Retrospective clinical study on the comprehensive treatment of retinoblastoma_Chinese Journal of Ocular Fundus Diseases

Authors：

Cheng Yong , Jia Zhongxu ,  Zhao Mingwei , Liang Jianhong

Department of Ophthalmology, Peking University People’s Hospital, Eye Diseases and Optometry Institute, Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, College of Optometry, Peking University Health Science Center, Beijing 100044, China;

Corresponding author：

Zhao Mingwei, Email: zhaomingwei64@163.com

Keywords：

Retinoblastoma/therapy; Chemotherapy, cancer, regional perfusion; Ophthalmic artery; Eye enucleation

DOI：

10.3760/cma.j.cn511434-20200205-00040

Video：

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Objective To observe the curative effect, survival rate, enucleation rate and pathological characteristics of retinoblastoma (RB) in children.Methods Retrospective clinical study. From March 1999 to December 2018, a total of 313 patients (445 eyes) with RB diagnosed in Ophthalmology Department of Peking University People’s Hospital were enrolled in the study. Among them, 175 were male (55.9%), 138 were female (44.1%); 181 were monocular and 132 were binocular. The international standard of intraocular RB staging (IIRC) was 6, 13, 6, 52, 227 and 9 patients of A, B, C, D, E and extraocular stages respectively. Among the 313 patients, 245 patients were confirmed to the survivance, of which 22 cases (9.0%, 22/245) died. Among 445 eyes, 330 eyes definitely whether or not were enucleated; 184 eyes had definite IIRC stage, eye examination results, definite treatment plan and times before enucleation and definite pathological tumor node metastasis stage after operation. The basic information, demographic characteristics, clinical information, enucleation and treatment plan, pathological and immunohistochemical results were recorded. Binary logistic regression was used to analyze the risk factors of high risk pathological features (HRF) and prognosis in patients with RB.Results From 1999 to 2018, the survival rate of 245 patients was increased from 82.6% to 96.3% year by year; the enucleation rate of 330 eyes with final enucleation was reduced from 68.8% to 58.3% year by year. The rate of enucleation in stage D and stage E decreased from 83.3% and 100% before 2005 to 37.5% and 85.4% after 2014, respectively. Monocular disease (β=－1.551, P=0.005), stage D, stage E and extraocular stage in IIRC stage (P＜0.005) were the independent risk factors of RB enucleation, while the protective factors were Interventional chemotherapy of ophthalmic artery (IAC) (β=－0.877, P＜0.001). HRF was found in 51 eyes (27.7%). Age of onset (β=0.019, P=0.016) and glaucoma (β=0.816, P=0.050) were independent risk factors for HRF in RB pathology, while IAC treatment was the protective factor for enucleation (β=21.432, P＜0.001).Conclusions After comprehensive treatment, the general trend of RB enucleation rate is gradually decreasing. IAC treatment can reduce the enucleation rate of stage D and E. The older age of onset and glaucoma stage are the independent risk factors of HRF, and IAC can reduce the risk factors of HRF.

Citation： Cheng Yong, Jia Zhongxu, Zhao Mingwei, Liang Jianhong. Retrospective clinical study on the comprehensive treatment of retinoblastoma. Chinese Journal of Ocular Fundus Diseases, 2020, 36(6): 419-424. doi: 10.3760/cma.j.cn511434-20200205-00040 Copy

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1. Dimaras H, Kimani K, Dimba EAO, et al. Retinoblastoma[J]. Lancet, 2012, 379(9824): 1436-1446. DOI: 10.1016/S0140-6736(11)61137-9.
2. Gao J, Zeng JH, Guo B, et al. Clinical presentation and treatment outcome of retinoblastoma in children of South Western China[J/OL]. Medicine (Baltimore), 2016, 95(42): 5204[2016-10-01]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5079341/. DOI: 10.1097/MD.0000000000005204.
3. Rodriguez-Galindo C, Orbach DB, Vanderveen D. Retinoblastoma[J]. Pediatr Clin North Am, 2015, 62(1): 201-223. DOI: 10.1016/j.pcl.2014.09.014.
4. Broaddus E, Topham A, Singh AD. Incidence of retinoblastoma in the USA: 1975-2004[J]. Br J Ophthalmol, 2009, 93(1): 21-23. DOI: 10.1136/bjo.2008.138750.
5. Gallie B. Canadian guidelines for retinoblastoma care[J]. Can J Ophthalmol, 2009, 44(6): 639-642. DOI: 10.1139/i09-229.
6. Jain M, Rojanaporn D, Chawla B, et al. Retinoblastoma in Asia[J]. Eye (Lond), 2019, 33(1): 87-96. DOI: 10.1038/s41433-018-0244-7.
7. Shields CL, Mashayekhi A, Cater J, et al. Chemoreduction for retinoblastoma: analysis of tumor control and risks for recurrence in 457 tumors[J]. Trans Am Ophthalmol Soc, 2004, 102: 35-45.
8. Abramson DH, Dunkel IJ, Brodie SE, et al. A phase I/Ⅱ study of direct intraarterial (ophthalmic artery) chemotherapy with melphalan for intraocular retinoblastoma initial results[J]. Ophthalmology, 2008, 115(8): 1398-1404. DOI: 10.1016/j.ophtha.2007.12.014.
9. Hayden BC, Jockovich ME, Murray TG, et al. Pharmacokinetics of systemic versus focal Carboplatin chemotherapy in the rabbit eye: possible implication in the treatment of retinoblastoma[J]. Invest Ophthalmol Vis Sci, 2004, 45(10): 3644-3649. DOI: 10.1167/iovs.04-0228.
10. Mendelsohn ME, Abramson DH, Madden T, et al. Intraocular concentrations of chemotherapeutic agents after systemic or local administration[J]. Arch Ophthalmol, 1998, 116(9): 1209-1212. DOI: 10.1001/archopht.116.9.1209.
11. Pekacka A. The role of intraarterial chemotherapy in the management of retinoblastoma[J/OL]. J Ophthalmol, 2020, 2020: 3638410[2020-01-24]. https://doi.org/10.1155/2020/3638410. DOI: 10.1155/2020/3638410.
12. Scott IU, Murray TG, Feuer WJ, et al. External beam radiotherapy in retinoblastoma: tumor control and comparison of 2 techniques[J]. Arch Ophthalmol, 1999, 117(6): 766-770. DOI: 10.1001/archopht.117.6.766.
13. Toma NM, Hungerford JL, Plowman PN, et al. External beam radiotherapy for retinoblastoma: Ⅱ. Lens sparing technique[J]. Br J Ophthalmol, 1995, 79(2): 112-117. DOI: 10.1136/bjo.79.2.112.
14. Hungerford JL, Toma NM, Plowman PN, et al. External beam radiotherapy for retinoblastoma: Ⅰ.Whole eye technique[J]. Br J Ophthalmol, 1995, 79(2): 109-111. DOI: 10.1136/bjo.79.2.109.
15. Shields JA, Shields CL, De Potter P. Photocoagulation of retinoblastoma[J]. Int Ophthalmol Clin, 1993, 33(3): 95-99. DOI: 10.1097/00004397-199303330-00014.
16. Shields JA, Shields CL, De Potter P. Cryotherapy for retinoblastoma[J]. Int Ophthalmol Clin, 1993, 33(3): 101-105. DOI: 10.1097/00004397-199303330-00015.
17. 梁建宏. 视网膜母细胞瘤治疗中需要考虑的要点[J]. 中华眼底病杂志, 2018, 34(3): 208-211. DOI: 10.3760/cma.j.issn.1005-1015.2018.03.001.Liang JH. The main points in the treatment for retinoblastoma[J]. Chin J Ocul Fundus Dis, 2018, 34(3): 208-211. DOI: 10.3760/cma.j.issn.1005-1015.2018.03.001.
18. 范先群. 重视视网膜母细胞瘤的国际分期应用和综合序列治疗[J]. 中华眼科杂志, 2017, 53(8): 561. DOI: 10.3760/cma.j.issn.0412-4081.2017.08.001.Fan XQ. Pay attention to the application of the international intraocular retinoblastoma classification and sequential multiple modality treatment[J]. Chin J Ophthalmol, 2017, 53(8): 561. DOI: 10.3760/cma.j.issn.0412-4081.2017.08.001.
19. Honavar SG, Singh AD, Shields CL, et al. Postenucleation adjuvant therapy in high-risk retinoblastoma[J]. Arch Ophthalmol, 2002, 120(7): 923-931. DOI: 10.1001/archopht.120.7.923.
20. Uusitalo MS, van Quill KR, Scott IU, et al. Evaluation of chemoprophylaxis in patients with unilateral retinoblastoma with high-risk features on histopathologic examination[J]. Arch Ophthalmol, 2001, 119(1): 41-48.
21. Kaliki S, Shields CL, Shah SU, et al. Postenucleation adjuvant chemotherapy with vincristine, etoposide, and carboplatin for the treatment of high-risk retinoblastoma[J]. Arch Ophthalmol, 2011, 129(11): 1422-1427. DOI: 10.1001/archophthalmol.2011.289.
22. Junyang Z, Songfeng L, Jitong S, et al. Clinical presentation and group classification of newly diagnosed intraocular retinoblastoma in China[J]. Br J Ophthalmol, 2011, 95(10): 1372-1375. DOI: 10.1136/bjo.2010.191130.
23. Chung SE, Sa HS, Koo HH, et al. Clinical manifestations and treatment of retinoblastoma in Korea[J]. Br J Ophthalmol, 2008, 92(9): 1180-1184. DOI: 10.1136/bjo.2008.140046.
24. Shanmugam MP, Biswas J, Gopal L, et al. The clinical spectrum and treatment outcome of retinoblastoma in Indian children[J]. J Pediatr Ophthalmol Strabismus, 2005, 42(2): 75-81. DOI: 10.3928/01913913-20050301-01.
25. Ayari-Jeridi H, Moran K, Chebbi A, et al. Mutation spectrum of RB1 gene in unilateral retinoblastoma cases from Tunisia and correlations with clinical features[J/OL]. PLoS One, 2015, 10(1): 0116615[2015-01-20]. https://doi.org/10.1371/journal.pone.0116615. DOI: 10.1371/journal.pone.0116615.
26. Gaikwad N, Vanniarajan A, Husain A, et al. Knudson’s hypothesis revisited in Indian retinoblastoma patients[J]. Asia Pac J Clin Oncol, 2015, 11(4): 299-307. DOI: 10.1111/ajco.12401.
27. Little MP, Kleinerman RA, Stiller CA, et al. Analysis of retinoblastoma age incidence data using a fully stochastic cancer model[J]. Int J Cancer, 2012, 130(3): 631-640. DOI: 10.1002/ijc.26039.
28. Paton EL, Turner JA, Schlaepfer IR. Overcoming resistance to therapies targeting the MAPK pathway in BRAF-mutated tumours[J/OL]. J Oncol, 2020, 2020: 1079827[2020-01-03]. https://doi.org/10.1155/2020/1079827. DOI: 10.1155/2020/1079827.
29. Kivela T. The epidemiological challenge of the most frequent eye cancer: retinoblastoma, an issue of birth and death[J]. Br J Ophthalmol, 2009, 93(9): 1129-1131. DOI: 10.1136/bjo.2008.150292.
30. Maccarthy A, Draper GJ, Steliarova-Foucher E, et al. Retinoblastoma incidence and survival in European children (1978-1997): report from the automated childhood cancer information system project[J]. Eur J Cancer, 2006, 42(13): 2092-2102. DOI: 10.1016/j.ejca.2006.06.003.
31. Canadian Retinoblastoma Society. National retinoblastoma strategy Canadian guidelines for care: strategie therapeutique du retinoblastome guide clinique canadien[J]. Can J Ophthalmol, 2009, 44 Suppl 2: S1-88. DOI: 10.3129/i09-194.
32. Nyamori JM, Kimani K, Njuguna MW, et al. The incidence and distribution of retinoblastoma in Kenya[J]. Br J Ophthalmol, 2012, 96(1): 141-143. DOI: 10.1136/bjophthalmol-2011-300739.
33. Leal-Leal C, Flores-Rojo M, Medina-Sanson A, et al. A multicentre report from the Mexican Retinoblastoma Group[J]. Br J Ophthalmol, 2004, 88(8): 1074-1077. DOI: 10.1136/bjo.2003.035642.
34. Barr RD. "Delays" in diagnosis: a misleading concept, yet providing opportunities for advancing clinical care[J]. J Pediatr Hematol Oncol, 2014, 36(3): 169-172. DOI: 10.1097/MPH.0000000000000108.
35. Shields CL, Mashayekhi A, Au AK, et al. The International Classification of Retinoblastoma predicts chemoreduction success[J]. Ophthalmology, 2006, 113(12): 2276-2280. DOI: 10.1016/j.ophtha.2006.06.018.
36. Fabian ID, Onadim Z, Karaa E, et al. The management of retinoblastoma[J]. Oncogene, 2018, 37(12): 1551-1560. DOI: 10.1038/s41388-017-0050-x.
37. Grigorovski N, Lucena E, Mattosinho C, et al. Use of intra-arterial chemotherapy for retinoblastoma: results of a survey[J]. Int J Ophthalmol, 2014, 7(4): 726-730. DOI: 10.3980/j.issn.2222-3959.2014.04.26.
38. Tuncer S, Sencer S, Kebudi R, et al. Superselective intra-arterial chemotherapy in the primary management of advanced intra-ocular retinoblastoma: first 4-year experience from a single institution in Turkey[J]. Acta Ophthalmol, 2016, 94(7): 644-651. DOI: 10.1111/aos.13077.
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