Risks of long-term mortality and chronic health conditions experienced by Wilms tumor survivors.
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ABSTRACT:
SUBMITTER: Theilen TM
PROVIDER: S-EPMC10644020 | biostudies-literature | 2023 Oct
REPOSITORIES: biostudies-literature
Publications
Risks of long-term mortality and chronic health conditions experienced by Wilms tumor survivors.
Theilen Till-Martin TM Braun Yannick Y Rolle Udo U Fiegel Henning C HC Friedmacher Florian F
Translational pediatrics 20231023 10
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Project description:BackgroundRelationships between genetic risks for chronic diseases and long-run wellbeing are largely unexplored. We examined the associations between genetic predispositions to several chronic conditions and long-term functional health and socioeconomic status (SES).MethodsWe used data on a nationally representative sample of 9,317 adults aged 65 years or older from the 1992 to 2012 Health and Retirement Survey (HRS) in the US. Survey data were linked to genetic data on nearly 2 million single-nucleotide polymorphisms (SNPs). We measured individual-level genetic predispositions for coronary-artery disease, type 2 diabetes (T2D), obesity, rheumatoid arthritis (RA), Alzheimer's disease, and major depressive disorder (MDD) by polygenic risk scores (PRS) derived from genome-wide association studies (GWAS). The outcomes were self-rated health, depressive symptoms, cognitive ability, activities of everyday life, educational attainment, and wealth. We employed regression analyses for the outcomes including all polygenic scores and adjusting for gender, birth period, and genetic ancestry.ResultsThe polygenic scores had important associations with functional health and SES. An increase in genetic risk for all conditions except T2D was significantly (p < .01) associated with reduced functional health and socioeconomic outcomes. The magnitudes of functional health declines were meaningful and in many cases equivalent in magnitude to several years of aging. These associations were robust to several sensitivity checks for ancestry and adjustment for parental educational attainment and age at death or the last interview if alive.ConclusionStronger genetic predispositions for leading chronic conditions are related to worse long-run health and SES outcomes, likely reflecting the adverse effects of the onset of these conditions on one's wellbeing.
| S-EPMC5861924 | biostudies-literature
Project description:PURPOSE:To examine prevalence and predictors of neurocognitive outcomes, social attainment, emotional distress, and health-related quality of life (HRQOL) in long-term survivors of pediatric Wilms tumor (WT). METHODS:One hundred fifty-eight WT survivors (59% female; mean [SD] age 33 [9.1] years; time since diagnosis 29 [9.1] years) and 354 community controls (55.6% female; 35 [10.2] years) completed comprehensive neuropsychological testing and physical examination, including echocardiography/electrocardiography, pulmonary function tests, and endocrine evaluation. Self-report of emotional distress, HRQOL, and social attainment were collected. Impairment was defined in relation to both controls and normative data. Generalized linear models were developed to examine impact of treatment and chronic health conditions on outcomes. RESULTS:WT survivors performed poorer than norms and controls in 6 of 16 cognitive variables and 1 of 8 HRQOL variables, with scores ranging from - 0.64 (mathematics) to - 0.21 (verbal fluency) standard deviations below expectations. Compared to controls, WT survivors were less likely to graduate college (odds ratio 2.23, 95% confidence interval 1.46-3.41) and had more moderate to severe neurologic conditions (18.4% vs 8.2%, p < 0.001), which were associated with poor memory (β = - 0.90, p < 0.001), attention (β = - 1.02, p < 0.001), and HRQOL general health (β = - 0.80, p = 0.0015). Treatment variables and cardiopulmonary morbidity (higher in survivors) were not associated with outcomes. CONCLUSIONS:Survivors of WT demonstrate impairment in neurocognitive function and have lower social attainment during adulthood, with poorer neurocognitive function associated with neurologic morbidity. IMPLICATIONS FOR CANCER SURVIVORS:Survivors of WT should be offered neurocognitive evaluations and rehabilitation. Neurologic conditions should be routinely assessed, and appropriate support offered to reduce risk for functional limitations.
| S-EPMC6679797 | biostudies-literature
Project description:BackgroundSurvival after Wilms tumor has significantly increased and focus on late effects has become increasingly important. However, knowledge about long-term renal function in survivors of Wilms tumor is missing. Our aim was to investigate evidence of kidney disease in 20- or more-year survivors of Wilms tumor in a clinical setting, with siblings as comparisons.MethodsIn this cross-sectional study, we established a cohort of Danish 20-plus-year survivors of Wilms tumor and siblings as controls. Participants answered a comprehensive health questionnaire supplemented by measurements of estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio, and blood pressure and were categorized according to the chronic kidney disease classification. Multiple linear regression analysis, taking family membership into account, was used to describe the differences in eGFR. Logistic regression analysis was performed to describe risk factors for the development of kidney disease.ResultsWe included 99 survivors of Wilms tumor and 38 sibling controls with a median of 37 years of follow-up. The eGFR of Wilms tumor survivors was 13 ml/min/1.73 m2 (95% CI -20; -5) lower when compared to sibling control. Evidence of kidney disease, with risk factors as hypertension and diabetes, was found in 19% of the Wilms tumor survivors and 2% developed end-stage renal disease. Ninety-two percent of the Wilms tumor survivors had an eGFR >60 ml/min/1.732 .ConclusionLong-term Wilms tumor survivors have on average a significantly decreased renal function along with the increased prevalence of kidney disease and end-stage renal disease when compared to sibling controls. Still, most survivors had kidney function within the normal range.
| S-EPMC9883410 | biostudies-literature
Project description:BackgroundTestis cancer (TC) patients are young with excellent cancer prognosis. Hence, the risk of late-onset treatment-related morbidity and mortality is of concern due to longer survival after treatment.ObjectiveWe set to characterize long-term survival of TC patients through a Canadian population dataset.Design setting and participantsWe used a population-based dataset, the Canadian Census Health and Environment Cohort (CanCHEC), to identify individuals diagnosed with TC between 1991 and 2010. We compared them with all other male individuals without TC.Outcome measurements and statistical analysisThe primary outcome was mortality due to cardiovascular disease (CVD) or nontesticular malignancy. Mann-Whitney or chi-square test was used where applicable. Data were analyzed using a Cox proportional hazard model with and without matching.Results and limitationsWe identified 1950 individuals with TC. We compared them with 1 300 295 men with no TC. There were 335 deaths in the study group during the study period (17.2%) with a mean follow-up of 19.6 yr. TC patients were at increased risk of death from secondary malignancies (hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.39-1.91; p < 0.0001) with specific risks for hematologic neoplasms (HR 3.86, 95% CI 2.78-5.37; p < 0.001) and other malignancies (HR 2.41, 95% CI 1.76-3.29; p < 0.001). Gastrointestinal, hematologic, and respiratory toxicities were the most common secondary malignancies leading to death. When stratified according to histology, nonseminoma (NS) patients were at significantly increased risk of death from CVD (HR 2.03, 95% CI 1.27-3.25; p = 0.0032). Individuals with seminoma were at increased risk of death from other nontestis neoplasms (HR 1.46, 95% CI 1.17-1.82; p = 0.0007), specifically hematologic neoplasms (HR 2.09, 95% CI 1.18-3.72; p = 0.0118).ConclusionsNS patients are at increased risk of CVD-related death, whereas seminoma patients are at increased risk of death from non-testis-related malignancies.Patient summaryWe report long-term mortality following diagnosis of testis cancer. Nonseminoma patients have an increased risk of death from cardiovascular disease, while seminoma patients have an increased risk of death from secondary malignancies.
| S-EPMC8317812 | biostudies-literature
Project description:PurposeThis study was undertaken to evaluate the incidence of pulmonary disease among patients treated with radiation therapy (RT) for pulmonary metastases (PM) from Wilms tumor (WT).Patients and methodsWe reviewed records of 6,449 patients treated on National Wilms Tumor Studies-1, -2, -3, and -4 whose flow sheets or annual status reports documented one of several pulmonary conditions. Cases were fully evaluable if pulmonary function test (PFT) results were available, pulmonary fibrosis was identified on a chest radiograph or was listed as the primary or a contributing factor to death. Partially evaluable cases were those for whom PFT results could not be obtained. We evaluated the relationship between RT factors and the occurrence of pulmonary disease using hazard ratios (HRs) and cumulative incidence, treating death as a competing risk.ResultsSixty-four fully evaluable and 16 partially evaluable cases of pulmonary disease were identified. The cumulative incidence of pulmonary disease at 15 years since WT diagnosis was 4.0% (95% confidence interval [CI] 2.6-5.4%) among fully evaluable and 4.8% (95% CI 3.3-6.4%) among fully and partially evaluable patients who received lung RT for PM at initial diagnosis. Rates of pulmonary disease were substantially higher among those who received lung RT for PM present at initial diagnosis or relapse compared to those who received no RT or only abdominal RT (HR 30.2, 95% CI 16.9-53.9).ConclusionThe risk of pulmonary disease must be considered in evaluating the risk:benefit ratio of lung RT for the management of PM from WT.
| S-EPMC3933277 | biostudies-literature
Project description: Not available
| S-EPMC10915446 | biostudies-literature
Project description: Not available
| S-EPMC10730964 | biostudies-literature
Project description:Glioblastoma (GBM) is a highly aggressive type of glioma with poor prognosis. However, a small number of patients live much longer than the median survival. A better understanding of these long-term survivors (LTS) may provide important insight into the biology of GBM. We identified 7 patients with GBM treated at Memorial Sloan-Kettering Cancer Center (MSKCC) with survival greater than 48 months. We characterized the transcriptome of each patient and determined rates of MGMT promoter methylation and IDH1 and IDH2 mutational status. We identified LTS in two independent cohorts (TCGA and REMBRANDT) and analyzed the transcriptomal characteristics of these LTS. The median overall survival of our cohort was 62.5 months. LTS were distributed between the proneural (n=2), neural (n=2), classical (n=2) and mesenchymal (n=1) subtypes. Similarly, LTS in the TCGA and REMBRANDT cohorts demonstrated diverse transcriptomal subclassification identity. The majority of the MSKCC LTS (71%) were found to have methylation of the MGMT promoter. None of the patients had an IDH1 or IDH2 mutations, and IDH mutation occurred in a minority of the TCGA LTS as well. A set of 42 genes was found to be differentially expressed in the MSKCC and TCGA LTS. While IDH mutant proneural tumors impart a better prognosis in the short-term, survival beyond 4 years does not require IDH mutation and is not dictated by a single transcriptional subclass. In contrast, MGMT methylation continues to have strong prognostic value for survival beyond 4 years. These findings have substantial impact for understanding GBM biology and progression. All tumors (n = 7) were obtained following surgical resection at the MSKCC as part of routine clinical care, and snap frozen. Tumors were obtained in accordance with Institutional Review Board policies at the MSKCC. Each sample was examined histologically by 3 independent neuropathologists and confirmed to be World Health Organization (WHO) grade IV glioma (GBM). Before analysis, tumors were sectioned and microdissected. Genomic DNA or RNA was extracted using the DNeasy kit (Qiagen) or RNeasy Lipid Tissue Mini Kit (Qiagen) as per the manufacturer’s instructions. Expression analysis of tumors was performed using the Affymetrics U133 2.0 microarray (Affymetrix). Affymetrix CEL files were imported into the Partek Genomics Suite (Partek). The TCGA gene expression data (HT-HG-U133A) was accessed from the TCGA data repositories (http://cancergenome.nih.gov, date of download 12/2013).
2014-05-02 | E-GEOD-54077 | biostudies-arrayexpress
Project description:BackgroundSurvivors of germ-cell tumors (GCT) may suffer from long-term adverse consequences. Our study was conducted to assess a long-term sexual functioning in GCT survivors.MethodsGCT survivors (N = 170) from the National Cancer Institute in Slovakia completed a Sexual Function Questionnaire that was modified from PROMIS Sexual Function and Satisfaction Questionnaire 9-year median follow up (range 5-32) as a primary exploratory aim. Study groups consisted of 17 survivors (10%) who had active surveillance (AS, controls), and 153 (90%) survivors who received treatment beyond orchiectomy (Tx), including cisplatin-based chemotherapy (CT, N = 132; 78%), radiotherapy to the retroperitoneal lymph nodes (RT, N = 12; 7%) or both (CTRT, N = 9; 5%).ResultsIn univariate analysis, treatment of any type resulted in difficulty to maintain erection during sexual intercourse compared to patients treated with AS (P = 0.04). Survivors who received CTRT had lower ability to achieve orgasm during sexual activities (P = 0.04) and they reported disappointment with their overall quality of sex life (P = 0.002). The number of attempts to initiate sexual intercourse did not differ. Sexual relationships caused none or mild anxiety and the desire to be sexually active was higher after CTRT (P = 0.05). Multivariable analysis confirmed that orgasmic dysfunction after ≥400 mg/m2 of cisplatin and issues in maintaining erection after Tx were independent of retroperitoneal lymph-node dissection (P = 0.03 and P = 0.04, respectively). Survivors were disappointed with the quality of sex life and had stronger desire to be sexually active independent of age, (P = 0.01 and P = 0.05, respectively).ConclusionsThis study identified an impairment in sexual function may represent an issue for long-term GCT survivors. Treatment with chemotherapy plus radiotherapy were associated with disappointment and stronger sexual desire, while a higher cumulative dose of cisplatin may be responsible for orgasmic dysfunction.
| S-EPMC7439516 | biostudies-literature
Project description:BackgroundWe investigated excess mortality after endometrial cancer using conditional relative survival estimates and standardized mortality ratios (SMR).MethodsWomen diagnosed with endometrial cancer during 2000-2017 (N = 183,153) were identified in the Surveillance Epidemiology and End Results database. SMRs were calculated as observed deaths among endometrial cancer survivors over expected deaths among demographically similar women in the general U.S.PopulationFive-year relative survival was estimated at diagnosis and each additional year survived up to 12 years post-diagnosis, conditional on survival up to that year.ResultsFor the full cohort, 5-year relative survival was 87.7%, 96.2%, and 97.1% at 1, 5, and 10 years post-diagnosis, respectively. Conditional 5-year relative survival first exceeded 95%, reflecting minimal excess mortality compared with the general population, at 4 years post-diagnosis overall. However, in subgroup analyses, conditional relative survival remained lower for Black women (vs. White) and for those with regional/distant stage disease (vs. localized) throughout the study period. The overall SMR for all-cause mortality decreased from 5.90 [95% confidence interval (CI), 5.81-5.99] in the first year after diagnosis to 1.16 (95% CI, 1.13-1.19) at 10+ years; SMRs were consistently higher for non-White women and for those with higher stage or grade disease.ConclusionsOverall, endometrial cancer survivors had only a small survival deficit beyond 4 years post-diagnosis. However, excess mortality was greater in magnitude and persisted longer into survivorship for Black women and for those with more advanced disease.ImpactStrategies to mitigate disparities in mortality after endometrial cancer will be needed as the number of survivors continues to increase.
| S-EPMC8172460 | biostudies-literature