惡性胸膜間皮瘤的治療進展

1、惡性胸膜間皮瘤的治療進展,Introduction,Functions of mesothelial cells,Pathology-WHO,上皮型 50%肉瘤型 20%混合型 30%,與肺腺癌的鑒別診斷,Respiratory Medicine (1996) 90, 191-199,Int

2、roduction,M:F 1.8～7.5:1, mostly 40~60yrs Rare but ascending morbidity World 0.97~3.54/105 (Australia)China 0.1~0.6 /105, 云南大姚8.5/105 Pleural:peritoneum 10:1Primary:metastat

3、ic 1:100Pericardium:pleural 1:100Might get its peak at around 2025Mostly fatal:natural history<1 year,我國1980～2004年間發(fā)表的 2219例MPM常見癥狀,表一 Butchart 分期,Butchart EG et al. Thorax 1976;31:15-24.,表二 國際間皮瘤學會（IMIG)TNM 分期,Che

4、st 1995, 108(4):1122．,表二 國際間皮瘤學會（IMIG)TNM 分期,Chest 1995, 108(4):1122．,表二 國際間皮瘤學會（IMIG)TNM 分期,Chest 1995, 108(4):1122．,影響預后的因素,Rusch VW,et al.J. of Thorac. & Cardiovasc. Surg. 122( 4) 788-795,影響預后的因素,Rusch VW,et al

5、.J. of Thorac. & Cardiovasc. Surg. 122( 4) 788-795,Sandra Tomeka,Lung Cancer (2004) 45S, S103—S119,影響預后的因素,影響預后的因素,分期KPS組織學類型男性體重下降血紅蛋白降低白細胞計數(shù)高于8.5 G/ L,,,伴有血管生成 腫瘤壞死 EGFR COX-2 基質(zhì)金屬蛋白酶MMPs,Treatment,外科手術(shù)

6、治療,手術(shù)治療是否優(yōu)于其他治療手段？手術(shù)治療并發(fā)癥發(fā)生率？大范圍手術(shù)的必要性？,手術(shù)治療,胸膜外肺切除術(shù)（胸膜全肺切除術(shù)） （extrapleural pneumonectomy,EPP)胸膜剝脫術(shù)(pleurectomy/decortication,P/D)胸膜固定術(shù),胸膜全肺切除術(shù)（EPP）,Introduced in 1940’sUsed in MPM for more than 30 yearsOperative m

7、ortalities 8% ~ 31%.,Morbidity distribution (%; n 328). AFIB, Atrial fibrillation;MI, myocardial infarction; GI, gastrointestinal. The overall morbidity was 60.4%.,Complications of 328 patients undergoing EPP,Sugarbaker

8、 et al. J. of Thorac. & Cardiovasc. Surg. 128( 1);138-146,,EPP not better than P/D,RUSCH & VENKATRAMAN，Ann Thorac Surg 1999;68:1799–804,手術(shù)治療,沒有證據(jù)表明，手術(shù)治療優(yōu)于任何其他治療手段！,綜合治療優(yōu)于單純手術(shù),RUSCH & VENKATRAMAN，Ann Thorac Su

9、rg 1999;68:1799–804,EPP盡管圍手術(shù)期死亡率下降，但并發(fā)癥仍然高達60%以上現(xiàn)有證據(jù)（III類）表明，EPP的療效并不優(yōu)于P/D沒有證據(jù)表明手術(shù)作為單一治療優(yōu)于其他治療手段,手術(shù)治療,化學治療,Sandra Tomeka,Lung Cancer (2004) 45S, S103—S119,Sandra Tomeka,Lung Cancer (2004) 45S, S103—S119,Sandra Tomeka,L

10、ung Cancer (2004) 45S, S103—S119,Meta analysis of chemo,1965-2001年6月間發(fā)表的II期臨床研究83項研究，共2320例病人 (80 phase II, 3 randomized phase II),T. Berghmans et al. / Lung Cancer 38 (2002) 111-121,Meta analysis for chemo,Group

11、 1, trials testing cisplatin but not doxorubicin; Group 2, trials testing doxorubicin but not cisplatin; Group 3, trials testing cisplatin and doxorubicin; Group 4, trials without cisplatin and doxorubicin. R/E, number

12、 of patients responding to the allowed treatment between the number of evaluable patients according to ELCWP criteria. P?0.001.,T. Berghmans et al. / Lung Cancer 38 (2002) 111-121,Meta for Chemo-conclusion,順鉑+阿霉素是反應率最高的聯(lián)

13、合化療方案 (28.5%; P?0.001)順鉑是最有效的單藥.,T. Berghmans et al. / Lung Cancer 38 (2002) 111-121,Phase III trial of chemo -Eligibility,histologically provenChemotherapy-naive patientsnot eligible for curative surgeryuni- or bidi

14、mensionally measurable diseaseage 18 years with life expectancy 12 weeks KPS no less than 70. no second primary malignancyno brain metastasesexcluded if unable to interrupt nonsteroidal anti-inflammatory drugs.,Voge

15、lzang NJ, et al.JCO 2003, 21( 14 ): 2636-2644,Vogelzang NJ, et al.JCO 2003, 21( 14 ): 2636-2644,Vogelzang NJ, et al.JCO 2003, 21( 14 ): 2636-2644,Phase III trial of chemo,456 pts : 226 received pemetrexed+ cisplatin, 2

16、22 received cisplatin alone, 8 never received therapy.pemetrexed 500 mg/m2 and cisplatin75 mg/m2 on day 1 in combined group cisplatin 75 mg/m2 on day 1 in PDD only groupregimens were given intravenously every 21 day

17、s.,Vogelzang NJ, et al.JCO 2003, 21( 14 ): 2636-2644,*:all PRHazard ratio: 0.77,Phase III trial of chemo,Vogelzang NJ, et al.JCO 2003, 21( 14 ): 2636-2644,Vogelzang NJ, et al.JCO 2003, 21( 14 ): 2636-2644,Vogelzang NJ,

18、et al.JCO 2003, 21( 14 ): 2636-2644,化學治療,MPM對化療敏感性不佳，大多數(shù)化療方案有效率僅10~20%1個meta：鉑類是最有效的單藥鉑類為主的聯(lián)合方案更優(yōu)III期臨床：PDD+Alimta優(yōu)于PDD證據(jù)級別：I 治療建議級別：A,放射治療,體外試驗表明MPM對放療敏感RCT表明預防照射可以明顯減少針道/引流口種植發(fā)生傳統(tǒng)放療難以提高劑量IMRT的出現(xiàn)使得提高劑量的同時不增加乃至

19、降低并發(fā)癥成為可能含有放療的綜合治療可改善生存,放射治療預防針道種植,,胸腔鏡檢后種植發(fā)生率高達45%,Boutin C,et al.Cancer 1993;72:389-93.,放療預防種植—RCT(France),40pts,(33 male,7 female),20 for radio,20 for surveillance Life expectancy no less than 3 mReceived thoracosc

20、opy < 1 m after biopsyPuncture sites still visible28 received chemo,none succeededRadiotherapy :21Gy/3f/3d,12.5-15Mev-ß, 1cm paraffin bolus,Boutin c,et al. Chest 1995,108(

21、3),754-758,Chest 1995,108(3),754-758,放療預防種植—RCT(France),Boutin c,et al. Chest 1995,108(3),754-758,Result subcutaneous nodules: 0/20 of R group vs 8/20 of control group p<0.001,20cases

22、,38 sites irradiated140 kV or 250 kV X-rays, 21Gy /3f/3dNo recurrence in radiation field4 patients act as self-control. Nodules were found in untreated sites.,放療預防種植—retrospective(UK),Clinical Oncology (1995) 7:317-31

23、8,姑息止痛,Graaf-strukowska L等[14]對189例病人的共227程姑息放療進行了回顧性分析，局部有效率40-50%，中位緩解期僅69天(32-363天) 。Bisset D等[15]對胸痛患者進行了30Gy的半胸照射, 近期有效率68%，但在五個月以后幾乎無一例外出現(xiàn)疼痛復發(fā)。,傳統(tǒng)放療合并癥發(fā)生率較高,,TOBLER M，et al.IJROBP 1999, 43（ 3）, 511–516,,,,精確放療技術(shù)可

24、安全提高劑量,IMRT在提高劑量同時可較好保護正常器官,IMRT在提高劑量同時可較好保護正常器官,放療作為綜合治療手段,綜合治療,P/D＋IMRT＋/-CT,放射治療,可有效預防針道種植可姑息止痛，但緩解期較短作為綜合治療的一部分，療效優(yōu)于單純手術(shù)放療新技術(shù)的出現(xiàn)使得提高劑量同時保護正常組織成為可能需要進一步開展臨床研究,Conclusion,惡性胸膜間皮瘤惡性度高，預后差，目前尚無有效治療手段發(fā)病率逐年上升，需重視胸膜外肺

25、切除術(shù)并不優(yōu)于胸膜剝脫術(shù)以手術(shù)＋放療為主的綜合治療可改善生存化療方案以順鉑+阿霉素/Alimta為優(yōu),治療建議,局限性病變推薦手術(shù)＋放療為主的綜合治療晚期以緩解癥狀，改善生存質(zhì)量為主曾行穿刺/胸腔鏡活檢或手術(shù)者盡早進行預防照射以避免種植化療建議采用順鉑+阿霉素/Alimta,展望,可開展前瞻性臨床試驗，探討縮小手術(shù)范圍的可行性放療新技術(shù)與其他治療手段的結(jié)合可否進一步提高療效更有效的化療生物治療，靶向治療等其他治療手段不