Childhood cancer survivors have nearly five times the risk for secondary gastrointestinal (GI) cancer as the general population, and that risk increases if abdominal radiotherapy was part of the initial treatment plan, according to a database review.
At a median follow-up of nearly 23 years, the standardized incidence ratio (SIR) for GI subsequent malignant neoplasms was 4.6 (95% CI 3.4 to 6.1) and the SIR jumped to 11.2 (95% CI 7.6 to 16.4) in childhood cancer survivors who had undergone abdominal radiation, reported Tara Henderson MD, MPH, from the University of Chicago, and colleagues. The SIR for colorectal cancer was 4.2 (95% CI 2.8 to 6.3).
Action Points
- Childhood cancer survivors face a nearly five-fold risk for secondary gastrointestinal (GI) cancer compared with the general population, and that risk increases if abdominal radiotherapy was part of the initial treatment plan, a study has found.
- Note that the findings suggest that surveillance of at-risk childhood cancer survivors should begin at a younger age than that recommended for the general population.
They also found that the cumulative incidence of subsequent GI neoplasms by 30 years after primary cancer diagnosis was 0.64% (95% CI 0.45% to 0.86%). The cumulative incidence was 1.97% (95% CI 1.15% to 2.80%) for those who had undergone abdominal radiotherapy, the authors reported in the June 5 issue of Annals of Internal Medicine.
"These findings suggest that surveillance of at-risk childhood cancer survivors should begin at a younger age than that recommended for the general population," they wrote.
Subsequent malignant neoplasms are the second leading cause of premature death in childhood cancer survivors after recurrence of primary cancer, and most of these patients develop GI tumors. The Children's Oncology Group has published guidelines for colon cancer surveillance in survivors, and they recommend screening every 5 years beginning a decade after radiation (of more than 30 Gy) or at age 35.
With the current study, the authors said they wanted to offer a "more precise identification of which groups of childhood cancer survivors are at greatest risk for GI subsequent malignant neoplasms."
They looked at data on 14,358 patients in the Childhood Cancer Survivor Study (CCSS). The CCSS collected baseline data in 1994 through questionnaires, which were then administered annually until 1998. Follow-up questionnaires were sent in 2000, 2003, and 2005. If a patient had died after 5 years of survivorship, the next of kin supplied the information for CCSS.
Henderson's group defined GI subsequent malignant neoplasms as tumors of the oral cavity and pharynx -- but not the salivary glands -- and tumors of the digestive system. Only GI tumors that occurred 5 years or more after primary cancer diagnosis were included in this analysis.
The incidence rate of GI neoplasms in the study cohort was compared with that of the general population using the federal Surveillance Epidemiology and End Results (SEER) database.
Among the nearly 15,000 childhood cancer survivors, there were 802 subsequent malignant neoplasms found in 732 people. Of those cancers, 45 (5.6%) were identified as GI cancers, occurring in 45 people at a median follow-up of 22.8 years from primary diagnosis. The median age at subsequent cancer diagnosis was 35.5.
Survivors of Wilms tumor, Hodgkins lymphoma, and bone and brain tumors faced a higher risk for GI secondary cancer versus the general population.
Many of the subsequent tumors (80%) occurred nearly a quarter of a century after the primary cancer. The most frequent site for the subsequent cancer was the colon, and 56% were adenocarcinomas.
The authors noted that GI secondary cancers appeared in survivors as young as 9 years old, and all observed cases happened before age 45. Among the 45 patients, 23 were deceased and 56% of them died of GI subsequent neoplasms.
Among the childhood cancer survivors who developed GI secondary neoplasms, 87% had received radiation therapy for their primary disease, and 82% developed subsequent disease in or near the radiation field.
After abdominal radiation, exposure to high-dose procarbazine (Matulane) and platinum were independently associated with an increased risk for GI secondary malignant neoplasms in the radiation field, which suggests that these agents may increase the carcinogenic effects of radiotherapy.
The study had some limitations. The total number of observed GI secondary neoplasms was small so the authors could not examine the effects of race, geography, or other demographics on risk levels. Also, the CCSS relies on self-reporting of secondary disease as well as family history, which may lead to underestimation or inaccuracies.
Finally, the authors could not identify risks for early GI secondary neoplasms because the data was limited to those that occurred 5 or more years after primary diagnosis.
However, they pointed out that while abdominal radiotherapy did increase the risk for secondary neoplasms, they still saw cases – colon cancer in particular – occurring outside of the radiation field and in patients who had no radiation at all.
"If the findings of this study are confirmed, physicians should also consider chemotherapy exposures when determining the indications for early colorectal cancer surveillance in childhood cancer survivors," they concluded.
Disclosures
This study was funded by the National Cancer Institute (NCI). Additional grants came from the Intramural Research Program of the National Institutes of Health and NCI, and by the American Lebanese-Syrian Associated Charities.
Disclosure information was not available.
Primary Source
Annals of Internal Medicine
Henderson T, et al "Secondary gastrointestinal cancer in childhood cancer survivors: A cohort study" Ann Intern Med 2012; 156: 757-766.