Secondary gastrointestinal cancer in childhood cancer survivors: a cohort study

Ann Intern Med. 2012 Jun 5;156(11):757-66, W-260. doi: 10.7326/0003-4819-156-11-201206050-00002.

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.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Canada / epidemiology
  • Child
  • Colorectal Neoplasms / epidemiology
  • Gastrointestinal Neoplasms / epidemiology*
  • Humans
  • Incidence
  • Neoplasms, Second Primary / epidemiology*
  • Platinum Compounds / administration & dosage
  • Platinum Compounds / adverse effects
  • Population Surveillance
  • Procarbazine / administration & dosage
  • Procarbazine / adverse effects
  • Proportional Hazards Models
  • Radiotherapy / adverse effects
  • Retrospective Studies
  • Risk Factors
  • Survivors*
  • United States / epidemiology
  • Young Adult

Substances

  • Antineoplastic Agents
  • Platinum Compounds
  • Procarbazine