This cancer treatment information summary provides an overview
of the prognosis, diagnosis, classification, staging, and treatment of childhood rhabdomyosarcoma.
The National Cancer Institute provides the PDQ pediatric cancer treatment information summaries as a public service to increase the availability of evidence-based cancer information to health professionals, patients, and the public. These summaries are updated regularly according to the latest published research findings by an Editorial Board of pediatric oncology specialists.
Cancer in children and adolescents is rare. Children and adolescents with
cancer should be referred to medical centers that have a multidisciplinary team
of cancer specialists with experience treating the cancers that occur during
childhood and adolescence. This multidisciplinary team approach incorporates the skills
of the primary care physician, pediatric surgical subspecialists, radiation
oncologist, pediatric oncologist/hematologist, rehabilitation specialist,
pediatric nurse specialists, social workers, and others to ensure that
children receive treatment, supportive care, and rehabilitation that will
achieve optimal survival and quality of life. (Refer to the PDQ Supportive Care summaries for specific information about supportive care for children and adolescents with cancer.)
Guidelines for pediatric cancer
centers and their role in the treatment of pediatric patients with cancer have
been outlined by the American Academy of Pediatrics. At these pediatric
cancer centers, clinical trials are available for most types of cancer
that occur in children and adolescents, and the opportunity to participate in
these trials is offered to most patients/families. Clinical trials for
children and adolescents with cancer are generally designed to compare
potentially better therapy with therapy that is currently accepted as standard.
Most of the progress made in identifying curative therapies for
childhood cancers has been achieved through clinical trials. Information about
ongoing clinical trials is available from the NCI Web site.
In recent decades, dramatic improvements in survival have been achieved for children and adolescents with cancer. Childhood and adolescent cancer survivors require close follow-up because cancer therapy side effects may persist or develop months or years after treatment. (Refer to the PDQ Late Effects of Treatment for Childhood Cancer summary for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.)
Childhood rhabdomyosarcoma, a soft tissue malignant tumor of skeletal muscle
origin, accounts for approximately 3.5% of the cases of cancer among children 0
to 14 years and 2% of the cases among adolescents and young adults aged 15 to 19
years.[2,3] It is usually a curable disease in most children with localized disease who
receive combined modality therapy, with more than 70% surviving 5 years after
diagnosis.[4-6] Relapses are uncommon after 5 years of disease-free survival, with a 9% late-event rate at 10 years. Relapses, however, are more common for patients who have gross residual disease in unfavorable sites following initial surgery and those who have metastatic disease at diagnosis. The most common primary sites for rhabdomyosarcoma are the
head and neck (e.g., parameningeal, orbit, pharyngeal, etc.), the genitourinary
tract, and the extremities.[4,5] Other less common primary sites include the
trunk, chest wall, the abdomen (including the retroperitoneum and
biliary tract), and the perineal/anal region.
Most cases of rhabdomyosarcoma occur sporadically with no
recognized predisposing factor or risk factor, though a small proportion
are associated with genetic conditions. These conditions include Li-Fraumeni
cancer susceptibility syndrome (with germline p53 mutations),[9,10]
neurofibromatosis type I,[11,12] Costello syndrome (with germline HRAS mutations),[13-15] and Beckwith-Wiedemann syndrome (Wilms’
tumor and hepatoblastoma are more commonly associated with the latter syndrome).[16,17]
The prognosis for a child or adolescent with rhabdomyosarcoma is related to the
age of the patient, site of origin, resectability, presence of metastases, number of metastatic sites or tissues involved, presence or absence of lymph node involvement, histopathology,[4,5,18-24] and unique biological characteristics of rhabdomyosarcoma tumor cells. Examples of both
clinical and biological factors with proven or possible prognostic significance
are briefly described below.
- Children younger than 1 year may pose a problem in terms of the ability to deliver aggressive therapy including full-dose radiation and appropriate chemotherapy on schedule; therefore, outcome may be adversely affected.[6,25] Children between 1 and 9 years have the best overall survival.
- Primary sites with more favorable prognoses include the orbit and
nonparameningeal head and neck, paratestis and vagina (nonbladder, nonprostate
genitourinary), and the biliary tract.[4,5,26-28]
- Tumor burden at diagnosis has prognostic significance. Patients with
smaller tumors (<5 cm) have improved survival compared with children with
larger tumors; children with metastatic disease at diagnosis have the
poorest prognosis.[4,26,29] The prognostic significance of metastatic disease
is modified by tumor histology (embryonal is more favorable than other histologies) and by the number of metastatic sites.
Similarly, patients with metastatic genitourinary (nonbladder, nonprostate)
primary tumors have a more favorable outcome compared with patients with
metastatic disease and primary tumors at other sites. In addition,
patients with otherwise localized disease but with proven regional lymph node
involvement have a poorer prognosis than patients without regional nodal
- The extent of disease following the primary surgical procedure (i.e., the
Clinical Group) is also correlated with outcome. In the Intergroup
Rhabdomyosarcoma Study (IRS)-III, patients with gross residual disease after
initial surgery (Clinical Group III) had a 5-year survival rate of
approximately 70% compared with a greater than 90% 5-year survival rate for
patients with no residual tumor after surgery (Clinical Group I) and an
approximately 80% 5-year survival rate for patients with microscopic residual
tumor following surgery (Clinical Group II).[4,18]
- The alveolar subtype is more prevalent among patients with less favorable
clinical features (e.g., younger than 1 year or older than 10 years,
extremity primaries, and metastatic disease), and is generally associated with
a worse outcome. In the IRS-I and IRS-II studies, the alveolar subtype was
associated with a less favorable outcome even in patients whose primary
tumor was completely resected (Clinical Group I). Statistically-significant
differences in survival for histopathologic subtype were not, however, noted
when all patients with rhabdomyosarcoma were analyzed,[31,32] nor were differences
noted by histologic subtype in a large group of German children with
rhabdomyosarcoma. In the IRS-III study, outcome for patients with Clinical
Group I alveolar subtype tumors was similar to those of other patients with
Clinical Group I tumors, but the patients with alveolar subtype received more
- Patients with undifferentiated sarcoma were eligible for participation in rhabdomyosarcoma trials coordinated by the Intergroup Rhabdomyosarcoma Study Group (IRSG) and the Children’s Oncology Group (COG) from 1972 until 2006. The rationale for this inclusion was the observation that patients with undifferentiated sarcoma have similar sites of disease and outcome to those with alveolar rhabdomyosarcoma (ARMS). The patients with undifferentiated sarcoma will be treated on a non-rhabdomyosarcomatous soft tissue sarcoma protocol using agents active in adult soft tissue sarcoma. In therapeutic trials for adults with soft tissue sarcoma, patients with undifferentiated sarcoma are included with all other histologies and treated in a similar manner. Contemporary treatment for adult soft tissue sarcoma utilizes ifosfamide and doxorubicin, sometimes with the addition of other chemotherapeutic agents, surgery, and radiation therapy. There are no data to compare these two approaches.
Because treatment and prognosis depend, in part, on the histology and molecular genetics of the tumor,
it is necessary that the tumor tissue be reviewed by pathologists with
experience in the evaluation and diagnosis of tumors in children.
Additionally, the diversity of primary sites, the distinctive surgical and
radiation therapy treatments for each primary site, and the subsequent
site-specific rehabilitation underscore the importance of treating children
with rhabdomyosarcoma in medical centers with appropriate experience in all
- Guidelines for the pediatric cancer center and role of such centers in diagnosis and treatment. American Academy of Pediatrics Section Statement Section on Hematology/Oncology. Pediatrics 99 (1): 139-41, 1997.
- Gurney JG, Severson RK, Davis S, et al.: Incidence of cancer in children in the United States. Sex-, race-, and 1-year age-specific rates by histologic type. Cancer 75 (8): 2186-95, 1995.
- Ries LA, Kosary CL, Hankey BF, et al., eds.: SEER Cancer Statistics Review, 1973-1996. Bethesda, Md: National Cancer Institute, 1999. Also available online. Last accessed April 19, 2007.
- Crist W, Gehan EA, Ragab AH, et al.: The Third Intergroup Rhabdomyosarcoma Study. J Clin Oncol 13 (3): 610-30, 1995.
- Maurer HM, Gehan EA, Beltangady M, et al.: The Intergroup Rhabdomyosarcoma Study-II. Cancer 71 (5): 1904-22, 1993.
- Crist WM, Anderson JR, Meza JL, et al.: Intergroup rhabdomyosarcoma study-IV: results for patients with nonmetastatic disease. J Clin Oncol 19 (12): 3091-102, 2001.
- 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 40 (12): 1878-85, 2004.
- Gurney JG, Young JL Jr, Roffers SD, et al.: Soft tissue sarcomas. In: Ries LA, Smith MA, Gurney JG, et al., eds.: Cancer incidence and survival among children and adolescents: United States SEER Program 1975-1995. Bethesda, Md: National Cancer Institute, SEER Program, 1999. NIH Pub.No. 99-4649., pp 111-123. Also available online. Last accessed July 20, 2006.
- Li FP, Fraumeni JF Jr: Rhabdomyosarcoma in children: epidemiologic study and identification of a familial cancer syndrome. J Natl Cancer Inst 43 (6): 1365-73, 1969.
- Diller L, Sexsmith E, Gottlieb A, et al.: Germline p53 mutations are frequently detected in young children with rhabdomyosarcoma. J Clin Invest 95 (4): 1606-11, 1995.
- Matsui I, Tanimura M, Kobayashi N, et al.: Neurofibromatosis type 1 and childhood cancer. Cancer 72 (9): 2746-54, 1993.
- Hartley AL, Birch JM, Marsden HB, et al.: Neurofibromatosis in children with soft tissue sarcoma. Pediatr Hematol Oncol 5 (1): 7-16, 1988.
- Gripp KW, Lin AE, Stabley DL, et al.: HRAS mutation analysis in Costello syndrome: genotype and phenotype correlation. Am J Med Genet A 140 (1): 1-7, 2006.
- Aoki Y, Niihori T, Kawame H, et al.: Germline mutations in HRAS proto-oncogene cause Costello syndrome. Nat Genet 37 (10): 1038-40, 2005.
- Gripp KW: Tumor predisposition in Costello syndrome. Am J Med Genet C Semin Med Genet 137 (1): 72-7, 2005.
- Samuel DP, Tsokos M, DeBaun MR: Hemihypertrophy and a poorly differentiated embryonal rhabdomyosarcoma of the pelvis. Med Pediatr Oncol 32 (1): 38-43, 1999.
- DeBaun MR, Tucker MA: Risk of cancer during the first four years of life in children from The Beckwith-Wiedemann Syndrome Registry. J Pediatr 132 (3 Pt 1): 398-400, 1998.
- 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 19 (20): 4058-64, 2001.
- Joshi D, Anderson JR, Paidas C, et al.: Age is an independent prognostic factor in rhabdomyosarcoma: a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group. Pediatr Blood Cancer 42 (1): 64-73, 2004.
- 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 21 (1): 78-84, 2003.
- La Quaglia MP, Heller G, Ghavimi F, et al.: The effect of age at diagnosis on outcome in rhabdomyosarcoma. Cancer 73 (1): 109-17, 1994.
- Punyko JA, Mertens AC, Baker KS, et al.: Long-term survival probabilities for childhood rhabdomyosarcoma. A population-based evaluation. Cancer 103 (7): 1475-83, 2005.
- Lawrence W Jr, Hays DM, Heyn R, et al.: Lymphatic metastases with childhood rhabdomyosarcoma. A report from the Intergroup Rhabdomyosarcoma Study. Cancer 60 (4): 910-5, 1987.
- Mandell L, Ghavimi F, LaQuaglia M, et al.: Prognostic significance of regional lymph node involvement in childhood extremity rhabdomyosarcoma. Med Pediatr Oncol 18 (6): 466-71, 1990.
- Ferrari A, Casanova M, Bisogno G, et al.: Rhabdomyosarcoma in infants younger than one year old: a report from the Italian Cooperative Group. Cancer 97 (10): 2597-604, 2003.
- Koscielniak E, Jürgens 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 70 (10): 2557-67, 1992.
- Crist WM, Garnsey L, Beltangady MS, et al.: Prognosis in children with rhabdomyosarcoma: a report of the intergroup rhabdomyosarcoma studies I and II. Intergroup Rhabdomyosarcoma Committee. J Clin Oncol 8 (3): 443-52, 1990.
- Spunt SL, Lobe TE, Pappo AS, et al.: Aggressive surgery is unwarranted for biliary tract rhabdomyosarcoma. J Pediatr Surg 35 (2): 309-16, 2000.
- Lawrence W Jr, Anderson JR, Gehan EA, et al.: 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): 1165-70, 1997.
- Koscielniak E, Rodary C, Flamant F, et al.: Metastatic rhabdomyosarcoma and histologically similar tumors in childhood: a retrospective European multi-center analysis. Med Pediatr Oncol 20 (3): 209-14, 1992.
- Lawrence W Jr, Gehan EA, Hays DM, et al.: Prognostic significance of staging factors of the UICC staging system in childhood rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Study (IRS-II). J Clin Oncol 5 (1): 46-54, 1987.
- 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 24 (24): 3844-51, 2006.
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