Detecting Accelerated Aging in Adult Survivors of Childhood Cancer

A Conversation With Kirsten K. Ness, PhD


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Kirsten K. Ness, PhD

Evaluating the causes of this phenomenon is important because frailty predicts onset of chronic conditions and mortality. If we can figure out what causes the phenotype, we may be able to find an effective intervention and either prevent it or stop the process from progressing.

—Kirsten K. Ness, PhD

Last fall, Kirsten K. Ness, PhD, published her study1 on the prevalence of frailty as a sign of accelerated aging in adult survivors of childhood cancer, and the results are startling. Among the 1,922 participants in the study, the prevalence of prefrailty was 31.5% among women and 12.9% among men; the prevalence of frailty was 13.1% among women and 2.7% among men. And prevalence increased with age.

Prefrailty and frailty were defined as experiencing two and three of the following: low muscle mass, self-reported exhaustion, low energy expenditure, slow walking speed, and weakness—problems often found among adults who are 65 years and older. (Nationally, an estimated 9.6% of women and 5.2% of men aged 65 and older are frail.)

Participants in the study were members of the St. Jude Lifetime cohort, an institutional review board–approved clinical study designed to evaluate health among survivors of childhood cancers as they age. All the survivors were treated at St. Jude Children’s Research Hospital between 1962 and 2003, are at least 18 years old, and are at least 10 years from their original cancer diagnosis. Most survivors in this study were younger than age 40. In a comparison group of 341 adults with no history of childhood cancer, none qualified as frail.

The ASCO Post talked with Dr. Ness, Associate Member of the Department of Epidemiology and Cancer Control at St. Jude Children’s Research Hospital, Memphis, about the results of the study, the causes of accelerated aging in young adult survivors, and what oncologists can do to spot and stop the process of accelerated aging in their patients.

Role of Gender

In the study, female survivors were more susceptible to frailty than their male counterparts. Do you know why?

As a general rule, female childhood cancer survivors have worse outcomes than males. We don’t know why. Women have low levels of testosterone, and one of the side effects of insufficient testosterone among men is low-muscle mass, so the reason could be hormonal. But we don’t really know the exact reason because hormonal factors weren’t part of our analysis.

Pathobiology

In your study, the prevalence of frailty among young adult childhood cancer survivors was similar to that among adults aged 65 and older. What causes the accelerated aging in these survivors?

We do not know the pathobiology of that finding yet. We are going to be studying what I consider an aging phenotype in these survivors next. We have to look at what is causing accelerated aging, and whether it is related to damage to the survivors’ organs or organ function caused by chemotherapy, radiation, or surgery, or the cancer itself.

Evaluating the causes of this phenomenon is important because frailty predicts onset of chronic conditions and mortality. If we can figure out what causes the phenotype, we may be able to find an effective intervention and either prevent it or stop the process from progressing.

Cancer Type

Were there certain cancers that put these childhood cancer survivors at greater risk for frailty?

Survivors of brain tumors and soft-tissue sarcomas were at the highest risk for frailty. Most survivors of brain tumors had brain surgery, and many also were treated with cranial irradiation, the most common treatment factor associated with the frailty outcome.

Children who receive radiation to the hypothalamic-pituitary axis can have growth hormone deficiency. Even if the deficiency is subtle, growth hormone is necessary for the formation of organs, especially muscle, which may explain low muscle mass and weakness.

Effects of Cancer vs Aging

Did the conditions of frailty manifest differently in cancer survivors than in older adults?

In older adults, we usually see an onset of muscle weakness before we see a loss of muscle mass, and in this cohort that wasn’t the case. In older adults, the initial problem with function is likely a result of age-related changes in neurologic function, rather than muscle wasting. In this younger group of cancer survivors we speculate that low-lean mass may be related to suboptimal muscle development related to cancer or its treatment.

Prevention Measures

How can prefrailty and frailty be prevented or slowed in adult survivors of childhood cancers?

Clinical screening for frailty should include evaluation of unexplained weight loss, handgrip strength, an assessment of walking speed, and questions about fatigue and weekly physical activity levels. Health-care providers who identify patients at risk for becoming frail or who are already frail, should refer them for a proper rehabilitation intervention that includes resistance training and nutritional counseling.

Although there are ongoing phase I and phase II clinical trials investigating hormone mimetics in cancer patients with muscle wasting, potential application in a childhood cancer survivor population has not been evaluated. The best way to prevent frailty in young cancer survivors and ensure that they have optimal muscle function is to provide appropriate rehabilitation and nutrition as soon as they finish their cancer therapy. Lifestyle counseling is also important. Smoking should be discouraged, and physical activity encouraged.

How much exercise should young cancer survivors engage in to minimize the threat of accelerated aging or prevent it from happening altogether?

Cancer survivors who were exposed to certain chemotherapeutic agents, such as anthracyclines, need to be evaluated by their oncologist and/or cardiologist before starting an exercise program. This doesn’t mean they can’t exercise, but that their exercise may need to be modified or supervised.

In general, children and adolescents should participate in at least 60 minutes of exercise every day. Young adult survivors should have at least 30 minutes of exercise five times a week and resistance training 2 days a week. ■

Disclosure: Dr. Ness reported no potential conflicts of interest.

Reference

1. Ness KK, Krull KR, Jones KE, et al: Physiologic frailty as a sign of accelerated aging among adult survivors of childhood cancer: A report from the St Jude lifetime cohort study. J Clin Oncol 31:4496-4503, 2013.



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