Biological Aspect Of Proton And High LET

Source PREPARED BY MAHRAN ALNAHMI

SUPERVISOR PROF.DR. ANWAR MICHAEL

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• Modern radiotherapy is usually given by linear accelerators producing X-rays with high-energy of 4–25 MV

– Energetic enough to ionize molecules in tissues

– this ionization that results in the biological effects seen in radiotherapy

– have roughly the same biological effect per unit dose

INTRODUCTION

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• Electron beams are quantum-mechanically similar to X-rays and produce similar biological effects

• Two other classes of radiations

– Light particles – e.g. protons, neutrons and α-particles

– Heavy particles – e.g. fully stripped carbon, neon, silicon or argon ions

INTRODUCTION

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These light and heavy particles may have a greater biological effect per unit dose than conventional X- and γ-rays

INTRODUCTION

Advantages of protons compared to conventional radiation:

- targeting radiation dose precisely into the tumour,- sparing neighboring healthy tissue.

Physical qual ities of protons

•small lateral scattering

• Energy loss per unit length – linear energy transfer (LET) – increases while the proton slows down.

• range directly proportional to energy.

• depth-dose distribution:- slow increase of dose – plateau region,- rapid build-up to a sharp maximum almost at the end of range – the Bragg peak,- distal swift fall-off.

Practical approach – to del iver uniform dose over large volume at a given depth:

• Spread-out Bragg peak (SOBP) – modulation of proton energy at the price of a slight increase of the entrance dose.

• Modulation of proton energy, i.e., range, is achieved by degrading initial proton energy which results in superimposition of a number of monoenergetic proton beams of closely spaced energies, thus the position of the Bragg peak is pooled back towards the beam source as energy is reduced.

• The Bragg peak and SOBP have a higher LET than the beam entering the tissue.

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MICRODOSIMETRY

the photon beams deposit much of their energy as single isolated ionizations or excitations and much of the resulting DNA damage is efficiently repaired by enzymes within the nucleus.

About 1000 of these sparse tracks are produced per gray of absorbed radiation dose.

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MICRODOSIMETRY

The α-particles produce fewer tracks but the intense ionization within each track leads to more severe damage where the track intersects vital structures such as DNA

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MICRODOSIMETRY

Linear energy transfer (LET) is the term used to describe the density of ionization in particle tracks

◦ LET is the average energy (in keV) given up by a charged particle traversing a distance of 1μm

◦ the γ-rays have an LET of about 0.3 keV/μm and are described as low-LET radiation.

◦ The α-particles have an LET of about 100 keV/μm and are an example of high-LET radiation

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LINEAR ENERGY TRANSFER (LET)

the energy transferred per unit length of the track (keV/mm)

In 1962, the ICRU defined:

◦ The linear energy transfer (L) of charged particles in medium is the quotient of dE/dl, where dE is the average energy locally imparted to the medium by a charged particle of specified energy in traversing a distance of dl.

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LINEAR ENERGY TRANSFER (LET)

charged particle, the higher the energy, the lowerthe LET and therefore the lower its biologic effectiveness.

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BIOLOGICAL EFFECTS DEPEND UPON LET

As LET increases, radiation produces more cell killing per gray

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BIOLOGICAL EFFECTS DEPEND UPON LET

As LET increases, the survival curves become steeper; they also become straighter with less shoulder.

In the LQ model, these straighter cell survival curves have a higher α/β ratio, thus higher LET radiations usually give responses with higher α/β.

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BIOLOGICAL EFFECTS DEPEND UPON LET

The relative biological effectiveness (RBE)

◦ to give the same biological effect

◦ The reference low-LET radiation is commonly 250 kVp X-rays or 60Co γ-rays

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BIOLOGICAL EFFECTS DEPEND UPON LET

The relative biological effectiveness (RBE)

RBE is not constant but depends on the level of biological damage and hence on the dose level.

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BIOLOGICAL EFFECTS DEPEND UPON LET

As LET increases, the oxygen enhancement ratio(OER)decreases.

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THE BIOLOGICAL BASIS FOR HIGH-LET RADIOTHERAPY

hypoxia is a problem in radiotherapy might benefit from high-LET radiotherapy

The effect of low-LET radiation on cells is strongly influenced by their position in the cell cycle, with cells in S-phase being more radioresistant than cells in G2 or mitosis

Cells in stationary (i.e. plateau) phase also tend to be more radioresistant than cells in active proliferation.

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THE BIOLOGICAL BASIS FOR

HIGH-LET RADIOTHERAPY

the effect of fractionated radiotherapy on more rapidly cycling cells compared with those cycling slowly or not at all.

◦ ‘cel l -cycle resensitization ’

This differential radiosensitivity due to cell-cycle position is considerably reduced with high-LET radiation.

might expect high-LET radiotherapy to be beneficial in some slowly growing, X-ray-resistant tumours.

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THE BIOLOGICAL BASIS FOR HIGH-LET RADIOTHERAPY

the range of radiation response of different cell types is reduced with high-LET radiation

if tumour cells are already more radiosensitive to X-rays than the critical normal-cell population, high-LET radiation should not be used

◦ Possible examples are seminomas, lymphomas and Hodgkin’s disease .

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THE PHYSICAL BASIS FORCHARGED-PARTICLE

THERAPY Neutrons are also uncharged and their depth–dose

characteristics are similar

◦ comparable to 4 MV X-rays.

◦ The only rationale for neutron therapy is therefore radiobiological.

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THE PHYSICAL BASIS FORCHARGED-PARTICLE

THERAPY Figure shows some possible treatment plans with heavy-ion

beams of helium and carbon

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THE PHYSICAL BASIS FORCHARGED-PARTICLE

THERAPY

The LET of a charged particle is proportional to the square of its charge divided by the square of its velocity.

Figure -The biological effect of charged particle beams is increased further in the Bragg peak. Depth–dose curves are shown for three types of ion beam, each with a 4-cm or 10-cm spread peak. Full lines show the dose distribution; upper broken lines (full symbols) show the biologically effective dose (i.e. doserelative biological effectiveness, RBE). The lower broken lines (open symbols) show the reduction in oxygen enhancement ratio (OER) within the spread peak. From Blakely (1982), with permission.

LET∝ Q2/V2

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THE PHYSICAL BASIS FORCHARGED-PARTICLE

THERAPY summarizes the relative physical and radiobiological properties

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Key points

X-rays and γ-rays are low LET. Some particle radiations (e.g. neutrons, α-particles or heavy ions) have a high LET

High-LET radiations are biologically more effective per gray than low-LET radiations. Measured by the RBE.

RBE increases as the LET increases up to about 100 keV/μm above which RBE decreases because of cellular overkill.

The OER also decreases rapidly over the same range of LET.

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Key points

Heavy particles such as He, C and Ne ions have a high-LET and in addition they have improved physical depth–dose distributions.

Proton beams provide the best improvement in dose distribution for the lowest cost; their RBE is similar to low-energy photons.

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