睾丸生殖细胞瘤患者细胞毒性治疗对精子DNA断裂的长期影响。
Long-term effect of cytotoxic treatments on sperm DNA fragmentation in patients affected by testicular germ cell tumor.
发表日期:2023 Mar 17
作者:
Ginevra Farnetani, Maria Grazia Fino, Francesca Cioppi, Antoni Riera-Escamilla, Lara Tamburrino, Matteo Vannucci, Viktoria Rosta, Serena Vinci, Elena Casamonti, Leila Turki, Selene Degl'Innocenti, Matilde Spinelli, Sara Marchiani, Francesco Lotti, Monica Muratori, Csilla Krausz
来源:
Andrology
摘要:
睾丸生殖细胞肿瘤(TGCT)是男性生殖期最常见的肿瘤,5年生存率为95%。抗肿瘤治疗会诱导精子DNA碎裂(SDF),特别是在治疗后的第一年内。文献中的数据在更长的随访期间是异质的,大部分限于2年。为了确定精子DNA损伤恢复的时间和2年和3年治疗后有严重DNA损伤(SDD)的患者比例,使用TUNEL法和流式细胞术评估了115名TGCT患者的SDF,分别在治疗前(T0),治疗后2(T2)和3年(T3)。将患者分为三组,分别接受卡铂(CP)、博莱霉素-依托泊苷-顺铂(BEP)和放疗(RT)治疗。对24名患者进行了配对SDF数据的分析,79名无癌症、肥沃、正常精子形态的男性作为对照组。将SDD定义为控制组中的95th百分位数(SDF = 50%)。比较患者与对照组的结果显示:在T0和T3时没有差异,在所有治疗组中,在T2时SDF水平显着较高(p <0.05)。与治疗前相比,在115名患者中,所有组在T2时的中位SDF值都更高,在CP组中达到了显着水平(p<0.05)。虽然在严格配对的队列中,在T2时中位SDF值也更高,但约50%的患者恢复到了基线。整个队列中SDD的比例为23.4%和4.8%的患者在T2和T3时,分别达到。目前,建议TGCT患者在治疗后两年等待自然怀孕。我们的结果表明,这段时间可能对所有患者都不够。对SDF的分析可能代表了肿瘤治疗后孕前咨询有用的生物标志物。本文受版权保护。保留所有权利。
Testicular germ cell tumor (TGCT) is the most frequent neoplasia in men of reproductive age, with a 5-year survival rate of 95%. Antineoplastic treatments induce sperm DNA fragmentation (SDF), especially within the first year post-therapy. Data in the literature are heterogeneous concerning longer follow-up periods and the large majority is limited to 2 years.To define the timing for the recovery of sperm DNA damage and the proportion of patients with severe DNA damage (SDD) at 2 and 3 years from the end of therapy.SDF was evaluated in 115 TGCT patients using TUNEL assay coupled with flow cytometry before (T0 ) and 2 (T2 ) and 3 (T3 ) years post-treatment. Patients were divided based on the type of treatment: carboplatin (CP), bleomycin-etoposide-cisplatin (BEP), radiotherapy (RT). For 24 patients paired SDF data were available at all time-points (T0 -T2 -T3 ). 79 cancer-free, fertile normozoospermic men served as controls. SDD was defined as the 95th percentile in controls (SDF = 50%).Comparing patients versus controls we observed: i) no differences at T0 and T3 ; ii) significantly higher SDF levels (p<0.05) at T2 in all treatment groups. Comparing pre and post-therapy in the 115 patients, the median SDF values were higher in all groups at T2 , reaching significance (p<0.05) only in the CP group. While the median SDF values were higher also in the strictly paired cohort at T2 , about 50% of patients returned to baseline. The proportion of SDD in the entire cohort was 23.4% and 4.8% of patients at T2 and T3 , respectively.Currently, TGCT patients are advised to wait two years post-therapy before seeking natural pregnancy. Our results suggest that this period may not be sufficient for all patients.The analysis of SDF may represent a useful biomarker for pre-conception counselling following cancer treatment. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.