Late Health Effects of Childhood Nasopharyngeal Radium Irradiation: Nonmelanoma Skin Cancers, Benign Tumors, and Hormonal Disorders

Abstract

Nasopharyngeal radium irradiation (NRI) was widely used from 1940 through 1970 to treat otitis serosa in children and barotrauma in airmen and submariners. We assessed whether NRI-exposed individuals were at higher risk for benign tumors, nonmelanoma skin cancer, thyroid disorders, and conditions related to regulatory control of anterior pituitary hormones, such as growth and reproductive characteristics. We conducted a retrospective cohort study in 3440 NRI-exposed and 3088 nonexposed subjects, who as children were treated at nine ear, nose and throat clinics in The Netherlands between 1945 and 1981. Based on information from original medical records, we traced vital status through follow-up at municipal population registries. Disease status (including medical confirmation) and indicators of pituitary gland radiation damage were assessed from a selfadministered questionnaire in 1997. The average radiation doses were 11, 7, and 1.5 cGy for pituitary, parotid, and thyroid gland, respectively, and 3.2 cGy for the facial skin. Among exposed subjects, 23 benign head and neck tumors were observed, compared with 21 among nonexposed subjects. Elevated risk of basal cell carcinoma of the head and neck area was observed in exposed subjects (odds ratio ϭ 2.6; 95% confidence interval: 1.0 -6.7). Exposed and nonexposed groups did not differ substantially with regard to thyroid disorders, height, and reproductive characteristics, although exposed males more frequently reported a history of fertility problems compared with nonexposed males (odds ratio ϭ 1.4; 95% confidence interval: 1.0 -2.1). We found no evidence of highly elevated risk of benign head and neck tumors, nonmelanoma skin cancer, thyroid disorders, or indicators of pituitary radiation damage after childhood NRI in The Netherlands. From the early 1940s until 1960, NRI was regarded as a safe and effective treatment for (childhood) otitis serosa (1-4) and barotrauma (aerotitis media) in military submariners and airmen (5, 6). These conditions are characterized by lymphoid hyperplasia in the nasopharynx, causing impaired eustachian tube functioning, hearing loss, and pain. In the late 1920s, Dr. S.J. Crowe developed a small radium applicator attached to a pin that could be inserted through the nostrils into the nasopharynx, where the radium exerted its activity on the "overflow of lymphoid tissue" (1, 2). NRI was used in several European countries, the United States, and Canada (7,8). The Centers for Disease Control and Prevention has estimated that between 0.5 and 2 million children were treated in the United States, as well as 8000 military submariners and aviators (7).After childhood radiation exposure, elevated risks of benign head and neck tumors and NMSC have been reported (9 -12), as well as benign radiation-related disorders of the thyroid, e.g. nodular disease and hypothyroidism (13,14). However, compared with NRI-exposed subjects, radiation doses to relevant organs were higher in the latter studies. In NRI, the pituitary gland receives relatively high dose...

Epidemiology of basal cell carcinoma: scholarly review

“…Patient groups at risk are those irradiated in the past for benign disorders such as tinea capitis, acne and otitis serosa, [58][59][60][61] and those irradiated for different types of cancer, including childhood cancer survivors and haematopoietic cell transplantation survivors. 62,63 Nonmedical groups at risk are atomic bomb survivors and occupational groups such as radiological technologists.…”

Exposure to radiation therapy is associated with female reproductive health among childhood cancer survivors: a meta-analysis study

“…The included studies were published between 1999 and 2014, and all of them were cohort studies [4,[6][7][8][9][10][11][12][13][14][15][16][17][18]. A total of 10,717 women with radiation therapy and 11,128 women without radiation therapy from 13 studies were evaluated [4, 6-15, 17, 18].…”

“…Among the 14 studies analyzed, 1 study did not have the exact number of included participants, but only had effect estimates [16]. A total of 10 studies were performed in North America [4, 6-8, 10, 11, 13-15, 18], and 4 studies in Europe [9,12,16,17]. In fertility factors, 5 studies were described about infertility [6,9.12,14, 18], 2 studies were based on AMH values [4,17], 2 studies on AOF [10,16], 3 studies on stillbirth or neonatal death [7,8,13], 2 studies on spontaneous abortion [7,12], 2 studies on congenital anomaly [7,15], 2 studies on low birth weight [7,11] and 1 study on preterm birth [11].…”

“…In fertility factors, 5 studies were described about infertility [6,9.12,14, 18], 2 studies were based on AMH values [4,17], 2 studies on AOF [10,16], 3 studies on stillbirth or neonatal death [7,8,13], 2 studies on spontaneous abortion [7,12], 2 studies on congenital anomaly [7,15], 2 studies on low birth weight [7,11] and 1 study on preterm birth [11]. In radiation therapy methods, 4 studies were performed in radiation therapy without specific description [10,12,16,2], 2 studies on abd-pelvic radiation [6,7], 2 studies on ovarian radiation [8,15] and each of the 6 last studies were performed on pelvic radiation [4], abdominal or total body radiation [17], hypothalamic or pituitary radiation [14], nasopharyngeal radium irradiation [9], uterus radiation [11], uterus and ovarian radiation [13].…”

“…Infertility Among the 5 included studies that identified the relationship between radiotherapy and infertility [6][7][8][9][10], the study-specific RRs for infertility range were from 1.20 to 1.54. The pooled RR (exposed to radiotherapy vs. non-exposed) for infertility was 1.28 (95 % CI was 1.16-1.42) with low heterogeneity (I 2 =24.9 %) (Fig.…”