By Rance Gamblin. DVM Diplomate ACVIM (Oncology)
In October, I was able to attend the Veterinary Cancer Society (VCS) annual meeting in Austin, TX. This is a meeting I look forward to every year, for a wide variety of reasons. Certainly there is all the fun and fellowship of seeing friends you haven’t seen since last year, and the “Live Music Capital of the World” made for a great backdrop for the social side of this conference. The most amazing thing to me, however, is the dramatic growth of this meeting, both in number of attendees as well as the depth and quality of the information presented there. I can remember some of my early VCS meetings, which I feel could likely have easily been held in Metro’s conference room. Contrast that to the last meeting, with 519 attendees! There were many I wanted to talk to that I never saw over the course of the conference!
One of the most enjoyable parts of the meeting is listening to the Resident Abstract Presentations, which are split into Basic and Clinical Science divisions. While I am a clinician exclusively, the Basic Science Program commonly still provides information potentially very clinically relevant.
Residents from Cornell presented information regarding the synergistic antiproliferative effects of calcitriol with lomustine, vinblastine and imatinib on canine mast cell tumor lines in vitro. You can bet a study of the clinical utility of this combined therapy is in the works.
Texas A&M residents demonstrated inhibition of feline vaccine associated sarcoma cell lines by mastinib, in combination with radiation therapy or doxorubicin/carboplatin chemotherapy.
NCSU residents proved differential gene expression between metastatic and nonmetastatic canine soft tissue sarcomas, providing information on potential new therapeutic targets.
In the Resident Clinical Sciences division there were MANY excellent and relevant abstracts presented, including:
Increased neutrophil counts and increased levels of monocyte chemotactic protein –1(MCP-1) predict poorer treatment response and decreased survival in dogs with lymphoma.
Radiation therapy may significantly improve control time and survival in dogs with oral lymphoma, but adjuvant chemotherapy may still be indicated.
Cerenia® is effective at preventing delayed vomiting in dogs receiving doxorubicin. Prophylactic use may eliminate the need for dose reductions due to GI side effects.
Hydropulsion of nasal masses resulted in recovery of diagnostic material in 90% of cases. Additionally, the procedure often debulked the mass improving clinical signs, however, this procedure should not be undertaken in animals with compromise to the cribiform plate.
Re-irradiation of nasal tumors at time of relapse resulted in second remissions in most treated dogs. All dogs did develop late radiation side effects, but most were mild. Total blindness due to radiation retinopathy was reported in 2 of 9 treated dogs.
Cytology was shown to have poor sensitivity in the diagnosis of oral neoplasia.
Periarticular histiocytic sarcomas appear to have a better prognosis than histiocytic sarcomas of other locations (median survival time of 391 days vs. 128 days).
In the General Sessions, there were so many good presentations that I had to be very selective about those I shared here. Some of the most relevant for the veterinary practitioner included:
For dogs treated with the tyrosine kinase inhibitor, mastinib (Kinavet®), control of mast cell disease at 6 months was significantly more important in predicting long-term control than was tumor response at 6 weeks. Short-term responses may be irrelevant in assessing clinical efficacy.
Rhabdomyosarcomas are relatively uncommon tumors in veterinary medicine but when they do occur, they are commonly in younger patients and can have very aggressive clinical behavior. A University of Illinois study revealed a 73% metastatic rate at presentation with a stunningly short median survival time of only 14 days.
There were several great presentations on canine osteosarcoma with these “pearls” of wisdom shared:
Administration of chemotherapy post development of metastasis in long-term (>1 year) survivors did not improve survival.
Addition of gemcitabine to carboplatin did not improve survival times versus administration of carboplatin alone. This is interesting given the reported synergism between these two chemotherapy agents.
Interim data suggests that alternating 3 doses each of carboplatin and doxorubicin is NOT superior to 6 doses of carboplatin given as a single agent.
Increased monocyte counts, increased lymphocyte counts, increased ALP, humeral location and young age at presentation were all associated with poor outcomes in dogs with osteosarcoma.
My two favorite presentations:
A veterinary student working in a private oncology referral practice in New Mexico presented data showing a 100% resolution rate for acanthomatous epulides treated with intralesional bleomycin. No recurrences were noted, with a median follow-up time of 842 days!!
Private oncologists from Arizona presented evidence that we likely should manage T cell lymphomas differently. Dogs with T and B cell lymphomas were given 1 dose of doxorubicin and the response determined. Dogs with B cell lymphoma responded 100% of the time, but those with T cell lymphomas responded only 50%! Certainly, this lends support to the fact we need to find a better way of treating T cell lymphoma than relying on doxorubicin-based regimens.
As you can see, there was a lot to see and hear at the VCS. For those of you with an interest in cutting-edge cancer medicine, consider joining the VCS by going to vetcancersociety.org. Perhaps I will see you at the next meeting!!
By Rance Gamblin. DVM Diplomate ACVIM (Oncology)
Oral tumors are a common problem in the dog, being the 4th most commonly reported site. Of the reported oral malignancies, malignant melanoma is the most common and certainly the most devastating. Any breed can be affected but smaller breeds seem to be more commonly reported. Males seem predisposed and the average age at presentation is 11 years.
Oral melanoma can arise from either the gingival, buccal or labial mucosa. They can be confused with anaplastic sarcomas or even carcinomas if they are amelanotic, which occurs in approximately one-third of cases. Special immunohistochemical stains such as MelanA or S100 may be needed for definitive diagnosis.
Oral melanoma is a highly malignant tumor on multiple levels. The first problem is local tissue invasion and destruction. Bone involvement is reported in approximately 60% of cases, making aggressive resection necessary for local tumor control. Without adequate local tumor control, euthanasia is commonly necessary because of mechanical impairment of eating, swallowing, secondary infection, pain and other oral issues. The second major issue is that of frequent metastasis. The draining lymph nodes and lungs are the most commonly reported sites, with metastatic rates of 41-74% and 14-92%, respectively. Metastatic rate is dependent on the site, size and stage of the primary tumor. Historically, even with good local tumor control, any sizeable melanoma generally resulted in the death of the patient within 9 months due to development of metastasis.
Therapy has traditionally been a “two-pronged” approach, local tumor control with either surgery or coarse-fractionated radiation and treatment of regional and distant microscopic metastatic disease with chemotherapy. The major problem has been, in both human and veterinary medicine, that melanomas appear to be generally resistant to most commonly used chemotherapeutics. Carboplatin has become the standard of care chemotherapy drug; with response rates reported around 30%. However, there has largely been poor supportive evidence for prolongation of survival.
Researchers have long tried to stimulate an effective immune response to aid in the treatment of melanoma. Numerous immunomodulators and crude vaccination protocols have been attempted, most with poor results. However, with current DNA engineering techniques, a novel vaccine product has entered the market that is revolutionizing melanoma therapy.
The Canine Melanoma Vaccine produced by Merial became commercially available via a conditional USDA license earlier this summer. However, this product has been in limited multicenter trials for several years. This vaccine utilizes a DNA plasmid that encodes for HUMAN tyrosinase, a protein expressed on the surface of melanoma cells, regardless of species. While human tyrosinase is very similar in composition to canine tyrosinase, there is enough difference to stimulate an immune response against the tyrosinase molecule. This immune response recognizes not only the human molecule, but the canine as well, leading to eventual cell death.
The improvement in survival rates has been impressive. Median survival for dogs with Stage II or III oral melanoma is reported to be less than 150 days. However, for dogs receiving the melanoma vaccine, median survival times are reported to be almost 400 days! The vaccine is given as an intramuscular injection using a high-speed transdermal device every 14 days for 4 administrations, and boostered every 6 months.
As with any treatment, proper case selection and adjunctive therapy is important. We have learned several things about proper utilization of the vaccine. First, complete local control (preferably with surgery) is very important. Local treatment failures are being reported for some treated patients that still had microscopic residual disease. Appropriate staging, including lymph node aspirates and chest radiographs is also important in assessing response and effectiveness. If positive nodes are detected and are not fixed to surrounding tissues, lymphadenectomy can remove a large tumor burden, improving likelihood of response. Lastly, adequate time is needed to allow mounting an effective immune response. Studies indicate at least 6-8 weeks are required after the last induction vaccine to see maximal immune response. This is especially important in patients with advanced disease at presentation, as their life expectancy may not allow for adequate response time to the vaccine.
I am commonly asked about efficacy of the melanoma vaccine for treatment of malignant melanoma of other sites, such as nailbeds, footpads, etc. The conditional license is for oral melanoma, but “off study” research of these other sites has indicated similar response rates as for oral melanoma. We presently are offering vaccine therapy to any pet with a diagnosis of malignant melanoma, regardless of site.
Lastly, melanoma vaccine therapy is not inexpensive. Typical cost of treatment for the initial vaccine series is approximately $2300, not including any surgery or other treatment costs. However, when compared to the previous “standard of care” therapy, carboplatin chemotherapy, costs are essentially equal, with significantly improved results.
If you have additional questions regarding melanoma vaccine therapy, or if you have a patient you would like to have evaluated, please feel free to contact me at 330-666-2976.