Week 2 Radiobiology Flashcards
Radiobiology
the study of the action of ionizing radiation on living things
Bergonie and Tribondeau, 1906
any cells that are immature, undifferentiated and actively dividing (i.e., stomach mucosa, basal layer of skin, stem cells) are more radiosensitive
Cells that are mature, differentiated and not actively dividing (i.e., neurons) are more radioresistant
Types of ionizing radiation
Electromagnetic
X-rays
produced in an electrical device that accelerates electron to high energy and abruptly stops them in a target (tungsten or gold)
Gamma rays
Emitted by radioactive isotopes
Types of ionizing radiation
Particulate
Electrons Protons α-particles Neutrons Heavy charged particles
Absorption of x-rays
Directly Ionization
Disrupt the atomic structure, producing chemical and biologic changes
α particles, protons
electrons, β-, β+
High LET radiation
Absorption of x-rays
Indirect ionization
Give up energy to charged particles, which are able to produce damage.
Neutrons
EM Radiation
Interact with other atoms or molecules to produce free radicals
Mitosis
process of cell division that results in two genetically identical daughter cells developing from a single parent cell.
Cell cycle
There are 4 phases of mitosis:
M Phase, in which cells divide in 2
most radiosensitive
G1Phase (gap one), in which cells prepare for DNA replication
S Phase, in which DNA doubles by replication
G2Phase (gap two), in which cells prepare for mitosis
Undifferentiated cells
are precursor or stem cells and have less specialized functions. Their major role is to reproduce to replace themselves and to provide cells which mature into more differentiated cells.
Examples: bone marrow cells, intestinal crypt cells and basal cells of the skin
The more specialized a cells function is, the more differentiated it is
examples are the major organ cells, muscle and neurons
Highly differentiated cell usually have less reproductive activity than undifferentiated cells
radiosensitivity
The most radio-sensitive cells are those which: have a high division rate have a high metabolic rate are of a non-specialized type are well nourished
Single Target-Single Hit
Only one target in the cell associated with cell death and a singal hit on this target is adequate to inactivate the target (viruses and some bacteria)
Multiple-Target Single Hit
Multiple targets per cell, a single hit of any of these targets is required for cell death. Not all targets are hit, some of them are killed, while others are damaged by low doses (sublethal damage) Cells with SLD may repair themselves during interfractional periods
This is valid for mammalian cells
Linear energy transfer (LET)
LET → loss of energy per unit tract length
A function of the charge and velocity of the ionizing radiation
increases as the charge on the ionizing radiation increases and its velocity decreases
Relative biological effectiveness (RBE)
The RBE is the ratio of the 250 kV X-ray dose that produces a specific biological effect to the test dose of any radiation that produces the same effect. The RBE is related to the LET.
High LET (pariculate)
deposits more energy per unit length, more destructive
than same dose of external beam rad.
Alpha particles are slow and positively charged
Beta particle fast and negatively charged
LET alpha>LET beta
RBE-Radiobiologic Effect
RBE=250 kV x-ray dose required for a specific effect/Tested dose of any radiation required for a specific event
Cell survival curves
Relationship between dose and proportion of cells that survive
Linear Quadratic Model
Respones at low levels of radiation are linear, while higher doses are quadratic No threshold (although may be inaccurate at 7Gy+)
Extrapolation number (n)
Determinated by extrapolating the linear of the curve back until it intersects the y-axis (#of critical targets in the cell)
D(0) dose:
D37 dose, reduces surviving fraction (SF) by 63%
D(q) dose:
Quasithreshold dose: measure of width of the shoulder region. also a measure of the cells ability to repair sublethal damage
Oxygen Enhancement Ratio (OER)
Radiosensitizer
Oxygen must be present during the radiation exposure for sensitization to occur
As the availability of oxygen decreases, cell response also decreases and the survival curve shifts to the right because Dq and Do increase
OER = Radiation dose under hypoxic/anoxic conditions
Radiation dose under oxic conditions to produce the same biological effect
BED
Biological Effective Dose Model
Derived from LQ equation for cell survival
Used to calculate treatment regimes that are equally effective biologically
Use with caution for extrapolation to normal tissue limits
Conventional
1.8 – 2.2Gy /fx & 5 fx per week
Hyperfractionation
More than 1 fraction a day
1.2 – 1.3Gy/fx
Dose increased ~ 20% to allow for increased repair at lower dose/fx
Accelerated Fractionation
For rapidly growing tumors
Treat 6-7 days a week, same dose/fx as conventional
Accelerated Hyperfractionation
CHART: Acute side effects are a problem
1.5Gy/fx three times a day, 7 days per week
Patients are done with treatment before the acute side effects start
Hypofractionation
Palliative
30Gy/10fx; 20Gy/5fx; 8Gy/1fx
5 R’s of radiobiology
Fractioned radiotherapy is founded on five main features:
Repopulation
Increases the number of tumor cells to be destroyed → against treatment
Increases the number of normal tissue cells following irradiation → in favor of treatment
Repair
The application of radiotherapy in fractionated doses allows normal tissues time to repair
If an optimal interval is left between fractions (6–12 h), normal tissue cells responding late to radiation have the capacity for faster repair than tumor cells.
The repair of SLD in spinal cord is much slower than that in other normal tissues. Thus, the interfraction interval should be at least 8 h in spinal cord irradiation.
Redistribution (= reassortment)
Cells in resistant phases of the cell cycle may progress into a sensitive phase during the next dose fraction.
Reoxygenation
Oxygen is required for the indirect effect to occur, therefore hypoxic cells are 2-3 times more radioresistant
Radiosensitivity
involves multiple components
Radiosensitivity may be affected by environmental conditions.
radiosensitivity is directly proportional to mitosis and inversely proportional to differentiation.
Brainstem
TD 5/5 of 50Gy to entire brainstem and 60Gy to 1/3 of the brainstem
QUANTEC
Entire brainstem can tolerate 54Gy with a < 5% risk of brainstem necrosis or neurological toxicity.
Small volumes (1-10 cc) can tolerate up to 59 Gy while a point (< 1 cc) may receive up to 64Gy.
Spinal cord
Max dose of 50 Gy to spinal cord <0.2% risk of myelopathy
Paralysis, sensory, deficits, pain, and bowel/bladder incontinence
Chiasm & Optic Nerves
Infrequent Rapid painless visual loss Whole organ dose of 50Gy has a < 1% risk of blindness < max 55Gy = rare Max 55 -60 Gy = 3 – 7% risk > 60Gy risk greatly increases
retina
Recommendation of max dose < 50Gy
Retinopathy- results in loss of vision
cochlea
Hearing loss
High frequency more common
Recommended mean ≤ 45Gy
Cisplatin-based chemotherapy can have an additional adverse effect on hearing loss
parotid
Xerostomia
Sparing 1 parotid (mean < 20Gy) reduces incidence of grade 4 xerostomia
Or both means < 25Gy
mandible
Osteoradionecrosis
Recommended point dose dmax of ≤70Gy
Pharyngeal Constrictors
Dysphagia & aspiration
Recommended mean dose of < 60Gy when possible
larynx
Vocal dysfunction & laryngeal edema
Mean <44Gy <20% Edema
Brachial plexus
Pain, paresthesias or motor deficits of the upper extremity
Muscular atrophy and edema may develop
Late effect
5-20 years post radiation
Max dose of 60Gy has < 5% risk of nerve damage after 5 years
lung
Seen in lung, breast & mediastinal lymphatics
V20 is the most useful parameter for predicting the risk of radiation pneumonitis
V20 <30%, <20% risk
Mean 20Gy, <20% risk
esophagus
Acute esophagitis
During radiotherapy
Mean < 34Gy
heart
Clinical pericarditis & long-term cardiac mortality
Breast & Hodgkin’s Lymphoma
V25 < 10% has a <1% probability of cardiac mortality at 15 years after radiotherapy
liver
Radiation-induced liver disease typically occurs between 2 weeks and 3 months after radiotherapy
Mean 30-32Gy, <5% risk,
kidney
Renal dysfunction
bilateral mean <15-18m, V20 <32%
stomach
Dyspepsia & ulceration
D100 <45Gy
Small bowel
Individual loops V15 <120cc
Peritoneal Cavity V45 <195cc
rectum
High doses are most important in determining risk of toxicity
V50 <50%
V70 <20%
bladder
<65
