Linear energy transfer and Radiation fractionation

PROF.S.SUBBIAH et.al
LINEAR ENERGY TRANSFER
AND RADIATION
FRACTIONATION
Department of Surgical Oncology
Centre for Oncology
GRH,Royapettah

IONIZATION
• Ionization is the process of ejecting one or more
electrons from an atom and the radiation
producing such effect is known as Ionizing
radiation.

Types of ionizing radiations
• Directly ionizing: When absorbed in material, they
directly cause ionization leading to damage. Eg:
electrons, α-particles, β-particles
• Indirectly ionizing: When absorbed in material,
they give up their energy to produce fast moving
charged particles which produce the damage. Eg:
Electromagnetic radiation

Types of ionizing radiations
• Electromagnetic radiations (Indirect)
• Particulate radiations (Direct)

Particulate Radiations
• Electrons are small, negatively charged particles
that can be accelerated to high speed close to that
of light by means of electrical device
• Protons are positively charged particles and can be
accelerated to useful energies
• α-particles are nuclei of helium atom consisting of
2 protons and 2 neutrons and emitted during the
decay of radionuclides like uranium, radium.

Particulate Radiations
• Neutrons are particles with mass similar to proton
but are chargeless and cannot be accelerated in an
electrical device.
• They are produced if charged particle like
deuterium is accelerated to high energy and made
to hit on a suitable target.

• Linear energy transfer (LET) is the amount of
energy transferred per unit length of the track.
• Unit: kiloelectron volt per micrometer (keV/μm) of
unit density material.
• The International Commission on Radiological
Units (1962) defined as:
• The linear energy transfer (L) of the charged
particles in the medium is the quotient of the dE/L
where dE is the average energy locally imparted to
the medium by a charged particle of specified
energy in traversing a distance of dl. That is L=dE/dl

Deposition of radiant energy
• If radiation is absorbed in biologic material, the
events(ionization) tend to localize along the tracks
of individual particles in a pattern that depends
upon the type of radiation involved.

• Xray photons give rise to fast moving electrons
Which carries a charge and have very less mass.
The primary events(ionisation) of x-rays are well
separated in space and hence said to be sparsely
ionizing.
• Cobalt 60-γ-rays are even more sparsely ionizing
than x-rays.

• Neutrons give rise to recoil protons carrying
charged unit but mass 2000 times greater than that
of electrons. Neutrons are intermediately ionizing.
• α-particles carry 2 electrical charges and 4 times
heavier than a proton. They are densely ionizing

High and Low LET Radiations
• High LET Radiation:
• This is a type of ionizing radiation that deposit a
large amount of energy in a small distance.
• Eg: Neutrons, alpha particles
• Low LET Radiation:
• This is a type of ionizing radiation that deposit less
amount of energy along the track or have
infrequent or widely spaced ionizing events.
• Eg: x-rays, gamma rays

The Optimal LET
• LET of about 100keV/μm is optimal in terms of
producing biologic effect.
• At this density of ionisation the average separation
between the ionizing events just about coincides
with the diameter of DNA double helix (2nm) and
has highest probability of causing Double Strand
Breaking by passage of a single charged particle.

HIGH VS LOW LET RADIATIONS
• High LET radiation ionizes water into H and OH radicals over a
very short track. In fig. two events occur in a single cell so as to
form a pair of adjacent OH radicals that recombine to form
peroxide, H2O2, which can produce oxidative damage in the
cell.
• Low LET radiation also ionizes water molecules, but over a
much longer track. In fig. two events occur in separate cells,
such that adjacent radicals are of the opposite type: the H and
OH radicals reunite and reform H₂O.

High vs Low LET Radiations
• High-LET radiations are more destructive to
biological material than low-LET radiations.
• The localized DNA damage caused by dense
ionizations from high-LET radiations is more
difficult to repair than the diffuse DNA damage
caused by the sparse ionizations from low-LET
radiations.

• High LET radiation results in lower cell survival per
absorbed dose than low LET radiation.
• High LET radiation is aimed at efficiently killing
tumor cells.
• Biological effectivenessof high LET radiation is not
affected by the time or stage in the life cycle of
cancer cells, as it is with low LET radiation.

In x-rays, probability of a single track causing a Double strand
Break is low and requires more than one track.
Much more densely ionizing radiations (eg. LET of 200keV) readily
produce DSBs but energy is wasted as events coincide with each
other.

• Radioprotectors containing a sulfhydryl group exert their
effect by scavenging Free radicals and by reducing free-
radical damage to DNA.
• They are most effective for radiations characterized by
low linear energy transfer (LET), becoming progressively
less effective with increasing LET because the amount of
local damage is so great.

RADIATION
FRACTIONATION

• Fractionation in the context of radiotherapy is the
process of dividing a dose of radiation into multiple
“fractions”.
• This practice seeks to maximize the destruction of
malignant cells while minimizing damage to healthy
tissues.

TYPES
1) Conventional fractionation
2) Altered fractionation
• Hyper fractionation
• Accelerated fractionation
• Split course
• Hypofractionation

CONVENTIONAL
• Division of dose into multiple, spares normal tissue
through repair of cells and repopulation of cells.
• Concurrently , fractionation increases tumor
damage through reoxygenation & redistribution of
tumor cells.

• Most common conventional fractionation for
curative radiotherapy is 1.8 to 2.2Gy.

HYPERFRACTIONATION
• Hyperfractionation~ delivery of radiation in
multiple small-dose fractions( 2-3 times per day)
• Aims to improve the therapeutic ratio, reducing the
dose given in each fraction, so as to reduce the late
side effects while also permitting an increased total
dose to the tumor.

• A hyper fractionated schedule of 80.5Gy/70#(1.15Gy
twice/day)/7wks compared with 70Gy/35#/7wks in
head & neck cancer.
• IMPLICATIONS
• Increased local tumor control at 5yr from 40 to59%.
• Reflected in improved survival.
• No increase in side effects.

ACCLERATED FRACTIONATION
• Alternative to hyper fractionation
• Rationale – To reduce repopulation in rapidly
proliferating tumors by reducing overall treatment
time.
• Pure accelerated treatment – same total dose delivered
in half the overall time by giving 2or more
fractions/day. but it is not possible to achieve as acute
effects become limiting factor.
• Impure accelerated treatment – dose is reduced or rest
period is interposed in the middle of treatment.

• comparison of head & neck cases accelerated
regimen 72Gy/45 (1.6Gy,3/day)/5wks with
70Gy/35/7wks
• Implications – 15% increase in loco regional control.
• No survival advantage.
• Increased acute effects.

SPLIT COURSE
• Total dose is delivered in two halves with a gap in
b/w with interval of 4wks.
• Purpose of gap is to allow elderly pts. to recover
from acute reactions of treatment
• Applied to elderly pts. in radical treatment of ca
bladder & prostate & lung cancer.

HYPOFRACTIONATION
• High dose is delivered in 2-3Days/wk. E.g.
50Gy/10#/5wks treating 2 days a wk in head & neck
cancer.
• Rationale - Treatment completed in a shorter period of
time.
• Machine time well utilized for busy centers.
• Higher dose gives better control for larger tumors.
Higher dose also useful for hypoxic fraction of large
tumor.
• Disadv. Higher potential for late normal tissue
complications.

THANK YOU

Linear energy transfer and Radiation fractionation

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