Perceived barriers and facilitators to health behaviors in European childhood cancer survivors: A qualitative PanCareFollowUp study.

BACKGROUND: Healthy behaviors, that is, engaging in regular physical activities, maintaining a healthy diet, limiting alcohol consumption, and avoiding tobacco and drug use, decrease the risk of developing late adverse health conditions in childhood cancer survivors. However, childhood cancer survivors may experience barriers to adopting and maintaining healthy behaviors. This study aimed to assess these barriers and facilitators to health behavior adoption and maintenance in childhood cancer survivors. METHODS: A focus group ( n = 12) and semi-structured telephone interviews ( n = 20) were conducted with a selected sample of European and Dutch childhood cancer survivors, respectively. The Theoretical Domains Framework (TDF) was used to inform the topic guide and analysis. Inductive thematic analysis was applied to identify categories relating to barriers and facilitators of health behavior adoption and maintenance, after which they were deductively mapped onto the TDF. RESULTS: Ten TDF domains were identified in the data of which "Knowledge," "Beliefs about consequences," "Environmental context and resources," and "Social influences" were most commonly reported. Childhood cancer survivors expressed a need for knowledge on the importance of healthy behaviors, possibly provided by healthcare professionals. They indicated physical and long-term benefits of healthy behaviors, available professional support, and a supporting and health-consciously minded work and social environment to be facilitators. Barriers were mostly related to a lack of available time and an unhealthy environment. Lastly, (social) media was perceived as both a barrier and a facilitator to healthy behaviors. CONCLUSION: This study has identified education and available professional support in health behaviors and the relevance of healthy behaviors for childhood cancer survivors as key opportunities for stimulating health behavior adoption in childhood cancer survivors. Incorporating health behavior support and interventions for this population should therefore be a high priority.

Childhood cancer survivorship care during the COVID-19 pandemic: an international report of practice implications and provider concerns.

PURPOSE: Long-term follow-up (LTFU) care is essential to optimise health outcomes in childhood cancer survivors (CCS). We aimed to assess the impact of the COVID-19 pandemic on LTFU services and providers. METHODS: A COVID-19 working group within the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG) distributed a questionnaire to LTFU service providers in 37 countries across Europe, Asia, North America, Central/South America, and Australia. The questionnaire assessed how care delivery methods changed during the pandemic and respondents' level of worry about the pandemic's impact on LTFU care delivery, their finances, their health, and that of their family and friends. RESULTS: Among 226 institutions, providers from 178 (79%) responded. Shortly after the initial outbreak, 42% of LTFU clinics closed. Restrictions during the pandemic resulted in fewer in-person consultations and an increased use of telemedicine, telephone, and email consultations. The use of a risk assessment to prioritise the method of LTFU consultation for individual CCS increased from 12 to 47%. While respondents anticipated in-person consultations to remain the primary method for LTFU service delivery, they expected significantly increased use of telemedicine and telephone consultations after the pandemic. On average, respondents reported highest levels of worry about psychosocial well-being of survivors. CONCLUSIONS: The pandemic necessitated changes in LTFU service delivery, including greater use of virtual LTFU care and risk-stratification to identify CCS that need in-person evaluations. IMPLICATIONS FOR CANCER SURVIVORS: Increased utilisation of virtual LTFU care and risk stratification is likely to persist post-pandemic.

The European multistakeholder PanCareFollowUp project: novel, person-centred survivorship care to improve care quality, effectiveness, cost-effectiveness and accessibility for cancer survivors and caregivers.

BACKGROUND: The majority of childhood cancer survivors are at risk of treatment-related adverse health outcomes. Survivorship care to mitigate these late effects is endorsed, but it is not available for many adult survivors of childhood cancer in Europe. The PanCareFollowUp project was initiated to improve their health and quality of life (QoL) by facilitating person-centred survivorship care. METHODS: The PanCareFollowUp consortium was established in 2018, consisting of 14 project partners from ten European countries, including survivor representatives. The consortium will develop two PanCareFollowUp Interventions, including a person-centred guideline-based model of care (Care Intervention) and eHealth lifestyle coaching (Lifestyle Intervention). Their development will be informed by several qualitative studies and systematic reviews on barriers and facilitators for implementation and needs and preferences of healthcare providers (HCPs) and survivors. Implementation of the PanCareFollowUp Care Intervention as usual care will be evaluated prospectively among 800 survivors from Belgium, Czech Republic, Italy and Sweden for survivor empowerment, detection of adverse health conditions, satisfaction among survivors and HCPs, cost-effectiveness and feasibility. The feasibility of the PanCareFollowUp Lifestyle Intervention will be evaluated in the Netherlands among 60 survivors. RESULTS: Replication manuals, allowing for replication of the PanCareFollowUp Care and Lifestyle Intervention, will be published and made freely available after the project. Moreover, results of the corresponding studies are expected within the next five years. CONCLUSIONS: The PanCareFollowUp project is a novel European collaboration aiming to improve the health and QoL of all survivors across Europe by developing and prospectively evaluating the person-centred PanCareFollowUp Care and Lifestyle Interventions.

Counseling and surveillance of obstetrical risks for female childhood, adolescent, and young adult cancer survivors: recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Female childhood, adolescent, and young adult cancer survivors have an increased risk of adverse pregnancy outcomes related to their cancer- or treatment-associated sequelae. Optimal care for childhood, adolescent, and young adult cancer survivors can be facilitated by clinical practice guidelines that identify specific adverse pregnancy outcomes and the clinical characteristics of at-risk subgroups. However, national guidelines are scarce and vary in content. Here, the International Late Effects of Childhood Cancer Guideline Harmonization Group offers recommendations for the counseling and surveillance of obstetrical risks of childhood, adolescent, and young adult survivors. A systematic literature search in MEDLINE database (through PubMed) to identify all available evidence published between January 1990 and December 2018. Published articles on pregnancy and perinatal or congenital risks in female cancer survivors were screened for eligibility. Study designs with a sample size larger than 40 pregnancies in childhood, adolescent, and young adult cancer survivors (diagnosed before the age of 25 years, not pregnant at that time) were eligible. This guideline from the International Late Effects of Childhood Cancer Guideline Harmonization Group systematically appraised the quality of available evidence for adverse obstetrical outcomes in childhood, adolescent, and young adult cancer survivors using Grading of Recommendations Assessment, Development, and Evaluation methodology and formulated recommendations to enhance evidence-based obstetrical care and preconception counseling of female childhood, adolescent, and young adult cancer survivors. Healthcare providers should discuss the risk of adverse obstetrical outcomes based on cancer treatment exposures with all female childhood, adolescent, and young adult cancer survivors of reproductive age, before conception. Healthcare providers should be aware that there is no evidence to support an increased risk of giving birth to a child with congenital anomalies (high-quality evidence). Survivors treated with radiotherapy to volumes exposing the uterus and their healthcare providers should be aware of the risk of adverse obstetrical outcomes such as miscarriage (moderate-quality evidence), premature birth (high-quality evidence), and low birthweight (high-quality evidence); therefore, high-risk obstetrical surveillance is recommended. Cardiomyopathy surveillance is reasonable before pregnancy or in the first trimester for all female survivors treated with anthracyclines and chest radiation. Female cancer survivors have increased risks of premature delivery and low birthweight associated with radiotherapy targeting the lower body and thereby exposing the uterus, which warrant high-risk pregnancy surveillance.

Large variation in assessment and outcome definitions to describe the burden of long-term morbidity in childhood cancer survivors: A systematic review.

We systematically reviewed outcome assessment methods, outcome classification, and severity grading of reported outcomes in studies investigating the burden of physical long-term morbidity in childhood cancer survivors (CCS). A MEDLINE and EMBASE search identified 56 studies reporting on three or more types of health conditions in 5-year CCS, for which information was extracted on outcome types and classification, methods of outcome ascertainment, and severity grading. There was substantial variability in classification and types of health conditions reported and in methods of outcome ascertainment. Only 59% of the included studies applied severity grading, mainly the common terminology criteria of adverse events. This large variation in assessment and definition of the burden of physical long-term morbidity in CCS challenges interpretation, comparison, and pooling data across studies. Global collaboration is needed to standardize assessments and harmonize definitions of long-term physical morbidity and associated outcomes in childhood cancer survivorship research.

Accuracy of cystatin C for the detection of abnormal renal function in children undergoing chemotherapy for malignancy: a systematic review using individual patient data.

PURPOSE: We conducted a systematic review and individual patient data (IPD) meta-analysis to examine the utility of cystatin C for evaluation of glomerular function in children with cancer. METHODS: Eligible studies evaluated the accuracy of cystatin C for detecting poor renal function in children undergoing chemotherapy. Study quality was assessed using QUADAS-2. Authors of four studies shared IPD. We calculated the correlation between log cystatin C and GFR stratified by study and measure of cystatin C. We dichotomized the reference standard at GFR 80 ml/min/1.73m2 and stratified cystatin C at 1 mg/l, to calculate sensitivity and specificity in each study and according to age group (0-4, 5-12, and ≥ 13 years). In sensitivity analyses, we investigated different GFR and cystatin C cut points. We used logistic regression to estimate the association of impaired renal function with log cystatin C and quantified diagnostic accuracy using the area under the ROC curve (AUC). RESULTS: Six studies, which used different test and reference standard thresholds, suggested that cystatin C has the potential to monitor renal function in children undergoing chemotherapy for malignancy. IPD data (504 samples, 209 children) showed that cystatin C has poor sensitivity (63%) and moderate specificity (89%), although use of a GFR cut point of < 60 ml/min/1.73m2 (data only available from two of the studies) estimated sensitivity to be 92% and specificity 81.3%. The AUC for the combined data set was 0.890 (95% CI 0.826, 0.951). Diagnostic accuracy appeared to decrease with age. CONCLUSIONS: Cystatin C has better diagnostic accuracy than creatinine as a test for glomerular dysfunction in young people undergoing treatment for cancer. Diagnostic accuracy is not sufficient for it to replace current reference standards for predicting clinically relevant impairments that may alter dosing of important nephrotoxic agents.

Long term cause specific mortality among 34 489 five year survivors of childhood cancer in Great Britain: population based cohort study.

OBJECTIVE:  To determine whether modern treatments for cancer are associated with a net increased or decreased risk of death from neoplastic and non-neoplastic causes among survivors of childhood cancer. DESIGN:  Population based cohort study. SETTING:  British Childhood Cancer Survivor Study. PARTICIPANTS:  Nationwide population based cohort of 34 489 five year survivors of childhood cancer with a diagnosis from 1940 to 2006 and followed up until 28 February 2014. MAIN OUTCOME MEASURES:  Cause specific standardised mortality ratios and absolute excess risks are reported. Multivariable Poisson regression models were utilised to evaluate the simultaneous effect of risk factors. Likelihood ratio tests were used to test for heterogeneity or trend. RESULTS:  Overall, 4475 deaths were observed, which was 9.1 (95% confidence interval 8.9 to 9.4) times that expected in the general population, corresponding to 64.2 (95% confidence interval 62.1 to 66.3) excess deaths per 10 000 person years. The number of excess deaths from all causes declined among those treated more recently; those treated during 1990-2006 experienced 30% of the excess number of deaths experienced by those treated before 1970. The corresponding percentages for the decline in excess deaths from recurrence or progression and non-neoplastic causes were 30% and 60%, respectively. Among survivors aged 50-59 years, 41% and 22% of excess deaths were attributable to subsequent primary neoplasms and circulatory conditions, respectively, whereas the corresponding percentages among those aged 60 years or more were 31% and 37%. CONCLUSIONS:  The net effects of changes in cancer treatments, and surveillance and management for late effects, over the period 1940 to 2006 was to reduce the excess number of deaths from both recurrence or progression and non-neoplastic causes among those treated more recently. Among survivors aged 60 years or more, the excess number of deaths from circulatory causes exceeds the excess number of deaths from subsequent primary neoplasms. The important message for the evidence based surveillance aimed at preventing excess mortality and morbidity in survivors aged 60 years or more is that circulatory disease overtakes subsequent primary neoplasms as the leading cause of excess mortality.

An Association of Cancer Physicians' strategy for improving services and outcomes for cancer patients.

The Association of Cancer Physicians in the United Kingdom has developed a strategy to improve outcomes for cancer patients and identified the goals and commitments of the Association and its members.

Single amino acid charge switch defines clinically distinct proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1)-associated inflammatory diseases.

BACKGROUND: Hyperzincemia and hypercalprotectinemia (Hz/Hc) is a distinct autoinflammatory entity involving extremely high serum concentrations of the proinflammatory alarmin myeloid-related protein (MRP) 8/14 (S100A8/S100A9 and calprotectin). OBJECTIVE: We sought to characterize the genetic cause and clinical spectrum of Hz/Hc. METHODS: Proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) gene sequencing was performed in 14 patients with Hz/Hc, and their clinical phenotype was compared with that of 11 patients with pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome. PSTPIP1-pyrin interactions were analyzed by means of immunoprecipitation and Western blotting. A structural model of the PSTPIP1 dimer was generated. Cytokine profiles were analyzed by using the multiplex immunoassay, and MRP8/14 serum concentrations were analyzed by using an ELISA. RESULTS: Thirteen patients were heterozygous for a missense mutation in the PSTPIP1 gene, resulting in a p.E250K mutation, and 1 carried a mutation resulting in p.E257K. Both mutations substantially alter the electrostatic potential of the PSTPIP1 dimer model in a region critical for protein-protein interaction. Patients with Hz/Hc have extremely high MRP8/14 concentrations (2045 ± 1300 µg/mL) compared with those with PAPA syndrome (116 ± 74 µg/mL) and have a distinct clinical phenotype. A specific cytokine profile is associated with Hz/Hc. Hz/Hc mutations altered protein binding of PSTPIP1, increasing interaction with pyrin through phosphorylation of PSTPIP1. CONCLUSION: Mutations resulting in charge reversal in the y-domain of PSTPIP1 (E→K) and increased interaction with pyrin cause a distinct autoinflammatory disorder defined by clinical and biochemical features not found in patients with PAPA syndrome, indicating a unique genotype-phenotype correlation for mutations in the PSTPIP1 gene. This is the first inborn autoinflammatory syndrome in which inflammation is driven by uncontrolled release of members of the alarmin family.

Recommendations for cardiomyopathy surveillance for survivors of childhood cancer: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group.

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.

Developing international consensus for late effects screening and guidance.

PURPOSE OF REVIEW: Long-term follow-up (LTFU) of childhood cancer survivors is important in view of their high frequency of chronic medical problems, many of which may be serious, disabling or life-threatening. Several LTFU guidelines for the care of survivors have been developed by different national groups but provide varied recommendations with areas of both agreement and of disagreement. This diversity has generated uncertainty about the ideal nature and content of LTFU. RECENT FINDINGS: The EU-funded PanCareSurFup project is developing pan-European guidelines for the prevention, early detection and treatment of physical or psychosocial late effects of childhood cancer and its treatment, as well as the organization of LTFU care including age-appropriate transitional care as survivors approach adulthood and optimal health-promotion advice for individual survivors and their families. The International Late Effects of Childhood Cancer Guideline Harmonization Group aims to achieve consensus concerning clinical practice guidelines for LTFU of major late effects in survivors. The overall aim is to produce harmonized recommendations of value to all the participating countries despite their potentially disparate needs and healthcare settings. SUMMARY: These initiatives seek to standardize and increase the efficiency of LTFU care and improve long-term health outcomes and quality of life in survivors.

Excellent outcome of matched unrelated donor transplantation in paediatric aplastic anaemia following failure with immunosuppressive therapy: a United Kingdom multicentre retrospective experience.

We retrospectively analysed the outcome of consecutive children with idiopathic severe aplastic anaemia in the United Kingdom who received immunosuppressive therapy (IST) or matched unrelated donor (MUD) haematopoietic stem cell transplantation (HSCT). The 6-month cumulative response rate following rabbit antithymocyte globulin (ATG)/ciclosporin (IST) was 32·5% (95% CI 19·3-46·6) (n = 43). The 5-year estimated failure-free survival (FFS) following IST was 13·3% (95% confidence interval [CI] 4·0-27·8). In contrast, in 44 successive children who received a 10-antigen (HLA-A, -B, -C, -DRB1, -DQB1) MUD HSCT there was an excellent estimated 5-year FFS of 95·01% (95% CI 81·38-98·74). Forty of these children had failed IST previously. HSCT conditioning was a fludarabine, cyclophosphamide and alemtuzumab (FCC) regimen and did not include radiotherapy. There were no cases of graft failure. Median donor chimerism was 100% (range 88-100%). A conditioning regimen, such as FCC that avoids total body irradiation is ideally suited in children. Our data suggest that MUD HSCT following IST failure offers an excellent outcome and furthermore, if a suitable MUD can be found quickly, MUD HSCT may be a reasonable alternative to IST.

Evaluation of infection control advice for patients at risk of chemotherapy-induced neutropenia in 2 pediatric oncology centers: Cape Town, South Africa, and Newcastle-Upon-Tyne, UK.

Childhood cancers are treated with myelotoxic chemotherapy. Resultant neutropenia can lead to life-threatening infections. There is no consistent guidance on infection control precautions for neutropenic patients who are not yet febrile or infected. Although it is not possible to eradicate infection risk, it is conceivable that the risk could be reduced by effective infection prevention. This study compared infection control measures advised to pediatric and adolescent oncology patients receiving chemotherapy in 2 centers (Cape Town, South Africa, and Newcastle, UK). Prospective, observational, cross-sectional surveys of staff and patients/parents were undertaken using standardized, study-specific questionnaires. Seventy-eight staff and 56 patients/parents participated. Precautions advised in Newcastle were significantly different to Cape Town (all P < .05), except both agreed inpatient isolation was unnecessary. Over 40% of patients/parents felt isolation was important (P < .01). In Cape Town, staff and patients had similar views. In Newcastle, patients/parents had stricter opinions on particular precautions than staff, for example, attending school, playing outside and avoiding busy places (P < .01). Patient/parent responses were similar between centers. Over 90% of staff felt advising patients/parents about hand washing was important. Currently infection prevention advice is inconsistent. Further research is needed to elucidate effective guidance for infection prevention in pediatric neutropenic patients.

PEPtalk: postexposure prophylaxis against varicella in children with cancer.

OBJECTIVES: To describe postexposure prophylaxis (PEP) against varicella zoster virus (VZV) in children being treated for malignancy in the UK and Ireland: the population at risk, frequency of exposure, clinical practice and attitudes among healthcare providers. DESIGN: An observational study in three parts: (1) a retrospective survey of serostatus at diagnosis of malignancy, (2) collation of varicella zoster immune globulin (VZIG) dispensing data over a 3-year period and (3) an online survey of paediatric oncologists' clinical practice and beliefs in relation to VZV disease and its prevention. SETTING: UK and Ireland. PARTICIPANTS: Children diagnosed with malignancy in 2009 (serostatus survey) or receiving VZIG between April 2006 and March 2009 (VZIG dispensing study). Paediatric oncologists and haematologists working in tertiary paediatric oncology centres and related shared care units in the UK and Ireland (physician survey). RESULTS: Of 1500 children diagnosed with malignancy each year, at least 24% are VZV seronegative. Few centres make efforts to prevent household exposure by vaccinating VZV-susceptible family members. Exposures to VZV result in the administration of PEP to approximately 250 children with cancer annually: half receive an intramuscular injection of VZIG while the remainder receive a course of oral aciclovir. The choice of PEP is made by doctors. There is no consensus among paediatric oncologists as to which is the better option, reflecting the lack of a secure evidence base. CONCLUSIONS: A randomised controlled trial to compare the effectiveness and acceptability of VZIG and aciclovir as PEP against varicella is both desirable and feasible.

Epidemiology of leukaemia and lymphoma in children and young adults from the north of England, 1990-2002.

AIM: We aimed to describe and contrast the epidemiology of haematological malignancies among 0-14 and 15-24-year-olds in northern England from 1990 to 2002 and compare clinical trial entry by age group. PATIENTS AND METHODS: Incidence rates were examined by age, sex and period of diagnosis and differences were tested using Poisson regression. Differences and trends in survival were assessed using Cox regression. RESULTS: 1680 subjects were included comprising 948 leukaemias and 732 lymphomas. Incidence rates for acute lymphoblastic leukaemia were significantly higher for 0-14 compared to 15-24-year-olds, whilst Hodgkin lymphoma showed the reverse. No significant changes in incidence were observed. 60% of leukaemia patients aged 15-24 years entered trials compared to 92% of 0-14-year-olds. Survival rates were significantly lower and improved less markedly over time for 15-24 compared to 0-14-year-olds, particularly for leukaemia. CONCLUSIONS: Trial accrual rates need to be improved amongst 15-24-year-olds and a more structured follow-up approach adopted for this unique population.