非小细胞肺癌三维适形放疗剂量递增的临床研究

A Phase Ⅰ/Ⅱ Study of Dose Escalation in Non-Small-Cell Lung Cancer Using Three-Dimensional Conformal Radiotherapy

目的通过临床剂量递增获得非小细胞肺癌(NSCLC)三维适形放射治疗的最大耐受剂量并观察其疗效。方法对84例Ⅰ～Ⅲ期NSCLC采用三维适形放射治疗(3D-CRT),不进行区域淋巴结预防性照射。在CTV照射患者60Gy(2Gy/次,1次/天,5天/周)后,开始对GTV进行剂量递增。2～4Gy/次,递增次数为3～11次。根据肺V20和将患者分为V20<25%组和V2025%～36%组,两组患者再根据总剂量分剂量亚组,观察放射性损伤发生率和疗效。以≥15%的患者出现3级以上急性放射性肺损伤(RTOG)为限制剂量递增标准。结果全组84例。V20<25%组45例,剂量亚组分别为70Gy、74Gy、78Gy、82Gy。3级放射性肺炎发生率为4.4%(2/45)。V2025%～36%组39例,剂量亚组分别为66Gy、70Gy、74Gy、78Gy。3级放射性肺炎发生率为5.1%(2/39)。全组中位生存时间14个月,1、2年总生存率分别为69.5%、52.8%,1、2年局部控制率分别为79.7%、53.6%。随着剂量增加,1、2年生存率和局部控制率有所增高,但统计学检验均无统计学差异(P>0.05)。结论采用3DCRT治疗NSCLC时,提高局部放射剂量应考虑正常肺组织所受照射的剂量和体积。当V20<25%时,可以安全地递增到82Gy,其放射性损伤可以接受;当V20为25%～36%时,可以递增到76Gy。但当V20>30%时,增加到更高的放射剂量应谨慎,而提高局部剂量对生存率和局部控制率的意义仍有待进一步研究。

Objective To obtain the maximum tolerated dose （MTD） of three-dimensional conformal radiotherapy in non-small-cell lung cancer and observe its therapeutic effect. Methods Involved field of 84 patients with stage I - III non-small- cell lung cancer were treated by three-dimensional conformal radiotherapy （3-DCRT）. Dose escalation to the GTV began after the CTV had received 60Gy. The escalation doses were given in 5 to 11 fractions ,2Gy per fraction. According to the percentage of lung volume receiving 〉 20 Gy,the patients were divided into two groups （V20 〈 25 % or V20 25% -36% ）. The groups based on the total dose were divided into subgroup. The incidence of radiotherapy induced lung damage and therapeutic effect were analyzed. The criteria for cessation of further dose escalation was that more than or equal to 15% of patients developed grade 3 radiation pneumonitis （RTOG）. Results A total dose of 70 Gy, 74 Gy, 78 Gy or 82Gy was given to 45 patients with V20 〈 25%, and 4.4% （2/45） patients experienced grade 3 pneumonitis;Whereas the total dose given to the 39 patients with V20 25% -36% was 66 Gy,70 Gy ,74 Gy or 78 Gy ,and 5.1% （2/39） patients experienced grade 3 pneumonitis. The median survival time of the entire groups was 14 months. The 1,2-year overall survival rate were 69.5% and 52.8% ,and the 1,2-year local control rate were 79.7% and 53.6%. There was trend toward increased overall survival and local control with the increase of the total dose （ P 〉 0.05 ）. Conclusion 82 Gy and 76Gy could be tolerated by patients with V20 〈 25 % and 25% - 36%. With V20 〉 30%, any dose escalation should be prudent. The value of dose escalation to overall survival and local control in patients with non small cell lung cancer needs further study.