Phase Ⅰ clinical trial of dose escalation on three dimensional conformal radiation therapy for non-small cell lung cancer

Abstract

目的 建立非小细胞肺癌适形放疗技术，试图获得患者适形放疗的最大耐受剂量（MTD），并观察其即期疗效。方法 1999年6月至2000年6月，38例Ⅱ～ⅢB期非小细胞肺癌患者进入本研究。常规放疗42Gy后用适形放疗做肿瘤剂量递增。根据接受20Gy照射的总肺体积百分比，计划的肿瘤剂量递增水平分别为69、72、75、78和81Gy。大于RTOG Ⅲ级放射性肺损伤为停止剂量递增的标准。结果 已完成放疗计划者有36例，实际可评估疗效者有33例。各剂量递增组至少已递增一次，目前最高剂量为78Gy。即期疗效为完全缓解率61％，部分缓解率27％，无变化率12％。急性放射性食管炎发生率Ⅰ、Ⅱ级61％，Ⅲ级9％；急性放射性肺炎Ⅰ、Ⅱ级26％，Ⅲ级3％；急性骨髓抑制Ⅰ、Ⅱ级58％，Ⅲ级9％。结论 用正常肺组织受一定剂量照射的百分体积数决定递增剂量的方法能为大多数患者所耐受，有较好的即期疗效。目前的最高递增剂量已达78Gy，MTD尚未获得，放射后期毒副作用及远期疗效有待进一步观察。

Objective To establish the technique of 3-dimensional conformal radiation therapy (3DCRT) for non-small cell lung cancer (NSCLC) in stage Ⅱ-ⅢB,and to assess its acute side-effects and to obtain the maximum tolerance dose (MTD).Methods From June,1999 to June,2000,38 cases of NSCLC in stage Ⅱ-ⅢB were enrolled in this study.MTD was identified by dose escalation study.After 42Gy／21Fx／4.2wks by conventional fractionated irradiation through AP／PA fields,which covered the primary tumor and lymph nodes,the technique of 3DCRT was used as boost.The boost fields encompassed the clinical lesions showed on chest CT.The planning of total dose escalation depended on the percentage,i.e., 37％ of normal lung volume irradiated to over 20Gy.The scheduled dose escalation ranged from 69 to 81Gy.The criteria for stopping dose escalation was grade Ⅲ or more worse radiation pneumonitis (RTOG).The boost doses were delivered with 3Gy／fraction,once a day,5 fractions a week.Results Thirty-three cases had completed their treatments and could be evaluated by now.Acute radiation pneumonitis occurred in 26％ of patients with grade Ⅰ-Ⅱ and 3％ with grade Ⅲ,and acute radiation esophagitis in 61％ with grade Ⅰ-Ⅱ and 9％ with grade Ⅲ,and the hematopoietic toxicity in 58％ with grade Ⅰ-Ⅱ and 9％ with grade Ⅲ.The current doses implemented were 78,78,and 75Gy respectively for patients with 37％ of normal lung volume irradiated.The overall immediate response rate of tumors was 88％(29／33).Conclusion Dose escalation in a volume-dependent organ as the lungs is acceptable and applicable.The immediate response is encouraging.MTD is to be determined.The long-term follow-up is needed to observe late complications and treatment efficacy.