Jasmine H Francis1, Scott E Brodie2, Brian Marr3, Emily C Zabor4, Ijah Mondesire-Crump5, David H Abramson3. 1. Ophthalmic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York; Weill-Cornell Medical Center, New York, New York. Electronic address: francij1@mskcc.org. 2. Ophthalmic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York; Icahn School of Medicine at Mount Sinai, New York, New York. 3. Ophthalmic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York; Weill-Cornell Medical Center, New York, New York. 4. Department of Epidemiology & Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York. 5. Ophthalmic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York.
Abstract
PURPOSE: To investigate the efficacy and toxicity of intravitreous melphalan for treatment of retinoblastoma, as a single agent or with concomitant topotecan. PARTICIPANTS: A total of 130 eyes of 120 patients with retinoblastoma receiving 630 intravitreous (melphalan, topotecan) or topotecan periocular injections. A total of 83 (64%) of these eyes were treated with concomitant ophthalmic artery chemosurgery (OAC). DESIGN: Retrospective cohort study. METHODS: Indirect ophthalmoscopy and clinical imaging were used to evaluate clinical response. Ocular survival and disease-free survival were estimated using Kaplan-Meier methods in 130 eyes. Ocular toxicity was evaluated by clinical findings and electroretinography (ERG) on 244 evaluable injections in 63 patients using 30-Hz flicker responses. Analysis was performed using linear mixed effects models with a random intercept and slope for each patient and a fixed effect for number of injections, in addition to any other fixed effect of interest. MAIN OUTCOME MEASURES: Ocular survival, disease-free survival, ERG: peak-to-peak ERG amplitudes in response to 30-Hz photopic flicker stimulation. RESULTS: There were no disease- or treatment-related deaths, and no patient developed externalization of tumor or metastatic disease. Two-year Kaplan-Meier estimates of ocular survival and disease-free survival were 94.2% (95% confidence interval, 89.2-99.4) and 86.2% (95% confidence interval, 78.7-94.5), respectively. There was a significant association between the number of injections and diminished ERG responses, such that on average each intravitreous melphalan injection was associated with a 5.3-μV decrease in ERG amplitude (P < 0.001). Concomitant intra-arterial chemotherapy (P = 0.01) and greater inherent ocular pigment also were significantly associated with a reduction in ERG (P = 0.045). Patient age and weight, new injection site location, addition of topotecan, concomitant focal treatment, and time interval between injections were not significantly associated with toxicity. CONCLUSIONS: Intravitreous melphalan is an effective treatment for vitreous seeding in retinoblastoma, resulting in high rates of ocular survival and disease-free survival. However, in this study, each injection of melphalan was associated, on average, with a decrement in ERG response. The findings suggest increased toxicity (1) when OAC is given within 1 week of the intravitreous injection and (2) in more deeply pigmented eyes.
PURPOSE: To investigate the efficacy and toxicity of intravitreous melphalan for treatment of retinoblastoma, as a single agent or with concomitant topotecan. PARTICIPANTS: A total of 130 eyes of 120 patients with retinoblastoma receiving 630 intravitreous (melphalan, topotecan) or topotecan periocular injections. A total of 83 (64%) of these eyes were treated with concomitant ophthalmic artery chemosurgery (OAC). DESIGN: Retrospective cohort study. METHODS: Indirect ophthalmoscopy and clinical imaging were used to evaluate clinical response. Ocular survival and disease-free survival were estimated using Kaplan-Meier methods in 130 eyes. Ocular toxicity was evaluated by clinical findings and electroretinography (ERG) on 244 evaluable injections in 63 patients using 30-Hz flicker responses. Analysis was performed using linear mixed effects models with a random intercept and slope for each patient and a fixed effect for number of injections, in addition to any other fixed effect of interest. MAIN OUTCOME MEASURES: Ocular survival, disease-free survival, ERG: peak-to-peak ERG amplitudes in response to 30-Hz photopic flicker stimulation. RESULTS: There were no disease- or treatment-related deaths, and no patient developed externalization of tumor or metastatic disease. Two-year Kaplan-Meier estimates of ocular survival and disease-free survival were 94.2% (95% confidence interval, 89.2-99.4) and 86.2% (95% confidence interval, 78.7-94.5), respectively. There was a significant association between the number of injections and diminished ERG responses, such that on average each intravitreous melphalan injection was associated with a 5.3-μV decrease in ERG amplitude (P < 0.001). Concomitant intra-arterial chemotherapy (P = 0.01) and greater inherent ocular pigment also were significantly associated with a reduction in ERG (P = 0.045). Patient age and weight, new injection site location, addition of topotecan, concomitant focal treatment, and time interval between injections were not significantly associated with toxicity. CONCLUSIONS: Intravitreous melphalan is an effective treatment for vitreous seeding in retinoblastoma, resulting in high rates of ocular survival and disease-free survival. However, in this study, each injection of melphalan was associated, on average, with a decrement in ERG response. The findings suggest increased toxicity (1) when OAC is given within 1 week of the intravitreous injection and (2) in more deeply pigmented eyes.
Authors: Carol L Shields; Fairooz P Manjandavida; Sruthi Arepalli; Swathi Kaliki; Sara E Lally; Jerry A Shields Journal: JAMA Ophthalmol Date: 2014-03 Impact factor: 7.389
Authors: Scott E Brodie; Yannis M Paulus; Mrinali Patel; Y Pierre Gobin; Ira J Dunkel; Brian P Marr; David H Abramson Journal: Br J Ophthalmol Date: 2012-03-18 Impact factor: 4.638
Authors: Catherine Y Liu; Gowtham Jonna; Jasmine H Francis; Brian P Marr; David H Abramson; Scott E Brodie Journal: Doc Ophthalmol Date: 2013-11-09 Impact factor: 2.379
Authors: Jasmine H Francis; Paula Schaiquevich; Emiliano Buitrago; María José Del Sole; Gustavo Zapata; J Oscar Croxatto; Brian P Marr; Scott E Brodie; Alejandro Berra; Guillermo L Chantada; David H Abramson Journal: Ophthalmology Date: 2014-05-10 Impact factor: 12.079
Authors: Jasmine H Francis; David H Abramson; Y Pierre Gobin; Brian P Marr; Ira J Dunkel; Elyn R Riedel; Scott E Brodie Journal: PLoS One Date: 2014-01-20 Impact factor: 3.240
Authors: Jasmine H Francis; Duncan Berry; David H Abramson; Christopher A Barker; Chris Bergstrom; Hakan Demirci; Michael Engelbert; Hans Grossniklaus; Baker Hubbard; Codrin E Iacob; Korey Jaben; Madhavi Kurli; Michael A Postow; Jedd D Wolchok; Ivana K Kim; Jill R Wells Journal: Ophthalmology Date: 2019-09-24 Impact factor: 12.079
Authors: David H Abramson; Xunda Ji; Jasmine H Francis; Federica Catalanotti; Scott E Brodie; Larissa Habib Journal: Br J Ophthalmol Date: 2018-06-06 Impact factor: 4.638
Authors: Liya Xu; Ashley Polski; Rishvanth K Prabakar; Mark W Reid; Patricia Chevez-Barrios; Rima Jubran; Jonathan W Kim; Peter Kuhn; David Cobrinik; James Hicks; Jesse L Berry Journal: Mol Cancer Res Date: 2020-05-20 Impact factor: 5.852
Authors: Carley M Bogan; Janene M Pierce; Stephanie D Doss; Yuankai K Tao; Sheau-Chiann Chen; Kelli L Boyd; Albert Liao; Terry Hsieh; David H Abramson; Jasmine H Francis; Debra L Friedman; Ann Richmond; Anthony B Daniels Journal: Exp Eye Res Date: 2021-01-11 Impact factor: 3.467