Ⅳ期 NSCLC 化疗同期3DRT 的前瞻性多中心Ⅱ期临床研究-PPRA-RTOG003

A prospective, multicenter, phase II clinical study of three-dimensional radiotherapy with concurrent chemotherapy for stage IV non-small-cell lung cancer-PPRA-RTOG003

目的：探讨Ⅳ期 NSCLC 化疗同期3DRT 的疗效和安全性。方法2008—2012年共198例患者符合以下入组标准：年龄18～80岁，KPS≥70，无放化疗禁忌，组织或细胞病理学确诊的初治 NSCLC，临床分期为Ⅳ期，转移器官数≤3个。主要研究终点为生存率及急性不良反应。结果随访率98.5％，3年样本量为165例。中位 OS 期和 PFS 期分别为13.0（95％ CI为11．7～14.3）和9.0（95％ CI为7．7～10.3）个月，1、2、3年OS 率分别为53.5％、15.8％、9.2％。多因素分析显示原发肿瘤体积＜134 cm3（P＝0.008）、治疗后 KPS 稳定或增加（P＝0.010）及放疗剂量≥63 Gy （P＝0.014）是延长生存因素。3—4级中性粒细胞降低占37.9％、血小板降低占10.1％、血红蛋白降低占6.9％，3级急性放射性食管炎和肺炎分别占2.5％和6.6％。主要死因为远处转移，仅10％单纯复发死亡。结论Ⅳ期 NSCLC 化疗同期3DRT 取得较好疗效且不良反应可耐受。原发肿瘤体积、治疗后 KPS 变化和放疗剂量是影响 OS 因素。临床试验注册中国临床试验注册中心，注册号：ChiCTRTNC10001026。

Objective To investigate the efficacy and safety of three.dimensional radiotherapy （3DRT） with concurrent chemotherapy for stage IV non.small.cell lung cancer （ NSCLC）. Methods A total of 198 eligible patients from 2008 to 2012 were enrolled as subjects. With an age ranging between 18 and 80 years and a Karnofsky Performance Status （ KPS） score of 70 or more, those patients had no contraindication for radiotherapy and chemotherapy, and were newly diagnosed with stage IV NSCLC confirmed by histology or cytology, as well as limited metastatic disease （≤3 organs）. Survival rates and acute toxicities in those patients were evaluated. Results The 3.year follow.up rate was 98. 5% and the 3.year sample size was 165. The median overall survival （OS） and progression.free survival （PFS） were 13. 0 months （95% CI,11. 7 .14. 3 months） and 9. 0 months （95% CI,7. 7 .10. 3 months）, respectively, while the 1., 2., and 3.year OS rates were 53. 5%, 15. 8%, and 9. 2%, respectively. Multivariate analysis showed that a primary tumor volume smaller than 134 cm3 , a stable or increased KPS score after treatment, and a radiation dose of 63 Gy or more were independent prognostic factors for longer survival time （ P=0. 008;P= 0. 010;P= 0. 014）. The incidence rates of grade 3.4 neutropenia, thrombocytopenia, anemia, grade 3 radiation esophagitis, and grade 3 radiation pneumonitis were 37. 9%, 10. 1%, 6. 9%, 2. 5%, and 6. 6%, respectively. The main cause of death was distant metastasis, and only 10% of the patients died of recurrence alone. Conclusions 3DRT with concurrent chemotherapy achieves satisfactory treatment outcomes with tolerable toxicities for stage IV NSCLC. Primary tumor volume, change in the KPS score after treatment, and radiation dose are independent prognostic factors for OS.Clinical Trial Registry Chinese Clinical Reistry,registration number：ChiCTRC10001026.