Radiobio part 3 Flashcards
Acute tissue damage
- <90 days, early responding tissues
- cell death after irradiation occurs mostly after cells attempt to divide
- Therefore mainly effect ‘hierarchical tissues’ in high turnover compartments e.g GI tract, bone marrow, skin.
- Have a rapidly proliferating stem cell compartment
- high A/B
Processes:
- inflammatory paracrine mediators released
- Differentiated cells undergo depletion
- Vascular endothelium - increased permeability, - erythema, oedema
Mediated by cytokines - ILa & IL 6 that attract immune cells & TNF-a that promotes apoptosis
- Stem cell replenishment
- varies with life span of involved cells (eg. GI tract = days, bladder = months) - NOT dose dependent
- consequential late effect - if intensive fractionation schedules deplete stem cell population below levels needed for tissue restoration.
Late Tissue Damage
- > 90 days, late responding tissues
- Mainly affects flexible tissues (cells that rarely divide but can be induced to by damage)
- Pathogenesis more complex - is progressive and irreversible
- Doesn’t have a rapidly dividing stem cell compartment.
- Clinical manifestation due to clinical depletion of functional cells
- Late effects are progressive
- Latent time & progression rate are dose dependent - decreased time to functional loss, increased endothelial cell damage, increased capillary loss, increased fibroblast differentiation.
Examples of early & late toxicity for:
Skin
CNS
Lung
GI
GU
Haem
H&N
SKIN
- E = vascular - erythema (vasodilation), oedema. Epidermal cells - desquamation.
- L = vascular - telangiectasis. Epidermal cells - atrophy & necrosis. Stromal cells - Fibrosis
CNS
E = nausea, vomiting, fatigue
L = necrosis
Lung. E= pneumoninit. L = fibrosis
GI. E = mucositis, diarrhoea. L = stricture, proctitis, telangiectasia.
GU. E = subfertility. L = infertile.
Haem. E = myelosuppression. L = aplasia
H&N. E = mucositis, oedema, erythema. L = xerostomia, loss of taste.
Normal Tissue Tolerance
= max dose in 2Gy fractions that a tissue can be given with an acceptable complication rate (usually 5%) for a given complication.
TD5/5 = max tolerance dose yielding risks of complication of 5% over 5 years.
TD50/5 = max tolerated dose yielding a complication rate of 50% over 5 years
TD = tolerance dose
EUD
= equivalent uniform dose
EUD assumes that any 2 dose distributions are equivalent if they cause the same biological effect.
- considers dose heterogeneity.
- reflects overall cell kill (hence TCP) produced by non-uniform dose distribution and is therefore potentially a better indicator of biological outcome than assessments based on the simple average of the physical dose.
- It shows that even a small cold spot can play a disproportionate role in reducing overall treatment effectiveness.
- BUT does not inherently allow for the possibility that clonogenic cells themselves may be non uniformly distributed.
TD5/5 Brain & endopoint
45 Gy
Infarction, necrosis.
- most important injuries to brain post IR are late syndromes (months to years).
- 1st year - changes nvolve white matter
- beyond first 6 months - grey matter changes & vascular changes
- Radionecrosis occurs 1-2 years post IR and accompanied by cognitive defects
TD5/5 Spinal cord
20cm = 45Gy
5-10cm - 50Gy
Simular to brain in terms of latency, tolerance dose and histology.
1. Early = l’hermittes sign - can be reversible. appearance does not predict future toxicity
2.Late = demyelination & necrosis of white matter (6-18 months later), vasculopathy = 1-4 years.
Tolerance depends on dose per fraction, need at least 6 hours between doses
SERIAL organ
TD5/5 Lens
10 GY
cataract
lacriam gland - dry eyes
optic nerve/chiasm - blindenss (50gy)
TD5/5 Lung
17.5 Gy
V20 = 30%
One of the msot sensitive of late responding organs.
Pneumonitis (2-6 months), fibrosis (months to years)
V sensitive to fractionation (a/b =3)
FSUs are arranged in parrallel. IR to lungs is only dose limiting if large volumes are irradiated and if remaining lung cannot provide adequate function.
Liver TD5/5
30Gy
V30 = 40%
3rd most sensitive late responding organ.
Acute & chronic hepatitis.
Parenchyma = parallel FSU, bile duct/hepatic artery can be thought of as serial.
Heart TD5/5
V40 = 50%
40GY
Acute pericarditis - most common, seldom occurs in 1st year. Varies in severity.
Cardiomyopathy (at 10 years)
Increased risk of IHD
a/b is low (1) so fractionation results in a substantial sparing effect
Oesophagus TD5/5
55Gy
oesophagitis 10-12 days - resolves soon after treatment.
Late effects related to muscle layer - perforation/stricture
Stomach TD5/5
50Gy
Small bowel TD5/5
40Gy
obstruction/perforation
Colon TD 5/5
45 Gy
obstruction/perforation
Rectum TD5/5
60Gy
Proctitis/fistula
Bladder TD5/5
75GY
cystitis at 20-30GY
Late effect = fibrosis
Shrinkage & ulceration at 50Gy
Urethral stricture at 60Gy
Urethra TD5/5
70 Gy
Kidney TD5/5
23 Gy
2nd mot sensitive late responding organ
V20 = 20%
In contrast to most tissues, increasing treatment time does not allow higher doses to be tolerated.
Parrallel FSUs.
Nephropathy with arterial hypertension & anaemia.
Part of one or even both kidneys can receive a much higher dose.
Femoral head TD 5/5
52 Gy
avascular necrosis
Testes TD 5/5
Sterilisation 1 Gy
(spermatocytes - temporary sterilisation at LD, permanent at HD)
Hormone failure 30Gy
(Leydig cells can tolerate much higher doses - secrete testosterone)
therefore see sterilisation with minimal effect on libido
Ovary Td5/5
2Gy - sterilisation
(different to testis fixed number from birth - EXTREMELY RADIOSENSITIVE & IMMEDIATE)
20GY - menopause. (hormonal secretion is assocaited with follicular maturation, sterilisation by radiation leads to loss of libido & menopause).
Marrow td5/5
2.5 Gy
Aplasia, pancytopenia
Skin TD5/5
2gy - temporary erythema (1 day) - vasodilation
7gy - permanent epilation (3 days)
14 Gy - desquamation (4 weeks) - depletion of basal cell layer
- telangiectaisa (> year - late developing vascular injury)
- ulceration/necrosis
- Epidermis (outer layer) - site of early radiation reactions
- Dermis (deeper layer) - actively dividing stem cells which then takes 14 days to migrate to epidermis & desquamate. Site of late reactions.
Parotid TD 5/5
Radiation damage primarily occurs to serous acinar cells.
Occurs early and cells die by apoptosis. Mucous cells are more radioresistant.
Demonstrates little response to change in does/fraction.
Quantec 1 gland dose <20GY.
Deterministic Effects
increases in severity with increasing dose
only above a threshold dose because effects arise in a population of cells e.g. lens/cataract
Stochastic effects
probability of occurrence increased with higher dose BUT severity is not dose related.
No threshold dose as these effects arise in single cells eg. cancer induction/genetic effects.
Total Body Irradiation
Unplanned whole body exposure to radiation - acute radiation syndrome leading to death.
LD 50/60 = the dose that leads to death within 60 days of 50% of the population
= 3.5Gy without medical care, 7Gy with medical care
Time course and severity of clinical features are a function of overall body volume irradiated, inhomogeneity of dose exposure, absorbed dose, dose rate & particle type.
TBI
Doses of 1Gy or more = prodromal reaction - fatigue, anorexia, vomiting.
Doses of 2.5 GY or more = HPO syndrome - death within 30 days
Doses of 10 Gy or more = GI syndrome. N&V, bloody diarrhoea (depopulation of epithelial lining due to sterilisation of crypt cells).
Very high doses= cerebovascular syndrome - death within 24-48 hours
Haematopoietic Syndrome
BM stem cells are very radiosensitive with little sparing from reduced dose rate or fractionating the dose. Transit time for each component varies hence the differences in time to drop.
- Macrophages very radioresistant.
- Granulocytes (neuts, basophilis, eosinophils) = temporary increased (mobilisation from reserve pool) to rapid fall by day 7
- Lymphocytes (b then t) 0 drop around day 10
- Platelets at 20 days
Hb drops last
1ory cause of death from infection & haemorrhage
4 phases to radiation sickness
- Prodromal
- initial phase appears within 1-3 days, N&V, headache, fever, skin erythema. Duration of phase is inversely proportional to dose. V high doses there is no latent phase.Onset of vomiting is also related to absorbed dose and can be seen within a few minutes after a high exposure. - Latent Phase - characterised by improvement in symptoms and apparent cure. Pts look & feel well but lab tests become abnormal with granulopenia/lymphopenia
Also dose dependent and may last hours to weeks. - Manifest illness phase
- specific signs & symptoms of each syndrome appear depending on the dose.
- HPO develops at 1-8Gy (can see changes in blood counts at <1Gy)
- GI syndrome 5-20Gy - small bowel paneth cells are most sensitive
- CVS syndrome at >20 Gy - Final phase - recovery or death depending on the adsorbed dose, dose rate & heterogeneity of exposure.
