Investigators in the Skeletal Oncology Program Area of the Purdue Comparative Oncology Program study bone cancer that arises in the bone (primary bone cancer, most often osteosarcoma) and cancer that spread to the bone from other sites (metastatic cancer).

OSTEOSARCOMA

What is osteosarcoma?  Osteosarcoma is the most common primary bone tumor in man with approximately 2000 new cases diagnosed in the United States each year.  Osteosarcoma most commonly occurs in children and young adults.  Osteosarcoma is also the most common bone tumor in the dog with approximately 10,000 new cases diagnosed each year in the United States.   Osteosarcoma primarily affects middle-aged large and giant purebred dogs.  Osteosarcoma in man and dog is a highly aggressive cancer.

What causes osteosarcoma?  To date, little is known about the etiology of osteosarcoma. Rapid skeletal growth and large body size have been hypothesized to be relevant, given that most osteosarcomas occur during the pubertal years. It is speculated that sex hormones may be important, although it is unclear how these hormones may play a role in the development of osteosarcoma. Males are more often affected and may have a poorer prognosis.  Similar to the situation in humans, relatively little is known about factors that influence the development of osteosarcoma in dogs.  Thirty-five years ago, a study showed that the risk of bone sarcoma in large and giant breed dogs exceeds that of small breed dogs by as much as 185-fold.  Breeds with an apparent increased risk of developing osteosarcoma include Rottweiler, Saint Bernard, Great Dane, Greyhound, Great Pyrenees, Golden Retriever, and Irish Setter.  Osteosarcoma most likely develops from a number of factors including genetic predisposition and environmental factors such as radiation, microtrauma, and nutrition.

Investigators at Purdue University and the Gerald P. Murphy Cancer Foundation recently conducted a nationwide study of Rottweiler dogs, a breed plagued by osteosarcoma, in order to study possible factors that contribute to the risk of bone sarcoma development.  The findings of this study were published in November 2002 in Cancer Epidemiology, Biomarkers and Prevention (volume 11: pp.1434-1440), the world’s most widely read scientific journal focused on cancer prevention.  The results of this study suggest that similar to breast and prostate cancer the spontaneous development of bone cancer in Rottweiler dogs may be significantly influenced by sex hormones.  To access the scientific abstract, please visit the website: http://cebp.aacrjournals.org/cgi/content/abstract/11/11/1434.

What are common clinical signs or symptoms for dogs with osteosarcoma?  The bones of the limbs are affected much more often than bones of the spine, skull, or ribs.  Osteosarcoma of the limbs is called appendicular osteosarcoma.  The most common sites occurring away from the elbow and close to the knee.  Dogs with osteosarcoma show various degrees of pain and lameness which can be intermittent or constant.  Obvious swelling of the bone may become evidence as the tumor progresses and grows beyond the normal bone.  Because tumorous bone is not as strong as normal bone, some dogs may fracture the bone with only minor injury.

How is osteosarcoma diagnosed?  Initial evaluation of a dog with a suspected bone tumor includes a physical examination, bloodwork, and radiographs (X-rays) of the bone and lungs.  Radiographs generally show a classic pattern of bone loss (lysis) and bone production (proliferation).  Because this radiographic appearance can also be caused by other types of bone cancer or non-cancerous diseases, a biopsy of the bone is required to make a diagnosis of osteosarcoma.  Biopsy entails the surgical collection of a small core of tissue from the abnormal bone.  Sometimes a bone tumor is surrounded by an area of inflammation and it may be difficult to obtain a diagnosis and several samples must be taken.

What evaluation is needed for a dog with osteosarcoma?  Once a diagnosis of osteosarcoma is made, it is important to determine the extent of the tumor, i.e. to perform tumor staging.  Staging is performed in order to determine the best way to treat the cancer and to provide information regarding prognosis.  Staging entails a thorough radiographic evaluation of the lungs, evaluation of the skeleton for other potential affected bones, and other radiographs and blood tests to help determine the best treatment protocol.  Based on the results of this clinical staging, dogs with osteosarcoma can be subdivided into three categories:  (1) dogs with disease confined to the limb, which accounts for the majority of cases; (2) dogs with lung metastasis at diagnosis; and (3) dogs with multiple bone lesions at presentation.  Treatment is based upon the results of clinical staging at the time of diagnosis.  
 

How is appendicular osteosarcoma treated?  The treatment of osteosarcoma involves two aspects:  treating the pain caused by the bone tumor and fighting the spread of the cancer (metastasis). 

Treatment of the primary tumor usually involves amputation of the affected limb, but limb-sparing procedures may be an option in selected cases.  Amputation or limb-sparing surgery removes the primary tumor which serves two purposes:  removal of a source of pain and a source of tumor cells which are continually being shed to the rest of the body.  The removal of the painful limb often dramatically improves quality of life.  After amputation, recovery from surgery and adaptation to life on three legs is generally fast.  However, for dogs in which surgery is not an option due to other orthopedic conditions, radiation therapy of the affected limb can be used to control pain in some patients.

How rapidly dogs with osteosarcoma succumb to metastatic disease after removal of the primary tumor is influenced by treatment with adjuvant cytotoxic chemotherapy.  The best-known chemotherapeutic agent for the treatment of dogs with ostesoarcoma is cisplatin.  Other cytotoxic chemotherapeutic drugs which have been used to prevent osteosarcoma metastases are carboplatin and doxorubicin (Adriamycin).  Most dogs tolerate chemotherapy well, with only mild side effects such as decreased appetite and occasional vomiting and diarrhea.  Chemotherapy is not likely to cure most dogs with osteosarcoma, but can prolong survival with a good quality of life.

What is the prognosis for dogs with osteosarcoma?  Osteosarcoma is unfortunately a fast spreading tumor – by the time the tumor is found in the limb, it is considered to have already metastasized.  Over 90% of dogs with osteosarcoma of the limb will die with metastatic disease, most often to the lungs.  Dogs treated with limb amputation alone will survive approximately 4 months.  With the addition of adjuvant cytotoxic chemotherapy dogs survive 10-12 months. 

What can be learned from dogs with osteosarcoma that can help children with osteosarcoma?  In children with osteosarcoma, if no tumor spread is present at diagnosis, the 5-year survival after treatment is approximately 60%.  In contrast, for those children who have metastases at diagnosis the 5-year survival is only 15%.  Experts acknowledge that no important advances in the treatment of osteosarcoma have taken place in the past 30 years.  Because of the striking similarities between osteosarcoma that develops in children and dogs, spontaneous osteosarcoma in the dog is an excellent model in which to test new therapeutic approaches against metastatic disease.  Throughout the years, the Purdue Comparative Oncology Program has been involved in the evaluation of novel therapies against osteosarcoma such as antiangiogenic therapy and gene therapy.  Investigators at Purdue are continuously looking for promising new therapies to improve the survival and enhance the quality of life of dogs and children with osteosarcoma.  If you are interested in how your dog with osteosarcoma could help children and other dogs with osteosarcoma, please contact Oncology faculty or staff at (765) 494-1107.