small animal oncology

Prince Nanda

Nikunj Gupta

Cancer is the major cause of death in pets greater than 10 years old

45% of all dogs older than 10 years of age die of cancer

23% of all dogs die of cancer

Neoplasms: defined as growth of new cells that proliferates without control, serves no useful function and has an orderly arrangement.

Tumour: neoplastic masses that causes swelling on the body surface.

Cancer: it is specifically referred to the malignant tumours

Oncology: defined as field of medicine which deals with cancerous tumors, monitoring its development, diagnosis and the course of the treatment and follow-up

James EWING & BJ Kennedy-Father of Oncology

TERMINOLOGY

Characteristic Benign Malignant

Shape Round, wart like or pedunculated

Irregular

Metastasis Not present Present

Mitotic figures Less More

Blood supply Less Marked

Mesenchymal tumours: tumours derived from connective tissue (cartilage, bone, muscle, fibrous tissue)

Benign : Name of the tissue (suffix oma) e.g. fibroma

Malignant: name of the tissue (suffix -sarcoma) e.g. fibrosarcoma

Epithelial tumours: tumours derived from embryonic cell layers viz. mesoderm, endoderm and ectoderm

Benign:

Malignant: name of the tissue (suffix -carcinoma)

Papilloma –Epithelial surfacePolyp -Mucosal surfaceAdenoma – Glandular surface

Undifferentiated tumours: these tumours give no clue about their cell of origin

Mixed tumours: contains multiple cell types derived from single or multiple germ layers. E.g.

• Teratomas – contain more than one germ layer

• Mixed mammary tumour – contains epithelial elements + mesenchymal elements (Fat, bone, cartilage)

Anaplasia of cells (poor cellular and nuclear disintegration)

Cells are hyperchromatic because of increased DNA content

Increased nuclear : Cytoplasmic ratio (Becomes 1:1 instead of 1:4 / 1:6)

Numerous mitotic figures (are the chromosomal aggregations in the mitotic cells)

Basophillic cytoplasm: because of large number of ribosomes

Cancers result because of transformations of normal proto oncogenes to its mutant form – ONCOGENES

Target of genetic damage

Growth promoting proto-oncogenes

Growth inhibiting cancer suppressor genes

Genes that regulate apoptosis

GENETIC DAMAGE MUST BE NON-LETHAL

Self sufficiency in growth signals – coz of production of oncoproteins which don’t depend on external signals

Evasion of apoptosis

Limitless replicative potential coz of increase production of enzyme Telomerase – this enzyme restores the length of DNA and makes the cell immortal and continuously dividing.

Sustained angiogenesis

Ability to invade and metastize.

Localised tumour

HaematogenouslymphaticsTrans coelomic

Invasion of extra cellular Matrix

Detached tumour penetrate basement membrane

Integrins helps to bind to ECM Invasion is assisted by secretion of ProteasesFurther Migration also occurs

in same manner

CELL MEDIATED RESPONSE

Three type of cells are involved

NK cells: first line of defense against tumour cells

Cytotoxic T-lymphocytes (CD8 + T-cells) by recognising MHC class-I antigens expressed on tumour cells

Activated macrophages

HUMORAL RESPONSE By ADCC (antibody dependent cellular toxicity) - by NK-

CELLS

By activation of complement.

1.)By altered MHC expression

2.)By antigen masking – when complexed with gyycocalyx molecules

3.)Tolerance

4.)Immunosuppression – tumours produce TGF – alpha which inhibit proliferation of lymphocytes and macrophages

Heriditary factors:

DOGS : Heriditary multifocal Renal cystadenocarcinoma & nodular dermatofibrosis in German Shepherd.

Brain Tumors :Boston Terrier & Bull Dog.

Chemicals: Toxins from bracken fern causes urinary bladder

Radiation : UV-Rays:

Squamous Cell Carcinoma. In ear in white cats.

Squamous Cell Carcinoma in eyes in Herford Cattle

INFECTIOUS AGENTS:

Mostly oncogenic RNA Retroviruses.

Papovaviruses.

Marek’s diease (Herpes virus)

HORMONES:

Increase testosterone level causes Prostate Cancer in dogs.

CACHEXIA: Loss of body weight, loss of body muscle & fat.Due to annorexia, nutritional demand of cancer tissue.

Hypertrophy osteopathy in dogs & cats.

Thrombocytopenia is seen in one-third of all dogs suffering with cancer.

Anemia & DIC are seen in dogs with hemengiosarcoma.

Parneoplastic Syndrome: Related to hypercalcemia & hyperglycemia.

Histological and cytological method

Biochemical Assays

Molecular Dx

Samples can be taken by Biopsy

Fine needle aspiration

Cytological smears

Exfoliative cytology

Tumour associated enzymes, hormones and other tumour markers in the blood are estimated

Two tumour markers in the blood are –

Carcino-embryonic antigen (CEA)

Alpha-foeto proteins

PCR

FISH technique (Flourescent Insitu Hybridisation)

DNA micro array analysis

Gene chip technology

Southern blot analysis

Flow cytometry

Immunocytochemistry

DNA probe analysis

Radiographs

CAT scan

MRI

Ultrasonography

What about extent?

What about its stage?

Number of LN involvement

Whether it is metastatic or not?

Lets see….

T = primary tumor size or extent

Tis: preinvasive tumor (in situ)

T0: no evidence of tumor

T1: tumor <5 cm in diameter but confined to primary site

T2: tumor >5 cm in diameter or ruptured tumor

T3: infiltrative tumor

a: no bone invasion

b: bone invasion

N = nodes

N0: no evidence of lymph node enlargement

N1: moveable ipsilateral nodes enlarged

N2: moveable contralateral/bilateral nodes enlarged

N3: fixed nodes

M = metastasis

M0: no metastasis

M1: metastasis detected

Surgery

Radiation therapy

Chemotherapy

Hyperthermia

Photodynamic therapy

Others

Gene therapy

Anti-angiogenic drugs

Immunotherapy

Alternative therapies

Mammary tumors (except inflammatory mammary cancer)

Prostate tumors

Oropharyngeal tumors

Skin cancers

GI tumors

Lung tumors

Bone tumors

Risks increase with age of patient

Most mortalities resulting from surgery are associated with:

pulmonary emboli

Pneumonia

cardiovascular collapse

primary disease

Other complications include:

Abscesses

wound infections

blood loss

incomplete wound healing

Brain tumors

Curative: small pituitary tumors

Longer survival time: intracranial tumors and spinal lymphomas

Tumors of the nasal cavity

Thyroid tumors

Soft tissue sarcomas

Mast cell tumors

Survival of cancer cells at the center of larger tumors

Local effects to skin, lining of GI tract, and hair

Long term effects:

Necrosis

Non-healing ulcerations

Organ dysfunction

blindness

Used prior to surgery to shrink tumor size

Used following surgery to destroy remaining cancer cells that were left behind

Limitations:

Radiation must be postponed until surgical incision has completely healed

Cancer cells in the area of scar tissue are often more resistant to radiation

As sole agentSystemic

cancers hematologic

malignancies

metastatic carcinomas

Metastatic sarcomas

As adjunct therapyGiven to

patients with no overt evidence of residual cancer following surgery or radiation

Toxicities are particularly against cells of the bone marrow, GI lining, and hair follicles and can result in:

Immunosuppression

Anemia

Nausea and vomitting

Delayed wound healing

Hair loss

Chemotherapy + Radiation

Certain drugs are radiosensitizers

This increases the efficacy of the radiation

Help slow down metastatic growth

Chemotherapy + Surgery

Shrink large tumors prior to surgery

Help eradicate microscopic cancer cells which remain after surgery

Help slow down metastatic growth

Most effective in the treatment of localized tumors in combination with radiation or chemotherapy

Used to treat small (<1.0 cm in diameter) benign and malignant superficial tumors

Equally damaging to both cancer and normal cells

Frequency of skin burns and infarcts can be as high as 45%

Hyperthermia + Radiation

In humans, combining these two therapies to treat cancer was found to double the number of complete responses

In dogs, this combination improved the rate of complete response in primary tumors resulting in prolonged survival time

However, many dogs later succumb to metastatic disease

Hyperthermia + Chemo.

Some drugs work more efficiently above normal body temperatures

Hyperthermia may offer a protective effect for normal tissues against drug toxicities

Some studies have shown that combining these therapies actually increases toxicity

Has been used limitedly in veterinary medicine

Used in dogs with localized, superficial, and minimally invasive tumors such as those affecting skin and linings of urinary bladder and oral cavity

Inability of light to penetrate deeply into tumor tissue

Tissue retention time of photosensitizers

Patient must remain in subdued light for 4-6 weeks

Not all tumors absorb photosensitizers at same rate and at same concentration

Gene therapy

Anti-angiogenic drugs

Immunotherapy

Alternative therapies

Acupuncture

Massage

Herbal and botanical medicine

Suicide gene therapy

Genetic immunotherapy

Tumor suppressor gene therapy

Drug resistance gene therapy

Inhibit tumor growth by cutting off tumor’s blood supply

Many of these drugs are in the early stages of clinical development in the treatment of both human and canine cancer

Biologic Reponse Modifiers:

Nonspecific immunomodulators

Lymphokines/monokines

Adoptive cellular therapy

Antibody therapy

Growth factors

Indications:

Lymphoma

Melanoma

Mastocytoma

Oteosarcoma

Soft tissue sarcomas, including fibrosarcoma and hemangiosarcoma

Acupuncture

Palliative treatment

Pain

Post-op & chemo-induced nausea and vomiting

Massage

May be contraindicated

Herbal and Botanical Medicine

Herbs are used in conjunction with chemotherapy or radiation to help strengthen the individual and mitigate side effects

Often ignored aspect of cancer treatment

Important in treating cancer cachexia

May control growth of certain tumors

Decrease side effects of cancer treatments

Animals with cancer have alterations in metabolism which results in clinical alterations

This occurs early in all cancers and decreases quality and quantity of life

Broken in four phases

Specific nutritional requirements of animals with cancer is unknown

Nutrients in order of importance

water

calories and protein

minerals and vitamins

Carbohydrate metabolism

Tumors preferentially metabolize glucose for energy by anaerobic glycolysis forming lactate

buildup of lactate results in net energy loss by the body and net gain by the tumor (uses ATP to convert lactate to glucose)

Protein metabolism

Good source of energy for tumor

Can result in clinically significant deficiency in AA

decreased immune function

surgery healing

decreased GI function

Benefits of certain AA

Arginine- decrease tumor growth and metastatic rate in some rodents

Glycine-shown to decrease cisplatin induced nephrotoxicity

others as well…

Lipid metabolism

Some tumors cells have problems utilizing lipids as fuel source

fats are usually last to be depleted

type of lipid verses amount of lipid

polyunsaturated n-3 fatty acids

Vitamins- some evidence indicate might be helpful in cancer patients

Retinoids, beta carotene, Vitamin C, D, and E

Minerals- May be helpful

Zinc, Cu, Se, etc…

Fiber- insoluble and soluble

Garlic- may help cancer patients

Green/Black tea- Black tea may have soothing properties associated with radiation-induced oral mucositis.

Shark cartilage-NO

Food aversion- a common outcome of side effects of cancer and cancer treatments in humans

Difficult to prove it occurs in animals

What food to feed?

How to feed the food?

Monitor and reassess feeding plan constantly (Is the patient getting better)?

Ideal diet would have

minimal simple carbohydrates, fiber

highly bioavailable protein with certain AA

higher fat levels with polyunsaturated n-3 fatty acids

adequate levels of antioxidants

a great smell and taste great!

Achieve with homemade diets or various commercial diets

Should be discussed constantly with client

Educate client on options

Final humane treatment

•Meningioma is the most common primary brain tumor in dogs and cats.•Glioma is the most common primary brain tumor in brachycephalic breeds.•Seizure is the most common clinical sign of brain tumors in dogs•Lymphoma is the most common spinal cord tumor in cats, whereas meningioma is most common in dogs.• Dogs with peripheral nerve sheath tumors commonly present with chronic lameness and severe muscle atrophy.

Melanoma, squamous cell carcinoma (SCC), andfibrosarcoma are the most common malignant oral tumors in dogs;

Approximately 5% of oral tumors in dogs are benigndental tumors (epulides), which do not metastasize and warrant an excellent prognosis.

The presence of loose teeth in a patient with otherwise good dentition warrants a search for oral neoplasia.

Maxillary fibrosarcoma (FSA) Epulides

Dogs with intranasal tumors are often presented for unilateral or bilateral nasal discharge that may be hemorrhagic and is often initially antibiotic responsive.

Radiation therapy is the primary treatment for canine intranasal tumors, with a median survival time of approximately 1 year.

Facial deformity which may be due malignancy

Exophthalmos and strabismus are the two mostcommon presenting signs associated with orbitaltumors

Diffuse iris melanoma extending from the 1 o’clock to 6 o’clock position.

Nodular granulomatous episcleritis Meibomian adenomas

Chondrosarcoma with severe local infiltration of the calvarium and frontal sinus

• Laryngeal tumors encompass a wide variety of histologic types but nearly identical clinical signs ofvoice changes, dyspnea, and cough.

Primary tracheal tumors most frequently lead to development of chronic cough, stridor, and wheezing.

Advanced diagnostics, including laryngoscopy, bronchoscopy, and CT or MRI, are often necessary to definitively diagnose laryngeal and tracheal tumors.

This bronchoscopic image from a dog demonstrates a large mass that extends from the wall of the trachea and nearly occludes the entire tracheal lumen.

Lateral cervical radiograph of a dog with a spaceoccupying soft tissue mass within the laryngeal lumen (arrow). Biopsy of this mass revealed a rhabdomyosarcoma.

Identification of a solitary, well-circumscribed lung parenchymal mass with plain radiography in a middle- aged to older dog or cat should raise suspicion for a primary lung tumor

Surgical excision is the treatment of choice for primary lung tumors. Those amenable to complete resection are associated with longer patient post-surgical survival time

Thymoma and lymphoma are the most common tumors of the cranial mediastinum.

Metastases in Lung

Primary cardiac tumors are uncommon in dogs and cats.

HSA (Haemagiosarcoma) is the most common cardiac tumor of dogs

An intraluminal leiomyoma protruding from the vulva

Ovarian carcinoma

Squamous cell carcinomas

Cutaneous plasma cell tumors

Melanoma Mast Cell Tumour

cecum is the most common site forGastrointestinalstromal tumors (GISTs

Surgical resection is the treatment of choice

Osteosarcoma

Most common tumours in female dogs

Can be prevented upto a higher extent by OH

Found with greatest frequency in poodles, boston terriers, fox terriers, daschunds.

Most commonly occur in middle aged in old dogs

Most common site is caudal mammary gland

Normally seen intact and aged bithes (which is due to hormonal imbalance)

Gross swelling which can be bleeding.

Cytology can also be done but not usually preferred.

Radiographs are taken to rule out malignancy

Surgery

Chemotherapy

Radiotherapy

Immunotherapy

Hormonal Therapy

5-FU (150 mg/m2 IV and cyclophosphamide (100 mg/m2 IV) once weekly for 4 weeks to that of dogs.

Successful in human beings but still unexplored in canines

Dogs less than 6 years of age are more commonly affected

Usually present in prepuce or vagina but can also be found on nose or on skin.

Endemic in free roaming dogs

The glans penis and prepuce are often concurrently affected.

Masses may have a cauliflower-like appearance or be friable and bleed easily.

These tumours have low metastatic rate.

First neoplasm to be successfully transmitted from one animal to another done by M A Novinsky

Tumour transmitted at coitus by transfer of intact tumour cells

It is tumour of young dogs (1-6 years of age)

More common in females

Present in vaginal mucosa protude from vulva and in males protude from prepucial cavity

H/O: Stray roaming

Continuous dribbling of urine and frequent licking of penis by dog

Oozing of blood may be there from prepucial cavity

Cauliflower like friable masses are found on vaginal or prepucial examination.

Cytopathologic sample of a canine TVT. Note the discrete round cells, somewhat eccentric nuclei, moderate amount of cytoplasm, and characteristic

multiple discrete clear cytoplasmic vacuoles.

Chemotherapy (treatment of choice)

Surgical resection

Radiation Therapy

Most effective approach remains monotherapy with the tubulin binding agent vincristine.

Vincristine is relatively safe, inexpensive, and provides a complete and durable response in over 90% to 95% of treated dogs, typically following two to six weekly treatments.

Vincristine is generally administered at a dosage of 0.5 to 0.75 mg/m2 IV once weekly for three to six treatments.

The anthracycline doxorubicin, at 25 to 30 mg/m2 IV every 21 days for two to three cycles (used in Vincristine resistance cases)

Before vincristine therapy After vincristine therapy

Thank You!

AnyQuestions?