Zobrazit v EDS

Neurofilament light chain as a biomarker of axonal damage in sensory neurons and paclitaxel-induced peripheral neuropathy in patients with ovarian cancer

Uloženo v:
Podrobná bibliografie
Název: Neurofilament light chain as a biomarker of axonal damage in sensory neurons and paclitaxel-induced peripheral neuropathy in patients with ovarian cancer
Autoři: Christina Mortensen, Karina Dahl Steffensen, Emma Simonsen, Kamille Herskind, Jonna Skov Madsen, Dorte Aalund Olsen, Ditte Bork Iversen, Troels Korshøj Bergmann, Anton Pottegård, Tore Bjerregaard Stage
Zdroj: Pain. 164:1502-1511
Informace o vydavateli: Ovid Technologies (Wolters Kluwer Health), 2022.
Rok vydání: 2022
Témata: Ovarian Neoplasms, Paclitaxel, Sensory Receptor Cells, Peripheral Nervous System Diseases/chemically induced, Induced Pluripotent Stem Cells, Intermediate Filaments, Ovarian Neoplasms/drug therapy, Peripheral Nervous System Diseases, 3. Good health, Carboplatin, 03 medical and health sciences, Carboplatin/adverse effects, 0302 clinical medicine, Neurofilament Proteins, Paclitaxel/adverse effects, Quality of Life, Humans, Female, Biomarkers, Retrospective Studies
Popis: Paclitaxel-induced peripheral neuropathy (PIPN) is a barrier to effective cancer treatment and impacts quality of life among patients with cancer. We used a translational approach to assess the utility of neurofilament light chain (NFL) as a biomarker of PIPN in a human cell model and in patients with ovarian cancer. We measured NFL in medium from human induced pluripotent stem cell–derived sensory neurons (iPSC-SNs) exposed to paclitaxel. Serum NFL (sNFL) levels were quantified in 190 patients with ovarian cancer receiving paclitaxel/carboplatin chemotherapy at baseline and after each of the following 2 or 6 cycles. Adverse outcomes related to PIPN were retrospectively obtained, and Cox regression model was performed with different sNFL cut-offs after first cycle. The apparent elimination half-life of sNFL was estimated in patients who discontinued paclitaxel. Paclitaxel neurotoxicity in iPSC-SNs was accompanied by NFL release in a concentration-dependent manner (P < 0.001, analysis of variance). Serum NFL levels increased substantially in patients during paclitaxel/carboplatin chemotherapy with considerable interindividual variability. Patients with sNFL >150 pg/mL after first cycle had increased risk to discontinue paclitaxel early (unadjusted HR: 2.47 [95% CI 1.16-5.22], adjusted HR: 2.25 [95% CI: 0.88-5.79]). Similar trends were shown for risk of severe PIPN and paclitaxel dose reduction because of PIPN. The median elimination half-life of sNFL was 43 days (IQR 27-82 days). Neurofilament light chain constitutes an objective biomarker of neurotoxicity in iPSC-SNs and in ovarian cancer patients with high sNFL predicting PIPN-related adverse outcomes. If prospectively validated, NFL can be used to study PIPN and may guide clinical decision making and personalize treatment with paclitaxel.
Druh dokumentu: Article
Jazyk: English
ISSN: 1872-6623
0304-3959
DOI: 10.1097/j.pain.0000000000002840
Přístupová URL adresa: https://pubmed.ncbi.nlm.nih.gov/36508173
Rights: unspecified
Přístupové číslo: edsair.doi.dedup.....95b67b39a09b3bf86ec432732803f870
Databáze: OpenAIRE
Popis
Abstrakt:Paclitaxel-induced peripheral neuropathy (PIPN) is a barrier to effective cancer treatment and impacts quality of life among patients with cancer. We used a translational approach to assess the utility of neurofilament light chain (NFL) as a biomarker of PIPN in a human cell model and in patients with ovarian cancer. We measured NFL in medium from human induced pluripotent stem cell–derived sensory neurons (iPSC-SNs) exposed to paclitaxel. Serum NFL (sNFL) levels were quantified in 190 patients with ovarian cancer receiving paclitaxel/carboplatin chemotherapy at baseline and after each of the following 2 or 6 cycles. Adverse outcomes related to PIPN were retrospectively obtained, and Cox regression model was performed with different sNFL cut-offs after first cycle. The apparent elimination half-life of sNFL was estimated in patients who discontinued paclitaxel. Paclitaxel neurotoxicity in iPSC-SNs was accompanied by NFL release in a concentration-dependent manner (P < 0.001, analysis of variance). Serum NFL levels increased substantially in patients during paclitaxel/carboplatin chemotherapy with considerable interindividual variability. Patients with sNFL >150 pg/mL after first cycle had increased risk to discontinue paclitaxel early (unadjusted HR: 2.47 [95% CI 1.16-5.22], adjusted HR: 2.25 [95% CI: 0.88-5.79]). Similar trends were shown for risk of severe PIPN and paclitaxel dose reduction because of PIPN. The median elimination half-life of sNFL was 43 days (IQR 27-82 days). Neurofilament light chain constitutes an objective biomarker of neurotoxicity in iPSC-SNs and in ovarian cancer patients with high sNFL predicting PIPN-related adverse outcomes. If prospectively validated, NFL can be used to study PIPN and may guide clinical decision making and personalize treatment with paclitaxel.
ISSN:18726623
03043959
DOI:10.1097/j.pain.0000000000002840