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Rhabdomyosarcoma in childhood, adolescence, and adulthood: Treatment

Authors
M Fatih Okcu, MD, MPH
John Hicks, MD, DDS, PhD
Marc Horowitz, MD
Section Editors
Alberto S Pappo, MD
Thomas F DeLaney, MD
Deputy Editor
Diane MF Savarese, MD

INTRODUCTION

Rhabdomyosarcomas (RMS) are malignant soft tissue tumors that are thought to originate from immature cells that are destined to form striated skeletal muscle; however, these tumors can arise in locations where skeletal muscle is not typically found (eg, the urinary bladder).

The treatment of RMS has evolved considerably over the past several decades. Cure rates have risen, largely due to the use of combined modality therapy trials conducted by large international cooperative groups, such as the Intergroup Rhabdomyosarcoma Study Group (IRSG), which is now known as the Soft Tissue Sarcoma Committee of the Children's Oncology Group [1-3].

This topic review will provide an overview of treatment for RMS. The epidemiology, pathology, molecular pathogenesis, clinical presentation, diagnostic evaluation, and staging of RMS are discussed elsewhere. (See "Rhabdomyosarcoma in childhood and adolescence: Epidemiology, pathology, and molecular pathogenesis" and "Rhabdomyosarcoma in childhood and adolescence: Clinical presentation, diagnostic evaluation, and staging".)

TREATMENT IN CHILDHOOD AND ADOLESCENCE

Overview of risk-adapted therapy — In the past, fewer than 20 percent of patients with rhabdomyosarcoma (RMS) were cured with surgery alone, implying that micrometastatic disease was present at diagnosis in the majority of these patients [4]. In contrast, with the use of modern combined modality therapy, over 70 percent of children with localized RMS can be cured of their disease [3,5,6].

These improved outcomes are the direct result of multimodality therapeutic protocols that have been developed by large international cooperative groups, such as the Intergroup Rhabdomyosarcoma Study Group (IRSG, now known as the Soft Tissue Sarcoma Committee of the Children's Oncology Group). Modern treatment for RMS includes chemotherapy for primary cytoreduction and eradication of both macroscopic and microscopic metastatic disease, surgery if feasible, and radiation therapy (RT) to control microscopic local residual disease.

                                   

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Literature review current through: Nov 2016. | This topic last updated: Fri Dec 11 00:00:00 GMT+00:00 2015.
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References
Top
  1. Ries LAG, Harkins D, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2003, National Cancer Institute. Bethesda, MD. http://seer.cancer.gov/csr/1975_2003 (Accessed on June 10, 2011).
  2. Gatta G, Capocaccia R, Stiller C, et al. Childhood cancer survival trends in Europe: a EUROCARE Working Group study. J Clin Oncol 2005; 23:3742.
  3. Punyko JA, Mertens AC, Baker KS, et al. Long-term survival probabilities for childhood rhabdomyosarcoma. A population-based evaluation. Cancer 2005; 103:1475.
  4. Sutow WW, Sullivan MP, Ried HL, et al. Prognosis in childhood rhabdomyosarcoma. Cancer 1970; 25:1384.
  5. Crist W, Gehan EA, Ragab AH, et al. The Third Intergroup Rhabdomyosarcoma Study. J Clin Oncol 1995; 13:610.
  6. Crist WM, Anderson JR, Meza JL, et al. Intergroup rhabdomyosarcoma study-IV: results for patients with nonmetastatic disease. J Clin Oncol 2001; 19:3091.
  7. Maurer HM, Beltangady M, Gehan EA, et al. The Intergroup Rhabdomyosarcoma Study-I. A final report. Cancer 1988; 61:209.
  8. Maurer HM, Gehan EA, Beltangady M, et al. The Intergroup Rhabdomyosarcoma Study-II. Cancer 1993; 71:1904.
  9. Breneman JC, Lyden E, Pappo AS, et al. Prognostic factors and clinical outcomes in children and adolescents with metastatic rhabdomyosarcoma--a report from the Intergroup Rhabdomyosarcoma Study IV. J Clin Oncol 2003; 21:78.
  10. Raney RB, Walterhouse DO, Meza JL, et al. 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 2011; 29:1312.
  11. Breneman J, Meza J, Donaldson SS, et al. 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 2012; 83:720.
  12. Arndt CA, Stoner JA, Hawkins DS, et al. 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 2009; 27:5182.
  13. Donaldson SS, Meza J, Breneman JC, et al. 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 2001; 51:718.
  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. J Pediatr Hematol Oncol 2001; 23:215.
  15. Lawrence W Jr, Anderson JR, Gehan EA, Maurer H. Pretreatment TNM staging of childhood rhabdomyosarcoma: a report of the Intergroup Rhabdomyosarcoma Study Group. Children's Cancer Study Group. Pediatric Oncology Group. Cancer 1997; 80:1165.
  16. Blakely ML, Lobe TE, Anderson JR, et al. Does debulking improve survival rate in advanced-stage retroperitoneal embryonal rhabdomyosarcoma? J Pediatr Surg 1999; 34:736.
  17. Cecchetto G, Bisogno G, De Corti F, et al. Biopsy or debulking surgery as initial surgery for locally advanced rhabdomyosarcomas in children?: the experience of the Italian Cooperative Group studies. Cancer 2007; 110:2561.
  18. Daya H, Chan HS, Sirkin W, Forte V. Pediatric rhabdomyosarcoma of the head and neck: is there a place for surgical management? Arch Otolaryngol Head Neck Surg 2000; 126:468.
  19. Pappo AS, Meza JL, Donaldson SS, et al. Treatment of localized nonorbital, nonparameningeal head and neck rhabdomyosarcoma: lessons learned from intergroup rhabdomyosarcoma studies III and IV. J Clin Oncol 2003; 21:638.
  20. Seitz G, Dantonello TM, Kosztyla D, et al. Impact of hemiscrotectomy on outcome of patients with embryonal paratesticular rhabdomyosarcoma: results from the Cooperative Soft Tissue Sarcoma Group Studies CWS-86, 91, 96 and 2002P. J Urol 2014; 192:902.
  21. Andrassy RJ, Wiener ES, Raney RB, et al. Thoracic sarcomas in children. Ann Surg 1998; 227:170.
  22. Wiener ES, Anderson JR, Ojimba JI, et al. Controversies in the management of paratesticular rhabdomyosarcoma: is staging retroperitoneal lymph node dissection necessary for adolescents with resected paratesticular rhabdomyosarcoma? Semin Pediatr Surg 2001; 10:146.
  23. Michalkiewicz EL, Rao BN, Gross E, et al. Complications of pelvic exenteration in children who have genitourinary rhabdomyosarcoma. J Pediatr Surg 1997; 32:1277.
  24. Martelli H, Oberlin O, Rey A, et al. Conservative treatment for girls with nonmetastatic rhabdomyosarcoma of the genital tract: A report from the Study Committee of the International Society of Pediatric Oncology. J Clin Oncol 1999; 17:2117.
  25. Andrassy RJ, Wiener ES, Raney RB, et al. Progress in the surgical management of vaginal rhabdomyosarcoma: a 25-year review from the Intergroup Rhabdomyosarcoma Study Group. J Pediatr Surg 1999; 34:731.
  26. Filipas D, Fisch M, Stein R, et al. Rhabdomyosarcoma of the bladder, prostate or vagina: the role of surgery. BJU Int 2004; 93:125.
  27. Heyn R, Newton WA, Raney RB, et al. Preservation of the bladder in patients with rhabdomyosarcoma. J Clin Oncol 1997; 15:69.
  28. Hays DM, Lawrence W Jr, Crist WM, et al. Partial cystectomy in the management of rhabdomyosarcoma of the bladder: a report from the Intergroup Rhabdomyosarcoma Study. J Pediatr Surg 1990; 25:719.
  29. Hays DM, Raney RB, Wharam MD, et al. Children with vesical rhabdomyosarcoma (RMS) treated by partial cystectomy with neoadjuvant or adjuvant chemotherapy, with or without radiotherapy. A report from the Intergroup Rhabdomyosarcoma Study (IRS) Committee. J Pediatr Hematol Oncol 1995; 17:46.
  30. Ferrer FA, Isakoff M, Koyle MA. Bladder/prostate rhabdomyosarcoma: past, present and future. J Urol 2006; 176:1283.
  31. Andrassy RJ, Corpron CA, Hays D, et al. Extremity sarcomas: an analysis of prognostic factors from the Intergroup Rhabdomyosarcoma Study III. J Pediatr Surg 1996; 31:191.
  32. Neville HL, Andrassy RJ, Lobe TE, et al. Preoperative staging, prognostic factors, and outcome for extremity rhabdomyosarcoma: a preliminary report from the Intergroup Rhabdomyosarcoma Study IV (1991-1997). J Pediatr Surg 2000; 35:317.
  33. La TH, Wolden SL, Su Z, et al. Local therapy for rhabdomyosarcoma of the hands and feet: is amputation necessary? A report from the Children's Oncology Group. Int J Radiat Oncol Biol Phys 2011; 80:206.
  34. McMulkin HM, Yanchar NL, Fernandez CV, Giacomantonio C. Sentinel lymph node mapping and biopsy: a potentially valuable tool in the management of childhood extremity rhabdomyosarcoma. Pediatr Surg Int 2003; 19:453.
  35. Neville HL, Andrassy RJ, Lally KP, et al. Lymphatic mapping with sentinel node biopsy in pediatric patients. J Pediatr Surg 2000; 35:961.
  36. Blakely ML, Andrassy RJ, Raney RB, et al. Prognostic factors and surgical treatment guidelines for children with rhabdomyosarcoma of the perineum or anus: a report of Intergroup Rhabdomyosarcoma Studies I through IV, 1972 through 1997. J Pediatr Surg 2003; 38:347.
  37. Beech TR, Moss RL, Anderson JA, et al. What comprises appropriate therapy for children/adolescents with rhabdomyosarcoma arising in the abdominal wall? A report from the Intergroup Rhabdomyosarcoma Study Group. J Pediatr Surg 1999; 34:668.
  38. Saenz NC, Ghavimi F, Gerald W, et al. Chest wall rhabdomyosarcoma. Cancer 1997; 80:1513.
  39. Rodeberg DA, Stoner JA, Hayes-Jordan A, et al. 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 2009; 27:3705.
  40. Dantonello TM, Stark M, Timmermann B, et al. Tumour volume reduction after neoadjuvant chemotherapy impacts outcome in localised embryonal rhabdomyosarcoma. Pediatr Blood Cancer 2015; 62:16.
  41. Godzinski J, Flamant F, Rey A, et al. Value of postchemotherapy bioptical verification of complete clinical remission in previously incompletely resected (stage I and II pT3) malignant mesenchymal tumors in children: International Society of Pediatric Oncology 1984 Malignant Mesenchymal Tumors Study. Med Pediatr Oncol 1994; 22:22.
  42. Raney B, Stoner J, Anderson J, et al. 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 2010; 45:2160.
  43. Rodeberg DA, Wharam MD, Lyden ER, et al. Delayed primary excision with subsequent modification of radiotherapy dose for intermediate-risk rhabdomyosarcoma: a report from the Children's Oncology Group Soft Tissue Sarcoma Committee. Int J Cancer 2015; 137:204.
  44. Temeck BK, Wexler LH, Steinberg SM, et al. Metastasectomy for sarcomatous pediatric histologies: results and prognostic factors. Ann Thorac Surg 1995; 59:1385.
  45. Ben Arush M, Minard-Colin V, Mosseri V, et al. Does aggressive local treatment have an impact on survival in children with metastatic rhabdomyosarcoma? Eur J Cancer 2015; 51:193.
  46. Wolden SL, La TH, LaQuaglia MP, et al. Long-term results of three-dimensional conformal radiation therapy for patients with rhabdomyosarcoma. Cancer 2003; 97:179.
  47. Ladra MM, Szymonifka JD, Mahajan A, et al. Preliminary results of a phase II trial of proton radiotherapy for pediatric rhabdomyosarcoma. J Clin Oncol 2014; 32:3762.
  48. Hug EB, Adams J, Fitzek M, et al. Fractionated, three-dimensional, planning-assisted proton-radiation therapy for orbital rhabdomyosarcoma: a novel technique. Int J Radiat Oncol Biol Phys 2000; 47:979.
  49. Childs SK, Kozak KR, Friedmann AM, et al. Proton radiotherapy for parameningeal rhabdomyosarcoma: clinical outcomes and late effects. Int J Radiat Oncol Biol Phys 2012; 82:635.
  50. Douglas JG, Arndt CA, Hawkins DS. Delayed radiotherapy following dose intensive chemotherapy for parameningeal rhabdomyosarcoma (PM-RMS) of childhood. Eur J Cancer 2007; 43:1045.
  51. Spalding AC, Hawkins DS, Donaldson SS, et al. The effect of radiation timing on patients with high-risk features of parameningeal rhabdomyosarcoma: an analysis of IRS-IV and D9803. Int J Radiat Oncol Biol Phys 2013; 87:512.
  52. Puri DR, Wexler LH, Meyers PA, et al. The challenging role of radiation therapy for very young children with rhabdomyosarcoma. Int J Radiat Oncol Biol Phys 2006; 65:1177.
  53. Defachelles AS, Rey A, Oberlin O, et al. Treatment of nonmetastatic cranial parameningeal rhabdomyosarcoma in children younger than 3 years old: results from international society of pediatric oncology studies MMT 89 and 95. J Clin Oncol 2009; 27:1310.
  54. 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.
  55. Raney RB, Anderson JR, Brown KL, et al. 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 2010; 55:612.
  56. Schuck A, Mattke AC, Schmidt B, et al. Group II rhabdomyosarcoma and rhabdomyosarcomalike tumors: is radiotherapy necessary? J Clin Oncol 2004; 22:143.
  57. Smith LM, Anderson JR, Qualman SJ, et al. 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 2001; 19:4058.
  58. Mandell L, Ghavimi F, Peretz T, et al. Radiocurability of microscopic disease in childhood rhabdomyosarcoma with radiation doses less than 4,000 cGy. J Clin Oncol 1990; 8:1536.
  59. Regine WF, Fontanesi J, Kumar P, et al. Local tumor control in rhabdomyosarcoma following low-dose irradiation: comparison of group II and select group III patients. Int J Radiat Oncol Biol Phys 1995; 31:485.
  60. Wharam MD, Meza J, Anderson J, et al. Failure pattern and factors predictive of local failure in rhabdomyosarcoma: a report of group III patients on the third Intergroup Rhabdomyosarcoma Study. J Clin Oncol 2004; 22:1902.
  61. Rodeberg DA, Anderson JR, Arndt CA, et al. Comparison of outcomes based on treatment algorithms for rhabdomyosarcoma of the bladder/prostate: combined results from the Children's Oncology Group, German Cooperative Soft Tissue Sarcoma Study, Italian Cooperative Group, and International Society of Pediatric Oncology Malignant Mesenchymal Tumors Committee. Int J Cancer 2011; 128:1232.
  62. Walterhouse DO, Meza JL, Breneman JC, et al. 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 2011; 57:76.
  63. Michalski JM, Meza J, Breneman JC, et al. 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 2004; 59:1027.
  64. Kozak KR, Adams J, Krejcarek SJ, et al. A dosimetric comparison of proton and intensity-modulated photon radiotherapy for pediatric parameningeal rhabdomyosarcomas. Int J Radiat Oncol Biol Phys 2009; 74:179.
  65. Raney RB, Meza J, Anderson JR, et al. Treatment of children and adolescents with localized parameningeal sarcoma: experience of the Intergroup Rhabdomyosarcoma Study Group protocols IRS-II through -IV, 1978-1997. Med Pediatr Oncol 2002; 38:22.
  66. Benk V, Rodary C, Donaldson SS, et al. Parameningeal rhabdomyosarcoma: results of an international workshop. Int J Radiat Oncol Biol Phys 1996; 36:533.
  67. Meazza C, Ferrari A, Casanova M, et al. Evolving treatment strategies for parameningeal rhabdomyosarcoma: the experience of the Istituto Nazionale Tumori of Milan. Head Neck 2005; 27:49.
  68. Merks JH, De Salvo GL, Bergeron C, et al. Parameningeal rhabdomyosarcoma in pediatric age: results of a pooled analysis from North American and European cooperative groups. Ann Oncol 2014; 25:231.
  69. Magné N, Oberlin O, Martelli H, et al. Vulval and vaginal rhabdomyosarcoma in children: update and reappraisal of Institut Gustave Roussy brachytherapy experience. Int J Radiat Oncol Biol Phys 2008; 72:878.
  70. Nag S, Cano ER, Demanes DJ, et al. The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for head-and-neck carcinoma. Int J Radiat Oncol Biol Phys 2001; 50:1190.
  71. Meza JL, Anderson J, Pappo AS, et al. 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 2006; 24:3844.
  72. Burke M, Anderson JR, Kao SC, et al. Assessment of response to induction therapy and its influence on 5-year failure-free survival in group III rhabdomyosarcoma: the Intergroup Rhabdomyosarcoma Study-IV experience--a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group. J Clin Oncol 2007; 25:4909.
  73. Little DJ, Ballo MT, Zagars GK, et al. Adult rhabdomyosarcoma: outcome following multimodality treatment. Cancer 2002; 95:377.
  74. Ferrari A, Dileo P, Casanova M, et al. Rhabdomyosarcoma in adults. A retrospective analysis of 171 patients treated at a single institution. Cancer 2003; 98:571.
  75. Raney RB, Asmar L, Vassilopoulou-Sellin R, et al. Late complications of therapy in 213 children with localized, nonorbital soft-tissue sarcoma of the head and neck: A descriptive report from the Intergroup Rhabdomyosarcoma Studies (IRS)-II and - III. IRS Group of the Children's Cancer Group and the Pediatric Oncology Group. Med Pediatr Oncol 1999; 33:362.
  76. Children's Oncology Group long-term follow-up guidelines available online at www.survivorshipguidelines.org (Accessed on June 10, 2011).
  77. 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.
  78. Breitfeld PP, Lyden E, Raney RB, et al. Ifosfamide and etoposide are superior to vincristine and melphalan for pediatric metastatic rhabdomyosarcoma when administered with irradiation and combination chemotherapy: a report from the Intergroup Rhabdomyosarcoma Study Group. J Pediatr Hematol Oncol 2001; 23:225.
  79. Walterhouse DO, Pappo AS, Meza JL, et al. Shorter-duration therapy using vincristine, dactinomycin, and lower-dose cyclophosphamide with or without radiotherapy for patients with newly diagnosed low-risk rhabdomyosarcoma: a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group. J Clin Oncol 2014; 32:3547.
  80. Walterhouse D, Pappo AS, Meza JL, et al. Shorter duration therapy that includes vincristine (V), dactinomycon (A), and lower doses of cyclophosphamide (C) with or without radiation therapy for patients with newly diagnosed low-risk embryonal rhabdomyosarcoma (ERMS): A report from the Childreen's Oncology Group (COG). (Abstract 9516). J Clin oncol 2011; 29:589s. (Abstract available online at http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=102&abstractID=77259 (Accessed on September 20, 2011).
  81. Russell H, Swint JM, Lal L, et al. Cost minimization analysis of two treatment regimens for low-risk rhabdomyosarcoma in children: a report from the Children's Oncology Group. Pediatr Blood Cancer 2014; 61:970.
  82. Hawkins DS, Anderson JR, Mascarenhas L, et al. Vincristine, dactinomycin, cyclophosphamide (VAC) versus VAC/V plus irinotecan (VI) for intermediate-risk rhabdomyosarcoma (IRRMS): A report from the Children's Oncology Group Soft Tissue Sarcoma Committee (abstr). J Clin Oncol 32:5s, 2014 (abstractr 10004). Abstract available online at http://meetinglibrary.asco.org/content/126983-144 (Accessed on December 08, 2014).
  83. Oberlin O, Rey A, Lyden E, et al. Prognostic factors in metastatic rhabdomyosarcomas: results of a pooled analysis from United States and European cooperative groups. J Clin Oncol 2008; 26:2384.
  84. Weigel BJ, Lyden E, Anderson JR, et al. Intensive Multiagent Therapy, Including Dose-Compressed Cycles of Ifosfamide/Etoposide and Vincristine/Doxorubicin/Cyclophosphamide, Irinotecan, and Radiation, in Patients With High-Risk Rhabdomyosarcoma: A Report From the Children's Oncology Group. J Clin Oncol 2016; 34:117.
  85. Soft Tissue Sarcoma Committee of the Children's Oncology Group, Lager JJ, Lyden ER, et al. Pooled analysis of phase II window studies in children with contemporary high-risk metastatic rhabdomyosarcoma: a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group. J Clin Oncol 2006; 24:3415.
  86. Information of Clinical trial ARST 08P1 available online at http://clinicaltrials.gov/ct2/show/NCT01055314?term=ARST+08P1&rank=1 (Accessed on May 02, 2011).
  87. Carli M, Colombatti R, Oberlin O, et al. European intergroup studies (MMT4-89 and MMT4-91) on childhood metastatic rhabdomyosarcoma: final results and analysis of prognostic factors. J Clin Oncol 2004; 22:4787.
  88. Boulad F, Kernan NA, LaQuaglia MP, et al. High-dose induction chemoradiotherapy followed by autologous bone marrow transplantation as consolidation therapy in rhabdomyosarcoma, extraosseous Ewing's sarcoma, and undifferentiated sarcoma. J Clin Oncol 1998; 16:1697.
  89. Walterhouse DO, Hoover ML, Marymont MA, Kletzel M. High-dose chemotherapy followed by peripheral blood stem cell rescue for metastatic rhabdomyosarcoma: the experience at Chicago Children's Memorial Hospital. Med Pediatr Oncol 1999; 32:88.
  90. 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.
  91. Klingebiel T, Boos J, Beske F, et al. Treatment of children with metastatic soft tissue sarcoma with oral maintenance compared to high dose chemotherapy: report of the HD CWS-96 trial. Pediatr Blood Cancer 2008; 50:739.
  92. Admiraal R, van der Paardt M, Kobes J, et al. High-dose chemotherapy for children and young adults with stage IV rhabdomyosarcoma. Cochrane Database Syst Rev 2010; :CD006669.
  93. Peinemann F, Kröger N, Bartel C, et al. High-dose chemotherapy followed by autologous stem cell transplantation for metastatic rhabdomyosarcoma--a systematic review. PLoS One 2011; 6:e17127.
  94. Sung L, Anderson JR, Donaldson SS, et al. Late events occurring five years or more after successful therapy for childhood rhabdomyosarcoma: a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group. Eur J Cancer 2004; 40:1878.
  95. Pappo AS, Anderson JR, Crist WM, et al. Survival after relapse in children and adolescents with rhabdomyosarcoma: A report from the Intergroup Rhabdomyosarcoma Study Group. J Clin Oncol 1999; 17:3487.
  96. Mazzoleni S, Bisogno G, Garaventa A, et al. Outcomes and prognostic factors after recurrence in children and adolescents with nonmetastatic rhabdomyosarcoma. Cancer 2005; 104:183.
  97. Dantonello TM, Int-Veen C, Winkler P, et al. Initial patient characteristics can predict pattern and risk of relapse in localized rhabdomyosarcoma. J Clin Oncol 2008; 26:406.
  98. Winter S, Fasola S, Brisse H, et al. Relapse after localized rhabdomyosarcoma: Evaluation of the efficacy of second-line chemotherapy. Pediatr Blood Cancer 2015; 62:1935.
  99. Chisholm JC, Marandet J, Rey A, et al. Prognostic factors after relapse in nonmetastatic rhabdomyosarcoma: a nomogram to better define patients who can be salvaged with further therapy. J Clin Oncol 2011; 29:1319.
  100. Hayes-Jordan A, Doherty DK, West SD, et al. Outcome after surgical resection of recurrent rhabdomyosarcoma. J Pediatr Surg 2006; 41:633.
  101. Miser JS, Kinsella TJ, Triche TJ, et al. Ifosfamide with mesna uroprotection and etoposide: an effective regimen in the treatment of recurrent sarcomas and other tumors of children and young adults. J Clin Oncol 1987; 5:1191.
  102. Vassal G, Couanet D, Stockdale E, et al. Phase II trial of irinotecan in children with relapsed or refractory rhabdomyosarcoma: a joint study of the French Society of Pediatric Oncology and the United Kingdom Children's Cancer Study Group. J Clin Oncol 2007; 25:356.
  103. Antman K, Crowley J, Balcerzak SP, et al. A Southwest Oncology Group and Cancer and Leukemia Group B phase II study of doxorubicin, dacarbazine, ifosfamide, and mesna in adults with advanced osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma. Cancer 1998; 82:1288.
  104. Pappo AS, Bowman LC, Furman WL, et al. A phase II trial of high-dose methotrexate in previously untreated children and adolescents with high-risk unresectable or metastatic rhabdomyosarcoma. J Pediatr Hematol Oncol 1997; 19:438.
  105. Carpenter PA, White L, McCowage GB, et al. A dose-intensive, cyclophosphamide-based regimen for the treatment of recurrent/progressive or advanced solid tumors of childhood: a report from the Australia and New Zealand Children's Cancer Study Group. Cancer 1997; 80:489.
  106. Carli M, Perilongo G, di Montezemolo LC, et al. Phase II trial of cisplatin and etoposide in children with advanced soft tissue sarcoma: a report from the Italian Cooperative Rhabdomyosarcoma Group. Cancer Treat Rep 1987; 71:525.
  107. Saylors RL 3rd, Stine KC, Sullivan J, et al. Cyclophosphamide plus topotecan in children with recurrent or refractory solid tumors: a Pediatric Oncology Group phase II study. J Clin Oncol 2001; 19:3463.
  108. Blanchette P, Hogg D, Ferguson P, et al. Topotecan and cyclophosphamide in adults with relapsed sarcoma. Sarcoma 2012; 2012:749067.
  109. Mascarenhas L, Meyer WH, Lyden E, et al. Randomized phase II trial of bevacizumab and temsirolimus in combination with vinorelbine (V) and cyclophosphmide (C) for first relapse/disease progression of rhabdomyosarcoma (RMS): A report from the Children's Oncology Group (COG) (abstract). J Clin Oncol 32:5s, 2014 (suppl; abstr 10003). Abstract available online at http://meetinglibrary.asco.org/content/126151-144 (Accessed on December 08, 2014).
  110. Atra A, Ward HC, Aitken K, et al. Conservative surgery in multimodal therapy for pelvic rhabdomyosarcoma in children. Br J Cancer 1994; 70:1004.
  111. Raney B Jr, Heyn R, Hays DM, et al. 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 1993; 71:2387.
  112. Yeung CK, Ward HC, Ransley PG, et al. Bladder and kidney function after cure of pelvic rhabdomyosarcoma in childhood. Br J Cancer 1994; 70:1000.
  113. Kaste SC, Hopkins KP, Bowman LC. Dental abnormalities in long-term survivors of head and neck rhabdomyosarcoma. Med Pediatr Oncol 1995; 25:96.
  114. Estilo CL, Huryn JM, Kraus DH, et al. Effects of therapy on dentofacial development in long-term survivors of head and neck rhabdomyosarcoma: the memorial sloan-kettering cancer center experience. J Pediatr Hematol Oncol 2003; 25:215.
  115. Lipshultz SE, Colan SD, Gelber RD, et al. Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood. N Engl J Med 1991; 324:808.
  116. Heyn R, Haeberlen V, Newton WA, et al. Second malignant neoplasms in children treated for rhabdomyosarcoma. Intergroup Rhabdomyosarcoma Study Committee. J Clin Oncol 1993; 11:262.
  117. Heyn R, Khan F, Ensign LG, et al. Acute myeloid leukemia in patients treated for rhabdomyosarcoma with cyclophosphamide and low-dose etoposide on Intergroup Rhabdomyosarcoma Study III: an interim report. Med Pediatr Oncol 1994; 23:99.
  118. Scaradavou A, Heller G, Sklar CA, et al. Second malignant neoplasms in long-term survivors of childhood rhabdomyosarcoma. Cancer 1995; 76:1860.
  119. Bisogno G, Sotti G, Nowicki Y, et al. Soft tissue sarcoma as a second malignant neoplasm in the pediatric age group. Cancer 2004; 100:1758.
  120. Cohen RJ, Curtis RE, Inskip PD, Fraumeni JF Jr. The risk of developing second cancers among survivors of childhood soft tissue sarcoma. Cancer 2005; 103:2391.
  121. Paulino AC, Simon JH, Zhen W, Wen BC. Long-term effects in children treated with radiotherapy for head and neck rhabdomyosarcoma. Int J Radiat Oncol Biol Phys 2000; 48:1489.
  122. Katz JR, Bareille P, Levitt G, Stanhope R. Growth hormone and segmental growth in survivors of head and neck embryonal rhabdomyosarcoma. Arch Dis Child 2001; 84:436.
  123. Raney RB, Anderson JR, Kollath J, et al. 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 2000; 34:413.
  124. Hawkins WG, Hoos A, Antonescu CR, et al. Clinicopathologic analysis of patients with adult rhabdomyosarcoma. Cancer 2001; 91:794.
  125. Ogilvie CM, Crawford EA, Slotcavage RL, et al. Treatment of adult rhabdomyosarcoma. Am J Clin Oncol 2010; 33:128.
  126. Esnaola NF, Rubin BP, Baldini EH, et al. Response to chemotherapy and predictors of survival in adult rhabdomyosarcoma. Ann Surg 2001; 234:215.
  127. Hulse N, Raja S, Kumar A, Paul AS. Rhabdomyosarcoma of the extremities in adults. Acta Orthop Belg 2006; 72:199.
  128. Sultan I, Qaddoumi I, Yaser S, et al. Comparing adult and pediatric rhabdomyosarcoma in the surveillance, epidemiology and end results program, 1973 to 2005: an analysis of 2,600 patients. J Clin Oncol 2009; 27:3391.
  129. Gerber NK, Wexler LH, Singer S, et al. Adult rhabdomyosarcoma survival improved with treatment on multimodality protocols. Int J Radiat Oncol Biol Phys 2013; 86:58.