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1.
JAMA Oncol ; 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38842797

RESUMEN

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. Design, Setting, and Participants: The Platinum Study is a longitudinal study of cisplatin-treated testicular cancer survivors (TCS) enrolled from 2012 to 2018 with follow-up ongoing. Longitudinal comprehensive audiologic assessments at Indiana University and Memorial Sloan Kettering Cancer Center included 100 participants without audiometrically defined profound hearing loss (HL) at baseline and at least 3.5 years from their first audiologic assessment. Data were analyzed from December 2013 to December 2022. Exposures: Factors associated with risk included cumulative cisplatin dose, hypertension, hypercholesterolemia, diabetes, tobacco use, physical inactivity, body mass index, family history of HL, cognitive dysfunction, psychosocial symptoms, and tinnitus. Main Outcomes and Measures: Main outcomes were audiometrically measured HL defined as combined-ears high-frequency pure-tone average (4-12 kHz) and speech-recognition in noise performance measured with WIN. Multivariable analyses evaluated factors associated with risk for WIN scores and progression of audiometrically defined HL. Results: Median (range) age of 100 participants at evaluation was 48 (25-67) years; median (range) time since chemotherapy: 14 (4-31) years. At follow-up, 78 (78%) TCS had audiometrically defined HL; those self-reporting HL had 2-fold worse hearing than TCS without self-reported HL (48 vs 24 dB HL; P < .001). A total of 54 (54%) patients with self-reported HL showed clinically significant functional impairment on WIN testing. Poorer WIN performance was associated with hypercholesterolemia (ß = 0.88; 95% CI, 0.08 to 1.69; P = .03), lower-education (F1 = 5.95; P = .004), and severity of audiometrically defined HL (ß̂ = 0.07; 95% CI, 0.06 to 0.09; P < .001). CRHL progression was associated with hypercholesterolemia (ß̂ = -4.38; 95% CI, -7.42 to -1.34; P = .01) and increasing age (ß̂ = 0.33; 95% CI, 0.15 to 0.50; P < .001). Importantly, relative to age-matched male normative data, audiometrically defined CRHL progression significantly interacted with cumulative cisplatin dose (F1 = 5.98; P = .02); patients given 300 mg/m2 or less experienced significantly less progression, whereas greater temporal progression followed doses greater than 300 mg/m2. Conclusions and Relevance: Follow-up of cisplatin-treated cancer survivors should include strict hypercholesterolemia control and regular audiological assessments. Risk stratification through validated instruments should include querying hearing concerns. CRHL progression relative to age-matched norms is likely associated with cumulative cisplatin dose; investigation over longer follow-up is warranted.

2.
Cancer ; 130(14): 2538-2551, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38520382

RESUMEN

BACKGROUND: Androgen deprivation therapy (ADT) inhibits prostate cancer growth. However, ADT causes loss of bone mineral density (BMD) and an increase in fracture risk; effective interventions for ADT-induced bone loss are limited. METHODS: A phase 2 randomized controlled trial investigated the feasibility, safety, and preliminary efficacy of high-dose weekly vitamin D (HDVD, 50,000 IU/week) versus placebo for 24 weeks in patients with prostate cancer receiving ADT, with all subjects receiving 600 IU/day vitamin D and 1000 mg/day calcium. Participants were ≥60 years (mean years, 67.7), had a serum 25-hydroxyvitamin D level <32 ng/mL, and initiated ADT within the previous 6 months. At baseline and after intervention, dual-energy x-ray absorptiometry was used to assess BMD, and levels of bone cell, bone formation, and resorption were measured. RESULTS: The HDVD group (N = 29) lost 1.5% BMD at the total hip vs. 4.1% for the low-dose group (N = 30; p = .03) and 1.7% BMD at the femoral neck vs. 4.4% in the low-dose group (p = .06). Stratified analyses showed that, for those with baseline 25-hydroxyvitamin D level <27 ng/mL, the HDVD group lost 2.3% BMD at the total hip vs 7.1% for the low-dose group (p < .01). Those in the HDVD arm showed significant changes in parathyroid hormone (p < .01), osteoprotegerin (p < 0.01), N-terminal telopeptide of type 1 collagen (p < 0.01) and C-terminal telopeptide of type 1 collagen (p < 0.01). No difference in adverse events or toxicity was noted between the groups. CONCLUSIONS: HDVD supplementation significantly reduced hip and femoral neck BMD loss, especially for patients with low baseline serum 25-hydroxyvitamin D levels, although demonstrating safety and feasibility in prostate cancer patients on ADT.


Asunto(s)
Antagonistas de Andrógenos , Densidad Ósea , Neoplasias de la Próstata , Vitamina D , Humanos , Masculino , Neoplasias de la Próstata/tratamiento farmacológico , Vitamina D/sangre , Vitamina D/análogos & derivados , Vitamina D/administración & dosificación , Anciano , Antagonistas de Andrógenos/efectos adversos , Antagonistas de Andrógenos/administración & dosificación , Antagonistas de Andrógenos/uso terapéutico , Densidad Ósea/efectos de los fármacos , Persona de Mediana Edad , Osteoporosis/inducido químicamente , Osteoporosis/prevención & control
3.
Support Care Cancer ; 32(3): 165, 2024 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-38368466

RESUMEN

PURPOSE: The American Society of Clinical Oncology Cancer Survivorship Committee established a task force to determine which survivorship care services were being denied by public and private payers for coverage and reimbursement. METHODS: A quantitative survey instrument was developed to determine the clinical practice-reported rates of coverage denials for evidence-based cancer survivorship care services. Additionally, qualitative interviews were conducted to understand whether coverage denials were based on payer policies, cost-sharing, or prior authorization. RESULTS: Of 122 respondents from 50 states, respondents reported that coverage denials were common ("always," "most of the time," or "some of the time") for maintenance therapies, screening for new primary cancers or cancer recurrence. Respondents reported that denials in coverage for maintenance therapies were highest for immunotherapy (41.74%) and maintenance chemotherapy (40.17%). Coverage denials for new primary cancer screenings were highest for Hodgkin lymphoma survivors needing a PET/CT scan (49.04%) and breast cancer survivors at a high risk of recurrence who needed an MRI (63.46%), respectively. More than half of survey respondents reported denials for symptom management and supportive care services. Fertility services, dental services when indicated, and mental health services were denied "always" or "most of the time" 23.1%, 22.5%, and 12.8%, respectively. Respondents reported they often had a process in place to automatically appeal denials for evidence-based services. The denial process, however, resulted in greater stress for the patient and provider. CONCLUSION: Our study demonstrates that additional advocacy with payers is needed to ensure that reimbursement policies are consistent with evidence-based survivorship care services.


Asunto(s)
Supervivientes de Cáncer , Supervivencia , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Recurrencia Local de Neoplasia , Mama , Cobertura del Seguro
4.
J Natl Cancer Inst ; 116(3): 455-467, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-37966940

RESUMEN

BACKGROUND: No study has quantified the impact of pain and other adverse health outcomes on global physical and mental health in long-term US testicular cancer survivors or evaluated patient-reported functional impairment due to pain. METHODS: Testicular cancer survivors given cisplatin-based chemotherapy completed validated surveys, including Patient-Reported Outcomes Measurement Information System v1.2 global physical and mental health, Patient-Reported Outcomes Measurement Information System pain questionnaires, and others. Multivariable linear regression examined relationships between 25 adverse health outcomes with global physical and mental health and pain-interference scores. Adverse health outcomes with a ß^ of more than 2 are clinically important and reported below. RESULTS: Among 358 testicular cancer survivors (median age = 46 years, interquartile range [IQR] = 38-53 years; median time since chemotherapy = 10.7 years, IQR = 7.2-16.0 years), median adverse health outcomes number was 5 (IQR = 3-7). A total of 12% testicular cancer survivors had 10 or more adverse health outcomes, and 19% reported chemotherapy-induced neuropathic pain. Increasing adverse health outcome numbers were associated with decreases in physical and mental health (P < .0001 each). In multivariable analyses, chemotherapy-induced neuropathic pain (ß^ = -3.72; P = .001), diabetes (ß^ = -4.41; P = .037), obesity (ß^ = -2.01; P = .036), and fatigue (ß^ = -8.58; P < .0001) were associated with worse global mental health, while being married or living as married benefited global mental health (ß^ = 3.63; P = .0006). Risk factors for pain-related functional impairment included lower extremity location (ß^ = 2.15; P = .04) and concomitant peripheral artery disease (ß^ = 4.68; P < .001). Global physical health score reductions were associated with diabetes (ß^ = -3.81; P = .012), balance or equilibrium problems (ß^ = -3.82; P = .003), cognitive dysfunction (ß^ = -4.43; P < .0001), obesity (ß^ = -3.09; P < .0001), peripheral neuropathy score (ß^ = -2.12; P < .0001), and depression (ß^ = -3.17; P < .0001). CONCLUSIONS: Testicular cancer survivors suffer adverse health outcomes that negatively impact long-term global mental health, global physical health, and pain-related functional status. Clinically important factors associated with worse physical and mental health identify testicular cancer survivors requiring closer monitoring, counseling, and interventions. Chemotherapy-induced neuropathic pain must be addressed, given its detrimental impact on patient-reported functional status and mental health 10 or more years after treatment.


Asunto(s)
Antineoplásicos , Diabetes Mellitus , Neoplasias de Células Germinales y Embrionarias , Neuralgia , Neoplasias Testiculares , Masculino , Humanos , Adulto , Persona de Mediana Edad , Neoplasias Testiculares/complicaciones , Neoplasias Testiculares/tratamiento farmacológico , Sobrevivientes , Obesidad , Neuralgia/tratamiento farmacológico , Diabetes Mellitus/epidemiología , Diabetes Mellitus/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Evaluación de Resultado en la Atención de Salud , Medición de Resultados Informados por el Paciente , Calidad de Vida
5.
J Clin Oncol ; 42(6): 696-706, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-37820296

RESUMEN

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. However, as the severity of accompanying late effects (ototoxicity, neurotoxicity, cardiovascular disease, second malignant neoplasms, nephrotoxicity, and others) has emerged, efforts to deintensity treatment and find alternatives to cisplatin have taken on new urgency. Current innovations include the collaborative design of clinical trials that accrue GCTs across all ages and both sexes, including adolescents (previously on pediatric trials), and OvGCT (previously on gynecologic-only trials). Joint trials accrue larger sample sizes at a faster rate and therefore evaluate new approaches more rapidly. These joint trials also allow for biospecimen collection to further probe GCT etiology and underlying mechanisms of tumor growth, thus providing new therapeutic options. This AYA approach has been fostered by The Malignant Germ Cell International Consortium, which includes over 115 GCT disease experts from pediatric, gynecologic, and genitourinary oncologies in 16 countries. Trials in development incorporate, to our knowledge, for the first time, molecular risk stratification and precision oncology approaches on the basis of specific GCT biology. This collaborative AYA approach pioneering successfully in GCT could serve as a model for impactful research for other AYA cancer types.


Asunto(s)
Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Masculino , Humanos , Femenino , Adolescente , Adulto Joven , Niño , Adulto , Cisplatino , Supervivencia , Medicina de Precisión , Neoplasias de Células Germinales y Embrionarias/epidemiología , Neoplasias de Células Germinales y Embrionarias/genética , Neoplasias de Células Germinales y Embrionarias/terapia , Neoplasias Testiculares/epidemiología , Neoplasias Testiculares/genética , Neoplasias Testiculares/terapia , Genómica
6.
JCO Oncol Pract ; 19(11): 959-966, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37793079

RESUMEN

In 2017, ASCO issued the position statement, Strategies for Reducing Cancer Health Disparities Among Sexual and Gender Minority Populations, outlining five areas of recommendations to address the needs of both sexual and gender minority (SGM, eg, LGBTQ+) populations affected by cancer and members of the oncology workforce who identify as SGM: (1) patient education and support; (2) workforce development and diversity; (3) quality improvement strategies; (4) policy solutions; and (5) research strategies. In 2019, ASCO convened the SGM Task Force to help actualize the recommendations of the 2017 position statement. The percentage of the US population who publicly identify as SGM has increased dramatically over the past few years. Although increased national interest in SGM health equity has accompanied a general interest in research, policy change, and education around diversity, equity, and inclusion, resulting from public concern over discrimination in health care against Black, Indigenous, and People of Color, this has been accompanied by a surge in discriminatory legislation directly impacting the SGM community. Although much progress has been made in advancing SGM cancer health equity since 2017, more progress is needed to reduce disparities and advance equity. The five focus areas outlined in the 2017 ASCO position statement remain relevant, as we must continue to promote and advance equity in quality improvement, workforce development, patient care, research, and SGM-affirming policies. This article reports on the progress toward reducing SGM cancer disparities and achieving equity across these five areas and identifies future directions for the work that still remains.


Asunto(s)
Equidad en Salud , Neoplasias , Minorías Sexuales y de Género , Humanos , Neoplasias/epidemiología , Neoplasias/terapia , Oncología Médica , Atención a la Salud
7.
Curr Oncol Rep ; 25(5): 445-454, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36867377

RESUMEN

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). Additionally, low testosterone levels and hypogonadism contribute to MetS and may further drive CVD. RECENT FINDINGS: CVD in TCS has been associated with worse physical functioning accompanied by role limitations, decreased energy, and decreased overall health. Exercise may play a role in ameliorating these effects. Systematic CVD screening practices are needed at TC diagnosis and in survivorship. We encourage a multidisciplinary partnership between primary care physicians, cardiologists, cardio-oncologists, medical oncologists, and survivorship providers to address these needs.


Asunto(s)
Enfermedades Cardiovasculares , Neoplasias Testiculares , Masculino , Humanos , Neoplasias Testiculares/complicaciones , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/prevención & control , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Factores de Riesgo , Factores de Riesgo de Enfermedad Cardiaca
8.
Environ Mol Mutagen ; 64(3): 167-175, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36841969

RESUMEN

Hydroxyurea is approved for treating children and adults with sickle cell anemia (SCA). Despite its proven efficacy, concerns remain about its mutagenic and carcinogenic potential that hamper its widespread use. Cell culture- and animal-based investigations indicate that hydroxyurea's genotoxic effects are due to indirect clastogenicity in select cell types when high dose and time thresholds are exceeded (reviewed by Ware & Dertinger, 2021). The current study extends these preclinical observations to pediatric patients receiving hydroxyurea for treatment of SCA. First, proof-of-principle experiments with testicular cancer patients exposed to a cisplatin-based regimen validated the ability of flow cytometric blood-based micronucleated reticulocyte (MN-RET) and PIG-A mutant reticulocyte (MUT RET) assays to detect clastogenicity and gene mutations, respectively. Second, these biomarkers were measured in a cross-sectional study with 26 SCA patients receiving hydroxyurea and 13 SCA patients without exposure. Finally, a prospective study was conducted with 10 SCA patients using pretreatment blood samples and after 6 or 12 months of therapy. Cancer patients exposed to cisplatin exhibited increased MN-RET within days of exposure, while the MUT RET endpoint required more time to reach maximal levels. In SCA patients, hydroxyurea induced MN-RET in both the cross-sectional and prospective studies. However, no evidence of PIG-A gene mutation was found in hydroxyurea-treated children, despite the fact that the two assays use the same rapidly-dividing, highly-exposed cell type. Collectively, these results reinforce the complementary nature of MN-RET and MUT RET biomarkers, and indicate that hydroxyurea can be clastogenic but was not mutagenic in young patients with SCA.


Asunto(s)
Anemia de Células Falciformes , Neoplasias Testiculares , Humanos , Masculino , Animales , Hidroxiurea/efectos adversos , Estudios Prospectivos , Estudios Transversales , Neoplasias Testiculares/inducido químicamente , Neoplasias Testiculares/tratamiento farmacológico , Cisplatino/efectos adversos , Anemia de Células Falciformes/tratamiento farmacológico , Anemia de Células Falciformes/genética , Mutagénesis , Mutágenos/uso terapéutico
9.
J Natl Compr Canc Netw ; 21(2): 153-162.e2, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36791754

RESUMEN

BACKGROUND: Cancer-related fatigue (CRF) negatively affects survivors' walking, engagement in physical activity (PA), and quality of life (QoL). Yoga is an effective therapy for treating CRF; however, evidence from large clinical trials regarding how reducing CRF through yoga influences CRF's interference with survivors' walking, engagement in PA, and QoL is not available. We examined the effects of yoga and the mediational influence of CRF on CRF's interference with walking, PA, and QoL among cancer survivors in a multicenter phase III randomized controlled trial. PATIENTS AND METHODS: Cancer survivors (n=410) with insomnia 2 to 24 months posttreatment were randomized to a 4-week yoga intervention-Yoga for Cancer Survivors (YOCAS)-or standard care. A symptom inventory was used to assess how much CRF interfered with survivors' walking, PA, and QoL. The Multidimensional Fatigue Symptom Inventory-Short Form was used to assess CRF. Two-tailed t tests and analyses of covariance were used to examine within-group and between-group differences. Path analysis was used to evaluate mediational relationships between CRF and changes in CRF's interference with walking, PA, and QoL among survivors. RESULTS: Compared with standard care controls, YOCAS participants reported significant improvements in CRF's interference with walking, PA, and QoL at postintervention (all effect size = -0.33; all P≤.05). Improvements in CRF resulting from yoga accounted for significant proportions of the improvements in walking (44%), PA (53%), and QoL (45%; all P≤.05). CONCLUSIONS: A significant proportion (44%-53%) of the YOCAS effect on CRF's interference with walking, PA, and QoL was due to improvements in CRF among cancer survivors. Yoga should be introduced and included as a treatment option for survivors experiencing fatigue. By reducing fatigue, survivors further improve their walking, engagement in PA, and QoL.


Asunto(s)
Supervivientes de Cáncer , Neoplasias , Yoga , Humanos , Calidad de Vida , Ejercicio Físico , Caminata , Neoplasias/complicaciones , Fatiga/etiología , Fatiga/terapia
10.
J Cancer Surviv ; 17(1): 27-39, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36637632

RESUMEN

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. Descriptive statistics evaluated the prevalence of ototoxicity, defined as self-reported hearing loss and/or tinnitus. We compared patients with and without tinnitus or hearing loss using Chi-square test, two-sided Fisher's exact test, or two-sided Wilcoxon rank sum test. To evaluate ototoxicity risk factors, a backward selection logistic regression procedure was performed. RESULTS: Of 145 TC survivors, 74% reported ototoxicity: 68% tinnitus; 59% hearing loss; and 52% reported both. TC survivors with tinnitus were more likely to indicate hypercholesterolemia (P = 0.008), and difficulty hearing (P < .001). Tinnitus was also significantly related to age at survey completion (OR = 1.79; P = 0.003) and cumulative cisplatin dose (OR = 5.17; P < 0.001). TC survivors with hearing loss were more likely to report diabetes (P = 0.042), hypertension (P = 0.007), hypercholesterolemia (P < 0.001), and family history of hearing loss (P = 0.044). Risk factors for hearing loss included age at survey completion (OR = 1.57; P = 0.036), hypercholesterolemia (OR = 3.45; P = 0.007), cumulative cisplatin dose (OR = 1.94; P = 0.049), and family history of hearing loss (OR = 2.87; P = 0.071). CONCLUSIONS: Ototoxicity risk factors included age, cisplatin dose, cardiovascular risk factors, and family history of hearing loss. Three of four TC survivors report some type of ototoxicity; thus, follow-up of cisplatin-treated survivors should include routine assessment for ototoxicity with provision of indicated treatments. IMPLICATIONS FOR CANCER SURVIVORS: Survivors should be aware of risk factors associated with ototoxicity. Referrals to audiologists before, during, and after cisplatin treatment is recommended.


Asunto(s)
Antineoplásicos , Supervivientes de Cáncer , Pérdida Auditiva , Hipercolesterolemia , Ototoxicidad , Neoplasias Testiculares , Acúfeno , Masculino , Humanos , Cisplatino/efectos adversos , Antineoplásicos/efectos adversos , Acúfeno/inducido químicamente , Acúfeno/epidemiología , Ototoxicidad/tratamiento farmacológico , Ototoxicidad/etiología , Prevalencia , Hipercolesterolemia/complicaciones , Pérdida Auditiva/inducido químicamente , Pérdida Auditiva/epidemiología , Factores de Riesgo
11.
J Clin Oncol ; 41(12): 2211-2226, 2023 04 20.
Artículo en Inglés | MEDLINE | ID: mdl-36626694

RESUMEN

PURPOSE: Cisplatin is widely used and highly ototoxic, but patient-reported functional impairment because of cisplatin-related hearing loss (HL) and tinnitus has not been comprehensively evaluated. PATIENTS AND METHODS: Testicular cancer survivors (TCS) given first-line cisplatin-based chemotherapy completed validated questionnaires, including the Hearing Handicap Inventory for Adults (HHIA) and Tinnitus Primary Function Questionnaire (TPFQ), each of which quantifies toxicity-specific functional impairment. Spearman correlations evaluated associations between HL and tinnitus severity and level of functional handicap quantified with the HHIA and TPFQ, respectively. Associations between HL or tinnitus and five prespecified adverse health outcomes (cognitive dysfunction, fatigue, depression, anxiety, and overall health) were evaluated. RESULTS: HL and tinnitus affected 137 (56.4%) and 147 (60.5%) of 243 TCS, respectively. Hearing aids were used by 10% TCS (14/137). Of TCS with HL, 35.8% reported clinically significant functional impairment. Severe HHIA-assessed functional impairment was associated with cognitive dysfunction (odds ratio [OR], 10.62; P < .001), fatigue (OR, 5.48; P = .003), and worse overall health (OR, 0.19; P = .012). Significant relationships existed between HL severity and HHIA score, and tinnitus severity and TPFQ score (P < .0001 each). TCS with either greater hearing difficulty or more severe tinnitus were more likely to report cognitive dysfunction (OR, 5.52; P = .002; and OR, 2.56; P = .05), fatigue (OR, 6.18; P < .001; and OR, 4.04; P < .001), depression (OR, 3.93; P < .01; and OR, 3.83; P < .01), and lower overall health (OR, 0.39; P = .03; and OR, 0.46; P = .02, respectively). CONCLUSION: One in three TCS with HL report clinically significant functional impairment. Follow-up of cisplatin-treated survivors should include routine assessment for HL and tinnitus. Use of the HHIA and TPFQ permit risk stratification and referral to audiologists as needed, since HL adversely affects functional status and is the single largest modifiable risk factor for cognitive decline and dementia in the general population.


Asunto(s)
Pérdida Auditiva , Neoplasias Testiculares , Acúfeno , Adulto , Masculino , Humanos , Cisplatino/efectos adversos , Neoplasias Testiculares/tratamiento farmacológico , Acúfeno/inducido químicamente , Acúfeno/epidemiología , Pérdida Auditiva/inducido químicamente , Pérdida Auditiva/epidemiología , Medición de Resultados Informados por el Paciente
12.
Cancer Med ; 12(3): 2999-3012, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36097363

RESUMEN

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. For clinical associations, SRT-based hearing disability (SHD) was defined as SRT≥15 dB hearing loss and clinical variables were derived from the study dataset. Genotyped blood samples were used for GWAS with rank-based inverse normal transformed SRT values as the response variable. Age was used as a covariate in association analyses. RESULTS: SHD was inversely associated with self-reported health (p = 0.004). Current smoking (p = 0.002), years of smoking (p = 0.02), BMI (p < 0.001), and peripheral motor neuropathy (p = 0.003) were positively associated with SHD, while physical activity was inversely associated with SHD (p = 0.005). In contrast, cumulative cisplatin dose, peripheral sensory neuropathy, hypertension, and hypercholesterolemia were not associated with SHD. Although no genetic variants had an association p value < 5 × 10-8 , 22 genetic variants were suggestively associated (p < 10-5 ) with SRT deterioration. Three of the top variants in 10 respective linkage disequilibrium regions were either positioned within the coding sequence or were eQTLs for genes involved in neuronal development (ATE1, ENAH, and ZFHX3). CONCLUSION: Current results improve our understanding of risk factors for SRT deterioration in cancer survivors. Higher BMI, lower physical activity, and smoking are associated with SHD. Larger samples would allow for expansion of the current findings on the genetic architecture of SRT.


Asunto(s)
Pérdida Auditiva , Neoplasias , Percepción del Habla , Adulto , Humanos , Cisplatino/efectos adversos , Habla , Pérdida Auditiva/inducido químicamente , Sobrevivientes
14.
J Am Geriatr Soc ; 70(10): 2764-2774, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35689461

RESUMEN

This report summarizes the presentations, discussions, and recommendations of the most recent American Geriatrics Society and National Institute on Aging research conference, "Cancer and Cardiovascular Disease," on October 18-19, 2021. The purpose of this virtual meeting was to address the interface between cancer and heart disease, which are the two leading causes of death among older Americans. Age-related physiologic changes are implicated in the pathogenesis of both conditions. Emerging data suggest that cancer-related cardiovascular disease (CVD) involves disrupted cell signaling and cellular senescence. The risk factors for CVD are also risk factors for cancer and an increased likelihood of cancer death, and people who have both cancer and CVD do more poorly than those who have only cancer or only CVD. Issues addressed in this bench-to-bedside conference include mechanisms of cancer and CVD co-development in older adults, cardiotoxic effects of cancer therapy, and management of comorbid cancer and CVD. Presenters discussed approaches to ensure equitable access to clinical trials and health care for diverse populations of adults with CVD and cancer, mechanisms of cancer therapy cardiotoxicity, and management of comorbid CVD and cancer, including the role of patient values and preferences in treatment decisions. Workshop participants identified many research gaps and questions that could lead to an enhanced understanding of comorbid CVD and cancer and to better and more equitable management strategies.


Asunto(s)
Enfermedades Cardiovasculares , Geriatría , Neoplasias , Anciano , Enfermedades Cardiovasculares/terapia , Humanos , National Institute on Aging (U.S.) , Neoplasias/complicaciones , Neoplasias/terapia , Factores de Riesgo , Estados Unidos/epidemiología
15.
Urology ; 167: 102-108, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35772480

RESUMEN

OBJECTIVE: To evaluate association between Medicare accountable care organizations (ACOs) participation of hospitals on post-acute care (PAC) use and spending, and post-surgical outcomes in Medicare beneficiaries undergoing urologic cancer surgeries. Despite increasing prevalence of urologic cancer and surgical care contributing to a large proportion of total health care costs, and recent Medicare payment reforms such as accountable care organizations, the role of ACOs in urologic cancer care has been unexplored. METHODS: We conducted a longitudinal analysis of 2011-2017 Medicare claims data to compare post-surgical outcomes between Medicare ACO and non-ACO patients before and after implementation of Medicare shared savings program (MSSP). Our outcomes of interest were Post-acute care (PAC) use (overall, institutional, and home health), Skilled Nursing Facility (SNF) length of stay and Medicare spending for SNF patients, 30-day and 90-day unplanned readmissions and complications after index procedure. RESULTS: Study sample included a total of 334,514 Medicare patients undergoing bladder, prostate, kidney cancer surgeries at 524 Medicare ACO and 2066 non-ACO hospitals. For bladder cancer surgery, Medicare ACO participation was associated with significantly reduced overall post-acute care use, but not with changes in readmission or complication rate. For prostate cancer and kidney cancer surgery, we found no significant association between hospital participation in Medicare ACOs and PAC use or post-surgical outcomes. CONCLUSION: Hospital participation in MSSP ACOs leads to lower post-acute care use without compromising patient outcomes for Medicare beneficiaries undergoing bladder cancer surgery. Future research is needed to understand longer-term impact of ACO participation on urologic cancer surgery outcomes.


Asunto(s)
Organizaciones Responsables por la Atención , Neoplasias Renales , Neoplasias de la Vejiga Urinaria , Anciano , Ahorro de Costo , Humanos , Masculino , Medicare , Atención Subaguda , Resultado del Tratamiento , Estados Unidos
16.
Cancer Med ; 11(14): 2801-2816, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35322580

RESUMEN

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. Genome-wide association studies and gene-based analyses were performed on each phenotype. RESULTS: Hearing loss, tinnitus, and peripheral neuropathy, accounting for age and cisplatin dose, were interdependent. Survivors with these neurotoxicities experienced more hypertension and poorer self-reported health. In addition, hearing loss was positively associated with BMIs at clinical evaluation and nonwork-related noise exposure (>5 h/week). Tinnitus was positively associated with tobacco use, hypercholesterolemia, and noise exposure. We observed positive associations between peripheral neuropathy and persistent vertigo, tobacco use, and excess alcohol consumption. Hearing loss and TXNRD1, which plays a key role in redox regulation, showed borderline significance (p = 4.2 × 10-6 ) in gene-based analysis. rs62283056 in WFS1 previously found to be significantly associated with hearing loss (n = 511), was marginally significant in an independent replication cohort (p = 0.06; n = 606). Gene-based analyses identified significant associations between tinnitus and WNT8A (p = 2.5 × 10-6 ), encoding a signaling protein important in germ cell tumors. CONCLUSIONS: Genetics variants in TXNRD1 and WNT8A are notable risk factors for hearing loss and tinnitus, respectively. Future studies should investigate these genes and if replicated, identify their potential impact on preventive strategies.


Asunto(s)
Antineoplásicos , Pérdida Auditiva , Síndromes de Neurotoxicidad , Enfermedades del Sistema Nervioso Periférico , Neoplasias Testiculares , Acúfeno , Antineoplásicos/efectos adversos , Cisplatino/uso terapéutico , Estudio de Asociación del Genoma Completo , Pérdida Auditiva/inducido químicamente , Pérdida Auditiva/genética , Humanos , Masculino , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/genética , Farmacogenética , Trastornos de la Sensación , Neoplasias Testiculares/genética , Acúfeno/inducido químicamente , Acúfeno/genética
17.
PLoS One ; 17(2): e0263573, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35157714

RESUMEN

INTRODUCTION: Testicular cancer survivors (TCS) have an increased risk of additional cancers, including prostate cancer. Our understanding of the natural history of prostate cancer in testicular cancer survivors is very limited due to its rare incidence. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) Registry from 1978 to 2011, we identified 282 TCS with subsequent prostate cancer and examined the tumor grade and clinical outcomes in contrast to men with primary prostate cancer in the general population. RESULTS: TCS with a subsequent prostate cancer diagnosis were more likely to be diagnosed at a younger age than men with primary prostate cancer (65.2% vs. 37.6% for age ≤65, 34.8% vs. 62.4% for age >65, p<0.001) and were more likely to have grade III/IV tumors (46.2% vs. 37.0%, p<0.002). Longer latency between testicular and prostate cancer diagnoses was associated with a higher risk of grade III/IV (p<0.001) cancer. Despite the increased risk for high-grade tumors, 10-year prostate cancer-specific survival and overall survival were not significantly different between TCS and men with primary prostate cancer. Based on the available information in SEER, we found that prior history of radiotherapy for testicular cancer had no impact on tumor grade or survival outcomes. CONCLUSIONS: Prostate cancer in TCS was more likely to be diagnosed at a younger age and with higher grades. Risks of grade III/IV disease increased with longer latency between testicular and prostate cancer diagnoses. Radiotherapy for testicular cancer did not appear to have a significant impact on the outcome of subsequent prostate cancer.


Asunto(s)
Supervivientes de Cáncer/estadística & datos numéricos , Neoplasias de la Próstata/epidemiología , Neoplasias Testiculares/epidemiología , Factores de Edad , Edad de Inicio , Anciano , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Neoplasias de la Próstata/patología , Programa de VERF , Neoplasias Testiculares/radioterapia
18.
Ear Hear ; 43(3): 794-807, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35067571

RESUMEN

OBJECTIVES: To provide new information on factors associated with discrepancies between patient-reported and audiometrically defined hearing loss (HL) in adult-onset cancer survivors after cisplatin-based chemotherapy (CBCT) and to comprehensively investigate risk factors associated with audiometrically defined HL. DESIGN: A total of 1410 testicular cancer survivors (TCS) ≥6 months post-CBCT underwent comprehensive audiometric assessments (0.25 to 12 kHz) and completed questionnaires. HL severity was defined using American Speech-Language-Hearing Association criteria. Multivariable multinomial regression identified factors associated with discrepancies between patient-reported and audiometrically defined HL and multivariable ordinal regression evaluated factors associated with the latter. RESULTS: Overall, 34.8% of TCS self-reported HL. Among TCS without tinnitus, those with audiometrically defined HL at only extended high frequencies (EHFs) (10 to 12 kHz) (17.8%) or at both EHFs and standard frequencies (0.25 to 8 kHz) (23.4%) were significantly more likely to self-report HL than those with no audiometrically defined HL (8.1%) [odds ratio (OR) = 2.48; 95% confidence interval (CI), 1.31 to 4.68; and OR = 3.49; 95% CI, 1.89 to 6.44, respectively]. Older age (OR = 1.09; 95% CI, 1.07 to 1.11, p < 0.0001), absence of prior noise exposure (OR = 1.40; 95% CI, 1.06 to 1.84, p = 0.02), mixed/conductive HL (OR = 2.01; 95% CI, 1.34 to 3.02, p = 0.0007), no hearing aid use (OR = 5.64; 95% CI, 1.84 to 17.32, p = 0.003), and lower education (OR = 2.12; 95% CI, 1.23 to 3.67, p = 0.007 for high school or less education versus postgraduate education) were associated with greater underestimation of audiometrically defined HL severity, while tinnitus was associated with greater overestimation (OR = 4.65; 95% CI, 2.64 to 8.20 for a little tinnitus, OR = 5.87; 95% CI, 2.65 to 13.04 for quite a bit tinnitus, and OR = 10.57; 95% CI, 4.91 to 22.79 for very much tinnitus p < 0.0001). Older age (OR = 1.13; 95% CI, 1.12 to 1.15, p < 0.0001), cumulative cisplatin dose (>300 mg/m2, OR = 1.47; 95% CI, 1.21 to 1.80, p = 0.0001), and hypertension (OR = 1.80; 95% CI, 1.28 to 2.52, p = 0.0007) were associated with greater American Speech-Language-Hearing Association-defined HL severity, whereas postgraduate education (OR = 0.58; 95% CI, 0.40 to 0.85, p = 0.005) was associated with less severe HL. CONCLUSIONS: Discrepancies between patient-reported and audiometrically defined HL after CBCT are due to several factors. For survivors who self-report HL but have normal audiometric findings at standard frequencies, referral to an audiologist for additional testing and inclusion of EHFs in audiometric assessments should be considered.


Asunto(s)
Pérdida Auditiva , Ototoxicidad , Neoplasias Testiculares , Acúfeno , Adulto , Cisplatino/efectos adversos , Pérdida Auditiva/inducido químicamente , Pérdida Auditiva/complicaciones , Pérdida Auditiva/diagnóstico , Humanos , Masculino , Neoplasias de Células Germinales y Embrionarias , Medición de Resultados Informados por el Paciente , Neoplasias Testiculares/inducido químicamente , Neoplasias Testiculares/complicaciones , Neoplasias Testiculares/tratamiento farmacológico
20.
Cardiooncology ; 7(1): 34, 2021 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-34629110

RESUMEN

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. The vascular toxicity seen in large epidemiologic studies of testicular cancer survivors may in part be similar and mechanistically linked to the risk seen in environmental heavy metal contaminants linked to cardiovascular disease. Future research should be directed to better understand the magnitude of the adverse cardiovascular effects of platinum and to elucidate the underlying mechanisms of action.

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