Sarcoma

Definition:

• Malignant tumors of mesenchymal origin, arising from connective tissue, muscle, fat, bone, cartilage, blood vessels, or peripheral nerves.
• Represent <1% of adult malignancies but are clinically heterogeneous with >50 histologic subtypes.

Classification

1. Soft Tissue Sarcomas (STS) – ~80% of adult sarcomas
   • Liposarcoma (fat)
   • Leiomyosarcoma (smooth muscle)
   • Synovial sarcoma
   • Malignant peripheral nerve sheath tumor
   • Angiosarcoma (blood vessels)
2. Bone Sarcomas – ~20%
   • Osteosarcoma
   • Chondrosarcoma
   • Ewing sarcoma (can be soft tissue or bone)

Epidemiology

• Adult incidence: ~13,000 cases/year in the US.
• Peak incidence: 4th–6th decade, varies by subtype.
• Risk factors: prior radiation, genetic syndromes (Li-Fraumeni, NF1), chronic lymphedema, environmental exposures.

Clinical Features

• Often presents as a painless, enlarging mass
• Deep-seated tumors may grow large before detection
• Symptoms depend on location: pain, functional impairment, compression of nearby structures
• Metastasis commonly to lungs, liver, bone

Treatment Overview

1. Surgery (Mainstay)

• Goal: complete resection with negative margins
• Limb-sparing surgery preferred for extremity STS

2. Radiotherapy

• Often adjuvant or neoadjuvant in STS to improve local control

3. Systemic Therapy (Chemotherapy / Targeted Therapy)

• Conventional chemo for advanced/metastatic STS:
  • Doxorubicin ± Ifosfamide
  • Gemcitabine + Docetaxel for leiomyosarcoma
  • High-dose ifosfamide for select subtypes
• Bone sarcoma chemo:
  • Osteosarcoma: MAP (Methotrexate, Adriamycin, Cisplatin)
  • Ewing sarcoma: VDC/IE (Vincristine, Doxorubicin, Cyclophosphamide / Ifosfamide, Etoposide)
• Targeted / novel agents:
  • Pazopanib, trabectedin, eribulin, olaratumab (depending on histology)

Pharmacist Considerations

1. Drug-specific toxicities:
   • Anthracyclines (doxorubicin): cardiotoxicity
   • Ifosfamide/cyclophosphamide: hemorrhagic cystitis (MESNA + hydration), nephrotoxicity
   • Gemcitabine/docetaxel: myelosuppression, neuropathy, edema
2. Supportive care:
   • Antiemetics, hydration, growth factors for neutropenia
   • Monitor organ function (renal, hepatic, cardiac)
3. Route & administration:
   • IV infusion mainstay
   • Dose adjustments for organ dysfunction
4. Long-term follow-up:
   • Monitor for secondary malignancies, cardiomyopathy, fertility, chronic organ toxicity

High-Yield Clinical Pearls

• Surgery is curative for localized disease; chemo mainly for advanced, metastatic, or high-risk subtypes
• Sarcomas are histology-driven → chemotherapy sensitivity varies widely
• Soft tissue sarcomas rarely metastasize early; bone sarcomas often hematogenous spread