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S85

ESTRO 36 2017

_______________________________________________________________________________________________

higher values between 2-10

keV.µm

-1

can be found in

treatment plans.

Methods and Results

:

Studies concluding that the mid-SOBP relative biological

effect (RBE) of protons is 1.1 for all tissues and tumours

at all doses per fraction have recently been criticised due

to their use

of:

1. kilovoltage x-ray controls (which mostly provide RBE

values less than 1 and should be excluded),

2. a very limited number of cell lines,

3. a predominance of high doses per fraction (as used for

eye melanomas),

4. linear-only fitting (rather than linear quadratic),

5. animal based studies that used only acute reacting

tissues (with high α/β ratios), known to show little RBE

change with dose per fraction when using fast neutrons

(which ionise mostly by forming recoil protons).

No classical late reacting (low α/β) tissue RBEs have been

published so far: it is these tissues that will influence PT

late effects for important normal tissues within the PTV

and closely around it. Of prime concern is neurological

tissue with α/β of 2 Gy. Using a scaling model based on

the original work of Wilkens & Oelfke, but with added

saturation effects for increases in both α and β with LET,

figures 1 and 2 shows the predicted RBEs in the range of

LET normally in the SOBP

(1-2keV.µm

-1

) and the general

increase in RBE with LET and decrease of RBE with dose

per fraction; at higher values of LET (2-10) further

increases in RBE occur, in some cases to beyond 2 at LETs

of 6-10.

Outside the brain, other normal tissue types may carry

lesser importance so that, for example, a slightly raised

RBE in muscle may not produce enhanced late effects in a

very confined volume, as may serially organised tissues

such as lung and liver, but cardiac tissue, bowel and

kidney remain at risk depending on the volume irradiated.

One intriguing aspect is the fall of RBE with increased dose

per fraction, especially in tisses with low α/β values,

which may encourage the use of carefully estimated

hypofractionated total doses, using BED equations with

imbedded RBE limits: the RBEmax and RBEmin

(respectively reflecting the change in α and β with LET):

Figures 1 and 2 show how different α/β ratio bio-systems

may behave with the lowest α/β system crossing over to

have the lowest RBE at higher doses. Values lower than

1.1 can occur in high α/β systems, with risk of

underdosage if a 1.1 RBE is used.

Conclusions

. There should be no complacency about RBE

values, even within SOBP`s: 1.1 is not be appropriate.

These higher values may explain some reported adverse

toxicities following PT, such as necrosis of the optic

chiasm and temporal lobe, and failure to cure some very

radiosensitive tumour types with high α/β (lymphomas and

many childhood cancers). Comprehensive RBE studies are

urgently indicated.

References:

Jones, B in Cancers (Basle) 2015, 7, 460-480;

also, Brit J Radiol, Why RBE must be a variable and not a

constant. Published Online: May 05, 2016.

Figures 1&2

SP-0169 A small animal tumour model for low-energy

laser-accelerated particles

J. Pawelke

1,2

, K. Brüchner

3,4

, M. Krause

4,5,6

, E. Leßmann

2

,

M. Schmidt

5

, E. Beyreuther

2

1

OncoRay - National Center for Radiation Research in

Oncology- Faculty of Medicine and University Hospital

Carl Gustav Carus-Technische Universität Dresden,

Department of Medical Physics- Laser Radiooncology

Group, Dresden, Germany

2

Helmholtz-Zentrum Dresden - Rossendorf, Institute of

Radiation Physics, Dresden, Germany

3

Faculty of Medicine and University Hospital Carl Gustav

Carus- Technische Universität Dresden, Experimental

Center, Dresden, Germany

4

Helmholtz-Zentrum Dresden - Rossendorf, Institute of

Radiooncology, Dresden, Germany

5

OncoRay - National Center for Radiation Research in

Oncology- Faculty of Medicine and University Hospital

Carl Gustav Carus-Technische Universität Dresden,

Department of Radiation Oncology, Dresden, Germany

6

German Consortium for Translational Cancer Research

DKTK and German Cancer Research Center DKFZ,

Dresden Site, Dresden, Germany

Introduction:

The long-term aim of decveloping laser-

based acceleration of protons and heavier ions towards

clinical radiation therapy application requires not only

substantial technological progress, but also the

radiobiological characterization of the resulting ultra-

short and ultra-intensive particle beam pulses. Recent in

vitro data showed similar effects of laser-accelerated

versus conventional proton beams on clonogenic cell

survival and DNA double-strand breaks. As the proton

energies currently achieved for radiobiological

experiments by laser-driven acceleration are too low to

penetrate standard tumour models on mouse legs, a small

animal tumour model allowing for the penetration of low

energy protons (~20 MeV) was developed to further verify

the effects in vivo.

Methods:

The mouse ear tumour model was established

for human HNSCC FaDu and human glioblastoma LN229

cells. For this, cells were injected subcutaneously in the

right ear of NMRI nude mice and the growing tumours were

characterized with respect to growth parameters and

histology. After optimizing the number of injected cells

and used medium (PBS, Matrigel) the radiation response

was studied by 200 kV X-ray irradiation. Furthermore, a

proof-of-principle full scale experiment with laser-

accelerated electrons was performed to validate the FaDu