Second primary tumors in patients with hereditary retinoblastoma: A register-based follow-up study, 1945–1994

Abstract

The aim of this register-based follow-up study was to evaluate the long-term cumulative incidence of second primary tumors (SPT) among survivors of hereditary retinoblastoma, with special interest for the incidence of pineoblastoma in retinoblastoma patients born after 1970. The Dutch Retinoblastoma Register was completed and updated: in the period 1945-1994, 639 retinoblastoma patients were registered. The vital status of each patient was obtained from the municipal registries and the Central Office of Genealogy. SPT were traced and histopathologically confirmed. Survival curves and cumulative incidence of SPT were calculated by the Kaplan-Meier method. The survival of patients with hereditary retinoblastoma was significantly shorter than that of patients with non-hereditary retinoblastoma. The cumulative incidence of SPT in hereditary patients was 3.7 and 17.7% at the ages of I0 and 35 years, respectively.Long-term follow-up revealed a high proportion of melanomas (7 melanomas out of 28 SPT). In the sub-cohort of the hereditaryretinoblastoma patient group born after 1970, the cumulative incidence of pineoblastomas at the age of 5 years was 9.3%. Our results suggest that patients with hereditary retinoblastoma should have careful follow-up, and procedures for diagnosing SPT and pineoblastomas at an early and potentially treatable stage should be developed.o 1996 Wiley-Lin, OK. Retinoblastoma is a rare pediatric eye tumor which occurs in both a hereditary and a non-hereditary form. An estimated 30 to 40% of retinoblastomas are hereditary (Vogel, 1979). In some o f the hereditary cases, deletion of chromosome 13q14 was shown to be present in all cells of the body (Knudson etaf., 1976). All bilateral (familial and/or sporadic) cases and the familial unilateral cases can be considered to be hereditary. In familial cases, the patient inherits the retinoblastoma mutation from a parent, and, in sporadic bilateral cases, from a healthy parent in whom a fresh germinal mutation has occured. In the non-hereditary patients (60-70% of all cases), including all sporadic unilateral cases, the tumors are thought to arise as a consequence of somatic mutation in the embryonic retinal cells during fetal life (Vogel, 1979).Although the cure rate of retinoblastoma is excellent after enucleat ion or irradiation, the likelihood of long-term survival in the hereditarygroup is reduced because of the occurrence of second primary tumors (SPT) years after treatment; nonhereditary-retinoblastoma patients do not seem to be at risk for SPT (Draper et al., 1986;DerKinderen et al., 1988;Eng et al., 1993). SPT may appear inside or outside the radiation field (Abramson er al., 1984; DerKinderen et al., 19SQ and adjuvant chemotherapy may enhance their frequency (Draper et al., 1986). Reports on the cumulative incidence of SPT in retinoblastoma are conflicting, ranging from 8.4% 18 years after diagnosis (Draper et al., 1986) to 90% after 30 years (Abramson et al., 1984). In order to resolve this conflict, we instituted an in-depth, retrospective...

High parental age is associated with sporadic hereditary retinoblastoma: the Dutch retinoblastoma register 1862-1994

“…The national retinoblastoma register of the Netherlands (Schappert- Kimmijser et al 1966;DerKinderen 1987) was used. For our study, the register has recently been updated and the data verified (Moll et al 1995). We extracted the date of birth of the 941 registered Dutch retinoblastoma patients born during the period from 1862 to 1994 and, if available, the date of birth of their parents.…”

Familial and genetic risk of transitional cell carcinoma of the urinary tract

“…[65] The elevated risk of second primary bladder cancer among retinoblastoma survivors has been attributed to radiation treatment or cyclophosphamide chemotherapy [66][67][68]. However, Fletcher et al, found that hereditary retinoblastoma survivors who were not exposed to highdose radiation or chemotherapy had a substantially higher mortality from bladder cancer versus the general population (standardized mortality ratio [SMR] = 26.3; 95%, CI 8.5-61.4).…”

Diagnosis and Management of Retinoblastoma

“…[58][59][60] The 30-year cumulative incidence for second cancers in bilateral retinoblastoma has been reported at 35% for patients who received radiation therapy compared with 6% for those who did not receive radiation. 59 Abramson and Frank 61 found that external beam radiotherapy increased the incidence of second cancers in the field of radiation but did not stimulate second cancers outside the field of irradiation.…”