Long‐term outcomes of Group D retinoblastoma eyes during the intravitreal melphalan era

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

doi:10.1002/pbc.26696

Cited by 46 publications

(38 citation statements)

References 52 publications

(160 reference statements)

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“…In both these eyes, combined cataract and iris atrophy occurred. In comparison, previous data from our center reported grade 3 or higher retinal toxicity and/or anterior segment toxicity, including cataract, focal iris atrophy, and transient anterior segment inflammation developing in about 43% of patients [5, 6]. Our data from this small case series reflect higher rates of toxicity than previously demonstrated by our center, which examined all patients who received IVM with systemic chemoreduction.…”

Section: Discussioncontrasting

confidence: 42%

“…The injection procedure closely adheres to the protocol outlined by Munier and colleagues [13-15] and previously published [6]. Although a standardized dosage of melphalan has not been fully established due to the relative novelty of the treatment modality, previous publications support the usage of 20–40 µg.…”

Section: Methodsmentioning

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%

“…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: Discussioncontrasting

confidence: 42%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

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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“…Intravitreal administration of chemotherapy has been found to be very effective in treating vitreous seeding and has not been associated with extraocular dissemination of disease 21,22 . Intravitreal administration of melphalan and/or topotecan has been used postprimary therapy or concomitantly with systemic or IA chemotherapy to treat intravitreal seeding 23 . Intraocular toxicities associated with this approach include focal retinal pigment epithelial mottling at the site of injection, lens opacity, transient hypotony, transient retinal, or vitreous hemorrhage or optic disc edema 24…”

Section: Discussionmentioning

confidence: 99%

A single‐arm study of systemic and sub‐Tenon chemotherapy for Groups C and D intraocular retinoblastoma: A Children's Oncology Group study (ARET 0231)

Jubran

Villablanca

Krailo

et al. 2020

Pediatric Blood & Cancer

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Background Eyes with Group D intraocular retinoblastoma have low salvage rates. A pilot study showed safety and efficacy of sub‐Tenon's fascia carboplatin with systemic chemotherapy supporting further study. Methods Children with newly diagnosed bilateral intraocular retinoblastoma with at least one remaining Group C or D eye were treated with six courses of carboplatin/etoposide/vincristine (CEV) with sub‐Tenon's fascia carboplatin for Group C/D eyes during courses 2‐4. Local ophthalmic therapy started at course 3. The primary study objective was to determine the 1‐year failure rate of Group D eyes. Results The study closed prematurely due to poor accrual and 22 of 30 patients were evaluable for failure rate, contributing 25 Group D and four Group C eyes. Among the 25 Group D eyes, there were 13 failures within the first year of study enrollment including eight needing external beam radiotherapy (EBR) and five needing enucleation, resulting in 1‐year failure rate of 52%. The failure rate was significantly lower than the historical rate of 70% (P = .039). The 1‐year eye preservation rate for Group D eyes was 80% (20/25). One‐year failure rate for Group C eyes was 25% (1/4); 1‐year preservation rate was 100% without need for EBR. Systemic toxicity included Grade 3 hearing loss in two subjects, infections, neutropenia, and thrombocytopenia. Ocular toxicities included periorbital fat atrophy (13/29 = 45% eyes), optic nerve atrophy (1/29 = 3% eyes), and restrictive fibrosis (1/29 = 3% eyes). Conclusions Sub‐Tenon's fascia carboplatin plus CEV was partially effective in Group D intraocular retinoblastoma but had unacceptable ocular toxicities.

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Incidence and Risk Factors for Neutropenia After Intra-Arterial Chemotherapy for Retinoblastoma

Lee,

Donkor,

Parvus

et al. 2023

JAMA Ophthalmol

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ImportanceIntra-arterial chemotherapy (IAC) has quickly gained popularity as a mainstay of treatment for retinoblastoma. Intra-articular chemotherapy has been described as having several advantages over systemic chemotherapy, including reduced systemic toxicity and neutropenia; however, studies on the risk of neutropenia after IAC remain limited.ObjectiveTo estimate the incidence of neutropenia after IAC, as well as identify risk factors associated with the development of neutropenia.Design, Setting, and ParticipantsThis case series included pediatric patients with unilateral or bilateral retinoblastoma who were treated with IAC at a single quaternary care center from July 13, 2013, to January 6, 2023.ExposureAll patients were treated with IAC and underwent multiple IAC cycles depending on treatment response. The primary chemotherapy agent used was melphalan, but topotecan or carboplatin could be used along with melphalan. Melphalan doses were kept to 0.4 mg/kg or less per cycle. After each IAC cycle, complete blood cell counts were obtained within 10 to 12 days and repeated until the absolute neutrophil count (ANC) was greater than or equal to 1000/μL.Main Outcomes and MeasuresThe primary outcome was the minimum ANC after each IAC cycle. The secondary outcome was the development of severe (grade 3 or 4) neutropenia (ANC &lt;1000/μL). Regression analyses were used to identify associations between variables and outcomes. Receiver operating characteristic curves were used to calculate threshold dose for each chemotherapy agent potentially associated with the development of severe neutropenia.ResultsA total of 64 eyes of 49 patients (mean [SD] age, 1.7 [1.2] years; 25 females [51.0%]) with retinoblastoma were treated with 171 cycles of IAC. The mean (SD) nadir ANC was 1325.3 (890.7)/μL and occurred a median (IQR) of 10 (10-14) days (range, 6-28 days) after IAC administration. The frequency distribution of post-IAC neutropenia grades 0, 1, 2, 3, 4, and missing was 31 (18.1% of cycles), 25 (14.6%), 40 (23.4%), 37 (21.6%), 26 (15.2%), and 12 (7.0%), respectively. Factors weakly correlated with a lower ANC were higher melphalan dose (β = −2356 [95% CI, –4120.6 to −611.2]; adjusted R2 = 0.251; P = .01) and higher topotecan dose (β = −4056 [95% CI, –7003.6 to −1344.5]; adjusted R2 = 0.251; P = .006).Conclusions and RelevanceIn this case series of patients with retinoblastoma, the incidence of severe neutropenia after IAC was nearly 40%, which is higher than previously reported. Extended laboratory monitoring may aid in capturing previously overlooked cases of neutropenia. Topotecan may be associated with the development of neutropenia; limiting topotecan doses, especially in the setting of a high melphalan dose, may be beneficial in reducing the risk of neutropenia.

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Long‐term outcomes of Group D retinoblastoma eyes during the intravitreal melphalan era

Cited by 46 publications

References 52 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

A single‐arm study of systemic and sub‐Tenon chemotherapy for Groups C and D intraocular retinoblastoma: A Children's Oncology Group study (ARET 0231)

Incidence and Risk Factors for Neutropenia After Intra-Arterial Chemotherapy for Retinoblastoma

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