Radiation Therapy Flashcards
What are the 2 mechanisms of action of ionizing radiation?
- Direct damage
- Indirect damage (free radicals)
What is the unit of radiation dose
-grey (Gy)
What is needed for radiation therapy to be effective?
Water and Oxygen to produce free radicals
Why is radiation able to work more effectively on tumour cells cf. normal cells?
normal healthy cells better at repairing their DNA than tumour cells
What effects on cell division do differing levels of radiation cause?
- Mitosis delayed (< 10Gy)
- Intermitotic death (Usually 10-100Gy)
Radiation dmaged cells usually die after 1 or 2 attempts at mitosis
> cells with high mitotic rate express radiation damage quicker than slowly divideing cells
What is the normal range of radiation used in RT?
10-100 (20-60 more likely)
What are the most radiation sensitive cells in the body?
- undifferentiated
- high mitotic rate
> bone marrow, intestinal crypts, germinal layer of epidermis - tumours! esp. high grade
Why is fractionation necessary?
4 Rs of RT
- allows REPAIR of sublethal damage and REPOPULATION
- ^ damage to tumour because of REOXYGENATION and REDISTRIBUTION of cells into radiosensitive phases of cell cycle
How does it take normal healthy cells to regenerate?
6-24hrs
What is repopulation?
- cells may respond to death of adjacent cells by accelerated repopulation
- as tumour population is heterogeneous in their cell cycle position some cells will be killed off before others allowing the oppportinuty to repopulate
> must deliver another fraction before tumour cells begin to repopulate
What is reoxygenation and why is it important?
- tumours have necrotic poorly oxygenated centres, which is NOT AFFECTED by radiation
- by destroying the outer oxygenated tumour cellsyou make more room for the surviving hypoxic cells which become vascularised and need to be hit by another fraction of radiation before the tumour begins to grow again
Which phases of the cell cycle are most affected by radiation? What effect does this selective toxicity have on the remaining cell population?
M > G2 > G1 > ES > LS
- remaining cells will be synchronised and in same stage of cell cycle
- eventually all cells will enter a radiation-sensitive phase of the cell cycle
WHat are the 3 main types of radiotherapy used in animals?
> x rays
- old, not really used much, side effects
gamma rays
particles
- B particles (electrons) in radioisotopes eg. strontium PLESIOTHERAPY and iridium BRACHYTHERAPY
What is the therapeutically useful depth of electron beams? Pros of using these?
- various energies possible
- rapid dose reduction
- single fields, simple dose calculations
> therapeutically useful depth: 1.5-5.6cm - good for skin and subcut
How does a photon beam differ from an electron beam?
- hig penetration
- slow dose reduction
- field arrangements necessary
- penetration of normal tissue
- CT-based treatment planning
> best for internal organs or those surrounded by a lot of tissue - esp. brain lesions
What is important when using fractionated RT?
Animal is repositioned in exactly the same place each time
- use bite block
- use vacuum cushions q
What tumour types is RT definitely indicated for above all other tx?
- Nasal tumours
- CNS tumours
What must you be careful to avoid if irradiating the head?
Eye and esp. lacrimal glands
What are the 2 potential goals of RT?
> curative/definitive (cure or long term tumour control)
> palliative (palliation, stabilising disease, pain reduction) less frequent, high doses so animal can remain at home
What are the 3 potential uses of RT as a curative measure?
- Absolute indications (RT shows better results than other therapies, eg. nasal and brain tumours)
- Relative indications (RT shows some tumour control, but other advantages [functional/cosmetic] may sway decision to RT) eg. oral SCC, MCT, epulis
- Combination Tx (gold standard (RT + sx +- chemo)
Which tumours is post- surgical RT often advocated?
- MCT
- soft tiussue sarcoma
- feline vaccine-associated sarcoma
Where do dogs aften get SCC? What age?
- middle aged dogs
- rostral mandible
- often cauliflower like
- locally invasive
- metastases (non-tonsillar ~20%. tonsillar ~70%)
Prognosis of canine oral SCC?
- site-dependant
> rostral: local control, curable
> tonsillar: <10% survival 1 year
How are SCC in cats different to those in dogs?
More aggressive
- require BID RT to be affective
What is epulis?
- Benign growth in the mouth
- Would require bone removal and extensive surgery to remove
- 90% cure rate with curative RT
Why is RT advocated for ISSs?
High probability of recurrence even with clean margins
What prognostic factors affect recurrence rates of ISS?
- number of surgeries
- margins
What grade of tumour are oral fibrosarcomas?
- histologically low grade
- biologically high grade
> very locally invasive but epithlium often intact
> mets in ~20% (LNs and lungs)
Which breeed are predisposed to oral fibrosarcoma?
Golden retrievers
Maxilla<mandible
For what 3 reasons may palliative RT be indicated? Egs. of specific tumours?
> radiosensitive tumours with ^ met rate - histiocytic sarcoma - oral melanoma - hemangiosarcoma - mast cell tumour grade III > mass effect - large head/neck tumours - brain - large sublumbar LN - prostatic tumour > pain control - osteosarcoma, metastatic bone tumours > also age and concurrent disease status
What is the most common tumour in dogs?
Malignant melanoma
- mainly older dogs (~11yrs)
- 1/3 amelanotic
Are malignant melanomas responsive to RT?
50 - 80% response to RT
Negative prognostic factors for malignant melanoma?
- macroscopic disease
- bone lysis
- caudal location
Why may RT side effects not be immediately apparent?
- may not appear until irradiated cells attempt mitosis.
What are the 2 types of RT side effects?
- Accute effects [self-limiting]
- rapidly dividing cells eg. tumour, skin, mucosa, Gi epithlium - Late effects [more serious, permenant]
- slowly/non-dividing tissues eg. bone, muscle, brian, CNS, lens, retina etc.
- seen months/years after tx
- usually accepted for palliative protocols as animal will not live long enough to experience side effects
When are acute RT side effects often seen? What specifically may be seen?
- after 3rd week RT
- 7-20d post RT = max
> normal tissue reactions - mms = mucositis
- skin = alopecia and dermatitis
- eyes = keratitis/conjunctivitis
- CNS = transient demyelination
What Tx is necessary for acute side effects
Symptomatic only
Which cells in the skin are affected most by radiation? Potential tx to deal with acute side effects?
- target cells: stratum basale -> erythema, scaly or mosit dermatitis, alopecia
- Tx: protect from mechanical trauma eg. collar
- analgesia
- black or green tea?!
- NO CREAM/OINTMENT! will delay healing q
How may mucous membranes be affected acutely by radiation? Tx options?
- Hypersalivation. nasal discharge, mucositis (fibrinous plaques) eg. perianal mucositis
- Pain -> anorexia (rare in dogs, frequent in cats)
> Tx: - Pain medication, Abx, feeding tube (PEG), oesophageal tube
- Metamucil/lactulose for colitis and proctitis
How may eyes be affected acutely by radiation? Tx options?
- v tear production, conjunctivitis, blepharitis, corneal ulceration
> Tx: - optimmune/vit A eye ointment
- check tear production
How may CNS be affected acutely by radiation? Tx options?
- oedema 8-12 weeks post RT
- transient demyelination (transient recurrence of neurological symptoms
> Tx: - corticosteroids
What is the earliest possible onset of late side effects after RT?
6 months
What are late side effects generally due to? Specifc egs?
Damage in stroma and vasculature
- fibrosis
- contractions
- strictures
- non-healing ulcerations
- necrosis of bone, skin and CNS
- cataract, KCS (keratoconjunctivitis sicca)
- Infarctions and haemorrhages
Tx of late side effects?
Difficult - try to avoid!!
How may skin be affected chronicaaly (late side effects) by radiation?
- damage of vasculature and fibroblasta
- fibrosis
- alopecia and pigment changes
How are the brain and spinal cord affected by late side effects? Why may this be problematic clinically?
- necrosis of white matter (6-18 months)
- Vasculopathy (1-4 years)
> differentiating side effect from recurrent disease difficult
> try corticosteroid tx
