7th ICHNO Abstract book

page 48 7 th ICHNO Conference International Conference on innovative approaches in Head and Neck Oncology 14 – 16 March 2019 Barcelona, Spain __________________________________________________________________________________________ 7th ICHNO

Material and Methods Apoptosis assays have been firstly performed on 6 different cell lines representative of different forms of thyroid cancer (8505C, CAL-62, FTC-133, TT2609-CO2, BCPAP, TPC-1). These analyzes consisted to treat cells during 48h, with a panel of concentrations of the molecules alone or in combination, in T75 plate and assess the percentage of apoptosis via the Annexin V staining and FACS analysis. Secondly, the aspect of proliferation in response to the molecules alone or combined has been evaluated by crystal violet staining. Combination index, allowing to characterize the combination, have been calculated with Calcusyn software (Biosoft, UK). Mechanisms implicated in targeted cellular pathways such as MAPK, PI3K, SRC or p53 have been studied by Western blot. Finally, the subcellular localization of proteins targeted by the treatment has been observed by immunofluorescence assays. Results A higher rate of apoptosis, suggesting a synergistic activity, has been observed with the combination of dasatinib and PRIMA-1 Met on anaplastic thyroid cell line (8505C- Cal-62) and follicular thyroid cell line (FTC-133) in comparison to the results obtained for the molecules alone. Apoptosis results obtained for the other thyroid cancer cell lines are more moderate but still suggesting an additive effect of the molecules. Combination index calculation reveals a strong synergistic action on 8505C and FTC-133 treated by the combination. Phosphorylations of key proteins implicated in MAPK, PI3K, SRC and p53 are affected according to the treatment with the molecules alone or in combination. Finally, the morphology of the cells is strongly affected by dasatinib while the re- expression of nuclear p53 by PRIMA-1 Met is clearly observable thanks to the immunofluorescence assays. Conclusion Complementary experiments are necessary to completely understand the success of our combined treatment in vitro depending on the thyroid cancer type. However, preliminary results demonstrate a real and strong synergistic effectsof dasatinib and PRIMA-1 Met on different cell lines representative of the different forms of thyroid cancer and especially of the anaplastic one which is still incurable until now. PO-094 Relocation of inadequate resection margins in the wound bed in oral cavity oncological surgery Abstract withdrawn PO-095 Objective intra-operative assessment of resection margins in Head and Neck cancer surgery Y. Aaboubout 1 , E.M.L. Barroso 1 , C.G.F. Van Lanschot 2 , T. Bakker Schut 3 , I. Ten Hove 4 , H. Mast 4 , R. Smits 2 , M. Van der Kamp 1 , A. Sewnaik 2 , J. Hardillo 2 , C. Meeuwis 2 , D. Monserez 2 , S. Keereweer 2 , V. Noordhoek Hegt 1 , P. Caspers 3 , R.J. Baatenburg de Jong 2 , E. Wolvius 4 , A. Bocharnikov 5 , G.J. Puppels 3 , S. Koljenović 1 1 Erasmusmc, Pathology, Rotterdam, The Netherlands; 2 Erasmusmc, Otorhinolaryngology, Rotterdam, The Netherlands; 3 Erasmusmc, Dermatology, Rotterdam, The Netherlands; 4 Erasmusmc, Oral and Maxillofacial Surgery, Rotterdam, The Netherlands; 5 Art Photonics, Optical Fibers, Berlin, Germany Purpose or Objective The goal of head and neck oncological surgery is to achieve a complete tumor resection with acceptable remaining function and appearance. Resection margins are a crucial prognostic factor. However, due the complex anatomy,

1 Jupiter Hospital, Radiation Oncology, Mumbai, India; 2 Jupiter Hospital, Radiation Oncology, Thane, India Purpose or Objective Dysphagia/ Aspiration related structures (DARS) receiving the brachytherapy dose has been gaining importance and there are research articles on the same with respected to intensity modulated radiation therapy (IMRT). However, the role of brachytherapy to spare these structures has not been explored yet. In this study at our institute, we evaluate the role of brachytherapy in sparing DARS with respect to dosimetric comparison and clinical toxicity outcomes. Material and Methods From January 2009 to Dec 2016, total of 35 patients with oropharyngeal cancers were evaluated, who received brachytherapy as a treatment following external beam radiation therapy as a boost or brachytherapy alone as radical treatment. CT based planning was done for brachytherapy and the DARS structures were delineated including superior, middle and inferior constrictors and larynx. The parameters noted were structure volume, maximum dose to structure at a given point (Dmax) and total volume as a whole (MDTV) along with dose to 30%, 50% and 95% of the volume (D30, D50, D80 and D95). The conformity and homogeneity index were evaluated for each plan. The patients were followed up as per the protocol and toxicities assessed as per the swallowing performance status scale. Results The median Brachytherapy dose per fraction was 4Gy (Range 3.5 – 4.5Gy). The median volume of the DARS was 23.5 cc (Range 18.4 – 28.6 cc) of superior constrictor (SC), 5.6 cc (3.1 – 6.2 cc) of middle constrictor (MC), 3.9 cc (Range 3.1 – 5.8 cc) of inferior constrictor (IC) and 29.8 cc (Range 20.6 – 36.7 cc) for larynx (L). The MDTV, Dmax, D30 and D80 for SC was 65%, 118%, 78% and 66%; for MC was 61%, 70%, 63%, 60%; for IC was 55%, 59%, 57%, 55%; for L was 58%, 99%, 66%, 62%. After a median follow up of 20 months, 15% patients had Grade III status and 25% had Grade II status and the rest were in normal Grade I swallowing status. On univariate analysis, the risk factors associated with higher grades of dysfunction were found to be age, stage of disease, smoking, Dmax to the structures and D95. Conclusion Brachytherapy has shown to have an important impact, both clinically and dosimetrically to preserve the DARS. In our country, the application of brachytherapy as a boost or radical approach can be a better substitute for IMRT boost which is not easily available across all the centers. Brachytherapy combined with conformal EBRT can help improve the quality of life of patients. PO-093 New combination of targeted therapies for thyroid cancer treatment L. Gheysen 1 , G. Attardo 1 , F. Journe 1 , S. Saussez 1 1 University of Mons, Department of human anatomy and experimental oncology, Mons, Belgium Purpose or Objective The aim of the present work is to overcome resistance difficulties in thyroid cancer treatment and respond to a lack of efficient therapeutic strategy especially for the anaplastic thyroid cancer. We investigate the synergistic potential activity of two small molecules in combination: dasatinib (multi-kinase inhibitor) and PRIMA-1 Met (p53 reactivator).