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S254
ESTRO 36
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Symposium with Proffered Papers: Novel approaches in
thoracic tumour treatment
SP-0479 Primary human Lung (stem) cell models to
study adverse effects of cancer treatments
M. Vooijs
1
1
MAASTRO GROW Research Institute, Radiation Oncology,
Maastricht, The Netherlands
Lung cancer represents the leading cause of cancer death
worldwide. The current standard of care includes
combinations of surgery,
,
chemotherapy and radiotherapy.
New treatments based on molecular insight of driver
mutations in cancers are urgently needed to obtain more
durable responses and longer survival. We and others have
previously reported that deregulation of the NOTCH
signaling pathway is associated with poor outcome and
treatment resistance in non-small cell lung cancer in
patients and in preclinical models. Cancer treatments are
always limited by dose-limiting side-effects which
negatively affects tumour control and quality of life.
Reducing side effects may improve tumor control by
increasing dose and treatment duration. What is currently
lacking are robust primary human tissue models that
enable evaluation of deleterious normal tissue effects.
Here I will discuss the use of 2D and 3D primary human
lung tissue models to study the effects of lung cancer
treatments on normal tissue response. Such models may
useful in parallel to in vitro tumor cell models to select
the most optimal personalized precision treatment.
SP-0480 Secretome as novel target for lung cancer
M. Pruschy
1
1
University Hospital Zürich, Department of Radiation
Oncology, Zurich, Switzerland
For lung carcinoma, the initial biopsy material, fine
needle aspirates, and in case of surgery the resected
tumor, are often the only biological materials available for
direct molecular analysis. The gold standard for molecular
analysis therefore includes histological and cytogenetic
analysis and DNA-extraction followed by mutational
analysis. However, it is also of high importance to have
access to tumor material during and in response to
radiotherapy to gain insights into the treatment response
on the molecular and cellular level and to develop
putative (surrogate) markers. As such biomarker analysis
of tumor-derived blood serum factors in tumor patients
represents an additional minimally invasive approach to
eventually identify predictive and prognostic factors. The
serum proteome (secretome) can be analyzed prior to
therapy start (basal level), following single high dose
irradiation but also consecutively during the time course
of a fractionated treatment regimen in order to identify
(dynamic) responses to treatment. Such serum factors also
affect the radiation resistance in an auto- and/or
paracrine way via the tumor microenvironment and might
act as potential targets for combined treatment
modalities with ionizing radiation. Here we will discuss
recent preclinical and clinical approaches and
achievements to analyze the treatment-induced
secretome from lung carcinoma and to exploit specific
secretome factors as part of a combined treatment
modality with radiotherapy.
OC-0481 Effects of nitroglycerin on perfusion and
hypoxia in non-small cell lung cancer lesions.
B. Reymen
1
, A.J.G. Even
1
, C.M.L. Zegers
1
, W. Van Elmpt
1
,
M. Das
2
, J. Wldberger
2
, F. Mottaghy
3
, E. Vegt
4
, D. De
Ruysscher
1
, P. Lambin
1
1
MAASTRO Clinic, Radiation Oncology, Maastricht, The
Netherlands
2
Maastricht University Medical Centre, Radiology,
Maastricht, The Netherlands
3
Maastricht University Medical Centre, Nuclear Medicine,
Maastricht, The Netherlands
4
Netherlands Cancer Institute-Antoni Van Leeuwenhoek
Hospital, Nuclear Medicine, Amsterdam, The
Netherlands
Purpose or Objective
Nitroglycerin is a nitric oxide donor being investigated
because of its potential to increase tumour oxygenation.
In phase II trial NCT01210378 nitroglycerin is added to
radical radiotherapy in patients with NSCLC stage IB-IV.
Using hypoxia PET tracer [
18
F]HX4 and dynamic contrast
enhanced CT-scans (DCE-CT) we investigate in a subtrial
the effect of nitroglycerin on tumour hypoxia and
perfusion. Here, we report the final results of all patients
that entered the subtrial.
Material and Methods
Prior to the start of radiotherapy baseline [
18
F]HX4 PET (4h
p.i.) and DCE-CT scans were performed to measure
hypoxia and perfusion in the primary gross tumour volume
(GTVp) and nodes (GTVn). At least 48 hours later, DCE-CT
and [
18
F]HX4 PET scans were repeated after application of
a Transiderm nitro 5 mg patch. Between scans, patients
did not receive any treatment. GTVp and GTVn were
defined on the planning FDG-PET-CT scan and copied onto
the HX4 and DCE-CT scans after registration of the images
to the planning CT. For HX4, tumour-to-blood ratio (HX4-
TBR), hypoxic fraction (HX4-HF; fraction of volume with
TBR >1.4) and hypoxic volume (HX4-HV; volume with TBR
>1.4) were calculated for all lesions. Perfusion parameters
blood volume (BV) and blood flow (BF) were calculated.
Differences between paired measurements were assessed
using the Wilcoxon Signed rank test. Correlation
coefficients were calculated using Spearman’s correlation
coefficient (SPSS, IBM, Germany).
Results
Performed scans are summarized in table 1.
In total 22/32 patients (69%) showed hypoxia at baseline
in primary tumor and/or lymph nodes. In the 11 hypoxic
tumors a significant negative correlation was found
between baseline HX4-TBR and tumor blood flow (r=-
0.618, p=0.043) and blood volume (r=-0.736, p=0.010).
(Fig 1).