Predictive Factors for Thyroid Complications After Radiation Therapy

Data From a Cohort of Cancer Patients Closely Followed Since They Were Irradiated

Vitoria Duarte; Joana Maciel; Daniela Cavaco; Sara Donato; Inês Damásio; Sara Pinheiro; Ana Figueiredo; Ana Ferreira; Joana S. Pereira

Disclosures

Clin Endocrinol. 2022;96(5):728-733. 

In This Article

Abstract and Introduction

Abstract

Introduction: Cancer survivors are at an increased risk of adverse outcomes, including thyroid neoplasms, given the high radiosensitivity of this gland. The aim of this study is to assess the incidence and timeframe of thyroid complications in cancer patients, followed systematically since their radiation therapy, and to identify risk factors for the development of hypothyroidism and thyroid cancer.

Methods: We performed a retrospective study, including 282 subjects, who received neck, craniospinal, or total body irradiation (TBI). Patients were grouped into four primary diagnostic clusters: leukaemia, Hodgkin's disease, central nervous system, and head and neck tumours.

Results: Hypothyroidism was observed in 56.7% of patients, on average 6.8 ± 5.9 years after the treatment. Neck and craniospinal irradiation presented a 3.5-fold increased risk for the development of hypothyroidism compared to TBI. Papillary thyroid cancer was diagnosed in 8.5% of the patients, on average, 18.5 ± 4.9 years after radiotherapy (RT). Female gender, younger age, and lower irradiation doses were independently associated with thyroid cancer development.

Conclusion: Our study provides useful information about the risk of hypothyroidism and thyroid cancer after RT, as it was performed in a cohort of patients closely followed since the oncological therapies, and, thus, may give new insights into the follow-up management of these patients.

Introduction

Radiation therapy plays an important role in the treatment of several types of malignancies. As a result, cancer survivors are at an increased risk of adverse outcomes, including thyroid neoplasms, due to the radiosensitivity of the thyroid gland. The thyroid gland may be included in the radiation field or may be exposed to scatter irradiation in different contexts.[1,2]

The paediatric thyroid is particularly vulnerable to the oncogenic effects of radiation. Results from the childhood cancer survivor study[3] reported a higher radiation risk with younger age.

Hypothyroidism is the most common late effect of thyroid gland irradiation.[4] The incidences range from 24% to 48% in survivors of Hodgkin's disease (HD).[5,6] There have been several reports concerning the risk factors for hypothyroidism after radiation therapy. A combination of age, gender, race, the radiation field, chemotherapy, and smoking have been proposed.[7]

The association between radiation exposure and thyroid cancer has been well documented. Thyroid carcinoma was the first solid malignant tumour found, with an increased incidence, among the Japanese atomic bomb survivors. Later, an augmented risk of thyroid cancer was observed as a consequence of the Chernobyl accident.[8] Typically, radiation-induced thyroid carcinomas include a higher proportion of papillary cancers. The prevalence of RET/PTC rearrangements and other fusion alterations, including ALK and NTRK genes is higher than in thyroid cancers without previous radiation exposure.[1] The reported incidence of thyroid neoplasms among survivors of paediatric cancers varies greatly between authors.[9] Moreover, the conclusions of many studies might be biased due to the small number of patients included or the short follow-up period. Large national cohorts bear the limitation of reliance on self-reported surveys from patients.

The risk of developing a thyroid complication and its temporal pattern of occurrence is paramount for the long-term surveillance of cancer survivors. As chemotherapy alone usually does not lead to an increased risk of late thyroid complications,[10] our study was focused on survivors of solid and haematological malignancies who received radiation treatment.

Therefore, our aims were: to assess the incidence and timeframe of thyroid complications in a cohort of cancer survivors after radiation therapy who were followed, from an endocrine point of view, since they finished their oncological therapy; to identify risk factors for the development of hypothyroidism and thyroid cancer following RT; to develop risk-based guidelines for follow-up of thyroid complications in cancer survivors.

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