Reduction in Late Mortality among 5-Year Survivors of Childhood Cancer

Gregory T. Armstrong, From the Departments of Epidemiology and Cancer Control (G.T.A., Y.Y., T.M.G., K.R.K., D.M.G., M.M.H., L.L.R.) and Oncology (G.T.A., M.M.H.), St. Jude Children's Research Hospital, Memphis, TN; the School of Public Health, University of Alberta, Edmonton (Y.C., Y.Y.), and the Hospital for Sick Children, Toronto (P.C.N.) - both in Canada; the Cancer Prevention and Clinical Statistics Programs, Fred Hutchinson Cancer Research Center, Seattle (W.L.); the Department of Pediatrics, Emory University, Atlanta (A.C.M.); the Department of Radiation Physics, the University of Texas M.D. Anderson Cancer Center, Houston (M.S.); the Departments of Pediatrics and Medicine, Memorial Sloan Kettering Cancer Center, New York (K.C.O.); the Department of Pediatrics, University of Alabama School of Medicine, Birmingham (S.B.); and the Department of Pediatrics, University of Minnesota Medical School, Minneapolis (J.P.N.).Follow
Yan Chen, From the Departments of Epidemiology and Cancer Control (G.T.A., Y.Y., T.M.G., K.R.K., D.M.G., M.M.H., L.L.R.) and Oncology (G.T.A., M.M.H.), St. Jude Children's Research Hospital, Memphis, TN; the School of Public Health, University of Alberta, Edmonton (Y.C., Y.Y.), and the Hospital for Sick Children, Toronto (P.C.N.) - both in Canada; the Cancer Prevention and Clinical Statistics Programs, Fred Hutchinson Cancer Research Center, Seattle (W.L.); the Department of Pediatrics, Emory University, Atlanta (A.C.M.); the Department of Radiation Physics, the University of Texas M.D. Anderson Cancer Center, Houston (M.S.); the Departments of Pediatrics and Medicine, Memorial Sloan Kettering Cancer Center, New York (K.C.O.); the Department of Pediatrics, University of Alabama School of Medicine, Birmingham (S.B.); and the Department of Pediatrics, University of Minnesota Medical School, Minneapolis (J.P.N.).
Yutaka Yasui, From the Departments of Epidemiology and Cancer Control (G.T.A., Y.Y., T.M.G., K.R.K., D.M.G., M.M.H., L.L.R.) and Oncology (G.T.A., M.M.H.), St. Jude Children's Research Hospital, Memphis, TN; the School of Public Health, University of Alberta, Edmonton (Y.C., Y.Y.), and the Hospital for Sick Children, Toronto (P.C.N.) - both in Canada; the Cancer Prevention and Clinical Statistics Programs, Fred Hutchinson Cancer Research Center, Seattle (W.L.); the Department of Pediatrics, Emory University, Atlanta (A.C.M.); the Department of Radiation Physics, the University of Texas M.D. Anderson Cancer Center, Houston (M.S.); the Departments of Pediatrics and Medicine, Memorial Sloan Kettering Cancer Center, New York (K.C.O.); the Department of Pediatrics, University of Alabama School of Medicine, Birmingham (S.B.); and the Department of Pediatrics, University of Minnesota Medical School, Minneapolis (J.P.N.).Follow
Wendy Leisenring, From the Departments of Epidemiology and Cancer Control (G.T.A., Y.Y., T.M.G., K.R.K., D.M.G., M.M.H., L.L.R.) and Oncology (G.T.A., M.M.H.), St. Jude Children's Research Hospital, Memphis, TN; the School of Public Health, University of Alberta, Edmonton (Y.C., Y.Y.), and the Hospital for Sick Children, Toronto (P.C.N.) - both in Canada; the Cancer Prevention and Clinical Statistics Programs, Fred Hutchinson Cancer Research Center, Seattle (W.L.); the Department of Pediatrics, Emory University, Atlanta (A.C.M.); the Department of Radiation Physics, the University of Texas M.D. Anderson Cancer Center, Houston (M.S.); the Departments of Pediatrics and Medicine, Memorial Sloan Kettering Cancer Center, New York (K.C.O.); the Department of Pediatrics, University of Alabama School of Medicine, Birmingham (S.B.); and the Department of Pediatrics, University of Minnesota Medical School, Minneapolis (J.P.N.).
Todd M. Gibson, From the Departments of Epidemiology and Cancer Control (G.T.A., Y.Y., T.M.G., K.R.K., D.M.G., M.M.H., L.L.R.) and Oncology (G.T.A., M.M.H.), St. Jude Children's Research Hospital, Memphis, TN; the School of Public Health, University of Alberta, Edmonton (Y.C., Y.Y.), and the Hospital for Sick Children, Toronto (P.C.N.) - both in Canada; the Cancer Prevention and Clinical Statistics Programs, Fred Hutchinson Cancer Research Center, Seattle (W.L.); the Department of Pediatrics, Emory University, Atlanta (A.C.M.); the Department of Radiation Physics, the University of Texas M.D. Anderson Cancer Center, Houston (M.S.); the Departments of Pediatrics and Medicine, Memorial Sloan Kettering Cancer Center, New York (K.C.O.); the Department of Pediatrics, University of Alabama School of Medicine, Birmingham (S.B.); and the Department of Pediatrics, University of Minnesota Medical School, Minneapolis (J.P.N.).Follow
Ann C. Mertens, From the Departments of Epidemiology and Cancer Control (G.T.A., Y.Y., T.M.G., K.R.K., D.M.G., M.M.H., L.L.R.) and Oncology (G.T.A., M.M.H.), St. Jude Children's Research Hospital, Memphis, TN; the School of Public Health, University of Alberta, Edmonton (Y.C., Y.Y.), and the Hospital for Sick Children, Toronto (P.C.N.) - both in Canada; the Cancer Prevention and Clinical Statistics Programs, Fred Hutchinson Cancer Research Center, Seattle (W.L.); the Department of Pediatrics, Emory University, Atlanta (A.C.M.); the Department of Radiation Physics, the University of Texas M.D. Anderson Cancer Center, Houston (M.S.); the Departments of Pediatrics and Medicine, Memorial Sloan Kettering Cancer Center, New York (K.C.O.); the Department of Pediatrics, University of Alabama School of Medicine, Birmingham (S.B.); and the Department of Pediatrics, University of Minnesota Medical School, Minneapolis (J.P.N.).
Marilyn Stovall, From the Departments of Epidemiology and Cancer Control (G.T.A., Y.Y., T.M.G., K.R.K., D.M.G., M.M.H., L.L.R.) and Oncology (G.T.A., M.M.H.), St. Jude Children's Research Hospital, Memphis, TN; the School of Public Health, University of Alberta, Edmonton (Y.C., Y.Y.), and the Hospital for Sick Children, Toronto (P.C.N.) - both in Canada; the Cancer Prevention and Clinical Statistics Programs, Fred Hutchinson Cancer Research Center, Seattle (W.L.); the Department of Pediatrics, Emory University, Atlanta (A.C.M.); the Department of Radiation Physics, the University of Texas M.D. Anderson Cancer Center, Houston (M.S.); the Departments of Pediatrics and Medicine, Memorial Sloan Kettering Cancer Center, New York (K.C.O.); the Department of Pediatrics, University of Alabama School of Medicine, Birmingham (S.B.); and the Department of Pediatrics, University of Minnesota Medical School, Minneapolis (J.P.N.).
Kevin C. Oeffinger, From the Departments of Epidemiology and Cancer Control (G.T.A., Y.Y., T.M.G., K.R.K., D.M.G., M.M.H., L.L.R.) and Oncology (G.T.A., M.M.H.), St. Jude Children's Research Hospital, Memphis, TN; the School of Public Health, University of Alberta, Edmonton (Y.C., Y.Y.), and the Hospital for Sick Children, Toronto (P.C.N.) - both in Canada; the Cancer Prevention and Clinical Statistics Programs, Fred Hutchinson Cancer Research Center, Seattle (W.L.); the Department of Pediatrics, Emory University, Atlanta (A.C.M.); the Department of Radiation Physics, the University of Texas M.D. Anderson Cancer Center, Houston (M.S.); the Departments of Pediatrics and Medicine, Memorial Sloan Kettering Cancer Center, New York (K.C.O.); the Department of Pediatrics, University of Alabama School of Medicine, Birmingham (S.B.); and the Department of Pediatrics, University of Minnesota Medical School, Minneapolis (J.P.N.).
Smita Bhatia, From the Departments of Epidemiology and Cancer Control (G.T.A., Y.Y., T.M.G., K.R.K., D.M.G., M.M.H., L.L.R.) and Oncology (G.T.A., M.M.H.), St. Jude Children's Research Hospital, Memphis, TN; the School of Public Health, University of Alberta, Edmonton (Y.C., Y.Y.), and the Hospital for Sick Children, Toronto (P.C.N.) - both in Canada; the Cancer Prevention and Clinical Statistics Programs, Fred Hutchinson Cancer Research Center, Seattle (W.L.); the Department of Pediatrics, Emory University, Atlanta (A.C.M.); the Department of Radiation Physics, the University of Texas M.D. Anderson Cancer Center, Houston (M.S.); the Departments of Pediatrics and Medicine, Memorial Sloan Kettering Cancer Center, New York (K.C.O.); the Department of Pediatrics, University of Alabama School of Medicine, Birmingham (S.B.); and the Department of Pediatrics, University of Minnesota Medical School, Minneapolis (J.P.N.).Follow
Kevin R. Krull, From the Departments of Epidemiology and Cancer Control (G.T.A., Y.Y., T.M.G., K.R.K., D.M.G., M.M.H., L.L.R.) and Oncology (G.T.A., M.M.H.), St. Jude Children's Research Hospital, Memphis, TN; the School of Public Health, University of Alberta, Edmonton (Y.C., Y.Y.), and the Hospital for Sick Children, Toronto (P.C.N.) - both in Canada; the Cancer Prevention and Clinical Statistics Programs, Fred Hutchinson Cancer Research Center, Seattle (W.L.); the Department of Pediatrics, Emory University, Atlanta (A.C.M.); the Department of Radiation Physics, the University of Texas M.D. Anderson Cancer Center, Houston (M.S.); the Departments of Pediatrics and Medicine, Memorial Sloan Kettering Cancer Center, New York (K.C.O.); the Department of Pediatrics, University of Alabama School of Medicine, Birmingham (S.B.); and the Department of Pediatrics, University of Minnesota Medical School, Minneapolis (J.P.N.).
Paul C. Nathan, From the Departments of Epidemiology and Cancer Control (G.T.A., Y.Y., T.M.G., K.R.K., D.M.G., M.M.H., L.L.R.) and Oncology (G.T.A., M.M.H.), St. Jude Children's Research Hospital, Memphis, TN; the School of Public Health, University of Alberta, Edmonton (Y.C., Y.Y.), and the Hospital for Sick Children, Toronto (P.C.N.) - both in Canada; the Cancer Prevention and Clinical Statistics Programs, Fred Hutchinson Cancer Research Center, Seattle (W.L.); the Department of Pediatrics, Emory University, Atlanta (A.C.M.); the Department of Radiation Physics, the University of Texas M.D. Anderson Cancer Center, Houston (M.S.); the Departments of Pediatrics and Medicine, Memorial Sloan Kettering Cancer Center, New York (K.C.O.); the Department of Pediatrics, University of Alabama School of Medicine, Birmingham (S.B.); and the Department of Pediatrics, University of Minnesota Medical School, Minneapolis (J.P.N.).
Joseph P. Neglia, From the Departments of Epidemiology and Cancer Control (G.T.A., Y.Y., T.M.G., K.R.K., D.M.G., M.M.H., L.L.R.) and Oncology (G.T.A., M.M.H.), St. Jude Children's Research Hospital, Memphis, TN; the School of Public Health, University of Alberta, Edmonton (Y.C., Y.Y.), and the Hospital for Sick Children, Toronto (P.C.N.) - both in Canada; the Cancer Prevention and Clinical Statistics Programs, Fred Hutchinson Cancer Research Center, Seattle (W.L.); the Department of Pediatrics, Emory University, Atlanta (A.C.M.); the Department of Radiation Physics, the University of Texas M.D. Anderson Cancer Center, Houston (M.S.); the Departments of Pediatrics and Medicine, Memorial Sloan Kettering Cancer Center, New York (K.C.O.); the Department of Pediatrics, University of Alabama School of Medicine, Birmingham (S.B.); and the Department of Pediatrics, University of Minnesota Medical School, Minneapolis (J.P.N.).
Daniel M. Green, From the Departments of Epidemiology and Cancer Control (G.T.A., Y.Y., T.M.G., K.R.K., D.M.G., M.M.H., L.L.R.) and Oncology (G.T.A., M.M.H.), St. Jude Children's Research Hospital, Memphis, TN; the School of Public Health, University of Alberta, Edmonton (Y.C., Y.Y.), and the Hospital for Sick Children, Toronto (P.C.N.) - both in Canada; the Cancer Prevention and Clinical Statistics Programs, Fred Hutchinson Cancer Research Center, Seattle (W.L.); the Department of Pediatrics, Emory University, Atlanta (A.C.M.); the Department of Radiation Physics, the University of Texas M.D. Anderson Cancer Center, Houston (M.S.); the Departments of Pediatrics and Medicine, Memorial Sloan Kettering Cancer Center, New York (K.C.O.); the Department of Pediatrics, University of Alabama School of Medicine, Birmingham (S.B.); and the Department of Pediatrics, University of Minnesota Medical School, Minneapolis (J.P.N.).
Melissa M. Hudson, From the Departments of Epidemiology and Cancer Control (G.T.A., Y.Y., T.M.G., K.R.K., D.M.G., M.M.H., L.L.R.) and Oncology (G.T.A., M.M.H.), St. Jude Children's Research Hospital, Memphis, TN; the School of Public Health, University of Alberta, Edmonton (Y.C., Y.Y.), and the Hospital for Sick Children, Toronto (P.C.N.) - both in Canada; the Cancer Prevention and Clinical Statistics Programs, Fred Hutchinson Cancer Research Center, Seattle (W.L.); the Department of Pediatrics, Emory University, Atlanta (A.C.M.); the Department of Radiation Physics, the University of Texas M.D. Anderson Cancer Center, Houston (M.S.); the Departments of Pediatrics and Medicine, Memorial Sloan Kettering Cancer Center, New York (K.C.O.); the Department of Pediatrics, University of Alabama School of Medicine, Birmingham (S.B.); and the Department of Pediatrics, University of Minnesota Medical School, Minneapolis (J.P.N.).
Leslie L. Robison, From the Departments of Epidemiology and Cancer Control (G.T.A., Y.Y., T.M.G., K.R.K., D.M.G., M.M.H., L.L.R.) and Oncology (G.T.A., M.M.H.), St. Jude Children's Research Hospital, Memphis, TN; the School of Public Health, University of Alberta, Edmonton (Y.C., Y.Y.), and the Hospital for Sick Children, Toronto (P.C.N.) - both in Canada; the Cancer Prevention and Clinical Statistics Programs, Fred Hutchinson Cancer Research Center, Seattle (W.L.); the Department of Pediatrics, Emory University, Atlanta (A.C.M.); the Department of Radiation Physics, the University of Texas M.D. Anderson Cancer Center, Houston (M.S.); the Departments of Pediatrics and Medicine, Memorial Sloan Kettering Cancer Center, New York (K.C.O.); the Department of Pediatrics, University of Alabama School of Medicine, Birmingham (S.B.); and the Department of Pediatrics, University of Minnesota Medical School, Minneapolis (J.P.N.).

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. (Funded by the National Cancer Institute and the American Lebanese-Syrian Associated Charities.).

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The New England journal of medicine

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