The 'Survivorship Passport' for childhood cancer survivors

Background: Currently, there are between 300,000 and 500,000 childhood cancer survivors (CCSs) in Europe. A significant proportion is at high risk, and at least 60% of them develop adverse health-related outcomes that can appear several years after treatment completion. Many survivors are unaware of their personal risk, and there seems to be a general lack of information among healthcare providers about pathophysiology and natural history of treatment-related complications. This can generate incorrect or delayed diagnosis and treatments. Method: The Survivorship Passport (SurPass) consists of electronic documents, which summarise the clinical history of the childhood or adolescent cancer survivor. It was developed by paediatric oncologists of the PanCare and SIOPE networks and IT experts of Cineca, together with parents, patients, and survivors' organisations within the European Union–funded European Network for Cancer research in Children and Adolescents. It consists of a template of a web-based, simply written document, translatable in all European languages, to be given to each CCS. The SurPass provides a summary of each survivor's clinical history, with detailed information about the original cancer and of treatments received, together with personalised follow-up and screening recommendations based on guidelines published by the International Guidelines Harmonization Group and PanCareSurFup. Results: The SurPass data schema contains a maximum of 168 variables and uses internationally approved nomenclature, except for radiotherapy fields, where a new classification was defined by radiotherapy experts. The survivor-specific screening recommendations are mainly based on treatment received and are automatically suggested, thanks to built-in algorithms. These may be adapted and further individualised by the treating physician in case of special disease and survivor circumstances. The SurPass was tested at the Istituto Giannina Gaslini, Italy, and received positive feedback. It is now being integrated at the institutional, regional and national level. Conclusions: The SurPass is potentially an essential tool for improved and more harmonised follow-up of CCS. It also has the potential to be a useful tool for empowering CCSs to be responsible for their own well-being and preventing adverse events whenever possible. With sufficient commitment on the European level, this solution should increase the capacity to respond more effectively to the needs of European CCS

Possible modification of BRSK1 on the risk of alkylating chemotherapy-related reduced ovarian function

STUDY QUESTION: Do genetic variations in the DNA damage response pathway modify the adverse effect of alkylating agents on ovarian function in female childhood cancer survivors (CCS)? SUMMARY ANSWER: Female CCS carrying a common BR serine/threonine kinase 1 (BRSK1) gene variant appear to be at 2.5-fold increased odds of reduced ovarian function after treatment with high doses of alkylating chemotherapy. WHAT IS KNOWN ALREADY: Female CCS show large inter-individual variability in the impact of DNA-damaging alkylating chemotherapy, given as treatment of childhood cancer, on adult ovarian function. Genetic variants in DNA repair genes affecting ovarian function might explain this variability. STUDY DESIGN, SIZE, DURATION: CCS for the discovery cohort were identified from the Dutch Childhood Oncology Group (DCOG) LATER VEVO-study, a multi-centre retrospective cohort study evaluating fertility, ovarian reserve and risk of premature menopause among adult female 5-year survivors of childhood cancer. Female 5-year CCS, diagnosed with cancer and treated with chemotherapy before the age of 25 years, and aged 18 years or older at time of study were enrolled in the current study. Results from the discovery Dutch DCOG-LATER VEVO cohort (n = 285) were validated in the pan-European PanCareLIFE (n =465) and the USA-based St. Jude Lifetime Cohort (n = 391). PARTICIPANTS/MATERIALS, SETTING, METHODS: To evaluate ovarian function, anti-Miillerian hormone (AMH) levels were assessed in both the discovery cohort and the replication cohorts. Using additive genetic models in linear and logistic regression, five genetic variants involved in DNA damage response were analysed in relation to cyclophosphamide equivalent dose (CED) score and their impact on ovarian function. Results were then examined using fixed-effect meta-analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Meta-analysis across the three independent cohorts showed a significant interaction effect (P= 3.0 x 10(-4)) between rs11668344 of BRSK 1 (allele frequency = 0.34) among CCS treated with high-dose alkylating agents (CED score >= 8000 mg/m(2)), resulting in a 2.5-fold increased odds of a reduced ovarian function (lowest AMH tertile) for CCS carrying one G allele compared to CCS without this allele (odds ratio genotype AA: 2.01 vs AG: 5.00). LIMITATIONS, REASONS FOR CAUTION: While low AMH levels can also identify poor responders in assisted reproductive technology, it needs to be emphasized that AMH remains a surrogate marker of ovarian function. WIDER IMPLICATIONS OF THE FINDINGS: Further research, validating our findings and identifying additional risk contributing genetic variants, may enable individualized counselling regarding treatment-related risks and necessity of fertility preservation procedures in girls with cancer

Genetic variation in gonadal impairment in female survivors of childhood cancer: a PanCareLIFE study protocol

BACKGROUND: Improved risk stratification, more effective therapy and better supportive care have resulted in survival rates after childhood cancer of around 80% in developed countries. Treatment however can be harsh, and three in every four childhood cancer survivors (CCS) develop at least one late effect, such as gonadal impairment. Gonadal impairment can cause involuntary childlessness, with serious consequences for the well-being of CCS. In addition, early menopause increases the risk of comorbidities such as cardiovascular disease and osteoporosis. Inter-individual variability in susceptibility to therapy related gonadal impairment suggests a role for genetic variation. Currently, only one candidate gene study investigated genetic determinants in relation to gonadal impairment in female CCS; it yielded one single nucleotide polymorphism (SNP) that was previously linked with the predicted age at menopause in the general population of women, now associated with gonadal impairment in CCS. Additionally, one genome wide association study (GWAS) evaluated an association with premature menopause, but no GWAS has been performed using endocrine measurements for gonadal impairment  as the primary outcome in CCS.METHODS: As part of the PanCareLIFE study, the genetic variability of chemotherapy induced gonadal impairment among CCS will be addressed. Gonadal impairment will be determined by anti-Müllerian hormone (AMH) levels or alternatively by fertility and reproductive medical history retrieved by questionnaire. Clinical and genetic data from 837 non-brain or non-bilateral gonadal irradiated long-term CCS will result in the largest clinical European cohort assembled for this late-effect study to date. A candidate gene study will examine SNPs that have already been associated with age at natural menopause and DNA maintenance in the general population. In addition, a GWAS will be performed to identify novel allelic variants. The results will be validated in an independent CCS cohort.DISCUSSION: This international collaboration aims to enhance knowledge of genetic variation which may be includ

Sun Exposure and Protection Habits in Pediatric Patients with a History of Malignancy.

Survivors of childhood cancer are at high risk for developing non-melanoma skin cancer and therefore are firmly advised to avoid or minimize sun exposure and adopt skin protection measures. We aimed to compare sun exposure and protection habits in a cohort of pediatric patients with a history of malignancy to those of healthy controls.Case-control study of 143 pediatric patients with a history of malignancy (aged 11.2±4.6 y, Male = 68, mean interval from diagnosis 4.4±3.8 y) and 150 healthy controls (aged 10.4±4.8 y, Male = 67). Sun exposure and protection habits were assessed using validated questionnaires.Patients and controls reported similar sun exposure time during weekdays (94±82 minutes/day vs. 81±65 minutes/day; p = 0.83), while during weekends patients spent significantly less time outside compared to controls (103±85 minutes/day vs. 124±87 minutes/day; p = 0.02). Time elapsed from diagnosis positively correlated with time spent outside both during weekdays (r = 0.194, p = 0.02) and weekends (r = 0.217, p = 0.01), and there was a step-up in sun exposure starting three years after diagnosis. There was no significant difference regarding composite sun protection score between patients and controls. Age was positively correlated with number of sunburns per year and sun exposure for the purpose of tanning, and was negatively correlated with the use of sun protection measures.Although childhood cancer survivors are firmly instructed to adopt sun protection habits, the adherence to these instructions is incomplete, and more attention should be paid to improve these habits throughout their lives. Since sunlight avoidance may results in vitamin D deficiency, dietary supplementation will likely be needed

Impact of COVID-19 on Lifestyle Habits and Emotional State of Childhood Cancer Survivors and Their Parents

Objective: The COVID-19 pandemic and associated social distancing measures affected the physical and emotional state of children and parents worldwide. Survivors of childhood cancer may be particularly vulnerable to these effects. We aimed to evaluate the lifestyle habits and emotional states of childhood cancer survivors and their parents during the COVID-19 outbreak. Methods: Lifestyle habits and emotional distress were assessed in 43 childhood cancer survivors (aged 8–21 years) and their parents before and during the COVID-19 lockdown, using the PROMIS anxiety and depression modules and the “Mabat Youth” questionnaire. Results: Most parents (80.5%) reported eating more family meals during home confinement compared to their usual routine. Patients’ physical activity levels did not change significantly during confinement, leisure-related screen time nearly doubled (p p = 0.006). Anxiety levels of children (p = 0.045) and parents (p = 0.02) increased during confinement compared to pre-pandemic levels, with no significant changes in depression levels. Conclusions: Contrary to concerns regarding lifestyle habits during the COVID-19 lockdown, eating behaviors of childhood cancer survivors improved, sleep duration increased, and physical activity remained unchanged. Still, screen time increased significantly. Parents of childhood cancer survivors reported higher anxiety levels for themselves and their children during home confinement. Our findings may assist medical and psycho-social teams in guiding parents of cancer survivors during similar circumstances in the future

Minutes/day (mean±SD) spent outside in the summer between 10 a.m and 4 p.m of the two study groups.

<p>Minutes/day (mean±SD) spent outside in the summer between 10 a.m and 4 p.m of the two study groups.</p