Chemotherapy induced peripheral neuropathy (CIPN) and biomarkers of gut microbial translocation in long-term survivors of testicular germ cell tumors.

Abstract

e17032 Background: Survivors of testicular germ cell tumors (GCT) may suffer from long-term treatment induced peripheral neuropathy. We hypothesized markers of gut microbial translocation after chemotherapy and/or radiotherapy may be contributing factors of peripheral neuropathy. Methods: GCT survivors (N = 194) from National Cancer Institute of Slovakia completed the EORTC QLQ Chemotherapy-Induced Peripheral Neuropathy (CIPN20) questionnaires during their annual follow-up visit at 10-year median (range 2-25). Biomarkers of gut microbial translocaion and dysbiosis (GMT) lipopolysaccharide (LPS), high mobility group box-1 (HMGB-1), d-lactate and sCD14 were measured from peripheral blood obtained during the same visit. Upon obtaining the scores from questionnaires per recommended guidelines, each score was correlated with biomarkers of GMT scored as as high or low (above and below median). Survivors were treated with orchiectomy only (N = 30), cisplatin-based chemotherapy (N = 135), radiotherapy to the retroperitoneum (N = 14) or both chemotherapy and radiotherapy (N = 10). Results: GCT survivors with higher vs lower plasma levels of HMGB-1 had worse overall CIPN20 score (median ± SD = 18 229.0 ± 13 644.2 vs 17 387.0 ± 5106.6 p = 0.048). Patients with higher vs lower plasma HMGB-1 also had worse motor function (9.0 ± 1.8 vs 8.0 ± 2.3, p = 0.036). Sensory and autonomy subscales of CIPN20 qestionaire did not show significant association with HMGB-1 (both P > 0.05). There was no significant difference in CIPN20 symptom burden associated with LPS, d-lactate and sCD14 (all P > 0.05). Conclusions: HMGB-1 may serve as a promising biomarker of CIPN20 in long-term cancer survivors. Proinflammatory pathways are suggested as underlying mechanism of CIPN. Furhter research and larger patient cohorts are needed to explore the pathogenesis of CIPN in GCT survivors.