Nahum Alan E
Clatterbridge Cancer Centre, Bebington, UK.
Clin Oncol (R Coll Radiol). 2015 May;27(5):260-9. doi: 10.1016/j.clon.2015.02.001. Epub 2015 Mar 18.
If the α/β ratio is high (e.g. 10 Gy) for tumour clonogen killing, but low (e.g. 3 Gy) for late normal tissue complications, then delivering external beam radiotherapy in a large number (20-30) of small (≈2 Gy) dose fractions should yield the highest 'therapeutic ratio'; this is demonstrated via the linear-quadratic model of cell killing. However, this 'conventional wisdom' is increasingly being challenged, partly by the success of stereotactic body radiotherapy (SBRT) or stereotactic ablative radiotherapy (SABR) extreme hypofractionation regimens of three to five large fractions for early stage non-small cell lung cancer and partly by indications that for certain tumours (prostate, breast) the α/β ratio may be of the same order or even lower than that characterising late complications. It is shown how highly conformal dose delivery combined with quasi-parallel normal tissue behaviour (n close to 1) enables 'safe' hypofractionation; this can be predicted by the (α/β)eff concept for normal tissues. Recent analyses of the clinical outcomes of non-small cell lung cancer radiotherapy covering 'conventional' hyper- to extreme hypofractionation (stereotactic ablative radiotherapy) regimens are consistent with linear-quadratic radiobiology, even at the largest fraction sizes, despite there being theoretical reasons to expect 'LQ violation' above a certain dose. Impairment of re-oxygenation between fractions and the very high (α/β) for hypoxic cells can complicate the picture regarding the analysis of clinical outcomes; it has also been suggested that vascular damage may play a role for very large dose fractions. Finally, the link between high values of (α/β)eff and normal-tissue sparing for quasi-parallel normal tissues, thereby favouring hypofractionation, may be particularly important for proton therapy, but more generally, improved conformality, achieved by whatever technique, can be translated into individualisation of both prescription dose and fraction number via the 'isotoxic' (iso-normal tissue complication probability) concept.
如果肿瘤克隆源性细胞杀灭的α/β比值较高（例如10 Gy），而晚期正常组织并发症的α/β比值较低（例如3 Gy），那么采用大量（20 - 30次）小剂量（约2 Gy）的外照射放疗应能产生最高的“治疗比”；这通过细胞杀灭的线性二次模型得到了证实。然而，这种“传统观念”正日益受到挑战，部分原因是立体定向体部放疗（SBRT）或立体定向消融放疗（SABR）对早期非小细胞肺癌采用三到五个大分割的极端低分割方案取得了成功，部分原因是有迹象表明，对于某些肿瘤（前列腺癌、乳腺癌），α/β比值可能与表征晚期并发症的比值处于同一量级，甚至更低。研究表明，高度适形的剂量给予与近似平行的正常组织行为（n接近1）相结合能够实现“安全”的低分割；这可以通过正常组织的（α/β）eff概念来预测。最近对非小细胞肺癌放疗的临床结果分析涵盖了从“传统”的超分割到极端低分割（立体定向消融放疗）方案，即使在最大分割剂量下，也与线性二次放射生物学一致，尽管存在理论上的原因预计在超过一定剂量时会出现“LQ违背”。分割间再氧合的受损以及缺氧细胞的非常高的（α/β）值会使临床结果分析的情况变得复杂；也有人提出血管损伤可能在非常大的分割剂量中起作用。最后，（α/β）eff的高值与近似平行正常组织的正常组织保护之间的联系，从而有利于低分割，这对于质子治疗可能尤为重要，但更一般地说，无论通过何种技术实现的更好的适形性，都可以通过“等毒性”（等正常组织并发症概率）概念转化为处方剂量和分割次数的个体化。
