Osteosarcoma
(OSA) is the most common primary bone tumor of dogs. Unfortunately, it is a very
common disease seen in veterinary medicine with greater than 10,000 dogs being
affected every year in the United States alone. Although our canine patients
are most commonly affected, osteosarcoma has been reported in horses, ferrets,
rabbits, cats and human beings. In Cats,
OSA, as well as all other primary bone tumors, is less common. Approximately 4.9 at risk cats per 100,000 develop
primary bone tumors per year, with 80-90% of those tumors being
osteosarcoma. Although the disease is
less common in humans than in dogs, osteosarcoma can be a devastating diagnosis
in human beings affecting mainly children in their teenage years. Canine
osteosarcoma has proven to be a very important comparative model in studying
the disease and treatment options for children. There has been significant
improvement in survival times of human beings with osteosarcoma. In 1980 there
was a 20% 5 year-survival rate for human beings with OSA compared to a current
long-term survival rate of 60%.
Osteosarcoma
most commonly affects large and giant breed dogs. Breeds found to be at the
highest risk of developing OSA include the Great Dane, Saint Bernard, Irish
Setter, Greyhound, Rottweiler, German Shepherd and Golden Retriever. Most
commonly patients are middle aged to geriatric (median of 7 years), although
there is a peak in incidence at 18 to 24 months.
Most
commonly the disease occurs in the appendicular skeleton (~75% of cases)
although it can also be seen in the axial skeleton as well as soft tissue
sites. The forelimbs are affected much more commonly than the hindlimbs with the
metaphyseal region of long bones being the most common primary site. The distal
radius and the proximal humerus are frequently affected, as are the distal
femur and proximal tibia leading to the saying “towards the elbow, away from
the knee”. In the axial skeleton the
tumor can present in the mandible, maxilla, spine, cranium, ribs, nasal cavity
and pelvis. Extraskeletal sites are much less common but sites reported include
the mammary tissue, subcutaneous tissue, spleen, bowel, liver, kidney, eye,
gastric ligament, synovium, meninges and adrenal gland. OSA of extraskeletal
sites tends to be very aggressive and is often associated with a poor
prognosis.
Patients
with appendicular lesions most commonly present with lameness and swelling of
the tumor site. Owners often associate a recent, minor trauma with the limping
and present the patient for evaluation. If the patient has a pathologic
fracture (not uncommon with OSA) they may present with severe pain and non-weight
bearing lameness.
Radiographs
of the affected limb (lateral and craniocaudal views of the lesion) should be
pursued following a thorough history and physical exam. Radiographic
abnormalities most commonly noted include cortical lysis and osseous proliferation,
often with soft tissue extension and/or swelling. A presumptive diagnosis if often made based on
the radiographic appearance of the lesion, signalment, history and physical
exam findings. However, differential diagnosis should include other primary
bone tumors (chondrosarcoma, fibrosarcoma, hemangiosarcoma, etc.), metastatic
lesions, multiple myeloma, solitary plasma cell tumor, lymphoma, systemic
mycosis, bacterial osteomyelitis and a bone cyst.
If
there is a strong suspicion of osteosarcoma based on the radiographs and case
findings, three-view thoracic radiographs should be obtained as the next step.
Osteosarcoma is aggressive both locally and systemically and metastatic disease
is common. At the time of diagnosis only about 15% of patients will have gross
metastatic disease; however, approximately 90% of patients will have
micrometastatic disease. OSA spreads hematogenously and the most common
metastatic site is the lungs, although spread to other bones or soft tissue
structures is possible. Along with thoracic radiographs a minimum metabolic
database is recommended including a complete blood cell count, serum chemistry
and urinalysis. Several studies have reported that dogs with an elevated
alkaline phosphatase have a poorer prognosis and may develop metastatic lesions
earlier than patients with a normal alkaline phosphatase.
In
order to confirm diagnosis a sample (either cytology or biopsy) needs to be
obtained. Cytology can be difficult as samples are often poorly cellular and
non-diagnostic. Biopsy is the preferred method and can be obtained as an open
incisional biopsy or a closed needle biopsy. If biopsy is performed the sample
should be collected from the center of the lesion and in a location that will
allow removal of the incision and biopsy tract at the time of definitive surgery.
Bone fracture is a concern with this tumor, especially when a biopsy is
performed. Owners should be warned of this risk and care taken to avoid
fracture. If a primary bone tumor is highly suspected, many owners will forego
a definitive diagnosis prior to pursuing definitive therapy.
Although
OSA is an aggressive disease with survival times of 2-4 months without therapy;
there are multiple treatment options available to these patients. These treatments
are aimed at treating the local disease and managing the associated pain while
decreasing the potential for systemic spread. Local therapies include amputation, limb
sparing surgery, palliative radiation therapy and bisphosphonates. All of these options are palliative in nature
and do not extend survival times.
·
Amputation
is a readily available option and the majority of orthopedically sound dogs
(even giant breeds and dogs with mild to moderate arthritis) handle this option
very well.
·
Limb sparing
surgeries can be very beneficial in orthopedically unsound dogs when amputation
is not possible. Limb sparing surgeries
are most beneficial for tumors of the distal radius or ulna with absence of a
pathologic fracture. However, these surgeries need to be performed by experienced
surgeons at specialized surgical centers.
·
Radiation
therapy and bisphosphonates are surgical alternatives for pain control. Survival
time is not extended by either of these therapies but can be very beneficial in
managing discomfort. Radiation therapy typically consists of one treatment per
week for 3-4 weeks. Approximately 70-90%
of patients experience 2-3 months of pain relief from this treatment. Side
effects are minimal and the patients do not experience systemic side effects as
a result of radiation.
·
Bisphosphonates,
such as pamidronate, are another option for pain relief. They are administered
intravenously along with a fluid diuresis. These drugs reduce bone pain by
inhibiting formation of osteoclasts and decreasing their ability to resorb
bone. Bisphosphonates can be administered every 4 weeks and pain relief may
last weeks to months.
As a
result of the high metastatic rate chemotherapy is used in conjunction with
local therapy in an effort to slow or prevent disease spread. The most common chemotheraputic drugs used to
treat OSA include carboplatin, cisplatin and adriamycin. Cisplatin is used much less commonly as a
result of its potential for nephrotoxicity necessitating a 6-hour diuresis at
the time of drug administration. Carboplatin and adriamycin are used more
commonly either as single agents or as part of a multiagent protocol
(alternating carboplatin and adriamycin). Both carboplatin and adriamycin are
administered intravenously every 3 weeks. Carboplatin is given for 4-6
treatments and adriamycin is given 5 times.
The majority of patients
(approximately 85%) handle these treatments very well with few to no
side effects. When side effects are noted, we most commonly see vomiting,
diarrhea, decreased appetite, decreased energy level and bone marrow
suppression. These side effects tend to be short lived and self-limiting and
most patients recover with no intervention. A smaller percentage of patients
will require oral anti-emetic or anti-diarrheal drugs and less than 1% of
patients have side effects that necessitate hospitalization.
Currently
there are studies looking at the benefit of using the oral tyrosine kinase
inhibitor, Palladia, or oral metronomic chemotherapy in addition to
conventional chemotherapy. With the
addition of these therapies we may see survival times of greater than one year.
In addition, osteosarcomas have been shown to overexpress Cox-2 and thus the
use of non-steroidal anti-inflammatory drugs may also be beneficial in slowing
disease progression and are commonly used in chemotherapy protocols.
With
local therapy alone (surgery, radiation therapy, bisphosphonates) average
survival times are 3-4 months. With surgery and chemotherapy survival times
increase to approximately 12 months with 25% of patients living two years.
The
goal with treatment is not only to improve our patient’s length of life but
also to ensure an excellent quality of life. With the treatments discussed, the
majority of patients will maintain an excellent quality of life and enjoy a
significant extension of life.
References
