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Background Retinoblastoma (Rb) is the most common primary ocular malignancy of childhood. Left untreated, it is 100% fatal and carries a substantial risk of impaired vision and removal of one or both eyes. Intra-arterial chemotherapy (IAC) has become a pillar in the treatment paradigm for Rb that allows for better eye salvage and vision preservation without compromising survival. We describe the evolution of our technique over 15 years. Methods A retrospective chart review was conducted of 571 patients (697 eyes) and 2391 successful IAC sessions over 15 years. This cohort was separated into three 5-year periods (P1, P2, P3) to assess trends in IAC catheterization technique, complications, and drug delivery. Results From a total of 2402 attempted IAC sessions, there were 2391 successful IAC deliveries, consistent with a 99.5% success rate. The rate of successful super-selective catheterizations over the three periods ranged from 80% in P1 to 84.9% in P2 and 89.2% in P3. Catheterization-related complication rates were 0.7% in P1, 1.1% in P2, and 0.6% in P3. Chemotherapeutics used included combinations of melphalan, topotecan and carboplatin. The rate of patients receiving triple therapy among all groups was 128 (21%) in P1, 487 (41.9%) in P2, and 413 (66.7%) in P3. Conclusions The overall rate of successful catheterization and IAC started high and has improved over 15 years, and catheterization-related complications are rare. There has been a significant trend towards triple chemotherapy over time. [ABSTRACT FROM AUTHOR]

Summary: Little is known about outcomes following interruption of targeted therapy in adult patients with histiocytic neoplasms. This is an IRB‐approved study of patients with histiocytic neoplasms whose BRAF and MEK inhibitors were interrupted after achieving complete or partial response by 18‐fluorodeoxyglucose positron emission tomography (FDG‐PET). 17/22 (77%) of patients experienced disease relapse following treatment interruption. Achieving a complete response prior to interruption, having a mutation other than BRAFV600E, and receiving MEK inhibition only were each associated with a statistically significant improvement in relapse‐free survival. Relapse is common following treatment interruption however some patients may be suitable for limited‐duration treatment. [ABSTRACT FROM AUTHOR]

Background: Despite improvements in the treatment of primary uveal melanoma (UM), patients with metastatic disease continue to exhibit poor survival. Methods: A retrospective review of metastatic UM patients at Yale (initial cohort) and Memorial Sloan Kettering (validation cohort) was conducted. Cox proportional hazards regression was used to determine baseline factors that are associated with overall survival, including sex, Eastern Cooperative Oncology Group (ECOG) Performance Status Scale, laboratory measurements, metastasis location, and use of anti‐CTLA‐4 and anti‐PD‐1 therapies. Differences in overall survival were analyzed using Kaplan–Meier analysis. Results: A total of 89 patients with metastatic UM were identified; 71 and 18, in the initial and validation cohorts, respectively. In the initial cohort, median follow‐up was 19.8 months (range, 2–127 months) and median overall survival was 21.8 months (95% CI, 16.6–31.3). Female sex, anti–CTLA‐4, and anti–PD‐1 therapy were associated with better survival outcomes with adjusted death hazard ratios (HRs) of 0.40 (95% CI, 0.20–0.78), 0.44 (0.20–0.97), and 0.42 (0.22–0.84), respectively, whereas development of hepatic metastases and ECOG score ≥1 (per 1 U/L) were associated with worse survival outcomes with HRs of 2.86 (1.28–7.13) and 2.84 (1.29–6.09), respectively. In both the initial and validation cohorts, use of immune checkpoint inhibitors was associated with improved overall survival after adjusting for sex and ECOG score, with death HRs of 0.22 (0.08–0.56) and 0.04 (0.002–0.26), respectively. Conclusions: Development of extrahepatic‐only metastases, ECOG of 0, immune checkpoint therapy, and female sex were each associated with more than 2‐fold reductions in risk of death. Plain Language Summary: Metastatic uveal melanoma patients face limited treatment options and poor survival rates. Results from this retrospective analysis indicate that immune checkpoint inhibitors, such as anti–CTLA‐4 and anti–PD‐1 therapies, were associated with improved survival outcomes. Factors such as extrahepatic‐only metastases, better baseline performance status, and female sex contributed to a more than 2‐fold reduction in death risk. These findings highlight the potential of immunotherapy in treating metastatic uveal melanoma. Despite advancements in treatment, metastatic uveal melanoma outcomes remain poor. Female sex, higher baseline performance status, extrahepatic‐only metastases, and immune checkpoint therapy are associated with improved survival. [ABSTRACT FROM AUTHOR]

Background/Aims Sheet-like type of epithelial downgrowth (EDG) is not easily amenable to surgical excision. We describe long-term outcomes in patients with EDG treated with intraocular methotrexate (MTX). Methods This is a retrospective, multicentric case series including 10 eyes (nine patients) treated with intraocular MTX for sheet-like EDG. Relevant ocular history, previous EDG treatments, MTX injection regimen, long-term outcomes and complications are reported. Results All cases were associated with intraocular surgery. Most patients were treated with 400 µm/0.1mL MTX injections with a starting frequency of two times per week or weekly injections. Mean and SD number of injections per eye was 16±13 injections and duration of follow-up was 54±36 months (range: 7-120 months). Eradication of EDG was achieved in seven eyes of which one required a second MTX treatment course to achieve eradication, while clinical resolution with recurrence was observed in two. One treatment failure occurred despite eightweekly injections which slowed but did not halt EDG progression; the patient later requested that treatments be stopped given difficulty to come to followups. Surface epitheliopathy developed in eight patients and was used to titrate MTX treatment. Six patients also developed endothelial failure. Conclusion We report the largest case series of diffuse, sheet-like EDG treated with intraocular MTX with follow-ups up to 10 years. Intraocular MTX may be used effectively to achieve eradication of EDG in cases where surgery is not amenable. However, further recommendations to guide treatment remain warranted. [ABSTRACT FROM AUTHOR]