6th ICHNO
page 59
6
th
ICHNO Conference
International Conference on innovative approaches in Head and Neck Oncology
16 – 18 March 2017
Barcelona, Spain
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PO-123 Hypothyroidism after radiotherapy of head and
neck – incidence and risk factors.
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
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.Tu320-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
activation.
Conclusion
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




