Noncancer-related mortality risks in adult survivors of pediatric malignancies: The childhood cancer survivor study

Purpose: We sought to identify factors, other than cancer-related treatment and presence/severity of chronic health conditions, which may be associated with late mortality risk among adult survivors of pediatric malignancies. Methods: Using the Childhood Cancer Survivor Study cohort and a case-control design, 445 participants who died from causes other than cancer recurrence/progression or non-health-related events were compared with 7,162 surviving participants matched for primary diagnosis, age at baseline questionnaire, time from diagnosis to baseline questionnaire, and time at-risk. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated for overall/cause-specific mortality. Independent measures included number/severity of chronic conditions, medical care, health-related behaviors, and health perceptions/concerns. Results: Adjusting for education, income, chemotherapy/radiation exposures, and number/severity of chronic health conditions, an increased risk for all-cause mortality was associated with exercising fewer than 3 days/week (OR = 1.72, CI 1.27-2.34), being underweight (OR = 2.58, CI 1.55-4.28), increased medical care utilization (P \u3c 0.001), and self-reported fair to poor health (P \u3c 0.001). Physical activity was associated with a higher risk of death among males (OR = 3.26, CI 1.90-5.61) reporting no exercise compared to those who exercised ≥3 times per week. Ever consuming alcohol was associated with a reduced risk of all-cause (OR = 0.61, CI 0.41-0.89) and other nonexternal causes of death (OR = 0.40, CI 0.20-0.79). Concerns/worries about future health (OR = 1.54, CI 1.10-2.71) were associated with increased all-cause mortality. Conclusions: Factors independent of cancer treatment and chronic health conditions modify the risk of death among adult survivors of pediatric cancer. Implications for Cancer Survivors: Continued cohort observation may inform interventions to reduce mortality. © 2014 Springer Science+Business Media New York

Recurrent stroke in childhood cancer survivors

OBJECTIVE: To estimate the rates and predictors of recurrent stroke among survivors of pediatric cancer who have had a first stroke. METHODS: The Childhood Cancer Survivor Study is a retrospective cohort study with longitudinal follow-up that enrolled 14,358 survivors (<21 years old at diagnosis; diagnosed 1970–1986; survived ≥5 years after cancer diagnosis) and followed them prospectively since 1994. We surveyed 443 survivors who reported a first stroke to identify recurrent stroke, and estimated recurrent stroke rates ≥5 years after cancer diagnosis. RESULTS: Among 329 respondents (74% response rate), 271 confirmed a first stroke at a median age of 19 years (range 0–53), and 70 reported a second stroke at a median age of 32 years (range 1–56). In a multivariable Cox proportional hazards model, independent predictors of recurrent stroke included cranial radiation therapy (CRT) dose of ≥50 Gy (vs none, hazard ratio [HR] 4.4; 95% confidence interval [CI] 1.4–13.7), hypertension (HR 1.9; 95% CI 1.0–3.5), and older age at first stroke (HR 6.4; 95% CI 1.8–23; for age ≥40 vs age 0–17 years). The 10-year cumulative incidence of late recurrent stroke was 21% (95% CI 16%–27%) overall, and 33% (95% CI 21%–44%) for those treated with ≥50 Gy of CRT. CONCLUSION: Survivors of childhood cancer, particularly those previously treated with high-dose cranial radiation, have a high risk of recurrent stroke for decades after a first stroke. Although these strokes are mostly occurring in young adulthood, hypertension, an established atherosclerotic risk factor, independently predicts recurrent stroke in this population

Recurrent stroke in childhood cancer survivors.

ObjectiveTo estimate the rates and predictors of recurrent stroke among survivors of pediatric cancer who have had a first stroke.MethodsThe Childhood Cancer Survivor Study is a retrospective cohort study with longitudinal follow-up that enrolled 14,358 survivors (&lt;21 years old at diagnosis; diagnosed 1970-1986; survived ≥5 years after cancer diagnosis) and followed them prospectively since 1994. We surveyed 443 survivors who reported a first stroke to identify recurrent stroke, and estimated recurrent stroke rates ≥5 years after cancer diagnosis.ResultsAmong 329 respondents (74% response rate), 271 confirmed a first stroke at a median age of 19 years (range 0-53), and 70 reported a second stroke at a median age of 32 years (range 1-56). In a multivariable Cox proportional hazards model, independent predictors of recurrent stroke included cranial radiation therapy (CRT) dose of ≥50 Gy (vs none, hazard ratio [HR] 4.4; 95% confidence interval [CI] 1.4-13.7), hypertension (HR 1.9; 95% CI 1.0-3.5), and older age at first stroke (HR 6.4; 95% CI 1.8-23; for age ≥40 vs age 0-17 years). The 10-year cumulative incidence of late recurrent stroke was 21% (95% CI 16%-27%) overall, and 33% (95% CI 21%-44%) for those treated with ≥50 Gy of CRT.ConclusionSurvivors of childhood cancer, particularly those previously treated with high-dose cranial radiation, have a high risk of recurrent stroke for decades after a first stroke. Although these strokes are mostly occurring in young adulthood, hypertension, an established atherosclerotic risk factor, independently predicts recurrent stroke in this population

The global burden of childhood and adolescent cancer in 2017. An analysis of the Global Burden of Disease Study 2017

Force LM, Abdollahpour I, Advani SM, et al. The global burden of childhood and adolescent cancer in 2017. An analysis of the Global Burden of Disease Study 2017. Lancet Oncology. 2019;20(9):1211-1225.Background Accurate childhood cancer burden data are crucial for resource planning and health policy prioritisation. Model-based estimates are necessary because cancer surveillance data are scarce or non-existent in many countries. Although global incidence and mortality estimates are available, there are no previous analyses of the global burden of childhood cancer represented in disability-adjusted life-years (DALYs). Methods Using the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 methodology, childhood (ages 0-19 years) cancer mortality was estimated by use of vital registration system data, verbal autopsy data, and population-based cancer registry incidence data, which were transformed to mortality estimates through modelled mortality-to-incidence ratios (MIRs). Childhood cancer incidence was estimated using the mortality estimates and corresponding MIRs. Prevalence estimates were calculated by using MIR to model survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated by multiplying age-specific cancer deaths by the difference between the age of death and a reference life expectancy. DALYs were calculated as the sum of YLLs and YLDs. Final point estimates are reported with 95% uncertainty intervals. Findings Globally, in 2017, there were 11.5 million (95% uncertainty interval 10.6-12.3) DALYs due to childhood cancer, 97.3% (97.3-97.3) of which were attributable to YLLs and 2.7% (2.7-2.7) of which were attributable to YLDs. Childhood cancer was the sixth leading cause of total cancer burden globally and the ninth leading cause of childhood disease burden globally. 82.2% (82.1-82.2) of global childhood cancer DALYs occurred in low, low-middle, or middle Socio-demographic Index locations, whereas 50.3% (50.3-50.3) of adult cancer DALYs occurred in these same locations. Cancers that are uncategorised in the current GBD framework comprised 26.5% (26.5-26.5) of global childhood cancer DALYs. Interpretation The GBD 2017 results call attention to the substantial burden of childhood cancer globally, which disproportionately affects populations in resource-limited settings. The use of DALY-based estimates is crucial in demonstrating that childhood cancer burden represents an important global cancer and child health concern. (C) 2019 The Author(s). Published by Elsevier Ltd

Risk of COVID-19 after natural infection or vaccinationResearch in context

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health

Risk of COVID-19 after natural infection or vaccinationResearch in context

Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health