Mortality among five-year survivors of childhood cancer: Results over five decades of follow-up in the Childhood Cancer Survivor Study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10013-10013
Author(s):  
Stephanie B Dixon ◽  
Qi Liu ◽  
Matthew J. Ehrhardt ◽  
Eric Jessen Chow ◽  
Kevin C. Oeffinger ◽  
...  
Keyword(s):  
Childhood Cancer ◽  
Primary Cancer ◽  
Cumulative Mortality ◽  
Late Mortality ◽  
Risk Of Death ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Health Related ◽  
Survivors Of Childhood Cancer

10013 Background: Adult survivors of childhood cancer are at greater risk for late mortality compared to the general population due to cancer and its treatment. Risk factors, patterns and specific causes of late mortality across the lifespan are not well established. Methods: All-cause, cause-specific, and health-related late mortality (HRM; excludes death from primary cancer and external causes) > 5 years from diagnosis were evaluated in survivors diagnosed < 21 years of age between 1970-1999. Cause of death was based on ICD codes from the National Death Index through December 2017. Cumulative mortality, mortality rates and standardized mortality ratios (SMRs) with 95% confidence intervals (CIs) were estimated, overall and in 5- and 10-year survival periods. Results: Among 34,230 survivors (median time from diagnosis 29.1 years, range 5.0 - 48.0) the 40-year cumulative mortality was 23.3% (95% CI 22.7 - 24.0). Of 5,916 deaths, 3,061 (51.2%) were attributable to health-related causes including subsequent neoplasm (n = 1,458), cardiac (n = 504), and pulmonary causes (n = 238). All-cause mortality by time from diagnosis demonstrated a U-shaped distribution: 10.1 deaths/1000 person-years at 5-9 years, largely due to recurrence of the primary cancer, decreasing to 4.1 at 15-19 years before increasing to 18.5 at 40-48 years, attributable to an increasing mortality rate from HRM (2.3 at 5-9 years; 17.0 at 40-48 years). For the interval 5-9 years from diagnosis, survivors had an 18.1-fold (95% CI 17.3-18.9) higher risk of death from any cause, and a 13.1-fold (11.9-13.4) higher risk for HRM when compared to the general population. Although the SMRs declined with duration of follow-up, survivors had a 4-fold higher risk of death overall, attributable to a more than 4-fold increased risk of HRM. HRM 40-48 years from diagnosis was largely attributable to an increased risk of death due to subsequent neoplasm (SMR 6.0, 95% CI 4.9-7.2), cardiac (3.9, 2.9-5.0) and pulmonary (5.6, 3.6-8.4) causes. Cause-specific mortality remained markedly elevated at 40-48 years from diagnosis: CNS malignancy (SMR 11.7, 95% CI 5.4-22.3), benign meningioma (171.3, 34.4-500.5), valvular heart disease (39.8, 21.2-68.1), cardiomyopathy (10.4, 4.5-20.5), stroke (7.9, 4.6-12.6), and renal failure (5.6, 1.8-13.2). HRM was significantly higher among the youngest group of survivors (0-4 years at diagnosis), non-Hispanic blacks and those who received radiation to the brain, chest or total body, or who were exposed to anthracycline, alkylating or platinum chemotherapy. Conclusions: After five decades, aging survivors consistently remain at higher risk of all-cause mortality compared to the general, aging population, primarily due to a persistent 4-fold increased risk of HRM. Continued late-effects surveillance and reduction of therapies associated with long-term morbidity and increased mortality is essential.

Comparing late mortality risks among childhood cancer survivors: A report from the Childhood Cancer Survivor Study and British Childhood Cancer Survivor Study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 10017-10017
Author(s):  
Miranda Marie Fidler ◽  
Kevin C. Oeffinger ◽  
Yutaka Yasui ◽  
David L Winter ◽  
Wendy Leisenring ◽  
...  
Keyword(s):  
Childhood Cancer ◽  
Cancer Survivor ◽  
Childhood Cancer Survivor ◽  
Late Effect ◽  
Cumulative Mortality ◽  
Late Mortality ◽  
Mortality Risks ◽  
All Cause Mortality ◽  
Health Related ◽  
Childhood Cancer Survivor Study

10017 Background: It is unclear whether late-effect risks are comparable across international settings. We compared late mortality risks in the Childhood Cancer Survivor Study (CCSS) and British Childhood Cancer Survivor Study (BCCSS). Methods: 46,474 5-year survivors of childhood cancer diagnosed from 1970-1999 and < 15 years age were included: 28,248 from the CCSS and 18,226 from the BCCSS. Late mortality (death ≥5 years from diagnosis) was assessed by linking to national vital statistics records. Adjusted ratios of the standardized mortality ratio (RSMR) and cumulative mortality probabilities were used to compare risks between cohorts. Treatment exposures were not available for the BCCSS, precluding comparison. Results: The cumulative all-cause mortality at 10 years from diagnosis was significantly lower in the CCSS (4.8%;95%CI:4.6%-5.0%) compared to the BCCSS (6.9%;95%CI:6.5%-7.2%); this was due to a lower probability of death from recurrence/progression of the primary cancer (CCSS = 3.3% vs. BCCSS = 5.8%), with significant differences observed in survivors of leukemia (7.9% vs 4.0%), Hodgkin lymphoma (2.5% vs 1.3%), CNS tumors (6.4% vs 4.4%), and sarcoma (6.5% vs 4.0%). However, with increasing time from diagnosis, risks became more similar. The CCSS ultimately had a greater cumulative mortality at 40 years from diagnosis, attributable to a 2-fold higher mortality from subsequent neoplasms (SNs) (RSMR:2.0;95%CI:1.8-2.3), cardiac (RSMR:1.7;95%CI:1.4-2.3) and pulmonary (RSMR:1.9;95%CI:1.4-2.5) causes, and other health-related deaths (RSMR:2.4;95%CI:2.1-2.9). When assessed by follow-up interval, the differences between the CCSS and BCCSS increased significantly for deaths due to SNs, cardiac and pulmonary causes, and other health-related deaths as time increased. Among those diagnosed more recently, the gap in all-cause mortality widened, with CCSS survivors diagnosed 1990-1999 experiencing approximately half the excess (RSMR:0.5;95%CI:0.5-0.6) observed in the BCCSS; this widening was driven by declines in the RSMR for most non-recurrence/progression causes of death. Conclusions: Our findings suggest that North American survivors may have received more intensive regimens during this time period to achieve sustainable remission and cure. However, the cost of this approach was a higher risk of death from late-effects. Which approach confers a net survival advantage will depend critically on the magnitude of the excess risk of late-effect deaths as the cohorts age.

Accelerated aging and mortality in long-term survivors of childhood cancer: A report from the St. Jude Lifetime Cohort (SJLIFE).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10045-10045
Author(s):  
AnnaLynn M. Williams ◽  
Jeanne S. Mandelblatt ◽  
Mingjuan Wang ◽  
Kirsten K. Ness ◽  
Gregory T. Armstrong ◽  
...  
Keyword(s):  
Childhood Cancer ◽  
Proportional Hazards ◽  
Accelerated Aging ◽  
Cox Proportional Hazards ◽  
Premature Aging ◽  
Self Report ◽  
Deficit Accumulation ◽  
Risk Of Death ◽  
Increased Risk ◽  
Survivors Of Childhood Cancer

10045 Background: Survivors of childhood cancer have functional limitations and health-related morbidity consistent with an accelerated aging phenotype. We characterized aging using a Deficit Accumulation Index (DAI) which examines the accumulation of multiple aging-related deficits readily available from medical records and self-report. DAI’s are used as surrogates of biologic aging and are validated to predict mortality in adult cancer patients. Methods: We included childhood cancer survivors (N = 3,758, mean age 30 [SD 8], 22 [9] years post diagnosis, 52% male) and community controls (N = 575, mean age 34 [10] 44% male) who completed clinical assessments and questionnaires and who were followed for mortality through December 31st, 2018 (mean follow-up 6.1 [3.1] years). Using the initial SJLIFE clinical assessment, a DAI score was generated as the proportion of deficits out of 44 items related to aging, including chronic conditions (e.g. hearing loss, hypertension), psychosocial and physical function, and activities of daily living. The total score ranged 0 to 1; scores > 0.20 are robust, while moderate and large clinically meaningful differences are 0.02 and 0.06, respectively. Linear regression compared the DAI in survivors and controls with an age*survivor/control interaction and examined treatment associations in survivors. Cox-proportional hazards models estimated risk of death associated with DAI. All models were adjusted for age, sex, and race. Results: Mean [SD] of DAI was 0.17 [0.11] for survivors and 0.10 [0.08] for controls. 32% of survivors had a DAI above the 90th percentile of the control distribution (p < 0.001). After adjustment for covariates, survivors had a statistically and clinically meaningfully higher DAI score than controls (β = 0.072 95%CI 0.062, 0.081; p < 0.001). When plotted against age, the adjusted DAI at the average age of survivors (30 years) was 0.166 (95% CI 0.160,0.171), which corresponded to 60 years of age in controls, suggesting premature aging of 30 years. The mean difference in DAI between survivors and controls increased with age from 0.06 (95% CI 0.04, 0.07) at age 20 to 0.11 (95% CI 0.08, 0.13) at age 60, consistent with an accelerated aging phenotype (p = 0.014). Cranial radiation, abdominal radiation, cyclophosphamide, platinum agents, neurosurgery, and amputation were each associated with a higher DAI (all p≤0.001). Among survivors, a 0.06 increase in DAI was associated with a 41% increased risk of all-cause mortality (HR 1.41 95%CI 1.32, 1.50; p < 0.001). Conclusions: Survivors of childhood cancer experience significant age acceleration that is associated with an increased risk of mortality; longitudinal analyses are underway to validate these findings. Given the ease of estimating a DAI, this may be a feasible method to quickly identify survivors for novel and tailored interventions that can improve health and prevent premature mortality.

D-dimer and the incidence of heart failure and mortality after acute myocardial infarction

Heart ◽  
2020 ◽  
pp. heartjnl-2020-316880 ◽  
Author(s):  
Xiaoyuan Zhang ◽  
Shanjie Wang ◽  
Jinxin Liu ◽  
Yini Wang ◽  
Hengxuan Cai ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Acute Myocardial Infarction ◽  
Plaque Rupture ◽  
Risk Of Death ◽  
Increased Risk ◽  
Clinical Covariates ◽  
All Cause Mortality ◽  
D Dimer

ObjectiveD-dimer might serve as a marker of thrombogenesis and a hypercoagulable state following plaque rupture. Few studies explore the association between baseline D-dimer levels and the incidence of heart failure (HF), all-cause mortality in an acute myocardial infarction (AMI) population. We aimed to explore this association.MethodsWe enrolled 4504 consecutive patients with AMI with complete data in a prospective cohort study and explored the association of plasma D-dimer levels on admission and the incidence of HF, all-cause mortality.ResultsOver a median follow-up of 1 year, 1112 (24.7%) patients developed in-hospital HF, 542 (16.7%) patients developed HF after hospitalisation and 233 (7.1%) patients died. After full adjustments for other relevant clinical covariates, patients with D-dimer values in quartile 3 (Q3) had 1.51 times (95% CI 1.12 to 2.04) and in Q4 had 1.49 times (95% CI 1.09 to 2.04) as high as the risk of HF after hospitalisation compared with patients in Q1. Patients with D-dimer values in Q4 had more than a twofold (HR 2.34; 95% CI 1.33 to 4.13) increased risk of death compared with patients in Q1 (p<0.001). But there was no association between D-dimer levels and in-hospital HF in the adjusted models.ConclusionsD-dimer was found to be associated with the incidence of HF after hospitalisation and all-cause mortality in patients with AMI.

Long-term incidence of venous thromboembolism (VTE) among survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 10562-10562
Author(s):  
Arin L Madenci ◽  
Brent Weil ◽  
Qi Liu ◽  
Todd M. Gibson ◽  
Yutaka Yasui ◽  
...  
Keyword(s):  
High Risk ◽  
Childhood Cancer ◽  
Chronic Conditions ◽  
Malignant Neoplasm ◽  
Cancer Recurrence ◽  
Care Providers ◽  
Second Malignant Neoplasm ◽  
Increased Risk ◽  
Survivors Of Childhood Cancer

10562 Background: This study aimed to estimate the incidence of late-occurring VTE among survivors of childhood cancer, and to identify associated demographic and clinical factors that define high-risk subgroups for potential screening and prevention. Methods: Using data from CCSS, a multi-institutional, longitudinal cohort of 5-year survivors of childhood cancer (diagnosed 1970-1999) and their siblings, the primary endpoint of self-reported late VTE (occurring ≥5 years after diagnosis) was estimated using multivariable piecewise exponential models adjusted for age, sex, and race. Generalized estimating equations accounted for potential within-family correlation where applicable. Results: Among 23,601 survivors and 5051 siblings, the incidence of VTE was 1.15 and 0.48 events per 1000 person-years, respectively. For survivors, median age at last follow-up was 28.6 years (range 5.6-58.3) and median follow-up time from diagnosis was 21.2 years (range 5.0-39.3). The adjusted rate ratio (RR) for survivors compared to siblings was 2.2 (95% confidence interval [CI] = 1.7-2.8, P< 0.01). Among survivors, risk factors for VTE included BMI≥30kg/m2 (ref. BMI 18.5-24.5; RR = 1.5, CI = 1.2-2.0, P< 0.01), increasing number of severe or life-threatening (i.e. CTCAE grades 3 or 4) non-VTE chronic conditions (ref. 0 conditions; 1-2 conditions: RR = 2.5, CI = 2.0-3.1, P< 0.01 ; ≥3 conditions: RR = 3.5, CI = 2.5-4.9, P< 0.01), and cancer recurrence or second malignant neoplasm (RR = 3.5, CI = 2.7-4.6, P< 0.01). Incidence of late VTE was associated with increased subsequent mortality, independent of non-VTE chronic conditions (RR 2.2, 95% CI = 1.7-2.8, P< 0.01). Conclusions: Survivors of childhood cancer remain at increased risk for VTE across their lifespan. While typically not causal, late VTE was associated with subsequent mortality. Care providers should be aware of this increased risk and consider interventions that target modifiable co-morbidities such as obesity. Surveillance and education should be directed toward high-risk survivors.

Asymptomatic Deep Vein Thrombosis is Associated with an Increased Risk of Death: Insights from the APEX Trial

2018 ◽  
Vol 118 (12) ◽  
pp. 2046-2052 ◽  
Author(s):  
Arzu Kalayci ◽  
C. Gibson ◽  
Gerald Chi ◽  
Megan Yee ◽  
Serge Korjian ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Cardiovascular Diseases ◽  
Linear Trend ◽  
Vein Thrombosis ◽  
Risk Of Death ◽  
Increased Risk ◽  
Compression Ultrasound ◽  
All Cause Mortality ◽  
Deep Vein

Aim Asymptomatic deep vein thrombosis (DVT) diagnosed with compression ultrasound (CUS) is a common endpoint in trials assessing the efficacy of anticoagulants to prevent venous thromboembolism (VTE), but the relationship of asymptomatic thrombus to mortality remains uncertain. Methods In the APEX trial (ClinicalTrials.gov: NCT01583218), 7,513 acutely ill hospitalized medical patients were randomly assigned to extended-duration betrixaban (35–42 days) or enoxaparin (10 ± 4 days). Asymptomatic DVT was assessed once with CUS between day 32 and 47, and mortality was assessed through 77 days. Results A total of 309 asymptomatic DVTs were detected through CUS. Of these, 133 (4.27%) subjects were in the betrixaban group, and 176 (5.55%) subjects were in the enoxaparin group (relative risk = 0.77, 95% confidence interval [CI] = 0.62–0.97, p = 0.025, number needed to treat = 79). With respect to all-cause mortality due to cardiovascular diseases, non-cardiovascular diseases and unknown causes, the number of the deaths was 5 (1.67%), 4 (1.34%) and 1 (0.33%) in the asymptomatic DVT group and 25 (0.42%), 33 (0.56%) and 11 (0.19%) in the no DVT group, respectively. Subjects with an asymptomatic DVT had an almost threefold increase in the risk of all-cause mortality compared with subjects without DVT (hazard ratio = 2.87, 95% CI = 1.48–5.57, p = 0.001). A positive linear trend was observed between greater thrombus burden and mortality during the follow-up (p = 0.019). Conclusion Asymptomatic DVT was associated with approximately threefold increased risk of short-term all-cause mortality in patients hospitalized with an acute medical illness within the prior 77 days. A positive linear trend was observed between greater thrombus burden and mortality during the follow-up.

Abstract P009: Risk of Mortality According to Burden of Atrial Fibrillation: Results From a 60-year Cohort Study

Circulation ◽  
2016 ◽  
Vol 133 (suppl_1) ◽  
Author(s):  
William F McIntyre ◽  
Mahmoud Tourabi ◽  
Philip D St John ◽  
Robert B Tate
Keyword(s):  
Atrial Fibrillation ◽  
Adverse Events ◽  
Sinus Rhythm ◽  
Proportional Hazards ◽  
Anticoagulation Therapy ◽  
Cox Proportional Hazards ◽  
Risk Of Death ◽  
Increased Risk ◽  
All Cause Mortality

Introduction: Atrial Fibrillation (AF) is the most common serious cardiac arrhythmia and is associated with an increased risk of stroke and mortality. These risks can be modified with oral anticoagulation therapy. Clinically, the arrhythmia can be permanent or intermittent. Prior studies that have used time-constant, categorical covariates to examine the relationship between the pattern of AF and the occurrence of adverse events have produced conflicting results. We hypothesized that the amount of time that patients spend in AF, hereinafter termed arrhythmia “burden”, may be important in predicting adverse events. Objective: To examine the effects of the burden of AF on all-cause mortality. Methods: The Manitoba Follow-Up Study is a longitudinal, prospective study of 3983 originally healthy young men (mean age at entry 30 years) who have been followed with routine medical and electrocardiographic examinations since 1948. After 60 years of follow-up to July 1, 2008, AF had been documented on the electrocardiograms of 581 men (15% of the cohort) and 3182 (80%) of the original cohort had died. We created a Cox proportional hazards model with time-dependent covariates to estimate relative risks for mortality according to AF burden. AF status during each follow-up visit was classified as persistent when the patient was in AF on consecutive examinations, transient when the patient reverted to sinus rhythm after being in AF and incident when the patient developed AF after a period in sinus rhythm. Results: Results of the Cox proportional hazards regression model are displayed in the Table. Age, persistent AF and incident AF were all significant variables in the model. Holding all the other variables constant, persistent AF increased the risk of death by two times and incident AF increased the risk of death by 87%. Conclusions: Persistent AF and incident AF are associated with increased all-cause mortality. Estimating AF burden may have implications for risk stratification in patients with AF.

scholarly journals Endocrine Abnormalities in Aging Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study

2016 ◽  
Vol 34 (27) ◽  
pp. 3240-3247 ◽  
Author(s):  
Sogol Mostoufi-Moab ◽  
Kristy Seidel ◽  
Wendy M. Leisenring ◽  
Gregory T. Armstrong ◽  
Kevin C. Oeffinger ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
High Risk ◽  
Childhood Cancer ◽  
Cancer Survivor ◽  
Primary Hypothyroidism ◽  
Childhood Cancer Survivor ◽  
Increased Risk ◽  
Childhood Cancer Survivor Study ◽  
Survivors Of Childhood Cancer

Purpose The development of endocrinopathies in survivors of childhood cancer as they age remains understudied. We characterized endocrine outcomes in aging survivors from the Childhood Cancer Survivor Study on the basis of therapeutic exposures. Patients and Methods We analyzed self-reported conditions in 14,290 5-year survivors from the Childhood Cancer Survivor Study, with a median age 6 years (range, < 1 to 20 years) at diagnosis and 32 years (range, 5 to 58 years) at last follow-up. Identification of high-risk therapeutic exposures was adopted from the Children’s Oncology Group Long-Term Follow-Up Guidelines. Cumulative incidence curves and prevalence estimates quantified and regression models compared risks of primary hypothyroidism, hyperthyroidism, thyroid neoplasms, hypopituitarism, obesity, diabetes mellitus, or gonadal dysfunction between survivors and siblings. Results The cumulative incidence and prevalence of endocrine abnormalities increased across the lifespan of survivors (P < .01 for all). Risk was significantly higher in survivors exposed to high-risk therapies compared with survivors not so exposed for primary hypothyroidism (hazard ratio [HR], 6.6; 95% CI, 5.6 to 7.8), hyperthyroidism (HR, 1.8; 95% CI, 1.2 to 2.8), thyroid nodules (HR, 6.3; 95% CI, 5.2 to 7.5), thyroid cancer (HR, 9.2; 95% CI, 6.2 to 13.7), growth hormone deficiency (HR, 5.3; 95% CI, 4.3 to 6.4), obesity (relative risk, 1.8; 95% CI, 1.7 to 2.0), and diabetes mellitus (relative risk, 1.9; 95% CI, 1.6 to 2.4). Women exposed to high-risk therapies had six-fold increased risk for premature ovarian insufficiency (P < .001), and men demonstrated higher prevalence of testosterone replacement (P < .001) after cyclophosphamide equivalent dose of 20 g/m2 or greater or testicular irradiation with 20 Gy or greater. Survivors demonstrated an increased risk for all thyroid disorders and diabetes mellitus regardless of treatment exposures compared with siblings (P < .001 for all). Conclusion Endocrinopathies in survivors increased substantially over time, underscoring the need for lifelong subspecialty follow-up of those at risk.

scholarly journals Association Between Fasting Plasma Triglycerides, All-Cause and Cardiovascular Mortality in Czech Population. Results From the HAPIEE Study

2015 ◽  
pp. S355-S361 ◽  
Author(s):  
H. PIKHART ◽  
J. A. HUBÁČEK ◽  
A. PEASEY ◽  
R. KUBÍNOVÁ ◽  
M. BOBÁK
Keyword(s):  
Cardiovascular Mortality ◽  
Reference Group ◽  
Statistical Significance ◽  
Elevated Risk ◽  
Plasma Triglycerides ◽  
Risk Of Death ◽  
Increased Risk ◽  
All Cause Mortality ◽  
The Relationship

Dyslipidemia is the risk factor of cardiovascular disease, but the relationship between the plasma triglyceride (TG) levels and total/cardiovascular mortality has not yet been analyzed in Slavs. The aim of our study was to analyze the association between the fasting TG levels and all-cause/cardiovascular mortality. We have examined 3,143 males and 3,650 females, aged 58.3±7.1 years. 729 deaths (274 cardiovascular deaths) have been registered during up to 11.8 years of follow-up. Age-sex adjusted all-cause mortality was higher in individuals with TG values 3.01-4.00 mmol/l (HR 1.37, 95 % CI 1.02-1.83, P=0.035) and over 4.00 mmol/l (HR 1.66, 95 % CI 1.21-2.27, P=0.002) when compared with a reference group (TG 1.41-1.80 mmol/l). Elevated risk remains significant when adjusted for education, marital status and unemployment. When further adjusted for smoking, BMI and dyslipidemia interventions, HR for those in above 4.00 mmol/l group decreased (1.42, P=0.04). The results have been similar when cardiovascular mortality has been examined, however, results reached statistical significance only for the TG over 4.0 mmol/l (P=0.028). Our results confirmed that enhanced plasma levels of plasma triglycerides are dose dependently associated with increased risk of all-cause mortality, however, it seems that individuals with TG values 1.8-3.0 mmol/l are not in higher risk of death.

Long-Term Risk of Venous Thromboembolism in Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study

2018 ◽  
Vol 36 (31) ◽  
pp. 3144-3151 ◽  
Author(s):  
Arin L. Madenci ◽  
Brent R. Weil ◽  
Qi Liu ◽  
Andrew J. Murphy ◽  
Todd M. Gibson ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Cancer Survivor ◽  
Childhood Cancer Survivors ◽  
Increased Risk ◽  
Childhood Cancer Survivor Study ◽  
Survivors Of Childhood Cancer

Purpose To estimate the incidence of late-occurring venous thromboembolism (VTE) among survivors of childhood cancer and to identify risk factors for VTE to facilitate diagnosis and prevention. Methods The Childhood Cancer Survivor Study is a multi-institutional cohort of 24,355 5-year childhood cancer survivors (diagnosed between 1970 and 1999; median age at last follow-up, 28.7 years [range, 5.6 to 58.9 years]; median follow-up since diagnosis, 21.3 years [range, 5.0 to 39.2 years]) and 5,051 sibling participants. The primary end point was self-reported late (≥ 5 years after cancer diagnosis) VTE. Rate ratios (RRs) were estimated with multivariable piecewise exponential models. Results Late VTE incidence among survivors and siblings was 1.1 and 0.5 events per 1,000 person-years, respectively (RR, 2.2; 95% CI, 1.7 to 2.8), with 2.5 excess events per 100 survivors over 35 years. Among survivors, risk factors for VTE were female sex (RR, 1.3; 95% CI, 1.1 to 1.6), cisplatin (reference none; 1 to 199 mg/m2: RR, 3.0 [95% CI, 1.4 to 6.5]; 200 to 399 mg/m2: RR, 1.9 [95% CI, 1.0 to 3.6]; ≥ 400 mg/m2: RR, 2.0 [95% CI, 1.2 to 3.3]), l-asparaginase (RR, 1.3; 95% CI, 1.0 to 1.7), obesity or underweight (reference body mass index [BMI] 18.5 to 24.9 kg/m2; BMI ≥ 30.0 kg/m2: RR, 1.6 [95% CI, 1.2 to 2.0]; BMI < 18.5 kg/m2: RR, 2.4 [95% CI, 1.7 to 3.4]), and late cancer recurrence or subsequent malignant neoplasm (RR, 4.6; 95% CI, 3.6 to 5.8). Among lower-extremity osteosarcoma survivors, limb salvage (reference amputation; RR, 3.1; 95% CI, 1.2 to 7.5) and cisplatin 200 to 399 or ≥ 400 mg/m2 (reference none; RR, 4.0 [95% CI, 1.1 to 14.6] and 2.9 [95% CI, 1.1 to 8.0], respectively) were independently associated with late VTE. VTE was associated with increased risk for nonexternal cause late mortality (RR, 1.9; 95% CI, 1.6 to 2.3). Conclusion Childhood cancer survivors are at increased risk for VTE across their lifespan and a diagnosis of VTE increases mortality risk. Interventions that target potentially modifiable comorbidities, such as obesity, warrant consideration, with prophylaxis for high-risk survivors, including those treated with cisplatin and limb-sparing approaches.

scholarly journals Predicting the probability of death using proteomics

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Thjodbjorg Eiriksdottir ◽  
Steinthor Ardal ◽  
Benedikt A. Jonsson ◽  
Sigrun H. Lund ◽  
Erna V. Ivarsdottir ◽  
...  
Keyword(s):  
Mortality Risk ◽  
Large Scale ◽  
Survival Prediction ◽  
Risk Of Death ◽  
All Cause Mortality ◽  
Health Related ◽  
Short And Long Term ◽  
Probability Of Death

AbstractPredicting all-cause mortality risk is challenging and requires extensive medical data. Recently, large-scale proteomics datasets have proven useful for predicting health-related outcomes. Here, we use measurements of levels of 4,684 plasma proteins in 22,913 Icelanders to develop all-cause mortality predictors both for short- and long-term risk. The participants were 18-101 years old with a mean follow up of 13.7 (sd. 4.7) years. During the study period, 7,061 participants died. Our proposed predictor outperformed, in survival prediction, a predictor based on conventional mortality risk factors. We could identify the 5% at highest risk in a group of 60-80 years old, where 88% died within ten years and 5% at the lowest risk where only 1% died. Furthermore, the predicted risk of death correlates with measures of frailty in an independent dataset. Our results show that the plasma proteome can be used to assess general health and estimate the risk of death.

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