食管癌同步放化療【治療】課件

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 XIAN 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1腸道相關(guān)概述藥物臨床進(jìn)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 XIAN JIAOTONG UNIVERSITY2腸道相關(guān)Cancer statistics, 2008. CA Cancer J Clin.

2、 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 XIAN JIAOTONG UNIVERSITY3腸道相關(guān)2004年全國40個觀察點(diǎn)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

3、HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG UNIVERSITY概述我國食管癌4腸道相關(guān) 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 XIAN JIAOTONG UNIVERSITYSurgical OncologyRadiation OncologyMedical OncologyBiological and Target TherapyThe traditional Chinese medicine治療手段概述5腸道相關(guān) 西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院SECON

4、D AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN 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6腸道相關(guān)近年，綜合治療顯示優(yōu)勢 先進(jìn)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 XIAN JIAOTONG UNIVERSITY概述7腸道相關(guān)離體細(xì)胞研究、分子生物學(xué)機(jī)制的

5、研究有助于闡明綜合治療的生物學(xué)機(jī)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SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG UNIVERSITY機(jī)制概述8腸道相關(guān)Spatial cooperationTemporal cooperationSelecting toxicity depending on cell cycle phaseDecrease in tumor mass and reoxygenationSelecting toxicity for hypoxic cells

6、Cytokinetic 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 XIAN JIAOTONG UNIVERSITY機(jī)制概述9腸道相關(guān)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 XIAN JIAOTONG UNIVERSITY10腸道相關(guān)一線藥物（90年代以前的 ）順鉑、5Fu、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

7、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 XIAN JIAOTONG UNIVERSITY藥物11腸道相關(guān) 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 XIAN JIAOTONG UNIVERSITY5Fu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(xì)胞有相同的殺傷作用藥物12腸道相關(guān)5Fu增敏機(jī)

8、制作用于放射抗拒的S期細(xì)胞干擾S期調(diào)控點(diǎn)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 XIAN JIAOTONG UNIVERSITY藥物13腸道相關(guān) 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 XIAN JIAOTONG UNIVERSITY甲酰四氫葉酸順鉑加強(qiáng)5Fu生化調(diào)節(jié)機(jī)制4 用藥時間放療后5min8h5 用藥量200375mg/m25Fu特點(diǎn)：藥物14腸道相關(guān)特點(diǎn)：吸收后在體內(nèi)逐漸變

9、為氟尿嘧啶而起作用 其作用機(jī)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1/41/7 化療指數(shù)為氟尿嘧啶的2倍 血液中半衰期為5h 用藥量，一般5001000mg/day慢性毒性試驗中未見到嚴(yán)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 XIAN JIAOTONG UNIVERSITY新一代 替加氟 Tegafur Injection 藥物15腸道相關(guān)卡莫氟(Carmofure)特點(diǎn)：不需經(jīng)過肝臟的藥物代謝而釋放出5-Fu在血液、淋

10、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 XIAN JIAOTONG UNIVERSITY藥物16腸道相關(guān)卡培他濱(Caoecitabine)希羅達(dá)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 XIAN JIAOTONG UNIVERSITY藥物17腸道

11、相關(guān) 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 XIAN JIAOTONG UNIVERSITY順鉑 Cisplatin,PDD，DDP 1 鉑的金屬絡(luò)合物，作用似烷化劑2 主要作用靶點(diǎn)為DNA作用于DNA鏈間及鏈內(nèi)交鏈，形成DDPDNA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18腸道相關(guān)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 XIAN JIAOTONG UNIVER

12、SITY濃度依賴性時間依賴性順鉑小劑量長期用藥抑制腫瘤細(xì)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/d19腸道相關(guān)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 XIAN JIAOTONG UNIVERSITY藥物20腸道相關(guān) 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 XIAN JIAOTONG U

13、NIVERSITY5Fu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16h5Fu持續(xù)給藥增敏效果最佳藥物21腸道相關(guān)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(jī)制不同 抗瘤譜不同萘達(dá)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 XIAN JIAOTONG UNIVERSITY藥物22腸道相關(guān) 西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院SECOND AFFILIATED H

14、OSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG UNIVERSITY紫杉類醇藥物(taxanes) 泰素、紫素、特素、紫脘素，Paclitaxel, Taxol, PTX機(jī)制使微管不可逆的聚集干擾細(xì)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23腸道相關(guān) 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 XIAN JIAOTONG UNIVERSITY是微管解聚抑制劑，其作用于微管/微管蛋白系統(tǒng)，通過促進(jìn)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)

15、定，阻滯細(xì)胞于G2和M期，從而抑制癌細(xì)胞的有絲分裂和增殖。 多西紫杉醇泰索帝、多西他賽、Docetaxel/TXT機(jī)制特點(diǎn)穩(wěn)定微管的作用比紫杉醇強(qiáng)2倍藥物24腸道相關(guān) 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 XIAN JIAOTONG UNIVERSITY健擇gemcitabine hydrochloride,鹽酸吉西他濱細(xì)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(xì)胞在一定的條件下，可以阻止G1期向S期的進(jìn)展 藥物25腸道相關(guān)分子靶向藥物EGFRI (EGFR抑制劑）放射激活EGFR 抗拒

16、放射EGFRI增加腫瘤細(xì)胞的放射敏感性機(jī)制阻止細(xì)胞進(jìn)入S期增加放射誘導(dǎo)的細(xì)胞凋亡抑制放射誘導(dǎo)的EGFR磷酸化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SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG UNIVERSITY藥物26腸道相關(guān)臨床進(jìn)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 XIAN JIAOTONG UNIVERSITY臨床進(jìn)展27腸道相關(guān)N Engl J Med. 1992 Jun 11;326(24):162

17、9-31. （RTOG8501）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 XIAN JIAOTONG UNIVERSITYMETHODS. This phase III prospective, randomized, and stratified trial was undertak

18、en to evaluate the efficacy of four courses of combined fluorouracil (1000 mg per square meter of body-surface area daily for four days) 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

19、squamous-cell carcinoma or adenocarcinoma of the thoracic 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 survival rates at 12 and 24 month

20、s 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 group and 25 in the combined-therapy group were alive at the time of the analysis. Severe and life-threatenin

21、g side effects occurred in 44 percent and 20 percent, respectively, of the patients who received combined therapy, as compared with 25 percent and 3 percent of those treated with radiation alone. 28腸道相關(guān)RTOG85-01隨機(jī)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(rèn)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(biāo)準(zhǔn)治療方案。同步放化療已

22、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)院第二附屬醫(yī)院SECOND AFFILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG UNIVERSITY29腸道相關(guān)1: JAMA. 1999 May 5;281(17):1623-7. Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Onco

23、logy 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 XIAN JIAOTONG UNIVERSITYPATIENTS: Patients had squamous cell or adenocarcinoma of the esophagus, T1-3 N0-1 M0( stage), adequate renal and bone marrow reserve, and a Karnofsky score of at least 50. MethodsInterventions Combin

24、ed modality therapy (n = 134): 50 Gy in 25 fractions over 5 weeks, plus cisplatin 75 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 comp

25、ared 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 the succeeding nonrandomized part, combined therapy produced a 5-year overall sur

26、vival of 14% (95% CI, 6%-23%). Severe acute toxic effects also were greater in the combined therapy groups. There were no significant differences in severe late toxic effects between the groups. CONCLUSION: Combined therapy increases the survival of patients who have squamous cell or adenocarcinoma

27、of the esophagus, T1-3 N0-1 M0, compared with RT alone.1級NCCN30腸道相關(guān)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. 西安交通大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院SECOND AFF

28、ILIATED HOSPITAL OF MEDICAL COLLEGE OF XIAN JIAOTONG UNIVERSITYPURPOSE: To compare the local/regional control, survival, and toxicity of combined-modality therapy using high-dose (64.8 Gy) versus standard-dose (50.4 Gy) radiation therapy for the treatment of patients with esophageal cancer. PATIENTS

29、 AND METHODS: A total of 236 patients with clinical stage T1 to T4, N0/1, M0 squamous cell carcinoma or adenocarcinoma 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 b

30、ut with concurrent 50.4 Gy. 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 and local/regional persistence of disease (56% v 52%

31、) between the high-dose and standard-dose arms. CONCLUSION: The higher radiation dose did not increase survival or local/regional control. RTOG 94 0531腸道相關(guān)RTOG 0113.試驗fluorouracil, cisplatin, and paclitaxel 誘導(dǎo)化療然后 fluorouracil paclitaxel50.4 Gy RT (arm A) (37/41)paclitaxel plus cisplatin誘導(dǎo)化療然后 fluor

32、ouracil paclitaxel50.4 Gy RT (arm B) (35/43). 結(jié)果中位生存時間 28.7 months (arm A)，14.9 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(dá)到 77.5%目標(biāo). 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 XIAN J

33、IAOTONG UNIVERSITYJ 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 carcinoma of the esophagus: RTOG 0113.32腸道相關(guān)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

34、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40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)生度、度血液學(xué)毒性及度非血液學(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

35、生存(OS)率為72%,預(yù)計1年無病生存(DFS)率為39%。這項多中心前瞻性期研究提示,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 XIAN JIAOTONG UNIVERSITY33腸道相關(guān)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) 胸部鱗狀細(xì)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.

36、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: 30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

37、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 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 XIAN JIAOTONG UNIVERSITY1: Jpn J Clin Oncol. 2001 Aug;31(8):375-

38、81. LinksConcurrent chemoradiotherapy for squamous cell carcinoma of thoracic esophagus: feasibility and outcome of large regional field and high-dose external beam boost irradiation.34腸道相關(guān)復(fù)旦大學(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)性食管癌的期隨機(jī)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

39、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,d1d3, 5-FU600mg/m2, d1d3,28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(rèn)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 M

40、EDICAL COLLEGE OF XIAN JIAOTONG UNIVERSITYZhao 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 randomized study J . Int J Radiat Oncol Biol Phys, 2005, 62 ( 4 ) : 1014- 1020. 35腸道相關(guān)

41、 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 XIAN JIAOTONG UNIVERSITY目的：評價聯(lián)合放療和化療與單獨(dú)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(xiàn)文摘數(shù)據(jù)庫（Cancer LIT）、聯(lián)機(jī)醫(yī)學(xué)文獻(xiàn)分析與檢索系統(tǒng)（MEDLINE）, 醫(yī)學(xué)文摘數(shù)據(jù)庫（ EMBASE）

42、 主要結(jié)果：19個隨機(jī)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) 0.64 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(yán)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。 Cochrane Database Sy

43、st Rev36腸道相關(guān)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 significant toxicities. In patients who are in good general condition, and the risk benefit has been th

44、oroughly discussed with the patient, concomitant RTCT should be considered for the management of esophageal cancer compared with 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 XIAN JIAOTONG UNIVERSITYCochrane Database Syst Rev. 2001;(2):CD002092.Combined chemothe

45、rapy and radiotherapy (without surgery) compared 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 localized carcinoma of the esophagus. 1: Cochr

46、ane Database Syst Rev. 2006 Jan 25;(1):CD002092.Combined chemotherapy and radiotherapy (without surgery) compared with radiotherapy alone in localized carcinoma of the esophagus.Wong R, Malthaner R. 37腸道相關(guān)Philip進(jìn)行多中心前瞻隨機(jī)試驗比較了標(biāo)準(zhǔn)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,d1d42)、順鉑(60mg/m2,d1

47、、d22),對腫瘤區(qū)和區(qū)域淋巴結(jié)同時照射,總劑量5060Gy44例接受標(biāo)準(zhǔn)手術(shù),手術(shù)死亡率618% ,術(shù)后并發(fā)癥發(fā)生率達(dá)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%、54.5%。提示同步放化療與手術(shù)治療療效相當(dāng),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 XIAN JIAOTONG UNIVERSITYChiu PW, Chan AC, Leung SF, et al. Multicenter prosp

48、ective randomized 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, 9 (6) : 794 - 802. 38腸道相關(guān)同步放化療后是否可以延緩手術(shù),也是目前研究的熱點(diǎn)法國Bedenne 法國Bedenne

49、FFCD9102試驗,Eligible patients had operable T3N0-1M0 thoracic esophageal cancer. Patients received two cycles of fluorouracil (FU) and cisplatin (days 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 random

50、ly assigned to surgery (arm A) or continuation of chemoradiation (arm 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(jìn)一步的手術(shù)切除,其余患者接受進(jìn)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 suggest that, in p

51、atients 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 additional chemoradiation. 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 XIAN JIAOTONG UN

52、IVERSITYBedenne L,Michel P, Bouche O, et al. Chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus: FFCD9102 J . J Clin Oncol, 2007, 25(10) : 1160 - 1168. 39腸道相關(guān)日本Yamada對早期(I期)食管癌同步放化療的可行性進(jìn)行研究63例患者,其中T1a(粘膜癌)有23例,T1b(粘膜下癌)40例放療外照射5560Gy/5060d,同步13周

53、期FP方案化療,隨后腔內(nèi)照射1012Gy/23次。5年總生存率及無疾病生存率分別為66.4%和63.7%; T1a、T1b 5年無疾病生存率分別為84.4%、50.5% 作者認(rèn)為同步放化療對I期食管癌的器官保存率為89.2% ,長期生存率與手術(shù)相當(dāng)。 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 XIAN JIAOTONG UNIVERSITYYamada K, MurakamiM,Okamoto Y, et al. Treatment results of chemoradiotherapy for clini

54、cal stage I ( T1N0M0) esophageal carcinoma J . Int J Radiat Oncol Biol Phys, 2006, 64 ( 4 ) : 1106- 1111. 40腸道相關(guān)同步放化療后手術(shù):術(shù)后病理完全緩解是提高生存率的唯一因素 美國馬里蘭醫(yī)學(xué)中心報告術(shù)前采用同步放化療(放療劑量為50.4 Gy,化療方案為順鉑+5-氟尿嘧啶,放療中進(jìn)行2個周期的化療),中位時間間隔7周后手術(shù)。 多因素分析顯示,T分期、病變長度、組織學(xué)及手術(shù)時間間隔對OS率沒有影響,只有術(shù)后病理完全緩解(pCR)是唯一可以提高生存率的因素。而組織學(xué)是唯一可以預(yù)測術(shù)后病理結(jié)果的

55、因素,鱗癌比腺癌有更高的術(shù)后pCR率(56%對35%)。腺癌中,淋巴結(jié)陰性者和陽性者的pCR率分別為45%和28%(P=0.049),因此,淋巴結(jié)狀態(tài)也是預(yù)測術(shù)后病理結(jié)果的指標(biāo)之一。術(shù)后病理殘存腫瘤組的3年OS率也達(dá)到了36%(RTOG 8501試驗的3年OS率為30%)。 對期食管癌進(jìn)行了分層研究,期包括M1a(有腹腔淋巴結(jié)轉(zhuǎn)移)和M1b(有其他部位淋巴結(jié)轉(zhuǎn)移,但不包括結(jié)外轉(zhuǎn)移)。期(27例)和期的OS相比,無顯著差異(25.2個月對27個月)。此外,這組期病例中,61%的受累淋巴結(jié)沒有在術(shù)前通過PET或CT檢測出來,因此,術(shù)前精確辨別M1a和M1b的淋巴結(jié)病變將會進(jìn)一步指導(dǎo)放療,提高可手術(shù)

56、、無結(jié)外轉(zhuǎn)移的a和b患者的療效。 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 XIAN JIAOTONG UNIVERSITY第49屆ASTRO年會報道(三)食管癌放療進(jìn)展 北京醫(yī)院放療科 高鴻 李高峰 41腸道相關(guān) 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 XIAN JIAOTONG UNIVERSITY英國的Geh系統(tǒng)評價了19802001年的相關(guān)資料對26個隨機(jī)對照試驗的1335位患者進(jìn)行系統(tǒng)評價, 其中311 例患者(

57、24%)取得pCRpCR的發(fā)生率與放療(P=0.006)、5-FU(P=0.003)、順鉑(P=0.018)劑量增加有關(guān)而絲裂霉素C的同步化療不影響pCR同時放射治療時間及中位年齡的增長減少了pCR食管癌/估計值約為4.9Gy,在放療增敏中, 1g/m2的5-FU相當(dāng)于放療劑量1.9Gy(95% CI:0.85.2Gy),100mg/m2的順鉑為7.2Gy(95% CI:2.128Gy)結(jié)論認(rèn)為放射、5-FU、順鉑的劑量與pCR存在劑量反應(yīng)關(guān)系。 Geh J I, Bond SJ, Bentzen SM, et al. Systematic overview of p reoperative

58、( neoadjuvant) chemoradiotherapy trials in oesophageal cancer: evidence of a radiation and chemotherapy dose response J . Radiother Oncol, 2006, 78 (3) : 236 - 244. 42腸道相關(guān)J Clin Oncol. 2002 Jun 15;20(12):2844-50 Oxaliplatin in combination with protracted-infusion fluorouracil and radiation: report o

59、f a clinical trial for patients with esophageal cancer. 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 XIAN JIAOTONG UNIVERSITYCONCLUSION: OXP 85 mg/m(2) on days 1, 15, and 29 administered with PI 5-FU and XRT is safe, tolerable, and seems effective against primary esophageal carcin

60、oma . The role of OXP in multimodality regimens against esophageal carcinoma deserves further evaluation. OXP 85 mg/m2 on days 1, 15, and 29; PI 5-FU 180 mg/m2for 24 hours for 35 days; XRT 1.8 Gy in 28 fractions starting on day 8； 2B2B級是基于低水平證據(jù)，專家組無統(tǒng)一認(rèn)識，但爭議不大 43腸道相關(guān)Active, not recruiting Combination