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Publication Record


Metastases and death rates after primary enucleation of unilateral retinoblastoma in the USA 2007-2017.
Lu JE, Francis JH, Dunkel IJ, Shields CL, Yu MD, Berry JL, Kogachi K, Skalet AH, Miller AK, Santapuram PR, Daniels AB, Abramson DH
(2019) Br J Ophthalmol 103: 1272-1277
MeSH Terms: Child, Child, Preschool, Eye Enucleation, Female, Humans, Incidence, Infant, Kaplan-Meier Estimate, Male, Retinal Neoplasms, Retinoblastoma, Retrospective Studies, Risk Factors, United States
Show Abstract · Added March 30, 2020
BACKGROUND/AIMS - Enucleation for retinoblastoma is performed less often in the past decade due to increasingly widespread alternative therapies, but enucleation remains an important option. There is a paucity of reports on the current incidence of metastases and metastatic deaths in unilateral retinoblastoma from US centres.
METHODS - Retrospective chart review at five tertiary retinoblastoma centres in the USA for unilateral retinoblastoma patients treated with primary enucleation, 2007-2017, with 1 year of follow-up or treatment failure.
RESULTS - Among 228 patients (228 eyes), there were nine metastases (3.9%) and four deaths (1.7%). The Kaplan-Meier estimate at 5 years for metastasis-free survival was 96% (95% CI, 94% to 99 %), and for overall survival was 98% (95% CI 96% to 100%). All metastases were evident within 12 months. Histopathology revealed higher risk pathology (postlaminar optic nerve and/or massive choroidal invasion) in 62 of 228 eyes (27%). Of these higher risk eyes, 39 received adjuvant chemotherapy. There were four subsequent metastases in this higher risk pathology with adjuvant chemotherapy group, with three deaths. Of the nine overall with metastases, seven (78%) showed higher risk pathology. All metastatic patients were classified as Reese-Ellsworth V and International Classification of Retinoblastoma Groups D or E. Initial metastases presented as orbital invasion in seven of nine cases.
CONCLUSIONS - Primary enucleation for unilateral retinoblastoma results in a low rate of metastatic death, but is still associated with a 3.9% chance of metastases within a year of enucleation. Most but not all patients who developed metastases had higher risk histopathological findings.
© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.
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MeSH Terms
Modern Surgical Techniques in the Management of Retinoblastoma.
Daniels AB, Mukai S
(2017) Int Ophthalmol Clin 57: 195-218
MeSH Terms: Anophthalmos, Eye Enucleation, Humans, Neoplasm Recurrence, Local, Ophthalmologic Surgical Procedures, Retinal Neoplasms, Retinoblastoma
Added March 30, 2020
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MeSH Terms
Chemoreduction plus focal therapy for retinoblastoma: factors predictive of need for treatment with external beam radiotherapy or enucleation.
Shields CL, Honavar SG, Meadows AT, Shields JA, Demirci H, Singh A, Friedman DL, Naduvilath TJ
(2002) Am J Ophthalmol 133: 657-64
MeSH Terms: Antineoplastic Combined Chemotherapy Protocols, Brachytherapy, Carboplatin, Child, Child, Preschool, Combined Modality Therapy, Cryotherapy, Etoposide, Eye Enucleation, Female, Humans, Hyperthermia, Induced, Infant, Male, Prospective Studies, Retinal Neoplasms, Retinoblastoma, Treatment Failure, Treatment Outcome, Vincristine
Show Abstract · Added March 27, 2014
PURPOSE - To report the results of chemoreduction and focal therapy for retinoblastoma with determination of factors predictive of the need for treatment with external beam radiotherapy or enucleation.
DESIGN - Interventional case series.
METHODS - One-hundred three patients with retinoblastoma (158 eyes with 364 tumors) at the Ocular Oncology Service at Wills Eye Hospital of Thomas Jefferson University in conjunction with the Division of Oncology at Children's Hospital of Philadelphia from June 1994 to August 1999 were enrolled for this prospective clinical trial. The patients received treatment for retinoblastoma with six planned cycles (one cycle per month) of chemoreduction using vincristine, etoposide, and carboplatin combined with focal treatments (cryotherapy, thermotherapy, or plaque radiotherapy). The two main outcome measures after chemoreduction and focal therapy were the need for external beam radiotherapy and the need for enucleation. The clinical features at the time of patient presentation were analyzed for impact on the main outcome measures using a series of Cox proportional hazards regressions.
RESULTS - Using Reese-Ellsworth (RE) staging for retinoblastoma, there were nine (6%) eyes with group I disease, 26 (16%) eyes with group II disease, 16 (10%) eyes with group III disease, 32 (20%) eyes with group IV disease, and 75 (48%) eyes with group V retinoblastoma. All eyes showed initial favorable response with tumor regression. The median follow-up was 28 months (range, 2-63 months). Failure of chemoreduction and need for treatment with external beam radiotherapy occurred in 25% of eyes at 1 year, 27% at 3 years, and no further increase at 5 years. More specifically, external beam radiotherapy was necessary at 5 years in 10% of RE groups I-IV eyes and 47% of RE group V eyes. Multivariate factors predictive of treatment with external beam radiotherapy included non-Caucasian race, male sex, and RE group V disease. Failure of chemoreduction and the need for treatment with enucleation occurred in 13% eyes at 1 year, 29% at 3 years, and 34% at 5 years. More specifically, enucleation was necessary in 15% of RE groups I-IV eyes at 5 years and in 53% of RE group V at 5 years. Multivariate factors predictive of treatment with enucleation included patient age older than 12 months, single tumor in eye, and tumor proximity to foveola within 2 mm. Overall, of the 158 eyes, 50% required external beam radiotherapy or enucleation and 50% were successfully managed without these treatments. No patient developed retinoblastoma metastasis, pinealoblastoma, or second malignant neoplasms over the 5-year follow up.
CONCLUSIONS - Chemoreduction offers satisfactory retinoblastoma control for RE groups I-IV eyes, with treatment failure necessitating additional external beam radiotherapy in only 10% of eyes and enucleation in 15% of eyes at 5-year follow-up. Patients with RE group V eyes require external beam radiotherapy in 47% and enucleation in 53% at 5 years.
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20 MeSH Terms
Altered expression of Rb and p53 in uveal melanomas following plaque radiotherapy.
Brantley MA, Worley L, Harbour JW
(2002) Am J Ophthalmol 133: 242-8
MeSH Terms: Adult, Aged, Brachytherapy, Cobalt Radioisotopes, Cyclin D1, Cyclin-Dependent Kinase Inhibitor p16, DNA Damage, DNA, Neoplasm, Eye Enucleation, Female, Humans, Immunoenzyme Techniques, Iodine Radioisotopes, Male, Melanoma, Middle Aged, Nuclear Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-2, Proto-Oncogene Proteins c-mdm2, Retinoblastoma Protein, Tumor Cells, Cultured, Tumor Suppressor Protein p53, Uveal Neoplasms
Show Abstract · Added December 10, 2013
PURPOSE - To examine the expression of proteins in the Rb and p53 tumor suppressor pathways in uveal melanomas following plaque radiotherapy.
METHODS - Immunohistochemistry and cell culture studies. Immunohistochemistry for Rb, p16, cyclin D1, p53, HDM2, and Bcl-2 was performed on twelve eyes containing posterior uveal melanomas that were enucleated following plaque radiotherapy. Cell culture studies were performed in three cases.
RESULTS - The irradiated eyes were enucleated for radiation complications (five cases), local tumor recurrence (three cases), and other reasons (four cases). On histopathologic examination, all cases showed evidence of tumor cell loss. However, residual tumor cells were present in all cases, including those that were clinically regressed. Residual cells from three of the clinically regressed cases were cultured and demonstrated minimal cell division, marked cell death, and extensive chromosomal damage. Strong p53 staining was observed in six cases (50%) and was significantly associated with recent radiotherapy (P = .04). Abnormal cytoplasmic staining for Rb was observed in four cases (33%).
CONCLUSIONS - Plaque radiotherapy of uveal melanomas induces DNA damage, inhibits cell division, and promotes cell death. These changes may be due, at least in part, to induction of p53, which activates genes involved in both cell cycle arrest and apoptosis. Plaque radiotherapy can also cause alterations in the expression of Rb, but the significance of this finding will require further study.
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24 MeSH Terms
Transient developmental expression of monoamine transporters in the rodent forebrain.
Lebrand C, Cases O, Wehrlé R, Blakely RD, Edwards RH, Gaspar P
(1998) J Comp Neurol 401: 506-24
MeSH Terms: Animals, Brain Chemistry, Carrier Proteins, Cell Membrane, Dopamine Plasma Membrane Transport Proteins, Eye Enucleation, Gene Expression Regulation, Developmental, Membrane Glycoproteins, Membrane Transport Proteins, Mice, Mice, Inbred C3H, Nerve Tissue Proteins, Neurons, Afferent, Neuropeptides, Neurotransmitter Agents, Norepinephrine Plasma Membrane Transport Proteins, Prosencephalon, RNA, Messenger, Rats, Rats, Sprague-Dawley, Serotonin, Symporters, Thalamus, Time Factors, Trigeminal Nerve, Vesicular Biogenic Amine Transport Proteins, Vesicular Monoamine Transport Proteins, Vision, Monocular
Show Abstract · Added July 10, 2013
Neurons in first-order sensory thalamic nuclei have been shown to express functional plasma membrane serotonin (SERT) and vesicular monoamine (VMAT2) transporters during early postnatal development. In the present study, we provide an extensive description of the spatial and the temporal patterns of VMAT2 and SERT expression, during early embryonic development and postnatal life, by using in situ hybridization and immunocytochemistry. VMAT2 and SERT genes are transiently expressed in a wide population of non-monoaminergic neurons in the central and peripheral nervous system with a large overlap in the temporal and spatial pattern of expression of both genes. A selective pattern of expression of both genes was observed in the thalamus with expression limited to the dorsal thalamus and more particularly to primary sensory relay nuclei that convey point to point projection maps. Transient expression of the transporters was also observed in sensory cranial nerves, in the hippocampus, cerebral cortex, septum, and amygdala. VMAT2 and SERT gene expression was not necessarily linked, as some neural populations expressed only VMAT2, while others only contained SERT. Since VMAT2 serves to transport catecholamines besides serotonin, we examined the developmental expression of the plasma membrane dopamine and norepinephrine transporters but found no transient expression of these genes. Despite minor temporal disparities, VMAT2 and SERT extinguished almost simultaneously during the second and third weeks of post-natal life. These expressions did not seem to be dependent on peripheral neural inputs, since monocular enucleations and infraorbital nerve cuts effected on the day of birth, did not modify the period of transporter expression or of extinction.
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28 MeSH Terms