Alveolar Soft Part Sarcoma

Alveolar Soft Part Sarcoma (ASPS) – Treatment Overview

Introduction
Alveolar soft part sarcoma (ASPS) is a rare, slow-growing but highly metastatic soft tissue sarcoma. It accounts for less than 1% of all soft tissue sarcomas. ASPS typically arises in the deep soft tissues of the extremities in young adults, but it may also occur in the head and neck (especially the tongue and orbit) in children. Despite its indolent growth, ASPS has a strong tendency to metastasize, especially to the lungs, brain, and bones. Histologically, it is characterized by an ASPSCR1–TFE3 gene fusion caused by a t(X;17)(p11;q25) translocation.

Because ASPS is largely resistant to standard chemotherapy, treatment focuses on surgical resection, radiotherapy for local control, and targeted/immune therapies for advanced disease.

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Treatment Options

1. Surgery (Primary Local Treatment)

• Wide surgical excision with negative margins is the cornerstone for localized ASPS.

• Lymph node dissection is rarely required (low nodal involvement).

• Limb-sparing surgery is prioritized when possible.

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2. Radiotherapy

• Used as adjuvant therapy when surgical margins are positive or resection is incomplete.

• May be considered in inoperable tumors for local control.

• Typical dose: 50–60 Gy in conventional fractions.

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3. Chemotherapy

• Traditional sarcoma regimens (e.g., doxorubicin, ifosfamide) show minimal efficacy in ASPS.

• Not routinely recommended except in rare pediatric protocols.

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4. Targeted Therapy (Mainstay for Advanced/Metastatic Disease)

• Tyrosine kinase inhibitors (anti-angiogenic agents):

  • Sunitinib: 37.5–50 mg orally once daily.

  • Cediranib: 30 mg orally once daily (investigational but showed promising activity).

  • Pazopanib: 800 mg orally once daily.

  • Axitinib: 5 mg orally twice daily.

• These agents inhibit VEGF/VEGFR pathways, which are highly active in ASPS.

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5. Immunotherapy (Checkpoint Inhibitors)

• PD-1/PD-L1 inhibitors have shown activity in advanced ASPS:

  • Pembrolizumab: 200 mg IV every 3 weeks.

  • Nivolumab: 240 mg IV every 2 weeks (± ipilimumab in trials).

• Durable responses have been reported, especially in metastatic disease.

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6. Brain Metastases Management

• Stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT) as indicated.

• Neurosurgical resection for accessible symptomatic lesions.

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Prognosis

• Localized disease (resectable): 5-year survival ~60–70%.

• Metastatic disease: Long-term survival is poor (~20–30%), though responses to targeted and immune therapies are improving outcomes.

• Indolent but progressive nature → long follow-up is essential.