Conducting reproductive research during a new childhood cancer diagnosis: ethical considerations and impact on participants

Abstract Background Childhood cancer survivors (CCS) treated with anthracyclines and/or chest-directed radiotherapy receive life-long echocardiographic surveillance to detect cardiomyopathy early. Current risk stratification and surveillance frequency recommendations are based on anthracycline- and chest-directed radiotherapy dose. We assessed the added prognostic value of an initial left ventricular ejection fraction (EF) measurement at >5 years after cancer diagnosis. Patients and methods Echocardiographic follow-up was performed in asymptomatic CCS from the Emma Children's Hospital (derivation; n=299; median time after diagnosis, 16.7 years [inter quartile range (IQR) 11.8–23.15]) and from the Radboud University Medical Center (validation; n=218, median time after diagnosis, 17.0 years [IQR 13.0–21.7]) in the Netherlands. CCS with cardiomyopathy at baseline were excluded (n=16). The endpoint was cardiomyopathy, defined as a clinically significant decreased EF (EF<40%). The predictive value of the initial EF at >5 years after cancer diagnosis was analyzed with multivariable Cox regression models in the derivation cohort and the model was validated in the validation cohort. Results The median follow-up after the initial EF was 10.9 years and 8.9 years in the derivation and validation cohort, respectively, with cardiomyopathy developing in 11/299 (3.7%) and 7/218 (3.2%), respectively. Addition of the initial EF on top of anthracycline and chest radiotherapy dose increased the C-index from 0.75 to 0.85 in the derivation cohort and from 0.71 to 0.92 in the validation cohort (p<0.01). The model was well calibrated at 10-year predicted probabilities up to 5%. An initial EF between 40–49% was associated with a hazard ratio of 6.8 (95% CI 1.8–25) for development of cardiomyopathy during follow-up. For those with a predicted 10-year cardiomyopathy probability <3% (76.9% of the derivation cohort and 74.3% of validation cohort) the negative predictive value was >99% in both cohorts. Conclusion The addition of the initial EF >5 years after cancer diagnosis to anthracycline- and chest-directed radiotherapy dose improves the 10-year cardiomyopathy prediction in CCS. Our validated prediction model identifies low-risk survivors in whom the surveillance frequency may be reduced to every 10 years. Calibration in both cohorts Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Dutch Heart Foundation

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Palliative care of cancer survivors

Oxford Textbook of Palliative Nursing ◽

10.1093/med/9780199332342.003.0043 ◽

2015 ◽

pp. 661-670

Author(s):

Mary S. McCabe ◽

Stacie Corcoran

Keyword(s):

Quality Of Life ◽

Palliative Care ◽

Cancer Survivors ◽

Childhood Cancer ◽

Cancer Diagnosis ◽

Childhood Cancer Survivors ◽

The Family ◽

Heavy Burden ◽

Optimal Quality

Being told you are cancer-free does not mean you are free of the consequences of the disease. Seventy-six percent of cancer survivors are over age 60 years and have coexisting medical conditions that complicate posttreatment recovery to maximum health. Childhood cancer survivors also carry a heavy burden of medical and psychological problems resulting from their experience with cancer. Cancer diagnosis and treatment affects the family as well as the patient. Improvements are needed in the coordination of care for cancer survivors to assure optimal quality of life.

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The Impact of Cancer on Early Childhood Development: A Linked Data Study

Journal of Pediatric Psychology ◽

10.1093/jpepsy/jsaa084 ◽

2020 ◽

Author(s):

Julia N Morris ◽

David Roder ◽

Deborah Turnbull ◽

Hugh Hunkin

Keyword(s):

Physical Health ◽

Childhood Cancer ◽

Cancer Diagnosis ◽

Protective Factor ◽

Developmental Outcomes ◽

Population Data ◽

Childhood Cancer Survivors ◽

General Knowledge ◽

Health And Wellbeing ◽

The Impact

Abstract Objective This study used retrospective linked population data to investigate the impact of early childhood cancer on developmental outcomes. Methods Children aged <9 years with a recorded malignant neoplasm were identified in the South Australian Cancer Registry. They were then linked to developmental data recorded in the Australian Early Development Census (AEDC) for the 2009, 2012, and 2015 data collection periods; and assigned five matched controls from the same AEDC year. Results Between 2000 and 2015, 43 children had a malignant cancer diagnosis and also participated in the AEDC. Compared to controls, childhood cancer survivors exhibited greater developmental vulnerability in their physical health and wellbeing. Between survivors and controls, no significant developmental differences were observed in social, emotional, language and cognitive, and communication and general knowledge domains. Rural or remote location had a significant positive effect on developmental outcomes for childhood cancer survivors relative to controls, suggesting this was a protective factor in terms of physical health and wellbeing, social competence, communication, and general knowledge. Among all children, socioeconomic advantage was linked to better developmental outcomes on all domains except physical health and wellbeing. Conclusion Following an early cancer diagnosis, children may require targeted care to support their physical health and wellbeing. Geographic variation in developmental outcomes indicates remoteness was a protective factor and requires further investigation. This study highlights the feasibility of using administrative whole-population data to investigate cancer outcomes.

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Individual Prediction of Heart Failure Among Childhood Cancer Survivors

Journal of Clinical Oncology ◽

10.1200/jco.2014.56.1373 ◽

2015 ◽

Vol 33 (5) ◽

pp. 394-402 ◽

Cited By ~ 112

Author(s):

Eric J. Chow ◽

Yan Chen ◽

Leontien C. Kremer ◽

Norman E. Breslow ◽

Melissa M. Hudson ◽

...

Keyword(s):

Heart Failure ◽

Childhood Cancer ◽

Cancer Diagnosis ◽

Prediction Models ◽

Wilms Tumor ◽

Area Under The Curve ◽

Risk Groups ◽

Childhood Cancer Survivors ◽

Risk Scores ◽

Individual Risk

Purpose To create clinically useful models that incorporate readily available demographic and cancer treatment characteristics to predict individual risk of heart failure among 5-year survivors of childhood cancer. Patients and Methods Survivors in the Childhood Cancer Survivor Study (CCSS) free of significant cardiovascular disease 5 years after cancer diagnosis (n = 13,060) were observed through age 40 years for the development of heart failure (ie, requiring medications or heart transplantation or leading to death). Siblings (n = 4,023) established the baseline population risk. An additional 3,421 survivors from Emma Children's Hospital (Amsterdam, the Netherlands), the National Wilms Tumor Study, and the St Jude Lifetime Cohort Study were used to validate the CCSS prediction models. Results Heart failure occurred in 285 CCSS participants. Risk scores based on selected exposures (sex, age at cancer diagnosis, and anthracycline and chest radiotherapy doses) achieved an area under the curve of 0.74 and concordance statistic of 0.76 at or through age 40 years. Validation cohort estimates ranged from 0.68 to 0.82. Risk scores were collapsed to form statistically distinct low-, moderate-, and high-risk groups, corresponding to cumulative incidences of heart failure at age 40 years of 0.5% (95% CI, 0.2% to 0.8%), 2.4% (95% CI, 1.8% to 3.0%), and 11.7% (95% CI, 8.8% to 14.5%), respectively. In comparison, siblings had a cumulative incidence of 0.3% (95% CI, 0.1% to 0.5%). Conclusion Using information available to clinicians soon after completion of childhood cancer therapy, individual risk for subsequent heart failure can be predicted with reasonable accuracy and discrimination. These validated models provide a framework on which to base future screening strategies and interventions.

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Secondary cancers after a childhood cancer diagnosis: a nationwide hospital-based retrospective cohort study in Japan

International Journal of Clinical Oncology ◽

10.1007/s10147-015-0927-z ◽

2015 ◽

Vol 21 (3) ◽

pp. 506-516 ◽

Cited By ~ 11

Author(s):

Yasushi Ishida ◽

Dongmei Qiu ◽

Miho Maeda ◽

Junichiro Fujimoto ◽

Hisato Kigasawa ◽

...

Keyword(s):

Cohort Study ◽

Childhood Cancer ◽

Cancer Diagnosis ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Secondary Cancers

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Utilisation of primary care before a childhood cancer diagnosis: do socioeconomic factors matter?: A Danish nationwide population-based matched cohort study

BMJ Open ◽

10.1136/bmjopen-2018-023569 ◽

2018 ◽

Vol 8 (8) ◽

pp. e023569 ◽

Cited By ~ 3

Author(s):

Christina Friis Abrahamsen ◽

Jette Møller Ahrensberg ◽

Peter Vedsted

Keyword(s):

Primary Care ◽

General Practice ◽

Childhood Cancer ◽

Socioeconomic Factors ◽

Cancer Diagnosis ◽

Low Income ◽

Diagnostic Tests ◽

Population Based ◽

Matched Cohort ◽

Frequent Use

ObjectivesEarly diagnosis of childhood cancer is critical. Nevertheless, little is known about the potential role of inequality. This study aims to describe the use of primary care 2 years before a childhood cancer diagnosis and to investigate whether socioeconomic factors influence the use of consultations and diagnostic tests in primary care.DesignA national population-based matched cohort study.Setting and participantsThis study uses observational data from four Danish nationwide registers. All children aged 0–15 diagnosed with cancer during 2008–2015 were included (n=1386). Each case was matched based on gender and age with 10 references (n=13 860).Primary and secondary outcome measuresThe primary outcome was additional rates for consultations and for invoiced diagnostic tests for children with cancer according to parental socioeconomic factors. Furthermore, we estimated the association between socioeconomic factors and frequent use of consultations, defined as at least four consultations, and the odds of receiving a diagnostic test within 3 months of diagnosis.ResultsChildren with cancer from families with high income had 1.46 (95% CI 1.23 to 1.69) additional consultations 3 months before diagnosis, whereas children from families with low income had 1.85 (95% CI 1.60 to 2.11) additional consultations. The highest odds of frequent use of consultations was observed among children from low-income families (OR: 1.94, 95% CI 1.24 to 3.03). A higher odds of receiving an invoiced diagnostic test was seen for children from families with mid-educational level (OR: 1.46, 95% CI 1.09 to 1.95).ConclusionWe found a socioeconomic gradient in the use of general practice before a childhood cancer diagnosis. This suggests that social inequalities exist in the pattern of healthcare utilisation in general practice.

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Hospitalization rates among survivors of childhood and adolescent cancer: A report from the Childhood Cancer Survivor Study (CCSS)

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.9556 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 9556-9556

Author(s):

B. A. Kurt ◽

V. G. Nolan ◽

K. K. Ness ◽

J. P. Neglia ◽

J. M. Tersak ◽

...

Keyword(s):

Childhood Cancer ◽

Cancer Diagnosis ◽

Chronic Health Conditions ◽

Health Conditions ◽

Severe Toxicity ◽

Chronic Health ◽

Adolescent Cancer ◽

Hospitalization Rates ◽

Survivors Of Childhood Cancer

9556 Background: Survivors of childhood cancer have a high burden of chronic health conditions following cancer therapy, but the risk for subsequent hospitalization has not been reported. Methods: Hospitalizations during 1996–2000 among a cohort of 10,367 5-yr survivors of childhood cancer (diagnosed 1970–1986) and 2,540 siblings were ascertained. Age-and gender-stratified standardized incidence ratios (SIRs) for hospitalization were calculated using the sibling cohort and U.S. population from the National Hospital Discharge Survey (NHDS). Associations between demographic, cancer/treatment-related risk factors and non-obstetrical hospitalization among survivors were evaluated in multiple variable logistic regression models. Results: At follow-up, survivors were a mean of 20.9 yrs. from diagnosis (SD: 4.6, range: 13.3–32.2) and mean age of 28.6 yrs. (SD: 7.7, range: 13–51). Overall hospitalization rates among survivors were 1.5 times (95% CI 1.44–1.52) that of siblings and 1.2 times (95% CI 1.16–1.22) that of the U.S. general population. Increased risk of hospitalization was noted irrespective of gender, age at follow-up, or cancer diagnosis, with highest SIRs noted for male (SIR=12.7, 95% CI 9.5–15.8) and female (SIR=72.1, 95% CI 58.8–85.5) survivors aged 45–54. Females (OR=1.2, 95% CI 1.04–1.3) and survivors with a chronic health condition (OR=1.6, 95% CI 1.5–1.8) were more likely to have been hospitalized for non-obstetrical causes after adjusting for age at diagnosis, age at follow-up, cancer diagnosis, household income, insurance, and history of relapse/second malignancy. Among survivors, those with Hodgkin's lymphoma had the highest hospitalization rates for neoplastic, infectious, endocrine, pulmonary and cardiovascular causes. CNS malignancy survivors had the highest hospitalization rates for neurologic, psychological and external (e.g. traumatic) causes. Conclusions: Therapy for childhood and adolescent cancer is associated with a significant increase in subsequent hospitalization rates. Regular medical follow-up and early intervention for chronic health conditions may help to limit severe toxicity that would require hospitalization. No significant financial relationships to disclose.

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Overall and cardiac-specific mortality following serious cardiovascular events in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.12073 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 12073-12073

Author(s):

Wendy Bottinor ◽

Cindy Im ◽

Saro Armenian ◽

Borah Hong ◽

Rebecca M. Howell ◽

...

Keyword(s):

Cancer Treatment ◽

Childhood Cancer ◽

Cancer Diagnosis ◽

Cox Regression ◽

Childhood Cancer Survivors ◽

Heart Dose ◽

All Cause Mortality ◽

Specific Mortality ◽

Mortality Table ◽

Survivors Of Childhood Cancer

12073 Background: The direct impact of a major cardiovascular (CV) event on mortality among childhood cancer survivors is not well described. We hypothesized that mortality following a major CV event would be higher among survivors compared with siblings and that mortality would be influenced by primary cancer treatment. Methods: The CCSS cohort has conducted longitudinal follow-up of 25,658 survivors of childhood cancer and 5,051 siblings. All-cause and CV-cause specific mortality after a first event of heart failure (HF), coronary artery disease (CAD), or stroke occurring at least 5 years after cancer diagnosis, was estimated using the Kaplan-Meier method. The relative hazards (HR) and 95% confidence intervals (CI) between survivors and siblings as well as the influence of demographic (sex, age, race/ethnicity) and cancer treatment factors were estimated via Cox regression. Results: In total, 1780 survivors and 91 siblings experienced a serious CV event. Total deaths included 706 survivors (271 cardiac causes, 381 non-cardiac causes, 54 unknown causes) and 14 siblings. Survivors were a median age of 31.5 years (range 6.5-61.5) and 20.0 years (range 5.0-44.6) since cancer diagnosis at time of CV event. After a CV event, estimated 10- and 20-y all-cause mortality was significantly higher among survivors than siblings (Table). The HR for all-cause mortality was significantly higher among survivors than siblings after HF (HR 5.2, CI 2.1-13.0), CAD (HR 4.2, CI 2.0-9.0), and stroke (HR 4.6, CI 1.5-14.6). HF and stroke-specific mortality were not significantly increased among survivors versus siblings, in contrast to CAD-specific mortality (HR 3.5, CI 1.1-11.0). Among survivors, heart dose from radiotherapy (per 10 Gy) was associated with increased all-cause and cause-specific mortality after HF (HR 1.2, CI 1.0-1.3; HR 1.3, CI 1.0-1.7), all-cause mortality after CAD (HR 1.2, CI 1.0-1.3), and cause-specific mortality after stroke (HR 2.5, CI 1.2-4.9). Brain dose from radiotherapy was associated with increased all-cause mortality (HR 1.1, CI, 1.0-1.2, per 10 Gy) after stroke. Anthracycline dose was not associated with increased overall or cause-specific mortality risk after a CV event. Conclusions: After a CV event, mortality is higher among survivors than siblings. In survivors, mortality is primarily driven by non-cardiac causes. CAD and prior radiotherapy exposure to the heart and brain also influenced mortality.[Table: see text]

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Endocrine health conditions in adult survivors of childhood cancer: the need for specialized adult-focused follow-up clinics

Acta Endocrinologica ◽

10.1530/eje-12-1043 ◽

2013 ◽

Vol 168 (3) ◽

pp. 465-472 ◽

Cited By ~ 87

Author(s):

E Brignardello ◽

F Felicetti ◽

A Castiglione ◽

P Chiabotto ◽

A Corrias ◽

...

Keyword(s):

Cancer Survivors ◽

Childhood Cancer ◽

Cancer Diagnosis ◽

Late Effects ◽

Cumulative Incidence ◽

Endocrine Disease ◽

Male Sex ◽

Monitoring Protocols ◽

Over Time

BackgroundSurvival rates among childhood cancer survivors (CCS) have enormously increased in the last 40 years. However, this improvement has been achieved at the expense of serious late effects that frequently involve the endocrine system.AimTo evaluate the cumulative incidence of endocrine diseases in a cohort of long-term CCS.Materials and methodsWe analyzed the clinical data of 310 adults, followed for a median time of 16.0 years after the first cancer diagnosis. The monitoring protocols applied to each patient were personalized on the basis of cancer diagnosis and previous treatments, according to the Children's Oncology Group guidelines.ResultsThe cumulative incidence of endocrine late effects steadily increased over time. At the last follow-up visit available, 48.46% of females and 62.78% of males were affected by at least one endocrine disease. The most common disorders were gonadal dysfunction, primary hypothyroidism, and GH deficiency (GHD). The main risk factors for endocrine disease were male sex (hazard ratio (HR)=1.45, 95% confidence interval (95% CI) 1.05–1.99), radiotherapy (HR=1.91, 95% CI 1.28–2.84), hematopoietic stem cells transplantation (HR=3.11, 95% CI 2.23–4.34), and older age at cancer diagnosis (HR=1.89, 95% CI 1.25–2.85). Male sex was associated with a higher risk of gonadal disorders, whereas radiotherapy specifically increased the risk of GHD and thyroid dysfunction.ConclusionsEndocrine disorders among CCS have a high prevalence and increase over time. Thus, endocrinologists need to cope with an increasing demand for health care in a field that is still little developed and that, in perspective, could also be extended to some selected types of adult cancer survivors.

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