MORTALITY FROM 2ND TUMORS AMONG LONG-TERM SURVIVORS OF RETINOBLASTOMA

Background: Children diagnosed with retinoblastoma, a rare cancer of t he eye, tend to develop and die of second primary cancers in childhood and adolescence, but few investigations have followed patients into a dulthood. Retinoblastoma is frequently caused by inherited mutations o f the RB1 tumor suppressor gene. Most patients with germline (heredita ry) mutations have bilateral disease. Purpose: We sought to quantify t he mortality from second malignancies among long-term survivors of ret inoblastoma and to identify factors that predispose to these deaths. M ethods: A retrospective cohort study examined mortality among 1603 pat ients enrolled at 1 year after diagnosis of retinoblastoma during the period 1914-1984. Data on demography, family history, and retinoblasto ma treatment were collected by medical chart review and questionnaire interview. Number of deaths, by cause, was compared with the correspon ding expected figure based on U.S. mortality data for the general popu lation for 1925-1990. Results: Follow-up was complete for 1458 patient s (91%) for a median of 17 years after retinoblastoma diagnosis. A tot al of 305 deaths occurred, 167 of them from retinoblastoma. There were 96 deaths from second primary tumors (relative risk [RR] = 30), 21 fr om other known causes (RR = 1.0), and 21 from ill-defined or unknown c auses. Statistically significant excess mortality was found for second primary cancers of bone, connective tissue, and malignant melanoma an d benign and malignant neoplasms of brain and meninges. Among 919 chil dren with bilateral retinoblastoma, 90 deaths from second primary tumo rs occurred (RR = 60). Deaths from second tumors were more frequent am ong females (RR = 39) than males (RR = 22) (P = .007). The cumulative probability of death from second primary neoplasms was 26% at 40 years after bilateral retinoblastoma diagnosis, and additional cancer death s occurred thereafter. Radiotherapy for retinoblastoma further increas ed the risk of mortality from second neoplasms. An excess of mortality from a second cancer, not seen in prior studies, was found among the 684 children with unilateral disease (RR = 3.1; 95% confidence interva l = 1.0-7.3). Conclusions: These findings implicate germinal mutations in the retinoblastoma gene in second cancer mortality. Radiotherapy t reatment for retinoblastoma appears to further enhance the inborn susc eptibility to development of a second cancer. Implications: Patients w ith retinoblastoma, particularly bilateral retinoblastoma, should have careful follow-up, and interventions should be developed to reduce mo rtality from a second cancer.