Department of Oncology, Univesity Hospital of North Norway, Tromsø, Norway
Line veronika Hjelle , Roy M. Bremnes , per Ole Gundersen , Mette Sprauten , Marianne Brydoy , Torgrim Tandstad , Tom Wilsgaard , Sophie D. Fossa , Jan Oldenburg , Hege Sagstuen Haugnes
Background: Previous studies have identified several long-term complications following cisplatin-based treatment in testicular cancer survivors (TCS). We evaluated the impact of long-term serum levels of platinum (Pt) on neuro- and ototoxicity (NTX), cardiovascular disease (CVD) and hypogonadism in TCS. Methods: 292 cisplatin-treated TCS (1980-1994) participated in a national follow-up study (2007-2008), including laboratory tests and a questionnaire. Serum Pt was quantified by Inductively Coupled Plasma-Mass Spectrometry. Symptoms of NTX were assessed with Scale for Chemotherapy-Induced Neurotoxicity (SCIN), with each symptom categorized in 4 categories ranging from 0, “not at all” to 3, “very much”. Total SCIN score was the sum of six scores, ranging from 0 to 18, and categorized into quartiles. Information about CVD (validated) and medication were retrieved from the questionnaire. Hypogonadism was defined as using testosterone substitution and/or having testosterone <10nmol/l. Associations between NTX and long-term Pt levels were analyzed with ordinal logistic regression. Cox regression was performed to evaluate the risk for CVD, and logistic regression for hypogonadism according to levels of Pt and cisplatin dose. The results are presented as odds ratio (OR) or hazard ratio (HR) with 95% confidence intervals (CI), and are adjusted for age. Results: Median follow-up was 20 years (range 11-28). Median Pt was 86 ng/L (range 0-725). There was a significant association between the highest Pt quartile (yes/no) and quartiles of total SCIN-score (OR 1.67, 95% CI 1.03-2.70), tinnitus (OR 1.77, 95% CI 1.08-2.89) and hearing impairment (OR 1.79, 95% CI 1.10-2.92). In total 24 (8.2%) TCS had a CVD event during follow-up. Increasing cisplatin dose, per 100 mg, was significantly associated with CVD (HR 1.14, 95% CI 1.01- 1.28) and hypogonadism (OR 1.09, 95% CI 1.00-1.19). No association was found between residual Pt versus CVD and hypogonadism. Conclusions: 20 years after chemotherapy, residual serum Pt was significantly associated with NTX. The risk of CVD and hypogonadism increased with higher cisplatin dose, but was not associated with serum Pt.
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