Saakyan S.V., Tadevosyan S.S., Tsygankov A.Yu., Ivanova O.A. Long-term follow-up in retinoblastoma suvivors: second nonocular malignant tumors (series of incidents). Head and neck. Russian Journal. 2021;9(1):83–90 (In Russian). The authors are responsible for the originality of the data presented and the possibility of publishing illustrative material – tables, figures, photographs of patients.


Aim. To determine the incidence and the time of the occurrence of second nonocular malignant tumors (SMT) among survivors of retinoblastoma.
Materal and methods. 903 children with retinoblastoma were examined and treated in the ocular oncology and radiology department of Helmholtz National Medical Research Center of Eye Diseases from January 1986 to December 2008. The study included 140 patients with retinoblastoma (70 men, 70 women) who received treatment from the age of 1.5 months to 108 months (average age at the start of treatment was 21.5±19.0 months, median 16 months), in whom it was possible to evaluate complete information about the health condition. When assessing vital status, the average age of patients was 244.6±78.4 months (median 228 months, max. 420 months, min. 120 months). The median of follow-up period was 228 months. (interquartile range from 168 to 288 months). The monolateral disease was diagnosed in 62.1% of cases (n=87), the bilateral – in 37.9% (n=53).

Results. In a retrospective study of 140 patients, the SMT were detected in 9 cases (6.4%): osteosarcoma of femoral bone (n=4), parotid adenocarcinoma (n=1), femoral leiomyosarcoma (n=1), bladder lymphosarcoma (n=1), cervical cancer (n=1), histiocytoma (n=1). In 1 case, after osteosarcoma of the femoral bone, the third and fourth tumors in the form of thyroid cancer and soft tissue sarcoma of the shoulder metachronously developed. The median from the start of treatment to the appearance of the SMT was 216 months. Survival in the general group was 98.6% (n=138 out of 140). Among 9 patients with SMT 2 cases were fatal. The risk of developing SMT with bilateral disease (15.1%, n=8 out of 53) was significantly higher than with monolateral disease (1.1%, n=1 out of 87; p=0.00186). Among patients who received radiation therapy (RT) (29.3%, n=41), SMT were detected in 9.8% of cases (n=4), among patients who did not receive RT (70.7%, n=99), SMT detected 2 times less often — in 5.0% of cases (n=5). However, no reliable relationships between the risk of developing of SMT and RT were found (p=0.44846). Among patients with SMT, only 4 cases were able to conduct a genetic study. In a patient with bladder lymphosarcoma and her mother, homozygous mutations were detected at the Q433P locus of the RB1 gene in both of them, indicating hereditary RB. Mutations in this locus are associated with the development of SMT in patients with retinoblastoma localized in the urogenital system. Homozygous mutations in the RB1 gene were absent in 3 patients.

Conclusions. The findings suggest the need for regular life-long follow-up of patients due to the high risk of developing SMT. Patients need to conduct molecular genetic studies to determine the risk of a SMT in accordance with literature data and the OMIM database.
Key words: retinoblastoma, second nonocular malignant tumors, long-term follow-up

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