High Risk for Endocrinopathies in Childhood Cancer Survivors

Fran Lowry

March 03, 2014

Childhood cancer survivors have nearly a 5-fold increase in the risk of developing an endocrine disorder in later life that often requires hospitalization, according to a large population-based cohort study of 5 Nordic countries.

Results of the study, by Adult Life After Childhood Cancer in Scandinavia (ALiCCS) study group, were published online February 18 in the Lancet.

This is the latest of several studies on the delayed consequences of cancer therapy in children in different countries, but the first conducted in Scandinavian countries, said lead author Sofie de Fine Licht, MSc, from the Danish Cancer Society Research Centre in Copenhagen.

In an accompanying comment, Kevin C. Oeffinger, MD, and Charles A. Sklar, MD, both from the Memorial Sloan-Kettering Cancer Center in New York City, note that "this study makes several substantial and novel contributions to our understanding of the long-term and late effects of curative treatment for childhood cancer, and has important research and clinical implications."

Health Registries in Nordic Countries Aid Research

Dr. Sofie de Fine Licht

"Similar research has been done in the United States and other countries, but we wanted to investigate the late effects of Nordic treatment protocols for childhood cancer," de Fine Licht told Medscape Medical News. "Furthermore, we had the opportunity to overcome some of the methodological shortcomings of previous studies."

de Fine Licht noted that the Nordic countries — Denmark, Finland, Iceland, Norway, and Sweden — have "unique" health registries that enable researchers to link health data on an individual level because all citizens have their own personal identification number.

No Loss to Follow-up

"This means that virtually no study participants were lost to follow-up, and we were also able to select a random control group from the general population. The cancer registries started in the 1940s and 1950s; therefore, some of the survivors in this study had reached older ages. No previous studies have looked at late effects in groups above 50 years," she said.

"We combined information from all survivors of childhood cancer in the Nordic countries. In fact, this is the largest study of late effects after childhood cancer," she said.

To assess lifetime risk for endocrine disorders, de Fine Licht and her colleagues examined the national cancer registries of the Nordic countries, from their inception to 2008. They identified 31,723 people who survived a childhood cancer for at least 1 year.

They used an age-, sex-, and country-matched cohort of 211,261 people who did not have a childhood cancer a control group.

Of the childhood cancer survivors, 3292 had visited a hospital for an endocrine disorder. Overall, patients in the survivor group had 4.8 times the risk of being hospitalized with an endocrine disorder than those in the control group (standardized hospitalization rate ratio [SHRR], 4.8; 95% confidence interval [CI], 4.6 - 5.0).

Leukemia survivors had the highest risk for hospitalization (SHRR, 7.3; 95% CI, 6.7 - 7.9), followed by survivors of central nervous system tumors (SHRR, 6.6; 95% CI, 6.2 - 7.0) and Hodgkin's lymphoma (SHRR, 6.2; 95% CI, 5.6 - 7.0).

Children whose cancer was diagnosed when they were 5 to 9 years of age were particularly vulnerable to developing an endocrine disorder in later life. In this group, 35% of survivors were affected by age 40 and 43% were affected by age 60.

The most common endocrine disorders in childhood cancer survivors were pituitary hypofunction (SHRR, 88.0), hypothyroidism (SHRR, 9.9), testicular dysfunction (SHRR, 42.5), and ovarian dysfunction (SHRR, 4.7).

The Tip of the Iceberg

"This is just the tip of the iceberg," de Fine Licht said. "Because we used hospitalizations as a measure of endocrine disorders, we only caught severe cases leading to hospitalization. Therefore, our results likely underestimate the true risk of endocrine disorders in survivors."

Her hope is that this study will bring attention to endocrine late effects in childhood cancer survivors, not only for survivors, but also for healthcare providers.

"Endocrine disorders might lead to further nonendocrine morbidity. Most survivors in the Nordic countries are not followed in a specialized late-effect setting, so it's important that GPs and medical specialists outside the late-effect field know of this growing challenge. With more children surviving their cancer, endocrine problems in survivors will be more apparent," she said.

Nested Case–Control Studies Now Possible

Dr. Kevin Oeffinger

This ALiCCS study is "immensely powerful" because it linked nearly all childhood cancer survivors in 5 countries to the development of endocrine disorders, Dr. Oeffinger noted.

The next step is to learn about treatment exposure, he told Medscape Medical News.

"The evolution of research on the late effects of treatment of childhood cancer has been tremendous. Now, with this study, they can conduct nested case–control studies that will help us learn which treatments are responsible for the endocrinopathies," Dr. Oeffinger explained. "We also must continue to investigate curative cancer treatments that have less potential to cause endocrine and other serious late effects."

The study was funded by the Danish Council for Strategic Research. Ms. de Fine Licht reports financial relationships with Novo Nordisk. Dr. Oeffinger has disclosed no relevant financial relationships.

Lancet. Published online February 18, 2014. Abstract, Comment


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