Childhood cancer survivors at increased risk for subsequent gastrointestinal and genitourinary neoplasms

Article Outline

• Question
• Design
• Setting
• Participants
• Intervention
• Outcomes
• Main Results
• Conclusions
• Commentary
• References
• Copyright

Reulen RC, Frobisher C, Winter DL, Kelly J, Lancashire ER, Stiller CA, et al. Long-term Risks of Subsequent Primary Neoplasms Among Survivors of Childhood Cancer. JAMA 2011;305:2311-9.

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Question 

Among survivors of childhood cancer, what is the long-term risk of developing subsequent primary neoplasms?

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Design 

Population-based cohort study.

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Setting 

Great Britain.

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Participants 

17 981 5-year survivors of childhood cancer diagnosed with cancer at younger than 15 years between 1940 and 1991 who are participating in the British Childhood Cancer Survivor Study. Median follow-up time was 24.3 years through December 2006.

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Intervention 

Subsequent primary neoplasms were identified through the National Health Service Central Registers.

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Outcomes 

Standardized incidence ratios (SIRs), absolute excess risks (AERs), and cumulative incidence of subsequent primary neoplasms.

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Main Results 

Among this cohort, 1354 subsequent primary neoplasms were ascertained; the most frequently observed being central nervous system (n=344), nonmelanoma skin cancer (n=278), digestive (n=105), genitourinary (n=100), breast (n=97), and bone (n=94). The overall SIR was 4 times more than expected (SIR, 3.9; 95% CI, 3.6-4.2; AER, 16.8 per 10 000 person-years). The AER at older than 40 years was highest for digestive and genitourinary subsequent primary neoplasms (AER, 5.9 [95% CI, 2.5-9.3]; and AER, 6.0 [95%CI, 2.3-9.6] per 10 000 person-years, respectively); 36% of the total AER was attributable to these 2 subsequent primary neoplasm sites. The cumulative incidence of colorectal cancer for survivors treated with direct abdominopelvic irradiation was 1.4% (95% CI, 0.7%-2.6%) by age 50 years, comparable with the 1.2% risk in individuals with at least 2 first-degree relatives affected by colorectal cancer.

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Conclusions 

Among a cohort of British childhood cancer survivors, the greatest excess risk associated with subsequent primary neoplasms at older than 40 years was for digestive and genitourinary neoplasms.

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Commentary 

More than 30 years ago, it was recognized that treatment effective in producing cure for children with cancer could also be responsible for initiating second cancers in survivors, especially as radiation was a well-known carcinogen. Pediatric oncologists have since learned to successfully limit radiation. This report from the British Childhood Cancer Survivor Study (CCSS) provides an extensive analysis of their data on second cancers focusing on the elevated risks for gastrointestinal and genitourinary cancers in older adult survivors. It is important to consider how these new data add to our knowledge and how they differ from the cancer risks reported from the North American¹ cohort. Also important is how this information can inform best clinical practice. Both groups have accrued large 5-year survivor cohorts (now 14 000 in North America and almost 18 000 in Britain), and have followed them for 23 and 24 years, respectively after the diagnosis of cancer (when less than 15 years or 21 years of age from 1970-1986 or 1940-1991). Both groups estimate that as childhood cancer survivors age they will develop cancer 4 to 6 times more often than age-matched individuals in the general population; radiation therapy appears to be significantly responsible for this increase. Several major differences in the studies are worth noting. The British study includes survivors of retinoblastoma, both heritable and non-heritable, providing a strong baseline for studies of second cancers in children with retinoblastoma treated with chemotherapy since 1995. In addition, the British data are population-based, and those from North America are not (and therefore subject to ascertainment bias). However, the risk estimates are less important than the implication for follow-up care and surveillance, especially with regard to the risk of colon cancer. Early diagnosis of colon cancer is essential for the success of curative surgery. Guidelines for colonoscopy have been published in the US ² but they have not been adopted in Britain. If they are adopted in Britain, all survivors would be eligible for this life-saving and cost-saving procedure. This is not true in the US, where young adults are more frequently uninsured and very often do not avail themselves of the care recommended. The authors of both reports also have collected detailed information on therapy; this will enable them to refine the estimates of subsequent morbidity, such as that affecting the heart and other vital organs, fertility and offspring, and psychosocial adjustment. We look forward to the results of those analyses. It also will be important to monitor the effectiveness of the recommended guidelines and to study other aspects of long-term survival. Which survivors need what specific care and where should they receive it?

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References 

1. Friedman DL, Whitton J, Leisenring W, Mertens AC, Hammond S, Stovall M, et al. Subsequent neoplasms in 5-year survivors of childhood cancer: The Childhood Cancer Survivor Study. J Natl Cancer Inst. 2010;102:1083–1095
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   • CrossRef
2. Children's Oncology Group. Long term follow-up guidelines for survivors of childhood, adolescent and young adult cancers. Version 3.0. Arcadia, CA: Children's Oncology Group; 2008. http://www.survivorshipguidelines.org.
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