Clinical and genetic associations for carboplatin‐related ototoxicity in children treated for retinoblastoma: A retrospective noncomparative single‐institute experience

Soliman, Sameh E.; D'Silva, Crystal Nelita; Dimaras, Helen; Dzneladze, Irakli; Chan, Helen S. L.; Gallie, Brenda L.

doi:10.1002/pbc.26931

Cited by 34 publications

(38 citation statements)

References 59 publications

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“…As previously discussed (see 3.8.3.2.2), intravenous etoposide may induce secondary leukemias, even in patients who received what are considered safe cumulative dosages (Chantada et al, 2014;Gombos et al, 2007). Permanent ototoxicity is an important late effect of carboplatin-based chemoreduction regimens reported in up to 5-25% of the cases, especially if given at a younger age and with prolonged exposure (Jehanne et al, 2009;Qaddoumi et al, 2012;Soliman et al, 2018).…”

Section: Expected Toxicities Systemic Chemoreduction With Standardmentioning

confidence: 95%

Conservative management of retinoblastoma: Challenging orthodoxy without compromising the state of metastatic grace. “Alive, with good vision and no comorbidity”

Munier

Beck‐Popovic

Chantada

et al. 2019

Progress in Retinal and Eye Research

160

157

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Retinoblastoma is lethal by metastasis if left untreated, so the primary goal of therapy is to preserve life, with ocular survival, visual preservation and quality of life as secondary aims. Historically, enucleation was the first successful therapeutic approach to decrease mortality, followed over 100 years ago by the first eye salvage attempts with radiotherapy. This led to the empiric delineation of a window for conservative management subject to a "state of metastatic grace" never to be violated. Over the last two decades, conservative management of retinoblastoma witnessed an impressive acceleration of improvements, culminating in two major paradigm shifts in therapeutic strategy. Firstly, the introduction of systemic chemotherapy and focal treatments in the late 1990s enabled radiotherapy to be progressively abandoned. Around 10 years later, the advent of chemotherapy in situ, with the capitalization of new routes of targeted drug delivery, namely intra-arterial, intravitreal and now intracameral injections, allowed significant increase in eye preservation rate, definitive eradication of radiotherapy and reduction of systemic chemotherapy. Here we intend to review the relevant knowledge susceptible to improve the conservative management of retinoblastoma in compliance with the "state of metastatic grace", with particular attention to (i) reviewing how new imaging modalities impact the frontiers of conservative management, (ii) dissecting retinoblastoma genesis, growth patterns, and intraocular routes of tumor propagation, (iii) assessing major therapeutic changes and trends, (iv) proposing a classification of relapsing retinoblastoma, (v) examining treatable/preventable disease-related or treatment-induced complications, and (vi) appraising new therapeutic targets and concepts, as well as liquid biopsy potentiality.

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Section: Expected Toxicities Systemic Chemoreduction With Standardmentioning

confidence: 95%

Conservative management of retinoblastoma: Challenging orthodoxy without compromising the state of metastatic grace. “Alive, with good vision and no comorbidity”

Munier

Beck‐Popovic

Chantada

et al. 2019

Progress in Retinal and Eye Research

160

157

View full text Add to dashboard Cite

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“…Tumors become advanced if treatment is delayed, hindering vision and globe salvages with a risk of metastasis [ 8 , 9 , 10 ]. Chemotherapy is the standard of care for patients with a high risk of metastasis but has inevitable toxicity [ 10 , 11 , 12 , 13 , 14 , 15 ]. Such treatment is also commonly used for globe sparing with different routes of drug delivery depending on the clinical features and anticipated outcomes [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Retinoblastoma: Etiology, Modeling, and Treatment

Kaewkhaw

Rojanaporn

2020

Cancers

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Retinoblastoma is a retinal cancer that is initiated in response to biallelic loss of RB1 in almost all cases, together with other genetic/epigenetic changes culminating in the development of cancer. RB1 deficiency makes the retinoblastoma cell-of-origin extremely susceptible to cancerous transformation, and the tumor cell-of-origin appears to depend on the developmental stage and species. These are important to establish reliable preclinical models to study the disease and develop therapies. Although retinoblastoma is the most curable pediatric cancer with a high survival rate, advanced tumors limit globe salvage and are often associated with high-risk histopathological features predictive of dissemination. The advent of chemotherapy has improved treatment outcomes, which is effective for globe preservation with new routes of targeted drug delivery. However, molecularly targeted therapeutics with more effectiveness and less toxicity are needed. Here, we review the current knowledge concerning retinoblastoma genesis with particular attention to the genomic and transcriptomic landscapes with correlations to clinicopathological characteristics, as well as the retinoblastoma cell-of-origin and current disease models. We further discuss current treatments, clinicopathological correlations, which assist in guiding treatment and may facilitate globe preservation, and finally we discuss targeted therapeutics for future treatments.

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“…All these approaches are still widely used in combination. However, systemic chemotherapy exposes the patient to risks of moderate haematological toxicity, rare risks of hearing toxicity and, potentially, increased risk of secondary cancers in children with an inherited form of Rb. Furthermore, its poor efficacy on vitreous seeds (which are avascular) and subretinal masses led to the development of local delivery of chemotherapy around or directly into the eye.…”

Section: Introductionmentioning

confidence: 99%

Low retinal toxicity of intravitreal carboplatin associated with good retinal tumour control in transgenic murine retinoblastoma

Lemaître

Poyer

Fréneaux

et al. 2020

Clinical Exper Ophthalmology

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Background: Retinoblastoma is a rare intraocular malignancy in children. Current treatments have many adverse effects. New therapeutic approaches like intravitreal injections of chemotherapies are currently being developed but their toxicities need to be evaluated on animal models. This study compares the efficacy and toxicity of intravitreal melphalan, topotecan and carboplatin, alone or in combination (sequential administration), in the LHBetaTag retinoblastoma mice. Methods: Mice were divided into nine groups: control, carboplatin 1.5 and 4 μg, melphalan 0.1 and 1 μg, topotecan 0.1 and 1 μg, carboplatin 4 μg/ topotecan 0.1 μg and melphalan 1 μg/topotecan 0.1 μg. The follow-up was performed using fundus imaging and optical coherence tomography combined with histopathological analysis. Absence of tumour and presence of calcified tumours were the criteria for therapeutic response assessment. Ocular complications were assessed after four weekly injections. Retinal toxicity was defined by the decrease of retinal thickness and of the number of retinal layers.Results: Topotecan was inactive on retinal tumours. Melphalan (1 μg) led to a complete tumour control in 91.7% of eyes. Carboplatin strongly decreased the tumour burden (85.7-93.8% of eyes without retinal tumour). The intravitreal injection itself led to ocular complications (25% of media opacities and 45.7% of retinal detachment). Only melphalan at 1 μg showed a strong retinal toxicity. The two combinations showed a good efficacy in reducing the number of eyes with retinal tumours with a reduced retinal toxicity.Conclusions: This preclinical study suggests that intravitreal injection of carboplatin has a low toxicity and could be evaluated in clinical practice to treat patients suffering from retinoblastoma. K E Y W O R D Scarboplatin, fundus imaging and optical coherence tomography, intravitreal injection, melphalan, retinoblastoma, topotecan

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Clinical and genetic associations for carboplatin‐related ototoxicity in children treated for retinoblastoma: A retrospective noncomparative single‐institute experience

Abstract: We observed a 25% prevalence of ototoxicity in patients with retinoblastoma treated with carboplatin, higher than previously published. Age at chemotherapy initiation was associated with carboplatin-induced ototoxicity, with children <4.25 months of age at highest risk.

Cited by 34 publications

References 59 publications

Conservative management of retinoblastoma: Challenging orthodoxy without compromising the state of metastatic grace. “Alive, with good vision and no comorbidity”

Conservative management of retinoblastoma: Challenging orthodoxy without compromising the state of metastatic grace. “Alive, with good vision and no comorbidity”

Retinoblastoma: Etiology, Modeling, and Treatment

Low retinal toxicity of intravitreal carboplatin associated with good retinal tumour control in transgenic murine retinoblastoma

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