Debus, J.

Jäkel, O.

Karger, C.P.

Peschke, P.

Elsevier - Publisher Connector 

SP-0219: Risk of normal tissue injury from protons and heavy ions 

S110                                                                                                                                         3rd ESTRO Forum 2015 
 
SP-0217   
Prone breast radiotherapy: a paradigm shift towards 
standard practice? 
T. Mulliez1 
1University Hospital Ghent, Radiotherapy, Gent, Belgium  
 
Background and purpose: Whole breast irradiation (WBI) in 
the prone position enables a drastical lung dose reduction 
compared to the standard supine position, however in a small 
subset of patients heart dose is increased in prone position. 
Deep inspiration breath hold (DIBH) has been successfully 
implemented in supine position to reduce heart dose for left-
sided WBI. If the effect of DIBH also occurs in prone position, 
DIBH might further reduce heart dose in the majority of 
patients and may address the problem of higher heart dose in 
prone than supine for the specific subgroup of patients. 
Material and methods: Fifty patients underwent CT-
simulation in prone shallow or normal breathing (SB) and 
prone DIBH; the last 30 patients were accepted for prone 
DIBH treatment. WBI was planned with a median prescription 
dose of 40.05Gy.  
Results: Mean heart dose was lowered from 2.2Gy for prone 
SB to 1.3Gy for prone DIBH (p<0.001), while preserving the 
lung sparing ability of prone positioning. The reductions in 
mean heart dose with DIBH according to breast volume 
<750cc (18 patients), 750-1500cc (22 patients) and >1500cc 
(10 patients) were 1.3 ± 0.9Gy, 0.7 ± 0.7Gy and 0.4 ± 0.4Gy, 
respectively. Prone DIBH nearly consistently reduced mean 
heart dose to <2Gy. All patients were able to perform prone 
positioning while holding their breaths for repetitive periods 
of at least 15 seconds during simulation. Two of the 30 
patients addressed for prone DIBH treatment were eventually 
treated in supine position; one patient with a nearly 
presternal located tumorbed and one patient with severe 
abdominal pain caused by prone positioning during the first 
treatment fraction. None of the prone DIBH treated patients 
developed acute grade III toxicity. 
Conclusions: Prone DIBH combines the heart sparing ability 
of DIBH with a drastic reduction in lung dose due to prone 
positioning. This opens the window for prone treatment in a 
specific subgroup of (small breasted) patients in which higher 
heart doses in prone than supine position were observed. 
These results need to be validated in a confirmatory phase II 
trial.  
  
SP-0218   
Psycho social aspects of breast cancer from a patient's 
point of view 
C. Boronat1 
1Europa Donna, Foro de España - FECMA, Barcelona, Spain  
   
The psycho social aspects of breast cancer must be dealt as a 
whole, not treated separately for each treatment.  In most 
cases, women undergoing radiotherapy suffer considerable 
emotional distress after a devastating diagnostic and side 
effects from surgery and chemotherapy. When they start 
receiving radiotherapy breast cancer patients are in an 
emotional and physical distress. Psycho social issues faced 
are both emotional (fear, depression, low self esteem) and 
social (loss of self image, loss of income) among many others. 
Thus perception of radiotherapy and its impact on the 
patient will depend on how she is living her illness. 
Therefore, the background of each patient must be taken 
into account when planning each treatment.  How can 
Radiation therapists help? Giving the patient information in a 
plain, sensitive language about the treatment, adverse 
effects and tips for counteracting them (nutrition, skin care, 
physical activity), would help reducing anxiety; emotional 
support an inclusive communication in which treatment is 
discussed with the patient would be key to reduce stress. 
Implementing high dose treatment, or even concurrent 
chemotherapy and radiotherapy when possible in order to 
shorten length of treatment and adjusting appointments to 
patient’s needs would also help improve patient experience. 
Key words: psycho social aspects, breast cancer, 
radiotherapy, side effects. 
   
 
Symposium: Targeted therapy, stem cells, and normal 
tissue toxicity  
 
 
SP-0219   
Risk of normal tissue injury from protons and heavy ions  
P. Peschke1, C.P. Karger2, O. Jäkel2, J. Debus3 
1German Cancer Research Center (DKFZ), Molecular 
Radiooncology, Heidelberg, Germany  
2German Cancer Research Center (DKFZ), Medical Physics in 
Radiation Oncology, Heidelberg, Germany  
3University Hospital Heidelberg, Radiation Oncology, 
Heidelberg, Germany  
 
Worldwide, there is an increasing interest in particles, such 
as protons and carbon ions as this therapeutic strategy allows 
for highly conformal treatments of deep-seated tumors due 
to the finite range and the inverted depth dose profile 
(Bragg-curve) of charged particles. While for protons the 
more narrow range of RBE results in smaller variations of the 
actual delivered RBE-weighted doses, for carbon ions the 
linear energy transfer (LET) is higher in the Bragg-peak region 
as compared to the beam entrance region (plateau), which 
increases the relative biological effectiveness (RBE) towards 
the distal edge of the depth dose curve. In addition, the 
degree of conformity of charged particles is further enhanced 
by introducing active scanning techniques, which allow dose 
conformation not only at the distal but also at the proximal 
edge of the tumor for each treatment field. Generally, 
particles have demonstrated safety and effectiveness for a 
variety of tumors, showing approximate equivalence of both 
modalities. Yet, randomized controlled multicenter trials on 
large patient cohorts are still pending, which presently makes 
final conclusions rather difficult. 
From the radiobiological point of view, a central demand is 
that treatment planning for carbon ions is performed in terms 
of RBE-weighted rather than absorbed dose. As the depth 
modulation for active techniques is varying throughout the 
complete radiation field, RBEs have to be calculated locally 
at each beam spot. The RBE is a complex quantity, which 
depends on physical parameters such as dose, LET and 
particle type as well as on biological properties like the 
tissue type and the biological endpoint. As complication free 
tumor cure can only be attained, when tumor control 
probability and the risk of morbidity are balanced, the 
impact of high-LET on both, tumor and normal tissues, is 
important.  
To consider the RBE in treatment planning, bio-mathematical 
models are required. In case of patient treatments at GSI/HIT 
using the raster scanning method, all RBEs calculated with 
the Local Effect Model (LEM) are based on normal tissues 
response. Yet, for normal tissues, there exist a presently not 
fully understood relationship between fractionation, spatial 
dose distribution and the clinical outcome of radiation 
therapy. For the validation of these models, the availability 
systematically and consistently collected data for various 
normal tissues is critical. Ultimately, it is the normal tissue 
effect including the risk of secondary cancers, which will 
3rd ESTRO Forum 2015                                                                                                                                         S111 
 
determine the treatment outcome. In this context, central 
questions in clinical particle radiobiology focus on the 
validation of RBE models, on the decipherment of underlying 
mechanisms, and on the question if a differential RBE 
between tumor and normal tissues exist. 
The presentation will summarize the present knowledge of 
normal tissue effects after particle therapy with special 
emphasis on the RBE and its dependencies on physical and 
biological factors, on examples how RBEs for normal tissues 
are determined in preclinical models and from patient data 
as well as on needs of future investigations. 
   
SP-0220   
Novel radiation responses in normal tissue stem cells ñ 
Andante project 
R.P. Coppes1 
1University Medical Center Groningen, Departments of 
Radiation Oncology and Cell Biology, Groningen, The 
Netherlands  
   
There is growing evidence that the presence of stem cells is 
an important determinant for treatment outcome, not only 
for normal tissues but also tumours. Tissue/cancer stem cells 
are considered to be a main driver for tissue tolerance and 
regeneration and tumour growth, therapy resistance and 
relapse of disease. Recent developments in the field of adult 
stem cell technology have provided the possibilities of the 3D 
culture of multiple tissues and tumours as stem cell 
derived/containing spheres and organoids. These organoids 
closely resemble the composition of an organ or tumour and 
upon transplantation regrow the tissue and tumour closely 
resembling the original. Moreover, it has been suggested that 
adult stem are a critical target for radiation carcinogenesis. 
Stem cells are able to self-renew in tissues for a long period 
of time, which increases their lifetime risk of accumulating 
mutations required for cancer formation. Now using organoid 
cultures of salivary gland and thyroid gland we are able to 
study the radiation response of tissue and cancer stem cells 
in vitro. Examples of the response of spheres and organoids 
to X-rays, Carbon ions and Neutrons will be shown. Remaining 
organoid formation potential, self-renewal potential, stem 
cell marker expression, and differentiation potential, DNA 
repair and gene expression upon irradiation will be shown. 
Moreover, (xeno-)transplantation experiments allow 
assessment of actual regeneration potential of (cancer)stem 
cells. As such we now are potentially able to monitor and 
modulate the in vitro the response of tissues and tumours 
upon (chemo-) radiation and relate these to patient response 
and radiation-induced carcinogenesis. 
This project was financed by the EU, as part of the FP7 
project ANDANTE. 
   
SP-0221   
EGFR-inhibitors, radiotherapy and normal tissue toxicity 
J.G. Eriksen1 
1Odense University Hospital, Department of Oncology, 
Odense, Denmark  
   
EGFR-inhibitors have been used in several clinical settings 
during the last decade and side-effects related to normal 
tissues like the skin, mucosa and kidney has been well 
described. However, when EGFR-inhibitors are combined with 
radiotherapy, then different skin and mucosa toxicity profiles 
can be seen. The presentation will focus on typical as well as 
atypical clinical presentations of the combined treatment 
modalities in skin and mucosa. This will be with an emphasis 
on recent data from a randomized phase III trial on 
chemoradiation plus/minus EGFR-inhibition. The clinical 
presentations will be explained with references to the 
current knowledge of the biology of skin toxicity. 
Treatment options for acute side-effects in skin and mucosa 
after bio-radiotherapy is rarely causal. A few attempts have 
been done; some of them aiming to rephosphorylate the EGF-
receptor in the skin with vitamin K3. The talk will discuss the 
available data from these studies.  
Across several tumour sites and for different EGFR-inhibitors, 
a correlation between skin toxicity and tumour response has 
also been documented. The reason for this correlation is not 
obvious but probably related to genetic alterations or certain 
genetic variations that are shared between tumour and 
normal tissue like skin and mucosa. At present, it is not 
possible to predict which patients that will develop severe 
skin toxicity and thereby potentially benefit from EGFR-
inhibition in terms of tumour response. However, emerging 
data suggests that certain single nucleotide polymorphisms in 
the EGF-gene that alter the ligand-receptor binding might be 
responsible for the observed clinical correlation. These data 
will be discussed in the light of EGFR-inhibition in 
combination with chemotherapy and/or radiotherapy. 
   
 
Symposium: Role of brachytherapy and contact X-ray in 
the treatment of rectal cancer  
 
 
SP-0222   
Role of endoluminal brachytherapy for rectal cancer: 
current status and challenges 
T. Vuong1, T. Niazi1, S. Devic1 
1Jewish General Hospital, Radiation Oncology Department, 
Montreal, Canada  
  
Clinical applications: High dose rate endorectal 
brachytherapy (HDREBT) is a highly targeted radiation 
modality that uses Magnetic Resonance Imaging (MRI) for 
target definition and computed tomography (CT) based 
treatment planning. The treatment is given on an outpatient 
basis and does not require anesthesia but conscious sedation 
as needed. In the era of Total Mesorectal Excision (TME) 
surgery, pre-operative external beam radiation therapy 
(EBRT) contributes by reducing the local recurrence from 11 
to 5%. HDREBT was tested and validated clinically as an 
effective neoadjuvant modality for tumor down-staging in 
patients with operable rectal cancer having an advantage 
over the EBRT in providing limited normal tissues exposure to 
radiation. In patients unfitted for surgery, HDREBT was used 
as a boost after an initial course of external beam therapy to 
improve local control. 
Technical applications: Pre-treatment includes imaging with 
pelvic MRI and tumor mapping with radio-opaque clips to 
improve the accuracy of treatment delivery. The patient is 
planned at the CT-simulator in supine position after bowel 
preparation with the Oncosmart intracavitary mold applicator 
(Elekta). Position of the applicator is adjusted to the level of 
the radio-opaque clips, as seen on the pilot, prior to CT 
scanning. Subsequently, the CTV contouring is performed 
based on MRI images. In the pre-operative setting, dose 
distribution is optimized in order for the target to receive 26 
Gy in 4 fractions. In the boost setting, a repeated pelvic MRI 
is obtained 2-3 weeks after the external beam radiation 
treatment, period that allows tumor down-sizing, and the 
total dose 30 Gy is given weekly in 3 fractions. For this 
treatment the same applicator is used with tungsten shielding 
rod placed in the central applicator hole to protect the 
contralateral healthy tissue. Dose is optimized on the 
residual tumor gross tumor volume (GTV) with the addition of 


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SP-0219: Risk of normal tissue injury from protons and heavy ions

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