Not All Seeds Are Created Equal: Seed Classification Is Predictive of Outcomes in Retinoblastoma

Berry, Jesse L.; Bechtold, Mercy; Shah, Sona; Zolfaghari, Emily; Reid, Mark W; Jubran, Rima; Kim, Jonathan W.

doi:10.1016/j.ophtha.2017.05.034

Cited by 46 publications

(64 citation statements)

References 29 publications

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“…A previous series examining all eyes treated with IVM for persistent or recurrent vitreous seeding demonstrated a salvage rate of 68% with 100% success of the IVM therapy in eradicating vitreous seeds [5]. The 67% salvage rate of this case series suggests that concurrent chemotherapy and IVM may be a viable treatment option for patients with persistent seeding.…”

Section: Discussionmentioning

confidence: 69%

“…Comparisons to the larger previously published cohort, which included 28 eyes receiving systemic chemotherapy and IVM [5], are displayed in Table 2 by seed class [7, 14]. In this group of 28 eyes, 6 eyes demonstrated persistent seeding during systemic chemotherapy.…”

Section: Resultsmentioning

confidence: 99%

“…This protocol was utilized for patients with persistently active vitreous seeding diagnosed after 3 cycles of systemic chemotherapy, with patients receiving IVM on the same day as the 4th, 5th, and 6th cycles of chemoreduction. For persistent or recurrent seeding diagnosed after the completion of systemic chemoreduction, another series of weekly injections was performed following the previously described protocol [5, 6]. One patient received 5 total injections within cycles 4–6 of chemotherapy.…”

Section: Methodsmentioning

confidence: 99%

“…The advent of a safe and efficacious method for delivering intravitreal injection of melphalan (IVM) has revolutionized the current approach for treating seeding in advanced retinoblastoma [4]. Previous reports on the efficacy of intravitreal melphalan demonstrate 100% success in eradicating vitreous seeding and high globe salvage rates of 68–86% on par with rates previously attained with external beam radiation therapy [5-10]. …”

Section: Introductionmentioning

confidence: 99%

“…One hypothesis is to combine therapy and initiate concurrent IVM with cycles 4–6 of systemic chemotherapy. This approach has the potential benefit of providing synergistic antineoplastic effects against vitreous seeds while decreasing the overall number of examinations under anesthesia (EUA) that these children experience, given that IVM after systemic chemoreduction often requires 3 or more weekly injections [5, 6]. …”

Section: Introductionmentioning

confidence: 99%

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Integrated Treatment during the Intravitreal Melphalan Era: Concurrent Intravitreal Melphalan and Systemic Chemoreduction

et al. 2018

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Background: Intravitreal injection of melphalan (IVM) is safe and effective for the treatment of seeding in retinoblastoma. Current protocols require weekly injections during examination under anesthesia (EUA). To avoid additional anesthesia exposure for these children, IVM was initiated at the EUA concurrent with the 4th cycle of systemic chemoreduction in a series of 6 patients with persistent seeding. Methods: A retrospective review was completed to assess treatment response compared to all patients at our center treated with IVM and systemic chemotherapy. Overall, 6 eyes of 6 patients were included; salvage therapy included systemic chemoreduction with vincristine, etoposide, and carboplatin and IVM for persistent seeding. Results: IVM was initiated in all eyes at cycle 4 of their chemotherapy. Success in eradicating vitreous seeds was 100%; overall salvage rate was 67%. Anterior toxicity was observed in 2 out of 6 eyes and posterior toxicity in 4 out of 6 eyes. Conclusion: The concurrent chemoreduction and IVM protocol demonstrated a similar efficacy of globe salvage while sparing children additional EUAs. However, the increased rates of observed melphalan-related toxicities for concurrent therapy are concerning. Further clinical experience is necessary to define the best initiation time and dosing schedule for IVM.

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Section: Discussionmentioning

confidence: 69%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Integrated Treatment during the Intravitreal Melphalan Era: Concurrent Intravitreal Melphalan and Systemic Chemoreduction

et al. 2018

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Single vesicle analysis of aqueous humor in pediatric ocular diseases reveals eye specific CD63‐dominant subpopulations

Peng

Sirivolu

et al. 2022

J of Extracellular Bio

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Aqueous humor (AH), the clear fluid in front of the eye, maintains the pressure and vitality of ocular tissues. This fluid is accessible via the clear cornea which enables use of AH as a liquid biopsy source of biomarkers for intraocular disease. Extracellular vesicles are detectable in the AH and small extracellular vesicles (sEVs) are present in the AH from adults. However, EVs in AH from pediatric eyes in vivo have never previously been explored. We know very little about the heterogeneity of AH EV populations in ocular disease. Twenty-seven processing-free AH samples from 19 patients across four different pediatric ocular diseases were subjected to Nanoparticle Tracking Analysis (NTA) and Single Particle-Interferometric Reflectance Imaging Sensor (SP-IRIS) analysis. NTA demonstrated the concentration of AH EV/EPs is 3.11 × 10 9 -1.38 × 10 10 particles/ml; the majority sized 76.8-103 nm. SP-IRIS revealed distinct patterns of tetraspanin expression of AH sEVs. An enriched mono-CD63+ sEV subpopulation identified in AH indicates this is a potential AH-specific biomarker. In the setting of retinoblastoma there was a more heterogeneous population of sEVs which normalized with treatment. This suggests a potential clinical application of direct measurement of sEV subpopulations in AH samples to monitor successful tumor response to therapy.

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Response criteria for intraocular retinoblastoma: RB‐RECIST

Berry

Munier

Gallie

et al. 2021

Pediatric Blood & Cancer

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Standardized guidelines for assessing tumor response to therapy are essential for designing and conducting clinical trials. The Response Evaluation Criteria In Solid Tumors (RECIST) provide radiological standards for assessment of solid tumors. However, no such guidelines exist for the evaluation of intraocular cancer, and ocular oncology clinical trials have largely relied on indirect measures of therapeutic response—such as progression‐free survival—to evaluate the efficacy of treatment agents. Herein, we propose specific criteria for evaluating treatment response of retinoblastoma, the most common pediatric intraocular cancer, and emphasize a multimodal imaging approach for comprehensive assessment of retinoblastoma tumors in clinical trials.

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Not All Seeds Are Created Equal: Seed Classification Is Predictive of Outcomes in Retinoblastoma

Cited by 46 publications

References 29 publications

Integrated Treatment during the Intravitreal Melphalan Era: Concurrent Intravitreal Melphalan and Systemic Chemoreduction

Integrated Treatment during the Intravitreal Melphalan Era: Concurrent Intravitreal Melphalan and Systemic Chemoreduction

Single vesicle analysis of aqueous humor in pediatric ocular diseases reveals eye specific CD63‐dominant subpopulations

Response criteria for intraocular retinoblastoma: RB‐RECIST

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