局限期小细胞肺癌化疗联合加速超分割放疗.docx

1、局限期小细胞肺癌化疗联合加速超分割放疗局限期小细胞肺癌化疗联合加速超分割放疗疗效初步分析胡 晓1,2,包 勇1，2,陈媛媛1，2,高剑铭1，2,王卫华1，2,刘 源1，2,何 瀚1，2,孙宗文1，2,SHIVAJI Poudel1，2,王 彦1，2,庄婷婷1，2,张 力1，3,陈 明1，21. 华南肿瘤学国家重点实验室，广东 广州 5100602. 中山大学肿瘤防治中心放疗科，广东 广州 5100603. 中山大学肿瘤防治中心内科，广东 广州 510060刘源现在单位：广州医学院附属肿瘤医院，广东 广州 510059何瀚现在单位：佛山市第一人民医院，广东 佛山 528000【摘 要】 背景与目

2、的：局限期小细胞肺癌 (limited small-cell lung cancer, limited SCLC) 对放疗和化疗均敏感。放疗已被证实可提高局限期SCLC患者总生存率，降低局部复发率。本研究总结在化疗基础上应用加速超分割放射治疗 (hyperfractionated accelerated radiotherapy, HART) 对局限期SCLC的疗效，评价相关治疗毒性，归纳治疗失败方式。方法：55例局限期SCLC患者经过EP 方案 (etoposide, 120mg/m2, d1d3; cisplatin, 60mg/m2, d1) 诱导化疗24程，化疗后12周开始放疗，累及野

3、放疗总剂量45Gy，1.5Gy/次，2次/日，5日/周。放疗后再以EP方案巩固化疗24程，完全缓解 (complete remission, CR) 者行预防性全脑照射 (prophylactic cranial irradiation, PCI)。结果：55例患者放化疗结束时总有效率(CR+PR)87.3%。1、3、5年总生存率分别为79.1%、40.3%、16.1%。中位生存时间18.7个月。3度和4度血液学毒性分别为23例（41.8%）和16例（29.1%）；1度和2度急性放射性肺炎分别为21例（38.2%）和2例（3.6%）；1度和2度放射性食管炎分别为29例（52.7%）和12例（2

4、1.8%）；未发生34度非血液学毒性。11例(20.0%)患者出现1度肺纤维化，5例（9.1%) 为2度。2例（3.6%）发生1度后期食管损伤。16例(29.1%）局部/区域复发，21例(38.2%)发生远处转移。结论：EP方案化疗合并HART治疗局限期SCLC毒性轻至中度，易于耐受。局部复发和远处转移为主要治疗失败原因。关键词：肺肿瘤；癌，小细胞性；局限期；HART中图分类号：R734.2 文献标识码：A文章编号：1000467XEfficacy of Chemotherapy Combined Hyperfractionated Accelerated Radiotherapy on Li

5、mited Small Cell Lung CancerHU Xiao1,2, BAO Yong1,2, CHEN Yuan-Yuan1,2, Gao Jian-Ming1,2, WANG Wei-Hua1,2, LIU Yuan1,2, HE Han1,2, SUN Zong-Wen1,2, SHIVAJI Poudel1,2, WANG Yan1,2, ZHUANG Ting-Ting1,2, ZHANG Li1,2, CHEN Ming1,21. State Key Laboratory of Oncology in South China, Guangzhou, Guangdong,

6、510060, P. R. China2. Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, 510060, P. R. China3. Department of Medical Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, 510060, P. R. ChinaPresent address of LIU Yuan: Affiliated Cancer Ho

7、spital, Guangzhou Medical College, Guangzhou, Guangdong, 510059, P. R. ChinaPresent address of HE Han: The First Peoples Hospital, Foshan, Guangdong, 528000, P. R. ChinaABSTRACT BACKGROUND & OBJECTIVE: Limited small cell lung cancer (SCLC) is sensitive to both radiotherapy and chemotherapy. Radiothe

8、rapy can enhance survival rate and reduce the local/regional recurrence rate of SCLC. This study was to analyze the efficacy of chemotherapy combined hyperfractionated accelerated radiotherpay (HART) on limited SCLC, observe treatment-related adverse events and summarize the treatment failure patter

9、ns. METHODS: A total of 55 limited SCLC patients were treated with 24 cycles of EP regimens (etoposide, 120mg/m2, d1d3; cisplatin, 60mg/m2, d1) then received involved field radiotherapy delivered in 1.5Gy fractions, twice daily, 5 days a week, to a total dose of 45Gy in 30 fractions followed with an

10、other 24 cycles of EP regimens. Prophylactic cranial irradiation (PCI) was given to those patients who had achieved complete remission (CR) of tumor after chemoradiotherapy. RESULTS: Fifty-five patients were enrolled in the study. At the end of chemoradiotherapy, the overall response rate was 87.3%.

11、 The 1-year, 3-year, 5-year overall suvival rates were 79.1%, 40.3% and 16.1% respectively, with the median survival time 18.7 months. Grade 3/4 hematologic toxicitis were observed in 23 (41.8%) and 16 (29.1%) patients respectively. Grade 1/2 radiation-induced pneumonitis and esophagitis occurred in

12、 21 (38.2%)/2 (3.6%) patients and 29 (52.7%)/12 (21.8%) patients respectively, no grade 3/4 non-hematologic toxicity was observed. Grade 1/2 pulmonary fibrosis occured in 11 (20.0%) and 5 (9.1%) patients respectively and grade 1 esophageal stricture was observed in 2 (3.6%) patients. Of 55 patients,

13、 16 (29.1%) had local/regional recurrence, 21 (38.2%) suffered distant metastasis. CONCLUSIONS: The toxicity of EP regimen chemotherapy combined with HART is tolerable. Local/regional recurrence and distant metastasis are the main treatment failure reasons. KEYWORDS: Lung neoplasm; Carcinoma, small

14、cell; Limited stage; HART肺癌是常见胸部恶性肿瘤，临床所见肺癌患者中约20为小细胞肺癌（small cell lung cancer, SCLC）。SCLC恶性度高，易于发生远处转移，在确诊的SCLC患者中仅有40%为局限期SCLC患者。SCLC对放化疗均敏感，然而，单独接受化疗的局限期SCLC患者的局部复发率为7590 1。胸部放射治疗使局部复发率降低到50，且使局限期SCLC患者的长期生存率提高52,3。因此，放化综合治疗成为局限期SCLC标准治疗方案。目前局限期SCLC化疗以EP为标准方案4-6。但胸部放疗在放疗剂量、分割方式、照射靶区、与化疗联合的方式和时机等诸

15、多方面均存在争议7。中山大学肿瘤防治中心胸部放疗组自2002年6月开始采用EP方案化疗联合胸部加速超分割放疗 ( hyperfractionated accelerated radiotherapy, HART ) 治疗局限期SCLC患者。本研究目的是分析采用该方式治疗局限期SCLC的疗效、评价相关治疗毒性及归纳治疗失败方式。1 资料与方法11病例选择111 入组标准 经病理或细胞学确诊为SCLC；经影像学证实为局限期SCLC（包括脑CT或MRI、胸腹部CT、全身骨扫描），局限期SCLC按美国退伍军人医院定义8：肿瘤局限于一侧胸腔及其区域淋巴结，包括双侧肺门淋巴结和/或双侧纵隔淋巴结和/或双侧

16、锁骨上淋巴结，同侧胸水不论细胞学是否阳性，左侧喉返神经受累，上腔静脉压迫综合征也列入局限期。年龄18岁且75岁，既往无胸部放射治疗史,无化疗和生物治疗史；有可测量或可评价的病灶；患者本人及家属同意并签署知情同意书。外周血中性粒细胞1.5109/L,血小板100109/L, 血红蛋白100g/L。血肌酐、胆红素1.5倍正常上限, 转氨酶2倍正常上限；诊断前半年内体重减轻10。112 剔除标准 既往或治疗时合并有其他恶性肿瘤（非黑色素皮肤癌或宫颈原位癌除外）；任何放、化疗禁忌的疾病或情况；有恶性胸腔积液或心包积液者。12 治疗方法121 化疗 诱导化疗采用EP方案（etoposide, 120mg/m2, d1d3；cisplatin, 60mg/m2, d1）静脉点滴，3周重复；24周期化疗结束后12周内行放疗。放疗后再行EP方案静脉化疗24程，3周重复。