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

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 12004-12004
Author(s):  
Xindi Zhang ◽  
Matthew R. Trendowski ◽  
Emma Wilkinson ◽  
Darren R. Feldman ◽  
Robert James Hamilton ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hearing Loss ◽  
Testicular Cancer ◽  
Cancer Survivors ◽  
Sensory Neuropathy ◽  
Central Nervous System Tumor ◽  
Peripheral Sensory Neuropathy ◽  
Current Population ◽  
Testicular Cancer Survivors ◽  
Peripheral Sensory

12004 Background: Cisplatin is an essential component of first-line chemotherapy for many cancers, but causes neurotoxicity, including hearing loss (CisHL), tinnitus (CisTinn), and peripheral sensory neuropathy (CisPNeuro). However, few opportunities exist to identify risk factors and comorbidities for cisplatin-induced neurotoxicities among large numbers of homogenously treated patients without the confounding effect of cranial radiotherapy. Methods: Within a well-characterized clinical cohort of 1,680 cisplatin-treated testicular cancer survivors, linear and logistic regression analysis were utilized to analyze associations of CisHL (n = 1,258), CisTinn (n = 1,217), and CisPNeuro (n = 1,653) with non-genetic risk factors. Genome-wide association studies and gene-based analysis were performed on each phenotype. Results: Cisplatin-induced neurotoxicities (CisHL CisTinn, CisPNeuro), adjusting for age and cisplatin dose, were interdependent. Survivors with these neurotoxicities experienced more hypertension (CisTinn: OR = 2.62, p < 0.0001; CisHL: β = 0.25, p = 8.5 x10-4; CisPNeuro: OR = 1.86, p < 0.0001) and were more likely to report their health as poor (CisTinn: OR = 0.54, p < 0.0001; CisHL: β = -0.11, p < 0.0001; CisPNeuro: OR = 0.61, p < 0.0001). Persistent vertigo was significantly associated with both CisTinn (OR = 7.18, p < 0.0001) and CisPNeuro (OR = 4.29, p < 0.0001). In addition, CisTinn was significantly associated with hypercholesterolemia (OR = 1.78, p = 0.01). Importantly, gene-based association analyses identified significant associations between CisTinn and WNT8A (n = 1,037, p = 2.52x10-6) , encoding a signaling protein important in germ cell tumors; and marginal significance between CisHL and TXNRD1 (n = 1,071, p = 4.21x10-6) , thioredoxin reductase-1, which plays a key role in redox regulation. In silico analysis showed high expression levels of TXNRD1 were significantly correlated with cellular resistance to cisplatin in central nervous system tumor cells (Spearman Rho = 0.35, p = 0.04; R2= 0.14, p = 0.03), indicating TXNRD1 is protective for cisplatin-induced cytotoxicity. Previously, rs62283056 in WFS1 found to be significantly associated with CisHL (n = 511; subset of current population), was marginally significant in an independent replication cohort (p = 0.06; n = 606; subset of current population). Conclusions: Cisplatin-induced neurotoxicities are significantly associated with multiple clinical characteristics, including hypertension and self-reported poor health. WNT8A and TXNRD1 are notable risk factors for CisTinn and CisHL, respectively . Future studies should further investigate these genes and their potential impact on chemotherapy strategies. This study, based on the largest number of testicular cancer survivors investigated to date, highlights the clinical importance of these iatrogenic toxicities and their associated risk factors.

scholarly journals Chronic fatigue in 812 testicular cancer survivors during long-term follow-up: increasing prevalence and risk factors

2015 ◽  
Vol 26 (10) ◽  
pp. 2133-2140 ◽  
Author(s):  
M. Sprauten ◽  
H.S. Haugnes ◽  
M. Brydøy ◽  
C. Kiserud ◽  
T. Tandstad ◽  
...  
Keyword(s):  
Risk Factors ◽  
Testicular Cancer ◽  
Cancer Survivors ◽  
Chronic Fatigue ◽  
Long Term Follow Up ◽  
Testicular Cancer Survivors

Comprehensive characterization of cisplatin-related hearing loss in U.S. and Canadian Testicular Cancer Survivors (TCS).

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 9570-9570 ◽  
Author(s):  
Heather E. Wheeler ◽  
Lois B. Travis ◽  
Amy Budnick ◽  
Darren Richard Feldman ◽  
Lawrence H. Einhorn ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Testicular Cancer ◽  
Cancer Survivors ◽  
Testicular Cancer Survivors ◽  
Comprehensive Characterization

Prevalence and Risk Factors for HIV-associated Peripheral Sensory Neuropathy in HIV-infected Adults in Daegu, Korea

2009 ◽  
Vol 45 (3) ◽  
pp. 161
Author(s):  
Hee-Young Hwang ◽  
Hyun-Ha Chang ◽  
Shin-Woo Kim ◽  
Seong Yeol Ryu ◽  
Hye-In Kim ◽  
...  
Keyword(s):  
Risk Factors ◽  
Sensory Neuropathy ◽  
Peripheral Sensory Neuropathy ◽  
Peripheral Sensory

150 The Auditory and Vestibular Manifestations of Charcot Marie-Tooth Disease

1995 ◽  
Vol 113 (2) ◽  
pp. P203-P203
Author(s):  
Daniel R. Fear ◽  
C. Bruce MacDonald ◽  
L. Clarke Cox
Keyword(s):  
Hearing Loss ◽  
Muscle Atrophy ◽  
Sensory Neuropathy ◽  
Peripheral Sensory Neuropathy ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Postural Changes ◽  
Brainstem Response ◽  
Peripheral Sensory ◽  
Tooth Disease

Objective: To present the auditory-vestibular manifestations of Charcot Marie-Tooth Disease (CMT). Case Report: A 53-year-old woman complained of progressive imbalance over 1 year. Imbalance was described as the sense that she was about to fall to one side, was exacerbated by rapid head acceleration, and had no relation to postural changes. Symptoms were continuous, and she fell multiple times. She used a cane for 1 year, but for the last month required a walker. Bilateral tinnitus and hearing loss developed over the last year. CMT had been diagnosed about 20 years earlier, with progressive distal limb weakness and wasting and peripheral sensory neuropathy. The neurotologic examination was normal except for the following: There was mild tremor in the left hand. Unsupported stance was unsteady, and she fell with eye closure. Vibrotactile sensation was reduced at the hands and ankles. Audiometry demonstrated a mild, somewhat asymmetric sensorineural hearing loss (SNHL). Auditory brainstem response showed poor waveform morphology bilaterally; however, the latencies for waves III and IV were within the normal range. Electronystagmography with rotary chair data showed hypofunction and reduced vestibulo-ocular gain. Ophthalmologic evaluation was refused. Discussion: CMT is an autosomal-dominant disorder manifested by progressive peripheral neuropathy, resulting in distal muscle atrophy and a peripheral sensory neuropathy. SNHL has been described in CMT. The Rosenberg-Chutorian Syndrome involves CMT with SNHL and optic atrophy. Other cranial neuropathies have also been described in CMT. Results: We describe a patient with CMT patient who had hearing loss and imbalance. The combination of vestibulopathy, sensory (proprioceptive) neuropathy, and muscle atrophy produced a devastating balance disorder. The literature on otologic manifestations of CMT is reviewed.

Risk Factors for Diabetic Peripheral Sensory Neuropathy: Results of the Seattle Prospective Diabetic Foot Study

Diabetes Care ◽  
1997 ◽  
Vol 20 (7) ◽  
pp. 1162-1167 ◽  
Author(s):  
A. I. Adler ◽  
E. J. Boyko ◽  
J. H. Ahroni ◽  
V. Stensel ◽  
R. C. Forsberg ◽  
...  
Keyword(s):  
Risk Factors ◽  
Diabetic Foot ◽  
Sensory Neuropathy ◽  
Peripheral Sensory Neuropathy ◽  
Peripheral Sensory

Factors associated with use of medications for anxiety and depression in testicular cancer survivors after cisplatin-based chemotherapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5025-5025
Author(s):  
Shirin Ardeshirrouhanifard ◽  
Paul C Dinh ◽  
Patrick O. Monahan ◽  
Sophie Fosså ◽  
Robert A Huddart ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Testicular Cancer ◽  
Cancer Survivors ◽  
Vigorous Physical Activity ◽  
Medication Use ◽  
Sensory Neuropathy ◽  
Anxiety And Depression ◽  
Care Plans ◽  
Increased Risk ◽  
Testicular Cancer Survivors

5025 Background: Cancer survivors are at increased risk of anxiety and depression that can affect health-related quality of life. There is no study to date that has examined the characteristics of testicular cancer survivors (TCS) taking medications for anxiety or depression since pharmacological interventions are typically reserved for more severe cases of these disorders. In this study, we aimed to examine sociodemographic factors, cisplatin-related adverse health outcomes (AHOs), and cumulative burden of morbidity (CBMPt) scores associated with medication use for anxiety and/or depression in TCS. Methods: A total of 1,802 TCS who completed CBCT ≥12 months previously completed validated questionnaires regarding sociodemographic features and cisplatin-related AHOs (hearing impairment, tinnitus, peripheral sensory neuropathy (PSN), kidney disease). Patients were recognized as users of medications for anxiety and/or depression if they used pharmacological classes of these medications and also indicated that the reason for use was for anxiety or depression. Individual AHOs were graded 0-to-4 based on severity according to NCI Common Terminology Criteria for Adverse Events version 4.03. A CBMPt score encompassed the number and severity of cisplatin-related AHOs. Multivariable logistic regression models assessed the relationship of individual AHOs and CBMPt with medication use for anxiety and/or depression. Results: A total of 151 TCS (8.4%) used medications for anxiety and/or depression. Any grade of HL, tinnitus, PSN, and kidney disease were reported by 37.9%, 39.5%, 55.2%, and 2.4% of 1,802 participants, respectively. No cisplatin-related AHO were reported by 511 (28.4%) participants, whereas 622 (34.5%), 334 (18.5%), 287 (15.9%), and 48 (2.7%), respectively, had very low, low, medium, and high CBMPt scores. Higher CBMPt scores were significantly associated with greater medication use for anxiety and/or depression (CBMPt scores of low (OR = 2.96, 95%CI, 1.67-5.24), medium (OR = 3.47, 95%CI, 1.95-6.18), and high (OR = 3.18, 95%CI, 1.22-8.3). A multivariable model including individual AHOs indicated that tinnitus ( P= 0.0009), PSN ( P= 0.02), and having health insurance (OR = 2.15, 95%CI, 1.01-4.56) were associated with significantly greater use of these medications; whereas being employed (OR = 0.39, 95%CI, 0.23-0.66) and vigorous physical activity (OR = 0.63, 95%CI,0.44-0.89) were associated with significantly diminished use. Conclusions: We found that TCS with higher CBMPt scores had a higher probability of using medications for anxiety and/or depression and conversely, those who were employed and physically active tended to have reduced use. These findings deserve further investigation in longitudinal studies. In the interim, healthcare providers should be aware of these associations in formulating survivorship care plans.

scholarly journals Hearing loss before and after cisplatin-based chemotherapy in testicular cancer survivors: a longitudinal study

2018 ◽  
Vol 57 (8) ◽  
pp. 1075-1083 ◽  
Author(s):  
Hege S. Haugnes ◽  
Niels Christian Stenklev ◽  
Marianne Brydøy ◽  
Olav Dahl ◽  
Tom Wilsgaard ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Longitudinal Study ◽  
Testicular Cancer ◽  
Cancer Survivors ◽  
Before And After ◽  
Testicular Cancer Survivors

scholarly journals Relationship of Cisplatin-Related Adverse Health Outcomes With Disability and Unemployment Among Testicular Cancer Survivors

2020 ◽  
Vol 4 (4) ◽  
Author(s):  
Sarah L Kerns ◽  
Chunkit Fung ◽  
Sophie D Fossa ◽  
Paul C Dinh ◽  
Patrick Monahan ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Testicular Cancer ◽  
Health Outcomes ◽  
Cancer Survivors ◽  
Disability Leave ◽  
Adverse Health ◽  
Adverse Health Outcomes ◽  
Grade 3 ◽  
Testicular Cancer Survivors ◽  
Relationship Of

Abstract Background Few data exist on the relationship of cisplatin-related adverse health outcomes (AHOs) with disability, unemployment, and self-reported health (SRH) among testicular cancer survivors (TCS). Methods A total of 1815 TCS at least 1 year postchemotherapy underwent clinical examination and completed questionnaires. Treatment data were abstracted from medical records. A cumulative burden of morbidity score (CBMPt) encompassed the number and severity of platinum-related AHOs (peripheral sensory neuropathy [PSN], hearing loss, tinnitus, renal disease). Multivariable regression assessed the association of AHOs and CBMPt with employment status and SRH, adjusting for sociodemographic and clinical characteristics. Unemployment was compared with a male normative population of similar age, race, and ethnicity. Results Almost 1 in 10 TCS was out of work (2.4%, disability leave; 6.8%, unemployed) at a median age of 37 years (median follow-up = 4 years). PSN (odds ratio [OR] = 2.89, 95% confidence interval [CI] = 1.01 to 8.26, grade 3 vs 0, P = .048), renal dysfunction defined by estimated glomerular filtration rate (OR = 12.1, 95% CI = 2.06 to 70.8, grade 2 vs 0, P = .01), pain (OR = 10.6, 95% CI = 4.40 to 25.40, grade 2 or 3 vs 0, P &lt; .001), and CBMPt (OR = 1.46, 95% CI = 1.03 to 2.08, P = .03) were associated with disability leave; pain strongly correlated with PSN (r2 = 0.40, P &lt; .001). Statistically significantly higher percentages of TCS were unemployed vs population norms (age-adjusted OR = 2.67, 95% CI = 2.49 to 3.02, P &lt; .001). PSN (OR = 2.44, 95% CI = 1.28 to 4.62, grade 3 vs 0, P = .006), patient-reported hearing loss (OR = 1.82, 95% CI = 1.04 to 3.17, grade 2 or 3 vs 0, P = .04), and pain (OR = 3.75, 95% CI = 2.06 to 6.81, grade 2 or 3 vs 0, P &lt; .001) were associated with unemployment. Increasing severity of most cisplatin-related AHOs and pain were associated with statistically significantly worse SRH. Conclusions Our findings have important implications regarding treatment-associated productivity losses and socioeconomic costs in this young population. Survivorship care strategies should include inquiries about disability and unemployment status, with efforts made to assist affected TCS in returning to the workforce.

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

2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Vaibhav Agrawal ◽  
Paul C Dinh ◽  
Chunkit Fung ◽  
Patrick O Monahan ◽  
Sandra K Althouse ◽  
...  
Keyword(s):  
Risk Factors ◽  
Testicular Cancer ◽  
Health Outcomes ◽  
Cancer Survivors ◽  
Hearing Impairment ◽  
Noise Exposure ◽  
Modifiable Risk Factors ◽  
Raynaud Phenomenon ◽  
Adverse Health Outcomes ◽  
Testicular Cancer Survivors

Abstract 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 (12.2%, 40.8%, 52.5%, 54.8%; P &lt; .0001). Multivariable modeling assessed associations of risk factors and treatment with hearing impairment, tinnitus, peripheral neuropathy, and Raynaud phenomenon. Risk for each AHO statistically increased with both increasing chemotherapy burden (P &lt; .0001) and selected modifiable risk factors (P &lt; .05): hypertension (odds ratio [OR] = 2.40) and noise exposure (OR ≥ 2.3) for hearing impairment; noise exposure for tinnitus (OR ≥ 1.69); peripheral vascular disease for neuropathy (OR = 8.72); and current smoking for Raynaud phenomenon (OR = 2.41). Clinicians should manage modifiable risk factors for AHOs among TCS.

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