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High risk of second cancers in survivors of childhood soft tissue sarcomas


Children treated for soft tissue sarcomas have a significantly higher risk of developing subsequent cancers later in life, according to a new study. The study appears in the June 1, 2005 issue of CANCER (, a peer-reviewed journal of the American Cancer Society, and indicates children treated with combined chemotherapy and radiation therapy, in particular, had greater risks of developing a new malignancy.

With improvements in cancer treatments over the last two decades, children with soft tissue sarcomas are living longer. Several investigations have reported that these children have an increased risk of second cancer, but estimates of the risk have varied widely, ranging from three to thirteen times the risk among the general population. Moreover, due to the small size of many previous studies, few have evaluated risk by type of soft tissue sarcoma or have estimated risks for specific second cancers.

Randi J. Cohen, M.S. and a team of researchers from the National Cancer Institute (NCI) evaluated data from 1499 children included in one of the largest, most comprehensive cancer databases in the U.S., called the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. Their goal was to quantify the risk of developing a second malignancy in soft tissue sarcoma patients by second cancer site, initial therapy, histologic type of the primary sarcoma, age at primary cancer diagnosis, and gender.

The investigators found that survivors of pediatric soft tissue sarcomas had a six-fold increased risk of developing a second cancer, as compared to the general population. However, the authors noted that while the relative risk appears high, the absolute risk is quite low. The NCI study found that approximately 3 percent of children with soft tissue sarcoma would be expected to develop a second malignancy by 20 years after their initial diagnosis. The relative risk was highest within the first five years of post-treatment follow-up. Females had slightly higher risks of second cancers than males; however, when gender-specific cancers of the breast and genital tract were excluded, the risks were identical.

Cohen et al. also found that second cancer risks were increased for all subtypes of childhood soft tissue sarcoma, with estimates ranging from 6-fold elevations in risk for fibromatous neoplasms to nearly 8-fold risks for rhabdomyosarcoma. Children initially treated with radiation or those with radiation combined with chemotherapy had substantially higher risks of second cancers than those treated with surgery alone.

Previous studies have reported increased risks of acute myelogenous leukemia following treatment of children with soft tissue sarcoma, particularly in those receiving chemotherapy for rhabdomyosarcoma. In addition, both clinical and registry-based surveys have reported that these children have an increased risk of second bone or soft tissue sarcoma, many of which were related to high dose radiation and chemotherapy or, in some cases, to genetic predisposition. In the current NCI study, the research team confirmed the excess of subsequent leukemia and sarcomas, but also found an increased risk of melanoma and cancers of the breast and oral cavity, although the results were based on small numbers. For several children the pattern of multiple cancers including soft tissue sarcomas was consistent with underlying genetic syndromes, particularly Li-Fraumeni syndrome and neurofibromatosis type 1.

The authors concluded, "both treatment effects and genetic factors contributed to the increased risk of second cancers in this series of children with soft tissue sarcomas."

David Greenberg | EurekAlert!
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