Determinants of late diagnosis and treatment of children with retinoblastoma. Analytical review of the organizational and methodological department of the Research Institute of Pediatric Oncology and Hematology at N.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of Russia

Introduction. Early diagnosis of oncological diseases is one of the most important tasks of public health, because improves the quality of medical care for patients and the prognosis of the disease. Despite advances in oncology, pediatric tumors continue to be diagnosed at advanced stages, which may be associated with a delayed visit to a doctor and a delay in diagnosis due to several factors. Many foreign articles are devoted to the search and analysis of significant factors of untimely diagnosis of oncological diseases, but few similar works in Russia.
Purpose of the study – to identify factors of late diagnosis and treatment of children with retinal tumors using the example of a common childhood tumor of retinoblastoma (RB).
Material and methods. A retrospective cohort study of patients diagnosed with RB at the of the Research Institute of Pediatric Oncology and Hematology at N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia (Research Institute of Pediatric Oncology and Hematology) was performed using the database of the hospital cancer registry. The study group included RB patients from Russia with a first diagnosis in the period from 2016 to 2019 and receiving treatment at the Research Institute of Pediatric Oncology and Hematology. Time intervals were calculated based on the dates of the first symptom of RB, the initial medical consultation, the date of the final diagnosis by an oncologist or ophthalmologist, and the date of the first therapy for a child with RB. The intervals were calculated in days.
Results. Data from 197 patients (aged 0 to 15 years) were analyzed, which corresponded to 262 cases and the number of eyes with bilateral or unilateral Rb. The median diagnostic interval for patients with localized RB (groups A and B) was 30 days, for patients with locally advanced RB (groups C, D and E) 41 days. The median treatment initiation interval for localized and locally advanced RB was 15 days. Age (p = 0.0067) and patient gender were statistically significantly correlated with the diagnostic interval. For strabismus, the median diagnostic interval was 91 days (p < 0.0001), and when RB was detected during a preventive medical examination, the median diagnostic interval was 17 days (p < 0.0001). The event-free survival of the eyes depended on the prevalence of the process (in groups A, B, C) and the duration of the doctors’ interval (p = 0.0394). The distance to the cancer center was not statistically significant.
Conclusion. Predictors of late diagnosis and initiation of treatment in our study: gender, age of the patient at the time of diagnosis, and the first specific symptom of RB.

1. Demographic Yearbook of Russia, 2020. ROSSTAT. [Electronic resource]: https://gks.ru/bgd/regl/B19_16/Main.htm (appeal date 10.12.2021). (In Russ.).

2. Dang‐Tan T., Franco E.L. Diagnosis delays in childhood cancer: a review. Cancer. 2007;110(4):703–13. doi:10.1002/cncr.22849.

3. Kaprin A.D., Starinskii V.V., Aleksandrova L.M., Chissov V.I., Balashov P.Yu., Lutkovskii A.S., Savinov V.V. The development of oncological care in the Russian Federation in view of implementation of public programs. Rossiiskii meditsinskii zhurnal = Medical Journal of the Russian Federation. 2015;21(2):4–9. (In Russ.).

4. Mehta M., Sethi S., Pushker N., Kashyap S., Sen S., Bajaj M.S., Ghose S. Retinoblastoma. Singapore Med J. 2012;53(2):128–35; quiz 136. PMID:22337189.

5. Ward E., DeSantis C., Robbins A., Kohler B., Jemal A. Childhood and Adolescent Cancer Statistics. CA Cancer J Clin. 2014;64(2):83–103. doi:10.3322/caac.21219.

6. Men T.Kh., Polyakov V.G., Aliev M.D. Epidemiology of childhood cancer in Russia. Onkopediatriya = Oncopediatria. 2014;1:7–12. (In Russ.).

7. Tomar A.S., Finger P T., Gallie B., Mallipatna A., Kivelä T.T., Zhang C., Zhao J., Wilson M.W., Brenna R.C., Burges M., Kim J., Khetan V., Ganesan S., Yarovoy A., Yarovaya V., Kotova E., Yousef Y.A., Nummi K., Ushakova T.L., Yugay O.V., Polyakov V.G., Ramirez-Ortiz M.A., Esparza-Aguiar E., Chantada G., Schaiquevich P., Fandino A., Yam J.C., Lau W.W., Lam C.P., Sharwood P., Moorthy S., Long Q.B., Essuman V.A., Renner L.A., Semenova E., Català J., Correa-Llano G., Carreras E., American Joint Committee on Cancer Ophthalmic Oncology Task Force. Multicenter, International Collaborative Study for AJCC-Staging of Retinoblastoma: Treatment Success and Globe Salvage. Ophthalmology. 2020;127(12):1733–46. doi:10.1016/j.ophtha.2020.05.051.

8. Wieland R., Lohmann D., Schüler A., Bornfeld N., Havers W. Retinoblastom. Die Onkologie. Springer, Berlin, Heidelberg, 2004. Pp. 1697–707. doi:10.1007/978-3-662-06670-6-70.

9. Balmer A., Zografos L., Munier F. Diagnosis, and current management of retinoblastoma. Oncogene. 2006;25:5341–9. doi:10.1038/sj.onc.1209622.

10. Kiss S., Leiderman Y., Mukai S. Diagnosis, classification, and treatment of retinoblastoma. Int Ophthalmol Clin. 2008;48(2):135–47. doi:10.1097/IIO.0b013e3181693670.

11. Rivas-Perea P., Baker E., Hamerly G., Shaw B.F. Detection of leukocoria using a soft fusion of expert classifiers under non-clinical settings. BMC Ophthalmol. 2014;14:110. doi:10.1186/1471-2415-14-110.

12. Katargina L.A., Arestova N.N., Michaylova L.A. Achievements of pediatric ophthalmology of the russian federation for 10 years. Rossiyskaya pediatricheskaya oftalʼmologiya = Russian Pediatric Ophthalmology. 2018;13(2):62–6. (In Russ.).

13. Order of the Ministry of Health of Russia dated 31.10.2012 No. 560n (as amended on 02.09.2013) «On approval of the Procedure for the provision of medical care in the fi eld of “pediatric oncology”» (Registered with the Ministry of Justice of Russia 22.03.2013 No. 27833). (In Russ.).

14. Murphree A.L. Intraocular retinoblastoma: the case for a new group classification. Ophthalmol Clin North Am. 2005;18(1):41–53. doi:10.1016/j.ohc.2004.11.003.

15. Fabian I.D., Abdallah E., Abdullahi S.U., Abdulqader R.A., Boubacar S.A., Ademola-Popoola D.S., Gole G.A. Global retinoblastoma presentation and analysis by national income level. JAMA Oncol. 2020;6(5):685–95. doi:10.1001/jamaoncol.2019.6716.

16. Loh A.H.P., Ha C., Chua J.H.Y., Seow W.T., Chan M.Y., Tan A.M., Chui C.H. Delays in Diagnosis of Pediatric Solid Tumors in Singapore. J Pediatr Hematol Oncol. 2009;31(10):734–8. doi:10.1097/MPH.0b013e3181b78725.

17. Berhane A., Hailu T., Mulugeta A. Determinants of delayed diagnosis among pediatric cancer patients from Ayder Comprehensive Specialized Hospital, Mekelle, Northern Ethiopia. BMC Pediatr. 2019;19(1):478. doi:10.1186/s12887-019-1848-1.

18. Klein‐Geltink J.E., Pogany L.M., Barr R.D., Greenberg M.L., Mery L.S. Waiting times for cancer care in Canadian children: impact of distance, clinical, and demographic factors. Pediatr Blood Cancer. 2005;44(4):318–27. doi:10.1002/pbc.20156.

19. Haimi M., Peretz Nahum M., Ben Arush M.W. Delay in diagnosis of children with cancer: a retrospective study of 315 children. Pediatr Hematol Oncol. 2004;21(1):37–48. doi:10.1080/pho.21.1.37.48.