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was observed between the 95% confidence ellipses for the
three positions in the SOBP (see Fig 1). An RBE increase up
to 1.46 was determined for the distal fall-off position (see
Fig 2).
Conclusion
The results obtained in the current study with V-79
fibroblast cells confirm the expected increase in RBE along
the proton Bragg curve.
Poster: Radiobiology track: Radiobiology of head and
neck cancer
PO-0964 Biomarkers in wound drainage fluids affect
response to radiations of head and neck cancer cells
M. Mangoni
1
, M. Sottili
1
, T. Gualtieri
2
, A. Javarone
2
, M.
Loi
1
, I. Meattini
1
, P. Bonomo
1
, I. Desideri
1
, A. Deganello
2
,
L. Livi
1
1
University of Florence, Experimental and Clinical
Biomedical Sciences, Firenze, Italy
2
University of Florence, Academic Clinic of
Otorynolaryngology and Head and Neck Surgery, Firenze,
Italy
Purpose or Objective
In recent years in head and neck oncology many efforts
have been made in order to characterize molecular
biomarkers with potential prognostic and therapeutic
value. The detection of significant features in the early
perioperative setting could possibly lead to a refinement
of current adjuvant treatments in high-risk patients. The
purpose of our study is to report the feasibility and
preliminary results of a pilot prospective study on wound
drainage fluids (WDF) analysis in head and neck squamous
cells carcinoma (HNSCC) and to evaluate effect of WDF
microenvironment on HNSCC response to radiation.
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).