ESTRO 36 Abstract Book

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.

Acceleratated fractionation only (ASO) 1 ; n=283 40; 2/1.8/1.5;33 Wk 1-2: 10 x 2 Gy

ARCON study 2

Fractionation (HAS) 1 n=28

n=86 p

n (fractions); d (Gy); T (overall treatment time in days)Total Dose: ERD (α=0.3, α/ β =10, Tpot=5)

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

4; 2; 37 Wk 1-4: 20 x 2 Gy Wk >5, 14 x 2Gy, BID68 Gy

Wk 3-5: 15 x 1.8/1.5 Gy, BID69.5 Gy

67.7

66.5

64.5

ETD (α/ β=10) 5 yr local control 5 yr disease free Serious late toxicity (larynx)

103.7

116.9

113

56%

83%

75%

0.004

50%

76%

65%

0.02

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