T_1声门癌加大分割剂量放疗的随机对照研究

A randomized control trial of increased fraction-dose radiotherapy for patients with T_1 glottic carcinoma

目的通过随机对照研究,分析比较每次分割剂量为2.3 Gy与常规分割2.0 Gy治疗T1声门癌的疗效及其毒副反应情况。方法 1995年1月至2005年12月我院首次接受单纯放射治疗的T1声门型喉鳞癌患者165例,男158例,女7例,抽烟患者占95.8%(158/165),随机分组研究,加大分割剂量组(LF组)83例,每次分割量2.3 Gy,原发灶靶区中心参考点剂量中位值为66.7 Gy(66.7～71.3 Gy),中位放疗时间为40 d(40～42 d);常规分割剂量组(CF组)82例,每次分割量2.0Gy,原发灶靶区中心参考点剂量中位值为70.0 Gy(70.0～74.0 Gy),中位放疗时间分别为49 d(49～51 d)。Kaplan-Meier法计算肿瘤专项生存率(CSSR)及肿瘤局部控制率(LCR),Log-rank法检验生存及肿瘤局部控制率差异,Cox比例风险模型进行多变量分析。结果 (1)LF组与CF组相比,5、10年肿瘤专项生存率分别为95.18%和95.12%、91.57%和91.46%,χ2=0.071,P=0.789,差异无显著性。(2)治疗结束后观察12周,LF与CF组的客观有效率均为100%,完全缓解率(CR)分别为100.0%(83/83)、97.6%(80/82)(χ2=0.518,P=0.471)。(3)LF组及CF组放疗后5年及10年局部控制率分别为95.18%和80.49%、92.77%和78.05%,差异具显著性(χ2=7.944,P=0.005)。(4)多变量分析结果显示,分割方式及前联合是否受侵是影响T1声门癌放疗长期局部控制率的预后因子,较大的放疗分割量与常规分割相比有较高的局部控制率(HR=0.35,95%CI=0.13～0.7,P=0.002),而前联合受侵局控率较低(HR=3.54,95%CI=1.74～8.32,P=0.01)。(5)LF组及CF组急性放疗副反应及远期并发症相仿。结论 (1)放疗治疗T1声门癌的5、10年肿瘤专项生存率很高,分别达95%及91%以上。(2)加大分割剂量及缩短放疗时间能显著提高5、10年的局控率,未见增加近期及远期毒副反应。(3)分割方式及前联合是否受侵影响T1声门癌放疗的局部控制率。

Objective To analyze and compare radiotherapy effects and its adverse reactions through a randomized control trial between fraction-dose 2.3 Gy and 2.0 Gy respectively.Methods 165 patients with T1 glottic squamous cell carcinoma treated in our hospital from January 1995 to December 2005 were randomized to Increased fraction-dose radiotherapy Group（LF Group） and Conventional fraction-dose Group（CF Group）.Male/femal=22.6：1（158/7）.Smokers accounted for 95.8%（158/165）.Increased fraction-dose radiotherapy Group（LF Group） included 83 cases with fraction-dose 2.3 Gy,the median dose of reference point of primary tumor 66.7Gy（66.7~71.3 Gy） and median radiation time 40 days（40~42 days）.The conventional fraction-dose group（CF Group） had 82 patients with fraction-dose 2.0 Gy,the median dose of reference point of primary tumor 70.9 Gy（70.0~74.0 Gy） and median radiation time 49 days（49~51 days）.Kaplan-Meier method was used to calculate cancer-specific survival rate（CSSR） and local control rate（LCR）,Log-rank test to compare the difference of CSSR and LCR,and Cox＇s proportional hazards model for multivariate analysis.Results（1）To compare LF Group with CF Group,the 5 and 10 year cancer-specific survival rates（CSSR） were 95.18% vs 95.12% and 91.57% vs.91.46%,respectively,having no significant difference（χ2=0.071,P=0.789）.（2）At 12 weeks from the end of radiotherapy,the objective effective rate was both 100% for LF and CF Group,and the complete remission rate（CR） was 100%（83/83） for LF Group and 97.6%（80/82） for CF Group（χ2=0.518,P=0.471）.（3） The 5 and 10-year local control rates（LCR） of LF group were 95.18% and 92.77%,compared with that of CF Group,being 80.49% and 78.05%,respectively,reaching significant difference（χ2=7.944,P=0.005）.（4）Multivariable analysis revealed that fraction size and whether anterior commissure was involved or not had influence on the long-term LCR of T1 glottic carcinoma who had received radiotherapy.Compared with conventional fraction-dose,larger fraction-dose resulted in higher LCR（HR=0.35,95%CI=0.13~0.7,P=0.002）,while the invasion of anterior commissure got lower LCR（HR=3.54,95%CI=1.74~8.32,P=0.01）.（5）There was no significant difference between LF and CF Group in both the incidences of radiation acute adverse reactions and long-term complications.Conclusions（1）The 5 and 10-year CSSR for T1 glottic carcinoma received radiotherapy were rather high,beyond 95% and 91% respectively.（2）Increased fraction-dose and shortened radiation time could significantly improve the 5 and 10-year LCR,having no increased the incidence of recent and long-term side effects.（3）The LCR of radiotherapy for T1glottic carcinoma could be influenced by the fraction size and whether anterior commissure was invaded or not.