ESTRO 36 Abstract Book

S212

ESTRO 36 2017

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treatment options have failed. For that reason, only

sporadic cases with advanced disease and large bulky

tumours have been treated with grid therapy. Large in-

beam peak doses,

e.g.

15 Gy, have been given to the

target volume in a single treatment fraction. Although

certain sub-volumes of the target (in-between the beams)

are given low doses, significant reductions of the size of

large tumours have been demonstrated. Grid therapy has

been found to produce limited toxicity in the surrounding

sensitive tissues. The high normal-tissue tolerance to

beam grids is closely related to the so-called dose-volume

effect which has been characterized for single beams.

Experiments with beam sizes in the millimetre to

centimetre range with both proton- and photon-beams

have demonstrated that the tolerance doses for various

biological endpoints,

e.g

. different skin reactions and

nervous-system white-matter necrosis, are rising with

reduced beam sizes. Research carried out within the

American space exploration program in the 1950s showed

that the tolerance doses increased dramatically for

micrometer-wide beams. Certain endpoints,

e.g.

moist

desquamation, are never observed for sufficiently small

beam widths, even for extremely high doses. The

migration of cells from unirradiated to irradiated volumes

and an improved vascular repair if only a short segment of

a vessel is irradiated have been stated as reasons for the

improved tissue repair observed. Experiments and

preclinical radiotherapy trials with photon- and ion-beam

grids, containing beam elements of widths in the

micrometre to millimetre range, have recently been

carried out. These experiments have demonstrated the

high degree of normal-tissue tolerance to irradiation with

grids of narrow beams up to doses (hundreds of Grays)

which are much higher than those used clinically. In

ongoing radiobiological research, there are still some open

questions regarding the tumour response to spatially

modulated beams. A differential effect on the tumour

vasculature has been reported. The so-called bystander

effect has also attracted many researchers´ interests.

However, the direct effects of radiation, due to radiation

that directly hits the cell nuclei and cause DNA double-

strand breaks, are generally believed to be much more

important for the cell survival. Whether the bystander

effect significantly changes the outcome of grid therapy

has not been proven because both beneficial and

destructive bystander responses have been reported. The

x-ray beams produced by the early machines were of low

energy and highly divergent. Therefore, the beam

elements in the grid began to overlap already close to the

patient surface. The large divergence made it difficult to

produce a tissue-sparing effect at larger depths and also

made it nearly impossible to produce a uniform dose in the

target by cross-firing irradiation grids with opposing

beams. Nowadays, more parallel x-ray beams of high

energy and fluence rate are available. Thus, there is a real

possibility to exploit the normal-tissue sparing effect of

radiation grids for the treatment of more deep-seated

organs. Development in beam technology has provided

new possibilities to cross-fire radiation grids with the aim

of producing a uniform dose in the target volume.

Furthermore, beams containing charged particles,

e.g.

electrons, protons and carbon ions, have recently been

suggested for use in grid therapy. The limited range, and

the sometimes increased radiobiological effectiveness of

charged-particle beams, may be found advantageous.

Some results from the most recent research on grid

therapy will be shown in this presentation.

SP-0402 Strategies for radiosensitization with gold

nanoparticles

S. Krishnan

UT MD Anderson Cancer Center Radiation Physics,

Houston- TX, USA

Radiation therapy is a long-established component of

modern therapy for localized cancers. However, its

ultimate utility is limited by the inherent resistance of

some cancer cells to ionizing radiation. To circumvent this

problem, radiation dose escalation, targeting resistance

pathways or resistant cells with novel agents, or image-

guided tumor-targeted therapy are currently being

investigated. Emerging evidence from an explosion of

knowledge and research regarding oncologic uses of gold

nanoparticles suggests that unique solutions to each of

these problems of radiation resistance can be formulated

via the use of gold nanoparticles. Gold nanoparticles can

be used to augment the efficacy of radiation therapy via

physical dose enhancement based on an increase in

photoelectric absorption due to the high atomic number

(Z) of gold that accumulates preferentially within the

tumor due to passive extravasation of nanoparticles

through “leaky” tumor vasculature. This radiation dose

enhancement can be heightened via biological

targeting. Enhancement of radiation therapy efficacy can

also be achieved via extrinsic actuation of tumor-homing

nanoparticles to generate mild temperature hyperthermia

which enhances vascular perfusion and reduces hypoxia

initially and causes vascular disruption subsequently to

improve radioresponse. The extrinsic energy source is light

for colloidal gold nanoparticles with a large absorption

cross section that absorb and scatter light strongly at a

characteristic wavelength (their plasmon resonance) and

have a high thermal conductivity to couple this heat to the

surrounding tissue.

The interface between nanotechnology and radiation

oncology warrants continued investigation by

interdisciplinary teams of physicists, chemists, biologists,

clinicians, and engineers in industry and academia. This

talk will review the current understanding of the use of

gold nanoparticles as radiosensitizers, and outline a path

to potential clinical translation of these concepts of

radiation sensitization.

SP-0403 Potentials of Cerenkov imaging in

radiotherapy

A. Spinelli

Fondazione Centro San Raffaele, Medical Physics,

Milano, Italy

In this talk we will provide an overview of Cerenkov

radiation (CR) production mechanism, we will then show

examples of Cerenkov luminescence imaging (CLI) of small

animals and humans. The potential uses of CLI for quality

assurance (QA) and real time in vivo dosimetry during

external-beam radiation therapy (RT) will be also

presented.

The mechanism of CR production is quite unique with

respect to other and more common charged particles and

matter interaction mechanisms. In this case when a

charged particle travels through a dielectric medium, it

becomes locally polarized, with the atoms comprising the

medium behaving such as elementary dipoles. If the speed

of the particle is less than the speed of light in the

medium, symmetry of the polarization results in a

negligible field at larger distances. However, if the

particle's speed exceeds that light in this medium, the

polarization field becomes asymmetric along the particle

track producing a resultant dipole field at larger distances

from the track [1].

For a beta particle travelling in water the energy threshold

for Cerenkov emission is equal to 261 keV. This energy

threshold is relatively low and thus CLI can be applied to

image most of the beta plus and minus emitters commonly

used in nuclear medicine, and as will be described in this

talk, also to provide a novel method to monitor external-

beam RT.

CLI is becoming a well-established method for preclinical

in vivo small animal optical imaging and has been also

applied to humans for example to image a patient treated