CHARACTERIZATION AND ASSESSMENT OF FOOT STRUCTURAL AND FUNCTIONAL ALTERATIONS RELEVANT TO CHEMOTHERAPY-INDUCED PERIPHERAL NEUROPATHY IN ADULTS WITH CANCER

Abstract

BACKGROUND/PURPOSE: Peripheral neuropathy (PN) will affect the feet of 60-90% of adults who receive a neurotoxic anticancer agent. In 40%, symptoms will persist for years. Most chemotherapy-induced PN (CIPN) is characterized as primarily a sensory deficit, but sensory impairments interfere with motor control of the feet for balance and walking. Motor nerves can also sustain direct toxicity; foot drop is a severe motor sign, but toe weakness is more common. In the coming decade, if chemotherapy use increases by 50% as projected, the burden of CIPN will also rise. Although well-published in individuals with diabetes, little is known about how CIPN sensorimotor deficits affect the foot alignment of cancer survivors. This dissertation aims to (1) investigate the potential for CIPN to change foot alignment, and (2) validate the Laser- Equipped Rearfoot Angle Assessment (LERAA™), a novel method to measure rearfoot alignment when imbalance or pain limits standard goniometric protocol. METHODS: This dissertation is organized as three related manuscripts: (1) an integrative literature review to identify evidence for chemotherapy-related pathomechanics in the feet of adult survivors, (2) an exploratory secondary analysis for changes in the foot progression angle (FPA) of 25 women with breast and gynecological cancers from before to after taxane-platinum exposure, and longitudinal associations between FPA and hallux strength and sensation in the foot with more severe strength or sensory loss (More Involved Foot, MIF) and the Less Involved foot (LIF), and (3) a cross-sectional study of 30 healthy adults to quantify LERAA’s reliability and concurrent validity while exploring associations with the medial longitudinal arch (MLA), foot contact area (FCA), and hallux strength. RESULTS: (1) We identified 11 publications documenting biomechanical foot abnormalities after chemotherapy, all descriptive studies or case reports of breast, hematologic, and liver cancer survivors. Six focused on foot drop, but others reported more subtle deficits, including arch abnormalities, especially pes planus (flat arch), and toe deformities. Many deformities emerged asymmetrically or unilaterally despite CIPN being a bilaterally symmetrical pathology. (2) In breast and gynecological cancer survivors, we found no 10 significant group-level changes in FPA after taxane-platinum exposure, but after establishing a minimal detectable change (MDC) of 5°, analysis of individual patients revealed meaningful inward shifts in 21% of the sample and external shifts in 11%, mostly during fast-paced walking. Likewise, in longitudinal group analyses by degree of foot involvement, losses of hallux strength and sensation correlated with an internal FPA shift of the MIF, but an external shift of the LIF. (3) LERAA demonstrated excellent intra-rater reliability, good inter-rater reliability, and strong agreement relative to goniometry, the current clinical standard of care. Additionally, higher rearfoot valgus by LERAA was associated with a lower MLA, greater contact area when walking, and stronger hallux extension strength. DISCUSSION/CONCLUSION: The findings support CIPN as having neuromechanical consequences for foot and toe alignment even without foot drop, and LERAA holds promise to quantify rearfoot alignment when traditional methods are unsafe and gold standard methods are impractical. In other populations, changes in FPA contribute to mobility limitations and postural instability, and abnormal foot loading leads to structural compromise over time. Research is needed on the relationships between subtle early biomechanical changes, impaired balance, and foot deformities in cancer survivorship. Early identification and rehabilitation could improve mobility-related quality of life outcomes.