Osteosarcomas Flashcards by Monica Leslie

What is the typical signalment for Osteosarcoma patient?

Dogs/Cats, Breed, Sex, Age

DOGS >> Cats

LARGE to GIANT Breeds (esp. Great Dane, ROTTWEILER, Greyhound, Irish Wolfhound)

NEUTERED MALES

Age: 1-2 yrs and 7-9 yrs (Bimodal Distribution)

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Between the axial and appendicular skeleton where is the predilection site for Osteosarcoma? What is the exception to this rule?

80% OSA is appendicular

20% OSA is axial

Small Dog OSA (<15kg) = Predilection for Axial Skeleton (59%)

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What are some etiologies of OSA in dogs?

Hormonal (intact males)

Genetic (breeds)

Repetitive Microtrauma - late closing bone at physis (initiator)

Molecular Factors - overexpression of proto-oncogenes, MET, TRK (Tropomyosin-related kinase), HER-2

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How does the overexpression of proto-oncogenes, MET, tropomyosin-related kinase and HER-2 play a role in development of OSA?

They all encode TK receptors and control the growth/proliferation of cells.

Excessive Insulin-like Growth Factor

Excessive signaling through mammlian target of rapamycin (mTOR) pathway (which regulates the cell cycle progression/growth)

Presence of Telomerase (allows cells to replicate infinitely)

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What is typically the presenting complaint for OSA?

LAMENESS & localized swelling

Lameness = d/t periosteal inflammation, microfractures, pathological fx

Localized Swelling = extracompartmental extension of the tissue into the adjacent soft tissue

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What are some possible differentials for OSA?

Chondrosarcoma

Fibrosarcoma, Hemangiosarcoma, Histiocytic Sarcoma, Extra Medullaty Plasmacytoma, Metastatic Lesions (Myeloma, LSA), Atypical Bone Cysts

Valley Fever (Coccidioides immitis), Blastomyces dermatitidis

-fungal dogs usually systemically ill

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Where on the body is OSA most likely to be found?

**AWAY FROM THE ELBOW, TOWARDS THE KNEE**

Forelimbs 2x more likely than Hindlimbs

Distal Radius = most common site (23.1%)

Proximal Humerus = 2nd most common (18.5%)

DEVELOPMENT IN METAPHYSEAL REGION OF BONE

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What are the 3 basic types of OSA and which is the most common?

1) ENDOSTEAL (MOST COMMON)
2) Periosteal
3) Parosteal

2/3 rare = rarely invade endosteum/medullary cavity

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What are some diagnostic/staging techniques you would use in OSA?

1) CBC/CHEM - **look for increased ALP** (worse prognosis)
2) Locoregional LN Assessment **DON’T NEED TO DO - exception**
3) Thoracic Met Check/CT - 90% have micrometastasis at dx - <15% are clinically detectable
4) Localized Radiography - 2 view of affected limb
5) Nuclear Scintigraphy (Technetium) vs. Full Body Radiography - 7-8% bone to bone mets
6) FNA/Cytology - U/S Guided or Rad Assisted **PREFERRED OVER BIOPSY** **Dx ACCURACY = 85%** -needle must go through defect in cortex and into medullary cavity
7) Bone Biopsy - Jam Shedi or Michele Trephine

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Describe the benefits of Locoregional LN Assessment in OSA?

THERE ISN’T MUCH - DON’T NEED TO DO LN ASSESSMENT IN OSA!!

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What is the BEST/MOST PREFERRED diagnostic technique in OSA? Describe the technique.

U/S Guided or Rad Assisted FNA/Cytology

**needle needs to go through the defect in the cortex and into the medullary cavity**

If you plan to do a limb sparing surgery DON’T DO A BIOPSY

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What are the 2 techniques for bone biopsy & describe each?

Jam Shedi - small lumen, sharp needle

get 3 uni-cortical samples from periphery and center of lesion
82% diagnostic accuracy

Michele Trephine - much more aggressive - larger core samples

94% diagnostic accuracy
higher risk of pathologic fx b/c much larger defect from biopsy

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What is the radiographic appearance of OSA?

**DOES NOT CROSS JOINTS**

**CORTICAL LYSIS**

**PERIOSTEAL PROLIFERATION WITH EXTENSION INTO SOFT TISSUE**

**LACK OF DISTINCT BORDER B/W NORMAL AND ABNORMAL**

Codman’s Triangle = periosteal lifting caused by subperiosteal hemorrhage

Loss of find trabecular pattern in metaphyseal bone

Pathologic fracture with metaphyseal collapse

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What is the gold standard for local management of OSA?

LIMB AMPUTATION

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What are the techniques called for the surgical amputation of thoracic limb and pelvic limb?

Thoracic Limb Involvement: FOREQUARTER TECHNIQUE

-remove limb and scapula

Pelvic Limb: COXOFEMORAL DISARTICULATION

-but if there is a proximal femoral lesion –> need more aggressive surgery: EN BLOC ACETABULECTOMY or SUBTOTAL HEMIPELVECTOMY for adequate tumor control

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What are the indications for limbs salvage techniques?

Severe Osteoarthritis

Neurologic Disease

Morbid Obesity

Reluctance of Owners (most common reason)

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What are some contraindications for a limb salvage procedure?

Large lesion - >50% of diaphysis involved

Extensive soft tissue involvement

Pathologic Fracture (cancer cells spill out)

Poorly compliant owner or patient

Advanced Disease

**Inappropriate Location of Tumor**

What is the most preferred site for a limb salvage procedure?

Distal Radius

What are the limb salvage surgical procedures done for a distal ulna site of OSA?

Ulnectomy with excision of styloid process

ulna is not really a weight bearing bone
can have altered biomechanics with proximal ostectomies - annular ligament reinforcement is lost

What limb salvage surgical procedues can be considered for a scapula site? digit or metacarpus/tarsus site?

Scapula: PARTIAL SCAPULECTOMY - can preserve limb function

Digit/Metacarpus/Metatarsus - amputation of just that area

What limb salvage surgical procedures can be considered for a distal radius site?

Radius transected 3-5cm proximal to tumor with sagittal saw (CT best for margin assessment, radiographs OVERESTIMATE)

Affected radial segment removed by opening joint capsule and incising just proximal to carpal bones

Soft tissue dissected to level of pseudocapsule - ensure you include any biopsy tracts

Reconstruction wth steel endoprosthesis attached to pancarpal arthrodesis plate –> wrist joint will be fused

What are some complications with limb salvage surgeries? What is the frequency of these complications?

Complications in >50% of cases

Implant failure in 40% of cases

Local tumor recurrence (10-28%) –> <10% if use locally released chemotherapeutic agents (biodegradable implants) & appropriate case selection

Infection >50% of cases

**Good to excellent function in 80% of dogs despite these complications**

T/F Infection in a limb salvage surgery will result in a decreased survival time. Why or Why Not?

False. Infection results in an INCREASED MST

probably d/t activation of immune effector cells and response to cytokines (IL-1, TNF)

Why is Stereotactic Radiosurgery (SRS) better than Conventional Radiation Therapy?

Entire dose is delivered in one treatment.

Use multiple, noncoplanar beams of radiation that are stereotactically focused on the target.

This minimizes damage to healthy surrounding tissues.

Briefly describe the steps of SRS.

1. Mount docking station (bite plate) for the fiducial array 2. CT affected limb and fiducial array. 3. CT images transfered to dosimetry planning computer at UF KmcKnight Brain Institute where 3D image of tumor is created and tx plan is generated 4. Isocenters of various diameters are designated on the CT images to build a tx volume of radiation that conforms to the shape of the tumor. Treatment plans are designed to ensure that the entire contrast enhanced target are included within the 50% isodense shell. 5. Patient is transported to linear accelerator suite and positioned 6. Infrared censors detect fiducial array - computer linked with Linac and CT images allow for prescision dleivery of radiation using numerous treatment arcs (10-26)

What is the outcome data for using SRS? Complications?

No survival advantage with SRS vs. limb amputation and chemotherapy (but you get to keep the limb) Complications = radiation effect on skin, **fracture of radiated bone** (36%)

What is the most preffered site of OSA for the use of SRS?

**Proximal Humerus** - d/t low post-op fx rate

When is adjunct Chemotherapy recommended in OSA?

In ALL cases of Canine OSA if only local control is done (w/o systemic control (chemo)) dog will succumb to metastasis is 6 months

What are the chemotherapeutic options for OSA? Which is the best?

Cisplatin Carboplatin Doxorubicin **ALL platinum containing protocols results in similar survival times** (choose most well-tolerated, affordable) Alternating Doxorubivin and Carboplatin did not results in increases MST

Describe the Carboplatin Protocol for OSA? When should the protocol be started?

300mg/m2 IV q 3 weeks - 4 treatments Monitor CBC and Renal Function **\*\*Survival Times NOT different when chemo started pre-op (like humans), intra-op or up to 21 days post-op\*\***

What are some **palliative** therapeutic options for OSA?

Amino-bisphosphonates RT Analgesia Metastasectomy

What are amino-bisphosphonates? How do amino-bisphosphonates work?

Synthetic analogs of inorganic pyrophosphate Specifically absorb to sites of active bone turnover and **inhibit osteoclastic bone resorption** & **reduce local release of factors that stimulate tumor growth** Several anti-neoplastic effects: inhibit cancer cell proliferation, induce apoptosis, inhibit angiogenesis, inhibit matrix metalloprotenase, have effects on cytokine and growth factors, immunomodulatory

What are some examples of amino-bisphosphonates?

**Zoledronate** (IV q month, expensive, renal toxicity, osteonecrosis of joints in ppl) **Pamidronate** (IV q month, renal toxicity, osteonecrosis of joints) **\*\*both demonstrated pain palliation in 30-50% of dogs\*\*** Oral formulations: not recommended - low bioavailability, GI complications

What is the protocol for palliative RT? What is the response like?

8Gy on 2 consecutive days followed by addition Gy monthly or as req. Reduces local inflammation, reduces pain, slows progression of metastatic lesions, improves QOL 50-92% response rates reported, duration of response only 73-130 days

What are the indication for pulmonary metastatectomy?

Development \>300 days after initial dx \<3 radiographically evident metastatic lesions No doubling in size of lesions or development of new lesions in a 4 week period Palliative relief for hypertrophix ostepathy \*nearly 3x MST than chemo

Aratona Canine OSA Vaccine. Describe what it is, goal, prelim data

Accenuated bacterial (Listeria monocytogenes) vx that is genetically modified to express a certain tumor protein (HER-2/nev) found to be expressed in OSA cells. Goal is to stimulate immune system to recognize primary and metastatic cancer cells and eliminate them MST 956 days vs. 423

Survival Times: Palliative? Surgery (or curative intent SRS) alone? Surgery and Chemo?

Palliative: Analgesia: **1-3 months** RT: **4**-10 months Sx or Curative Intent SRS Alone: **4-6 months** Sx (or SRS) & Chemo: **8-12 months** **\*\*3, 6, 12 RULE\*\***

What are some negative prognostic indicators?

Dogs \>40kg Dogs \<7 or \>10 Proximal Humerus location Larger tumor volume Higher Histiologic Grade **ALP** --\> pre-op **ALP \>110 u/L (HALF THE MST)** pre-op increase ALP that doesn't return to reference 40 days post-op \*\***Every 100u/L increase in ALP increases risk of tumor related death by 25%**

Where is the most common area of both affected in Feline OSA?

**Diaphysis** \>\> Metaphysis **PELVIC LIMB** \>\> Thoracic Limb Distal Femur, Proximal Tibia, Proximal Humerus

How does the aggressiveness of OSA in cats compare to that of dogs? What is the tx plan?

**LESS AGGRESSIVE** in cats than dogs Slower growth, metastatis is less common Amputation alone without chemo may be curative in cats with appendicular OSA (MST = 2-4 years)