3. Tumors of the Appendicular and Axial Skeleton Flashcards
Most common primary bone tumor in dogs and cats?
OSA 85% of bone tumors in dogs
What is most common primary bone tumor in dogs and cats?
OSA
Are dogs or cats more commonly affected with OSA?
Dogs
85% of bone tumors in dogs are OSA, are the majority axial or appendicular?
- Appendicular 80% (main)
- Axial 20%
Describe the size predlection for OSA?
- Large to Giant breeds (> 40 kg)
- Size and height are PROGNOSTIC
What’s interesting about the sex predilection for OSA?
• Male predisposition BUT neutering status more important
– 2X increased risk for gonadectomized dogs (Esp. Rotties)
– 1 in 4 EARLY (< 1Y) gonadectomized (Rotties) have lifetime risk of OSA (BREEDERS QUOTE, know the paper written on it)
Describe the age predilection for OSA? Which is pretty indicative of OSA possibility
Bimodal distribution = 1-2y & 7-9y (more common)
The younger one (1-2 years) is very telling because if a young dog presents for lameness you need to be performing rads ASAP
Do small dogs get OSA and if so describe the details of their OSA presentation?
• Small dog OSA (< 15 kg)
– Mainly found in axial skeleton (59%) instead of appendicular
Who are our lightning breeds known for OSA?
- Rottweiler
- Great Dane
- Irish Wolfhound
- Greyhound
Can ya tell these guys are GIANTTTTTT in size which is what OSA likessss
What are some other proposed etiologies for OSA (4) (4abcd)?
- Hormonal – Protective effect of being intact
- Genetic
– Rotties, greyhounds, Danes, Scottish Deerhounds, S. Bernard’s & Irish wolfhounds
• Repetitive Micro-trauma (chronic inflamm.)of late closing long bone at physis = “Initiator”
• Molecular Factors
– Overexpression of proto-oncogenes MET, tropomyosin-related kinase (Trk) & HER-2
• All encode TK receptors & control growth/proliferation of cells
– Aberrant/excessive insulin-like GF (IFG-1)
– Aberrant signaling through Mammalian target of rapamycin (mTOR) pathway
• Regulates cell cycle progression/growth
– Presence of Telomerase – Endows cells w/ infinite replicative capacity
What does OSA often present as int terms of CS?
• Lameness & localized limb swelling
– Lameness = Caused by periosteal inflammation, microfractures and occasionally pathologic fracture
– Swelling = Extracompartmental extension of tumor into adjacent soft tissue
What is the top ddx you need to diferentiate OSA from?
- OSA
- OSA
- OSA
4. Chondrosarcoma <10 %
Are dogs or cats are more commonly affected?
Dogs affected more commonly than cats
Describe the breed and predilection of animals with OSA?
• At risk breeds – Large to Giant breeds (> 40 kg) – SIZE & HEIGHT prognostic • Male predisposition BUT neutering status more important – 2X increased risk for gonadectomized dogs – 1 in 4 EARLY (< 1Y) gonadectomized (Rotties) have lifetime risk of OSA • Bimodal distribution = 1-2y & 7-9y (more common) • Small dog OSA (< 15 kg) – Predilection for axial skeleton (59%) Genetic– Rotties, greyhounds, Danes, Scottish Deerhounds, S. Bernard’s & Irish wolfhounds • Hormonal – Protective effect of being intact
What are some of the proposed etiologies of OSA?
• Hormonal – Protective effect of being intact • Genetic – Rotties, greyhounds, Danes, Scottish Deerhounds, S. Bernard’s & Irish wolfhounds • Repetitive Micro-trauma of late closing long bone at physis = “Initiator” • Molecular Factors – Overexpression of proto-oncogenes MET, tropomyosin-related kinase (Trk) & HER-2 • All encode TK receptors & control growth/proliferation of cells – Aberrant/excessive insulin-like GF (IFG-1) – Aberrant signaling through Mammalian target of rapamycin (mTOR) pathway • Regulates cell cycle progression/growth – Presence of Telomerase – Endows cells w/ infinite replicative capacity
What is the common presenting complaint with OSA?
• Lameness & localized limb swelling – Lameness = Caused by periosteal inflammation, microfractures & occasionally pathologic fracture – Swelling = Extra compartmental extension of tumor into adjacent soft tissue
What is the top tumor ddx for OSA?
Chondrosarcoma <10% primary tumors
WHat is the top infectious fungal OSA ddx?
• “Valley Fever” - Coccidioides immitis – San Joaquin River Valley (CA) – SW U.S. • Blastomyces dermatitidis • **Fungal dogs usually systemically ill**
**Review of bone tumor database at the Animal Cancer Center at CSU revealed that ______ accounted for 98% of 1,273 appendicular primary bone tumors diagnosed in dogs**
OSA
What is the difference between dogs with OSA or Chondrosarcoma and Infectious fungal diseases causing lameness? What are our top 2 fungal diseases?
**Fungal dogs usually systemically ill**
• “Valley Fever” - Coccidioides immitis
– San Joaquin River Valley (CA)
– SW U.S.
• Blastomyces dermatitidis
75 - 80% of OSA occurs in ________ skeleton. _____limbs affected 2x > than _____imbs
appendicular. Forelimbs affected 2x > than pelvic limbs
What are the #1 and #2 site for OSA? What is the saying?
– Distal radius = Most common site (23.1%)
– Proximal humerus = 2nd most common site (18.5%)
“Away from the elbow towards the knee”
Where does the OSA form in the bone normally?
**Favor development in the metaphyseal region of bone** (endosteal in origin)
What are the 3 basic types of OSA? What is the most common?
– Endosteal (most common)
– Periosteal
– Parosteal
RARE = originate from the periosteal surface & rarely involve the endosteum/ medullary canal
Describe the OSA diagnostic algorithm?
• CBC/CHEM
– Elevated ALP = BAD!******** multiple studies confirmed
• Locoregional LN assessment
– 5% incidence (LOW) doesn’t need local regional aspirate
• Thoracic metastasis (MANDATORY) check vs. CT
– 90% micrometastasis at dx BUT < 15% of dogs have clinically detectable metastasis at the time of initial diagnosis
• Localized imaging – Two-view radiographs of affected limb
• Nuclear scintigraphy ( technetium) vs. Full body radiography
– Bone to bone mets in 7-8%
What are you looking for with radiographic appearance with OSA? What do you not do?
• Patterns ranging from lytic to blastic
– Usually a mixture of both
- Loss of cortical bone
- Periosteal proliferation
- Palisading cortical bone
(sunburst effect)
- Codman’s triangle = Periosteal lifting caused by subperiosteal hemorrhage
- Loss of the fine trabecular pattern in metaphyseal bone
- Pathologic fracture w/ metaphyseal collapse
• Does NOT cross joints (synovial cell sarcoma does)
What am I looking at?
Cortical lysis
What am I looking at?
Periosteal proliferation w/ Extension into soft tissue
Cartilage provides a barrier due to _______ inhibitors which may inhibit _____ ____ _____ or neoangiogenesis
collagenase; tumor cell invasion
What sample procurement is preferred with OSA?
- FNA/CYTOLOGY **Preferred over biopsy** dx accuracy of 85%+** (Should be image guided) U/S Guided vs. Rad assisted, Need to get needle through defect in cortex & into medullary cavity
- BONE BIOPSY (If plan to do limb sparing sx DON’T DO SX BIOPSY!) Incisional biopsy
Which bone biopsy is more at risk?
- Michele trephine
- Larger core samples obtained
- Diagnostic accuracy rate = 94%
-Much higher risk of pathologic fracture d/t large defects from bx
What is the other bone biopsy method besides Michele trephine?
• Jam Shedi (do this first)
– Multiple (3), uni-cortical bx samples should be obtained from the center and periphery of the lesion
– Correct diagnosis is made for 82% (even higher) of samples using this technique
What is the gold standard for treatment for local management of primary bone tumors? What are the 2 types and the indications? Which needs more aggressive approach?
• Limb amputation = Gold standard for local management of primary bone tumors bc 90% chance for microscopic metastesis
• Thoracic limb involvement = Forequarter technique (include scapula) rec.
– For tumor control and cosmetic reasons (Esp. w/ proximal humeral lesion)
• Pelvic limb = Coxofemoral disarticulation technique recommended
_– Proximal femoral lesion = NEED more aggressive sx (amputation doesn’t serve them well!!!!!)_ so do either En-bloc acetabulectomy or subtotal hemipelvectomy to achieve adequate tumor control
Describe amputation results?
• Procedure well tolerated w/ low complication rate & rapid acclimation (typically w/in 4 weeks)
– Adjustment time frame shown to be influenced by a positive reaction from the family & is not associated with B.W., age or location of amputation (front vs. back limb) (POSITIVE OUTLOOK AFFECTS THE ANIMAL!!!)
• Behavioral changes occur in 32% dogs
– Increased fear, aggression, anxiety & reduced dominance
Describe what thoracic limb amputees might go through?
Thoracic limb amputees = More difficulty in keeping balance in the early PO period as the ability to break decreases resulting in loss of coordination bc 60% of their weight on forelimb
Describe what pelvic limb amputees might go through?
More difficulty in gaining speed
What are the indications for limb salvage? What is the most common reason of the 4?
- Severe osteoarthritis
- Neurologic disease
- Morbid obesity
- Reluctance of owners to proceed w/ amputation is the most common reason for performing limb-sparing procedures
What are the 6 contraindications for limb salvage? What is the bolded one? What is the classic limb spare site?
DISTAL RADIUS classic limb spare site
- Large Lesion - >50% of diaphysis involved
- Extensive soft-tissue involvement
- Pathologic fracture (tumor erroded through cortex spill cancer cells everywhere)
• Poorly compliant owner or patient
• Advanced disease
• Inappropriate location of tumor
Where is the preferred site for surgical limb salvage?
Distal radius
Where is the most common site of tumor occurance?
Distal radius
Which site does not require implants for reconstruction or post opp function?
Distal ulna (ulnectomy)
or Scapula (partial scapulectomy)
If it’s at this site it means amputation?
• Digit or metacarpus/tarsus
A Partial ______ can preserve limb function & may be considered a viable alternative to limb amputation
scapulectomy
Describe the technique for subtotal scapulectomy?
– At least 2 cm margins
– Preservation of the glenoid cavity/retention of the scapulo-humeral joint
• Limb function was found to be good in all cases PO
ISOLATED ULNAR LESIONS can be treated with ______ including excision of ____ ____ (also state what location is preffered?) bc ulna isnt really necessary weight baring bone
ulnectomy; styloid process
– Distal location is preferred for treatment
Generally rapid return to function w/ minimal complications
With ulnectomy’s we have altered biomechanics w/ proximal ostectomies and you need this?
Need annular ligament reinforcement
What limb salvage approach should you take for the distal radius?
• Dorsolateral approach to the tumor/radius being careful to account for and excise any biopsy tract
• Soft-tissue dissection carried to level of the pseudocapsule
What limb salvage approach should you take for transecting the distal radius, how do you best assess margins pre-op?
• Radius transected 3-5cm proximal to tumor using sagittal saw
– CT is best for margin assessment - Radiographs tend to overestimate extent
– Ulna can be removed completely or left in place
– Extensor tendons running through tumor transected 3-5cm from tumor as well
• Affected radial segment removed by opening opening joint capsule and incising just proximal to carpal bones
How is the reconstruction performed with limb salvage techniques to the distal radius?
• Reconstruction performed using a commercially available surgical steel endoprosthesis attached to a modified pancarpal arthrodesis plate
What are some of the complications and unique study information post limb salvage procedures?
- Complication rate for limb-sparing surgery often exceeds 50%
- Implant failure - ~40% of cases – Requires revision or amputation
- Infection occurs in more than 50% of cases & approximately 2/3rd’s of infectionsare diagnosed > 6 months after surgery
- What’s weird: dogs that get infected after limb spare have a significant longer survival than dogs who weren’t infected (685 days versus 289 days) stimulating the immune system!!
- **Good to excellent function in 80% of dogs despite these results**
What areas are ammenable by surgery?
- Scapula
- Ulna
- Digits
- distal radius
If surgery isn’t an option meaning the OSA is not in the Scapula Ulna Digits Distal radius, is there still limb salvage available?
• Conventional radiation therapy: Performed using a limited number of static fields
– Relies on the use of fractionation
_______ ________:
Entire radiation dose is delivered in a single treatment through
the use of multiple, noncoplanar beams of radiation that are
stereotactically focused on the target
Stereotactic Radiosurgery
How does stereotactic radiosurgery minimize damage, what does it rely on?
– Minimizes damage to healthy surrounding tissues by relying on extreme accuracy of radiation delivery to a tumor & a steep dose gradient between the tumor and surrounding healthy tissues
Nothing on earth can live after receiving ___gray of radiation
60
What is the survival advantage of SRS to conventional treatment like amputation and chemo?
• No survival advantage compared to conventional treatment (i.e. amputation & chemotherapy)
– But you get to keep the limb
What are some of the complications to SRS?
– Expected RT effects on skin (mild)
– **Fracture of radiated bone (36%)**
• You are essentially killing the tumor & surrounding bone
What is the best site for SRS?
• Proximal humerus (2nd most most common site) appears to be the best site for SRS based on low PO fracture rate because lots of surrounding soft tissue to support that bone after receiving radiation
What happens to the dog if local control is the only therapy provided to the dog? What is the best treatment for increased MST? What is recommended in all cases for OSA?
- If local control is the only therapy provided the dog will not die of local disease but will succumb from metastasis w/in 6 months
- – Amputation alone results in significantly better survival time than palliative management w/ analgesic drugs or radiation therapy
- **Adjunctive chemotherapy is recommended in all cases of canine OSA**
What is the adjunctive treatment of choice for OSA?
**Carboplatin** Monitor CBC & renal function
**survival times are not significantly different when chemotherapy is started preoperatively
(like in humans), intraoperatively, or up to 21 days PO in dogs**
(not 2 drugs together it didnt work better) what is metrogmonic therapy after (No)
- Alternating carboplatin & doxorubicin – No difference in survival when compared to single agent protocols
- ALL PLATINUM-CONTAINING PROTOCOLS RESULT IN SIMILAR SURVIVAL TIMES
– Chose the one that is the safest, most well tolerated & economically feasible
Describe how OSA Palliative Therapeutic Options -Bisphosphonates work?
- Synthetic analogs of inorganic pyrophosphate
- Specifically absorb to sites of active bone turnover
– Inhibit osteoclastic bone resorption
– Reduce the local release of factors that stimulate tumor growth in vitro
- Exert their effect on osteoclasts via inhibition of the mevalonate pathways which results in disruption of intracellular signaling & induction of apoptosis
- Have several in vitro anti-neoplastic effects:
– Inhibit cancer cell proliferation
– Induce apoptosis
– Inhibit angiogenesis
– Inhibit matrix metalloproteinase
– Have effects on cytokine & growth factors
– Immunomodulatory
Describe aminobiphosphates whats their big issue
- Low bioavailability
- Pamidronate
– Given IV over 2 hours q 3-4weeks
– Dose is 1 mg/kg
– Potential for renal toxicity give crystalloids
– Osteonecrosis of the jaw can happen
- Demonstrated pain palliation in 30-50% of treated dogs
- Not recommended for malignant bone pain or hypercalcemia
Duration of efficacy short lived
OSA – Palliative Therapeutic Options RT? Radiation (not curative)
- Dosing algorithm (usually) = 8 Gy on 2 consecutive days, followed by additional doses of 8 Gy either on a monthly basis or as required
- Reduces local inflammation, minimizes pain, slows progression of metastatic lesions & improves QOL
Whar can you always for for OSA patients that the owners cant afford surgery?
- Remember there is always SOMETHING you can do! (ANALGESIA PAIN CONTROL)
- Non-steroidal anti-inflammatory drugs (NSAIDs), opioid medications, NMDA antagonists (amantadine) & anticonvulsants (gabapentin)
- Complementary therapies including acupuncture, laser therapy, hydrotherapy & massage should be considered
- Don’t forget emotional
Must know these numbers
• Palliative
– Analgesia MST= __ - ___ months*
– Radiation therapy MST = ___ - ___ months
– Bisphosphonates – Limited data on survival
• Palliative
– Analgesia MST= 1 - 3 months*
– RT MST = 4 - 10 months
– Bisphosphonates – Limited data on survival
Must know these numbers
• Surgery (curative intent SRS/SRT) alone MST = __- __ months*
- Chemotherapy alone – Limited data (Not recommended)
- Surgery (or SRS) + Chemotherapy MST = ___ - ___ months*
- Surgery (curative intent SRS/SRT) alone MST = 4 - 6 months*
- Surgery (or SRS) + Chemotherapy MST = 8 - 12 months*
Prognostic considerations of OSA?
- Body weight: dogs < 40 kg have significantly longer DFI & MST
- Age: Dogs < 7 years & > 10 years
- Tumor site: Proximal humerus OSA has significantly shorter DFI and MST due to larger tumor volume before diagnosis
- Tumor volume: large tumors have a poor prognosis
- Histologic grade– Grade I OSA (4%), grade II (21%) and grade III (75%)
Preoperative total serum ALP > 110 U/L:
– median DFI 170 days v 366 days
– MST 177 days v 495 days
- Preoperative increased ALP activity which does not return to reference range within 40 days PO = Negative px
- For every 100 U/L increase in total ALP increases risk of tumor-related death by
25% RUSVM Confidential 57 Alkaline
What are some details regarding feline OSA, prognostic, location, MST etc?
• More common in the diaphysis than metaphyseal areas & the pelvic limb (50%) is more frequently affected than thoracic limb sites (30%)
– Distal femur, proximal tibia & proximal humerus
• Feline appendicular OSA is less aggressive than canine appendicular OSA with a slower growth & metastasis less common
– 5–10% met rate
• Amputation alone w/out chemotherapy may be curative in cats w/ appendicular OSA
– MST 24-49 months
