Frailty in childhood cancer survivors

Abstract

Young adult childhood cancer survivors are at an increased risk of frailty, a physiologic phenotype typically found among older adults. This phenotype is associated with new-onset chronic health conditions and mortality among both older adults and childhood cancer survivors. Mounting evidence suggests that poor fitness, muscular weakness, and cognitive decline are common among adults treated for childhood malignancies, and that risk factors for these outcomes are not limited to those treated with cranial radiation. Although the pathobiology of this phenotype is not known, early cellular senescence, sterile inflammation, and mitochondrial dysfunction in response to initial cancer or treatment-related insults are hypothesized to play a role. To the authors' knowledge, interventions to prevent or remediate frailty among childhood cancer survivors have not been tested to date. Pharmaceutical, nutraceutical, and lifestyle interventions have demonstrated some promise.

Keywords: aging; childhood cancer survivor; fitness; frailty; inflammation; mitochondrial dysfunction; senescence; weakness.

Figure 1

Frailty and function. The dashed line above the shading represents the cut-point between function and frailty. The dashed line with arrow represents decline in physiologic reserve with typical aging. The solid line with arrow represents potential decline in physiologic reserve among childhood cancer survivors whose acute insult occurs early in life. The solid line with arrow pointing directly down represents the potential impact of lifestyle on the trajectory of physiologic capacity; the additional arrows pointing upward potential recovery from loss of function based on access to intervention.

Figure 2

Pathobiology of frail health