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PURPOSE: Validated and accurate prognostic testing is critical for precision medicine in uveal melanoma (UM). Our aims were to (1) prospectively validate an integrated prognostic classifier combining a 15-gene expression profile (15-GEP) and PRAME RNA expression and (2) identify clinical variables that enhance the prognostic accuracy of the 15-GEP/PRAME classifier. MATERIALS AND METHODS: This study included 1,577 patients with UM of the choroid and/or ciliary body who were enrolled in the Collaborative Ocular Oncology Group Study Number 2 (COOG2) and prospectively monitored across 26 North American centers. Test results for 15-GEP (class 1 or class 2) and PRAME expression status (negative or positive) were available for all patients. The primary end point was metastasis-free survival (MFS). RESULTS: 15-GEP was class 1 in 1,082 (68.6%) and class 2 in 495 (31.4%) patients. PRAME status was negative in 1,106 (70.1%) and positive in 471 (29.9%) patients. Five-year MFS was 95.6% (95% CI, 93.9 to 97.4) for class 1/PRAME(-), 80.6% (95% CI, 73.9 to 87.9) for class 1/PRAME(+), 58.3% (95% CI, 51.1 to 66.4) for class 2/PRAME(-), and 44.8% (95% CI, 37.9 to 52.8) for class 2/PRAME(+). By multivariable Cox proportional hazards analysis, 15-GEP was the most important independent predictor of MFS (hazard ratio [HR], 5.95 [95% CI, 4.43 to 7.99]; P < .001), followed by PRAME status (HR, 1.82 [95% CI, 1.42 to 2.33]; P < .001). The only clinical variable demonstrating additional prognostic value was tumor diameter. CONCLUSION: In the largest prospective multicenter prognostic biomarker study performed to date in UM to our knowledge, the COOG2 study validated the superior prognostic accuracy of the integrated 15-GEP/PRAME classifier over 15-GEP alone and clinical prognostic variables. Tumor diameter was found to be the only clinical variable to provide additional prognostic information. This prognostic classifier provides an advanced resource for risk-adjusted metastatic surveillance and adjuvant trial stratification in patients with UM.
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OBJECTIVE: To analyze the genetic features of melanocytomas and melanomas of the anterior uvea and assess the value of molecular testing for diagnosis and prognostication. DESIGN: Retrospective case-control study. SUBJECTS: Patients with melanocytoma (n = 16) and melanoma (n = 19) of the anterior uvea. METHODS: Targeted next-generation sequencing was performed on formalin-fixed, paraffin-embedded tumor tissue from anterior uveal melanocytic tumors and correlated with clinicopathologic features. MAIN OUTCOME MEASURES: Presence or absence of accompanying oncogenic alterations beyond GNAQ/GNA11 and their association with histologic features and local recurrence. RESULTS: Hotspot missense mutations in GNAQ/GNA11 were identified in 91% (32/35) of all cases. None of the melanocytomas with or without atypia demonstrated chromosomal imbalances or additional oncogenic variants beyond GNAQ mutation, and none recurred over a median follow-up of 36 months. Additional alterations identified in a subset of melanomas include mutations in BAP1 (n = 3), EIF1AX (n = 4), SRSF2 (n = 1), PTEN (n = 1), and EP300 (n = 1); monosomy 3p (n = 6); trisomy 6p (n = 3); trisomy 8q (n = 2); and an ultraviolet mutational signature (n = 5). Local recurrences were limited to melanomas, all of which demonstrated oncogenic alterations in addition to GNAQ/GNA11 (n = 5). A single melanoma harboring GNAQ and BAP1 mutations and monosomy 3 was the only tumor that metastasized. CONCLUSIONS: In this study, anterior segment uveal melanocytomas did not display oncogenic alterations beyond GNAQ/GNA11. Therefore, they are genetically similar to uveal nevi rather than uveal melanoma based on their molecular features known from the literature. Molecular testing can be performed on borderline cases to aid risk stratification and clinical management decisions.
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Melanoma , Nevo Pigmentado , Neoplasias Cutáneas , Neoplasias de la Úvea , Humanos , Subunidades alfa de la Proteína de Unión al GTP/genética , Subunidades alfa de la Proteína de Unión al GTP/metabolismo , Análisis Mutacional de ADN , Cuerpo Ciliar/patología , Estudios Retrospectivos , Estudios de Casos y Controles , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/genética , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/metabolismo , Neoplasias de la Úvea/diagnóstico , Neoplasias de la Úvea/genética , Neoplasias de la Úvea/patología , Melanoma/patología , Mutación , Nevo Pigmentado/patología , Neoplasias Cutáneas/patología , Iris/patologíaRESUMEN
PURPOSE: To describe the first series of six young uveal melanoma (UM) patients with oral isotretinoin and/or topical retinoid therapy prior to diagnosis. OBSERVATIONS: The case series is based on clinical observations at our UM quaternary referral center. Six UM patient cases are reported, ages 16-44 years old. All had been using either oral (isotretinoin) and/or topical (tretinoin or tazarotene) retinoid treatment (3 months-~10 years) prior to or at the time of diagnosis (3 of 6 cases). All patients had ocular complaints on presentation, and the onset of certain symptoms corresponded with the course of retinoids. Other potential risk factors or relevant history included Caucasian background, cone-rod dystrophy and active smoker status (Case 2), family history of UM and pregnancy at time of diagnosis (Case 3), past smoking and possible secondary Chernobyl exposure as a baby (Case 5). All patients were treated with proton beam radiotherapy and currently have no sign of recurrent or metastatic disease. CONCLUSIONS AND IMPORTANCE: Retinoid therapy has been linked to various benign and/or reversible effects on the anterior and posterior eye, though pathophysiology remains not well understood. Uveal melanoma (UM) is a rare cancer diagnosis in young adults. We report here the first case series of young UM patients with a history of retinoid use and ocular complaints. No causal link is claimed and further systematic epidemiologic and biologic study of retinoid therapy and ocular impact may provide additional relevant data, particularly in young ocular melanoma patients.
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Uveal melanoma (UM) is a rare but life-threatening cancer of the eye. In light of the coronavirus disease (COVID-19) pandemic, hospitals and proton eye therapy facilities must analyze several factors to ensure appropriate treatment protocols for patients and provider teams. Practice considerations to limit COVID-19 transmission in the proton ocular treatment setting for UM are necessary. The Particle Therapy Co-Operative Group is the largest international community of particle/proton therapy providers. Participating experts have current or former affiliation with the member institutions of the Particle Therapy Co-Operative Group Ocular subcommittee with long-standing high-volume proton ocular programs. The practices reviewed in this document must be taken in conjunction with local hospital procedures, multidisciplinary recommendations, and regional/national guidelines, as each community may have its unique needs, supplies, and protocols. Importantly, as the pandemic evolves, so will the strategies and recommendations. Given the unique circumstances for UM patients, along with indications of potential ophthalmologic transmission as a result of health care providers working in close proximity to patients and intrinsic infectious risk from eyelashes, tears, and hair, practice strategies may be adapted to reduce the risk of viral transmission. Certainly, providers and health care systems will continue to examine and provide as safe and effective care as possible for patients in the current environment.
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PURPOSE: Establishing the correct diagnosis of a growing choroidal tumor can be difficult. METHODS: Clinical examination and ultrasound of a patient followed for what was thought to be a uveal melanoma. Fine-needle biopsy established the correct diagnosis. RESULTS: We demonstrate that fine-needle biopsy can correctly identify a very rare tumor, a myomelanocytic neoplasm. CONCLUSION: Myomelanocytic choroidal tumors can be diagnosed on fine-needle biopsy.
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Neoplasias de la Coroides/patología , Melanocitos/patología , Melanoma/patología , Neoplasias de la Úvea/patología , Citodiagnóstico , Diagnóstico Diferencial , Femenino , Humanos , Persona de Mediana EdadRESUMEN
PURPOSE: To perform an in-depth temporal analysis of visual acuity (VA) outcomes after proton beam radiation therapy (PBRT) in a large, uniformly treated cohort of uveal melanoma (UM) patients, to determine trends in VA evolution depending on pretreatment and temporally defined posttreatment VA measurements; and to investigate the relevance of specific patient, tumor and dose-volume parameters to posttreatment vision loss. METHODS AND MATERIALS: Uveal melanoma patients receiving PBRT were identified from a prospectively maintained database. Included patients (n=645) received 56 GyE in 4 fractions, had pretreatment best corrected VA (BCVA) in the affected eye of count fingers (CF) or better, with posttreatment VA assessment at specified post-PBRT time point(s). Patients were grouped according to the pretreatment BCVA into favorable (≥20/40) or unfavorable (20/50-20/400) and poor (CF) strata. Temporal analysis of BCVA changes was described, and univariate and forward stepwise multivariate logistic regression analyses were performed to identify predictors for VA loss. RESULTS: Median VA follow-up was 53 months (range, 3-213 months). At 60-month follow up, among evaluable treated eyes with favorable pretreatment BCVA, 45% retained BCVA ≥20/40, whereas among evaluable treated eyes with initially unfavorable/poor BCVA, 21% had vision ≥20/100. Among those with a favorable initial BCVA, attaining BCVA of ≥20/40 at any posttreatment time point was associated with subsequent maintenance of excellent BCVA. Multivariate analysis identified volume of the macula receiving 28GyE (P<.0001) and optic nerve (P=.0004) as independent dose-volume histogram predictors of 48-month post-PBRT vision loss among initially favorable treated eyes. CONCLUSIONS: Approximately half of PBRT-treated UM eyes with excellent pretreatment BCVA assessed at 5 years after treatment will retain excellent long-term vision. 28GyE macula and optic nerve dose-volume histogram parameters allow for rational treatment planning optimization that may lead to improved visual outcomes. The detailed temporal analysis with intermediate as well as long-term functional prognosis, and the relationship of outcomes with clinical and treatment planning parameters, is critical for informed care of UM patients before and after PBRT.
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Melanoma/radioterapia , Tratamientos Conservadores del Órgano/métodos , Terapia de Protones/métodos , Neoplasias de la Úvea/radioterapia , Agudeza Visual/efectos de la radiación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Fraccionamiento de la Dosis de Radiación , Femenino , Estudios de Seguimiento , Humanos , Mácula Lútea/efectos de la radiación , Masculino , Persona de Mediana Edad , Nervio Óptico/efectos de la radiación , Terapia de Protones/efectos adversos , Dosificación Radioterapéutica , Análisis de Regresión , Factores de Tiempo , Resultado del Tratamiento , Trastornos de la Visión/etiología , Trastornos de la Visión/prevención & control , Agudeza Visual/fisiologíaRESUMEN
PURPOSE: The aim of this study was to use massively parallel DNA sequencing to identify GNAQ/11, BAP1 and SF3B1 mutations in ophthalmic melanocytoma. PROCEDURES: Six ophthalmic melanocytoma specimens (1 iridociliary and 5 optic nerve) were profiled for genomic alterations in GNAQ/11, BAP1 and SF3B1 using a custom deep sequencing assay. This assay uses solution phase hybridization-based exon capture and deep-coverage massively parallel DNA sequencing to interrogate all protein-coding exons and select introns. RESULTS: The only iridociliary melanocytoma showed a mutation in GNAQ but not in BAP1. Of the 2 optic-nerve melanocytomas that developed into melanoma, one had a GNAQ mutation and both a BAP1 mutation and monosomy 3. The remaining 3 optic-nerve melanocytomas did not reveal mutations in GNAQ/11 or BAP1. SF3B1 mutations were not detected in any specimen. CONCLUSIONS: The presence of GNAQ mutation in some iridociliary and optic-nerve melanocytomas suggests a possible relationship between ophthalmic melanocytoma and other ophthalmic melanocytic neoplasms. BAP1 mutation may accompany the transformation of ophthalmic melanocytoma to melanoma.
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IMPORTANCE: Uveal melanoma (UM) can be divided into prognostically significant subgroups based on a prospectively validated and widely used 15-gene expression profile (GEP) test. Class 1 UMs have a low risk and class 2 UMs have a high risk for metastasis. OBJECTIVE: To determine whether any clinicopathologic factors provide independent prognostic information that may enhance the accuracy of the GEP classification. DESIGN, SETTING, AND PARTICIPANTS: This retrospective observational study performed at 2 ocular oncology referral centers included 339 patients in a primary cohort and 241 patients in a validation cohort. Both cohorts had a diagnosis of UM arising from the ciliary body and/or choroid. All patients underwent tumor biopsy for GEP prognostic testing. Clinicopathologic variables included patient age and sex, tumor thickness, largest basal tumor diameter (LBD), ciliary body involvement, and pathologic cell type. Patients from the primary cohort were enrolled from November 1, 1998, to March 16, 2012; from the validation cohort, from November 4, 1996, to November 7, 2013. Follow-up for the primary cohort was completed on August 18, 2013; for the validation cohort, December 10, 2013. Data were analyzed from November 12, 2013, to November 25, 2015. MAIN OUTCOME AND MEASURES: Progression-free survival (PFS). The secondary outcome was overall survival. RESULTS: The primary cohort included 339 patients (175 women [51.6%]; mean [SD] age, 61.8 [13.6] years). The most significant prognostic factor was GEP classification (exp[b], 10.33; 95% CI, 4.30-24.84; P < .001). The only other variable that provided independent prognostic information was LBD (exp[b], 1.13; 95% CI, 1.02-1.26; P = .02). Among class 2 UMs, LBD showed a modest but significant association with PFS (exp[b], 1.13; 95% CI, 1.04-1.24; P = .005). The 5-year actuarial metastasis-free survival estimates (SE) were 97% (3%) for class 1 UMs with LBD of less than 12 mm, 90% (4%) for class 1 UMs with LBD of at least 12 mm, 90% (9%) for class 2 UMs with LBD of less than 12 mm, and 30% (7%) for class 2 UMs with LBDs of at least 12 mm. The independent prognostic value of LBD and the 12-mm LBD cutoff were corroborated in the independent validation 241-patient cohort. CONCLUSIONS AND RELEVANCE: Class 2 UMs had better prognosis when the LBD was less than 12 mm at the time of treatment. These findings could have important implications for patient counseling, primary tumor treatment, clinical trial enrollment, metastatic surveillance, and adjuvant therapy.
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Regulación Neoplásica de la Expresión Génica/fisiología , Genes Relacionados con las Neoplasias/genética , Melanoma/genética , Melanoma/patología , Proteínas de Neoplasias/genética , Neoplasias de la Úvea/genética , Neoplasias de la Úvea/patología , Supervivencia sin Enfermedad , Femenino , Perfilación de la Expresión Génica , Humanos , Masculino , Melanoma/mortalidad , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Neoplasias de la Úvea/mortalidadRESUMEN
PURPOSE: Relevant clinical data are needed given the increasing national interest in charged particle radiation therapy (CPT) programs. Here we report long-term outcomes from the only randomized, stratified trial comparing CPT with iodine-125 plaque therapy for choroidal and ciliary body melanoma. METHODS AND MATERIALS: From 1985 to 1991, 184 patients met eligibility criteria and were randomized to receive particle (86 patients) or plaque therapy (98 patients). Patients were stratified by tumor diameter, thickness, distance to disc/fovea, anterior extension, and visual acuity. Tumors close to the optic disc were included. Local tumor control, as well as eye preservation, metastases due to melanoma, and survival were evaluated. RESULTS: Median follow-up times for particle and plaque arm patients were 14.6 years and 12.3 years, respectively (P=.22), and for those alive at last follow-up, 18.5 and 16.5 years, respectively (P=.81). Local control (LC) for particle versus plaque treatment was 100% versus 84% at 5 years, and 98% versus 79% at 12 years, respectively (log rank: P=.0006). If patients with tumors close to the disc (<2 mm) were excluded, CPT still resulted in significantly improved LC: 100% versus 90% at 5 years and 98% versus 86% at 12 years, respectively (log rank: P=.048). Enucleation rate was lower after CPT: 11% versus 22% at 5 years and 17% versus 37% at 12 years, respectively (log rank: P=.01). Using Cox regression model, likelihood ratio test, treatment was the most important predictor of LC (P=.0002) and eye preservation (P=.01). CPT was a significant predictor of prolonged disease-free survival (log rank: P=.001). CONCLUSIONS: Particle therapy resulted in significantly improved local control, eye preservation, and disease-free survival as confirmed by long-term outcomes from the only randomized study available to date comparing radiation modalities in choroidal and ciliary body melanoma.
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Neoplasias de la Coroides/radioterapia , Cuerpo Ciliar , Helio/uso terapéutico , Radioisótopos de Yodo/uso terapéutico , Melanoma/radioterapia , Neoplasias de la Úvea/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Braquiterapia/métodos , Neoplasias de la Coroides/mortalidad , Neoplasias de la Coroides/patología , Cuerpo Ciliar/patología , Supervivencia sin Enfermedad , Enucleación del Ojo/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Melanoma/mortalidad , Melanoma/patología , Persona de Mediana Edad , Tratamientos Conservadores del Órgano , Dosificación Radioterapéutica , Factores de Tiempo , Neoplasias de la Úvea/mortalidad , Neoplasias de la Úvea/patología , Adulto JovenAsunto(s)
Endoftalmitis/diagnóstico , Linfoma de Células B de la Zona Marginal/diagnóstico , Neoplasias de la Úvea/diagnóstico , Adulto , Antígenos CD20/metabolismo , Biomarcadores de Tumor/metabolismo , Diagnóstico Diferencial , Fraccionamiento de la Dosis de Radiación , Angiografía con Fluoresceína , Humanos , Técnicas para Inmunoenzimas , Inflamación/diagnóstico , Linfoma de Células B de la Zona Marginal/metabolismo , Linfoma de Células B de la Zona Marginal/radioterapia , Masculino , Microscopía Acústica , Radioterapia de Alta Energía , Neoplasias de la Úvea/metabolismo , Neoplasias de la Úvea/radioterapiaRESUMEN
BACKGROUND: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Early treatment may improve any chances of preventing metastatic disease, but diagnosis of small UM is challenging. Up to 95 % of all UMs carry somatic mutations in the G-coupled proteins GNAQ and GNA11 promoting anchorage-independent growth and proliferation. About 50 % of UMs are fatal. Once metastatic, patients have limited options for successful therapy. METHODS: We have developed functionalized gold nanoparticles (AuNPs) to visualize transcripts of mutant GNAQ mRNA in living cells. In addition to their suitability as a specific tool for GNAQ mutation detection, we have developed a novel linker that enables conjugation of siRNAs to AuNPs allowing for greater and more rapid intracellular release of siRNAs compared to previously described approaches. RESULTS: Binding of modified AuNPs to matching target mRNA leads to conformational changes, resulting in a detectable fluorescent signal that can be used for mutation detection in living cells. Knockdown of GNAQ with siRNA-AuNPs effectively reduced downstream signals and decreased cell viability in GNAQ mutant uveal melanoma cells. CONCLUSION: AuNPs may in future be developed to serve as sensors for mutations of vital importance. The new release system for siRNA-AuNP improves previous systems, which conceivably will be useful for future therapeutic gene regulatory approaches.
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Técnicas Biosensibles/métodos , Subunidades alfa de la Proteína de Unión al GTP , Técnicas de Silenciamiento del Gen/métodos , Oro/química , Melanoma , Nanopartículas del Metal/química , Mutación , Proteínas de Neoplasias , ARN Mensajero , ARN Neoplásico , Neoplasias de la Úvea , Adulto , Línea Celular Tumoral , Supervivencia Celular/genética , Subunidades alfa de la Proteína de Unión al GTP/genética , Subunidades alfa de la Proteína de Unión al GTP/metabolismo , Subunidades alfa de la Proteína de Unión al GTP Gq-G11 , Humanos , Melanoma/genética , Melanoma/metabolismo , Melanoma/patología , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismo , Neoplasias de la Úvea/genética , Neoplasias de la Úvea/metabolismo , Neoplasias de la Úvea/patologíaRESUMEN
IMPORTANCE: Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma and may rarely infiltrate the ocular structures. Ophthalmic findings in MF can be highly variable. The most commonly involved ocular tissue is the eyelid skin, but intraocular involvement can be seen in patients with extensive systemic disease. To our knowledge, an isolated eyelid mass as an initial manifestation of MF has not been previously reported. OBSERVATIONS: We report a series of 4 cases of ocular involvement in patients with MF demonstrating a highly variable ophthalmic presentation of this disease. The development of an isolated eyelid mass was an initial manifestation of MF in 1 of the patients. Isolated anterior uveitis, vitritis, and choroidal mass are described in 3 patients with aggressive systemic disease. CONCLUSIONS AND RELEVANCE: Infiltration of the ocular structures by MF is rare, but the involvement of different ocular tissues and a highly variable clinical presentation can be seen. Eyelid lesion may be an initial manifestation of MF. These cases suggest that intraocular involvement occurs in patients with aggressive systemic disease and usually portends a poor prognosis for survival.
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Neoplasias de la Coroides/patología , Oftalmopatías/patología , Neoplasias de los Párpados/patología , Micosis Fungoide/patología , Uveítis Anterior/patología , Cuerpo Vítreo/patología , Adulto , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/uso terapéutico , Neoplasias de la Coroides/terapia , Oftalmopatías/terapia , Neoplasias de los Párpados/terapia , Resultado Fatal , Femenino , Humanos , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Micosis Fungoide/terapia , Radioterapia , Uveítis Anterior/terapiaRESUMEN
PURPOSE: To determine neovascular glaucoma (NVG) incidence and identify contributing tumor and dosing factors in uveal melanoma patients treated with proton beam radiation therapy (PBRT). METHODS AND MATERIALS: A total of 704 PBRT patients treated by a single surgeon (DHC) for uveal melanoma (1996-2010) were reviewed for NVG in our prospectively maintained database. All patients received 56 GyE in 4 fractions. Median follow-up was 58.3 months. Analyses included the Kaplan-Meier method to estimate NVG distributions, univariate log-rank tests, and Cox's proportional hazards multivariate analysis using likelihood ratio tests to identify independent risk factors of NVG among patient, tumor, and dose-volume histogram parameters. RESULTS: The 5-year PBRT NVG rate was 12.7% (95% confidence interval [CI] 10.2%-15.9%). The 5-year rate of enucleation due to NVG was 4.9% (95% CI 3.4%-7.2%). Univariately, the NVG rate increased significantly with larger tumor diameter (P<.0001), greater height (P<.0001), higher T stage (P<.0001), and closer proximity to the disc (P=.002). Dose-volume histogram analysis revealed that if >30% of the lens or ciliary body received ≥50% dose (≥28 GyE), there was a higher probability of NVG (P<.0001 for both). Furthermore, if 100% of the disc or macula received ≥28 GyE, the NVG rate was higher (P<.0001 and P=.03, respectively). If both anterior and posterior doses were above specified cut points, NVG risk was highest (P<.0001). Multivariate analysis confirmed significant independent risk factors to include tumor height (P<.0001), age (P<.0001), %disc treated to ≥50% Dose (<100% vs 100%) (P=.0007), larger tumor diameter (P=.01), %lens treated to ≥90% Dose (0 vs >0%-30% vs >30%) (P=.01), and optic nerve length treated to ≥90% Dose (≤1 mm vs >1 mm) (P=.02). CONCLUSIONS: Our current PBRT patients experience a low rate of NVG and resultant enucleation compared with historical data. The present analysis shows that tumor height, diameter, and anterior as well as posterior critical structure dose-volume parameters may be used to predict NVG risk.
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Glaucoma Neovascular/etiología , Melanoma/radioterapia , Terapia de Protones/efectos adversos , Neoplasias de la Úvea/radioterapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Femenino , Humanos , Incidencia , Mácula Lútea , Masculino , Melanoma/epidemiología , Melanoma/etiología , Melanoma/patología , Persona de Mediana Edad , Estadificación de Neoplasias , Disco Óptico , Tratamientos Conservadores del Órgano/métodos , Órganos en Riesgo/efectos de la radiación , Dosificación Radioterapéutica , Factores de Riesgo , Carga Tumoral , Neoplasias de la Úvea/epidemiología , Neoplasias de la Úvea/etiología , Neoplasias de la Úvea/patología , Adulto JovenRESUMEN
OBJECTIVE: To review the evidence for molecular genetic testing of uveal melanoma in the context of prognostic indicators of metastasis and tumour-related mortality. DESIGN: Review of the literature and personal experiences of the authors. METHODS: We conducted a MEDLINE, Embase, and PubMed literature search (1980-2011) for English-language abstracts and full-text references regarding molecular genetic testing of uveal melanoma. Search terms included uveal, melanoma, cytogenetic, gene, and molecular. All studies in which patients with primary uveal melanoma underwent molecular genetic testing with survival data for disease-related metastasis and mortality were reviewed. RESULTS: From 176 identified articles, 40 were scientific studies of uveal melanomas that included histologic and molecular genetic analysis. Of those, 24 included survival data, correlation of molecular genetic features with other prognostic indicators, or both. Cytogenetic and microarray gene expression analysis allows uveal melanoma lesions to be classified as high risk or low risk for metastasis and disease-related mortality. Gene expression profiling supersedes clinical, histologic, and cytogenetic prognosticators. CONCLUSIONS: Uveal melanoma comprises a heterogeneous group of malignancies based on its molecular biology. Molecular class by gene expression profiling has the most strongly predictive value for uveal melanoma metastasis and mortality.
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Análisis Citogenético , Perfilación de la Expresión Génica , Melanoma/clasificación , Melanoma/genética , Neoplasias de la Úvea/clasificación , Neoplasias de la Úvea/genética , Aberraciones Cromosómicas , Bases de Datos Factuales , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Melanoma/mortalidad , Melanoma/secundario , Pronóstico , Tasa de Supervivencia , Neoplasias de la Úvea/mortalidad , Neoplasias de la Úvea/patologíaRESUMEN
PURPOSE: To characterize the clinical spectrum of class 1 and class 2 uveal melanomas and their relationship with intraocular proton radiation response. DESIGN: Masked retrospective case series of uveal melanoma patients with fine needle biopsy-based molecular profiles. METHODS: A total of 197 uveal melanoma patients from a single institution were analyzed for pathology, clinical characteristics, and response to radiation therapy. RESULTS: A total of 126 patients (64%) had class 1 tumors and 71 (36%) had class 2 tumors. Patients with class 2 tumors had more advanced age (mean: 64 years vs 57 years; P = .001), had thicker initial mean ultrasound measurements (7.4 mm vs 5.9 mm; P = .0007), and were more likely to have epithelioid or mixed cells on cytopathology (66% vs 38%; P = .0004). Although mean pretreatment and posttreatment ultrasound thicknesses were significantly different between class 1 and class 2 tumors, there was no difference in the mean change in thickness 24 months after radiation therapy (mean difference: class 1 = -1.64 mm, class 2 = -1.47; P = .47) or in the overall rate of thickness change (slope: P = .64). Class 2 tumors were more likely to metastasize and cause death than class 1 tumors (DSS: P < .0001). CONCLUSIONS: At the time of radiation therapy, thicker tumors, epithelioid pathology, and older patient age are significantly related to class 2 tumors, and class 2 tumors result in higher tumor-related mortality. We found no definitive clinical marker for differentiating class 1 and class 2 tumors.
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Melanoma/patología , Melanoma/radioterapia , Neoplasias de la Úvea/patología , Neoplasias de la Úvea/radioterapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia con Aguja , ADN de Neoplasias/análisis , Femenino , Angiografía con Fluoresceína , Perfilación de la Expresión Génica , Humanos , Masculino , Melanoma/genética , Melanoma/mortalidad , Persona de Mediana Edad , Metástasis de la Neoplasia , Protones , Radioterapia de Alta Energía , Estudios Retrospectivos , Neoplasias de la Úvea/genética , Neoplasias de la Úvea/mortalidad , Adulto JovenRESUMEN
Orbital fine needle aspiration biopsy is a useful diagnostic adjuvant. In this case, an FNAB showed lymphocytes. The surgeon felt that this diagnosis was possibly inaccurate, and therefore took out the tumor en bloc. This was a mucoepidermoid carcinoma involving the lacrimal gland that had been heavily infiltrated by lymphocytes.