Willers Henning, Held Kathryn D
Department of Radiation Oncology, Harvard Medical School/Massachusetts General Hospital, Cox 3, 55 Fruit Street, Boston, MA 02114, USA.
Hematol Oncol Clin North Am. 2006 Feb;20(1):1-24. doi: 10.1016/j.hoc.2006.01.007.
The authors have reviewed some of the most important and established factors that determine the effectiveness of IR in a wide variety of tumor types and normal tissues: the significance of increasing the dose of radiation, the importance of altered fractionation schemes, such as accelerated fractionation or hyperfractionation, and the need to address tumor hypoxia. Therapeutic gain can only be achieved when the increased tumor toxicity produced by these treatment modifications is balanced against injury to early-responding as well as late-responding normal tissues. In the not too distant future, therapeutic gain may be maximized by individualized therapies that are based on phenotypic and genotypic profiling of tumors and patients. For example, predicting which tumors respond to IR with accelerated tumor cell repopulation will allow us to apply more intense accelerated treatment regimens, while subjecting patients with slowly proliferating tumors to less toxic therapies. Similarly, the combination of radiation therapy with molecularly targeted pharmacologic agents will be a highly individualized treatment approach. However, to some degree, radiation therapy will always have to remain unselective and indiscriminant to inactivate the last surviving dormant and probably drug-resistant tumor clonogen. Although the field of radiation biology is rapidly evolving as a result of advances in molecular biology and genetics and the availability of new technologies, a thorough understanding of the established factors that determine radiation responses will remain an important prerequisite for the successful application of multimodal cancer therapies and molecularly targeted approaches in the future.
作者回顾了一些最重要且已确定的因素，这些因素决定了放射治疗（IR）在多种肿瘤类型和正常组织中的有效性：增加辐射剂量的意义、改变分割方案（如加速分割或超分割）的重要性以及解决肿瘤缺氧问题的必要性。只有当这些治疗调整所产生的肿瘤毒性增加与对早期反应和晚期反应正常组织的损伤相平衡时，才能实现治疗增益。在不久的将来，通过基于肿瘤和患者表型及基因型分析的个体化治疗，治疗增益可能会最大化。例如，预测哪些肿瘤对伴有加速肿瘤细胞再增殖的放射治疗有反应，将使我们能够应用更强烈的加速治疗方案，而让肿瘤增殖缓慢的患者接受毒性较小的治疗。同样，放射治疗与分子靶向药物的联合将是一种高度个体化的治疗方法。然而，在某种程度上，放射治疗将始终不得不保持非选择性和非特异性，以灭活最后存活的休眠且可能耐药的肿瘤克隆原。尽管由于分子生物学和遗传学的进展以及新技术的可用性，放射生物学领域正在迅速发展，但透彻理解决定放射反应的既定因素仍将是未来成功应用多模式癌症治疗和分子靶向方法的重要前提。
