Eye Salvage Rate Research Articles

External Beam Radiation Therapy for Retinoblastoma Resistant to Chemotherapy and Focal Treatment: Outcome and Predictive Factors

External Beam Radiation Therapy for Retinoblastoma Resistant to Chemotherapy and Focal Treatment: Outcome and Predictive Factors Abstract: Purpose: To evaluate the outcome of external beam radiation therapy (EBRT) for treatment of retinoblastoma resistant to chemotherapy and focal therapy. Methods and Materials: A retrospective case series of 24 eyes for 20 retinoblastoma patients treated by EBRT after failure of tumor control by chemotherapy and focal therapy. The main outcome measures included: international intraocular retinoblastoma stage (IIRC) and Reese Ellsworth (RE) stage, tumor seeding, treatment modalities, eye salvage, and survival. Results: The median age at diagnosis was 12 months. There were 12 (60%) males and 16 (80%) bilateral cases. All eyes were treated initially by systemic chemotherapy (range: 6-8 cycles). The dose of 45Gy was used in all eyes. The mean follow-up was 55months. Eye salvage rate after EBRT was 45% (11eyes); 67% ( 2/3) for IIRC group B, 63% (5/8) for group C, and 31% (4/13) for group D eyes. Vitreous seeds and tumor stage migration during management by chemotherapy were the most important significant predictive factors for tumor control (p=0.0327 and 0.0333 consecutively). Post EBRT complication rate was 80% (19/24) including; retinal detachment (3), vitreous hemorrhage (4), neovascular glaucoma (1), cataract (16), and radiation retinopathy (2). Conclusion: Eyes with retinoblastoma that failed chemotherapy were controlled with EBRT. However the presence of vitreous seeds, stage migration during chemotherapy, as well as good vision in the other eye may not justify the known risks of EBRT.

The role of intravitreal chemotherapy for retinoblastoma.

Targeted therapy in retinoblastoma (RB) is widely accepted as the current management tool with an aim of increasing drug availability at the tumor location. Inevitably the effect is several times higher compared to systemic delivery of chemotherapeutic drugs and carries less systemic toxicity. Despite tremendous advancement in saving life, eye salvage in advanced RB especially with active vitreous seeds remains a challenge. The hypoxic environment of the vitreous and reduced vitreous concentration of the drugs delivered makes these tumor seeds resistant to chemotherapy. Direct delivery of chemotherapeutic drugs into the vitreous cavity aids to overcome these challenges and is progressively being accepted worldwide. However, intraocular procedure in RB was abandoned due to high risk of extraocular tumor dissemination. Recently, the forbidden therapeutic technique was re-explored and modified for safe use. Although eye salvage rate has tremendously improved after intravitreal chemotherapy (IVitC), retinal toxicity, and vision salvage are yet to be validated. In our preliminary report of intravitreal melphalan in 11 eyes, we reported 100% eye salvage and 0% recurrence with an extended 15 months mean follow-up. In this review, we analyzed published reports on IVitC in RB via PubMed, Medline, and conference proceedings citation index, electronic database search, without language restriction that included case series and reports of humans and experimental animal eyes with RB receiving IVitC.

Abstract 767: Cyclosporin-modulated intensified-dosage chemotherapy for saving eyes with Group D intraocular retinoblastoma

Abstract PURPOSE: Cyclosporin (CSA) inhibits the multidrug resistance P-glycoprotein. Since 2000, we tested increased carboplatin and increased etoposide dosages in a cyclosporin-modulated carboplatin-etoposide-vincristine protocol, followed by focal laser/cryotherapy consolidation, to avoid elective radiation of newly diagnosed retinoblastoma (RB) patients, since radiation increases the secondary cancer risk in patients with heritable RB. We report the results for International Classification Groups A, B, C and D intraocular eyes (Ophthalmol Clinic North Am 2005; 18:41-53). METHOD: When Neupogen support became available, we increased the predominantly myelotoxic carboplatin to 28 mg/kg (from 18.7 mg/kg in our previous trial) and etoposide to 12 mg/kg (from 7.7 mg/kg in our previous trial), but kept the predominantly neurotoxic vincristine unchanged at 0.05 mg/kg, modulated by the same cyclosporin schedule (33 mg/kg over 3 hours on each of the 2 days per cycle). We treated 34 eyes in 23 patients: 2 A eyes, 11 B eyes, 6 C eyes and 15 D eyes. This report focuses only on the most difficult to save Group D eyes, and compares results with a non-cyclosporin carboplatin (26 mg/kg) and etoposide (10 mg/kg), vincristine (0.05 mg/kg) regimen. Radiation or enucleation for recurrence was considered failure. RESULTS: We report the long-term results of 15 Group D eyes in 10 patients, at mean followup of 11.1 years and median followup of 10.8 years (range 5.7-13.4 years). Eye event-free rate was 53% for Group D (8/15) eyes. Seven D eyes failed, and 6 were enucleated and 1 radiated. No child lost both eyes. Toxicity rates were acceptable with 15.7% fever-and-neutropenia, 0.7% bacterial sepsis, 9.7% blood transfusion and 27.6% platelet transfusion, and no long-term renotoxicity or ototoxicity. In comparison, at mean followup of 4.5 years (range 0.4-9.8 years), in a previously reported (Pediatr Blood Cancer 2013; 60:688-693) non-cyclosporin regimen, the non-radiation eye event-free rate was 47% for Group D (26/55) eyes, with 5 eyes enucleated, and 24 eyes radiated (19 irradiated eyes retained; 5 irradiated eyes required enucleation). CONCLUSION: This cyclosporin-modulated intensified-dosage protocol was well-tolerated, with a non-radiation eye salvage rate of 53%, and 60% overall if the one irradiated but retained eye was included, in the most difficult to save Group D eyes. No child lost both eyes, and most avoided radiation. This same protocol is being tested in a multicenter trial. Citation Format: Helen S.L. Chan, Elise Héon, A Linn Murphree, Paulita P. Astudillo, Helen Dimaras, Furqan Shaikh, Brenda L. Gallie. Cyclosporin-modulated intensified-dosage chemotherapy for saving eyes with Group D intraocular retinoblastoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 767. doi:10.1158/1538-7445.AM2014-767

Animal models in ocular oncology

AbstractRetinoblastoma is a rare cancer in childhood. The goal of current and future therapeutic strategies is to conserve the eye and visual function without using external beam radiotherapy that increases the risk of second cancer in genetically predisposed patients. Multimodality therapy (usual intravenous but also, intra‐arterial, intra‐vitreal chemotherapy, transpupillary thermotherapy, cryotherapy, brachytherapy) has recently improved eye salvage rate and allowed decreased need for external beam radiotherapy. However treatment of advanced intraocular retinoblastoma remains a real challenge, especially in case of vitreous and sub‐retinal seeding. There is a need of alternative and less toxic therapy and a need of new ways for administration of the drugs. Animal models are an integral part of preclinical research in the field of oncology. This paper described the different xenograft rodent models published in the literature. We have also developed a new orthotopic xenografted retinoblastoma model in immunodeficient mice, suitable for pre‐ clinical assays.

Brachytherapy of intra ocular tumors using ′BARC I-125 Ocu-Prosta seeds′: An Indian experience

Aim:To report our experience of brachytherapy using ‘BARC I-125 Ocu-Prosta seeds’ for the management of intraocular tumors with regard to tumor control, globe preservation visual outcome, and patient survival at Sankara Nethralaya, Chennai, India between September 2003 and May 2011.Materials and Methods:We reviewed records of 35 eyes of 35 patients who underwent ophthalmic brachytherapy between September 2003 and May 2011. Twenty-one cases had choroidal melanoma, nine had childhood retinoblastoma, two had adult-onset retinoblastoma, and there were one case each of vasoproliferative tumor, retinal angioma, and ciliary body melanoma. Brachytherapy was administered using a 15- or 20-mm gold plaque with or without a notch. Brachytherapy was the primary treatment modality in all tumors other than retinoblastoma, wherein brachytherapy was done post chemoreduction for residual tumor.Results:For choroidal melanomas, the mean radiation dose was 68.69 ± 15.07 (range, 47.72-94.2) Gy. The eye salvage rate was 13/20 (65%) and tumor control rate was 16/20 (80%) at an average follow-up of 24.43 ± 24.75 (range, 1.5-87.98) months. For retinoblastoma, the mean dose was 45.85 ± 3.90 (range, 39.51-50.92) Gy. The eye salvage rate and tumor control rate was 5/6 (83.3%) at an average follow-up of 38.36 ± 31.33 (range, 4.14-97.78) months. All eyes with retinoblastoma needed additional focal therapy for tumor control and eye salvage.Conclusion:The results of this retrospective study confirms that the use of ‘BARC I-125 Ocu-Prosta seeds’ in episcleral plaques to treat intraocular tumors offers a viable option for the management of intraocular cancers.

Chemotherapy plus cyclosporine A for the treatment of intraocular retinoblastoma: The University of Miami Miller School of Medicine experience

20005 Background: In the past decade chemotherapy and focal control became the standard of care in retinoblastoma. The ideal chemotherapy regimen has not yet been determined. We analyzed the results of treatment at the University of Miami Miller School of Medicine using the regimen carboplatin (20 mg/kg, day 1), vincristine (0.05 mg. /kg, day 1), etoposide (5 mg / kg, days 1 and 2) with or without cyclosporine A (10 mg. /kg over 2 hours followed by 45 mg/kg over 31 hours) every 3–4 weeks. We attempted to maintain peak CSA levels between 2,400 and 6,000 and steady state levels between 2,400 and 4,200 ng/ml. When CSA was given, vincristine was started at 0.0125 mg /kg. The dose was escalated by 25% with each cycle of therapy, as tolerated. Methods: A retrospective analysis was performed in 41 patients diagnosed with bilateral retinoblastoma from Dec 1996 to Jan 2006. Only eyes with intraocular disease (76 eyes) were included in this analysis. Before each cycle of chemotherapy ophthalmologic examination under anesthesia was performed and active tumor and seeding were treated with local ablation using laser therapy. Eyes in which enucleation was planned at diagnosis were excluded from this analysis. Results: Most patients received 9 cycles of chemotherapy. Sixty percent (46/76) of the eyes were treated with chemotherapy and CSA. The eye salvage rate for eyes classified by the International Classification of Retinoblastoma (ICRB) as groups A, B, C and D was 100%. The eye salvage rate for the 21 eyes classified as ICRB group E was 29%. No difference in salvage rate was observed in eyes treated with or without CSA. One patient died from disease progression. Only one patient required radiation therapy to both eyes. To date there have been no reports of development of secondary malignancies. Conclusion: The addition of CSA to the treatment of the eyes classified as ICRB groups A, B, C and D made no difference in the eye salvage rate. Also, we were not able to demonstrate any benefit from the addition of CSA in patients with stage E eyes- although our sample size was quite small. Aggressive focal control and chemotherapy beginning at diagnosis may be the reason for the excellent EFS in group A, B, C and D eyes. No significant financial relationships to disclose.