Short summary

Peripheral neuropathy is a common adverse effect to chemotherapeutics that reduces treatment success and impairs short- and long-term quality of life for cancer patients. It is challenging to diagnose peripheral neuropathy as no biomarker or clear consensus exists. A clinical study in ovarian cancer patients will elucidate whether neurofilament light chain reflects the severity of paclitaxel-induced peripheral neuropathy while studies in human sensory neurons will provide molecular insight.

Rationale

The number of cancer survivors is steadily increasing due to improvements in the diagnosis and treatment of cancers. Consequently, the number of cancer survivors suffering from adverse effects as peripheral neuropathy is increasing as well. Treatment with paclitaxel and other chemotherapeutics frequently cause nerve damage which leads to the development of peripheral neuropathy. Symptoms show as tingling, numbness and neuropathic pain in extremities and often leads to dose reduction in patients with intolerable symptoms. The current methods to diagnose peripheral neuropathy are not optimal since they are subjective and based on the patients' statements and the treating physicians' estimations. This approach is often inaccurate and cannot predict patients at risk for developing peripheral neuropathy. Therefore, there is a need for an objective and sensitive biomarker for risk prediction and for assessment of severity and progression of peripheral neuropathy. In this study, we aim to explore the applicability of neurofilament light chain (NFL) as a biomarker for paclitaxel-induced peripheral neuropathy in ovarian cancer patients and in human sensory neurons which are the symptom-relevant cell type in patients. We hypothesize that NFL levels increase with cumulative dosing of paclitaxel and that this correlates with worsening of clinical symptoms. If validated in future studies, NFL might be implemented into the clinic to personalize treatment with neurotoxic chemotherapeutics and hereby, helping clinicians to better manage peripheral neuropathy.

Description of the cohort

Patients receiving paclitaxel and carboplatin as first-line treatment for ovarian cancer.

Data and biological material

Blood samples and data from medical records

Collaborating researchers and departments

Clinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern Denmark

• Associate Professor, PhD, Tore Bjerregaard Stage
• Associate Professor, PhD, Troels Korshøj Bergmann
• Professor, PhD, Anton Pottegård

Department of Oncology, Lillebælt Hospital

• Professor, PhD, Karina Dahl Steffensen

Biochemistry and Immunology, Lillebælt Hospital

• Professor, PhD, Jonna Skov Madsen

Publications associated with the project

S.-H. Kim et al., "Serum neurofilament light chain levels as a biomarker of neuroaxonal injury and severity of oxaliplatin-induced peripheral neuropathy," Scientific Reports, vol. 10, no. 1, Art. no. 1, May 2020

Å. Sandelius et al., "Plasma neurofilament light chain concentration in the inherited peripheral neuropathies," Neurology, vol. 90, no. 6, pp. e518-e524, 06 2018.