Rhabdomyosarcoma

Rhabdomyosarcoma is a malignant tumor with skeletal muscle differentiation and the most common soft tissue sarcoma of childhood, with an incidence of about 4.5 per million children a year. It makes up about 3% of childhood cancers.

Histology and molecular type

• Embryonal (60 to 70%): children under 10, head and neck and genitourinary sites, with botryoid and spindle cell variants, loss of heterozygosity at 11p15, favorable outcome
• Alveolar (20 to 30%): adolescents, extremities and trunk, PAX3-FOXO1 or PAX7-FOXO1 fusion, worse outcome
• Pleomorphic: adults, aggressive

Predisposing conditions: Li-Fraumeni syndrome, neurofibromatosis type 1, Costello syndrome, DICER1 syndrome and Beckwith-Wiedemann syndrome.

Risk groups depend on histology, stage, extent of residual disease and fusion status: low risk has survival of about 90%, intermediate about 65 to 70% and metastatic disease about 20 to 30%.

Spread is local, lymphatic (alveolar, extremity, paratesticular) and hematogenous (lung, bone marrow, bone).

Complications: orbital and parameningeal extension with intracranial spread, urinary obstruction, metastases and late effects of treatment.

• A painless, enlarging mass
• Orbital: proptosis and ptosis
• Parameningeal: nasal obstruction, epistaxis, cranial nerve palsies, headache
• Genitourinary: hematuria, urinary retention, a grape-like vaginal mass, a paratesticular swelling
• Extremity and trunk: firm deep mass
• Red flags: airway obstruction, cranial nerve palsies, bone pain, cytopenias

1. Imaging of the primary: MRI (or contrast CT) of the primary site and regional nodes.
2. Staging: CT chest, PET-CT or bone scan, bone marrow aspirate and biopsy, and CSF cytology in parameningeal disease.
3. Biopsy: incisional or core, with adequate tissue. Histology of small round blue cells with desmin, myogenin and MyoD1 positivity. Test for FOXO1 fusion by FISH or RT-PCR, since it replaces alveolar histology in risk assignment.
4. Nodal evaluation: sentinel lymph node biopsy for extremity and paratesticular disease in adolescents.
5. Baseline tests: blood count, creatinine, liver tests, echocardiogram, audiology, fertility counseling.

Differentials: Ewing sarcoma, neuroblastoma, lymphoma, other small round cell tumors, synovial sarcoma, infantile fibrosarcoma.

Treatment combines chemotherapy, local control and, for most, radiotherapy.

Chemotherapy

• Low risk: vincristine 1.5 mg/m2 IV (maximum 2 mg) weekly, with dactinomycin 0.045 mg/kg IV (maximum 2.5 mg) every 3 weeks, and cyclophosphamide 1.2 g/m2 IV for 4 cycles with mesna, for about 24 weeks.
• Intermediate risk: alternating cycles for about 42 weeks, with vincristine, dactinomycin and cyclophosphamide 1.2 g/m2, alternating with vincristine and irinotecan 50 mg/m2 IV daily for 5 days (with cefixime or other prophylaxis and loperamide for diarrhea). Maintenance of vinorelbine 25 mg/m2 IV weekly with cyclophosphamide 25 mg/m2 orally daily for 6 months in high-risk disease.
• Support: mesna at 60% of the cyclophosphamide dose in divided IV doses, ondansetron 0.15 mg/kg IV (maximum 8 mg), filgrastim 5 micrograms/kg SC daily, trimethoprim-sulfamethoxazole (trimethoprim 150 mg/m2 a day in 2 divided doses on 3 days each week), and monitoring of blood count, creatinine and neurotoxicity.

Local control

• Surgery when complete resection preserves function. Delayed local control after chemotherapy for orbital, bladder and vaginal tumors to preserve organs.
• Radiotherapy from week 12 to 13 (earlier for parameningeal tumors with intracranial extension): 36 Gy for microscopic residual disease, 41.4 Gy for orbital tumors, 50.4 Gy for gross residual disease, with higher doses for alveolar histology.

Relapse: vincristine, irinotecan and temozolomide 100 mg/m2 orally for 5 days, or ifosfamide and doxorubicin.

Adults: similar combination chemotherapy with more intensive doxorubicin-based regimens.

Follow-up: imaging every 3 months for 2 years, then every 6 months to 5 years. Counsel on fertility preservation, cardiac and renal late effects, and secondary tumors.