Prevalence of anthracycline-related cardiac dysfunction in long-term survivors of adult-onset lymphoma.
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ABSTRACT:
SUBMITTER: Armenian SH
PROVIDER: S-EPMC5801059 | biostudies-literature | 2018 Feb
REPOSITORIES: biostudies-literature
Publications
Prevalence of anthracycline-related cardiac dysfunction in long-term survivors of adult-onset lymphoma.
Armenian Saro H SH Mertens Luc L Slorach Cameron C Venkataraman Kalyanasundaram K Mascarenhas Kristen K Nathwani Nitya N Wong F Lennie FL Forman Stephen J SJ Bhatia Smita S
Cancer 20171107 4
<h4>Background</h4>Anthracycline-related heart failure is a leading cause of morbidity in survivors of adult-onset lymphoma. There is a paucity of information on screening for late-occurring preclinical disease, which, in turn, has limited guidelines for early detection and intervention. The objectives of this study were to examine the prevalence and risk of cardiac dysfunction, as measured by echocardiography (abnormal left ventricular systolic/diastolic function or strain), in lymphoma survivo ...[more]
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Project description:PurposeEchocardiographic surveillance for asymptomatic left ventricular systolic dysfunction (ALVSD) is advised in childhood cancer survivors (CCS), because of their risk of heart failure after anthracycline treatment. ALVSD can be assessed with different echocardiographic parameters. We systematically reviewed the prevalence and risk factors of late ALVSD, as defined by contemporary and more traditional echocardiographic parameters.MethodsWe searched databases from 2001 to 2020 for studies on ≥ 100 asymptomatic 5-year CCS treated with anthracyclines, with or without radiotherapy involving the heart region. Outcomes of interest were prevalence of ALVSD-measured with volumetric methods (ejection fraction; LVEF), myocardial strain, or linear methods (fractional shortening; FS)-and its risk factors from multivariable analyses.ResultsEleven included studies represented 3840 CCS. All studies had methodological limitations. An LVEF < 50% was observed in three studies in 1-6% of CCS, and reduced global longitudinal strain (GLS) was reported in three studies in 9-30% of CCS, both after a median follow-up of 9 to 23 years. GLS was abnormal in 20-28% of subjects with normal LVEF. Abnormal FS was reported in six studies in 0.3-30% of CCS, defined with various cut-off values (< 25 to < 30%), at a median follow-up of 10 to 18 years. Across echocardiographic parameters, reported risk factors were cumulative anthracycline dose and radiotherapy involving the heart region, with no 'safe' dose for ALVSD.ConclusionsGLS identifies higher prevalence of ALVSD in anthracycline-treated CCS, than LVEF.Implications for cancer survivorsThe diagnostic and prognostic value of GLS should be evaluated within large cohorts.Protocol registrationPROSPERO CRD42019126588.
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Project description:Cancer-related cognitive impairment (CRCI) is a frequent side effect experienced by an increasing number of cancer survivors with a significant impact on their quality of life. Different definitions and means of evaluation have been used in available literature; hence the exact incidence of CRCI remains unknown. CRCI can be described as cognitive symptoms reported by cancer patients in self-reported questionnaires or as cognitive changes evaluated by formal neuropsychological tests. Nevertheless, association between cognitive symptoms and objectively assessed cognitive changes is relatively weak or absent. Studies have focused especially on breast cancer patients, but CRCI has been reported in multiple types of cancer, including colorectal, lung, ovarian, prostate, testicular cancer and hematological malignancies. While CRCI has been associated with various treatment modalities, including radiotherapy, chemotherapy, hormone therapy and novel systemic therapies, it has been also detected prior to cancer treatment. Therefore, the effects of cancer itself with or without the psychological distress may be involved in the pathogenesis of CRCI as a result of altered coping mechanisms after cancer diagnosis. The development of CRCI is probably multifactorial and the exact mechanisms are currently not completely understood. Possible risk factors include administered treatment, genetic predisposition, age and psychological factors such as anxiety, depression or fatigue. Multiple mechanisms are suggested to be responsible for CRCI, including direct neurotoxic injury of systemic treatment and radiation while other indirect contributing mechanisms are hypothesized. Chronic neuroinflammation mediated by active innate immune system, DNA-damage or endothelial dysfunction is hypothesized to be a central mechanism of CRCI pathogenesis. There is increasing evidence of potential plasma (e.g., damage associated molecular patterns, inflammatory components, circulating microRNAs, exosomes, short-chain fatty acids, and others), cerebrospinal fluid and radiological biomarkers of cognitive dysfunction in cancer patients. Discovery of biomarkers of cognitive impairment is crucial for early identification of cancer patients at increased risk for the development of CRCI or development of treatment strategies to lower the burden of CRCI on long-term quality of life. This review summarizes current literature on CRCI with a focus on long-term effects of different cancer treatments, possible risk factors, mechanisms and promising biomarkers.
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Project description:BACKGROUND AND OBJECTIVES: Because little is known about long-term treatment-related nephrotoxicity, the aim was to determine risk factors for renal impairment long after childhood cancer treatment. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data from 763 adult childhood cancer survivors (414 men) were obtained during regular visits at the late-effects clinic between 2003 and 2009. Median follow-up time was 18.3 years (range=5.0-58.2). Glomerular function was assessed by estimated GFR (using the Modification of Diet in Renal Disease formula), urinary albumin creatinine ratio, and tubular function by urinary ?2-microglobulin creatinine ratio. The association with treatment factors was analyzed with covariance analysis for estimated GFR and logistic regression for urinary albumin and urinary ?2-microglobulin creatinine ratios. RESULTS: Survivors treated with nephrectomy and abdominal irradiation had significantly lower estimated GFR than survivors not treated with nephrectomy/abdominal irradiation (estimated mean=90 ml/min per 1.73 m(2) versus 106, P<0.001). Estimated GFR was significantly lower in survivors after treatment with high-dose ifosfamide (88 versus 98, P=0.02) and high-dose cisplatin (83 versus 101, P=0.004) compared with survivors not treated with these regimen. Nephrectomy combined with abdominal radiotherapy (odds ratio=3.14, 95% confidence interval=1.02; 9.69) and high-dose cisplatin (odds ratio=5.19, 95% confidence interval=1.21; 22.21) was associated with albuminuria. High-dose ifosfamide (odds ratio=6.19, 95% confidence interval=2.45; 15.67) was associated with increased urinary ?2-microglobulin creatinine ratio. Hypertension was present in 23.4% of survivors and 31.4% of renal tumor survivors. CONCLUSIONS: Treatment with unilateral nephrectomy, abdominal radiotherapy, cisplatin, and ifosfamide was associated with lower estimated GFR. Persisting tubular damage was related to ifosfamide treatment.
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Project description:BACKGROUND:The National Comprehensive Cancer Network and American Society of Clinical Oncology recommend consideration of the use of echocardiography 6 to 12 months after completion of anthracycline-based chemotherapy in at-risk populations. Assessment of BNP (B-type natriuretic peptide) has also been suggested by the American College of Cardiology/American Heart Association/Heart Failure Society of America for the identification of Stage A (at risk) heart failure patients. The real-world frequency of the use of these tests in patients after receipt of anthracycline therapy, however, has not been studied previously. METHODS AND RESULTS:In this retrospective study, using administrative claims data from the OptumLabs Data Warehouse, we identified 31 447 breast cancer and lymphoma patients (age ?18 years) who were treated with an anthracycline in the United States between January 1, 2008 and January 31, 2018. Continuous medical and pharmacy coverage was required for at least 6 months before the initial anthracycline dose and 12 months after the final dose. Only 36.1% of patients had any type of cardiac surveillance (echocardiography, BNP, or cardiac imaging) in the year following completion of anthracycline therapy (29.7% echocardiography). Surveillance rate increased from 37.5% in 2008 to 42.7% in 2018 (25.6% in 2008 to 40.5% echocardiography in 2018). Lymphoma patients had a lower likelihood of any surveillance compared with patients with breast cancer (odds ratio, 0.79 [95% CI, 0.74-0.85]; P<0.001). Patients with preexisting diagnoses of coronary artery disease and arrhythmia had the highest likelihood of cardiac surveillance (odds ratio, 1.54 [95% CI, 1.39-1.69] and odds ratio, 1.42 [95% CI, 1.3-1.53]; P<0.001 for both), although no single comorbidity was associated with a >50% rate of surveillance. CONCLUSIONS:The majority of survivors of breast cancer and lymphoma who have received anthracycline-based chemotherapy do not undergo cardiac surveillance after treatment, including those with a history of cardiovascular comorbidities, such as heart failure.
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Project description:PurposeTo assess outcomes and predictors of long-term myocardial dysfunction after cardiac arrest (CA) of cardiac origin.MethodsWe retrospectively included consecutive, single-center, prospective-registry patients who survived to hospital discharge for adult out-of-hospital and in-hospital CA of cardiac origin in 2005-2019. The primary objective was to collect the 1-year New York Heart Association Functional Class (NYHA-FC) and major adverse cardiovascular events (MACE).ResultsOf 135 patients, 94 (72%) had their NYHA-FC determined after 1 year, including 75 (75/94, 80%) who were I, 17 (17/94, 18%) II, 2 (2/94, 2%) III, and none IV. The echocardiographic left ventricular ejection fraction was abnormal in 87/130 (67%) patients on day 1, 52/123 (42%) at hospital discharge, and 17/52 (33%) at 6 months. During the median follow-up of 796 [283-1975] days, 38/119 (32%) patients experienced a MACE. These events were predominantly related to acute heart failure (13/38) or ischemic cardiovascular events (16/38), with acute coronary syndrome being the most prevalent among them (8/16). Pre-CA cardiovascular disease was a risk factor for 1-year NYHA-FC > I (P = 0.01), absence of bystander cardiopulmonary resuscitation was significantly associated with NYHA-FC > I at 1 year.ConclusionMost patients had no heart-failure symptoms a year after adult out-of hospital or in-hospital CA of cardiac origin, and absence of bystander cardiopulmonary resuscitation was the only treatment component significantly associated with NYHA-FC > I at 1 year. Nearly a third experienced MACE and the most common types of MACE were ischemic cardiovascular events and acute heart failure. Early left ventricular dysfunction recovered within 6 months in half the patients with available values.
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Project description:ObjectiveTo examine the association between sepsis and the long-term risk of seizures.MethodsWe conducted a retrospective population-based cohort study using administrative claims data from all emergency department visits and hospitalizations at nonfederal acute care hospitals in California, Florida, and New York from 2005 to 2013. Using previously validated diagnosis codes, we identified all adult patients hospitalized with sepsis. Our outcome was any emergency department visit or hospitalization for seizure. Poisson regression and demographic data were used to calculate age-, sex-, and race-standardized incidence rate ratios (IRR). To confirm our findings, we used a matched cohort of hospitalized patients without sepsis for comparison and additionally assessed claims data from a nationally representative 5% sample of Medicare beneficiaries.ResultsWe identified 842,735 patients with sepsis. The annual incidence of seizure was 1.29% (95% confidence interval [CI] 1.27%-1.30%) in patients with sepsis vs 0.16% (95% CI 0.16%-0.16%) in the general population (IRR 4.98; 95% CI 4.92-5.04). A secondary analysis using matched hospitalized patients confirmed these findings (IRR 4.33; 95% CI 4.13-4.55), as did a separate analysis of Medicare beneficiaries, in whom we found a similar strength of association (IRR 2.72; 95% CI 2.60-2.83), as we did in patients ≥65 years of age in our primary statewide data (IRR 2.83; 95% CI 2.78-2.88).ConclusionsWe found that survivors of sepsis faced a significantly higher long-term risk of seizures than both the general population and other hospitalized patients. Our findings suggest that sepsis is associated with pathways that lead to permanent neurologic sequelae.
| S-EPMC5631168 | biostudies-literature
Project description:ImportanceLong-term health effects of cancer in adult survivors are a major concern; however, it is difficult to differentiate between the consequences of cancer and cancer treatment and those of normal aging or comorbidity.ObjectivesTo provide an overview and investigate the temporal pattern of hospitalizations for medically verified incident somatic disease in adult survivors compared with cancer-free comparison people, taking into consideration pretreatment comorbidity and the socioeconomic position of the participants.Design, setting, and participantsIn this nationwide, population-based cohort-cohort study, 458 646 survivors of the 12 most frequent first primary cancers listed in the Danish Cancer Registry between January 1, 1997, and December 31, 2014, and 2 121 567 matched cancer-free comparison people were identified from the Danish Central Population Registry. Hospitalizations for somatic diseases after cancer diagnosis or study entry were identified from the National Patient Register and stratified according to the 11 main diagnostic groups in the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. A cohort of cancer survivors was formed for each combination of cancer type and diagnostic group, with a corresponding group of cancer-free people, resulting in 132 unique cohorts. Data analysis was performed from September 1, 2017, to January 15, 2018.Main outcomes and measuresRisk of hospitalization and the temporal pattern of incidence were analyzed in Cox proportional hazards regression models. Cumulative incidence proportions were calculated by the pseudo-observation method.ResultsA total of 2 580 213 people were investigated, of whom 458 646 were cancer survivors (mean [SD] age, 69 [11.6] years; 230 793 [50.3%] male and 227 853 [49.7%] female) and 2 121 567 were comparison people (mean [SD] age, 69 [11.5] years; 1 054 465 [49.7%] male and 1 067 102 [50.3%] female). More cancer survivors vs comparison people had comorbid conditions at the time of cancer diagnosis or study entry (Charlson Comorbidity Index ≥1: 19% vs 13%). Overall, the risk of hospitalizations for somatic diseases was significantly higher for cancer survivors in almost all diagnostic groups (eg, diseases in the nervous system among breast cancer survivors: hazard ratio, 1.20; 95% CI, 1.17-1.22; diseases in the respiratory system in lung cancer survivors: hazard ratio, 5.85; 95% CI, 5.63-6.07; and diseases in blood and blood-forming organs in prostate cancer survivors: hazard ratio, 2.60; 95% CI, 2.50-2.71).Conclusions and relevanceThe findings suggest that adult survivors of the 12 most common cancers are at significantly higher risk for a broad range of somatic diseases that require hospitalization compared with matched cancer-free comparison people. The results of this study suggest the importance of close, targeted monitoring for new somatic disease during follow-up care of cancer survivors.
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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