Abstract：
Chemotherapy (CT) remains a backbone treatment of epithelial ovarian cancer (EOC) inducing persistent peripheral neuropathy (CIPN). Using a dedicated patient-reported outcome tool, this study investigated persistent CIPN and its pharmacogenetic predictors in a cohort of long-term EOC survivors.
Vivrovaire was a French multicenter cohort of patients with EOC free of disease 3 years after CT completion. Persistent CIPN was assessed using the FACT/GOG-Ntx4 self-questionnaire. The association of homozygous (hom) or heterozygous (het) single nucleotide polymorphisms (SNPs) in selected genes was evaluated.
130 patients were included with a median time from CT completion of 63 [35-180] months. The median CIPN score was 37 [18-44], with 35 (26.9%) patients reporting severe CIPN (<33). SNPs were identified as follows: CYP2C8 [hom, n = 32 (24.6%)/het, n = 99, (76.2%)]; CYP3A4 [hom, n = 0 (0%)/het, n = 8 (6.2%)], ERCC1 [hom, n = 21 (16.2%)/het, n = 57 (43.8%)], and XPC [hom, n = 45 (34.6%)/het, n = 66 (50.8%)]. In univariate analysis, the identification of ≥1 hom SNP was associated with a lower CIPN score (continuous variable; p = 0.045). Patients harboring hom or het CYP2C8_rs1934951 SNP reported more likely severe CIPN (threshold <33) score (OR 2.482; 95% CI [1.126-5.47], p = 0.024). In the multivariate analyses, age, interval from CT completion, type and number of CT courses were not significantly associated with CIPN score (OR 5.165, 95% CI [0.478-55.83], p = 0.176).
Persistent CIPN is common among ovarian cancer long-term survivors. CYP2C8_rs1934951 SNP may be associated with severe residual CIPN in EOC survivors. More studies are warranted to identify predictive factors of CIPN.
Vivrovaire was a French multicenter cohort of patients with EOC free of disease 3 years after CT completion. Persistent CIPN was assessed using the FACT/GOG-Ntx4 self-questionnaire. The association of homozygous (hom) or heterozygous (het) single nucleotide polymorphisms (SNPs) in selected genes was evaluated.
130 patients were included with a median time from CT completion of 63 [35-180] months. The median CIPN score was 37 [18-44], with 35 (26.9%) patients reporting severe CIPN (<33). SNPs were identified as follows: CYP2C8 [hom, n = 32 (24.6%)/het, n = 99, (76.2%)]; CYP3A4 [hom, n = 0 (0%)/het, n = 8 (6.2%)], ERCC1 [hom, n = 21 (16.2%)/het, n = 57 (43.8%)], and XPC [hom, n = 45 (34.6%)/het, n = 66 (50.8%)]. In univariate analysis, the identification of ≥1 hom SNP was associated with a lower CIPN score (continuous variable; p = 0.045). Patients harboring hom or het CYP2C8_rs1934951 SNP reported more likely severe CIPN (threshold <33) score (OR 2.482; 95% CI [1.126-5.47], p = 0.024). In the multivariate analyses, age, interval from CT completion, type and number of CT courses were not significantly associated with CIPN score (OR 5.165, 95% CI [0.478-55.83], p = 0.176).
Persistent CIPN is common among ovarian cancer long-term survivors. CYP2C8_rs1934951 SNP may be associated with severe residual CIPN in EOC survivors. More studies are warranted to identify predictive factors of CIPN.
摘要：
背景：化疗（CT）仍然是上皮性卵巢癌（EOC）引起的持续性周围神经病变（CIPN）的主要治疗方法。使用专用的患者报告结果工具，这项研究调查了长期EOC幸存者队列中的持续性CIPN及其药物遗传学预测因子.
方法：Vivrovaire是法国多中心队列研究，研究了CT完成后3年无疾病的EOC患者。使用FACT/GOG-Ntx4自我问卷评估PersistentCIPN。评估了所选基因中纯合（hom）或杂合（het）单核苷酸多态性（SNP）的关联。
结果：130例患者被纳入，CT完成的中位时间为63[35-180]个月。medianCIPN得分为37[18-44]，35例（26.9%）患者报告严重CIPN（<33）。SNP鉴定如下：CYP2C8[hom，n=32(24.6%)/het，n=99,(76.2%)];CYP3A4[hom,n=0（0%）/het，n=8（6.2%）]，ERCC1[hom，n=21（16.2%）/het，n=57（43.8%）]，和XPC[hom，n=45(34.6%)/het，n=66(50.8%)]。在单变量分析中，≥1个homSNP的鉴定与较低的CIPN评分相关(连续变量;p=0.045).携带hom或hetCYP2C8_rs1934951SNP的患者报告更可能严重CIPN（阈值<33）评分（OR2.482;95％CI[1.126-5.47]，p=0.024)。在多变量分析中，年龄,从CT完成的间隔，CT病程的类型和数量与CIPN评分无显著相关(OR5.165,95%CI[0.478-55.83],p=0.176）。
结论：持续CIPN在卵巢癌长期存活者中很常见。CYP2C8_rs1934951SNP可能与EOC幸存者的严重残留CIPN相关。有必要进行更多的研究来确定CIPN的预测因素。
方法：Vivrovaire是法国多中心队列研究，研究了CT完成后3年无疾病的EOC患者。使用FACT/GOG-Ntx4自我问卷评估PersistentCIPN。评估了所选基因中纯合（hom）或杂合（het）单核苷酸多态性（SNP）的关联。
结果：130例患者被纳入，CT完成的中位时间为63[35-180]个月。medianCIPN得分为37[18-44]，35例（26.9%）患者报告严重CIPN（<33）。SNP鉴定如下：CYP2C8[hom，n=32(24.6%)/het，n=99,(76.2%)];CYP3A4[hom,n=0（0%）/het，n=8（6.2%）]，ERCC1[hom，n=21（16.2%）/het，n=57（43.8%）]，和XPC[hom，n=45(34.6%)/het，n=66(50.8%)]。在单变量分析中，≥1个homSNP的鉴定与较低的CIPN评分相关(连续变量;p=0.045).携带hom或hetCYP2C8_rs1934951SNP的患者报告更可能严重CIPN（阈值<33）评分（OR2.482;95％CI[1.126-5.47]，p=0.024)。在多变量分析中，年龄,从CT完成的间隔，CT病程的类型和数量与CIPN评分无显著相关(OR5.165,95%CI[0.478-55.83],p=0.176）。
结论：持续CIPN在卵巢癌长期存活者中很常见。CYP2C8_rs1934951SNP可能与EOC幸存者的严重残留CIPN相关。有必要进行更多的研究来确定CIPN的预测因素。
