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The four R's of radiation therapy?
- Repopulation
- Reoxygenation
- Redistribution
- Repair of sublethal damage
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IMRT
Intensity Modulated Radiation Therapy
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TD
5/5
The tissue tolerance dose associated with a 5% injury rate within 5 years
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TD
50/5
The tissue tolerance dose associated with a 50% injury rate within 5 years
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Bladder TD 5/5
- Bladder TD 5/5:
- 6000 cGy
- (contracture)
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Rectum TD 5/5
- Rectum TD 5/5:
- 6000 cGy
- (ulcer, stricture)
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Lens of the Eye TD 5/5
- Lens of the Eye TD 5/5:
- 500 cGy
- (blindness)
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Fetus TD 5/5
- Fetus TD 5/5:
- 200 cGy
- (death)
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Heart TD 5/5
- Heart TD 5/5:
- 4500 cGy
- (pericarditis, pancarditis)
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Intestine TD 5/5
- Intestine TD 5/5:
- 4500 cGy
- (ulcer, perforation, hemorrhage)
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Kidney TD 5/5
- Kidney TD 5/5
- 1500 cGy
- (acute & chronic nephrosclerosis)
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Liver TD 5/5
- Liver TD 5/5
- 2500 cGy
- (acute & chronic hepatitis)
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Lung TD 5/5
- Lung TD 5/5
- 3000 cGy
- (acute & chronic pneumonitis)
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Spinal Cord TD 5/5
- Spinal cord TD 5/5
- 4500 cGy
- (infarction, necrosis)
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LD 50/60 for humans
350-450 cGy
The lethal dose for 50% of the population in 60 days
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Who is typically most sensitive to hematopoetic syndrome?
Men, the very old & very young, infirm
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Pancytopenia
The depression of all blood cell counts
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What is the most radiosensitive portion of the digestive system?
- The small intestine
- 4500cGy
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In hematopoetic syndrome is probability of survival dose dependent?
- yes
- probability of survival decreases as dose increases
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LD 100 for humans
1000 cGy
100% of humans exposed to 100cGy will die
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Fetal development
0-10 days
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Fetal development
Day 10-6 weeks
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Fetal development
Week 7 - birth
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Hematopoetic Syndrome
Dose
Time of death
- hematopoetic symdrome
- 100-1000cGy
- death in 3 weeks - 2 months
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Gastrointestinal Syndrome
Dose
Time of death
- gastrointestinal syndrome
- 1000-10,000 cGy
- death in 3-10 days
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Cerebrovascular Syndrome
Dose
Time of death
- cerebrovascular syndrome
- anything over 10,000cGy but can occur as low as 5,00cGy
- death in less than 3 days
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Doubling dose
The dose required to double the mutation frequency in a generation due to radiation exposure
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What is the maximum permissible dose to the fetus?
0.5rem (5mSv)
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What is the latent period for leukemia due to radiation?
4-7 years
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Latent period
The time interval between irradiation and the appearance of malignancy.
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NSD
Nominal Standard Dose
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NTTD
Normal Tissue Tolerance Dose
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What are the 2 factors that affect NTTD?
- 1. The volume irradiated
- 2. The fraction size
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How long does it usually take for people to recover from doses less than 300cGy?
3-6 months
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300-500cGy total body exposure
When will death occur?
-
500-1000 cGy total body exposure
When will death occur?
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How do the effects of radiation in utero manifest?
- -Lethal effect
- -Congenital abnormalities present at birth
- -Late effects observed years later
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What are the principle factors of fetal effects of radiation?
- - Dose
- - Stage of gestation at which it is delivered
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Late effects
The biological response to low doses, not observable for extended periods.
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Somatic effects
Late effects that involve body cells
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Genetic effects
Late effects that involve reproductive (germ) cells
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The most important late somatic effect induced by radiation is:
carcinogenesis
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Thyroid cancer can appear from doses as low as
100cGy
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Mutation frequency
the number of spontaneous mutations that occur in each generation of an organism
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Repair of Sublethal Damage
- -occurs within hours of exposure
- -oxygen dependent, cells require a certain amt of oxygen to carry out repair mechanisms.
- Because a proportion of tumor cells are hypoxic, tumors are presumed to be incapable of repairing sublethal damage
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Reoxygenation
Presumed to only apply to tumors
The process by which hypoxic cells gain access to oxygen & become radiosensitive between XRT fractions
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Describe the four sub-populations of parenchymal tumors
- Group 1: Growth Fraction (GF) viable, actively mitotic,
- Responsible for tumor growth.
- Group 2: G0 cells; typically viable but nondividing.
- Can re-enter the cell cycle when stimulated
- Group 3 & 4: Nonviable cells;
- Do not contribute to tumor growth
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The growth fraction (GF) typically as the size of the tumor increases.
The growth fraction (GF) typically DECREASES as the size of a tumor increases.
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3 major factors affecting tumor growth
- 1. The division rate of proliferating parenchymal cells
- 2. The percentage of these cells in the tumor (GF)
- 3. The degree of cell loss from the tumor (f)
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A tumor with a radius of less than generally does not contain necrotic areas
- less than 100um
- (no necrosis)
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A tumor with a radius of greater than generally contains a necrotic area surrounded by a viable rim of cells approx 100-180um thick
greater than 160um
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oxic
oxic- well oxygenated
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hypoxic
hypoxic- oxygen deficient; between oxic and anoxic
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Anoxic
anoxic- lack or absence of oxygen
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Diffusion distance
70um for oxygen in a tumor
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Hypoxic Cells
- Although hypoxic cells do not have normal levels of oxygen available to them, they are viable and capable of dividing.
- hypoxic fraction is approx ~ 15% of tumor volume
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Oxygen tension
During their early growth stages, tumors begin to outgrow their vascular supply. This results in differing levels of oxygen availability, known as oxygen tension (PO2)
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Viable Hypoxic cells
Resistant to low LET radiations by a factor of up to 2.5 to 3.0.
Presumed to be responsible for tumor regrowth after xrt
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A fractionated dose is biologically efficient than a single dose
LESS efficient
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Hyperfractionation
Bid (twice daily)
Tid (three times daily)
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As the volume of the organ treated increases, the tolerance dose for the whole organ
decreases
as the volume goes up; the tolerance goes down
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As the size of the daily fraction increases, the cell killing
, and the cell's ability to repair sublethal damage
.
As the size of the daily fraction increases, cell killing INCREASES and the cell's ability to repair sublethal damage DECREASES (thus resulting in a decrease in the radiation tolerance of normal tissue)
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Isoeffect Curves
Isoeffect curves relate the treatment schedule in terms of total dose & time w/ the clinical outcome, including early effects, late effects & tumor cure.
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