The Effect of Cold Therapy on Peripheral Neuropathy

An estimated 400,000 children and adolescents aged 0-19 years are diagnosed with cancer each year. More than 80% of children with cancer are cured in high-income countries, where comprehensive care is generally available, whereas survival remains below 30% in some low- and middle-income countries. Considering the global burden of childhood cancer, it is important to characterize the long-term adverse effects of cancer treatment and to develop strategies for their assessment, monitoring, prevention, and management.

Many chemotherapy agents can cause acute and chronic injury and dysfunction of the peripheral nervous system, termed chemotherapy-induced peripheral neuropathy (CIPN). CIPN is an important treatment-related complication and may affect sensory, motor, and autonomic functions. Peripheral nerve toxicity has been associated with several classes of chemotherapy, including vinca alkaloids, platinum compounds, taxanes, epothilones, bortezomib, and thalidomide. Acute CIPN may develop during chemotherapy and may necessitate dose reduction or treatment discontinuation. Reported CIPN incidence varies considerably according to patient characteristics, treatment regimens, and assessment methods. Common manifestations in children and adolescents include numbness, tingling, neuropathic pain in the upper and lower extremities, weakness, reduced ankle dorsiflexion, foot drop, and impaired balance. These symptoms and associated functional impairments may persist beyond completion of cancer treatment.

Vincristine (VCR) is a vinca alkaloid commonly used in pediatric oncology and is included in chemotherapy regimens for acute lymphoblastic leukemia, lymphomas, neuroblastoma, sarcomas, and central nervous system tumors. Vincristine-induced peripheral neuropathy (VIPN) is characterized by autonomic, sensory, and motor manifestations. Reported rates of VIPN vary substantially, partly because of differences in assessment methods. VIPN symptoms may develop after only a few VCR administrations and can include paresthesia, constipation, muscle weakness, areflexia, neuropathic pain, and sensory loss.

Management of VIPN primarily focuses on symptoms and may include medications used for neuropathic pain. VCR dose reduction or treatment interruption may be required in clinically significant cases, potentially limiting optimal cancer treatment. VIPN and associated neuropathic pain may negatively affect quality of life (QoL) during and after cancer treatment.

Both pharmacological and non-pharmacological approaches have been investigated for the management of peripheral neuropathy. However, the mechanisms underlying chemotherapy-related neurotoxicity are not fully understood, limiting the development of effective strategies for preventing VIPN in pediatric oncology patients. Cryotherapy has been investigated as a potential approach for preventing chemotherapy-induced peripheral neuropathy. Its proposed mechanism involves local vasoconstriction, which may reduce blood flow and consequently decrease chemotherapy exposure in cooled peripheral tissues. Potential limitations of cryotherapy include cold-related skin injury, discomfort or intolerance, practical difficulties with administration, and uncertainty regarding its effectiveness.

Although cryotherapy has been investigated for chemotherapy-induced peripheral neuropathy in adults, evidence regarding its use in children and adolescents with cancer is limited. Further research is therefore needed to evaluate its effectiveness, tolerability, and feasibility in pediatric oncology populations. This study aims to evaluate the effectiveness, tolerability, and acceptability of cold therapy for VIPN among pediatric oncology patients in Turkey.

Inclusion criteria

(i) aged 7-18 years; the lower age limit of 7 years was selected to ensure reliable completion of the self-report pain and quality-of-life instruments used in the study, (ii) receiving VCR therapy, (iii) diagnosed with leukemia, medulloblastoma, rhabdomyosarcoma, or Wilms tumor, (iv) able to speak and understand Turkish, (v) receiving initial treatment, and (vi) provision of written informed consent by legal guardians and assent from children.

Exclusion criteria

Risk factors for peripheral neuropathy were considered exclusion criteria (Kandula et al., 2016; Smith et al., 2021; van de Velde et al., 2017). Risk factor criteria were: (i) receiving a dose of VCR >2 mg/m2, (ii) receiving VCR and azole antifungal treatment simultaneously, (iii) a hematological malignancy with neurological disease, (iv) a history of peripheral neuropathy, (v) diabetes, or (vi) self-reported cold sensitivity. Additionally, children who received chemotherapy or other treatments via the peripheral veins of the hands or feet were not included, as cold application was contraindicated in these cases.