Soft Tissue Sarcoma

Background:

• Genetic Risks:

  • Li-Fraumeni syndrome (p53)

  • NF1 (malignant peripheral nerve sheath tumors)

  • Familial Rb

  • Gardeners/FAP (APC)

    • Desmoid tumors

• Most are sporadic tumors

Risk factors:

• Prior radiation is the #1 risk factor (esp within 10-30 years)

• HIV or HHV-8 (Kaposi Sarcoma)

• Chronic Lymphedema (Angiosarcoma)

Most common types:

• Gastrointestinal stromal tumor (GIST)

  • Characterized by c-KIT or PDGFRA mutations

• Liposarcoma

  • Well-differentiated/Dedifferentiated liposarcoma

    • MDM2 and CDK4 are highly sensitive and specific

  • Myxoid round cell liposarcoma

    • Associated with t(12;16) translocation involving DDIT3

• Leiomyosarcoma

• Synovial sarcoma

  • Associated with SYT-SSX

• Undifferentiated pleomorphic sarcoma

• malignant peripheral nerve sheath tumor (MPNST)

Diagnosis:

• Needle or excisional biopsy

• Staging:

  • Require MRI if in extremity or trunk

  • TNM Staging: T is variable based on the tumor location

  • CT chest: Tumors tend to metastasize to lungs

SCARE (higher propensity for lymphatic/LN metastasis):

• Synovial sarcoma

• Clear cell sarcoma

• Angiosarcoma

• Rhabdomyosarcoma

• Epithelioid sarcoma

Treatment:

• Localized disease:

  • Surgery

  • Consider pre-op vs post-op radiation

    • Post-op: larger volume of radiation, less wound healing complication

  • Benefit of chemotherapy is not very clear with soft tissue sarcoma

  • Consider use of adjuvant pembrolizumab in high grade/stage III sarcomas

• Local recurrence:

  • Re-excision +/- radiation is the preferred treatment

  • Systemic therapy is controversial

    • Consider for high-grade, rapidly growing, or multifocal recurrences

• Metastatic disease:

  • Resection for oligometastatic disease (potentially curative) 

  • Systemic Therapy:

    • Doxorubicin

    • AIM: Doxorubicin (Adriamycine), Ifosfamide, Mesna

      • Doubles response rates, but no change in OS

    • AD: Doxorubicin (Adriamycine), Dacarbazine

      • Used in leiomyosarcoma

    • Doxorubicin + Trabectidin

    • Gemicitabine +/- Docetaxel

    • Trabectidin

      • Liposarcoma and leiomyosarcoma

      • Associated with muscle injury

    • Eribulin

      • liposarcoma

    • Paclitaxel

      • Angiosarcoma and kaposi sarcoma

    • Pazopanib

      • Soft tissue sarcoma but not liposarcoma

    • Pembrolizumab (if TMB >10)

    • Palbociclib

      • Well/de-diff liposarcomas

    • Imatinib

      • Dermatofibrosaroma pertuburans 

    • Nabsirolimus

      • Pecoma

    • Tazametostat

      • Epithelioid sarcoma

  
  

Benign but locally aggressive tumors

Synovial giant cell tumor:

• High recurrence rate

• Treatment:

  • Surgery

  • Medication:

    • Paxidartinib (liver toxicity)

    • Vimsultinib (ORR 40%, no serious liver injury)

      
      

Desmoid tumor:

• Associated with FAP/Gardner syndrome

• Treatment:

  • Observation is preferred approach

    • Can be asymptomatic or spontaneously regress

  • Surgery

  • Ablation: Cryo or Radiofrequency ablation (RFA)

  • Nirogasestat 

    • Ovarian toxicity (early menopause)

  • Other TKIs such as sorafenib (off label)

    
    

Kaposi Sarcoma:

• Associated with HIV and HHV8

• Treatment:

  • HAART: if associated with HIV

  • Pomalidomide

    • If failure of HAART therapy

    • HIV negative patients

  • Paclitaxel

  • Doxorubicin

  • Local excision or radiation