Am Fam Physician. 2003 Sep 15;68(6):1016-1019.
to the editor: The article, “Thyroid Nodules,”1 was well written and concise. However, the list of “red flags” for thyroid cancer listed in Table 2 needs to be expanded to include an additional risk group. The item, “history of radiation to the head or neck” also should include chest or mantle radiation. At particular risk for this radiation exposure are survivors of Hodgkin's disease.
Hodgkin's disease is the most common cancer diagnosed in persons 15 to 19 years of age, and is the third most common cancer for all pediatric ages, zero to 19 years.2 Radiation therapy involving the chest or mantle area has been used in the treatment of Hodgkin's disease for decades. Standardized anatomic treatment fields, combined with the establishment of a curative dose range, produced the first cures in patients with Hodgkin's disease. Radiation treatment regimens used through the 1980s primarily prescribed doses of 35 to 44 Gy to extended fields for localized disease (stage I or IIA).
Concerns about growth impairment led to clinical trials designed to specifically address the needs of children with Hodgkin's disease. These protocols evaluated lower radiation doses (15 to 25.5 Gy) to reduced treatment fields combined with multi-agent chemotherapy. Many reports implicating radiation as a causative factor for excess cardiovascular disease and subsequent malignancy risk in long-term survivors of childhood Hodgkin's disease motivated further therapeutic refinements in the 1990s. The use of standard-dose, extended-field radiation in mature adolescents with localized Hodgkin's disease has been abandoned at most centers, because this treatment approach predisposes patients to a greater risk of cardiovascular disease and secondary solid tumor carcinogenesis. Contemporary risk-adapted treatment protocols have focused on further limiting radiation exposure of uninvolved tissues, especially the breast, and identifying patients for whom the addition of radiation optimizes disease-free survival.
The Childhood Cancer Survivor Study,3 a 26-institution retrospective cohort study following almost 14,000 long-term survivors of childhood cancer diagnosed between 1970 and 1986, highlighted the risk of thyroid cancer following treatment for Hodgkin's disease. A cohort of 1,791 long-term survivors of Hodgkin's disease, diagnosed before the age of 21 years, were analyzed. The median age at diagnosis was 14 years and was 30 years at follow-up. From this relatively young population, 20 patients were diagnosed with thyroid cancer. Fifteen had received previous radiation therapy for their Hodgkin's disease, one had not, and treatment records were unavailable for the remaining four. The relative risk for thyroid cancer was 18.3 for all Hodgkin's survivors. Since that report, the number of new cases of thyroid cancer in the study's cohort has increased. A nested case-control study of 72 survivors with thyroid cancer as a second malignancy, including 30 Hodgkin's survivors, is underway to determine the attributable excess risk related to radiation.
As risk-adapted therapy for Hodgkin's disease continues to evolve, it is important that clinicians recognize the significant increase in risk of thyroid cancer following mantle radiation. Annual examination and palpation of the neck and thyroid gland are recommended for all survivors of Hodgkin's disease who were treated with mantle or chest radiation, regardless of the dose amount.3
1. Welker MJ, Orlov D. Thyroid nodules. Am Fam Physician. 2003;67:559–66.
2. SEER Program (National Cancer Institute [U.S.]). Cancer incidence and survival among children and adolescents: United States SEER Program, 1975–1995. Bethesda, Md.: National Cancer Insitute, 1999; NIH Publication No. 99-4649.
3. Sklar C, Whitton J, Mertens A, Stovall M, Green D, Marina N, et al. Abnormalities of the thyroid in survivors of Hodgkin's disease: data from the Childhood Cancer Survivor Study. J Clin Endocrinol Metab. 2000;85:3227–32.
editor's note: This letter was sent to the authors of “Thyroid Nodules,” who declined to reply.
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