Second Malignancies in Retinoblastoma: The Real Problem

Retinoblastoma accounts for 6% of pediatric malignancies under the age of 5 years in the United States, (Broaddus et al., 2008) and epidemiological data suggest that the incidence is standard across populations (Kivelä, 2009). Despite its rarity, observations about the pathogenesis of this disease have enhanced our understanding of genetic cancer syndromes. Germinal or hereditary cases comprise approximately 40% of retinoblastoma cases, and all patients with the germinal RB1 mutation are at risk for secondary malignancies. According to recent reports, some retinoblastoma patients exhibit varying degrees of mosaicism for the RB1 mutation, allowing them to develop second primary malignancies in addition to those with standard hereditary retinoblastoma. These cancers occur in various anatomic locations such as the skull and long bones, soft tissues, skin, nasal cavity, brain, lung, and breast. The pattern of development and risk for these tumors are heavily influenced by the methods of treatment for retinoblastoma, which have shifted from enucleation to external-beam radiation to systemic chemotherapy with focal treatments. Investigations of the benefits of intra-arterial chemotherapy are ongoing with the hopes of reducing the morbidities associated with systemic therapy. Due to these improving treatment techniques, 10-year survival rates of primary retinoblastoma have been among the highest of all childhood cancers at greater than 92% in the United States and other developed countries since 1975 (Kaatsch, 2010; Linabery & Ross, 2008). Secondary malignancies have thus become an increasingly significant topic of interest as they are the leading cause of death of germinal retinoblastoma survivors in the United States.