恶性胸膜间皮瘤的治疗进展.ppt

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 10:1 Primary:metastatic 1:100 Pericardium:pleural 1:100 Might get its peak at around 2025 Mostly 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 1940s Used in MPM for more than 30 years Operative 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 proven Chemotherapy-naive patients not eligible for curative surgery uni- or bidimensionally measurable disease age 18 years with life expectancy 12 weeks KPS no less than 70. no second primary malignancy no brain metastases excluded 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 cisplatin 75 mg/m2 on day 1 in combined group cisplatin 75 mg/m2 on day 1 in PDD only group regimens were given intravenously every 21 days.,Vogelzang NJ, et al.JCO 2003, 21( 14 ): 2636-2644,*:all PR Hazard 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 m Received thoracoscopy 1 m after biopsy Puncture sites still visible 28 received chemo,none succeeded Radiotherapy :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 irradiated 140 kV or 250 kV X-rays, 21Gy /3f/3d No recurrence in radiation field 4 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，目前尚无有效治