Everyone there is so positive and professional, and, although we came there for a sad reason, we are so grateful to have met all of you.
West Orange, NJ
Dutch, a 6 year old, neutered male Great Dane presents to his primary care veterinarian for pain. His owners report that he seems like he has been getting older and slowing down, he has trouble getting up and down stairs, and this past weekend they noticed a swelling on his left front leg. Otherwise Dutch has been doing well.
On examination there is a large firm swelling of the distal antebrachium, Dutch is moderately lame on that limb and he has difficulty rising in his back end. Radiographs of the limb are performed and a lateral view is shown in Figure 1. The radiographs show a number of “classic” signs of an aggressive bone lesion:
- Irregular new bone formation – there is smooth new bone on the proximal aspect of the lesion in the shape of a triangle, often referred to as a Codman’s triangle. Also there is a large amount of patchy irregular new bone on the cranial aspect of the limb in what looks like a “sunburst” pattern.
- Loss of cortical detail – in the central aspect of the lesion the cortex is thinned out, consistent with bone loss.
- Location – as solitary lesion in this location, the metaphysis of the distal radius, is highly suspicious for osteosarcoma. Other common sites are the proximal humerus, distal femur, and proximal tibia
Three-view thoracic radiographs are performed and they are normal, with no evidence of metastases. After further discussion with the owners, Dutch has no history of travel out side of the North East United States. Based on signalment and radiographic findings the lesion is thought to be most consistent with a primary bone tumor, primarily osteosarcoma and a forelimb amputation is recommended. However, after a complete orthopedic exam it is determined that Dutch also has severe hip osteoarthritis and due to his large size, an amputation is not recommended.
A fine needle aspirate is performed, revealing spindloid cells, consistent with a sarcoma.
Dutch’s owners decide to start Dutch on oral pain medications and pursue palliative radiation. Dutch receives four radiation treatments to the distal forelimb. His owners report that two days after the first treatment Dutch starts using the leg more and they start to cut back on his pain medications.
Osteosarcoma is the most common bone tumor in dogs. Duke’s signalment and presentation are common – an aggressive bone lesion in the metaphyseal region of the long bones in a giant breed dog.
The ideal recommendation for treatment is surgical excision of the tumor, usually by amputation, followed by a course of chemotherapy. Survival times with surgery alone are approximately 4-6 months (Spodnick et al JAVMA 1992). Chemotherapy more than doubles this with average reported survival times of 12 months with 10 – 20 % of patients surviving 2 years or more (Withrow, Vail 2007)
In cases where an amputation may not be the ideal recommendation, palliative radiation therapy has been shown to be a very effective treatment option to provide pain control for the local tumor in 75 to >90% of dogs (Ramirez et al Vet Radiol Ultrasound, 1999; Green JAAHA 2002) Palliative radiation therapy usually involves between two and six treatments, delivered over one to three weeks. Side effects are typically very minimal, with mild irritation of the local skin. Pain control can occur within 48 hours and typically will happen within one week (Green JAAHA 2002).
Other palliative options include bisphosphonates, such as pamidronate. While less successful than radiation in controlling pain for bone tumors, they have been shown to have some benefit also with minimal side effects (Fan et al JVIM 2007). Also, the addition of pain medications and/or bisphosphonates to a course of radiation may result in significant pain control, although these types of combination treatments have not been fully investigated.
Spodnick GJ, Berg J, Rand WM, et al. Prognosis for dogs with appendicular osteosarcoma treated by amputation alone: 162 cases (1978-1988).J Am Vet Med Assoc. 1992 Apr 1;200(7):995-9.
Dernell WS, Ehrhart NP, Straw RC, Vail DM Tumors of the Skeletal System in Withrow and MacEwen’s Small Animal Clinical Oncology, 4th Ed. Saunders, St Louis Missouri 2007 pp. 559 – 563.
Ramirez O 3rd, Dodge RK, Page RL, et al Palliative radiotherapy of appendicular osteosarcoma in 95 dogs. Vet Radiol Ultrasound. 1999 Sep-Oct;40(5):517-22.
Green EM, Adams WM, Forrest LJ. Four fraction palliative radiotherapy for osteosarcoma in 24 dogs. J Am Anim Hosp Assoc. 2002 Sep-Oct;38(5):445-51.
Fan TM, de Lorimier LP, O’Dell-Anderson K, et al. Single-agent pamidronate for palliative therapy of canine appendicular osteosarcoma bone pain. J Vet Intern Med. 2007 May-Jun;21(3):431-9.
Mammary tumors are the third most common tumor type seen in the feline cat, and they account for approximately 20% of cancer in the female cat. These tumors arise from the mammary tissue and are typically very invasive with a high metastatic rate. Most mammary tumors in cats are classified as adenocarcinomas. Mammary cancer is often a disease of middle aged to older cats, with Siamese cats having a higher risk. Similar to breast cancer in women, hormonal influences are involved in the development of mammary cancer in cats. Several studies have found that cats spayed early in life had a 40-60% reduced risk of developing mammary cancer.
Surgery can be very effective at removing the masses, but the success of surgery may be hindered by the invasive nature of the disease. Therefore, an aggressive surgery is typically recommended, which involves removing all four mammary glands on the affected chain (or both chains if needed), called unilateral or bilateral mastectomy. Studies have shown that more aggressive (called radical chain resection) significantly reduces the chance for local tumor recurrence. Radical resection generally will entail the removal of the draining lymph node which is evaluated via histopathology and the presence/absence is prognostic. Due to the high rate of recurrence and metastasis, chemotherapy is recommended following surgery. Most effective protocols involve the use of the chemotherapeutic agent, doxorubicin, alone or in combination with other drugs. Doxorubicin is generally well tolerated with minimal side effects that are generally self-limiting in nature.
In human oncology, the use of targeted therapies like Herceptin (a treatment that targets certain molecular and genetic defects found in cancer cells) holds great promise for improving the outcome of therapy for the treatment of mammary cancer. The HER-2/neu protooncogene encodes a transmembrane tyrosine receptor kinase protein that has been associated with an increased metastatic propensity and a decreased prognosis. Approximately 25–30%of malignant cells in human breast cancer also overexpress this protein. This has been evaluated and shown to be over-expressed in feline mammary tumors. In veterinary medicine, two tyrosine kinase inhibitors exist Palladia (toceranib) and Masivet (masitinib) with anecdotal response noted in cats treated with Palladia.
Survival time for cats with mammary cancer is variable and depends on several factors including breed (Siamese = worse)size of the tumor, type of surgery (radical associated with better prognosis), tumor grade, proliferation indices (high indices – poor), Cox-2 expression (high-poor), presence/absence of metastasis, and is believed the addition of chemotherapy prolongs survival. The average survival times range from 4 months to over 3 years depending on these factors. Cats with tumors greater than 3 cm had a significantly worse overall prognosis, with survival times ranging from 5 to 10 months.
In canine dogs, mammary tumors are the most commonly diagnosed tumor in intact females older than 7 years of age. Male dogs can also develop mammary tumors, but rarely. Several breeds are prone to developing mammary cancer including Poodles, English Spaniels, English Setters, and Terriers. About 50% of mammary tumors are malignant and 50% are benign—this is very similar to the statistics for breast cancer in women. Hormonal influences have been found to be involved in the development of canine mammary cancer. It has been well documented that spaying (ovariohysterectomy) before the first heat cycle (typically before 6 months of age) dramatically decreases the risk of developing mammary tumors to a less than 1% risk. If spayed after the first heat cycle, the risk of getting mammary cancer increases to 8%. The risk increases to 26% if a dog is spayed after the third heat cycle.
As with felines, surgery is the treatment of choice for all dogs with mammary gland tumors. The type of surgery performed depends on the extent of disease. If only one or two tumors are present, removal of just those tumors is typically adequate. If there are multiple tumors present, a more aggressive surgery (removal of an entire chain, or both chains, of mammary glands) may be recommended. Chemotherapy may be recommended in some cases, such as with high grade, aggressive tumor type, very invasive and/or non-resectable tumors, or the presence of metastatic disease. Radiation therapy may be recommended for certain types of mammary cancers. This treatment is not as routinely used in veterinary oncology as it is for the treatment of breast cancer in people.
Survival time for dogs with mammary tumors is variable and depends on factors including the tumor size, grade of the tumor, tumor type, the presence of metastatic disease, lymphatic/vascular invasion as well as what treatment regimens are used. The average survival times range from less than a month (for aggressive inflammatory carcinomas) to several years.
- Borrego, J. F., J. C. Cartagena, and J. Engel. “Treatment of feline mammary tumours using chemotherapy, surgery and a COX‐2 inhibitor drug (meloxicam): a retrospective study of 23 cases (2002–2007)*.”Veterinary and comparative oncology 4 (2009): 213-221.
- Winston, J., et al. “Immunohistochemical detection of HER‐2/neu expression in spontaneous feline mammary tumours.”Veterinary and comparative oncology1 (2005): 8-15.
- Philibert, Jeffrey C., et al. “Influence of host factors on survival in dogs with malignant mammary gland tumors.”Journal of Veterinary Internal Medicine 1 (2003): 102-106.
A fourteen year old male neutered domestic short-haired cat presented with a several week history of weight loss. No vomiting, diarrhea, or other clinical signs were noted by the owner. Until three days prior to presentation, an oral steroid had been given. Thickened bowel loops were noted upon abdominal palpation, but not other remarkable findings were found on physical exam. The differential diagnoses were lymphoma, mast cell tumor, adenocarcinoma, or possibly inflammatory bowel disease (IBD). Ultrasound-guided aspirates of the thickened intestines were obtained and five slides were submitted for evaluation.
The five submitted slides were moderate to highly cellular and consisted of a moderate amount of cellular debris, many red blood cells, many extracellular and intracellular bacteria of mixed morphology, and a nucleated cell population predominated by poorly preserved neutrophils, with fewer small to intermediate-sized lymphocytes, macrophages, and many cells found in small to large clusters. These clusters consisted of round to polygonal cells with a small to moderate amount of very basophilic cytoplasm. The nuclei were large, round to oval in shape, and exhibited a coarsely-stippled chromatin pattern and one large central prominent nucleolus. The nuclear to cytoplasmic ratio of these cells was typically low; anisocytosis and anisokaryosis were moderate. Binucleation was occasionally noted. Neutrophils could be found imbedded within many of these basophilic clusters.
The cytologic diagnosis was carcinoma/adenocarcinoma with concurrent septic, neutrophilic inflammation.
Surgery is the next logical step in this case, assuming there is no evidence of pulmonary metastasis on thoracic radiographs. The abdomen could be staged preoperatively with a more comprehensive ultrasound or intra-operatively with evaluation of lesion impression smears by an on-site pathologist or by sending STAT digital images using your microscope and phone camera. The septic, neutrophilic inflammation represents either infection/inflammation +/- abscess formation within the tumor or possibly perforation of the bowel.
No mast cells were found, making mast cell tumor a very unlikely diagnosis. Had lymphoma been the cause of the intestinal thickening, a more numerous, very uniform population of lymphocytes would have been expected, without the presence of epithelial cells with so many malignant criteria.
Currently in veterinary oncology all chemotherapeutic agents are used on an off-label basis, however, this is about to change. The conditionally approved Paccal Vet® is a member of the taxane family and in human oncology, taxanes have been shown to have activity against many cancer histologies including mammary cancer, head and neck squamous cell carcinoma, ovarian cancer, lung cancer, Kaposi sarcoma, gastric cancer, prostate cancer, soft tissue sarcoma, and bladder cancer. Taxanes were first derived from natural sources, however, others have been synthesized artificially (Paclitaxel was originally derived from the Pacific yew). The primary mechanism of action involves disruption of microtubule function which is essential for cell division. Taxanes stabilize tubulin in the microtubule, thereby inhibiting the process of cell division. This leads to a “frozen mitosis” and is in stark contrast to the vinca alkaloids, which destroy mitotic spindles.
As a class, taxanes have poor water solubility and need to to be dissolved before administration. Cremophor® is composed of polyoxyethylated castor oil and dehydrated alcohol and was the first method used to dissolve taxanes for infusion. Since the ratio of Taxane: Cremaphor® in Paclitaxel (Taxol) is 1:88, this means that each ml of solution is composed mostly of solvent, not the active drug. This leads to prolonged infusion volume and infusion times (3 to 6 hours). Taxanes often cause an allergic reaction in humans necessitating the use of antihistamines and steroids before injection. Even with pre-treatments, allergic reactions to Taxol occur in ~41% of people treated. In humans, Cremaphor® hypersensitivity has been overcome by using nab-paclitaxel (Abraxane®). This solution cannot be used in dogs because it uses human albumin, thus limiting its use in veterinary oncology. Taxol has been evaluated in one study of dogs (n=25) against a variety of histologies and although a number of response were noted, 64% (16/25) experienced allergic reactions despite receiving antihistamines and corticosteroids. It was also noted that 56% (14/25) needed to receive a second dose of premedication. The general infusion times lasted between 3 to 6 hours.
Paccal Vet®-CA1 (paclitaxel for injection) differs from human generic paclitaxel as it eliminates the need for Cremophor® through the use of a patented combination of water-soluble retinoid derivatives (of vitamin A) called XR-17. This novel formulation has been evaluated in dogs. In 2 pilot studies, collectively 60% (6 out of 10 dogs) with mammary carcinoma treated with paclitaxel or Paccal Vet®-CA1 (paclitaxel for injection) were accessed as responders (complete or partial). Responders had progression-free survivals (PFS) ranging from 56 days – 1 year and overall survivals ranging from 56 to 498 days vs. non-responders that had PFS ranging from 20 to 56 days and overall survivals ranging from 40 to 56 days. In separate studies evaluating squamous cell carcinoma, 24% (4/17) patients responded to therapy. Responders (2/17) had PFS ranging from 260 to 388 days. Dogs with stable disease (2 /17) had PFS ranging from 91 to 144 days. Non-responders (13/17) had PFS ranging from 21 to 63 days. In a randomized trial investigating the efficacy and safety of this formulation in non-resectable Grade 2 or 3 mast cell tumors in dogs, the overall response rate at 14 weeks was 7%. Similar to all chemotherapy agents, most side effects were transient and clinically manageable (alopecia, neutropenia, vomiting, anorexia and lethargy). A dose delay was required in < 10% of dogs and in a large-scale study, only 1% (2/168) of dogs experienced allergic reactions.
Based upon data from these studies, Paccal Vet®‑CA1 has been granted conditional approval by the FDA for the treatment of:
- Non-resectable stage III, IV or V mammary carcinoma in dogs that have not received previous chemotherapy, or radiotherapy.
- Resectable and non-resectable squamous cell carcinoma in dogs that have not received previous chemotherapy, or radiotherapy.
Full approval will be based upon data from several current prospective studies. The dose (150 mg/m2) is administered intravenously over 15 to 30 minutes every 3 weeks for up to 4 doses. It is important to note, however, that a conditionally approved drug CANNOT be used in a “off label” manner per the FDA.
Paccal Vet®‑CA1 represents the first conditionally approved taxane in veterinary medicine and preliminary data suggests it is not only safe but has efficacy against mammary cancer and squamous cell carcinoma. Once fully approved, we will have the opportunity to test this agent against a wide variety of histologies and potentially incorporate its use into existing chemotherapy protocols.
Dr. Craig A Clifford DVM, MS, DACVIM (Oncology)
Hope Veterinary Specialists
Cremophor® is a registered trademark of BASF.
De Laurentiis et. al. J Clin Onc 26:44-53, 2008
Gelderblom et. al. European Journal of Cancer 37:1590-1598, 2001
Poirier et al. JVIM 2004:18:219-222
Von Euler H. et al. J. Vet Comp Onc: 2013;11:243-255
Vail et al. JVIM 2012;26:598-607
Paccal Vet®-CA1 package insert
News Release: 10/1/2014
Philly Puppy Up! Walk will Raise Money for Cancer Research
Hope Veterinary Specialists hosts November 1 event
(Malvern, PA) – Dogs and their owners are invited to participate in a two-mile Walk to raise funds for cancer research. The Walk will benefit the 2 Million Dogs Puppy Up! Foundation, an organization dedicated to supporting research that helps people with cancer as well as dogs with cancer. The Walk will be held in conjunction with an Open House at Hope Veterinary Specialists in Malvern, on Saturday, November 1.
“The meaning behind our name, Hope Veterinary Specialists, is quite simple,” explains Dennis Burkett, VMD, hospital owner. “It’s where the hopes for tomorrow reside today. By sponsoring the Philly Puppy Up! Walk and having an Open House together, we are able to show our commitment to our patients, to research and to the community.”
Hope Veterinary Specialists, a privately owned entity, has offered specialty care and 24/7 emergency and critical care treatment for dogs and cats in Chester County for the last 10 years. With a full-range of specialists including three board-certified Emergency and Critical Care veterinarians, the practice offers comprehensive care for pets and their families while working closely with the pet’s primary veterinarian. Specialty services include: acupuncture, anesthesia and pain management, cardiology, emergency and critical care, dermatology, diagnostic imaging/radiology, internal medicine, interventional radiology, neurology, oncology, and surgery.
The Philly Puppy Up Walk begins at 10 am, on Saturday, November 1. The Hope Veterinary Specialists Open House will be held from 11 am to 2pm at 40 Three Tun Road in Malvern, Pa. Open House festivities include hospital tours, an interactive adopt-a-pet program for children, live music, presentation of dog agility, police dog demonstrations, pet caricatures and more. To register to walk: http://puppyupphilly.kintera.org.
Hope Veterinary Specialists
Hope Veterinary Specialists first opened its doors in 2004 as the Animal Critical Care and Specialty Group. It changed its name in 2012 to better reflect its vision. Its 24/7 Emergency and Specialty Care hospital is at 40 Three Tun Road in Malvern, Pa. The practice recently captured the title of PHL 17’s HOT LIST’s Best Veterinarians as well as Petplan’s 2014 Best Veterinarian, Dr. Kim Slensky, and the Pennsylvania Medical Association Vet Tech of the Year, Brandy Terry..