550 / 1096
S535
ESTRO 36
_______________________________________________________________________________________________
analysis in vitro and on xenograft models and functional
radiobiological analyis was applied.
Results
Interestingly, global gene expression analysis revealed a
negative correlation of genes associated with cell motility
and migration in the IR derivatives of two HNSCC cell lines,
namely Cal33, FaDu. We functionally validated those
findings and screened for known EMT marks from
literature by functional migration assays and EMT-related
protein expression in several HNSCC model cell lines and
established xenografts as well as in their IR-derivatives in
order to correlate the acquired findings to radiotherapy
outcome. The only positive correlation was found for the
initial-before therapy protein expression
in vitro
and
in
vivo
for
Slug, a zinc-finger protein encoded by the
SNAI2
gene and c-Met, a receptor tyrosine kinase encoded by the
MET
gene. Functional knockdown of Slug or c-Met
expression let to radiosensitization in 3-D clonogenic
survival assays of several HNSCC cell lines.
Conclusion
Currently the expression of these molecules is scored for
clinical outcome to better understand the context of EMT
biomarkers for HNSCC progression and the development of
a
potential
well-directed
combinational
radiochemotherapy.
PO-0969 Accelerated fractionation should start early
for laryngeal/ hypopharyngeal cancer.
C. Terhaard
1
, N. Kasperts
1
, H. Dehnad
1
, E. Smid
1
, L.
Janssen
2
, R. Wigggenraad
3
, C. Raaijmakers
1
1
UMC Utrecht, Radiation Oncology Department, Utrecht,
The Netherlands
2
UMC Utrecht, Head and neck surgical oncology, Utrecht,
The Netherlands
3
RCWEST- Medisch Centrum Haaglanden, radiotherapy,
Den Haag, The Netherlands
Purpose or Objective
Accelerated repopulation during radiotherapy is a main
cause of local recurrence after conventional radiotherapy
for H&N cancer. Based on meta-analysis accelerated
fractionation (AF) is superior to conventional
fractionation. In most studies around 70 Gy is given in 6
weeks. The objective of this study is to analyze 3 AC
schedules with three start points of acceleration: at week
3, 4 and 5, looking for the optimum.
Material and Methods
Since 1995 we treat T2-3 larynx (including bulky T2
glottic) and hypopharynx cancer with AF. Three schedules
have been used. AF started in week 4 for the
hyperfractionated AF (HAS, n=28), in week 3 for the ASO
schedule (n=283), and in week 5 in the ARCON study
(n=86). Since local control was equal
2
, results of both
arms were combined. Mean follow-up was 75 months. Age
ranged from 32-87 years, 25% ≥ 70 years. WHO
performance was 0-1 in 95%. T2, T3,T4, was 57%, 35%, and
8%; 27% was N+. Distribution between the schedules was
equal for gender, stage, WHO p. , and age. Tumor
location was glottis, supraglottis and hypopharynx, in 44%
45% and 11%, respectively.
Results
Treatment delay was only seen in 5%, independent of the
schedule. Actuarial local control rates and disease free
survival rates differed significantly between the schedules
(table 1). In univariate analysis actuarial local control was
significantly correlated with T stage (T2,n=228, 82%,
T3,n=135 79%, T4 45%),sex (female fared better),
stage, and marginally significant years of treatment.
Local control was equal for patients < age 70 and above
(80%). In multivariate analysis the only independent
prognostic factors for local control were stage, sex and
treatment schedule. Independent factors for disease free
survival were stage and, marginally, treatment schedule.
Tube feeding during treatment was given in 24%, for HAS,
ASO and ARCON 32%, 25% and 17% (p=ns). Severe late
laryngeal was equal for the schedules (table 1).
HyperfractionatedAcc.
Fractionation
(HAS)
1
n=28
Acceleratated
fractionation
only
(ASO)
1
; n=283
ARCON
study
2
n=86 p
n
(fractions);
d (Gy); T
(overall
treatment
time in
days)Total
Dose:
50;1.2/1.7; 33
Wk 1-3: 30 x 1.2 Gy,
BID
Wk 4-5: 20 x 1.7 Gy,
BID70 Gy
40;
2/1.8/1.5;33
Wk 1-2: 10 x 2
Gy
Wk 3-5: 15 x
1.8/1.5 Gy,
BID69.5 Gy
4; 2; 37
Wk 1-4: 20 x 2 Gy
Wk >5, 14 x 2Gy,
BID68 Gy
ERD
(α=0.3, α/
β =10,
Tpot=5)
67.7
66.5
64.5
ETD (α/
β=10)
103.7
116.9
113
5 yr local
control
56%
83%
75%
0.004
5 yr
disease
free
50%
76%
65%
0.02
Serious
late
toxicity
(larynx)
12%
10%
12%
ns
Conclusion
In this large group of patients treated for intermediate
size laryngeal/ hypopharyngeal cancer superior local
control and disease free survival was seen when the
accelerated fractionation started in week three. The rate
of serious toxicity was equal for all three schedules. Also,
age ≥ 70 was not a negative prognostic factor for local
control, disease free survival and risk of complications..
For patients ≥ 70, with a WHO performance 0-1 excellent
outcome is shown.
1:
Terhaard IJRBP. 2005 May 1;62(1):62
2. Janssens C Oncol. 2012 May 20;30(15):1777-83.
Poster: Radiobiology track: Radiobiology of prostate
cancer
PO-0970 Prostate brachytherapy; DNA damage
biomarker (gH2AX) induction rate correlates with late
toxicity
S. Osman
1
, S. Horn
1
, D. Brady
1
, S.J. McMahon
1
, A.B.
Mohamed Yoosuf
2
, D. Mitchell
3
, K. Crowther
2
, C.A.
Lyons
1
, A.R. Hounsell
2
, K.M. Prise
1
, C.K. McGarry
2
, S.
Jain
1
, J.M. O’Sullivan
1
1
Queen's University Belfast, Centre for Cancer Research
& Cell Biology, Belfast, United Kingdom
2
Northern Ireland Cancer Centre- Belfast Health and
Social Care Trust, Radiotherapy Physics, Belfast, United
Kingdom
3
Northern Ireland Cancer Centre- Belfast Health and
Social Care Trust, Clinical Oncology, Belfast, United
Kingdom
Purpose or Objective
Low-dose-rate permanent prostate brachytherapy (PPB) is
an attractive treatment option and offers excellent
outcomes for patients with localised prostate cancer. As
standard CT-based post-implant dosimetry often
correlates poorly with late treatment toxicity, a study was
conducted to investigate correlations between radiations
induced DNA damage biomarker levels, bowel, urinary,
and sexual toxicity
Material and Methods
Twelve prostate cancer patients treated with
125
I PPB
monotherapy (145Gy) were included in this prospective
study. Post-implant CT based dosimetry assessed the
minimum dose encompassing 90% (D
90%
) of the whole
prostate volume (global), sub-regions of the prostate (12
sectors) and the near maximum doses (D
0.1cc
, D
2cc
) for the