Leaving the parental home, cohabitation, and marriage after a hematologic malignancy in childhood-A register-based cohort study from the SALiCCS research program.

INTRODUCTION: Transitioning to adulthood often involves achieving independence from the parental home. We assessed whether the likelihood of leaving the parental home, cohabitation, and marriage was similar between patients who experienced a hematologic malignancy at a young age and their peers. METHODS: We identified 11,575 patients diagnosed with a hematologic malignancy under the age of 20 years between 1971 and 2011 in Denmark, Finland, and Sweden, 57,727 country-, age-, and sex-matched population comparisons and 11,803 sibling comparisons and obtained annual information on family and marital status by linking to the statistical institute databases. Hazard ratios (HR) for leaving the parental home, cohabitation and marriage were estimated using Cox proportional hazards modeling. RESULTS: Young adults with a history of a hematologic malignancy were slightly less likely to leave the parental home (HR 0.89; 95% confidence interval [CI] 0.86-0.92; HR 0.87 [95% CI 0.82-0.92]), cohabit with a nonmarital partner (HR 0.83 [95%CI 0.78-0.87]; HR 0.84 [95% CI 0.77-0.92]) and be married (HR 0.87 [95% CI 0.82-0.91]; HR 0.86 [95% CI 0.79-0.93]), compared with population comparisons and siblings, respectively. CONCLUSIONS: Our findings provide reassurance that young adults with a history of a hematologic malignancy show only a slight decrease in their likelihood of gaining independence from their childhood family and forming close interpersonal relationships compared to peers. While most patients are coping well in the long term, integrating structured psychosocial support into long-term follow-up is recommended to facilitate a timely and adequate transition into adulthood.

EGFR-mutation testing, treatment patterns and clinical outcomes in patients with stage IB-IIIA non-small cell lung cancer in Norway-a nationwide cohort study.

INTRODUCTION: Testing for mutations of epidermal growth factor receptor (EGFR) is crucial to identify non-small cell lung cancer (NSCLC) patients eligible for treatment with EGFR tyrosine kinase inhibitors (EGFR-TKIs); This study aims to describe EGFR-mutation testing, treatment patterns, and overall survival (OS) in localized NSCLC patients. MATERIALS AND METHODS: Patients with localized (Stage IB-IIIA) NSCLC registered in the Norwegian Cancer Registry during 2010-2017 were followed from diagnosis until emigration, death, or end of study in 2018. The cohort was linked to data from the Norwegian Patient Registry, the Prescription Database, and the Cause of Death Registry. RESULTS: Of 2367 patients identified with localized NSCLC, 52 % were females and median age at diagnosis was 69 years. Most (66 %) were treated with surgery, while 16 % received curatively-intended radiotherapy (RT). EGFR-mutation testing increased significantly from 58 to 84 % during the study period. Testing frequencies varied across regions and comorbidity levels. Nine-percent of tested patients were EGFR-mutation positive (EGFRm+), of whom 27 % were treated with EGFR-TKIs. There was no correlation between initial treatment with either surgery or RT and EGFR-TKI use. The 3-year OS did not vary considerably by EGFR-mutation testing, but EGFRm+ patients had a higher 3-year OS (78.8 %) than wild-type EGFR (EGFRwt) patients (65.9 %). DISCUSSION: Although EGFR-mutation testing is increasingly being implemented in the early-stage setting in line with national recommendations, some patients are still not being tested for molecular markers as part of their diagnostic workup-a prerequisite for providing equal access to effective targeted treatments, such as EGFR-TKIs, to eligible patients.

Educational attainment in survivors of childhood cancer in Denmark, Finland, and Sweden.

BACKGROUND: Survivors of childhood cancer may face difficulties at school. We investigated whether childhood cancer affects attainment of upper secondary education, in a register-based cohort study from Denmark, Finland, and Sweden, where we limit bias from selection and participation. METHODS: From the national cancer registers, we identified all long-term survivors of childhood cancer diagnosed aged 0-14 years in 1971-2005 (n = 7629), compared them to matched population comparisons (n = 35,411) and siblings (n = 6114), using odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Overall, 6127 survivors (80%) had attained upper secondary education by age 25, compared to 84% among comparison groups. Elevated OR for not attaining this level were mainly confined to survivors of central nervous system (CNS) tumours (ORSurv_PopComp2.05, 95%CI: 1.83-2.29). Other risk groups were survivors who had spent more time in hospital around cancer diagnosis and those who had hospital contacts in early adulthood, particularly psychiatric. Survivors of all cancer types were less likely to have attained upper secondary education without delay. CONCLUSIONS: Although survivors of childhood cancer experienced delays in their education, many had caught up by age 25. Except for survivors of CNS tumours, survivors attained upper secondary education to almost the same extent as their peers.

Diagnostic Workup, Treatment Patterns, and Clinical Outcomes in Early-Stage IB-IIIA Non-Small-Cell Lung Cancer Patients in Denmark.

Despite recent improvements in early-stage non-small-cell lung cancer (NSCLC), disease relapse remains challenging. Moreover, real-world evidence on long-term follow-up of disease-free survival (DFS) and recurrence patterns in a large, unselected cohort of early-stage NSCLC patients is lacking. This cohort study aimed to assess clinical characteristics, diagnostic workup, treatment, survival, and risk of disease relapse among early-stage NSCLC patients. Adult patients with stage IB, II, or IIIA NSCLC diagnosed and/or treated at Aarhus University Hospital in Denmark from January 2010 to December 2020 were included and followed-up until May 2021. Comprehensive clinical data were collected from electronic medical records of eligible patients and linked to Danish register data. The study population comprised 1341 early-stage NSCLC patients: 22%, 40%, and 38% were diagnosed with stage IB, II, and IIIA disease, respectively. In total, 42% of patients were tested for epidermal growth factor receptor (EGFR), of whom 10% were EGFR-mutation-positive (EGFRm+). Half of all patients received surgery, and nine percent of patients received stereotactic body radiation therapy (SBRT). Disease-free survival 5 years post-diagnosis was 49%, 42%, and 22% for stage IB, II, and stage IIIA patients, respectively. DFS improved over time both for patients treated with surgery and SBRT. However, disease relapse remained a challenge, with approximately 40% of stage IIIA having relapsed 3 years post-diagnosis. This study contributes important knowledge that puts clinical trials on new perioperative treatment modalities for early-stage NSCLC patients into perspective. Our findings cover an essential evidence gap on real-world DFS and recurrence dynamics, confirming that despite an improvement in DFS over time and across different treatment modalities, disease relapse remains a monumental challenge. Therefore, better treatment strategies are needed.

Income disparities between adult childhood cancer survivors and their peers-A register-based cohort study from the SALiCCS research programme.

BACKGROUND: Childhood cancer survivors face various adverse consequences. This Nordic register-based cohort study aimed to assess whether survivors of childhood cancer are more likely to have low income than their peers. METHODS: We identified 17,392 childhood cancer survivors diagnosed at ages 0 to 19 between 1971 and 2009 with 83,221 age-, sex-, and country-matched population comparisons. Annual disposable income at ages 20 to 50 years was retrieved from statistical offices (for 1990-2017) and categorized into low income and middle/high income. The number of transitions between income categories were assessed using binomial regression analyses. RESULTS: The prevalence of annual low income among childhood cancer survivors was 18.1% and 15.6% among population comparisons (risk ratio [RR] 1.17; 95% confidence interval [CI] 1.16-1.18). Compared to population comparisons, childhood cancer survivors were 10% (95% CI 8%-11%) less likely to transition from low to middle/high income and 12% (10%-15%) more likely to transition from middle/high to low income during follow-up. Among those initially in the low income category, survivors were 7% (95% CI 3%-11%) more likely to remain in the low income category. If the initial category was middle/high income, childhood cancer survivors were 10% (95% CI 8%-11%) less likely to remain in the middle/high income and 45% (37%-53%) more likely to transition to the low income category permanently. CONCLUSIONS: Childhood cancer survivors are at higher risk for low income in adulthood than their peers. These disparities might be reduced by continued career counseling along with support in managing within the social security system.

Employment status and occupational positions of childhood cancer survivors from Denmark, Finland and Sweden: A Nordic register-based cohort study from the SALiCCS research programme.

BACKGROUND: A childhood cancer diagnosis and late effects of treatment may affect survivors' possibilities of employment or highly skilled occupations later in life. In this study, we compared the employment and occupational status of childhood cancer survivors with population comparisons and siblings. METHODS: In a cohort study based on Nordic registers, we identified 10 461 survivors of childhood cancer diagnosed before age 20 years in Denmark, Finland and Sweden since 1971. Survivors were compared with 48 928 population comparisons matched to survivors by age, sex and geographical region and 12 605 siblings of survivors. Annual outcome information on employment, unemployment, health-related unemployment and occupational position was obtained from the statistical institutes between 1980-2017 and assessed in multivariate logistic regression analyses from age 30 onwards. FINDINGS: By 30 years of age, 9.2% (95% CI, 8.6-9.9%) of survivors were unemployed for health reasons. Childhood cancer survivors had considerably higher odds of health-related unemployment at ages 30, 40 and 50 than population comparisons (ORage30, 2.57; 95% CI, 2.35-2.81) and siblings (ORage30, 2.50; 95% CI, 2.15-2.90). We observed no large difference in unemployment unrelated to health or in occupational position. Health-related unemployment was particularly pronounced among survivors of central nervous system tumours and survivors diagnosed below 15 years of age. INTERPRETATION: Survivors at risk of health-related unemployment should be offered comprehensive survivorship care and interventions for obtaining and maintaining suitable employment. FUNDING: NordForsk [76111], the Danish Childhood Cancer Foundation [2016-0293], Aarhus University [43239402], the Swedish Childhood Cancer Foundation [PR2020-0130] and [OB2019-0003], Tømrermester Jørgen Holm og Hustru Elisa F. Hansens Mindelegat [20088] and the Swiss National Science Foundation to LM [P2LUP3_175288].

Psychiatric disorders in childhood cancer survivors in Denmark, Finland, and Sweden: a register-based cohort study from the SALiCCS research programme.

BACKGROUND: A childhood cancer diagnosis and treatment-induced somatic late effects can affect the long-term mental health of survivors. We aimed to explore whether childhood cancer survivors are at higher risk of psychiatric disorders later in life than their siblings and the general population. METHODS: In this register-based cohort study (part of the Socioeconomic Consequences in Adult Life after Childhood Cancer [SALiCCS] research programme), we included 5-year survivors of childhood cancer diagnosed before 20 years of age between Jan 1, 1974 and Dec 31, 2011, in Denmark, Finland, and Sweden. In Denmark and Sweden, 94·7% of individuals were born in a Nordic country (ie, Denmark, Finland, Iceland, Norway, or Sweden); similar information was not available in Finland. Data on ethnicity were not collected. Survivors were compared with their siblings and randomly selected individuals from the general population who were matched to the survivors by year of birth, sex, and geographical region. We followed up our study population from 5 years after the childhood cancer diagnosis or corresponding calendar date for matched individuals (the index date) until Aug 11, 2017, and assessed information on hospital contacts for any and specific psychiatric disorders. For siblings, the index date was defined as 5 years from the date on which they were of the same age as their sibling survivor when diagnosed with cancer. FINDINGS: The study population included 18 621 childhood cancer survivors (9934 [53·3%] males and 8687 [46·7%] females), 24 775 siblings (12 594 [50·8%] males and 12 181 [49·2%] females), and 88 630 matched individuals (47 300 [53·4%] males and 41 330 [46·6%] females). The cumulative incidence proportion of having had a psychiatric hospital contact by 30 years of age between Jan 1, 1979, and Aug 11, 2017, was 15·9% (95% CI 15·3-16·5) for childhood cancer survivors, 14·0% (13·5-14·5) for siblings, and 12·7% (12·4-12·9) for matched individuals. Despite a small absolute difference, survivors were at higher relative risk of any psychiatric hospital contact than their siblings (1·39, 1·31-1·48) and matched individuals (hazard ratio 1·34, 95% CI 1·28-1·39). The higher risk persisted at the age of 50 years. Survivors had a higher burden of recurrent psychiatric hospital contacts and had more hospital contacts for different psychiatric disorders than their siblings and the matched individuals. INTERPRETATION: Childhood cancer survivors are at higher long-term risk of psychiatric disorders than their siblings and matched individuals from the general population. To improve mental health and the overall quality of life after childhood cancer, survivorship care should include a focus on early signs of mental health problems, especially among high-risk groups of survivors. FUNDING: NordForsk, Aarhus University, Swedish Childhood Cancer Foundation, Danish Health Foundation, and Swiss National Science Foundation.

Cohort Profile: The Socioeconomic Consequences in Adult Life After Childhood Cancer in Scandinavia (SALiCCS) Research Programme.

INTRODUCTION: The growing number of survivors of childhood cancer, with many years of life ahead, demonstrates the increasing clinical and public health relevance of investigating the risks of social and socioeconomic impairment after a childhood cancer diagnosis and the life-saving treatment. To enrich understanding of the mental, social and socioeconomic difficulties that childhood cancer survivors may face during their life-course, identify particularly vulnerable survivors and overcome the limitations of previous research, we initiated the Socioeconomic Consequences in Adult Life after Childhood Cancer in Scandinavia (SALiCCS) research programme. METHODS: This Nordic cross-border research programme is a collaboration between the Danish Cancer Society, the Finnish Cancer Registry and Karolinska Institutet to investigate a broad range of mental, social and socioeconomic conditions in long-term childhood cancer survivors in Denmark, Finland and Sweden. SALiCCS is based on a registry-based matched cohort design, comprising five-year survivors of cancer diagnosed at ages 0-19 years (1971-2008 in Denmark, 1971-2009 in Finland, 1971-2011 in Sweden), age-, sex- and country-matched population comparisons and sibling comparisons who were followed over time. Outcomes of interest included mental disorders, educational achievements, employment and profession, family life and the need of social security benefits. Individual-level data linkage among various national registries provided the data for the research programme. RESULTS: The SALiCCS core population comprises 21,292 five-year survivors, 103,303 population comparisons and 29,644 siblings as a second comparison group. The most common diagnoses in survivors were central nervous system tumours, leukaemias and lymphomas. DISCUSSION: SALiCCS is the largest, most comprehensive population-based research initiative in this field, based on high-quality registry data with minimal risk of bias. The findings will be informative for evidence-based survivorship care targeting not only somatic late effects but also psychosocial impairments.

Hospital Contacts for Psychiatric Disorders in Parents of Children With Cancer in Denmark.

Background: Having a child diagnosed with cancer is a devastating experience that may affect parents' mental health. We aimed to assess the risk of hospital contacts for psychiatric disorders in parents of children with cancer. Methods: We conducted a nationwide population-based cohort study using Danish registry data. Parents of children diagnosed with cancer between 1982 and 2014 (n = 6689 mothers, n = 5509 fathers) were matched with comparison parents of cancer-free children (n = 67 544 mothers, n = 55 756 fathers). We used Cox proportional hazards models to estimate the risk of hospital contacts for any psychiatric disorder and specific disorders. Cox models were also used to investigate sociodemographic and cancer-related risk factors for psychiatric disorders. Results: Incidence rates of hospital contacts for any psychiatric disorder were 426 per 100 000 person-years in mothers of children with cancer and 345 per 100 000 person-years in comparison mothers. For fathers, the respective incidence rates were 260 and 262 cases per 100 000 person-years. Compared with parents of cancer-free children, mothers of children with cancer were at an increased risk of hospital contacts for any psychiatric disorder (hazard ratio = 1.23, 95% confidence interval = 1.12 to 1.36), whereas no elevated risk was seen in fathers (hazard ratio = 0.99, 95% confidence interval = 0.87 to 1.13). Among mothers, risks were particularly elevated for affective and stress-related disorders. Parents of deceased children and children diagnosed at a younger age were at particular risk of hospital contacts for psychiatric disorders. Conclusion: Hospital contacts for psychiatric disorders were overall rare. Health-care professionals should draw attention to subgroups of vulnerable parents to meet their needs of support and adequate treatment.

Childhood cancer: Survival, treatment modalities, late effects and improvements over time.

Since the 1960s, paediatric oncologists have gradually become better organised in large study groups and participation in clinical trials is today considered as the standard of care, with most children with cancer in Europe and North America being enrolled on available treatment protocols. Chemotherapy is nowadays the main element of therapy, but irradiation is still required for some patients. With the advent of multimodality therapy and supportive care, five-year cancer survival exceeds 80 % in most European and North American countries today. The substantial improvements in survival led to a constantly growing population of childhood cancer survivors. Concerns regarding the risk of late effects of the intensive cancer treatment at a young age, together with increasing numbers of survivors, have directed attention towards survivorship research. Survivors of childhood cancer are at longstanding risk of various severe somatic and mental health conditions attributable to the cancer and its treatment, as well as adverse social and socioeconomic consequences, and diminished psychological well-being and quality of life. It is, however, important to stress that some survivors have no or very mild adverse health conditions. Nevertheless, joint efforts are warranted for the care and long-term follow-up of childhood cancer patients. With this article, we provide a comprehensive overview of improvements in survival and treatment modalities over time, as well as the related somatic and mental late effects, and social and socioeconomic difficulties that these children might encounter later in life.

The impact of childhood cancer on parental separation, divorce, and family planning in Denmark.

BACKGROUND: Childhood cancer is a devastating experience for the family. The objective of the current study was to assess the impact of having a child with cancer on parental separation, divorce, and future family planning among families residing in Denmark. METHODS: The authors conducted a nationwide cohort study using Danish registry data. Parents of children diagnosed with cancer between 1982 and 2014 (7066 children and 12,418 case parents) were matched with 10 comparison parents of cancer-free children per case parent (69,993 children and 125,014 comparison parents). We used discrete-time Cox regression models to compare the risk of separation (end of cohabitation) and divorce between case and comparison parents, and to identify risk factors for separation and divorce among case parents only. Descriptive statistics were used to compare family planning between case and comparison parents. RESULTS: Case parents were found to have a slightly lower risk of separation (hazard ratio, 0.96; 95% confidence interval, 0.93-0.99) and divorce (hazard ratio, 0.92; 95% confidence interval, 0.87-0.97) than comparison parents. The authors found that case parents who were aged <45 years, with short education (an International Standard Classification of Education code indicating early childhood education, primary education, and lower secondary education), and who were unemployed were at an increased risk of separation and divorce. Moreover, the parents of children diagnosed with cancer at a young age (aged <15 years) were more likely to separate or divorce. No differences with regard to the total number of children and time to a next child after the cancer diagnosis were observed between case and comparison parents. CONCLUSIONS: Having a child with cancer was not associated with an overall adverse impact on parents' risk of separation or divorce and future family planning. These encouraging findings should be communicated to parents to support them along their child's cancer trajectory.

Parental tobacco smoking and risk of childhood leukemia in Costa Rica: A population-based case-control study.

INTRODUCTION: The role of environmental and behavioral exposures on childhood leukemia etiology is poorly understood. We examined the association of maternal and paternal tobacco smoking at different time points with the risk of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) in Costa Rican children. MATERIALS AND METHODS: We conducted a population-based case-control study on childhood leukemia in Costa Rica. Cases (n ALL = 252; n AML = 40) were diagnosed between 1995 and 2000 (aged <15 years at diagnosis) and identified from the Costa Rican Cancer Registry and the National Children's Hospital. A total of 578 frequency-matched population controls were sampled from the National Birth Registry. Parental tobacco smoking was assessed via face-to-face interviews. We used logistic regression models to examine the association of paternal and maternal tobacco smoking before conception, during pregnancy, and after birth with childhood ALL and AML risk, adjusted for child sex, birth year, maternal/paternal age, and parental education. RESULTS: Paternal smoking before conception, during pregnancy, and after birth was associated with an increased risk of childhood AML (Odds Ratio (OR): 2.51, 95% CI: 1.21-5.17; OR: 3.21, 95% CI: 1.56-6.60; and OR: 2.83, 95% CI: 1.36-5.90, respectively). Maternal smoking during pregnancy was also associated with a modest, but imprecise increase in AML risk. We observed null associations of maternal and paternal smoking with ALL in the offspring. CONCLUSION: Our results suggest an association between parental smoking and risk of AML, but not ALL, in Costa Rican children. These findings add to the established evidence of numerous health risks associated with smoking and highlight the potential harm of smoking during sensitive windows of the development of fetus and child.

Surviving childhood cancer: a systematic review of studies on risk and determinants of adverse socioeconomic outcomes.

Substantial improvements in childhood cancer survival have resulted in a steadily increasing population of childhood cancer survivors. Whereas somatic late effects have been assessed in many studies, less is known about the impact of childhood cancer on socioeconomic outcomes in survivors. The aim of this article was to evaluate and summarise the evidence on the socioeconomic conditions of childhood cancer survivors and to identify survivors at particular risk of adverse socioeconomic outcomes. An extensive literature search of three electronic databases was conducted. Of 419 articles identified, 52 met the inclusion criteria. All the selected articles were appraised for quality, and findings were summarised in a narrative synthesis. Childhood cancer survivors were at higher risk of adverse socioeconomic outcomes with regard to educational achievement, income and social security benefits than the general population or a sibling comparison group. The risks for unemployment and a lower occupational position were significantly increased only for survivors of a central nervous system tumour. Notably, survivors of central nervous system tumours, survivors treated with cranial radiotherapy and those diagnosed at younger age independent of cancer type were determinants of particular adverse socioeconomic outcomes. Given the increasing population of childhood cancer survivors, targeted follow-up interventions and support strategies addressing not only the somatic and psychiatric late effects but also the socioeconomic difficulties that some childhood cancer survivors face is of high importance to reduce social inequity, and ensure a high quality of life after childhood cancer.

Risk of Adverse Pregnancy Outcomes at Advanced Maternal Age.

OBJECTIVE: To study the possible associations between advanced maternal age and risk of selected adverse pregnancy outcomes. METHODS: The study used a nationwide cohort of 369,516 singleton pregnancies in Denmark followed from 11-14 weeks of gestation to delivery or termination of pregnancy. Pregnant women aged 35 years or older were divided into two advanced maternal age groups, 35-39 years and 40 years or older, and compared with pregnant women aged 20-34 years. Adverse pregnancy outcomes were chromosomal abnormalities, congenital malformations, miscarriage, stillbirth, and birth before 34 weeks of gestation. Multivariable logistic regression analyses were performed to investigate associations between advanced maternal age and adverse pregnancy outcomes. Furthermore, a risk prediction model for a composite adverse pregnancy outcome was made with prespecified predicting factors. RESULTS: Among the pregnant women aged 40 years or older, 10.82% experienced one or more of the selected adverse pregnancy outcomes compared with 5.46% of pregnant women aged 20-34 years (odds ratio [OR] 2.02, 99.8% CI 1.78-2.29). When pregnant women 40 years or older were compared with women aged 20-34 years, they had a higher risk of chromosomal abnormalities (3.83% vs 0.56%, OR 7.44 [CI 5.93-9.34]), miscarriage (1.68% vs 0.42%, OR 3.10 [CI 2.19-4.38]), and birth before 34 weeks of gestation (2.01% vs 1.21%, OR 1.66 [CI 1.23-2.24]), but no increased risk of congenital malformations and stillbirth. The risk prediction chart showed that advanced maternal age, use of assisted reproductive technology, nulliparous pregnancy, smoking during pregnancy, and obesity increased the absolute predictive risk of an adverse pregnancy outcome. CONCLUSION: Women older than 40 years have a higher risk of chromosomal abnormalities, miscarriage, and birth before 34 weeks of gestation than younger women and should be monitored accordingly. No increased risk was observed for stillbirth and other congenital malformations. Several factors increase the risk of adverse pregnancy outcomes, but advanced maternal age drives a high proportion of the total risk score.