3 rd International Thoracic Oncology Congress Dresden, September 13 15, 2012 Malignant pleural mesothelioma P/D vs. EPP Walter Weder, MD Professor of Surgery
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Extrapleural Pneumonectomy Dokumentenname Datum Seite 2
Pleurectomy/Decortication Dokumentenname Datum Seite 3
Case 1 61 years old female chest pain, dyspnea Thoracoscopic biopsy: Epithelial Mesothelioma no asbestos exposure (ct2 cno) Dokumentenname Datum Seite 4
Treatment + Follow-up Neoadjuvant Chemotherapy with Cis/Pem (3 cycles) EPP ypt 2 ypn 0 (0/17) cm 0 Last CT-scan 04/12 (5.5 years later) recurrence in the right chest, local radiotherapy Patient plays Tennis and Golf Dokumentenname Datum Seite 5
Case 2 53-year old female, fit and sporty, developped dyspnea Epithelial mesothelioma on the right pleura (ct2, cn0) No asbestos exposure Tx: Neo-adjuvant chemotherapy with Cis/Pem 3 cycles followed by P/D Dokumentenname Datum Seite 6
Follow-up Excellent performance Local recurrence detected on the right chest after 26 months Second line chemotherapy with vinorelbine, good response After 38 months multiple nodules on the contralateral pleura Dokumentenname Datum Seite 7
EPP vs. P/D Dilemma Tumor biology of MPM is very hereogenous MPM is rare Only non-controlled cas series with relatively small sample size are available Different combination with other treatments Experience of a specialized team Dokumentenname Datum Seite 8
P/D or EPP Combined retrospective results of 3 centers including 663 patients stage I-IV Early Stage: P/D 35% vs. EPP 25% (p<0.001) Local Recurrences: 65% (P/D) vs 33% (EPP) Operative mortality: 4% (P/D), 7% (EPP) Prognosticator for longer overall survival: Multimodaltiy approach Flores, J Thoracic Cardiovasc Surg 2008 Dokumentenname Datum Seite 9
30-day mortality: MM treatment including EPP Total Patients Adjuvant Neoadjuvant Van Schil, 2010 57 (57 chemo, 42 EPP) 6.5 % (90d) De Perrot, 2009 60 (60 chemo, 45 EPP) 6.7% Buduhan, 2009 55 (55 chemo, 46 EPP) 4.3% Krug, 2009 77 (77 chemo, 54 EPP) 3.6% De Perrot, 2008 62 (44 chemo, 62 EPP) 6.5% Weder, 2007 61 (61 chemo, 45 EPP) 2.2% Opitz, 2006 63 (63 chemo, 63 EPP) 3.2 % Flores, 2008 663 (275 chemo, 385 EPP) 7% Schipper 2007 285 (x chemo, 73 EPP) 8.2% Pagan, 2006 54 (32 chemo, 44 EPP) 4.5% Aziz, 2002 111 (51 chemo, 64 EPP) 9.1% Sugarbaker, 1999 183 (183 chemo, 183 EPP) 3.8% Rusch,1999 115 (x chemo, 115 EPP) 5.2% Inclusion of studies with more than 50 patients Dokumentenname Datum Seite 10
OAS:MM treatment including EPP Total Patients Adjuvant Neoadjuvant Van Schil, 2010 57 (57 chemo, 42 EPP) 18.4 a, 33 b (TMT) Buduhan, 2009 55 (55 chemo, 46 EPP) 24 b (EPP), 25 b (TMT) De Perrot, 2009 60 (60 chemo, 45 EPP) 14 a, 59 b (TMT + N0) Krug, 2009 77 (77 chemo, 54 EPP) 16.8 a, 21.9 b (EPP), 29.1 b (TMT) Weder, 2007 61 (61 chemo, 45 EPP) 19.8 a, 23 b (EPP) Flores, 2008 663 (275 chemo, 385 EPP) 14 Schipper 2007 285 (x chemo, 73 EPP) 10.7 a, 16 b (EPP) Pagan, 2006 54 (32 chemo, 44 EPP) 20 b (EPP) Aziz, 2002 111 (51 chemo, 64 EPP) 35 b (EPP) Sugarbaker, 1999 183 (183 chemo, 183 EPP) 19 b (EPP) Rusch 1999 115 (x chemo, 115 EPP) 29.9 b (stage I) Median OAS (months): a intention to treat, b selected patients: TMT=trimodality treatment Inclusion of studies with more than 50 patients Dokumentenname Datum Seite 11
Neoadjuvant Chemotherapy and EPP-Zurich results Intention to treat 186 patients, 1999-2011 128 patients underwent neoadjuvant chemotherapy followed by EPP 113 male (88%) Median Age 61 years (36, 72) Chemotherapy cisplatin / gemcitabine: 37% (n=47) - 1999-2003 cisplatin / pemetrexed: 63% (n=81) since 03/2003 Adjuvant radiotherapy no: 61 (48%) yes: 67 (52%) Dokumentenname Datum Seite 12
OAS and ypt stage p=0.02 Median OAS: ypt1 (n=11) 39 months (95% CI: 13;66) ypt2 (n=40) 23 months (95% CI: 20;25) ypt3 (n=64) 22 months (95% CI: 17;26) ypt4 (n=13) 15 months (95% CI: 9;20) Opitz, Weder in preparation Dokumentenname Datum Seite 13
OAS and ypn stage (ypn0 vs ypn1/2) p=0.007 Median OAS: ypn0 (n=82) 23 months (95% CI: 20;27) ypn1/2 (n=45) 19 months (95% CI: 14;24) Opitz, Weder in preparation Dokumentenname Datum Seite 14
Zurich Score - a clinical based selection algorithm for multimodality (MM) treatment Every item represents one point => Score 0-3 (maximum) weight loss ( 10% of the bodyweight) non-epithelioid histology Progressive disease after induction chemotherapy (according to RECIST criteria) Opitz, Weder in preparation Dokumentenname Datum Seite 15
OAS and Zurich Score p=0.01 Median OAS: Score 0 (n=29) 23 months (95% CI: 21;24) Score 1 (n=25) 17 months (95% CI: 10;24) Score 2 (n=14) 11 months (95% CI: 3;20) Score 3 (n=2) 3 months (95% CI: -;-) Opitz, Weder in preparation Dokumentenname Datum Seite 16
Tumor volume Gill R R et al. 2012 Pass H. I. et al. 1998 Dokumentenname Datum Seite 17
Surgical Mortality after P/D Investigator Patients CTX Setting P/D Mortality Friedberg 2012 38 Neo + Adj. 38 3.2% Nakas 2008 102 51 7.2% Aziz 2007 302 47 0% Pass 1998 48 Adjuvant 25 2% Halstead 2005 79 51 3.5% Bölükbas 2009 102 Adjuvant 35 5.8% Flores et al. 2008 663 Adjuvant 278 4% Dokumentenname Datum Seite 18
Series with P/D in multimodality therapy Investigator Patients CTX Setting P/D Other Modalities MST (months) Friedberg 2012 38 Neo + Adj. 38 PDT 31.7 Nakas 2008 102 51 15.3 Aziz 2007 302 47 14 Pass 1998 48 Adjuvant 25 PDT, ICTX 22 Halstead 2005 79 51 RTX 13.8 Bölükbas 2009 102 Adjuvant 35 RTX 30 Flores et al. 2008 663 Adjuvant 278 161 16 Dokumentenname Datum Seite 19
Progression-free survival and overall survival for all 38 patients. Joseph S. Friedberg, Melissa J. Culligan, Rosemarie Mick, James Stevenson, Stephen M. Hahn, Daniel Sterman,... Radical Pleurectomy and Intraoperative Photodynamic Therapy for Malignant Pleural Mesothelioma The Annals of Thoracic Surgery Volume 93, Issue 5 2012 1658-1667 Dokumentenname Datum Seite 20
Survival by subtype. Joseph S. Friedberg, Melissa J. Culligan, Rosemarie Mick, James Stevenson, Stephen M. Hahn, Daniel Sterman,... Radical Pleurectomy and Intraoperative Photodynamic Therapy for Malignant Pleural Mesothelioma The Annals of Thoracic Surgery Volume 93, Issue 5 2012 1658-1667 Dokumentenname Datum Seite 21
Disease-free interval EPP vs. LSTP Nakas A et al. Eur J Cardiothorac Surg 2012 Dokumentenname Datum Seite 22
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Conclusion OS after EPP or P/D for MPM does not clearly differ when patients are treated in an experienced center Both procedures are technically demanding and experience is needed Mortality and major morbidity might be lower in P/D Preservation of the lung has an influence on future treatment EPP and P/D are both options to consider and their might be a role for both procedures Dokumentenname Datum Seite 24