548 / 1096
S533
ESTRO 36
_______________________________________________________________________________________________
Material and Methods
19 consecutive surgically resected HNSCCs were studied.
WDF were collected 1 day and 3 days after surgery from
the cancer operative bed. EGF, VEGF, SDF-1 and
osteopontin levels were measured in WDF using enzyme-
linked immunosorbent assay (ELISA) kits. Clonogenic
assays were performed using Cal27 HNSCC cells irradiated
with 1 to 6 Gy in presence or not of WDF and pretreated
or not with cetuximab 6 hours before irradiation.
Results
The correlations between molecular levels and
pathological cancer features showed that CXCL-12
expression was significantly increased in WDF in presence
of lymph node metastasis (p<0,05), lymph node density
(p<0,05) and extra capsular spread (ECS) (P<0,05).
Osteopontin expression was significantly increased in
presence of ECS (p<0,05). TGF-β expression was
significantly reduced in presence of ECS (P<0,0000001)
and for patients treated for a cancer relapse (p<0,001).
Clonogenic assays evidenced that WDF reduced efficacy of
irradiation on Cal27 cells with an increase of clonogenic
survival compared to control (that is irradiated cells
without WDF). Pretreatment of cells with cetuximab
reduced surviving fraction to values comparable to
control.
Conclusion
Preliminary data from pilot study evidenced that
microenvironment in WDF favors residual tumor cell
proliferation and affects response to radiation. Early
treatment with biological therapies can increase radio
sensitivity and improve outcome.
PO-0965 Imaging of the hypoxia related marker
Carbonic Anhydrase IX in human head and neck cancer
xenografts
F.J. Huizing
1
, B.A.W. Hoeben
1
, O.C. Boerman
2
, J.
Bussink
1
1
Radboudumc, Radiation oncology, Nijmegen, The
Netherlands
2
Radboudumc, Nuclear medicine, Nijmegen, The
Netherlands
Purpose or Objective
Tumor hypoxia forms a major factor in radio- and
chemoresistance in head and neck cancer and other solid
tumors. Assessment of tumor hypoxia may allow patient
selection for hypoxia or CAIX targeting treatment
combined with radiotherapy. Recently, the radioactive
tracer
111
In-girentuximab-F(ab’)
2
was designed to target
the endogenous hypoxia related marker carbonic
anhydrase IX (CAIX), in combination with a SPECT scan this
tracer can be used for imaging. The purpose of this study
was to characterize
111
In-girentuximab-F(ab’)
2
in a
preclinical setting.
Material and Methods
First the affinity and internalization kinetics of
111
In-
girentuximab-F(ab’)
2
were determined in vitro with the
use of SK-RC-52 cells. The optimal timing and optimal
protein dose for imaging were determined in athymic nude
mice with a subcutaneous xenografted human head and
neck carcinoma. Tracer uptake was measured using the U-
SPECT, by analyzing ex vivo activity counting and by
autoradiography of tumor sections. Immunohistochemical
staining was used to validate the tracer uptake to the CAIX
expression.
Results
In vitro 26% of the tracs internalized into the SK-RC-52
cells after 24 hours. The half maximal inhibitory
concentration was 0.69 ± 0.08 nM. As optimal time
between tracer injection and imaging we found 24 hours
to be optimal. The protein dose of 10 microgram will result
in the highest tumor to blood ratio after 24 hours.
Immunohistochemical images show a distinct spatial
correlation to autoradiography images (Fig. 1).
Conclusion
111
In-girentuximab-F(ab’)
2
has a high affinity to CAIX. For
optimal imaging of CAIX expression in human xenografts,
a tracer protein dose of 10 microgram should be
administrated 24 hours before scanning. These results
suggest that
111
In-girentuximab-F(ab’)
2
is a promising
tracer, in ongoing studies we will assess the tracer’s
applicability for treatment selection and monitoring.
PO-0966 Prognostic value of tissue necrosis,CD34 MVD
and CA-IX in head and neck cancer patients
D. Ou
1,2
, I. Garberis
3
, J. Adam
3
, P. Blanchard
1
, F.
Nguyen
1
, A. Levy
1
, O. Casiraghi
3
, P. Gorphe
4
, I. Breuskin
4
,
F. Janot
4
, S. Temam
4
, J. Scoazec
3
, E. Deutsch
1
, Y. Tao
1
1
Institut Gustave Roussy, Department of Radiation
Oncology, Villejuif, France
2
Fudan University Shanghai Cancer Center, Department
of Radiation Oncology, Shanghai, China
3
Institut Gustave Roussy, Department of Pathology,
Villejuif, France
4
Institut Gustave Roussy, Department of Head and Neck
Oncology, Villejuif, France
Purpose or Objective
Tumor hypoxia is adversely correlated to patient
prognosis. The aim of the present study was to investigate
the role of three hypoxia-related biomarkers in patients
with locally advanced head and neck squamous cell
carcinoma
(HNSCC)
treated
with
concurrent
chemoradiotherapy or bioradiotherapy.
Material and Methods
In tumor tissue material from 100 patients with known HPV
status, we evaluated the extent of tumor necrosis, the
expression level of CA-IX and the microvascular density
(MVD) measured as the density of CD34+ vascular
structures. The Kaplan–Meier method, univariate and
multivariate analyses, were used to analyze the
correlations
between
biomarker
status
and
clinicopathological characteristics and treatment
outcomes.
Results
We found a significant correlation between MVD and
overall stage (p=0.02) and T classification (p = 0.05). CA-