Radiotherapy – Piet Ost
1. Basic principles
Radiation= transmission of energy in the form of waves/particles through space/a
material
- Classified as ionizing and non-ionizing
o Ionizing= having energy more than that is required to ionize an
atom -> particles, protons and electrons
o Non ionizing radiation: visible light and radio waves
- Radiation oncology: use of megavoltage X- and gamma-rays and high
energy electrons for treating malignant diseases and sometimes benign
ones
- Dose deposition varies with different types of radiotherapy (RT)
How do electrons, photons and protons differ in how they deposit a dose?
- Electrons
o =negatively charged subatomic particles
o Electron beams have energies between 1-50 MeV
o Cause ionisation and excitation (collision loss)
o Rate of energy loss is greater for low atomic number material
o Produce Bremsstrahlung X-rays when interacting with nuclei
o Key features of electron beams
High surface dose
Rapid dose falloff
Selection of electron beam energy to cover the target volume
completely within the 90% isodose curve
- Photons
o Electromagnetic radiation such as X-rays/gamma rays have no
mass/charge -> indirectly ionize matter after producing secondary
electrons
o Conventional photon energy after incidence in the skin surface ->
interaction stars -> after a small build up region => maximum
energy deposited
o Energy deposition decreases exponentially with increasing depth in
tissue
- Protons
o =positively charges subatomic particles
o Dose delivered with protons prescribed as Cobalt Gray Equivalents
(CGE)
o Protons interact with both electrons and nuclei by inelastic collisions
and elastic scattering
o Proton dose distribution depends on linear energy transfer (LET)
o Rate of energy loss of a proton is proportional to the square of the
particle charge and inversely proportional to the square of its
velocity
o Bragg peak= energy loss is maximum particle when velocity
approaches 0 near the end of its range
1
,1.1 Radiation damages cells through both direct and indirect actions
Direct action
- Involved direct DNA damage
- Ionizing radiation interacts with the molecular infrastructure of the cell =>
chemical reactions that occur within 10-18 to 10-3 seconds
- Absorption of the photon energy destabilizes the target molecule =>
molecular breaks/release of energetic electrons and secondary energy-
attenuated photons which may interact with other cellular molecules =>
chain reaction that produces a variety of short-lived ions and chemically
unstable free radicals
- Complex/clustered DNA ds breaks most significant for radiation lethality
and carcinogenesis
Indirect action
- Involves DNA damage by means of free radicals
- Most common radicals are produced from the radiolysis of cellular water
o Hydroxyl radicals, hydrated electrons, hydrogen atoms and
hydrogen peroxide
- Free radicals are extremely unstable and interact nearly instantaneously
with neighbouring molecules to produce chemically stable lesions
2. Fractionation
=RT method where the total dose of radiation is divided into smaller doses which
are administered over a period of days/weeks => time and dose are 2 important
variables
Conventional fractionation
- Daily irradiation with a 2Gy dose per fraction to a homogenous field over 5-
8weeks to reach a specified total dose
- PURPOSE => to increase the dose to the tumor while preserving normal
tissue function
o Fractionation achieves this because normal tissues and tumors
respond differently to changes in fractionation due to variations in
their repair mechanisms
2.1 Alternative fractionation includes hyperfractionation and
hypofractionation
Fractionation
- Introduced because it was considered inefficient to deliver the total
radiation dose in one treatment because cells were in different states of
radiosensitivity + multiple exposures could hit the cells in a radiosensitive
phase
- Assumed to create a favourable therapeutic ratio because the tolerance of
normal tissue increased relative to that of tumors + malignant cells had a
greater reproductive capacity + more likely to be in a radiosensitive phase
Hyperfractionation
2
, - Divides the total dose into smaller doses administered more than once a
day over the same period as standard RT
- Rationale is to spare late-responding tissues
- Radiation is delivered in smaller dose per fraction with 2 or more fractions
delivered every day with a gap of 6h between fractions
- More helpful for tumors with higher /β ratio than that for the dose limiting
late responding normal tissue
- Head and neck cancers shown the maximum clinical benefit with this
fraction-survival benefit of 8% at 5years
Hypofractionation -> general tendency to move hypofractionation in many tumor
types
- Divides the total radiation dose into larger doses with treatments that are
less frequent => less is more
- Schedule uses a higher dose per fraction + best suited for tumors with low
/β ratio like breast and prostate cancer
Higher dose per day to reduce the amount of sessions => faster + more
comfort
Dose prescription
- GOAL: give a high dose to the tumor and low dose to OARs
- CHOOSE: total dose and dose per fraction and total duration of treatment
2.2 The 6R’s of radiotherapy -> EXAMEN
RT is an integral part of cancer treatment in most of the solid malignancies
Basis principle: to deliver maximum dose to the target while sparing normal
tissue as much as possible
Important factors affecting therapeutic ratio: total dose, dose per fraction, overall
treatment time, time interval between fractions, intrinsic radiosensitivity, dose
rate
4R’s of RT
For better understanding of time dose and fractionation in RT
- Dividing a dose into several fractions will spare normal tissue due to repair
of sublethal damage + repopulation of the cells if time between the 2
fractionation is sufficiently long
- At the same time tumor damage will be higher due to reoxygenation and
reassortant/redistribution of the cells in more radiosensitive phase (G2/M)
- Later on the concept of 4R’s changed to 6R’s => radiosensitivity and
remote (bystander effect)
6R’s are the basis of time dose and fractionation in RT
6R’s of RT
- Repair of sublethal damage in normal tissue – repair of recovery of
sublethal damage
o Cell kill by ionization radiation happens because of the DNA db
breaks
3
1. Basic principles
Radiation= transmission of energy in the form of waves/particles through space/a
material
- Classified as ionizing and non-ionizing
o Ionizing= having energy more than that is required to ionize an
atom -> particles, protons and electrons
o Non ionizing radiation: visible light and radio waves
- Radiation oncology: use of megavoltage X- and gamma-rays and high
energy electrons for treating malignant diseases and sometimes benign
ones
- Dose deposition varies with different types of radiotherapy (RT)
How do electrons, photons and protons differ in how they deposit a dose?
- Electrons
o =negatively charged subatomic particles
o Electron beams have energies between 1-50 MeV
o Cause ionisation and excitation (collision loss)
o Rate of energy loss is greater for low atomic number material
o Produce Bremsstrahlung X-rays when interacting with nuclei
o Key features of electron beams
High surface dose
Rapid dose falloff
Selection of electron beam energy to cover the target volume
completely within the 90% isodose curve
- Photons
o Electromagnetic radiation such as X-rays/gamma rays have no
mass/charge -> indirectly ionize matter after producing secondary
electrons
o Conventional photon energy after incidence in the skin surface ->
interaction stars -> after a small build up region => maximum
energy deposited
o Energy deposition decreases exponentially with increasing depth in
tissue
- Protons
o =positively charges subatomic particles
o Dose delivered with protons prescribed as Cobalt Gray Equivalents
(CGE)
o Protons interact with both electrons and nuclei by inelastic collisions
and elastic scattering
o Proton dose distribution depends on linear energy transfer (LET)
o Rate of energy loss of a proton is proportional to the square of the
particle charge and inversely proportional to the square of its
velocity
o Bragg peak= energy loss is maximum particle when velocity
approaches 0 near the end of its range
1
,1.1 Radiation damages cells through both direct and indirect actions
Direct action
- Involved direct DNA damage
- Ionizing radiation interacts with the molecular infrastructure of the cell =>
chemical reactions that occur within 10-18 to 10-3 seconds
- Absorption of the photon energy destabilizes the target molecule =>
molecular breaks/release of energetic electrons and secondary energy-
attenuated photons which may interact with other cellular molecules =>
chain reaction that produces a variety of short-lived ions and chemically
unstable free radicals
- Complex/clustered DNA ds breaks most significant for radiation lethality
and carcinogenesis
Indirect action
- Involves DNA damage by means of free radicals
- Most common radicals are produced from the radiolysis of cellular water
o Hydroxyl radicals, hydrated electrons, hydrogen atoms and
hydrogen peroxide
- Free radicals are extremely unstable and interact nearly instantaneously
with neighbouring molecules to produce chemically stable lesions
2. Fractionation
=RT method where the total dose of radiation is divided into smaller doses which
are administered over a period of days/weeks => time and dose are 2 important
variables
Conventional fractionation
- Daily irradiation with a 2Gy dose per fraction to a homogenous field over 5-
8weeks to reach a specified total dose
- PURPOSE => to increase the dose to the tumor while preserving normal
tissue function
o Fractionation achieves this because normal tissues and tumors
respond differently to changes in fractionation due to variations in
their repair mechanisms
2.1 Alternative fractionation includes hyperfractionation and
hypofractionation
Fractionation
- Introduced because it was considered inefficient to deliver the total
radiation dose in one treatment because cells were in different states of
radiosensitivity + multiple exposures could hit the cells in a radiosensitive
phase
- Assumed to create a favourable therapeutic ratio because the tolerance of
normal tissue increased relative to that of tumors + malignant cells had a
greater reproductive capacity + more likely to be in a radiosensitive phase
Hyperfractionation
2
, - Divides the total dose into smaller doses administered more than once a
day over the same period as standard RT
- Rationale is to spare late-responding tissues
- Radiation is delivered in smaller dose per fraction with 2 or more fractions
delivered every day with a gap of 6h between fractions
- More helpful for tumors with higher /β ratio than that for the dose limiting
late responding normal tissue
- Head and neck cancers shown the maximum clinical benefit with this
fraction-survival benefit of 8% at 5years
Hypofractionation -> general tendency to move hypofractionation in many tumor
types
- Divides the total radiation dose into larger doses with treatments that are
less frequent => less is more
- Schedule uses a higher dose per fraction + best suited for tumors with low
/β ratio like breast and prostate cancer
Higher dose per day to reduce the amount of sessions => faster + more
comfort
Dose prescription
- GOAL: give a high dose to the tumor and low dose to OARs
- CHOOSE: total dose and dose per fraction and total duration of treatment
2.2 The 6R’s of radiotherapy -> EXAMEN
RT is an integral part of cancer treatment in most of the solid malignancies
Basis principle: to deliver maximum dose to the target while sparing normal
tissue as much as possible
Important factors affecting therapeutic ratio: total dose, dose per fraction, overall
treatment time, time interval between fractions, intrinsic radiosensitivity, dose
rate
4R’s of RT
For better understanding of time dose and fractionation in RT
- Dividing a dose into several fractions will spare normal tissue due to repair
of sublethal damage + repopulation of the cells if time between the 2
fractionation is sufficiently long
- At the same time tumor damage will be higher due to reoxygenation and
reassortant/redistribution of the cells in more radiosensitive phase (G2/M)
- Later on the concept of 4R’s changed to 6R’s => radiosensitivity and
remote (bystander effect)
6R’s are the basis of time dose and fractionation in RT
6R’s of RT
- Repair of sublethal damage in normal tissue – repair of recovery of
sublethal damage
o Cell kill by ionization radiation happens because of the DNA db
breaks
3
