Subsequent Malignant Neoplasms in Retinoblastoma Survivors

Abstract

Retinoblastoma (Rb) is a pediatric malignant eye tumor. Subsequent malignant neoplasms (SMNs) and trilateral Rb (TRb) are the leading cause of death in heritable Rb patients in developed countries. The high rate of SMNs in heritable Rb patients is attributed to the presence of a mutation in the RB1 tumor suppressor gene. In addition, Rb therapy choices also influence SMN incidence in this patient group. The incidence rates and age of occurrence for the most frequent SMNs and TRb will be discussed. In addition, the impact of genetic predisposition and Rb treatments on the development of SMNs will be evaluated. Furthermore, screening and other prevention methods will be reviewed.

Keywords: heritable Rb; long-term surveillance; retinoblastoma; second primary malignancies; subsequent malignant neoplasms; trilateral Rb.

Figure 1

Use of specific Rb therapies over calendar time. Rb therapy changed over time. The relative use of specific Rb therapies (enucleation, radiotherapy, systemic chemotherapy and targeted chemotherapy) over calendar time is shown [7,16,27,29,30,31,32,34,35,36,37]. The scale bar indicates relative use (light grey = low and black=high). IVitC = intra-vitreal chemotherapy, IAC = intra-arterial chemotherapy, IVC = intravenous chemotherapy.

Figure 2

Factors that influence SMN reporting. A range of factors such as Rb study population, calendar period of Rb diagnosis, differential definitions for the same concepts and differences in therapy influence reported risks and incidences in SMN reports. Rb study populations have differential follow-up (f/u) can be either population-based or Rb treatment center-based with a different mix of heritable (her) and non-her Rb survivors. Also, different treatment centers might have slight preferences for certain therapies. Differences in therapy are also influenced by socioeconomic status in the country of treatment and cultural preferences of patients.

Figure 3

Division of SMN subtypes in Rb survivors and age at onset of SMNs and TRb. Data from the Woo and Harbour review has been adapted; (benign tumors and PNETs have been excluded) to create the pie charts and box plots for depicting the division of specific SMNs in Rb survivors. (a) Pie charts of the different SMN types (left) and the sarcoma SMN subtype (right) are shown. (b) Box plots of age at onset of diagnosis of SMN subtypes sarcoma, carcinoma, melanoma, leukemia/lymphoma and CNS tumors are shown. The boxes depict the interquartile range and the middle line represents the median. Furthermore, a line extends from the 10th to 90th percentile of values; excluding “outside” values. CNS = central nervous system. (c) Trilateral Rb locations and age at onset are adapted from de Jong and colleagues [3].

Figure 4

Long-term follow-up in heritable Rb survivors. A panel of providers from over the world recently assessed risk evidence and surveillance recommendations for heritable Rb [4]. This figure shows an adapted Table 1 from Tonorezos and colleagues [4] with (a) risk evidence (b) surveillance recommendations.