Temporal patterns in the risk of chronic health conditions in survivors of childhood cancer diagnosed 1970–99

a report from the Childhood Cancer Survivor Study cohort

Todd M. Gibson, Sogol Mostoufi-Moab, Kayla L. Stratton, Wendy M. Leisenring, Dana Barnea, Eric J. Chow, Sarah S. Donaldson, Rebecca M. Howell, Melissa M. Hudson, Anita Mahajan, Paul C. Nathan, Kirsten K. Ness, Charles A. Sklar, Emily S. Tonorezos, Christopher B. Weldon, Elizabeth M. Wells, Yutaka Yasui, Gregory Armstrong, Leslie L. Robison, Kevin C. Oeffinger

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: Treatments for childhood cancer have evolved over the past 50 years, with the goal of maximising the proportion of patients who achieve long-term survival, while minimising the adverse effects of therapy. We aimed to assess incidence patterns of serious chronic health conditions in long-term survivors of childhood cancer across three decades of diagnosis and treatment. Methods: We used data from the Childhood Cancer Survivor Study, a retrospective cohort with longitudinal follow-up of 5-year survivors of common childhood cancers (leukaemia, tumours of the CNS, Hodgkin lymphoma, non-Hodgkin lymphoma, Wilms tumour, neuroblastoma, soft tissue sarcoma, or bone tumours) who were diagnosed before the age of 21 years and from 1970 to 1999 in North America. We examined the cumulative incidence of severe to fatal chronic health conditions occurring up to 20 years post-diagnosis among survivors, compared by diagnosis decade. We used multivariable regression models to estimate hazard ratios per diagnosis decade, and we added treatment variables to assess whether treatment changes attenuated associations between diagnosis decade and chronic disease risk. Findings: Among 23 601 survivors with a median follow-up of 21 years (IQR 15–25), the 20-year cumulative incidence of at least one grade 3–5 chronic condition decreased significantly from 33·2% (95% CI 32·0–34·3) in those diagnosed 1970–79 to 29·3% (28·4–30·2; p<0·0001) in 1980–89, and 27·5% (26·4–28·6; p=0·012 vs 1980–89) in 1990–99. By comparison, the 20-year cumulative incidence of at least one grade 3–5 condition in 5051 siblings was 4·6% (95% CI 3·9–5·2). The 15-year cumulative incidence of at least one grade 3–5 condition was lower for survivors diagnosed 1990–99 compared with those diagnosed 1970–79 for Hodgkin lymphoma (17·7% [95% CI 15·0–20·5] vs 26·4% [23·8–29·1]; p<0·0001), non-Hodgkin lymphoma (16·9% [14·0–19·7] vs 23·8% [19·9–27·7]; p=0.0053), astrocytoma (30·5% [27·8–33·2] vs 47·3% [42·9–51·7]; p<0·0001), Wilms tumour (11·9% [9·5–14·3] vs 17·6% [14·3–20·8]; p=0·034), soft tissue sarcoma (28·3% [23·5–33·1] vs 36·5% [31·5–41·4]; p=0·021), and osteosarcoma (65·6% [60·6–70·6] vs 87·5% [84·1–91·0]; p<0·0001). By contrast, the 15-year cumulative incidence of at least one grade 3–5 condition was higher (1990–99 vs 1970–79) for medulloblastoma or primitive neuroectodermal tumour (58·9% [54·4–63·3] vs 42·9% [34·9–50·9]; p=0·00060), and neuroblastoma (25·0% [21·8–28·2] vs 18·0% [14·5–21·6]; p=0·0045). Results were consistent with changes in treatment as a significant mediator of the association between diagnosis decade and risk of grade 3–5 chronic conditions for astrocytoma (HR per decade without treatment in the model = 0·77, 95% CI 0·64–0·92; HR with treatment in the model=0·89, 95% CI 0·72–1·11; pmediation=0·0085) and Hodgkin lymphoma (HR without treatment=0·75, 95% CI 0·65–0·85; HR with treatment=0·91, 95% CI 0·73–1·12; pmediation=0·024). Temporal decreases in 15-year cumulative incidence comparing survivors diagnosed 1970–79 to survivors diagnosed 1990–99 were noted for endocrinopathies (5·9% [5·3–6·4] vs 2·8% [2·5–3·2]; p<0·0001), subsequent malignant neoplasms (2·7% [2·3–3·1] vs 1·9% [1·6–2·2]; p=0·0033), musculoskeletal conditions (5·8% [5·2–6·4] vs 3·3% [2·9–3·6]; p<0·0001), and gastrointestinal conditions (2·3% [2·0–2·7] vs 1·5% [1·3–1·8]; p=0·00037), while hearing loss increased (3·0% [2·6–3·5] vs 5·7% [5·2–6·1]; p<0·0001). Interpretation: Our results suggest that more recently treated survivors of childhood cancer had improvements in health outcomes, consistent with efforts over the same time period to modify childhood cancer treatment regimens to maximise overall survival, while reducing risk of long-term adverse events. Continuing advances in cancer therapy offer promise of further reducing the risk of long-term adverse events in childhood cancer survivors. However, achieving long-term survival for childhood cancer continues to come at a cost for many survivors, emphasising the importance of long-term follow-up care for this population. Funding: National Cancer Institute and the American Lebanese-Syrian Associated Charities.

Original languageEnglish (US)
Pages (from-to)1590-1601
Number of pages12
JournalThe Lancet Oncology
Volume19
Issue number12
DOIs
StatePublished - Dec 1 2018

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Survivors
Cohort Studies
Health
Neoplasms
Incidence
Therapeutics
Hodgkin Disease
Wilms Tumor
Astrocytoma
Neuroblastoma
Sarcoma
Non-Hodgkin's Lymphoma
Survival
Charities
Primitive Neuroectodermal Tumors
Aftercare
Medulloblastoma
National Cancer Institute (U.S.)
Osteosarcoma
North America

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Temporal patterns in the risk of chronic health conditions in survivors of childhood cancer diagnosed 1970–99 : a report from the Childhood Cancer Survivor Study cohort. / Gibson, Todd M.; Mostoufi-Moab, Sogol; Stratton, Kayla L.; Leisenring, Wendy M.; Barnea, Dana; Chow, Eric J.; Donaldson, Sarah S.; Howell, Rebecca M.; Hudson, Melissa M.; Mahajan, Anita; Nathan, Paul C.; Ness, Kirsten K.; Sklar, Charles A.; Tonorezos, Emily S.; Weldon, Christopher B.; Wells, Elizabeth M.; Yasui, Yutaka; Armstrong, Gregory; Robison, Leslie L.; Oeffinger, Kevin C.

In: The Lancet Oncology, Vol. 19, No. 12, 01.12.2018, p. 1590-1601.

Research output: Contribution to journalArticle

Gibson, TM, Mostoufi-Moab, S, Stratton, KL, Leisenring, WM, Barnea, D, Chow, EJ, Donaldson, SS, Howell, RM, Hudson, MM, Mahajan, A, Nathan, PC, Ness, KK, Sklar, CA, Tonorezos, ES, Weldon, CB, Wells, EM, Yasui, Y, Armstrong, G, Robison, LL & Oeffinger, KC 2018, 'Temporal patterns in the risk of chronic health conditions in survivors of childhood cancer diagnosed 1970–99: a report from the Childhood Cancer Survivor Study cohort', The Lancet Oncology, vol. 19, no. 12, pp. 1590-1601. https://doi.org/10.1016/S1470-2045(18)30537-0
Gibson, Todd M. ; Mostoufi-Moab, Sogol ; Stratton, Kayla L. ; Leisenring, Wendy M. ; Barnea, Dana ; Chow, Eric J. ; Donaldson, Sarah S. ; Howell, Rebecca M. ; Hudson, Melissa M. ; Mahajan, Anita ; Nathan, Paul C. ; Ness, Kirsten K. ; Sklar, Charles A. ; Tonorezos, Emily S. ; Weldon, Christopher B. ; Wells, Elizabeth M. ; Yasui, Yutaka ; Armstrong, Gregory ; Robison, Leslie L. ; Oeffinger, Kevin C. / Temporal patterns in the risk of chronic health conditions in survivors of childhood cancer diagnosed 1970–99 : a report from the Childhood Cancer Survivor Study cohort. In: The Lancet Oncology. 2018 ; Vol. 19, No. 12. pp. 1590-1601.
@article{52cdeaf68da14129a93ce7a1908e7673,
title = "Temporal patterns in the risk of chronic health conditions in survivors of childhood cancer diagnosed 1970–99: a report from the Childhood Cancer Survivor Study cohort",
abstract = "Background: Treatments for childhood cancer have evolved over the past 50 years, with the goal of maximising the proportion of patients who achieve long-term survival, while minimising the adverse effects of therapy. We aimed to assess incidence patterns of serious chronic health conditions in long-term survivors of childhood cancer across three decades of diagnosis and treatment. Methods: We used data from the Childhood Cancer Survivor Study, a retrospective cohort with longitudinal follow-up of 5-year survivors of common childhood cancers (leukaemia, tumours of the CNS, Hodgkin lymphoma, non-Hodgkin lymphoma, Wilms tumour, neuroblastoma, soft tissue sarcoma, or bone tumours) who were diagnosed before the age of 21 years and from 1970 to 1999 in North America. We examined the cumulative incidence of severe to fatal chronic health conditions occurring up to 20 years post-diagnosis among survivors, compared by diagnosis decade. We used multivariable regression models to estimate hazard ratios per diagnosis decade, and we added treatment variables to assess whether treatment changes attenuated associations between diagnosis decade and chronic disease risk. Findings: Among 23 601 survivors with a median follow-up of 21 years (IQR 15–25), the 20-year cumulative incidence of at least one grade 3–5 chronic condition decreased significantly from 33·2{\%} (95{\%} CI 32·0–34·3) in those diagnosed 1970–79 to 29·3{\%} (28·4–30·2; p<0·0001) in 1980–89, and 27·5{\%} (26·4–28·6; p=0·012 vs 1980–89) in 1990–99. By comparison, the 20-year cumulative incidence of at least one grade 3–5 condition in 5051 siblings was 4·6{\%} (95{\%} CI 3·9–5·2). The 15-year cumulative incidence of at least one grade 3–5 condition was lower for survivors diagnosed 1990–99 compared with those diagnosed 1970–79 for Hodgkin lymphoma (17·7{\%} [95{\%} CI 15·0–20·5] vs 26·4{\%} [23·8–29·1]; p<0·0001), non-Hodgkin lymphoma (16·9{\%} [14·0–19·7] vs 23·8{\%} [19·9–27·7]; p=0.0053), astrocytoma (30·5{\%} [27·8–33·2] vs 47·3{\%} [42·9–51·7]; p<0·0001), Wilms tumour (11·9{\%} [9·5–14·3] vs 17·6{\%} [14·3–20·8]; p=0·034), soft tissue sarcoma (28·3{\%} [23·5–33·1] vs 36·5{\%} [31·5–41·4]; p=0·021), and osteosarcoma (65·6{\%} [60·6–70·6] vs 87·5{\%} [84·1–91·0]; p<0·0001). By contrast, the 15-year cumulative incidence of at least one grade 3–5 condition was higher (1990–99 vs 1970–79) for medulloblastoma or primitive neuroectodermal tumour (58·9{\%} [54·4–63·3] vs 42·9{\%} [34·9–50·9]; p=0·00060), and neuroblastoma (25·0{\%} [21·8–28·2] vs 18·0{\%} [14·5–21·6]; p=0·0045). Results were consistent with changes in treatment as a significant mediator of the association between diagnosis decade and risk of grade 3–5 chronic conditions for astrocytoma (HR per decade without treatment in the model = 0·77, 95{\%} CI 0·64–0·92; HR with treatment in the model=0·89, 95{\%} CI 0·72–1·11; pmediation=0·0085) and Hodgkin lymphoma (HR without treatment=0·75, 95{\%} CI 0·65–0·85; HR with treatment=0·91, 95{\%} CI 0·73–1·12; pmediation=0·024). Temporal decreases in 15-year cumulative incidence comparing survivors diagnosed 1970–79 to survivors diagnosed 1990–99 were noted for endocrinopathies (5·9{\%} [5·3–6·4] vs 2·8{\%} [2·5–3·2]; p<0·0001), subsequent malignant neoplasms (2·7{\%} [2·3–3·1] vs 1·9{\%} [1·6–2·2]; p=0·0033), musculoskeletal conditions (5·8{\%} [5·2–6·4] vs 3·3{\%} [2·9–3·6]; p<0·0001), and gastrointestinal conditions (2·3{\%} [2·0–2·7] vs 1·5{\%} [1·3–1·8]; p=0·00037), while hearing loss increased (3·0{\%} [2·6–3·5] vs 5·7{\%} [5·2–6·1]; p<0·0001). Interpretation: Our results suggest that more recently treated survivors of childhood cancer had improvements in health outcomes, consistent with efforts over the same time period to modify childhood cancer treatment regimens to maximise overall survival, while reducing risk of long-term adverse events. Continuing advances in cancer therapy offer promise of further reducing the risk of long-term adverse events in childhood cancer survivors. However, achieving long-term survival for childhood cancer continues to come at a cost for many survivors, emphasising the importance of long-term follow-up care for this population. Funding: National Cancer Institute and the American Lebanese-Syrian Associated Charities.",
author = "Gibson, {Todd M.} and Sogol Mostoufi-Moab and Stratton, {Kayla L.} and Leisenring, {Wendy M.} and Dana Barnea and Chow, {Eric J.} and Donaldson, {Sarah S.} and Howell, {Rebecca M.} and Hudson, {Melissa M.} and Anita Mahajan and Nathan, {Paul C.} and Ness, {Kirsten K.} and Sklar, {Charles A.} and Tonorezos, {Emily S.} and Weldon, {Christopher B.} and Wells, {Elizabeth M.} and Yutaka Yasui and Gregory Armstrong and Robison, {Leslie L.} and Oeffinger, {Kevin C.}",
year = "2018",
month = "12",
day = "1",
doi = "10.1016/S1470-2045(18)30537-0",
language = "English (US)",
volume = "19",
pages = "1590--1601",
journal = "The Lancet Oncology",
issn = "1470-2045",
publisher = "Lancet Publishing Group",
number = "12",

}

TY - JOUR

T1 - Temporal patterns in the risk of chronic health conditions in survivors of childhood cancer diagnosed 1970–99

T2 - a report from the Childhood Cancer Survivor Study cohort

AU - Gibson, Todd M.

AU - Mostoufi-Moab, Sogol

AU - Stratton, Kayla L.

AU - Leisenring, Wendy M.

AU - Barnea, Dana

AU - Chow, Eric J.

AU - Donaldson, Sarah S.

AU - Howell, Rebecca M.

AU - Hudson, Melissa M.

AU - Mahajan, Anita

AU - Nathan, Paul C.

AU - Ness, Kirsten K.

AU - Sklar, Charles A.

AU - Tonorezos, Emily S.

AU - Weldon, Christopher B.

AU - Wells, Elizabeth M.

AU - Yasui, Yutaka

AU - Armstrong, Gregory

AU - Robison, Leslie L.

AU - Oeffinger, Kevin C.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Background: Treatments for childhood cancer have evolved over the past 50 years, with the goal of maximising the proportion of patients who achieve long-term survival, while minimising the adverse effects of therapy. We aimed to assess incidence patterns of serious chronic health conditions in long-term survivors of childhood cancer across three decades of diagnosis and treatment. Methods: We used data from the Childhood Cancer Survivor Study, a retrospective cohort with longitudinal follow-up of 5-year survivors of common childhood cancers (leukaemia, tumours of the CNS, Hodgkin lymphoma, non-Hodgkin lymphoma, Wilms tumour, neuroblastoma, soft tissue sarcoma, or bone tumours) who were diagnosed before the age of 21 years and from 1970 to 1999 in North America. We examined the cumulative incidence of severe to fatal chronic health conditions occurring up to 20 years post-diagnosis among survivors, compared by diagnosis decade. We used multivariable regression models to estimate hazard ratios per diagnosis decade, and we added treatment variables to assess whether treatment changes attenuated associations between diagnosis decade and chronic disease risk. Findings: Among 23 601 survivors with a median follow-up of 21 years (IQR 15–25), the 20-year cumulative incidence of at least one grade 3–5 chronic condition decreased significantly from 33·2% (95% CI 32·0–34·3) in those diagnosed 1970–79 to 29·3% (28·4–30·2; p<0·0001) in 1980–89, and 27·5% (26·4–28·6; p=0·012 vs 1980–89) in 1990–99. By comparison, the 20-year cumulative incidence of at least one grade 3–5 condition in 5051 siblings was 4·6% (95% CI 3·9–5·2). The 15-year cumulative incidence of at least one grade 3–5 condition was lower for survivors diagnosed 1990–99 compared with those diagnosed 1970–79 for Hodgkin lymphoma (17·7% [95% CI 15·0–20·5] vs 26·4% [23·8–29·1]; p<0·0001), non-Hodgkin lymphoma (16·9% [14·0–19·7] vs 23·8% [19·9–27·7]; p=0.0053), astrocytoma (30·5% [27·8–33·2] vs 47·3% [42·9–51·7]; p<0·0001), Wilms tumour (11·9% [9·5–14·3] vs 17·6% [14·3–20·8]; p=0·034), soft tissue sarcoma (28·3% [23·5–33·1] vs 36·5% [31·5–41·4]; p=0·021), and osteosarcoma (65·6% [60·6–70·6] vs 87·5% [84·1–91·0]; p<0·0001). By contrast, the 15-year cumulative incidence of at least one grade 3–5 condition was higher (1990–99 vs 1970–79) for medulloblastoma or primitive neuroectodermal tumour (58·9% [54·4–63·3] vs 42·9% [34·9–50·9]; p=0·00060), and neuroblastoma (25·0% [21·8–28·2] vs 18·0% [14·5–21·6]; p=0·0045). Results were consistent with changes in treatment as a significant mediator of the association between diagnosis decade and risk of grade 3–5 chronic conditions for astrocytoma (HR per decade without treatment in the model = 0·77, 95% CI 0·64–0·92; HR with treatment in the model=0·89, 95% CI 0·72–1·11; pmediation=0·0085) and Hodgkin lymphoma (HR without treatment=0·75, 95% CI 0·65–0·85; HR with treatment=0·91, 95% CI 0·73–1·12; pmediation=0·024). Temporal decreases in 15-year cumulative incidence comparing survivors diagnosed 1970–79 to survivors diagnosed 1990–99 were noted for endocrinopathies (5·9% [5·3–6·4] vs 2·8% [2·5–3·2]; p<0·0001), subsequent malignant neoplasms (2·7% [2·3–3·1] vs 1·9% [1·6–2·2]; p=0·0033), musculoskeletal conditions (5·8% [5·2–6·4] vs 3·3% [2·9–3·6]; p<0·0001), and gastrointestinal conditions (2·3% [2·0–2·7] vs 1·5% [1·3–1·8]; p=0·00037), while hearing loss increased (3·0% [2·6–3·5] vs 5·7% [5·2–6·1]; p<0·0001). Interpretation: Our results suggest that more recently treated survivors of childhood cancer had improvements in health outcomes, consistent with efforts over the same time period to modify childhood cancer treatment regimens to maximise overall survival, while reducing risk of long-term adverse events. Continuing advances in cancer therapy offer promise of further reducing the risk of long-term adverse events in childhood cancer survivors. However, achieving long-term survival for childhood cancer continues to come at a cost for many survivors, emphasising the importance of long-term follow-up care for this population. Funding: National Cancer Institute and the American Lebanese-Syrian Associated Charities.

AB - Background: Treatments for childhood cancer have evolved over the past 50 years, with the goal of maximising the proportion of patients who achieve long-term survival, while minimising the adverse effects of therapy. We aimed to assess incidence patterns of serious chronic health conditions in long-term survivors of childhood cancer across three decades of diagnosis and treatment. Methods: We used data from the Childhood Cancer Survivor Study, a retrospective cohort with longitudinal follow-up of 5-year survivors of common childhood cancers (leukaemia, tumours of the CNS, Hodgkin lymphoma, non-Hodgkin lymphoma, Wilms tumour, neuroblastoma, soft tissue sarcoma, or bone tumours) who were diagnosed before the age of 21 years and from 1970 to 1999 in North America. We examined the cumulative incidence of severe to fatal chronic health conditions occurring up to 20 years post-diagnosis among survivors, compared by diagnosis decade. We used multivariable regression models to estimate hazard ratios per diagnosis decade, and we added treatment variables to assess whether treatment changes attenuated associations between diagnosis decade and chronic disease risk. Findings: Among 23 601 survivors with a median follow-up of 21 years (IQR 15–25), the 20-year cumulative incidence of at least one grade 3–5 chronic condition decreased significantly from 33·2% (95% CI 32·0–34·3) in those diagnosed 1970–79 to 29·3% (28·4–30·2; p<0·0001) in 1980–89, and 27·5% (26·4–28·6; p=0·012 vs 1980–89) in 1990–99. By comparison, the 20-year cumulative incidence of at least one grade 3–5 condition in 5051 siblings was 4·6% (95% CI 3·9–5·2). The 15-year cumulative incidence of at least one grade 3–5 condition was lower for survivors diagnosed 1990–99 compared with those diagnosed 1970–79 for Hodgkin lymphoma (17·7% [95% CI 15·0–20·5] vs 26·4% [23·8–29·1]; p<0·0001), non-Hodgkin lymphoma (16·9% [14·0–19·7] vs 23·8% [19·9–27·7]; p=0.0053), astrocytoma (30·5% [27·8–33·2] vs 47·3% [42·9–51·7]; p<0·0001), Wilms tumour (11·9% [9·5–14·3] vs 17·6% [14·3–20·8]; p=0·034), soft tissue sarcoma (28·3% [23·5–33·1] vs 36·5% [31·5–41·4]; p=0·021), and osteosarcoma (65·6% [60·6–70·6] vs 87·5% [84·1–91·0]; p<0·0001). By contrast, the 15-year cumulative incidence of at least one grade 3–5 condition was higher (1990–99 vs 1970–79) for medulloblastoma or primitive neuroectodermal tumour (58·9% [54·4–63·3] vs 42·9% [34·9–50·9]; p=0·00060), and neuroblastoma (25·0% [21·8–28·2] vs 18·0% [14·5–21·6]; p=0·0045). Results were consistent with changes in treatment as a significant mediator of the association between diagnosis decade and risk of grade 3–5 chronic conditions for astrocytoma (HR per decade without treatment in the model = 0·77, 95% CI 0·64–0·92; HR with treatment in the model=0·89, 95% CI 0·72–1·11; pmediation=0·0085) and Hodgkin lymphoma (HR without treatment=0·75, 95% CI 0·65–0·85; HR with treatment=0·91, 95% CI 0·73–1·12; pmediation=0·024). Temporal decreases in 15-year cumulative incidence comparing survivors diagnosed 1970–79 to survivors diagnosed 1990–99 were noted for endocrinopathies (5·9% [5·3–6·4] vs 2·8% [2·5–3·2]; p<0·0001), subsequent malignant neoplasms (2·7% [2·3–3·1] vs 1·9% [1·6–2·2]; p=0·0033), musculoskeletal conditions (5·8% [5·2–6·4] vs 3·3% [2·9–3·6]; p<0·0001), and gastrointestinal conditions (2·3% [2·0–2·7] vs 1·5% [1·3–1·8]; p=0·00037), while hearing loss increased (3·0% [2·6–3·5] vs 5·7% [5·2–6·1]; p<0·0001). Interpretation: Our results suggest that more recently treated survivors of childhood cancer had improvements in health outcomes, consistent with efforts over the same time period to modify childhood cancer treatment regimens to maximise overall survival, while reducing risk of long-term adverse events. Continuing advances in cancer therapy offer promise of further reducing the risk of long-term adverse events in childhood cancer survivors. However, achieving long-term survival for childhood cancer continues to come at a cost for many survivors, emphasising the importance of long-term follow-up care for this population. Funding: National Cancer Institute and the American Lebanese-Syrian Associated Charities.

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U2 - 10.1016/S1470-2045(18)30537-0

DO - 10.1016/S1470-2045(18)30537-0

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SP - 1590

EP - 1601

JO - The Lancet Oncology

JF - The Lancet Oncology

SN - 1470-2045

IS - 12

ER -