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

Abstract

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.]

Comparing efficacy and side effects of two systemic chemotherapy regimens for eye‐preserving therapy in children with retinoblastoma

“…ICRB grouping predicted success of eye‐preserving systemic chemotherapy in multiple other study cohorts 17,18,34 . This finding is in line with a significantly lower EFES and OES for advanced intraocular tumors (ICRB D/E eyes) compared with ICRB A/B/C eyes after both chemotherapy regimens in our study.…”

“…ICRB grouping predicted success of eye-preserving systemic chemotherapy in multiple other study cohorts. 17,18,34 Until end of the study, no SPM has been reported in any of the two groups, but longer follow-up is required to validate this hypothesis because second cancers may occur decades after treatment for retinoblastoma. 35,36 Transient hematological toxicity, especially severe neutropenia, was a common side effect that occurred after about three-fourths of all chemotherapy cycles.…”

“…A retrospective study from the German referral center using CyVEC demonstrated a therapy failure‐free eye survival for ICRB A/B/C eyes with 67%–85% and 17% for ICRB D/E eyes. Other prognostic factors for recurrence of retinoblastoma after eye‐preserving chemotherapy described in the literature are younger age at diagnosis, presence of subretinal seeding, and heritable retinoblastoma that comes with the risk of developing new retinoblastomas 17 . The clinical factors age at diagnosis, laterality, and heritability are associated with each other because of the younger age at diagnosis and the risk for multiple retinoblastoma in children with heritable retinoblastoma.…”

“…[13][14][15][16] Younger age at diagnosis and advanced intraocular retinoblastoma according to the International Classification of Retinoblastoma (ICRB) have been described as risk factors for recurrences after eye-preserving systemic chemotherapy. 17,18 In the last two decades, local instead of systemic application of chemotherapy has been introduced into clinical care of retinoblastoma worldwide. Intra-arterial chemotherapy (IAC) administration into the ophthalmic artery has been shown to be highly effective and has replaced systemic chemotherapy as first-line chemotherapy in some centers.…”

“…Focal consolidation techniques include cryotherapy, brachytherapy, and laser photocoagulation 13–16 . Younger age at diagnosis and advanced intraocular retinoblastoma according to the International Classification of Retinoblastoma (ICRB) have been described as risk factors for recurrences after eye‐preserving systemic chemotherapy 17,18 . In the last two decades, local instead of systemic application of chemotherapy has been introduced into clinical care of retinoblastoma worldwide.…”