Summary Survivors of childhood cancer treated with anthracycline chemotherapy or chest radiation are at an increased risk of developing congestive heart failure. In this population, congestive heart ...failure is well recognised as a progressive disorder, with a variable period of asymptomatic cardiomyopathy that precedes signs and symptoms. As a result, several clinical practice guidelines have been developed independently to help with detection and treatment of asymptomatic cardiomyopathy. These guidelines differ with regards to definitions of at-risk populations, surveillance modality and frequency, and recommendations for interventions. Differences between these guidelines could hinder the effective implementation of these recommendations. We report on the results of an international collaboration to harmonise existing cardiomyopathy surveillance recommendations using an evidence-based approach that relied on standardised definitions for outcomes of interest and transparent presentation of the quality of the evidence. The resultant recommendations were graded according to the quality of the evidence and the potential benefit gained from early detection and intervention.
Health care systems and providers have a responsibility to ensure that access to cancer clinical trials, opportunities to complete the trial, and access to lifelong survivor care are all thoughtfully ...examined with an equity lens. This will allow the greatest possible number of pediatric and adolescent and young adult cancer patients to receive the highest quality of care possible, in treatment and beyond.
Among patients in whom childhood cancer was diagnosed in the 1970s and 1980s, 18% of those who survived for 5 years died within the subsequent 25 years. In recent decades, cancer treatments have been ...modified with the goal of reducing life-threatening late effects.
We evaluated late mortality among 34,033 patients in the Childhood Cancer Survivor Study cohort who survived at least 5 years after childhood cancer (i.e., cancer diagnosed before the age of 21 years) for which treatment was initiated during the period from 1970 through 1999. The median follow-up was 21 years (range, 5 to 38). We evaluated demographic and disease factors that were associated with death from health-related causes (i.e., conditions that exclude recurrence or progression of the original cancer and external causes but include the late effects of cancer therapy) using cumulative incidence and piecewise exponential models to estimate relative rates and 95% confidence intervals.
Of the 3958 deaths that occurred during the study period, 1618 (41%) were attributable to health-related causes, including 746 deaths from subsequent neoplasms, 241 from cardiac causes, 137 from pulmonary causes, and 494 from other causes. A reduction in 15-year mortality was observed for death from any cause (from 12.4% in the early 1970s to 6.0% in the 1990s, P<0.001 for trend) and from health-related causes (from 3.5% to 2.1%, P<0.001 for trend). These reductions were attributable to decreases in the rates of death from subsequent neoplasm (P<0.001), cardiac causes (P<0.001), and pulmonary causes (P=0.04). Changes in therapy according to decade included reduced rates of cranial radiotherapy for acute lymphoblastic leukemia (85% in the 1970s, 51% in the 1980s, and 19% in the 1990s), of abdominal radiotherapy for Wilms' tumor (78%, 53%, and 43%, respectively), of chest radiotherapy for Hodgkin's lymphoma (87%, 79%, and 61%, respectively), and of anthracycline exposure. Reduction in treatment exposure was associated with reduced late mortality among survivors of acute lymphoblastic leukemia and Wilms' tumor.
The strategy of lowering therapeutic exposure has contributed to an observed decline in late mortality among 5-year survivors of childhood cancer. (Funded by the National Cancer Institute and the American Lebanese-Syrian Associated Charities.).
Treatment outcomes among survivors of cancer diagnosed during adolescence and early young adulthood have not been characterised independently of survivors of cancers diagnosed during childhood. We ...aimed to describe chronic health conditions and all-cause and cause-specific mortality among survivors of early-adolescent and young adult cancer.
The Childhood Cancer Survivor Study (CCSS) is a retrospective cohort study with longitudinal follow-up of 5-year survivors diagnosed with cancer before the age of 21 years at 27 academic institutions in the USA and Canada between 1970 and 1999. We evaluated outcomes among survivors of early-adolescent and young adult cancer (aged 15–20 years at diagnosis) and survivors diagnosed at age younger than 15 years (matched on primary cancer diagnosis, including leukaemia, lymphoma, CNS tumours, neuroblastoma, Wilms tumour, soft-tissue sarcomas, and bone cancer) by comparing both groups to siblings of the same age. Mortality was ascertained with the National Death Index. Chronic health conditions were classified with the Common Terminology Criteria for Adverse Events. Standardised mortality ratios (SMRs) were estimated with age-specific, sex-specific, and calendar year-specific US rates. Cox proportional hazard models estimated hazard ratios (HRs) for chronic health conditions and 95% CIs.
Among 5804 early-adolescent and young adult survivors (median age 42 years, IQR 34–50) the SMR compared to the general population for all-cause mortality was 5·9 (95% CI 5·5–6·2) and among 5804 childhood cancer survivors (median age 34 years; 27–42), it was 6·2 (5·8–6·6). Early-adolescent and young adult survivors had lower SMRs for death from health-related causes (ie, conditions that exclude recurrence or progression of the primary cancer and external causes, but include the late effects of cancer therapy) than did childhood cancer survivors (SMR 4·8 95% CI 4·4–5·1 vs 6·8 6·2–7·4), which was primarily evident more than 20 years after cancer diagnosis. Early-adolescent and young adult cancer survivors and childhood cancer survivors were both at greater risk of developing severe and disabling, life-threatening, or fatal (grade 3–5) health conditions than siblings of the same age (HR 4·2 95% CI 3·7–4·8 for early adolescent and young adult cancer survivors and 5·6 4·9–6·3 for childhood cancer survivors), and at increased risk of developing grade 3–5 cardiac (4·3 3·5–5·4 and 5·6 4·5–7·1), endocrine (3·9 2·9–5·1 and 6·4 5·1–8·0), and musculoskeletal conditions (6·5 3·9–11·1 and 8·0 4·6–14·0) when compared with siblings of the same age, although all these risks were lower for early-adolescent and young adult survivors than for childhood cancer survivors.
Early-adolescent and young adult cancer survivors had higher risks of mortality and severe and life threatening chronic health conditions than the general population. However, early-adolescent and young adult cancer survivors had lower non-recurrent, health-related SMRs and relative risks of developing grade 3–5 chronic health conditions than childhood cancer survivors, by comparison with siblings of the same age, which were most notable more than 20 years after their original cancer. These results highlight the need for long-term screening of both childhood and early-adolescent and young adult cancer survivors.
National Cancer Institute and American Lebanese-Syrian Associated Charities.
Background
For parents, a diagnosis of cancer in their child is a traumatic experience. However, there is conflicting evidence about the risk of developing mental illness among parents following ...diagnosis. Our objective was to conduct a meta‐analysis to determine the prevalence of mental illness in parents of children with cancer.
Methods
Four databases were searched to identify articles describing the prevalence of anxiety, depression, or posttraumatic stress disorder (PTSD) in parents of pediatric cancer patients. Two reviewers independently screened and extracted data. Subgroup analyses by gender and phase of cancer experience were selected a priori. Studies were reviewed in accordance with PRISMA guidelines.
Results
Of 11 394 articles identified, 58 met inclusion criteria. Reported prevalence was highly heterogeneous, ranging from 5% to 65% for anxiety (pooled prevalence 21% 95% CI, 13%–35%), 7% to 91% for depression (pooled prevalence 28% 95% CI, 23%–35%), and 4% to 75% for PTSD (pooled prevalence 26% 95% CI, 22%–32%). Prevalence was consistently higher than noncancer parental controls. Heterogeneity was not explained by parental gender or child's cancer phase and was instead likely due to significant methodological differences in measurement tools and defined thresholds.
Conclusions
Parents of children with cancer have a higher prevalence of anxiety, depression, and PTSD compared with population controls. Yet, the reported prevalence of mental illness was highly variable, hampering any conclusive findings on absolute prevalence. To better understand the risk of long‐term mental illness in this population and target interventions, future studies must adhere to standardized reporting and methods.
Adolescents and young adults (AYA) with cancer are an understudied group. Much of what is known about long‐term outcomes after AYA cancer has been derived from cohorts of childhood cancer survivors, ...which seldom include patients at the older end of the AYA age spectrum. In general, AYA cancer survivors have a lower risk for premature mortality, subsequent primary neoplasms and chronic health conditions than childhood cancer survivors. However, AYA cancer survivors are vulnerable to psychosocial challenges, concerns about fertility and relationships and financial toxicity. No single model is optimal for the care of these survivors, but it is generally agreed that all survivors require a survivor care plan that promotes their adherence to evidence‐based surveillance guidelines. There is a need to create survivor cohorts that include the full range of AYA ages and diagnoses to be able to address the many pressing questions that remain unanswered in this vulnerable population.
Risk-stratified therapy, which modifies treatment on the basis of clinical and biologic features, has improved 5-year overall survival of childhood acute lymphoblastic leukemia (ALL) to 90%, but its ...impact on long-term toxicity remains unknown.
We assessed all-cause and health-related late mortality (including late effects of cancer therapy), subsequent malignant neoplasms (SMNs), chronic health conditions, and neurocognitive outcomes among 6,148 survivors of childhood ALL (median age, 27.9 years; range, 5.9-61.9 years) diagnosed between 1970 and 1999. Therapy combinations and treatment intensity defined 6 groups: 1970s-like (70s), standard- or high-risk 1980s-like (80sSR, 80sHR) and 1990s-like (90sSR, 90sHR), and relapse/transplantation (R/BMT). Cumulative incidence, standardized mortality ratios, and standardized incidence ratios were compared between treatment groups and with the US population.
Overall, 20-year all-cause late mortality was 6.6% (95% CI, 6.0 to 7.1). Compared with 70s, 90sSR and 90sHR experienced lower health-related late mortality (rate ratio 95% CI: 90sSR, 0.2 0.1 to 0.4; 90sHR, 0.3 0.1 to 0.7), comparable to the US population (standardized mortality ratio 95% CI: 90sSR, 1.3 0.8 to 2.0; 90sHR, 1.7 0.7 to 3.5). Compared with 70s, 90sSR had a lower rate of SMN (rate ratio 95% CI, 0.3 0.1 to 0.6) that was not different from that of the US population (standardized incidence ratio 95% CI, 1.0 0.6 to 1.6). The 90sSR group had fewer severe chronic health conditions than the 70s (20-year cumulative incidence 95% CI, 11.0% 9.7% to 12.3%
22.5% 19.4% to 25.5%) and a lower prevalence of impaired memory (prevalence ratio 95% CI, 0.7 0.6 to 0.9) and task efficiency (0.5 0.4 to 0.7).
Risk-stratified therapy has reduced late morbidity and mortality among contemporary survivors of standard-risk ALL, represented by 90sSR. Health-related late mortality and SMN risks among 5-year survivors of contemporary, standard-risk childhood ALL are comparable to the general population.
Disinfectant quaternary ammonium compounds (Quats) have diverse uses in a variety of consumer and commercial products, particularly cleaning products. With the emergence of the COVID-19 pandemic, ...they have become a primary tool to inactivate the SARS-CoV-2 virus on surfaces. Disinfectant Quats have very low vapor pressure, and following the use phase of the products in which they are found, disposal is typically “down-the-drain” to wastewater treatment systems. Consequently, the potential for the greatest environmental effect is to the aquatic environment, from treated effluent, and potentially to soils, which might be amended with wastewater biosolids. Among the earliest used and still common disinfectant Quats are the alkyl dimethyl benzyl ammonium chloride (ADBAC) compounds and the dialkyl dimethyl ammonium chloride (DDAC) compounds. They are cationic surfactants often found in consumer and commercial surface cleaners. Because of their biocidal properties, disinfectant Quats are heavily regulated for human and environmental safety around the world. Consequently, there is a robust database of information regarding the ecological hazards and environmental fate of ADBAC and DDAC; however, some of the data presented are from unpublished studies that have been submitted to and reviewed by regulatory agencies (i.e., EPA and European Chemicals Agency) to support antimicrobial product registration. We summarize the available environmental fate data and the acute and chronic aquatic ecotoxicity data for freshwater species, including algae, invertebrates, fish, and plants using peer-reviewed literature and unpublished data submitted to and summarized by regulatory agencies. The lower limit of the range of the ecotoxicity data for disinfectant Quats tends to be lower than that for other surface active agents, such as nonionic or anionic surfactants. However, ecotoxicity is mitigated by environmental fate characteristics, the data for which we also summarize, including high biodegradability and a strong tendency to sorb to wastewater biosolids, sediment, and soil. As a result, disinfectant Quats are largely removed during wastewater treatment, and those residues discharged in treated effluent are likely to rapidly bind to suspended solids or sediments, thus mitigating their toxicity.
•Robust databases exist for environmental toxicity and fate of ADBAC and DDAC.•Ecotoxicity of ADBAC and DDAC is greater than that for other surface active agents.•ADBAC/DDAC are removed during wastewater treatment by biodegradation and sorption.•The ecotoxicity of DDAC and ADBAC is mitigated by environmental fate characteristics.
Several randomized controlled trials (RCTs) have demonstrated that dexrazoxane reduces anthracycline cardiotoxicity in adults, but use in children has been hindered by lack of direct evidence of ...cardioprotection and concerns regarding second malignant neoplasms (SMNs). This study aimed to systematically review the evidence regarding dexrazoxane in children.
We searched Medline, Embase, the Cochrane Library, and abstracts for RCTs and nonrandomized studies (NRSs) that compared dexrazoxane to no cardioprotection among children. We combined findings using random-effects models. All statistical tests were two-sided.
Eleven eligible publications reported results from five RCTs (1254 patients), and 15 publications reported results from 12 NRSs (3385 patients). Dexrazoxane did not impact clinical cardiotoxicity in RCTs because of a low cardiotoxic event rate (three events among all patients) but was associated with a reduction in subclinical cardiotoxicity. Among NRSs, dexrazoxane was associated with a reduction in clinical cardiotoxicity (relative risk (RR) = 0.29, P = .001) and clinical+subclinical cardiotoxicity (RR = 0.43, P < .001). Among RCTs, 17 of 635 (2.7%) patients treated with dexrazoxane developed an SMN compared with seven of 619 (1.1%) who did not receive dexrazoxane (RR = 2.37, P = .06). Two RCTs that used concurrent etoposide reported an increased risk of acute myeloid leukemia, while one that used cranial radiation reported an increased risk of brain tumors. Event-free survival did not differ (P = .91).
Dexrazoxane is associated with a statistically significant risk reduction for most cardiotoxic outcomes. Dexrazoxane is associated with a statistically borderline increase in SMNs, possibly because of an interaction with concurrent cancer therapies. The decision to use dexrazoxane in children should balance the risks of cardiotoxicity and SMNs specific to each treatment protocol.
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