CAL: Feline injection site sarcomas

Give an example of an adjuvant

AI(OH)3 id a common vaccine adjuvant

What is the aetiology of injection site sarcomas

injection→ inflammatory reaction

• Transition zones from inflammation to neoplasia

• Microscopic foci or sarcoma located in areas of granulomatous inflammation

• Other tumours resulting from chronic inflammation

  • feline intraocular sarcoma, post-trauma or chronic uveitis

  • Bone tumours in areas of previous implants

describe the paracrine production of growth factors

• Chronic inflammation can lead to cell mutation

• Tumour microenvironment is rich in fibroblast like cells and inflammatory cells

  • cytokines and growth factor release

• Tumour infiltrating lymphocytes can produce platelet derived growth factors (PDGF)

• ISS cells have growth factor receptors

What is the typical history and clinical signs for injection site sarcomas

• Present with a mass in the area of vaccination or other SQ injection

  • Generally non painful

  • Adhered to underlying tissue

what do injection site sarcomas look like

What is the most common type of injection site sarcoma

fibrosarcoma

Highly locally invasive and v infiltrative

Can be cystic

How are injection site sarcomas diagnosed

• Physical exam and history

  • Location

  • Injection site

• Cytology

• Histopathology

What are the pros and cons of cytology, incisional and excisional biopsy

When do you consider an incisional biopsy

• It increases in size after 1 month post vaccine

• >2cm diameter

• mass persists >3 months

How do you stage injection site sarcoma

• Thoracic radiographs

• CT scan

  • Necessary to define extent of disease, and ca check for metastasis at the same time

What is the typical biological behaviour of injection site sarcomas

• 10-25% metastatic rate to lungs

• Potentially curable in >75% with aggressive therapy

• Local disease is the main cause of death

  • Recurrence

  • Unresectable

What are some prognostic factors of injection site sarcomas

• Marginal resection

  • conservative surgery: disease free interval 2 months

  • Aggressive surgery: DFI 11-14 months

    • >16m with complete resection

• More than 1 surgery

• if surgery is performed by a non referral surgeon

  • Recurs in 2 months vs 9 months

• Recurrence is possible after surgery despite clean margins

Who should perform injection site sarcoma surgery

• outcome is better than the first surgery is performed by a referral surgeon

• why is a second surgery less likely to be successful

Why is a second surgery less likely to be successful

• Original anatomy has been altered

• the surgical site will be altered

• seeding through tissue planes

  • Harder to assess by imaging

  • harder to assess at surgery

• Previously clean tissue considered contaminated

  • biopsy tracts, drains= contaminated

• At time of first surgery there has been less time to metastasize

What is surgery for treating injection site sarcoma

• Poor local control with 2-3cm

  • Histopathologically clean margins <50%

  • 35% disease free at 1 year, 9% at 2 years

• Amputation if possible

  • ± dorsal spinous processes, dorsal scapula

• Wide and deep surgical margins (3cm minimum and fascial plane)

  • 3 cm: 28-45% recurrence

• 4-5cm and 2 fascial planes

  • select cases but:

  • Histopathologically clean in 97%

  • only 14% recurred

• Anatomical resection of muscle compartment containing the tumour

  • cases also received chemo

  • 14% recurrence

What do you do after surgery

• Adjuvant radiation therapy after section

  • wait 10-14 days post op, as DFI/ST decreases the longer the wait

  • Surgery + RT: 40% cured

• RT protocols

  • Hyperfractionated (definitive, small doses more frequently)

    • ST 3.5 years, disease free period 3 years

  • Hypofractionated (palliative, large doses weekly)

    • ST 2 years, disease free period 10 months

• Pre operative RT

  • Very select cases as increased risk of wound dehiscence and RT more effective against microscopic disease

When do you consider chemotherapy for injection site sarcomas

Consider cytotoxic chemo if high grade, aggressive behaviour or metastatic disease

What protocol do you use for chemotherapy for injection site sarcomas

• AC protocol (3 week cycle)

  • Doxorubicin 1mg/kg IV

    • 40-50% response rate though short lived

  • Cyclophosphamide 200-250 mg/m2 PO

• Carboplatin

  • 250 mg/m2 IV q 3 weeks

  • 4-6 cycles

What are some types of targeted therapy

• Tyrosine kinase inhibitors

• metronomic chemotherapy

• COX inhibitors

• Metronomic chemotherapy

What do injection site sarcomas express

PDGFr

What are some treatments for ISS that are up and coming

• Electrochemotherapy

  • Intratumoural chemo (bleomycin) + electropulsation

    • Tumour recurred in 12-19 months vs 4 months

    • When recurred, some responded when treated again

• Immunotherapy (IL-2)

  • As vaccine or intratumoural

How can injection site sarcomas be reduced

• use common sense: dont over vaccinate

• avoid multiple vaccines in the same site and at the same time

• use single dose vials and non-adjuvant vaccines

• administer SQ in extremities as distal as possible or at base of tail

Where do you put rabies, FeLV, FVRCP ±C

Rabies- distal right hindlimb

FeLV- distal left hindlimb

FVRCP±C- distal right forelimb