11 research outputs found
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Macular Retinoblastoma: Evaluation of Tumor Control, Local Complications, and Visual Outcomes for Eyes Treated with Chemotherapy and Repetitive Foveal Laser Ablation
To determine tumor control rates, complication rates, and visual acuity (VA) for patients with macular retinoblastoma undergoing systemic chemotherapy and foveal diode laser ablation.
Noncomparative retrospective case series.
All patients with retinoblastoma in the macula at the Bascom Palmer Eye Institute between 1991 and 2004 were evaluated. Patients included in the study were managed by the same clinician with a planned therapeutic strategy.
Patients with Reese–Ellsworth groups I to IV disease underwent 4 to 9 cycles of systemic chemotherapy with vincristine, etoposide, and carboplatin, and patients with group V disease underwent 6 to 10 cycles with or without cyclosporine. All tumors underwent repetitive diode laser ablation (2–24 sessions) applied to the foveal and extrafoveal portions of tumors at each visit until tumors were deemed inactive for at least 6 months.
Recurrence requiring external beam radiation therapy or enucleation; VA; and complications including iris atrophy, peripheral focal lens opacity, peripheral anterior synechiae, and foveal neovascular membrane.
Forty-four eyes of 33 patients were treated. Eyes were classified as Reese–Ellsworth group I (1 [2%]), II (6 [12%]), III (3 [7%]), IV (5 [9%]), or V (29 [67%]). Thirty-eight eyes (86%) had successful tumor control and avoided enucleation at a median follow-up of 36 months. At 3 years, tumor control rates were 100% for Reese–Ellsworth groups I to IV and 83% for group V. All eyes requiring enucleation were in Reese–Ellsworth group V. No eyes required external beam radiation. The most common complications were iris atrophy (61%) and focal lens opacity (14%). Strabismus was noted in 16% of eyes. Snellen VA measured 20/40 or better in 36% of eyes, 20/80 or better in 57%, and 20/400 or better in 86%. An increasing number of laser applications and chemotherapy cycles was not associated with decreased VA, strabismus, or development of an afferent pupillary defect but was associated with development of local complications.
A unique approach to the application of diode laser therapy characterized by repetitive foveal treatments and aggressive chemotherapy resulted in tumor control rates that exceed those previously published. Furthermore, despite laser application directly to the fovea, 57% of patients retained 20/80 or better vision
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Pars Plana Lensectomy and Intraocular Lens Implantation in Pediatric Radiation-Induced Cataracts in Retinoblastoma
To investigate visual outcomes, surgical complications, and tumor recurrence among children with retinoblastoma (RB) undergoing pars plana lensectomy, vitrectomy, and simultaneous intraocular lens insertion for radiation-related cataract secondary to external beam radiotherapy (EBRT).
Retrospective, noncomparative, consecutive case series.
The medical records for all patients treated with pars plana lensectomy, vitrectomy, and posterior chamber intraocular lens implantation for radiation-induced cataract after EBRT for RB at a single institution between January 1, 1990, and December 31, 2000, were reviewed.
The study included 16 eyes of 12 children with Reese-Ellsworth stage V RB.
Visual acuity, surgical and postoperative complications, postoperative refraction, and tumor recurrence.
The median age at diagnosis of RB was 6 months (range, 1–49 months). All patients received EBRT as primary treatment and experienced radiation-induced cataracts. The median interval from RB diagnosis to cataract surgery was 42 months (range, 28–95 months). Preoperative mean visual acuity was 20/400, with 12 of 16 eyes (75%) having macular tumor involvement. All patients underwent pars plana lensectomy, vitrectomy, and posterior chamber intraocular lens insertion. Vitreous samples were evaluated by cytopathologic examination, and no viable tumor cells were identified in any of the vitreous specimens. Postoperative complications included transient cystoid macular edema in 5 eyes (31%) and iridocyclitis in 3 eyes (19%). The mean follow-up after cataract surgery was 66 months (range, 30–94 months). Final visual acuity was 20/40 or better in 11 of 16 eyes (69%). No late intraocular recurrence, orbital tumors, or metastatic disease was noted in this study.
Pars plana lensectomy, vitrectomy, and simultaneous intraocular lens implantation is an effective means of managing EBRT-induced cataracts in eyes with previously treated RB. There was no evidence of active tumor in eyes undergoing surgery at least 28 months after the diagnosis and commencement of therapy for RB, and no late intraocular, orbital, or metastatic tumors were detected. Visual acuity was limited by the presence of primary macular tumor pathologic features in a subset of patients, but final vision better than 20/400 may be achieved in these eyes
Motility Assessment and Clinical Outcomes of a Magnetically Integrated Microporous Implant
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Subconjunctival Carboplatin Therapy and Cryotherapy in the Treatment of Transgenic Murine Retinoblastoma
OBJECTIVES: To determine the efficacy and dose response of subconjunctival carboplatin with and without cryotherapy in the treatment of murine transgenic hereditary retinoblastoma. METHODS: Fifty-one 5-week-old transgenic BLH SV-40 (Charles Rivers Laboratories, Boston, Mass) T-antigen-positive mice with retinoblastoma were administered 6 subconjunctival injections of carboplatin in 1 eye at drug doses of 10, 15, 20, 25, 62.5, 125, and 250 μg. Six control eyes received 6 subconjunctival injections of balanced salt solution. Fourteen of the 51 subconjunctivally treated eyes received a single application of transconjunctival cryotherapy immediately prior to each carboplatin injection. Six control eyes received 6 single applications of transconjunctival cryotherapy using the above schedule but did not receive carboplatin. All experimental and control eyes were obtained at 16 weeks of age for histopathologic examination. RESULTS: A dose-dependent inhibition of intraocular tumor growth by subconjunctivally delivered carboplatin was observed in these transgenic retinoblastoma mice. Tumor development was inhibited in 50% of the mouse eyes at doses of 180 μg. In animals treated with cryotherapy alone, no tumor control was noted (0 of 6). In animals treated with subconjunctival carboplatin coupled with cryotherapy, a tumor control dose of 417 pg was found. No evidence of histopathologic treatment toxicity was noted. CONCLUSIONS: Subconjunctival delivery of carboplatin in serial doses effectively inhibits intraocular tumor growth in a dose-dependent fashion in a transgenic murine retinoblastoma model. Cryotherapy does not increase tumor control in this murine retinoblastoma model
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Subconjunctival carboplatin in retinoblastoma: Impact of tumor burden and dose schedule
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Comparison of retinoblastoma reduction for chemotherapy vs external beam radiotherapy
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Local Carboplatin and Radiation Therapy in the Treatment of Murine Transgenic Retinoblastoma
BACKGROUND: Combined modality therapy in the treatment of retinoblastoma may decrease treatment-related morbidity and second tumor—associated mortality, while maintaining excellent tumor control rates. OBJECTIVE: To evaluate tumor control and potential synergy between intravitreally delivered carboplatin and external beam radiation therapy (EBRT), using a transgenic murine model of spontaneous heritable retinoblastoma. METHODS: Sixty-six mouse eyes from 4-week-old transgenic mice positive for the simian virus 40 large T antigen were evaluated. Thirty-three mice were treated with 5 intravitreal injections of carboplatin (ranging from 0.1-4.0 μg) combined with concurrent bilateral EBRT (ranging from 10-30 Gy) delivered in twice daily 5-Gy fractions. All eyes were followed up for treatment complications. Twelve weeks following final treatment, all eyes were enucleated, serial histologic sections obtained, and the eyes examined for the presence of retinoblastoma. RESULTS: No eye treated with 0.1 μg of carboplatin and EBRT exhibited tumor control. Three (75%) of 4 mice receiving 1.0 μg of carboplatin combined with 10-Gy EBRT had complete tumor control. Four (100%) of 4 mice receiving 1.0 μg of carboplatin combined with 30-Gy EBRT had complete tumor control. Nine (100%) of 9 mice receiving 4.0 μg of carboplatin in combination with EBRT had complete tumor control. The chemotherapeutic enhancement ratio ranged from 1.07 to 3.24. CONCLUSIONS: Combined administration of intravitreal carboplatin and EBRT enhances local tumor control in murine retinoblastoma. Combining these treatment modalities may allow tumor control in selected patients with retinoblastoma while decreasing treatment-related morbidity and the mutagenic risks associated with radiation and systemic chemotherapy
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Radiation Therapy and Ferromagnetic Hyperthermia in the Treatment of Murine Transgenic Retinoblastoma
BACKGROUND: Combined modality therapy for childhood retinoblastoma holds the potential of decreasing treatment-related morbidity while maintaining excellent tumor control rates. OBJECTIVE: To evaluate the efficacy of external beam radiation therapy (EBRT), ferromagnetic hyperthermia (FMH), and the combination of both modalities in the control of ocular tumors in a transgenic murine model of retinoblastoma. METHODS: One hundred sixty-six mouse eyes from 4-week-old animals transgenically positive for simian virus 40 large T antigen were treated with a total dose of 10, 15, 20, 30, 40, 45, or 50 Gy of EBRT in 5-Gy fractions twice daily, with 48°C or 54°C FMH for 20 minutes, or with combined EBRT at 10 or 30 Gy and 48°C or 54°C FMH for 20 minutes. Serial histologic sections, obtained 8 weeks after treatment, were examined for the presence of tumor. RESULTS: The tumor control dose for 50% of eyes (TCD50) treated with EBRT occurred at 27.6 Gy. Ferromagnetic hyperthermia at 48°C cured 30% (6/20) of eyes, while 54°C FMH resulted in a 100% (20/20) cure rate. Combined treatment with 48°C FMH and EBRT exhibited a TCD50 at 3.3 Gy. The thermal enhancement ratio was 8.4. Ferromagnetic hyperthermia at 54°C exhibited tumor cure in all animals, but 25% of eyes were lost owing to secondary treatment complications. CONCLUSIONS: This represents the first documentation of tumor control via EBRT, ocular FMH, and a combination of these treatment modalities in this murine transgenic retinoblastoma model. The extent of treatment synergy in this model suggests that combined treatment application may allow a reduction in total ocular and periocular radiation dose while maintaining excellent local tumor control
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External beam radiation "salvage" therapy in transgenic murine retinoblastoma
To determine the efficacy of low-dose "salvage" external beam radiation therapy (EBRT) following failed subconjunctival carboplatin chemotherapy in a murine model of heritable retinoblastoma.
Eighty-four eyes from 8-week-old, simian virus 40, T-antigen-positive mice were treated with 6 serial subconjunctival carboplatin injections (100 microg/25 microL). At 12 weeks of age, 64 eyes received EBRT for a total dose of 480 (4.8 Gy), 1200 (12.0 Gy), 1560 (15.6 Gy), or 3000 (30.0 Gy) rad. Twenty eyes received no additional therapy following subconjunctival carboplatin injections. Ten eyes received a total dose EBRT of only 3000 rad. Eight eyes received subconjuctival injections of only an isotonic sodium chloride solution. Ten eyes served as untreated controls.
Eyes were enucleated at 20 weeks to assess the presence of tumor on histopathological examination.
Salvage therapy using low-dose EBRT was able to reestablish tumor control in a dose-dependent manner. Increasing the EBRT dose to 3000 rad resulted in 100% tumor control. The dose-dependent curves were significantly different between the treatment groups-EBRT alone vs salvage EBRT after receiving subconjunctival carboplatin injections (P<.001).
Low-dose hyperfractionated salvage EBRT following failed primary subconjunctival carboplatin chemotherapy is efficacious in the treatment of retinoblastoma in this animal model. Clinical Relevance Salvage EBRT using a reduced total radiation dose could be associated with a radiation-related treatment enhancement in pediatric retinoblastoma
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Hyperfractionated external beam radiation therapy in the treatment of murine transgenic retinoblastoma
To determine the in vivo efficacy of hyperfractionated external beam radiation therapy (EBRT) in comparison with standard daily EBRT in a murine model of heritable retinoblastoma.
Two hundred twenty eyes from 6-week-old simian virus-40 large T-antigen--positive mice were treated with a total dose of EBRT ranging from 10-76 Gy (1000 to 7600 rad). One hundred ten eyes underwent EBRT administered in 2.0-Gy (200-rad) fractions once per day. Forty-two eyes received hyperfractionated EBRT administered in 1.2-Gy (120-rad) fractions twice per day, while 48 eyes received EBRT twice daily in fractions of 5.0 Gy (500 rad). Twenty eyes served as untreated controls. All eyes were obtained for histopathologic examination and graded positive if any tumor was present.
A dose-dependent inhibition of ocular tumor was observed for EBRT in these transgenic retinoblastoma mice. The tumor control dose for 50% of eyes (TCD(50)) treated with 2.0 Gy fractions of EBRT was 45 Gy (4500 rad) when treatments were administered once daily. A significant increase in tumor control was observed when treatments were administered twice per day at fractions of 1.2 Gy, resulting in a TCD(50) of 33 Gy (3300 rad) (P =.003). A further increase in tumor control was observed when twice-daily EBRT was administered in 5.0 Gy fractions resulting in a TCD(50) of 28 Gy (2800 rad).
Hyperfractionated EBRT safely and effectively controls intraocular retinoblastoma in this transgenic animal model. Use of hyperfractionation allows for a reduction in total radiation delivered dose, while shortening the total treatment time.
This treatment approach may be applicable in the management of pediatric retinoblastoma by maintaining excellent tumor control, while reducing treatment-associated complications