Childhood Cancer Survivors Face Cancer Again in Middle Age

Fran Lowry

June 06, 2011

June 6, 2011 — Childhood cancer survivors are at increased risk of developing a subsequent primary tumor when they are in their 40s and older, although the absolute excess risks (AERs) of such an occurrence are generally small, according to a study published online June 6, to coincide with the American Society of Clinical Oncology (ASCO) 2011 Annual Meeting, and in the June 8 print issue of JAMA.

"Survivors of childhood cancer are at increased risk of developing subsequent primary neoplasms with the risk being estimated at 3- to 6-fold that expected," write Raoul C. Reulen, PhD, from the University of Birmingham, Edgbaston, United Kingdom, and colleagues for the British Childhood Cancer Survivor Study Steering Group. "However, the magnitude of the long-term risks of developing a subsequent primary neoplasm, in particular beyond ages at which the background cancer incidence in the general population starts to increase substantially, are unknown."

The aims of this study were to investigate the long-term risks for subsequent primary tumors in a population-based cohort of childhood cancer survivors, to identify the types of cancers that contribute most to long-term excess risk, and to identify subgroups of survivors who may be at particularly high risk, and thus in need of specific interventions.

The British Childhood Cancer Survivor Study included 17,981 5-year survivors of childhood cancer who were diagnosed at age younger than 15 years between 1940 and 1991 in Great Britain, and who were followed up through December 2006.

The study found that 1354 subsequent primary tumors were diagnosed in 1222 of the survivors. The median follow-up was 24.3 years, and the mean was 25.6 years.

The most frequently observed subsequent primary tumors were central nervous system tumors (n = 344), of which 105 were gliomas; nonmelanoma skin cancer (n = 278); digestive cancer (n = 105); genitourinary cancer (n = 100); breast cancer (n = 97); and bone cancer (n = 94).

Survivors were 4 times more likely to develop a subsequent primary neoplasm than expected (standardized incidence ratio, 3.9; 95% confidence interval [CI], 3.6 - 4.2; AER, 16.8 per 10,000 person-years).

In addition, the study found that beyond age 40 years, the AER was highest for digestive (AER, 5.9 per 10,000 person years; 95% CI, 2.5 - 9.3 per 10,000 person years) and genitourinary (AER, 6.0 per 10,000 person years; 95% CI, 2.3 - 9.6 per 10,000 person years) subsequent primary tumors. In fact, these 2 tumor sites accounted for 36% of the total AER, the authors report.

Overall, 52% of the total AER was attributable to digestive, genitourinary, breast, or respiratory sites at age older than 40 years.

The researchers found that the cumulative percentage of survivors developing a subsequent primary tumor increased steadily with age, from 1.6% at age 20 years to 13.8% at age 60 years, whereas 8.4% was expected at age 60 years, based on rates from the general population. They also found that 5% of survivors had developed a subsequent primary tumor by age 38 years, whereas it took until age 54 years for 5% of a comparable cohort, based on general population rates, to develop a cancer.

The cumulative incidence of developing colorectal cancer by age 50 years was 1.4% (95% CI, 0.7% - 2.6%) for survivors treated with direct abdominopelvic irradiation — a risk comparable to that in individuals with at least 2 first-degree relatives with colorectal cancer.

"Given the excesses observed among those older than 40 years, these survivors should be encouraged to participate in existing general population screening programs," the authors write.

Study limitations include the lack of detailed data on radiotherapy and chemotherapy exposures and the fact that the cohort were treated between 1940 and 1991, which may make it difficult to translate the study findings to survivors treated more recently.

"Efforts to reduce the absolute number of survivors developing a subsequent primary neoplasm should...focus on digestive and genitourinary subsequent primary neoplasms," the authors conclude.

They also suggest that childhood cancer survivors who received direct abdominopelvic irradiation be considered for routine colonoscopy to screen for colorectal cancer.

The study was supported by Cancer Research UK and Kay Kendall Leukaemia Fund. The Childhood Cancer Research Group receives support from the Department of Health and the Scottish Ministers. The authors have disclosed no relevant financial relationships.

JAMA. 2011;305:2311-2319. Published online June 6, 2011. Abstract