Prevalence and risk factors for vitamin D deficiency in long-term childhood cancer survivors.

BACKGROUND: Childhood cancer survivors (CCS) have increased risk of developing chronic health conditions, including musculoskeletal disorders. Little is known regarding vitamin D deficiency (VDD, <20 ng/ml) and its association with bone mineral density (BMD) in long-term CCS. We evaluated the prevalence and risk factors for VDD in a large, diverse population of long-term CCS, and examined the association between VDD and BMD in patients who underwent guideline-recommended dual-energy X-ray absorptiometry (DXA) screening. METHODS: This cross-sectional study included 446 consecutive CCS seen from March 2018 to September 2020. Univariate analyses examined associations between CCS demographics, socioeconomic status, and treatment exposures and VDD. Multivariable logistic regressions identified factors associated with odds of VDD and reduced BMD. RESULTS: Median age at evaluation was 27.5 years (range 7-67 years); median time from completing therapy was 14.2 years (range 2-65 years). Fifty percent were female, and 45% were Hispanic. Twenty-four percent had VDD. In multivariable analysis, overweight and obese BMI were associated with VDD (overweight: OR 1.78, 95% CI 1.03-3.07, p = 0.04; obese: OR 2.40, 95% CI 1.39-4.13, p < 0.01; reference: normal/underweight), as was Hispanic or black race/ethnicity (OR 2.40, 95% CI 1.41-4.09, p < 0.01; reference: non-Hispanic white). In the 118 CCS with DXA results, VDD was independently associated with reduced BMD (OR 3.58, 95%CI 1.33-9.59, p = 0.01). CONCLUSIONS: CCS have a high prevalence of VDD. High BMI and Hispanic or black race/ethnicity were associated with VDD. Survivors with VDD had a greater than threefold risk of reduced BMD. Risk-based screening may facilitate timely interventions to mitigate VDD and improve BMD in CCS.

Adaptation of an Intervention to Reduce Disparities in School HRQOL for Latino Childhood Cancer Survivors.

OBJECTIVE: Survivors of childhood leukemia, especially those from low socioeconomic status households, often experience persistent neurocognitive and academic impairment. This study adapted an existing parent training intervention to improve outcomes for low-acculturated, Spanish-speaking Latino parents of children with leukemia and pilot tested that intervention for feasibility. METHODS: Semistructured interviews were conducted with a focus group of 20 Latino parents of children treated for leukemia. Ten Latino families participated in a pilot study of the adapted parenting intervention, consisting of eight sessions over 6 months. RESULTS: Focus groups revealed that parents unanimously supported a parenting intervention but barriers to participation included time constraints, transportation issues, and anxiety in the hospital environment. The parents also highlighted cultural factors that could contribute to the health disparity, such as lack of knowledge and efficacy in facilitating their child's progress with learning and school. In the pilot study, adherence was 90%, establishing feasibility, and the adapted intervention was considered beneficial. The median parenting efficacy scores improved from preintervention to postintervention (median 3.40 vs. 3.94; p < .011), as did parent-reported school functioning of the child (median 50.00 vs. 60.00; p = .088). CONCLUSIONS: This study addressed a health disparity by culturally adapting a parenting intervention, which was designed to improve school functioning, to meet the needs and preferences of low-acculturated, Spanish-speaking families of children with leukemia in Southern California. The pilot study demonstrated that the adapted intervention is feasible and acceptable in the target population. A larger trial is underway to test the efficacy of this adapted parenting intervention.

Accuracy of a Novel Handheld Wireless Platform for Detection of Cardiac Dysfunction in Anthracycline-Exposed Survivors of Childhood Cancer.

Purpose: Childhood cancer survivors are at risk for anthracycline-related cardiac dysfunction, often developing at a time when they are least engaged in long-term survivorship care. New paradigms in survivorship care and chronic disease screening are needed in this population. We compared the accuracy of a novel handheld mHealth platform (Vivio) as well as echocardiography for assessment of cardiac function [left ventricular ejection fraction (EF)] in childhood cancer survivors with cardiac magnetic resonance (CMR) imaging (reference).Experimental Design: Cross-sectional study design was used. Concurrent evaluation of EF was performed using Vivio, two-dimensional (2D) echocardiography, and CMR. Differences in mean EF (2D echocardiography vs. CMR; Vivio vs. CMR) were compared using Bland-Altman plots. Linear regression was used to evaluate proportional bias.Results: A total of 191 consecutive survivors participated [50.7% female; median time from diagnosis: 15.8 years (2-44); median anthracycline dose: 225 mg/m2 (25-642)]. Echocardiography overestimated mean EF by 4.9% (P < 0.001); linear regression analysis confirmed a proportional bias, when compared with CMR (t = 3.1, P < 0.001). There was no difference between mean EF derived from Vivio and from CMR (-0.2%, P = 0.68). The detection of cardiac dysfunction via echocardiography was poor when compared with CMR [Echo EF < 45% (sensitivity 14.3%), Echo EF < 50% (sensitivity 28.6%)]. Sensitivity was substantially better for Vivio-based measurements [EF < 45% or EF < 50% (sensitivity 85.7%)].Conclusions: This accessible technology has the potential to change the day-to-day practice of clinicians caring for the large number of patients diagnosed with cardiac dysfunction and heart failure each year, allowing real-time monitoring and management of their disease without the lag-time between imaging and interpretation of results. Clin Cancer Res; 24(13); 3119-25. ©2018 AACR.

Late Effects Surveillance Recommendations among Survivors of Childhood Hematopoietic Cell Transplantation: A Children's Oncology Group Report.

Hematopoietic cell transplantation (HCT) is an important curative treatment for children with high-risk hematologic malignancies, solid tumors, and, increasingly, nonmalignant diseases. Given improvements in care, there are a growing number of long-term survivors of pediatric HCT. Compared with childhood cancer survivors who did not undergo transplantation, HCT survivors have a substantially increased burden of serious chronic conditions and impairments involving virtually every organ system and overall quality of life. This likely reflects the joint contributions of pretransplantation treatment exposures and organ dysfunction, the transplantation conditioning regimen, and any post-transplantation graft-versus-host disease (GVHD). In response, the Children's Oncology Group (COG) has created long-term follow-up guidelines (www.survivorshipguidelines.org) for survivors of childhood, adolescent, and young adult cancer, including those who were treated with HCT. Guideline task forces, consisting of HCT specialists, other pediatric oncologists, radiation oncologists, organ-specific subspecialists, nurses, social workers, other health care professionals, and patient advocates systematically reviewed the literature with regards to late effects after childhood cancer and HCT since 2002, with the most recent review completed in 2013. For the most recent review cycle, over 800 articles from the medical literature relevant to childhood cancer and HCT survivorship were reviewed, including 586 original research articles. Provided herein is an organ system-based overview that emphasizes the most relevant COG recommendations (with accompanying evidence grade) for the long-term follow-up care of childhood HCT survivors (regardless of current age) based on a rigorous review of the available evidence. These recommendations cover both autologous and allogeneic HCT survivors, those who underwent transplantation for nonmalignant diseases, and those with a history of chronic GVHD.

Impact of Tailored Education on Awareness of Personal Risk for Therapy-Related Complications Among Childhood Cancer Survivors.

PURPOSE: Survivors of childhood cancer carry a substantial burden of long-term morbidity; personal risk awareness is critical to ensure survivors' engagement in early detection/management of complications. The impact of education provided in survivorship clinics on survivors' understanding of their personal health risks is unclear. METHODS: Patients diagnosed with cancer at age 21 years or younger and at 2 or more years off therapy completed questionnaires about awareness of personal risk for therapy-related complications at T0 (first survivorship clinic visit) and at T1 to T5 (subsequent visits). After questionnaire completion at each clinic visit, survivors received education tailored to personal risk. RESULTS: A total of 369 survivors completed 1,248 visits (median, three visits; range, one to six visits). The median age at cancer diagnosis was 11 years (range, 0 to 21 years); the median age at T0 was 24 years (range, 5 to 57 years); 38% were white; 45% had leukemia; and 34% received hematopoietic cell transplantation. The cohort was at risk for a median of six (range, one to nine) complications. Awareness increased from 38.6% at T0 to 66.3% at T3. Generalized estimating equations (that adjusted for diagnosis, hematopoietic cell transplantation, race/ethnicity, and patient/parent education) showed significant gains in awareness from T0 to T1 (P < .001), T1 to T2 (P = .03), and T2 to T3 (P < .001) but no significant gain thereafter through T5 (P = .7). Predictors of low awareness included education less than a college degree (odds ratio [OR], 1.9; P = .02), longer time from diagnosis (OR, 1.03/year; P = .04), diagnosis of leukemia (OR, 2.1; P = .004), nonwhite race (OR, 2.8; P < .001), and risk for six or fewer complications (OR, 2.1; P = .002). CONCLUSION: Risk-based education in a survivorship clinic significantly increases awareness of personal health risk through three sessions, with saturation thereafter. Vulnerable populations with minimal gain in awareness identified in this study could inform targeted interventions.

Long-term pulmonary function in survivors of childhood cancer.

PURPOSE: This study was undertaken to determine the magnitude of pulmonary dysfunction in childhood cancer survivors when compared with healthy controls and the extent (and predictors) of decline over time. PATIENTS AND METHODS: Survivors underwent baseline (t1) pulmonary function tests, followed by a second comprehensive evaluation (t2) after a median of 5 years (range, 1.0 to 10.3 years). Survivors were also compared with age- and sex-matched healthy controls at t2. RESULTS: Median age at cancer diagnosis was 16.5 years (range, 0.2 to 21.9 years), and time from diagnosis to t2 was 17.1 years (range, 6.3 to 40.1 years). Compared with odds for healthy controls, the odds of restrictive defects were increased 6.5-fold (odds ratio [OR], 6.5; 95% CI, 1.5 to 28.4; P < .01), and the odds of diffusion abnormalities were increased 5.2-fold (OR, 5.2; 95% CI, 1.8 to 15.5; P < .01). Among survivors, age younger than 16 years at diagnosis (OR, 3.0; 95% CI, 1.2 to 7.8; P = .02) and exposure to more than 20 Gy chest radiation (OR, 5.6; 95% CI, 1.5 to 21.0; P = .02, referent, no chest radiation) were associated with restrictive defects. Female sex (OR, 3.9; 95% CI, 1.7 to 9.5; P < .01) and chest radiation dose (referent: no chest radiation; ≤ 20 Gy: OR, 6.4; 95% CI, 1.7 to 24.4; P < .01; > 20 Gy: OR, 11.3; 95% CI, 2.6 to 49.5; P < .01) were associated with diffusion abnormalities. Among survivors with normal pulmonary function tests at t1, females and survivors treated with more than 20 Gy chest radiation demonstrated decline in diffusion function over time. CONCLUSION: Childhood cancer survivors exposed to pulmonary-toxic therapy are significantly more likely to have restrictive and diffusion defects when compared with healthy controls. Diffusion capacity declines with time after exposure to pulmonary-toxic therapy, particularly among females and survivors treated with high-dose chest radiation. These individuals could benefit from subsequent monitoring.

Screening for cardiac dysfunction in anthracycline-exposed childhood cancer survivors.

PURPOSE: To examine the utility and reliability of obtaining early echocardiographic measurements of left ventricular (LV) remodeling as well as blood biomarkers of cardiac injury in asymptomatic childhood cancer survivors at risk for LV dysfunction and congestive heart failure due to past exposure to anthracycline chemotherapy. EXPERIMENTAL DESIGN: Using a cross-sectional design, anthracycline-exposed childhood cancer survivors with preserved ejection fraction (EF; ≥50%) were evaluated using early echocardiographic indices and blood biomarkers of LV dysfunction. Survivors treated with ≥300 mg/m(2) anthracyclines [high risk (HR): n = 100] were compared with those treated with <300 mg/m(2) anthracyclines [low risk (LR): n = 50] and matched healthy controls (HC: n = 50). All echocardiograms were interpreted by an institutional cardiologist and a study cardiologist blinded to risk status. RESULTS: Time from diagnosis was comparable for HR (12.0 years) and LR (13.2 years, P = 0.8) survivors. Echocardiograms: HR had lower LV thickness-dimension ratio (Z-score: HR: -0.62, LR: -0.03, HC: -0.02; P < 0.001), increased LV wall stress (HR: 66.7 g/cm(2), LR: 56.6 g/cm(2), HC: 54.2 g/cm(2); P < 0.01), and higher myocardial performance index (HR: 0.51, LR: 0.46, HC: 0.46; P < 0.01). Interobserver correlation (clinical/blinded reading) for all echocardiographic indices was excellent (range: R = 0.76-0.97, P < 0.001). Blood biomarkers: With the exception of NT-proBNP (r = 0.28, P < 0.01), there was no correlation between blood biomarkers (B-type natriuretic peptide, Troponin-T, ST-2, Galectin-3) and LV dysfunction. CONCLUSION: Childhood cancer survivors with preserved EF 10+ years from anthracycline exposure had dose-dependent changes in echocardiographic markers of LV dysfunction.

Carnitine and cardiac dysfunction in childhood cancer survivors treated with anthracyclines.

Childhood cancer survivors are at high risk of developing congestive heart failure (CHF) compared with the general population, and there is a dose-dependent increase in CHF risk by anthracycline dose. The mechanism by which this occurs has not been fully elucidated. Metabolomics, the comprehensive profile of small-molecule metabolites, has the potential to provide insight into the pathogenesis of disease states and discover diagnostic markers for therapeutic targets. We performed echocardiographic testing and blood plasma metabolomic analyses (8 pathways; 354 metabolites) in 150 asymptomatic childhood cancer survivors previously treated with anthracyclines. Median time from cancer diagnosis to study participation was 12.4 years (2.6-37.9 years); 64% were treated for a hematologic malignancy; median anthracycline dose was 350 mg/m(2) (25-642 mg/m(2)). Thirty-five (23%) participants had cardiac dysfunction-defined as left ventricular end-systolic wall stress >2SD by echocardiogram. Plasma levels of 15 compounds in three metabolic pathways (carbohydrate, amino acid, and lipid metabolism) were significantly different between individuals with cardiac dysfunction and those with normal systolic function. After adjusting for multiple comparisons, individuals with cardiac dysfunction had significantly lower plasma carnitine levels [relative ratio (RR), 0.89; P < 0.01] in relation to those with normal systolic function. These findings may facilitate the development of primary prevention (treatment of carnitine deficiency before/during anthracycline administration) and secondary prevention strategies (screening and treatment in long-term survivors) in patients at highest risk for CHF. Cancer Epidemiol Biomarkers Prev; 23(6); 1109-14. ©2014 AACR.

Yield of screening for long-term complications using the children's oncology group long-term follow-up guidelines.

PURPOSE: The Children's Oncology Group Long-Term Follow-Up (COG-LTFU) Guidelines use consensus-based recommendations for exposure-driven, risk-based screening for early detection of long-term complications in childhood cancer survivors. However, the yield from these recommendations is not known. METHODS: Survivors underwent COG-LTFU Guideline-directed screening. Yield was classified as negligible/negative (< 1%), intermediate (≥ 1% to < 10%), or high (≥ 10%). For long-term complications with high yield, logistic regression was used to identify subgroups more likely to screen positive. RESULTS: Over the course of 1,188 clinic visits, 370 childhood cancer survivors (53% male; 47% Hispanic; 69% leukemia/lymphoma survivors; median age at diagnosis, 11.1 years [range, 0.3 to 21.9 years]; time from diagnosis, 10.5 years [range, 5 to 55.8 years]) underwent 4,992 screening tests. High-yield tests included thyroid function (hypothyroidism, 10.1%), audiometry (hearing loss, 22.6%), dual-energy x-ray absorptiometry scans (low bone mineral density [BMD], 23.2%), serum ferritin (iron overload, 24.0%), and pulmonary function testing/chest x-ray (pulmonary dysfunction, 84.1%). Regression analysis failed to identify subgroups more likely to result in high screening yield, with the exception of low BMD (2.5-fold increased risk for males [P = .04]; 3.3-fold increased risk for nonobese survivors [P = .01]). Screening tests with negligible/negative (< 1%) yield included complete blood counts (therapy-related leukemia), dipstick urinalysis for proteinuria and serum blood urea nitrogen/creatinine (glomerular defects), microscopic urinalysis for hematuria (hemorrhagic cystitis, bladder cancer), ECG (anthracycline-related conduction disorder), and hepatitis B and HIV serology. CONCLUSION: Screening tests with a high yield are appropriate for risk groups targeted for screening by the COG-LTFU Guidelines. Elimination of screening tests with negligible/negative yield should be given consideration.

A glimpse into the lives of 3 children: their cancer journey.

Three stories of children with advanced cancer are presented in this article. The goal was to ascertain what these children were experiencing and thinking as well as what interventions were helpful. Interviews used open-ended questions as well as the Memorial Symptom Assessment Scale, Symptom Management Record, the Body Outline, Child Depression Inventory, Revised Children's Manifest Anxiety Scale, Pediatric Quality of Life Inventory, Common Toxicity Criteria, Lansky's Play Performance Scale, and Spirituality quality of life (QOL) and provided an opportunity for the children to describe their symptoms and QOL. The findings illustrated that the child's social, psychological, and spiritual concerns are important for nurses to address along with the child's physical needs.

Palliative care education for pediatric nurses.

Of all the various healthcare professionals that provide care to children and their families facing life's end, no one spends more time at the bedside observing, critically thinking, consulting, and providing direct care than the pediatric nurse. Previous research, however, demonstrates that undergraduate education has not prepared nurses to provide optimum end-of-life (EOL) care (Ferrell, Grant, & Virani, 1999; Ferrell, Virani, & Grant, 1999). Although many reasons have been cited in the literature for this inadequacy, the fact remains that when nurses complete their basic education and enter practice, they often are grossly unprepared to care for children and families in need of end-of-life care (Field & Behrman, 2003).

The evolution of the role of nurses: the history of nurse practitioners in pediatric oncology.

The role of nursing has been around since the beginning of time as demonstrated historically by caretakers who have attempted to relieve the suffering of children and of the sick within their community. In the late 1940s, the field of pediatric oncology nursing began emerging, and by the early 1970s, there were 2 pediatric nurse practitioner programs specific for pediatric oncology. The practice strategies for this role include not only directing and providing patient care to children with oncologic diseases but also negotiating the healthcare delivery system, monitoring and ensuring the quality of health care practice, offering family-centered care, and demonstrating cultural competency. In essence, the nurse practitioner role is multifaceted, requiring independent and interdependent decision making and direct accountability for clinical judgment in managing the care of children with cancer and their families.