Hereditary retinoblastoma survivors face second ca risk

ABSTRACT: Cause-specific mortality was examined in one-year survivors of retinoblastoma. Germ line mutations tend to persist.

NIAGARA-ON-THE-LAKE, Canada- Retinoblastoma is a rare form of pediatric cancer, affecting approximately 300 new patients in the United States each year. The two variants of this cancer, hereditary and nonhereditary, have excellent survival rates, but there is a tremendous risk of secondary malignant cancers in those with the hereditary form, especially if they are treated with radiotherapy.

“Patients with the hereditary form of retinoblastoma have a germ line mutation in their RB1 gene on chromosome 13. Thus, while they can be treated to eliminate the primary cancer, they remain at risk for bone and soft tissue sarcomas, melanoma, and cancers of the brain and lung,” explained Chu-Ling Yu, ScD. “We have come to realize that at this point, these survivors’ risk of secondary cancer remains elevated throughout their lives, even in those patients who have survived their primary cancer for 40 years.”

Dr. Yu is from the Radiation Epidemiology Branch in the Division of Cancer Epidemiology and Genetics at NCI. She spoke at the 2008 International Conference on the Long-Term Complications of Treatment of Children and Adolescents for Cancer. The meeting was sponsored by Roswell Park Cancer Institute and the National Cancer Institutes.

Led by senior researcher Ruth A. Kleinerman, MPH, Dr. Yu and her colleagues examined cause-specific mortality in 1,854 one-year survivors of retinoblastoma (1,092 hereditary and 762 nonhereditary) who were diagnosed between 1914 and 1996 at medical centers in New York and Boston.

Standardized mortality ratios were calculated using U.S. mortality data to estimate expected numbers. Cause-specific cumulative mortality was calculated by treating other causes of death as competing risks.

“We found that 151 hereditary patients died of secondary cancer, compared to 12 nonhereditary patients, and that the risk for a secondary remained significantly elevated beyond 40 years among hereditary patients,” Dr. Yu said.

Different cancers were identified at different ages. Excess mortality from sarcomas, melanoma, and brain cancers was seen in the earlier years, compared to later years when lung cancer and uterine sarcomas appeared.

“Patients with the hereditary form of retinoblastoma are at increased risk of second cancers throughout their lives,” Dr. Yu concluded. The team will continue to follow these patients and monitor them for risk of second cancers, she said.

Daniel Green, MD, of the department of epidemiology and cancer control at St. Jude Children’s Research Hospital in Memphis, said he hopes that these data will encourage both survivors and their primary care providers to “focus on close surveillance in this population of patients. There is still no good intervention to prevent these secondary cancers,” he said.