National Cancer Institute


Treatment of children with rhabdomyosarcoma often includes chemotherapy, radiation therapy, and surgery. For pediatric embryonal, alveolar, and anaplastic rhabdomyosarcoma, learn about the signs, diagnosis, prognosis, treatment regimens, and clinical trials in this expert-reviewed summary.

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood rhabdomyosarcoma. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Childhood Rhabdomyosarcoma Treatment

General Information About Childhood Rhabdomyosarcoma

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 monitoring 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.)

Incidence

Childhood rhabdomyosarcoma is a soft tissue malignant tumor of mesenchymal origin. It 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 cases 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, as follows:

  • Embryonal: Patients with embryonal rhabdomyosarcoma are predominantly male (male to female ratio, 1.5). The peak incidence is in the 0- to 4-year age group at approximately 4 cases per 1 million children, with a lower rate in adolescents, approximately 1.5 cases per 1 million adolescents. This subtype constitutes 57% of patients in the Surveillance, Epidemiology, and End Results (SEER) database.
  • Alveolar: The incidence of alveolar rhabdomyosarcoma does not vary by sex and is constant from ages 0 to 19 years at approximately 1 case per 1 million children and adolescents. This subtype constitutes 23% of patients in the SEER database.
  • Other: Pleomorphic/anaplastic, mixed type, and spindle cell subtypes each constitute less than 2% of children with rhabdomyosarcoma.

The following are the most common primary sites for rhabdomyosarcoma:

  • Head and neck region (approximately 25%).
  • Genitourinary tract (approximately 22%).
  • Extremities (approximately 18%). Within extremity tumors, tumors of the hand and foot occur more often in older patients and have an alveolar histology.

Other less common primary sites include the trunk, chest wall, perineal/anal region, and abdomen, including the retroperitoneum and biliary tract.

Risk Factors

Most cases of rhabdomyosarcoma occur sporadically, with no recognized predisposing risk factor, with the exception of the following:

  • Genetic conditions associated with rhabdomyosarcoma:
    • Li-Fraumeni cancer susceptibility syndrome (with germline mutations).
    • Pleuropulmonary blastoma (with mutations).
    • Neurofibromatosis type I.
    • Costello syndrome (with germline mutations).
    • Beckwith-Wiedemann syndrome (with which Wilms tumor and hepatoblastoma are more commonly associated).
    • Noonan syndrome.
  • High birth weight and large size for gestational age are associated with an increased incidence of embryonal rhabdomyosarcoma.

Prognostic Factors

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.

The prognosis for a child or adolescent with rhabdomyosarcoma is related to the following clinical and biological factors with proven or possible prognostic significance:

  • Age: Children aged 1 to 9 years have the best prognosis, while those younger and older fare less well. In recent Intergroup Rhabdomyosarcoma Study Group (IRSG) trials, 5-year failure-free survival (FFS) was 57% for patients younger than 1 year, 81% for patients aged 1 to 9 years, and 68% for patients older than 10 years. Five-year survival for these groups was 76%, 87%, and 76%, respectively. Historical data show that adults fare less well than children (5-year overall survival [OS] rates, 27% ± 1.4% and 61% ± 1.4%, respectively; < .0001).
    • Infants: Infants may do poorly because their bone marrow is less tolerant of chemotherapy doses that older children can receive; thus, infants are relatively underdosed compared with older patients. In addition, infants younger than 1 year are less likely to receive radiation therapy for local control, because of bias and/or concern about the high incidence of late effects in this age group. The 5-year FFS for infants was found to be 67%, compared with 81% in a matched group of older patients treated by the Children's Oncology Group (COG). This inferior FFS was largely because of a relatively high rate of local failure.
    • Older children: In older children, vincristine and dactinomycin have upper dosage limits based on body surface area (BSA), and these patients may also require reduced vincristine doses because of neurotoxicity.
    • Adolescents: A report from the AIEOP (Italian) Soft Tissue Sarcoma Committee suggests that adolescents may have more frequent unfavorable tumor characteristics, including alveolar histology, regional lymph node involvement, and metastatic disease at diagnosis, accounting for their poor prognosis. This study also found that 5-year OS and progression-free survival (PFS) rates were somewhat lower in adolescents than in children, but the differences among age groups younger than 1 year and aged 10 to 19 years at diagnosis were significantly worse than those in the group aged 1 to 9 years.
  • Site of origin: Prognosis for childhood rhabdomyosarcoma varies according to the primary tumor site (refer to Table 1).
  • Tumor size: Children with smaller tumors (≤5 cm) have improved survival compared with children with larger tumors (>5 cm). Both tumor volume and maximum tumor diameter are associated with outcome.[]

    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 BSA. This was not confirmed by a COG study of patients with intermediate-risk rhabdomyosarcoma. This relationship requires prospective study to determine the therapeutic implications of the observation.

  • Resectability: The extent of disease after the primary surgical procedure (i.e., the Surgical-pathologic Group, also called the Clinical Group) is also correlated with outcome. In the IRS-III study, patients with localized, gross residual disease after initial surgery (Surgical-pathologic Group III) had a 5-year survival rate of approximately 70%, compared with a more than 90% 5-year survival rate for patients without residual tumor after surgery (Group I) and an approximately 80% 5-year survival rate for patients with microscopic residual tumor after surgery (Group II).

    Resectability without functional impairment is related to initial size and site of the tumor, making the Grouping system less useful than a TNM system. Regardless, outcome is optimized with the use of multimodality therapy. All patients require chemotherapy and at least 85% also benefit from radiation therapy, with favorable outcome even for those patients with nonresectable disease. In IRS-IV, the Group III patients with localized unresectable disease who were treated with chemotherapy and radiation therapy had a 5-year FFS of about 75% and a local control rate of 87%.

  • Histopathologic subtype: 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 primary tumors, and metastatic disease at diagnosis), and is generally associated with a worse outcome than in similar patients with embryonal rhabdomyosarcoma.
    • 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 (Group I).
    • A statistically significant difference in 5-year survival by histopathologic subtype (82% for embryonal rhabdomyosarcoma vs. 65% for alveolar rhabdomyosarcoma), was not noted when 1,258 IRS-III and IRS-IV patients with rhabdomyosarcoma were analyzed.
    • In the IRS-III study, outcome for patients with Group I alveolar subtype tumors was similar to that for other patients with Group I tumors, but the alveolar patients received more intensive therapy.
    • 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 embryonal rhabdomyosarcoma cases 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 ( = .081).

  • : Occasionally, patients with histology consistent with alveolar rhabdomyosarcoma do not have one of the two gene fusions that are characteristic of the disease. Patients with translocation-negative alveolar rhabdomyosarcoma have outcomes similar to those for patients with embryonal rhabdomyosarcoma and do better than patients with fusion-positive alveolar rhabdomyosarcoma. For example, in a study from the Soft Tissue Sarcoma Committee of the COG of 434 cases of intermediate-risk rhabdomyosarcoma, fusion-positive patients had a lower event-free survival (EFS) (, 54% and , 65%) than did those with embryonal rhabdomyosarcoma (EFS, 77%). Patients with fusion-negative alveolar rhabdomyosarcoma had outcomes similar to those for patients with embryonal rhabdomyosarcoma. These studies also demonstrated that fusion status was a better predictor of outcome than was histology and will replace histology in COG studies going forward. Similar conclusions were reached in a retrospective study of three consecutive trials in the United Kingdom. The authors underscored the probable value of treating fusion-negative patients whose tumors have alveolar histology with therapy that is stage appropriate for embryonal histology tumors.[]
  • Metastases at diagnosis: Children with metastatic disease at diagnosis have the worst prognosis.

    The prognostic significance of metastatic disease is modified by the following:

    • Tumor histology (embryonal rhabdomyosarcoma is more favorable than alveolar). Only patients with alveolar histology and regional node disease have a worse prognosis provided that regional disease is treated with radiation therapy.
    • Age at diagnosis (<10 years for children with embryonal rhabdomyosarcoma).
    • The site of metastatic disease. Patients with metastatic genitourinary (nonbladder, nonprostate) primary tumors have a more favorable outcome than do patients with metastatic disease from other primary sites.
    • The number of metastatic sites.
  • Lymph node involvement at diagnosis: Lymph node involvement at diagnosis is associated with an inferior prognosis, and clinical and/or imaging evaluation is performed before treatment and preoperatively. Sentinel lymph node identification by appropriate methodology can aid in this evaluation. Suspicious nodes are sampled surgically with open biopsy preferred to needle aspiration, although this may occasionally be appropriate. Pathologic evaluation of clinically uninvolved nodes is site specific; in the United States, it is performed for extremity sites or for boys older than 10 years with paratesticular primaries.

    Data on the frequency of lymph node involvement in various sites is informative in clinical decision making. For example, up to 40% of patients with rhabdomyosarcoma in genitourinary sites have lymph node involvement, while patients with head and neck sites have a much lower likelihood (<10%). Patients with nongenitourinary pelvic sites (e.g. anus/perineum) have an intermediate frequency of lymph node involvement.

    In the extremities and trunk, sentinel lymph node evaluation is a more accurate form of diagnosis than is random regional lymph node sampling. In clinically negative lymph nodes of the extremity or trunk, sentinel lymph node biopsy is the preferred form of node sampling by the COG. Technical considerations are obtained from surgical experts. Needle or open biopsy of clinically enlarged nodes is appropriate.

    Adjuvant radiation therapy is administered to patients with lymph node involvement to enhance regional control.

  • Biological characteristics: Refer to the Molecular Characteristics of Rhabdomyosarcoma section of this summary for more information.

It is unlikely that response to induction chemotherapy, as judged by anatomic imaging, correlates with the likelihood of survival in patients with rhabdomyosarcoma, based on the IRSG and COG studies that found no association.; [] However, an Italian study did find that patient response correlated with likelihood of survival.[] Other studies have investigated response to induction therapy, showing benefit to response. These data are somewhat flawed because therapy is usually tailored based on response and thus, the situation is not as clear as the COG data suggests.

Response as judged by sequential functional imaging studies with fluorine F 18-fludeoxyglucose positron emission tomography (PET) may be an early indicator of outcome and is under investigation by several pediatric cooperative groups. A retrospective analysis of 107 patients from a single institution examined PET scans performed at baseline, after induction chemotherapy, and after local therapy. Standardized uptake value measured at baseline predicted PFS and OS, but not local control. A negative scan after induction chemotherapy correlated with statistically significantly better PFS. A positive scan after local therapy predicted worse PFS, OS, and local control.

Adult patients with rhabdomyosarcoma have a higher incidence of pleomorphic histology (19%) than do children (<2%). 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 therapeutic modalities.

Cellular Classification for Childhood Rhabdomyosarcoma

Histologic Subtypes

Rhabdomyosarcoma can be divided into several histologic subsets, as follows:

  • Embryonal rhabdomyosarcoma, which has embryonal, botryoid, and spindle/sclerosing cell subtypes.
  • Alveolar rhabdomyosarcoma.
  • Pleomorphic (anaplastic) rhabdomyosarcoma.

Embryonal rhabdomyosarcoma

Embryonal rhabdomyosarcoma has the following three subtypes:

  • Embryonal.
  • Botryoid.
  • Spindle cell/sclerosing.

Embryonal-subtype rhabdomyosarcoma. The embryonal subtype is the most frequently observed subtype in children, accounting for approximately 60% to 70% of childhood rhabdomyosarcomas. 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.

Anaplasia has been observed in 13% of embryonal rhabdomyosarcoma cases, 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 ( = .081).

Botryoid-subtype rhabdomyosarcoma. 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 World Health Organization (WHO) Classification of Tumours of Soft Tissue and Bone (4th edition) eliminated botryoid rhabdomyosarcoma, with these cases classified as typical embryonal rhabdomyosarcoma.

A study of 2,192 children with rhabdomyosarcoma enrolled on clinical trials and diagnosed with embryonal histology (including botryoid and spindle cell variants) showed improved event-free survival (EFS) for patients with botryoid tumors (80%; 95% confidence interval [CI], 74%–84%) compared with typical embryonal rhabdomyosarcoma (73%; 95% CI, 71%–75%). However, after adjusting for primary site, resection, and metastatic status, there was no difference in EFS by histologic subtype. This observation supports the elimination of the botryoid variant as a specific histologic subtype of rhabdomyosarcoma.

Spindle cell/sclerosing-subtype rhabdomyosarcoma. The 4th edition of the WHO Classification of Tumours of Soft Tissue and Bone added spindle cell/sclerosing rhabdomyosarcoma as a separate subtype of rhabdomyosarcoma. The spindle cell variant of embryonal rhabdomyosarcoma is most frequently observed at the paratesticular site.

A study of 2,192 children with rhabdomyosarcoma enrolled on clinical trials and diagnosed with embryonal histology (including botryoid and spindle cell variants) showed improved EFS for patients with spindle cell rhabdomyosarcoma (83%; 95% CI, 77%–87%) compared with typical embryonal rhabdomyosarcoma (73%; 95% CI, 71%–75%). Patients with spindle cell rhabdomyosarcoma with parameningeal primary tumors (n = 18) were the exception to the overall favorable prognosis for this subtype; they had a 5-year EFS of 28% (compared with >70% EFS for parameningeal non-spindle cell embryonal rhabdomyosarcoma). As discussed in the Molecular Characteristics of Rhabdomyosarcoma section of this summary, the variable outcome by primary site for spindle cell rhabdomyosarcoma may reflect distinctive molecular subtypes with divergent prognostic significance within this histology.

In the WHO classification, sclerosing rhabdomyosarcoma is considered a variant pattern of spindle cell rhabdomyosarcoma, as descriptions note increasing degrees of hyalinization and matrix formation in spindle cell tumors. Sclerosing rhabdomyosarcoma is more common in adults, arises in the extremities and head and neck region, and has a more aggressive course. Recurrent mutations in sclerosing rhabdomyosarcoma were also identified. Data on the outcome of sclerosing rhabdomyosarcoma in the pediatric population are limited, however. The largest previous study of sclerosing rhabdomyosarcoma in children had a follow-up of 0.01 to 3.58 years; of 13 patients, three relapsed and one died from the disease.

Alveolar rhabdomyosarcoma

Approximately 30% of children with rhabdomyosarcoma have the alveolar subtype when histology alone is used to determine 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. Eighty percent of patients with alveolar histology will have one of two gene fusions, on chromosome 2 or on chromosome 1, with gene on chromosome 13. Patients without a fusion have outcomes that are similar to those for patients with embryonal rhabdomyosarcoma.

The current trial for intermediate-risk patients from the Soft Tissue Sarcoma Committee of the Children's Oncology Group () and all future trials will use fusion status rather than histology to determine eligibility; fusion-negative patients with alveolar histology will undergo the same treatments as patients with embryonal histology.

Pleomorphic (anaplastic) rhabdomyosarcoma

Pleomorphic 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 is preferred.

Molecular Characteristics of Rhabdomyosarcoma

The embryonal and alveolar histologies have distinctive molecular characteristics that have been used for diagnostic confirmation, and may be useful for assigning risk group, determining therapy, and monitoring residual disease during treatment.

These findings highlight the important differences between embryonal and alveolar tumors. Data demonstrate that fusion-positive alveolar tumors are biologically and clinically different from fusion-negative alveolar tumors and embryonal tumors. In a study of Intergroup Rhabdomyosarcoma Study Group cases, which captured an entire cohort from a single prospective clinical trial, the outcome for patients with translocation-negative alveolar rhabdomyosarcoma was better than that observed for translocation-positive cases. The outcome was similar to that seen in patients with embryonal rhabdomyosarcoma and demonstrated that fusion status is a critical factor for risk stratification in pediatric rhabdomyosarcoma.

Stage Information for Childhood Rhabdomyosarcoma

Staging Evaluation

Before a biopsy of a suspected tumor mass is performed, imaging studies of the mass and baseline laboratory studies should be obtained. After the patient is diagnosed with rhabdomyosarcoma, an extensive evaluation to determine the extent of the disease should be performed before instituting therapy. This evaluation typically includes the following:

  • Chest x-ray.
  • Computed tomography (CT) scan of the chest.
  • CT scan of the abdomen and pelvis (for lower extremity or genitourinary primary tumors).
  • Magnetic resonance imaging (MRI) of the base of the skull and brain (for parameningeal primary tumors).
  • Regional lymph node evaluation.

    Cross-sectional imaging (CT or MRI scan) of regional lymph nodes should be obtained. Abnormal-appearing lymph nodes should be biopsied when possible. Many studies have demonstrated that sentinel lymph node biopsies can be safely performed in children with rhabdomyosarcoma, and tumor-positive biopsies alter the treatment plan. Positron emission tomography (PET) with fluorine F 18-fludeoxyglucose scans can identify areas of possible metastatic disease not seen by other imaging modalities. The efficacy of these imaging studies for identifying involved lymph nodes or other sites of disease is important for staging, and PET imaging is recommended on current Soft Tissue Sarcoma Committee of the Children's Oncology Group (COG-STS) treatment protocols.

    Pathologic evaluation of regional nodes is currently required for all COG-STS study participants 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.)

  • Bilateral bone marrow aspirates and biopsies for selected patients.
  • Bone scan for selected patients.

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 negative regional lymph nodes, noninvasive embryonal tumors, and Group I alveolar tumors) can have limited staging procedures that eliminate bone marrow and bone scan examinations at diagnosis.

Staging Process

Staging of rhabdomyosarcoma is complex. The process includes the following steps:

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 patient assignment 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 COG. New protocols for children with soft tissue sarcoma are developed by the COG-STS.

Assignment of Stage

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 3 below.

Terms defining the TNM criteria are described in Table 2.

Assignment of Group

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 4 below.

Assignment of Risk Group

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 5.

Treatment Option Overview for Childhood Rhabdomyosarcoma

Multimodality Therapy

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 is performed before chemotherapy if it will not result in disfigurement, functional compromise, or organ dysfunction. If this is not possible, only an initial biopsy is performed.

Most patients (about 50%) have Group III (gross residual) disease; the remaining patients have Group I (about 15%), Group II (about 20%), and Group IV (about 15%) disease. After initial chemotherapy, Group III patients receive definitive RT for control of the primary tumor. Some patients with initially unresected tumors may undergo delayed primary excision to remove residual tumor before the initiation of RT. This is appropriate only if the delayed excision is deemed feasible with acceptable functional/cosmetic outcome and if a grossly complete resection is anticipated. If a delayed primary excision results in complete resection or microscopic residual disease, a modest reduction in RT could be utilized. 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 divided into the following separate sections:

  • Surgery (local control management).
  • RT (local control management).
  • Chemotherapy.

Rhabdomyosarcoma treatment options used by the Children's Oncology Group (COG) and by groups in Europe (as exemplified by trials from the Soft Tissue Sarcoma Committee of the COG [COG-STS], the Intergroup Rhabdomyosarcoma Study Group [IRSG], and the International Society of Pediatric Oncology Malignant Mesenchymal Tumor [MMT] Group) differ in management and overall treatment philosophy, as noted below:

  • 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.
  • In the MMT trials, the main objective has been 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.

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. In the MMT trials, some patients have been spared aggressive local therapy, which may reduce the potential for morbidities associated with such therapy.

Special Considerations for the Treatment of Children With Cancer

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 following individuals to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life:

  • Primary care physician.
  • Pediatric surgeon.
  • Radiation oncologist.
  • Pediatric oncologist and hematologist.
  • Pediatric radiologist.
  • Rehabilitation specialist.
  • Pediatric nurse specialist.
  • Social workers.
  • Psychologist.

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 website.

Treatment of Previously Untreated Childhood Rhabdomyosarcoma

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.

Surgery (Local Control Management)

In recent years, the predominant site of treatment failure in patients with initially localized rhabdomyosarcoma has been local recurrence. Both surgery and radiation therapy (RT) 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 functional and cosmetic impairment will not result. With that stipulation, complete resection of the primary tumor, with a surrounding margin of normal tissue and sampling of 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 an alternative approach if easily accomplished without loss of form (cosmesis) and function.

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 without loss of form and function.

There is little evidence that debulking surgery (i.e., surgery that is expected to leave macroscopic residual tumor) improves outcome, compared with biopsy alone; therefore, debulking surgery is not recommended for patients with rhabdomyosarcoma.[] In a retrospective study of 73 selected patients, second-look procedures (also called delayed primary excision) identified viable tumor that remained after initial chemotherapy; 65 of these patients had also received RT. 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, delaying surgery until after chemotherapy is preferred.

For children with low-risk rhabdomyosarcoma, local control was not diminished with reduced doses of RT after surgical resection. Subsequently, delayed primary excision was evaluated by the COG-STS in 73 intermediate-risk rhabdomyosarcoma patients enrolled on D9803 (1999–2005). Delayed primary excision was completed in 45% of Group III rhabdomyosarcoma patients with tumors of the bladder dome, extremity, and trunk; 84% of those who had a delayed primary excision with no gross residual disease remaining were eligible for modest radiation dose reduction (patients with no or only microresidual tumor after delayed primary excision). Local control outcomes were similar to IRS-IV results with RT alone.

Radiation Therapy (RT) (Local Control Management)

Local control remains a significant problem in children with rhabdomyosarcoma. In IRS II, of patients who achieved a complete remission with chemotherapy and surgery, almost 20% of patients with Groups I to III disease relapsed locally or regionally, and 30% of patients with Group IV disease relapsed locally or regionally. Local or regional relapses accounted for 70% to 80% of all relapses in children with Groups I to III disease and 46% of all relapses in patients with Group IV disease. 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. However, because approximately 75% of embryonal rhabdomyosarcoma patients are Groups II to IV, RT is used in most patients with rhabdomyosarcoma.
  • 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 Stage 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.[]

In more than 50% of Group II rhabdomyosarcoma patients, local recurrence was the result of noncompliance with guidelines or omission of RT. A review of European trials was conducted by the German Cooperative Weichteilsarkom Studiengruppe (CWS) between 1981 and 1998, in which RT was omitted for some Group II patients. This review 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. Approximately 35% of patients with Group III disease either fail to achieve a complete remission or relapse locally. 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.

External-beam RT

As with the surgical management of patients with rhabdomyosarcoma, recommendations for RT depend on the following:

  • Site of primary tumor.
  • Postsurgical amount of residual disease (none vs. microscopic vs. macroscopic), if surgery was performed.
  • Presence of involved lymph nodes.

For optimal care of pediatric patients undergoing radiation treatments, it is imperative that radiation oncologists, radiation technicians, and nurses who are experienced in treating children are available. An anesthesiologist may be necessary to sedate 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], volumetrical modulated arc therapy [VMAT], proton-beam therapy [charged-particle radiation therapy], or brachytherapy) are appropriate.

Evidence (radiation delivery techniques):

The radiation dose according to Group, histology, and disease site for children with rhabdomyosarcoma is described in Table 6:

The RT dose depends predominantly on the histology and amount of residual disease, if any, after the primary surgical resection.

  • Group II. In general, patients with microscopic residual disease (Group II) receive 36 Gy of RT if they do not have involved lymph nodes and 41 Gy in the presence of involved nodes. Low-risk patients (embryonal histology and favorable sites with microscopic residual disease) treated on a COG study had excellent local control with 36 Gy, which was comparable to historic controls who received 41.4 Gy. For Group II patients, 36 Gy to 41.4 Gy is recommended depending on nodal status.
  • Group III. IRS-II patients with gross residual disease (Group III) who received 40 Gy to more than 50 Gy had locoregional relapse rates greater than 30%, but higher doses of radiation (>60 Gy) were associated with unacceptable long-term toxic effects. Group III patients on the IRS-IV standard treatment arm received 50.4 Gy to 59.4 Gy, with 5-year progression-free survival of 55% to 75% and a local control rate of 85% to 88%. Select COG subgroups with Group III disease received somewhat reduced radiation doses of 36 Gy after delayed gross total resection with negative margins, and 41.4 Gy if the margins were microscopically involved or the nodes were positive. In the recent study, a limited number of low-risk patients had a greater than 85% likelihood of local control with 36 Gy. This approach is only appropriate for select site-specific subgroups.

In the D9803 study of patients with intermediate-risk rhabdomyosarcoma, local control was 90% in 41 patients with Groups I and II alveolar rhabdomyosarcoma, but was lower in 280 patients with Group III embryonal (80%) and alveolar (83%) rhabdomyosarcoma. Histology, regional lymph node status, and primary site were not related to the likelihood of local failure; however, the local failure rate for 47 patients with retroperitoneal tumors was 33% (probably caused by tumors ≥5 cm in diameter) compared with 14% to 19% for patients with bladder/prostate, extremity, and parameningeal tumors. Tumor size was the strongest predictor of local failure (10% for patients with primary tumors <5 cm vs. 25% for larger tumors; = .0004).[]

The treated radiation volume should be determined by the extent of tumor at diagnosis before surgical resection and before chemotherapy. A margin of 2 cm is generally used, including clinically involved regional lymph nodes. However, with conformal plans and image-guided RT, a margin of 1 cm to 1.3 cm to a clinical target volume or planning target volume may be used. While the volume irradiated may be modified because of considerations for normal tissue tolerance, gross residual disease at the time of radiation should receive full-dose radiation. A reduction in volume after 36 Gy is appropriate in chemoresponsive disease for patients with noninvasive displacement (T1) that have regressed in size, but not for invasive tumors (T2).

The timing of RT generally allows for chemotherapy to be given for 1 to 3 months before RT is initiated. RT is usually given over 5 to 6 weeks (e.g., 1.8 Gy once per day, 5 days per week), during which time chemotherapy is usually modified to avoid the radiosensitizing agents dactinomycin and doxorubicin.

  • The IRS-IV trial included a randomized study that reported that 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 (Group III) were randomly assigned to receive conventional, once-daily RT (total dose of 50.4 Gy) or the twice-daily hyperfractionated schedule (total dose of 59.4 Gy). There was no demonstrated advantage in terms of local control, but increased acute toxicity was observed with the increased dose.

Thus, conventional RT remains the standard for treating patients who have rhabdomyosarcoma with gross residual disease.

Brachytherapy

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 for patients with primary tumors at a vaginal site and selected bladder/prostate sites.[] 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 more.

Treatment of children aged 3 years and younger

Very young children (aged ≤36 months) diagnosed with rhabdomyosarcoma pose a therapeutic challenge because of their increased risk of treatment-related morbidity. As suggested above, reduced radiation doses may be appropriate if delayed surgery can provide negative margins. However, for patients 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.

Delayed primary excision and radiation dose reduction are appropriate for all ages. However, the youngest patients frequently do not get appropriate RT because of concerns about normal tissue toxicity, and these are ideal patients for whom surgical resection by delayed primary excision is a particularly important consideration. Local control can be achieved by both RT and surgery; it may be optimal if both treatments are used, but at least one approach is necessary in addition to chemotherapy.

One of the few studies of infants younger than 1 year included 77 patients with nonmetastatic rhabdomyosarcoma (median age, 7.4 months); 57% of patients had embryonal rhabdomyosarcoma. In this study, the 5-year failure-free survival (FFS) was 57%, and OS was 76%. Most failures were local, often because RT was withheld in violation of protocol guidelines. In contrast, for infants treated according to guidelines, both FFS and OS were clearly superior.

Local Control Management With Surgery and RT by Primary Site of Disease

Head and neck

Primary sites for childhood rhabdomyosarcoma within the head and neck include the orbit; nonorbital head and neck and cranial parameningeal; and nonparameningeal, nonorbital head and neck. Specific considerations for the surgical and radiotherapeutic management of tumors arising at each of these sites are discussed below.

For 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 proton RT, 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.; []

Extremity sites

Delayed primary excision has been studied in the D9803 intermediate-risk rhabdomyosarcoma trial. (Refer to the Surgery (Local Control Management) section of this summary for more information.) Delayed primary excision may be most appropriate for infants because the late effects of RT are more severe than they are in older patients; thus, even a moderate reduction in radiation dose is desirable.

A pooled analysis of 642 patients from four international cooperative groups in Europe and North America was performed to identify prognostic factors in patients with localized extremity rhabdomyosarcoma. Regional lymph node involvement was approximately 2.5 times higher with alveolar rhabdomyosarcoma than with embryonal rhabdomyosarcoma. The overall 5-year survival rate was 67%. Multivariate analysis showed that decreased OS was correlated with age older than 3 years, T2 and N1 status, incomplete initial surgery, treatment before 1995, and treatment by European groups. This analysis also suggested that duration of chemotherapy might have an impact on outcome in these patients.

IMRT can be used to spare the bone, yet provide optimal soft tissue coverage, and it 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.[] 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.[] Definitive RT and chemotherapy for Group III tumors resulted in 90% to 95% local control in the IRS-IV trial.

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. Chemotherapy and RT or delayed primary excision with or without RT results in comparable outcomes.

Regional and in-transit lymph nodes

For patients enrolled in clinical trials, the COG-STS recommends biopsy of all enlarged or clinically suspicious lymph nodes. In the trunk and extremity, if no enlarged lymph nodes are identified in the draining nodal basin, a sentinel lymph node biopsy is recommended; this is a more accurate way of assessing regional lymph nodes, instead of random lymph node sampling. Techniques for sentinel lymph node biopsy are standardized and should be completed by an experienced surgeon.

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 also in-transit) nodes is warranted.; [] In-transit nodes are defined as epitrochlear and brachial for upper-extremity tumors and popliteal for lower-extremity tumors. Regional lymph nodes are defined as axillary/infraclavicular nodes for upper-extremity tumors and inguinal/femoral nodes for lower-extremity tumors.

  • 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.

Positron emission tomography (PET) scanning is recommended for evaluation and staging of extremity primary tumors before initiation of therapy.

Truncal sites

Primary sites for childhood rhabdomyosarcoma within the trunk include the chest wall or abdominal wall, intrathoracic or intra-abdominal area, biliary tree, and perineum or anus. Specific considerations for the surgical and radiotherapeutic management of tumors arising at each of these sites are discussed below.

Genitourinary system

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 below.

Unusual primary sites

Rhabdomyosarcoma occasionally arises in sites other than those previously discussed.

Metastatic sites

Primary resection of metastatic disease at diagnosis (Stage 4, M1, Group IV) is rarely indicated.

Evidence (treatment of lung-only metastatic disease):

Chemotherapy Treatment Options

All children with rhabdomyosarcoma should receive chemotherapy. The intensity and duration of the chemotherapy are dependent on the Risk Group assignment. (Refer to Table 5 in the Stage Information for Childhood Rhabdomyosarcoma section of this summary 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.

Low-risk Group

Low-risk patients have localized (nonmetastatic) embryonal histology tumors in favorable sites that have been grossly resected (Groups I and II), embryonal tumors in the orbit that have not been completely resected (Group III), and localized tumors in an unfavorable site that have been grossly resected (Groups I and II). (Refer to Table 4 in the Stage Information for Childhood Rhabdomyosarcoma section of this summary for more information.) Only approximately 25% of newly diagnosed patients are, by definition, low risk.

Certain subgroups of low-risk patients have achieved survival rates higher than 90% when treated with a two-drug chemotherapy regimen that includes vincristine and dactinomycin (VA) plus RT for residual tumor. (Refer to Table 7 below.)

Evidence (chemotherapy for low-risk Group patients):

Intermediate-risk Group

Approximately 50% of newly diagnosed patients are in the intermediate-risk category. VAC is the standard multiagent chemotherapy regimen used for intermediate-risk patients.

Evidence (chemotherapy for intermediate-risk Group patients):

Approximately 20% of Group III patients will have a residual mass at the completion of therapy. The presence of a residual mass had no adverse prognostic significance. Aggressive alternative therapy is not warranted for rhabdomyosarcoma patients with a residual mass at the end of planned therapy unless it has biopsy-proven residual malignant disease. For Group III patients, best response (complete remission versus partial or no response) to initial chemotherapy had no impact on overall outcome. While induction chemotherapy is commonly administered for 9 to 12 weeks, 2.2% of patients with intermediate-risk rhabdomyosarcoma on the IRS-IV and studies were found to have early disease progression and did not receive their planned course of RT.

High-risk Group

High-risk patients have metastatic disease in one or more sites at diagnosis (Stage IV, Group IV). These patients continue to have a relatively poor prognosis with current therapy (5-year survival rate of ≤50%), and new approaches to treatment are needed to improve survival in this group. Two retrospective studies have examined patients who present with metastases limited to the lungs; results are summarized in the Metastatic sites section of this summary.

The standard systemic therapy for children with metastatic rhabdomyosarcoma is the three-drug combination of VAC.

Evidence (chemotherapy for high-risk Group patients):

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:

Other Therapeutic Approaches

  • High-dose chemotherapy with autologous and allogeneic stem cell rescue has been evaluated in a limited number of patients with rhabdomyosarcoma. The use of this modality has failed to improve the outcomes of patients with newly diagnosed or recurrent rhabdomyosarcoma.
  • The National Cancer Institute's intramural Pediatric Oncology Branch conducted a pilot study of cytoreductive treatment followed by consolidative immunotherapy incorporating T-cell reconstitution, plus a dendritic-cell and tumor-peptide vaccine that was given with minimal toxicity to patients with translocation-positive metastatic or recurrent Ewing sarcoma (n = 37) and alveolar rhabdomyosarcoma (n = 15). Ten patients with alveolar rhabdomyosarcoma had improved survival compared with five patients who did not receive immunotherapy.[]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

Treatment of Recurrent Childhood Rhabdomyosarcoma

Prognosis and Prognostic Factors

Although patients with recurrent or progressive rhabdomyosarcoma sometimes achieve complete remission with secondary therapy, the long-term prognosis is usually poor.

The following studies reported on the prognostic factors associated with recurrent or progressive disease:

  • In a 1999 study of 605 children, the prognosis was most favorable (5-year survival rates, 50%–70%) for children who initially presented with Stage 1 or Group I disease and embryonal/botryoid histology with small tumors and for those with local or regional nodal recurrence. Patients with Group I alveolar rhabdomyosarcoma or undifferentiated sarcoma had a 5-year overall survival (OS) of 40% to 50%. Only 20% of the relapsed patients were in these groups.[]
  • In a 2014 study of 24 children, 22 (82%) children with initially localized orbital sarcoma survived at least 5 years after relapse following re-treatment with curative intent.[]
  • A 2005 study of 125 patients with nonmetastatic rhabdomyosarcoma who recurred after previous complete remission observed that favorable factors at initial diagnosis included: nonalveolar histology, primary site in the orbit, genitourinary/nonbladder-prostate or head/neck nonparameningeal regions, tumor size of 5 cm or smaller, local relapse, relapse after 18 months from the primary diagnosis, and lack of initial radiation therapy.
  • A report of 337 patients with nonmetastatic rhabdomyosarcoma in 2008 observed that favorable factors at initial diagnosis were age 10 years or younger, embryonal histology, tumor size of 5 cm or smaller, favorable site, and lack of initial radiation therapy.
  • In a 2009 study of 234 patients who relapsed after achieving complete remission and completing primary treatment, the favorable prognostic factors for 3-year OS were reported; the factors were favorable primary site, local relapse, time to relapse more than 12 months, tumor size of 5 cm or smaller, and no previous radiation therapy.[]
  • A study of 474 patients in 2011 with nonmetastatic rhabdomyosarcoma who had complete local control at the primary site noted the unfavorable factors for survival 3 years after first relapse. These unfavorable factors included relapse with metastatic disease, previous (initial) radiation therapy, tumor size more than 5 cm, time to relapse less than 18 months, regional lymph node involvement, alveolar histology, and unfavorable disease at primary diagnosis.
  • In 2013, 90 patients with nonmetastatic alveolar rhabdomyosarcoma were re-treated with additional chemotherapy with or without local re-excision of the primary site (if indicated) with or without radiation therapy. The four most important factors for survival after relapse were no lymph node involvement, no metastases, adequate local therapy, and achieving a second complete remission. OS at 5 years was 21%.[]

Treatment Options for Recurrent Childhood Rhabdomyosarcoma

The selection of further treatment depends on many factors, including the site(s) of recurrence, previous treatment, and individual patient considerations.

Treatment options for recurrent childhood rhabdomyosarcoma include the following:

The following 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 website.

  • Intensive chemotherapy followed by autologous bone marrow transplantation. Very intensive chemotherapy followed by autologous bone marrow reinfusion is also under investigation for patients with recurrent rhabdomyosarcoma. However, a review of the published data did not determine a significant benefit for patients who underwent this salvage treatment approach.
  • (Lorvotuzumab Mertansine in Treating Younger Patients with Relapsed or Refractory Wilms Tumor, Rhabdomyosarcoma, Neuroblastoma, Pleuropulmonary Blastoma, Malignant Peripheral Nerve Sheath Tumor, or Synovial Sarcoma): This is a phase II study of IMGN901 (lorvotuzumab mertansine) in children with relapsed or refractory Wilms tumor, rhabdomyosarcoma, neuroblastoma, pleuropulmonary blastoma, malignant peripheral nerve sheath tumor, and synovial sarcoma. This trial is studying the effects of IMGN901, an antibody-drug conjugate that links a potent antimitotic to antibodies that target CD56.
  • (Nivolumab With or Without Ipilimumab in Treating Younger Patients With Recurrent or Refractory Solid Tumors or Sarcomas): This phase I/II trial is studying the side effects and best dose of nivolumab when given with or without ipilimumab to see how well they work in treating younger patients with solid tumors or sarcomas that have come back (recurrent) or do not respond to treatment (refractory). Monoclonal antibodies such as nivolumab and ipilimumab may block tumor growth in different ways by targeting certain cells. It is not yet known whether nivolumab works better alone or with ipilimumab in treating patients with recurrent or refractory solid tumors or sarcomas.
  • (A Study of Pembrolizumab [MK-3475] in Pediatric Participants With Advanced Melanoma or Advanced, Relapsed, or Refractory PD-L1-Positive Solid Tumors or Lymphoma [MK-3475-051/KEYNOTE-051]): This is a two-part study of pembrolizumab (MK-3475) in pediatric participants who have either advanced melanoma or a programmed cell death ligand 1 (PD-L1)-positive advanced, relapsed, or refractory solid tumor or lymphoma. Part 1 will find the maximum tolerated dose/maximum administered dose, confirm the dose, and find the recommended phase II dose for pembrolizumab therapy. Part 2 will further evaluate the safety and efficacy at the pediatric recommended phase II dose.
  • ( Inhibitor MK-1775 and Irinotecan Hydrochloride in Treating Younger Patients With Relapsed or Refractory Solid Tumors): This phase I/II trial is studying the side effects and best dose of inhibitor MK-1775 and irinotecan hydrochloride in treating younger patients with solid tumors that have come back or that have not responded to standard therapy. inhibitor MK-1775 and irinotecan hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
  • (Pediatric MATCH: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients with Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders): NCI-COG Pediatric Molecular Analysis for Therapeutic Choice (MATCH), referred to as Pediatric MATCH, will match targeted agents with specific molecular changes identified using a next-generation sequencing targeted assay of more than 3,000 different mutations across more than 160 genes in refractory and recurrent solid tumors. Children and adolescents aged 1 to 21 years are eligible for the trial.

    Tumor tissue from progression or recurrence must be available for molecular characterization. Patients with tumors that have molecular variants addressed by treatment arms included in the trial will be offered treatment on Pediatric MATCH. Additional information can be obtained on the ClinicalTrials.gov website for APEC1621 (NCT03155620).

  • New agents under clinical evaluation in phase I and phase II trials should be considered for relapsed patients.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

Changes to This Summary (09/28/2017)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Treatment of Previously Untreated Childhood Rhabdomyosarcoma

Revised text to state that the high frequency of nodal involvement and the prognostic association between nodal involvement and poorer outcome suggest that nodal sampling is appropriate. The current recommendation is to sample the regional lymph nodes.

Treatment of Recurrent Childhood Rhabdomyosarcoma

Added text about the APEC1621 (NCT03155620) trial as a treatment option under clinical evaluation for recurrent rhabdomyosarcoma.

This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood rhabdomyosarcoma. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

  • be discussed at a meeting,
  • be cited with text, or
  • replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewers for Childhood Rhabdomyosarcoma Treatment are:

  • Louis S. Constine, MD (James P. Wilmot Cancer Center at University of Rochester Medical Center)
  • Holcombe Edwin Grier, MD (Dana-Farber Cancer Institute/Boston Children's Hospital)
  • Andrea A. Hayes-Jordan, MD, FACS, FAAP (M.D. Anderson Cancer Center)
  • Paul A. Meyers, MD (Memorial Sloan-Kettering Cancer Center)
  • Alberto S. Pappo, MD (St. Jude Children's Research Hospital)
  • R Beverly Raney, MD (Consultant)
  • Stephen J. Shochat, MD (St. Jude Children's Research Hospital)

Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Pediatric Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

Permission to Use This Summary

PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”

The preferred citation for this PDQ summary is:

PDQ® Pediatric Treatment Editorial Board. PDQ Childhood Rhabdomyosarcoma Treatment. Bethesda, MD: National Cancer Institute. Updated . Available at: https://www.cancer.gov/types/soft-tissue-sarcoma/hp/rhabdomyosarcoma-treatment-pdq. Accessed . [PMID: 26389243]

Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.

Disclaimer

Based on the strength of the available evidence, treatment options may be described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.

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