Figure 1.

Cumulative incidence of second cancers. Because the age at second cancer is a censored observation, we used survival analysis to estimate the rate of SMN diagnosis in each of the groups and analyze any associations with presence of a non-RB1 variant. The cumulative incidence of SMN in the overall study population is presented in Figure 1. The cumulative incidence of SMN was 48% at 15 years in the hereditary group versus 0% in the non-hereditary group, although the difference was not statistically significant (P = .07). Likewise, there was no evidence of a significant difference in the time to second cancer between patients with and without non-RB1 variants in the overall study population nor within the subgroup of patients with hereditary disease. Tick marks represent censoring times. The subgroup of patients with non-hereditary disease was not analyzed because of the small number of second cancers in that group. Time to SMN was defined as the time from the age at RB diagnosis to the age at the first SMN diagnosis. Patients without SMN diagnoses were censored at the current age. Deaths before the occurrence of SMN were treated as competing risks. The cumulative incidence of SMN was estimated using an Aalen-Johansen estimator,¹³ and the curves were compared using a Gray’s test.¹⁴ Analyses were done using R v.3.6.3.