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01-06-2013 | Review

Current strategies and challenges in treatment of childhood rhabdomyosarcoma

Authors: Natia Esiashvili, Roshan Prabhu, Shannon Kahn, Arnold C. Paulino

Published in: Journal of Radiation Oncology | Issue 2/2013

Abstract

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children, affecting very young patients. These tumors often cause significant functional damage because of their aggressive growth pattern. In addition, their metastatic potential can present as a complex and challenging situation. RMS can present in various anatomical sites and often pose significant obstacle in choosing local control modalities. When feasible, surgery plays an important role for initial diagnosis and complete tumor removal; delayed primary re-excision and second-look surgery after initial chemotherapy are gaining more acceptance. Because of high-metastatic risk, systemic chemotherapy is also necessary. Novel agents are emerging which may alter the disease course in high-risk disease where the cure rate is still low. Radiation therapy is an important tool in the management of RMS and has gone through significant evolution during past four decades. This review will outline treatment strategies adopted in children RMS. The primary focus will be the North American approach with attention to advancements in radiation therapy, surgical techniques, and systemic therapies.

Malempati S, Hawkins DS (2012) Rhabdomyosarcoma: review of the Children's Oncology Group (COG) Soft-Tissue Sarcoma Committee experience and rationale for current COG studies. Pediatr Blood Cancer 59(1):5–10PubMedCrossRef

Meza JL et al (2006) Analysis of prognostic factors in patients with nonmetastatic rhabdomyosarcoma treated on intergroup rhabdomyosarcoma studies III and IV: the children's oncology group. J Clin Oncol 24(24):3844–3851PubMedCrossRef

Ognjanovic S et al (2009) Trends in childhood rhabdomyosarcoma incidence and survival in the United States, 1975–2005. Cancer 115(18):4218–4226PubMedCrossRef

Newton WA Jr et al (1988) Histopathology of childhood sarcomas, Intergroup Rhabdomyosarcoma Studies I and II: clinicopathologic correlation. J Clin Oncol 6(1):67–75PubMed

Kelly KM et al (1997) Common and variant gene fusions predict distinct clinical phenotypes in rhabdomyosarcoma. J Clin Oncol 15(5):1831–1836PubMed

Maurer HM et al (1988) The intergroup rhabdomyosarcoma study—I. A final report Cancer 61(2):209–220

Crist WM et al (1990) Prognosis in children with rhabdomyosarcoma: a report of the intergroup rhabdomyosarcoma studies I and II intergroup rhabdomyosarcoma committee. J Clin Oncol 8(3):443–452PubMed

Lawrence W Jr et al (1997) Pretreatment TNM staging of childhood rhabdomyosarcoma: a report of the intergroup rhabdomyosarcoma study group. Children's cancer study group. Pediatric Oncology Group Cancer 80(6):1165–1170

Rodeberg DA et al (2011) Prognostic significance and tumor biology of regional lymph node disease in patients with rhabdomyosarcoma: a report from the children's oncology group. J Clin Oncol 29(10):1304–1311PubMedCrossRef

10.

Raney RB et al (2001) 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. J Pediatr Hematol Oncol 23(4):215–220PubMedCrossRef

11.

Breneman JC et al (2003) Prognostic factors and clinical outcomes in children and adolescents with metastatic rhabdomyosarcoma—a report from the Intergroup Rhabdomyosarcoma Study IV. J Clin Oncol 21(1):78–84PubMedCrossRef

12.

Wiener ES et al (2001) Controversies in the management of paratesticular rhabdomyosarcoma: is staging retroperitoneal lymph node dissection necessary for adolescents with resected paratesticular rhabdomyosarcoma? Semin Pediatr Surg 10(3):146–152PubMedCrossRef

13.

Hayes-Jordan A et al (2008) The impact of surgical excision in chest wall rhabdomyosarcoma: a report from the children's oncology group. J Pediatr Surg 43(5):831–836PubMedCrossRef

14.

Breneman J et al (2012) Local control with reduced-dose radiotherapy for low-risk rhabdomyosarcoma: a report from the Children's Oncology Group D9602 study. Int J Radiat Oncol Biol Phys 83(2):720–726PubMed

15.

Raney B et al (2010) Impact of tumor viability at second-look procedures performed before completing treatment on the Intergroup Rhabdomyosarcoma Study Group protocol IRS-IV, 1991–1997: a report from the children's oncology group. J Pediatr Surg 45(11):2160–2168PubMedCrossRef

16.

Blakely ML (1999) Does debulking improve survival rate in advanced-stage retroperitoneal embryonal rhabdomyosarcoma. J Pediatr Surg 34(5):736–741, discussion 741–2PubMedCrossRef

17.

Rodeberg D A, et al (2010) Tumor volume and patient weight as predictors of outcome in children with intermediate risk rhabdomyosarcoma: a report from the children's oncology group. Cancer

18.

Rodeberg DA et al (2009) Prognostic significance of tumor response at the end of therapy in group III rhabdomyosarcoma: a report from the children's oncology group. J Clin Oncol 27(22):3705–3711PubMedCrossRef

19.

Raney RB et al (2001) The intergroup rhabdomyosarcoma study group (IRSG): major lessons from the IRS-I through IRS-IV studies as background for the current IRS-V treatment protocols. Sarcoma 5(1):9–15PubMedCrossRef

20.

Maurer HM et al (1993) The intergroup rhabdomyosarcoma study—II. Cancer 71(5):1904–1922PubMedCrossRef

21.

Wharam MD et al (1997) Radiation therapy for rhabdomyosarcoma: local failure risk for clinical group III patients on intergroup rhabdomyosarcoma study II. Int J Radiat Oncol Biol Phys 38(4):797–804PubMedCrossRef

22.

Wolden SL et al (1999) Indications for radiotherapy and chemotherapy after complete resection in rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Studies I to III. J Clin Oncol 17(11):3468–3475PubMed

23.

Donaldson SS et al (2001) Results from the IRS-IV randomized trial of hyperfractionated radiotherapy in children with rhabdomyosarcoma—a report from the IRSG. Int J Radiat Oncol Biol Phys 51(3):718–728PubMedCrossRef

24.

Minn AY et al (2010) Early treatment failure in intermediate-risk rhabdomyosarcoma: results from IRS-IV and D9803—a report from the Children's Oncology Group. J Clin Oncol 28(27):4228–4232PubMedCrossRef

25.

Raney RB et al (2011) Results of the Intergroup Rhabdomyosarcoma Study Group D9602 protocol, using vincristine and dactinomycin with or without cyclophosphamide and radiation therapy, for newly diagnosed patients with low-risk embryonal rhabdomyosarcoma: a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group. J Clin Oncol 29(10):1312–1318PubMedCrossRef

26.

Smith LM et al (2001) Which patients with microscopic disease and rhabdomyosarcoma experience relapse after therapy? A report from the soft tissue sarcoma committee of the children's oncology group. J Clin Oncol 19(20):4058–4064PubMed

27.

Walterhouse DO et al (2011) Local control and outcome in children with localized vaginal rhabdomyosarcoma: a report from the Soft Tissue Sarcoma committee of the Children's Oncology Group. Pediatr Blood Cancer 57(1):76–83PubMedCrossRef

28.

Crist WM et al (2001) Intergroup rhabdomyosarcoma study—IV: results for patients with nonmetastatic disease. J Clin Oncol 19(12):3091–3102PubMed

29.

Arndt CA et al (2009) Vincristine, actinomycin, and cyclophosphamide compared with vincristine, actinomycin, and cyclophosphamide alternating with vincristine, topotecan, and cyclophosphamide for intermediate-risk rhabdomyosarcoma: children's oncology group study D9803. J Clin Oncol 27(31):5182–5188PubMedCrossRef

30.

Pappo AS et al (2007) Two consecutive phase II window trials of irinotecan alone or in combination with vincristine for the treatment of metastatic rhabdomyosarcoma: the Children's Oncology Group. J Clin Oncol 25(4):362–369PubMedCrossRef

31.

Raney RB et al (2010) Treatment results for patients with localized, completely resected (Group I) alveolar rhabdomyosarcoma on Intergroup Rhabdomyosarcoma Study Group (IRSG) protocols III and IV, 1984–1997: a report from the Children's Oncology Group. Pediatr Blood Cancer 55(4):612–616PubMedCrossRef

32.

Crist W et al (1995) The third intergroup rhabdomyosarcoma study. J Clin Oncol 13(3):610–630PubMed

33.

Million L et al (2011) Influence of noncompliance with radiation therapy protocol guidelines and operative bed recurrences for children with rhabdomyosarcoma and microscopic residual disease: a report from the Children's Oncology Group. Int J Radiat Oncol Biol Phys 80(2):333–338PubMedCrossRef

34.

Monti AF et al (1995) An ICRU 50 radiotherapy treatment chart. Radiother Oncol 35(2):145–150PubMedCrossRef

35.

Chen C et al (2003) Volumetric considerations in radiotherapy for pediatric parameningeal rhabdomyosarcomas. Int J Radiat Oncol Biol Phys 55(5):1294–1299PubMedCrossRef

36.

McDonald MW et al (2008) Intensity-modulated radiotherapy with use of cone-down boost for pediatric head-and-neck rhabdomyosarcoma. Int J Radiat Oncol Biol Phys 72(3):884–891PubMedCrossRef

37.

Combs SE et al (2007) Intensity modulated radiotherapy (IMRT) and fractionated stereotactic radiotherapy (FSRT) for children with head-and-neck-rhabdomyosarcoma. BMC Cancer 7:177PubMedCrossRef

38.

Lin C (2012) Effect of radiotherapy techniques (IMRT vs. 3D-CRT) on outcome in patients with intermediate-risk rhabdomyosarcoma enrolled in COG D9803—a report from the Children's Oncology Group. Int J Radiat Oncol Biol Phys 82(5):1764–1770PubMedCrossRef

39.

Wolden SL et al (2005) Intensity-modulated radiotherapy for head-and-neck rhabdomyosarcoma. Int J Radiat Oncol Biol Phys 61(5):1432–1438PubMedCrossRef

40.

Childs SK et al (2012) Proton radiotherapy for parameningeal rhabdomyosarcoma: clinical outcomes and late effects. Int J Radiat Oncol Biol Phys 82(2):635–642PubMedCrossRef

41.

Kozak KR et al (2009) A dosimetric comparison of proton and intensity-modulated photon radiotherapy for pediatric parameningeal rhabdomyosarcomas. Int J Radiat Oncol Biol Phys 74(1):179–186PubMedCrossRef

42.

Cotter SE et al (2011) Proton radiotherapy for pediatric bladder/prostate rhabdomyosarcoma: clinical outcomes and dosimetry compared to intensity-modulated radiation therapy. Int J Radiat Oncol Biol Phys 81(5):1367–1373PubMedCrossRef

43.

Yang JC et al (2012) Intensity modulated radiation therapy with dose painting to treat rhabdomyosarcoma. Int J Radiat Oncol Biol Phys 84(3):e371–e377PubMedCrossRef

44.

Michalski JM et al (2004) Influence of radiation therapy parameters on outcome in children treated with radiation therapy for localized parameningeal rhabdomyosarcoma in Intergroup Rhabdomyosarcoma Study Group trials II through IV. Int J Radiat Oncol Biol Phys 59(4):1027–1038PubMedCrossRef

45.

Douglas JG, Arndt CA, Hawkins DS (2007) Delayed radiotherapy following dose intensive chemotherapy for parameningeal rhabdomyosarcoma (PM-RMS) of childhood. Eur J Cancer 43(6):1045–1050PubMedCrossRef

46.

Dantonello TM et al (2011) Embryonal rhabdomyosarcoma with metastases confined to the lungs: report from the CWS Study Group. Pediatr Blood Cancer 56(5):725–732PubMedCrossRef

47.

La TH et al (2011) Regional nodal involvement and patterns of spread along in-transit pathways in children with rhabdomyosarcoma of the extremity: a report from the Children's Oncology Group. Int J Radiat Oncol Biol Phys 80(4):1151–1157PubMedCrossRef

48.

La TH et al (2009) Local therapy for rhabdomyosarcoma of the hands and feet: is there a role for amputation? A report from the children's oncology group. Int J Radiat Oncol Biol Phys 75(3):S40–S41CrossRef

49.

Paulino AC, Pappo A (2009) Alveolar rhabdomyosarcoma of the extremity and nodal metastasis: is the in-transit lymphatic system at risk. Pediatr Blood Cancer 53(7):1332–1333PubMedCrossRef

50.

Flamant F et al (1990) Long-term sequelae of conservative treatment by surgery, brachytherapy, and chemotherapy for vulval and vaginal rhabdomyosarcoma in children. J Clin Oncol 8(11):1847–1853PubMed

51.

Magne N et al (2008) Vulval and vaginal rhabdomyosarcoma in children: update and reappraisal of Institut Gustave Roussy brachytherapy experience. Int J Radiat Oncol Biol Phys 72(3):878–883PubMedCrossRef

52.

Nag S, Grecula J, Ruymann FB (1993) Aggressive chemotherapy, organ-preserving surgery, and high-dose-rate remote brachytherapy in the treatment of rhabdomyosarcoma in infants and young children. Cancer 72(9):2769–2776PubMedCrossRef

53.

Abramson DH et al (1997) Implant brachytherapy: a novel treatment for recurrent orbital rhabdomyosarcoma. J AAPOS 1(3):154–157PubMedCrossRef

54.

Blank LE et al (2009) The AMORE protocol for advanced-stage and recurrent nonorbital rhabdomyosarcoma in the head-and-neck region of children: a radiation oncology view. Int J Radiat Oncol Biol Phys 74(5):1555–1562PubMedCrossRef

55.

Blank LE et al (2010) Brachytherapy as part of the multidisciplinary treatment of childhood rhabdomyosarcomas of the orbit. Int J Radiat Oncol Biol Phys 77(5):1463–1469PubMedCrossRef

56.

Puri DR et al (2006) The challenging role of radiation therapy for very young children with rhabdomyosarcoma. Int J Radiat Oncol Biol Phys 65(4):1177–1184PubMedCrossRef

57.

Malempati S et al (2011) Rhabdomyosarcoma in infants younger than 1 year: a report from the Children's Oncology Group. Cancer 117(15):3493–3501PubMedCrossRef

58.

Gupta AA et al (2012) Patterns of chemotherapy-induced toxicities in younger children and adolescents with rhabdomyosarcoma: a report from the children's oncology group soft tissue sarcoma committee. Cancer 118(4):1130–1137PubMedCrossRef

59.

Paulino AC et al (2000) Long-term effects in children treated with radiotherapy for head and neck rhabdomyosarcoma. Int J Radiat Oncol Biol Phys 48(5):1489–1495PubMedCrossRef

60.

Krasin MJ et al (2012) Jaw dysfunction related to pterygoid and masseter muscle dosimetry after radiation therapy in children and young adults with head-and-neck sarcomas. Int J Radiat Oncol Biol Phys 82(1):355–360PubMedCrossRef

61.

Snyers A et al (2009) Malignant tumors of the nasal cavity and paranasal sinuses: long-term outcome and morbidity with emphasis on hypothalamic–pituitary deficiency. Int J Radiat Oncol Biol Phys 73(5):1343–1351PubMedCrossRef

62.

Gandhi PD et al (2011) Ophthalmic complications following treatment of paranasal sinus rhabdomyosarcoma in comparison to orbital disease. Ophthal Plast Reconstr Surg 27(4):241–246PubMedCrossRef

63.

Raney RB et al (2000) Late effects of therapy in 94 patients with localized rhabdomyosarcoma of the orbit: report from the intergroup rhabdomyosarcoma study (IRS)-III, 1984–1991. Med Pediatr Oncol 34(6):413–420PubMedCrossRef

64.

Macedo A Jr et al (2010) Sexual function in teenagers after multimodal treatment of pelvic rhabdomyosarcoma: a preliminary report. J Pediatr Urol 6(6):605–608PubMedCrossRef

65.

Gruschow K et al (2007) Surgical repositioning of the contralateral testicle before irradiation of a paratesticular rhabdomyosarcoma for preservation of hormone production. Pediatr Hematol Oncol 24(5):371–377PubMedCrossRef

66.

Arndt C et al (2004) Does bladder preservation (as a surgical principle) lead to retaining bladder function in bladder/prostate rhabdomyosarcoma? Results from intergroup rhabdomyosarcoma study IV. J Urol 171(6 Pt 1):2396–2403PubMedCrossRef

67.

Cowles RA, Gewanter RM, Kandel JJ (2007) Ovarian repositioning in pediatric cancer patients: flexible techniques accommodate pelvic radiation fields. Pediatr Blood Cancer 49(3):339–341PubMedCrossRef

68.

Raney B Jr et al (1993) Sequelae of treatment in 109 patients followed for 5 to 15 years after diagnosis of sarcoma of the bladder and prostate. A report from the Intergroup Rhabdomyosarcoma Study Committee. Cancer 71(7):2387–2394PubMedCrossRef

69.

Heyn R et al (1993) Second malignant neoplasms in children treated for rhabdomyosarcoma. Intergroup Rhabdomyosarcoma Study Committee. J Clin Oncol 11(2):262–270PubMed

Title: Current strategies and challenges in treatment of childhood rhabdomyosarcoma
Authors: Natia Esiashvili
Roshan Prabhu
Shannon Kahn
Arnold C. Paulino
Publication date: 01-06-2013
Publisher: Springer-Verlag
Published in: Journal of Radiation Oncology / Issue 2/2013
Print ISSN: 1948-7894
Electronic ISSN: 1948-7908
DOI: https://doi.org/10.1007/s13566-012-0083-2

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