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Rhabdomyosarcoma

  • Matthew Ladra
  • Karen J. Marcus
  • Torunn Yock
Chapter
Part of the Practical Guides in Radiation Oncology book series (PGRO)

Abstract

  • With roughly 250 new cases each year, pediatric rhabdomyosarcoma (RMS) makes up slightly less than one half of all pediatric soft tissue sarcomas diagnosed within the United States [1].

  • Sites of origin are varied and tumors can arise anywhere within the body. Common sites include the head and neck (35%), genitourinary tract (24%), extremities (19%), and elsewhere (22%) [2].

  • Treatment for RMS depends on risk group stratification. The intensity of chemotherapy and the use of surgery and/or radiotherapy vary between high-, intermediate-, and low-risk groups, which are determined by primary site, stage, clinical group, and histology.
    • Primary Site: The primary sites of origin are categorized as favorable or unfavorable:
      • Favorable sites include the orbit, head and neck, genitourinary tract, and biliary tract.

      • Unfavorable sites include bladder, prostate, perineal/perianal and retroperitoneum, trunk and extremity, and parameningeal tumors.

      • Tumors that involve two adjacent sites with differing designations of favorability are classified as “unfavorable,” so as not to risk delivering inadequate treatment.

    • Stage: The staging for pediatric RMS utilizes the tumor, node, and metastasis (TNM) system but also takes into consideration the primary site (Table 8.1).

    • Clinical Group: The postsurgical extent of disease at the time of chemotherapy initiation determines the clinical group in RMS. The group designation represents the tumor extent before any chemotherapy has been given, and children who have a delayed surgical resection after chemotherapy has begun are still classified based on their initial pre-chemotherapy designation (Table 8.2).

    • Histology: RMS is segregated into favorable (embryonal, botryoid, and spindle cell) and unfavorable (alveolar) histologic subtypes. Embryonal histology comprises 60–70% of all cases, and alveolar histology is seen in 20% of cases [3]. Two translocations, PAX3-FOXO1 and PAX7-FOXO1, involving the transcription factor FOXO1 define alveolar genetics. The presence of these translocations portends a worse prognosis, whereas the absence of these translocations in histologically alveolar tumors indicates an outcome similar to embryonal tumors. In the current COG study, ARST1431, FOXO1 positivity is used to determine risk group and dose [4].

    • Risk Group: Currently, the RMS risk stratifications used by the Children’s Oncology Group (COG) studies separate children into three risk groups (low, intermediate, and high risk). Overall survival varies between the groups and is roughly 98% for low-risk patients, 78% for intermediate-risk patients, and 30% for high-risk patients [5–7]. The current designations for each group are as follows:
      • Low risk: Low-risk RMS is defined as nonmetastatic embryonal RMS arising in favorable sites (stage 1) with any clinical group (group I–III) or embryonal RMS arising in unfavorable sites with either completely resected disease (group I) or microscopic residual disease (group II)

      • Intermediate risk: Intermediate-risk RMS is defined as nonmetastatic (group I–III) alveolar RMS arising at any site (stage 1–3) or incompletely excised (group III) embryonal RMS arising in an unfavorable site (stages 2 and 3).

      • High risk: Patients with metastatic RMS (group IV, stage 4)

References

  1. 1.
    Li J, Thompson TD, Miller JW et al (2008) Cancer incidence among children and adolescents in the United States, 2001-2003. Pediatrics 121:e1470–e1477CrossRefGoogle Scholar
  2. 2.
    Pappo AS (1995) Rhabdomyosarcoma and other soft tissue sarcomas of childhood. Curr Opin Oncol 7:361–366CrossRefGoogle Scholar
  3. 3.
    Parham DM (2001) Pathologic classification of rhabdomyosarcomas and correlations with molecular studies. Mod Pathol 14:506–514CrossRefGoogle Scholar
  4. 4.
    Skapek SX, Anderson J, Barr FG et al (2013) PAX-FOXO1 fusion status drives unfavorable outcome for children with rhabdomyosarcoma: a children’s oncology group report. Pediatr Blood Cancer 60:1411–1417CrossRefGoogle Scholar
  5. 5.
    Arndt CA, Stoner JA, Hawkins DS 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 27:5182–5188CrossRefGoogle Scholar
  6. 6.
    Walterhouse DO, Pappo AS, Meza JL et al (2014) 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 32:3547–3552CrossRefGoogle Scholar
  7. 7.
    Oberlin O, Rey A, Lyden E et al (2008) Prognostic factors in metastatic rhabdomyosarcomas: results of a pooled analysis from United States and European cooperative groups. J Clin Oncol 26:2384–2389CrossRefGoogle Scholar
  8. 8.
    Klem ML, Grewal RK, Wexler LH et al (2007) PET for staging in rhabdomyosarcoma: an evaluation of PET as an adjunct to current staging tools. J Pediatr Hematol Oncol 29:9–14CrossRefGoogle Scholar
  9. 9.
    Eaton BR, McDonald MW, Kim S et al (2013) Radiation therapy target volume reduction in pediatric rhabdomyosarcoma: implications for patterns of disease recurrence and overall survival. Cancer 119:1578–1585CrossRefGoogle Scholar
  10. 10.
    Chen C, Shu HK, Goldwein JW et al (2003) Volumetric considerations in radiotherapy for pediatric parameningeal rhabdomyosarcomas. Int J Radiat Oncol Biol Phys 55:1294–1299CrossRefGoogle Scholar
  11. 11.
    Ermoian RP, Breneman JC, Walterhouse DO et al (2016) Is 45 Gy a sufficient radiation therapy dose for unresected orbital embryonal rhabdomyosarcoma ? A report from the Soft Tissue Sarcoma Committee of the children’s oncology group. Int J Radiat Oncol Biol Phys 96(suppl 2):E548CrossRefGoogle Scholar
  12. 12.
    Neville HL, Andrassy RJ, Lobe TE et al (2000) Preoperative staging, prognostic factors, and outcome for extremity rhabdomyosarcoma: a preliminary report from the Intergroup Rhabdomyosarcoma Study IV (1991-1997). J Pediatr Surg 35:317–321CrossRefGoogle Scholar
  13. 13.
    Wiener ES, Anderson JR, Ojimba JI 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 10:146–152CrossRefGoogle Scholar
  14. 14.
    Casey DL, Wexler LH, LaQuaglia MP et al (2014) Patterns of failure for rhabdomyosarcoma of the perineal and perianal region. Int J Radiat Oncol Biol Phys 89:82–87CrossRefGoogle Scholar
  15. 15.
    Blakely ML, Andrassy RJ, Raney RB et al (2003) 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 38:347–353CrossRefGoogle Scholar
  16. 16.
    Lawrence W Jr, Anderson JR, Gehan EA 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 80:1165–1170CrossRefGoogle Scholar
  17. 17.
    Walterhouse DO, Meza JL, Breneman JC 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 57:76–83CrossRefGoogle Scholar
  18. 18.
    Ladra MM, Edgington SK, Mahajan A et al (2014) A dosimetric comparison of proton and intensity modulated radiation therapy in pediatric rhabdomyosarcoma patients enrolled on a prospective phase II proton study. Radiother Oncol 113:77–83CrossRefGoogle Scholar
  19. 19.
    Cotter SE, Herrup DA, Friedmann A 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 81:1367–1373CrossRefGoogle Scholar
  20. 20.
    Yock T, Schneider R, Friedmann A et al (2005) Proton radiotherapy for orbital rhabdomyosarcoma: clinical outcome and a dosimetric comparison with photons. Int J Radiat Oncol Biol Phys 63:1161–1168CrossRefGoogle Scholar
  21. 21.
    Childs SK, Kozak KR, Friedmann AM et al (2012) Proton radiotherapy for parameningeal rhabdomyosarcoma: clinical outcomes and late effects. Int J Radiat Oncol Biol Phys 82:635–642CrossRefGoogle Scholar
  22. 22.
    Ladra MM, Szymonifka JD, Mahajan A et al (2014) Preliminary results of a phase II trial of proton radiotherapy for pediatric rhabdomyosarcoma. J Clin Oncol 32:3762–3770CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Radiation Oncology and Molecular Radiation SciencesJohns Hopkins School of Medicine/Sibley Memorial HospitalWashington, DCUSA
  2. 2.Dana Farber/Boston Children’s Cancer and Blood Disorders Center, Department of Radiation OncologyBrigham and Women’s Hospital, Harvard Medical SchoolBostonUSA
  3. 3.Department of Radiation OncologyMassachusetts General HospitalBostonUSA

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