title: Associations between long-term serum platinum and neurotoxicity and ototoxicity, endocrine gonadal function, and cardiovascular disease in testicular cancer survivors.
abstract: To evaluate the associations between long-term serum levels of platinum (se-Pt) and neurotoxicity and ototoxicity (NTX), endocrine gonadal function (endocrine-GF), and cardiovascular disease (CVD) in testicular cancer survivors.
  
  
  
  A total of 292 cisplatin-treated testicular cancer survivors (1980-1994) participated in a national follow-up study (2007-2008). Se-Pt was quantified by inductively coupled plasma mass spectrometry, and categorized in quartiles. Symptoms of NTX were assessed with scale for chemotherapy-induced neurotoxicity (SCIN), with each symptom in 4 categories and total SCIN score categorized in quartiles. Endocrine-GF was categorized according to cutoff values for the 25, 50, and 75 percentiles of luteinizing hormone (LH) and testosterone within each decadal age group established from a control group. CVD was defined as ischemic heart disease, stroke, or artery occlusion. Associations between se-Pt levels and NTX, endocrine-GF, or risk for CVD, were analyzed with ordinal logistic regression and Cox regression, respectively.
  
  
  
  Median follow-up was 19 years (range: 13-28). In ordinal regression analyses, increasing quartiles of se-Pt were significantly associated with increasing quartiles of SCIN (P for trend = 0.05), increased tinnitus (P<0.001), and increased hearing impairment (P = 0.04). The association remained significant for tinnitus when adjusting for cisplatin dose. Increasing LH quartiles was associated with increasing se-Pt quartiles (P = 0.04). No association between se-Pt in quartiles and CVD was established.
  
  
  
  Median 19 years after treatment, increasing quartiles of se-Pt are associated with increasing SCIN score, tinnitus, hearing impairment, and increasing LH levels. However, these associations remained significant only for tinnitus and LH when adjusting for administered cisplatin dose.
authors: Depatement of Clinical Medicine, Arctic University of Tromsø, Tromsø, Norway; Department of Oncology, University Hospital of North Norway, Tromsø, Norway. Electronic address: line.v.hjelle@uit.no.
authors: Line V
authors: LV
authors: Hjelle
authors: Depatement of Clinical Medicine, Arctic University of Tromsø, Tromsø, Norway; Department of Oncology, University Hospital of North Norway, Tromsø, Norway.
authors: Roy M
authors: RM
authors: Bremnes
authors: Department of Clinical Pharmacology, St. Olavs University Hospital, Trondheim, Norway.
authors: Per O M
authors: POM
authors: Gundersen
authors: Department of Oncology, Oslo University Hospital, Oslo, Norway.
authors: Mette
authors: M
authors: Sprauten
authors: Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway.
authors: Marianne
authors: M
authors: Brydøy
authors: The cancer Clinic, St. Olavs University Hospital, Trondheim, Norway.
authors: Torgrim
authors: T
authors: Tandstad
authors: Institute of Community Medicine, Arctic University of Tromsø, Tromsø, Norway.
authors: Tom
authors: T
authors: Wilsgaard
authors: Department of Oncology, Oslo University Hospital, Oslo, Norway; Medical faculty, University of Oslo, Oslo, Norway; Cancer Registry of Norway, Oslo, Norway.
authors: Sophie D
authors: SD
authors: Fosså
authors: Department of Oncology, Oslo University Hospital, Oslo, Norway; Medical faculty, University of Oslo, Oslo, Norway.
authors: Jan
authors: J
authors: Oldenburg
authors: Depatement of Clinical Medicine, Arctic University of Tromsø, Tromsø, Norway; Department of Oncology, University Hospital of North Norway, Tromsø, Norway.
authors: Hege S
authors: HS
authors: Haugnes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage; D000073116:Cancer Survivors; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D003131:Combined Modality Therapy; D015897:Comorbidity; D005047:Etoposide / Q000008:administration & dosage; D005500:Follow-Up Studies; D034381:Hearing Loss / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D007006:Hypogonadism / Q000453:epidemiology / Q000209:etiology; D007986:Luteinizing Hormone / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D009919:Orchiectomy; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000453:epidemiology; D011795:Surveys and Questionnaires; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000601:surgery; D014012:Tinnitus / Q000139:chemically induced* / Q000453:epidemiology; D014747:Vinblastine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D001761:Bleomycin; D014747:Vinblastine; D005047:Etoposide; D007986:Luteinizing Hormone; D016190:Carboplatin; D002945:Cisplatin
keywords: Cisplatin retention; Long-term follow-up; Testicular cancer