Secondary gastrointestinal cancer in childhood cancer survivors: A cohort study

Tara O. Henderson, Kevin C. Oeffinger, John Whitton, Wendy Leisenring, Joseph Neglia, Anna Meadows, Catherine Crotty, David T. Rubin, Lisa Diller, Peter Inskip, Susan A. Smith, Marilyn Stovall, Louis S. Constine, Sue Hammond, Gregory Armstrong, Leslie L. Robison, Paul C. Nathan

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Abstract

Background: Childhood cancer survivors develop gastrointestinal cancer more frequently and at a younger age than the general population, but the risk factors have not been well-characterized. Objective: To determine the risk and associated risk factors for gastrointestinal subsequent malignant neoplasms (SMNs) in childhood cancer survivors. Design: Retrospective cohort study. Setting: The Childhood Cancer Survivor Study, a multicenter study of childhood cancer survivors diagnosed between 1970 and 1986. Patients: 14 358 survivors of cancer diagnosed when they were younger than 21 years of age who survived for 5 or more years after the initial diagnosis. Measurements: Standardized incidence ratios (SIRs) for gastrointestinal SMNs were calculated by using age-specific population data. Multivariate Cox regression models identified associations between risk factors and gastrointestinal SMN development. Results: At median follow-up of 22.8 years (range, 5.5 to 30.2 years), 45 cases of gastrointestinal cancer were identified. The risk for gastrointestinal SMNs was 4.6-fold higher in childhood cancer survivors than in the general population (95% CI, 3.4 to 6.1). The SIR for colorectal cancer was 4.2 (CI, 2.8 to 6.3). The highest risk for gastrointestinal SMNs was associated with abdominal radiation (SIR, 11.2 [CI, 7.6 to 16.4]). However, survivors not exposed to radiation had a significantly increased risk (SIR, 2.4 [CI, 1.4 to 3.9]). In addition to abdominal radiation, high-dose procarbazine (relative risk, 3.2 [CI, 1.1 to 9.4]) and platinum drugs (relative risk, 7.6 [CI, 2.3 to 25.5]) independently increased the risk for gastrointestinal SMNs. Limitation: This cohort has not yet attained an age at which risk for gastrointestinal cancer is greatest. Conclusion: Childhood cancer survivors, particularly those exposed to abdominal radiation, are at increased risk for gastrointestinal SMNs. These findings suggest that surveillance of at-risk childhood cancer survivors should begin at a younger age than that recommended for the general population. Primary Funding Source: National Cancer Institute.

Original languageEnglish (US)
Pages (from-to)757-766
Number of pages10
JournalAnnals of internal medicine
Volume156
Issue number11
DOIs
StatePublished - Jan 1 2012
Externally publishedYes

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Gastrointestinal Neoplasms
Survivors
Cohort Studies
Neoplasms
Radiation
Incidence
Population
Procarbazine
National Cancer Institute (U.S.)
Platinum
Proportional Hazards Models
Multicenter Studies

All Science Journal Classification (ASJC) codes

  • Internal Medicine

Cite this

Henderson, T. O., Oeffinger, K. C., Whitton, J., Leisenring, W., Neglia, J., Meadows, A., ... Nathan, P. C. (2012). Secondary gastrointestinal cancer in childhood cancer survivors: A cohort study. Annals of internal medicine, 156(11), 757-766. https://doi.org/10.7326/0003-4819-156-11-201206050-00002

Secondary gastrointestinal cancer in childhood cancer survivors : A cohort study. / Henderson, Tara O.; Oeffinger, Kevin C.; Whitton, John; Leisenring, Wendy; Neglia, Joseph; Meadows, Anna; Crotty, Catherine; Rubin, David T.; Diller, Lisa; Inskip, Peter; Smith, Susan A.; Stovall, Marilyn; Constine, Louis S.; Hammond, Sue; Armstrong, Gregory; Robison, Leslie L.; Nathan, Paul C.

In: Annals of internal medicine, Vol. 156, No. 11, 01.01.2012, p. 757-766.

Research output: Contribution to journalArticle

Henderson, TO, Oeffinger, KC, Whitton, J, Leisenring, W, Neglia, J, Meadows, A, Crotty, C, Rubin, DT, Diller, L, Inskip, P, Smith, SA, Stovall, M, Constine, LS, Hammond, S, Armstrong, G, Robison, LL & Nathan, PC 2012, 'Secondary gastrointestinal cancer in childhood cancer survivors: A cohort study', Annals of internal medicine, vol. 156, no. 11, pp. 757-766. https://doi.org/10.7326/0003-4819-156-11-201206050-00002
Henderson TO, Oeffinger KC, Whitton J, Leisenring W, Neglia J, Meadows A et al. Secondary gastrointestinal cancer in childhood cancer survivors: A cohort study. Annals of internal medicine. 2012 Jan 1;156(11):757-766. https://doi.org/10.7326/0003-4819-156-11-201206050-00002
Henderson, Tara O. ; Oeffinger, Kevin C. ; Whitton, John ; Leisenring, Wendy ; Neglia, Joseph ; Meadows, Anna ; Crotty, Catherine ; Rubin, David T. ; Diller, Lisa ; Inskip, Peter ; Smith, Susan A. ; Stovall, Marilyn ; Constine, Louis S. ; Hammond, Sue ; Armstrong, Gregory ; Robison, Leslie L. ; Nathan, Paul C. / Secondary gastrointestinal cancer in childhood cancer survivors : A cohort study. In: Annals of internal medicine. 2012 ; Vol. 156, No. 11. pp. 757-766.
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abstract = "Background: Childhood cancer survivors develop gastrointestinal cancer more frequently and at a younger age than the general population, but the risk factors have not been well-characterized. Objective: To determine the risk and associated risk factors for gastrointestinal subsequent malignant neoplasms (SMNs) in childhood cancer survivors. Design: Retrospective cohort study. Setting: The Childhood Cancer Survivor Study, a multicenter study of childhood cancer survivors diagnosed between 1970 and 1986. Patients: 14 358 survivors of cancer diagnosed when they were younger than 21 years of age who survived for 5 or more years after the initial diagnosis. Measurements: Standardized incidence ratios (SIRs) for gastrointestinal SMNs were calculated by using age-specific population data. Multivariate Cox regression models identified associations between risk factors and gastrointestinal SMN development. Results: At median follow-up of 22.8 years (range, 5.5 to 30.2 years), 45 cases of gastrointestinal cancer were identified. The risk for gastrointestinal SMNs was 4.6-fold higher in childhood cancer survivors than in the general population (95{\%} CI, 3.4 to 6.1). The SIR for colorectal cancer was 4.2 (CI, 2.8 to 6.3). The highest risk for gastrointestinal SMNs was associated with abdominal radiation (SIR, 11.2 [CI, 7.6 to 16.4]). However, survivors not exposed to radiation had a significantly increased risk (SIR, 2.4 [CI, 1.4 to 3.9]). In addition to abdominal radiation, high-dose procarbazine (relative risk, 3.2 [CI, 1.1 to 9.4]) and platinum drugs (relative risk, 7.6 [CI, 2.3 to 25.5]) independently increased the risk for gastrointestinal SMNs. Limitation: This cohort has not yet attained an age at which risk for gastrointestinal cancer is greatest. Conclusion: Childhood cancer survivors, particularly those exposed to abdominal radiation, are at increased risk for gastrointestinal SMNs. These findings suggest that surveillance of at-risk childhood cancer survivors should begin at a younger age than that recommended for the general population. Primary Funding Source: National Cancer Institute.",
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T2 - A cohort study

AU - Henderson, Tara O.

AU - Oeffinger, Kevin C.

AU - Whitton, John

AU - Leisenring, Wendy

AU - Neglia, Joseph

AU - Meadows, Anna

AU - Crotty, Catherine

AU - Rubin, David T.

AU - Diller, Lisa

AU - Inskip, Peter

AU - Smith, Susan A.

AU - Stovall, Marilyn

AU - Constine, Louis S.

AU - Hammond, Sue

AU - Armstrong, Gregory

AU - Robison, Leslie L.

AU - Nathan, Paul C.

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N2 - Background: Childhood cancer survivors develop gastrointestinal cancer more frequently and at a younger age than the general population, but the risk factors have not been well-characterized. Objective: To determine the risk and associated risk factors for gastrointestinal subsequent malignant neoplasms (SMNs) in childhood cancer survivors. Design: Retrospective cohort study. Setting: The Childhood Cancer Survivor Study, a multicenter study of childhood cancer survivors diagnosed between 1970 and 1986. Patients: 14 358 survivors of cancer diagnosed when they were younger than 21 years of age who survived for 5 or more years after the initial diagnosis. Measurements: Standardized incidence ratios (SIRs) for gastrointestinal SMNs were calculated by using age-specific population data. Multivariate Cox regression models identified associations between risk factors and gastrointestinal SMN development. Results: At median follow-up of 22.8 years (range, 5.5 to 30.2 years), 45 cases of gastrointestinal cancer were identified. The risk for gastrointestinal SMNs was 4.6-fold higher in childhood cancer survivors than in the general population (95% CI, 3.4 to 6.1). The SIR for colorectal cancer was 4.2 (CI, 2.8 to 6.3). The highest risk for gastrointestinal SMNs was associated with abdominal radiation (SIR, 11.2 [CI, 7.6 to 16.4]). However, survivors not exposed to radiation had a significantly increased risk (SIR, 2.4 [CI, 1.4 to 3.9]). In addition to abdominal radiation, high-dose procarbazine (relative risk, 3.2 [CI, 1.1 to 9.4]) and platinum drugs (relative risk, 7.6 [CI, 2.3 to 25.5]) independently increased the risk for gastrointestinal SMNs. Limitation: This cohort has not yet attained an age at which risk for gastrointestinal cancer is greatest. Conclusion: Childhood cancer survivors, particularly those exposed to abdominal radiation, are at increased risk for gastrointestinal SMNs. These findings suggest that surveillance of at-risk childhood cancer survivors should begin at a younger age than that recommended for the general population. Primary Funding Source: National Cancer Institute.

AB - Background: Childhood cancer survivors develop gastrointestinal cancer more frequently and at a younger age than the general population, but the risk factors have not been well-characterized. Objective: To determine the risk and associated risk factors for gastrointestinal subsequent malignant neoplasms (SMNs) in childhood cancer survivors. Design: Retrospective cohort study. Setting: The Childhood Cancer Survivor Study, a multicenter study of childhood cancer survivors diagnosed between 1970 and 1986. Patients: 14 358 survivors of cancer diagnosed when they were younger than 21 years of age who survived for 5 or more years after the initial diagnosis. Measurements: Standardized incidence ratios (SIRs) for gastrointestinal SMNs were calculated by using age-specific population data. Multivariate Cox regression models identified associations between risk factors and gastrointestinal SMN development. Results: At median follow-up of 22.8 years (range, 5.5 to 30.2 years), 45 cases of gastrointestinal cancer were identified. The risk for gastrointestinal SMNs was 4.6-fold higher in childhood cancer survivors than in the general population (95% CI, 3.4 to 6.1). The SIR for colorectal cancer was 4.2 (CI, 2.8 to 6.3). The highest risk for gastrointestinal SMNs was associated with abdominal radiation (SIR, 11.2 [CI, 7.6 to 16.4]). However, survivors not exposed to radiation had a significantly increased risk (SIR, 2.4 [CI, 1.4 to 3.9]). In addition to abdominal radiation, high-dose procarbazine (relative risk, 3.2 [CI, 1.1 to 9.4]) and platinum drugs (relative risk, 7.6 [CI, 2.3 to 25.5]) independently increased the risk for gastrointestinal SMNs. Limitation: This cohort has not yet attained an age at which risk for gastrointestinal cancer is greatest. Conclusion: Childhood cancer survivors, particularly those exposed to abdominal radiation, are at increased risk for gastrointestinal SMNs. These findings suggest that surveillance of at-risk childhood cancer survivors should begin at a younger age than that recommended for the general population. Primary Funding Source: National Cancer Institute.

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