Chemotherapy-Related Neuropathic Symptoms and Functional Impairment in Adult Survivors of Extracranial Solid Tumors of Childhood: Results From the St. Jude Lifetime Cohort Study

Abstract

Objective To ascertain prevalence of peripheral sensory and motor neuropathy; to evaluate impairments in relation to function. Design St. Jude Lifetime Cohort Study, a clinical follow-up study designed to evaluate adverse late effects in adult survivors of childhood cancer. Setting St. Jude Children’s Research Hospital (SJCRH). Participants Eligibility required treatment for an extracranial solid malignancy between 1962 and 2002, age ≥18 years, ≥10 years post-diagnosis, no history of cranial radiation. 531 survivors were included in the evaluation: median age 32 years, median time from diagnosis 25 years. Interventions Not applicable. Main Outcome Measures Primary exposure measures were cumulative doses of vinca-alkaloid and platinum-based chemotherapies. Survivors with scores ≥ 1 on the sensory subscale of the modified Total Neuropathy Score were classified with prevalent sensory impairment. Those with sex-specific Z-scores of ≤−1.3 for dorsiflexion strength were classified with prevalent motor impairment. Participants completed the 6-minute walk test (endurance), the timed up and go test (mobility), and the sensory organization test (balance). Results The prevalence of sensory and motor impairment was 20% and 17.5%, respectively. Vinca-alkaloid exposure was associated with an increased risk of motor impairment (adjusted odds ratio (OR)=1.66, 95% Confidence Interval (CI): 1.04–2.64) without evidence for a dose response. Platinum exposure was associated with increased risk of sensory impairment (adjusted OR= 1.62, 95% CI: 0.97–2.72) without evidence of a dose response. Sensory impairment was associated with poor endurance (OR=1.99, 95% CI: 0.99–4.00) and mobility (OR=1.65, 95% CI: 0.96–2.83). Conclusion Vincristine and cisplatin exposure may increase risk for long-term motor and sensory impairment, respectively. Survivors with sensory impairment are at increased risk for functional performance limitations.

Identification and Characterization of New Chemical Entities Targeting Apurinic/Apyrimidinic Endonuclease 1 for the Prevention of Chemotherapy-Induced Peripheral Neuropathy

“…The platinum agents are still one of the major families of chemotherapy used as standard of care in a wide variety of cancer scenarios. However, despite the abundant use of platinum-based chemotherapy, little is known about the mechanisms by which these drugs cause neuropathy or how to prevent or treat this debilitating toxicity (Ness et al, 2013). Furthermore, unlike a number of other major chemotherapy side effects (e.g., nausea, hair loss, bone marrow failure; Zafar et al, 2010), there are no standard, Fig.…”

Limitations in Ankle Dorsiflexion Range of Motion, Gait, and Walking Efficiency in Childhood Cancer Survivors

“…10 In terms of assessment methods, only active DF-ROM has been measured, although previous studies reported that passive DF-ROM, as well as strength of ankle dorsiflexors, is reduced as well. 8,9,12,14,19,20,27 In addition, there are 2 other important limitations. The assessors were not blinded.…”

“…These limitations may cause functional impairments, such as reduced walking efficiency, a reported late effect in pediatric oncology. 8,19,20 In practice, our team has noticed the tendency to run on tiptoes and the inability to walk on heels in a mixed childhood cancer survivor cohort. Therefore, we hypothesize that limitations in ankle DF-ROM, gait, and walking efficiency may affect various types of childhood cancer.…”

Chemotherapy‐induced neuropathies—a growing problem for patients and health care providers

“…Vinca alkaloids trigger neuropathy in about 20% of cancer patients; typical symptoms include lower limb weakness, sensory impairment, altered gait, and diminished reflexes. Using electrophysical techniques, nerve changes are diagnosed as predominantly moderate to severe sensory or sensorimotor polyneuropathies (Ness et al., 2013). Mechanisms underlying neurotoxicity of vinca alkaloids remain unclear; however, available evidence suggests that genetic polymorphism of genes crucial for microtubule formation might play a role in developing neuropathy in cancer patients (Diouf et al., 2015).…”