33 results on '"Abramson, David"'
Search Results
2. Successful Treatment of Massive Choroidal Invasion in Retinoblastoma with Intra-arterial Chemotherapy (Ophthalmic Artery Chemosurgery).
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Abramson DH, Gobin YP, Dunkel IJ, and Francis JH
- Subjects
- Antineoplastic Agents, Alkylating administration & dosage, Humans, Infant, Injections, Intra-Arterial methods, Ophthalmic Artery, Retinoblastoma pathology, Choroid pathology, Melphalan administration & dosage, Neoplasm Invasiveness pathology, Retinoblastoma drug therapy
- Published
- 2021
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3. Intra-arterial Melphalan for Neurologic Non-Langerhans Cell Histiocytosis.
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Francis JH, Gobin YP, Alshiekh Nasany R, Knopman J, Ulaner GA, Panageas KS, Hatzoglou V, Salvaggio K, Abramson DH, Patsalides A, and Diamond EL
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- Adult, Antineoplastic Agents, Alkylating administration & dosage, Female, Histiocytosis, Sinus drug therapy, Humans, Infusions, Intra-Arterial, Male, Melphalan administration & dosage, Middle Aged, Antineoplastic Agents, Alkylating pharmacology, Histiocytosis, Non-Langerhans-Cell drug therapy, Melphalan pharmacology
- Published
- 2021
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4. Intravitreal melphalan hydrochloride vs propylene glycol-free melphalan for retinoblastoma vitreous seeds: Efficacy, toxicity and stability in rabbits models and patients.
- Author
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Bogan CM, Pierce JM, Doss SD, Tao YK, Chen SC, Boyd KL, Liao A, Hsieh T, Abramson DH, Francis JH, Friedman DL, Richmond A, and Daniels AB
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- Animals, Antineoplastic Agents, Alkylating toxicity, Electroretinography, Female, Fluorescein Angiography, Humans, In Situ Nick-End Labeling, Infant, Intravitreal Injections, Male, Melphalan toxicity, Neoplasm Seeding, Pharmaceutical Preparations, Rabbits, Retina physiopathology, Retinal Neoplasms pathology, Retinoblastoma pathology, Retrospective Studies, Tomography, Optical Coherence, Treatment Outcome, Tumor Cells, Cultured, Xenograft Model Antitumor Assays, Antineoplastic Agents, Alkylating therapeutic use, Melphalan therapeutic use, Retinal Neoplasms drug therapy, Retinoblastoma drug therapy, Vitreous Body pathology
- Abstract
The use of intravitreal chemotherapy has revolutionized the treatment of advanced intraocular retinoblastoma, as intravitreal melphalan has enabled difficult-to-treat vitreous tumor seeds to be controlled, leading to many more eyes being saved. However, melphalan hydrochloride (MH) degrades rapidly in solution, increasing logistical complexity with respect to time between medication preparation and administration for intravitreal administration under anesthesia for retinoblastoma. A new propylene glycol-free melphalan (PGFM) formulation has greater stability and could therefore improve access and adoption of intravitreal chemotherapy, allowing more children to retain their eye(s). We compared the efficacy and toxicity of both formulations, using our rabbit xenograft model and clinical patient experience. Three weekly 12.5 μg intravitreal injections of MH or PGFM (right eye), and saline (left eye), were administered to immunosuppressed rabbits harboring human WERI-Rb1 vitreous seed xenografts. Residual live cells were quantified directly, and viability determined by TUNEL staining. Vitreous seeds were reduced 91% by PGFM (p = 0.009), and 88% by MH (p = 0.004; PGFM vs. MH: p = 0.68). All residual cells were TUNEL-positive (non-viable). In separate experiments to assess toxicity, three weekly 12.5 μg injections of MH, PGFM, or saline were administered to non-tumor-bearing rabbits. Serial electroretinography, optical coherence tomography (OCT) and OCT-angiography were performed. PGFM and MH both caused equivalent reductions in electroretinography amplitudes, and loss of retinal microvasculature on OCT-angiography. The pattern of retinal degeneration observed on histopathology suggested that segmental retinal toxicity associated with all melphalan formulations was due to a vitreous concentration gradient-effect. Efficacy and toxicity were assessed for PGFM given immediately (within 1 h of reconstitution) vs. 4 h after reconstitution. Immediate- and delayed-administration of PGFM showed equivalent efficacy and toxicity. In addition, we evaluated efficacy and toxicity in patients (205 eyes) with retinoblastoma vitreous seeds, who were treated with a total of 833 intravitreal injections of either MH or PGFM as standard of care. Of these, we analyzed 118 MH and 131 PGFM monotherapy injections in whom serial ERG measurements were available to model retinal toxicity. Both MH and PGFM caused reductions in electroretinography amplitudes, but with no statistical difference between formulations. Comparing those patient eyes treated exclusively with PGFM versus those treated exclusively with MH, efficacy for tumor control and globe salvage was equivalent (PGFM vs. MH: 96.2% vs. 93.8%, p = 0.56), but PGFM-treated eyes received fewer injections than MH-treated eyes (average 3.2 ± 1.9 vs. 6.4 ± 2.1 injections, p < 0.0001). Taken together, these rabbit experiments and our clinical experience in retinoblastoma patients demonstrate that MH and PGFM have equivalent efficacy and toxicity. PGFM was more stable, with no decreased efficacy or increased toxicity even 4 h after reconstitution. We therefore now use PGFM over traditional MH for our patients for intravitreal treatment of retinoblastoma., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2021
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5. TOXICITY AND EFFICACY OF INTRAVITREAL MELPHALAN FOR RETINOBLASTOMA: 25 µg Versus 30 µg.
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Liao A, Hsieh T, Francis JH, Lavery JA, Mauguen A, Brodie SE, and Abramson DH
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- Adolescent, Antineoplastic Agents, Alkylating administration & dosage, Antineoplastic Agents, Alkylating adverse effects, Child, Child, Preschool, Electroretinography, Female, Follow-Up Studies, Humans, Infant, Infant, Newborn, Intravitreal Injections, Male, Melphalan adverse effects, Neoplasm Seeding, Retinal Neoplasms diagnosis, Retinoblastoma diagnosis, Retrospective Studies, Treatment Outcome, Melphalan administration & dosage, Retinal Neoplasms drug therapy, Retinoblastoma drug therapy, Vitreous Body pathology
- Abstract
Purpose: To compare retinal toxicity as measured by electroretinogram, ocular, and patient survival in retinoblastoma treated with intravitreal melphalan at two concentrations (25 vs. 30 µg)., Methods: Single-center, retrospective analysis of retinoblastoma eyes receiving 25-µg or 30-µg intravitreal melphalan from September 2012 to January 2019. Ocular toxicity was measured by electroretinogram of evaluable injections in 449 injections in 136 eyes. A repeated-measures linear mixed model with a random intercept and slope was applied to account for repeated measures for each eye., Results: Average decline in electroretinogram after each additional injection was -4.9 µV (95% confidence interval -6.3 to -3.4); electroretinogram declined by -4.6 µV (95% confidence interval -7.0 to -2.2) after 25-µg injections and -5.2 µV (95% confidence interval -6.6 to -3.8) after 30-µg injections (P = 0.66). Injection at a new clock site hour was associated with a -3.91-µV lower average (95% confidence interval -7.8 to -0.04)., Conclusion: Electroretinogram-measured toxicity in retinoblastoma eyes treated with intravitreal injections was not found to be different across 25-µg and 30-µg injections. There were no cases of extraocular extension or metastatic deaths in our patient population.
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- 2021
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6. Comparison of efficacy and toxicity of intravitreal melphalan formulations for retinoblastoma.
- Author
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Hsieh T, Liao A, Francis JH, Lavery JA, Mauguen A, Brodie SE, and Abramson DH
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- Adolescent, Antineoplastic Agents, Alkylating administration & dosage, Antineoplastic Agents, Alkylating adverse effects, Child, Child, Preschool, Humans, Infant, Intravitreal Injections, Melphalan administration & dosage, Melphalan adverse effects, Retina drug effects, Treatment Outcome, Antineoplastic Agents, Alkylating therapeutic use, Melphalan therapeutic use, Retinal Neoplasms drug therapy, Retinoblastoma drug therapy
- Abstract
Objective: Intravitreal melphalan injections are commonly used in the treatment for intraocular retinoblastoma. This study compares retinal toxicity and ocular survival between two formulations, with and without propylene glycol (Alkeran vs. Evomela, respectively)., Methods: A retrospective cohort study of retinoblastoma patients who received intravitreal injections of Alkeran and Evomela at 30 μg from September 2012 to January 2019 at a single tertiary care center were enrolled. Retinal toxicity was measured using electroretinogram (ERG) and compared using a multivariate analysis of 338 injections in 101 eyes of 96 patients. Ocular survival of 163 eyes in 150 patients was compared across formulations using Cox proportional hazards model. Eyes were censored at the time a patient received a dose other than 30 μg., Results: Overall, ERG decline (mean, 95% CI) for each injection was -5.58 μV (-7.17, -3.99). No significant differences in ERG decrement were found between Alkeran (with alcohol) -5.52uV (-6.99, -4.05). and Evomela (without alcohol) -5.65uV (-8.31 to -2.98) formulations (p = 0.93). Ocular survival at 24 months was 93.6% (95% CI 86.2, 97.1) with alcohol and 91.7% (95% CI 53.9, 98.8) without alcohol. The hazard ratio (HR) for without vs with alcohol was 0.50 (95% CI 0.06 to 4.07); no significant difference in ocular survival was found between formulations (p = 0.52)., Conclusions and Relevance: No differences were found in retinal toxicity and ocular survival between 30 μg intravitreal injections of Alkeran or Evomela for intraocular retinoblastoma. Given the increased stability of Evomela, intravitreal treatment could be expanded to centers without the ability to supply Alkeran due to its shorter safety window; however, Alkeran is less expensive. For those with existing infrastructure, Alkeran is a comparable, cost-effective alternative., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2020
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7. Intravitreous Cutaneous Metastatic Melanoma in the Era of Checkpoint Inhibition: Unmasking and Masquerading.
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Francis JH, Berry D, Abramson DH, Barker CA, Bergstrom C, Demirci H, Engelbert M, Grossniklaus H, Hubbard B, Iacob CE, Jaben K, Kurli M, Postow MA, Wolchok JD, Kim IK, and Wells JR
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- Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Retrospective Studies, Young Adult, Melanoma, Cutaneous Malignant, Antineoplastic Agents, Alkylating therapeutic use, Eye Neoplasms drug therapy, Eye Neoplasms secondary, Immunotherapy methods, Melanoma pathology, Melphalan therapeutic use, Skin Neoplasms pathology, Vitreous Body pathology
- Abstract
Purpose: Cutaneous melanoma metastatic to the vitreous is very rare. This study investigated the clinical findings, treatment, and outcome of patients with metastatic cutaneous melanoma to the vitreous. Most patients received checkpoint inhibition for the treatment of systemic disease, and the significance of this was explored., Design: Multicenter, retrospective cohort study., Participants: Fourteen eyes of 11 patients with metastatic cutaneous melanoma to the vitreous., Methods: Clinical records, including fundus photography and ultrasound results, were reviewed retrospectively, and relevant data were recorded for each patient eye., Main Outcome Measures: Clinical features at presentation, ophthalmic and systemic treatments, and outcomes., Results: The median age at presentation of ophthalmic disease was 66 years (range, 23-88 years), and the median follow-up from diagnosis of ophthalmic disease was 23 months. Ten of 11 patients were treated with immune checkpoint inhibition at some point in the treatment course. The median time from starting immunotherapy to ocular symptoms was 17 months (range, 4.5-38 months). Half of eyes demonstrated amelanotic vitreous debris. Five eyes demonstrated elevated intraocular pressure, and 4 eyes demonstrated a retinal detachment. Six patients showed metastatic disease in the central nervous system. Ophthalmic treatment included external beam radiation (30-40 Gy) in 6 eyes, intravitreous melphalan (10-20 μg) in 4 eyes, enucleation of 1 eye, and local observation while receiving systemic treatment in 2 eyes. Three eyes received intravitreous bevacizumab for neovascularization. The final Snellen visual acuity ranged from 20/20 to no light perception., Conclusions: The differential diagnosis of vitreous debris in the context of metastatic cutaneous melanoma includes intravitreal metastasis, and this seems to be particularly apparent during this era of treatment with checkpoint inhibition. External beam radiation, intravitreous melphalan, and systemic checkpoint inhibition can be used in the treatment of ophthalmic disease. Neovascular glaucoma and retinal detachments may occur, and most eyes show poor visual potential. Approximately one quarter of patients demonstrated ocular disease that preceded central nervous system metastasis. Patients with visual symptoms or vitreous debris in the context of metastatic cutaneous melanoma would benefit from evaluation by an ophthalmic oncologist., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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8. Intravitreal chemotherapy in retinoblastoma: expanded use beyond intravitreal seeds.
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Abramson DH, Ji X, Francis JH, Catalanotti F, Brodie SE, and Habib L
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- Adolescent, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Alkylating administration & dosage, Child, Drug Implants, Electroretinography, Female, Follow-Up Studies, Humans, Incidence, Intravitreal Injections, Male, Middle Aged, Neoplasm Recurrence, Local epidemiology, Ophthalmoscopy, Retinal Neoplasms diagnosis, Retinoblastoma diagnosis, Retrospective Studies, Slit Lamp Microscopy, Treatment Outcome, United States epidemiology, Young Adult, Melphalan administration & dosage, Retinal Neoplasms drug therapy, Retinoblastoma drug therapy
- Abstract
Background/aims: Ophthalmic artery chemosurgery (OAC) has changed the face of retinoblastoma treatment and led to a higher rate of globe salvage. The introduction of intravitreal chemotherapy (IVitC) has further enhanced globe salvage with increased success in treatment of intravitreal seeds. Our group has seen success at treating non-vitreous disease that is refractory to OAC using IVitC. This study was undertaken to quantify and report on this success., Methods: A retrospective review was used to identify patients treated with IVitC for indications other than vitreous seeds from two centres. The indication, prior and concurrent treatment, response time and duration of treatment were documented. Kaplan-Meier estimates were used to evaluate ocular and recurrence-free survival. Ocular toxicity was evaluated using the 30 Hz flicker electroretinogram (ERG). Continuous and categorical variables were compared with Student's t-test and χ
2 test, respectively., Results: Fifty-six eyes from 52 retinoblastoma patients were identified. There were no disease-related or treatment-related deaths. One patient developed a second primary malignancy (pinealoblastoma) and subsequent leptomeningeal spread. Ninety-eight per cent of the eyes showed clinical regression. Recurrence was seen in 14.3%. Of the recurrences, five occurred in retinal tumours and three in subretinal seeds. The Kaplan-Meier estimated risk of recurrence in all patients treated was 83.5% (95% CI 7.9 to 14.1) at 10 months. The mean change in ERG over treatment course was -17.7 μV., Conclusions: Intravitreal chemotherapy is successful for the treatment of subretinal seeds and recurrent retinal tumours and could be considered as adjunctive therapy in globe-sparing treatment of retinoblastoma., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2019
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9. Retinal reattachment and ERG recovery after ophthalmic artery chemosurgery for advanced retinoblastoma in eyes with minimal baseline retinal function.
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Abdelhakim AH, Francis JH, Marr BP, Gobin YP, Abramson DH, and Brodie SE
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- Child, Disease-Free Survival, Electroretinography, Female, Humans, Infusions, Intra-Arterial, Male, Ophthalmic Artery surgery, Retinal Detachment pathology, Retinal Neoplasms pathology, Retinal Neoplasms physiopathology, Retinoblastoma pathology, Retinoblastoma physiopathology, Retrospective Studies, Salvage Therapy methods, Antineoplastic Agents administration & dosage, Melphalan administration & dosage, Retinal Neoplasms drug therapy, Retinoblastoma drug therapy
- Abstract
Aim: To report retinal function outcomes after ophthalmic artery chemosurgery (OAC) for advanced retinoblastoma (RB) in eyes with minimal pretreatment retinal function., Methods: For 72 advanced RB eyes with baseline electroretinograms (ERGs) indistinguishable from noise ('extinguished') or flicker ERG amplitudes <25 µV ('poor'), ERGs were obtained before OAC and at 3 months, 1 year and 2 years after OAC. Presence of baseline retinal detachments (RDs) and their subsequent resolution or persistence was also noted., Results: At 3 months, 1 year and 2 years post-OAC, 'extinguished' eyes showed 9/15, 4/11 and 2/6 detectable ERGs, respectively, and 'poor' eyes showed 19/55, 14/30 and 8/18 ERGs exceeding 25 μV, respectively. Correlations between baseline and post-OAC ERGs were poor; however, good correlation (R
2 ) existed between ERGs post-OAC at 3 months and 1 year (0.749), at 3 months and 2 years (0.773) and at 1 year and 2 years (0.771). Overall, 49/70 eyes presented with RD; 29 RDs resolved 3 months post-OAC, with an average ERG change of +20.6 μV. Eyes with persistent RD had an average ERG change of -2.2 μV. No eyes underwent ≥25 μV change without RD resolution., Conclusions: Minimal baseline ERGs do not preclude significant recovery of retinal function after OAC. Good correlation exists between ERG outcomes at 3 months and those at subsequent follow-ups, suggesting that ERG amplitudes at 3-month post-OAC can prognosticate longer term retinal function, and that improvement is durable. For eyes presenting with RD, RD resolution is necessary but not sufficient for significant (≥25 μV) increases in ERG amplitudes., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)- Published
- 2017
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10. Intraocular Pressure Changes Following Intravitreal Melphalan and Topotecan for the Treatment of Retinoblastoma With Vitreous Seeding.
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Karl MD, Francis JH, Iyer S, Marr B, and Abramson DH
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- Adolescent, Adult, Antineoplastic Agents, Alkylating administration & dosage, Dose-Response Relationship, Drug, Drug Therapy, Combination, Female, Humans, Intravitreal Injections, Male, Neoplasm Seeding, Retinal Neoplasms pathology, Retinal Neoplasms physiopathology, Retinoblastoma diagnosis, Retinoblastoma secondary, Retrospective Studies, Topoisomerase I Inhibitors administration & dosage, Treatment Outcome, Young Adult, Intraocular Pressure drug effects, Melphalan administration & dosage, Retinal Neoplasms drug therapy, Retinoblastoma drug therapy, Topotecan administration & dosage, Vitreous Body pathology
- Abstract
Purpose: To investigate the impact of intravitreal chemotherapy on intraocular pressure (IOP) in children with retinoblastoma., Methods: This was a retrospective study of 10 eyes of 10 patients with retinoblastoma (7 males, 3 females, mean age: 33.6 ± 9.4 months) with vitreous seeding injected with intravitreal melphalan and topotecan. IOP was measured with Tonopen (Reichert, Inc., Buffalo, NY) at baseline prior to injecting and then repeatedly following each intravitreal injection., Results: Mean pre-injection IOP was 8.2 ± 2.3 mm Hg (range: 4 to 12 mm Hg). Mean IOP 1 to 30 seconds after intravitreal melphalan (first injection) was 45.4 ± 14.3 mm Hg. The IOP of 89.5% of patients declined to 29 mm Hg or less in a mean 153.3 ± 97.5 seconds. Mean IOP 1 to 30 seconds after intravitreal topotecan (second injection) was 44.5 ± 11.0 mm Hg, which decreased to 31.0 ± 5.0 mm Hg by 150 seconds after injection. No significant relationship was found between age and post-injection IOP elevation. IOP exceeded the calculated mean arterial perfusion pressure in four encounters., Conclusions: Intravitreal chemotherapy caused a transient rise in IOP. Post-injection IOP elevations can reach levels that may exceed mean arterial pressure. [J Pediatr Ophthalmol Strabismus. 2017;54(3):185-190.]., (Copyright 2017, SLACK Incorporated.)
- Published
- 2017
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11. Efficacy and Toxicity of Intravitreous Chemotherapy for Retinoblastoma: Four-Year Experience.
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Francis JH, Brodie SE, Marr B, Zabor EC, Mondesire-Crump I, and Abramson DH
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- Antineoplastic Agents, Alkylating therapeutic use, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Child, Preschool, Cohort Studies, Disease-Free Survival, Female, Humans, Infant, Injections, Intraocular, Intravitreal Injections, Male, Melphalan therapeutic use, Ophthalmic Artery, Ophthalmoscopy, Retina physiopathology, Retinal Neoplasms pathology, Retinoblastoma pathology, Retrospective Studies, Topoisomerase I Inhibitors therapeutic use, Topotecan therapeutic use, Treatment Outcome, Vitreous Body pathology, Antineoplastic Agents, Alkylating toxicity, Electroretinography drug effects, Melphalan toxicity, Neoplasm Seeding, Retinal Neoplasms drug therapy, Retinoblastoma drug therapy, Vitreous Body drug effects
- 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., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
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12. OCULAR PHARMACOLOGY OF CHEMOTHERAPY FOR RETINOBLASTOMA.
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Schaiquevich P, Fabius AW, Francis JH, Chantada GL, and Abramson DH
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- Animals, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carboplatin administration & dosage, Carboplatin therapeutic use, Clinical Trials as Topic, Disease Models, Animal, Drug Evaluation, Preclinical, Humans, Infusions, Intra-Arterial, Injections, Intraocular, Melphalan administration & dosage, Melphalan pharmacokinetics, Topotecan administration & dosage, Topotecan therapeutic use, Antineoplastic Combined Chemotherapy Protocols pharmacokinetics, Carboplatin pharmacokinetics, Melphalan therapeutic use, Retinal Neoplasms drug therapy, Retinoblastoma drug therapy, Topotecan pharmacokinetics
- Abstract
Purpose: To review preclinical and clinical pharmacokinetic studies of the three most important chemotherapy drugs used for intraocular retinoblastoma and the contribution of the reported results to optimize treatment., Methods: Systemic review of pharmacokinetic studies identified by a literature search at Pubmed using the keywords carboplatin, melphalan, topotecan, intravitreal, ophthalmic artery chemosurgery, pharmacokinetics, and retinoblastoma., Results: A total of 21 studies were reviewed for assessing the preclinical and clinical pharmacokinetics of carboplatin, topotecan, and melphalan delivered by intravenous, periocular, ophthalmic artery, and intravitreal routes. Some preclinical studies were done before translation to the clinics. Others, despite encouraging preclinical data as reported for periocular topotecan did not correlate with clinical use. In addition, as was the case for melphalan after ophthalmic artery chemosurgery and despite nonfavorable preclinical information, some routes of drug delivery are clinically effective. Besides topotecan, complete knowledge of the pharmacokinetics of melphalan and carboplatin is still lacking., Conclusion: Pharmacokinetic knowledge of chemotherapy may aid to guide retinoblastoma treatment in favor of safety and efficacy. Nonetheless, results obtained in preclinical models should be translated with care to the clinics.
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- 2017
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13. INTRAVITREAL MELPHALAN AS SALVAGE THERAPY FOR REFRACTORY RETINAL AND SUBRETINAL RETINOBLASTOMA.
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Francis JH, Marr BP, Brodie SE, Gobin P, Dunkel IJ, and Abramson DH
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- Child, Preschool, Female, Humans, Infant, Intravitreal Injections, Male, Treatment Outcome, Antineoplastic Agents, Alkylating administration & dosage, Melphalan administration & dosage, Retinal Neoplasms drug therapy, Retinoblastoma drug therapy, Salvage Therapy methods
- Abstract
Purpose: This case series highlights the novel use of intravitreal melphalan for nonvitreous retinoblastoma. It assesses the efficacy and toxicity of intravitreal melphalan for nonvitreous retinoblastoma., Methods: This observational small case series investigates three patients treated with intravitreal melphalan for nonvitreous retinoblastoma that was refractory to multiple-course ophthalmic artery chemosurgery. Patients' demographics, response to treatment, and toxicity of treatment as clinically evaluated are measured by electroretinogram., Patients: Three eyes of three patients received a median of 7 weekly intravitreal melphalan injections (30 μg/0.07 cc) for persistent retinal or subretinal tumors refractory to treatment with multiple-course ophthalmic artery chemosurgery., Results: Eyes remain tumor free at a median of 14-month follow-up. One eye was enucleated because of a vitreous hemorrhage that obscured fundus details. One eye had extinguished electroretinogram recordings before injections and two eyes had a decrease in electroretinogram responses over the intravitreal treatment course. The eye with subretinal seeding demonstrated marked retinopathy by ophthalmoscopy and fluorescein angiography and one eye was enucleated because of the development of a vitreous hemorrhage., Conclusion: This small case series highlights that nonvitreous disease that is, refractory or persistent despite previous ophthalmic artery chemosurgery can regress with intravitreal melphalan. However, this treatment may result in retinal toxicity., Competing Interests: None of the authors have any financial disclosures or conflicts.
- Published
- 2016
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14. Reply.
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Francis JH, Abramson DH, Gaillard MC, Marr BP, Beck-Popovic M, and Munier FL
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- Humans, Antineoplastic Agents, Alkylating administration & dosage, Eye Neoplasms classification, Melphalan administration & dosage, Neoplasm Seeding, Retinal Neoplasms classification, Retinoblastoma classification, Vitreous Body drug effects, Vitreous Body pathology
- Published
- 2016
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15. Anterior Ocular Toxicity of Intravitreous Melphalan for Retinoblastoma.
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Francis JH, Marr BP, Brodie SE, and Abramson DH
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- Anterior Eye Segment diagnostic imaging, Anterior Eye Segment pathology, Child, Preschool, Eye Diseases diagnosis, Female, Humans, Infant, Intravitreal Injections, Male, Microscopy, Acoustic, Retinal Neoplasms pathology, Retinoblastoma pathology, Retrospective Studies, Tomography, Optical Coherence, Anterior Eye Segment drug effects, Antineoplastic Agents, Alkylating toxicity, Eye Diseases chemically induced, Melphalan toxicity, Retinal Neoplasms drug therapy, Retinoblastoma drug therapy
- Abstract
Importance: Intravitreous injections of melphalan hydrochloride are increasingly used in the treatment of vitreous seeding of retinoblastoma. Although this technique can save eyes otherwise destined for enucleation, ocular salvage may be accompanied by local toxic effects. Posterior segment toxic effects in this context are well established. This report describes the toxic effects on the anterior segment following intravitreous administration of melphalan., Observations: Our clinic cohort included 76 patients who received intravitreous injections of melphalan at Memorial Sloan Kettering Cancer Center from September 12, 2012, through April 15, 2015; data analysis was performed from April 15 through May 15, 2015. We report a series of 5 patients from this cohort who developed anterior segment toxic effects. These abnormalities were found at the injection site or within the meridian of the injection and included a traumatic cataract following an injection at an outside hospital, iris depigmentation and thinning, iris recession with retinal necrosis and hypotony, a filtering conjunctival bleb, and focal scleromalacia with localized pigmentation., Conclusions and Relevance: Intravitreous injection of melphalan may result in toxic effects on the anterior segment of the eye, in addition to retinal abnormalities, and appears to be more common in the meridian of the injection where the drug concentration is highest.
- Published
- 2015
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16. The classification of vitreous seeds in retinoblastoma and response to intravitreal melphalan.
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Francis JH, Abramson DH, Gaillard MC, Marr BP, Beck-Popovic M, and Munier FL
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- Adolescent, Antineoplastic Agents, Alkylating therapeutic use, Child, Child, Preschool, Cohort Studies, Disease-Free Survival, Eye Neoplasms drug therapy, Eye Neoplasms secondary, Follow-Up Studies, Humans, Infant, Intravitreal Injections, Melphalan therapeutic use, Retinal Neoplasms drug therapy, Retinal Neoplasms pathology, Retinoblastoma drug therapy, Retinoblastoma secondary, Retrospective Studies, Survival Rate, Antineoplastic Agents, Alkylating administration & dosage, Eye Neoplasms classification, Melphalan administration & dosage, Neoplasm Seeding, Retinal Neoplasms classification, Retinoblastoma classification, Vitreous Body drug effects, Vitreous Body pathology
- Abstract
Purpose: To evaluate the clinical characteristics of the 3 classifications of vitreous seeds in retinoblastoma-dust (class 1), spheres (class 2), and clouds (class 3)-and their responses to intravitreal melphalan., Design: Retrospective, bi-institutional cohort study., Participants: A total of 87 patient eyes received 475 intravitreal injections of melphalan (median dose, 30 μg) given weekly, a median of 5 times (range, 1-12 times)., Methods: At presentation, the vitreous seeds were classified into 3 groups: dust, spheres, and clouds. Indirect ophthalmoscopy, fundus photography, ultrasonography, and ultrasonic biomicroscopy were used to evaluate clinical response to weekly intravitreal melphalan injections and time to regression of vitreous seeds. Kaplan-Meier estimates of time to regression and ocular survival, patient survival, and event-free survival (EFS) were calculated and then compared using the Mantel-Cox test of curve., Main Outcome Measures: Time to regression of vitreous seeds, patient survival, ocular survival, and EFS., Results: The difference in time to regression was significantly different for the 3 seed classes (P < 0.0001): the median time to regression was 0.6, 1.7, and 7.7 months for dust, spheres, and clouds, respectively. Eyes with dust received significantly fewer injections and a lower median and cumulative dose of melphalan, whereas eyes with clouds received significantly more injections and a higher median and cumulative dose of melphalan. Overall, the 2-year Kaplan-Meier estimates for ocular survival, patient survival, and EFS (related to target seeds) were 90.4% (95% confidence interval [CI], 79.7-95.6), 100%, and 98.5% (95% CI, 90-99.7), respectively., Conclusions: The regression and response of vitreous seeds to intravitreal melphalan are different for each seed classification. The vitreous seed classification can be predictive of time to regression, number, median dose, and cumulative dose of intravitreal melphalan injections required., (Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
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17. Efficacy and toxicity of second-course ophthalmic artery chemosurgery for retinoblastoma.
- Author
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Francis JH, Abramson DH, Gobin YP, Marr BP, Tendler I, Brodie SE, and Dunkel IJ
- Subjects
- Adolescent, Antineoplastic Agents, Alkylating adverse effects, Child, Child, Preschool, Disease-Free Survival, Electroretinography drug effects, Female, Humans, Infant, Male, Melphalan adverse effects, Neoplasm Seeding, Ophthalmic Artery, Retina physiopathology, Retinal Neoplasms physiopathology, Retinoblastoma physiopathology, Retreatment, Retrospective Studies, Salvage Therapy, Treatment Outcome, Vitreous Body pathology, Antineoplastic Agents, Alkylating therapeutic use, Infusions, Intra-Arterial, Melphalan therapeutic use, Neoplasm Recurrence, Local drug therapy, Retinal Neoplasms drug therapy, Retinoblastoma drug therapy
- Abstract
Objective: Assess the usefulness of second-course ophthalmic artery chemosurgery (OAC) for patients with intraocular retinoblastoma that recurred after prior OAC. This study evaluated the efficacy and toxicity of second-course OAC., Design: Single-arm retrospective study of 29 eyes of 30 patients treated with second-course OAC at Memorial Sloan Kettering Cancer Center between May 2006 and July 2013, with a median follow-up of 25.9 months., Participants: Retinoblastoma patients who underwent a course of OAC, with a minimum of 2 months of progression-free follow-up at monthly examinations, but who subsequently received additional OAC for recurrent tumor., Methods: To determine efficacy, Kaplan-Meier survival estimates were generated and the Mantel-Cox test was used to compare curves. To determine toxicity, electroretinography (ERG) amplitudes were measured in response to 30-Hz photopic flicker stimulation before and after OAC treatment; systemic adverse events were graded according to the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE 4.0)., Main Outcome Measures: For efficacy, ocular progression-free survival, ocular event-free survival (e.g., enucleation, external-beam radiation, or intravitreal melphalan), and ocular survival. For toxicity, peak-to-peak comparisons between ERG studies before and after OAC treatment and CTCAE 4.0-graded systemic adverse events., Results: Fifty percent of all recurrences were within 4.4 months and 90% were within 16 months of completion of the first course of OAC. The 2-year Kaplan-Meier ocular survival, event-free survival, and progression-free survival estimates after second-course OAC were 82.8% (95% confidence interval [CI], 60.1%-93.2%), 57.3% (95% CI, 36.1%-73.7%), and 26.5% (95% CI, 11.0%-45.0%), respectively. All eyes without vitreous seeding were progression free, whereas eyes with vitreous seeding were associated significantly with worse ocular survival after second-course OAC (P = 0.03). After second-course OAC, 90% of eyes had stable or improved ERG responses. Of all evaluable cases, there was no increased risk of systemic toxicity during the second course compared with the initial course of OAC., Conclusions: Retinoblastoma eyes requiring second-course OAC after initial OAC treatment have good salvage rates, and the treatment has an acceptable ocular and systemic toxicity profile. However, these eyes often require additional (third- or fourth-course) OAC or other treatment methods because of progression of disease after second-line OAC, particularly if vitreous seeds are present at the time of initial OAC failure., Competing Interests: No conflicting relationship exists for any author., (Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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18. Risk factors for severe neutropenia following intra-arterial chemotherapy for intra-ocular retinoblastoma.
- Author
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Dunkel IJ, Shi W, Salvaggio K, Marr BP, Brodie SE, Gobin YP, and Abramson DH
- Subjects
- Antineoplastic Agents, Alkylating administration & dosage, Antineoplastic Agents, Alkylating therapeutic use, Child, Preschool, Humans, Infant, Infusions, Intra-Arterial, Melphalan administration & dosage, Melphalan therapeutic use, Neutropenia pathology, Neutrophils drug effects, Neutrophils pathology, Retina drug effects, Retrospective Studies, Risk Factors, Antineoplastic Agents, Alkylating adverse effects, Melphalan adverse effects, Neutropenia chemically induced, Retinal Neoplasms drug therapy, Retinoblastoma drug therapy
- Abstract
Purpose: Intra-arterial chemotherapy is a promising strategy for intra-ocular retinoblastoma. Neutropenia is the most commonly encountered systemic toxicity and in this study we aimed to determine the risk factors associated with the development of severe (≥ grade 3) neutropenia., Methods: Retrospective review of 187 evaluable cycles of melphalan-containing intra-arterial chemotherapy from the first three cycles administered to 106 patients with intra-ocular retinoblastoma from May 2006 to June 2011. Cycles were considered to be evaluable if (1) blood count results were available in the 7 to 14 days post-treatment interval and (2) concurrent intravenous chemotherapy was not administered. Toxicity was assessed via the Common Terminology Criteria for Adverse Events version 4.0., Results: 54 cycles (29%) were associated with grade 3 (n = 43) or grade 4 (n = 11) neutropenia. Multivariate stepwise logistic regression revealed that a higher melphalan dose (>0.40 mg/kg) was significantly associated with severe neutropenia during all 3 cycles (odds ratio during cycle one 4.11, 95% confidence interval 1.33-12.73, p = 0.01), but the addition of topotecan and/or carboplatin were not. Prior treatment with systemic chemotherapy was not associated with severe neutropenia risk in any analysis., Conclusions: Intra-arterial melphalan-based chemotherapy can cause severe neutropenia, especially when a dose of greater than 0.40 mg/kg is administered. Further study with a larger sample may be warranted.
- Published
- 2014
- Full Text
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19. Local and systemic toxicity of intravitreal melphalan for vitreous seeding in retinoblastoma: a preclinical and clinical study.
- Author
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Francis JH, Schaiquevich P, Buitrago E, Del Sole MJ, Zapata G, Croxatto JO, Marr BP, Brodie SE, Berra A, Chantada GL, and Abramson DH
- Subjects
- Animals, Antineoplastic Agents, Alkylating administration & dosage, Antineoplastic Agents, Alkylating adverse effects, Blood Cell Count, Child, Child, Preschool, Drug Evaluation, Preclinical, Electroretinography, Female, Fluorescein Angiography, Humans, Infant, Intravitreal Injections, Male, Melphalan administration & dosage, Melphalan adverse effects, Prospective Studies, Rabbits, Regression Analysis, Retinal Neoplasms physiopathology, Retinoblastoma physiopathology, Vitreous Body pathology, Antineoplastic Agents, Alkylating toxicity, Melphalan toxicity, Neoplasm Seeding, Retinal Neoplasms drug therapy, Retinoblastoma drug therapy
- Abstract
Purpose: Intravitreal melphalan is emerging as an effective treatment for refractory vitreous seeds in retinoblastoma, but there is limited understanding regarding its toxicity. This study evaluates the retinal and systemic toxicity of intravitreal melphalan in retinoblastoma patients, with preclinical validation in a rabbit model., Design: Clinical and preclinical, prospective, cohort study., Participants: In the clinical study, 16 patient eyes received 107 intravitreal injections of 30 μg melphalan given weekly, a median of 6.5 times (range, 5-8). In the animal study, 12 New Zealand/Dutch Belt pigmented rabbits were given 3 weekly injections of 15 μg of intravitreal melphalan or vehicle to the right eye., Methods: Electroretinogram (ERG) responses were recorded in both humans and rabbits. For the clinical study, ERG responses were recorded at baseline, immediately before each injection, and at each follow-up visit; 82 of these studies were deemed evaluable. Median follow-up time was 5.2 months (range, 1-11). Complete blood counts (CBCs) were obtained on the day of injection at 46 patient visits. In the animal study, ERG responses were obtained along with fluorescein angiography, CBCs, and melphalan plasma concentration. After humane killing, the histopathology of the eyes was evaluated., Main Outcome Measures: For the clinical study, we measured peak-to-peak ERG amplitudes in response to 30-Hz photopic flicker stimulation with comparisons between ERG studies before and after intravitreal melphalan. For the animal study, we collected ERG parameters before and after intravitreal melphalan injections with histopathologic findings., Results: By linear regression analysis, over the course of weekly intravitreal injections in retinoblastoma patients, for every additional injection, the ERG amplitude decreased by approximately 5.8 μV. The ERG remained stable once the treatment course was completed. In retinoblastoma patients, there were no grade 3 or 4 hematologic events. One week after the second injection in rabbits, the a- and b-wave amplitude declined significantly in the melphalan treated eyes compared with vehicle-treated eyes (P<0.05). Histopathology revealed severely atrophic retina., Conclusions: Weekly injections of 30 μg of melphalan can result in a decreased ERG response, which is indicative of retinal toxicity. These findings are confirmed at an equivalent dose in rabbit eyes by ERG measurements and by histopathologic evidence of severe retinal damage. Systemic toxicity with intravitreal melphalan at these doses in humans or rabbits was not detected., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
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20. Tethered vitreous seeds following intravitreal melphalan for retinoblastoma.
- Author
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Francis JH, Marr BP, Brodie SE, Gobin YP, and Abramson DH
- Subjects
- Humans, Intravitreal Injections, Male, Retinal Neoplasms pathology, Retinoblastoma pathology, Antineoplastic Agents, Alkylating administration & dosage, Melphalan administration & dosage, Neoplasm Seeding, Retinal Neoplasms drug therapy, Retinoblastoma drug therapy, Vitreous Body pathology
- Published
- 2014
- Full Text
- View/download PDF
21. Persistence of retinal function after intravitreal melphalan injection for retinoblastoma.
- Author
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Brodie SE, Munier FL, Francis JH, Marr B, Gobin YP, and Abramson DH
- Subjects
- Antineoplastic Agents, Alkylating administration & dosage, Female, Follow-Up Studies, Humans, Infant, Intravitreal Injections, Ophthalmoscopy, Retina drug effects, Retina pathology, Retinal Neoplasms drug therapy, Retinal Neoplasms pathology, Retinoblastoma pathology, Retinoblastoma physiopathology, Electroretinography drug effects, Melphalan administration & dosage, Retina physiopathology, Retinoblastoma drug therapy
- Abstract
Background: The risk/benefit profile of intravitreal melphalan injection for treatment of active vitreous seeds in retinoblastoma remains uncertain. We report clinical and electroretinography results after 6 months of one patient who has shown a favorable initial clinical response to intravitreal melphalan injections for treatment of refractory vitreous seeds., Methods: Clinical case report., Patient: The patient presented at age 17 months with bilateral retinoblastoma [OD: International Classification (ICRB) group E, Reese-Ellsworth (R-E) class Vb; OS: ICRB D, R-E Vb] with no known prior family history. The right eye was enucleated primarily. The patient received systemic chemotherapy and extensive local treatment to the left eye. Ten months later, she presented with recurrent disease, including fine, diffuse vitreous seeds. Tumor control was established with intra-arterial chemotherapy and local treatment. Subsequent recurrence was treated with further intra-arterial chemotherapy, local treatment, and plaque radiotherapy with iodine-125. Persistent free-floating spherical vitreous seeds were treated with 4 cycles of intravitreal melphalan injection via the pars plana, with doses of 30, 30, 30, and 20 μg., Results: After 6 months of follow-up, the left eye remained free of active tumor. Visual acuity was 20/40. Photopic ERGs amplitudes were unchanged compared with those recorded prior to the intravitreal injection treatments., Conclusions: Intravitreal melphalan injection for refractory spherical vitreous seeds of retinoblastoma with favorable tumor response is compatible with good central visual acuity and preservation of retinal function as indicated by photopic ERG recordings.
- Published
- 2013
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22. Pharmacokinetic analysis of melphalan after superselective ophthalmic artery infusion in preclinical models and retinoblastoma patients.
- Author
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Schaiquevich P, Buitrago E, Taich P, Torbidoni A, Ceciliano A, Fandino A, Asprea M, Requejo F, Abramson DH, Bramuglia GF, and Chantada GL
- Subjects
- Animals, Antineoplastic Agents, Alkylating administration & dosage, Antineoplastic Agents, Alkylating pharmacokinetics, Cell Line, Tumor, Child, Child, Preschool, Female, Humans, Infant, Infusions, Intra-Arterial, Male, Melphalan administration & dosage, Neoplasms, Experimental, Ophthalmic Artery, Retinal Neoplasms metabolism, Retinal Neoplasms pathology, Retinoblastoma metabolism, Retinoblastoma pathology, Swine, Vitreous Body metabolism, Vitreous Body pathology, Melphalan pharmacokinetics, Retinal Neoplasms drug therapy, Retinoblastoma drug therapy
- Abstract
Purpose: To characterize melphalan pharmacokinetics after superselective ophthalmic artery infusion (SSOAI) in animals and children with retinoblastoma., Methods: Vitreous and plasma samples of five Landrace pigs were obtained over a 4-hour period after SSOAI of melphalan (7 mg). Melphalan cytotoxicity was evaluated in retinoblastoma cell lines with and without topotecan. Plasma samples were obtained from 17 retinoblastoma patients after SSOAI of 3 to 6 mg of melphalan to one (n=14) or two eyes (n=3). Correlation between plasma pharmacokinetics and age, dosage, and systemic toxicity was studied in patients., Results: In animals, melphalan peak vitreous levels were greater than its IC50 and resulted in 3-fold vitreous-to-plasma exposure. In patients, a large variability in pharmacokinetic parameters was observed and it was explained mainly by body weight (P<0.05). A significantly higher systemic area under the curve was obtained in children receiving more than 0.48 mg/kg for bilateral tandem infusions (P<0.05). These children had 50% probability of grades 3-4 neutropenia. Plasma concentrations after 2 and 4 hours of SSOAI were significantly higher in these children (P<0.05). A synergistic cytotoxic effect of melphalan and topotecan was evident in cell lines., Conclusions: Potentially active levels of melphalan after SSOAI were achieved in the vitreous of animals. Low systemic exposure was found in animals and children. Doses greater than 0.48 mg/kg, given for bilateral tandem infusions, were associated with significantly higher plasma levels and increased risk of neutropenia. Synergistic in vitro cytotoxicity between melphalan and topotecan favors combination treatment.
- Published
- 2012
- Full Text
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23. Ophthalmic artery chemosurgery for less advanced intraocular retinoblastoma: five year review.
- Author
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Abramson DH, Marr BP, Brodie SE, Dunkel I, Palioura S, and Gobin YP
- Subjects
- Adolescent, Adult, Antineoplastic Agents therapeutic use, Child, Child, Preschool, Disease-Free Survival, Eye drug effects, Eye pathology, Follow-Up Studies, Humans, Infant, Melphalan therapeutic use, Ophthalmic Artery drug effects, Ophthalmic Artery pathology, Ophthalmologic Surgical Procedures methods, Retinal Neoplasms pathology, Retinoblastoma pathology, Retrospective Studies, Topotecan therapeutic use, Young Adult, Antineoplastic Agents administration & dosage, Melphalan administration & dosage, Ophthalmic Artery surgery, Retinal Neoplasms drug therapy, Retinal Neoplasms surgery, Retinoblastoma drug therapy, Retinoblastoma surgery, Topotecan administration & dosage
- Abstract
Background: Ophthalmic artery chemosurgery (OAC) for retinoblastoma was introduced by us 5 years ago for advanced intraocular retinoblastoma. Because the success was higher than with existing alternatives and systemic side effects limited we have now treated less advanced intraocular retinoblastoma (Reese-Ellsworth (RE) I-III and International Classification Retinoblastoma (ICRB) B and C)., Methodology/principal Findings: Retrospective review of 5 year experience in eyes with Reese Ellsworth (Table 1) I (7 eyes), II (6 eyes) or III (6 eyes) and/or International Classification (Table 2) B (19 eyes) and C (11 eyes) treated with OAC (melphalan with or without topotecan) introduced directly into the ophthalmic artery. Patient survival was 100%. Ocular event-free survival was 100% for Reese-Ellsworth Groups I, II and III (and 96% for ICRB B and C) at a median of 16 months follow-up. One ICRB Group C (Reese-Ellsworth Vb) eye could not be treated on the second attempt for technical reasons and was therefore enucleated. No patient required a port and only one patient required transfusion of blood products. The electroretinogram (ERG) was unchanged or improved in 14/19 eyes., Conclusions/significance: Ophthalmic artery chemosurgery for retinoblastoma that was Reese-Ellsworth I, II and III (or International Classification B or C) was associated with high success (100% of treatable eyes were retained) and limited toxicity with results that equal or exceed conventional therapy with less toxicity.
- Published
- 2012
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24. Highlighting complications over successes in occurrence of sectoral choroidal occlusive vasculopathy.
- Author
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Abramson DH, Gobin YP, Dunkel I, Marr BP, Brodie S, and Freund KB
- Subjects
- Humans, Antineoplastic Agents, Alkylating adverse effects, Choroid Diseases chemically induced, Melphalan adverse effects, Ophthalmic Artery, Retinal Artery Occlusion chemically induced, Retinal Neoplasms drug therapy, Retinoblastoma drug therapy
- Published
- 2011
- Full Text
- View/download PDF
25. A phase I/II study of direct intraarterial (ophthalmic artery) chemotherapy with melphalan for intraocular retinoblastoma initial results.
- Author
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Abramson DH, Dunkel IJ, Brodie SE, Kim JW, and Gobin YP
- Subjects
- Antineoplastic Agents, Alkylating adverse effects, Blood Cell Count, Catheterization, Child, Preschool, Electroretinography, Follow-Up Studies, Humans, Infant, Melphalan adverse effects, Photography, Retinal Neoplasms pathology, Retinoblastoma pathology, Antineoplastic Agents, Alkylating administration & dosage, Infusions, Intra-Arterial, Melphalan administration & dosage, Ophthalmic Artery drug effects, Retinal Neoplasms drug therapy, Retinoblastoma drug therapy
- Abstract
Objective: To develop a technique that would allow us to cannulate repeatedly the ophthalmic artery of young children with advanced retinoblastoma, to find a dose of melphalan that would be tolerable and tumoricidal for retinoblastoma when given intraarterially, and to study the local ocular and systemic side effects of intraarterial melphalan in these children., Design: Phase I/II clinical trial., Participants: Ten children with advanced retinoblastoma (Reese-Ellsworth V) eyes who were indicated for enucleation were entered into an institutional review board-approved protocol of ophthalmic artery infusion of melphalan to avoid enucleation., Methods: Cannulation of the ophthalmic artery was performed by a femoral artery approach using microcatheters while the children were under anesthesia and anticoagulated. Chemotherapy (melphalan) was infused into the artery over a 30-minute period., Main Outcome Measures: Ophthalmic examinations, retinal photography, and electroretinograms were used to document local toxicity, whereas physical examinations and complete blood counts were used to measure systemic toxicity., Results: The ophthalmic arteries were successfully cannulated in 9 cases (total, 27 times), as many as 6 times in 1 patient. Dramatic regression of tumors, vitreous seeds, and subretinal seeds were seen in each case. No severe systemic side effects (sepsis, anemia, neutropenia, fever, or death) occurred. No transfusions were required (red cells or platelets). Three patients developed conjunctival and lid edema that resolved without treatment. There was no toxicity to the cornea, anterior segment, pupil, or motility. One (previously irradiated) eye developed retinal ischemia; another eye had no toxicity after intraarterial chemotherapy but did develop a radiationlike retinopathy after brachytherapy. Vision stabilized or improved in all but 1 patient after treatment. Electroretinograms were generally poor (advanced eyes were treated), but in 2 cases, the electroretinogram improved after treatment (and resolution of a retinal detachment). Seven eyes avoided enucleation. Two intraarterially treated eyes were enucleated, with no viable tumors identified pathologically., Conclusions: We developed a technique of direct ophthalmic artery infusion of melphalan for children with retinoblastoma. The technique had minimal systemic side effects (one patient had grade 3 neutropenia) and minimal local toxicity. Among the first 9 cases treated with this technique, 7 eyes destined to be enucleated were salvaged.
- Published
- 2008
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26. What have we learnt about intraarterial chemotherapy (Ophthalmic Artery Chemosurgery) for retinoblastoma in the past 18 years? The third A. Linn Murphree Lecture.
- Author
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Abramson, David H.
- Subjects
- *
CANCER chemotherapy , *OPHTHALMIC artery , *PEDIATRIC oncology , *RETINOBLASTOMA , *ETIOLOGY of cancer - Abstract
Intraarterial chemotherapy (Ophthalmic Artery Chemosurgery/OAC) for retinoblastoma has transformed management of retinoblastoma worldwide since Pierre Gobin MD and I introduced it in 2006. Case reports, institutional series, meta-analyses, and randomized trials have validated its effectiveness and safety. It allows more eyes to be saved (at Memorial Sloan Kettering Cancer Center (MSKCC) as a result, we have gone from removing 96% of retinoblastoma eyes that presented with leukocoria (comparable to modern day International Classification “D” and “E” eyes) to saving 95% of these eyes with primary OAC management allows the majority of advanced intraocular eyes to be salvaged (both “D” and “E” eyes) prior to the chemoreduction era to saving 95% of these eyes with primary OAC management. OAC attains cures faster than intravenous protocols, has fewer systemic side effects, and is overall cheaper than intravenous approaches (because of the absence of side effects which are the main driver of cost in pediatric oncology). Unlike systemic chemotherapy no ports are needed (and no removal of ports for life threatening infections), it does not alter the immune system (so children can be immunized), it does not affect patient growth (and children who had received systemic chemotherapy catch up in growth during OAC), it does not affect hearing (which systemic Carboplatin does-especially in children <6 months of age), it eliminates the second cancers caused by radiation and systemic chemotherapy and does not compromise survival with all series showing patient survival >98%. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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27. Ten things you learned in your residency about retinoblastoma that have changed the 2023 Victor T. Curtin Lecture.
- Author
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Abramson, David H.
- Subjects
- *
RETINOBLASTOMA , *CHILDHOOD cancer , *OPHTHALMOLOGISTS , *LECTURES & lecturing , *CONQUERORS - Abstract
Retinoblatoma is now the pediatric cancer with the highest cure rate. More than any other ocular malignancy the approach to this cancer has changed dramatically in the past 10 years. Most of the things taught to the majority of all Ophthalmology residents is out of date. Because few Ophthalmologists deal with retinoblastoma they are not aware of these seismic changes so this summary of my Curtin lectures outlines some of the major changes all Ophthalmologists should be familiar with. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
28. Persistence of retinal function after selective ophthalmic artery chemotherapy infusion for retinoblastoma
- Author
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Brodie, Scott E., Pierre Gobin, Y., Dunkel, Ira J., Kim, Jonathan W., and Abramson, David H.
- Published
- 2009
- Full Text
- View/download PDF
29. Biochemical measures of ovarian function in female survivors of retinoblastoma treated with intra-arterial melphalan: an initial report.
- Author
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Marathe, Priya H., Dunkel, Ira J., Francis, Jasmine H., Antal, Zoltan, Gobin, Y. Pierre, Abramson, David H., and Friedman, Danielle N.
- Subjects
MELPHALAN ,RETINOBLASTOMA ,OPHTHALMIC artery ,INDUCED ovulation ,FEMALES - Abstract
Since 2006, ophthalmic artery chemosurgery (OAC) has been used for ocular-sparing treatment of retinoblastoma. Systemic exposure to melphalan is known to cause ovarian dysfunction, but the effect of melphalan-based OAC has not yet been determined. Here, we assess biochemical and symptomatic measures of ovarian function in a cohort of pubertal female survivors of retinoblastoma treated with melphalan-based OAC. These 13 patients all had normal gonadotropins at a median age of 11.1 years, 9.6 years from the completion of therapy. None had symptoms of ovarian dysfunction. This study provides initial evidence that ovarian function remains intact after melphalan-based OAC. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
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30. Cytopathological Evaluation of Ocular Surface and Needle Washings Following Intravitreal Melphalan Injections for Retinoblastoma.
- Author
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Francis, Jasmine H., Mondesire-Crump, Ijah, Marr, Brian P., Brodie, Scott E., and Abramson, David H.
- Subjects
RETINOBLASTOMA ,MELPHALAN ,CELLULAR pathology ,CANCER cells ,INJECTIONS ,THERAPEUTICS - Abstract
Purpose: There is concern that injections into eyes with retinoblastoma are dangerous and allow tumor escapement. This study attempted to determine this risk by investigating the presence of malignant cells in ocular surface and needle washings of eyes with retinoblastoma receiving intravitreal injections. Methods: Two hundred ocular surface and 202 needle washings were obtained from 280 injections into eyes with retinoblastoma. Each specimen underwent cytopathlogical assessment for the presence of malignant cells. Results: Cytopathological results revealed no malignant cells in all 200 ocular surface and 202 needle washing specimens. In the ocular surface washings, squamous cells, red blood cells, and inflammatory cells were found in 15, 2, and 2 specimens, respectively. In the needle washings, 4 specimens contained squamous cells but no red blood cells or inflammatory cells were found in any specimen. Conclusion: With this injection and evaluation technique, no malignant cells were recovered, highlighting the low risk of the procedure. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
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31. Spontaneously Resolving Periocular Erythema and Ciliary Madarosis Following Intra-arterial Chemotherapy for Retinoblastoma.
- Author
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Marr, Brian, Gobin, Y. Pierre, Dunkel, Ira J., Brodie, Scott E., and Abramson, David H.
- Subjects
DRUG therapy ,RETINOBLASTOMA ,PEDIATRIC therapy ,ERYTHEMA ,EDEMA ,DRUG side effects ,CUTANEOUS manifestations of general diseases ,PATIENTS ,RETROSPECTIVE studies - Abstract
Purpose and Design: To describe an unusual clinical finding seen in children undergoing intra-arterial chemotherapy for retinoblastoma. Materials and Methods: A retrospective review of 69 eyes of 63 patients receiving intra-arterial chemotherapy over a 3-year period. Charts and photographs of 69 consecutive cases were reviewed, and data were collected on patients with clinical evidence of a hyperemic cutaneous periocular abnormality following the procedure. Results: A blanching erythematous and edematous patch was noted in the periocular region in 16% (11 of 69) of the children who received intraarterial chemotherapy. The plaque extended into the region of the supertrochlear and medial marginal artery distribution on the ipsilateral side of the intra-arterial chemotherapy. All patches of erythema spontaneously resolved within 3 months following completion of the intra-arterial chemotherapy. Conclusion: Periocular erythema and swelling is a self-limited clinical finding associated with intra-arterial chemotherapy in a small number of patients. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
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32. Pharmacokinetics of Chemotherapy Delivered by Ophthalmic Artery Chemosurgery
- Author
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Schaiquevich, Paula, Chantada, Guillermo L., Singh, Arun D., Series editor, Francis, Jasmine H., editor, and Abramson, David H., editor
- Published
- 2015
- Full Text
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33. Vitreous Disease and the Technique, Safety and Toxicity of Intravitreal Chemotherapy for Retinoblastoma
- Author
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Francis, Jasmine H., Singh, Arun D., Series editor, Francis, Jasmine H., editor, and Abramson, David H., editor
- Published
- 2015
- Full Text
- View/download PDF
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