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Value of local treatment in extrapulmonary metastatic Ewing sarcoma

Value of local treatment in extrapulmonary metastatic Ewing sarcoma. Uta Dirksen , Julia Häusler, Andreas Ranft, Tobias Bölling, Georg Gosheger, Volker Vieth, Heribert Jürgens. LONDON 2008. Ewing sarcoma require multimodal treatment concepts. Current paradigm:

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Value of local treatment in extrapulmonary metastatic Ewing sarcoma

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  1. Value of local treatment in extrapulmonary metastaticEwing sarcoma Uta Dirksen , Julia Häusler, Andreas Ranft, Tobias Bölling, Georg Gosheger, Volker Vieth, Heribert Jürgens LONDON 2008

  2. Ewing sarcoma require multimodal treatment concepts • Current paradigm: Ewing sarcoma cannot be cured by chemotherapy alone, but require additional local treatment 1,2,3,4,5,6,7,8. What then is the impact of local treatment in the therapeutic concept in primary disseminated Ewing sarcoma with extrapulmonary metastases (EPMET)? 1) Jurgens H et al. Cancer 1988, 2) Paulussen M et al. J Clin Oncol 2001, 3) Burgert EO et al. J Clin Oncol 1990, 4) Nesbit ME et al. J Clin Oncol 1990, 5) Craft AW et al. Eur J Cancer 1997, 6) Bacci G et al. Cancer 1998, 7) Rosito P et al. Cancer 1999, 8) Elomaa I et al. Eur J Cancer 2000

  3. Patients • 120 patients EURO-E.W.I.N.G. 99 trial centre Münster (1999-2006) age 16.2 y (4.2-54.1 y) median follow-up 1.38 y (0.3-8 y) sex 54 f (45%); 66 m (55%) 3-year EFS 0.24 [95% CI 0.16-0.33] median tumour volume 493 ml

  4. Patients` characteristics • Primary tumour 82 pts (68%) central axial (pelvis, spine, abdomen, chest, head, neck) 34 pts (28.5%) extremities (upper and lower extremities) 4 pts (3.5%) not defined

  5. Patients` characteristics • Metastatic sites 97 pts (82.2%) bone 1 met (11 pts; 11.7%), 2-5 met (30 pts; 31.9%), >5 met (53 pts; 56.4%) 49 pts (43.8%) (+) bone marrow 47 pts (39.5%) + lung 48 pts (40%) (+) other ln (26 pts; 22.8%), liver (11 pts; 9.4%), CNS (1 pt; 0.9%), other (10 pts; 9.3%)

  6. Analyses of risk factors • Prognostic factors: - number of bone metastases • - tumour volume • - age • Treatment: - value of high dose chemotherapy - value of local therapy to primary tumour • and /or metastases

  7. 1 3y-EFS:0.61 (N=11)2-5 3y-EFS:0.16 (N=30)>5 3y-EFS:0.19 (N=53)p<.001 Cumulative Survival Time from diagnosis (years) Number of bone metastases

  8. <200ml 3y-EFS: 0.33 (n=36) >200ml 3y-EFS: 0.23 (n=65)p=.188 Cumulative Survival Time from diagnosis (years) Tumour volume of the primary tumour

  9. <15y 3y-EFS: 0.30 (n=49) >15y 3y-EFS: 0.21 (n=71)p=.114 Cumulative Survival Time from diagnosis (years) Age

  10. EURO - E.W.I.N.G. 99 Treo-Mel 10

  11. other HD 3y-EFS: 0.41 (n=15) Bu-Mel 3y-EFS: 0.26 (n=71)no HD 3y-EFS: 0.13 (n=34)p<.001 Cumulative Survival Time from diagnosis (years) High dose chemotherapy

  12. LT of PT and MET 3y-EFS: 0.37 (n=49) LT of PT or MET 3y-EFS: 0.17 (n=41)no LT 3y-EFS: 0.15 (n=30) p<.001 Cumulative Survival Time from diagnosis (years) Local therapy of primary tumour and/or metastases

  13. OP&RT 3y-EFS:0.47 (n=21)RT 3y-EFS:0.23 (n=40) OP 3y-EFS:0.25 (n=26) no LT 3y-EFS:0.13 (n=33) p<.001 Cumulative Survival Time from diagnosis (years) Local treatment modalities of primary tumour

  14. Risk profile comb. LT= combined local treatment (surgery and radiotherapy), PT= primary tumour, PT-Vol.= tumour volume of the primary tumour • no significant difference in risk profile between patients with combined LT vs no combined LT.

  15. OP&RT 3y-EFS: 0.86 (n=7) RT 3y-EFS: 0.27 (n=37) OP 3y-EFS: 0.25 (n=8) no LT 3y-EFS: 0.17 (n=68) p=.002 Cumulative Survival Time from diagnosis (years) Modalities of local treatment to extrapulmonary metastases

  16. Risk profile comb. LT= combined local treatment (surgeryand radiotherapy), EPM= extrapulmonary metastases, PTV = primary tumour volume • comparable risk profile between patients with combined LT vs no combined LT.

  17. Multivariate analyses (N=101)

  18. Multivariate Analyses (N=101) • Bias: • Patients showing progression within the first 6 monthsof treatment receive - no local treatment - no high dose chemotherapy  Exclusion of patients showing progressive disease within the first 6 months of therapy

  19. Multivariate analyses (N=87)

  20. Conclusion • Combined local treatment (OP&RT) of primary tumour and /or extrapulmonary metastases significantly improves the prognosis in pts with primary disseminated Ewing tumor. • Local treatment of primary tumour and /or extrapulmonary metastases significantly improves the prognosis in pts with primary disseminated Ewing tumor. • High dose chemotherapy must be compatible with local treatment.

  21. Interdisciplinary care 21

  22. THANKS to you Regina Kloss Gabriele Braun-Munzinger Institutions for their support in completing the data set concerning local treatment of metastases. ewing@uni-muenster.de

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