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6th ICHNO

page 59

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.

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.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

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