Cancer

Hyperplasia

an increase in the number of cells in a tissue

Hypertrophy

an increase in the size of cells in a tissue

Neoplasia

an abnormal growth of cells

Tumor

Swelling of a tissue caused by an abnormal growth of cells

Metastasis

the spread of cancer from its place of origin to another site in the body

Benign tumor

a tumor that is unlikely to metastasize

• can still have a negative impact on quality of life (e.g. brain tumor)

Malignant tumor

has the potential to metastasize to other sites in the body; synonymous with cancer

Cancer

a neoplasia or tumor with the potential to metastasize to other sites in the body

Staging

The process of performing diagnostic tests to determine the extent of cancer within the body

• Based on factors including the local extent of the tumor and the presence of metastasis in lymph nodes and distant sites

• typically holds prognostic significance for a patient and is important in developing an appropriate treatment plan

Grading

performed by pathologists examining biopsy specimens; pathologists assign a grade based on microscopic features (including mitotic index, necrosis, invasion into lymphatics and abnormal nuclear or cytoplasmic features) that are correlated to the biologic behavior of a particular tumor type; ideally, a grading system holds prognostic significance and can predict a tumor’s future behavior

Acute effects

expected side effects of definitive radiation therapy in rapidly dividing normal tissues like the skin and mucous membranes; these effect occur after starting radiation therapy and usually heal within a few weeks of completing treatment

Late effects

Uncommon side effects of radiation therapy that occur in slowly dividing normal tissues like nerves and bone; these effects occur months to years after finishing radiation therapy

Palliation

Treatment designed to reduce the clinical signs of disease without necessarily curing the disease

Progressive disease

used to describe when a cancer has worsened characterized by an increase in tumor size or the development of new tumors or metastatic lesions in response to therapy

Stable disease

used to describe when cancer has neither worsened nor improved overall in response to therapy

Partial remission

When the cancer has improved beyond the limits of stable disease but there is still gross, measurable tumor present in response to therapy

Complete remission

when all gross measurable tumor has disappeared in response to therapy

Fraction

a portion of the total prescribed dose of radiation administered as a single dose (more, small fractions are delivered with definitive radiation therapy while fewer, larger fractions are delivered with palliative radiation therapy)

Approach to Oncology

1. What type of tumor are you dealing with?

2. Has the tumor spread anywhere else in the body?

To determine what type of tumor you are dealing with

1. Fine Needle Aspirate (cytology

   • easy, quick and cheap

2. Biopsy (histopathology)

Biopsy (Histopathology)

• Gold standard

• Cutting out a small piece of tissue (using scalpel, punch biopsy)

• Allows a pathologist to assign a grade

  • Grading is based on microscopic features correlated to a tumor's likely behavior

  • Ideally, a grading system can predict a tumor's future behavior

Treatment options

1. Local Therapy

2. Systemic Therapy

Local Therapy

• Surgery

  • "A chance to cut is a chance to cure…"

  • Surgery alone can't cure if you can't get all the tumor or if the tumor has already spread

  • Typically surgery is one part and is done with also chemotherapy

• Radiation therapy

  • Palliative radiation therapy

  • Definitive radiation therapy

Systemic Therapy

• Cytotoxic chemotherapy drugs (traditional chemotherapy)

  • Kill rapidly dividing drugs

• Small-molecule inhibitors (targeted chemotherapy drugs)

• Immunotherapy (vaccines, antibodies, immune system stimulants)

Communicating about cancer in pets

2 categories

• Response to therapy

• Managing client expectations about treatment and survival

Response to therapy terms

• Complete remission

• Partial remission

• Stable disease

• Progressive disease

Managing client expectations about treatment and survival

• How long is the lifespan of a normal dog or cat?

• How long do we expect aggressive tumors to respond in dogs and cats?

• How well dogs and cats tolerate surgery, radiation and chemotherapy

Radiation Therapy side effects

Generally limited to the area of the body where radiation was delivered

• Acute effects

• Late effects

Acute effects of radiation

• Occur in rapidly dividing tissues (think skin and GI)

• Occur DURING the course of radiation therapy delivery (typically to the area where the radiation is being targeted)

• Alopecia - hair loss

• Dry Desquamation - dryness and flakiness of the skin

• Moist desquamation

• Mucositis - inflammation of the mucous membranes (often the oral cavity)

Late effects of radiation

• Occur in slowly dividing tissues (think connective tissues, bone and nerves)

• Occur a long time AFTER radiation therapy is delivered (can be months or years later)

• Permanent alopecia

• Leukotrichia - white hair follicles

• Fibrosis

• Osteonecrosis - bones that die

• Keratoconjunctivitis sicca - dry eye

• Cataracts

• Second cancer - rare

Chemotherapy side effects

These are a result of injury to rapidly dividing cells other than cancer cells (the target of chemotherapy) including precursor cells in the bone marrow, intestinal crypt cells in the intestine and hair follicles

• Myelosuppression

• Gastrointestinal Disturbances

• Alopecia

• Extravasation injury

  • Doxorubicin, vincristine, vinblastine

• Other Toxicity

  • Cardiotoxicity - doxorubicin (dogs)

  • Nephrotoxicity - cisplatin, doxorubicin (cats), NSAIDS (especially cats)

  • Hepatotoxicity - CCNU (dogs), NSAIDS

  • Fatal pulmonary edema in cats - cisplatin

  • Sterile hemorrhagic cystitis - cyclophosphamide

  • PU/PD/polyphagia/panting - steroids

Selected Tumors in the Dog

• Lymphoma

• Osteosarcoma

• Mast Cell Tumor

• Hemangiosarcoma

  • Dermal hemangiosarcoma

  • Soft tissue Sarcoma

• Transitional Cell Carcinoma (TCC)

Dog: Lymphoma - age/breed

• Middle aged to older dogs most common

  • Golden Retriever

  • Boxer

  • Basset Hound

  • Labrador Retriever

  • German Shepherd Dogs

  • Thers are all over-represented

    • 4x increased risk in Boxers

    • 1 in 8 lifetime risk for Golden Retrievers

Dog: Lymphoma - Location

• Most common presenting sign is non-painful generalized peripheral lymphadenomegly (enlargement of lymph nodes)

  • "B is better (or bad), T is terrible

• Superficial Lymph Nodes

  • Mandibular lymph nodes

  • Prescapular Lymph node

  • Axillary lymph nodes

  • Inguinal lymph nodes

  • Popliteal lymph nodes

Dog: Lymphoma - Treatment

• CHOP protocol - 'gold standard'

  • Cyclophosphamide (Cytoxan)

  • Vincristine (Oncovin)

  • Doxorubicin (Adriamycin)

  • Prednisone

Dog: Lymphoma - Prognosis

• >90% remission rate in dogs with B-cell lymphoma

  • Median survival time for dogs treated with CHOP is 12 months

• When LSA relapses, CHOP can be repeated or other rescue chemotherapy protocols can be started

Dog: Osteosarcoma - age/breed

• Most common primary tumor of bone in the dog

• Large to giant breed dogs most common

  • Rottweilers

  • Saint Bernard’s

  • Golden Retrievers

  • Great Danes

  • German Shepherd dogs

Dog: Osteosarcoma - clinical signs

Are initially similar to an injury to a joint and may progress from mild or intermittent lameness to complete non-weight bearing lameness, with swelling of the local soft tissues

Dog: Osteosarcoma - Location

• "Away from the Elbow"

  • Proximal humerus

  • Distal radius

• "Toward the knee"

  • Distal femur

  • Proximal tibia

Dog: Osteosarcoma - Treatment

• Often extremely painful and leaves the bone weakened and prone to pathologic fracture

• Amputation is often the first step of treatment, and is generally well-tolerated

• NSAIDS, Tramadol, gabapentin, bisphosphonates and radiation therapy may be helpful for pain if amputation is not pursued

Dog: Osteosarcoma - Prognosis

• Median survival post-amputation alone is <5 months

  • >90% of dogs treated with amputation alone develop metastatic disease and die within 1 year of diagnosis

• Systemic chemotherapy is indicated due the highly metastatic behavior of osteosarcoma

  • Doxorubicin and carboplatin - most effective

  • Chemo + amputation result in median survival times of 10 to 12 month

Dog: Mast cell Tumor - Breed

• Most common skin cancer in the dog

  • These originate from the white cell-mast cells

• Brachycephalic are predisposed

  • Pugs

  • Boxers

  • Boston Terriers

• Many others are also seen

  • Labrador Retrievers

  • Staffordshire Terriers

  • Shar-Peis (get bad ones!)

Dog: Mast cell Tumor - Look

• Most frequently seen as a discrete cutaneous tumor

  • May be raised and pink, haired or unhaired, ulcerated or warm to the touch

  • Owners may report that the tumor appears to increase and decrease in size

Dog: Mast cell Tumor - Granules

• Mast cells are involved in hypersensitivity/allergic reactions and are filled with granules containing histamine, proteases and heparin

• Ask owners about vomiting, diarrhea, dark colored stools and anorexia which may indicate GI ulceration due to histamine release

Dog: Mast cell Tumor - Treatment

• Wide local resection whenever possible

  • If tumor margins are not clean, treat with additional surgery or radiation therapy

• Chemotherapy indicated for high grade or metastatic MCTs

  • Vinblastine, lomustine (CCNU) and Palladia are the most commonly used drugs

• Always start antihistamines to reduce the risk of systemic or local signs associated with mast cell degranulation

  • H1 receptor antagonist (e.g. diphenhydramine or Benadryl)

  • H2 receptors antagonist (e.g. famotidine or Pepcid AC)

  • Give these medication before any FNA, biopsy or surgery and as long as any tumor is present

Dog: Mast cell Tumor - Prognosis

• Its highly variable

  • Median survival time for high grade MCTs is <6 months

  • Long term survival and even cure is not uncommon for low grade MCTs

• High grade MCTs most frequently metastasize to local lymph nodes, liver, spleen and the bone marrow, and rarely to the lungs

  • Bone marrow involvement is a strong negative prognostic indicator

• Dogs that develop one cutaneous MCT are more likely to develop new mast cell tumors in the future

Dog: Hemangiosarcoma - Breed

• Often a devastating and surprising cancer diagnosis in the dog

• German shepherds

• Golden Retrievers

• Labrador Retrievers

Dog: Hemangiosarcoma - Location

• Most frequently occurs in the spleen

  • Undetected until they rupture

  • Acute, non-traumatic hemoabdomen

• Also occurs on the heart

  • Pericardial effusion and cardiac tamponade

  • Typically the right side(low pressure side) of the heart

Dog: Hemangiosarcoma - Clinical Signs

• Pale gums

• Distended abdomen

• Palpable "fluid wave"

• Weak femoral pulse

• Exercise intolerance

• Weakness

• Collapse

• Tachypnea

Dog: Hemangiosarcoma - Treatment and Prognosis

• Emergency treatment of choice for splenic HSA is splenectomy

  • Not curative on its own

  • Surgery alone extends survival by a few months

  • Frequently mets to the liver and lungs

• Surgery + chemotherapy extends survival

  • Still rarely beyond 6 to 9 months

    • Doxorubicin

    • Low dose oral cyclophosphamide + piroxicam

    • Low Dose oral Chlorambucil + piroxicam

Dog: Dermal Hemangiosarcoma

• Low-grade malignancy

  • Induced by UV light

  • Common on the ventrum

    • Fur is sparse and UV exposure increased

• Curable with surgical excision

• Multiple lesions very common

  • "field effect

Dog: Soft Tissue sarcoma

• Fairly common in dog (esp. limbs)

  • Can occur anywhere on the body

• Tend to be locally invasive, but rarely metastasize

• Wide surgical excision is needed to effectively treat them

  • May include amputation

• Surgery + XRT

  • Definitive radiation therapy can be used following a surgery with narrow margins

• Palliative radiation

  • For large, unresectable tumors, palliative radiation can slow tumor growth or reduce tumor

• Outcomes

  • Can include a cure if appropriate surgical margins are possible or definitve radiation therapy is used after surgery

Dog: Transitional Cell Carcinoma - Breeds

• Most common tumor of the urinary tract in the dog, but an uncommon tumor in general

  • Scottish terries have an 18-fold increased risk

  • West Highland White terriers

  • Shetland sheep dogs

  • Beagles

  • Wire Haired Fox terrier

Dog: Transitional Cell Carcinoma - Clinical Signs

• Most commonly present with lower urinary tract signs

  • Stranguria

  • Hematuria

  • Pollakuria

  • Dysuria

  • Recurrent urinary tract infection

• Other vague clinical signs may be reported

  • Lameness

  • Weight loss

  • Lethargy

Risk factors for TCC

• Increased risk:

  • Breed

  • Exposure to old flea dips

  • Exposure to herbicides

  • Cystocentesis risks speading

• Decreased Risk

  • Eating vegatables, like broccoli or carrots, several times/week

Dog: Transitional Cell Carcinoma - Treatment

• Injectable chemotherapy

  • Mitoxantrone, vinblastine and carboplatin

• NSAIDS

  • Piroxicam, deracoxib (Deramaxx)

• Radiation, urethral or ureteral stents

  • To alleviate obstruction

• Average survival at Purdue is about 400 days

Tumor Types in Cats

• Lymphoma

• Feline Injection Site Sarcomas (FISS)

• Oral Squamous Cell Carcinoma

Cat: Lymphoma

• Generally take on different anatomic forms in the cat compared to the dog

• Anatomic Forms of Lymphoma in the cat include:

  • Alimentary/gastrointestinal tract

  • Mediastinal lymphoma

  • Extranodal - including nasal, renal, CNS and retrobulbar

Cat: Gastrointestinal Lymphoma

• Most common type of GI lymphoma in cats is low-grade, small cell variant

  • Clinical signs

    • are usually anorexia

    • Diarrhea

    • vomiting

    • weight loss

  • Ultrasound reveals thickening of the intestinal wall

• Treated with chlorambucil (Leukeran, an oral chemo drug) and prednisolone

  • Good prognosis - remission rates of >90% and median survival times of greater than 2 years

Cat: Nasal Lymphoma

• Clinical signs:

  • Nasal discharge

  • Sneezing

  • Stridor or stertor

  • Ocular discharge

• CT is recommended to localize the mass and guide a biopsy

• If there is no evidence of systemic spread, can be effectively treated with radiation

  • >75% achieve complete remission with median survival times of 1.5 to 3 years

  • If no radiation available, chemo is also effective

Cat: Feline Injection Site Sarcomas

• Associated with vaccination and other injection sites

• Incidence rate is low at around 1/10,000 vaccine dose administered

  • Many cat owners will have read about or heard about it and will be concerned about vaccinating their cat

• Very locally invasive and extensive; around 25% will metastasize

Cat: Feline Injection Site Sarcomas - Treatment and Prognosis

• Aggressive surgery is indicated with a goal of 5 cm lateral margins and 2 fascial planes deep to the tumor

  • Recurrence in a little as 2 weeks with incomplete resection

  • Wide SX w/clean margins - DFI > 700 days, but up to 50% recurrence

  • SX + radiation, SX + chemo, SX +Radiation + chemo can also be effective

AAFP Recommended Vaccine locations for cats

• Right front

  • Feline Panleukopenia

  • Feline Herpesvirus - 1

  • Feline Calicivirus

• Right Rear

  • Rabies

• Left rear

  • FeLV

AAFP’s Post vaccine 3-2-1 rule

• Recommends performing an incision biopsy of any lump that develops post-vaccination if:

  • A lump persists for 3 months or longer

  • A lump becomes larger than 2 cm in diameter

  • A lump continues to increase in size for >1 month after an injection

Cat: Oral Squamous Cell Carcinoma

• Most common oral tumor of cats

• Can develop anywhere in the mouth

  • Tongue, pharynx, tonsils, and gingiva

• Locally invasive

  • Invades and destroys underlying bone

• DENTALS are very important in helping find this earlier!

Cat: Oral Squamous Cell Carcinoma - Risk Factors

• Environmental tobacco smoke

• High intake of canned food

• Use of flea collars

Cat: Oral Squamous Cell Carcinoma - Clinical Signs

• Blood-stained water or saliva

• Ptyalism (excessive salivation)

• Pain on palpation of face or jaw

• Halitosis (a fetid odor to breath)

• Scratching or pawing at face

• Anorexia and/or weight loss

• +/- observing the mass

Cat: Oral Squamous Cell Carcinoma - Treatment

• Radiation and chemotherapy are often attempted for palliation, but response rates are low

• Most cats diagnosed with OSCC succumb to the effects of local disease progression within a year

• What does this cat have in place that may extend it's survival?

Cat: Surgery for OSCC

• Is a very locally invasive tumor and most cats die due to local disease, rather than metastasis

• Due to the small size of a cat's mouth and the local extend of disease by the time the tumor is diagnosed, curative surgery is rarely possible