ENUCLEATION TRENDS AND RISK FACTORS OF RETINOBLASTOMA PATIENTS IN MALAYSIA
Vishel S., Sangeetha T., Norhafizah H. & Jamalia R.
abstract
A study was conducted to investigate the clinical presentation of retinoblastoma cases in Malaysia, with a focus on identifying risk factors associated with enucleation. We conducted a cross-sectional analysis of registry data from the National Retinoblastoma Registry spanning from 2004 to 2022. Results based on a cohort of 277 retinoblastoma patients, yield noteworthy insights. The median age at diagnosis was 16 months, with a predilection for unilateral presentation (65%) over bilateral (35%). Gender distribution exhibited no significant bias, with 55.6% males and 44.4% females. Ethnicity-wise, the Malay group demonstrated the highest incidence at 57.0%, followed by Chinese (19.1%) and Indian (7.2%) populations. Leukocoria emerged as the predominant initial symptom, manifesting in 65.4% of cases. Combining leukocoria and strabismus accounted for 12.3% of cases, while strabismus alone was observed in 4.5% of cases. Extraocular extensions, detected radiographically, were noted in 12% of patients, with optic pathway involvement being the most prevalent (3.5% unilaterally and 2.9% bilaterally). Risk factors for enucleation were also examined, revealing that unilateral cases carried a significantly higher enucleation risk (10.48 times) compared to bilateral cases. A family history of retinoblastoma was associated with a noteworthy 89% reduction in enucleation risk. Additionally, advanced International Intraocular Retinoblastoma Classification (IIRC) stages D and E correlated with an elevated likelihood of enucleation. In conclusion, our study underscores the importance of early detection, particularly in unilateral cases and advanced stages of retinoblastoma. These findings hold significant clinical relevance and can inform more informed clinical decision-making and patient counselling.
references
1. Kivela T. The epidemiological challenge of the most frequent eye cancer: retinoblastoma, an issue of birth and death. British Journal of Ophthalmology. 2009 Aug 24;93(9):1129–31.https://doi.org/10.1136/bjo.2008.150292
2. Godbout R, Dryja TP, Squire J, Gallie BL, Phillips RA. Somatic inactivation of genes on chromosome 13 is a common event in retinoblastoma. Nature. 1983 Aug;304(5925):451–3. https://doi.org/ 10.1038/304451a0.
3. Daphna Landau Prat, Zondervan M, Ido Didi Fabian. Worldwide Analysis: The Global Presentation of Retinoblastoma. 2022 Jan 1;13–8. https://doi.org/10.1007/978-3-031-08250-4_3
4. Subramaniam S, Rahmat J, Rahman NA, Ramasamy S, Bhoo-Pathy N, Pin GP, et al. Presentation of Retinoblastoma Patients in Malaysia. Asian Pacific Journal of Cancer Prevention. 2014 Oct 11;15(18):7863–7. https://doi.org/10.7314/apjcp.2014.15.18.7863
5. de Graaf P, Göricke S, Rodjan F, Galluzzi P, Maeder P, Castelijns JA, et al. Guidelines for imaging retinoblastoma: imaging principles and MRI standardization. Pediatric Radiology. 2011 Aug 18;42(1):2–14. https://doi.org/10.1007/s00247-011-2201-5
6. Ellsworth RW. The practical management of retinoblastoma. 1969 Jan 1;67:462–534.
7. Linnmurphree A. Intraocular Retinoblastoma: the Case for a New Group Classification. Ophthalmology Clinics of North America. 2005 Mar;18(1):41–53. https://doi.org/10.1016/j.ohc.2004.11.003.
8. Shields CL, Mashayekhi A, Au AK, Czyz C, Leahey A, Meadows AT, et al. The International Classification of Retinoblastoma Predicts Chemoreduction Success. Ophthalmology. 2006 Dec;113(12):2276–80. https://doi.org/10.1016/j.ophtha.2006.06.018
9. Mallipatna AC, Gallie BL, Chévez-Barrios P, Lumbroso-Le Rouic L, Chantada G, Doz F, Munier FL, et al. AJCC Cancer Staging Manual. 8th ed. New York: Springer; 2017.
10. Shridevi et al. Anophthalmic Sockets in Retinoblastoma: A Single Center Experience. Asia-Pacific Journal of Ophthalmology. 2018; https://doi.org/10.22608/APO.201892
11. Mendoza PR, Grossniklaus HE. Therapeutic Options for Retinoblastoma. Cancer Control. 2016 Apr;23(2):99–109. https://doi.org/10.1177/107327481602300203
12. Shields CL, Lally SE, Leahey AM, Jabbour PM, Caywood EH, Schwendeman R, et al. Targeted retinoblastoma management. Current Opinion in Ophthalmology. 2014 Sep;25(5):374–85. https://doi.org/10.1097/ICU.0000000000000091
13. Munier FL, Beck-Popovic M, Chantada GL, Cobrinik D, Kivelä TT, Lohmann D, et al. Conservative management of retinoblastoma: Challenging orthodoxy without compromising the state of metastatic grace. “Alive, with good vision and no comorbidity.” Progress in Retinal and Eye Research. 2019 Nov;73:100764. https://doi.org/10.1016/j.preteyeres.2019.05.005
14. Shields CL, Shields JA. Retinoblastoma management: advances in enucleation, intravenous chemoreduction, and intra-arterial chemotherapy. Current Opinion in Ophthalmology. 2010 May;21(3):203–12. https://doi.org/10.1097/icu.0b013e328338676a
15. Jain M, Rojanaporn D, Chawla B, Sundar G, Gopal L, Khetan V. Retinoblastoma in Asia. Eye. 2018 Nov 1;33(1):87–96. https://doi.org/10.1038/s41433-018-0244-7
16. Global Retinoblastoma Study Group, Fabian ID, Abdallah E, Abdullahi SU, Abdulqader RA, Adamou Boubacar S, et al. Global Retinoblastoma Presentation and Analysis by National Income Level. JAMA oncology [Internet]. 2020 May 1;6(5):685–95. Available from: https://pubmed.ncbi.nlm.nih.gov/32105305/ https://doi.org/10.1001/jamaoncol.2019.6716.
17. Hussain Z. Impact of Laterality on Cumulative Survival in Patients Diagnosed with Retinoblastoma: A Retrospective Cohort Analysis of 1925 Cases in the Surveillance, Epidemiology, and End Results (SEER) Program. Clinical Ophthalmology. 2021 Mar;Volume 15:991–1001. https://doi.org/10.2147/opth.S298209
18. Sanjay Kumar Sahu, Banavali SD, Pai SA, Nair Cn, Purna Kurkure, Motwani SA, et al. Retinoblastoma: Problems and Perspectives from India. 1998 Nov 1;15(6):501–8. https://doi.org/10.3109/08880019809018311
19. Fabian ID, Khetan V, Stacey AW, Allen Foster null, Ademola-Popoola DS, Berry JL, et al. Sex, gender, and retinoblastoma: analysis of 4351 patients from 153 countries. Eye (London, England) [Internet]. 2022 Aug 1 [cited 2022 Oct 26];36(8):1571–7. Available from: https://pubmed.ncbi.nlm.nih.gov/34272514/ https://doi.org/10.1038/s41433-021-01675-y.
20. MyGovernment. MyGOV - The Government of Malaysia’s Official Portal [Internet]. Malaysia.gov.my. 2020. Available from: https://www.malaysia.gov.my/portal/content/30114
21. Kase S, Parikh J, Youssef P, A. Linn Murphree, Rao NA. Transforming Growth Factor β in Retinoblastoma-Related Cataract. 2008 Nov 10;126(11):1539–9. https://doi.org/10.1001/archopht.126.11.1539.
22. Jijelava KP, Grossniklaus HE. Diffuse anterior retinoblastoma: A review. Saudi Journal of Ophthalmology. 2013 Jul;27(3):135–9.
23. Rodriguez-Galindo C, Chantada GL, Haik BG, Wilson MW. Treatment of retinoblastoma: Current status and future perspectives. Current Treatment Options in Neurology. 2007 Jul;9(4):294–307. https://doi.org/10.1007/s11940-007-0015-4
24. Shields CL. Chemoreduction for Unilateral Retinoblastoma. Archives of Ophthalmology. 2002 Dec 1;120(12):1653. https://doi.org/10.1001/archopht.120.12.1653
25. Lu JE, Francis JH, Dunkel IJ, Shields CL, Yu MD, Berry JL, et al. Metastases and death rates after primary enucleation of unilateral retinoblastoma in the USA 2007-2017. The British Journal of Ophthalmology [Internet]. 2019 Sep 1 [cited 2023 Jan 17];103(9):1272–7. Available from: https://pubmed.ncbi.nlm.nih.gov/30361279/ https://doi.org/10.1136/bjophthalmol-2018-312915.
26. Malaysia. Child Act 2001 (Act 611). 2001.
27. Kim J. Enucleated eyes after failed intra-arterial infusion of chemotherapy for unilateral retinoblastoma: histopathologic evaluation of vitreous seeding. Clinical Ophthalmology. 2011 Nov;1655. https://doi.org/10.2147/OPTH.S24318.
28. Zhao J, Feng Z, Wei M, Liu G, Solarte CE, Li B, et al. Impact of Systemic Chemotherapy and Delayed Enucleation on Survival of Children with Advanced Intraocular Retinoblastoma. 2020 Jun 1;4(6):630–9. https://doi.org/10.1016/j.oret.2020.02.015
29. Jagadeesan M, Khetan V, Mallipatna A. Genetic perspective of retinoblastoma: From present to future. Indian Journal of Ophthalmology [Internet]. 2016;64(5):332. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966369/ https://doi.org/10.4103/0301-4738.185585.
30. Draper G, Sanders B, Brownbill P, Hawkins M. Patterns of risk of hereditary retinoblastoma and applications to genetic counselling. British Journal of Cancer. 1992 Jul;66(1):211–9. https://doi.org/10.1038/bjc.1992.244
2. Godbout R, Dryja TP, Squire J, Gallie BL, Phillips RA. Somatic inactivation of genes on chromosome 13 is a common event in retinoblastoma. Nature. 1983 Aug;304(5925):451–3. https://doi.org/ 10.1038/304451a0.
3. Daphna Landau Prat, Zondervan M, Ido Didi Fabian. Worldwide Analysis: The Global Presentation of Retinoblastoma. 2022 Jan 1;13–8. https://doi.org/10.1007/978-3-031-08250-4_3
4. Subramaniam S, Rahmat J, Rahman NA, Ramasamy S, Bhoo-Pathy N, Pin GP, et al. Presentation of Retinoblastoma Patients in Malaysia. Asian Pacific Journal of Cancer Prevention. 2014 Oct 11;15(18):7863–7. https://doi.org/10.7314/apjcp.2014.15.18.7863
5. de Graaf P, Göricke S, Rodjan F, Galluzzi P, Maeder P, Castelijns JA, et al. Guidelines for imaging retinoblastoma: imaging principles and MRI standardization. Pediatric Radiology. 2011 Aug 18;42(1):2–14. https://doi.org/10.1007/s00247-011-2201-5
6. Ellsworth RW. The practical management of retinoblastoma. 1969 Jan 1;67:462–534.
7. Linnmurphree A. Intraocular Retinoblastoma: the Case for a New Group Classification. Ophthalmology Clinics of North America. 2005 Mar;18(1):41–53. https://doi.org/10.1016/j.ohc.2004.11.003.
8. Shields CL, Mashayekhi A, Au AK, Czyz C, Leahey A, Meadows AT, et al. The International Classification of Retinoblastoma Predicts Chemoreduction Success. Ophthalmology. 2006 Dec;113(12):2276–80. https://doi.org/10.1016/j.ophtha.2006.06.018
9. Mallipatna AC, Gallie BL, Chévez-Barrios P, Lumbroso-Le Rouic L, Chantada G, Doz F, Munier FL, et al. AJCC Cancer Staging Manual. 8th ed. New York: Springer; 2017.
10. Shridevi et al. Anophthalmic Sockets in Retinoblastoma: A Single Center Experience. Asia-Pacific Journal of Ophthalmology. 2018; https://doi.org/10.22608/APO.201892
11. Mendoza PR, Grossniklaus HE. Therapeutic Options for Retinoblastoma. Cancer Control. 2016 Apr;23(2):99–109. https://doi.org/10.1177/107327481602300203
12. Shields CL, Lally SE, Leahey AM, Jabbour PM, Caywood EH, Schwendeman R, et al. Targeted retinoblastoma management. Current Opinion in Ophthalmology. 2014 Sep;25(5):374–85. https://doi.org/10.1097/ICU.0000000000000091
13. Munier FL, Beck-Popovic M, Chantada GL, Cobrinik D, Kivelä TT, Lohmann D, et al. Conservative management of retinoblastoma: Challenging orthodoxy without compromising the state of metastatic grace. “Alive, with good vision and no comorbidity.” Progress in Retinal and Eye Research. 2019 Nov;73:100764. https://doi.org/10.1016/j.preteyeres.2019.05.005
14. Shields CL, Shields JA. Retinoblastoma management: advances in enucleation, intravenous chemoreduction, and intra-arterial chemotherapy. Current Opinion in Ophthalmology. 2010 May;21(3):203–12. https://doi.org/10.1097/icu.0b013e328338676a
15. Jain M, Rojanaporn D, Chawla B, Sundar G, Gopal L, Khetan V. Retinoblastoma in Asia. Eye. 2018 Nov 1;33(1):87–96. https://doi.org/10.1038/s41433-018-0244-7
16. Global Retinoblastoma Study Group, Fabian ID, Abdallah E, Abdullahi SU, Abdulqader RA, Adamou Boubacar S, et al. Global Retinoblastoma Presentation and Analysis by National Income Level. JAMA oncology [Internet]. 2020 May 1;6(5):685–95. Available from: https://pubmed.ncbi.nlm.nih.gov/32105305/ https://doi.org/10.1001/jamaoncol.2019.6716.
17. Hussain Z. Impact of Laterality on Cumulative Survival in Patients Diagnosed with Retinoblastoma: A Retrospective Cohort Analysis of 1925 Cases in the Surveillance, Epidemiology, and End Results (SEER) Program. Clinical Ophthalmology. 2021 Mar;Volume 15:991–1001. https://doi.org/10.2147/opth.S298209
18. Sanjay Kumar Sahu, Banavali SD, Pai SA, Nair Cn, Purna Kurkure, Motwani SA, et al. Retinoblastoma: Problems and Perspectives from India. 1998 Nov 1;15(6):501–8. https://doi.org/10.3109/08880019809018311
19. Fabian ID, Khetan V, Stacey AW, Allen Foster null, Ademola-Popoola DS, Berry JL, et al. Sex, gender, and retinoblastoma: analysis of 4351 patients from 153 countries. Eye (London, England) [Internet]. 2022 Aug 1 [cited 2022 Oct 26];36(8):1571–7. Available from: https://pubmed.ncbi.nlm.nih.gov/34272514/ https://doi.org/10.1038/s41433-021-01675-y.
20. MyGovernment. MyGOV - The Government of Malaysia’s Official Portal [Internet]. Malaysia.gov.my. 2020. Available from: https://www.malaysia.gov.my/portal/content/30114
21. Kase S, Parikh J, Youssef P, A. Linn Murphree, Rao NA. Transforming Growth Factor β in Retinoblastoma-Related Cataract. 2008 Nov 10;126(11):1539–9. https://doi.org/10.1001/archopht.126.11.1539.
22. Jijelava KP, Grossniklaus HE. Diffuse anterior retinoblastoma: A review. Saudi Journal of Ophthalmology. 2013 Jul;27(3):135–9.
23. Rodriguez-Galindo C, Chantada GL, Haik BG, Wilson MW. Treatment of retinoblastoma: Current status and future perspectives. Current Treatment Options in Neurology. 2007 Jul;9(4):294–307. https://doi.org/10.1007/s11940-007-0015-4
24. Shields CL. Chemoreduction for Unilateral Retinoblastoma. Archives of Ophthalmology. 2002 Dec 1;120(12):1653. https://doi.org/10.1001/archopht.120.12.1653
25. Lu JE, Francis JH, Dunkel IJ, Shields CL, Yu MD, Berry JL, et al. Metastases and death rates after primary enucleation of unilateral retinoblastoma in the USA 2007-2017. The British Journal of Ophthalmology [Internet]. 2019 Sep 1 [cited 2023 Jan 17];103(9):1272–7. Available from: https://pubmed.ncbi.nlm.nih.gov/30361279/ https://doi.org/10.1136/bjophthalmol-2018-312915.
26. Malaysia. Child Act 2001 (Act 611). 2001.
27. Kim J. Enucleated eyes after failed intra-arterial infusion of chemotherapy for unilateral retinoblastoma: histopathologic evaluation of vitreous seeding. Clinical Ophthalmology. 2011 Nov;1655. https://doi.org/10.2147/OPTH.S24318.
28. Zhao J, Feng Z, Wei M, Liu G, Solarte CE, Li B, et al. Impact of Systemic Chemotherapy and Delayed Enucleation on Survival of Children with Advanced Intraocular Retinoblastoma. 2020 Jun 1;4(6):630–9. https://doi.org/10.1016/j.oret.2020.02.015
29. Jagadeesan M, Khetan V, Mallipatna A. Genetic perspective of retinoblastoma: From present to future. Indian Journal of Ophthalmology [Internet]. 2016;64(5):332. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966369/ https://doi.org/10.4103/0301-4738.185585.
30. Draper G, Sanders B, Brownbill P, Hawkins M. Patterns of risk of hereditary retinoblastoma and applications to genetic counselling. British Journal of Cancer. 1992 Jul;66(1):211–9. https://doi.org/10.1038/bjc.1992.244