DÄ internationalArchive47/2017Unemployment Following Childhood Cancer

Original article

Unemployment Following Childhood Cancer

A systematic review and meta-analysis

Dtsch Arztebl Int 2017; 114: 805-12. DOI: 10.3238/arztebl.2017.0805

Mader, L; Michel, G; Roser, K

Background: Childhood cancer survivors are at risk of physical and mental long-term sequelae that may interfere with their employment situation in adulthood. We updated a systematic review from 2006 and assessed unemployment in adult childhood cancer survivors compared to the general population, and its predictors.

Methods: Systematic literature searches for articles published between February 2006 and August 2016 were performed in CINAHL, EMBASE, PubMed, PsycINFO, and SocINDEX. We extracted unemployment rates in studies with and without population controls (controlled /uncontrolled studies). Unemployment in controlled studies was evaluated using a meta-analytic approach.

Results: We included 56 studies, of which 27 were controlled studies. Approximately one in six survivors was unemployed. The overall meta-analysis of controlled studies showed that survivors were more likely to be unemployed than controls (Odds Ratio [OR] = 1.48, 95% confidence interval [CI]: [1.14; 1.93]). Elevated odds were found in survivors in the US and Canada (OR = 1.86, 95% CI: [1.26; 2.75]), as well as in Europe (OR = 1.39, 95% CI: [0.97; 1.97]). Survivors of brain tumors in particular were more likely to be unemployed (OR = 4.62, 95% CI: [2.56; 8.31]). Narrative synthesis across all included studies revealed younger age at study and diagnosis, female sex, radiotherapy, and physical late effects as further predictors of unemployment.

Conclusion: Childhood cancer survivors are at considerable risk of unemployment in adulthood. They may benefit from psycho-social care services along the cancer trajectory to support labor market integration.

LNSLNS

Survival after childhood cancer has substantially improved in the last decades resulting in a growing population of survivors reaching adulthood (1). However, childhood cancer survivors are at high risk of adverse chronic health conditions (27). Approximately two thirds of long-term survivors reported at least one chronic health condition and nearly 30% were suffering from severe or life-threatening conditions (2). Although many survivors cope well with such conditions, a considerable number of survivors experienced impaired psycho-social functioning in adult life, particularly in terms of employment (8).

A review published in 2006 showed that adult survivors of childhood cancer were nearly twice as likely to be unemployed than controls (9). Since 2006, the body of literature on unemployment after childhood cancer has steadily grown. Recent studies showed that survivors more often applied for governmental social security benefits than cancer-free individuals (1012), indicating a relatively high economic burden of childhood cancer on an individual and societal level.

As unemployment is a time-dependent phenomenon, a more up-to-date understanding of unemployment after childhood cancer and a careful identification of predictors is necessary in order to advocate interventions to decrease the individual and societal burden. We therefore updated a systematic review and meta-analysis by de Boer and colleagues (9). Specifically, we aimed to 1) assess the prevalence of unemployment in adult childhood cancer survivors compared to the general population, and 2) identify predictors of unemployment in studies published after January 2006.

Methods

This review complies with the PRISMA statement regarding the reporting of systematic reviews and meta-analyses (13).

Search strategy

The literature search included articles published in peer-reviewed journals between February 2006 and August 2016. We searched the following electronic databases without language restrictions: CINAHL, EMBASE, PubMed, PsycINFO, and SocINDEX. We used search terms (eFigure 1) similar to the previous review (9). Reference lists of included studies were hand-searched to identify further articles.

Search terms used in electronic databases
eFigure 1
Search terms used in electronic databases

Study selection

We used the following inclusion criteria to select eligible studies:

  • Quantitative methodology
  • Sample size >20
  • Age at diagnosis <18 years
  • Completed treatment or were diagnosed ≥ 5 years prior to the study
  • Age at study ≥18 years.

Review articles, editorials, commentaries, and conference abstracts were excluded. Two reviewers (LM, KR) independently assessed the eligibility of studies by first screening titles/abstracts and second, full-texts of the remaining studies. Discrepancies between the reviewers were resolved by discussion.

Data extraction

Data were extracted into a Microsoft Access database including the following:

  • First author
  • Publication year
  • Study origin
  • Study design
  • Sample size
  • Response rate
  • Whether or not the study included a control population (controlled or uncontrolled study)
  • Type of control population
  • Demographic (age, sex) and cancer-related characteristics (diagnosis, age at diagnosis, time since diagnosis)
  • Employment data and their stratification (i.e. by diagnosis)
  • Predictors of unemployment.

The extracted data were independently double-checked by a second reviewer (KR).

Quality assessment

Study quality was independently assessed by two reviewers (LM, KR) using five criteria displayed in eTable 1. These criteria were based on those in the previous review (9).

Quality assessment of included studies
eTable 1
Quality assessment of included studies

Statistical analysis

Analyses were performed using Stata version 14.1 (StataCorp LP, College Station, TX). We excluded students and homemakers whenever possible to include only participants eligible for employment. Employment was dichotomized into employed (full-time, part-time, sheltered employment, or parental/sick leave) and unemployed. Six studies did not report the number of controls with the respective employment status because national averages or the number of expected cases were reported (e1e6). For these studies, we imputed the number of controls using a 1:1 ratio to the respective survivor population.

We performed a meta-analysis including all controlled studies. Employment outcomes were summarized using odds ratios (ORs) with the corresponding 95% confidence interval (95% CI). We used random effect meta-analysis to calculate pooled estimates because we expected substantial between-study variability for two reasons: we included observational studies that are prone to higher variability, and there are large differences across countries in labor markets, social welfare, and health care systems. In a random effect meta-analysis effect estimates of individual studies are assumed to vary around an overall average effect, whereas a fixed effect meta-analysis assumes the same effect across studies (14).

Statistical heterogeneity was identified using I2 statistics (15). Publication bias was examined using visual checking for asymmetry in funnel plots and Harbord’s modified test was used to detect small-study effects (16). We performed sensitivity analyses using other imputation ratios (1:5, 1:20, 1:50) for studies not reporting the number of controls. Furthermore, we compared unemployment rates weighted for sample size between uncontrolled and controlled studies to evaluate the representativeness of the controlled studies.

We then performed similar analyses stratified by:

  • Region (Europe, US/Canada, and Asia)
  • Diagnostic group

– blood cancers (leukemia, lymphoma)

– central nervous system (CNS) tumors

– bone tumors/soft tissue sarcomas)

  • Study quality.

Other predictors of unemployment were investigated using meta-regression to assess associations of the factors age at study, age at diagnosis, and time since diagnosis with the respective OR in controlled studies. Additionally, we narratively synthesized further predictors reported in all included studies.

Results

Literature search and study selection

We identified 1416 articles in the literature search including 102 eligible articles (Figure 1). For multiple articles based on the same study, we included only the most recent publication with the largest sample and/or most complete employment data. Therefore, we excluded 46 articles resulting in 56 studies finally included in the systematic review (e1e56), of which 27 were controlled studies (eTable 2).

Flow diagram of studies excluded and included for systematic review and meta-analysis CCS, childhood cancer survivors
Figure 1
Flow diagram of studies excluded and included for systematic review and meta-analysis CCS, childhood cancer survivors
Characteristics of included studies by study origin
eTable 2
Characteristics of included studies by study origin

Study characteristics

Twenty-four studies were performed in Europe, 23 studies in the US or Canada, and 9 studies in Asia (eTable 2). Eighteen studies provided stratified employment data for blood cancer, 15 for CNS tumor, and 7 for bone tumor/soft tissue sarcoma survivors. Across all included studies, average age at diagnosis ranged from 2–16 years, mean age at study ranged from 18–38 years, and the percentage of male survivors ranged from 19% to 69%.

Unemployment

The overall meta-analysis of controlled studies showed that survivors were 1.5 times more likely to be unemployed than controls (Figure 2; OR: 1.48, 95% confidence interval: [1.14; 1.93]). We observed large differences in unemployment rates among survivors between and within regions (eTable 2). Unemployment weighted for sample size was similar in controlled (17%) and uncontrolled (15%) studies. The funnel plot was symmetrical with no indication of small-study effects (p = 0.326). Findings remained stable in sensitivity analyses with different imputation ratios for studies not reporting the number of controls.

Unemployment by region

The meta-analysis of European studies showed that survivors had increased odds of unemployment compared to controls (Figure 2; OR: 1.39 [0.97; 1.97]). Survivors from the US and Canada were nearly twice as likely as controls to be unemployed (OR = 1.86 [1.26; 2.75]). No increased odds were found for survivors from Asia (OR: 0.87 [0.42; 1.81]). We observed comparable unemployment rates in controlled studies from Europe, the US and Canada, and Asia (16%, n = 17; 17%, n = 8; 24%, n = 2). Unemployment rates in uncontrolled studies were lower in Europe (8%, n = 7) and higher in the US and Canada (26%, n = 15), and Asia (48%, n = 7).

Unemployment in adult survivors of childhood cancer, stratified by region (Europe, Asia, and United States and Canada)
Figure 2
Unemployment in adult survivors of childhood cancer, stratified by region (Europe, Asia, and United States and Canada)

Unemployment by diagnostic group

CNS tumor survivors were nearly 5 times more likely to be unemployed compared to controls (Figure 3; OR: 4.62 [2.56; 8.31]). Although not statistically significant, elevated odds were also found for blood cancer (OR: 1.35 [0.89; 2.06]) and bone tumor/soft tissue sarcoma survivors (OR: 1.25 [0.80; 1.95]). For all diagnostic groups, unemployment was higher in uncontrolled compared to controlled studies: CNS tumors (46%, n = 6 vs. 27%, n = 9), blood cancers (27%, n = 6 vs. 13%, n = 12), and bone tumors/soft tissue sarcomas (20%, n = 2 vs. 16%, n = 5).

Unemployment in adult survivors, stratified by diagnostic group (blood cancer, central nervous system tumor and bone tumor/soft tissue sarcoma)
Figure 3
Unemployment in adult survivors, stratified by diagnostic group (blood cancer, central nervous system tumor and bone tumor/soft tissue sarcoma)

Quality assessment

Nineteen (34%) studies included a representative survivor and 14 (52%) a representative control population (eTable 1). Ten (37%) controlled studies adjusted the comparison of employment for age and sex. Among controlled studies, 7 (26%) studies were of low to moderate and 20 (74%) of high quality. We found similar effect estimates for studies of low to moderate (eFigure 2; OR: 1.52 [1.16; 2.00]) and high quality (OR: 1.53 [1.10; 2.12]).

Unemployment in adult survivors of childhood cancer stratified by study quality
eFigure 2
Unemployment in adult survivors of childhood cancer stratified by study quality

Predictors of unemployment

Meta-regression showed no association between unemployment and survivors’ age at study (p = 0.624), age at diagnosis (p = 0.566), and time since diagnosis (p = 0.422) in controlled studies. Across all included studies, four identified younger age at study (e1, e5, e37, e47) and three younger age at diagnosis (e16, e22, e47) as predictors of unemployment. Other socio-demographic predictors were female sex (e2, e5, e16, e37, e47), school dropout (e51), and lower parental education (e16). Clinical predictors of unemployment were (cranial) radiation (e2, e9, e22, e31, e37, e47, e50), stem cell transplantation (e50), and cancer-related late effects (e1, e4, e29, e31, e37, e50, e51) including neurocognitive impairment (e29, e31, e37) or hearing loss (e29).

Discussion

This study updated a previous systematic review on unemployment after childhood cancer (9) to address the growing body of literature on this topic showing inconsistent findings. We found that a considerable number of survivors experienced employment-related problems in adulthood. Approximately one in six survivors was unemployed. Compared to population controls, survivors were 1.5 times more likely to be unemployed. In Germany, a study based on the German Childhood Cancer Registry revealed an unemployment rate of 21% among survivors compared to 16% in controls (e13). However, we observed substantial differences across regions and diagnostic groups. In particular, survivors from the US and Canada and survivors of CNS tumors had increased odds of unemployment.

Our meta-analysis showed that survivors’ odds of unemployment was lower compared to a previous review of studies published between 1966 and 2006 (9). Although it is difficult to conclusively determine the reasons for these differences given the broader economic circumstances (e.g. recession in 2008), stratification by region revealed that this decrease was mainly driven by lower unemployment rates in survivors from the US and Canada in more recent studies. In 2006, de Boer and colleagues hypothesized that cancer-related work discrimination may be relatively high in the US with employers being more reluctant to hire cancer survivors due to fears of lower productivity (9); this may have changed in recent years.

Nevertheless, survivors’ odds of unemployment remained higher in the US and Canada compared to Europe. This is of particular concern as in contrast to most other developed countries, health insurance in the US is mainly provided and financially covered by employers (17). Employers in Europe may provide more flexible working conditions with better sick leave compensations (10) that help survivors to stay in the work force despite relatively frequent hospitalizations due to cancer-related late effects (18). Country-specific social welfare systems are important in supporting successful labor market integration. For example, recipients of unemployment benefits often have access to vocational counseling or re-training, and have to meet specific requirements including a minimum number of job applications per month. Typically, social welfare systems are well-established in Scandinavia (10, 12). Besides the many positive aspects of social welfare systems, they may provide wrong incentives by making unemployment financially attractive and thereby obscure negative implications of unemployment (12).

Similar to de Boer and colleagues (9), we found that unemployment is particularly prevalent among CNS tumor survivors. Previous reviews showed that neurocognitive impairments related to intelligence, memory, and executive functioning are common in CNS tumor survivors (1921), encompassing essential attributes for staying in the workforce. Those survivors may benefit from specific on-the-job training or opportunities for sheltered employment. Several studies also identified female sex as a risk factor of unemployment. Studies in the US found that female survivors encountered higher health-related barriers for employment (22, 23). Another possible explanation might be that female survivors may experience higher work-related discrimination or may have other priorities in life, such as childcare.

Limitations

A limitation of our review is the large heterogeneity in the overall meta-analysis (I2 = 95%). Stratification by region, diagnostic group, and study quality did not substantially decrease heterogeneity. The remaining heterogeneity may rather be caused by factors inherent in the respective labor market systems or due to different data collection periods. Employment-related problems may also vary between treatment centers according to the extent of psycho-social care provided (9). Our electronic search may have missed potentially relevant studies as we also included studies in which employment was not the primary outcome. This was addressed with an extensive hand search, resulting in the includion of studies from various countries covering a broad range of childhood cancer diagnoses. We found no indication of publication bias in terms of small-study effects. Study quality varied considerably. Our quality assessment emphasized the inclusion of a control population resulting in a high number of studies rated as low-quality. Unemployment was higher in uncontrolled than in controlled studies in the US and Canada and Asia, and across all diagnostic groups. Therefore, effects in the respective meta-analyses may be underestimated. However, among controlled studies, we found similar effect estimates for studies of high and low to moderate quality. Finally, the meta-analysis of Asian studies only included two studies and should therefore be interpreted with caution.

Summary

Establishing a satisfactory employment situation is challenging, particularly for those growing up with a chronic illness. Childhood onset of cancer, heart disease, diabetes, or epilepsy were all related to poorer vocational outcomes in adulthood (24). Moreover, among childhood cancer survivors, several studies revealed lower marriage rates (2528) and educational achievement (2934) compared to cancer-free individuals. Lower education is of concern regarding survivors’ vocational progress, as it may compromise the ability to engage in competitive working environments. Survivors encountering educational difficulties might benefit from special education services to minimize disparities compared to controls (35). The implementation of consistent monitoring of childhood cancer survivors’ vocational progress has been suggested as a standard of care in pediatric oncology (8). Currently, the availability of cancer-specific vocational rehabilitation services is limited. Moreover, existing services for the general population are often not systematically offered to survivors, even though previous studies have shown that more than half of survivors who received state assistance in job search, placement, and maintenance achieved successful employment (36, 37). In conclusion, childhood cancer survivors are at risk of unemployment and further effort is needed to systematically implement psycho-social care services along the cancer trajectory to support successful labor market integration.

Acknowledgement

We thank Simone Rosenkranz for her support in the development of our search strategy and particularly for her input related to the different electronic databases used for the literature search. This study was financially supported by the Swiss National Science Foundation (SNF Grant No. 100019_153268/1).

Conflict of intrest statement

The authors declare that no conflict of interest exists.

Manuscript received on 24 March 2017; revised version accepted on
8 August 2017.

Corresponding author
Luzius Mader, MSc

Seminar für Gesundheitswissenschaften und Gesundheitspolitik

Universität Luzern

Frohburgstr. 3, CH-6002 Luzern

luzius.mader@unilu.ch

Supplementary material
For eReferences please refer to:
www.aerzteblatt-international.de/ref4717

eFigures, eTables:
www.aerzteblatt-international.de/17m0805

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Berg C, Hayashi RJ: Participation and self-management strategies of young adult childhood cancer survivors. OTJR: Occupation, Participation and Health 2013; 33: 21–30 CrossRef
e29.
Brinkman TM, Bass JK, Li Z, et al.: Treatment-induced hearing loss and adult social outcomes in survivors of childhood CNS and non-CNS solid tumors: results from the St. Jude Lifetime Cohort Study. Cancer 2015; 121: 4053–61 CrossRef MEDLINE PubMed Central
e30.
Brinkman TM, Merchant TE, Li Z, et al.: Cognitive function and social attainment in adult survivors of retinoblastoma: a report from the St. Jude Lifetime Cohort Study. Cancer 2015; 121: 123–31 CrossRef MEDLINE PubMed Central
e31.
Brinkman TM, Krasin MJ, Liu W, et al.: Long-term neurocognitive functioning and social attainment in adult survivors of pediatric CNS tumors: results from the St Jude lifetime cohort study. J Clin Oncol 2016; 34: 1358–67 CrossRef MEDLINE PubMed Central
e32.
Crom DB, Li Z, Brinkman TM, et al.: Life satisfaction in adult survivors of childhood brain tumors. J Pediatr Oncol Nurs 2014; 31: 317–26 CrossRef MEDLINE PubMed Central
e33.
Dowling E, Yabroff KR, Mariotto A, McNeel T, Zeruto C, Buckman D: Burden of illness in adult survivors of childhood cancers: findings from a population-based national sample. Cancer 2010; 116: 3712–21 CrossRef MEDLINE MEDLINE
e34.
Fernandez-Pineda I, Hudson MM, Pappo AS, et al.: Long-term functional outcomes and quality of life in adult survivors of childhood extremity sarcomas: a report from the St. Jude Lifetime Cohort Study. J Cancer Surviv 2017; 11: 1–12 CrossRef MEDLINE
e35.
Gerhardt CA, Dixon M, Miller K, et al.: Educational and occupational outcomes among survivors of childhood cancer during the transition to emerging adulthood. J Dev Behav Pediatr 2007; 28: 448–55 CrossRef MEDLINE
e36.
Krull KR, Sabin ND, Reddick WE, et al.: Neurocognitive function and CNS integrity in adult survivors of childhood hodgkin lymphoma. J Clin Oncol 2012; 30: 3618–24 CrossRef MEDLINE PubMed Central
e37.
Krull KR, Brinkman TM, Li C, et al.: Neurocognitive outcomes decades after treatment for childhood acute lymphoblastic leukemia: a report from the St Jude lifetime cohort study. J Clin Oncol 2013; 31: 4407–15 CrossRef MEDLINE PubMed Central
e38.
Lee YL, Santacroce SJ: Posttraumatic stress in long-term young adult survivors of childhood cancer: a questionnaire survey. Int J Nurs Stud 2007; 44: 1406–17 CrossRef MEDLINE
e39.
Phillips-Salimi CR, Lommel K, Andrykowski MA: Physical and mental health status and health behaviors of childhood cancer survivors: findings from the 2009 BRFSS survey. Pediatr Blood Cancer 2012; 58: 964–70 CrossRef MEDLINE PubMed Central
e40.
Rourke MT, Hobbie WL, Schwartz L, Kazak AE: Posttraumatic stress disorder (PTSD) in young adult survivors of childhood cancer. Pediatr Blood Cancer 2007; 49: 177–82 CrossRef MEDLINE
e41.
Schwartz LD, Drotar D: Posttraumatic stress and related impairment in survivors of childhood cancer in early adulthood compared to healthy peers. J Pediatr Psychol 2006; 31: 356–66 CrossRef MEDLINE
e42.
Sharp LK, Kinahan KE, Didwania A, Stolley M: Quality of life in adult survivors of childhood cancer. J Pediatr Oncol Nurs 2007; 24: 220–6 CrossRef MEDLINE
e43.
Strauser D, Klosky JL, Brinkman TM, et al.: Career readiness in adult survivors of childhood cancer: a report from the St. Jude Lifetime Cohort Study. J Cancer Surviv 2015; 9: 20–9 CrossRef MEDLINE PubMed Central
e44.
Wiener L, Battles H, Bernstein D, et al.: Persistent psychological distress in long-term survivors of pediatric sarcoma: the experience at a single institution. Psychooncology 2006; 15: 898–910 CrossRef MEDLINE PubMed Central
e45.
Zebrack BJ, Landier W: The perceived impact of cancer on quality of life for post-treatment survivors of childhood cancer. Qual Life Res 2011; 20: 1595–608 CrossRef MEDLINE
e46.
de Moor JS, Puleo E, Ford JS, et al.: Disseminating a smoking cessation intervention to childhood and young adult cancer survivors: baseline characteristics and study design of the partnership for health-2 study. BMC cancer 2011; 11: 165 CrossRef MEDLINE PubMed Central
e47.
Pang JW, Friedman DL, Whitton JA, et al.: Employment status among adult survivors in the Childhood Cancer Survivor Study. Pediatr Blood Cancer 2008; 50: 104–10 CrossRef MEDLINE
e48.
Cheung C, Mok B: Psychosocial adaptation of childhood cancer survivors and their siblings. J Child Fam Stud 2013; 22: 253–67 CrossRef
e49.
Yuen ANY, HO SMY, Chan CKY: The mediating roles of cancer-related rumination in the relationship between dispositional hope and psychological outcomes among childhood cancer survivors. Psychooncology 2014; 23: 412–9 CrossRef MEDLINE
e50.
Ishida Y, Honda M, Kamibeppu K, et al.: Social outcomes and quality of life of childhood cancer survivors in Japan: a cross-sectional study on marriage, education, employment and health-related QOL (SF-36). Int J Hematol 2011; 93: 633–44 CrossRef MEDLINE
e51.
Ishida Y, Hayashi M, Inoue F, Ozawa M: Recent employment trend of childhood cancer survivors in Japan: a cross-sectional survey. Int J Clin Oncol 2014; 19: 973–81 CrossRef MEDLINE
e52.
Sugiyama K, Yamasaki F, Kurisu K, Kenjo M: Quality of life of extremely long-time germinoma survivors mainly treated with radiotherapy. Prog Neurol Surg 2009; 23: 130–9 CrossRef MEDLINE
e53.
Yano S, Kudo M, Hide T, et al.: Quality of life and clinical features of long-term survivors surgically treated for pediatric craniopharyngioma. World Neurosurgery 2016; 85: 153–62 CrossRef MEDLINE
e54.
Yonemoto T, Ishii T, Takeuchi Y, Kimura K, Hagiwara Y, Tatezaki S: Education and employment in long-term survivors of high-grade osteosarcoma: a Japanese single-center experience. Oncology 2007; 72: 274–8 CrossRef MEDLINE
e55.
Kim MA, Yi J: Psychological distress in adolescent and young adult survivors of childhood cancer in Korea. J Pediatr Oncol Nurs 2013; 30: 99–108 CrossRef MEDLINE
e56.
Chou LN, Hunter A: Factors affecting quality of life in Taiwanese survivors of childhood cancer. J Adv Nurs 2009; 65: 2131–41 CrossRef MEDLINE
Department of Health Sciences & Health Policy, University of Luzern, Switzerland: Mader, MSc; Prof. Dr. Michel, Dr. Roser
Flow diagram of studies excluded and included for systematic review and meta-analysis CCS, childhood cancer survivors
Figure 1
Flow diagram of studies excluded and included for systematic review and meta-analysis CCS, childhood cancer survivors
Unemployment in adult survivors of childhood cancer, stratified by region (Europe, Asia, and United States and Canada)
Figure 2
Unemployment in adult survivors of childhood cancer, stratified by region (Europe, Asia, and United States and Canada)
Unemployment in adult survivors, stratified by diagnostic group (blood cancer, central nervous system tumor and bone tumor/soft tissue sarcoma)
Figure 3
Unemployment in adult survivors, stratified by diagnostic group (blood cancer, central nervous system tumor and bone tumor/soft tissue sarcoma)
Key messages
The clinical perspective
Search terms used in electronic databases
eFigure 1
Search terms used in electronic databases
Unemployment in adult survivors of childhood cancer stratified by study quality
eFigure 2
Unemployment in adult survivors of childhood cancer stratified by study quality
Quality assessment of included studies
eTable 1
Quality assessment of included studies
Characteristics of included studies by study origin
eTable 2
Characteristics of included studies by study origin
1. Gatta G, Botta L, Rossi S, et al.: Childhood cancer survival in Europe 1999–2007: results of EUROCARE-5—a population-based study. Lancet Oncol 2014; 15: 35–47 CrossRef
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3. Geenen MM, Cardous-Ubbink MC, Kremer LC, et al.: Medical assessment of adverse health outcomes in long-term survivors of childhood cancer. JAMA 2007; 297: 2705–15 CrossRef MEDLINE
4. Hudson MM, Ness KK, Gurney JG, et al.: Clinical ascertainment of health outcomes among adults treated for childhood cancer. JAMA 2013; 309: 2371–81 CrossRef MEDLINE PubMed Central
5. Hudson MM, Oeffinger KC, Jones K, et al.: Age-dependent changes in health status in the childhood cancer survivor cohort. J Clin Oncol 2015; 33: 479–91 CrossRef MEDLINE PubMed Central
6.Doerffel W, Riepenhausen M, Lüders H, Braemswig J, Schellong G: Secondary malignancies following treatment for Hodgkin’s lymphoma in childhood and adolescence—a cohort study with more than 30 years’ follow-up. Dtsch Arztebl Int 2015; 112: 320–7 VOLLTEXT
7.Schellong G, Riepenhausen M, Ehlert K, et al.: Breast cancer in young women after treatment for Hodgkin´s lymphoma during childhood or adolescence—an observational study with up to 33-year follow up. Dtsch Arztebl Int 2014; 111(1–2): 3–9 VOLLTEXT
8. Lown EA, Phillips F, Schwartz LA, Rosenberg AR, Jones B: Psychosocial follow-up in survivorship as a standard of care in pediatric oncology. Pediatr Blood Cancer 2015; 62 (Suppl 5): S514–84 CrossRef MEDLINE PubMed Central
9. de Boer AG, Verbeek JH, van Dijk FJ: Adult survivors of childhood cancer and unemployment: a metaanalysis. Cancer 2006; 107: 1–11 CrossRef MEDLINE
10. Ghaderi S, Engeland A, Moster D, et al.: Increased uptake of social security benefits among long-term survivors of cancer in childhood, adolescence and young adulthood: a Norwegian population-based cohort study. Br J Cancer 2013; 108: 1525–33 CrossRef MEDLINE PubMed Central
11. Kirchhoff AC, Parsons HM, Kuhlthau KA, et al.: Supplemental security income and social security disability insurance coverage among long-term childhood cancer survivors. J Natl Cancer Inst 2015; 107: 1–4 CrossRef MEDLINE PubMed Central
12. Hjern A, Lindblad F, Boman KK: Disability in adult survivors of childhood cancer: a Swedish national cohort study. J Clin Oncol 2007; 25: 5262–6 CrossRef MEDLINE
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15. Higgins JPT, Thompson SG, Deeks JJ, Altman DG: Measuring inconsistency in meta-analyses. BMJ (Clin Res Ed) 2003; 327: 557–60 CrossRef MEDLINE PubMed Central
16. Harbord RM, Egger M, Sterne JA: A modified test for small-study effects in meta-analyses of controlled trials with binary endpoints. Stat Med 2006; 25: 3443–57 CrossRef MEDLINE
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18. Sieswerda E, Font-Gonzalez A, Reitsma JB, et al.: High hospitalization rates in survivors of childhood cancer: a longitudinal follow-up study using medical record linkage. PloS one 2016; 11: e0159518 CrossRef MEDLINE PubMed Central
19. Mulhern RK, Merchant TE, Gajjar A, Reddick WE, Kun LE: Late neurocognitive sequelae in survivors of brain tumours in childhood. Lancet Oncol 2004; 5: 399–408 CrossRef
20. Askins MA, Moore BD, 3rd: Preventing neurocognitive late effects in childhood cancer survivors. J Child Neurol 2008; 23: 1160–71 CrossRef MEDLINE PubMed Central
21. Ullrich NJ, Embry L: Neurocognitive dysfunction in survivors of childhood brain tumors. Semin Pediatr Neurol 2012; 19: 35–42 CrossRef MEDLINE
22. Kirchhoff AC, Krull KR, Ness KK, et al.: Occupational outcomes of adult childhood cancer survivors: a report from the childhood cancer survivor study. Cancer 2011; 117: 3033–44 CrossRef MEDLINE PubMed Central
23. Kirchhoff AC, Leisenring W, Krull KR, et al.: Unemployment among adult survivors of childhood cancer: a report from the childhood cancer survivor study. Med Care 2010; 48: 1015–25 CrossRef MEDLINE PubMed Central
24. Maslow GR, Haydon A, McRee AL, Ford CA, Halpern CT: Growing up with a chronic illness: social success, educational/vocational distress. J Adolesc Health 2011; 49: 206–12 CrossRef MEDLINE PubMed Central
25. Frobisher C, Lancashire ER, Winter DL, Jenkinson HC, Hawkins MM: Long-term population-based marriage rates among adult survivors of childhood cancer in Britain. Int J Cancer 2007; 121: 846–55 CrossRef MEDLINE
26. Janson C, Leisenring W, Cox C, et al.: Predictors of marriage and divorce in adult survivors of childhood cancers: a report from the Childhood Cancer Survivor Study. Cancer Epidemiol Biomarkers Prev 2009; 18: 2626–35 CrossRef MEDLINE PubMed Central
27. Pivetta E, Maule MM, Pisani P, et al.: Marriage and parenthood among childhood cancer survivors: a report from the Italian AIEOP Off-Therapy Registry. Haematologica 2011; 96: 744–51 CrossRef MEDLINE PubMed Central
28. Wengenroth L, Rueegg CS, Michel G, et al.: Life partnerships in childhood cancer survivors, their siblings, and the general population. Pediatr Blood Cancer 2014; 61: 538–45 CrossRef MEDLINE
29. Lancashire ER, Frobisher C, Reulen RC, Winter DL, Glaser A, Hawkins MM: Educational attainment among adult survivors of childhood cancer in Great Britain: a population-based cohort study. J Natl Cancer Inst 2010; 102: 254–70 CrossRef MEDLINE
30. Ghaderi S, Engeland A, Gunnes MW, et al.: Educational attainment among long-term survivors of cancer in childhood and adolescence: a Norwegian population-based cohort study. J Cancer Surviv 2016; 10: 87–95 CrossRef MEDLINE
31. Koch SV, Kejs AM, Engholm G, Johansen C, Schmiegelow K: Educational attainment among survivors of childhood cancer: a population-based cohort study in Denmark. Br J Cancer 2004; 91: 923–8 CrossRef MEDLINE PubMed Central
32. Langeveld NE, Ubbink MC, Last BF, Grootenhuis MA, Voute PA, De Haan RJ: Educational achievement, employment and living situation in long-term young adult survivors of childhood cancer in the Netherlands. Psychooncology 2003; 12: 213–25 CrossRef MEDLINE
33. Lorenzi M, McMillan AJ, Siegel LS, et al.: Educational outcomes among survivors of childhood cancer in British Columbia, Canada: report of the Childhood/Adolescent/Young Adult Cancer Survivors (CAYACS) Program. Cancer 2009; 115: 2234–45 CrossRef MEDLINE
34. Ahomaki R, Harila-Saari A, Matomaki J, Lahteenmaki PM: Non-graduation after comprehensive school, and early retirement but not unemployment are prominent in childhood cancer survivors— a Finnish registry-based study. J Cancer Surviv 2017; 11: 284–94 CrossRef MEDLINE
35. Mitby PA, Robison LL, Whitton JA, et al.: Utilization of special education services and educational attainment among long-term survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Cancer 2003; 97: 1115–26 CrossRef MEDLINE
36. Chan F, Strauser D, da Silva Cardoso E, Xi Zheng L, Chan JY, Feuerstein M: State vocational services and employment in cancer survivors. J Cancer Surviv 2008; 2: 169–78 CrossRef MEDLINE
37. Strauser D, Feuerstein M, Chan F, Arango J, da Silva Cardoso E, Chiu CY: Vocational services associated with competitive employment in 18–25 year old cancer survivors. J Cancer Surviv 2010; 4: 179–86 CrossRef MEDLINE
e1. Berbis J, Reggio C, Michel G, et al.: Employment in French young adult survivors of childhood leukemia: an LEA study (for Leucemies de l‘Enfant et de l‘Adolescent-childhood and adolescent leukemia). J Cancer Surviv 2016; 10: 1058–66 CrossRef MEDLINE
e2. Dumas A, Berger C, Auquier P, et al.: Educational and occupational outcomes of childhood cancer survivors 30 years after diagnosis: a French cohort study. Br J Cancer 2016; 114: 1060–8 CrossRef MEDLINE PubMed Central
e3. Freycon F, Trombert-Paviot B, Casagranda L, et al.: Academic difficulties and occupational outcomes of adult survivors of childhood leukemia who have undergone allogeneic hematopoietic stem cell transplantation and fractionated total body irradiation conditioning. Pediatr Hematol Oncol 2014; 31: 225–36 CrossRef MEDLINE
e4. Pillon M, Tridello G, Boaro MP, et al.: Psychosocial life achievements in adults even if they received prophylactic cranial irradiation for acute lymphoblastic leukemia during childhood. Leuk Lymphoma 2013; 54: 315–20 CrossRef MEDLINE
e5. Yagci-Kupeli B, Yalcin B, Kupeli S, et al.: Educational achievement, employment, smoking, marital, and insurance statuses in long-term survivors of childhood malignant solid tumors. J Pediatr Hematol Oncol 2013; 35: 129–33 CrossRef MEDLINE
e6. Crom DB, Lensing SY, Rai SN, Snider MA, Cash DK, Hudson MM: Marriage, employment, and health insurance in adult survivors of childhood cancer. J Cancer Surviv 2007; 1: 237–45 CrossRef MEDLINE
e7. Johannsdottir IM, Hjermstad MJ, Moum T, et al.: Social outcomes in young adult survivors of low incidence childhood cancers. J Cancer Surviv 2010; 4: 110–8 CrossRef MEDLINE
e8. Fidler MM, Ziff OJ, Wang S, et al.: Aspects of mental health dysfunction among survivors of childhood cancer. Br J Cancer 2015; 113: 1121–32 CrossRef MEDLINE PubMed Central
e9. Harila MJ, Niinivirta TIT, Winqvist S, Harila-Saari AH: Low depressive symptom and mental distress scores in adult long-term survivors of childhood acute lymphoblastic leukemia. J Pediatr Hematol Oncol 2011; 33: 194–8 CrossRef MEDLINE
e10. Chaume AG, Berger C, Cathebras P: Sequelae and quality of life in young adult survivors of childhood cancer. Rev Med Interne 2007; 28: 450–7 MEDLINE
e11. Frange P, Alapetite C, Gaboriaud G, et al.: From childhood to adulthood: long-term outcome of medulloblastoma patients. The Institut Curie experience (1980–2000). J Neurooncol 2009; 95: 271–9 CrossRef MEDLINE
e12. Vinchon M, Baroncini M, Leblond P, Delestret I: Morbidity and tumor-related mortality among adult survivors of pediatric brain tumors: a review. Childs Nerv Syst 2011; 27: 697–704 CrossRef MEDLINE
e13. Seitz DC, Besier T, Debatin KM, et al.: Posttraumatic stress, depression and anxiety among adult long-term survivors of cancer in adolescence. Eur J Cancer 2010; 46: 1596–606 CrossRef MEDLINE
e14. Wenninger K, Helmes A, Bengel J, Lauten M, Volkel S, Niemeyer CM: Coping in long-term survivors of childhood cancer:relations to psychological distress. Psychooncology 2013; 22: 854–61 CrossRef MEDLINE
e15. Servitzoglou M, Papadatou D, Tsiantis I, Vasilatou-Kosmidis H: Psychosocial functioning of young adolescent and adult survivors of childhood cancer. Support Care Cancer 2008; 16: 29–36 CrossRef MEDLINE
e16. Maule M, Zugna D, Migliore E, et al.: Surviving a childhood cancer: impact on education and employment. Eur J Cancer Prev 2017; 26: 351–6 CrossRef MEDLINE
e17. Tremolada M, Schiavo S, Varotto S, Basso G, Pillon M: Patient satisfaction in Italian childhood cancer survivors: human aspects of treatment as a key factor in patients‘ quality of life. Health Soc Work 2015; 40: e148–e55 CrossRef
e18. Gunnes MW, Lie RT, Bjorge T, et al.: Economic independence in survivors of cancer diagnosed at a young age: a Norwegian national cohort study. Cancer 2016; 122: 3873–85 CrossRef MEDLINE PubMed Central
e19. Johannesen TB, Langmark F, Wesenberg F, Lote K: Prevalence of Norwegian patients diagnosed with childhood cancer, their working ability and need of health insurance benefits. Acta Oncol 2007; 46: 60–6 CrossRef
e20. Boman KK, Hovén E, Anclair M, Lannering B, Gustafsson G: Health and persistent functional late effects in adult survivors of childhood CNS tumours: a population-based cohort study. Eur J Cancer 2009; 45: 2552–61 CrossRef MEDLINE
e21. Boman KK, Lindblad F, Hjern A: Long-term outcomes of childhood cancer survivors in Sweden: a population-based study of education, employment, and income. Cancer 2010; 116: 1385–91 CrossRef MEDLINE
e22. Holmqvist AS, Wiebe T, Hjorth L, Lindgren A, Ora I, Moell C: Young age at diagnosis is a risk factor for negative late socio-economic effects after acute lymphoblastic leukemia in childhood. Pediatr Blood Cancer 2010; 55: 698–707 CrossRef MEDLINE
e23. Sundberg KK, Lampic C, Arvidson J, Helstrom L, Wettergren L: Sexual function and experience among long-term survivors of childhood cancer. Eur J Cancer 2011; 47: 397–403 CrossRef MEDLINE
e24. Sundberg KK, Wettergren L, Frisk P, Arvidson J: Self-reported quality of life in long-term survivors of childhood lymphoblastic malignancy treated with hematopoietic stem cell transplantation versus conventional therapy. Pediatr Blood Cancer 2013; 60: 1382–7 CrossRef MEDLINE
e25. Wengenroth L, Sommer G, Schindler M, et al.: Income in adult survivors of childhood cancer. PLoS One 2016; 11: e0155546.
e26. Edelstein K, D‘Agostino N, Bernstein LJ, et al.: Long-term neurocognitive outcomes in young adult survivors of childhood acute lymphoblastic leukemia. J Pediatr Hematol Oncol 2011; 33: 450–8 CrossRef MEDLINE
e27. Armstrong GT, Reddick WE, Petersen RC, et al.: Evaluation of memory impairment in aging adult survivors of childhood acute lymphoblastic leukemia treated with cranial radiotherapy. J Natl Cancer Inst 2013; 105: 899–907 CrossRef MEDLINE PubMed Central
e28. Berg C, Hayashi RJ: Participation and self-management strategies of young adult childhood cancer survivors. OTJR: Occupation, Participation and Health 2013; 33: 21–30 CrossRef
e29. Brinkman TM, Bass JK, Li Z, et al.: Treatment-induced hearing loss and adult social outcomes in survivors of childhood CNS and non-CNS solid tumors: results from the St. Jude Lifetime Cohort Study. Cancer 2015; 121: 4053–61 CrossRef MEDLINE PubMed Central
e30. Brinkman TM, Merchant TE, Li Z, et al.: Cognitive function and social attainment in adult survivors of retinoblastoma: a report from the St. Jude Lifetime Cohort Study. Cancer 2015; 121: 123–31 CrossRef MEDLINE PubMed Central
e31. Brinkman TM, Krasin MJ, Liu W, et al.: Long-term neurocognitive functioning and social attainment in adult survivors of pediatric CNS tumors: results from the St Jude lifetime cohort study. J Clin Oncol 2016; 34: 1358–67 CrossRef MEDLINE PubMed Central
e32. Crom DB, Li Z, Brinkman TM, et al.: Life satisfaction in adult survivors of childhood brain tumors. J Pediatr Oncol Nurs 2014; 31: 317–26 CrossRef MEDLINE PubMed Central
e33. Dowling E, Yabroff KR, Mariotto A, McNeel T, Zeruto C, Buckman D: Burden of illness in adult survivors of childhood cancers: findings from a population-based national sample. Cancer 2010; 116: 3712–21 CrossRef MEDLINE MEDLINE
e34. Fernandez-Pineda I, Hudson MM, Pappo AS, et al.: Long-term functional outcomes and quality of life in adult survivors of childhood extremity sarcomas: a report from the St. Jude Lifetime Cohort Study. J Cancer Surviv 2017; 11: 1–12 CrossRef MEDLINE
e35. Gerhardt CA, Dixon M, Miller K, et al.: Educational and occupational outcomes among survivors of childhood cancer during the transition to emerging adulthood. J Dev Behav Pediatr 2007; 28: 448–55 CrossRef MEDLINE
e36. Krull KR, Sabin ND, Reddick WE, et al.: Neurocognitive function and CNS integrity in adult survivors of childhood hodgkin lymphoma. J Clin Oncol 2012; 30: 3618–24 CrossRef MEDLINE PubMed Central
e37. Krull KR, Brinkman TM, Li C, et al.: Neurocognitive outcomes decades after treatment for childhood acute lymphoblastic leukemia: a report from the St Jude lifetime cohort study. J Clin Oncol 2013; 31: 4407–15 CrossRef MEDLINE PubMed Central
e38. Lee YL, Santacroce SJ: Posttraumatic stress in long-term young adult survivors of childhood cancer: a questionnaire survey. Int J Nurs Stud 2007; 44: 1406–17 CrossRef MEDLINE
e39. Phillips-Salimi CR, Lommel K, Andrykowski MA: Physical and mental health status and health behaviors of childhood cancer survivors: findings from the 2009 BRFSS survey. Pediatr Blood Cancer 2012; 58: 964–70 CrossRef MEDLINE PubMed Central
e40. Rourke MT, Hobbie WL, Schwartz L, Kazak AE: Posttraumatic stress disorder (PTSD) in young adult survivors of childhood cancer. Pediatr Blood Cancer 2007; 49: 177–82 CrossRef MEDLINE
e41. Schwartz LD, Drotar D: Posttraumatic stress and related impairment in survivors of childhood cancer in early adulthood compared to healthy peers. J Pediatr Psychol 2006; 31: 356–66 CrossRef MEDLINE
e42. Sharp LK, Kinahan KE, Didwania A, Stolley M: Quality of life in adult survivors of childhood cancer. J Pediatr Oncol Nurs 2007; 24: 220–6 CrossRef MEDLINE
e43. Strauser D, Klosky JL, Brinkman TM, et al.: Career readiness in adult survivors of childhood cancer: a report from the St. Jude Lifetime Cohort Study. J Cancer Surviv 2015; 9: 20–9 CrossRef MEDLINE PubMed Central
e44. Wiener L, Battles H, Bernstein D, et al.: Persistent psychological distress in long-term survivors of pediatric sarcoma: the experience at a single institution. Psychooncology 2006; 15: 898–910 CrossRef MEDLINE PubMed Central
e45. Zebrack BJ, Landier W: The perceived impact of cancer on quality of life for post-treatment survivors of childhood cancer. Qual Life Res 2011; 20: 1595–608 CrossRef MEDLINE
e46. de Moor JS, Puleo E, Ford JS, et al.: Disseminating a smoking cessation intervention to childhood and young adult cancer survivors: baseline characteristics and study design of the partnership for health-2 study. BMC cancer 2011; 11: 165 CrossRef MEDLINE PubMed Central
e47. Pang JW, Friedman DL, Whitton JA, et al.: Employment status among adult survivors in the Childhood Cancer Survivor Study. Pediatr Blood Cancer 2008; 50: 104–10 CrossRef MEDLINE
e48. Cheung C, Mok B: Psychosocial adaptation of childhood cancer survivors and their siblings. J Child Fam Stud 2013; 22: 253–67 CrossRef
e49. Yuen ANY, HO SMY, Chan CKY: The mediating roles of cancer-related rumination in the relationship between dispositional hope and psychological outcomes among childhood cancer survivors. Psychooncology 2014; 23: 412–9 CrossRef MEDLINE
e50. Ishida Y, Honda M, Kamibeppu K, et al.: Social outcomes and quality of life of childhood cancer survivors in Japan: a cross-sectional study on marriage, education, employment and health-related QOL (SF-36). Int J Hematol 2011; 93: 633–44 CrossRef MEDLINE
e51. Ishida Y, Hayashi M, Inoue F, Ozawa M: Recent employment trend of childhood cancer survivors in Japan: a cross-sectional survey. Int J Clin Oncol 2014; 19: 973–81 CrossRef MEDLINE
e52. Sugiyama K, Yamasaki F, Kurisu K, Kenjo M: Quality of life of extremely long-time germinoma survivors mainly treated with radiotherapy. Prog Neurol Surg 2009; 23: 130–9 CrossRef MEDLINE
e53. Yano S, Kudo M, Hide T, et al.: Quality of life and clinical features of long-term survivors surgically treated for pediatric craniopharyngioma. World Neurosurgery 2016; 85: 153–62 CrossRef MEDLINE
e54. Yonemoto T, Ishii T, Takeuchi Y, Kimura K, Hagiwara Y, Tatezaki S: Education and employment in long-term survivors of high-grade osteosarcoma: a Japanese single-center experience. Oncology 2007; 72: 274–8 CrossRef MEDLINE
e55. Kim MA, Yi J: Psychological distress in adolescent and young adult survivors of childhood cancer in Korea. J Pediatr Oncol Nurs 2013; 30: 99–108 CrossRef MEDLINE
e56. Chou LN, Hunter A: Factors affecting quality of life in Taiwanese survivors of childhood cancer. J Adv Nurs 2009; 65: 2131–41 CrossRef MEDLINE