Cardiac Dysfunction Among Breast Cancer Survivors: Role of Cardiotoxic Therapy and Cardiovascular Risk Factors.

PURPOSE: Cardiac dysfunction is the leading cause of mortality among 10-year breast cancer survivors. Limited information regarding long-term risks of cardiac dysfunction after cardiotoxic therapy (anthracyclines, trastuzumab/pertuzumab, radiation) has precluded development of surveillance guidelines for the survivors. METHODS: Patients with breast cancer who completed cardiotoxic therapy underwent echocardiographic screening every 2 years. New-onset cardiac dysfunction was defined as left ventricular ejection fraction (LVEF) <50% after cardiotoxic therapy initiation and included early- and late-onset cardiac dysfunction. RESULTS: We evaluated 2,808 echocardiograms in 829 breast cancer survivors; the median age at breast cancer diagnosis was 54.2 years (range, 20.3-86.3); the median follow-up was 8.6 years (1.8-39.8); 39.7% received anthracyclines, 16% received trastuzumab/pertuzumab, 6.2% received both anthracyclines and trastuzumab/pertuzumab, and 38.1% received radiation alone. The cumulative incidence of cardiac dysfunction increased from 1.8% at 2 years to 15.3% at 15 years from cardiotoxic therapy initiation. Multivariable Cox regression analysis identified the following risk factors: non-Hispanic Black race (hazard ratio [HR], 2.15 [95% CI], 1.37 to 3.38), cardiotoxic therapies (anthracyclines: HR, 2.35 [95% CI, 1.25 to 4.4]; anthracyclines and trastuzumab/pertuzumab: HR, 3.92 [95% CI, 1.74 to 8.85]; reference: left breast radiation alone), selective estrogen receptor modulators (HR, 2.0 [95% CI, 1.2 to 3.33]), and precancer hypertension (HR, 3.16 [95% CI, 1.63 to 6.1]). Late-onset cardiac dysfunction was most prevalent among anthracycline- and radiation-exposed patients; early-onset cardiac dysfunction was most prevalent among patients exposed to anthracyclines and trastuzumab/pertuzumab; equal prevalence of both early- and late-onset cardiac dysfunction was observed in trastuzumab-/pertuzumab-exposed patients. Adjusted longitudinal analyses revealed an annual decline in LVEF by 0.29% (P = .009) over 20 years from breast cancer diagnosis. CONCLUSION: These findings provide evidence to support echocardiographic surveillance for several years after cardiotoxic therapy and also suggest a need to examine the efficacy of management of cardiovascular risk factors to mitigate risk.

Body composition and late-occurring chronic health conditions after autologous stem cell transplantation for lymphoma.

BACKGROUND: Autologous peripheral blood stem cell transplantation (aPBSCT) is the standard of care for adults with relapsed lymphoma, yet recipients remain at risk of developing chronic health conditions (CHCs). It was hypothesized that body composition measurements of skeletal muscle and fat are associated with late-onset CHCs and nonrelapse mortality after aPBSCT. METHODS: Leveraging the Blood or Marrow Transplant Survivor Study, we examined association between pre-aPBSCT body composition and new-onset grade 3-5 CHCs among 187 adults with lymphoma treated with aPBSCT (2011-2014) surviving ≥2 years after aPBSCT. Using computed tomography scans at the L3 level, skeletal muscle mass (skeletal muscle area and skeletal muscle density [SMD]) and body fat (subcutaneous adipose tissue and visceral adipose tissue) were measured and quantified as sex-specific z-scores. Competing risk models were built to study the impact of body composition on incident grade 3 through 5 CHCs and nonrelapse mortality (NRM) adjusting for confounders. RESULTS: The study cohort had a median age at aPBSCT of 57 years with 63% males, 77% non-Hispanic Whites and 81% with non-Hodgkin lymphoma. The 5-year cumulative incidence of grade 3 through 5 CHCs was 47% (95% Confidence Interval, CI, 38%-56%). Each SD increase in SMD was associated with 30% reduced risk of grade 3 through 5 CHCs (95% CI, 0.50-0.96). The 10-year cumulative incidence of NRM was 16% (95% CI, 10-22). No body composition measure was associated with NRM. CONCLUSIONS: The association between SMD and grade 3 through 5 CHCs following aPBSCT could inform development of prognostic models to identify adults with lymphoma at greatest risk of morbidity following aPBSCT.

Pre-frailty after blood or marrow transplantation and the risk of subsequent mortality.

We examined the prevalence, risk factors, and association between pre-frailty and subsequent mortality after blood or marrow transplantation (BMT). Study participants were drawn from the BMT Survivor Study (BMTSS) and included 3346 individuals who underwent BMT between 1974 and 2014 at one of three transplant centers and survived ≥2 years post-BMT. Participants completed the BMTSS survey at a median of 9 years from BMT and were followed for subsequent mortality for a median of 5 years after survey completion. Closest-age and same-sex biological siblings also completed the survey. Previously published self-reported indices (exhaustion, weakness, low energy expenditure, slowness, unintentional weight loss) classified participants as non-frail (0-1 indices) or pre-frail (2 indices). National Death Index was used to determine vital status and cause of death. Overall, 626 (18.7%) BMT survivors were pre-frail. BMT survivors had a 3.2-fold higher odds of being pre-frail (95% CI = 1.9-5.3) compared to siblings. Compared to non-frail survivors, pre-frail survivors had higher hazards of all-cause mortality (adjusted hazard ratio [aHR] = 1.6, 95% CI = 1.4-2.0). Female sex, pre-BMT radiation, smoking, lack of exercise, anxiety, and severe/life-threatening chronic health conditions were associated with pre-frailty. The novel association between pre-frailty and subsequent mortality provides evidence for interventions as pre-frail individuals may transition back to their robust state.

Reflections on the Past Decade in Evidence-Based Practice Within the Children's Oncology Group.

Background: The Children's Oncology Group (COG) is the only National Cancer Institute-supported clinical trials organization focused exclusively on childhood and adolescent cancer research. The COG Nursing Discipline Committee has embedded the tenets of evidence-based practice (EBP) into clinical trials nursing in order to standardize the nursing care delivered to children enrolled on these trials. The COG nursing EBP initiative is aimed at developing evidence-based clinical resources and tools to provide guidance to clinicians regarding topics relevant to the provision of cancer treatment for patients enrolled on COG clinical trials from diagnosis through survivorship. A rigorous, evidence-based process designed to guide development of the evidence-based clinical tools and resources within the COG nursing discipline was developed and was implemented with the first nurse expert team beginning in 2012. Method: The standardized process included (a) selecting EBP projects and nursing expert teams (NETs), (b) providing leadership, mentoring, and championship for NETs; (c) approving clinical content developed through the NETs; and (d) providing guidance and oversight over planned dissemination of the COG EBP projects. Results: The COG Nursing EBP Subcommittee has developed 15 publications to date that include 90 authors. Eleven of these authors contributed to multiple publications. Discussion: On this 10th anniversary of the development of the EBP within the COG nursing discipline, we recognize its contributions to the professional growth of many of the discipline's members and to advances in nursing care for children enrolled in pediatric cancer clinical trials.

Parental entrustment of healthcare responsibilities to youth with chronic conditions: A concept analysis.

PURPOSE: Chronic health conditions impact nearly 40% of children in the United States, necessitating parents/caregivers to entrust healthcare responsibilities to youth aging into adulthood. Understanding the parental entrustment process may lead to tailored transition support; however, the concept lacks conceptual clarity, limiting its research and practical applications. DESIGN AND METHODS: Rodgers' evolutionary concept analysis method was used to clarify the parental entrustment of healthcare responsibilities to youth with chronic health conditions. PubMed, CINAHL, and PsycINFO databases were searched without date restrictions, including full-text, English-language, primary source articles related to parent-child healthcare transition preparation. Following title, abstract, and full-text screenings, data were analyzed using a hybrid thematic approach to identify antecedents, attributes, and consequences. RESULTS: Forty-three studies from August 1996 to September 2023 were identified. Antecedents encompass social cues and readiness factors, while attributes involve a) responsibility transfer, support, and facilitation, b) a dynamic process, c) balancing trust and fear, d) navigating conflict, and e) parental letting go. Consequences entail shifts in parental and adolescent roles. Parental entrustment is an iterative process wherein parents guide their maturing child through responsibility transfer via facilitation, support, conflict navigation, and trust building. CONCLUSION: The clarified concept underscores the role of parents/caregivers in empowering youth to manage their health. Introducing a working definition and conceptual model contributes to understanding the processes families navigate in the larger landscape of healthcare transition. PRACTICE IMPLICATIONS: This clarification holds implications for clinicians and policymakers, offering insights to enhance support and guidance for families navigating healthcare transition.

Late morbidity and mortality after autologous blood or marrow transplantation for lymphoma in children, adolescents and young adults-a BMTSS report.

We determined the risk of late morbidity and mortality after autologous blood or marrow transplantation (BMT) for lymphoma performed before age 40. The cohort included autologous BMT recipients who had survived ≥2 years after transplantation (N = 583 [HL = 59.9%; NHL = 40.1%]) and a comparison cohort (N = 1070). Participants self-reported sociodemographics and chronic health conditions. A severity score (grade 3 [severe], 4 [life threatening] or 5 [fatal]) was assigned to the conditions using CTCAE v5.0. Logistic regression estimated the odds of grade 3-4 conditions in survivors vs. comparison subjects. Proportional subdistribution hazards models identified predictors of grade 3-5 conditions among BMT recipients. Median age at BMT was 30.0 years (range: 2.0-40.0) and median follow-up was 9.8 years (2.0-32.1). Survivors were at a 3-fold higher adjusted odds for grade 3-4 conditions (95% CI = 2.3-4.1) vs. comparison subjects. Factors associated with grade 3-5 conditions among BMT recipients included age at BMT (>30 years: adjusted hazard ratio [aHR] = 2.31; 95% CI = 1.27-4.19; reference: ≤21 years), pre-BMT radiation (aHR = 1.52; 95% CI = 1.13-2.03; reference: non-irradiated), and year of BMT (≥2000: aHR = 0.54; 95% CI = 0.34-0.85; reference: <1990). The 25 years cumulative incidence of relapse-related and non-relapse-related mortality was 18.2% and 25.9%, respectively. The high risk for late morbidity and mortality after autologous BMT for lymphoma performed at age <40 calls for long-term anticipatory risk-based follow-up.

Health care utilization by long-term survivors of blood or marrow transplantation-A Bone Marrow Transplant Survivor Study report.

BACKGROUND: Blood or marrow transplantation (BMT) survivors carry a high burden of morbidity, yet health care utilization by this vulnerable population remains understudied. Patterns and predictors of various domains of health care utilization in long-term BMT survivors were evaluated. METHODS: Study participants were drawn from the Bone Marrow Transplant Survivor Study (BMTSS). Patients transplanted between 1974 and 2014 at one of three transplant centers who had survived ≥2 years after BMT and were aged ≥18 years at the time of the study were included. A BMTSS survey served as the source of data for health care utilization, sociodemographics, and chronic health conditions. Domains of health care utilization in the 2 years preceding study participation included routine checkups, BMT-related visits, transplant/cancer center visits, emergency room (ER) visits, hospitalizations, and high health care utilization (≥7 physician visits during the 2 years before the study). Clinical characteristics and therapeutic exposures were abstracted from medical records. RESULTS: In this cohort of 3342 BMT survivors (52% allogeneic), the prevalence of health care utilization declined over time since BMT for both allogeneic and autologous BMT survivors, such that among those who had survived ≥20 years, only 49%-53% had undergone routine checkups, 37%-38% reported BMT-related visits, and 28%-29% reported transplant/cancer center visits. The presence of severe/life-threatening conditions and chronic graft-vs-host disease increased the odds of health care utilization across all domains. Lower education, lack of insurance, and Hispanic ethnicity were associated with a lower prevalence of routine checkups and/or transplant/cancer center visits. Lower income increased the odds of ER visits but reduced the odds of hospitalizations or high health care utilization. CONCLUSIONS: This study identified vulnerable populations of long-term BMT survivors who would benefit from specialized risk-based anticipatory care to reduce high health care utilization, ER visits, and hospitalizations.

Risky health behaviors and subsequent late mortality after blood or marrow transplantation: a BMTSS report.

We examined the association between risky health behaviors (smoking, heavy alcohol consumption, and lack of vigorous physical activity) and all-cause and cause-specific late mortality after blood or marrow transplantation (BMT) to understand the role played by potentially modifiable risk factors. Study participants were drawn from the BMT Survivor Study (BMTSS) and included patients who received transplantation between 1974 and 2014, had survived ≥2 years after BMT, and were aged ≥18 years at study entry. Survivors provided information on sociodemographic characteristics, chronic health conditions, and health behaviors. National Death Index was used to determine survival and cause of death. Multivariable regression analyses determined the association between risky health behaviors and all-cause mortality (Cox regression) and nonrecurrence-related mortality (NRM; subdistribution hazard regression), after adjusting for relevant sociodemographic, clinical variables and therapeutic exposures. Overall, 3866 participants completed the BMTSS survey and were followed for a median of 5 years to death or 31 December 2021; and 856 participants (22.1%) died after survey completion. Risky health behaviors were associated with increased hazard of all-cause mortality (adjusted hazard ratio [aHR] former smoker, 1.2; aHR current smoker, 1.7; reference, nonsmoker; aHR heavy drinker, 1.4; reference, nonheavy drinker; and aHR no vigorous activity, 1.2; reference, vigorous activity) and NRM (aHR former smoker, 1.3; aHR current smoker, 1.6; reference, nonsmoker; aHR heavy drinker, 1.4; reference: nonheavy drinker; and aHR no vigorous activity, 1.2; reference, vigorous activity). The association between potentially modifiable risky health behaviors and late mortality offers opportunities for development of interventions to improve both the quality and quantity of life after BMT.

Altered Peripheral Blood Gene Expression in Childhood Cancer Survivors With Anthracycline-Induced Cardiomyopathy - A COG-ALTE03N1 Report.

Background Anthracycline-induced cardiomyopathy is a leading cause of premature death in childhood cancer survivors, presenting a need to understand the underlying pathogenesis. We sought to examine differential blood-based mRNA expression profiles in anthracycline-exposed childhood cancer survivors with and without cardiomyopathy. Methods and Results We designed a matched case-control study (Children's Oncology Group-ALTE03N1) with mRNA sequencing on total RNA from peripheral blood in 40 anthracycline-exposed survivors with cardiomyopathy (cases) and 64 matched survivors without (controls). DESeq2 identified differentially expressed genes. Ingenuity Pathway Analyses (IPA) and Gene Set Enrichment Analyses determined the potential roles of altered genes in biological pathways. Functional validation was performed by gene knockout in human-induced pluripotent stem cell-derived cardiomyocytes using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) technology. Median age at primary cancer diagnosis for cases and controls was 8.2 and 9.7 years, respectively. Thirty-six differentially expressed genes with fold change ≥±2 were identified; 35 were upregulated. IPA identified "hepatic fibrosis" and "iron homeostasis" pathways to be significantly modulated by differentially expressed genes, including toxicology functions of myocardial infarction, cardiac damage, and cardiac dilation. Leading edge analysis from Gene Set Enrichment Analyses identified lactate dehydrogenase A (LDHA) and cluster of differentiation 36 (CD36) genes to be significantly upregulated in cases. Interleukin 1 receptor type 1, 2 (IL1R1, IL1R2), and matrix metalloproteinase 8, 9 (MMP8, MMP9) appeared in multiple canonical pathways. LDHA-knockout human-induced pluripotent stem cell-derived cardiomyocytes showed increased sensitivity to doxorubicin. Conclusions We identified differential mRNA expression profiles in peripheral blood of anthracycline-exposed childhood cancer survivors with and without cardiomyopathy. Upregulation of LDHA and CD36 genes suggests metabolic perturbations in a failing heart. Dysregulation of proinflammatory cytokine receptors IL1R1 and IL1R2 and matrix metalloproteinases, MMP8 and MMP9 indicates structural remodeling that accompanies the clinical manifestation of symptomatic cardiotoxicity.

Clinical Care for People Who Survive Childhood Cancer: A Review.

Importance: An estimated 15 000 children and adolescents aged 0 to 19 years are diagnosed with cancer each year in the US, and more than 85% survive for at least 5 years. By 45 years of age, approximately 95% of people who survive childhood cancer will develop a significant health problem related to the childhood cancer diagnosis or its treatment. Observations: Approximately 500 000 people currently alive in the US have survived childhood cancer. The most common severe or life-threatening chronic health problems related to childhood cancer or its treatment are endocrine disorders such as hypothyroidism or growth hormone deficiency (44%), subsequent neoplasms such as breast cancer or thyroid cancer (7%), and cardiovascular disease such as cardiomyopathy or congestive heart failure, coronary artery disease, and cerebrovascular disease (5.3%). Medical conditions related to a cancer diagnosis during childhood or adolescence are most commonly caused by the radiation therapy and the chemotherapies used to treat cancer and may develop at varying lengths of time after exposure to these treatments. Individuals at highest risk for developing treatment-related health problems include patients with brain cancer treated with cranial irradiation (approximately 70% develop severe or life-threatening health problems) and allogeneic hematopoietic stem cell transplant recipients (approximately 60% develop severe or life-threatening health problems). Individuals at the lowest risk for developing treatment-related health problems include those who survived solid tumors (such as Wilms tumor) treated with surgical resection alone or with minimal chemotherapy, for whom the prevalence of subsequent health problems is similar to people who did not have cancer during childhood or adolescence. People diagnosed with childhood cancer in the 1990s who survived for at least 5 years after the cancer diagnosis have a shorter lifespan (by about 9 years) vs children who were not diagnosed with cancer in the 1990s. Conclusions and Relevance: Approximately 500 000 individuals currently alive in the US have survived childhood cancer. The most common adverse effects in individuals who survived childhood cancer are endocrine disorders, subsequent neoplasms, and cardiovascular disease. There is a need for clinicians and patients to have heightened awareness of these complications.

Prediction of Coronary Heart Disease Events in Blood or Marrow Transplantation Recipients.

Background: The long-term risk of coronary heart disease (CHD) and clinical models that predict this risk remain understudied in blood or marrow transplantation (BMT) recipients. Objectives: This study sought to examine the risk of CHD after BMT and identify the associated risk factors. Methods: Participants included patients transplanted between 1974 and 2014 at City of Hope, University of Minnesota, or University of Alabama at Birmingham and those who survived ≥2 years after BMT. Multivariable logistic regression models assessed CHD risk in BMT survivors compared with a sibling cohort. A self-reported questionnaire and medical records provided information regarding sociodemographics, comorbidities, and therapeutic exposures, which were used to develop a CHD risk prediction nomogram. Results: Overall, 6,677 BMT recipients participated; the mean age at BMT was 43.9 ± 17.7 years, 58.3% were male, and 73.3% were non-Hispanic Whites. The median length of follow-up was 6.9 years (range: 2-46.2 years) from BMT. CHD was reported in 249 participants, with a 20-year cumulative incidence of 5.45% ± 0.39%. BMT survivors had a 1.6-fold greater odds of CHD compared with a sibling cohort (95% CI: 1.09-2.40). A nomogram was then developed to predict the risk of CHD at 10 and 20 years after BMT including age at BMT (HR: 1.06/y; 95% CI: 1.04-1.08), male sex (HR: 1.89; 95% CI: 1.15-3.11), a history of smoking (HR: 1.61; 95% CI: 1.01-2.58), diabetes (HR: 2.45; 95% CI: 1.23-4.89), hypertension (HR: 2.02; 95% CI: 1.15-3.54), arrhythmia (HR: 1.90; 95% CI: 0.89-4.06), and pre-BMT chest radiation (yes vs no: HR: 2.83; 95% CI: 1.20-6.67; unknown vs no: HR: 0.88; 95% CI: 0.34-2.28). The C-statistic was 0.77 in the test set (95% CI: 0.70-0.83). Conclusions: This study identified BMT recipients at high risk for CHD, informing targeted screening for early detection and aggressive control of risk factors.

Improving medication adherence monitoring and clinical outcomes through mHealth: A randomized controlled trial protocol in pediatric stem cell transplant.

Medication non-adherence rates in children range between 50% and 80% in the United States. Due to multifaceted outpatient routines, children receiving hematopoietic stem cell transplant (HCT) are at especially high risk of non-adherence, which can be life-threatening. Although digital health interventions have been effective in improving non-adherence in many pediatric conditions, limited research has examined their benefits among families of children receiving HCT. To address this gap, we created the BMT4me© mobile health app, an innovative intervention serving as a "virtual assistant" to send medication-taking reminders for caregivers and to track, in real-time, the child's medication taking, barriers to missed doses, symptoms or side effects, and other notes regarding their child's treatment. In this randomized controlled trial, caregivers will be randomized to either the control (standard of care) group or the intervention (BMT4me© app) group at initial discharge post-HCT. Both groups will receive an electronic adherence monitoring device (i.e., medication event monitoring system "MEMS" cap, Medy Remote Patient Management "MedyRPM" medication adherence box) to store their child's immunosuppressant medication. Caregivers who agree to participate will be asked to complete enrollment, weekly, and monthly parent-proxy measures of their child's medication adherence until the child reaches Day 100 or complete taper from immunosuppression. Caregivers will also participate in a 15 to 30-minute exit interview at the conclusion of the study. Descriptive statistics and correlations will be used to assess phone activity and use behavior over time. Independent samples t-tests will examine the efficacy of the intervention to improve adherence monitoring and reduce readmission rates. The primary expected outcome of this study is that the BMT4me© app will improve the real-time monitoring and medication adherence in children receiving hematopoietic stem cell transplant following discharge, thus improving clinical outcomes.

Identification of novel hypermethylated or hypomethylated CpG sites and genes associated with anthracycline-induced cardiomyopathy.

Anthracycline-induced cardiomyopathy is a leading cause of late morbidity in childhood cancer survivors. Aberrant DNA methylation plays a role in de novo cardiovascular disease. Epigenetic processes could play a role in anthracycline-induced cardiomyopathy but remain unstudied. We sought to examine if genome-wide differential methylation at 'CpG' sites in peripheral blood DNA is associated with anthracycline-induced cardiomyopathy. This report used participants from a matched case-control study; 52 non-Hispanic White, anthracycline-exposed childhood cancer survivors with cardiomyopathy were matched 1:1 with 52 survivors with no cardiomyopathy. Paired ChAMP (Chip Analysis Methylation Pipeline) with integrated reference-based deconvolution of adult peripheral blood DNA methylation was used to analyze data from Illumina HumanMethylation EPIC BeadChip arrays. An epigenome-wide association study (EWAS) was performed, and the model was adjusted for GrimAge, sex, interaction terms of age at enrollment, chest radiation, age at diagnosis squared, and cardiovascular risk factors (CVRFs: diabetes, hypertension, dyslipidemia). Prioritized genes were functionally validated by gene knockout in human induced pluripotent stem cell cardiomyocytes (hiPSC-CMs) using CRISPR/Cas9 technology. DNA-methylation EPIC array analyses identified 32 differentially methylated probes (DMP: 15 hyper-methylated and 17 hypo-methylated probes) that overlap with 23 genes and 9 intergenic regions. Three hundred and fifty-four differential methylated regions (DMRs) were also identified. Several of these genes are associated with cardiac dysfunction. Knockout of genes EXO6CB, FCHSD2, NIPAL2, and SYNPO2 in hiPSC-CMs increased sensitivity to doxorubicin. In addition, EWAS analysis identified hypo-methylation of probe 'cg15939386' in gene RORA to be significantly associated with anthracycline-induced cardiomyopathy. In this genome-wide DNA methylation profile study, we observed significant differences in DNA methylation at the CpG level between anthracycline-exposed childhood cancer survivors with and without cardiomyopathy, implicating differential DNA methylation of certain genes could play a role in pathogenesis of anthracycline-induced cardiomyopathy.

Haptoglobin Gene Expression and Anthracycline-Related Cardiomyopathy in Childhood Cancer Survivors: A COG-ALTE03N1 Report.

Background: Anthracycline-related cardiomyopathy is a leading cause of premature death in childhood cancer survivors. The high interindividual variability in risk suggests the need to understand the underlying pathogenesis. Objectives: The authors interrogated differentially expressed genes (DEGs) to identify genetic variants serving regulatory functions or genetic variants not easily identified when using genomewide array platforms. Using leads from DEGs, candidate copy number variants (CNVs) and single-nucleotide variants (SNVs) were genotyped. Methods: Messenger RNA sequencing was performed on total RNA from peripheral blood of 40 survivors with cardiomyopathy (cases) and 64 matched survivors without cardiomyopathy (control subjects). Conditional logistic regression analysis adjusting for sex, age at cancer diagnosis, anthracycline dose, and chest radiation was used to assess the associations between gene expression and cardiomyopathy and between CNVs and SNVs and cardiomyopathy. Results: Haptoglobin (HP) was identified as the top DEG. Participants with higher HP gene expression had 6-fold greater odds of developing cardiomyopathy (OR: 6.4; 95% CI: 1.4-28.6). The HP2-specific allele among the HP genotypes (HP1-1, HP1-2, and HP2-2) had higher transcript levels, as did the G allele among SNVs previously reported to be associated with HP gene expression (rs35283911 and rs2000999). The HP1-2 and HP2-2 genotypes combined with the G/G genotype for rs35283911 and/or rs2000999 placed the survivors at 4-fold greater risk (OR: 3.9; 95% CI: 1.0-14.5) for developing cardiomyopathy. Conclusions: These findings provide evidence of a novel association between HP2 allele and cardiomyopathy. HP binds to free hemoglobin to form an HP-hemoglobin complex, thereby preventing oxidative damage from free heme iron, thus providing biological plausibility to the mechanistic basis of the present observation.

Children's Oncology Group 2023 blueprint: Nursing discipline.

In contrast to other Children's Oncology Group (COG) committees, the COG nursing discipline is unique in that it provides the infrastructure necessary for nurses to support COG clinical trials and implements a research agenda aimed at scientific discovery. This hybrid focus of the discipline reflects the varied roles and expertise within pediatric oncology clinical trials nursing that encompass clinical care, leadership, and research. Nurses are broadly represented across COG disease, domain, and administrative committees, and are assigned to all clinically focused protocols. Equally important is the provision of clinical trials-specific education and training for nurses caring for patients on COG trials. Nurses involved in the discipline's evidence-based practice initiative have published a wide array of systematic reviews on topics of clinical importance to the discipline. Nurses also develop and lead research studies within COG, including stand-alone studies and aims embedded in disease/ treatment trials. Additionally, the nursing discipline is charged with responsibility for developing patient/family educational resources within COG. Looking to the future, the nursing discipline will continue to support COG clinical trials through a multifaceted approach, with a particular focus on patient-reported outcomes and health equity/disparities, and development of interventions to better understand and address illness-related distress in children with cancer.

Association of unmet basic resource needs with frailty and quality of life among older adults with cancer-Results from the CARE registry.

BACKGROUND: Basic resource needs related to transportation, housing, food, and medications are important social determinants of health and modifiable indicators of poverty, but their role in modifying the risk of frailty and health-related quality of life (HRQoL) remains unknown. The goal of our study was to examine the prevalence of unmet basic needs and their association with frailty and HRQoL in a cohort of older adults with cancer. METHODS: The CARE registry prospectively enrolls older adults (≥60 years) with cancer. Assessments of transportation, housing, and material hardship were added to the CARE tool in 8/2020. The 44-item CARE Frailty Index was used to define frailty, and subdomains of physical and mental HRQoL were assessed using the PROMIS® 10-global. Multivariable analysis examined the association between unmet needs with frailty and HRQoL subdomains, adjusting for covariates. RESULTS: The cohort included 494 participants. Median age of 69 years, 63.6% were male and 20.2% were Non-Hispanic (NH) Black. Unmet basic needs were reported in 17.8% (transportation 11.5%, housing 2.8%, and material hardship 7.5%). Those with unmet needs were more often NH Black (33.0% vs. 17.8%, p = 0.006) and less educated (

Health Literacy in Parents of Children Newly Diagnosed With Cancer and Comprehension of Key Concepts Related to Their Child's Care.

Background: There is a paucity of literature regarding health literacy in pediatric oncology. We sought to understand the relationship between health literacy and comprehension of key new diagnosis education concepts in parents of children newly diagnosed with cancer. Methods: Using data from a study evaluating a structured new diagnosis discharge teaching intervention, we performed a secondary analysis to understand the relationship between parental health literacy (Brief Health Literacy Screener: BHLS) and comprehension of six key concepts (child's diagnosis, primary oncologist, and treatment plan; seeking emergent care; fever definition; re-dosing medication). We also evaluated the association between parents self-reported sociodemographic characteristics, preferred learning style (one-item ordinal assessment) and health literacy. We tested relationships using Fisher's exact tests, independent samples t-tests, and Pearson correlations. Results: Fifty parents participated (age 35.4 ± 8.2 years [M ± SD]; 86% female; 60% non-Hispanic white; 24% with ≤high school education); nine parents (18%) scored in the BHLS low literacy range; 80% correctly responded to all six items on the key concepts questionnaire (100% comprehension). Health literacy was not significantly related to 100% comprehension or to individual key concept responses, with the exception of "child's treatment plan" (correct responses: 55.6% in low vs. 100% in adequate literacy groups; p < .001). Parental sociodemographic characteristics and preferred learning styles were not significantly related to health literacy. Discussion:Despite variability in health literacy levels, 80% of the parents comprehended all key concepts, suggesting that the intervention was effective for most parents, regardless of health literacy level.

Poverty and relapse risk in children with acute lymphoblastic leukemia: a Children's Oncology Group study AALL03N1 report.

The association between individual-level poverty and relapse in children receiving maintenance treatment for acute lymphoblastic leukemia (ALL) remains unclear. In a secondary analysis of COG-AALL03N1, we used data from US Census Bureau to categorize patients living below year-specific federal poverty thresholds, calculated using self-reported annual household income and size of household. Participants with federal poverty thresholds above 120% of their yearly household income were categorized as living in extreme poverty. Hazard of relapse was estimated using multivariable proportional subdistributional hazards regression for patients living in extreme poverty while receiving ALL maintenance therapy after adjusting for relevant predictors. Among 592 patients in this analysis, 12.3% of the patients were living in extreme poverty. After a median follow-up of 7.9 years, the cumulative incidence of relapse at 3 years from study enrollment among those living in extreme poverty was significantly higher (14.3%) than those not living in extreme poverty (7.6%). Multivariable analysis demonstrated that children living in extreme poverty had a 1.95-fold greater hazard of relapse than those not living in extreme poverty; this association was mitigated after the inclusion of race/ethnicity in the model, likely because of collinearity between race/ethnicity and poverty. A greater proportion of children living in extreme poverty were nonadherent to mercaptopurine (57.1% vs 40.9%); however, poor adherence did not completely explain the association between poverty and relapse risk. Future studies need to understand the mechanisms underlying the association between extreme poverty and relapse risk. This trial was registered at www.clinicaltrials.gov as #NCT00268528.

Children's Oncology Group KidsCare smartphone application for parents of children with cancer.

BACKGROUND: Parents of children with cancer must learn and retain crucial information necessary to provide safe care for their child. Smartphone applications (apps) provide a significant opportunity to meet the informational needs of these parents. We aimed to develop, refine, and evaluate a smartphone app, informed by the Children's Oncology Group (COG) expert consensus recommendations, to support the informational needs of parents of children with cancer. PROCEDURE: We employed a user-centered iterative mixed-methods approach in two phases (prototype development/refinement and pilot testing). We engaged parents and clinicians in evaluating the app via qualitative interviews and standardized tools that measured app quality (Mobile Application Rating Scale [MARS]), usability (System Usability Scale [SUS]), and acceptability (System Acceptability Scale [SAS]). We evaluated early usage patterns after public release. RESULTS: Thirty-two parents and 17 clinicians participated. Mean (± standard deviation [SD]) scores for app quality, usability, and acceptability were: MARS: 4.5 ± 0.7 on a 5-point scale; SUS: 86.7 ± 23.8 on a 100-point scale; and SAS: superior (61%); similar (28%); inferior (11%) to written materials. Qualitative findings largely confirmed the quantitative data. Downloads of the app during the first year following public release have exceeded 5000. CONCLUSIONS: The COG KidsCare app prototype was found to be of high quality and received high usability and acceptability ratings. Further testing is needed to determine app effectiveness in improving parental knowledge regarding care of children with cancer.