Childhood cancer survivors are at an increased risk of developing a secondary thyroid malignancy, and this risk may be related to factors other than prior treatment, according to data from the American Society of Clinical Oncology Annual Meeting.
These studies also highlight the importance of regular surveillance and survivorship care, said Denise Rokitka, MD, MPH, Director of the Long-Term Follow-Up Clinic and Assistant Professor in the Department of Pediatric Oncology at Roswell Park Cancer Institute, commenting via email.
The risk of developing thyroid cancer after being treated for a first cancer in childhood is well known, said Carlos Rodriguez-Galindo, MD, senior author of one of the studies (Abstract 10084) and Clinical Director of the Solid Tumors Center of Dana-Farber/Boston Children's Cancer and Blood Disorders.
“We assume that this risk is mostly related to radiation,” he said. However based on his study data, this may not always be the case.
He and his colleagues evaluated data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program to identify 40,876 patients age 19 and younger diagnosed with any cancer from 1973 to 2010. The researchers found 131 cases of secondary thyroid cancer, with a standardized incidence ratio (SIR) of 5.10.
The risk of secondary thyroid malignancy was higher in males than females (SIR 8.93 vs. 4.29) and for blacks compared with whites (SIR 10.96 vs. SIR 4.86).
Patients younger than 10 at diagnosis had a higher risk than patients diagnosed at an older age (SIR 8.73 vs. 4.03). Radiation therapy was associated with a higher risk of secondary cancer in blacks compared with whites (SIR 15.85 vs. 7.21) and in males compared with females (15.23 vs 5.76).
Notably, black patients younger than 10 who underwent radiation had the highest risk of secondary thyroid cancer (SIR 42.67).
However, an elevated risk was also seen even among children who did not receive radiation treatment. For example, in patients who had primary leukemia, those who received radiation had an SIR of 9.30, while those who did not undergo this therapy had an SIR of 6.57.
Radiation exposure from imaging studies and even chemotherapy may be contributing factors to an increased risk of secondary thyroid malignancy in patients who did not undergo radiation treatment, Rodriquez-Galindo said.
Overall cancer risk may also be a factor in these patients, Rokitka noted.
Shorter Latency Associated with More Aggressive Cancer
In a second study, available online only in conjunction with the meeting (Abstract e20582), adolescents and young adults who developed an early secondary thyroid cancer were found to have an increased risk of death compared with those who developed such a malignancy many years later.
A shorter latency of secondary thyroid malignancy may be a marker of genetic instability or a biologically more aggressive primary cancer of adolescent and young adults, rather than a consequence of prior treatment, concluded the authors, led by Melanie Goldfarb, MD, Assistant Professor of Surgery, in the Section of Endocrine Surgery at the University of Southern California Keck School of Medicine.
These researchers also used SEER data, from 1973 to 2010, and identified 660 patients who developed a secondary thyroid cancer. Of these individuals, 86.5 percent were female and 85.5 percent were white. Overall, 68.2 percent developed a thyroid malignancy before age 45. Lymphoma, melanoma, breast, germ cell, and cervical cancers were the most common primary malignancies.
Multivariate analysis indicated that the stage of primary cancer increased the risk of death from any cause with hazard ratios (HRs) of 2.36 for regional and 3.47 for distant metastases compared with those for localized disease. Additionally, having three or more tumors (HR 3.66), a poor or undifferentiated primary malignancy (HR 2.11), and thyroid tumor size of more than four centimeters (HR 2.99) also increased this risk.
Decreased latency to developing thyroid cancer was the most significant risk of death. The researchers reported a hazard ratio of 93.95 for less than a one-year latency period when compared with more than 20 years. Hazard ratios were 25.33, 9.49, and 8.28 for latency periods of one to five years, five to 10 years, and 10 to 15 years.
Whether the primary cancer was a solid tumor or hematologic did not affect overall survival, the team noted.
Reiterating the study authors' theory, Lynn Meyering, MD, a medical oncologist and hematologist at Los Robles Hospital in Thousand Oaks, California, explained that people who had a short latency likely have an occult genetic instability, which would cause them to develop a secondary malignancy regardless of the treatment for the initial cancer. Physicians need to be screening these survivors more carefully in young adulthood, she added.
Rokitka noted that the two abstracts bring into question the best mechanism for surveillance of childhood cancer survivors, whether this is a physical exam or routine serial ultrasounds.
Secondary thyroid cancer is so rare that systemic screening is not practical, Rodriguez-Galindo explained. Instead increased awareness of the condition in certain populations may ensure that physical exams of the thyroid occur.
A formal screening program is difficult to justify, agreed Bryan McIver, MD, an endocrinologist at Moffitt Cancer Center. However, physicians should be aware that a small risk exists and that they should palpate the thyroid gland during routine checkups.
Right now, the risk of a secondary thyroid malignancy in childhood cancer survivors is not on the radar of primary care physicians who may be following these patients, Meyering said. “This isn't necessarily a shortcoming of these physicians but perhaps falls more to the oncology community to help educate and provide surveillance care plans to the primary care physicians who will be following these patients.”
Rodriguez-Galindo said that physicians are already aware that there are risks associated with radiation to the head and chest and thus check for thyroid growths on physical exam, but they also need to know that the risk is increased in patients who did not undergo radiation and in younger African American males.
And Meyering noted that while the Rodriguez-Galindo abstract concludes that the risk of secondary thyroid cancer is higher in black males, all childhood cancer survivors should be closely monitored.