Second primary tumors in hereditary retinoblastoma: a register-based study, 1945–1997

Genes and environment: effects on the development of second malignancies in retinoblastoma survivors

“…A subsequent retrospective study of a similar large population of both unilateral and bilateral hereditary retinoblastoma patients performed in The Netherlands confirmed an increased risk of development of second malignancies in patients treated with external-beam radiation before the age of 12 months [3]. However, the major discrepancy in the findings of this study compared with that of our group was that The Netherlands cohort developed similar numbers of second malignancies inside and outside the field of radiation.…”

“…The increased risk of second malignancies conferred by radiation in this patient population is well established in epidemiologic studies (FlGURE 1) [3,6,20]. Long-term follow-up indicates that the risk of a second malignancy in patients with the germinal mutation who underwent radiation is 3.…”

“…Treatment approaches for retinoblastoma in developed countries are now so effective that in the USA, Europe, and developed countries throughout the world, the leading cause of death among retinoblastoma survivors is not retinoblastoma itself, but second malignancies [1]. The incidence of second malignancies in survivors of retinoblastoma who carry the rb1 mutation has been reviewed extensively [1][2][3][4][5][6][7][8][9][10][11][12][13]. Cumulative incidence reports of second malignancies have varied, at least in part because of the wide range in design and population size of these reports.…”

“…Cumulative incidence reports of second malignancies have varied, at least in part because of the wide range in design and population size of these reports. Most large studies with adequate long-term follow-up have reported incidence rates of approximately 0.5-1 % per year when a constant risk of cancer development per year of survival is calculated based on reported cumulative risk rates [1,3,7,10,14]. The study with †…”

“…We and others have observed several rare cases in which these tumors present prior to the presentation of the ocular disease and for this reason, there has been some controversy as to whether to these tumors should be considered second malignancies or a variant of the primary tumor [3]. There are several clinical characteristics that seem anecdotally to be more common in patients with these tumors, representing markers for particularly devastating rb1 mutations that may be more likely to confer a risk for the development of the second malignancy.…”