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ABSTRACT: High-dose radiotherapy can cause contracture of the anophthalmic socket, but the incidence of this complication in patients with enucleation for uveal melanoma has not been reported previously. The authors reviewed the surgical management and outcomes in terms of successful prosthesis wear in patients with severe contracture of the anophthalmic socket treated with high-dose radiotherapy for high-risk uveal melanoma, and they estimated the relative risk of this complication.
The medical records of all consecutive patients enrolled in a prospective uveal-melanoma tissue-banking protocol at the authors' institution who underwent enucleation between January 2003 and December 2010 were reviewed. Patients who underwent adjuvant radiotherapy of the enucleated socket were further studied.
Of the 68 patients enrolled in the prospective tissue-banking protocol, 12 had high-risk histologic features (e.g., extrascleral spread or vortex vein invasion) and were treated with 60 Gy of external beam radiotherapy after enucleation. Five of these patients (41.7%) experienced severe socket contracture precluding prosthesis wear. The median time to onset of contracture following completion of radiotherapy was 20 months. Three patients underwent surgery, which entailed scar tissue release, oral mucous membrane grafting, and socket reconstruction; 2 patients declined surgery. All 3 patients who had surgery experienced significant improvement of socket contracture that enabled patients to wear a prosthesis again.
High-dose radiotherapy after enucleation in patients with uveal melanoma caused severe socket contracture and inability to wear a prosthesis in approximately 40% of patients. Surgical repair of the contracted socket using oral mucous membrane grafting can allow resumption of prosthesis wear.
Ophthalmic plastic and reconstructive surgery 05/2012; 28(3):208-12. · 0.69 Impact Factor
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Archives of ophthalmology 11/2011; 129(11):1487-9. · 3.86 Impact Factor
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ABSTRACT: About 3% of all melanomas are of ocular origin; of these, 85% are uveal. Uveal melanomas are rare, with standardized incidence
rates ranging from approximately 2 to 8 cases per 1 million people in the United States and Europe. The typical presentation
of uveal melanoma depends on the site of origin: choroid, iris, or ciliary body. About 80–90% of all uveal melanomas develop
in the posterior choroid. Uveal melanoma is typically a clinical rather than a pathologic diagnosis. Currently, several options
are available for the management of uveal melanoma, including observation, transpupillary thermotherapy, brachytherapy, stereotactic
radiotherapy, proton radiotherapy, and tumor resection.
12/2010: pages 201-213;
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ABSTRACT: Melanocytic neoplasms of the conjunctiva include nevus, primary acquired melanosis (PAM) without atypia, PAM with atypia,
and conjunctival melanoma. The most common nonmelanocytic tumors of the conjunctiva are squamous cell neoplasms. Surgical
excision is the cornerstone of therapy for conjunctival tumors. Proper specimen handling is critical to ensure that lesion
orientation is clear to the ocular pathologist. Adjuvant therapy for conjunctival tumors can include cryotherapy and/or topical
chemotherapy with mitomycin C, 5-fluorouracil, or interferon, or adjuvant radiation therapy. Tumor thickness and ulceration
are important prognostic factors for local control and survival for conjunctival melanomas. Sentinel lymph node biopsy is
an important recent consideration for conjunctival melanomas that are thicker than 2mm or those that have histologic evidence
of ulceration.
12/2010: pages 127-138;
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ABSTRACT: Uveal melanoma is an aggressive disease without effective adjuvant therapy for metastases. Despite genomic differences between cutaneous and uveal melanomas, therapies based on shared biological factors could be effective against both tumor types. High expression of glycoprotein-NMB (GPNMB) in cutaneous melanomas led to the development of CDX-011 (glembatumumab vedotin), a fully human monoclonal antibody against the extracellular domain of GPNMB conjugated to the cytotoxic microtubule toxin monomethylauristatin E. Ongoing phase II trials suggest that CDX-011 has activity against advanced cutaneous melanomas. To determine the potential role of CDX-011 in uveal melanomas, we studied their GPNMB expression. Paraffin-embedded tissues from 22 uveal melanomas treated by enucleation from 2004-2007 at one institution were evaluated immunohistochemically for expression of GPNMB using biotinylated CDX-011 (unconjugated) antibody. Melanoma cells were evaluated for percentage and intensity of expression. Spectral imaging was used in one case with high melanin content. Clinical data were reviewed. Twelve women and 10 men with a median age of 58.7 years (range: 28-83 years) were included. Eighteen of 21 tumors evaluated immunohistochemically (85.7%) expressed GPNMB in 10-90% of tumor cells with variable intensity (5 tumors, 1+; 11, 2+; and 2, 3+). Eleven of 18 tumors (61.1%) expressed GPNMB in >or=50% of cells. Spectral imaging showed diffuse CDX-011 (unconjugated) reactivity in the remaining case. Uveal melanoma, like cutaneous melanoma, commonly expresses GPNMB. Ongoing clinical trials of CDX-011 should be extended to patients with metastatic uveal melanoma to determine potential efficacy in this subset of patients with melanoma.
Melanoma research 04/2010; 20(3):184-90. · 2.06 Impact Factor
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American journal of clinical oncology 09/2009; 32(4):448-9. · 2.21 Impact Factor
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American journal of clinical oncology 03/2009; 32(1):86-7. · 2.21 Impact Factor
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ABSTRACT: Von Hippel Lindau disease is a common cause of apparently sporadic pheochromocytomas. Herein, we describe a 20-year-old man with an apparently sporadic pheochromocytoma associated with a novel, relatively conservative germline Gly104Val VHL gene mutation, which is localized within exon 1 of the VHL gene corresponding to the beta -domain of the VHL protein (pVHL). The nearly asymptomatic patient's father also carries the same mutation. Similar to other mutations localized in the same codon, the Gly104Val VHL mutation seems to have an attenuated disease phenotype.
Cancer Investigation 08/2008; 26(6):642-6. · 1.85 Impact Factor
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ABSTRACT: Retinoblastoma was traditionally treated with enucleation and external-beam radiotherapy. However, in the past decade, systemic chemotherapy has become the primary globe-salvaging approach. This approach is generally combined with focal treatment, allowing for tumor consolidation following initial chemoreduction. A recently developed classification scheme may improve our ability to predict outcomes with this treatment modality. The Children's Oncology Group has initiated a series of prospective multicenter trials to improve treatment outcomes with systemic chemotherapy.
Current Oncology Reports 12/2007; 9(6):453-8. · 2.55 Impact Factor
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ABSTRACT: Metallic fiducial markers are frequently implanted in patients prior to external-beam radiation therapy to facilitate tumor localization. There is little information in the literature, however, about the perturbations in proton absorbed-dose distribution these objects cause. The aim of this study was to assess the dosimetric impact of perturbations caused by 2.5 mm diameter by 0.2 mm thick tantalum fiducial markers when used in proton therapy for treating uveal melanoma. Absorbed dose perturbations were measured using radiochromic film and confirmed by Monte Carlo simulations of the experiment. Additional Monte Carlo simulations were performed to study the effects of range modulation and fiducial placement location on the magnitude of the dose shadow for a representative uveal melanoma treatment. The simulations revealed that the fiducials caused perturbations in the absorbed-dose distribution, including absorbed-dose shadows of 22% to 82% in a typical proton beam for treating uveal melanoma, depending on the marker depth and orientation. The clinical implication of this study is that implanted fiducials may, in certain circumstances, cause dose shadows that could lower the tumor dose and theoretically compromise local tumor control. To avoid this situation, fiducials should be positioned laterally or distally with respect to the target volume.
Physics in Medicine and Biology 08/2007; 52(13):3979-90. · 2.83 Impact Factor
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Dan S Gombos,
John Hungerford,
David H Abramson,
Judith Kingston,
Guillermo Chantada,
Ira J Dunkel,
Celia B G Antoneli,
Mark Greenwald,
Barret G Haik,
Carlos A Leal,
Aurora Medina-Sanson,
Amy C Schefler,
Gavivann Veerakul,
Regina Wieland,
Norbert Bornfeld,
Mathew W Wilson,
Christopher Bing On Yu
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ABSTRACT: To describe a series of patients with secondary acute myelogenous leukemia (sAML) and retinoblastoma (RB).
Retrospective observational cases series.
Ocular and pediatric oncologists at referral centers in Europe and the Americas and the RB databases at the National Institutes of Health and the Ophthalmic Oncology Service at Memorial Sloan-Kettering Cancer Center.
Physician survey, retrospective database review, and literature search.
History of RB and development of sAML, management of RB (surgery, radiotherapy, chemotherapy), age at diagnosis of RB and leukemia, French-American-British (FAB) subtype, and current status of patient (alive or dead).
Fifteen patients with sAML were identified; 13 occurred in childhood. Mean latent period from RB to AML diagnosis was 9.8 years (median, 42 months). Nine cases were of the M2 or M5 FAB subtypes. Twelve patients (79 %) had received chemotherapy with a topoisomerase II inhibitor, 8 (43%) had received chemotherapy with an epipodophyllotoxin. Ten children died of their leukemia.
Acute myelogenous leukemia is a rare secondary malignancy among retinoblastoma patients, many of whom were treated with primary or adjuvant chemotherapy. Additional studies are needed to assess potential risk factors contributing to sAML development in this cohort.
Ophthalmology 08/2007; 114(7):1378-83. · 5.45 Impact Factor
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Texas medicine 08/2005; 101(7):9.
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ABSTRACT: The purpose of this study was to estimate the number of retinoblastoma cases anticipated each year in various urban and rural areas in Texas. We obtained the most recent data on the number of live births in Texas from the Texas Department of Health. Using those data and the retinoblastoma incidence rate of 1 in 15,000 live births, we estimated that 26 cases of the disease will be diagnosed in Texas each year. Nearly half of those cases will occur in infants in rural areas of the state. We compared those values with data from the Texas Cancer Registry. Primary care physicians, particularly in rural areas of Texas, must screen patients for retinoblastoma and consider arrangements for rapid referral when the diagnosis is suspected.
Texas medicine 08/2005; 101(7):70-2.
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ABSTRACT: To evaluate current practice patterns in diagnostic screening for asymptomatic metastatic uveal melanoma.
Survey.
Ocular oncologists practicing in North America (United States, Canada) and Europe.
Questionnaire sent to specialists participating in the Collaborative Ocular Melanoma Study (COMS) or listed in the Ophthalmic Oncology Task Force of the European Organization for Research and Treatment of Cancer.
Methods used to screen patients with uveal melanoma for asymptomatic metastasis at initial presentation and follow-up.
Thirty-six of 43 (84%) North American (COMS) specialists and 57 of 103 (55%) European specialists responded to the survey. At presentation, 6 of 36 (17%) North American specialists, versus 54 of 57 (95%) European specialists, performed at least one type of liver imaging study (computed tomography, magnetic resonance imaging, ultrasonography, or nuclear medicine) (P<0.0001). On follow-up, only 1 of 36 (3%) North American specialists, versus 45 of 57 (79%) European specialists, obtained a liver imaging study (P<0.0001). Thirty-six of 36 (100%) North American specialists, versus 49 of 57 (86%) European specialists, ordered chest x-rays at presentation (P<0.02). This disparity was greater at the time of follow-up, when 28 of 36 (78%) North American specialists, versus 28 of 57 (49%) European specialists, ordered chest x-rays (P<0.01). Similar proportions of specialists in North America and Europe obtained a physical examination and liver function tests at the time of presentation and on subsequent follow-up examination.
Significant differences exist between ocular oncologists in North America and Europe in the use of techniques to screen for metastatic uveal melanoma. North American COMS centers rely primarily upon liver function tests and chest x-rays. The majority of European centers use liver ultrasonography at initial diagnosis and continue to do so every 6 months. Cost-effective screening protocols for patients with uveal melanoma should be designed and implemented uniformly among ocular oncologists.
Ophthalmology 01/2005; 111(12):2254-8. · 5.45 Impact Factor
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Dan S Gombos
Retina 01/2005; 24(6):825-7. · 2.81 Impact Factor
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Acta Ophthalmologica Scandinavica 06/2003; 76(3):334 - 338. · 1.85 Impact Factor
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ABSTRACT: To evaluate how tumour size, retinal location, and patient age affect the outcome of retinoblastoma foci treated with chemotherapy.
Retrospective review of retinoblastoma foci treated with primary chemotherapy alone. Individual tumours were coded with regard to their largest basal diameter, location within the eye (macula, macula to equator, equator to ora serrata), and patient's age at diagnosis. Successfully treated tumours required no further intervention while those requiring additional treatment were coded as failures.
56 (72%) tumours responded successfully to chemotherapy alone while 22 (28%) required additional therapy. 26 of 31 macular tumours (84%) and 30 of 47 extramacular tumours (64%) responded to chemotherapy (p <0.060). Relative to size, 46 of 60 tumours (77%) greater than 2 mm in basal diameter were successfully treated with chemotherapy, while only 10 of 18 tumours (56%) less than or equal to 2 mm responded (p <0.088). Among the eight tumour foci diagnosed in children less than 2 months of age, five (63%) failed to respond to chemotherapy alone (p <0.032).
Retinoblastoma is more likely to respond to primary chemotherapy if it is located in the macula and if the patient is older than 2 months of age. Tumours measuring less than 2 mm in diameter may be less responsive to this treatment.
British Journal of Ophthalmology 01/2002; 86(1):80-3. · 2.90 Impact Factor
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Dan S. Gombos,
John Hungerford,
David H. Abramson,
Judith Kingston,
Guillermo Chantada,
Ira J. Dunkel,
Celia B.G. Antoneli,
Mark Greenwald,
Barret G. Haik,
Carlos A. Leal,
Aurora Medina-Sanson,
Amy C. Schefler,
Gavivann Veerakul,
Regina Wieland,
Norbert Bornfeld,
Mathew W. Wilson,
Christopher Bing On Yu
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ABSTRACT: PurposeTo describe a series of patients with secondary acute myelogenous leukemia (sAML) and retinoblastoma (RB).DesignRetrospective observational cases series.ParticipantsOcular and pediatric oncologists at referral centers in Europe and the Americas and the RB databases at the National Institutes of Health and the Ophthalmic Oncology Service at Memorial Sloan-Kettering Cancer Center.MethodsPhysician survey, retrospective database review, and literature search.Main Outcome MeasuresHistory of RB and development of sAML, management of RB (surgery, radiotherapy, chemotherapy), age at diagnosis of RB and leukemia, French-American-British (FAB) subtype, and current status of patient (alive or dead).ResultsFifteen patients with sAML were identified; 13 occurred in childhood. Mean latent period from RB to AML diagnosis was 9.8 years (median, 42 months). Nine cases were of the M2 or M5 FAB subtypes. Twelve patients (79 %) had received chemotherapy with a topoisomerase II inhibitor, 8 (43%) had received chemotherapy with an epipodophyllotoxin. Ten children died of their leukemia.ConclusionsAcute myelogenous leukemia is a rare secondary malignancy among retinoblastoma patients, many of whom were treated with primary or adjuvant chemotherapy. Additional studies are needed to assess potential risk factors contributing to sAML development in this cohort.
Ophthalmology.
