This information is produced and provided by the National Cancer Institute (NCI). The information in this topic may have changed since it was written. For the most current information, contact the National Cancer Institute via the Internet web site at http://cancer.gov or call 1-800-4-CANCER.
The National Cancer Institute (NCI) provides the PDQ pediatric cancer treatment information summaries as a public service to increase the availability of evidence-based cancer information to health professionals, patients, and the public.
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 2002, childhood cancer mortality has decreased by more than 50%. For rhabdomyosarcoma, the 5-year survival rate has increased over the same time from 53% to 65% for children younger than 15 years and from 30% to 47% 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 skeletal muscle 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.[3,4] The incidence is 4.5 per million children and 50% of cases are seen in the first decade of life. There is a bimodal distribution for embryonal rhabdomyosarcoma with the second, smaller peak in adolescence noted for males only. The incidence of alveolar rhabdomyosarcoma does not vary by age or gender. Infants younger than 1 year have a higher incidence of undifferentiated sarcoma, a lower incidence of parameningeal tumors, and a higher incidence of tumors in the trunk and abdomen compared with older patients. Rhabdomyosarcoma is usually curable in most children with localized disease who receive combined modality therapy, with more than 70% surviving 5 years after diagnosis.[7,8,9] Relapses are uncommon after 5 years of disease-free survival, with a 9% late-event rate at 10 years. Relapses, however, are more common for patients who have gross residual disease in unfavorable sites following initial surgery and those who have metastatic disease at diagnosis. The most common primary sites for rhabdomyosarcoma are the head, the genitourinary tract, and the extremities.[7,8] 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 biliary tract.
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),[14,15,16] neurofibromatosis type I, Costello syndrome (with germline HRAS mutations),[18,19,20] Beckwith-Wiedemann syndrome (with which Wilms tumor and hepatoblastoma are more commonly associated),[21,22] Noonan syndrome, and MEN2A.
The prognosis for a child or adolescent with rhabdomyosarcoma is related to the age of the patient, site of origin, widest diameter of the tumor, 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 (RT) in selected cases,[7,8,25,26,27,28,29,30,31]; [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, as one study found an association and another study did not.[Level of evidence: 3iiA];  Examples of both clinical and biological factors with proven or possible prognostic significance are briefly described below.
Patients with alveolar rhabdomyosarcoma who have regional lymph node involvement have significantly worse outcomes (5-year failure-free survival [FFS] 43%) than patients who do not have regional lymph node involvement (5-year FFS 73%).
Patients with undifferentiated sarcomas were treated in trials coordinated by the IRSG from 1972 until 2006, but they are currently eligible for the nonrhabdomyosarcoma soft tissue sarcoma protocol using agents active in adult soft tissue sarcoma, ifosfamide and doxorubicin (COG-ARST0332). (Refer to the PDQ summary on Childhood Soft Tissue Sarcoma for more information.)
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 RT 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.
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|31.||Mandell L, Ghavimi F, LaQuaglia M, et al.: Prognostic significance of regional lymph node involvement in childhood extremity rhabdomyosarcoma. Med Pediatr Oncol 18 (6): 466-71, 1990.|
|32.||Dantonello TM, Int-Veen C, Winkler P, et al.: Initial patient characteristics can predict pattern and risk of relapse in localized rhabdomyosarcoma. J Clin Oncol 26 (3): 406-13, 2008.|
|33.||Sorensen PH, Lynch JC, Qualman SJ, et al.: PAX3-FKHR and PAX7-FKHR gene fusions are prognostic indicators in alveolar rhabdomyosarcoma: a report from the children's oncology group. J Clin Oncol 20 (11): 2672-9, 2002.|
|34.||Ferrari A, Miceli R, Meazza C, et al.: Comparison of the prognostic value of assessing tumor diameter versus tumor volume at diagnosis or in response to initial chemotherapy in rhabdomyosarcoma. J Clin Oncol 28 (8): 1322-8, 2010.|
|35.||Burke M, Anderson JR, Kao SC, et al.: Assessment of response to induction therapy and its influence on 5-year failure-free survival in group III rhabdomyosarcoma: the Intergroup Rhabdomyosarcoma Study-IV experience--a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group. J Clin Oncol 25 (31): 4909-13, 2007.|
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|39.||Crist WM, Garnsey L, Beltangady MS, et al.: Prognosis in children with rhabdomyosarcoma: a report of the intergroup rhabdomyosarcoma studies I and II. Intergroup Rhabdomyosarcoma Committee. J Clin Oncol 8 (3): 443-52, 1990.|
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|50.||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.|
Rhabdomyosarcoma can be divided into several histologic subsets: embryonal rhabdomyosarcoma, which has embryonal, botryoid, and spindle cell subtypes; alveolar rhabdomyosarcoma; and pleomorphic rhabdomyosarcoma.[1,2]
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 and spindle cell subtypes
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.
To be considered alveolar histology, the tumor must have greater than 50% alveolar elements; if the alveolar component is 50% or less, the tumor is considered embryonal.
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 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.[7,8,9,10,11] Unique translocations between the FKHR gene on chromosome 13 and either the PAX3 gene on chromosome 2 or the PAX7 gene on chromosome 1 are found in 70% to 80% of patients with alveolar histology tumors.[7,12] Translocations involving the PAX3 gene occur in approximately 59% of alveolar rhabdomyosarcoma cases, while the PAX7 gene appears to be involved in about 19% of cases. Patients with solid variant alveolar histology have a lower incidence of PAX-FKHR gene fusions than do patients showing classical alveolar histology.
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.[14,15,16,17] 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.[11,13] Embryonal tumors, on the other hand, often show loss of specific genomic material from the short arm of chromosome 11.[12,18,19] The consistent loss of genomic material from the chromosome 11p15 region in embryonal tumors suggests the presence of a tumor suppressor gene, though no such gene has yet been identified. Breakpoints involving the 1p11-1q11 region are relatively common (36%) in embryonal rhabdomyosarcoma.
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) or embryonal tumors.[11,21,22,23] A study has shown that the clinical characteristics and gene profile of translocation-negative alveolar rhabdomyosarcoma is indistinguishable from that seen in embryonal rhabdomyosarcoma cases. 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-FKHR–positive compared with those who were translocation-negative.
A 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.
|1.||Parham DM, Ellison DA: Rhabdomyosarcomas in adults and children: an update. Arch Pathol Lab Med 130 (10): 1454-65, 2006.|
|2.||Newton WA Jr, Gehan EA, Webber BL, et al.: Classification of rhabdomyosarcomas and related sarcomas. Pathologic aspects and proposal for a new classification--an Intergroup Rhabdomyosarcoma Study. Cancer 76 (6): 1073-85, 1995.|
|3.||Leuschner I: Spindle cell rhabdomyosarcoma: histologic variant of embryonal rhabdomyosarcoma with association to favorable prognosis. Curr Top Pathol 89: 261-72, 1995.|
|4.||Sultan I, Qaddoumi I, Yaser S, et al.: Comparing adult and pediatric rhabdomyosarcoma in the surveillance, epidemiology and end results program, 1973 to 2005: an analysis of 2,600 patients. J Clin Oncol 27 (20): 3391-7, 2009.|
|5.||Kodet R, Newton WA Jr, Hamoudi AB, et al.: Childhood rhabdomyosarcoma with anaplastic (pleomorphic) features. A report of the Intergroup Rhabdomyosarcoma Study. Am J Surg Pathol 17 (5): 443-53, 1993.|
|6.||Qualman S, Lynch J, Bridge J, et al.: Prevalence and clinical impact of anaplasia in childhood rhabdomyosarcoma : a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group. Cancer 113 (11): 3242-7, 2008.|
|7.||Barr FG, Smith LM, Lynch JC, et al.: Examination of gene fusion status in archival samples of alveolar rhabdomyosarcoma entered on the Intergroup Rhabdomyosarcoma Study-III trial: a report from the Children's Oncology Group. J Mol Diagn 8 (2): 202-8, 2006.|
|8.||Kelly KM, Womer RB, Barr FG: Minimal disease detection in patients with alveolar rhabdomyosarcoma using a reverse transcriptase-polymerase chain reaction method. Cancer 78 (6): 1320-7, 1996.|
|9.||Edwards RH, Chatten J, Xiong QB, et al.: Detection of gene fusions in rhabdomyosarcoma by reverse transcriptase-polymerase chain reaction assay of archival samples. Diagn Mol Pathol 6 (2): 91-7, 1997.|
|10.||Sartori F, Alaggio R, Zanazzo G, et al.: Results of a prospective minimal disseminated disease study in human rhabdomyosarcoma using three different molecular markers. Cancer 106 (8): 1766-75, 2006.|
|11.||Davicioni E, Anderson MJ, Finckenstein FG, et al.: Molecular classification of rhabdomyosarcoma--genotypic and phenotypic determinants of diagnosis: a report from the Children's Oncology Group. Am J Pathol 174 (2): 550-64, 2009.|
|12.||Merlino G, Helman LJ: Rhabdomyosarcoma--working out the pathways. Oncogene 18 (38): 5340-8, 1999.|
|13.||Parham DM, Qualman SJ, Teot L, et al.: Correlation between histology and PAX/FKHR fusion status in alveolar rhabdomyosarcoma: a report from the Children's Oncology Group. Am J Surg Pathol 31 (6): 895-901, 2007.|
|14.||Sorensen PH, Lynch JC, Qualman SJ, et al.: PAX3-FKHR and PAX7-FKHR gene fusions are prognostic indicators in alveolar rhabdomyosarcoma: a report from the children's oncology group. J Clin Oncol 20 (11): 2672-9, 2002.|
|15.||Krsková L, Mrhalová M, Sumerauer D, et al.: Rhabdomyosarcoma: molecular diagnostics of patients classified by morphology and immunohistochemistry with emphasis on bone marrow and purged peripheral blood progenitor cells involvement. Virchows Arch 448 (4): 449-58, 2006.|
|16.||Kelly KM, Womer RB, Sorensen PH, et al.: Common and variant gene fusions predict distinct clinical phenotypes in rhabdomyosarcoma. J Clin Oncol 15 (5): 1831-6, 1997.|
|17.||Barr FG, Qualman SJ, Macris MH, et al.: Genetic heterogeneity in the alveolar rhabdomyosarcoma subset without typical gene fusions. Cancer Res 62 (16): 4704-10, 2002.|
|18.||Koufos A, Hansen MF, Copeland NG, et al.: Loss of heterozygosity in three embryonal tumours suggests a common pathogenetic mechanism. Nature 316 (6026): 330-4, 1985 Jul 25-31.|
|19.||Scrable H, Witte D, Shimada H, et al.: Molecular differential pathology of rhabdomyosarcoma. Genes Chromosomes Cancer 1 (1): 23-35, 1989.|
|20.||Gordon T, McManus A, Anderson J, et al.: Cytogenetic abnormalities in 42 rhabdomyosarcoma: a United Kingdom Cancer Cytogenetics Group Study. Med Pediatr Oncol 36 (2): 259-67, 2001.|
|21.||Davicioni E, Anderson JR, Buckley JD, et al.: Gene expression profiling for survival prediction in pediatric rhabdomyosarcomas: a report from the children's oncology group. J Clin Oncol 28 (7): 1240-6, 2010.|
|22.||Williamson D, Missiaglia E, de Reyniès A, et al.: Fusion gene-negative alveolar rhabdomyosarcoma is clinically and molecularly indistinguishable from embryonal rhabdomyosarcoma. J Clin Oncol 28 (13): 2151-8, 2010.|
|23.||Davicioni E, Finckenstein FG, Shahbazian V, et al.: Identification of a PAX-FKHR gene expression signature that defines molecular classes and determines the prognosis of alveolar rhabdomyosarcomas. Cancer Res 66 (14): 6936-46, 2006.|
|24.||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 done prior to 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 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 scan of regional lymph nodes should be considered. Enlarged lymph nodes should be biopsied. 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.[2,3] However, the efficacy of these two procedures for identifying involved lymph nodes or other sites is under evaluation, and these procedures are not required by current treatment protocols.
Terms used in this summary section are defined below in Table 1.
|Favorable site||Orbit; nonparameningeal head and neck; genitourinary tract excluding kidney, bladder, and prostate; biliary tract.|
|Unfavorable site||Any site other than favorable.|
|T1||Tumor confined to anatomic site of origin.|
|T2||Tumor extension and/or fixation to surrounding tissue.|
|a||Tumor ≤5 cm in maximum diameter.|
|b||Tumor >5 cm in maximum diameter.|
|N0||No clinical regional lymph node involvement.|
|N1||Clinical regional lymph node involvement.|
|NX||Regional lymph nodes not examined; no information.|
|M0||No metastatic disease.|
Staging of rhabdomyosarcoma is relatively complex. The process includes the following steps:
|1.||Assigning a stage (consider site, size, Surgico-pathologic Group, and presence/absence of metastases).|
|2.||Assigning a local tumor Surgico-pathologic Group (status postsurgical resection/biopsy, with pathologic assessment of the tumor margin).|
|3.||Assigning a Risk Group (classified by Stage, Group, and histology).|
As noted previously, prognosis for children with rhabdomyosarcoma depends 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 with the 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 a TNM-based pretreatment staging system that incorporates the Surgico-pathologic Group, primary tumor site, regional lymph node status, and the presence or absence of metastases. This staging system is described in Table 2 below.[4,5]
|Stage||Sites of Primary Tumor||T Stage||Tumor Size||Regional Lymph Nodes||Distant Metastasis|
|I||Favorable sites||T1 or T2||Any size||N0 or N1 or NX||M0|
|II||Unfavorable sites||T1 or T2||a, ≤ 5 cm||N0 or NX||M0|
|III||Unfavorable sites||T1 or T2||a, ≤ 5 cm||N1||M0|
|b, > 5 cm||N0 or N1 or NX|
|IV||Any site||T1 or T2||Any size||N0 or N1 or NX||M1|
|M0 = absence of metastatic spread; M1 = presence of metastatic spread beyond the primary site; N0 = absence of nodal spread; N1 = presence of nodal spread beyond the primary site; X = unknown N status.|
The IRS-I, IRS-II (POG-7898), and IRS-III studies prescribed treatment plans based on the Surgico-pathologic Group system. In this system, Groups are defined by the extent of disease and by the extent of initial surgical resection after pathologic review of the tumor specimen(s). The definitions for these Groups are shown in Table 3 below.[6,7]
|I (Approximately 13% of all patients are in this group.)||A localized tumor that is completely removed with pathologically clear margins and no regional lymph node involvement.|
|II (Approximately 20% of all patients are in this group.)||A localized tumor that is grossly removed with (a) microscopic disease at the margin, (b) involved, grossly removed regional lymph nodes,or(c) both (a) and (b).|
|III (Approximately 48% of all patients are in this group.)||A localized tumor with gross residual disease after incomplete removal or biopsy only.|
|IV (Approximately 18% of all patients are in this group.)||Distant metastases are present at diagnosis.|
After patients are categorized by Stage and Surgico-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.[8,9] Treatment assignment is based on Risk Group, as shown in Table 4. To be considered alveolar histology, the tumor must have greater than 50% alveolar elements; if the alveolar component is 50% or less, the tumor is considered embryonal.
|Low risk||Embryonal||1||I, II, III|
|Embryonal||2, 3||I, II|
|Intermediate risk||Embryonal||2, 3||III|
|Alveolar||1, 2, 3||I, II, III|
|High risk||Embryonal or Alveolar||4||IV|
Since 2006, patients with undifferentiated sarcomas are treated on the COG-STS protocol for non-rhabdomyosarcomatous soft tissue sarcoma. Refer to the PDQ summary on Childhood Soft Tissue Sarcoma for more information.
|1.||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.|
|2.||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.|
|3.||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.|
|4.||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.|
|5.||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.|
|6.||Crist WM, Garnsey L, Beltangady MS, et al.: Prognosis in children with rhabdomyosarcoma: a report of the intergroup rhabdomyosarcoma studies I and II. Intergroup Rhabdomyosarcoma Committee. J Clin Oncol 8 (3): 443-52, 1990.|
|7.||Crist W, Gehan EA, Ragab AH, et al.: The Third Intergroup Rhabdomyosarcoma Study. J Clin Oncol 13 (3): 610-30, 1995.|
|8.||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.|
|9.||Breneman JC, Lyden E, Pappo AS, et al.: Prognostic factors and clinical outcomes in children and adolescents with metastatic rhabdomyosarcoma--a report from the Intergroup Rhabdomyosarcoma Study IV. J Clin Oncol 21 (1): 78-84, 2003.|
All children with rhabdomyosarcoma require multimodality therapy with systemic chemotherapy, in conjunction with either surgery, radiation therapy (RT), or both modalities for local tumor control.[1,2,3] Treatment generally entails surgical resection, if feasible without major functional/cosmetic impairment, followed by chemotherapy. Some patients with initially unresected tumors may undergo second-look surgery to remove residual tumor. Because rhabdomyosarcoma is sensitive to chemotherapy and RT, surgery is delayed if it will result in disfigurement or if it will interfere with organ function. Chemotherapy and possibly RT are administered in advance with the hope that subsequent surgical resection will be successful without undesirable side effects. A second-look procedure is only warranted if complete resection is deemed feasible. RT is indicated for patients with microscopic residual (Group II) disease and gross residual (Group III) disease. It is also recommended for Group I patients with alveolar histology. The discussion of treatment options for children with rhabdomyosarcoma is therefore divided into separate sections describing surgery, chemotherapy, and RT.
The treatment of rhabdomyosarcoma by the Children's Oncology Group and in Europe—as exemplified by trials from the Intergroup Rhabdomyosarcoma Study Group (IRSG), the Children's Oncology Group Soft Tissue Sarcoma Committee (COG-STS), and the International Society of Pediatric Oncology Malignant Mesenchymal Tumor (MMT)—differs in management and overall treatment philosophy. In the MMT trials, a primary objective is to reduce the use of radiation therapy, relying on initial chemotherapy followed by alternate chemotherapy in the event of a poor response to initial therapy and then surgical resection, reserving RT for use 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 especially RT, with their attendant morbidities. Overall survival (OS) is the primary end point, accepting the possibility of an inferior event-free survival (EFS) that might accompany nonaggressive local therapy when compared with more routine and earlier use of surgery and RT. The necessity of second-line salvage therapy for those who relapse is accepted in these trials. Conversely, the primary COG-STS objective has been to employ local therapy soon after initial chemotherapy, using RT for patients with residual disease after initial operation or biopsy only, and for patients with alveolar histology. EFS is the target end point, attempting to avoid relapse and salvage therapy. Results of these two approaches confirm that the IRSG trials resulted in superior EFS and better OS than the most recently published MMT 89 therapy. In some subsets of patients defined by primary site, the survival differences were greater (extremities, nonparameningeal head and neck); in others, the results were largely similar (genitourinary tract). Nevertheless, 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.[1,2,3]
|1.||Donaldson SS, Meza J, Breneman JC, et al.: Results from the IRS-IV randomized trial of hyperfractionated radiotherapy in children with rhabdomyosarcoma--a report from the IRSG. Int J Radiat Oncol Biol Phys 51 (3): 718-28, 2001.|
|2.||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.|
|3.||Donaldson SS, Anderson JR: Rhabdomyosarcoma: many similarities, a few philosophical differences. J Clin Oncol 23 (12): 2586-7, 2005.|
Note: Some citations in the text of this section are followed by a level of evidence. The PDQ Editorial Boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence.)
Surgical Management Treatment Options
The basic principle for the initial surgical treatment of children with rhabdomyosarcoma is complete resection of the primary tumor with a surrounding margin of normal tissue, along with sampling lymph nodes in the draining nodal basin, provided that major functional/cosmetic impairment will not result.[Level of evidence: 3iii] Important exceptions to the rule of normal margins exist (e.g., tumors of the orbit and of the genitourinary region).[2,3] 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 following their initial excisional procedure appear to have improved prognoses if a second operative procedure to re-excise the primary tumor bed before beginning chemotherapy can achieve complete removal of tumor. There is little evidence that debulking surgery that leaves macroscopic residual tumor improves outcome, compared with biopsy alone.[Level of evidence: 2A] Second-look procedures can show whether there is viable tumor after starting treatment; 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). The exact role of second-look surgery remains undefined in rhabdomyosarcoma. Because rhabdomyosarcoma can arise from multiple sites, surgical care must be tailored to the unique aspects of each site. Surgical management of the more common primary sites is provided below.
Head and neck
If the tumors are parameningeal (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 through the dura. If skull erosion and/or transdural extension is equivocal, a computed tomography (CT) scan of the same regions with contrast is indicated. 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. Despite its parameningeal site, middle ear rhabdomyosarcoma has a favorable prognosis.
Rhabdomyosarcomas of the orbit should not undergo exenteration, but biopsy is needed for diagnosis.[8,9] Biopsy is followed by chemotherapy and RT, with orbital exenteration reserved for the small number of patients with locally persistent or recurrent disease.[10,11]
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 following chemotherapy and radiation therapy (RT). For patients with head and neck primary tumors that are considered unresectable, chemotherapy and RT are the mainstay of primary management.[7,10,13,14,15,16]
The definitive surgical procedure involves wide local excision with en bloc removal of a cuff of normal tissue. Complete tumor removal from the hand or foot is not feasible in most cases because of functional impairment.[Level of evidence: 3iiA] Primary re-excision may be appropriate in patients whose initial surgical procedure leaves microscopic residual disease that is resectable by a second procedure. Amputation should be avoided because primary RT results in excellent local control.[Level of evidence: 3iiiA]
Because of the significant incidence of nodal spread for extremity primary tumors (often without clinical evidence of involvement) and because of the prognostic and therapeutic implications of nodal involvement, extensive pretreatment assessment for regional nodal involvement is warranted.[19,20,21,22] The Children's Oncology Group Soft Tissue Sarcoma Committee (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 prior to sampling of the involved nodal region. Sentinel lymph node (SLN) mapping is employed at some centers to identify the regional nodes that are the most likely to be involved.[22,23,24,25] The contribution of SLN mapping is not yet clearly defined in pediatric patients.
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 therapy and is therefore associated with excellent long-term survival.[26,27,28,29]
Intrathoracic or intraabdominal 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 following chemotherapy, with or without RT, offers a significant survival advantage (73% vs. 34% to 44% without removal).
With rhabdomyosarcoma of the biliary tree, total resection is rarely feasible. Outcome 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 lymph nodes. When feasible, without unacceptable morbidity, removing all gross tumor before chemotherapy is begun improves the likelihood of cure. In Intergroup Rhabdomyosarcoma Study Group (IRSG) Protocols I through IV, the OS after aggressive therapy for tumors in this location was 49%.
Primary sites for childhood rhabdomyosarcoma within the genitourinary system include the paratesticular area, bladder, prostate, kidney, vagina, uterus, and vulva. Specific considerations for the surgical 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 entire 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. Paratesticular tumors have been found to have a relatively high incidence of lymphatic spread (26% in IRS-I and IRS-II [POG-7898]), 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 are younger than 10 years and who have Group I disease, and whose 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.[35,36] 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.[3,37,38] A staging ipsilateral retroperitoneal lymph node dissection is currently required for all children 10 years and older with paratesticular rhabdomyosarcoma on IRSG and COG-STS studies. Node dissection is not routine in Europe for adolescents with resected paratesticular rhabdomyosarcoma. European investigators tend to rely on radiographic rather than surgico-pathologic assessment of retroperitoneal lymph node involvement.[34,35] It appears, however, that the ability of the CT scan to predict the presence of lymph node involvement needs further study. For patients with incompletely removed paratesticular tumors that require radiation therapy, temporarily repositioning the contralateral testicle into the adjacent thigh prior to scrotal radiation therapy may preserve hormone production.[Level of evidence: 3iiiC]
Bladder salvage is a major goal of therapy for patients with tumors arising in the prostate and bladder. An important review providing information about historical, current, and future treatment approaches for prostate and bladder rhabdomyosarcomas has been published. 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 to reduce tumor bulk,[42,43] 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 following diagnosis (3-year OS was 70% in IRS-II [POG-7898]).[44,45] The more recent experience from IRS-III and IRS-IV-STAGE- 1, 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%.[43,46,47] Thus, 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. The initial 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. For patients with biopsy-proven, residual malignant tumor following 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.
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 surgical procedure such as total cystectomy.[46,49,50] 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 following 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.
For patients with genitourinary primary tumors of the vagina/vulva/uterus, the initial surgical procedure is usually a transvaginal biopsy. Initial radical surgery is not indicated for rhabdomyosarcoma of the vagina/vulva/uterus. Conservative surgical intervention for vaginal rhabdomyosarcoma, with primary chemotherapy and adjunctive radiation (often brachytherapy) for residual disease (Group IIA or III), results in excellent disease-free survival.[51,52] Because of the smaller number of patients with uterine rhabdomyosarcoma, it is difficult to make a definitive treatment decision, but chemotherapy or RT is also effective.[51,53] 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.
Unusual primary sites
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 should be initiated after diagnostic biopsy, with the intent to try to remove residual tumor at a later date.
The kidney is occasionally the primary site for rhabdomyosarcoma or undifferentiated sarcoma; ten cases have been identified from among 5,746 eligible patients (0.17%) enrolled on IRSG protocols. The tumors were large (median diameter, 12 cm), and anaplasia was present in 60% of patients. Six patients with grossly complete tumor removal at diagnosis survived; the four with incomplete removal and gross or metastatic disease died of infection or metastatic tumor.
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 cases 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 is rarely indicated. The European Cooperative Rhabdomyosarcoma Study Group reviewed four consecutive trials and identified 29 patients with embryonal rhabdomyosarcoma and metastasis limited to the lung. They reported approximately 40% 5-year EFS for the cohort and did not identify any benefit for local control of the pulmonary metastasis.[Level of evidence: 3iiiA]
Chemotherapy Treatment Options
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 Staging Information section for more information on Risk Groups.
Standard treatment options
|Orbital||Any||I, II, III||N0|
|Unfavorable||≤5 cm||I, IIA||N0|
The COG-D9602 study of the Children's Oncology Group 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 VA plus cyclophosphamide (total dose 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. At 5 years for subgroup A patients, the overall failure-free survival (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 higher than 90% by undergoing three-drug chemotherapy with VA and cyclophosphamide (VAC) plus RT for residual tumor. The total cyclophosphamide dose used in completed COG protocols was 28.6 g/m2. See Table 6 below.
|Favorable (orbital or non-orbital)||Any||IIB, IIC, III||N0, N1|
|Unfavorable||>5 cm||I, II||N0, N1|
Standard treatment options
A comparison of survival in patients with tumors of embryonal histology treated on IRS-IV-STAGE-1 (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.
Treatment options under clinical evaluation
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.
Standard treatment options
In a pooled analysis of high-risk rhabdomyosarcoma patients treated with multiagent chemotherapy (all chemotherapy regimens used a cyclophosphamide or ifosfamide plus dactinomycin and vincristine-based backbone with variation as to the use of additional chemotherapy agents) followed by local therapy (surgery with or without RT) within 3 to 5 months of starting chemotherapy, adverse prognostic factors in patients presenting with metastatic disease included: age younger than 1 year or age 10 years or older, unfavorable primary site, bone and/or bone marrow involvement, and three or more 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.[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:
Treatment options under clinical evaluation
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.
Radiation Therapy Management Options
RT is an effective method for achieving local control of tumor for patients with microscopic or gross residual disease following biopsy, initial surgical resection, or chemotherapy. In Group II rhabdomyosarcoma patients, over 50% experienced local recurrence associated with noncompliance or omission of RT. Patients with completely resected tumors (Group I) of embryonal histology do well without RT,[63,64] but RT benefits patients with Group I tumors with alveolar or undifferentiated histology. A review of European trials conducted by the Cooperative Soft Tissue Sarcoma Study 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 (defined by tumor histology, tumor size, and tumor site). Local failure is the predominant type of relapse for patients with Group III disease. Patients with tumor-involved regional lymph nodes at diagnosis have a higher risk of local and distant failure compared with patients whose lymph nodes are negative. As with the surgical management of patients with rhabdomyosarcoma, recommendations for RT depend on the site of primary tumor and on the amount of residual disease, if any, following surgical resection. For patients with head and neck rhabdomyosarcoma, four studies reported excellent local control in patients treated with intensity-modulated radiation therapy (IMRT) or fractionated stereotactic radiation therapy and chemotherapy over a 4-year period. 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.[96,97,98,99]; [Level of evidence: 3iiiA]
For optimal care of pediatric patients undergoing radiation treatments, it is imperative to have a radiation oncologist, radiation technicians, and nurses who are experienced in treating children. An anesthesiologist may be necessary to help sedate and immobilize young patients. The facility should be equipped with a linear accelerator and have the capabilities to administer electron beam therapy. Computerized treatment planning with a three-dimensional planning system should be available. Techniques to deliver radiation specifically to the tumor while sparing normal tissue (e.g., conformal radiation therapy , IMRT, proton-beam therapy [charged-particle radiation therapy], or brachytherapy) should be considered (see below).[101,102,103]
Standard treatment options
The IRSG conducted a randomized study within the IRS-IV-STAGE-1 protocol and showed that giving 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 RT (50.4 Gy vs. 59.4 Gy) given by the twice-daily hyperfractionated schedule. There was no demonstrated advantage in terms of local control. Therefore, conventional RT remains the standard for treating patients with rhabdomyosarcoma and gross residual disease.
Very young children (age <36 months or younger) diagnosed with rhabdomyosarcoma pose a therapeutic challenge because of their increased risk for treatment-related morbidity. Recent experience  supports using a somewhat reduced dose of RT in settings where surgery alone is insufficient to provide a high likelihood of local control. For children with initially unresectable tumors, delayed gross total resection followed by 36 Gy beam RT provides an excellent likelihood of local control. For infants with unresectable tumors, 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.
Treatment options under clinical evaluation
The following are examples of national and/or institutional clinical trials involving RT that are currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.
Current Clinical Trials
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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Although patients with recurrent or progressive rhabdomyosarcoma sometimes achieve complete remission with secondary therapy, the long-term prognosis is usually poor.[1,2] The prognosis is most favorable (50% to 70% 5-year survival rates) for children who initially present with stage I or Group I disease and embryonal histology and who have smaller tumors or present with a local or regional recurrence.[1,2,3] 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 post recurrence.
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. RT should be considered for patients who have not already received RT in the area of recurrence, or rarely for those who have received RT 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:
Current Clinical Trials
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.
General information about clinical trials is also available from the NCI Web site.
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|15.||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.|
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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.
Previously Untreated Childhood Rhabdomyosarcoma
Added text to state that in Group II rhabdomyosarcoma patients, over 50% experienced local recurrence associated with noncompliance or omission of radiation therapy (RT) (cited Million et al. as reference 92).
Added text about how in a retrospective review of 41 patients on two sequential studies for patients with low-risk embryonal rhabdomyosarcoma conducted by IRSG/COG, 33 girls with Group IIA or III N0 localized vaginal tumors received no primary irradiation and 12 (36%) recurred locally after vincristine and dactinomycin (VA), VA and cyclophosphamide (VAC), or VAc (low-dose cyclophosphamide) chemotherapy. A response-based approach that eliminates RT in children with vaginal tumors treated with VA or low-dose VAC appears to increase the rate of local recurrences; patients choosing to not undergo therapy have a 50% chance risk of needing intensive chemotherapy followed by RT (added level of evidence 3iiiDiii).
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
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National Cancer Institute: PDQ® Childhood Rhabdomyosarcoma Treatment. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://cancer.gov/cancertopics/pdq/treatment/childrhabdomyosarcoma/HealthProfessional. Accessed <MM/DD/YYYY>.
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Last Revised: 2012-02-03
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