Childhood Cancer Survivors Face Risk of 2nd Malignancy

NEW ORLEANS—Pediatric cancer survivors face an increased risk of second malignancies later in life, especially breast cancer, according to a large database of some 14,000 persons diagnosed with cancer before age 21 and alive 5 years or longer.

About one out of 1,000 persons 20 to 30 years old is a survivor of childhood cancer. More than two thirds of childhood cancers are being cured, resulting in long-term survivorship with unknown consequences, said Joseph Neglia, MD, associate professor of pediatrics, University of Minnesota, Minneapolis.

The study, presented at the 92^nd Annual Meeting of the American Association for Cancer Research, is one of the largest retrospective studies to focus on the risk of second malignancies in persons successfully treated for cancer as children. The database comes from 25 centers in the United States and Canada.

The study found 314 invasive cancers among 298 individuals. The most common form of newly diagnosed cancer was breast cancer, accounting for 60 of the new cases, followed by thyroid cancer (43) and brain tumors (36).

These figures amount to a sixfold increase in the incidence of new cancers over what would be expected in the general population, Dr. Neglia reported.

For breast cancer, however, the increase was 16-fold. Contrary to current belief, there was no association between age at treatment and risk. Prepubertal and teenaged girls who were treated with chest irradiation were at higher risk for breast cancer than has been commonly believed, as previous studies found an elevated risk only among girls who had already reached puberty when treated for cancer.

While the sixfold risk for second cancers seems high, Dr. Neglia pointed out that this translates into only 1.8 excess cases of cancer per 1,000 years of follow-up. "If you follow 100 people for 10 years, fewer than two new cancers occur. In other words, people treated for cancer as children are at increased risk for second cancers, though this risk is very small in contrast with the remarkable benefits of their cancer therapy," he stressed.

The highest risk occurred in patients treated for Hodgkin’s disease, particularly with radiotherapy; however, this amounted to only about five excess cancers per 1,000 years of follow-up. Further, he said, since aggressive radiotherapy is no longer standard for Hodgkin’s disease, children treated today presumably have a lower risk of second malignancies than was seen in this study.

Dr. Neglia suggested that childhood cancer survivors require greater surveillance and should be engaged in discussions with their physicians about their possible risks. For instance, women treated with irradiation as children should consider beginning mammography screening as early as their 20s, he said.

Oncologists need to modify treatment regimens to reduce patients’ risk for second cancers without compromising efficacy, he further suggested. Many pediatric oncology centers are already reducing the use of certain chemotherapeutic agents known to increase secondary cancer risk, and new methodologies for reducing irradiation are being employed.

Marriage Study

A related report, from the Childhood Cancer Survivor Study, found that survivors of central nervous system (CNS) malignancies, particularly males, were less likely to marry than survivors of other cancer diagnoses or the general US population. The study included 1,477 subjects, who were found to have a fourfold increased likelihood of never marrying.

The type of treatment was significantly associated with the odds of marrying, especially among males, said Amanda M. Rauck, MD, of Columbus Children’s Hospital, Ohio State University.

Surgery alone, surgery plus irradiation, and surgery plus irradiation and chemotherapy accounted for 98% of the treatment of these patients. Only 7.5% of the CNS tumor survivors receiving the trimodality therapy reported having married (4% of males and 12% of females), compared with 36% of those treated surgically (26% of males and 48% of females) and 25% of those treated with surgery and irradiation (20% of males and 30% of females).

More females than males in each group reported getting married (P = .0001), and age at diagnosis was not associated with marital status, Dr. Rauck said.