Osteosarcoma
What is osteosarcoma and what causes it?
Osteosarcoma is a tumor that arises in the bone (mostly the long bones of the legs). Common clinical signs include pain, lameness, loss of appetite, depression and sometimes associated swelling at the region of tumor site. This tumor tends to occur most often in large to giant breed dogs with an average age of 7 years or older.
What are common clinical signs?
Clinical signs are variable for the individual patients. In the early stages of the disease there may be no clinical signs at all. Lameness, depression and loss of appetite or energy develop as the disease progresses.
How is osteocarcoma diagnosed?
Diagnosis is usually made by a combination of history, physical exam, radiographic (x-ray) findings, and sometimes bone biopsy. Osteosarcoma is the most common type of tumor found in the bone (accounts for 85% of bone tumors).
What additional tests are recommended and why?
Osteosarcoma spreads (metastasizes) to other organs within the body as the tumor grows. Additional tests help to detect the spread of disease as well as to evaluate for underlying organ disease that may impact follow up chemotherapy.
1. Thoracic (chest) x-rays: help to detect spread of tumor to the lungs (the primary site of metastasis). Very small nodules may not be detectable on x-rays.
2. Long bone x-rays: help to detect spread of tumor to the other long bones of the body(another common site of tumor spread).
3. Lymph node evaluation: if regional lymph nodes are enlarged, aspiration (samples obtained by insertion of a very small needle) help to look for evidence of tumor spread.
4. Internal organs: osteosarcoma does not commonly spread to the internal organs in the abdomen.
5. Overall patient assessment: general health screening tests (CBC, profile, UA) are performed in the initial evaluation of the patient with osteosarcoma. These tests give valuable information about the function of the body’s major organ systems and allow detection of other diseases that may influence chemotherapy protocol.
6. In certain circumstances, more specialized testing to evaluate the kidneys (abdominal ultrasound, dye clearance studies) or the heart (ECG, cardiac echo) may be recommended.
Preparing to Take Bone X-Rays
X-Ray of Tumor in Humerus Bone
Is a bone biopsy necessary to make a diagnosis of osteosarcoma?
There are very few other diseases that cause the classic signs of bone lysis (bone breakdown) and simultaneous excess bone production on x-rays. The breed of patient, age of patient, and location of lesion noted on x-rays also provide supportive clues to the diagnosis. Other tumor types (chondrosarcoma, fibrosarcoma and hemangiosarcoma-which also benefit from amputation) and infection (fungal or bacterial) may cause similar radiographic signs. Patients that have infection (fungal or bacterial) typically also have other clues on history, exam and labwork. Most surgeons and oncologists are confident in making the diagnosis of osteosarcoma based on history, signalment (breed and age of dog, exam findings, laboratory findings, and radiographic findings. In selected cases, the surgeon may recommend a bone biopsy for definitive diagnosis prior to amputation.
How is osteosarcoma treated? What are the treatment options?
1. Amputation is usually recommended in order to alleviate the major source of pain and discomfort from the tumor. Amputation alone does not change the overall survival time with osteosarcoma but will immediately remove the major source of pain and discomfort and significantly improves the quality of life.
2. Localized radiation therapy can be palliative in alleviating discomfort short term (for up to several months) if amputation is declined or cannot be performed for other medical reasons.
3. Chemotherapy is recommended after amputation to improve the mean survival time as well as quality of life.
When is the optimum time to start chemotherapy after amputation?
Chemotherapy may be started anytime from just prior to amputation to up to two weeks after. Starting chemotherapy earlier (prior to, or immediately after surgery) does not confer any additional survival benefit. If chemotherapy is administered too close to surgery the risk of adverse effects increases (as patient is also trying to heal from the immediate effects of surgery). For these reasons, we recommend starting chemotherapy 10 – 14 days after amputation, which coincides with the recheck visit for suture removal.
What is the best chemotherapy protocol for the patient with osteosarcoma?
1. The three most effective drugs for treatment of osteosarcoma include cisplatin, carboplatin, and doxorubicin. As a general rule, most protocols use just one of these drugs. Multiple agent protocols (using more than one of these drugs together) does not provide any improved survival benefit over single agent protocols.
2. Which drug is best? Cisplatin historically has been associated with more severe kidney side effects, and has now been largely replaced by carboplatin (a newer drug with less toxic side effects to the kidneys).
3. Doxorubicin is given more frequently than carboplatin (every two weeks versus every three weeks) and has the potential for more severe cardiac (heart) side effects. The efficacy (effectiveness) of doxorubicin and carboplatin are similar in regards to mean survival times.
4. For the reasons noted above, carboplatin is currently our chemotherapy agent of choice for treatment of osteosarcoma. The protocol for carboplatin is 300 mgs/m2 administered intravenously every 21 days for 4 treatments. The median survival time with this protocol is approximately 11 to 12 months.
 
What are the common side effects associated with chemotherapy?
1. Animals are very different than people in regards to side effects associated with chemotherapy. The side effects noted in people (nausea, vomiting, inappetence, and hair loss) are considerably less severe in the dog and cat. One of our primary goals with chemotherapy is to improve and maintain the quality of life.
2. The most common side effects seen with chemotherapy include bone marrow suppression (a low white blood cell count that is detected via regular blood tests), intestinal upset, and hair loss. Side effects are somewhat predictable based on the specific chemotherapeutic agent used and preventative measures can often be taken ahead of time to counteract likely side effects. The overall goal of therapy is always to provide a pain free and excellent quality of life for the patient.
3. The most common side effect seen with carboplatin is myelosuppression (reduced production of white blood cells from the bone marrow). White blood cells are important in helping to protect the body against infection). Patients with altered kidney function may not be candidates for carboplatin chemotherapy (or require altered dosages) as this drug is excreted by the kidneys.
4. The most common side effects associated with doxorubicin (second agent of choice for treatment of osteosarcoma) include myelosuppression, intestinal upset (potential loss of appetite, vomiting), and cardiac (heart) side effects.
5. Medications can often be given in conjunction with chemotherapy to help alleviate side effects.
What is the protocol that my dog will undergo for the scheduled chemotherapy treatments?
1. We will ask you to drop off your dog in the morning on the day of the appointment. A medicine nurse will greet you and obtain a history about how things are going at home, as well as to help address any additional questions or concerns that may have come up since your previous visit.
2. The doctor will review the history with the nurse and perform a physical exam to identify any problems or concerns that could alter the scheduled chemotherapy treatment.
3. At the time of the first chemotherapy visit, additional diagnostics to completely stage the disease process and assess the major organ systems may need to be completed (if not done already). These tests usually consist of a CBC, biochemistry profile, urinalysis, long bone radiographs, and aspirates of regional lymph nodes (if indicated).
4. After review and approval of the labwork, an intravenous catheter is placed. If needed, mild sedation will be given to help your dog remain calm and relaxed during the time period of chemotherapy administration.
5. A nurse will be dedicated to your dog during the entire time of chemotherapy administration.
6. After chemotherapy is complete, your dog will be ready for discharge from the hospital (usually in the early afternoon).
Protocol for Osteosarcoma chemotherapy
Week 1 (Day 1) (10 to 14 days after surgery)
1. Suture removal and evaluation of healing amputation site.
2. Physical exam and labwork evaluation in preparation for first chemotherapy treatment (CBC, profile, UA, and long bone radiographs).
3. Treatment number 1 of 4 with carboplatin 300 mgs/m2 IV.
Week 2 (Day 10 – 14)
1. Recheck exam to address any questions or concerns that may have arisen since first chemotherapy treatment.
2. Blood test (CBC) to look for evidence of myelosuppression (the peak effect of administered chemotherapy occurs 10 to 14 days after administration). Based on results of CBC, adjustments in future chemotherapy doses may be considered, and if the white blood cell count is very low, oral antibiotics may be prescribed.
Week 3 (Day 21)
1. Recheck history, physical exam and CBC.
2. If recheck CBC count is within normal limits, treatment number 2 of 4 with carboplatin 300 mgs/m2 IV.
Week 6 (Day 42)
1. Recheck history, physical exam, CBC. biochemistry profile, and urinalysis.
2. If recheck CBC count is within normal limits, treatment number 3 of 4 with carboplatin 300 mgs/m2 IV.
Week 9 (Day 63)
1. Recheck history, physical exam and CBC.
2. If recheck CBC count is within normal limits, treatment number 4 of 4 with carboplatin 300 mgs/m2 IV.
Are any special precautions necessary after I return home with my dog?
Chemotherapeutic drugs are excreted in the urine and feces for several days after administration. It is best to avoid any direct contact with urine and feces and to wear gloves for disposing of urine or feces for the first two days after chemotherapy administration.
What other supportive therapies may be helpful?
1. Diet: optimal nutrition plays an important role in the overall management of the patient with cancer. Diets higher in fat, protein and supplemented with omega-3 fatty acids are beneficial in helping to support and maintain body weight. Examples of such diets include Hill’s n/d canned diet (660 kcals/can), Eukanuba Maximum-Calorie canine dry diet (634 kcals/cup), and Hill’s a/d canned diet (1.3 kcals/ml). Other options include performance or puppy food diets.
2. Pain medications: many patients with cancer will have associated discomfort that can be greatly alleviated by medications. Behavioral changes that may be seen include decreased activity, loss of appetite, change in normal attitude, discomfort on palpation of affected area, and licking at affected area. One or more of the following medications may be recommended for your dog:
a. Non-steroidal anti-inflammatory drugs (NSAID’s): These drugs alleviate inflammation and may also have some impact against tumor progression. Options include one of the following: meloxicam, piroxicam, or carprofen. Patients on NSAID’s are monitored for side effects (stomach and kidney toxicity) with baseline labwork prior to start of therapy, and recheck lab values during therapy (CBC, profile, UA in 2 – 4 weeks, and then every 2 – 4 months thereafter).
b. Opiods: these medications are narcotics that alleviate pain. Options include: butorphanol and tramadol. Side effects of opiods may include diarrhea, vomiting, sedation and constipation.
c. NMDA antagonists (amantadine): helps to counteract pain pathways at the level of the brain. Takes 1 - 2 weeks to see beneficial effects.
d. Gabapentin: helpful in neuropathic pain (such as after limb amputation) as well as with chronic pain.
e. Biphosphates: helpful in alleviating pain associated with primary bone tumors or tumor that has spread to other bone sites. This medication (pamidronate) is administered in the hospital as a slow intravenous injection (into the vein) over several hours.
f. Glucosamine/chondroitin sulphate combinations (Dasequin): are helpful in the ongoing management of concurrent arthritis present in other limbs.
3. Combination therapy: the most effective control over pain and discomfort involves using multimodal (more than one) drug therapy. A combination that is often effective and helpful includes a NSAID (+) Opiod, and (+/-) additional agent (NMDA, gabapentin).
What is the prognosis for dogs diagnosed with osteosarcoma?
1. Without treatment, the mean survival time for patients diagnosed with osteosarcoma is approximately 3 – 4 months.
2. With amputation alone, the mean reported survival time does not change (that is, an average of 3 – 4 months). The major goal of amputation is to provide relief of pain associated with the tumor.
3. With amputation followed by chemotherapy, the median survival time is approximately 8 – 14 months, with 25% of patients surviving up to two years.
What are the recommendations for follow up visits after completion of chemotherapy?
Recheck physical exam and chest radiographs are recommended at 4, 8, and 12 months following completion of chemotherapy (or sooner if any questions or concerns arise).
Wendy Yaphe, DVM, DACVIM & Corinne Fabrick, DVM, DACVIM-Aspen Meadow Veterinary Specialists
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