Department of Medicine, University of Arizona, Tucson, AZ, USA.
University of Arizona Cancer Center, 1515 N Campbell Ave, PO Box 245024, Tucson, AZ, 85724, USA.
Breast Cancer Res Treat. 2020 Dec;184(3):771-778. doi: 10.1007/s10549-020-05897-8. Epub 2020 Aug 28.
Chemotherapy-induced peripheral neuropathy (CIPN) is caused by drug-induced damage to the axons which is not detected easily due to lack of reliable, clinically applicable modalities. Diffuse tensor imaging (DTI) allows for quantitative measurements of fractional anisotropy (FA) and apparent diffusion coefficient (ADC), which have been shown to detect nerve injury by Magnetic Resonance Imaging (MRI).
We sought to evaluate if DTI could be used for detection of CIPN in patients with breast cancer treated with a taxane. Patients with h/o exposure to neurotoxic chemotherapy, diabetes, or peripheral neuropathy were excluded. Patients completed pre- and post-chemotherapy MRI of bilateral legs and FACT&GOG-Ntx. Genotyping of single-nucleotide variations (SNVs) was performed to detect known associations with CIPN.
We had 14 evaluable patients in this prospective trial. Mean FA values post-chemotherapy were significantly lower than baseline at mid-calf (p < 0.0001) and ankle (p = 0.03). We did not find any significant change in mean ADC values. In patients without symptomatic neuropathy, mean FA values decreased more than symptomatic patients at mid-calf (p < 0.001). Of the 41 genotyped SNVs, only rs8110536 was found to be significantly associated with development of CIPN.
Our results show that FA values are indicative of CIPN and differential changes in FA values in symptomatic versus asymptomatic patients highlights its potential to be further studied as a predictive biomarker for CIPN. This is the first study to highlight a non-invasive, imaging based, objective biomarker which, if validated, can be translated into clinic easily.
化疗引起的周围神经病（CIPN）是由药物引起的轴突损伤引起的，但由于缺乏可靠的、临床适用的方法，这种损伤不易被发现。弥散张量成像（DTI）允许对分数各向异性（FA）和表观扩散系数（ADC）进行定量测量，磁共振成像（MRI）已经证明这些指标可以检测神经损伤。
我们试图评估 DTI 是否可用于检测接受紫杉烷治疗的乳腺癌患者的 CIPN。排除有神经毒性化疗、糖尿病或周围神经病病史的患者。患者在化疗前后完成双侧腿部 MRI 和 FACT&GOG-Ntx 检查。对单核苷酸变异（SNVs）进行基因分型，以检测与 CIPN 相关的已知关联。
我们在这项前瞻性试验中纳入了 14 例可评估的患者。化疗后平均 FA 值在中踝（p<0.0001）和踝关节（p=0.03）明显低于基线。我们没有发现平均 ADC 值有任何显著变化。在无症状神经病变患者中，中踝的平均 FA 值下降幅度大于有症状患者（p<0.001）。在 41 个基因分型的 SNVs 中，只有 rs8110536 与 CIPN 的发生显著相关。
我们的结果表明 FA 值提示 CIPN，无症状与有症状患者的 FA 值差异变化突出了其作为 CIPN 预测生物标志物进一步研究的潜力。这是第一项强调非侵入性、基于成像、客观生物标志物的研究，如果得到验证，可以很容易地转化为临床应用。
