Abstract
In this review we discuss several recent concepts regarding retinoblastoma control and its impact. In a cohort of 482 patients with solitary unilateral retinoblastoma revealed germline mutation in 16% and the likelihood of germline retinoblastoma was greater for younger children (≤1 year versus (vs.) >1 year at presentation) with odds ratio (OR) 2.96 (p = 0.001), and greatest for the youngest infants (≤3 months vs. >3–12 months) (OR 5.52) (p = 0.002). Retinocytoma/retinoma, a benign variant of retinoblastoma, was studied in 78 tumours and demonstrated transformation into retinoblastoma in 9.2% by 5 years and 15.3% by 10 years and 20 years. An international global study on retinoblastoma over 1.5 years revealed 4351 new patients and 85% from low- and middle-income countries, notably with older age at detection and greater risk for metastasis. Management of retinoblastoma in 964 eyes using intravenous chemotherapy showed 20-year globe salvage at 96% in group A, 90% in group B, 90% in group C, 68% in group D, and 32% in group E eyes. The 5-year globe salvage with intra-arterial chemotherapy for 160 eyes (655 infusions) with retinoblastoma showed success in 100% for group B, 80% for group C, 78% for group D, and 55% for group E. The psychological impact of retinoblastoma on the parents revealed depression (73%), anxiety (64%), and/or stress (100%), and on the patient revealed deficits in quality of life issues. Retinoblastoma is a challenging disease and chemotherapy provides reliable tumour control and globe salvage. Continuing efforts to improve quality of life issues is important.
摘要
本综述讨论了视网膜母细胞瘤控制及其影响的几个最新概念。在一组拥有482例独立性单侧视网膜母细胞瘤患者的队列中, 16%的患者发现有胚系突变, 其中年龄较小的孩子患有遗传性视网膜母细胞瘤的可能性更大 (≤1岁 vs. å 1岁, OR = 2.96, p = 0.001), 年龄最小的婴儿可能性最大 (≤3个月vs.å 3-12个月, OR = 5.52, p = 0.002) 。对78例视网膜母细胞瘤的良性变异型视网膜细胞瘤/视网膜瘤进行了研究, 发现5年内有9.2%的患者转化为视网膜母细胞瘤, 10年和20年里有15.3%的患者转化为视网膜母细胞瘤。一项为期1.5年的全球研究显示: 在4351位新确诊的视网膜母细胞瘤的病人中, 85%来自中等和低等收入的国家, 尤其是确诊年龄大和转移风险高的病人。采用静脉化疗治疗964只视网膜母细胞瘤患眼的研究显示: 20年后眼球保留率A组为96%, B组为90%, C组为90%, D组为68%, E组为32%。对160只视网膜母细胞瘤患眼 (655次输液) 进行动脉内化疗, 其5年眼球保留率显示: B组成功率为100%, C组为80%, D组为78%, E组为55%。视网膜母细胞瘤对患者父母的心理影响表现为抑郁 (73%) 、焦虑 (64%) 和/或压力 (100%), 患者则存在生活质量低下的问题。视网膜母细胞瘤是一种具有挑战性的疾病, 化疗对于肿瘤的控制和眼球的保留来说是可靠的治疗方法。此外, 继续致力于患者生活质量的提高是十分必要的。
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References
Shields CL, Lally SE, Leahey AM, Jabbour PM, Caywood EH, Schwendeman R, et al. Targeted retinoblastoma management: when to use intravenous, intra-arterial, periocular, and intravitreal chemotherapy. Curr Opin Ophthalmol. 2014;25:374–85.
Ancona-Lezama D, Dalvin LA, Shields CL. Modern treatment of retinoblastoma: a 2020 review. Ind J Ophthalmol. 2020;68:2356–65.
Honavar SG, Singh AD, Shields CL, Meadows AM, Demirci H, Cater J, et al. Postenucleation adjuvant therapy in high-risk retinoblastoma. Arch Ophthalmol. 2002;120:923–31.
Kaliki S, Shields CL, Shah SU, Eagle RC Jr, Shields JA, Leahey A. Postenucleation adjuvant chemotherapy with vincristine, etoposide, and carboplatin for the treatment of high-risk retinoblastoma. Arch Ophthalmol. 2011;129:1422–7.
Kivela T. The epidemiological challenge of the most frequent eye cancer: retinoblastoma, an issue of birth and death. Br J Opthalmol. 2009;93:1129–31.
Global Retinoblastoma Study Group. Global retinoblastoma presentation and analysis by national income level. JAMA Oncol. 2020;6:685–95.
Shields JA, Shields CL. Intraocular Tumors. An Atlas and Textbook. 3rd edition. Philadelphia, Lippincott Wolters Kluwers, 2016:335–72.
Ramasubramanian A, Shields CL, editors. Retinoblastoma. New Delhi, India: Jaypee Brothers Medical Publishers; 2012:37–78.
Schüler A, Weber S, Neuhäuser M, Jurklies C, Lehnert T, Heimann H, et al. Age at diagnosis of isolated unilateral retinoblastoma does not distinguish patients with and without a constitutional RB1 gene mutation but is influenced by a parent-of-origin effect. Eur J Cancer. 2005;41:735–40.
Brichard B, Heusterspreute M, De Potter P, Chantrain C, Vermylen C, Sibille C, et al. Unilateral retinoblastoma, lack of familial history and older age does not exclude germline RB1 gene mutation. Eur J Cancer. 2006;42:65–72.
Nichols KE, Walther S, Chao E, Shields CL, Ganguly A. Recent advances in retinoblastoma genetic research. Curr Opin Ophthalmol. 2009;20:351–5.
Gregersen PA, Urbak SF, Funding M, Overgaard J, Jensen UB, Alsner J. Danish retinoblastoma patients 1943–2013 - genetic testing and clinical implications. Acta Oncol. 2016;55:412–7.
Berry JL, Lewis L, Zolfaghari E, Green S, Le BHA, Lee TC, et al. Lack of correlation between age at diagnosis and RB1 mutations for unilateral retinoblastoma: The importance of genetic testing. Ophthalmic Genet. 2018;39:407–9.
Yousef YA, Tbakhi A, Al-Hussaini M, AlNawaiseh I, Saab A, Afifi A, et al. Mutational analysis of the RB1 gene and the inheritance patterns of retinoblastoma in Jordan. Fam Cancer. 2018;17:261–8.
Rojanaporn D, Boontawon T, Chareonsirisuthigul T, Thanapanpanich O, Atteseth T, Saengwimol D, et al. Spectrum of germline RB1 mutations and clinical manifestations in retinoblastoma patients from Thailand. Mol Vis. 2018;24:778–88.
Shields CL, Dockery PW, Ruben M, Yaghy A, Sunday MA, Levin HJ, et al. Likelihood of germline mutation with solitary unilateral retinoblastoma based on patient age at presentation. Analysis of 482 consecutive patients. J Pediatr Ophthalmol Strabism. 2021;1:1–10. https://doi.org/10.3928/01913913-20210414-02. Jun. Online ahead of print. PMID: 34180289.
Gudiseva HV, Berry JL, Polski A, Tummina SJ, O’Brien JM. Next-generation technologies and strategies for the management of retinoblastoma. Genes. 2019;10:1032. https://doi.org/10.3390/genes10121032.
Shields CL, Dockery PW, Yaghy A, Ruben M, Sunday MA, Calotti M, et al. Conditional analysis on new tumor formation with solitary unilateral retinoblastoma in 482 consecutive eyes. Saudi J Ophthalmol. 2022; in press.
Abramson DH. Retinoma, retinocytoma, and the retinoblastoma gene. Arch Ophthalmol. 1983;101:1517–8.
Gallie BA, Ellsworth RM, Abramson DH, Phillips RA. Retinoma: Spontaneous regression of retinoblastoma or benign manifestation of the mutation? Br J Cancer. 1982;45:513–21.
Margo CH, Hidayat A, Kopelman J, Zimmerman LE. Retinocytoma: a benign variant of retinoblastoma. Arch Ophthalmol. 1983;101:1519–31.
Gallie BA, Phillips RA, Ellsworth RM, Abramson DH. Significance of retinoma and phthisis bulbi for retinoblastoma. Ophthalmology. 1982;89:1393–9.
Balmer A, Munier F, Gailloud C. Retinoma: case studies. Ophthalmic Pediatr Genet. 1991;12:131–7.
Singh AD, Santos MC, Shields CL, Shields JA, Eagle RC. Observations on 17 patients with retinocytoma. Arch Ophthalmol. 2000;118:199–205.
Dimaris H, Khetan V, Halliday W, Orlic M, Prigoda NL, Piovesan B, et al. Loss of RB1 induces non-proliferative retinocytoma: Increasing genomic instability correlates with progression to retinoblastoma. Hum Mol Genet. 2008;17:1363–7.
Shields CL, Srinivasan A, Alvarez JAL, Shields JA. Retinocytoma/retinoma: comparative analysis of clinical features in 78 tumors and rate of transformation into retinoblastoma over 20 years. J J Aapos. 2021;25:147.e1–147.e8. https://doi.org/10.1016/j.jaapos.2020.11.024. Jun. Epub 2021 May 26. PMID: 34051357.
Fabian ID, Stacey AW, Bowman R, Khetan V, Blum S, Keren-Froim N, et al. on behalf of the Global Retinoblastoma Study Group. Retinoblastoma management during the COVID-19 pandemic: a report by the Global Retinoblastoma Study Group including 194 centers from 94 countries. Pediatr Blood Cancer. 2021;68:e28584.
Tomar AS, Finger PT, Gallie B, Kivelä TT, Mallipatna A, Zhang C, et al. For the American Joint Committee on Cancer Ophthalmic Oncology Task Force. A multicenter, international collaborative study for American Joint Committee on Cancer staging of retinoblastoma. Ophthalmology. 2020;127:1719–32.
De Potter P, Shields CL, Shields JA. Clinical variations of trilateral retinoblastoma. A report of 13 cases. J Pediatr Ophthalmol Strabism. 1994;31:26–31.
Kivela T. Trilateral retinoblastoma: a meta-analysis of hereditary retinoblastoma associated with primary ectopic intracranial retinoblastoma. J Clin Oncol. 1999;17:1829–37.
Shields CL, Meadows AT, Shields JA, Carvalho C, Smith A. Chemoreduction for retinoblastoma may prevent intracranial neuroblastic malignancy (trilateral retinoblastoma). Arch Ophthalmol. 2001;119:1269–72.
De Jong MC, Kors WA, Moll AC, de Graaf P, Castelijns JA, Jansen RW, et al. Screening for pineal trilateral retinoblastoma revisited: a meta-analysis. Ophthalmology. 2020;127:601–7.
Kingston JE, Hungerford JL, Madreperla SA, Plowman PN. Results of combined chemotherapy and radiotherapy for advanced intraocular retinoblastoma. Arch Ophthalmol. 1996;114:1339–43.
Gallie BL, Budning A, DeBoer G, Thiessen JJ, Koren G, Verjee Z, et al. Chemotherapy with focal therapy can cure intraocular retinoblastoma without radiotherapy. Arch Ophthalmol. 1996;114:1321–8.
Murphree AL, Villablanca JG, Deegan WF III, Sato JK, Malogolowkin M, Fisher A, et al. Chemotherapy plus local treatment in the management of intraocular retinoblastoma. Arch Ophthalmol. 1996;114:1348–56.
Shields CL, De Potter P, Himelstein BP, Shields JA, Meadows AT, Maris J. Chemoreduction in the initial management of intraocular retinoblastoma. Arch Ophthalmol. 1996;114:1330–8.
Ferris FL III, Chew EY. A new era for the treatment of retinoblastoma. Arch Ophthalmol. 1996;114:1412.
Shields CL, Mashayekhi A, Au AK, Czyz C, Leahey A, Meadows AT, et al. The International Classification of Retinoblastoma predicts chemoreduction success. Ophthalmology. 2006;113:2276–80.
Shields CL, Bas Z, Tadepalli S, Dalvin LA, Rao R, Schwendeman R, et al. Long-Term (20-year) real-world outcomes of intravenous chemotherapy (chemoreduction) for retinoblastoma in 964 eyes of 554 patients at a single centre. Br J Ophthalmol. 2020;104:1548–55.
Bas Z, Dalvin LA, Tadepalli S, Rao R, Shah A, Leahey AM, et al. Outcomes of intravenous chemotherapy (chemoreduction) for retinoblastoma based on patient age in 964 eyes of 554 cases. Asia Pac J Ophthalmol. 2021;10:373–80.
Shields CL, Shields JA. Here comes the sun for retinoblastoma. Asia Pac J Ophthalmol. 2021;10:341–2.
Shields CL, Shields JA. Intra-arterial chemotherapy for retinoblastoma: The beginning of a long journey. Clin Exp Ophthalmol. 2010;38:638–43.
Suzuki S, Yamane T, Mohri M, Kaneko A. Selective ophthalmic arterial injection therapy for intraocular retinoblastoma: The long‑term prognosis. Ophthalmology. 2011;118:2081–7.
Manjandavida FP, Honavar SG, Shields CL, Shields JA. Retinoblastoma: Recent update and management frontiers. Asia Pac J Ophthalmol. 2013;2:351–3.
Shields CL, Manjandavida FP, Lally SE, Pieretti G, Arepalli SA, Caywood EH, et al. Intra‑arterial chemotherapy for retinoblastoma in 70 eyes: Outcomes based on the international classification of retinoblastoma. Ophthalmology. 2014;121:1453–60.
Manjandavida FP, Stathopoulos C, Zhang J, Honavar SG, Shields CL. Intra-arterial chemotherapy in retinoblastoma - A paradigm change. Indian J Ophthalmol. 2019;67:740–54.
Shields CL, Dockery PW, Yaghy A, Duffner ER, Levin HJ, Taylor OS, et al. Intra-arterial chemotherapy for retinoblastoma in 341 consecutive eyes (1292 infusions): comparative analysis of outcomes based on patient age, race, and sex. J Aapos 2021. 2021;25:150.e1–9.
Abramson DH, Shields CL, Munier FL, Chantada GL. Treatment of retinoblastoma in 2015: Agreement and disagreement. JAMA Ophthalmol. 2015;133:1341–7.
Abramson DH, Shields CL, Jabbour PJ, Teixeira LF, Fonseca JRF, Marques MCP, et al. Metastatic deaths in retinoblastoma patients treated with intraarterial chemotherapy (ophthalmic artery chemosurgery) worldwide. Int J Retin Vitreous. 2017;3:40–4.
Yousef YA, Soliman SE, Astudillo PP, Durairaj P, Dimaras H, Chan HSL, et al. Intra-arterial chemotherapy for retinoblastoma: a systematic review. JAMA Ophthalmol. 2016;134:584–91.
Munier FL, Gaillard M-C, Balmer A, Soliman S, Podilsky G, Moulin AP, et al. Intravitreal chemotherapy for vitreous disease in retinoblastoma revisited:from prohibition to conditional indications. Br J Ophthalmol. 2012;96:1078–83.
Ghassemi F, Shields CL. Intravitreal melphalan for refractory or recurrent vitreous seeding from retinoblastoma. Arch Ophthalmol. 2012;130:1268–71.
Shields CL, Douglass AM, Beggache M, Say EAT, Shields JA. Intravitreous chemotherapy for active vitreous seeding from retinoblastoma: Outcomes after 192 consecutive injections. The 2015 Howard Naquin Lecture. Retina. 2016;36:1184–90.
Francis J, Abramson DH, Ji X, Shields CL, Teixeira LF, Schefler AC, et al. Risk of extraocular extension in eyes with retinoblastoma receiving intravitreous chemotherapy. JAMA Ophthalmol. 2017;135:1426–9.
Collins ML, Bregman J, Ford JS, Shields CL. Depression, anxiety, and stress in parents of patients with retinoblastoma. AOS thesis. Am J Ophthalmol. 2019;207:130–43.
Parravano M, Petri D, Maurutto E, Lucenteforte E, Menchibni F, Lanzetta P, et al. Association between visual impairment and depression in patients attending eye clinics: a meta-analysis. JAMA Ophthalmol. 2021;139:753–61.
Dhingra H, Arya D, Taluja A, Das S, Mahajan A. A study analyzing the health-related quality of life of retinoblastoma survivors in India. Ind J Ophthalmol. 2021;69:1482–6.
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Support provided in part by the Eye Tumor Research Foundation, Philadelphia, PA (CLS). The funders had no role in the design and conduct of the study, in the collection, analysis and interpretation of the data, and in the preparation, review or approval of the manuscript. CLS has had full access to all the data in the study and takes responsibility for the integrity of the data.
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CLS, ZB: Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work. CS, ZB, AL, AMVS, AS, SEL, JAS: Drafting the work or revising it critically for important intellectual content. Final approval of the version to be published. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. AL, AMVS, AS, SEL, JAS: Substantial contributions to the interpretation of data for the work.
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Shields, C.L., Bas, Z., Laiton, A. et al. Retinoblastoma: emerging concepts in genetics, global disease burden, chemotherapy outcomes, and psychological impact. Eye 37, 815–822 (2023). https://doi.org/10.1038/s41433-022-01980-0
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DOI: https://doi.org/10.1038/s41433-022-01980-0
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