New malignancies following childhood cancer in the United States, 1973–2002

Abstract

The objectives of our study were to quantify risks for developing new malignancies among childhood cancer survivors, identify links between particular types of first and subsequent cancer, and evaluate the possible role of treatment. A cohort of 25,965 2-month survivors of childhood cancer diagnosed in the U.S. during 1973-2002 was identified and followed through SEER cancer registries. Observed-to-expected ratios (O/E) were calculated, and Poisson regression was used to compare risks among treatment groups. Childhood cancer survivors were at nearly 6-fold risk of developing a new cancer relative to the general population (O/E 5 5.9, 95% CI: 5.4-6.5). Most common were subsequent primary cancers of the female breast, central nervous system, bone, thyroid gland and soft tissue, as well as cutaneous melanoma and acute non-lymphocytic leukemia (ANLL). The greatest risks of subsequent cancers occurred among patients diagnosed previously with Hodgkin lymphoma (HL), Ewing sarcoma, primitive neuroectodermal tumor, or retinoblastoma. Risk of subsequent solid cancers was higher among persons whose initial treatment for childhood cancer included radiotherapy, whereas the excess of subsequent ANLL was strongly related to chemotherapy. The O/E for subsequent ANLL increased with increasing calendar year of initial cancer diagnosis among survivors of cancers other than HL, most likely due to increasing use of leukemogenic drugs for solid cancers and nonHodgkin lymphoma. Childhood cancer survivors are at markedly increased risk of developing a variety of new cancers relative to the general population, but the magnitude of excess risk and specific types of second cancer vary widely by type of first cancer. ' 2007 Wiley-Liss, Inc.Key words: second cancers; multiple primary cancers; childhood cancer; epidemiology; surveillance, epidemiology and end results (SEER) registriesThe dramatic advances that have been made in the treatment of childhood cancer over the past several decades have created a large and growing population of long-term survivors.1 Although many childhood cancers now can be cured, the aggressive therapies used are associated with increased risks of a variety of adverse health effects, including new primary cancers.2-7 Opportunities for addressing second cancer risks in large populations of childhood cancer survivors followed over many years are uncommon. Rarely can individual medical centers achieve adequate sample sizes or follow-up, necessitating costly multicenter studies or the use of large, population-based cancer registries. Populationbased studies have advantages over most clinic-based studies in that study populations are unaffected by referral patterns, and completeness of follow-up is less likely to be related to the occurrence of a new cancer. We used data from the National Cancer Institute's Surveillance, Epidemiology and End-Results (SEER) population-based cancer registry in the U.S. to assess the risk of new primary cancers among persons diagnosed with childhood cancer between 1973 and 2002. Material ...

Secondary hematopoietic malignancies in survivors of childhood cancer

“…In this cohort, survivors of lymphomas most frequently developed secondary AML, as also shown by Kaldor et al 20 The relative risk of secondary AML increases 1 to 5 years after therapy for primary cancer, remains elevated through the first 15 years of follow-up, and increases with increasing calendar year for the latency interval between 1 and 5 years. 1 The 5-year survival of secondary AML patients in our cohort was 18% AE 5.3% (P ¼ .044), consistent with earlier reports.…”

“…1 Among solid tumors survivors, those with ESFT had the highest excess risk of developing a secondary hematological malignancy, consistent with previous reports.…”

“…Thus, it is essential to study the host-, environment-, and treatment-related factors predisposing this growing population of survivors to the development of secondary malignancies. 1,2 Secondary hematological malignancies are among the most common types of secondary malignancies that are frequently associated with serious long-term consequences and poor outcome. 3,4 One example of treatment-related secondary hematological malignancy is the monoblastic or myelomonocytic subtype that develops after a short median latency period after the use of topoisomerase II inhibitors.…”

Oncology protocols: how can we do better?

“…The risk associated with exposure to ionizing radiation from medical imaging in the general pediatric population is compounded by the notable fact that childhood cancer survivors bear an additional 6-fold increased risk of developing a second cancer when compared to the general population. For those children who also received radiotherapy for their cancers, the 5-year risk for an additional cancer rises to 8-fold increased risk [5,6]. Further, because of their genetic makeup, a selected pediatric population is further predisposed to cancer-related syndromes and to second malignancies.…”

“…Monitoring for recurrent disease and for development of second malignancies is ongoing for several years after treatment completion [6,14,15]. These regimens are typically tailored to salvage rates of relapse disease but vary widely among institutions and cooperative groups.…”