Childhood Cancer Survivors May Have 'Premature Aging'

Risk-Based Screening

Nick Mulcahy

June 12, 2013

Childhood cancer survivors have an "extraordinarily high" prevalence of chronic health conditions and could suffer from "premature aging," according to a new study.

The authors found that 98% of 1713 adult survivors of childhood cancer had at least 1 chronic health condition.

In addition, by middle age, the problems tended to be quite serious. In fact, for people in the study cohort who were 45 years of age, the estimated prevalence of a serious/disabling or life-threatening condition was 80.5%.

The rates of neurology-related deficits, heart valve disorders, and pulmonary dysfunction were "particularly striking," write the authors, led by Melissa Hudson, MD, from St. Jude Children's Research Hospital and the University of Tennessee College of Medicine in Memphis.

Because the median age of the cohort was only 32 years, the frequency of these problems could "indicate a pattern of accelerated or premature aging," Dr. Hudson and colleagues write. Their findings were published in the June 12 issue of JAMA.

"The results suggest accelerating aging because many conditions identified — cardiac dysfunction, ovarian failure, neurocognitive deficits, neurosensory deficits, second cancers — are typically seen in much older individuals, Dr. Hudson told Medscape Medical News in an email.

However, the team wants to do further evaluation of predisposing host and treatment factors before applying a label such as "premature aging" to the circumstances.

More Accurate Than Previous Studies?

These results on the prevalence of the late health effects of childhood cancer treatments are likely more accurate than those from previous studies because the researchers used risk-based screening to quantify the burden of disease, as opposed to self-reporting or other methods, the authors note.

In addition, the findings are based on an average of 26.3 years of follow-up, which is unprecedented in this area of research. In effect, the study extends the knowledge base from other, smaller studies with less follow-up.

The most common adverse health outcomes were abnormal pulmonary function (65.2%), hearing loss (62.1%), and endocrine or reproductive disorders, such as hypothalamic–pituitary axis disorders and male germ cell dysfunction (62.0%).

There was also a high prevalence of cardiac conditions, such as heart valve disorders (56.4%) and neurocognitive problems (48.0%).

Less common were hepatic abnormalities such as liver dysfunction (13.0%), skeletal disorders such as osteoporosis (9.6%), renal problems (5.0%), and hematopoietic abnormalities (3%).

Most of the survivors in this study were part of the St. Jude Lifetime Cohort Study. The various rates of chronic conditions are probably underestimates, the authors note, because some patients who would have been eligible to participate and who had various morbidities died before study enrollment.

"Curative therapy for pediatric malignancies has produced a growing population of adults formerly treated for childhood cancer who are at risk for health problems that appear to increase with aging," write the authors.

They conclude that the study underscores "the importance of ongoing health monitoring for adults who survive childhood cancer."

Specific Treatments, Specific Late Effects

The study involved exposure-driven risk-based screening and surveillance of the participants. In this portion of the study, there were periodic assessments (with lab tests) of organ function.

In part, these assessments were correlated with an individual's previous pediatric cancer treatments.

Of the survivors exposed to pulmonary toxic cancer treatments, 65.2% had abnormal pulmonary function. The highest prevalences were in those treated with lung radiation (74.4%), bleomycin (73.3%), and thoracotomy (53.2%).

Of the survivors exposed to cardiotoxic therapies, 56.4% had cardiac abnormalities. Heart valve abnormalities were diagnosed in 56.7% of survivors exposed to cardiac-directed radiation. In survivors exposed to anthracyclines and/or radiation to the heart area, 6.2% experienced systolic dysfunction.

Hearing loss was the most common nervous system abnormality, and occurred in 62.1% of the survivors exposed to platinum agents or ear irradiation.

Another treatment-related late effect was cataract, which was detected in 20.6% of the population exposed to eye radiation, glucocorticoids, or busulfan.

The risk-based screening had a tendency to drive up the prevalence of specific conditions, the authors report.

For example, in survivors 40 years of age who had been treated with chest irradiation, the estimated prevalence of a heart valve disorder increased from 5.7% to 37.2% after echocardiographic screening. This highlights the "subclinical nature of many outcomes," write the authors.

Of the 1713 survivors studied, 272 developed at least 1 adult cancer.

The study was supported by the National Cancer Institute and the American Lebanese Syrian Associated Charities. Some of the study authors report financial relationships with industry, as detailed in the paper.

JAMA. 2013;309:2371-2381. Abstract

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