerated tumor cell repopulation. Light ions with the lowest possible LET in normal tissues and high LET only in the tumor imply the use of the lightest ions, from lithium to boron. The high microscopic heterogeneity in the tumor will cause local microscopic cold spots; thus, in the last week of curative ion therapy, when there are few remaining viable tumor clonogens randomly spread in the target volume, the patient should preferably receive the last 10 GyE via low LET, ensuring perfect tumor coverage, a high cure probability, and a reduced risk for adverse normal tissue reactions. Interestingly, such an approach would also ensure a steeper rise in tumor cure probability and a higher complication-free cure, as the few remaining clonogens are often fairly well oxygenated, eliminating a shallower tumor response due to inherent ion beam heterogeneity. With the improved fractionation proposal, these approaches may improve the complication-free cure probability by about 10–25% or even more.
基于新型生物相互作用截面的可修复-同源可修复（RHR）损伤模型被应用于优化放射治疗，该模型描述了辐射诱导的细胞失活、修复、错误修复及凋亡过程。这一新模型促使我们重新思考生物优化放射治疗策略，指出大多数TP53完整的正常组织具有低剂量超敏性（LDHS）和低剂量凋亡（LDA）特性。这为LDHS正常组织创造了一个分次剂量窗口，提示危险器官的最大单次照射剂量应≤2.3 Gy/次，且宜采用低传能线密度（LET）辐射。这要求采用生物优化的治疗方案，即使用少数高肿瘤剂量强度调制的轻离子束进行治疗，从而避免继发癌症风险，并实现真正的肿瘤根治，同时规避caspase-3诱导的肿瘤细胞加速再增殖效应。在正常组织中保持尽可能低的LET、仅在肿瘤中实现高LET的特性，意味着应选用从锂到硼的最轻离子。肿瘤内部高度的微观异质性会导致局部微观冷区；因此，在根治性离子治疗的最后一周，当靶区内随机散布的存活肿瘤克隆原所剩无几时，患者最好接受最后10 GyE的低LET照射，以确保完美的肿瘤覆盖、提高治愈概率并降低正常组织不良反应风险。值得注意的是，由于残存的少量克隆原通常氧合状态较好，这种方法还能确保肿瘤治愈概率更陡峭地上升，并实现更高的无并发症治愈率，从而消除因离子束固有异质性导致的肿瘤反应平缓现象。结合改进的分次照射方案，这些策略有望将无并发症治愈概率提高约10-25%甚至更高。
TP53 and the Ultimate Biological Optimization Steps of Curative Radiation Oncology
肿瘤(癌症)患者之家