Approach to the management of the feline cancer patient

Question 1

Explain what is the mechaanism of action of radiotherapy

Answer 1

The major beneficial effect of radiation is mediated through radiation-induced damage to DNA

The dose of radiation is measured in units of energy per mass of tissue
- the Gray (Gy) is the standard unit of measurempent for radiation oncology

Question 2

Explain why some cells are radiosensitive and others are less radiosensitive

Answer 2

Because tumor cells are generally less differentiated and are involved in active cell division, their ability to repair any nuclear damage is less than normal, healthy, differentiated tissue
- cells going through mitosis are more radiosensitive

The presence of oxygen enhances DNA damage and thus poorly oxygenated tumors are less radiosensitive

Question 3

Explain why using smaller doses of radiotherapy and repeating the treatment at regular intervals (i.e., fractionated therapy) permits greater tumor kill with fewer effects on normal tissue

Answer 3

Repair of DNA in damaged cells will occur after each cycle of therapy
- as normal tissue has a greater ability to repair compared with neoplastic tissue, this allows greater sparing of the healthy tissue

Radiation will help induce re-oxygenation of tissues
- thus repeated smaller doses of radiation ae more effective in tumor killing (reduction in the resistance caused by tumor hypoxia)

Repeating the radiation therapy at regular intervals allows recruitment of cells into the sensitive phases of cell cycling
- thus increases tumor kill

Question 4

What are the two major types of radiotherapy

Answer 4

Tele-therapy (external beam radiotherapy)
- delivering radiation from a source distant from the patient

Brachytherapy
- delivering radiation through a radioactive source delievered into the tumor/body

Question 5

Describe the two categories of radiation toxicity

Answer 5

Acute (early) radiation toxicity
- result of radiation effects on rapidly dividing cells
- skin or mucous membranes in the radiation field may become swollen, inflamed and there may be moist desquamation
- supportive and symptomatic care is indicated for these complications

Late (delayed) radiation toxicity
- less predictable than acute toxicity and can affect all normal tissues
- persistent alopecia and coat color changes can be late cutaneous effects, as can ocular cataracts and keratoconjunctivitis sicca if the eyes are in the radiation field

Question 6

What are the cell cycle phases

Answer 6

The cell division cycle is divided into four distinct phases:
- G1 phase (Gap 1 phase)
- RNA and proteins required for DNA synthesis are prepared
- there is expansion of the cytoplasm and cellular organelles

- S phase (Synthesis phase)
    - duplication of the DNA occurs
    - typically has a duration of 6-8 hours

- G2 phase (Gap 2 phase)
    - RNA and proteins are synthesized
    - the cell continues to grow
    - the mitotic spindle is formed

- M phase (Mitotic phase)
    - there is segregation of the DNA into chromosomes
    - usually lasts 60-90 min
    - mitosis progresses through four stages: prophase, metaphase, anaphase, telophase

Question 7

What is the mitotic index

Answer 7

The mitotic index is a term referring to the number of mitoses that are seen in a high power field when tissue is examined microscopically
- it gives an indication of the aggressiveness of the tumor

Question 8

What are the characteristics of agents binding to DNA

Answer 8

They stop DNA synthesis during S phase (e.g., alkylating agents, antitumor antibiotics)

Question 9

What are the characteristics of anti-metabolites

Answer 9

They stop cells making the building blocks of DNA during G1 phase (e.g., methotrexate, 5-FU)

Question 10

What are the characteristics of microtubule inhibitors

Answer 10

They stop cells making components needed for cell division during G2 phase (e.g., plant alkaloids)