Reglas relativas a la competencia Están prohibidos todos los

In an attempt to better define patients at high risk of relapse, an analysis of the High risk arm of the CWS/RMS 96 has been made. The group of patients with alveolar RMS and nodal involvement had the poorest outcome, comparable to that of group IV patients. In CWS/RMS 96 the 3 years EFS was 28% and OS 29%.

Results in the SIOP experience were only partially better with 5-year EFS of 39%.

These patients consequently will be treated with the more intensive strategy outlined in this protocol comprising the IVADo regimen and the maintenance chemotherapy to improve the results in comparison with historical controls.

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9. References

1. Newton WA, Jr., Gehan EA, Webber BL, et al. Classification of rhabdomyosarcomas and related sarcomas. Pathologic aspects and proposal for a new classification--an Intergroup Rhabdomyosarcoma Study. Cancer 1995;76:1073-1085.

2. Barr FG. Molecular genetics and pathogenesis of rhabdomyosarcoma. J Pediatr Hematol Oncol

1997;19:483-491.

3. Scrable H, Witte D, Shimada H, et al. Molecular differential pathology of rhabdomyosarcoma.

Genes Chromosomes Cancer 1989;1:23-35.

4. Crist WM, Anderson JR, Meza JL, et al. Intergroup rhabdomyosarcoma study-IV: results for patients with nonmetastatic disease. J Clin Oncol 2001;19:3091-3102.

5. Flamant F, Rodary C, Voute PA, Otten J. Primary chemotherapy in the treatment of

rhabdomyosarcoma in children: trial of the International Society of Pediatric Oncology (SIOP) preliminary results. Radiother Oncol 1985;3:227-236.

6. Flamant F, Rodary C, Rey A, et al. Treatment of non-metastatic rhabdomyosarcomas in childhood and adolescence. Results of the second study of the International Society of Paediatric Oncology MMT84.

Eur J Cancer 1998;34:1050-1056.

7. Oberlin O, Rey A, Anderson J, et al. Treatment of orbital rhabdomyosarcoma: survival and late effects of treatment--results of an international workshop. J Clin Oncol 2001;19:197-204.

8. Anderson J, Raney RB, Carli M, al. e. International study of characteristics and outcome of patients with primary rhabdomyosarcoma of the bladder / prostate. Med Pediatr Oncol 2001;37:181.

9. Koscielniak E, Jurgens H, Winkler K, et al. Treatment of soft tissue sarcoma in childhood and adolescence. A report of the German Cooperative Soft Tissue Sarcoma Study. Cancer 1992;15:2557-2567.

10. Koscielniak E, Harms D, Henze G, et al. Results of treatment for soft tissue sarcoma in

childhood and adolescence: a final report of the German Cooperative Soft Tissue Sarcoma Study CWS-86. J Clin Oncol 1999;17:3706-3719.

11. Koscielniak E, Schmidt B, Knietig R, al. e. Effectiviy of a 32 Gy radiation dose in children with rhabdomyosarcoma: Report of the German Cooperative Soft Tissue Sarcoma Studies (CWS). Med Pediatr Oncol 2001;37:186.

12. Carli M, Bisogno G, Cecchetto G, al. e. Childhood Rhabdomyosarcoma: Results of the Italian Cooperative study RMS88. Medical and Pediatric Oncology 1998;31:262.

13. Ferrari A, Bisogno G, Casanova M, et al. Paratesticular rhabdomyosarcoma: report from the Italian and German Cooperative Group. J Clin Oncol 2002;20:449-455.

14. Raney RB, Anderson JR, Barr FG, et al. Rhabdomyosarcoma and Undifferentiated Sarcoma in the First Two Decades of Life: A Selective Review of Intergroup Rhabdomyosarcoma Study Group Experience and Rationale for Intergroup Rhabdomyosarcoma Study V. Am J Pediatr Hematol Oncol

2001;23:215-220.

15. Pappo AS, Shapiro DN, Crist WM, Maurer HM. Biology and therapy of pediatric rhabdomyosarcoma. J Clin Oncol 1995;13:2123-2139.

16. Wolden SL, Anderson JR, Crist WM, et al. Indications for radiotherapy and chemotherapy after complete resection in rhabdomyosarcoma: A report from the Intergroup Rhabdomyosarcoma Studies I to III.

J Clin Oncol 1999;17:3468-3475.

17. Crist W, Gehan EA, Ragab AH, et al. The Third Intergroup Rhabdomyosarcoma Study. J Clin Oncol 1995;13:610-630.

18. Stewart RJ, Martelli H, Oberlin O, et al. Treatment of children with nonmetastatic paratesticular rhabdomyosarcoma: results of the Malignant Mesenchymal Tumours studies (MMT 84 and MMT 89) of the International Society of Pediatric Oncology. J Clin Oncol 2003;21:793-798.

19. Sandler E, Lyden E, Ruymann F, et al. Efficacy of ifosfamide and doxorubicin given as a phase II "window" in children with newly diagnosed metastatic rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Study Group. Med Pediatr Oncol 2001;37:442-448.

20. Rodriguez-Galindo C, Spunt SL, Pappo AS. Treatment of Ewing sarcoma family of tumors: current status and outlook for the future. Med Pediatr Oncol 2003;40:276-287.

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21. Smith MA, Ungerleider RS, Horowitz ME, Simon R. Influence of doxorubicin dose intensity on response and outcome for patients with osteogenic sarcoma and Ewing's sarcoma. J Natl Cancer Inst

1991;83:1460-1470.

22. Spira AI, Ettinger DS. The use of chemotherapy in soft-tissue sarcomas. Oncologist 2002;7:348- 359.

23. Maurer HM, Beltangady M, Gehan EA, et al. The Intergroup Rhabdomyosarcoma Study-I. A final report. Cancer 1988;61:209-220.

24. Maurer HM, Gehan EA, Beltangady M, et al. The Intergroup Rhabdomyosarcoma Study-II.

Cancer 1993;71:1904-1922.

25. Baker KS, Anderson JR, Link MP, et al. Benefit of intensified therapy for patients with local or regional embryonal rhabdomyosarcoma: results from the Intergroup Rhabdomyosarcoma Study IV. J Clin Oncol 2000;18:2427-2434.

26. Carli M, Colombatti R, Oberlin O, et al. High-dose melphalan with autologous stem-cell rescue in metastatic rhabdomyosarcoma. J Clin Oncol 1999;17:2796-2803.

27. Kushner BH, Kramer K, Cheung NK. Oral etoposide for refractory and relapsed neuroblastoma.

J Clin Oncol 1999;17:3221-3225.

28. Kamen BA, Rubin E, Aisner J, Glatstein E. High-time chemotherapy or high time for low dose. J Clin Oncol 2000;18:2935-2937.

29. Casanova M, Ferrari A, Spreafico F, et al. Vinorelbine in previously treated advanced childhood sarcomas: evidence of activity in rhabdomyosarcoma. Cancer 2002;94:3263-3268.

30. Casanova M, Ferrari A, Bisogno G, Merks JH, De Salvo GL, Meazza C, Tettoni, K, Provenzi M, Mazzarino I, Carli M. Vinorelbine and low-dose cyclophosphamide in the treatment of pediatric sarcomas: pilot study for the upcoming European Rhabdomyosarcoma Protocol. Cancer. 2004; 101:1664-71.

31. Ferrari A, Bisogno G, Casanova M, et al. Is alveolar histotype a prognostic factor in

paratesticular rhabdomyosarcoma? The experience of Italian and German Soft Tissue Sarcoma Cooperative Group. Pediatr Blood Cancer 2004;42:134-138.

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10. Study structure

This protocol includes:

- an observation study

for patients in the low, standard and very high risk groups.

- an investigational study (randomised trial)

for children within the high risk group