Modern treatment of retinoblastoma: A 2020 review.

Retinoblastoma management remains complex, requiring individualized treatment based on International Classification of Retinoblastoma (ICRB) staging, germline mutation status, family psychosocial factors and cultural beliefs, and available institutional resources. For this 2020 retinoblastoma review, PubMed was searched for articles dated as early as 1931, with an emphasis on articles from 1990 to the present day, using keywords of retinoblastoma, chemotherapy, intravenous chemotherapy, chemoreduction, intra-arterial chemotherapy, ophthalmic artery chemosurgery, intravitreal chemotherapy, intracameral chemotherapy, cryotherapy, transpupillary thermotherapy, laser, radiation, external beam radiotherapy, plaque radiotherapy, brachytherapy, and enucleation. We discuss current treatment modalities as used in the year 2020, including intravenous chemotherapy (IVC), intra-arterial chemotherapy (IAC), intravitreal chemotherapy (IvitC), intracameral chemotherapy (IcamC), consolidation therapies (cryotherapy and transpupillary thermotherapy [TTT]), radiation-based therapies (external beam radiotherapy [EBRT] and plaque radiotherapy), and enucleation. Additionally, we present a consensus treatment algorithm based on the agreement of three North American retinoblastoma treatment centers, and encourage further collaboration amongst the world's most expert retinoblastoma treatment centers in order to develop consensus management plans and continue advancement in the identification and treatment of this childhood cancer.

Risk Factors for Tumor Recurrence Following Primary Intravenous Chemotherapy (Chemoreduction) for Retinoblastoma in 869 Eyes of 551 Patients.

PURPOSE: To identify risk factors for retinoblastoma recurrence following chemoreduction. METHODS: This was a retrospective review of patients with retinoblastoma treated from 1994 to 2019 using chemoreduction with analysis for recurrence using Kaplan-Meier, Cox regression, and logistic regression. RESULTS: There were 869 eyes of 551 patients with retinoblastoma treated with chemoreduction. Follow-up in 556 eyes revealed main solid tumor recurrence (n = 355, 64%), subretinal seed recurrence (n = 244, 44%), vitreous seed recurrence (n = 162, 29%), and/or new tumor (n = 118, 21%) requiring management with focal therapy (transpupillary thermotherapy, cryotherapy) (n = 294, 53%), intra-arterial chemotherapy (n = 125, 22%), intravitreal chemotherapy (n = 36, 6%), plaque radiotherapy (n = 120, 22%), external beam radiotherapy (n = 57, 10%), and/or enucleation (n = 49, 9%). Of all recurrences, 62% were detected by 1 year, 86% by 2 years, 94% by 3 years, 98% by 5 years, 99% by 10 years, and 100% by 15 years. Risk factors for recurrence on multivariate analysis included younger patient age at presentation (odds ratio [OR] = 1.02 [1.00 to 1.04] per 1 month decrease, P = .02), greater International Classification of Retinoblastoma group (OR = 1.24 [1.05 to 1.47] per 1 more advanced group, P = .01), shorter tumor distance to optic disc (OR = 1.11 [1.01 to 1.21] per 1 mm decrease, P = .03), and presence of subretinal seeds (OR = 1.66 [1.09 to 2.53], P = .02). CONCLUSIONS: Retinoblastoma recurrence after chemoreduction is usually detected within the first 3 years following treatment. Younger patients with more advanced, posteriorly located tumors and subretinal seeds at presentation are at increased risk, but recurrence can often be managed with globe-sparing therapy. [J Pediatr Ophthalmol Strabismus. 2020;57(4):224-234.].

Circumscribed Choroidal Hemangioma: Visual Outcome in the Pre-Photodynamic Therapy Era versus Photodynamic Therapy Era in 458 Cases.

PURPOSE: To analyze visual outcomes after treatment of choroidal hemangioma in the pre-photodynamic therapy (PDT) era versus PDT era. DESIGN: Retrospective, comparative case series. PARTICIPANTS: A total of 458 patients with circumscribed choroidal hemangioma. METHODS: Comparison of hemangioma managed in the pre-PDT (1967-2001) era versus PDT (2002-2018) era. MAIN OUTCOME MEASURE: Visual acuity outcome. RESULTS: A total of 458 tumors were treated over this 51-year period. A comparison (pre-PDT [n = 220 cases] vs. PDT [n = 238 cases]) revealed PDT era patients were of older mean age (48.9 vs. 53.8 years, P = 0.002) and were more likely to have systemic hypertension (17.7% vs. 33.8%, P < 0.001), tumor location in the macula (57.4% vs. 67.5%, P = 0.01), subretinal fluid on OCT (33.3% vs. 70.7%, P = 0.01), and greater extent of overlying lipofuscin (P = 0.001). Findings of tumor basal diameter and thickness and fluorescein and indocyanine green angiography were no different in the 2 eras. Treatment (pre-PDT vs. PDT) included argon laser photocoagulation (42.1% vs. 0.4%), PDT (0% vs. 43.8%), transpupillary thermotherapy (0% vs. 0.4%), plaque radiotherapy (7.0% vs. 5.2%), external beam radiotherapy (1.4% vs. 1.3%), enucleation (0.9% vs. 0.4%), and observation (48.6% vs. 47.6%). After treatment, patients in the PDT era demonstrated better mean logarithm of the minimum angle of resolution visual acuity (1.28 vs. 0.51, P < 0.001) (Snellen equivalent 20/400 vs. 20/63, P < 0.001). Final visual acuity was ≥20/40 for those with entering vision of ≥20/40 (59.6% vs. 74.7%, P = 0.001) and for those with entering vision of 20/50-20/200 (25.4% vs. 47.3%, P < 0.001). CONCLUSIONS: Management of choroidal hemangioma in the PDT era has allowed for significantly better visual outcome compared with the pre-PDT era, with mean final visual acuity of 20/400 (pre-PDT era) versus 20/63 (PDT era).

Nomogram for visual acuity outcome after iodine-125 plaque radiotherapy and prophylactic intravitreal bevacizumab for uveal melanoma in 1131 patients.

AIMS: To develop a nomogram for prediction of visual acuity outcome following plaque radiotherapy for uveal melanoma. METHODS: Retrospective review of uveal melanoma treated with plaque radiotherapy and prophylactic intravitreal bevacizumab injections at 4-month intervals for 2 years duration. Two nomograms for poor visual acuity outcome (Snellen <20/200) were developed based on (1) Clinical risk factors. (2) Or clinical and treatment risk factors. RESULTS: There were 1131 included cases. The most important clinical risk factors (points for nomogram) for poor visual acuity outcome included subretinal fluid involving four quadrants (100), tumour thickness >4 mm (69), presenting visual acuity ≤20/30 (65), non-Caucasian race (58), tumour shape mushroom, bilobed, or multilobulated (57), and insulin-dependent diabetes (54). Risk of poor visual acuity at 2 years and 4 years increased from 11% and 24% with 40 points to 97% and >99% with 304 points. A second analysis was performed using both clinical and treatment risk factors. The most important factors included presenting visual acuity ≤20/30 (100), tumour largest basal diameter >11 mm (80), radiation dose rate to tumour base ≥164 cGy/hour (78), tumour thickness >4 mm (76), insulin-dependent diabetes (75) and abnormal foveolar status by optical coherence tomography at presentation (72). Risk of poor visual acuity at 2 years and 4 years increased from 6% and 14% with 56 points to 88% and 99% with 496 points. CONCLUSIONS: A nomogram using clinical or treatment risk factors can predict visual acuity outcome following plaque radiotherapy and prophylactic intravitreal bevacizumab for uveal melanoma and is available online at https://fighteyecancer.com/nomograms/.

Outcomes of neonatal retinoblastoma in pre-chemotherapy and chemotherapy eras.

Purpose: To quantify outcomes for neonatal retinoblastoma patients treated during the pre-chemotherapy (1980-1994) and chemotherapy (1995-2018) eras. Methods: Retrospective review of retinoblastoma patients diagnosed within the first 28 days of life between 1/1/1980 and 11/30/2018. Student's t-test, Chi-square, and Fisher's exact test were performed to compare treatments and outcomes by era. Results: There were 68 patients with neonatal retinoblastoma (12% unilateral and 88% bilateral). According to era (pre-chemotherapy vs. chemotherapy), the number of treated patients was 26 (38%) vs. 42 (62%). Primary treatment was external beam radiotherapy (50% vs. 1%,P < 0.001), plaque radiotherapy (17% vs. 0%,P < 0.001), focal treatment (transpupillary thermotherapy or cryotherapy) only (21% vs. 14%,P= 0.33), intravenous chemotherapy (0% vs. 81%,P < 0.001), enucleation (10% vs. 4%,P= 0.26), or exenteration (2% vs. 0%,P= 0.37). Outcomes included tumor control (79% vs. 94%,P= 0.02), globe salvage (75% vs. 91%,P= 0.02), final gross visual acuity for salvaged eyes 20/200 or better (66% vs. 89%,P < 0.01), and death (19% vs. 0%,P < 0.01). Conclusion: Chemotherapy advancements for neonatal retinoblastoma have improved tumor control, globe salvage, visual acuity, and patient survival.