AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Rhabdomyosarcoma (RMS) (from Greek, rhabdo, meaning rod shape, and myo, meaning muscle) is the most common soft tissue sarcoma in children. Although Weber first described RMS in 1854, a clear histologic definition was not available until 1946, when Stout recognized the distinct morphology of rhabdomyoblasts. Stout described rhabdomyoblasts as appearing in round, strap, racquet, and spider forms. As its name suggests, the tumor is believed to arise from a primitive muscle cells. Rhabdomyoblasts sometimes have discernible muscle striations that are visible on specimens under light microscopy, though electron microscopy may be needed to detect subcellular elements. Cells are usually positive for intermediate filaments and other proteins typical of differentiated muscle cells, such as desmin, vimentin, myoglobin, actin, and transcription factor myoD.

Several distinct histologic groups have prognostic significance, including embryonal RMS (ERMS, which occurs in 55% of patients), the botryoid variant of ERMS (5% of patients), alveolar RMS (ARMS, 20% of patients), and undifferentiated sarcoma (UDS, 20% of patients).

Treatment responses and prognoses vary widely depending on location and histology. Studies tumor biology and treatment in patients with RMS at a single institution, or even at regional centers, are not possible because of the variable nature and uncommon occurrence of the tumors. Therefore, most advances in knowledge and treatment have resulted from cooperative group studies.

Pathophysiology

Although the tumor is believed to arise from primitive muscle cells, tumors can occur anywhere in the body except bone. The most common sites are the head and neck (28%), extremities (24%), and genitourinary (GU) tract (18%). Other notable sites include the trunk (11%), orbit (7%), and retroperitoneum (6%). RMS occurs at other sites in <3% of patients. The botryoid variant of ERMS arises in mucosal cavities, such as the bladder, vagina, nasopharynx, and middle ear. Lesions in the extremities are most likely to have an alveolar type of histology. Metastases are found predominantly in the lungs, bone marrow, bones, lymph nodes, breasts, and brain.

As with most tumors of childhood, the cause of RMS is unknown. The alveolar variant is so named because of the thin criss-crossing fibrous bands that appear as spaces between cellular regions of the tumor (reminiscent of lung alveoli). This variant is usually associated with 1 of 2 chromosomal translocations, namely, t(2;13) or t(1;13). These result in the fusion of the DNA-binding domain of the neuromuscular developmental transcription factors, encoded by PAX3 on chromosome 2 or PAX7 on chromosome 1. The transcriptional activation domain of a relatively ubiquitous transcription factor, FKHR (or FOXO1a) is encoded on chromosome 13.

The resulting hybrid molecule is a potent transcription activator. It is believed to contribute to the cancerous phenotype by abnormally activating or repressing other genes. The embryonal subtype usually has a loss of heterozygosity at band 11p15.5; this observation suggests the presence of a tumor suppressor gene. Other molecular aberrations that may provide clues to the origin of the tumor and that may be useful for future treatment strategies include TP53 mutations (which occurs in approximately one half of patients), an elevated N-myc level (in 10% of patients with ARMS), and point mutations in N-ras and K-ras oncogenes (usually embryonal). In addition, levels of insulinlike growth factor-2 may be elevated, suggesting pathways involving autocrine and paracrine growth factors.

Frequency

United States

The incidence is 6 cases per 1,000,000 population per year (approximately 250 cases) in children and adolescents younger than 15 years.

International

No notable geographic predilection is reported.

Mortality/Morbidity

In patients with localized disease, overall 5-year survival rates have improved to >80% with the combined use of surgery, radiation therapy, and chemotherapy. However, in patients with metastatic disease, little progress has been made in survival rates, with a 5-year event-free survival rate <30%. The use of high-dose myeloablative therapy with autologous stem-cell rescue has not improved outcomes for these patients.

In a recent analysis of data collected by the Surveillance, Epidemiology, and End Results (SEER) program, mortality was highly related to age, site, and histology. The 5-year survival was highest for children aged 1-4 years (77%) and worst for infants and adolescents (47% and 48%, respectively). Orbital and GU sites were the most favorable (86% and 80%, respectively). Unfavorable sites included tumors of the extremities (50%), retroperitoneum (52%), and trunk (52%). Embryonal histology was best (67%) compared with alveolar histology (49%).

Race

No racial predilection is obvious.

Sex

Overall, the male-to-female ratio is 1.2-1.4:1. Differences exist according to the site of primary disease.

• GU tract: The male-to-female ratio is 3.3:1 in patients with bladder or prostate involvement and 2.1:1 in RMS of the GU tract without bladder or prostate involvement.
• Extremity: The male-to-female ratio is 0.79:1.
• Orbit: The male-to-female ratio is 0.88:1.

Age

Approximately 87% of patients are younger than 15 years, and 13% of patients are aged 15-21 years. RMS rarely affects adults. Age-related differences are observed for the different sites of primary disease. Two age peaks tend to be associated with different locations. Patients ages 2-6 years tend to have head and neck or GU tract primary tumors, whereas adolescents aged 14-18 y tend to have primary tumors in extremity, truncal, or paratesticular locations.

• GU tract: In patients with bladder or prostate involvement, 73% are younger than 5 years. In patients with RMS of the GU tract without bladder or prostate involvement, 27% are older than 15 years.
• Orbit: About 42% of patients with orbital RMS are aged 5-9 years.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

RMS usually manifests as an expanding mass; symptoms depend on the location of the tumor. Pain may be present. If metastatic disease is present, symptoms of bone pain, respiratory difficulty (secondary to lung nodules or to pleural effusion), anemia, thrombocytopenia, and neutropenia may be present. Disseminated rhabdomyoblasts in the bone marrow may mimic leukemia, both in symptoms and light microscopic findings.

Typical presentations by the location of nonmetastatic disease are as follows:

• Orbit - Proptosis or dysconjugate gaze
• Paratesticular - Painless scrotal mass
• Prostate - Bladder or bowel difficulties
• Uterus, cervix, bladder - Menorrhagia or metrorrhagia
• Vagina - Protruding polypoid mass (botryoid, meaning a grapelike cluster)
• Extremity - Painless mass
• Parameningeal (ear, mastoid, nasal cavity, paranasal sinuses, infratemporal fossa, pterygopalatine fossa) - Upper respiratory symptoms or pain

Physical

Physical findings depend on the location of the tumor. Tumors in superficial locations may be palpable and detected relatively early, but those in deep locations (eg, retroperitoneum) may grow large before causing symptoms.

Causes

The cause of RMS is unclear. Several genetic syndromes and environmental factors are associated with increased prevalence of RMS.

• Genetic syndromes include the following:
• • Neurofibromatosis (4-5% risk of any of a number of malignancies)
  • Li-Fraumeni syndrome (germline mutation of the tumor suppressor gene TP53)
  • Rubinstein-Taybi syndrome
  • Gorlin basal cell nevus syndrome
  • Beckwith-Wiedemann syndrome
  • Costello syndrome
• A higher prevalence of congenital anomalies exists in patients who later develop RMS with locations as follows:
• • GU tract
  • CNS (ie, Arnold-Chiari malformation)
  • GI tract
  • Cardiovascular system
• Environmental factors appear to influence the development of RMS, as follows:
• • Parental use of marijuana and cocaine
  • Intrauterine exposure to X-rays
  • Previous exposure to alkylating agents

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• CBC: Anemia may be present because of inflammation, or pancytopenia may be present from bone marrow involvement.
• Liver function tests, including measurement of lactic acid dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, and bilirubin levels: Metastatic disease of the liver may affect values of these proteins. Liver function must be assessed before chemotherapy.
• Renal function tests, including measurements of BUN and creatinine levels: Renal function must be assessed before chemotherapy.
• Urinalysis (UA): Hematuria may indicate involvement of the GU tract.
• Blood electrolyte and chemistry, including evaluation of sodium, potassium, chlorine, carbon dioxide, calcium, phosphorous, and albumin values: Assess for abnormalities before chemotherapy.

Imaging Studies

• Plain radiography: Radiographs of the primary site and of the chest are helpful to determine the presence of calcifications and bone involvement of the primary tumor and to search for metastatic lung lesions.
• CT scanning
• • Obtain a chest CT scan to evaluate for metastases to the lungs. Chest CT scanning is best performed before surgery to avoid atelectasis, which can be confused with metastasis.
  • A CT scan of the primary site may also be helpful in evaluating for bone erosion, if present, and to follow up the patient's response to therapy.
  • Obtain a CT scan of the liver in patients with abdominal or pelvic primary tumors to assess for metastatic spread. Ultrasonography is an alternative.
• MRI: MRI improves definition of the mass and its invasion of adjacent organs, especially in orbital, paraspinal, or parameningeal regions. Obtain an MRI of the head if the patient is symptomatic at diagnosis.
• Bone scanning: Search for metastases to the bones.
• Ultrasonography: Obtain sonograms of the liver in patients with abdominal or pelvic tumors. CT scanning is an alternative.
• Echocardiography: Assess cardiac function before chemotherapy.

Procedures

• Biopsy: Open biopsy best enables adequate tissue sampling for diagnosis and molecular studies. Core needle biopsy is an alternative. Depending on the location, definitive surgery can be postponed to allow for neoadjuvant chemotherapy to shrink the tumor.
• Cytogenetics, fluorescent in situ hybridization (FISH)
• • This study helps in determining if the translocations t(1;13) or t(2;13), which are associated with the alveolar subtype, are present.
  • FISH also helps in the differential diagnosis if a translocation characteristic of another tumor type is present.
  • FISH is most sensitive for these translocations and can be helpful in evaluating residual disease.
• Reverse transcriptase–polymerase chain reaction (RT-PCR) testing
• • When cytogenetic testing is unavailable (eg, culture failure) or when its results are uninformative, order a RT-PCR reaction to assess for the characteristic translocations associated with ARMS and other small, round blue-cell tumors of childhood.
  • In many centers, the use of RT-PCR to screen for a panel of translocations associated with soft tissue sarcomas is becoming a routine adjunct to morphologic analysis to help ascertain the diagnosis.
• Bone marrow aspiration and biopsy: Assess for metastatic spread to bone marrow.

Histologic Findings

RMS is one of the small, round blue-cell tumors of childhood. On occasion, these types of tumors can be difficult to differentiate. RMS cells tend to have variable differentiation along the myogenesis pathway and may appear as strap cells or myotubes that sometimes contain muscle cross-striations. RMS cells may demonstrate positive immunohistochemical results for muscle-specific markers such as myoglobin, actin, and desmin.

Cells from the RMS subtypes have the following distinctive features:

• Botryoid: The cambium layer is characteristic, containing a condensation of loose tumor cells below an epithelial surface.
• Alveolar: Cells line up along membranes that may be imperceptibly thin or that may be obvious collagen bands resembling the lung alveoli. A tumor should be classified as this type if any portion of it appears to be alveolar.
• Undifferentiated: No evidence of myogenesis differentiation is usually present.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Treatment in patients with RMS involves a combination of surgery, chemotherapy, and radiation therapy. Because the treatment plan is complicated and prolonged and because many medical issues are unique to pediatric oncology, all patients should be referred (at least initially) to a center with personnel who are skilled in caring for children with cancer.

At present, patients are categorized according to their risk, which takes into account the location of the tumor and the histologic and surgical results. Low-risk patients are those who have the best prognosis, whereas intermediate- or high-risk patients have an increased of having relapses and incurable disease. To separate the features into meaningful categories, patients are assigned to both a surgicopathologic clinical group (Roman numeral) and a stage (Arabic numeral). All patients with metastatic disease (group IV, stage 4) are considered high risk, except children and adolescents younger than 14 years with ERMS. (In some studies, these patients appear to do better than others, for unknown reasons.) Although all patients require chemotherapy, regimens vary depending on the stage and group.

• Surgicopathologic (clinical) group (Groups I-III are for localized disease.)
• • Group I - Tumor completely removed
  • Group II - Microscopic residual tumor, involved regional nodes, or both
  • Group III - Gross residual tumor
  • Group IV - Distant metastatic disease
• Tumor, nodes, and metastases (TNM) staging system
  • Tumor - Confined to the site of origin (T1) or extends beyond the site of origin (T2)
  • Node - No regional node involvement (N0), regional node involvement (N1), or nodes unknown (NX)
  • Metastasis - No metastasis (M0), or metastases present at diagnosis (M1)
• RMS staging system
  • Stage 1 - Orbit, head, and/or neck (not parameningeal) involvement, and involvement of the GU tract (not bladder or prostate)
  • Stage 2 - Other locations, N0 or NX
  • Stage 3 - Other locations, N1 if the tumor is <5 cm or N0 or NX if the tumor > 5 cm
  • Stage 4 - Any site with distant metastases
• Low-risk patients are those with the following embryonal histology:
  • Stages 1-3 in groups I-II (or III for only orbital involvement)
  • Stage 1 in group III
• Intermediate-risk patients are those with the following embryonal histology:
  • Stages 2-3 in clinical group III (nonorbital involvement)
  • Stage 4 in clinical group IV if patient is younger than 14 years

Surgical Care

Surgical management of RMS varies depending on the location of the tumor. If feasible, remove tumors promptly and without unacceptable disfigurement or loss of function. Even if metastatic disease is present, surgical excision of the primary site should be performed, if possible. The surgical result helps determine the clinical grouping to be used for treatment stratification.

Surgical guidelines for the various sites can be found in the protocols of the Children's Oncology Group Soft Tissue Sarcoma Committee (formerly, Intergroup Rhabdomyosarcoma Study Group [IRSG]) and are beyond the scope of this article. However, common principles are noteworthy and described below.

• Primary tumor
• • Because relapses often occur at the site of the original primary tumor, adequate local control is essential.
  • Data from Europe suggest that chemotherapy alone can be effective for achieving adequate local control in some patients who have a complete response of the primary tumor. However, surgery and/or irradiation are needed for local control of residual disease.
  • If possible, complete excision of the lesion should be performed with wide (2-cm) margin of healthy tissue. Wide margins of normal tissue often are impossible to achieve at certain sites, such as the head and neck. If margins are narrow, obtain several biopsy specimens from the surrounding tissue to assess for residual local disease.
  • For tumors that cannot be excised at diagnosis, a second-look procedure may be appropriate after a period of chemotherapy (usually 12 wk).
• Lymph nodes
• • Regional lymph nodes that appear to be clinically or radiographically involved should be sampled to determine the clinical group and the need for later radiation therapy.
  • Radical node dissection is not appropriate.
  • Axillary and femoral node sampling should be performed for lesions in the extremities, even if clinical findings are negative because of the high prevalence of metastatic disease arising from extremity lesions.

Consultations

The care of patients with RMS is complicated and extensive, and it touches all aspects of their lives. Initial evaluation and treatment should be undertaken at a center with a comprehensive program for children with cancer.

• Radiotherapist
• • Most patients with RMS require radiotherapy to achieve adequate local control, though radiotherapy is not usually performed until after initial surgical resection and the start of chemotherapy. Exceptions are patients with parameningeal primary tumors, for which initial radiotherapy has been shown to be beneficial.
  • A radiotherapist familiar with the requirements for clinical trials should be consulted at diagnosis for most patients in North America to determine if they have any special needs for treatment planning.
  • In initial studies, new techniques such as intensity-modulated radiotherapy (IMRT) and proton-beam radiotherapy appear to achieve adequate tumor control with reduced exposure to normal tissues.
• Psychosocial team: The psychosocial team is critical for helping patients and families cope with the stresses associated with the diagnosis and treatment of cancer. The social worker usually plays an intimate role in helping families navigate complicated insurance and financial issues.
• Dentist: A thorough dental evaluation is required to identify potential problems that may arise during chemotherapy.
• Pediatric therapists: Activities and therapy can be critical in helping the patient through the phases of medical therapy.

Diet

No specific dietary recommendations are needed. However, patients may require nasogastric feedings or parenteral nutrition during some phases of chemotherapy. This is especially true for patients with primary tumors in head and neck, who may have severe mucositis after radiation therapy.

Activity

No specific activity limitations are required. The patient's activity is restricted only as the location of the tumor and the adverse effects of treatment dictate.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Standard therapy for RMS includes chemotherapy combined with surgical resection and/or radiotherapy for local control, if necessary. These modalities have not improved survival rates in patients with metastatic disease; however, new agents active against RMS are being sought, and agents are being tested in phase I and II clinical trials. Among the novel therapies in development are oncolytic viruses and immunotherapies, such as monoclonal antibodies and dendritic-cell vaccines.

Drug Category: Antineoplastics agents

This therapy is aimed at killing tumor cells. Cancer chemotherapy is based on an understanding of how tumor cell grow and of how drugs affect this growth. After cells divide, they enter a period of growth (phase G1), followed by DNA synthesis (phase S). The next phase is a premitotic phase (G2) and, finally, mitotic cell division (phase M) occurs.

The cell-division rate varies for different tumors. Tumors of most common cancers grow slowly compared with normal tissues, and the rate of growth may decrease further in large tumors. This difference allows normal cells to recover from chemotherapy more quickly than malignant cells can and is the rationale behind current cyclic dosing schedules.

Antineoplastic agents interfere with cell reproduction. Some agents are phase specific, whereas others (eg, alkylating agents, anthracyclines, cisplatin) are not. Cellular apoptosis (ie, programmed cell death) is a potential mechanism of many antineoplastic agents.

Drug Name	Dactinomycin (Cosmegen, actinomycin D)
Description	Antibiotic derived from Streptomyces bacteria.
Adult Dose	0.5 mg/d IV push for 5 d
Pediatric Dose	0.015 mg/kg/d IV push for 5 d or 1.5 mg IV push q3wk
Contraindications	Documented hypersensitivity; varicella; herpes zoster; concomitant radiation therapy
Interactions	May interfere with immune response to live virus vaccine (MMR) and reduce efficacy
Pregnancy	D - Unsafe in pregnancy
Precautions	Vesicant (avoid extravasation); may cause nausea, vomiting, diarrhea, stomatitis, myelosuppression, hepatotoxicity, dermatitis, or hyperpigmentation (especially with previous radiation exposure)

Drug Name	Cyclophosphamide (Cytoxan)
Description	Alkylating agent believed to be cytotoxic to dividing cells by cross-linking cellular DNA. Processed in liver to active metabolites. Byproducts (eg, acrolein) accumulate in bladder and cause cystitis.
Adult Dose	400 mg/m2/d PO for 5 d or 1-1.5 g/m2 IV q3-4wk
Pediatric Dose	1.2-2.2 g/m2/d IV for 1-3 d
Contraindications	Documented hypersensitivity; severely depressed bone marrow function; severe hemorrhagic cystitis
Interactions	Allopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; toxicity may increase with chloramphenicol; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leukopenia; coadministration with succinylcholine may increase neuromuscular blockade by inhibiting cholinesterase activity; may interfere with immune response to live virus vaccine (MMR) and reduce efficacy
Pregnancy	D - Unsafe in pregnancy
Precautions	Regularly examine hematologic profiles (particularly neutrophils and platelets) to monitor for hematopoietic suppression; regularly examine urine for RBCs, which may precede hemorrhagic cystitis; cardiotoxicity occurs with high doses

Drug Name	Etoposide (Toposar, VP16)
Description	Inhibits topoisomerase II and therefore toxic to cells undergoing DNA replication.
Adult Dose	50-100 mg/m2/d IV for 5 d PO dose: 2 times IV dose rounded to nearest 50 mg
Pediatric Dose	100 mg/m2/d IV for 5 d
Contraindications	Documented hypersensitivity
Interactions	May prolong effects of warfarin and increase methotrexate clearance; cyclosporine and etoposide have additive effects in cytotoxicity of tumor cells; may interfere with immune response to live virus vaccine (MMR) and reduce efficacy
Pregnancy	D - Unsafe in pregnancy
Precautions	May cause nausea, vomiting, myelosuppression, or alopecia; adjust dose for renal or liver impairment, low serum albumin level, or bone marrow suppression; monitor for hypotension during infusion

Drug Name	Ifosfamide (Ifex)
Description	Alkylating agent. Inhibits DNA and protein synthesis and therefore cell proliferation by causing DNA cross-linking and denaturation of double helix.
Adult Dose	1.8 g/m2/d IV for 5 d
Pediatric Dose	1.6-2.4 g/m2/d IV for 5 d
Contraindications	Documented hypersensitivity; severe bone marrow depression; severe hemorrhagic cystitis
Interactions	Phenobarbital, phenytoin, chloral hydrate, and other drugs that interfere with CYP activity may alter effects of ifosfamide; coadministration with warfarin may result in increased international normalized ratio (INR); may interfere with immune response to live virus vaccine (MMR) and reduce efficacy
Pregnancy	D - Unsafe in pregnancy
Precautions	May cause hemorrhagic cystitis and severe myelosuppression; caution in renal function impairment or compromised bone-marrow reserve

Drug Name	Irinotecan (Camptosar, CPT-11)
Description	Topoisomerase I inhibitor. Use in RMS currently investigational.
Adult Dose	150 mg/m2 IV qwk
Pediatric Dose	20 mg/m2/d IV for 5 d
Contraindications	Documented hypersensitivity; severe diarrhea; febrile neutropenia; unresponsive or progressive adenocarcinoma; pregnancy
Interactions	Concomitant administration with other antineoplastic agents may prolong neutropenia and thrombocytopenia and increase morbidity and/or mortality; coadministration with dexamethasone increases risk of lymphocytopenia
Pregnancy	D - Unsafe in pregnancy
Precautions	Adverse effects include myelosuppression, alopecia, nausea, vomiting, and diarrhea; monitor bone marrow function

Drug Category: Uroprotective antidote

Mesna is a prophylactic detoxifying agent used to inhibit hemorrhagic cystitis caused by ifosfamide and cyclophosphamide. In the kidney, mesna disulfide is reduced to free mesna. Free mesna has thiol groups that react with acrolein, the ifosfamide and cyclophosphamide metabolite considered to be responsible for urotoxicity.

Drug Category: Colony-stimulating factors

These agents act as hematopoietic growth factors that stimulate the development of granulocytes. They are used to treat or prevent neutropenia when patients are receiving myelosuppressive cancer chemotherapy and to reduce the period of neutropenia associated with bone marrow transplantation. They are also used to mobilize autologous peripheral blood progenitor cells for bone marrow transplantation and in the management of chronic neutropenia. They shorten the time to neutrophilic recovery after chemotherapy.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Chemotherapy: Chemotherapy cycles are usually administered every 3 weeks (though vincristine is periodically given weekly), depending on recovery of the bone marrow. Patients receiving cycles that include cyclophosphamide, ifosfamide, and etoposide generally require inpatient admission for drug administration and monitoring.
• Fever and neutropenia: Admission is required to administer intravenous (IV) antibiotics and to monitor patients.
• Other reasons for inpatient care: Patients may require admission for a multitude of other medical problems during the chemotherapy phase of treatment, including varicella infection (to administer IV acyclovir and to monitor), mucositis (resulting from narcotics use), dehydration, meningitis, constipation, fungal pneumonia, and cystitis, among others.

Further Outpatient Care

• CBC: Perform a CBC twice each week in patients receiving therapy by using G-CSF so that G-CSF can be discontinued when the absolute neutrophil count has reached a predetermined level (usually 1.0 or 5.0 X 10⁹/L [1000 or 5000/µL]).
• Blood chemistry: Monitor blood chemistry results and liver function in patients receiving parenteral nutrition or in those who have a history of toxicity, especially if the patient continues to receive nephrotoxic or hepatotoxic antibiotics or other drugs.
• Chemotherapy: Depending on the protocol, some chemotherapy regimens (eg, vincristine, dactinomycin in particular) can be administered on an outpatient basis.
• Monitoring for recurrence: Continue to perform blood tests and radiographic scans on an outpatient basis, with the frequency decreasing over time. In general, patients should be examined every 3 months for the first year, every 6 months for the second and third years, and yearly thereafter.
• Long-term follow-up care: At 5 or longer after the end of therapy, patients are considered to be long-term survivors. Patients should be examined annually at a late-effects clinic and monitored with appropriate studies depending on the type of therapy they received. Visits may include hormonal, psychosocial, and neurologic evaluations, as well as follow-up examinations by the radiotherapist.

In/Out Patient Meds

• Trimethoprim-sulfamethoxazole: Prophylaxis against pneumocystic pneumonia should continue until 6 months after the end of chemotherapy.
• Fluconazole: Systemic fungal prophylaxis is not necessary.
• Clotrimazole: Prophylactic therapy for thrush may be discontinued after chemotherapy is completed.
• Chlorhexidine mouth rinse: Prophylaxis against gingivitis and other mouth infections may be discontinued after chemotherapy is completed.

Transfer

• Although major cancer therapy should take place at a center with pediatric oncologists, the child's referring pediatrician or general practitioner should continue to play an important role in the child's care throughout treatment.
• The referring physician can be critical in performing the first evaluation of an illness, particularly if the child lives far from an oncology center.

Deterrence/Prevention

• No preventive measures are known for childhood cancers.

Complications

• Cardiomyopathy
• • In patients who receive an anthracycline, cardiac function must be monitored to assess for the development of cardiomyopathy.
  • Cardiomyopathy may also from cyclophosphamide use.
• Pulmonary failure
• Metabolic derangements: Ifosfamide use, in particular, can lead to renal electrolyte wasting (Fanconi syndrome).
• Secondary malignant neoplasms
• • Secondary malignant neoplasms may arise as a result of radiotherapy and chemotherapy, particularly with alkylating agents.
  • Etoposide markedly increases the risk for acute myelogenous leukemia, particularly when regimens with frequent dosing schedules are used.
  • Radiation therapy increases the risk of second malignancies, including skin and bone tumors.

Patient Education

• Chemotherapy: Parents and patients (if appropriate) must undergo formal training to learn about the adverse effects of chemotherapy. They must know what is expected to happen as a result of the therapy and are encouraged to ask questions.
• Central venous catheters
• • When patients have central venous catheters that exit the skin (eg, Hickman or Broviac catheters), the parents or the patient must learn to properly care for the line. This care usually involves daily heparin flushes.
  • Patients and parents must understand the limitations on activities because of central venous catheters. For example, swimming is not permitted.
  • Patients with subcutaneous catheters (eg, Mediport catheters) do not need to perform daily care, but they should learn to apply a topical anesthetic (eg, EMLA cream, or lidocaine-prilocaine cream) at least 1 hour before an anticipated needle stick.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Although uncommon, legal issues associated with delayed diagnosis are becoming more important now than before, especially to primary care providers.
• Therefore, RMS must be considered in the differential diagnosis in any patient with symptoms suggestive of cancer or a palpable mass.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Arndt CA, Crist WM. Common musculoskeletal tumors of childhood and adolescence. N Engl J Med. Jul 29 1999;341(5):342-52. [Medline].
• Barr FG. Molecular genetics and pathogenesis of rhabdomyosarcoma. J Pediatr Hematol Oncol. Nov-Dec 1997;19(6):483-91. [Medline].
• Carli M, Colombatti R, Oberlin O, et al. High-dose melphalan with autologous stem-cell rescue in metastatic rhabdomyosarcoma. J Clin Oncol. Sep 1999;17(9):2796-803. [Medline].
• Currier MA, Adams LC, Mahller YY, Cripe TP. Widespread intratumoral virus distribution with fractionated injection enables local control of large human rhabdomyosarcoma xenografts by oncolytic herpes simplex viruses. Cancer Gene Ther. Apr 2005;12(4):407-16. [Medline].
• Flamant F, Rodary C, Rey A, et al. Treatment of non-metastatic rhabdomyosarcomas in childhood and adolescence. Results of the second study of the International Society of Paediatric Oncology: MMT84. Eur J Cancer. Jun 1998;34(7):1050-62. [Medline].
• Gripp KW. Tumor predisposition in Costello syndrome. Am J Med Genet C Semin Med Genet. Aug 15 2005;137(1):72-7. [Medline].
• Mazzoleni S, Bisogno G, Garaventa A, et al. Outcomes and prognostic factors after recurrence in children and adolescents with nonmetastatic rhabdomyosarcoma. Cancer. Jul 1 2005;104(1):183-90. [Medline].
• Merlino G, Helman LJ. Rhabdomyosarcoma--working out the pathways. Oncogene. Sep 20 1999;18(38):5340-8. [Medline].
• Modak S, Guo HF, Humm JL, et al. Radioimmunotargeting of human rhabdomyosarcoma using monoclonal antibody 8H9. Cancer Biother Radiopharm. Oct 2005;20(5):534-46. [Medline].
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Article Last Updated: Oct 4, 2006