INJECTION SITE AND VACCINE ASSOCIATED SARCOMAS
AS Moore, MvSc, Diplomate ACVIM (Oncology)
Tufts Animal Expo Conference Proceedings
September 1, 2001
AS Moore, MvSc, Diplomate ACVIM (Oncology)
INJECTION SITE AND VACCINE ASSOCIATED SARCOMAS:
New Advances for the New Millenium
SMALL ANIMAL ONCOLOGY
AS Moore, MvSc, Diplomate ACVIM (Oncology)
Keywords: vaccine, sarcoma, cat, diagnosis, surgery, chemotherapy, home care
There are two types of emergencies: true life threatening emergencies, and emergencies in the hearts and minds of our clients. There is no question that for many clients, the development of a life threatening cancer in their cat is a perceived emergency and as veterinarians we must respond appropriately and completely. When the diagnosis of a cancer is coupled with the supposition that it may be the result of a vaccine or injection that was given with the intent of preventing a disease, the result is an entirely new level of concern. In this situation, issues of trust and perceptions of who and what our profession is all about arise. In this situation, the veterinary profession is responding to perhaps the greatest threat to preventative health care: the association between vaccines and the subsequent development of malignancies. The impact of this serious problem has forced organized veterinary medicine as well as state, regional and local officials to respond to the question: is this cancer-associated vaccine threat important enough to change the way we approach vaccinating cats? The profession has had to respond quickly to determine how to treat and prevent this devastating disease. In essence, this is a critical care concern for the health and well being of the profession as much as it is for our feline patients and the clients that entrust us with their care.
In a hallmark epidemiological study1, sarcomas were temporally associated with previous injection of various vaccines into specific body locations. Feline leukemia virus, rabies vaccination, and development of fibrosarcomas at the injection site within a year following vaccination were statistically associated. More recently, other injections have been linked to tumor development prompting recommendations to change the name from vaccine associated, to injection associated sarcomas. This study demonstrated a 5.5% increased risk of developing sarcomas in response to feline leukemia virus vaccination and a twofold increase in risk of development of sarcomas after rabies vaccination. Subsequent research has led to the conclusion that there is no specific vaccine that is absolutely known to be the major causative agent of these vaccine/injection-induced cancers. Originally, Kass et al1 reported the actual incidence of the tumor was estimated to be approximately one sarcoma per 10,000 feline-leukemia virus and rabies vaccines administered. Many others within the profession have suggested that this estimate is too low. No association between sex, breed, and concurrent viral infections in the development of these sarcomas was found. Some have hinted that the aluminum adjuvant in many of these vaccines may be associated with development of vaccine/injection-associated sarcomas. However, Kass, et al.,2 demonstrated that certain aluminum-free vaccines may also be associated with development of these soft-tissue sarcomas. Increase in development of soft-tissue sarcomas following one vaccination was 50%, following two vaccinations was 127%, and following three or four vaccines simultaneously administered at the same location was approximately 175%.2 Therefore, there appears to be a multi-factorial association between vaccines and growth of sarcomas.
Gender: No specific gender consistently noted.
Age: Middle to older aged cats.
Note that vaccine/injection associated sarcomas appear to occur in cats at a younger age compared to other sarcomas of similar histologic types.
Breed: No specific breed predisposition consistently noted.
Owner observation: Lump in or near a site of vaccination.
Other historical considerations/predisposition: The more often a cat is vaccinated, the higher the risk of vaccine associated sarcomas. Vaccine/injection associated malignancies have been reported to develop within weeks to years after injection.
Clients with cats with vaccine or injection associated malignancies are often scared and overwhelmed. They may be angry with the vaccine manufacturers and the veterinarian or feel guilty for authorizing a preventative procedure that resulted in harm for their cat.
Cancer is an evil, frightening, and threatening disease that is emotionally overwhelming. These feelings of vulnerability and lack of control need be acknowledged as the truth about this disease and the treatment options are carefully explained.
Due to the emotional nature of this disease, clients with cats with these malignances are often initially unable to process information and make decisions. Therefore, all explanations, facts, figures and decisions should be written or recorded for subsequent review. Although the disease may be perceived as an emergency, decisions regarding treatment need not be made quickly. These significant decisions may best be made after the client has had time to thoughtfully and rationally consider the treatment options and all the information presented.
Physical Examination Findings:
Firm swelling at or near site of previous vaccination. Note that this lump or thickening may appear days to years after vaccination.
Occasionally, the lump may occur in sites ventral to site of vaccination presumably due to ventral migration of causative agent.
Metastatic disease, while relatively rare, can result in regional lymphadenopathy or respiratory signs such as tachypnea or dsypnea.
Step 1: Obtain a Tissue Diagnosis of the Primary Tumor
A fine needle aspirate cytology can be very helpful in eliminating other etiologies of a mass such as abscess, granuloma, foreign body, or persistent vaccine/injection associated “reaction”. Note that some vaccine granulomas can have very “reactive” fibroblasts that may have characteristics that can be confused with a malignant process. These changes include multiple nucleoli, mitotic figures, etc. When there is any doubt, a histologic biopsy of these lesions is imperative.
A preoperative, incisional biopsy is a vital prelude to definitive treatment of this highly invasive malignancy. .
The aspirate and biopsy must be done such that the biopsy track can be completely surgically excised or included in the radiation therapy field.
Vaccine/Injection Associated Sarcomas can come under a number of histologic diagnoses including fibrosarcoma, neurofibrosarcoma, nerve sheath tumor, hemangioperictoma, malignant fibrous histiocytoma, schwanoma, leiomyosarcoma, rhabdomyosarcoma, etc.
Step 2: Determine the Extent of the Tumor by Staging the Disease
Chest and regional (tumor) radiographs are essential to identify metastatic disease, the extent of the primary neoplasia, or to evaluate the patient for underlying disease.
Palpation of, and an aspirate or biopsy of enlarged lymph nodes is vital to document any metastatic disease to the regional lymph nodes.
Computerized tomography (CT) or magnetic resonance imagine (MRI) are ideal to determine the extent of the primary tumor.
Ultrasound evaluation of the soft tissue structures around the primary tumor is also ideal to determine the extent of the primary tumor.
Step 3: Determine the Condition of the Patient
Hemogram, platelet count, biochemical profile, urinalysis, T4, FeLV and FIV are essential to document malignancy related disorders or problems unrelated to the cancer that would potentially affect treatment decisions and prognosis.
Step 4: Support, Educate and Empower the Client
Cancer steals power and control from the client. The results of diagnostic tests not only direct therapy and allow the clinician to provide a prognosis, but they empower a client with information, thus allowing them to be able to make intelligent, appropriate decisions in this stressful setting.
Provide decision making and directing empowerment to the client by educating them about the individual risks and benefits of each diagnostic test. By including them as a member of the veterinary health care team most clients will take an active roll to benefit the patient and the veterinary health care team.
Other Diagnostic Findings:
No one test will definitively distinguish a vaccine or injection associated sarcoma from a sarcoma of unrelated origin. Histopathology may provide indirect evidence that the sarcoma in question may be vaccine associated. Regardless, the treatment is the same (see below).
Summary of Diagnostic Criteria:
Lymph Node Aspirates or Biopsy
Hemogram, Biochemical Profile, Urinalysis, T4, FeLV, FIV
Primary tumor (diagnosed with a biopsy and/or aspirate)
Metastatic tumor (diagnosed with a biopsy and/or aspirate)
Abscess (diagnosed with fine needle aspirate cytology, elevated body temperature and a neutrophilia)
Granuloma (diagnosed with fine needle aspirate cytology and/or biopsy, and possibly a monocytosis)
Foreign body (diagnosed with a fine needle aspirate cytology and/or biopsy)
Post vaccine reaction (Diagnosed with a fine needle aspirate and or biopsy)
Small to Medium Sized Tumors: Wide and deep surgical excision taking the tumor and a ‘cuff’ of normal tissue around these highly locally invasive tumors is essential. Adjunctive therapy with radiation and chemotherapy are often recommended (see below). Radiation therapy is initiated at suture removal and chemotherapy is initiated approximately 2 weeks after the completion of radiation therapy. Concurrent supportive, nutritional and pain management are essential for these patients (see below).
Large, Unresectable Tumors: Tumors that cannot be comfortably excised with one definitive procedure may be downsized with radiation therapy, or in some cases, chemotherapy. These tumors can sometimes be surgically removed subsequently. If radiation is used initially followed by surgery, chemotherapy is recommended at the time of suture removal. Radiation therapy dosages are determined with CT or MRI guided, two or three dimensional radiation planning and frequently involves 3-6 weeks of therapy using daily 18-30 dosages of 2-3.3 Gy fractions to a total dosage of 54-64 Gy. Chemotherapy is as listed blow. Concurrent supportive, nutritional, nausea, and pain management are often essential for these patients (see below).
Microscopic Metastatic Disease
Doxorubicin (25 mg/m2 body surface area q3 weeks IV slowly over 20 minutes with normal renal and cardiac function) or carboplatin (200-220 mg/m2 body surface area q4 weeks slowly over 20 minutes with normal renal function) therapy is intiated after surgery and radiation therapy.
The goals, risk and benefits of each treatment must be carefully outlined recognizing that the only words more frightening then cancer are chemotherapy and radiation therapy.
The client must be empowered with the ability to intervene one behalf of their cat to support, nurture and prevent any adverse effects associated with surgery (pain, 2.5 mg fentanyl transdermal patch q 72 hrs prn or acupuncture), chemotherapy (nausea, metaclopramide 2.5 mg PO q8 hrs prn), and radiation (pain, 2.5 mg fentanyl transdermal patch or acupuncture). The common goal of compassionate care must be carefully reviewed.
Palliative radiation therapy (3-8 Gy fractions prn or on days 0, 7, 21 may be helpful in some cases.
Pain: 2.5 mg fentanyl transdermal patch q 72 hrs prn or acupuncture
Nausea: metaclopramide 2.5 mg PO q8 hrs prn and/or dolasetron mesylate (0.6-1 mg/kg IV slowly q24 hours or ondansetron HCl 0.1-0.3 mg/kg IV or PO q12 hours)
Appetite: cyproheptadine 2 mg PO orally q12-24 hrs and/or 0.25-5 mg/kg megesterol acetate PO daily for 3 days then q4872 hrs prn anorexia
Patient Monitoring-Home Management:
Surgery: keep incision clean and dry. Monitor cat to ensure that incision is not hot or swollen. Watch sutures to make sure that patient does not remove them. Monitor for signs of discomfort.
Radiation therapy: Hair loss, skin color change, altered hair color regrowth are all expected. Moist or dry desquamation is possible requiring cleaning with mild soap and water. Petroleum based oils or creams are contraindicated.
Chemotherapy: See supportive therapy. Preemptively treat nausea. Monitor for elevated body temperature, especially at the time of chemotherapy nadir (doxorubicin, 7-10 days; carboplatin, day 21)
Clients should receive detailed home instructions on each treatment, their risks and benefits. Surgery: A patient that is at high risk for anesthesia (eg: organ failure, anemia) Chemotherapy: Patient with concurrent infection or neutropenia (<3,000/ul prior tothe administration of doxorubicin or carboplatin), Cardiac or renal disease.
Radiation therapy: A patient that is at high risk for repeated anesthesia (eg: organ failure, anemia)
Lack of metastatic disease
Tumor “free” margins
Presence of metastatic disease
Prior unsuccessful surgery
Tumor at surgical margins
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