Article

Secondary gastrointestinal cancer in childhood cancer survivors: a cohort study.

University of Chicago Department of Pediatrics, Section of Hematology, Oncology and Stem Cell Transplantation, 5841 South Maryland Avenue, MC 4060, Chicago, IL 60637, USA.
Annals of internal medicine (Impact Factor: 16.1). 06/2012; 156(11):757-66, W-260. DOI: 10.1059/0003-4819-156-11-201206050-00002
Source: PubMed

ABSTRACT 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.
To determine the risk and associated risk factors for gastrointestinal subsequent malignant neoplasms (SMNs) in childhood cancer survivors.
Retrospective cohort study.
The Childhood Cancer Survivor Study, a multicenter study of childhood cancer survivors diagnosed between 1970 and 1986.
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.
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.
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.
This cohort has not yet attained an age at which risk for gastrointestinal cancer is greatest.
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.
National Cancer Institute.

3 Followers
 · 
98 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Epidemiological data reveals the gastrointestinal (GI) tract as one of the main sites for low-LET radiation-induced cancers. Importantly, the use of particle therapy is increasing, but cancer risk by high-LET particles is still poorly understood. This gap in our knowledge also remains a major limiting factor in planning long-term space missions. Therefore, assessing risks and identifying predisposing factors for carcinogenesis induced by particle radiation is crucial for both astronauts and cancer survivors. We have previously shown that exposure to relatively high doses of high-energy (56)Fe ions induced higher intestinal tumor frequency and grade in the small intestine of Apc(Min/+) mice than γ rays. However, due to the high number of spontaneous lesions (∼30) that develop in Apc(Min/+) animals, this Apc mutant model is not suitable to investigate effects of cumulative doses <1 Gy, which are relevant for risk assessment in astronauts and particle radiotherapy patients. However, Apc(1638N/+) mice develop a relatively small number of spontaneous lesions (∼3 per animal) in both small intestine and colon, and thus we propose a better model for studies on radiation-induced carcinogenesis. Here, we investigated model particle radiation increases tumor frequency and grade in the entire gastrointestinal tract (stomach and more distal intestine) after high- and low-radiation doses whether in the Apc(1638N/+). We have previously reported that an increase in small intestinal tumor multiplicity after exposure to γ rays was dependent on gender in Apc(1638N/+) mice, and here we investigated responses to particle radiation in the same model. Phenotypical and histopathological observations were accompanied by late changes in number and position of mitotic cells in intestinal crypts from animals exposed to different radiation types.
    Radiation Research 02/2014; DOI:10.1667/RR13502.1 · 2.45 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We assessed risk, localization, and timing of third malignancies in Hodgkin lymphoma (HL) survivors. In a cohort of 3,122 5-year HL survivors, diagnosed before age 51 and treated between 1965-1995, we examined whether risk factors for second and third malignancies differ and whether the occurrence of a second malignancy affects the risk of a subsequent malignancy, using recurrent event analyses. After a median follow-up of 22.6 years, 832 patients developed a second malignancy and 126 patients a third one. The risk of a second malignancy was 4.7-fold (95% confidence interval (CI) 4.4-5.1) increased compared to risk in the general population; the standardized incidence ratio for a third malignancy after a second malignancy was 5.4 (95%CI 4.4-6.5). The 10-year cumulative incidence of any third malignancy was 17.1% among females and 9.2% among males (p=0.000). Compared to patients still free of a second malignancy, patients with a second malignancy had a higher risk to develop a subsequent malignancy. This risk depended on age, with hazard ratios of 2.2, 1.6 and 1.1 for patients aged <25, 25-34 and 35-50 years at HL treatment, respectively. In HL survivors who had a second malignancy, treating physicians should be aware of the increased risk of subsequent malignancies.
    Blood 04/2014; 124(3). DOI:10.1182/blood-2013-10-532184 · 9.78 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Survivors of childhood cancers are at increased risk of developing secondary gastrointestinal cancers, including colorectal cancer, later in life, possibly from exposure to abdomino-pelvic radiotherapy and/or alkylating chemotherapy. Profuse gastrointestinal polyposis is associated with rare, inherited colorectal cancer predisposition syndromes, most commonly caused by mutations in the adenomatous polyposis coli (APC) or mutY homolog (MYH) genes. We describe 5 patients who developed gastrointestinal polyposis many years after radiotherapy and chemotherapy for a childhood cancer. Genetic analysis of all 5 subjects did not identify pathogenic germline mutations in APC or MYH. Chemotherapy and/or radiotherapy might therefore cause gastrointestinal polyposis in some patients by undiscovered mechanisms.
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 12/2013; DOI:10.1016/j.cgh.2013.11.040 · 6.53 Impact Factor