Medical Physics Department, Centro di Riferimento Oncologico, Aviano 33081, Italy.
Phys Med. 2012 Oct;28(4):296-306. doi: 10.1016/j.ejmp.2011.11.002. Epub 2011 Nov 26.
To extend the application of current radiation therapy (RT) based normal tissue complication probability (NTCP) models of radiation-induced fibrosis (RIF) of the breast to include the effects of fractionation, inhomogeneous dose, incomplete recovery, and time after the end of radiotherapy in partial breast irradiation (PBI).
An NTCP Lyman model with biologically effective uniform dose (BEUD) with and without a correction for the effect of incomplete repair was used. The time to occurrence of RIF was also taken into account. The radiobiological parameters were determined by fitting incidences of moderate/severe RIF in published randomized studies on RT of the breast. The NTCP model was used to calculate the risk of toxicity in 35 patients treated with intensity modulated, non-accelerated PBI and the result was compared with observed incidence of RIF.
With α/β fixed at 3Gy the parameters of the model without correction for incomplete repair extracted from fitting were: 50% complication probability biologically effective dose BEUD(50) = 107.2 Gy (95%CI = 95.9-118.6 Gy), volume parameter n = 0.06 (95%CI = 0-0.23), and slope of dose response m = 0.22, (95%CI = 0.20-0.23). After including the correction for incomplete repair with repair halftime for subcutaneous tissue of τ = 4.4 h we obtained BEUD(50) = 105.8 Gy (95%CI = 96.9-114.6Gy), n = 0.15 (95%CI = 0-0.33), m = 0.22 (95%CI = 0.20-0.23). Average NTCP predicted by these models, 4.3% and 2.0% respectively, offered a good agreement with RIF incidence in our patients, 5.7%, after an average follow-up of 12 months.
The NTCP models of RIF, incorporating the effects of fractionation, volume effect, and latency of toxicity look promising to model PBI. Clinical validation from a prospective PBI treatment study is under development and will help test this preliminary result.
将现有的基于放射治疗（RT）的放射性纤维化（RIF）的正常组织并发症概率（NTCP）模型应用于部分乳房照射（PBI）中，以包括分割、不均匀剂量、不完全恢复以及放疗结束后时间的影响。
使用具有生物有效均匀剂量（BEUD）的 Lyman NTCP 模型，以及是否校正不完全修复的效果。还考虑了 RIF 发生的时间。通过拟合发表的关于乳房 RT 的随机研究中中度/重度 RIF 的发生率来确定放射生物学参数。使用 NTCP 模型计算了 35 例接受强度调制、非加速 PBI 治疗的患者的毒性风险，并将结果与观察到的 RIF 发生率进行了比较。
当 α/β 固定为 3Gy 时，从拟合中提取的未校正不完全修复模型的参数为：50%并发症概率的生物有效剂量 BEUD(50)=107.2Gy（95%CI=95.9-118.6Gy），体积参数 n=0.06（95%CI=0-0.23），剂量反应斜率 m=0.22（95%CI=0.20-0.23）。包括皮下组织修复半衰期为 τ=4.4 小时的不完全修复校正后，我们得到 BEUD(50)=105.8Gy（95%CI=96.9-114.6Gy），n=0.15（95%CI=0-0.33），m=0.22（95%CI=0.20-0.23）。这些模型预测的平均 NTCP 分别为 4.3%和 2.0%，与我们患者的 RIF 发生率 5.7%（平均随访 12 个月后）吻合良好。
将分割、体积效应和毒性潜伏期的影响纳入 RIF 的 NTCP 模型有望对 PBI 进行建模。一项前瞻性 PBI 治疗研究的临床验证正在进行中，这将有助于验证这一初步结果。
