Reduction in late mortality among 5-year survivors of childhood cancer

Gregory T. Armstrong, Yan Chen, Yutaka Yasui, Wendy Leisenring, Todd M. Gibson, Ann C. Mertens, Marilyn Stovall, Kevin C. Oeffinger, Smita Bhatia, Kevin R. Krull, Paul C. Nathan, Joseph P. Neglia, Daniel M. Green, Melissa M. Hudson, Leslie L. Robison

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Abstract

Background Among patients in whom childhood cancer was diagnosed in the 1970s and 1980s, 18% of those who survived for 5 years died within the subsequent 25 years. In recent decades, cancer treatments have been modified with the goal of reducing life-threatening late effects. Methods We evaluated late mortality among 34,033 patients in the Childhood Cancer Survivor Study cohort who survived at least 5 years after childhood cancer (i.e., cancer diagnosed before the age of 21 years) for which treatment was initiated during the period from 1970 through 1999. The median follow-up was 21 years (range, 5 to 38). We evaluated demographic and disease factors that were associated with death from health-related causes (i.e., conditions that exclude recurrence or progression of the original cancer and external causes but include the late effects of cancer therapy) using cumulative incidence and piecewise exponential models to estimate relative rates and 95% confidence intervals. Results Of the 3958 deaths that occurred during the study period, 1618 (41%) were attributable to health-related causes, including 746 deaths from subsequent neoplasms, 241 from cardiac causes, 137 from pulmonary causes, and 494 from other causes. A reduction in 15-year mortality was observed for death from any cause (from 12.4% in the early 1970s to 6.0% in the 1990s, P<0.001 for trend) and from health-related causes (from 3.5% to 2.1%, P<0.001 for trend). These reductions were attributable to decreases in the rates of death from subsequent neoplasm (P<0.001), cardiac causes (P<0.001), and pulmonary causes (P=0.04). Changes in therapy according to decade included reduced rates of cranial radiotherapy for acute lymphoblastic leukemia (85% in the 1970s, 51% in the 1980s, and 19% in the 1990s), of abdominal radiotherapy for Wilms' tumor (78%, 53%, and 43%, respectively), of chest radiotherapy for Hodgkin's lymphoma (87%, 79%, and 61%, respectively), and of anthracycline exposure. Reduction in treatment exposure was associated with reduced late mortality among survivors of acute lymphoblastic leukemia and Wilms' tumor. Conclusions The strategy of lowering therapeutic exposure has contributed to an observed decline in late mortality among 5-year survivors of childhood cancer.

Original languageEnglish (US)
Pages (from-to)833-842
Number of pages10
JournalNew England Journal of Medicine
Volume374
Issue number9
DOIs
StatePublished - Mar 3 2016

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Survivors
Mortality
Neoplasms
Radiotherapy
Wilms Tumor
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Health
Therapeutics
Lung
Heart Neoplasms
Anthracyclines
Hodgkin Disease
Cause of Death
Cohort Studies
Thorax
Demography
Confidence Intervals
Recurrence
Incidence

Cite this

Armstrong, G. T., Chen, Y., Yasui, Y., Leisenring, W., Gibson, T. M., Mertens, A. C., ... Robison, L. L. (2016). Reduction in late mortality among 5-year survivors of childhood cancer. New England Journal of Medicine, 374(9), 833-842. https://doi.org/10.1056/NEJMoa1510795

Reduction in late mortality among 5-year survivors of childhood cancer. / Armstrong, Gregory T.; Chen, Yan; Yasui, Yutaka; Leisenring, Wendy; Gibson, Todd M.; Mertens, Ann C.; Stovall, Marilyn; Oeffinger, Kevin C.; Bhatia, Smita; Krull, Kevin R.; Nathan, Paul C.; Neglia, Joseph P.; Green, Daniel M.; Hudson, Melissa M.; Robison, Leslie L.

In: New England Journal of Medicine, Vol. 374, No. 9, 03.03.2016, p. 833-842.

Research output: Contribution to journalArticle

Armstrong, GT, Chen, Y, Yasui, Y, Leisenring, W, Gibson, TM, Mertens, AC, Stovall, M, Oeffinger, KC, Bhatia, S, Krull, KR, Nathan, PC, Neglia, JP, Green, DM, Hudson, MM & Robison, LL 2016, 'Reduction in late mortality among 5-year survivors of childhood cancer', New England Journal of Medicine, vol. 374, no. 9, pp. 833-842. https://doi.org/10.1056/NEJMoa1510795
Armstrong GT, Chen Y, Yasui Y, Leisenring W, Gibson TM, Mertens AC et al. Reduction in late mortality among 5-year survivors of childhood cancer. New England Journal of Medicine. 2016 Mar 3;374(9):833-842. https://doi.org/10.1056/NEJMoa1510795
Armstrong, Gregory T. ; Chen, Yan ; Yasui, Yutaka ; Leisenring, Wendy ; Gibson, Todd M. ; Mertens, Ann C. ; Stovall, Marilyn ; Oeffinger, Kevin C. ; Bhatia, Smita ; Krull, Kevin R. ; Nathan, Paul C. ; Neglia, Joseph P. ; Green, Daniel M. ; Hudson, Melissa M. ; Robison, Leslie L. / Reduction in late mortality among 5-year survivors of childhood cancer. In: New England Journal of Medicine. 2016 ; Vol. 374, No. 9. pp. 833-842.
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abstract = "Background Among patients in whom childhood cancer was diagnosed in the 1970s and 1980s, 18{\%} of those who survived for 5 years died within the subsequent 25 years. In recent decades, cancer treatments have been modified with the goal of reducing life-threatening late effects. Methods We evaluated late mortality among 34,033 patients in the Childhood Cancer Survivor Study cohort who survived at least 5 years after childhood cancer (i.e., cancer diagnosed before the age of 21 years) for which treatment was initiated during the period from 1970 through 1999. The median follow-up was 21 years (range, 5 to 38). We evaluated demographic and disease factors that were associated with death from health-related causes (i.e., conditions that exclude recurrence or progression of the original cancer and external causes but include the late effects of cancer therapy) using cumulative incidence and piecewise exponential models to estimate relative rates and 95{\%} confidence intervals. Results Of the 3958 deaths that occurred during the study period, 1618 (41{\%}) were attributable to health-related causes, including 746 deaths from subsequent neoplasms, 241 from cardiac causes, 137 from pulmonary causes, and 494 from other causes. A reduction in 15-year mortality was observed for death from any cause (from 12.4{\%} in the early 1970s to 6.0{\%} in the 1990s, P<0.001 for trend) and from health-related causes (from 3.5{\%} to 2.1{\%}, P<0.001 for trend). These reductions were attributable to decreases in the rates of death from subsequent neoplasm (P<0.001), cardiac causes (P<0.001), and pulmonary causes (P=0.04). Changes in therapy according to decade included reduced rates of cranial radiotherapy for acute lymphoblastic leukemia (85{\%} in the 1970s, 51{\%} in the 1980s, and 19{\%} in the 1990s), of abdominal radiotherapy for Wilms' tumor (78{\%}, 53{\%}, and 43{\%}, respectively), of chest radiotherapy for Hodgkin's lymphoma (87{\%}, 79{\%}, and 61{\%}, respectively), and of anthracycline exposure. Reduction in treatment exposure was associated with reduced late mortality among survivors of acute lymphoblastic leukemia and Wilms' tumor. Conclusions The strategy of lowering therapeutic exposure has contributed to an observed decline in late mortality among 5-year survivors of childhood cancer.",
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T1 - Reduction in late mortality among 5-year survivors of childhood cancer

AU - Armstrong, Gregory T.

AU - Chen, Yan

AU - Yasui, Yutaka

AU - Leisenring, Wendy

AU - Gibson, Todd M.

AU - Mertens, Ann C.

AU - Stovall, Marilyn

AU - Oeffinger, Kevin C.

AU - Bhatia, Smita

AU - Krull, Kevin R.

AU - Nathan, Paul C.

AU - Neglia, Joseph P.

AU - Green, Daniel M.

AU - Hudson, Melissa M.

AU - Robison, Leslie L.

PY - 2016/3/3

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N2 - Background Among patients in whom childhood cancer was diagnosed in the 1970s and 1980s, 18% of those who survived for 5 years died within the subsequent 25 years. In recent decades, cancer treatments have been modified with the goal of reducing life-threatening late effects. Methods We evaluated late mortality among 34,033 patients in the Childhood Cancer Survivor Study cohort who survived at least 5 years after childhood cancer (i.e., cancer diagnosed before the age of 21 years) for which treatment was initiated during the period from 1970 through 1999. The median follow-up was 21 years (range, 5 to 38). We evaluated demographic and disease factors that were associated with death from health-related causes (i.e., conditions that exclude recurrence or progression of the original cancer and external causes but include the late effects of cancer therapy) using cumulative incidence and piecewise exponential models to estimate relative rates and 95% confidence intervals. Results Of the 3958 deaths that occurred during the study period, 1618 (41%) were attributable to health-related causes, including 746 deaths from subsequent neoplasms, 241 from cardiac causes, 137 from pulmonary causes, and 494 from other causes. A reduction in 15-year mortality was observed for death from any cause (from 12.4% in the early 1970s to 6.0% in the 1990s, P<0.001 for trend) and from health-related causes (from 3.5% to 2.1%, P<0.001 for trend). These reductions were attributable to decreases in the rates of death from subsequent neoplasm (P<0.001), cardiac causes (P<0.001), and pulmonary causes (P=0.04). Changes in therapy according to decade included reduced rates of cranial radiotherapy for acute lymphoblastic leukemia (85% in the 1970s, 51% in the 1980s, and 19% in the 1990s), of abdominal radiotherapy for Wilms' tumor (78%, 53%, and 43%, respectively), of chest radiotherapy for Hodgkin's lymphoma (87%, 79%, and 61%, respectively), and of anthracycline exposure. Reduction in treatment exposure was associated with reduced late mortality among survivors of acute lymphoblastic leukemia and Wilms' tumor. Conclusions The strategy of lowering therapeutic exposure has contributed to an observed decline in late mortality among 5-year survivors of childhood cancer.

AB - Background Among patients in whom childhood cancer was diagnosed in the 1970s and 1980s, 18% of those who survived for 5 years died within the subsequent 25 years. In recent decades, cancer treatments have been modified with the goal of reducing life-threatening late effects. Methods We evaluated late mortality among 34,033 patients in the Childhood Cancer Survivor Study cohort who survived at least 5 years after childhood cancer (i.e., cancer diagnosed before the age of 21 years) for which treatment was initiated during the period from 1970 through 1999. The median follow-up was 21 years (range, 5 to 38). We evaluated demographic and disease factors that were associated with death from health-related causes (i.e., conditions that exclude recurrence or progression of the original cancer and external causes but include the late effects of cancer therapy) using cumulative incidence and piecewise exponential models to estimate relative rates and 95% confidence intervals. Results Of the 3958 deaths that occurred during the study period, 1618 (41%) were attributable to health-related causes, including 746 deaths from subsequent neoplasms, 241 from cardiac causes, 137 from pulmonary causes, and 494 from other causes. A reduction in 15-year mortality was observed for death from any cause (from 12.4% in the early 1970s to 6.0% in the 1990s, P<0.001 for trend) and from health-related causes (from 3.5% to 2.1%, P<0.001 for trend). These reductions were attributable to decreases in the rates of death from subsequent neoplasm (P<0.001), cardiac causes (P<0.001), and pulmonary causes (P=0.04). Changes in therapy according to decade included reduced rates of cranial radiotherapy for acute lymphoblastic leukemia (85% in the 1970s, 51% in the 1980s, and 19% in the 1990s), of abdominal radiotherapy for Wilms' tumor (78%, 53%, and 43%, respectively), of chest radiotherapy for Hodgkin's lymphoma (87%, 79%, and 61%, respectively), and of anthracycline exposure. Reduction in treatment exposure was associated with reduced late mortality among survivors of acute lymphoblastic leukemia and Wilms' tumor. Conclusions The strategy of lowering therapeutic exposure has contributed to an observed decline in late mortality among 5-year survivors of childhood cancer.

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