The status and progress of intravitreal chemotherapy for resistant or recurrent retinoblastoma_Chinese Journal of Ocular Fundus Diseases

Authors：

GaoXiang ,  WangHaiyan , WangYusheng

Department of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Eye Institute of Chinese PLA, Xi'an 710032, China;

Corresponding author：

WangHaiyan, Email: whyeye@126.com

Keywords：

Retinoblastoma/drug therapy; Chemotherapy; cancer; regional perfusion; Intravitreal injections; Review

DOI：

10.3760/cma.j.issn.1005-1015.2016.04.028

Video：

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Nowadays, one of the most challenging aspects of retinoblastoma (RB) therapy is how to control the resistant or recurrent viable vitreous seeds, for which intravenous chemotherapy appears to be ineffective. Recently, intravitreal chemotherapy offers another option to control advanced stage and vitreous seeds of RB, and may be a promising new approach to RB therapy. However, intravitreal injection for RB patients raises considerable controversy due to concerns of possible extraocular extension along the injection route, and should not replace the primary standard of care for bilateral RB or group E eyes of RB. Close follow-up and further studies are needed to determine appropriate indications, to determine the effective drugs and concentrations, to optimize RB therapy protocols and to investigate the relationship between long-term efficacy and toxicities.

Citation： GaoXiang, WangHaiyan, WangYusheng. The status and progress of intravitreal chemotherapy for resistant or recurrent retinoblastoma. Chinese Journal of Ocular Fundus Diseases, 2016, 32(4): 449-453. doi: 10.3760/cma.j.issn.1005-1015.2016.04.028 Copy

1.	Gallie BL, Budning A, DeBoer G,et al.Chemotherapy with focal therapy can cure intraocular retinoblastoma without radiotherapy[J].Arch Ophthalmol,1996,114(11):1321-1328.
2.	Murphree AL, Villablanca JG, Deegan WF 3rd,et al.Chemotherapy plus local treatment in the management of intraocular retinoblastoma[J].Arch Ophthalmol,1996, 114(11):1348-1356.
3.	Abramson DH, Beaverson K, Sangani P,et al.Screening for retinoblastoma:presenting signs as prognosticators of patient and ocular survival[J].Pediatrics, 2003,112(6 Pt 1):1248-1255.
4.	Shields CL, Bianciotto CG, Jabbour P,et al.Intra-arterial chemotherapy for retinoblastoma:report No. 1, control of retinal tumors, subretinal seeds, and vitreous seeds[J].Arch Ophthalmol,2011,129(11):1399-1406. DOI:10.1001/archophthalmol.2011.150.
5.	Kaneko A, Suzuki S.Eye-preservation treatment of retinoblastoma with vitreous seeding[J].Jpn J Clin Oncol,2003,33(12):601-607.
6.	Kivelä T, Eskelin S, Paloheimo M.Intravitreal methotrexate for retinoblastoma[J].Ophthalmology,2011,118(8):1689. DOI:10.1016/j.ophtha.2011.02.005.
7.	Suzuki S, Aihara Y, Fujiwara M, et al. Intravitreal injection of melphalan for intraocular retinoblastoma[J]. Jpn J Ophthalmol,2015,59(3):164-172. DOI:10.1007/s10384-015-0378-0.
8.	Shields CL, Mashayekhi A, Au AK, et al.The International Classification of Retinoblastoma predicts chemoreduction success[J]. Ophthalmology, 2006, 113(12):2276-2280.
9.	Shields CL, Ramasubramanian A, Thangappan A,et al.Chemoreduction for group E retinoblastoma:comparison of chemoreduction alone versus chemoreduction plus low-dose external radiotherapy in 76 eyes[J].Ophthalmology,2009,116(3):544-551. DOI:10.1016/j.ophtha.2008.10.014.
10.	Shields CL, Fulco EM, Arias JD,et al.Retinoblastoma frontiers with intravenous, intra-arterial, periocular, and intravitreal chemotherapy[J].Eye (Lond),2013, 27(2):253-264. DOI:10.1038/eye.2012.175.
11.	Shields CL, Lally SE, Leahey AM, et al. Targeted retinoblastoma management:when to use intravenous, intra-arterial, periocular, and intravitreal chemotherapy[J]. Curr Opin Ophthalmol, 2014,25(5):374-385. 10.1097/ICU.0000000000000091.
12.	Munier FL, Soliman S, Moulin AP, et al. Profiling safety of intravitreal injections for retinoblastoma using an anti-reflux procedure and sterilisation of the needle track[J].Br J Ophthalmol,2012,96(8):1084-1087. DOI:10.1136/bjophthalmol-2011-301016.
13.	Ericson L, Karlberg B, Rosengren BH.Trials of intravitreal injections of chemotherapeutic agents in rabbits[J].Acta Ophthalmol (Copenh),1964,42(4):721-726.
14.	Inomata M, Kaneko A.Chemosensitivity profiles of primary and cultured human retinoblastoma cells in a human tumor clonogenic assay[J].Jpn J Cancer Res,198778(8):858-868.
15.	Ueda M, Tanabe J, Inomata M,et al.Study on conservative treatment of retinoblastoma——effect of intravitreal injection of melphalan on the rabbit retina[J].Nippon Ganka Gakkai Zasshi, 1995, 99(11):1230-1235.
16.	Munier FL, Gaillard MC, Balmer A,et al.Intravitreal chemotherapy for vitreous seeding in retinoblastoma:recent advances and perspectives[J].Saudi J Ophthalmol, 2013,27(3):147-150. DOI:10.1016/j.sjopt.2013.06.003.
17.	Ghassemi F, Shields CL.Intravitreal melphalan for refractory or recurrent vitreous seeding from retinoblastoma[J].Arch Ophthalmol, 2012,130(10):1268-1271. DOI:10.1001/archophthalmol.2012.1983.
18.	Manjandavida FP, Shields CL.The role of intravitreal chemotherapy for retinoblastoma[J]. Indian J Ophthalmol, 2015,63(2):141-145. DOI:10.4103/0301-4738.154390.
19.	Shields CL, Manjandavida FP, Arepalli S, et al. Intravitreal melphalan for persistent or recurrent retinoblastoma vitreous seeds:preliminary results[J]. JAMA Ophthalmol, 2014, 132(3):319-325. DOI:10.1001/jamaophthalmol.2013.7666.
20.	Munier FL. Classification and management of seeds in retinoblastoma. Ellsworth Lecture Ghent August 24th 2013[J].Ophthalmic Genet,2014,35(4):193-207. DOI:10.3109/13816810.2014.973045.
21.	Francis JH, Abramson DH, Gaillard MC,et al.The classification of vitreous seeds in retinoblastoma and response to intravitreal melphalan[J].Ophthalmology,2015,122(6):1173-1179. DOI:10.1016/j.ophtha.2015.01.017.
22.	Schaiquevich P, Carcaboso AM, Buitrago E, et al. Ocular pharmacology of topotecan and its activity in retinoblastoma[J]. Retina,2014,34(9):1719-1727. DOI:10.1097/IAE.0000000000000253.
23.	Francis JH, Marr BP, Schaiquevich P, et al.Properties and clinical utility of topotecan fluorescence:uses for retinoblastoma[J].Br J Ophthalmol,2015,99(10):1320-1322. DOI:10.1136/bjophthalmol-2015-306633.
24.	Buitrago E, Del Sole MJ, Torbidoni A,et al.Ocular and systemic toxicity of intravitreal topotecan in rabbits for potential treatment of retinoblastoma[J].Exp Eye Res,2013,108:103-109. DOI:10.1016/j.exer.2013.01.002.
25.	Ghassemi F, Shields CL, Ghadimi H,et al.Combined intravitreal melphalan and topotecan for refractory or recurrent vitreous seeding from retinoblastoma[J].JAMA Ophthalmol, 2014,132(8):936-941. DOI:10.1001/jamaophthalmol.2014.414.
26.	Ghassemi F, Amoli FA.Pathological findings in enucleated eyes after intravitreal melphalan injection[J].Int Ophthalmol,2014,34(3):533-540. DOI:10.1007/s10792-013-9851-2.
27.	侯宪如, 程湧, 张琦, 等. 玻璃体腔注射卡铂联合贝伐单抗治疗难治型视网膜母细胞瘤的疗效观察[J]. 中华眼科杂志, 2015, 51(2):126-129.DOI:10.3760/cma.j.issn.0412-4081.2015.02.013. Hou XR,Cheng Y,Zhang Q,et al.Efficacy of intravitreal carboplatin plus bevacizumab in refractory retinoblastoma[J].Chin J Ophthalmol,2015, 51(2):126-129.DOI:10.3760/cma.j.issn.0412-4081.2015.02.013.
28.	Smith SJ, Pulido JS, Salomão DR,et al.Combined intravitreal and subconjunctival carboplatin for retinoblastoma with vitreous seeds[J].Br J Ophthalmol,2012, 96(8):1073-1077. DOI:10.1136/bjophthalmol-2011-300829.
29.	Chévez-Barrios P, Chintagumpala M, Mieler W,et al.Response of retinoblastoma with vitreous tumor seeding to adenovirus-mediated delivery of thymidine kinase followed by ganciclovir[J].J Clin Oncol,2005,23(31):7927-7935.
30.	Shih CS, Laurie N, Holzmacher J, et al. AAV-mediated local delivery of interferon-beta for the treatment of retinoblastoma in preclinical models[J]. Neuromolecular Med,2009,11(1):43-52. DOI:10.1007/s12017-009-8059-0.
31.	Harbour JW, Worley L, Ma D, et al. Transducible peptide therapy for uveal melanoma and retinoblastoma[J]. Arch ophthalmol, 2002, 120(10):1341-1346.
32.	Francis JH, Schaiquevich P, Buitrago E, et al. Local and systemic toxicity of intravitreal melphalan for vitreous seeding in retinoblastoma:a preclinical and clinical study[J]. Ophthalmology,2014, 121(9):1810-1817.DOI:10.1016/j.ophtha.2014.03.028.
33.	Smith SJ, Smith BD. Evaluating the risk of extraocular tumour spread following intravitreal injection therapy for retinoblastoma:a systematic review[J]. Br J Ophthalmol,2013, 97(10):1231-1236. DOI:10.1136/bjophthalmol-2013-303188.

1. Gallie BL, Budning A, DeBoer G,et al.Chemotherapy with focal therapy can cure intraocular retinoblastoma without radiotherapy[J].Arch Ophthalmol,1996,114(11):1321-1328.
2. Murphree AL, Villablanca JG, Deegan WF 3rd,et al.Chemotherapy plus local treatment in the management of intraocular retinoblastoma[J].Arch Ophthalmol,1996, 114(11):1348-1356.
3. Abramson DH, Beaverson K, Sangani P,et al.Screening for retinoblastoma:presenting signs as prognosticators of patient and ocular survival[J].Pediatrics, 2003,112(6 Pt 1):1248-1255.
4. Shields CL, Bianciotto CG, Jabbour P,et al.Intra-arterial chemotherapy for retinoblastoma:report No. 1, control of retinal tumors, subretinal seeds, and vitreous seeds[J].Arch Ophthalmol,2011,129(11):1399-1406. DOI:10.1001/archophthalmol.2011.150.
5. Kaneko A, Suzuki S.Eye-preservation treatment of retinoblastoma with vitreous seeding[J].Jpn J Clin Oncol,2003,33(12):601-607.
6. Kivelä T, Eskelin S, Paloheimo M.Intravitreal methotrexate for retinoblastoma[J].Ophthalmology,2011,118(8):1689. DOI:10.1016/j.ophtha.2011.02.005.
7. Suzuki S, Aihara Y, Fujiwara M, et al. Intravitreal injection of melphalan for intraocular retinoblastoma[J]. Jpn J Ophthalmol,2015,59(3):164-172. DOI:10.1007/s10384-015-0378-0.
8. Shields CL, Mashayekhi A, Au AK, et al.The International Classification of Retinoblastoma predicts chemoreduction success[J]. Ophthalmology, 2006, 113(12):2276-2280.
9. Shields CL, Ramasubramanian A, Thangappan A,et al.Chemoreduction for group E retinoblastoma:comparison of chemoreduction alone versus chemoreduction plus low-dose external radiotherapy in 76 eyes[J].Ophthalmology,2009,116(3):544-551. DOI:10.1016/j.ophtha.2008.10.014.
10. Shields CL, Fulco EM, Arias JD,et al.Retinoblastoma frontiers with intravenous, intra-arterial, periocular, and intravitreal chemotherapy[J].Eye (Lond),2013, 27(2):253-264. DOI:10.1038/eye.2012.175.
11. Shields CL, Lally SE, Leahey AM, et al. Targeted retinoblastoma management:when to use intravenous, intra-arterial, periocular, and intravitreal chemotherapy[J]. Curr Opin Ophthalmol, 2014,25(5):374-385. 10.1097/ICU.0000000000000091.
12. Munier FL, Soliman S, Moulin AP, et al. Profiling safety of intravitreal injections for retinoblastoma using an anti-reflux procedure and sterilisation of the needle track[J].Br J Ophthalmol,2012,96(8):1084-1087. DOI:10.1136/bjophthalmol-2011-301016.
13. Ericson L, Karlberg B, Rosengren BH.Trials of intravitreal injections of chemotherapeutic agents in rabbits[J].Acta Ophthalmol (Copenh),1964,42(4):721-726.
14. Inomata M, Kaneko A.Chemosensitivity profiles of primary and cultured human retinoblastoma cells in a human tumor clonogenic assay[J].Jpn J Cancer Res,198778(8):858-868.
15. Ueda M, Tanabe J, Inomata M,et al.Study on conservative treatment of retinoblastoma——effect of intravitreal injection of melphalan on the rabbit retina[J].Nippon Ganka Gakkai Zasshi, 1995, 99(11):1230-1235.
16. Munier FL, Gaillard MC, Balmer A,et al.Intravitreal chemotherapy for vitreous seeding in retinoblastoma:recent advances and perspectives[J].Saudi J Ophthalmol, 2013,27(3):147-150. DOI:10.1016/j.sjopt.2013.06.003.
17. Ghassemi F, Shields CL.Intravitreal melphalan for refractory or recurrent vitreous seeding from retinoblastoma[J].Arch Ophthalmol, 2012,130(10):1268-1271. DOI:10.1001/archophthalmol.2012.1983.
18. Manjandavida FP, Shields CL.The role of intravitreal chemotherapy for retinoblastoma[J]. Indian J Ophthalmol, 2015,63(2):141-145. DOI:10.4103/0301-4738.154390.
19. Shields CL, Manjandavida FP, Arepalli S, et al. Intravitreal melphalan for persistent or recurrent retinoblastoma vitreous seeds:preliminary results[J]. JAMA Ophthalmol, 2014, 132(3):319-325. DOI:10.1001/jamaophthalmol.2013.7666.
20. Munier FL. Classification and management of seeds in retinoblastoma. Ellsworth Lecture Ghent August 24th 2013[J].Ophthalmic Genet,2014,35(4):193-207. DOI:10.3109/13816810.2014.973045.
21. Francis JH, Abramson DH, Gaillard MC,et al.The classification of vitreous seeds in retinoblastoma and response to intravitreal melphalan[J].Ophthalmology,2015,122(6):1173-1179. DOI:10.1016/j.ophtha.2015.01.017.
22. Schaiquevich P, Carcaboso AM, Buitrago E, et al. Ocular pharmacology of topotecan and its activity in retinoblastoma[J]. Retina,2014,34(9):1719-1727. DOI:10.1097/IAE.0000000000000253.
23. Francis JH, Marr BP, Schaiquevich P, et al.Properties and clinical utility of topotecan fluorescence:uses for retinoblastoma[J].Br J Ophthalmol,2015,99(10):1320-1322. DOI:10.1136/bjophthalmol-2015-306633.
24. Buitrago E, Del Sole MJ, Torbidoni A,et al.Ocular and systemic toxicity of intravitreal topotecan in rabbits for potential treatment of retinoblastoma[J].Exp Eye Res,2013,108:103-109. DOI:10.1016/j.exer.2013.01.002.
25. Ghassemi F, Shields CL, Ghadimi H,et al.Combined intravitreal melphalan and topotecan for refractory or recurrent vitreous seeding from retinoblastoma[J].JAMA Ophthalmol, 2014,132(8):936-941. DOI:10.1001/jamaophthalmol.2014.414.
26. Ghassemi F, Amoli FA.Pathological findings in enucleated eyes after intravitreal melphalan injection[J].Int Ophthalmol,2014,34(3):533-540. DOI:10.1007/s10792-013-9851-2.
27. 侯宪如, 程湧, 张琦, 等. 玻璃体腔注射卡铂联合贝伐单抗治疗难治型视网膜母细胞瘤的疗效观察[J]. 中华眼科杂志, 2015, 51(2):126-129.DOI:10.3760/cma.j.issn.0412-4081.2015.02.013. Hou XR,Cheng Y,Zhang Q,et al.Efficacy of intravitreal carboplatin plus bevacizumab in refractory retinoblastoma[J].Chin J Ophthalmol,2015, 51(2):126-129.DOI:10.3760/cma.j.issn.0412-4081.2015.02.013.
28. Smith SJ, Pulido JS, Salomão DR,et al.Combined intravitreal and subconjunctival carboplatin for retinoblastoma with vitreous seeds[J].Br J Ophthalmol,2012, 96(8):1073-1077. DOI:10.1136/bjophthalmol-2011-300829.
29. Chévez-Barrios P, Chintagumpala M, Mieler W,et al.Response of retinoblastoma with vitreous tumor seeding to adenovirus-mediated delivery of thymidine kinase followed by ganciclovir[J].J Clin Oncol,2005,23(31):7927-7935.
30. Shih CS, Laurie N, Holzmacher J, et al. AAV-mediated local delivery of interferon-beta for the treatment of retinoblastoma in preclinical models[J]. Neuromolecular Med,2009,11(1):43-52. DOI:10.1007/s12017-009-8059-0.
31. Harbour JW, Worley L, Ma D, et al. Transducible peptide therapy for uveal melanoma and retinoblastoma[J]. Arch ophthalmol, 2002, 120(10):1341-1346.
32. Francis JH, Schaiquevich P, Buitrago E, et al. Local and systemic toxicity of intravitreal melphalan for vitreous seeding in retinoblastoma:a preclinical and clinical study[J]. Ophthalmology,2014, 121(9):1810-1817.DOI:10.1016/j.ophtha.2014.03.028.
33. Smith SJ, Smith BD. Evaluating the risk of extraocular tumour spread following intravitreal injection therapy for retinoblastoma:a systematic review[J]. Br J Ophthalmol,2013, 97(10):1231-1236. DOI:10.1136/bjophthalmol-2013-303188.

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