Alveolar rhabdomyosarcoma (Soft Tissue Sarcoma)

Alveolar Rhabdomyosarcoma (ARMS) – Treatment Overview

Introduction
Alveolar rhabdomyosarcoma (ARMS) is a highly aggressive soft tissue sarcoma that arises from primitive mesenchymal cells with skeletal muscle differentiation. It accounts for about 20–30% of childhood rhabdomyosarcomas and is most common in adolescents and young adults. ARMS typically presents in the extremities, trunk, or perineal regions, often with metastatic spread at diagnosis. It is associated with specific chromosomal translocations (e.g., PAX3-FOXO1 and PAX7-FOXO1 fusions), which contribute to its aggressive biology and poor prognosis compared to embryonal rhabdomyosarcoma.

Treatment requires a multimodal approach including chemotherapy, surgery, and radiotherapy, with therapy tailored to risk stratification.

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Treatment Options and Doses

1. Chemotherapy (Backbone of Treatment)

• VAC regimen (Vincristine, Actinomycin D, Cyclophosphamide):

  • Vincristine: 1.5 mg/m² IV weekly (max 2 mg).

  • Actinomycin D (Dactinomycin): 0.045 mg/kg IV every 3 weeks.

  • Cyclophosphamide: 1.2 g/m² IV every 3 weeks.

• Duration: Typically 6–12 months, depending on risk category.

• High-risk or metastatic disease: Intensified regimens may include ifosfamide, etoposide, or doxorubicin.

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2. Local Control (Surgery and/or Radiotherapy)

• Surgery:

  • Aim for complete resection with negative margins where possible.

  • Limb-sparing approaches are preferred; radical surgery may be needed in advanced cases.

• Radiotherapy:

  • Indicated for unresectable tumors, positive margins, or residual disease.

  • Dose: 45–50.4 Gy (localized disease); up to 55.8 Gy for gross residual disease.

  • May be combined with chemotherapy for synergistic effect.

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3. Targeted and Novel Therapies (Investigational / Select Cases)

• IGF-1R inhibitors (e.g., ganitumab) under clinical study.

• Multikinase inhibitors (pazopanib, regorafenib) used in relapsed/refractory cases.

• Immune therapies: Ongoing trials with checkpoint inhibitors and CAR-T cell approaches.

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4. Supportive Care

• Growth factor support (G-CSF): To reduce neutropenia risk during chemotherapy.

• Fertility preservation counseling (especially important in adolescents/young adults).

• Rehabilitation and psychosocial support.

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Prognosis

• Localized disease (without metastasis): 5-year survival ~65–70%.

• Metastatic disease at diagnosis: 5-year survival ~20–30%.

• Prognosis is worse with PAX3-FOXO1 fusion compared to PAX7-FOXO1.