A prospective cohort study on radiation-induced hypothyroidism: development of an NTCP model.
OBJECTIVE
To establish a multivariate normal tissue complication probability (NTCP) model for radiation-induced hypothyroidism.


METHODS
The thyroid-stimulating hormone (TSH) level of 105 patients treated with (chemo-) radiation therapy for head-and-neck cancer was prospectively measured during a median follow-up of 2.5 years. Hypothyroidism was defined as elevated serum TSH with decreased or normal free thyroxin (T4). A multivariate logistic regression model with bootstrapping was used to determine the most important prognostic variables for radiation-induced hypothyroidism.


RESULTS
Thirty-five patients (33%) developed primary hypothyroidism within 2 years after radiation therapy. An NTCP model based on 2 variables, including the mean thyroid gland dose and the thyroid gland volume, was most predictive for radiation-induced hypothyroidism. NTCP values increased with higher mean thyroid gland dose (odds ratio [OR]: 1.064/Gy) and decreased with higher thyroid gland volume (OR: 0.826/cm(3)). Model performance was good with an area under the curve (AUC) of 0.85.


CONCLUSIONS
This is the first prospective study resulting in an NTCP model for radiation-induced hypothyroidism. The probability of hypothyroidism rises with increasing dose to the thyroid gland, whereas it reduces with increasing thyroid gland volume.
Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Marjolein J
MJ
Boomsma
Hendrik P
HP
Bijl
Miranda E M C
ME
Christianen
Ivo
I
Beetz
Olga
O
Chouvalova
Roel J H M
RJ
Steenbakkers
Bernard F A M
BF
van der Laan
Bruce H R
BH
Wolffenbuttel
Sjoukje F
SF
Oosting
Cornelis
C
Schilstra
Johannes A
JA
Langendijk
D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D019540:Area Under Curve; D059248:Chemoradiotherapy / Q000009:adverse effects*; D015331:Cohort Studies; D005260:Female; D006258:Head and Neck Neoplasms / Q000097:blood / Q000188:drug therapy / Q000532:radiotherapy*; D006801:Humans; D007037:Hypothyroidism / Q000097:blood / Q000188:drug therapy / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D016017:Odds Ratio; D009929:Organ Size; D058958:Organs at Risk / Q000033:anatomy & histology / Q000528:radiation effects; D011446:Prospective Studies; D011829:Radiation Dosage; D013961:Thyroid Gland / Q000033:anatomy & histology / Q000528:radiation effects*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood / Q000627:therapeutic use; D055815:Young Adult
D013972:Thyrotropin; D013974:Thyroxine