The cumulative burden of surviving childhood cancer: an initial report from the St Jude Lifetime Cohort Study (SJLIFE)

Survivors of childhood cancer develop early and severe chronic health conditions (CHCs). A quantitative landscape of morbidity of survivors, however, has not been described. We aimed to describe the cumulative burden of curative cancer therapy in a clinically assessed ageing population of long-term...

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Veröffentlicht in:The Lancet (British edition) Jg. 390; H. 10112; S. 2569 - 2582
Hauptverfasser: Bhakta, Nickhill, Liu, Qi, Ness, Kirsten K, Baassiri, Malek, Eissa, Hesham, Yeo, Frederick, Chemaitilly, Wassim, Ehrhardt, Matthew J, Bass, Johnnie, Bishop, Michael W, Shelton, Kyla, Lu, Lu, Huang, Sujuan, Li, Zhenghong, Caron, Eric, Lanctot, Jennifer, Howell, Carrie, Folse, Timothy, Joshi, Vijaya, Green, Daniel M, Mulrooney, Daniel A, Armstrong, Gregory T, Krull, Kevin R, Brinkman, Tara M, Khan, Raja B, Srivastava, Deo K, Hudson, Melissa M, Yasui, Yutaka, Robison, Leslie L
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England Elsevier Ltd 09.12.2017
Elsevier Limited
Schlagworte:
Adolescent
Adult
Age Factors
Cancer
Cancer Survivors - statistics & numerical data
Cancer therapies
Chemotherapy
Child
Child, Preschool
Childhood
Children
Childrens health
Chronic illnesses
Cohort analysis
Cost of Illness
Female
Health risk assessment
Humans
Infant
Infant, Newborn
Male
Medical records
Middle Aged
Morbidity
Mortality
Neoplasms - complications
Neoplasms - mortality
Pediatrics
Retrospective Studies
Side effects
Survival Analysis
Time Factors
Young Adult
ISSN:0140-6736, 1474-547X, 1474-547X
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Abstract Survivors of childhood cancer develop early and severe chronic health conditions (CHCs). A quantitative landscape of morbidity of survivors, however, has not been described. We aimed to describe the cumulative burden of curative cancer therapy in a clinically assessed ageing population of long-term survivors of childhood cancer. The St Jude Lifetime Cohort Study (SJLIFE) retrospectively collected data on CHCs in all patients treated for childhood cancer at the St Jude Children's Research Hospital who survived 10 years or longer from initial diagnosis and were 18 years or older as of June 30, 2015. Age-matched and sex-frequency-matched community controls were used for comparison. 21 treatment exposure variables were included in the analysis, with data abstracted from medical records. 168 CHCs for all participants were graded for severity using a modified Common Terminology Criteria of Adverse Events. Multiple imputation with predictive mean matching was used for missing occurrences and grades of CHCs in the survivors who were not clinically evaluable. Mean cumulative count was used for descriptive cumulative burden analysis and marked-point-process regression was used for inferential cumulative burden analysis. Of 5522 patients treated for childhood cancer at St Jude Children's Research Hospital who had complete records, survived 10 years or longer, and were 18 years or older at time of study, 3010 (54·5%) were alive, had enrolled, and had had prospective clinical assessment. 2512 (45·5%) of the 5522 patients were not clinically evaluable. The cumulative incidence of CHCs at age 50 years was 99·9% (95% CI 99·9–99·9) for grade 1–5 CHCs and 96·0% (95% CI 95·3–96·8%) for grade 3–5 CHCs. By age 50 years, a survivor had experienced, on average, 17·1 (95% CI 16·2–18·1) CHCs of any grade, of which 4·7 (4·6–4·9) were CHCs of grade 3–5. The cumulative burden in matched community controls of grade 1–5 CHCs was 9·2 (95% CI 7·9–10·6; p<0·0001 vs total study population) and of grade 3–5 CHCs was 2·3 (1·9–2·7, p<0·0001 vs total study population). Second neoplasms, spinal disorders, and pulmonary disease were major contributors to the excess total cumulative burden. Notable heterogeneity in the distribution of CHC burden in survivors with differing primary cancer diagnoses was observed. The cumulative burden of grade 1–5 CHCs at age 50 years was highest in survivors of CNS malignancies (24·2 [95% CI 20·9–27·5]) and lowest in survivors of germ cell tumours (14·0 [11·5–16·6]). Multivariable analyses showed that older age at diagnosis, treatment era, and higher doses of brain and chest radiation are significantly associated with a greater cumulative burden and severity of CHCs. The burden of CHCs in survivors of childhood cancer is substantial and highly variable. Our assessment of total cumulative burden in survivors of paediatric cancer, with detailed characterisation of long-term CHCs, provide data to better inform future clinical guidelines, research investigations, and health services planning for this vulnerable, medically complex population. The US National Cancer Institute, St Baldrick's Foundation, and the American Lebanese Syrian Associated Charities.
AbstractList Survivors of childhood cancer develop early and severe chronic health conditions (CHCs). A quantitative landscape of morbidity of survivors, however, has not been described. We aimed to describe the cumulative burden of curative cancer therapy in a clinically assessed ageing population of long-term survivors of childhood cancer. The St Jude Lifetime Cohort Study (SJLIFE) retrospectively collected data on CHCs in all patients treated for childhood cancer at the St Jude Children's Research Hospital who survived 10 years or longer from initial diagnosis and were 18 years or older as of June 30, 2015. Age-matched and sex-frequency-matched community controls were used for comparison. 21 treatment exposure variables were included in the analysis, with data abstracted from medical records. 168 CHCs for all participants were graded for severity using a modified Common Terminology Criteria of Adverse Events. Multiple imputation with predictive mean matching was used for missing occurrences and grades of CHCs in the survivors who were not clinically evaluable. Mean cumulative count was used for descriptive cumulative burden analysis and marked-point-process regression was used for inferential cumulative burden analysis. Of 5522 patients treated for childhood cancer at St Jude Children's Research Hospital who had complete records, survived 10 years or longer, and were 18 years or older at time of study, 3010 (54·5%) were alive, had enrolled, and had had prospective clinical assessment. 2512 (45·5%) of the 5522 patients were not clinically evaluable. The cumulative incidence of CHCs at age 50 years was 99·9% (95% CI 99·9–99·9) for grade 1–5 CHCs and 96·0% (95% CI 95·3–96·8%) for grade 3–5 CHCs. By age 50 years, a survivor had experienced, on average, 17·1 (95% CI 16·2–18·1) CHCs of any grade, of which 4·7 (4·6–4·9) were CHCs of grade 3–5. The cumulative burden in matched community controls of grade 1–5 CHCs was 9·2 (95% CI 7·9–10·6; p<0·0001 vs total study population) and of grade 3–5 CHCs was 2·3 (1·9–2·7, p<0·0001 vs total study population). Second neoplasms, spinal disorders, and pulmonary disease were major contributors to the excess total cumulative burden. Notable heterogeneity in the distribution of CHC burden in survivors with differing primary cancer diagnoses was observed. The cumulative burden of grade 1–5 CHCs at age 50 years was highest in survivors of CNS malignancies (24·2 [95% CI 20·9–27·5]) and lowest in survivors of germ cell tumours (14·0 [11·5–16·6]). Multivariable analyses showed that older age at diagnosis, treatment era, and higher doses of brain and chest radiation are significantly associated with a greater cumulative burden and severity of CHCs. The burden of CHCs in survivors of childhood cancer is substantial and highly variable. Our assessment of total cumulative burden in survivors of paediatric cancer, with detailed characterisation of long-term CHCs, provide data to better inform future clinical guidelines, research investigations, and health services planning for this vulnerable, medically complex population. The US National Cancer Institute, St Baldrick's Foundation, and the American Lebanese Syrian Associated Charities.
With 10-year survival for paediatric cancer now more than 80%, and late mortality decreasing in long-term survivors, the population of survivors of paediatric cancer is ever increasing.1-4 Incidence and prevalence data, mostly generated by cohort studies, have documented that survivors have a lifelong increased risk of morbidity associated with their curative therapies.5-10 However, the true price of cure is reflected by the cumulative burden of disease, or total disease morbidity, after taking into account the occurrences and severities of multiple medical conditions and recurrent events.
Survivors of childhood cancer develop early and severe chronic health conditions (CHCs). A quantitative landscape of morbidity of survivors, however, has not been described. We aimed to describe the cumulative burden of curative cancer therapy in a clinically assessed ageing population of long-term survivors of childhood cancer.BACKGROUNDSurvivors of childhood cancer develop early and severe chronic health conditions (CHCs). A quantitative landscape of morbidity of survivors, however, has not been described. We aimed to describe the cumulative burden of curative cancer therapy in a clinically assessed ageing population of long-term survivors of childhood cancer.The St Jude Lifetime Cohort Study (SJLIFE) retrospectively collected data on CHCs in all patients treated for childhood cancer at the St Jude Children's Research Hospital who survived 10 years or longer from initial diagnosis and were 18 years or older as of June 30, 2015. Age-matched and sex-frequency-matched community controls were used for comparison. 21 treatment exposure variables were included in the analysis, with data abstracted from medical records. 168 CHCs for all participants were graded for severity using a modified Common Terminology Criteria of Adverse Events. Multiple imputation with predictive mean matching was used for missing occurrences and grades of CHCs in the survivors who were not clinically evaluable. Mean cumulative count was used for descriptive cumulative burden analysis and marked-point-process regression was used for inferential cumulative burden analysis.METHODSThe St Jude Lifetime Cohort Study (SJLIFE) retrospectively collected data on CHCs in all patients treated for childhood cancer at the St Jude Children's Research Hospital who survived 10 years or longer from initial diagnosis and were 18 years or older as of June 30, 2015. Age-matched and sex-frequency-matched community controls were used for comparison. 21 treatment exposure variables were included in the analysis, with data abstracted from medical records. 168 CHCs for all participants were graded for severity using a modified Common Terminology Criteria of Adverse Events. Multiple imputation with predictive mean matching was used for missing occurrences and grades of CHCs in the survivors who were not clinically evaluable. Mean cumulative count was used for descriptive cumulative burden analysis and marked-point-process regression was used for inferential cumulative burden analysis.Of 5522 patients treated for childhood cancer at St Jude Children's Research Hospital who had complete records, survived 10 years or longer, and were 18 years or older at time of study, 3010 (54·5%) were alive, had enrolled, and had had prospective clinical assessment. 2512 (45·5%) of the 5522 patients were not clinically evaluable. The cumulative incidence of CHCs at age 50 years was 99·9% (95% CI 99·9-99·9) for grade 1-5 CHCs and 96·0% (95% CI 95·3-96·8%) for grade 3-5 CHCs. By age 50 years, a survivor had experienced, on average, 17·1 (95% CI 16·2-18·1) CHCs of any grade, of which 4·7 (4·6-4·9) were CHCs of grade 3-5. The cumulative burden in matched community controls of grade 1-5 CHCs was 9·2 (95% CI 7·9-10·6; p<0·0001 vs total study population) and of grade 3-5 CHCs was 2·3 (1·9-2·7, p<0·0001 vs total study population). Second neoplasms, spinal disorders, and pulmonary disease were major contributors to the excess total cumulative burden. Notable heterogeneity in the distribution of CHC burden in survivors with differing primary cancer diagnoses was observed. The cumulative burden of grade 1-5 CHCs at age 50 years was highest in survivors of CNS malignancies (24·2 [95% CI 20·9-27·5]) and lowest in survivors of germ cell tumours (14·0 [11·5-16·6]). Multivariable analyses showed that older age at diagnosis, treatment era, and higher doses of brain and chest radiation are significantly associated with a greater cumulative burden and severity of CHCs.FINDINGSOf 5522 patients treated for childhood cancer at St Jude Children's Research Hospital who had complete records, survived 10 years or longer, and were 18 years or older at time of study, 3010 (54·5%) were alive, had enrolled, and had had prospective clinical assessment. 2512 (45·5%) of the 5522 patients were not clinically evaluable. The cumulative incidence of CHCs at age 50 years was 99·9% (95% CI 99·9-99·9) for grade 1-5 CHCs and 96·0% (95% CI 95·3-96·8%) for grade 3-5 CHCs. By age 50 years, a survivor had experienced, on average, 17·1 (95% CI 16·2-18·1) CHCs of any grade, of which 4·7 (4·6-4·9) were CHCs of grade 3-5. The cumulative burden in matched community controls of grade 1-5 CHCs was 9·2 (95% CI 7·9-10·6; p<0·0001 vs total study population) and of grade 3-5 CHCs was 2·3 (1·9-2·7, p<0·0001 vs total study population). Second neoplasms, spinal disorders, and pulmonary disease were major contributors to the excess total cumulative burden. Notable heterogeneity in the distribution of CHC burden in survivors with differing primary cancer diagnoses was observed. The cumulative burden of grade 1-5 CHCs at age 50 years was highest in survivors of CNS malignancies (24·2 [95% CI 20·9-27·5]) and lowest in survivors of germ cell tumours (14·0 [11·5-16·6]). Multivariable analyses showed that older age at diagnosis, treatment era, and higher doses of brain and chest radiation are significantly associated with a greater cumulative burden and severity of CHCs.The burden of CHCs in survivors of childhood cancer is substantial and highly variable. Our assessment of total cumulative burden in survivors of paediatric cancer, with detailed characterisation of long-term CHCs, provide data to better inform future clinical guidelines, research investigations, and health services planning for this vulnerable, medically complex population.INTERPRETATIONThe burden of CHCs in survivors of childhood cancer is substantial and highly variable. Our assessment of total cumulative burden in survivors of paediatric cancer, with detailed characterisation of long-term CHCs, provide data to better inform future clinical guidelines, research investigations, and health services planning for this vulnerable, medically complex population.The US National Cancer Institute, St Baldrick's Foundation, and the American Lebanese Syrian Associated Charities.FUNDINGThe US National Cancer Institute, St Baldrick's Foundation, and the American Lebanese Syrian Associated Charities.
Author Shelton, Kyla
Hudson, Melissa M
Yeo, Frederick
Bishop, Michael W
Joshi, Vijaya
Chemaitilly, Wassim
Brinkman, Tara M
Srivastava, Deo K
Green, Daniel M
Folse, Timothy
Bhakta, Nickhill
Baassiri, Malek
Ehrhardt, Matthew J
Robison, Leslie L
Caron, Eric
Ness, Kirsten K
Khan, Raja B
Yasui, Yutaka
Liu, Qi
Li, Zhenghong
Mulrooney, Daniel A
Krull, Kevin R
Bass, Johnnie
Huang, Sujuan
Lu, Lu
Howell, Carrie
Lanctot, Jennifer
Eissa, Hesham
Armstrong, Gregory T
AuthorAffiliation 3 Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN, USA
6 Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, USA
8 Department of Psychology, St. Jude Children’s Research Hospital, Memphis, TN, USA
2 Department of Epidemiology and Cancer Control, St. Jude Children’s Research Hospital, Memphis, TN, USA
4 School of Public Health, University of Alberta, Edmonton, AB, Canada
7 Department of Pediatric Medicine, St. Jude Children’s Research Hospital, Memphis, TN, USA
5 Rehabilitation Services, St. Jude Children’s Research Hospital, Memphis, TN, USA
9 Department of Biostatistics, St. Jude Children’s Research Hospital, Memphis, TN, USA
1 Department of Global Pediatric Medicine, St. Jude Children’s Research Hospital, Memphis, TN, USA
AuthorAffiliation_xml – name: 3 Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN, USA
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– name: 4 School of Public Health, University of Alberta, Edmonton, AB, Canada
– name: 9 Department of Biostatistics, St. Jude Children’s Research Hospital, Memphis, TN, USA
– name: 8 Department of Psychology, St. Jude Children’s Research Hospital, Memphis, TN, USA
– name: 1 Department of Global Pediatric Medicine, St. Jude Children’s Research Hospital, Memphis, TN, USA
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  organization: School of Public Health, University of Alberta, Edmonton, AB, Canada
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  givenname: Eric
  surname: Caron
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  organization: Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis, TN, USA
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– sequence: 19
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  surname: Khan
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  organization: Department of Pediatric Medicine, St Jude Children's Research Hospital, Memphis, TN, USA
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  surname: Srivastava
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  givenname: Melissa M
  surname: Hudson
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  organization: Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis, TN, USA
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  givenname: Leslie L
  surname: Robison
  fullname: Robison, Leslie L
  organization: Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis, TN, USA
BackLink https://www.ncbi.nlm.nih.gov/pubmed/28890157$$D View this record in MEDLINE/PubMed
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Snippet Survivors of childhood cancer develop early and severe chronic health conditions (CHCs). A quantitative landscape of morbidity of survivors, however, has not...
With 10-year survival for paediatric cancer now more than 80%, and late mortality decreasing in long-term survivors, the population of survivors of paediatric...
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SourceType Open Access Repository
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Index Database
Enrichment Source
Publisher
StartPage 2569
SubjectTerms Adolescent
Adult
Age Factors
Cancer
Cancer Survivors - statistics & numerical data
Cancer therapies
Chemotherapy
Child
Child, Preschool
Childhood
Children
Childrens health
Chronic illnesses
Cohort analysis
Cost of Illness
Female
Health risk assessment
Humans
Infant
Infant, Newborn
Male
Medical records
Middle Aged
Morbidity
Mortality
Neoplasms - complications
Neoplasms - mortality
Pediatrics
Retrospective Studies
Side effects
Survival Analysis
Time Factors
Young Adult
Title The cumulative burden of surviving childhood cancer: an initial report from the St Jude Lifetime Cohort Study (SJLIFE)
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https://dx.doi.org/10.1016/S0140-6736(17)31610-0
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https://pubmed.ncbi.nlm.nih.gov/PMC5798235
Volume 390
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