Radiotherapy

Question 1

What are different form of radiotherapy?

Answer 1

• Brachytherapy
• Direct application (Pleisiotherapy, Eg strontium 90 wand)
• Implantation – Iridium wires (gamma rays)
• Systemic administration – Iodine 131 in feline
• Teletherapy
• External beam
  – Orthovoltage source
  – Linear accelerator
  – Cobalt 60

Question 2

How is teletherapy used therapeutically?

Answer 2

1. Radiation produced = Linear accelerators / Natural radioactive decay
2. Electromagnetic radiation = X-rays, gamma rays, Electrons
3. Particle beam therapy - heavy particle

Question 3

What is the compton effect?

Answer 3

• When x-ray Photons interact with electrons they deflect + move in a different direction and lose energy
• If needed to treat a superficial tumour (skin) need to use a bolus over skin to ensure maximum dose at surface

Question 4

How is DNA damaged by radiation? What is needed to inhibit repair?

Answer 4

• Critical target for therapeutic radiation is probably DNA
  – DNA is very small, so chances of an incident photon directly damaging it are low
• Damage is caused by ionisation of water molecules
  – Water molecules around the DNA are ionised
  – Free radicals are generated
  – DNA is damaged by the free radicals - O2 is needed to inhibit repair of free radical induced damage

Question 5

What causes cell death?

Answer 5

– Induction of apoptosis
– Permanent cell cycle arrest
– Mitotic catastrophe

Question 6

How is the beam shaped in a linear accelerator?

Answer 6

• With jaws - like x-ray (rectangular field)
• Tumour shaped = multileaf collimator

Question 7

Is single beam or multiple beams better for radiotherapy?

Answer 7

• Multiple beam = can increase tumour dose while sparing surrounding tissue

Question 8

Why are electrons good for superficial tumours?

Answer 8

• Directly ionising
• Loses energy rapidly as passes through tissues = ionises superficially

Question 9

What are the 4 R’s of radiotherapy?

Answer 9

• Repair
• Repopulation
• Redistribution / reassortment
• Reoxygenation

Question 10

What is repair to radiotherapy?

Answer 10

• Repair of sublethal or potentially lethal damage to cells after exposure – Occurs rapidly
• Tumour cells and normal cells generally have similar repair capacities – Some tumours are really good at it e.g. malignant melanoma
• Total dose of radiation required to kill cells is less if a few large doses rather than lots of smaller doses are given – Fractionation

Question 11

What is repopulation after radiotherapy? What tumours are good at repopulating?

Answer 11

• Seen in rapidly dividing tissues
• Cells are recruited from G0 (resting phase)
• Protects rapidly dividing normal tissues
• Rapidly dividing tumours also repopulate effectively

Question 12

What is redistribution / reassortment after radiotherapy?

Answer 12

• Cells are more sensitive to radiation in some phases of the cell cycle than others (late G2 (pre-mitotic interval) and M (mitosis))
  – Cells may become synchronised in the post treatment period
  – Synchrony is soon lost
  – Timescale over which redistribution occurs is variable and poorly defined

Question 13

What is reoxygenation after radiotherapy?

Answer 13

• Important factor
• Many solid tumours have poor blood supply – Sinusoidal vessels, poorly formed microvasculature
• Areas of hypoxia/necrosis
• Reoxygenation may occur after therapy
  – Euoxic cell death
  – Changes in tumour vascularity

Question 14

What is fractionation?

Answer 14

• Two doses of radiation given at separate times have less effect than the sum of the two doses given as a single treatment
  – Between treatments cells can REPAIR sublethal damage
  – Normal tissue and tumour tissue can REPOPULATE from cells that are in resting phases/cycle arrest
• Fractionation is the practice of giving multiple small doses instead of one big one

Question 15

Why bother with fractionation?

Answer 15

• Reduce normal tissue toxicity =
  – REPAIR
  – REPOPULATION
• Achieve better tumour cell kill =
  – REOXYGENATION
  – REDISTRIBUTION

Question 16

What are limitations of fractionation for animals?

Answer 16

• Requirement for GA
• Cost
• Owner reluctance - inconvenient, frequent visits, long hospitalisation

Question 17

What is response also affected by?

Answer 17

– Tumour growth characteristics
– Tumour size
– Inherent sensitivity
– Tumour type
– Tumour site
– Patient species

Question 18

What are examples of highly radiosensitive tumours?

Answer 18

• Lymphoma
• Transmissible venereal tumour
• Gingival basal cell carcinoma (acanthomatous ameloblastoma)

Question 19

What are examples of moderately radiosensitive tumours?

Answer 19

• Oral SCC (dogs)
• Oral malignant melanoma (dogs)
• Nasal tumours
• Perianal adenocarcinoma
• Mast Cell Tumours
• Rhinarial SCC (cats)
• Thyroid carcinomas
• Brain tumours

Question 20

What are examples of poorly radiosensitive tumours?

Answer 20

• Fibrosarcomas
• Haemangiopericytomas
• Oral SCC (cats)
• Osteosarcomas - radiotherapy can be used for analgesia
• Rhinarial SCC – in dogs

Question 21

What are acute side effects of radiotherapy?

Answer 21

• Affect rapidly dividing tissues
  – Skin
  – Mucous membranes
  – Erythema/desquamation
• Develop during or soon after treatment
• Resolve within a few weeks of cessation of therapy
• Worse of treatment course is compressed

Question 22

What are late side effects of radiotherapy?

Answer 22

• Affect slowly dividing tissues
• Develop many weeks, months or even years after treatment
• Damage to tissues and their microvasculature
• Potentially very serious – Ischaemic necrosis of brain or bone tissue
• Many inconsequential/ less serious late effects
  – Alopecia
  – Skin fibrosis etc
• Reduced healing capacity
• Carcinogenesis - DNA damage + mutagenesis - takes years (avoid irradiation in young patients)