scholarly journals Cranial Irradiation as an Additional Risk Factor for Anthracycline Cardiotoxicity in Childhood Cancer Survivors: An Analysis from the Cardiac Risk Factors in Childhood Cancer Survivors Study

2012 ◽  
Vol 34 (4) ◽  
pp. 826-834 ◽  
Author(s):  
David C. Landy ◽  
Tracie L. Miller ◽  
Stuart R. Lipsitz ◽  
Gabriela Lopez-Mitnik ◽  
Andrea S. Hinkle ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Childhood Cancer Survivors ◽  
Cardiac Risk ◽  
Cranial Irradiation ◽  
Additional Risk Factor ◽  
Anthracycline Cardiotoxicity ◽  
Additional Risk

Exercise capacity in long-term survivors of pediatric cancer: An analysis from the cardiac risk factors in childhood cancer survivors study

2012 ◽  
Vol 60 (4) ◽  
pp. 663-668 ◽  
Author(s):  
Angela M. Miller ◽  
Gabriela Lopez-Mitnik ◽  
Gabriel Somarriba ◽  
Stuart R. Lipsitz ◽  
Andrea S. Hinkle ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Exercise Capacity ◽  
Pediatric Cancer ◽  
Childhood Cancer Survivors ◽  
Cardiac Risk ◽  
Cardiac Risk Factors ◽  
Long Term Survivors

Prevalence and prognostic impact of left ventricular systolic dysfunction after acute myocardial infarction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T.J Jernberg ◽  
E.O Omerovic ◽  
E.H Hamilton ◽  
K.L Lindmark ◽  
L.D Desta ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Myocardial Infarction ◽  
Atrial Fibrillation ◽  
Risk Factor ◽  
Reperfusion Therapy ◽  
Left Ventricular ◽  
Funding Source ◽  
Additional Risk Factor ◽  
Additional Risk

Abstract Background Left ventricular dysfunction after an acute myocardial infarction (MI) is associated with poor outcome. The PARADISE-MI trial is examining whether an angiotensin receptor-neprilysin inhibitor reduces the risk of cardiovascular death or worsening heart failure (HF) in this population. The aim of this study was to examine the prevalence and prognosis of different subsets of post-MI patients in a real-world setting. Additionally, the prognostic importance of some common risk factors used as risk enrichment criteria in the PARADISE-MI trial were specifically examined. Methods In a nationwide myocardial infarction registry (SWEDEHEART), including 87 177 patients with type 1 MI between 2011–2018, 3 subsets of patients were identified in the overall MI cohort (where patients with previous HF were excluded); population 1 (n=27 568 (32%)) with signs of acute HF or an ejection fraction (EF) <50%, population 2 (n=13 038 (15%)) with signs of acute HF or an EF <40%, and population 3 (PARADISE-MI like) (n=11 175 (13%)) with signs of acute HF or an EF <40% and at least one risk factor (Age ≥70, eGFR <60, diabetes mellitus, prior MI, atrial fibrillation, EF <30%, Killip III-IV and STEMI without reperfusion therapy). Results When all MIs, population 1 (HF or EF <50%), 2 (HF or EF <40%) and 3 (HF or EF <40% + additional risk factor (PARADISE-MI like)) were compared, the median (IQR) age increased from 70 (61–79) to 77 (70–84). Also, the proportion of diabetes (22% to 33%), STEMI (38% to 50%), atrial fibrillation (10% to 24%) and Killip-class >2 (1% to 7%) increased. After 3 years of follow-up, the cumulative probability of death or readmission because of heart failure in the overall MI population and in population 1 to 3 was 17.4%, 26.9%, 37.6% and 41.8%, respectively. In population 2, all risk factors were independently associated with death or readmission because of HF (Age ≥70 (HR (95% CI): 1.80 (1.66–1.95)), eGFR <60 (1.62 (1.52–1.74)), diabetes mellitus (1.35 (1.26–1.44)), prior MI (1.16 (1.07–1.25)), atrial fibrillation (1.35 (1.26–1.45)), EF <30% (1.69 (1.58–1.81)), Killip III-IV (1.34 (1.19–1.51)) and STEMI without reperfusion therapy (1.34 (1.21–1.48))) in a multivariable Cox regression analysis. The risk increased with increasing number of risk factors (Figure 1). Conclusion Depending on definition, post MI HF is present in 13–32% of all MI patients and is associated with a high risk of subsequent death or readmission because of HF. The risk increases significantly with every additional risk factor. There is a need to optimize management and improve outcomes for this high risk population. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Novartis

scholarly journals Validation of questionnaire-reported chest wall abnormalities with a telephone interview in Swiss childhood cancer survivors

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Rahel Kasteler ◽  
Christa Lichtensteiger ◽  
Christina Schindera ◽  
Marc Ansari ◽  
Claudia E. Kuehni ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Chest Wall ◽  
Daily Life ◽  
Well Being ◽  
Childhood Cancer Survivors ◽  
Thoracic Wall ◽  
Medical Attention ◽  
The Impact

Abstract Background Chest wall abnormalities are a poorly studied complication after treatment for childhood cancer. Chest wall abnormalities are not well-described in the literature, and little is known on the impact on daily life of survivors. Methods We investigated prevalence and risk factors of chest wall abnormalities in childhood cancer survivors in a nationwide, population-based cohort study (Swiss Childhood Cancer Survivor Study) with a questionnaire survey. We then interviewed a nested sample of survivors to validate types of chest wall abnormalities and understand their impact on the daily life of survivors. Results Forty-eight of 2382 (95%CI 2–3%) survivors reported a chest wall abnormality. Risk factors were older age at cancer diagnosis (16–20 years; OR 2.5, 95%CI 1.0–6.1), lymphoma (OR 3.8, 95%CI 1.2–11.4), and central nervous system tumors (OR 9.5, 95%CI 3.0–30.1) as underlying disease, and treatment with thoracic radiotherapy (OR 2.0, 95%CI 1.0–4.2), surgery to the chest (OR 4.5, 95%CI 1.8–11.5), or chemotherapy (OR 2.9, 95%CI 1.0–8.1). The nature of the chest wall abnormalities varied and included thoracic wall deformities (30%), deformations of the spine (5%) or both (55%), and scars (10%). Chest wall abnormalities affected daily life in two thirds (13/20) of those who reported these problems and necessitated medical attention for 15 (75%) survivors. Conclusion It is important that, during follow-up care, physicians pay attention to chest wall abnormalities, which are rare late effects of cancer treatment, but can considerably affect the well-being of cancer survivors.

Abstract P341: Juvenile Exposure To Doxorubicin Differentially Alters The Cardiac Response To Angiotensin II And Isoproterenol In Adult Mice

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Marianne K Grant ◽  
Beshay N Zordoky
Keyword(s):  
Heart Failure ◽  
Risk Factor ◽  
Angiotensin Ii ◽  
Cardiac Function ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Childhood Cancer Survivors ◽  
Cardiac Response

Hypertension is the most significant risk factor for heart failure in doxorubicin (DOX)-treated childhood cancer survivors. We previously developed a two-hit mouse model of juvenile DOX-induced latent cardiotoxicity that is exacerbated by adult-onset angiotensin II (ANGII)-induced hypertension. Nevertheless, it is still not known how juvenile exposure to DOX would predispose the heart to other cardiovascular pathologic stimuli that do not cause hypertension. The objective of this work was to compare the effects of ANGII to those of isoproterenol (ISO) in adult C57BL6/N mice pre-exposed to DOX as juveniles. Five-week-old male mice were administered a low dose of DOX (4 mg/kg/week) or saline for 3 weeks and then allowed to recover for 5 weeks. Thereafter, mice were either infused with ANGII (1.4 mg/kg/day) or injected with ISO (10 mg/kg/day) for 14 days. Juvenile exposure to DOX abrogated the hypertrophic response to both ANGII and ISO, while it failed to correct ANGII- and ISO-induced upregulation in the hypertrophic markers ANP and BNP. ANGII, but not ISO, worsened cardiac function in DOX-exposed mice as measured by echocardiography. Cardiac fibrosis was also exacerbated by ANGII, but not ISO, in DOX-exposed mice as evident by Masson’s trichrome staining and upregulation of the inflammatory and fibrotic markers, Cox-2, Col1a1, Col3a1 , and galectin-3 . In conclusion, the current work demonstrates that ANGII causes more severe deterioration in cardiac function and adverse cardiac remodeling in DOX-exposed mice when compared to ISO. The comparison between DOX/ANGII and DOX/ISO models is critical to understanding why hypertension is the most significant risk factor for heart failure in DOX-treated childhood cancer survivors and thereby devising effective therapeutic strategies against this significant clinical problem.

Genetic and treatment risks for diabetes mellitus (DM) in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS) and St. Jude Lifetime (SJLIFE) cohorts.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10014-10014
Author(s):  
Melissa A. Richard ◽  
Sogol Mostoufi-Moab ◽  
Nisha Rathore ◽  
Austin L. Brown ◽  
Stephen J. Chanock ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cancer Survivors ◽  
Cancer Treatment ◽  
Childhood Cancer ◽  
Regulatory Region ◽  
Childhood Cancer Survivors ◽  
Population Based ◽  
European Ancestry ◽  
Radiation Group ◽  
Increased Risk

10014 Background: Childhood cancer survivors face increased risk for DM, a polygenic trait also attributable to cancer treatment exposures, particularly abdominal radiation. We aimed to characterize the role of genetic and treatment risk factors for DM among two large cohorts of childhood cancer survivors. Methods: We performed a nested case-control genome-wide association study for DM managed with oral medications in the original CCSS cohort (diagnosed 1970-1986). Logistic regression was conducted in the total sample (N = 5083) and stratified by 1) European ancestry (EA) and 2) abdominal radiation. Replication of suggestive variants (P < 1×10-7) using Fisher’s exact test was performed in independent cohorts: i) CCSS expansion diagnosed 1987-1999 (N = 2588) and ii) SJLIFE diagnosed 1962-2012 (N = 2182). To evaluate the effect of cancer treatment on the background genetic predisposition to DM, we estimated standardized effect sizes (Z’) among EA survivors in each abdominal radiation group for 398 index variants from the largest population-based EA DM study. Radiation group Z’ estimates were compared using linear regression. Results: In the original CCSS cohort we identified nine variants associated with DM and provide further support for four linked variants in the ERCC6L2 locus. Among all survivors, the rs55849673-A allele was associated with increased odds for DM among survivors in the original CCSS cohort (minor allele frequency [MAF]-cases = 0.055; MAF-controls = 0.024; adjusted odds ratio [aOR] = 2.9, 95% CI: 2.0-4.2, P = 3.7×10-8). Allele frequencies were consistent in the CCSS expansion (MAF-cases = 0.075; MAF-controls = 0.028; P = 0.07) and SJLIFE (MAF-cases = 0.036; MAF-controls = 0.027; P = 0.5). Additionally, rs55849673-A estimates were consistent among EA survivors and stronger among survivors not treated with abdominal radiation (MAF-cases = 0.052; MAF-controls = 0.021; aOR = 3.6, P = 1.6×10-6). Notably, in the CCSS expansion all rs55849673-A EA carriers who developed DM did not receive abdominal radiation (MAF-cases = 0.1; MAF-controls = 0.026; P = 0.04). More broadly, the Z’ of population-based DM index variants were 78% lower in survivors treated with abdominal radiation than survivors not treated with abdominal radiation (beta = 0.22; P = 0.01), indicating the background genetic risk for DM may be altered by treatment. Conclusions: We provide evidence for a novel locus of DM in childhood cancer survivors. This locus is a regulatory region associated with expression of ERCC6L2, a gene implicated in an East Asian population-based DM study. Taken together, our findings support the overwhelming effect of abdominal radiation on DM risk in childhood cancer survivors, relative to other risk factors, and provide insight on a genetic locus that may be useful for DM risk prediction in the context of cancer treatment.

scholarly journals Pneumonia hospitalisation and case-fatality rates in older Australians with and without risk factors for pneumococcal disease: implications for vaccine policy

2019 ◽  
Vol 147 ◽  
Author(s):  
S. Dirmesropian ◽  
B. Liu ◽  
J. G. Wood ◽  
C. R. MacIntyre ◽  
P. McIntyre ◽  
...  
Keyword(s):  
Risk Factors ◽  
Older Adults ◽  
Risk Factor ◽  
Pneumococcal Disease ◽  
Large Population ◽  
Case Fatality ◽  
Population Based ◽  
Additional Risk Factor ◽  
Additional Risk ◽  
Non Invasive

AbstractCommunity-acquired pneumonia (CAP) results in substantial numbers of hospitalisations and deaths in older adults. There are known lifestyle and medical risk factors for pneumococcal disease but the magnitude of the additional risk is not well quantified in Australia. We used a large population-based prospective cohort study of older adults in the state of New South Wales (45 and Up Study) linked to cause-specific hospitalisations, disease notifications and death registrations from 2006 to 2015. We estimated the age-specific incidence of CAP hospitalisation (ICD-10 J12-18), invasive pneumococcal disease (IPD) notification and presumptive non-invasive pneumococcal CAP hospitalisation (J13 + J18.1, excluding IPD), comparing those with at least one risk factor to those with no risk factors. The hospitalised case-fatality rate (CFR) included deaths in a 30-day window after hospitalisation. Among 266 951 participants followed for 1 850 000 person-years there were 8747 first hospitalisations for CAP, 157 IPD notifications and 305 non-invasive pneumococcal CAP hospitalisations. In persons 65–84 years, 54.7% had at least one identified risk factor, increasing to 57.0% in those ⩾85 years. The incidence of CAP hospitalisation in those ⩾65 years with at least one risk factor was twofold higher than in those without risk factors, 1091/100 000 (95% confidence interval (CI) 1060–1122) compared with 522/100 000 (95% CI 501–545) and IPD in equivalent groups was almost threefold higher (18.40/100 000 (95% CI 14.61–22.87) vs. 6.82/100 000 (95% CI 4.56–9.79)). The CFR increased with age but there were limited difference by risk status, except in those aged 45 to 64 years. Adults ⩾65 years with at least one risk factor have much higher rates of CAP and IPD suggesting that additional risk factor-based vaccination strategies may be cost-effective.

scholarly journals Cardiovascular Effects in Childhood Cancer Survivors Treated with Anthracyclines

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Vivian I. Franco ◽  
Jacqueline M. Henkel ◽  
Tracie L. Miller ◽  
Steven E. Lipshultz
Keyword(s):  
Cancer Survivors ◽  
Childhood Cancer ◽  
Cardiovascular Effects ◽  
Childhood Cancer Survivors ◽  
Cardiovascular Complications ◽  
Anthracycline Cardiotoxicity ◽  
Treatment And Prevention ◽  
Artery Disease

Anthracyclines are commonly used to treat childhood leukemias and lymphomas, as well as other malignancies, leading to a growing population of long-term childhood cancer survivors. However, their use is limited by cardiotoxicity, increasing survivors' vulnerability to treatment-related complications that can markedly affect their quality of life. Survivors are more likely to suffer from heart failure, coronary artery disease, and cerebrovascular accidents compared to the general population. The specific mechanisms of anthracycline cardiotoxicity are complex and remain unclear. Hence, determining the factors that may increase susceptibility to cardiotoxicity is of great importance, as is monitoring patients during and after treatment. Additionally, treatment and prevention options, such as limiting cumulative dosage, liposomal anthracyclines, and dexrazoxane, continue to be explored. Here, we review the cardiovascular complications associated with the use of anthracyclines in treating malignancies in children and discuss methods for preventing, screening, and treating such complications in childhood cancer survivors.

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