食管癌同步放化療

1、陜西腫瘤放療年會2008年12月,西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVERSITY,,,,食管癌同步放化療西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院腫瘤中心放療專業(yè)馬紅兵 王西京 任宏濤 王寶峰,概述藥物臨床進展,西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,,SECOND AFFILIATED HOSPITAL O

2、F MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVERSITY,Cancer statistics, 2008. CA Cancer J Clin. 2008 Mar-Apr;58(2):71-96. Epub 2008 Feb 20,西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVE

3、RSITY,,2004年全國40個觀察點統(tǒng)計分析，食管癌發(fā)病率居第四位。全世界每年新發(fā)食管癌病例約３０萬;我國的食管癌發(fā)病率居世界之首，發(fā)病人數(shù)占世界發(fā)病總數(shù)的60%, 13/10萬/年，男性的發(fā)病率是女性的二倍。 。接受手術(shù)的5年生存率為15%～39%而接受放療者為8%～15%,西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOT

4、ONG UNIVERSITY,,概述,我國食管癌,西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVERSITY,,Surgical OncologyRadiation OncologyMedical OncologyBiological and Target TherapyThe traditional Chi

5、nese medicine,治療手段,概述,西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVERSITY,,目前，食管癌還是一個需多學(xué)科部門聯(lián)合綜合治療以提高臨床療效的惡性腫瘤。,放射治療 局部病變藥物治療 微小轉(zhuǎn)移,,,,腫瘤治愈,一個美好的設(shè)想：,概述,近年，綜合治療顯示優(yōu)勢 －－－先

6、進的放療技術(shù)＋新的化療藥物精確放療、藥物、生物靶向治療 －－－－腫瘤綜合治療的希望,西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVERSITY,,概述,離體細胞研究、分子生物學(xué)機制的研究有助于闡明綜合治療的生物學(xué)機制，對探討臨床最佳綜合治療方案有著重要的意義。,西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,SECON

7、D AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVERSITY,,機制,概述,Spatial cooperationTemporal cooperationSelecting toxicity depending on cell cycle phaseDecrease in tumor mass and reoxygenationSelecting to

8、xicity for hypoxic cellsCytokinetic cooperationDNA damage Cell apoptosis,西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVERSITY,,機制,概述,藥物,西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,SECOND AFFILIATED HOSPITAL

9、 OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVERSITY,,一線藥物（90年代以前的 ）順鉑、5－Fu、阿霉素 二線藥物（90年代以后）泰素、泰索蒂、諾維本、健擇、 半合成的喜樹堿衍生物、新一代鉑類生物靶向藥物,西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVERSITY

10、,,藥物,西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVERSITY,,5－Fu,抗代謝藥2. 在體內(nèi)轉(zhuǎn)變?yōu)?－氟尿嘧啶脫氧核苷 抑制胸腺嘧啶核甙合成酶，影響DNA的生物合成3、能摻入RNA中干擾蛋白質(zhì)合成4. 對有氧和乏氧細胞有相同的殺傷作用,,藥物,5－Fu增敏機制作用于放射抗拒的S期細胞干擾S期

11、調(diào)控點實驗室證實，放療期間持續(xù)給藥可以增敏,西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVERSITY,,藥物,西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVERSITY,,,甲酰四氫葉酸,,順

12、鉑,加強,5－Fu,生化調(diào)節(jié)機制,,,4 用藥時間,放療后5min－8h,5 用藥量,200－375mg/m2,,,5－Fu特點：,藥物,特點：吸收后在體內(nèi)逐漸變?yōu)榉蜞奏ざ鹱饔?其作用機理與氟尿嘧啶相同， 在體內(nèi)能干擾、阻斷DNA、RNA及蛋白質(zhì)的合成 其毒性只有氟尿嘧啶的1/4～1/7 化療指數(shù)為氟尿嘧啶的2倍

13、 血液中半衰期為5h 用藥量，一般500－1000mg/day慢性毒性試驗中未見到嚴重的骨髓抑制，對免疫的影響較為輕微。,西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVERSITY,,新一代 替加氟 Tegafur Injection,,藥物,卡莫氟(Carmofure)特點：不

14、需經(jīng)過肝臟的藥物代謝而釋放出5-Fu在血液、淋巴液、腹腔積液以及腫瘤組織中保持高濃度。,西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVERSITY,,藥物,卡培他濱(Caoecitabine)希羅達由于最后催化后形成5-Fu的胸苷磷酸化酶在瘤組織中的濃度為正常組織中的4倍，口服后瘤組織中的5-Fu濃度是靜脈給予

15、相同劑量的127倍。,西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVERSITY,,,藥物,西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVERSITY,,順鉑 Cisplatin,PDD，DD

16、P,,1 鉑的金屬絡(luò)合物，作用似烷化劑,2 主要作用靶點為DNA,作用于DNA鏈間及鏈內(nèi)交鏈，形成DDP～DNA復(fù)合物,干擾DNA復(fù)制，或與核蛋白及胞漿蛋白結(jié)合。,3 屬周期非特異性藥,,藥物,用藥量順鉑的抗腫瘤作用,西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVERSITY,,濃度依賴性,,時間依賴性,

17、順鉑小劑量長期用藥抑制腫瘤細胞對放療所致亞致死性損傷修復(fù)抑制和潛在致死性損傷的修復(fù),藥物,順鉑最低臨床應(yīng)用劑量 6mg/m2/d,順鉑與放療的相互作用陽離子與DNA鏈堿基作用改變DNA修復(fù)輻射增加DNA單鏈的修復(fù),西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVERSITY,,藥物,西安交通大學(xué)醫(yī)學(xué)院第二附

18、屬醫(yī)院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVERSITY,,5－Fu,順鉑,二者對放射增敏有協(xié)同作用,增敏效果與給藥時間有關(guān),順鉑在放療前1－6h,5－Fu持續(xù)給藥,增敏效果最佳,藥物,卡鉑 Carboplatin在乏氧的條件下卡鉑的增敏作用高于順鉑奧沙利鉑（樂沙定, 草酸鉑）L-OHP復(fù)合體DDP復(fù)合體 靶分子和作用機制

19、不同 抗瘤譜不同萘達鉑 腎毒性、胃腸道反應(yīng)及骨髓抑制均較DDP輕,西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVERSITY,,,藥物,西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVER

20、SITY,,紫杉類醇藥物(taxanes),泰素、紫素、特素、紫脘素，Paclitaxel, Taxol, PTX,機制,使微管不可逆的聚集－－－干擾細胞的有絲分裂,主要作用于G2晚期和M期，具有顯著的放射增敏作用,藥物,西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVERSITY,,是微管解聚抑制劑，其作用于微管/微

21、管蛋白系統(tǒng)，通過促進微管雙聚體裝配成微管，且通過防止去多聚化過程而使微管穩(wěn)定，阻滯細胞于G2和M期，從而抑制癌細胞的有絲分裂和增殖。,多西紫杉醇,泰索帝、多西他賽、Docetaxel/TXT,機制,特點,穩(wěn)定微管的作用比紫杉醇強2倍,藥物,西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVERSITY,,健擇,gemci

22、tabine hydrochloride,鹽酸吉西他濱,細胞周期特異性抗代謝類藥物,作用于DNA合成期（S期）的腫瘤細胞在一定的條件下，可以阻止G1期向S期的進展,藥物,分子靶向藥物EGFRI (EGFR抑制劑）放射－－激活EGFR 抗拒放射EGFRI－－增加腫瘤細胞的放射敏感性機制①阻止細胞進入S期②增加放射誘導(dǎo)的細胞凋亡③抑制放射誘導(dǎo)的EGFR磷酸化④抑制放射損傷的修復(fù),西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,

23、SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVERSITY,,,,藥物,臨床進展,西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVERSITY,,臨床進展,N Engl J Med. 1992 Jun 11;326(24):162

24、9-31. （RTOG－－8501）Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus.,西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVERS

25、ITY,,METHODS. This phase III prospective, randomized, and stratified trial was undertaken to evaluate the efficacy of four courses of combined fluorouracil (1000 mg per square meter of body-surface area daily for four d

26、ays) and cisplatin (75 mg per square meter on the first day) plus 5000 cGy of radiation therapy, as compared with 6400 cGy of radiation therapy alone, in patients with squamous-cell carcinoma or adenocarcinoma of the tho

27、racic esophagus. RESULTS. The median survival was 8.9 months in the radiation-treated patients, as compared with 12.5 months in the patients treated with chemotherapy and radiation therapy. In the former group, the sur

28、vival rates at 12 and 24 months were 33 percent and 10 percent, respectively, whereas they were 50 percent and 38 percent in the patients receiving combined therapy (P less than 0.001). Seven patients in the radiotherapy

29、 group and 25 in the combined-therapy group were alive at the time of the analysis. Severe and life-threatening side effects occurred in 44 percent and 20 percent, respectively, of the patients who received combined the

30、rapy, as compared with 25 percent and 3 percent of those treated with radiation alone.,RTOG85-01隨機對照試驗首次證明同步放化療生存期明顯優(yōu)于單純放療這一篇文章被認為是食管癌非手術(shù)治療中，具有里程碑意義的重要論文。本文的發(fā)表使得同期放化療成為食管癌的標準治療方案。同步放化療已被美國NCCN推薦治療不可切除的食管癌患者。,西安交通大學(xué)醫(yī)學(xué)院

31、第二附屬醫(yī)院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVERSITY,,1: JAMA. 1999 May 5;281(17):1623-7. Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective random

32、ized trial (RTOG 85-01). Radiation Therapy Oncology Group.,西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVERSITY,,PATIENTS: Patients had squamous cell or adenocarcinoma of the esopha

33、gus, T1-3 N0-1 M0(Ⅲ stage), adequate renal and bone marrow reserve, and a Karnofsky score of at least 50. MethodsInterventions Combined modality therapy (n = 134): 50 Gy in 25 fractions over 5 weeks, plus cisplatin 75

34、mg/m2 intravenously on the first day of weeks 1, 5, 8, and 11, and fluorouracil, 1 g/m2 per day by continuous infusion on the first 4 days of weeks 1, 5, 8, and 11. In the randomized study, combined therapy was compared

35、 with RT only (n = 62): 64 Gy in 32 fractions over 6.4 weeks.RESULTS:at 5 years of follow-up the overall survival for combined therapy was 26% (95% confidence interval [CI], 15%-37%) compared with 0% following RT. In t

36、he succeeding nonrandomized part, combined therapy produced a 5-year overall survival of 14% (95% CI, 6%-23%). Severe acute toxic effects also were greater in the combined therapy groups. There were no significant diff

37、erences in severe late toxic effects between the groups. CONCLUSION: Combined therapy increases the survival of patients who have squamous cell or adenocarcinoma of the esophagus, T1-3 N0-1 M0, compared with RT alone.,,

38、,,,,,1級NCCN,J Clin Oncol. 2002 Mar 1;20(5):1167-74. INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy.,

39、西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVERSITY,,PURPOSE: To compare the local/regional control, survival, and toxicity of combined-modality therapy using high-dose (64.8 Gy) ve

40、rsus standard-dose (50.4 Gy) radiation therapy for the treatment of patients with esophageal cancer. PATIENTS AND METHODS: A total of 236 patients with clinical stage T1 to T4, N0/1, M0 squamous cell carcinoma or adenoc

41、arcinoma four monthly cycles of fluorouracil (5-FU) (1,000 mg/m(2)/24 hours for 4 days) and cisplatin (75 mg/m(2) bolus day 1) with concurrent 64.8 Gy versus the same chemotherapy schedule but with concurrent 50.4 Gy.

42、The trial was stopped after an interim analysis.RESULTS: For the 218 eligible patients, there was no significant difference in median survival (13.0 v 18.1 months), 2-year survival (31% v 40%), or local/regional failure

43、 and local/regional persistence of disease (56% v 52%) between the high-dose and standard-dose arms. CONCLUSION: The higher radiation dose did not increase survival or local/regional control.,RTOG 94 05,RTOG 0113.試驗flu

44、orouracil, cisplatin, and paclitaxel 誘導(dǎo)化療然后 fluorouracil＋ paclitaxel＋50.4 Gy RT (arm A) (37/41)paclitaxel plus cisplatin誘導(dǎo)化療然后 fluorouracil＋ paclitaxel＋50.4 Gy RT (arm B) (35/43). 結(jié)果中位生存時間 28.7 months (arm A)，14.9

45、 months (arm B) 1 年生存率75.7% (arm A)，2年生存率56%(arm A)37%(arm B) 3級毒性(armA=54%,armB=43%) 4級毒性(armA=27%,armB=40%) 死亡(arm A = 3%, arm B =6%) 但沒有達到 77.5%目標.,西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF

46、XI’AN JIAOTONG UNIVERSITY,,J Clin Oncol. 2008 Oct 1;26(28):4551-6. Epub 2008 Jun 23 Phase II randomized trial of two nonoperative regimens of induction chemotherapy followed by chemoradiation in patients with localized

47、carcinoma of the esophagus: RTOG 0113.,第49屆ASTRO年會  RTOG 0246試驗初步結(jié)果:根治性放化療聯(lián)合選擇性手術(shù)挽救治療局部晚期食管癌可行  RTOG 0246試驗(2003年9月5日-2006年3月17日),先給予以紫杉醇為基礎(chǔ)的誘導(dǎo)化療然后采用以紫杉醇為基礎(chǔ)的同步放化療聯(lián)合選擇性手術(shù)治療可以切除的局部晚期食管癌初步結(jié)果：研究納入43例無轉(zhuǎn)移食管癌患者,其中4

48、0例可分析,治療前分期為T3-4N1。結(jié)果顯示,40例完成了誘導(dǎo)化療,37例完成同步放化療,發(fā)生Ⅲ度、Ⅳ度血液學(xué)毒性及Ⅲ度非血液學(xué)毒性的患者分別有28例、7例和7例。18例接受了手術(shù),其中17例經(jīng)胸腹CT、超聲內(nèi)鏡或PET證實為復(fù)發(fā)或殘留,1例為患者自己選擇了手術(shù)。剩余22例沒有接受手術(shù)的患者中,15例未復(fù)發(fā),1例為醫(yī)學(xué)原因不能手術(shù),3例轉(zhuǎn)移,3例死亡。預(yù)計1年總生存(OS)率為72%,預(yù)計1年無病生存(DFS)率為39%。這項多中

49、心前瞻性Ⅱ期研究提示,根治性放化療聯(lián)合選擇性外科手術(shù)挽救治療局部晚期食管癌是可行的,西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVERSITY,,OBJECTIVE: 評價大野加局部小野推高劑量照射聯(lián)合同期放化療治療胸部食管癌的可行性。. METHODS: 病人： T1 -4N0-1M0 (UICC 1997)

50、 胸部鱗狀細胞食管癌. 大野：鎖骨上窩至縱隔39.6 Gy 小野：推量至66.6 Gy (1.8 Gy/day, 5/ week). 2小時 cisplatin (80 mg/m(2) on day 連續(xù) 5-fluorouracil (800 mg/m(2)/day on days 2-6) every 3-4 weeks, for two cycles. RESULTS: 3

51、0例 (stage I, 3; stage II, 11; stage III, 16) 納入觀察. 21例 (70%) 完成計劃.> or = 70 years老年病人, 4 / 6退出. 3級 (NCI-CTC)毒性反應(yīng)20 (67%) 例，4級毒性反應(yīng)3(10%)例 . 主要表現(xiàn)為血液、消化道和肺損傷. 沒有5級毒性反應(yīng). 中位生存期 27 months (range: 9-49 months). 平均生存時間 21

52、months. 1-、 2-year 生存率是 65 % and 49% . 食管狹窄 (grade 1-2: RTOG) was 21%. 沒有食管穿孔. 結(jié)論：大野加局部小野推高劑量照射聯(lián)合同期放化療治療胸部食管癌的可行 。,西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVERSITY,,1: Jpn J

53、 Clin Oncol. 2001 Aug;31(8):375-81. LinksConcurrent chemoradiotherapy for squamous cell carcinoma of thoracic esophagus: feasibility and outcome of large regional field and high-dose external beam boost irradiation.,復(fù)旦大

54、學(xué)附屬腫瘤醫(yī)院后程加速超分割(LCAF)與聯(lián)合同步化療(LCAF +CT)治療原發(fā)性食管癌的Ⅲ期隨機對照研究(患者111名)先予常規(guī)放療DT41.4Gy/23f, 4 ～ 5 W,(1.8Gy/次, 1次/天) 縮野行加速超分割, DT27Gy/18次(1.5Gy/次,2次/日) 累積放療總量6814 Gy/41f,44d完成。54例患者FP方案化療4個周期(順鉑25mg/m2,d1～d3, 5-FU600mg/m2, d

55、1～d3,28天為1周期) 中位生存期:30.8月vs. 23.9月(LCAF + CT vs. LCAF) LCAF + CT組與LCAF組1、3、5 年生存率分別為67%、44%、40% , 77%、39%、28% , ( P = 0.310) 結(jié)論：認為后程加速超分割結(jié)合同步化療有延長生存期的趨勢。,西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE

56、OF XI’AN JIAOTONG UNIVERSITY,,Zhao KL, Shi XH, J iang G, et al. Late course accelerated hyperfractionated radiotherapy plus concurrent chemotherapy for squamous cell carcinoma of the esophagus: a phase Ⅲ randomized study

57、[ J ]. Int J Radiat Oncol Biol Phys, 2005, 62 ( 4 ) : 1014- 1020.,西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVERSITY,,目的：評價聯(lián)合放療和化療與單獨放療治療局部食管癌的療效，從總生存率、 cause-specific生存、局部復(fù)發(fā)、吞咽困難緩

58、解、生活質(zhì)量以及急性和慢性毒性反應(yīng)方面予以評估。 藥物為cisplatin or 5-fluorouracil 方法： 檢索相關(guān)的MeSH主題詞、Cochrane圖書館、國際腫瘤文獻文摘數(shù)據(jù)庫（Cancer LIT）、聯(lián)機醫(yī)學(xué)文獻分析與檢索系統(tǒng)（MEDLINE）, 醫(yī)學(xué)文摘數(shù)據(jù)庫（ EMBASE） 主要結(jié)果：19個隨機試驗被納入，11個聯(lián)合放化療和8個續(xù)貫放化療聯(lián)合放化療死亡風(fēng)險比(HR) 0.73 (95% (CI) 0.6

59、4 to 0.84)，明顯下降. 絕對生存受益率為1年9% (95% CI 5 to 12%) ，2年4% (95% CI 3 to 6%)，局部復(fù)發(fā)率（NNT需治數(shù)為9）為 12% ，(95% CI 3 to 22%) 單放組為68%. 嚴重毒性和生命威脅毒性（NNH致成危害需要的人數(shù)為6）較顯著。續(xù)貫放化療對于局部控制和生存率方面沒有益處。結(jié)論：對于非手術(shù)的局部食管癌病人，相對單純放療同步放化療應(yīng)該優(yōu)選，但有毒性風(fēng)險。,Co

60、chrane Database Syst Rev,CONCLUSIONS: Based on the available data, when a non-operative approach is selected then concomitant RTCT is superior to RT alone for patients with localized esophageal cancer but with significan

61、t toxicities. In patients who are in good general condition, and the risk benefit has been thoroughly discussed with the patient, concomitant RTCT should be considered for the management of esophageal cancer compared wit

62、h radiotherapy alone.,西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVERSITY,,Cochrane Database Syst Rev. 2001;(2):CD002092.Combined chemotherapy and radiotherapy (without surgery) co

63、mpared with radiotherapy alone in localized carcinoma of the esophagus.,Cochrane Database Syst Rev. 2003;(1):CD002092. Combined chemotherapy and radiotherapy (without surgery) compared with radiotherapy alone in localiz

64、ed carcinoma of the esophagus.,,,1: Cochrane Database Syst Rev. 2006 Jan 25;(1):CD002092.Combined chemotherapy and radiotherapy (without surgery) compared with radiotherapy alone in localized carcinoma of the esophagus.

65、Wong R, Malthaner R.,Philip進行多中心前瞻隨機試驗比較了標準食管癌切除術(shù)與放化療的療效。80例患者中36例接受了同步放化療化療采用連續(xù)灌注5-FU(200mg/m2,d1～d42)、順鉑(60mg/m2,d1、d22),對腫瘤區(qū)和區(qū)域淋巴結(jié)同時照射,總劑量50～60Gy44例接受標準手術(shù),手術(shù)死亡率618% ,術(shù)后并發(fā)癥發(fā)生率達38.6%。放化組與手術(shù)組的早期生存率沒有區(qū)別, 2年生存率分別為58.3

66、%、54.5%。提示同步放化療與手術(shù)治療療效相當,該試驗還提示手術(shù)組縱隔復(fù)發(fā)率高于放化組,而放化組則在頸部及腹部復(fù)發(fā)率偏高。,西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院,SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XI’AN JIAOTONG UNIVERSITY,,Chiu PW, Chan AC, Leung SF, et al. Multicenter prospective rando

67、mized trial comparing standard esophagectomywith chemoradiotherapy for treatment of squamous esophageal cancer: early results from the chinese university research group for esophageal cancer[ J ]. Gastrointest Surg, 2005

68、, 9 (6) : 794 - 802.,同步放化療后是否可以延緩手術(shù),也是目前研究的熱點－－法國Bedenne 法國Bedenne－－－FFCD9102試驗,Eligible patients had operable T3N0-1M0 thoracic esophageal cancer. Patients received two cycles of fluorouracil (FU) and cisplatin (days

69、1 to 5 and 22 to 26) and either conventional (46 Gy in 4.5 weeks) or split-course (15 Gy, days 1 to 5 and 22 to 26) concomitant radiotherapy. 然后 randomly assigned to surgery (arm A) or continuation of chemoradiation (ar

70、m B; three cycles of FU/cisplatin and either conventional [20 Gy] or split-course [15 Gy] radiotherapy). 在該試驗中444例患者接受了放化療,其中259例患者接受了進一步的手術(shù)切除,其余患者接受進一步放化療單純放化療與手術(shù)組2年生存率分別為40%和34% ,治療相關(guān)致死率分別為1%和9% CONCLUSION: Our data

71、 suggest that, in patients with locally advanced thoracic esophageal cancers, who respond to chemoradiation, there is no benefit for the addition of surgery after chemoradiation compared with the continuation of addition