Malignant pleural mesothelioma P/D vs. EPP

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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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Dokumentenname Datum Seite 2

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61 years old female

chest pain, dyspnea

Thoracoscopic biopsy: Epithelial Mesothelioma

no asbestos exposure

(cT2 cNo)

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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

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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

(8)

Follow-up

Excellent performance

Local recurrence detected on the right chest after 26 months

Second line chemotherapy with vinorelbine, good response

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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

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Combined retrospective results of 3 centers including 663

patients stage I-IV

Flores, J Thoracic Cardiovasc Surg 2008

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

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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

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OAS:MM treatment including EPP

Total Patients Adjuvant Neoadjuvant Van Schil, 2010 57 (57 chemo, 42 EPP) 18.4a_{, 33}b _(TMT)

Buduhan, 2009 55 (55 chemo, 46 EPP) 24b_{(EPP), 25}b _(TMT)

De Perrot, 2009 60 (60 chemo, 45 EPP) 14a_,₅₉b_{(TMT + N0)}

Krug, 2009 77 (77 chemo, 54 EPP) 16.8a_{, 21.9}b _{(EPP), 29.1}b _(TMT)

Weder, 2007 61 (61 chemo, 45 EPP) 19.8a_{, 23}b _(EPP)

Flores, 2008 663 (275 chemo, 385 EPP) 14

Schipper 2007 285 (x chemo, 73 EPP) 10.7a_{, 16}b_(EPP)

Pagan, 2006 54 (32 chemo, 44 EPP) 20b _(EPP)

Aziz, 2002 111 (51 chemo, 64 EPP) 35b _(EPP)

Sugarbaker, 1999 183 (183 chemo, 183 EPP) 19b _(EPP)

Rusch 1999 115 (x chemo, 115 EPP) 29.9b _{(stage I)}

Median OAS (months): a_{intention to treat,}b_{selected patients: TMT=trimodality treatment}

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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%)

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OAS and ypT stage

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)

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OAS and ypN stage (ypN0 vs ypN1/2)

Median OAS: ypN0 (n=82) 23 months (95% CI: 20;27) ypN1/2 (n=45) 19 months (95% CI: 14;24)

p=0.007

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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)

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OAS and Zurich Score

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: -;-)

p=0.01

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Tumor volume

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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%

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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

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Progression-free survival and overall survival

for all 38 patients

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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

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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