Potential Role of pNF-H, a Biomarker of Axonal Damage in the Central Nervous System, as a Predictive Marker of Chemotherapy-Induced Cognitive Impairment

Abstract

Purpose: Chemotherapy-induced cognitive impairment (CICI) is a clinically significant problem. Previous studies using magnetic resonance imaging indicated structural changes in the cerebral white matter of patients with CICI. Phosphorylated neurofilament heavy subunit (pNF-H), a major structural protein in axons, was recently reported to be elevated in the serum of patients with some central nervous system disorders. We performed a cross-sectional analysis of neuropsychological test results and serum pNF-H levels in patients undergoing adjuvant chemotherapy for breast cancer. Our hypothesis was that CICI is accompanied by axonal damage that can be detected by elevated serum pNF-H levels. Experimental Design: Seventy-six patients with early breast cancer in various phases of treatment (naïve to chemotherapy; after one, three, or seven cycles of chemotherapy; or with a history of chemotherapy) were assessed by self-administered neuropsychological tests and a single pNF-H measurement. The χ2 and Mann–Whitney tests were used for statistical analysis. Results: Increased pNF-H levels were observed in 28.8% of the patients who underwent chemotherapy, but in none of the chemotherapy-naïve patients or patients with a history of chemotherapy. The pNF-H–positive rate increased significantly in proportion to the number of chemotherapy cycles (one cycle, 5.0%; three cycles, 31.6%; seven cycles, 55.0%; P < 0.05). No significant differences in neuropsychological test results were observed among the groups. Conclusions: The serum pNF-H level in patients undergoing chemotherapy for breast cancer increased in a cumulative dose-dependent manner, suggesting its potential application as a biomarker of neural damage after chemotherapy. Clin Cancer Res; 21(6); 1348–52. ©2015 AACR.

Poor efficacy of the phosphorylated high-molecular-weight neurofilament heavy subunit serum level, a biomarker of axonal damage, as a marker of chemotherapy-induced peripheral neuropathy

“…However, despite the presence of CIPN symptoms, CIPN(+) patients did not demonstrate elevated serum pNF-H levels compared to CIPN(-) patients. In our previous study (5), the chemotherapy-associated pNF-H positivity rate increased in a cumulative dose-dependent manner. Furthermore, as none of the patients who had completed chemotherapy ≥24 months previously showed increased serum pNF-H levels, neuronal toxicity by chemotherapy would operate temporally.…”

“…The present study was an ancillary analysis to our previous study (5), and the characteristics of the patients were as described previously. Briefly, 71 patients exhibited histological proof of early breast cancer and were at various stages of receiving chemotherapy (such as had received 1, 3 or 7 cycles of their regimen, and survivors who had previously completed chemotherapy).…”

“…Twenty patients had completed 1 cycle of chemotherapy, 20 had completed 3 cycles, 19 had completed 7 cycles, and 12 had completed chemotherapy ≥24 months prior to this study. The patient demographic data are summarized in our previous study (5). Eight patients were judged as CIPN positive [CIPN(+) group]; 1 had completed 1 cycle, 5 had completed 7 cycles, and 2 had a history of previously completed chemotherapy (Table I).…”

Chemotherapy-Induced Neurotoxicity: Evidence of a Protective Role of CC Homozygosis in the Interleukin-1β Gene-511 C>T Polymorphism

“…The mechanisms of a possible chemotherapy central neurotoxicity are much less explored and not yet understood, but many evidences highlighted the possible central role of activation of inflammatory cascade and neurodegeneration (Ahles et al 2002;Cleeland et al 2003;Natori et al 2015;Vichaya et al 2015;Wang et al 2015). Moreover, inflammatory responses, partially related to deregulation by the neuroendocrine system, may mediate the onset of behavioral symptoms in cancer patients.…”

The Serum Phosphorylated Neurofilament Heavy Subunit as a Predictive Marker for Outcome in Adult Patients after Traumatic Brain Injury

“…[13][14][15] The findings of the present study indicate that the serum pNF-H value is a reliable marker for predicting the long-term outcome of patients after TBI. Accurate prognosis prediction with this biomarker in the early stages after TBI will help streamline the allocation of healthcare resources and facilitate classification of patients to assess the effectiveness of novel therapies.…”