Long-term (20-year) real-world outcomes of intravenous chemotherapy (chemoreduction) for retinoblastoma in 964 eyes of 554 patients at a single centre.

BACKGROUND: Intravenous chemotherapy (IVC) remains an important globe salvage therapy for retinoblastoma. METHODS: Evaluation of long-term globe salvage at 5, 10, 15 and 20 years following frontline IVC for retinoblastoma. RESULTS: Of 994 eyes, comparison by International Classification of Retinoblastoma group (A vs B vs C vs D vs E) revealed more advanced group with older mean age at presentation (8 vs 7 vs 10 vs 11 vs 15 months, p<0.001). By clinical features, more advanced group demonstrated greater mean tumour diameter (3.2 vs 6.8 vs 9.4 vs 14.3 vs 16.4, p<0.001) and thickness (2.0 vs 3.7 vs 4.4 vs 7.3 vs 9.3, p<0.001), and greater frequency of vitreous seeds ≥1 quadrant (0% vs 0% vs 44% vs 42% vs 57%, p<0.001) and subretinal seeds (0% vs 0% vs 22% vs 65% vs 54%, p<0.001). By outcomes, less advanced group demonstrated greater tumour control (without need for enucleation or external beam radiotherapy (EBRT)) by year 2 (96% vs 91% vs 91% vs 71% vs 32%, p<0.001), and with minimal change up to 20 years. In order to achieve globe salvage, additional intra-arterial chemotherapy (IAC) or plaque radiotherapy was employed by year 2 (5% vs 26% vs 28% vs 27% vs 19%, p<0.001), with little further need up to 20 years. Pinealoblastoma (2%), metastasis (2%) and death (1%) were infrequent. CONCLUSION: Frontline IVC (plus additional IAC and/or plaque radiotherapy) for retinoblastoma provided complete tumour control for groups A (96%), B (91%), C (91%), D (71%) and E (32%), avoiding enucleation or EBRT and was lasting for up to 20 years.

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.

Indocyanine Green-Enhanced Transpupillary Thermotherapy for Retinoblastoma: Analysis of 42 Tumors.

PURPOSE: To evaluate the efficacy of indocyanine green-enhanced transpupillary thermotherapy (ICG-TTT) for retinoblastoma that shows suboptimal response to conventional treatments. METHODS: A single center, retrospective chart review. The technique involved ICG infusion (range: 0.3 to 0.5 mg/kg) 1 minute prior to applying TTT using the indirect ophthalmoscope technique with a spot size of 1.2 mm. RESULTS: There were 42 retinoblastomas in 30 eyes of 21 patients treated with ICG-TTT. The reasons for ICG enhancement included suboptimal response to standard TTT (n = 31, 74%), recurrence after standard TTT (n = 3, 7%), or minimally pigmented fundus with poor standard TTT uptake (n = 8, 19%). The mean patient age at treatment was 12 months (median: 11.6 months, range: 3 to 31 months). The mean tumor base was 3.5 mm (median: 3 mm), mean tumor thickness was 2.5 mm (median; 2 mm), mean distance to the foveola was 2.6 mm (median: 3 mm), and mean distance to the optic disc was 2.2 mm (median: 0.75 mm). Treatment parameters included a spot size of 1.2 mm, mean power of 760 mW (median: 800 mW, range: 400 to 1,200 mW), and mean duration of 4 minutes (median: 4 minutes, range: 0.5 to 14 minutes). Following a median of 2 sessions (range: 1 to 5 sessions) of ICG-TTT, 33 (79%) tumors demonstrated complete regression. The mean tumor thickness postoperatively was 1.7 mm. Two (5%) tumors showed minimal regression after ICG-TTT. During a mean follow-up of 46 months (median: 33 months), tumor recurrence after ICG-TTT developed in 7 (17%) cases at a mean interval of 7 months. Local complications of ICG-TTT included focal paraxial cataract (n = 2, 7%), iris atrophy (n = 1, 3%), and transient retinal hemorrhage (n = 2, 7%). Systemic problems included ICG allergy (n = 1, 5%). Overall, tumor control and globe salvage was achieved in all 30 (100%) eyes. There were no metastatic events. CONCLUSIONS: ICG-TTT is an effective alternative for reti-noblastoma control, particularly for small tumors that show suboptimal response to standard

Targeted retinoblastoma management: when to use intravenous, intra-arterial, periocular, and intravitreal chemotherapy.

PURPOSE OF REVIEW: The management of retinoblastoma is complex and involves strategically chosen methods of enucleation, radiotherapy, chemotherapy, laser photocoagulation, thermotherapy, and cryotherapy. Chemotherapy has become the most common eye-sparing modality. There are four routes of delivery of chemotherapy for retinoblastoma, including intravenous, intra-arterial, periocular, and intravitreal techniques. The purpose of this review is to discuss the current rationale for each method and the anticipated outcomes. RECENT FINDINGS: The diagnosis of retinoblastoma should be clinically established prior to embarking on a chemotherapy protocol. There are over 25 conditions that can closely simulate retinoblastoma in a young child. In addition, enucleation is an acceptable method for management, particularly with advanced retinoblastoma. Intravenous chemotherapy is generally used for germline mutation (bilateral, familial) retinoblastoma with excellent tumor control for groups A, B, and C and intermediate control for group D eyes. Intra-arterial chemotherapy is used as primary therapy in selected cases for nongermline mutation (unilateral) retinoblastoma with excellent control, and also used as secondary therapy for recurrent solid retinoblastoma, subretinal seeds, and vitreous seeds. Periocular chemotherapy is employed to boost local chemotherapy dose in advanced bilateral groups D and E eyes or for localized recurrences. Intravitreal chemotherapy is used for recurrent vitreous seeds from retinoblastoma. Patients at high risk for metastases should receive intravenous chemotherapy. SUMMARY: Chemotherapy is effective for retinoblastoma and the targeted treatment route depends on the clinical features and anticipated outcomes.