恶性胸膜间皮瘤的治疗进展

恶性胸膜间皮瘤的治疗进展,Introduction,Functions of mesothelial cells,Pathology-WHO,上皮型 50%肉瘤型 20%混合型 30%,与肺腺癌的鉴别诊断,Respiratory Medicine (1996) 90, 191-199,Introduction,M:F 1.87.5:1, mostly 4060yrs Rare but ascending morbidity World 0.973.54/105 (Australia)China 0.10.6 /105, 云南大姚8.5/105 Pleural:peritoneum 10:1Primary:metastatic 1:100Pericardium:pleural 1:100Might get its peak at around 2025Mostly fatal:natural history1 year,我国19802004年间发表的 2219例MPM常见症状,表一 Butchart 分期,Butchart EG et al. Thorax 1976;31:15-24.,表二 国际间皮瘤学会（IMIG)TNM 分期,Chest 1995, 108(4):1122,表二 国际间皮瘤学会（IMIG)TNM 分期,Chest 1995, 108(4):1122,表二 国际间皮瘤学会（IMIG)TNM 分期,Chest 1995, 108(4):1122,影响预后的因素,Rusch VW,et al.J. of Thorac. & Cardiovasc. Surg. 122( 4) 788-795,影响预后的因素,Rusch VW,et al.J. of Thorac. & Cardiovasc. Surg. 122( 4) 788-795,Sandra Tomeka,Lung Cancer (2004) 45S, S103S119,影响预后的因素,影响预后的因素,分期KPS组织学类型男性体重下降血红蛋白降低白细胞计数高于8.5 G/ L,伴有血管生成 肿瘤坏死 EGFR COX-2 基质金属蛋白酶MMPs,Treatment,外科手术治疗,手术治疗是否优于其他治疗手段？手术治疗并发症发生率？大范围手术的必要性？,手术治疗,胸膜外肺切除术（胸膜全肺切除术） （extrapleural pneumonectomy,EPP)胸膜剥脱术(pleurectomy/decortication,P/D)胸膜固定术,胸膜全肺切除术（EPP）,Introduced in 1940sUsed in MPM for more than 30 yearsOperative mortalities 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 et al. J. of Thorac. 138-146,EPP not better than P/D,RUSCH 68:1799804,手术治疗,没有证据表明，手术治疗优于任何其他治疗手段！,综合治疗优于单纯手术,RUSCH 68:1799804,EPP尽管围手术期死亡率下降，但并发症仍然高达60%以上现有证据（III类）表明，EPP的疗效并不优于P/D没有证据表明手术作为单一治疗优于其他治疗手段,手术治疗,化学治疗,Sandra Tomeka,Lung Cancer (2004) 45S, S103S119,Sandra Tomeka,Lung Cancer (2004) 45S, S103S119,Sandra Tomeka,Lung Cancer (2004) 45S, S103S119,Meta analysis of chemo,1965-2001年6月间发表的II期临床研究83项研究，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 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 of patients responding to the allowed treatment between the number of evaluable patients according to ELCWP criteria. P0.001.,T. Berghmans et al. / Lung Cancer 38 (2002) 111-121,Meta for Chemo-conclusion,顺铂+阿霉素是反应率最高的联合化疗方案 (28.5%; P0.001)顺铂是最有效的单药.,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 bidimensionally 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.,Vogelzang 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, 222 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 days.,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, et al.JCO 2003, 21( 14 ): 2636-2644,化学治疗,MPM对化疗敏感性不佳，大多数化疗方案有效率仅1020%1个meta：铂类是最有效的单药铂类为主的联合方案更优III期临床：PDD+Alimta优于PDD证据级别：I 治疗建议级别：A,放射治疗,体外试验表明MPM对放疗敏感RCT表明预防照射可以明显减少针道/引流口种植发生传统放疗难以提高剂量IMRT的出现使得提高剂量的同时不增加乃至降低并发症成为可能含有放疗的综合治疗可改善生存,放射治疗预防针道种植,胸腔镜检后种植发生率高达45%,Boutin C,et al.Cancer 1993;72:389-93.,放疗预防种植RCT(France),40pts,(33 male,7 female),20 for radio,20 for surveillance Life expectancy no less than 3 mReceived thoracoscopy 1 m after biopsyPuncture sites still visible28 received chemo,none succeededRadiotherapy :21Gy/3f/3d,12.5-15Mev-, 1cm paraffin bolus,Boutin c,et al. Chest 1995,108(3),754-758,Chest 1995,108(3),754-758,放疗预防种植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 p0.001,20cases,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.,放疗预防种植retrospective(UK),Clinical Oncology (1995) 7:317-318,姑息止痛,Graaf-strukowska L等14对189例病人的共227程姑息放疗进行了回顾性分析，局部有效率40-50%，中位缓解期仅69天(32-363天) 。Bisset D等15对胸痛患者进行了30Gy的半胸照射, 近期有效率68%，但在五个月以后几乎无一例外出现疼痛复发。,传统放疗合并症发生率较高,TOBLER M，et al.IJROBP 1999, 43（ 3）, 511516,精确放疗技术可安全提高剂量,IMRT在提高剂量同时可较好保护正常器官,IMRT在提高剂量同时可较好保护正常器官,放疗作为综合治疗手段,综合治疗,P/DIMRT/-CT,放射治疗,可有效预防针道种植可姑息止痛，但缓解期较短作为综合治疗的一部分，疗效优于单纯手术放疗新技术的出现使得提高剂量同时保护正常组织成为可能需要进一步开展临床研究,Conclusion,恶性胸膜间皮瘤恶性度高，预后差，