应用放射生物学模型比较早期鼻咽癌不同放疗剂量分割方案

Comparison of different fractionation regimens for early-stage nasopharyngeal carcinoma using radiobiological model

目的:通过放射生物学模型分析和剂量学比较为早期鼻咽癌放疗剂量分割方案的优化选择提供参考。方法:选取24个病例,采用3种剂量分割方案(总剂量均为70 Gy,分割数分别为30、33、35 Fr)分别制定3组容积弧形调强计划。采用考虑肿瘤克隆源性细胞再增殖与乏氧的Webb-Nahum模型预测肿瘤控制概率(TCP),使用Lyman-Kutcher-Burman模型预测危及器官正常组织并发症发生概率(NTCP)。然后结合TCP和NTCP计算无并发症肿瘤控制概率(UTCP)。比较并分析3种剂量分割方案的UTCP、TCP、NTCP值以及剂量学参数。结果:3种方案中,70 Gy/30 Fr方案的UTCP值(80.6%)最高,而70 Gy/35 Fr方案的UTCP值(78.0%)最低(P<0.05)。70 Gy/30 Fr方案能提高TCP值,最大幅度为7.3%(P<0.05),同时保持或略微增加了NTCP值,最大幅度仅为2.2%(P<0.05)。3种剂量分割方案的剂量学参数均无明显差异(P>0.05)。结论:通过放射生物学模型分析,早期鼻咽癌70 Gy/30 Fr方案的治疗增益比最大,能显著提高肿瘤局控率同时不显著增加正常组织毒性,本结论还需临床试验进一步确认。

Objective To provide a theoretical reference for selecting a preferable fractionation regimen(FR) for radiotherapy of early-stage nasopharyngeal carcinoma by comparing radiobiological and dosimetric responses of tumor to different FR. Methods A total of 24 patients were enrolled in this study, and 3 volumetric modulated arc therapy(VMAT) plans with different FR(70 Gy/30 Fr, 70 Gy/33 Fr and 70 Gy/35 Fr) were designed for each patient. Webb-Nahum radiobiological model considering the repopulation and hypoxia of tumor clonogenic cells was used to predict tumor control probability(TCP), and Lyman-KutcherBurman model was utilized to estimate the normal tissue complication probability(NTCP) for organs-at-risk. Subsequently, TCP was combined with NTCP to calculate uncomplicated TCP(UTCP). The UTCP, TCP, NTCP and dosimetric parameters of VMAT plans with different FR were compared and analyzed. Results Among 3 different VMAT plans, the VMAT plan with 70 Gy/30 Fr had the highest UTCP(80.6%), while the VMAT plan with 70 Gy/35 Fr had the lowest UTCP(78.0%)(P<0.05). The VMAT plan with 70 Gy/30 Fr increased TCP by up to 7.3%, and meanwhile maintained or slightly increased NTCP, only with a maximum increase of 2.2%(P<0.05). No significant dosimetric difference was found among 3 different FR. Conclusion Based on the radiobiological model analysis, the VMAT with 70 Gy/30 Fr for early-stage nasopharyngeal carcinoma provides the maximal therapeutic gain and improves improving local control rate of tumor, without significantly increasing the toxicity of normal tissues.However, more clinical trials are needed to validate the conclusion.