Cancer is a prevalent disease in our society with over 15.5 million cancer survivors in the United States in 2016. As screening and treatments improve survival rates from many cancers, increased effort is needed to address the quality of life-impairing adverse effects that result from commonly administered neurotoxic chemotherapeutic agents. These treatments can induce dysfunction in the peripheral and central nervous systems that are integral to coordinated and stable human movement. While cancer survivors are at an increased risk of falling, few details are known regarding the underlying mechanisms that contribute to this increased falls risk. Therefore, the purpose of this dissertation was to better understand the scope of functional instability in cancer survivors that result from neurotoxic chemotherapy and its adverse effects (e.g., chemotherapy-induced peripheral neuropathy, CIPN).

Chapter 1 provides background information on chemotherapy-related impairments to the central and peripheral nervous systems along with an overview of human postural stability and implications for cancer survivors. Chapter 2 discusses the first longitudinal investigation into postural instability during quiet stance and gait in breast cancer patients receiving taxane-based chemotherapy. Thirty-three breast cancer patients were assessed and demonstrated balance deficits that initiated early in chemotherapy treatment (medial-lateral root mean square center of pressure excursion:​ 28% increase from baseline, p = 0.016) along with worsening balance and more cautious gait (5% decrease in speed, p = 0.003) with cumulative taxane exposure. We then extended our understanding by pursuing more in-depth exploratory analyses into the system-level mechanisms of balance (Chapter 3) and gait (Chapter 4) impairments associated with chemotherapy and CIPN through a case-control study design. A cohort of 20 cancer survivors provided three groups, differing by exposure to chemotherapy and presence of sensory symptoms of CIPN. Chapter 3 consists of tests of vision and ankle proprioception as well as a sensory organization balance protocol that systematically altered the accuracy of visual, vestibular, and somatosensory information. Results from these tests identified impaired balance, particularly during conditions that excluded vision. Survivors with CIPN experienced the most severe balance impairments with an independent effect of CIPN on medial-lateral postural control compared to chemotherapy itself. These impairments were accompanied by an altered sensory organization strategy that decreased the reliance on somatosensation and seemingly increased the reliance on vision when all sensory information was available. Ankle proprioceptive ability and visual acuity were also significantly associated with balance function and the effect of sensory system interference. Chapter 4 focuses on single- and dual-task treadmill walking in this same cohort. Results from these tests identified decreased orbital stability during dual-task gait for survivors who received chemotherapy that were asymptomatic for CIPN (p = 0.019). Additionally, worse executive function was associated with a more severe negative effect of dual-task gait on orbital stability in survivors with CIPN (Spearman’s ρ = 0.94, p = 0.017). Ankle proprioception and visual acuity also appeared to have significant influences on gait stability and variability measures, with effects varying between groups.

The findings presented in this dissertation improve the basic understanding of the effects of neurotoxic chemotherapy on the functional stability of cancer survivors. The work described here and the future efforts that it may help guide will contribute toward the long-term goal of reducing the burden of cancer treatment and its adverse effects of survivor quality of life.