EDITORIALS For Whom the Bell Tolls: Susceptibility to Common Adult Cancers in Retinoblastoma Survivors

A priority in the management of patients with potentially curable or indolent cancers is to maximize tumor control while minimizing the iatrogenic complications that may occur many years later. A balance between these short-term and long-term goals can sometimes be elusive, as seen in the ongoing contro- versy over the role of external beam radiation therapy (EBRT) in the initial treatment of patients with early-stage Hodgkin's dis- ease (1). In the case of hereditary retinoblastoma, where more patients in the United States die of second primary cancers (many induced by EBRT) than from their initial eye tumor (2), the treatment for intraocular disease has recently undergone dramatic changes to minimize the delayed tumorigenic potential of EBRT. These changes focus on the substitution of EBRT with chemotherapy, followed by local consolidative modalities such as laser hyperthermia and cryotherapy. However, some patients are not responsive to chemotherapy and may still require EBRT in an attempt to avoid enucleation and blindness. In addition, there is increasing recognition that hereditary retinoblastoma patients who have never received EBRT also have an increased risk of second primary cancers (3). Therefore, a thorough un- derstanding of treatment-related cancer incidence and mortality in retinoblastoma survivors is essential for the counseling of patients and their families. To understand the risk estimates in retinoblastoma survivors, it is worth making several observations. First, an increased risk for second cancers has been substantiated only for retinoblas- toma patients who carry a constitutive RB1 mutation (2). It