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Rhabdomyosarcoma is a cancer that forms in the soft tissues in a type of muscle called striated muscle. This type of cancer can occur anywhere in the body. Learn about rhabdomyosarcoma and find information on how we support and care for children and teens with rhabdomyosarcoma before, during, and after treatment.
The Solid Tumor Center at Dana-Farber/Boston Children's Cancer and Blood Disorders Center treats children and teens with a variety of solid malignancies, including bone and soft tissue tumors, liver and kidney tumors, neuroblastomas, retinoblastomas and rare tumors. Our doctors provide unparalleled expertise in the diagnosis, treatment and management of these diseases.
Your child's care team will include pediatric oncologists, radiation oncologists, surgeons, pathologists, radiologists, and nurses with expertise in treating your child's specific type of cancer.
Our physicians are focused on family-centered care: From your first visit, you'll work with a team of professionals who are committed to supporting your family's needs. We consider you and your child integral parts of the care team. Our specialists will collaborate with you to customize a treatment plan that takes the needs of your child and your family into account.
As well as providing access to a range of innovative clinical trials through Dana-Farber/Boston Children's, we are New England's Phase I referral center for the Children's Oncology Group, which means we're able to offer clinical trials unavailable at other regional centers.
Your child will have access to long-term treatment and childhood cancer survivor support through Dana-Farber's David B. Perini, Jr. Quality of Life Clinic.
From diagnosis through treatment and survivorship, our team will be able to answer all of your questions about your child's care.
Find out more about our Solid Tumor Center, including the diseases we treat and our specialized programs for bone and soft tissue tumors, liver tumors, neuroblastoma, rare tumors, and retinoblastoma.
Rhabdomyosarcoma is a cancerous tumor that grows in the body's soft tissues (which connect, support or surround organs and other body structures), particularly in the muscles that attach to bone and help the body to move. Just weeks into the life of a developing embryo, rhabdomyoblast cells (which grow into muscle over time) begin to form. These are the cells that can develop into rhabdomyosarcoma.
Children with rhabdomyosarcoma are treated through our Bone and Soft Tissue Tumor Program. Because rhabdomyosarcoma can develop anywhere in a child's body and will require surgery as part of treatment, it is important that your child be treated at a center that offers surgical expertise in the part of the body where your child's tumor appears. At Dana-Farber/Boston Children's we have urology, gynecology, head and neck, and general surgeons who have specialized expertise in treating these types of tumors in children.
Find in-depth details on rhabdomyosarcoma on the Dana-Farber/Boston Children's website, including answers to:
Fortunately, cancer in children and adolescents is rare, although the overall incidence of childhood cancer has been slowly increasing since 1975. 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 specialists,
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 summary on Pediatric Supportive Care 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.
Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2010, childhood cancer mortality decreased by more than 50%. For rhabdomyosarcoma, the 5-year survival rate increased over the same time, from 53% to 67% for children younger than 15 years and from 30% to 51% for adolescents aged 15 to 19 years. 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 summary on Late Effects of Treatment for Childhood Cancer 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 mesenchymal
origin, accounts for approximately 3.5% of the cases of cancer among children aged 0
to 14 years and 2% of the cases among adolescents and young adults aged 15 to 19
years. The incidence is 4.5 per 1 million children and 50% of cases are seen in the first decade of life.
Incidence may depend on the histologic subtype of rhabdomyosarcoma:
The most common primary sites for rhabdomyosarcoma are the
head, the genitourinary
tract, and the extremities. Within extremity tumors, tumors of the hand and foot occur more often in older patients and have an alveolar histology; these tumors also have a higher rate of metastatic spread. Other less common primary sites include the
trunk, chest wall, perineal/anal region, and abdomen including the retroperitoneum and
Most cases of rhabdomyosarcoma occur sporadically, with no
recognized predisposing factor or risk factor. For patients with embryonal tumors, high birth weight and large size for gestational age are associated with an increased incidence of rhabdomyosarcoma. Genetic conditions associated with rhabdomyosarcoma include Li-Fraumeni
cancer susceptibility syndrome (with germline p53 mutations), pleuropulmonary blastoma (with DICER1 mutations),
neurofibromatosis type I, Costello syndrome (with germline HRAS mutations), Beckwith-Wiedemann syndrome (with which Wilms
tumor and hepatoblastoma are more commonly associated), and Noonan syndrome.
The prognosis for a child or adolescent with rhabdomyosarcoma is related to the
age of the patient, site of origin, tumor size (widest diameter), resectability, presence of metastases, number of metastatic sites or tissues involved, presence or absence of regional lymph node involvement, histopathologic subtype (alveolar vs. embryonal), and delivery of radiation therapy in selected cases,; [Level of evidence: 3iiiA] as well as unique biological characteristics of rhabdomyosarcoma tumor cells. It is unclear whether response to induction chemotherapy, as judged by anatomic imaging, correlates with the likelihood of survival in patients with rhabdomyosarcoma, because the Intergroup
Rhabdomyosarcoma Study Group (IRSG) and Children's Oncology Group studies found no association.; [Level of evidence: 3iiDi] However, an Italian study found that patient response did correlate with likelihood of survival.[Level of evidence: 3iiA]
Rhabdomyosarcoma is usually curable in most children with localized disease who
receive combined-modality therapy, with more than 70% surviving 5 years after
diagnosis. Relapses are uncommon after 5 years of disease-free survival, with a 9% late-event rate at 10 years. Relapses, however, are more common in patients who have gross residual disease in unfavorable sites after initial surgery and in those who have metastatic disease at diagnosis.
Examples of both
clinical and biological factors with proven or possible prognostic significance
include the following:
A retrospective review of soft tissue sarcomas in children and adolescents suggests that the 5 cm cutoff used for adults with soft tissue sarcoma may not be ideal for smaller children, especially infants. The review identified an interaction between tumor diameter and body surface area (BSA). This was not confirmed by a Children's Oncology Group study of patients with intermediate-risk rhabdomyosarcoma. This relationship requires prospective study to determine the therapeutic implications of the observation.
Patients with otherwise localized disease but with proven regional lymph node
involvement have a worse prognosis than do patients without regional nodal
Patients with alveolar rhabdomyosarcoma who have regional lymph node involvement have significantly worse outcomes (5-year FFS, 43%) than patients who do not have regional lymph node involvement (5-year FFS, 73%).
Anaplasia has been observed in 13% of cases of rhabdomyosarcoma and its presence may adversely influence clinical outcome in patients with intermediate-risk embryonal rhabdomyosarcoma. However, anaplasia was not shown to be an independent prognostic variable in a multivariate analysis (P = .081).
Adult patients with rhabdomyosarcoma have a high incidence of pleomorphic histology (19%). Pleomorphic histology is extremely rare in children and young adults with rhabdomyosarcoma. Adults also have a higher incidence of tumors in unfavorable sites than do children.
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 and cytogeneticists/molecular geneticists 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
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Rhabdomyosarcoma can be divided into several histologic subsets: embryonal rhabdomyosarcoma, which has embryonal,
botryoid, and spindle cell subtypes; alveolar rhabdomyosarcoma; and
The embryonal subtype is the most frequently observed
subtype in children, accounting for approximately 60% to 70% of
rhabdomyosarcomas of childhood. Tumors with embryonal histology typically
arise in the head and neck region or in the genitourinary tract, although they
may occur at any primary site.
Botryoid tumors represent about 10% of all
rhabdomyosarcoma cases and are embryonal tumors that arise under the mucosal
surface of body orifices such as the vagina, bladder, nasopharynx, and biliary tract.
The spindle cell variant of embryonal rhabdomyosarcoma is most frequently
observed at the paratesticular site. Both the botryoid and the spindle cell
subtypes are associated with very favorable outcomes.
Approximately 20% of
children with rhabdomyosarcoma have the alveolar subtype. An increased
frequency of this subtype is noted in adolescents and in patients with primary
sites involving the extremities, trunk, and perineum/perianal region.
For current trials developed by the Soft Tissue Sarcoma Committee of the Children's Oncology Group, to be designated as alveolar, the tumor must have greater than 50% alveolar elements; if the alveolar component is 50% or less, the tumor is considered embryonal. In some earlier studies (the D series, 1997–2005), any alveolar focus was sufficient, but that criterion was later abandoned.
rhabdomyosarcoma occurs predominantly in adults aged 30 to 50 years and is
rarely seen in children. In adults, pleomorphic rhabdomyosarcoma is associated with a worse prognosis. In children, the term anaplasia is preferred. In a retrospective review of 546 pediatric patients, the presence of anaplasia was only associated in univariate analysis with inferior clinical outcome in patients with intermediate-risk rhabdomyosarcoma.
The embryonal and alveolar histologies have distinctive molecular
characteristics that have been used for diagnostic confirmation, and may
be useful for assigning therapy and monitoring residual disease during treatment.
Alveolar cases associated with the PAX7 gene, with or without metastases, appear to occur in patients at a younger age, and may be associated with longer event-free survival (EFS) rates than those associated with PAX3 gene rearrangements. Alveolar cases associated with the PAX3 gene are older and have a higher incidence of invasive tumor (T2). Around 22% of cases showing alveolar histology have no detectable PAX gene translocation. In addition to FOXO1 rearrangements, alveolar tumors are characterized by a lower mutational burden than are fusion-negative tumors, with fewer genes having recurring mutations.BCOR and PIK3CA mutations and amplification of MYCN, MIR17HG, and CDK4 have also been described.
These findings highlight the important differences between embryonal and alveolar tumors. There are data that alveolar tumors carrying either a t(1;13) or a t(2;13) translocation (translocation-positive) are biologically and clinically different from alveolar tumors that do not have a translocation (translocation-negative) and from embryonal tumors. In a study of Intergroup
Rhabdomyosarcoma Study Group (IRSG) cases, the outcome for patients with translocation-negative alveolar rhabdomyosarcoma was better than that observed for translocation-positive cases and was similar to that seen in patients with embryonal rhabdomyosarcoma, suggesting that fusion status is a critical factor for risk stratification in pediatric rhabdomyosarcoma. However, a German study of 121 patients with alveolar rhabdomyosarcoma found no significant difference in EFS at 5 years among patients who were PAX-FOXO1–positive compared with those who were translocation-negative.
One study suggests that metagene expression analyses can classify patients with rhabdomyosarcoma into the three distinct risk groups and may be particularly helpful in identifying intermediate-risk patients with poor-risk features. Further studies are needed to confirm these findings. In another study, gene expression signature did not appear to add additional prognostic information beyond that available from the contribution of the PAX3/FOX01 fusion status.
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Stegmaier S, Poremba C, Schaefer KL, et al.: Prognostic value of PAX-FKHR fusion status in alveolar rhabdomyosarcoma: a report from the cooperative soft tissue sarcoma study group (CWS). Pediatr Blood Cancer 57 (3): 406-14, 2011.
Before a biopsy of a suspected tumor mass is performed, imaging studies of the mass and baseline laboratory studies should be obtained. After the diagnosis of rhabdomyosarcoma has been made, an extensive evaluation to determine the extent of the disease should be performed before instituting therapy. This evaluation should include a chest x-ray, computed tomography (CT) scan of the chest, bilateral bone marrow aspirates and biopsies, bone scan, magnetic resonance imaging (MRI) of the base of the skull and brain (for parameningeal primary tumors only), and CT scan of the abdomen and pelvis (for lower extremity or genitourinary primary tumors).
A CT or MRI scan of regional lymph nodes should be considered. Abnormal-appearing lymph nodes should be biopsied when possible. One study has demonstrated that sentinel lymph node biopsies can be safely performed in children with rhabdomyosarcoma, and tumor-positive biopsies may alter the treatment plan. Positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose (FDG) scans can identify areas of possible metastatic disease not seen by other imaging modalities. However, the efficacy of these two procedures for identifying involved lymph nodes or other sites is currently under investigation, and these procedures are not required by current treatment protocols.
A retrospective study of 1,687 children with rhabdomyosarcoma enrolled in Intergroup studies from 1991 to 2004 suggests that about one-third of patients (those with localized noninvasive embryonal tumors) can have limited staging procedures that eliminate bone marrow and bone scan examinations at diagnosis.
Terms used in this summary section are defined below in Table 1.
Orbit; nonparameningeal head and neck; genitourinary tract other than kidney, bladder, and prostate; biliary tract.
Any site other than favorable.
Tumor confined to anatomic site of origin (noninvasive).
Tumor extension and/or fixation to surrounding tissue (invasive).
Tumor ≤5 cm in maximum diameter.
Tumor >5 cm in maximum diameter.
No clinical regional lymph node involvement.
Clinical regional lymph node involvement.
Regional lymph nodes not examined; no information.
No metastatic disease.
Staging of rhabdomyosarcoma is relatively complex. The process includes the following steps:
As noted previously, prognosis for children with rhabdomyosarcoma depends
predominantly on the primary site, tumor size, Group, and histologic subtype. Favorable
prognostic groups were identified in previous Intergroup Rhabdomyosarcoma
Study Group (IRSG) studies, and treatment plans were designed on the basis of assignment of
patients to different treatment groups according to prognosis. Several years ago, the IRSG merged with the National Wilms Tumor Study Group and two large cooperative pediatric cancer treatment groups to form the Children's Oncology Group (COG). New protocols for children with soft tissue sarcoma are developed by the Soft Tissue Sarcoma Committee of the COG (COG-STS).
Current COG-STS protocols for rhabdomyosarcoma use the TNM-based pretreatment staging system that incorporates the primary tumor site, presence or absence of tumor invasion of surrounding tissues, tumor size, regional lymph node status, and the presence or absence of metastases. This staging system is described in Table 2 below.
Sites of Primary Tumor
Regional Lymph Nodes
T1 or T2
N0 or N1 or NX
a, ≤ 5 cm
N0 or NX
b, > 5 cm
N0 = absence of nodal spread; N1 = presence of regional nodal spread beyond the primary site; X = unknown N status; M0 = absence of metastatic spread; M1 = presence of metastatic spread beyond the primary site and regional lymph nodes; T1 = tumor confined to anatomic site of origin (noninvasive); T2a = tumor extension and/or fixation to surrounding tissue (invasive), tumor ≤5 cm in maximum diameter; T2b = tumor extension and/or fixation to surrounding tissue (invasive), tumor >5 cm in maximum diameter.
The IRS-I, IRS-II, and IRS-III studies prescribed treatment plans based on the Surgical-pathologic Group system. In this system, Groups are defined by the
extent of disease and by the completeness or extent of initial surgical resection after
pathologic review of the tumor specimen(s). The definitions for these
Groups are shown in Table 3 below.
Localized tumor, completely removed with microscopically clear margins and no regional lymph node involvement. Lymph node biopsy or sampling is encouraged if lymph nodes are clinically or radiographically suspicious.
Localized tumor, completely removed with: (a) microscopic disease at the margin, (b) regional disease with involved, grossly removed regional lymph nodes without microresidual disease, or (c) regional disease with involved nodes, grossly removed but with microscopic residual and/or histologic involvement of the most distal node from the primary tumor.
Localized tumor, incompletely removed with gross, residual disease after: (a) biopsy only, or (b) gross major resection of the primary tumor (>50%).
Distant metastases are present at diagnosis. This category includes: (a) radiographically identified evidence of tumor spread, and (b) positive tumor cells in cerebral spinal fluid, pleural, or peritoneal fluids, or implants in these regions.
After patients are categorized by Stage and Surgical-pathologic Group, a Risk Group is assigned. This takes into account Stage, Group, and histology. Patients are classified for protocol purposes as having a low risk, intermediate risk, or high risk of disease recurrence. Treatment assignment is based on Risk Group, as shown in Table 4. To be designated as alveolar, the tumor must have greater than 50% alveolar elements; if the alveolar component is 50% or less, the tumor is considered embryonal.
I, II, III
1, 2, 3
Embryonal or Alveolar
Since 2006, patients with undifferentiated sarcomas are treated on the COG-STS protocol for nonrhabdomyosarcomatous soft tissue sarcoma. Refer to the PDQ summary on Childhood Soft Tissue Sarcoma for more information.
Kayton ML, Delgado R, Busam K, et al.: Experience with 31 sentinel lymph node biopsies for sarcomas and carcinomas in pediatric patients. Cancer 112 (9): 2052-9, 2008.
Völker T, Denecke T, Steffen I, et al.: Positron emission tomography for staging of pediatric sarcoma patients: results of a prospective multicenter trial. J Clin Oncol 25 (34): 5435-41, 2007.
Tateishi U, Hosono A, Makimoto A, et al.: Comparative study of FDG PET/CT and conventional imaging in the staging of rhabdomyosarcoma. Ann Nucl Med 23 (2): 155-61, 2009.
Federico SM, Spunt SL, Krasin MJ, et al.: Comparison of PET-CT and conventional imaging in staging pediatric rhabdomyosarcoma. Pediatr Blood Cancer 60 (7): 1128-34, 2013.
Weiss AR, Lyden ER, Anderson JR, et al.: Histologic and clinical characteristics can guide staging evaluations for children and adolescents with rhabdomyosarcoma: a report from the Children's Oncology Group Soft Tissue Sarcoma Committee. J Clin Oncol 31 (26): 3226-32, 2013.
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.
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.
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 23 (4): 215-20, 2001.
All children with rhabdomyosarcoma require multimodality therapy with systemic chemotherapy, in conjunction with either surgery, radiation therapy (RT), or both modalities to maximize local tumor control. Surgical resection may be performed before chemotherapy if it will not result in disfigurement, substantial functional compromise, or organ dysfunction. In most cases, this is not possible, and therefore, only an initial biopsy is performed. The majority of patients have Group III (gross residual) disease. After initial chemotherapy, Group III patients receive definitive RT for control of the primary tumor. Some patients with initially unresected tumors may undergo second-look surgery (delayed primary excision) to remove residual tumor. This is most appropriate if the delayed excision is deemed feasible with acceptable functional/cosmetic outcome and if a modest reduction in radiation dose is expected to significantly reduce the risk of long-term adverse effects. RT is given to clinically suspicious lymph nodes (detected by palpation or imaging) unless the suspicious lymph nodes are biopsied and shown to be free of rhabdomyosarcoma.
The discussion of treatment options for children
with rhabdomyosarcoma is therefore divided into separate sections describing the following
local control options:
The treatment of rhabdomyosarcoma by the Children's Oncology Group (COG) and in Europe (as exemplified by trials from the Intergroup Rhabdomyosarcoma Study Group [IRSG], the Soft Tissue Sarcoma Committee of the COG [COG-STS], and the International Society of Pediatric Oncology Malignant Mesenchymal Tumor [MMT] Group) differs in management and overall treatment philosophy. In the MMT trials, the main objective is to reduce the use of local therapies using initial front-line chemotherapy followed by second-line therapy in the presence of poor response. Subsequent surgical resection is preferred over RT, which is used only after incomplete resection, documented regional lymph node involvement, or a poor clinical response to initial chemotherapy. This approach is designed to avoid major surgical procedures and long-term damaging effects from RT. Conversely, the primary COG-STS objective has been to employ local therapy soon after the initial operation or biopsy (except in patients with metastatic disease), using RT for patients with residual disease. Event-free survival (EFS) is the target endpoint, attempting to avoid relapse and subsequent salvage therapy. The MMT Group approach led to an overall survival (OS) rate of 71% in the European MMT89 study, compared with an OS rate of 84% in the IRS-IV study. Similarly, EFS rates at 5 years were 57% in the MMT89 study versus 78% in the IRS-IV study. Differences in outcome were most striking for patients with extremity and head and neck nonparameningeal tumors. Failure-free survival was lower for patients with bladder/prostate primary tumors who did not receive RT as part of their initial treatment, but there was no difference in OS between the two strategies for these patients. The overall impression is that survival for most patient subsets is superior with the use of early local therapy, including RT. However, in the MMT trials, some patients are spared aggressive local therapy, which may reduce the potential for morbidities associated with such therapy.
Patients with undifferentiated sarcomas were treated in trials coordinated by the IRSG from 1972 until 2006, and more recently were eligible for the nonrhabdomyosarcoma soft tissue sarcoma protocol using agents active in adult soft tissue sarcoma, ifosfamide and doxorubicin (COG-ARST0332). However, this trial has now been closed.
Stevens MC, Rey A, Bouvet N, et al.: Treatment of nonmetastatic rhabdomyosarcoma in childhood and adolescence: third study of the International Society of Paediatric Oncology--SIOP Malignant Mesenchymal Tumor 89. J Clin Oncol 23 (12): 2618-28, 2005.
Donaldson SS, Anderson JR: Rhabdomyosarcoma: many similarities, a few philosophical differences. J Clin Oncol 23 (12): 2586-7, 2005.
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 128 (5): 1232-9, 2011.
In recent years, the predominant site of treatment failure in patients with initially localized rhabdomyosarcoma has been local recurrence. Both surgery and radiation therapy are primarily measures taken to produce local control, but each has risks and benefits. Surgical removal of the entire tumor should be considered initially, but only if major functional/cosmetic impairment will not result. With that proviso, complete resection of the primary tumor with a surrounding margin of normal tissue and sampling possibly involved lymph nodes in the draining nodal basin is recommended. Important exceptions to the rule of normal margins exist (e.g., tumors of the
orbit and of the genitourinary region). The principle of wide and
complete resection of the primary tumor is less applicable to patients known to
have metastatic disease at the initial operation, but it is a reasonable concept
if easily accomplished.
Patients with microscopic residual tumor after
their initial excisional procedure appear to have improved prognoses if a
second operative procedure (primary re-excision) to resect the primary tumor bed
before beginning chemotherapy can achieve complete removal of the tumor.
Clinical and/or imaging evaluation of regional lymph nodes is an important part of pretreatment staging. Pathologic evaluation of regional nodes is currently required for all patients with extremity primary rhabdomyosarcoma and boys aged 10 years and older with paratesticular rhabdomyosarcoma, because microscopic tumor is often documented even when the nodes are not enlarged. (Refer to the Regional and in-transit lymph nodes section of this summary for more information.)
There is little evidence that debulking surgery (i.e., expected to leave macroscopic residual tumor) improves outcome, compared with biopsy alone.[Level of evidence: 2A] Second-look procedures (also known as delayed primary excision) can identify viable tumor that remains after initial chemotherapy; patients with viable tumor had shorter event-free survival (EFS) rates than did those without viable tumor, but there was no effect on overall survival (OS). Thus, the exact role of delayed primary excision remains undefined in rhabdomyosarcoma and is most appropriate if it is anticipated that a complete resection is possible and that the modest reduction in radiation dose will substantially decrease the risk for late effects.
Because rhabdomyosarcoma can arise from multiple sites, surgical care decisions and radiotherapeutic options must be tailored to the specific aspects of each site, and should be discussed with a multidisciplinary team including representatives of those specialties and pediatric oncologists.
Surgical management of the more common primary sites is provided in the Local Control Management with Surgery and RT by Primary Sites of Disease section of this summary.
Only 15% of patients present with Group I, completely resected disease, so RT is used in the majority of cases.
RT is an effective method for achieving local control of the tumor for patients with microscopic or gross residual disease after biopsy, initial surgical resection, or chemotherapy. Patients with completely resected embryonal rhabdomyosarcoma (Group I) do well without RT. An earlier study of Group I patients with alveolar rhabdomyosarcoma and undifferentiated soft tissue sarcoma found that omission of RT was followed by decreased local control. A subsequent review of patients with only alveolar rhabdomyosarcoma found that the improvement in outcome with RT did not reach statistical significance for patients with Stage 1 and 2 tumors. There were very few patients (n = 4) with large tumors (Stage 3, >5 cm) who did not receive RT, but their outcome was poor.[Level of evidence: 3iiiDii]
In more than 50% of Group II rhabdomyosarcoma patients, local recurrence was due to noncompliance with guidelines or omission of RT. A review of European trials conducted by the German Cooperative Weichteilsarkom Studien (CWS) Group between 1981 and 1998, in which RT was omitted for some Group II patients, demonstrated a benefit to using RT as a component of local tumor control for all Group II patient subsets, as defined by tumor histology, tumor size, and tumor site.
The predominant type of relapse for patients with Group III disease is local failure. Patients with tumor-involved regional lymph nodes at diagnosis also have a higher risk of local and distant failure than do patients whose lymph nodes are uninvolved. As with the surgical management of patients with rhabdomyosarcoma, recommendations for RT depend on the site of primary tumor, the postsurgical (if performed) amount of residual disease (none vs. microscopic vs. macroscopic), and the presence of involved lymph nodes.
For optimal care of pediatric patients undergoing radiation treatments, it is imperative to have available a radiation oncologist, radiation technicians, and nurses who are experienced in treating children. An anesthesiologist may be necessary to sedate and immobilize young patients. Computerized treatment planning with a 3-dimensional planning system should be available. Techniques to deliver radiation specifically to the tumor while sparing normal tissue (e.g., conformal radiation therapy, intensity-modulated radiation therapy [IMRT], proton-beam therapy [charged-particle radiation therapy], or brachytherapy) are appropriate.
Standard RT of children with rhabdomyosarcoma includes the following:
36 Gy to involved (prechemotherapy) site. The use of RT is under investigation.
N0 (microscopic residual disease after surgery)
36 Gy to involved (prechemotherapy) site.
N1 (resected regional lymph node involvement)
41.4 Gy to involved (prechemotherapy) site and nodes.
Orbital and nonorbital tumors
50.4 Gy with volume reduction after 36 Gy if excellent response to chemotherapy and noninvasive pushing tumors; no volume reduction for invasive tumors.
As for other groups and including all metastatic sites, if safe and possible. Exception: lung (pulmonary metastases) treated with 15 Gy if aged 6 years or older, 12 Gy if younger than 6 years.
The IRS-IV trial included a randomized study that reported the administration of RT twice a day, 6 to 8 hours apart, at 1.1 Gy per dose (hyperfractionated schedule), 5 days per week, was feasible but difficult to accomplish in small children who required sedation twice daily. Patients with localized, gross residual tumors were randomly assigned to receive conventional, once-daily RT (total dose of 50.4 Gy) versus the twice-daily hyperfractionated schedule (total dose of 59.4 Gy). There was no demonstrated advantage in terms of local control. Conventional RT remains the standard for treating patients who have rhabdomyosarcoma with gross residual disease.
Brachytherapy, using either intracavitary or interstitial implants, is another
method of local control and has been used in selected situations for children
with rhabdomyosarcoma, especially those with primary tumors at vaginal or
vulvar sites  and selected bladder/prostate sites.[Level of evidence: 3iiiA] In small series from one or two institutions, this treatment
approach was associated with a high survival rate and with retention of a
functional organ or tissue in most patients. Other sites, especially
head and neck, have also been treated with brachytherapy.
Patients with initial Group III disease, who subsequently have microscopic
residual disease after chemotherapy with or without delayed surgery are
likely to achieve local control with RT at doses of 40 Gy or
Very young children (aged ≤36 months) diagnosed with rhabdomyosarcoma pose a therapeutic challenge because of their increased risk for treatment-related morbidity. As suggested above, in older children, reduced radiation doses may be appropriate if delayed surgery can provide negative margins. However, for infants who are unable to undergo surgical resection, higher doses of RT remain appropriate. Radiation techniques are designed to maximize normal tissue sparing, and should include conformal approaches, often with intensity-modulated techniques.
Rhabdomyosarcomas of the orbit should not undergo exenteration, but biopsy is needed for diagnosis. Biopsy is followed by chemotherapy and RT, with orbital
exenteration reserved for the small number of patients with locally persistent
or recurrent disease. RT and chemotherapy are the standard of care, with survival in excess of 90% to 95%. For patients with orbital tumors, precautions should be taken to limit the RT dose to the lens and cornea.
If the tumors are nonorbital and cranial parameningeal (arising in the middle ear/mastoid, nasopharynx/nasal cavity, paranasal sinus, parapharyngeal region, or pterygopalatine/infratemporal fossa), a magnetic resonance imaging (MRI) scan with contrast of the primary site and brain should be obtained to check for presence of base-of-skull erosion and possible extension onto or through the dura. If skull erosion and/or transdural extension is equivocal, a computed tomography (CT) scan with contrast of the same regions is indicated. Also, if there is any suspicion of extension down the spinal cord, an MRI scan with contrast of the entire cord should be obtained. The cerebrospinal fluid (CSF) should be examined for malignant cells in all patients with parameningeal tumors. Because complete removal of these tumors is difficult, owing to their location, the initial surgical procedure for these patients is usually only a biopsy for diagnosis.
Nonorbital head and neck rhabdomyosarcomas, including cranial parameningeal tumors, are optimally managed by conformal RT and chemotherapy. Patients with parameningeal disease with intracranial extension in contiguity with the primary tumor, and/or signs of meningeal impingement (i.e., cranial base bone erosion, and/or cranial nerve palsy) do not require whole-brain irradiation or intrathecal therapy, unless tumor cells are present in the CSF at diagnosis. Patients should receive RT to the site of primary tumor with a 1.5 cm margin to include the meninges adjacent to the primary tumor and the region of intracranial extension, if present, with a 1.5 cm margin. In a retrospective trial, starting RT within 2 weeks of diagnosis for patients with signs of meningeal impingement was associated with lower rates of local failure but was of borderline significance. When no signs of meningeal impingement were present, delay of RT for more than 10 weeks did not impact local failure rates. A subsequent comparison of local control, failure-free survival, and overall survival rates showed no statistical difference between early irradiation (day 0) for Group III patients in IRS-IV with cranial nerve palsy and/or cranial base erosion versus later initiation of RT (week 12) for Group III patients in D9803 with similar evidence of meningeal involvement, suggesting that early RT for this group of patients is not necessary. However, both studies administered early irradiation to all patients with intracranial extension of the primary tumor.[Level of evidence: 2A] A retrospective analysis of 47 patients with parameningeal primary sites suggested that the subgroup of adolescent patients with alveolar rhabdomyosarcoma (n = 13) might benefit from the addition of prophylactic irradiation (36 Gy) to bilateral cervical nodes.[Level of evidence: 3iiDii]
Children who present with tumor cells in the CSF (Stage 4) may or may not have other evidence of diffuse meningeal disease and/or distant metastases. In a review of experience from IRSG Protocols II though IV, eight patients had tumor cells in the CSF at diagnosis; three of four without other distant metastases were alive at 6 to 16 years after diagnosis, as was one of four who had concomitant metastases elsewhere. Patients may also have multiple intraparenchymal brain metastases from a distant primary tumor. They may be treated with central nervous system-directed RT in addition to treatment with chemotherapy/RT for the primary tumor. Spinal RT may also be indicated.
For nonparameningeal and nonorbital head and neck tumors, wide excision of
the primary tumor (when feasible) and ipsilateral neck lymph node sampling of
clinically involved nodes are appropriate. Narrow resection margins (<1 mm)
are acceptable because of anatomic restrictions. Cosmetic and functional
factors should always be considered, but with modern techniques, complete
resection in patients with superficial tumors need not be inconsistent with
good cosmetic and functional results. Specialized, multidisciplinary surgical
teams also have performed resections of anterior skull-based tumors in areas
previously considered inaccessible to definitive surgical management, including
the nasal areas, paranasal sinuses, and temporal fossa. These procedures
should only be considered, however, in children with recurrent locoregional
disease or residual disease after chemotherapy and RT.
patients with head and neck primary tumors that are considered unresectable,
chemotherapy and RT with organ preservation are the mainstay of primary
management. Several studies have reported excellent local control in patients with rhabdomyosarcoma of the head and neck treated with IMRT, fractionated stereotactic radiation therapy, or protons and chemotherapy. Further study is needed, but the use of IMRT and chemotherapy in patients with head and neck rhabdomyosarcoma may result in less severe late effects.; [Level of evidence: 3iiiA]
Intensity-modulated radiation therapy (IMRT) can be used to spare the bone, yet provide optimal soft tissue coverage, and is used for the management of extremity rhabdomyosarcoma. Complete primary tumor removal from the hand or foot is not feasible in most cases because of functional impairment.[Level of evidence: 3iiA] For children presenting with a primary tumor of the hands or feet, COG studies have shown 100% 10-year local control using RT along with chemotherapy, avoiding amputation in these children.[Level of evidence: 3iiiA]
Primary re-excision before beginning chemotherapy (i.e., not delayed) may be appropriate in patients whose initial surgical procedure leaves microscopic residual disease that is deemed resectable by a second procedure.
The Soft Tissue Sarcoma Committee of the COG (COG-STS) recommends systematic aggressive axillary node sampling for patients with upper-extremity primary tumors, even with clinically and radiographically negative nodes. The COG-STS also recommends inguinal and femoral triangle node sampling for patients with lower-extremity primary tumors, even with clinically and radiographically negative nodes. If
clinically positive nodes are present, biopsy of more proximal nodes is
recommended before sampling of the involved nodal region. Sentinel
lymph node mapping is employed at some centers to identify the regional nodes
that are the most likely to be involved. However, the contribution of sentinel lymph node mapping is not yet clearly defined in pediatric patients.
Because of the significant incidence of regional nodal spread in patients with extremity primary tumors (often without clinical evidence of involvement) and because of the prognostic and therapeutic implications of nodal involvement, extensive pretreatment assessment of regional (and possibly in-transit) nodes is warranted.; [Level of evidence: 3iiDi] In-transit nodes are defined as epitrochlear and brachial for upper-extremity tumors and popliteal for lower-extremity tumors. Regional lymph nodes for those tumor sites are axillary/infraclavicular nodes and inguinal/femoral nodes, respectively. In a review of 226 patients with primary extremity rhabdomyosarcoma, 5% had tumor-involved in-transit nodes, and over 5 years, the rate of in-transit node recurrence was 12%. Very few patients (n = 11) underwent in-transit node examination at diagnosis, but five of them, all with alveolar rhabdomyosarcoma, had tumor-involved nodes. However, the EFS rates were not significantly different among those evaluated initially and those not evaluated initially for in-transit nodal disease.
The surgical management of patients with lesions of the chest wall or abdominal
wall should follow the same guidelines as those used for lesions of the extremities (i.e., wide local excision and an attempt to achieve negative microscopic
margins). These resections may require use of prosthetic materials. Very large
truncal masses should be biopsied initially. Chemotherapy, with or without RT, is then given. Initial surgery is performed if there is a realistic expectation of achieving negative margins. However, most patients who present with large tumors in these
sites have localized disease that becomes amenable to complete resection with
negative margins after preoperative chemoradiation therapy and those patients may have excellent long-term
Intrathoracic or intra-abdominal sarcomas may not be resectable at diagnosis because of the
massive size of the tumor and extension into vital
organs or vessels. For patients with initially unresectable retroperitoneal/pelvic tumors, complete surgical removal after chemotherapy, with or without RT, offers a significant survival advantage (73% vs. 34%–44% without removal). The International Society of Pediatric Oncology Malignant Mesenchymal Tumor (SIOP-MMT) group found that RT improved local control in patients with localized pelvic rhabdomyosarcoma whose initial surgical procedure was biopsy only, leaving macroscopic residual tumor. Age older than 10 years and lymph node involvement were unfavorable prognostic factors.[Level of evidence: 2A]
With rhabdomyosarcoma of the biliary tree, total resection is rarely feasible and standard treatment includes chemotherapy and RT. Outcome for patients with this primary site is
good despite residual disease after surgery. External biliary drains
significantly increase the risk of postoperative infectious complications.
Thus, external biliary drainage is not warranted.
Patients with rhabdomyosarcoma arising from tissue around the perineum or anus usually have advanced disease. These patients have a high likelihood of regional lymph node involvement, and about half of the tumors have alveolar histology. The current recommendation is to sample the regional lymph nodes. When feasible and without unacceptable morbidity, removing all gross tumor before chemotherapy improves the likelihood of cure. In Intergroup Rhabdomyosarcoma Study Group (IRSG) Protocols I through IV, the OS rate after aggressive therapy for 71 patients with tumors in this location was 49%, best for patients in Stage 2 (small tumors, negative regional nodes), intermediate for those in Stage 3, and worst for those in Stage 4 at diagnosis. However, with the goal of organ preservation, patients with tumors of the perineum/anus are preferentially managed with chemotherapy and RT without aggressive surgery, which may result in loss of sphincter control.
Primary sites for childhood rhabdomyosarcoma within the genitourinary system
include the paratesticular area, bladder, prostate, kidney, vulva, vagina, and uterus.
Specific considerations for the surgical and radiotherapeutic management of tumors arising at each
of these sites are discussed in the paragraphs below.
Lesions occurring adjacent to the testis or spermatic cord and up to the internal inguinal ring should be removed by
orchiectomy with resection of the spermatic cord, utilizing an inguinal
incision with proximal vascular control (i.e., radical orchiectomy). Resection of hemiscrotal skin is required when there is tumor fixation or
invasion, or when a previous transscrotal biopsy has been performed.
For patients with incompletely removed paratesticular tumors that require RT, temporarily repositioning the contralateral testicle into the adjacent thigh before scrotal radiation therapy may preserve hormone production.[Level of evidence: 3iiiC]
Paratesticular tumors have a relatively high incidence of
lymphatic spread (26% in IRS-I and IRS-II), and all patients with paratesticular primary tumors should have
thin-cut abdominal and pelvic CT scans with contrast
to evaluate nodal involvement. For patients who have Group I disease, are younger than 10 years, and in whom CT scans show no evidence of lymph node enlargement,
retroperitoneal node biopsy/sampling is unnecessary, but a repeat CT scan
every 3 months is recommended. For patients with suggestive or
positive CT scans, retroperitoneal lymph node sampling (but not formal node
dissection) is recommended, and treatment is based on the findings of this
procedure. A staging ipsilateral retroperitoneal lymph
node dissection is currently required for all children 10 years and older with paratesticular rhabdomyosarcoma on COG-STS studies. However, node dissection is not routine in Europe for adolescents with
resected paratesticular rhabdomyosarcoma. Many European investigators
rely on radiographic rather than surgical-pathologic assessment of retroperitoneal
lymph node involvement. It appears, however, that the ability of the CT
scan to predict the presence of lymph node involvement needs further study.
Bladder preservation is a major goal of therapy for patients with tumors
arising in the bladder and/or prostate. Two important reviews provide information about the historical, current, and future treatment approaches for patients with bladder and prostate rhabdomyosarcomas.
In rare cases, the tumor is confined to
the dome of the bladder and can be completely resected. Otherwise, to preserve
a functional bladder in patients with gross residual disease, chemotherapy and
RT have been used in North America and some parts of Europe to reduce tumor bulk, followed, when
necessary, by a more limited surgical procedure such as partial cystectomy.
Early experience with this approach was disappointing, with only 20% to 40% of
patients with bladder/prostate tumors remaining alive and with functional
bladders 3 years after diagnosis (3-year OS was 70% in IRS-II). The later experience from IRS-III and IRS-IV, which used
more intensive chemotherapy and RT, showed 55% of patients alive
with functional bladders at 3 years postdiagnosis, with 3-year OS
exceeding 80%. Patients with a primary tumor of the bladder/prostate who present with a large pelvic mass resulting from a distended bladder caused by outlet obstruction at diagnosis receive RT to a volume defined by imaging studies after initial chemotherapy to relieve outlet obstruction. This approach to therapy remains generally
accepted, with the belief that more effective chemotherapy and RT
will continue to increase the frequency of bladder salvage.
surgical procedure in most patients consists of a biopsy, which often can be
performed using ultrasound guidance or cystoscopy, or by a direct-vision transanal
route. In selected cases in one series, bladder-conserving surgery plus brachytherapy for boys with prostate or bladder-neck rhabdomyosarcoma led to excellent survival, bladder preservation, and short-term functional results.[Level of evidence: 3iiiB] For patients with biopsy-proven, residual malignant tumor after
chemotherapy and RT, appropriate surgical management may include
partial cystectomy, prostatectomy, or exenteration (usually approached anteriorly with
preservation of the rectum).
Very few studies have objective long-term assessments of bladder function, and urodynamic studies are important to obtain accurate evaluation of bladder function.
An alternative strategy, used in European SIOP protocols, has been to avoid major radical surgery when possible and omit external-beam RT if complete disappearance of tumor can be achieved by chemotherapy and conservative surgical procedures. The goal is to preserve a functional bladder and prostate without incurring the late effects of RT or having to perform a total cystectomy/prostatectomy. From 1984 to 2003, 172 patients with nonmetastatic bladder and/or bladder/prostate rhabdomyosarcoma were accrued, and the 5-year overall survival rate was 77%. Fifty percent of the 119 survivors had no significant local therapy, and only 26% received RT.[Level of evidence: 3iiA]
In patients who have been treated with chemotherapy and RT for rhabdomyosarcoma arising in the bladder/prostate region, the
presence of well-differentiated rhabdomyoblasts in surgical specimens or
biopsies obtained after treatment does not appear to be associated with a high
risk of recurrence and is not an indication for a major surgical procedure such as
total cystectomy. One study suggested that in patients with residual bladder tumors with
histologic evidence of maturation, additional courses of chemotherapy should be given before cystectomy is considered.
Surgery should be considered only if malignant tumor cells do not disappear
over time after initial chemotherapy and RT. Because of very
limited data, it is unclear whether this situation is analogous for patients
with rhabdomyosarcoma arising in other parts of the body.
The kidney is occasionally the primary site for rhabdomyosarcoma; six cases were identified from among 5,746 eligible patients enrolled on IRSG protocols. The tumors were large (mean widest diameter, 12.7 cm), and anaplasia was present in four (67%) patients. Three patients with grossly complete tumor removal at diagnosis survived; the three with incomplete removal and gross or metastatic disease died of infection or metastatic tumor.
For patients with genitourinary primary tumors of the vulva/vagina/uterus, the
initial surgical procedure is usually a vulvar or transvaginal biopsy. Initial radical surgery is not indicated for rhabdomyosarcoma of the vulva/vagina/uterus. Conservative
surgical intervention for vaginal rhabdomyosarcoma, with primary chemotherapy
and adjunctive radiation (often brachytherapy) for residual disease (Group II or III), results in excellent
disease-free survival.; [Level of evidence: 3iA]
In the COG-ARST0331 study, there was an unacceptably high rate of local recurrences in girls with Group III vaginal tumors who did not receive RT.[Level of evidence: 3iiiDiii] Therefore, the COG-STS recommends that RT be administered to patients with residual viable vaginal tumor, beginning at week 24.
Because of the smaller number of patients with
uterine rhabdomyosarcoma, it is difficult to make a definitive treatment
decision, but chemotherapy with or without RT is also effective. Twelve of 14 girls with primary cervical embryonal (mainly botryoid) rhabdomyosarcoma were disease-free after VAC (vincristine, dactinomycin, and cyclophosphamide) chemotherapy and conservative surgery. Of note, two girls also had a pleuropulmonary blastoma and another had Sertoli-Leydig cell tumor.
Exenteration is usually not required for primary tumors at these sites, but if
needed, it may be done, with rectal preservation possible in most cases.
Girls with genitourinary primary tumors should have their ovaries shielded or possibly moved, in an effort to preserve fertility when they are receiving RT to the lower abdomen and pelvis.
Rhabdomyosarcoma occasionally arises in sites other than those discussed above. Patients with localized primary rhabdomyosarcoma of the brain can occasionally be cured using a combination of tumor excision, RT, and chemotherapy.[Level of evidence: 3iiiDiii]
Patients with laryngeal rhabdomyosarcoma will usually be treated with chemotherapy and RT after biopsy in an attempt to preserve the larynx.
Patients with diaphragm tumors often have locally advanced disease that is not grossly resectable initially because of fixation to adjacent vital structures such as the lung, great vessels, pericardium, and/or liver. In such circumstances, chemotherapy and RT should be initiated after diagnostic biopsy, with the intent to consider removal of residual tumor at a later date if feasible.
Two well-documented cases of primary ovarian rhabdomyosarcoma (one Stage III and one Stage IV) have been reported to supplement the eight previously reported patients. These two patients were alive at 20 and 8 months after diagnosis. Six of the previously reported eight patients had died of their disease.[Level of evidence: 3iiiDiii] Treatment with combination chemotherapy followed by removal of the residual mass or masses can sometimes be successful.
Primary resection of metastatic disease at diagnosis (Stage 4, M1, Group IV) is rarely indicated.
The CWS Group
reviewed four consecutive trials and identified 29 patients with M1 embryonal rhabdomyosarcoma and metastasis limited to the lung at diagnosis. They reported approximately 38% 5-year EFS for the cohort and did not identify any benefit for local control of pulmonary metastasis, whether by lung irradiation (n = 9), pulmonary metastasectomy (n = 3), or no targeted pulmonary therapy (n = 19).[Level of evidence: 3iiiA]
The IRSG reviewed 46 IRS-IV (1991–1997) patients with metastatic disease at diagnosis confined to the lungs. Only 11 (24%) had a biopsy of the lung, including six at the time of primary diagnosis. They were compared with 234 patients with single non-lung metastatic sites or multiple other sites of metastases. The lung-only patients were more likely to have embryonal rhabdomyosarcoma and parameningeal primary tumors than the larger group of 234 patients, and were less likely to have regional lymph node disease at diagnosis. Failure-free survival (FFS) and OS rates at 4 years were 35% and 42%, respectively, better than for those with two or more sites of metastases (P = .005 and .002, respectively). Being younger than 10 years at diagnosis was also a favorable prognostic factor. Lung irradiation was recommended by the protocols for the lung-only group, but many did not receive it. Those who did receive lung irradiation had better FFS and OS at 4 years than those who did not (P = .01 and P = .039, respectively).[Level of evidence: 3iiiB]
All children with rhabdomyosarcoma should receive
chemotherapy. The intensity and duration of the chemotherapy are dependent on
the Risk Group assignment. See Table 4 in the Stage Information section for more information about Risk Groups.
Adolescents treated with therapy for rhabdomyosarcoma experience less hematologic toxicity and more peripheral nerve toxicity than do younger patients.
N0 = absence of nodal spread.
The COG-D9602 study stratified 388 patients with low-risk embryonal rhabdomyosarcoma into two groups. Treatment for subgroup A patients (n = 264; Stage 1 Group I/IIA, Stage 2 Group I, and Stage 1 Group III orbit) consisted of VA with or without RT for 48 weeks. Patients with subgroup B disease (n = 78; Stage 1 Group IIB/C, Stage I Group III nonorbit, Stage 2 Group II, and Stage 3 Group I/II disease) received VAC (total cumulative dose of 28.6 g/m2). Radiation doses were reduced from 41.4 Gy to 36 Gy for Stage 1 Group IIA patients and from 50 Gy or 59 Gy to 45 Gy for Group III orbit patients. For subgroup A patients, the 5-year overall FFS rate was 88% and the OS rate was 97%. For subgroup B patients, the 5-year FFS rate was 85% and the OS rate was 93%.
Other subgroups of low-risk patients have achieved survival rates of at least 90% with three-drug chemotherapy with VAC (total cyclophosphamide dose of 28.6 g/m2) plus RT for residual tumor. See Table 7 below.
Favorable (orbital or non-orbital)
IIB, IIC, III
N0 = absence of nodal spread; N1 = presence of regional nodal spread beyond the primary site.
A comparison of survival in patients with tumors of embryonal
histology treated on IRS-IV (who received higher doses of alkylating agents) compared with similar patients treated on IRS-III (who received lower
doses of alkylating agents) suggested a benefit with the use of higher doses of cyclophosphamide for certain groups of
intermediate-risk patients. These included patients with tumors at favorable
sites and positive lymph nodes, patients with gross residual disease, or patients with tumors at unfavorable sites who underwent grossly complete
resections, but not patients with unresected embryonal rhabdomyosarcoma at
unfavorable sites. For other groups of intermediate-risk patients, an intensification of cyclophosphamide was feasible but did not improve outcome.
A pooled analysis of 788 high-risk rhabdomyosarcoma patients treated with multiagent chemotherapy (all regimens used cyclophosphamide or ifosfamide plus dactinomycin and vincristine with or without additional chemotherapeutic agents), followed by local therapy (surgery with or without RT) within 3 to 5 months of starting chemotherapy, identified several adverse prognostic factors. These were age younger than 1 year, age 10 years or older, unfavorable primary site, bone and/or bone marrow involvement, and three or more different metastatic sites. The EFS rate at 3 years was 50% for patients without any of these adverse prognostic factors. The EFS rates were 42% for patients with one adverse prognostic factor, 18% for patients with two adverse prognostic factors, 12% for patients three adverse prognostic factors, and 5% for patients with four adverse prognostic factors (P < .0001).[Level of evidence: 3iiiA]
The standard systemic therapy for children with metastatic rhabdomyosarcoma is the three-drug combination of VAC. Despite many clinical trials attempting to improve outcome by adding additional agents to standard VAC chemotherapy (or substituting new agents for one or more components of VAC chemotherapy), to date, no chemotherapy regimens have been shown to be more effective than VAC, including the following:
The following is an example of a national and/or institutional clinical trial that is currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with previously untreated childhood rhabdomyosarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
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Pappo AS, Lyden E, Breneman J, et al.: Up-front window trial of topotecan in previously untreated children and adolescents with metastatic rhabdomyosarcoma: an intergroup rhabdomyosarcoma study. J Clin Oncol 19 (1): 213-9, 2001.
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 19 (15): 3463-9, 2001.
Walterhouse DO, Lyden ER, Breitfeld PP, et al.: Efficacy of topotecan and cyclophosphamide given in a phase II window trial in children with newly diagnosed metastatic rhabdomyosarcoma: a Children's Oncology Group study. J Clin Oncol 22 (8): 1398-403, 2004.
Arndt CA, Hawkins DS, Meyer WH, et al.: Comparison of results of a pilot study of alternating vincristine/doxorubicin/cyclophosphamide and etoposide/ifosfamide with IRS-IV in intermediate risk rhabdomyosarcoma: a report from the Children's Oncology Group. Pediatr Blood Cancer 50 (1): 33-6, 2008.
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 27 (31): 5182-8, 2009.
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 27 (22): 3705-11, 2009.
Minn AY, Lyden ER, Anderson JR, et al.: 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): 4228-32, 2010.
Oberlin O, Rey A, Sanchez de Toledo J, et al.: Randomized comparison of intensified six-drug versus standard three-drug chemotherapy for high-risk nonmetastatic rhabdomyosarcoma and other chemotherapy-sensitive childhood soft tissue sarcomas: long-term results from the International Society of Pediatric Oncology MMT95 study. J Clin Oncol 30 (20): 2457-65, 2012.
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 26 (14): 2384-9, 2008.
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 23 (4): 225-33, 2001.
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 37 (5): 442-8, 2001.
Pappo AS, Lyden E, Breitfeld P, et al.: 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): 362-9, 2007.
Bergeron C, Thiesse P, Rey A, et al.: Revisiting the role of doxorubicin in the treatment of rhabdomyosarcoma: an up-front window study in newly diagnosed children with high-risk metastatic disease. Eur J Cancer 44 (3): 427-31, 2008.
McDowell HP, Foot AB, Ellershaw C, et al.: Outcomes in paediatric metastatic rhabdomyosarcoma: results of The International Society of Paediatric Oncology (SIOP) study MMT-98. Eur J Cancer 46 (9): 1588-95, 2010.
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 (12): CD006669, 2010.
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 6 (2): e17127, 2011.
Thiel U, Koscielniak E, Blaeschke F, et al.: Allogeneic stem cell transplantation for patients with advanced rhabdomyosarcoma: a retrospective assessment. Br J Cancer 109 (10): 2523-32, 2013.
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 50 (4): 739-45, 2008.
Mackall CL, Rhee EH, Read EJ, et al.: A pilot study of consolidative immunotherapy in patients with high-risk pediatric sarcomas. Clin Cancer Res 14 (15): 4850-8, 2008.
Although patients with recurrent or progressive rhabdomyosarcoma sometimes
achieve complete remission with secondary therapy, the long-term prognosis
is usually poor. The prognosis is most
favorable (5-year survival rates, 50%–70%) for children who initially
present with Stage 1 or Group I disease and embryonal histology and who have small tumors, and for those who have a local or regional nodal recurrence. A retrospective analysis of children with recurrence after initial presentation with localized rhabdomyosarcoma of the orbit reported 80% survival 5 years after recurrence with aggressive retrieval therapy.[Level of evidence: 3iiA] The small number of children with botryoid
histology who relapse have a similarly favorable prognosis. Most other
children who relapse have an extremely poor prognosis. A retrospective review of rhabdomyosarcoma patients from German soft tissue sarcoma trials identified time to recurrence as an important independent prognostic factor. Shorter time to recurrence was associated with higher risk of mortality from recurrent rhabdomyosarcoma.[Level of evidence: 3iiB] European investigators performed a retrospective review of patients with rhabdomyosarcoma enrolled on cooperative group trials who experienced recurrence. They identified metastatic (as opposed to local) recurrence, prior radiation therapy, initial tumor size (>5 cm), and time to relapse (<18 months) as unfavorable prognostic features for survival after recurrence. In a retrospective review from the German Cooperative Soft Tissue Sarcoma Group, patients with alveolar rhabdomyosarcoma who relapsed with a single-disease focus and who received subsequent multiagent chemotherapy plus adequate local-relapse therapy (complete resection or gross resection with radiation therapy) had a better probability of long-term disease control than did patients with disseminated recurrences and/or tumors treated without adequate local-relapse therapy.[Level of evidence: 3iiA]
The selection of
further treatment depends on many factors, including the site(s) of recurrence,
previous treatment, and individual patient considerations. Treatment for local or regional recurrence may include wide local excision or aggressive surgical removal of tumor, particularly in the absence of widespread bony metastases. Some survivors have also been reported after surgical removal of only one or a few metastases in the lung. Radiation therapy should be considered for patients who have not already received radiation therapy in the area of recurrence, or rarely for those who have received radiation therapy but for whom surgical excision is not possible. Previously unused, active, single agents or combinations of drugs may also enhance the likelihood of disease control.
The following standard chemotherapy regimens have been used to treat recurrent rhabdomyosarcoma:
Treatment options under clinical evaluation for recurrent rhabdomyosarcoma:
The following are examples of national and/or institutional clinical trials that are currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent childhood rhabdomyosarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
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 17 (11): 3487-93, 1999.
Mazzoleni S, Bisogno G, Garaventa A, et al.: Outcomes and prognostic factors after recurrence in children and adolescents with nonmetastatic rhabdomyosarcoma. Cancer 104 (1): 183-90, 2005.
Raney B, Huh W, Hawkins D, et al.: Outcome of patients with localized orbital sarcoma who relapsed following treatment on Intergroup Rhabdomyosarcoma Study Group (IRSG) Protocols-III and -IV, 1984-1997: a report from the Children's Oncology Group. Pediatr Blood Cancer 60 (3): 371-6, 2013.
Mattke AC, Bailey EJ, Schuck A, et al.: Does the time-point of relapse influence outcome in pediatric rhabdomyosarcomas? Pediatr Blood Cancer 52 (7): 772-6, 2009.
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 29 (10): 1319-25, 2011.
Dantonello TM, Int-Veen C, Schuck A, et al.: Survival following disease recurrence of primary localized alveolar rhabdomyosarcoma. Pediatr Blood Cancer 60 (8): 1267-73, 2013.
Hayes-Jordan A, Doherty DK, West SD, et al.: Outcome after surgical resection of recurrent rhabdomyosarcoma. J Pediatr Surg 41 (4): 633-8; discussion 633-8, 2006.
De Corti F, Bisogno G, Dall'Igna P, et al.: Does surgery have a role in the treatment of local relapses of non-metastatic rhabdomyosarcoma? Pediatr Blood Cancer 57 (7): 1261-5, 2011.
Klingebiel T, Pertl U, Hess CF, et al.: Treatment of children with relapsed soft tissue sarcoma: report of the German CESS/CWS REZ 91 trial. Med Pediatr Oncol 30 (5): 269-75, 1998.
Kung FH, Desai SJ, Dickerman JD, et al.: Ifosfamide/carboplatin/etoposide (ICE) for recurrent malignant solid tumors of childhood: a Pediatric Oncology Group Phase I/II study. J Pediatr Hematol Oncol 17 (3): 265-9, 1995.
Van Winkle P, Angiolillo A, Krailo M, et al.: Ifosfamide, carboplatin, and etoposide (ICE) reinduction chemotherapy in a large cohort of children and adolescents with recurrent/refractory sarcoma: the Children's Cancer Group (CCG) experience. Pediatr Blood Cancer 44 (4): 338-47, 2005.
Cosetti M, Wexler LH, Calleja E, et al.: Irinotecan for pediatric solid tumors: the Memorial Sloan-Kettering experience. J Pediatr Hematol Oncol 24 (2): 101-5, 2002.
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 25 (4): 356-61, 2007.
Furman WL, Stewart CF, Poquette CA, et al.: Direct translation of a protracted irinotecan schedule from a xenograft model to a phase I trial in children. J Clin Oncol 17 (6): 1815-24, 1999.
Mascarenhas L, Lyden ER, Breitfeld PP, et al.: Randomized phase II window trial of two schedules of irinotecan with vincristine in patients with first relapse or progression of rhabdomyosarcoma: a report from the Children's Oncology Group. J Clin Oncol 28 (30): 4658-63, 2010.
Kuttesch JF Jr, Krailo MD, Madden T, et al.: Phase II evaluation of intravenous vinorelbine (Navelbine) in recurrent or refractory pediatric malignancies: a Children's Oncology Group study. Pediatr Blood Cancer 53 (4): 590-3, 2009.
Casanova M, Ferrari A, Spreafico F, et al.: Vinorelbine in previously treated advanced childhood sarcomas: evidence of activity in rhabdomyosarcoma. Cancer 94 (12): 3263-8, 2002.
Casanova M, Ferrari A, Bisogno G, et al.: Vinorelbine and low-dose cyclophosphamide in the treatment of pediatric sarcomas: pilot study for the upcoming European Rhabdomyosarcoma Protocol. Cancer 101 (7): 1664-71, 2004.
Minard-Colin V, Ichante JL, Nguyen L, et al.: Phase II study of vinorelbine and continuous low doses cyclophosphamide in children and young adults with a relapsed or refractory malignant solid tumour: good tolerance profile and efficacy in rhabdomyosarcoma--a report from the Société Française des Cancers et leucémies de l'Enfant et de l'adolescent (SFCE). Eur J Cancer 48 (15): 2409-16, 2012.
Rapkin L, Qayed M, Brill P, et al.: Gemcitabine and docetaxel (GEMDOX) for the treatment of relapsed and refractory pediatric sarcomas. Pediatr Blood Cancer 59 (5): 854-8, 2012.
Houghton PJ, Morton CL, Kolb EA, et al.: Initial testing (stage 1) of the mTOR inhibitor rapamycin by the pediatric preclinical testing program. Pediatr Blood Cancer 50 (4): 799-805, 2008.
Meazza C, Casanova M, Zaffignani E, et al.: Efficacy of topotecan plus vincristine and doxorubicin in children with recurrent/refractory rhabdomyosarcoma. Med Oncol 26 (1): 67-72, 2009.
McNall-Knapp RY, Williams CN, Reeves EN, et al.: Extended phase I evaluation of vincristine, irinotecan, temozolomide, and antibiotic in children with refractory solid tumors. Pediatr Blood Cancer 54 (7): 909-15, 2010.
Mixon BA, Eckrich MJ, Lowas S, et al.: Vincristine, irinotecan, and temozolomide for treatment of relapsed alveolar rhabdomyosarcoma. J Pediatr Hematol Oncol 35 (4): e163-6, 2013.
Weigel BJ, Breitfeld PP, Hawkins D, et al.: Role of high-dose chemotherapy with hematopoietic stem cell rescue in the treatment of metastatic or recurrent rhabdomyosarcoma. J Pediatr Hematol Oncol 23 (5): 272-6, 2001 Jun-Jul.
This information is provided by the National Cancer Institute.
This information was last updated on August 19, 2014.
Many children with cancer receive treatment in the outpatient setting, which allows them to stay in school and continue to develop intellectually and socially. However, returning to school can be an emotional experience; our Back to School Program is designed to ease your child's transition back to the classroom.
Concierge Services is your one-stop place to learn about Dana-Farber programs, services and resources, as well as information on getting around Boston, finding lodging or restaurants, and activities in the area.
The Expressive Arts Therapy program, sponsored by the Leonard P. Zakim Center for Integrative Therapies, provides adult patients, family members, and caregivers with a variety of options to support well-being during cancer treatment. From live music meditation to painting technique workshops, the program offers a range of creative outlets to suit every interest.
Dana-Farber and Children's Hospital, including parking facilities, are fully accessible to people with disabilities. There are wheelchairs at the main entrance, and security staff can provide personal assistance. We also have many educational materials available in large print and audiotape formats.
The Ethics Consultation Service is available for patients and families who may be facing difficult decisions and choices regarding care. Our goal is to bring together patients, families and health care providers to talk about ethical concerns and help everyone involved arrive at a resolution that is right for all.
Find practical tips and suggestions for individuals caring for a family member or friend with cancer, including creating a caregiving plan, finding community resources, and looking after your own well-being.
Friends' Place provides personal consultations to help cancer patients of all ages cope with changes in physical appearance that result from cancer treatment. Our experienced, compassionate team provides fittings for compression garments or breast prostheses, helps with wigs and other head coverings, and offers make-up and skincare advice.
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Every year, thousands of patients with cancer from around the world come to Dana-Farber for their care. We provide a wide array of logistical and other services for individuals who live outside the United States.
Dana-Farber provides interpreting services for patients whose first language is not English. Interpreters may be requested for any activity, including registration, booking appointments, attending treatments and exams, support groups, and meetings with doctors and other members of your health care team.
Just for Teens provides programs and activities for teens and young adults with cancer at the Jimmy Fund Clinic and Children's Hospital Boston. We offer activities and events both inside and out of the hospital so that you have creative ways to pass the time and can meet other teens who are going through similar experiences.
Our nutritionists are registered dietitians who can assist you in planning an optimal diet during any stage of your cancer journey, cope with any side effects you may experience, and answer your questions about the latest findings on cancer and nutrition.
The Eleanor and Maxwell Blum Patient and Family Resource Center and its satellite resource rooms are staffed by health care professionals and provide computer stations, books, brochures, videos, and CDs to help you find information and support on a variety of issues about cancer treatment and care.
Patients websites help friends and family members stay up-to-date on their loved ones' condition and write messages of support and encouragement.
The Dana-Farber pharmacy fills prescriptions for all pediatric and adult patients. Our pharmacists are an extension of the patient care team and work closely with your physicians to provide seamless, convenient, safe care.
More than 1,200 Dana-Farber patients and their families have enjoyed free trips to baseball games, theater shows, museums, and other attractions this year through the Recreational Resources program.
Through all stages of cancer treatment and survivorship, our Spiritual Care staff is available 24 hours a day to provide emotional and spiritual support for adults and pediatric patients and family members.
Integrative therapies, also known as complementary therapies, range from acupuncture and massage to nutritional guidance and music therapy. Patients treated at the Zakim Center credit its services with easing nausea, improving circulation, and reducing pain, stress, and anxiety associated with cancer treatment.
In this video, Dr. Simone Hettmer talks about her work as a pediatric oncologist at Dana-Farber/Children's Hospital Cancer Center.
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