indirect damage
- primary photon interaction producing high energy electrons
- high energy electrons in moving through the tissue produce free radicals in water [H+ and OH-]
- free radicals may produce changes in DNA from breakage of chemical bonds
- changes in chemical bonds result in biological effects
cell survival curves
describes the relationship between the surviving fraction of cells i.e. fraction of cells that maintain their reproductive integrity (clonogenic cells) and the absorbed dose
shape of the CS curve depends on
the type of radiation
- high LET densely ionising radiation is an exponential function of dose
- low LET sparsely ionising radiation has a shoulder region before becoming exponential
factors making cells less radiosensitive includes
- less oxygen or hypoxic state
- low dose rates
- fractionation
- cells synchronised in the late S phase of the cell cycle
physical planning
involves the use of physical quantities
- dose and dose-volume parameters that are assumed to correlate with biological outcome e.g. V20 for lung
- surrogates for biological response
biologically guided RT
- uses relevant information of individual patient biological response of the tumour and normal tissues to design dose distributions
- tumour and normal tissue radiosensitivity, oxygenation status, proliferation rate
biological based planning
- use of feedback from biological response models in the treatment planning process
- feedback could be automated (inverse planning) or manual (forward planning)
EUD
the uniform dose that would yield the same biological effect as non-uniform dose (delivered with the same number of fractions)
linear quadratic model
- used to describe the CS curve assuming there are two components to cell kill
- the a/b ratio gives the dose at which the linear and quadratic components of cell kill are equal
- alpha is a constant describing the initial slope of the survival curve
- represents the intrinsic radiosensitivity of the cell
- non-repairable type of cell damage
- linearly dependent on dose
- beta is a smaller constant describing the curvature of the cell survival curve
- repairable type of cell damage with time
- responsible for the dose/fraction variations
- proportional to the square of the dose
early responding tissue
- occurs immediately or during RT
- cell depletion within rapidly dividing cells
- e.g. skin, mucosal layer of gut
symptoms - pain, discomfort
late responding tissue
- starts 6-12 months after RT
- cell depletion within slowly diving cells
- e.g spinal cord, kidney
symptoms - progressive and irreversible, potentially life threatening
CS are more curved than those for the early responding tissues
oxygen effect (hypoxia)
- the presence or absence of molecular oxygen within a cell influences the biological effect of ionising radiation
- more pronounced for low LET radiations
OER equation
OER = dose to produce an effect (response) without oxygen / dose to produce same effect (response) with oxygen
5R’s of radiobiology
- reoxygenation of hypoxic cells during fractionated treatment makes them more sensitive to subsequent doses of radiation
- repopulation cells repopulate during fractionated RT
- radiosensitivity - cells have different radiosensitivities
- repair - cells can repair sub-lethal damage
- redistribution in proliferating cell population through the cell cycle increases the cell kill in fractionated therapy relative to a single session
radiobiological rationale for fractionation
- dividing of dose into multiple fractions spares normal tissues through a repair of sub-lethal damage between dose fractions and repopulation of cells
- the former is greater for late-reacting tissues, and the latter for early reacting tissues
- concurrently, fractionation increases tumour damage through reoxygenation and redistribution of tumour cells
sensitivity to fraction size
- rapidly proliferating cells (most tumour cells), with high a/b
- not very sensitive to changes in fraction size (or dose rate)
- true for most type of tumours
- evidence now that this is not true for prostate tumours
- slow proliferating cells, with low a/b
- plenty of repair capability
- very sensitive to dose/fraction
- late responding normal tissues are therefore sensitive to large doses/fraction
hyperfractionation
uses more than one fraction per day with smaller dose per fraction (<1.8Gy) to reduce long term complications and to allow delivery of higher total tumour dose
hypofractionations
increases dose per fraction minimising tumour cell proliferation during the course of treatment
a larger dose of radiation is delivered during each fraction
BED
biologically equivalent dose
Determine from a/b ratios if fractionation schemes for which BEDs are equal will be equally effective biologically
a/b values for skin
9-12Gy
a/b values for colon
9-11Gy
a/b values for testis
12-13Gy
a/b values for mucosa
9-10Gy
a/b values for kidney
2-2.4Gy
