Monday, May 5, 2008

Osteoscarcoma and Wolfhounds (Courtesy of Andie, Breeze's Mom)

(Photograph of Breeze on vacation)
Published in the Irish Wolfhound Foundation newsletter "Focus", volume 2, No 1, 2004 written by Kathy Wilson OSTEOSARCOMA: WHAT YOU NEED TO KNOW by Kathy Wilson

Osteosarcoma is the type of bone cancer that kills over 25% of all Irish Wolfhounds. It is an extremely aggressive and malignant tumor. Because of the swift progress of this disease, time is of the essence. New insights into the biology of tumor growth, along with an expanding arsenal of drugs available for treatment, have made it possible to extend quality life for our hounds. Early diagnosis is the key to capitalizing on the effectiveness of these treatments.This article was written to help you recognize the symptoms of this disease, and to prepare you and your veterinarian to deal with it as expeditiously as possible.DiagnosisThe classic scenario is a wolfhound who has lameness and swelling near a joint on one of his legs. When first brought to the vet, the IW was lame, but no swelling was detected. Often, rest and a little Rimadyl bring temporary improvement, but the lameness recurs, and this time the hard swelling is noticed. Radiographs (x-rays) of the affected limb go a long way toward a positive diagnosisMost malignancies occur in the major weight-bearing bones of either the front or hind legs, with about a 60%/40% split front to rear. The most common site is the distal radius (the foreleg near the pastern, or `wrist'), with the proximal humerus (upper arm near the shoulder joint) running a close second.

The old adage, "away from the elbow, toward the knee" is accurate in the front, but in the rear, tumors can occur in both the proximal and distal femur (thigh bone, close to and away from the knee) as well as the distal tibia (shin bone, near the rear pastern, or hock joint). Osteosarcoma is not found mid-shaft, but at the ends of the bone, in the metaphyseal area where growth occurs (growth plates).Investigate lameness promptly. Don't be afraid to be proactive! Ask your veterinarian to x-ray your wolfhound if he is limping and you can't recall an injury. By all means, investigate all options for treatment, but be aware that in most cases, survival time following diagnosis is measured in days and weeks, not months and years. Treatment begun immediately has a better chance of controlling this disease.PrognosisOsteosarcoma and hemangiosarcoma share a predilection for older, large and giant breeds, but dogs of any age and size can—and do—suffer from it.

A dog who weighs over 80 pounds is about 60 times more likely to develop osteosarcoma than a smaller dog. There are other malignancies found in bone, such as fibrosarcoma and chondrosarcoma, but this tumor is by far the most common type of primary bone tumor in dogs. Between 8,000 and 10,000 dogs in the US will develop it this year. Our breed is not alone.In humans, most osteosarcomas occur in adolescents, especially those undergoing growth spurts. It is likely that the rapidly-dividing cells found in the growth plates (both human and canine) are at a greater risk of genetic mutation.Blood chemistry is often performed at the time of diagnosis, and alkaline phosphatase levels are indicative of prognosis. Very high activity (i.e., two to four times normal) of alkaline phosphatase is a sign of poor prognosis. The tumor's location is also prognostic, with tumors on the proximal humerus faring worst.

Young dogs with osteo usually have very malignant tumors, with a poor prognosis. Also, dogs who show overt signs of metastases at time of diagnosis fare poorly.MetastasesCancer cells which break away and spread to other areas of the body are called metastases. Micrometastases have already spread in about 90% of dogs by the time of initial diagnosis. However, only about 10 % of these dogs will have metastases large enough to be found at the time of diagnosis. Bone cancer does not spread across the joint, but rather spreads through the blood stream or the lymph system. Common sites for metastases are the lungs and other long bones, but metastases can be found anywhere. Palpation for skeletal and extra-skeletal nodules and additional radiographs of the chest can aid in diagnosing metastases. Chest films should include two lateral thoracic views as well as a vetrodorsal view. Bone scans (scintigraphy) are also extremely useful in picking up metastases to the other limbs, but are available only at veterinary teaching hospitals and specialty referral centers, and require an overnight stay. Biopsy is not routinely recommended, because it carries additional risk of fracture to the already-weakened bone. In some cases, though, it may be essential to rule out fungal disease, which has a similar appearance on film.Tumor TypeThere are several subtypes of tumors, but, in general, osteosarcomas can be described as osteoblastic, osteolytic, or mixed (a combination of both cell types). In lytic (osteolytic) tumors, the destructive processes outstrip the laying down of new bone. Osteoblastic tumors stimulate production of excessive, unsound new bone matrix.It is believed that most tumors start out as lytic, but quickly progress to mixed. Tumor type, as well as staging (extent of the disease), account for much of the variation encountered in response to treatment.

TRADITIONAL PAIN MANAGEMENT -Osteosarcoma is one of the most painful types of cancer; most dogs are euthanized because of the pain. Pain increases as the tumor grows and destroys the bone from the inside out. Traditional methods of pain relief include use of analgesics (pain-relieving drugs), radiation of the primary tumor site, or amputation/limb salvage surgery. Acupuncture may also provide some relief.NSAIDS and SteroidsNSAIDs (non-steroidal anti-inflammatory drugs) available for veterinary use, include Rimadyl, Deramaxx, and Feldene, as well as aspirin. Acetaminophen is sometimes used in dogs, but probably will not give adequate pain relief. NSAIDs are usually well-tolerated, but a proton-pump inhibitor, such as Prilosec, may be added to lessen the possibility of GI tract problems, which are a primary side effect. Steroids such as prednisone are also excellent for reducing the inflammation and easing pain. The dose of steroids can be increased as the tumor grows and pain increases.OpioidsWhen other pain medications no longer provide adequate relief, opioids should be added. Opioids include morphine, codeine, fentanyl, hydromorphone, and oxycodone. Combined with NSAIDs, they can make your wolfhound more comfortable. Also, there are some new options, such as Tramadol, available.Radiation TherapyRadiation in canine osteosarcoma is used for pain palliation. About 70% of the dogs treated will have significant pain relief. Usually, four treatments are given at one-week intervals. This radiation is usually delivered by a machine that shoots high-energy x-ray beams to the tumor in a process called external beam radiation. However, radiation can increase the risk of fracture in dogs with lytic tumors.Amputation/Limb Sparing SurgeryAmputation of the affected leg will certainly relieve the pain of the primary tumor, as will limb-salvage surgery, which removes the primary tumor but attempts to save the affected leg by resection, or by implanting a bone harvested from a donor dog. Dogs who undergo either of these surgeries without chemotherapy to control metastasis have only a 5% survival rate at one year.

The primary tumor seems to send out some signal which keeps growth of the metastases in check. Once the primary tumor is removed, the metastatic lesions are free to grow unchecked. Chemotherapy is always added to the surgery to control the rate at which the secondary tumors develop. When chemotherapy is combined with amputation, survival approaches 50% after one year.There are some obvious drawbacks to either of these surgeries, and they are contraindicated in dogs with underlying health problems or ongoing orthopaedic or neurological issues.The three drugs most commonly used in chemotherapy are cisplatin, carboplatin, and doxorubicin. As a rule, dogs do not suffer as much as humans do to the side-effects common to chemotherapy.NEW TREATMENT OPTIONSBisphosphonatesThe class of drugs called bisphosphonates, including alendronate (Fosamax) used in the IW Osteosarcoma Treatment Study, and the aminobisphosphonate s in clinical trial at the University of Illinois, are a class of drugs which have proven extremely useful in reducing pain in humans with bone cancers, and may have anti-tumor effects as well. These drugs can be combined with NSAIDS or other pain-relievers. They work by slowing the action of the osteoclasts, cells that tear down bone. Early findings suggest that osteolytic tumors respond better than osteoblastic tumors.Radioisotope TherapyThe use of radioisotope therapy to treat people with metastatic bone pain has been very successful. Samarium-153 is a radio-pharmaceutical (a drug containing radioactive isotopes) which is designed to go to any areas where bone is being attacked by cancer cells. Because it is carried in the bloodstream, it can alleviate pain in many areas, but with minimal exposure to normal bone and healthy tissue because of the type of radiation emitted. It does, however, suppress bone marrow as an undesirable side-effect. A clinical trial testing its value in treating osteosarcoma pain in dogs, funded by the Morris Animal Foundation, is underway at the University of Missouri and the University of Florida. This study does not involve amputation of the affected limb, but does require a stay at the University.

Metronomic ChemotherapyMetronomic chemotherapy is a new approach to slowing the growth of tumors by using frequent low doses of conventional chemotherapy drugs, usually combined with another drug believed to have anti-angiogenic properties. Tumor angiogenesis is the proliferation of a network of blood vessels which penetrate into cancerous growths. Without this blood supply, tumor growth halts. Metronomic protocols have proven successful in mice, and data from human studies is promising. A combination which has been tried is chlorambucil (used most often in canine lymphoma and leukemia), with piroxicam (Feldene). One very real benefit of metronomic protocols is the lack of side effects so common to traditional chemotherapy.Current ResearchThere is some evidence that NSAIDS (non-steroidal anti-inflamatory drugs, such as Rimadyl) may have anti-cancer properties, but this has not been proven. The same is speculated about certain antibiotics, including doxycycline and enrofloxacin (Baytril). Although both classes of drugs may have some anti-tumor effect, neither of them is likely to produce enough of an effect to actually stop the tumor from growing. However, in combination with other therapies, researchers hope they may prove to be useful.Complicating research is the fact that this is a type of cancer which does have rare, but well-documented, cases of spontaneous remission.Mapping the Gene for Canine OsteosarcomaThe search for the gene(s) involved in canine osteosarcoma has begun. Blood Samples from every IW with osteosarcoma are needed! Please contact Karen Malone directly at if your wolfhound has been diagnosed with osteosarcoma. Also needed are blood samples from IWs over six years of age who are cancer-free. Karen can supply you with collection vials, mailers, and instructions for your vet.Deciding what's right for your IWUnfortunately, there is no real cure for canine osteosarcoma at this time. However, there is every reason to seek treatment for your wolfhound, and there is every reason to hope for truly significant progress in prolonging quality life for our wolfhounds in the near future.You are the only advocate your wolfhound has. At the very least, every wolfhound is entitled to adequate pain management, and to euthanasia when the pain is no longer tolerable.