Dulz Simon, Asselborn Niels H, Dieckmann Klaus-Peter, Matthies Cord, Wagner Walter, Weidmann Jens, Seidel Christoph, Oing Christoph, Berger Lars A, Alsdorf Winfried, Mankichian Blanche, Meyer Christian, Vetterlein Malte W, Gild Philipp, Ludwig Tim A, Soave Armin, Schriefer Philipp, Becker Andreas, Ahyai Sascha A, Oechsle Karin, Bokemeyer Carsten, Wagenfeld Lars, Fisch Margit, Hartmann Michael, Chun Felix K-H, Kluth Luis A
Department of Ophthalmology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Urology, Albertinen Medical Center, Hamburg, Germany.
J Cancer Res Clin Oncol. 2017 Jul;143(7):1319-1325. doi: 10.1007/s00432-017-2384-8. Epub 2017 Mar 9.
Visual impairment represents an infrequent form of cisplatin-induced neurotoxicity; however, visual deterioration has been reported in several studies. To evaluate potential morphological and functional retinal alterations in patients with germ cell cancer (GCC) treated with cisplatin-based chemotherapy (CBC).
Multi-disciplinary and multi-institutional study design. Examination of 28 eyes of 14 male GCC patients, who had received at least one cycle of CBC. A matched control group of healthy, untreated patients were included in this study. Subjects underwent a retinal nerve fiber thickness (RNFL) measurement, color vision, visual acuity testing, full-field electroretinograms (ff-ERG). To assess a correlation between cumulative cisplatin dose and measured RNFL and ff-ERG Pearson correlation coefficient analysis was performed.
Both study groups (CBC recipients vs. healthy controls) consisted each of 14 participants with a median patient age of 30 years (interquartile range (IQR) 26-37 years). Tumor histology was seminoma in 6 of 14 patients (43%), and non-seminomatous GCC in 8 of 14 patients (57%). Median cumulative cisplatin dosis at examination was 627 mg/m (IQR 413-1013 mg/m). Morphological assessment revealed reduced RNFL in 11 of 14 patients (78.6%). Reduction in RNFL was significantly correlated to the cumulative CBC dose received (rho = + 0.70; p = 0.004). ff-ERG showed significant differences between CBC recipients and the control group in 2 of 5 tested categories (all p values <0.001).
This study represents first evidence of chronic subclinical retinal toxicity due to cisplatin-based chemotherapy in patients with GCC. The reduction of RNFL might become clinically relevant in upcoming age-related chronic degenerative disorders such as glaucoma.
视力损害是顺铂诱导的神经毒性的一种罕见形式；然而，在多项研究中均有视力恶化的报道。为评估接受基于顺铂的化疗（CBC）的生殖细胞癌（GCC）患者视网膜潜在的形态学和功能改变。
多学科、多机构研究设计。对14例男性GCC患者的28只眼进行检查，这些患者至少接受了一个周期的CBC。本研究纳入了一组匹配的健康未治疗患者作为对照组。受试者接受视网膜神经纤维层（RNFL）厚度测量、色觉、视力测试、全视野视网膜电图（ff-ERG）检查。为评估累积顺铂剂量与测得的RNFL和ff-ERG之间的相关性，进行了Pearson相关系数分析。
两个研究组（接受CBC者与健康对照组）各有14名参与者，患者年龄中位数为30岁（四分位间距（IQR）26 - 37岁）。14例患者中有6例（43%）肿瘤组织学类型为精原细胞瘤，8例（57%）为非精原细胞性GCC。检查时顺铂累积剂量中位数为627mg/m²（IQR 413 - 1013mg/m²）。形态学评估显示，14例患者中有11例（78.6%）RNFL降低。RNFL降低与接受的累积CBC剂量显著相关（rho = +0.70；p = =0.004）。ff-ERG显示，在5个测试类别中的2个类别中，接受CBC者与对照组之间存在显著差异（所有p值<0.001）。
本研究首次证明了GCC患者接受基于顺铂的化疗会导致慢性亚临床视网膜毒性。RNFL的降低在未来诸如青光眼等与年龄相关的慢性退行性疾病中可能具有临床意义。
