Theoretical Analysis of Optimal Dose-fractionation of Intensity-modulated Radiotherapy in Head and Neck Squamous Cell Carcinoma
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摘要: 目的 理论分析头颈部鳞癌调强放疗时最佳的剂量分割模式。方法 分别用目前常用的33 次分割、保证物理剂量为70 Gy、用生物等效剂量（BED）84 Gy10和延长总治疗时间（1~7天）的剂量分割方案的前提下模拟不同分次剂量和分次数，用线性二次模型公式分别通过理论计算肿瘤、早反应组织（黏膜）、晚反应组织BED和肿瘤杀伤对数级，比较分析调强放疗最佳的剂量分割方案。结果 在33次每天一次的分割方案中分次剂量从2.12 Gy提升到2.30 Gy时，照射的总物理剂量相应从70.0 Gy提升到75.9 Gy，肿瘤、早反应组织和晚反应组织分别为69.6~78.2Gy10、55.5~64.1Gy10和119.4~129.5Gy3，肿瘤杀伤对数级为10.6~11.9。当总保持照射剂量分为70 Gy或84 Gy10的前提下而改变分次剂量和分次数目，分次剂量为2.0~2.80 Gy，照射次数为25~35次，总治疗时间为32~46天，肿瘤、早反应组织和晚反应组织分别为67.5~82.3Gy10、53.1~69.8Gy10和113.5~119.8 Gy3，肿瘤杀伤对数级为10.3~12.5。综合比较肿瘤、早反应组织BED、晚反应组织BED和肿瘤杀伤对数级4个参数提示30 次的分割方案中肿瘤控制和不良反应相对得到较好的平衡。总治疗时间每延长一天肿瘤BED降低1.4% （0.8Gy10）, 肿瘤杀伤对数级降低0.1。结论 理论上头颈部鳞癌IMRT的最佳剂量分割总治疗时间为6周的30次分割方案，总治疗时间延长导致肿瘤BED降低。Abstract: Objective To analyze theoretically the optimal dose-fractionation of intensity-modulated radiotherapy in head and neck squamous cell carcinoma (HNSCC). Methods The common dosefractionation of 33 division, keeping the irradiation dose of 70 Gy, biological effect dose (BED) of 84Gy10 and prolong overall treatment time was applied to simulate different dose and time treatment, respectively. The linear-quadric function was used to calculate the tumor, early response (mucosal), late response BED and the tumor log10 cell kill with different fraction number and/or dose to fi nd out the optimal fractionation. Results With 33 fractions, the fraction dose and total irradiation dose varied from 2.12-2.30 Gy and 70.0-75.9 Gy respectively. The doses of tumor, mucosal and late effect BED were 69.6Gy-78.2Gy10, 55.5-64.1Gy10, and 119.4-129.5Gy3 respectively. The tumor log10 cell kill was 10.6-11.9. While keeping the physical irradiation dose of 70 Gy or BED of 84Gy10, the fraction dose ranged from 2.20-2.80 Gy with 25-35 fractions and the total treatment day (TTD) was 32-46. The doses of tumor, early and late response BED were 67.5-82.3Gy10, 53.1-69.8Gy10, and 113.5-119.8Gy3 respectively and the tumor log10 cell kill was 10.3-12.5. Taking the tumor, early and late response BED and tumor cell log10 kill into comprehensive consideration, the regimen with 30 daily IMRT fractions can balance the tumor control and radiation-related toxicity well. For every single prolonged day, the tumor BED decreased 1.4% (0.8Gy10) and the tumor log10 cell kill did 0.1. Conclusion The optimal dose-fraction in IMRT of HNSCC is theatrically 30 daily fractions in six weeks. And the tumor BED will decrease with the prolonged overall treatment days.
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