Lind B K, Persson L M, Edgren M R, Hedlöf I, Brahme A
Medical Radiation Physics, Department of Oncology-Pathology, Karolinska Institutet, Stockholm University, SE-171 76 Stockholm, Sweden.
Radiat Res. 2003 Sep;160(3):366-75. doi: 10.1667/0033-7587(2003)160[0366:rrdmbo]2.0.co;2.
The advent of intensity-modulated radiation therapy makes it increasingly important to model the response accurately when large volumes of normal tissues are irradiated by controlled graded dose distributions aimed at maximizing tumor cure and minimizing normal tissue toxicity. The cell survival model proposed here is very useful and flexible for accurate description of the response of healthy tissues as well as tumors in classical and truly radiobiologically optimized radiation therapy. The repairable-conditionally repairable (RCR) model distinguishes between two different types of damage, namely the potentially repairable, which may also be lethal, i.e. if unrepaired or misrepaired, and the conditionally repairable, which may be repaired or may lead to apoptosis if it has not been repaired correctly. When potentially repairable damage is being repaired, for example by nonhomologous end joining, conditionally repairable damage may require in addition a high-fidelity correction by homologous repair. The induction of both types of damage is assumed to be described by Poisson statistics. The resultant cell survival expression has the unique ability to fit most experimental data well at low doses (the initial hypersensitive range), intermediate doses (on the shoulder of the survival curve), and high doses (on the quasi-exponential region of the survival curve). The complete Poisson expression can be approximated well by a simple bi-exponential cell survival expression, S(D) = e(-aD) + bDe(-cD), where the first term describes the survival of undamaged cells and the last term represents survival after complete repair of sublethal damage. The bi-exponential expression makes it easy to derive D(0), D(q), n and alpha, beta values to facilitate comparison with classical cell survival models.
调强放射治疗的出现使得当大量正常组织受到旨在使肿瘤治愈最大化和正常组织毒性最小化的可控梯度剂量分布照射时，准确模拟其反应变得越来越重要。本文提出的细胞存活模型对于准确描述健康组织以及经典和真正放射生物学优化放射治疗中的肿瘤反应非常有用且灵活。可修复 - 条件可修复（RCR）模型区分两种不同类型的损伤，即潜在可修复的损伤，这种损伤也可能是致命的，也就是说，如果未修复或修复错误；以及条件可修复的损伤，如果未正确修复，它可能被修复或可能导致细胞凋亡。当潜在可修复损伤正在被修复时，例如通过非同源末端连接，条件可修复损伤可能还需要通过同源修复进行高保真校正。假设这两种类型损伤的诱导都由泊松统计描述。所得的细胞存活表达式具有独特的能力，能够在低剂量（初始超敏范围）、中等剂量（存活曲线的肩部）和高剂量（存活曲线的准指数区域）下很好地拟合大多数实验数据。完整的泊松表达式可以通过一个简单的双指数细胞存活表达式很好地近似，即S(D) = e(-aD) + bDe(-cD)，其中第一项描述未受损细胞的存活，最后一项表示亚致死损伤完全修复后的存活。双指数表达式便于推导D(0)、D(q)、n以及α、β值，以利于与经典细胞存活模型进行比较。
