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OSTEOSARCOMA
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The following
information is simply informational. It's intent is not to replace
the advice of a veterinarian nor to assist you
in making a diagnosis of your pet. Please consult with
your own veterinary physician for confirmation of any diagnosis.
Your pets life may depend on it.
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OVERVIEW:*
Most primary bone tumors in dogs are malignant, and
approximately 85 % are osteosarcomas. Osteosarcomas are highly
aggressive tumors, characterized by local invasion/destruction and
distant metastasis (spread to other organs). Osteosarcoma commonly
affects the appendicular skeleton (limbs) of large to giant breed
dogs, but can also occur in the axial skeleton (skull, ribs,
vertebrae, pelvis), which is a more common primary site in smaller
dogs. Other bone tumors include chondrosarcoma, fibrosarcoma,
hemangiosarcoma, liposarcoma, multiple myeloma, and metastatic bone
tumors. The biological behavior, prognosis, and treatment of these
tumors depends on tumor type, primary site (location), and extent of
disease (stage). Therefore, various diagnostic tests such as
radiographs (X-rays), bloodwork, and a biopsy are required to
determine the most appropriate treatment.
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CLINICAL
SIGNS:*
The signs associated with a bone tumor may be
nonspecific and depend on the primary site. Tumors in the limbs
often cause various degrees of lameness and pain, and a firm
swelling may become evident as the tumor size increases. The pain
can cause other problems such as irritability, aggression, loss of
appetite, weight loss, whimpering, crying, sleeplessness, and
reluctance to exercise. Tumors in non-weight-bearing bones may
initially appear as a solid, firm mass. Other clinical signs may
vary, depending on the primary site and involvement of underlying
structures.
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DIAGNOSIS & WORKUP
(STAGING):*
Initial evaluation of a dog with a suspected bone
tumor often includes: complete physical exam, blood tests,
radiographs (both the primary site and the lungs), and a
biopsy. The biopsy can be incisional or excisional. An
incisional biopsy is performed for diagnosis only. A small sample of
the tumor is removed to determine the specific tumor type. An
excisional biopsy involves removing the entire tumor, both for
diagnostic as well as therapeutic purposes. The work-up and staging
are important for two reasons: it is necessary to determine the
tumor type and extent of the cancer, but also provides the clinician
with information regarding the dog's general health and may identify
concurrent medical or musculoskeletal problems, all of which may
influence the treatment recommendations.
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TREATMENT:*
As stated above, the
treatment recommendations for bone tumors depend on multiple
factors, and a complete physical exam and work-up may be necessary
to accurately determine the most appropriate treatment for an
individual dog.
Since osteosarcoma is
by far the most common tumor type, this treatment discussion will
focus on osteosarcoma. We often classify osteosarcomas as
appendicular or axial, because the location of the tumor may have
implications both for the surgical approach as well as the tumor's
biological behavior, and therefore require different follow-up
treatments.
Appendicular
(limb) osteosarcoma commonly causes lameness and pain because of
invasion and destruction of normal bone and periosteum (sensitive
structures surrounding bone). These tumors are also highly
metastatic (likely so spread to other organs), and the average dog
with appendicular osteosarcoma will live 4-6 months if treated with
surgery alone. Surgery at VHUP usually involves amputation of
the affected limb, but limbsparing
procedures may be an option in selected
cases. The surgery serves two purposes; it removes the
primary tumor which is necessary for cancer control, but it also
removes the source of pain, and may therefore dramatically improve
the quality of life of the patient.
The most common cause
of death is lung metastasis. Because of this, systemic chemotherapy
is recommended as follow-up therapy for dogs with appendicular
osteosarcoma. Chemotherapy is not likely to cure most dogs with
osteosarcoma, but can prolong a good quality survival. We
currently recommend to use a combination of 2 different drugs:
Adriamycin (doxorubicin) and cisplatin or carboplatin. Most dogs
tolerate this chemotherapy well, with only mild, self-limiting side
effects such as depressed appetite, nausea, occasional vomiting and
diarrhea for a few days. Less than 5 % of dogs will experience
severe, life-threatening side effects requiring hospitalization and
supportive care. If your dog's side effects are severe and
compromise his/her quality of life, the dosages of these drugs are
reduced in the subsequent treatments. The average survival in dogs
with osteosarcoma treated with surgery and chemotherapy is
approximately 1 year.
Axial osteosarcomas
are often diagnosed as a firm, solid mass. Other clinical signs
vary, depending on the tumor location and the involvement of normal
adjacent tissues. Because of the location of most axial
osteosarcomas, a complete surgical removal is often not possible.
Microscopic tumor cells are left behind, and the tumor is therefore
likely to recur at the same site. The average survival in dogs with
axial osteosarcomas is 4-5 months, and the most common cause of
treatment failure is local tumor recurrence. Therefore follow-up
treatment is focused on improving local tumor control, and
radiation
therapy is a reasonable choice.
There is currently limited information regarding the effect of
adjuvant radiation therapy in dogs with axial osteosarcomas. The
metastatic potential of these osteosarcomas vary depending on the
location, and chemotherapy may be indicated in some cases as well.
The above are general
treatment guidelines for dogs with osteosarcoma. In addition,
palliative measures might be suggested for dogs that are not
candidates for any of these options for various reasons. A
palliative treatment is given to alleviate pain and symptoms from
the tumor, and may involve the use of different types of pain
medication and/or a few high doses of radiation therapy. Such
treatments may help control the pain in dogs with osteosarcoma and
therefore provide the client and pet with additional good quality
time together.
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LINKS FOR ADDITIONAL INFORMATION ON
OSTEOSARCOMA:
MarVista Vet
Bath-Brunswick Veterinary
Associates
DaviesWhite Veterinary
Specialists
Flat Coated Retriever Society of
America
WSAVA/VIN
Shannon's Story
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ONGOING CLINICAL TRIALS FOR
OSTEOSARCOMA:
Clinic Seeks Dogs with Appendicular
Osteosarcoma for Trial
The University of Illinois Cancer
Care Clinic recently secured resources to initiate a funded clinical
trial involving osteosarcoma (OSA), by far the most common primary
bone tumor in dogs. The main goal of this trial is to objectively
assess the effectiveness of aminobisphosphonates for the management
of bone pain associated with canine appendicular OSA.
Aminobisphosphonates have been used effectively in humans for more
than 10 years, and our Cancer Care Clinic has been safely using them
in dogs since 1996.
Dogs with appendicular OSA
meeting study inclusion criteria will be provided FREE
aminobisphosphonate every 28 days for palliative therapy of bone
pain. (The normal cost of this aminobisphosphonate is fairly
expensive: for a dog weighing greater than 75 pounds, it would be
approximately $600/dog/treatment.) The provision of up to three
doses of aminobisphosphonate at no cost may serve as a significant
financial incentive. Additionally, owners will be compensated in the
amount of $300 when returning for the first monthly scheduled
recheck appointment.
Background on Treatment of OSA:
It is estimated that over 8,000
dogs per year will be diagnosed with OSA in the United States.
Canine patients diagnosed with OSA are often middle-aged to older
dogs of large or giant body size, with definite over-representation
of certain breeds such as the Rottweiler, Saint Bernard, Golden
retriever, Irish wolfhound, and Greyhound. Conventional standard
therapy for canine appendicular OSA includes amputation of the
affected limb, and administration of adjuvant
chemotherapy.
A fair number of patients may be
poor candidates for amputation, due to complicating factors such as
severe degenerative joint disease, significant obesity, and multiple
tumor sites, or because of owner reluctance for this radical
procedure. Therefore, other means to effectively control local bone
pain, and possibly halt or slow the progression of the primary bone
tumor growth, should be investigated. While pain management is
recommended through the use of non-steroidal anti-inflammatory drugs
(NSAIDs) and opioids, these analgesic agents usually do not provide
adequate pain control in dogs with advanced osteolytic diseases,
including OSA.
Although palliative radiation
therapy has proven to be effective in significantly decreasing bone
pain in 75 to 80 percent of dogs with OSA, this form of therapy is
not readily available everywhere, and can be relatively expensive.
In the past decade, human beings suffering from painful bone cancers
have demonstrated a survival advantage, and benefited from
significant pain reduction, when treated with a class of potent
antiresorptive agents known as aminobisphosphonates.
Contact Information:
For a more detailed description
of the Funded Clinical Trial for Appendicular Osteosarcoma, please
contact the following individuals at the University of Illinois
Veterinary Teaching Hospital:
Timothy M. Fan, DVM
(217) 333-5375 |
Louis-Philippe de
Lorimier, DVM
(217) 265-4088 |
Sarah Charney, DVM
(217)
244-8747 |
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CLINICAL TRIAL
RESULTS:**
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1. J Vet
Intern Med. 2000 Sep-Oct;14(5):495-8. |
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Cisplatin and doxorubicin
combination chemotherapy for the treatment of canine
osteosarcoma: a pilot study.
Chun R, Kurzman ID, Couto CG, Klausner J,
Henry C, MacEwen EG.
Kansas State University, Manhattan, USA.
chun@vet.ksu.edu
Sixteen dogs with histologically confirmed
appendicular osteosarcoma were treated by amputation followed
by cisplatin and doxorubicin chemotherapy. All dogs began
chemotherapy within 24 hours of surgery. Cisplatin was
administered at 50 mg/m2 intravenously (IV) concurrent with
saline-induced diuresis. Doxorubicin was administered 24 hours
later at 15 mg/m2 as a slow IV bolus. This protocol was given
on a 21-day cycle for 4 cycles. No dose delays were required,
but dose reduction of doxorubicin was required in 2 dogs
because of neutropenia. Thoracic radiography was performed
every 2 months after completion of therapy to monitor for
metastatic disease. Two dogs were still alive and free from
disease at the time of last contact (24 and 75 months,
respectively). Postmortem examinations were performed on 13 of
the 14 dogs that died. Eight of these dogs were euthanized
because of metastatic osteosarcoma. Of the remaining 5 dogs,
euthanasia was performed because of complications of
idiopathic megaesophagus (n = 1), arthritis (n = 2), and
hemangiosarcoma (n = 2). The median disease-free interval and
survival times were 15.7 and 18 months, respectively. When
compared to a historical group of 36 dogs with appendicular
osteosarcoma treated with surgery and 4 doses of cisplatin.
both disease-free interval and overall survival were
significantly longer in the study population (P < .015 and
P < .007, respectively).
PMID: 11012111
[PubMed - indexed for MEDLINE]
2. Mol
Ther. 2003 Feb;7(2):163-73
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A canine
conditionally replicating adenovirus for evaluating
oncolytic virotherapy in a syngeneic animal
model
Hemminki
A, Kanerva A, Kremer EJ, Bauerschmitz GJ, Smith BF, Liu
B, Wang M, Desmond RA, Keriel A, Barnett B, Baker HJ,
Siegal GP, Curiel DT.
Division of Human Gene Therapy,
Department of Medicine, Department of Pathology,
Department of Surgery, and the Gene Therapy Center,
Birmingham, Alabama, UK
Oncolytic
adenoviruses, which selectively replicate in and
subsequently kill cancer cells, have emerged as a
promising approach for treatment of tumors resistant to
other modalities. Although preclinical results have been
exciting, single-agent clinical efficacy has been less
impressive heretofore. The immunogenicity of
adenoviruses, and consequent premature abrogation of
replication, may have been a partial reason. Improving
the oncolytic potency of agents has been hampered by the
inability to study host-vector interactions in
immune-competent systems, since human serotype
adenoviruses do not productively replicate in animal
tissues. Therefore, approaches such as immunomodulation,
which could result in sustained replication and
subsequently increased oncolysis, have not been studied.
Utilizing the osteocalcin promoter for restricting the
replication of a canine adenovirus to dog osteosarcoma
cells, we generated and tested the first nonhuman
oncolytic adenovirus. This virus effectively killed
canine osteosarcoma cells in vitro and yielded a
therapeutic benefit in vivo. Canine osteosarcoma is the
most frequent malignant disease in large dogs, with over
8000 cases in the United States annually, and there is
no curative treatment. Therefore, immunomodulation for
increased oncolytic potency could be studied with
clinical trials in this population. This could
eventually translate into human
trials.
PMID: 12597904 [PubMed - in process]
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ACKNOWLEDGMENTS:
Any information on this site is published under
the "fair use" act. If you are the author, researcher or contributor
to any of the information contained herein and would prefer not to
have your information included on the site, please contact us and it
will be removed immediately.
*Canine Cancer Awareness
gratefully acknowledges the University of Pennsylvania Cancer Center
( OncoLink ) for granting us
permission for the use of the above information.
** PubMed, Published for MEDLINE, National
Library of Medicine |
