Comparison of GWAS results between de novo tinnitus and cancer treatment-related tinnitus suggests distinctive roles for genetic risk factors.

Tinnitus is a common sensorineural complication that can occur de novo or after cancer treatments involving cisplatin or radiotherapy. Considering the heterogeneous etiology and pathophysiology of tinnitus, the extent to which shared genetic risk factors contribute to de novo tinnitus and cancer treatment-induced tinnitus is not clear. Here we report a GWAS for de novo tinnitus using the UK Biobank cohort with nine loci showing significantly associated variants (p < 5 × 10).

Cognitive function in long-term testicular cancer survivors: impact of modifiable factors.

No study has comprehensively examined associated factors (adverse health outcomes, health behaviors, and demographics) affecting cognitive function in long-term testicular cancer survivors (TC survivors). TC survivors given cisplatin-based chemotherapy completed comprehensive, validated surveys, including those that assessed cognition. Medical record abstraction provided cancer and treatment history.

Comprehensive Audiologic Analyses After Cisplatin-Based Chemotherapy.

Importance: Cisplatin is highly ototoxic but widely used. Evidence is lacking regarding cisplatin-related hearing loss (CRHL) in adult-onset cancer survivors with comprehensive audiologic assessments (eg, Words-in-Noise [WIN] tests, full-spectrum audiometry, and additional otologic measures), as well as the progression of CRHL considering comorbidities, modifiable factors associated with risk, and cumulative cisplatin dose.

Objective: To assess CRHL with comprehensive audiologic assessments, including the WIN, evaluate the longitudinal progression of CRHL, and identify factors associated with risk.

Adolescent and Young Adult Germ Cell Tumors: Epidemiology, Genomics, Treatment, and Survivorship.

Innovations in the care of adolescent and young adult (AYA) germ cell tumors (GCTs) are needed for one of the most common AYA cancers for which treatment has not significantly changed for several decades. Testicular GCTs (TGCTs) are the most common cancers in 15- to 39-year-old men, and ovarian GCTs (OvGCTs) are the leading gynecologic malignancies in women younger than 25 years. Excellent outcomes, even in widely metastatic disease using cisplatin-based chemotherapy, can be achieved since Einhorn and Donohue's landmark 1977 study in TGCT.

Cardiovascular Risks in Testicular Cancer: Assessment, Prevention, and Treatment.

Purpose Of Review: Testicular cancer (TC) is the leading cancer in men between 18 and 39 years of age. Current treatment involves tumor resection followed by surveillance and/or one or more lines of cisplatin-based chemotherapy (CBCT) and/or bone marrow transplant (BMT). Ten years after treatment, CBCT has been associated with significant atherosclerotic cardiovascular disease (CVD) including myocardial infarction (MI), stroke, and heightened rates of hypertension, dyslipidemia, diabetes mellitus, and metabolic syndrome (MetS).

Prevalence and risk factors for ototoxicity after cisplatin-based chemotherapy.

Purpose: Ototoxicity is a prominent side effect of cisplatin-based chemotherapy. There are few reports, however, estimating its prevalence in well-defined cohorts and associated risk factors.

Methods: Testicular cancer (TC) survivors given first-line cisplatin-based chemotherapy completed validated questionnaires.

Comprehensive association analysis of speech recognition thresholds after cisplatin-based chemotherapy in survivors of adult-onset cancer.

Purpose: Deficits in speech understanding constitute one of the most severe consequences of hearing loss. Here we investigate the clinical and genetic risk factors for symmetric deterioration of speech recognition thresholds (SRT) among cancer survivors treated with cisplatin.

Methods: SRT was measured using spondaic words and calculating the mean of measurements for both ears with symmetric SRT values.

Associations of Body Fat Distribution and Cardiometabolic Risk of Testicular Cancer Survivors After Cisplatin-Based Chemotherapy.

Background: It is unknown how body fat distribution modulates the cardiometabolic risk of testicular cancer survivors after cisplatin-based chemotherapy.

Methods: For 455 patients enrolled in the Platinum Study at Memorial Sloan Kettering Cancer Center, visceral (VAT) and subcutaneous (SAT) adipose tissue was quantified on prechemotherapy computed tomography. The VAT-to-SAT ratio was calculated as a quantitative measure of central adiposity.

Pharmacogenomics of cisplatin-induced neurotoxicities: Hearing loss, tinnitus, and peripheral sensory neuropathy.

Purpose: Cisplatin is a critical component of first-line chemotherapy for several cancers, but causes peripheral sensory neuropathy, hearing loss, and tinnitus. We aimed to identify comorbidities for cisplatin-induced neurotoxicities among large numbers of similarly treated patients without the confounding effect of cranial radiotherapy.

Methods: Utilizing linear and logistic regression analyses on 1680 well-characterized cisplatin-treated testicular cancer survivors, we analyzed associations of hearing loss, tinnitus, and peripheral neuropathy with nongenetic comorbidities.

Cisplatin, environmental metals, and cardiovascular disease: an urgent need to understand underlying mechanisms.

Significantly increased risks of cardiovascular disease occur in testicular cancer survivors given cisplatin-based chemotherapy. The postulated mechanism of platinum-based chemotherapy's vascular toxicity has been thought secondary to its different early- and late- effects on vascular injury, endothelial dysfunction, and induction of a hypercoagulable state. We highlight for the first time the similarities between platinum-associated vascular adverse events and the vascular toxicity associated with other xenobiotic-metal contaminants.

Clinical and genetic risk factors for radiation-associated ototoxicity: A report from the Childhood Cancer Survivor Study and the St. Jude Lifetime Cohort.

Background: Cranial radiation therapy (CRT) is associated with ototoxicity, which manifests as hearing loss and tinnitus. The authors sought to identify clinical determinants and genetic risk factors for ototoxicity among adult survivors of pediatric cancer treated with CRT.

Methods: Logistic regression evaluated associations of tinnitus (n = 1991) and hearing loss (n = 2198) with nongenetic risk factors and comorbidities among CRT-treated survivors in the Childhood Cancer Survivor Study.

Use of Medications for Treating Anxiety or Depression among Testicular Cancer Survivors: A Multi-Institutional Study.

Background: This study examined sociodemographic factors, cisplatin-related adverse health outcomes (AHO), and cumulative burden of morbidity (CBM) scores associated with medication use for anxiety and/or depression in testicular cancer survivors (TCS).

Methods: A total of 1,802 TCS who completed cisplatin-based chemotherapy ≥12 months previously completed questionnaires regarding sociodemographic features and cisplatin-related AHOs [hearing impairment, tinnitus, peripheral sensory neuropathy (PSN), and kidney disease]. A CBM score encompassed the number and severity of cisplatin-related AHOs.

Young Adult Cancer Survivorship: Recommendations for Patient Follow-up, Exercise Therapy, and Research.

Survivors of adolescent and young adult cancers (AYAs) often live 50 to 60 years beyond their diagnosis. This rapidly growing cohort is at increased risk for cancer- and treatment-related 'late effects' that persist for decades into survivorship. Recognition of similar issues in pediatric cancer survivors has prompted the development of evidence-based guidelines for late effects screening and care.

Clinical and Genome-Wide Analysis of Multiple Severe Cisplatin-Induced Neurotoxicities in Adult-Onset Cancer Survivors.

Purpose: Cisplatin is a first-line chemotherapeutic for many cancers, but causes neurotoxicity including hearing loss, tinnitus, and peripheral sensory neuropathy. However, no study has comprehensively characterized risk factors for developing multiple (>1) severe neurotoxicities.

Experimental Design: The relationship between multiple severe neurotoxicities and age, cumulative cisplatin dose, medical history, and lifestyle/behavioral factors was evaluated in 300 cisplatin-treated testicular cancer survivors using logistic regression.

Solid and Hematologic Neoplasms After Testicular Cancer: A US Population-Based Study of 24 900 Survivors.

Background: No large US population-based study focusing on recent decades, to our knowledge, has comprehensively examined risks of second malignant solid and hematological neoplasms (solid-SMN and heme-SMN) after testicular cancer (TC), taking into account initial therapy and histological type.

Methods: Standardized incidence ratios (SIR) vs the general population and 95% confidence intervals (CI) for solid-SMN and heme-SMN were calculated for 24 900 TC survivors (TCS) reported to the National Cancer Institute's Surveillance, Epidemiology, and End Results registries (1973-2014). All statistical tests were two-sided.

Adverse Health Outcomes Among US Testicular Cancer Survivors After Cisplatin-Based Chemotherapy vs Surgical Management.

We evaluated for the first time, to our knowledge, adverse health outcomes (AHOs) among US testicular cancer survivors (TCS) given chemotherapy (n = 381) vs surgery-only patients (n = 98) managed at a single institution, accounting for non-treatment-related risk factors to delineate chemotherapy's impact. Chemotherapy consisted largely of bleomycin-etoposide-cisplatin (BEP) administered in three or four cycles (BEPx3, n = 235; BEPx4, n = 82). Incidence of at least 3 AHOs was lowest in surgery-only TCS and increased with BEPx3, BEPx4, and other cisplatin-based regimens (12.

Testicular Cancer Survivorship.

Testicular cancer (TC) is the most common cancer among men aged 18 to 39 years. It is highly curable, with a 10-year relative survival approaching 95% due to effective cisplatin-based chemotherapy. Given the increasing incidence of TC and improved survival, TC survivors (TCS) now account for approximately 4% of all US male cancer survivors.

Clinical and Genome-Wide Analysis of Serum Platinum Levels after Cisplatin-Based Chemotherapy.

Purpose: Serum platinum is measurable for years after completion of cisplatin-based chemotherapy (CBC). We report the largest investigation of serum platinum levels to date of 1,010 testicular cancer survivors (TCS) assessed 1-35 years after CBC and evaluate genetic contributions to these levels.

Experimental Design: Eligible TCS given 300 or 400 (±15) mg/m cisplatin underwent extensive audiometric testing, clinical examination, completed questionnaires, and had crude serum platinum levels measured.