ABSTRACT
The aim of this study was to investigate the primary sites, clinical characteristics, and treatment outcomes of patients with metastatic tumors in the eye and ocular adnexa. This retrospective case series consisted of 42 patients diagnosed with intraocular metastasis (IM) or ocular adnexal metastasis (OAM) at a tertiary center between January 2001 and June 2023. The patients comprised 18 men and 24 women; 24 (57%) and 18 (43%) patients were diagnosed with IM and OAM, respectively. In the IM group, the primary tumors originated from the lungs (79%), followed by the breasts (17%). In the OAM group, the primary tumors originated from the breasts (33%). Previously, 57% of the patients had been diagnosed with cancer. In the IM group, 38% exhibited bilateral involvement. Only 6% of the patients with OAM had bilateral diseases. The 1-, 3-, and 5-year overall survival (OS) was 42%, 18%, and 7%, respectively. The median OS since metastasis diagnosis in the lungs and breast was 11.8 and 10.5 months, respectively. Lung cancer remains the predominant primary cancer in IM, whereas breast cancer is the major cancer in OAM. Despite poor OS, early detection will facilitate the prompt treatment of primary cancer and metastatic sites.
Subject(s)
Eye Neoplasms , Humans , Male , Female , Middle Aged , Eye Neoplasms/pathology , Eye Neoplasms/therapy , Eye Neoplasms/mortality , Eye Neoplasms/secondary , Aged , Retrospective Studies , Adult , Treatment Outcome , Lung Neoplasms/pathology , Lung Neoplasms/mortality , Lung Neoplasms/secondary , Breast Neoplasms/pathology , Breast Neoplasms/therapy , Breast Neoplasms/mortality , Aged, 80 and over , Neoplasm MetastasisABSTRACT
OBJECTIVE: To comprehensively analyze reported cases of nasolacrimal squamous cell carcinoma (NLSCC), focusing on risk factors, treatment modalities, and outcomes. Additionally, investigate the impact of human Papillomavirus (HPV) status and histopathological subtypes' impact on prognosis. DATA SOURCES: Pubmed, Embase. REVIEW METHODS: We conducted a systematic literature review to identify relevant studies reporting cases of NLSCC. The review methods adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The final update was performed on May 31, 2023. RESULTS: The 72 studies included a total of 313 participants (mean age: 55; 60% male). Longer symptom duration (44.1 ± 59.2 months) correlated with recurrence (p = 0.004), and males exhibited higher mortality rates (19.6% vs. 2.4% in females, p = 0.01). The overall survival (OS) rate among all patients was 87.1%. Basaloid NLSCC had a worse death outcome (p ≤ 0.001). HPV-positive cases showed comparable OS, recurrence, and metastasis rates to the general population (p = 0.917, 0.851, 0.07, respectively). Comparing treatment approaches (surgery, surgery with adjuvant radiation, chemoradiotherapy [CRT] followed by surgery), no significant differences in 5 and 10-year OS rates or recurrence were observed (p = 0.4, 0.24, respectively), but 5-year metastasis events were significant (p = 0.024). Eye exenteration rates were 31.1%, 20%, and 0% for the respective treatments (p = 0.089). Induction chemotherapy saved four cases from potential exenteration with favorable prognosis. CONCLUSION: Early detection and diagnosis are of utmost importance in the management of NLSCC. Regardless of the treatment approach, HPV-related NLSCC demonstrated similar outcomes to the general population. Basaloid histology represents the worst subtype in terms of prognosis. Limited adjuvant CRT cases showed improved outcomes and induction chemotherapy's importance was emphasized in recent literature and our shared experience. Laryngoscope, 134:3892-3902, 2024.
Subject(s)
Eye Neoplasms , Humans , Male , Female , Middle Aged , Eye Neoplasms/therapy , Eye Neoplasms/mortality , Eye Neoplasms/pathology , Eye Neoplasms/drug therapy , Nasolacrimal Duct/pathology , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/virology , Papillomavirus Infections/complications , Induction Chemotherapy , Prognosis , Neoplasm Recurrence, LocalABSTRACT
BACKGROUND: This study aims to investigate the global disease burden, risk factors, and temporal trends of eye cancer by sex and age group. METHODS: Databases including Cancer Incidence in Five Continents volumes I-XI, the Nordic Cancer Registries, the Surveillance, Epidemiology, and End Results Program and the WHO IARC mortality database were accessed to extract incidence and mortality data. Joinpoint regression analyses were conducted to evaluate the Average Annual Percentage Change of the incidence and mortality. RESULTS: The age-standardised rates of eye cancer incidence and mortality were 0.49 and 0.08 globally in 2020. Higher incidence rates were observed in Sub-Saharan Africa (ASR = 4.06), Western Europe (ASR = 0.89), and Northern Europe (ASR = 0.84), but higher mortality was observed only in Sub-Saharan Africa (ASR = 1.59). Lower HDI, higher prevalence of UV exposure and lower prevalence of several lifestyle habits and metabolic syndromes were associated with higher incidence and mortality. There was an overall stable incidence trend and a decreasing mortality trend. Notably, all countries reporting decreasing trend in mortality were in the Asian or European region. CONCLUSIONS: Although higher incidence was observed in both African and European regions, only the Sub-Saharan Africa region reported high mortality, indicating inequity in the access of healthcare and treatment resource. Higher prevalence of UV exposure was associated with both higher incidence and mortality. Education should be provided to increase the awareness of eye protection. An overall declining mortality trend was found, but it was limited to only Asian and European countries.
Subject(s)
Eye Neoplasms , Global Health , Registries , Humans , Risk Factors , Incidence , Male , Female , Middle Aged , Eye Neoplasms/epidemiology , Eye Neoplasms/mortality , Aged , Sex Distribution , Adult , Age Distribution , Cost of Illness , Prevalence , Aged, 80 and over , Adolescent , Survival Rate/trendsABSTRACT
PURPOSE: VEGF and HIF-1α are important regulators of angiogenesis, overexpressed in various tumors. Lacrimal gland Adenoid cystic carcinoma (ACC) is a malignant tumor whose angiogenic properties remain unexplored. This study was designed to evaluate the expression of HIF-1α and VEGF in lacrimal gland ACC. METHODS: VEGF and HIF-1α immunoexpression was undertaken in 30 lacrimal gland ACC cases. mRNA expression of VEGF and HIF-1α was analysed in 17 cases by quantitative real time PCR. The results obtained were correlated with clinicopathological features and survival of the patients to determine the prognostic significance. RESULTS: Immunoexpression of HIF-1α and VEGF was seen in 36.6% and 46.6% ACC cases. HIF-1α expression showed significant association with advanced T-stage (P = 0.001) and VEGF with intracranial extension (P = 0.014) and solid histological pattern (P = 0.045). HIF-1α mRNA expression was seen in 29.4% cases and showed significant association with perineural invasion (P = 0.027). Recurrence occurred in 60%, distant metastasis in 20% and death in 20% cases. Survival analysis revealed that patients with HIF-1α, VEGF immunoexpression, solid histological pattern, perineural invasion, bone erosion, intracranial extension, metastasis, advanced T-stage, and exenteration had poor survival. On multivariate analysis VEGF immunoexpression (hazard ratio, 16.785; 95% confidence interval, 1.872-150.495; P = 0.012) was the most significant poor prognostic factor. CONCLUSIONS: This study demonstrates that VEGF is a potential predictor for poor clinical outcome in lacrimal gland Adenoid cystic carcinoma.
Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Adenoid Cystic/metabolism , Eye Neoplasms/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Lacrimal Apparatus Diseases/metabolism , Lacrimal Apparatus/metabolism , Vascular Endothelial Growth Factor A/metabolism , Adolescent , Adult , Aged , Carcinoma, Adenoid Cystic/diagnosis , Carcinoma, Adenoid Cystic/mortality , Eye Neoplasms/diagnosis , Eye Neoplasms/mortality , Female , Follow-Up Studies , Humans , Lacrimal Apparatus Diseases/diagnosis , Lacrimal Apparatus Diseases/mortality , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Analysis , Young AdultABSTRACT
ABSTRACT Objective: To assess the deaths caused by eye cancer from 2010 to 2019 in Brazil. Methods: Data were selected from SUS' Computer Department platform at the Ministry of Health, including death certificates, from 2010 to 2019, from all Brazilian states and the Federal District, filtering the codes C69.0 to C69.9 as the cause of death, according to the International Classification of Diseases, Tenth Revision. Results: There were 1,859 deaths from malignant neoplasm of eye and adnexa (C69), in Brazil, from 2010 to 2019, affecting 1,062 (57.1%) men. The site of neoplasm was unspecified (C69.9) in 719 cases, representing the most frequent etiology in the C69 group (38.67%). The malignant neoplasm of the orbit (C69.6) was the second most common cause of death (22.59%), followed by malignant neoplasm of retina (C69.2) (14.73%). Conclusion: The number of deaths due to malignant neoplasm of eye and adnexa slightly increased through the years of 2010 to 2019, in Brazil.
RESUMO Objetivo: Avaliar os óbitos causados por câncer ocular durante os anos de 2010 a 2019 no Brasil. Métodos: Os dados foram selecionados na plataforma do Departamento de Informática do SUS do Ministério da Saúde, incluindo declarações de óbito, durante os anos de 2010 a 2019, de todos os estados brasileiros e do Distrito Federal, filtrando os códigos C69.0 a C69.9 como causa básica de óbito, de acordo com a Classificação Internacional de Doenças e Problemas Relacionados à Saúde - 10ᵃ Revisão. Resultados: Houve 1.859 óbitos por neoplasia maligna de olho e anexos (C69), no Brasil, no período de 2010 a 2019, acometendo 1.062 (57,1%) homens. O sítio da neoplasia não foi especificado (C69.9) em 719 casos, representando a etiologia mais frequente no grupo C69 (38,67%). A neoplasia maligna da órbita (C69.6) foi a segunda causa mais comum de óbito (22,59%), seguida pela neoplasia maligna da retina (C69.2) (14,73%). Conclusão: O número de óbitos por neoplasia maligna de olho e anexos aumentou discretamente ao longo dos anos de 2010 a 2019, no Brasil.
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Eye Neoplasms/mortality , Brazil/epidemiology , Death Certificates , Mortality Registries/statistics & numerical data , Cross-Sectional Studies , Cause of Death , Eye Neoplasms/classificationABSTRACT
Material y métodos Se realizó un estudio de cohorte retrospectiva para analizar la tasa de mortalidad ajustada por edad según sexo y grupos de edad. Con estos datos se efectuó un análisis de la tendencia para la tasa de mortalidad estandarizada usando el análisis de regresión joinpoint, permitiendo estimar el porcentaje de cambio anual (PCA) para hallar cambios significativos en las tendencias. Resultados 407 personas (201 hombres y 206 mujeres) murieron por estas causas durante 1990-2018. La tasa de mortalidad tiene presentación bimodal: en la infancia y adultos mayores. Levemente más alta en hombres que mujeres (tasa estandarizada por edad: 0,12 vs 0,08 por 100.000, respectivamente) pero observándose una baja del 53% en ambos sexos. Se registró una caída estadísticamente significativa en el PCA de -3,43% anual en ambos sexos, más en hombres (-3,31%) que mujeres (-3,66%). Conclusiones La mortalidad cáncer de ojo y anexos tiene picos en la infancia y luego en adultos mayores. En niños la mayoría corresponde a neoplasias malignas de retina y en adultos mayores de órbita. La mortalidad es mayor en hombres que mujeres, pero ambas tasas han ido en disminución asemejándose a las de países industrializados. A pesar de la ausencia de datos de incidencia, esta caída podría deberse al mejoramiento de protocolos diagnóstico y tratamiento, traduciéndose en menores tasas de mortalidad.
Purpose To describe and analyze the characteristics and trends of mortality from eye and adnexal cancer in Chile, by age and sex during 1990-2018. Material and methods A retrospective cohort study to analyze the age-adjusted mortality rate, by sex and age groups was carried out. With these data, a trend analysis for the standardized mortality rate was performed using a joinpoint regression analysis, allowing the annual percentage change (APC) to be estimated to find significant changes in trends. Results 407 people (201 men and 206 women) died due to these causes from 1990-2018. Mortality rate has a bimodal presentation: in childhood and in old adults. Slightly higher in men than women (age-standardized rate: 0,12 vs 0,08 per 100.000, respectively), but a decrease of 53% was observed in both sexes. During the period, there was a statistically significant fall in the APC of -3,43% per year in both sexes, more in men (-3,31%) than in women (-3,66%). Conclusions Mortality from malignant neoplasm of eye and adnexa peaks in childhood and later in older adults. In children, the majority correspond to malignant neoplasm of retina and in older adults of the orbit. Mortality is higher in men than women, but both rates have been decreasing, resembling those of industrialized countries. Despite the absence of incidence data in Chile, this decline could be due to the improvement of diagnostic protocols and treatment, leading to lower mortality rates.
Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Eye Neoplasms/mortality , Chile/epidemiology , Regression Analysis , Retrospective Studies , Mortality/trends , Age and Sex DistributionABSTRACT
PURPOSE: Adenoid Cystic Carcinoma (ACC) is an aggressive malignant lacrimal gland tumour associated with poor prognosis. Aberrant Notch signalling has been investigated in various tumours. However, very few studies on Notch signalling in lacrimal gland ACC are reported. The aim of the present study was to evaluate the status of Notch1 receptor and activated Notch1 (NICD1) in lacrimal gland ACC and to correlate it with high-risk clinicopathological features. METHODS: A total of 23 cases of histopathologically proven lacrimal gland ACC, who underwent surgical treatment, were included in this study. Expression of Notch1 receptor and NICD1 was evaluated by immunohistochemistry on formalin fixed paraffin embedded tissues. The results obtained were correlated with clinicopathological high-risk features and survival of the patients. Kaplan-Meier survival and multivariate analysis was performed to determine the prognostic significance. RESULTS: Overexpression of Notch1 receptor and NICD1 was observed in 65% and 39% of lacrimal gland ACC cases, respectively. On Kaplan-Meier survival analysis, patients with Notch1 receptor overexpression had reduced disease free survival. On univariate analysis, male gender, bone erosion, perineural invasion, solid histologic pattern, intracranial extension and advanced tumour stage were also indicators of poor prognosis. On multivariate analysis bone erosion was the most significant poor prognostic indicator. CONCLUSION: Our study demonstrates that overexpression of Notch1 receptor plays a critical role in the biology and aggressive behaviour of lacrimal gland ACC. Bone erosion, solid histologic pattern, advanced T stage, perineural invasion and intracranial extension are other high-risk clinicopathological predictors of lacrimal gland ACC.
Subject(s)
Carcinoma, Adenoid Cystic/metabolism , Eye Neoplasms/metabolism , Lacrimal Apparatus Diseases/metabolism , Lacrimal Apparatus/metabolism , Receptor, Notch1/metabolism , Adolescent , Adult , Aged , Biomarkers, Tumor/metabolism , Biopsy , Carcinoma, Adenoid Cystic/diagnosis , Carcinoma, Adenoid Cystic/mortality , Eye Neoplasms/diagnosis , Eye Neoplasms/mortality , Follow-Up Studies , Humans , Immunohistochemistry , India/epidemiology , Lacrimal Apparatus/pathology , Lacrimal Apparatus Diseases/diagnosis , Lacrimal Apparatus Diseases/mortality , Male , Middle Aged , Retrospective Studies , Survival Rate/trends , Young AdultABSTRACT
BACKGROUND/AIMS: To identify prognostic factors for local recurrence, distant metastasis and disease-specific survival (DSS) for lacrimal gland carcinoma. METHODS: All consecutive patients with lacrimal gland carcinoma treated from January 1998 through December 2018 were included. Log-rank tests and univariate Cox proportional hazards regression models were used to study risk factors and survival. RESULTS: Overall, 55 patients were included in this study, and 5 patients were excluded from the survival analysis. Median age was 46 years (range: 10-76). 43 patients (78%) had adenoid cystic carcinoma (ACC). 31 patients (56%) had T2 disease at presentation. 28 patients (51%) underwent orbital exenteration with or without adjuvant radiotherapy or chemoradiation, 26 (47%) underwent eye-sparing surgery with or without adjuvant radiotherapy or chemoradiation, and 1 received palliative chemoradiation. 11 patients (22%) experienced local recurrence; 14 (29%) experienced distant metastasis. Five- and 10-year local-recurrence-free survival rates were 0.71 (95% CI 0.58 to 0.88), and 5- and 10-year distant-metastasis-free survival rates were 0.67 (95% CI 0.53 to 0.85) and 0.49 (95% CI 0.30 to 0.81), respectively. There was no significant difference in risks of local recurrence, distant metastasis or DSS between ACC patients who had orbital exenteration and those who had eye-sparing surgery. Perineural invasion was negatively associated with local-recurrence-free survival (p=0.02). Among patients with ACC, basaloid/solid histologic type was associated with significantly worse DSS than non-basaloid/solid histologic type (p<0.01). CONCLUSIONS: For lacrimal gland carcinoma, orbital exenteration with adjuvant therapy and eye-sparing surgery with adjuvant therapy are associated with similar recurrence outcomes. Eye-sparing surgery is associated with better DSS. Perineural invasion is a risk factor for local recurrence. ACC with basaloid/solid subtype correlates with worse DSS.
Subject(s)
Carcinoma, Adenoid Cystic/mortality , Eye Neoplasms/mortality , Lacrimal Apparatus Diseases/mortality , Neoplasm Recurrence, Local/epidemiology , Adolescent , Adult , Aged , Carcinoma, Adenoid Cystic/therapy , Child , Combined Modality Therapy , Eye Neoplasms/therapy , Female , Humans , Incidence , Lacrimal Apparatus Diseases/therapy , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Rate/trends , United States/epidemiology , Young AdultABSTRACT
BACKGROUND: To understand how to improve the effect of immune checkpoint inhibitors in uveal melanoma (UM), we need a better understanding of the expression of PD-1 and PD-L1, their relation with the presence of tumor-infiltrating lymphocytes (TILs), and their prognostic relevance in UM patients. MATERIALS AND METHODS: Expression of PD-1 and PD-L1 was assessed in 71 UM tissue samples by immunohistochemistry and quantitative real-time PCR (qRT-PCR), and further validated by western blotting. The effect of interferon gamma (IFN-γ) on PD-1/PD-L1 expression was determined on four UM cell lines. RESULTS: Immunoreactivity of PD-1 was found in 30/71 cases and of PD-L1 in 44/71 UM samples. Tumor-infiltrating lymphocytes were found in 46% of UM tissues. PD-1 was expressed on TILs while tumor cells expressed PD-L1. UM with and without TILs showed expression of PD-1 in 69% and 18% cases, respectively (p = 0.001). Similarly, PD-L1 was found in 75% of UM with TILs and in 50% of cases without TILs, respectively (p = 0.03). DFS rate were lower in patients with TILs with expression of PD-1 and PD-L1, but the rate of DFS was higher with expression of PD-L1 in patients without TILs. After treatment of UM cell lines with IFN-γ, PD-1 expression was induced in all UM cell lines whereas PD-L1 expression was found at a lower level in untreated cells, while expression also increased following treatment with IFN-γ. CONCLUSION: Our study suggests that increased infiltration with TILs promotes the aggressive behavior and suppresses the immune response of UM cells, thereby inhibiting immunotherapy.
Subject(s)
B7-H1 Antigen/metabolism , Eye Neoplasms/metabolism , Immunotherapy/methods , Lymphocytes, Tumor-Infiltrating/immunology , Melanoma/metabolism , Programmed Cell Death 1 Receptor/metabolism , Uveal Neoplasms/metabolism , B7-H1 Antigen/genetics , Cell Line, Tumor , Cell Movement , Eye Neoplasms/diagnosis , Eye Neoplasms/mortality , Follow-Up Studies , Humans , Immunohistochemistry , Interferon-gamma/metabolism , Melanoma/diagnosis , Melanoma/mortality , Polymerase Chain Reaction , Prognosis , Programmed Cell Death 1 Receptor/genetics , Survival Analysis , Uveal Neoplasms/diagnosis , Uveal Neoplasms/mortalityABSTRACT
BACKGROUND/AIMS: To validate the prognostic performance of the American Joint Committee on Cancer (AJCC) eighth edition classification for ocular adnexal lymphoma (OAL). METHODS: We performed a retrospective review of 140 consecutive patients treated for primary OAL between March 2010 and September 2017. Associations between T/N/M categories at presentation and disease-related outcomes, including relapse, progression-free survival (PFS) and overall survival (OS) were evaluated. RESULTS: Seventy-nine women and 61 men (median age, 52 (range 20-84) years; median follow-up, 57 (range 7-131) months) were included. Histological subtypes included mucosa-associated lymphoid tissue lymphoma (92.1%, n=129), diffuse large B-cell lymphoma (5.0%, n=7), follicular lymphoma (1.4%, n=2) and mantle cell lymphoma (1.4%, n=2). Patients with ≥T2 disease had significantly higher risks of overall relapse (unadjusted HR)=4.32, p=0.016), decreased PFS (uHR=5.19, p=0.004) and decreased OS (uHR=9.21, p=0.047). Patients with ≥N1 disease had significantly higher risks of overall relapse (uHR=9.17, p<0.001) and decreased PFS (uHR=9.24, p<0.001). M1 disease was significantly associated with higher risks of overall relapse (uHR=3.62, p=0.036), decreased PFS (uHR=5.13, p=0.001) and decreased OS (uHR=9.24, p=0.013). On considering TNM categories as continuous data, the uHRs for per level increase in T, N and M categories were 1.77, 1.83 and 2.30 for overall relapse and 1.72, 1.87 and 2.78 for decreased PFS, respectively (p<0.05 for each comparison). CONCLUSION: The T, N and M categories of the AJCC eighth edition classification have prognostic value for relapse and survival among patients with primary OAL. Particularly, nodal/metastatic involvement at presentation indicated less favourable outcome.
Subject(s)
Conjunctival Neoplasms/diagnosis , Eye Neoplasms/diagnosis , Eyelid Neoplasms/diagnosis , Lacrimal Apparatus Diseases/diagnosis , Lymphoma/diagnosis , Neoplasm Recurrence, Local/diagnosis , Orbital Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Conjunctival Neoplasms/classification , Conjunctival Neoplasms/mortality , Eye Neoplasms/classification , Eye Neoplasms/mortality , Eyelid Neoplasms/classification , Eyelid Neoplasms/mortality , Female , Humans , Lacrimal Apparatus Diseases/classification , Lacrimal Apparatus Diseases/mortality , Lymphoma/classification , Lymphoma/mortality , Lymphoma, B-Cell, Marginal Zone/classification , Lymphoma, B-Cell, Marginal Zone/diagnosis , Lymphoma, B-Cell, Marginal Zone/mortality , Lymphoma, Follicular/classification , Lymphoma, Follicular/diagnosis , Lymphoma, Follicular/mortality , Lymphoma, Large B-Cell, Diffuse/classification , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/mortality , Lymphoma, Mantle-Cell/classification , Lymphoma, Mantle-Cell/diagnosis , Lymphoma, Mantle-Cell/mortality , Male , Medical Oncology/organization & administration , Middle Aged , Neoplasm Recurrence, Local/classification , Neoplasm Recurrence, Local/mortality , Neoplasm Staging/methods , Orbital Neoplasms/classification , Orbital Neoplasms/mortality , Prognosis , Retrospective Studies , Societies, Medical , Survival Rate , Young AdultABSTRACT
BACKGROUND: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Many previous studies have demonstrated that the infiltrating of immune and stromal cells in the tumor microenvironment contributes significantly to prognosis. METHODS: Dataset TCGA-UVM, download from TCGA portal, was taken as the training cohort, and GSE22138, obtained from GEO database, was set as the validation cohort. ESTIMATE algorithm was applied to find intersection differentially expressed genes (DEGs) among tumor microenvironment. Kaplan-Meier analysis and univariate Cox regression model were performed on intersection DEGs to initial screen for potential prognostic genes. Then these genes entered into the validation cohort for validation using the same methods as that in the training cohort. Moreover, we conducted correlation analyses between the genes obtained in the validation cohort and the status of chromosome 3, chromosome 8q, and tumor metastasis to get prognosis genes. At last, the immune infiltration analysis was performed between the prognostic genes and 6 main kinds of tumor-infiltrating immune cells (TICs) for understanding the role of the genes in the tumor microenvironment. RESULTS: 959 intersection DEGs were found in the UM microenvironment. Kaplan-Meier and Cox analysis was then performed in the training and validation cohorts on these DEGs, and 52 genes were identified with potential prognostic value. After comparing the 52 genes to chromosome 3, chromosome 8q, and metastasis, we obtained 21 genes as the prognostic genes. The immune infiltration analysis showed that Neutrophil had the potential prognostic ability, and almost every prognostic gene we had identified was correlated with abundances of Neutrophil and CD8+ T Cell. CONCLUSIONS: Identifying 21 prognosis genes (SERPINB9, EDNRB, RAPGEF3, HFE, RNF43, ZNF415, IL12RB2, MTUS1, NEDD9, ZNF667, AZGP1, WARS, GEM, RAB31, CALHM2, CA12, MYEOV, CELF2, SLCO5A1, ISM1, and PAPSS2) could accurately identify patients' prognosis and had close interactions with Neutrophil in the tumor environment, which may provide UM patients with personalized prognosis prediction and new treatment insights.
Subject(s)
Eye Neoplasms/pathology , Melanoma/pathology , Tumor Microenvironment , Uveal Neoplasms/pathology , CD8-Positive T-Lymphocytes/cytology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Chromosomes, Human, Pair 3/genetics , Chromosomes, Human, Pair 8/genetics , Databases, Genetic , Eye Neoplasms/genetics , Eye Neoplasms/mortality , Female , Gene Expression Regulation, Neoplastic , Humans , Lymphocytes, Tumor-Infiltrating/cytology , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Male , Melanoma/genetics , Middle Aged , Neoplasm Metastasis , Neutrophils/cytology , Neutrophils/immunology , Neutrophils/metabolism , Prognosis , Proportional Hazards Models , Serpins/genetics , Ubiquitin-Protein Ligases/genetics , Uveal Neoplasms/geneticsABSTRACT
Ocular melanomas are uncommon cancers in Southeast Asia unlike in the West. We conducted a retrospective review of patients (n = 44) with histologically-proven ocular melanoma within a multi-ethnic Asian cohort from Singapore. Clinicopathological features and relapse patterns were examined, and survival outcomes of interest included recurrence-free survival (RFS) and overall survival (OS). Survival analysis was performed using the Kaplan-Meier method and multivariable Cox proportional regression. The study cohort included 18 male and 26 female patients, with a median age of 52 years (range 8-78). Median follow-up was 154 months. For uveal melanomas (n = 29), the 5-year RFS and OS was 56.8% and 76.6%, respectively; whilst for conjunctival melanomas (n = 15), the 5-year RFS and OS was 30.1% and 68.8%, respectively. Fifteen patients (38.5%) eventually developed metastasis, following which the median survival was only 17 months. Multivariate analysis demonstrated that higher T stage was a significant independent predictor for both OS (HR 8.69, 95% CI 1.03 to 73.09, p = 0.047) and RFS (HR 11.62, 95% CI 2.45 to 55.00, p = 0.002). Smoking history was independently predictive of better RFS (HR 0.08, 95% CI 0.01 to 0.78, p = 0.030). In conclusion, our study demonstrates the poor ocular melanoma outcomes in Southeast Asians, highlighting the necessity for urgent research in this area of unmet clinical need.
Subject(s)
Eye Neoplasms/diagnosis , Melanoma/diagnosis , Adolescent , Adult , Aged , Child , Disease-Free Survival , Ethnicity , Eye Neoplasms/mortality , Eye Neoplasms/pathology , Female , Humans , Male , Melanoma/mortality , Melanoma/pathology , Middle Aged , Neoplasm Staging , Prognosis , Retrospective Studies , Singapore , Survival Analysis , Survival Rate , Young AdultABSTRACT
OBJECTIVES: Tumors of the lacrimal sac are rare and life-threatening. Because of their rarity, no extensive clinical data on their management and prognosis exist. We investigated the application of definitive radiation therapy and its outcome in patients with lacrimal sac squamous cell carcinoma (LSSCC). METHODS: We retrospectively studied 17 patients with LSSCC at a single institution between 2003 and 2017. All the patients were treated with definitive radiotherapy, and 11 patients were delivered with cisplatin-based chemotherapy. The patients' clinical records were reviewed for symptoms, pathological types, the volume and dosimetry of the tumors and their adjacent structures, radiation coverage of lymph node drainage areas, treatment outcomes, and complications from definitive radiotherapy. RESULTS: Median follow-up was 38.9 months, and age at diagnosis was 48 years.The 2-year and 5-year overall survival, progression-free survival, locoregional control, and disease metastasis-free survival rates were 94.1 and 84.7%, 88.2 and 73.5%, 93.8%, 94.1, and 78.4%, respectively. A total dose of 6600-7000 cGy was prescribed to the tumor. Levels â b, â ¦a, â §, and â ¨ were covered with the clinical target volume regardless of lymph involvement. Acute Grade 3 radiation dermatitis occurred in seven patients (17.6%), but no acute Grade 4 or Grade 5 toxicity of any type occurred. Seven (41.2%, 7/17) of the treated eyes had moderated vision impairments; 17.6% (3/17) of patients developed cataracts, and glaucoma and radiation retinopathy were found in 5.9% (1/17) of patients. CONCLUSIONS: Definitive radiotherapy could be a treatment option for those who refuse surgery or have unresectable LSSCC. ADVANCES IN KNOWLEDGE: Radiation alone is a treatment option for LSSCC.
Subject(s)
Carcinoma, Squamous Cell/radiotherapy , Eye Neoplasms/radiotherapy , Nasolacrimal Duct , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/mortality , Cataract/etiology , Chemoradiotherapy/methods , Disease-Free Survival , Eye Neoplasms/drug therapy , Eye Neoplasms/mortality , Female , Glaucoma/etiology , Humans , Male , Middle Aged , Progression-Free Survival , Radiation Injuries/complications , Radiodermatitis/etiology , Radiotherapy Dosage , Radiotherapy, Conformal/methods , Retrospective Studies , Treatment Outcome , Vision Disorders/etiology , Young AdultABSTRACT
BACKGROUND: The optimal treatment for lacrimal gland cancer remains unclear. Eye-preserving surgery, as opposed to exenteration, followed by adjuvant radiotherapy (RT), has recently been reported to deliver satisfactory outcomes, but evidence is sparse. The aim of the present study was to evaluate outcomes in patients with lacrimal gland cancer treated at two tertiary medical centers. METHODS: We retrospectively examined data from patients with lacrimal gland cancer who had received eye-preserving surgical treatment followed by adjuvant RT with or without chemotherapy, or (if the tumor was inoperable) needle biopsy with definitive RT with or without chemotherapy. Baseline clinical and pathological characteristics were considered. Outcomes of interest included post-treatment complications, overall survival (OS), locoregional progression-free survival (LPFS), and distant metastasis-free survival (DMFS). RESULTS: Eighteen patients were included. Two-year OS, LPFS, and DMFS rates were 69.0, 76.7, and 71.4%, respectively. Patients with early-stage (T1-T2) lacrimal gland cancer had significantly better outcomes than those with advanced-stage disease (T3-T4). Two-year OS, LPFS, and DMFS rates were each 100% in patients with disease stages T1-T2, and 37.5, 50, and 37.5%, respectively, in those with disease stages T3-T4 (P < 0.05). Orbital complications were well tolerated. CONCLUSIONS: Eye-sparing surgery with adjuvant RT can achieve satisfactory results in patients with T1-T2 lacrimal gland carcinoma. Disease stage T3 and above was associated with poor outcomes even with post-operative RT, likely due to distant metastasis. Adding neoadjuvant chemotherapy or adjuvant chemotherapy to current treatment strategies might be a suitable choice for this group of patients.
Subject(s)
Eye Neoplasms/radiotherapy , Lacrimal Apparatus Diseases/radiotherapy , Adult , Aged , Aged, 80 and over , Combined Modality Therapy , Eye/radiation effects , Eye Neoplasms/mortality , Eye Neoplasms/surgery , Female , Humans , Lacrimal Apparatus Diseases/mortality , Lacrimal Apparatus Diseases/surgery , Male , Middle Aged , Ophthalmologic Surgical Procedures/methods , Radiation Injuries/etiology , Radiotherapy, Adjuvant/adverse effects , Retrospective Studies , Young AdultABSTRACT
BACKGROUND: To evaluate the long-term efficacy and toxicity of radiation therapy in patients with Stage IE primary ocular adnexal mucosa-associated lymphoid tissue lymphoma. METHODS: We designed a retrospective analysis to evaluate 81 patients with ocular adnexal mucosa-associated lymphoid tissue lymphoma treated with radiation therapy between 2006 and 2016. The median radiation dose was 30 Gy (range, 30-36 Gy in 15-18 fractions). Local control, progression-free survival, overall survival, and cumulative incidence of Grade 3 cataract were calculated by using the Kaplan-Meier method. RESULT: The median follow-up time was 74 months (range, 4-157 months). The 5-year local control was 100%. Although local relapse was suspected in 3 patients after radiation therapy, 2 patients were pathologically diagnosed as IgG4-related inflammation and in 1 patient as intense inflammatory cell infiltration. The 5-year progression-free survival was 94.4%. Five patients had relapse at distant sites. The 5-year overall survival was 98.8%. Twenty patients had Grade 3 cataract. The 5-year cumulative incidences of Grade ≥ 3 and Grade ≥ 2 cataract for 58 patients treated without a lens shield were 38 and 40%, respectively. The incidence of Grade ≥ 3 cataract was 42% for 50 patients treated with 6-MV X-rays (estimated lens dose: 29 Gy) and 17% for 8 patients treated with 9-MeV electrons (estimated lens dose: 24 Gy). CONCLUSIONS: Radiation therapy alone yielded excellent local control and long-term survival in Stage IE ocular adnexal mucosa-associated lymphoid tissue lymphoma. Long-term observation with careful attention to relapse at distant sites is necessary. In the case of suspected local relapse, IgG4-related disease should be carefully ruled out.
Subject(s)
Eye Neoplasms/radiotherapy , Lymphoma, B-Cell, Marginal Zone/radiotherapy , Adult , Aged , Aged, 80 and over , Cataract/epidemiology , Cataract/etiology , Dose Fractionation, Radiation , Eye Neoplasms/mortality , Eye Neoplasms/pathology , Female , Humans , Japan/epidemiology , Lymphoma, B-Cell, Marginal Zone/mortality , Lymphoma, B-Cell, Marginal Zone/pathology , Male , Middle Aged , Radiotherapy/adverse effects , Retrospective Studies , Survival Analysis , Treatment OutcomeABSTRACT
PURPOSE: The aim of this study was to identify clinical factors predictive of time to central nervous system (CNS) lymphoma or death in patients with vitreoretinal lymphoma (VRL). DESIGN: Retrospective cohort study. METHODS: Patients with VRL (nâ=â95 patients) from Januray 1, 1984 to July 30, 2018 were identified at a single ocular oncology center and records were retrospectively reviewed. Outcomes included Kaplan-Meier estimated time to CNS lymphoma and death. RESULTS: There were 95 patients with VRL diagnosed at mean age 67 years, of which 70 patients had follow-up with the ocular oncology service. Mean time to CNS lymphoma in patients with isolated VRL was 56 months and did not differ by age, sex, bilateral ocular involvement, retinal infiltration, subretinal pigment epithelial (sub-RPE) infiltration, or treatment with prophylactic systemic chemotherapy (Pâ>â0.05). Mean time to death was 66 months and did not differ when comparing those with CNS lymphoma diagnosed before VRL versus after VRL versus no CNS lymphoma at any time (67 vs 60 vs 64 months, Pâ>â0.05). Presence of sub-RPE infiltration was associated with shorter mean time to death (46 vs 76 months, Pâ=â0.04, odds ratio 1.9). Older patient age was associated with increased risk of death (odds ratio 1.0, Pâ=â0.02). The mean time to death did not differ by sex, bilateral ocular involvement, retinal infiltration, timing of CNS or systemic lymphoma, or treatment with prophylactic systemic chemotherapy (Pâ>â0.05). CONCLUSIONS: Patients with VRL presenting with sub-RPE infiltration could have shorter mean survival time. Further studies are required to confirm these findings and determine whether sub-RPE infiltration is associated with more aggressive CNS lymphoma.
Subject(s)
Eye Neoplasms/mortality , Intraocular Lymphoma/mortality , Retinal Neoplasms/mortality , Vitreous Body/pathology , Adult , Aged , Aged, 80 and over , Eye Neoplasms/pathology , Female , Fluorescein Angiography , Humans , Intraocular Lymphoma/pathology , Male , Medical Oncology , Middle Aged , Photography , Retinal Neoplasms/pathology , Retrospective Studies , Survival Rate , UltrasonographyABSTRACT
BACKGROUND: Dynamic N6-methyladenosine (m6A) RNA modification generated and erased by N6-methyltransferases and demethylases regulates gene expression, alternative splicing and cell fate. Ocular melanoma, comprising uveal melanoma (UM) and conjunctival melanoma (CM), is the most common primary eye tumor in adults and the 2nd most common melanoma. However, the functional role of m6A modification in ocular melanoma remains unclear. METHODS: m6A assays and survival analysis were used to explore decreased global m6A levels, indicating a late stage of ocular melanoma and a poor prognosis. Multiomic analysis of miCLIP-seq, RNA-seq and Label-free MS data revealed that m6A RNA modification posttranscriptionally promoted HINT2 expression. RNA immunoprecipitation (RIP)-qPCR and dual luciferase assays revealed that HINT2 mRNA specifically interacted with YTHDF1. Furthermore, polysome profiling analysis indicated a greater amount of HINT2 mRNA in the translation pool in ocular melanoma cells with higher m6A methylation. RESULTS: Here, we show that RNA methylation significantly inhibits the progression of UM and CM. Ocular melanoma samples showed decreased m6A levels, indicating a poor prognosis. Changes in global m6A modification were highly associated with tumor progression in vitro and in vivo. Mechanistically, YTHDF1 promoted the translation of methylated HINT2 mRNA, a tumor suppressor in ocular melanoma. CONCLUSIONS: Our work uncovers a critical function for m6A methylation in ocular melanoma and provides additional insight into the understanding of m6A modification.
Subject(s)
Adenosine/analogs & derivatives , Eye Neoplasms/genetics , Melanoma/genetics , Mitochondrial Proteins/genetics , RNA Processing, Post-Transcriptional , RNA, Messenger/genetics , Adenosine/metabolism , Apoptosis , Cell Line, Tumor , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/metabolism , Eye Neoplasms/metabolism , Eye Neoplasms/mortality , Eye Neoplasms/pathology , Gene Expression Profiling , Humans , Melanoma/metabolism , Melanoma/mortality , Melanoma/pathology , Methylation , Mitochondrial Proteins/metabolism , Prognosis , RNA, Messenger/metabolismABSTRACT
BACKGROUND: Differentiation between primary ocular adnexal mucosa-associated lymphoid tissue (POA-MALT) lymphoma and reactive lymphoid hyperplasias sometimes may be difficult. We have examined the treatment-associated mortality of POA-MALT lymphoma after confirmed diagnosis and evaluated their proper treatments. PATIENTS AND METHODS: From 1991 through 2016, cases of POA-MALT lymphoma were retrospectively analyzed based on their pathological and molecular/immunological diagnoses. RESULTS: A total of 78 cases with POA-MALT lymphoma with a median age of 66 years were analyzed over median/mean observations of 6.4/7.1 years. Forty-four patients (56%) were diagnosed with IgH gene clonality and 10 patients (13%) were diagnosed with flow cytometric analysis in addition to the pathological decision. The rest (24 patients, 31%) were diagnosed employing pathological decisions of hemato-pathologists and clinical decisions. All patients, except cases of watchful waiting, achieved complete remission. After initial treatment, 68 patients (87%) presented disease-free during the observation period. As treatment, a radiotherapy-based strategy was followed with 15 patients (19%, group A). Immuno-chemotherapy was administered to 24 patients (31%, B). Surgical extraction only was selected for 36 patients (46%, C). Watchful waiting was selected with three patients (4%). Recurrence after the initial treatment was found in one patient (7%) out of A, in three patients (13%) out of B, and in six patients (17%) out of C, respectively. Progression-free survivals at 5 and 10 years were 100 and 100% in A, 95 and 75% in B, and 88 and 81% in C, respectively. The recurrence rates between the patients who were diagnosed with only pathological decision (n = 24) and the patients who were diagnosed with molecular and immunological procedures (n = 54) did not show any statistical differences. CONCLUSION: Our results indicate that radiotherapy-based treatment strategies for patients with POA-MALT lymphoma show a low rate of recurrence and may improve their prognosis even after the accurate diagnosis. However, contamination of the cases with reactive (polyclonal) lymphoid hyperplasia into those with MALT lymphoma should be carefully removed to avoid unnecessary treatment for malignancies that do not exist.
Subject(s)
Eye Neoplasms/diagnosis , Eye Neoplasms/therapy , Lymphoma, B-Cell, Marginal Zone/diagnosis , Lymphoma, B-Cell, Marginal Zone/therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Eye Neoplasms/mortality , Female , Humans , Immunotherapy , Lymphoma, B-Cell, Marginal Zone/mortality , Male , Middle Aged , Neoplasm Recurrence, Local , Retrospective Studies , Treatment OutcomeABSTRACT
The adenovirus (Ad) E4orf4 protein contributes to efficient progression of virus infection. When expressed alone E4orf4 induces p53- and caspase-independent cell-death, which is more effective in cancer cells than in normal cells in tissue culture. Cancer selectivity of E4orf4-induced cell-death may result from interference with various regulatory pathways that cancer cells are more dependent on, including DNA damage signaling and proliferation control. E4orf4 signaling is conserved in several organisms, including yeast, Drosophila, and mammalian cells, indicating that E4orf4-induced cell-death can be investigated in these model organisms. The Drosophila genetic model system has contributed significantly to the study of cancer and to identification of novel cancer therapeutics. Here, we used the fly model to investigate the ability of E4orf4 to eliminate cancer tissues in a whole organism with minimal damage to normal tissues. We show that E4orf4 dramatically inhibited tumorigenesis and rescued survival of flies carrying a variety of tumors, including highly aggressive and metastatic tumors in the fly brain and eye discs. Moreover, E4orf4 rescued the morphology of adult eyes containing scrib- cancer clones even when expressed at a much later stage than scrib elimination. The E4orf4 partner protein phosphatase 2A (PP2A) was required for inhibition of tumorigenesis by E4orf4 in the system described here, whereas another E4orf4 partner, Src kinase, provided only minimal contribution to this process. Our results suggest that E4orf4 is an effective anticancer agent and reveal a promising potential for E4orf4-based cancer treatments.
Subject(s)
Drosophila/genetics , Neoplasms, Experimental/therapy , Viral Proteins/metabolism , Animals , Cell Death/genetics , Cell Differentiation/genetics , Disease Models, Animal , Drosophila/metabolism , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Eye/metabolism , Eye/pathology , Eye Neoplasms/genetics , Eye Neoplasms/metabolism , Eye Neoplasms/mortality , Eye Neoplasms/therapy , Membrane Proteins/genetics , Membrane Proteins/metabolism , Neoplasms, Experimental/genetics , PTEN Phosphohydrolase/genetics , PTEN Phosphohydrolase/metabolism , Protein Phosphatase 2/genetics , Protein Phosphatase 2/metabolism , Signal Transduction/genetics , Viral Proteins/genetics , ras Proteins/genetics , ras Proteins/metabolism , ras Proteins/toxicity , src-Family Kinases/genetics , src-Family Kinases/metabolismABSTRACT
PURPOSE: To survey adenoid cystic carcinoma of lacrimal glands in Asian population and investigate the predictability in prognosis following the 8th edition American Joint Committee on Cancer (AJCC) staging guideline. STUDY DESIGN: Retrospective study. METHODS: The clinical entities and surgical outcomes of the patients who were histologically confirmed with a diagnosis of lacrimal adenoid cystic carcinoma in National Taiwan University Hospital between January 1995 and December 2015 were retrospectively reviewed. RESULTS: Enrolled were 11 patients. The median follow-up was 7.2 years. Eight patients (72.7%) were diagnosed as T1 or T2 disease, and three patients (27.3%) were diagnosed as T3 or T4 disease according to the AJCC 8th edition guideline. Eye-sparing surgery with radiotherapy was performed in nine patients. Local recurrence was noted in six patients (54.5%) with median disease-free interval of 23.5 months. Six patients (54.5%) developed distant metastases, including lung, bone, and cranial invasions. Overall survival rate during the study period was 54.6%. Five-year overall survival was 81.8% and ten-year overall survival was 68.2%. The Log-rank test for overall survival and disease-free survival between patients with less than T3 disease (p=0.001) and patients with T3 or T4 disease (p=0.006) revealed significant differences. CONCLUSION: This study highlighted the aggressive nature of adenoid cystic carcinoma of lacrimal glands. Eye-sparing surgery with adjunctive radiotherapy may achieve relatively optimal disease control in diseases staged T1 or T2, but in advanced disease metastasis and mortality are usually inevitable.