External Beam Radiotherapy in Retinoblastoma

Scott, Ingrid U.; Murray, Timothy G.; Feuer, William J.; Quill, K. Van; Markoe, Arnold M.; Ling, Stella; Roth, Daniel B.; O’Brien, Joan M.

doi:10.1001/archopht.117.6.766

Cited by 53 publications

(9 citation statements)

References 28 publications

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“…[2] With timely diagnosis and aggressive multimodal therapy, cure rates for retinoblastoma in the developed world are high (~95%). Currently available efficacious treatments include photocoagulation, [3–4] thermotherapy, [5] cryotherapy, [6–7] , chemotherapy (intravenous and/or local) , [8] plaque radiotherapy, [9–10] external beam radiotherapy (EBRT), [11–[12] and enucleation (surgical removal of the eye). [13–14] Reviews of management strategies for retinoblastoma have been published.…”

Section: Introductionmentioning

confidence: 99%

Progress in Small Molecule Therapeutics for the Treatment of Retinoblastoma

Pritchard¹,

Dyer

Guy

2016

MRMC

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While mortality is low for intraocular retinoblastoma patients in the developed world who receive aggressive multimodal therapy, partial or full loss of vision occurs in approximately 50% of patients with advanced bilateral retinoblastoma. Therapies that preserve vision and reduce late effects are needed. Because clinical trials for retinoblastoma are difficult due to the young age of the patient population and relative rarity of the disease, robust preclinical testing of new therapies is critical. The last decade has seen advances towards identifying new therapies including the development of animal models of retinoblastoma for preclinical testing, progress in local drug delivery to reach intraocular targets, and improved understanding of the underlying biological mechanisms that give rise to retinoblastoma. This review discusses advances in these areas, with a focus on discovery and development of small molecules for the treatment of retinoblastoma, including novel targeted therapeutics such as inhibitors of the MDMX-p53 interaction (nutlin-3a), histone deacetylase (HDAC) inhibitors, and spleen tyrosine kinase (SYK) inhibitors.

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Section: Introductionmentioning

confidence: 99%

Progress in Small Molecule Therapeutics for the Treatment of Retinoblastoma

Pritchard¹,

Dyer

Guy

2016

MRMC

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“…Focal delivery to the eye, new megavoltage machines, and lens-sparing techniques have contributed to the increasing efficacy of this treatment modality, improving ocular and visual prognoses, while decreasing treatmentrelated morbidities. 34 The current study demonstrates that hyperfractionation (increasing the frequency of radiation treatment, while decreasing the fraction delivered per treatment) is significantly associated with increased tumor control in a murine transgenic model of retinoblastoma.…”

Section: Commentmentioning

confidence: 66%

Hyperfractionated External Beam Radiation Therapy in the Treatment of Murine Transgenic Retinoblastoma

Hayden¹,

Murray

Cicciarelli

et al. 2002

Arch Ophthalmol

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Objective: To determine the in vivo efficacy of hyperfractionated external beam radiation therapy (EBRT) in comparison with standard daily EBRT in a murine model of heritable retinoblastoma. Methods: Two hundred twenty eyes from 6-week-old simian virus-40 large T-antigen-positive mice were treated with a total dose of EBRT ranging from 10-76 Gy (1000 to 7600 rad). One hundred ten eyes underwent EBRT administered in 2.0-Gy (200-rad) fractions once per day. Forty-two eyes received hyperfractionated EBRT administered in 1.2-Gy (120-rad) fractions twice per day, while 48 eyes received EBRT twice daily in fractions of 5.0 Gy (500 rad). Twenty eyes served as untreated controls. All eyes were obtained for histopathologic examination and graded positive if any tumor was present. Results: A dose-dependent inhibition of ocular tumor was observed for EBRT in these transgenic retinoblastoma mice. The tumor control dose for 50% of eyes (TCD 50) treated with 2.0 Gy fractions of EBRT was 45 Gy (4500 rad) when treatments were administered once daily. A significant increase in tumor control was observed when treatments were administered twice per day at fractions of 1.2 Gy, resulting in a TCD 50 of 33 Gy (3300 rad) (P=.003). A further increase in tumor control was observed when twice-daily EBRT was administered in 5.0 Gy fractions resulting in a TCD 50 of 28 Gy (2800 rad). Conclusions: Hyperfractionated EBRT safely and effectively controls intraocular retinoblastoma in this transgenic animal model. Use of hyperfractionation allows for a reduction in total radiation delivered dose, while shortening the total treatment time. Clinical Relevance: This treatment approach may be applicable in the management of pediatric retinoblastoma by maintaining excellent tumor control, while reducing treatment-associated complications.

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“…Recently, clinical advances have focused on increasing tumor control and globe conservation with attendant preservation of sight. [2][3][4][5][6] Current available treatments include laser therapy, cryotherapy, external beam radiotherapy, charged-particle radiation, and systemic chemotherapy. 7,8 Serious concerns exist regarding the significant morbidity and potential mortality associated with current therapies in the treatment of retinoblastoma; therefore, newer therapeutic modalities are being investigated.…”

Section: Resultsmentioning

confidence: 99%