6th ICHNO Abstract Book

6th ICHNO 6 th ICHNO Conference International Conference on innovative approaches in Head and Neck Oncology 16 – 18 March 2017 Barcelona, Spain __________________________________________________________________________________________ PO-123 Hypothyroidism after radiotherapy of head and neck – incidence and risk factors. page 59

level, even within its range of norm) is the strongest risk factor of developing a posttreatment hypothyroidism. The product of initial TSH and median dose absorbed by thyroid (TSH0*Dmed) seems to be a usefull tool predicting a posttreatment hypothyroidism. It can be used to select a group of patients who should have very carefull thyroid function monitoring during their follow-up. PO-124 A melatonin gel protects the mitochondria from radiation damage preventing mucositis G. Escames 1 , F. Ortiz 1 , B. Fernández-Gil 1 , A. Guerra- Librero 1 , Y. Shen 1 , J. Florido 1 , D. Acuña-Castroviejo 1 1 Universidad de Granada, Instituto de Biotecnología/Dto Fisiología, Granada, Spain Purpose or Objective Mucositis is a common and distressing side effect of chemotherapy or radiotherapy that has potentially severe consequences, and no treatment is currently available. On the other hand, radiotherapy-induced gut toxicity is among the most prevalent dose-limiting toxicities following radiotherapy. The purpose of this study was to analyze the molecular pathways involved in the development of oral mucositis, to investigate the changes induced in the rat small intestine after external irradiation of the tongue, and to explore the potential radio- protective effects of melatonin gel. Material and Methods Male Wistar rats were subjected to irradiation, and their tongue and duodenum were obtained for subsequent determinations. The radiation was administered using a Ray-X YXLON Y.Tu 320-D03 irradiator, and the rats received a dose of 7.5 Gy/day for 5 days in their oral cavity. Rats were treated with 45 mg/day melatonin gel or vehicle during 21 days post-irradiation, by application in their mouths. Mitochondrial oxidative stress, mitochondrial bioenergetic capacity, NF-κB/NLRP3 inflammasome signaling activation, histology and electron microscopy, were determined. Results Tongue irradiation induced oral mucositis and gut toxicity. Our results showed that mitochondrial oxidative stress, bioenergetic impairment, and subsequent NLRP3 inflammasome activation were involved in the development of oral mucositis and radiotherapy-induced gut toxicity. Oral treatment with melatonin gel had a protective effect in the oral mucosa and in small intestine, which was associated with mitochondrial protection and, consequently, with a reduced inflammatory response, blunting the NF-κB/NLRP3 inflammasome signaling Our findings suggest that oral treatment with melatonin gel may be a potential preventive therapy for oral mucositis and also for radiotherapy-induced gut toxicity in cancer patients. These results have led to a clinical trial (Nº EudraCT: 2015-001534-13) Supported in part by grant nº SAF2009-14037 Ortiz F, et al. J Pineal Res 2015; 58: 34-49 Escames G, et al. Hum Genetics 2012; 131:161-173 PO-125 Effects of melatonin oral gel to prevent radiation-induced mucositis model in rat G. Escames 1 , C. Tarrago 2 , F. Ortiz 1 , B. Fernández-Gil 1 , N. Lluch 2 , A. Guerra-Librero 1 , Y. Shen 1 , J. Florido 1 , D. Acuña-Castroviejo 1 , R. Bosser 2 1 Universidad de Granada, Instituto de Biotecnología/Dto Fisiología, Granada, Spain 2 Spherium Biomed S.L., Project Management, Barcelona, Spain activation. Conclusion

U. Dworzecka 1 , A. Wygoda 1 , T. Rutkowski 1 , B. Pilecki 1 , K. Składowski 1 1 Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology III Dept., I Radiation and Clinical Oncology Department, Gliwice, Poland Purpose or Objective To establish the incidence of hypothyroidism after irradiation of the neck, and to determine risk factors Material and Methods Prospective study of 47 patients who received radical radiotherapy to the neck between 2008 and 2010 ; TSH measurements were taken before the start of radiotherapy (TSH0), at the end (TSH end), 3 and 6 months after the treatment, and then every 6 months. Statistical method: Cox regression and the Kaplan-Meier analysis. Results Average dosimetric finding were collected in the table 1. Hypothyroidism after radiotherapy of head and neck was diagnosed in 25,5% of patients. In the univariate Cox regression analysis statistical significance was achieved by: female gender, initial TSH (TSH 0), TSH at the end of treatment (TSHend). Patients age, type of the treatment or thyroid volume did not have a statisticly significant impact on posttreatment thyroid function. None of the dosimetric parameters (V10-V60, Dmean, Dmodal, Dmed, Dmin, Dmean) showed significant correlation with thyroid function (among all of them, Dmed was closest to statistical significance). In further analysis, a prognostic parameter that would include both initial thyroid function and influence of radiotherapy, was prospected. The factor which was a product of initial TSH (TSH 0) and the median dose absorbed by thyroid gland during radiotherapy was calculated for all of the patients (equation 1). This parameter showed a statistically significant impact in the univariate Cox regression analysis (p = 0,001). In the multivariate Cox regression analysis only the calculated product (p 0,001) ) and the TSHend (p 0,02) were statistically significant. In the Kaplan-Meyer analysis (figure 1), the 3yrs- hypothyroidism –free-survival was 93% in the the group with the calculated parameter < 70. In the group with the parameter > 70 the 3yrs-hypothyroidism free survival was 0%(p=0.0004) – all of that patient developed hypothyroidism.

Conclusion The risk of hypothyroidism after irradiation of head and neck is 25%. The initial thyroid function (based upon TSH