Abstract P6-12-26: The axonal damage marker, serum phosphorylated neurofilament heavy subunit, as a potential marker of chemotherapy-induced neuropathy
Authors: Kida K , Sumitani M , Ogata T , Kotake R , Natori A , Hashimoto J , Shimokawa T , Yamauchi H , Yamauchi T 
Published: February 2018

Background: Chemotherapy-induced neurologic disorders such as peripheral neuropathy and cognitive disturbance are clinically significant problems for cancer survivors, but their objective assessment methods have not been established. We previously reported in a cross-sectional study that the serum phosphorylated neurofilament heavy subunit (pNF-H), a biomarker of axonal damage, was increased in breast cancer patients treated with chemotherapy. The aim of this study is to temporally assess the neurological adverse events and evaluate the association of serum pNF-H level with cognitive functions and neuropathy following sequential chemotherapy.

Methods: Thirty-five breast cancer patients who received neoadjuvant or adjuvant chemotherapy were enrolled prospectively. They underwent brain MRI and cognitive function tests including Controlled Oral Word Association (COWA), Trail Making Test (TMT), and Hopkins Verbal Learning Test-Revised (HVLT-R) before chemotherapy (baseline), one month after completing sequential chemotherapy (post-phase) and more than six months after completing chemotherapy (late-phase). Serum pNF-H levels and questionnaires reporting peripheral neuropathy were measured at the three phases, and every 3 weeks during chemotherapy. Brain MRI volumetry was calculated by the automatic analysis software, BAAD® (Brain Anatomical Analysis using Dartel). The correlations among cognitive functions, brain volume, peripheral neuropathy and serum pNF-H levels were statistically analyzed.

Results: Patients' median age was 48 years (range 24-71). A decrease of more than 10% in cognitive function test (COWA) scores was seen in 10 cases (31%) at post-phase. A brain volume loss of more than 10% was seen in 5 cases (15%) at post-phase. The correlation between brain volume change and cognitive disturbance was not significant (p=0.45) and both changes were improved at late-phase. A peripheral neuropathy grade above CTCAE grade 2 was seen in 19 cases (54%). The neuropathy was significantly more severe in anthracycline followed by taxane regimen than taxane followed by anthracycline during chemotherapy (p=0.016), although this difference was not seen at the late-phase (p=0.08). An elevated serum pNF-H level at baseline was seen in only one case, and this case demonstrated the cognitive disturbance, brain volume loss, and peripheral neuropathy following chemotherapy. During chemotherapy, pNF-H was elevated in 24 patients (69%), with especially higher levels noted during the taxane regimen compared to the anthracycline regimen (p=0.019). In the cases treated with anthracycline followed by taxane, the taxane-phase elevation was especially significant (p=0.014). The maximum pNF-H level during taxane therapy was significantly correlated with peripheral neuropathy grade (p=0.002). At late-phase, the significant reduction of pNF-H level was seen in all cases.

Conclusions: Change of cognitive function, brain volume and peripheral neuropathy was observed following chemotherapy in breast cancer patients. This study suggests that the serum axonal damage marker, pNF-H, may reflect chemotherapy-induced neuropathy.

Citation Format: Kida K, Sumitani M, Ogata T, Kotake R, Natori A, Hashimoto J, Shimokawa T, Yamauchi H, Yamauchi T. The axonal damage marker, serum phosphorylated neurofilament heavy subunit, as a potential marker of chemotherapy-induced neuropathy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-12-26.