A detailed insight in the high risks of hospitalizations in long-term childhood cancer survivors—A Dutch LATER linkage study

Streefkerk, Nina; Tissing, Wim J. E.; Korevaar, Joke C.; Broeder, Eline van Dulmen‐den; Bresters, Dorine; Loo, Margriet van der Heiden‐van der; Heuvel-Eibrink, Marry M. van de; Leeuwen, Flora E. van; Loonen, Jacqueline; Pal, Helena H J van der; Ronckers, Cécile M.; Versluys, A. B.; Vries, Andrica C H de; Feijen, Elizabeth A M; Kremer, Leontien C. M.

doi:10.1371/journal.pone.0232708

Cited by 17 publications

(13 citation statements)

References 32 publications

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“…In the without treatment/surgery only group, 3% of CCS who developed symptomatic cardiac ischaemia, developed it before 30 years of age. Streefkerk et al 26 and Gudmundsdottir et al 27 compared the hospitalisation rate for ischaemic heart disease between a cohort of childhood cancer survivors and a matched general population and found a relative rate of 1.6 and 1.7 (95% CI 1.5 to 1.9), respectively, which are in line with our result. Gudmundsdottir et al also found a larger difference in the younger age groups (aged 20-50 years).…”

Section: Discussionsupporting

confidence: 91%

Increased risk of cardiac ischaemia in a pan-European cohort of 36 205 childhood cancer survivors: a PanCareSurFup study

Feijen

Dalen

Pal

et al. 2020

Heart

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ObjectiveIn this report, we determine the cumulative incidence of symptomatic cardiac ischaemia and its risk factors among European 5-year childhood cancer survivors (CCS) participating in the PanCareSurFup study.MethodsEight data providers (France, Hungary, Italy (two cohorts), the Netherlands, Slovenia, Switzerland and the UK) participating in PanCareSurFup ascertained and validated symptomatic cardiac events among their 36 205 eligible CCS. Data on symptomatic cardiac ischaemia were graded according to the Criteria for Adverse Events V.3.0 (grade 3–5). We calculated cumulative incidences, both overall and for different subgroups based on treatment and malignancy, and used multivariable Cox regression to analyse risk factors.ResultsOverall, 302 out of the 36 205 CCS developed symptomatic cardiac ischaemia during follow-up (median follow-up time after primary cancer diagnosis: 23.0 years). The cumulative incidence by age 60 was 5.4% (95% CI 4.6% to 6.2%). Men (7.1% (95% CI 5.8 to 8.4)) had higher rates than women (3.4% (95% CI 2.4 to 4.4)) (p<0.0001). Of importance is that a significant number of patients (41/302) were affected as teens or young adults (14–30 years). Treatment with radiotherapy/chemotherapy conferred twofold risk (95% CI 1.5 to 3.0) and cases in these patients appeared earlier than in CCS without treatment/surgery only (15% vs 3% prior to age 30 years, respectively (p=0.04)).ConclusionsIn this very large European childhood cancer cohort, we found that by age 60 years, 1 in 18 CCS will develop a severe, life-threatening or fatal cardiac ischaemia, especially in lymphoma survivors and CCS treated with radiotherapy and chemotherapy increases the risk significantly.

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Section: Discussionsupporting

confidence: 91%

Increased risk of cardiac ischaemia in a pan-European cohort of 36 205 childhood cancer survivors: a PanCareSurFup study

Feijen

Dalen

Pal

et al. 2020

Heart

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“…That children who survive ALL tend to have higher mortality and morbidity in later life, including subsequent cancers and a wide range of other therapy-related conditions (table 1), is established 4–7. With respect to the latter, however, much of the information on late effects among survivors has come either from analyses of hospitalisations or from questionnaires completed by consenting individuals 8–17. As is evident from the studies summarised in table 1 (which includes those that examined all leukaemias combined and those that also included young adults), less attention has been paid to chronic conditions that do not require hospital admission,7 18–20 and to morbidity patterns that change over time 7 12 21…”

Section: Introductionmentioning

confidence: 99%

“…[4][5][6][7] With respect to the latter, however, much of the information on late effects among survivors has come either from analyses of hospitalisations or from questionnaires completed by consenting individuals. [8][9][10][11][12][13][14][15][16][17] As is evident from the studies summarised in table 1 (which includes those that examined all leukaemias combined and those that also included young adults), less attention has been paid to chronic conditions that do not require hospital admission, 7 18-20 and to morbidity patterns that change over time. 7 12 21 The longitudinal data examined in this report contain information on hospital outpatient attendances, as well as inpatient episodes, cancer registrations and deaths.…”

Section: Introductionmentioning

confidence: 99%

Excess morbidity and mortality among survivors of childhood acute lymphoblastic leukaemia: 25 years of follow-up from the United Kingdom Childhood Cancer Study (UKCCS) population-based matched cohort

et al. 2022

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ObjectivesTo examine morbidity and mortality among teenagers and young adults (TYAs) previously diagnosed with acute lymphoblastic leukaemia (ALL) in childhood, and compare to the general TYA population.DesignNational population-based sex-matched and age-matched case-control study converted into a matched cohort, with follow-up linkage to administrative healthcare databases.SettingThe study population comprised all children (0–14 years) registered for primary care with the National Health Service (NHS) in England 1992–1996.Participants1082 5-year survivors of ALL diagnosed<15 years of age (1992–1996) and 2018 unaffected individuals; followed up to 15 March 2020.Main outcome measuresAssociations with hospital activity, cancer and mortality were assessed using incidence rate ratios (IRR) and differences.ResultsMortality in the 5-year ALL survivor cohort was 20 times higher than in the comparison cohort (rate ratio 21.3, 95% CI 11.2 to 45.6), and cancer incidence 10 times higher (IRR 9.9 95% CI 4.1 to 29.1). Hospital activity was increased for many clinical specialties, the strongest associations being for endocrinology; outpatient IRR 36.7, 95% CI 17.3 to 93.4 and inpatient 19.7, 95% CI 7.9 to 63.2 for males, and 11.0, 95% CI 6.2 to 21.1 and 6.2 95% CI 3.1 to 13.5, respectively, for females. Notable excesses were also evident for cardiology, neurology, ophthalmology, respiratory medicine and general medicine. Males were also more likely to attend gastroenterology; ear, nose and throat; urology; and dermatology, while females were more likely to be seen in plastic surgery and less likely in midwifery.ConclusionsAdding to excess risks of death and cancer, survivors of childhood ALL experience excess outpatient and inpatient activity across their TYA years, which is not related to routine follow-up monitoring. Involving most clinical specialties, associations are striking, showing no signs of diminishing over time. Recognising that all survivors are potentially at risk of late treatment-associated effects, our findings underscore the need to take prior ALL diagnosis into account when interpreting seemingly unrelated symptoms later in life.

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“…[5] In another long-term follow-up cohort, abdominopelvic radiotherapy was associated with an increased risk of hospitalization, among other causes due to endocrine, nutritional and metabolic diseases (relative hospitalization rate (RHR) 2.5), as well as subsequent neoplasms (RHR 1.7). [6] In paediatric literature, associations between RT and late toxicity have historically been based on prescribed dose to the target volume. However, for adequate quantification of toxicity, normal tissue complication probability (NTCP) data is required, describing the relation between radiation dose to a tissue in relation to the endpoint (toxicity) of interest.…”

Section: Introductionmentioning

confidence: 99%

Review – Late toxicity of abdominal and pelvic radiotherapy for childhood cancer

Hessels

Langendijk

Gawryszuk

et al. 2022

Radiotherapy and Oncology

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A detailed insight in the high risks of hospitalizations in long-term childhood cancer survivors—A Dutch LATER linkage study

Abstract: ☯ These authors contributed equally to this work. ¶ Membership of the Dutch LATER Study Group for burden of disease includes the listed coauthors and additional consortium members, as listed in the Acknowledgments.

Cited by 17 publications

References 32 publications

Increased risk of cardiac ischaemia in a pan-European cohort of 36 205 childhood cancer survivors: a PanCareSurFup study

Increased risk of cardiac ischaemia in a pan-European cohort of 36 205 childhood cancer survivors: a PanCareSurFup study

Excess morbidity and mortality among survivors of childhood acute lymphoblastic leukaemia: 25 years of follow-up from the United Kingdom Childhood Cancer Study (UKCCS) population-based matched cohort

Review – Late toxicity of abdominal and pelvic radiotherapy for childhood cancer

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