Die Tumorheterogenität des uvealen Melanoms: Diagnostisch und prognostisch wichtig?

2021 ◽  
pp. 1-3
Author(s):  
Ira Seibel
Keyword(s):  
Uveal Melanoma ◽  
Treatment Strategies ◽  
Intratumoral Heterogeneity ◽  
Correct Prediction ◽  
Patient Counseling ◽  
Clinical Behavior ◽  
Precise Information ◽  
Genetic Features ◽  
Metastatic Risk ◽  
Tumor Biopsies

Tumor biopsies in uveal melanoma (UM) serve mainly the purpose of prognostication and assessment of individual metastatic risk, but can be used for diagnosis in selected cases. The importance of precise information is paramount for selecting adequate surveillance protocols, patient counseling, and optimization of treatment strategies. However, intratumoral heterogeneity and sample representativity are major concerns and can interfere with the correct prediction of the patient’s prognosis. We report a series of cases of UM with distinct morphologically identifiable areas, highlighting the differences in clinical behavior, as well as histopathological and genetic features.

Uveal melanoma metastatic risk based on comprehensive genetic testing

2020 ◽  
pp. 178-179
Author(s):  
V.A. Yarovaya ◽  
◽  
A.A. Yarovoy ◽  
A.R. Zaretsky ◽  
L.V. Chudakova ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Uveal Melanoma ◽  
Metastatic Risk

scholarly journals Intratumor Heterogeneity in Uveal Melanoma BAP-1 Expression

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1143
Author(s):  
Gustav Stålhammar ◽  
Hans E. Grossniklaus
Keyword(s):  
Gene Expression ◽  
Uveal Melanoma ◽  
Tumor Size ◽  
Hot Spots ◽  
Malignant Tumors ◽  
Intratumor Heterogeneity ◽  
Prognostic Information ◽  
Size Category ◽  
Cold Spots ◽  
Metastatic Risk

Malignant tumors are rarely homogenous on the morphological, genome, transcriptome or proteome level. In this study, we investigate the intratumor heterogeneity of BAP-1 expression in uveal melanoma with digital image analysis of 40 tumors. The proportion of BAP-1 positive cells was measured in full tumor sections, hot spots, cold spots and in scleral margins. The mean difference between hot spots and cold spots was 41 percentage points (pp, SD 29). Tumors with gene expression class 1 (associated with low metastatic risk) and 2 (high metastatic risk) had similar intratumor heterogeneity. Similarly, the level of intratumor heterogeneity was comparable in tumors from patients that later developed metastases as in patients that did not. BAP-1 measured in any tumor region added significant prognostic information to both American Joint Committee on Cancer (AJCC) tumor size category (p ≤ 0.001) and gene expression class (p ≤ 0.04). We conclude that there is substantial intratumor heterogeneity in uveal melanoma BAP-1 expression. However, it is of limited prognostic importance. Regardless of region, analysis of BAP-1 expression adds significant prognostic information beyond tumor size and gene expression class.

scholarly journals Esophageal Cancer: 10-Year Survival After Surgery

2021 ◽  
Author(s):  
Oleg Kshivets
Keyword(s):  
Neural Networks ◽  
Esophageal Cancer ◽  
Blood Cells ◽  
Treatment Strategies ◽  
Rank Test ◽  
Correct Prediction ◽  
Algorithm Selection ◽  
Cell Ratio ◽  
Prothrombin Index ◽  
Area Under Roc Curve

Abstract OBJECTIVE: 10-Year survival (10YS) after radical surgery for esophageal cancer (EC) patients (ECP) (T1-4N0-2M0) was analyzed. METHODS: We analyzed data of 551 consecutive ECP (age=56.5±8.9 years; tumor size=6±3.5 cm) radically operated (R0) and monitored in 1975-2021 (m=411, f=140; esophagogastrectomies (EG) Garlock=284, EG Lewis=267, combined EG with resection of pancreas, liver, diaphragm, aorta, VCS, colon transversum, lung, trachea, pericardium, splenectomy=154; adenocarcinoma=314, squamous=227, mix=10; T1=128, T2=115, T3=181, T4=127; N0=278, N1=70, N2=203; G1=157, G2=141, G3=253; early EC=109, invasive=442; only surgery=423, adjuvant chemoimmunoradiotherapy-AT=128: 5-FU+thymalin/taktivin+radiotherapy 45-50Gy). Multivariate Cox modeling, clustering, SEPATH, Monte Carlo, bootstrap and neural networks computing were used to determine any significant dependence.RESULTS: Overall life span (LS) was 1881.1±2230.6 days and cumulative 5-year survival (5YS) reached 52.1%, 10 years – 45.9%, 20 years – 33.7%. 184 ECP lived more than 5 years (LS=4308.7±2413.3 days), 99 ECP – more than 10 years (LS=5883±2296.6 days). 226 ECP died because of EC (LS=628.3±319.9 days). AT significantly improved 5YS (68.8% vs. 48.5%) (P=0.00025 by log-rank test). Cox modeling displayed that 10YS of ECP significantly depended on: phase transition (PT) N0—N12 in terms of synergetics, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), T, G, histology, age, AT, localization, blood cells, prothrombin index, hemorrhage time, residual nitrogen, protein (P=0.000-0.021). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 10YS and PT N0—N12 (rank=1), healthy cells/CC (2), PT early-invasive EC (3), thrombocytes/CC (4), erythrocytes/CC (5), lymphocytes/CC (6), eosinophils/CC (7), stick neutrophils/CC (8), segmented neutrophils/CC (9), monocytes/CC (10). leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).CONCLUSIONS: 10-Year survival after radical procedures significantly depended on: 1) PT “early-invasive cancer”; 2) PT N0--N12; 3) Cell Ratio Factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) EC characteristics; 9) tumor localization; 10) anthropometric data; 11) surgery type. Optimal diagnosis and treatment strategies for EC are: 1) screening and early detection of EC; 2) availability of experienced thoracoabdominal surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for ECP with unfavorable prognosis.

scholarly journals The Tumorigenic Properties of EZH2 are Mediated by MiR-26a in Uveal Melanoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Yao Li ◽  
Mingmei Zhang ◽  
Huayin Feng ◽  
Shaya Mahati
Keyword(s):  
Uveal Melanoma ◽  
Cell Function ◽  
Treatment Strategies ◽  
Disease Free Survival ◽  
Polycomb Group ◽  
Luciferase Reporter ◽  
Polycomb Group Protein ◽  
Ezh2 Expression ◽  
Group Protein ◽  
Tumor Types

Background: The polycomb group protein enhancer of zeste homolog 2 (EZH2) has been found to be highly expressed in various tumors, and microRNA-26a (miR-26a) is often unmodulated in cancers. However, the functions of these two molecules in uveal melanoma (UM) and their relationships have not been reported.Methods: We explored the effects of the miR-26a–EZH2 axis in UM by examining the levels of miR-26a and EZH2. The EZH2 levels in various tumor types and the correlations between EZH2 levels and overall survival and disease-free survival were reanalyzed. The binding of miR-26a to the 3′-untranslated region of EZH2 mRNA was measured using the luciferase reporter assay. The regulation of EZH2 gene expression by miR-26a was also identified, and the effect of elevated EZH2 expression on UM cell function was further examined. Results: miR-26a was downregulated and EZH2 was upregulated in UM cells. Overexpression of miR-26a inhibited cell proliferation, and knockdown of EZH2 suppressed cell growth. EZH2 was a direct target of miR-26a in UM cells. The knockout of EZH2 mimicked the tumor inhibition of miR-26a in UM cells, whereas the reintroduction of EZH2 abolished this effect. In addition, a network of EZH2 and its interacting proteins (UBC, CDK1, HDAC1, SUZ12, EED) was found to participate in miR-26a-mediated tumor progression.Conclusion: The newly identified miR-26a–EZH2 axis may be a potential target for the development of treatment strategies for UM.

scholarly journals Nivolumab and Ipilimumab in the Treatment of Metastatic Uveal Melanoma: A Single-Center Experience

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Vidhya Karivedu ◽  
Ihab Eldessouki ◽  
Ahmad Taftaf ◽  
Zheng Zhu ◽  
Abouelmagd Makramalla ◽  
...  
Keyword(s):  
Partial Response ◽  
Clinical Outcome ◽  
Uveal Melanoma ◽  
Stable Disease ◽  
Checkpoint Inhibitors ◽  
Evaluation Criteria ◽  
Treatment Strategies ◽  
Case Series ◽  
Retrospective Case ◽  
Study Results

Background. Metastatic uveal melanoma (MUM) is associated with a poor prognosis, with a median overall survival (OS) of 4–15 months. Despite new insights into the genetic and molecular background of MUM, satisfactory systemic treatment approaches are currently lacking. The study results of innovative treatment strategies are urgently needed. Patients and Methods. This was a retrospective case series of 8 patients with MUM managed at the University of Cincinnati between January 2015 and January 2018. The immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) 1.1 criteria were used for patient evaluation, and magnetic resonance imaging was used for evaluation at treatment checkpoints. Objective. To assess the clinical outcome of patients with MUM treated with a combination of checkpoint inhibitors. Results. The series included eight patients, six men and two women, with MUM. Their median age at MUM diagnosis was 69 (range, 55–77) years. All patients were treated with ipilimumab and nivolumab combination along with transarterial chemoembolization (TACE), followed by nivolumab maintenance and monthly TACE procedures. The majority of patients had a partial response or stable disease. Two of the patients had partial response, while four others had stable disease. Two other patients experienced disease progression. Conclusion. We report the outcomes of eight patients with MUM treated with the combination of ipilimumab and nivolumab. We report the clinical outcome and toxicity associated with this treatment approach. Further studies are warranted to explore immunotherapy in MUM. These findings support the consideration of immunotherapy in MUM.

scholarly journals Prospective evaluation of risk-appropriate management of uveal melanoma patients informed by gene expression profiling

2020 ◽  
Vol 7 (1) ◽  
pp. 17-25 ◽  
Author(s):  
Amy C Schefler ◽  
Alison Skalet ◽  
Scott C N Oliver ◽  
John Mason ◽  
Anthony B Daniels ◽  
...  
Keyword(s):  
Gene Expression ◽  
Uveal Melanoma ◽  
Clinical Utility ◽  
Medical Oncology ◽  
Treatment Plan ◽  
Risk Class ◽  
Class 1 ◽  
Melanoma Patients ◽  
Metastatic Risk

Aim: The Clinical Application of DecisionDx-UM Gene Expression Assay Results study aimed to evaluate the clinical utility of the prognostic 15-gene expression profile (15-GEP) test for uveal melanoma (UM) patients in a large, prospective multicenter cohort. Patients & methods: Nine centers prospectively enrolled 138 UM patients clinically tested with the 15-GEP. Physician-recommended specialty referrals and metastatic surveillance regimens were collected. Results: A total of 93% of high-risk class 2 patients were referred to medical oncology for follow-up, compared with 51% of class 1 patients. A majority (62%) of class 2 patients were recommended overall high-intensity metastatic surveillance, while 85% of class 1 patients were recommended low-intensity metastatic surveillance. Conclusion: Treatment plan recommendations for UM patients are aligned with GEP-informed metastatic risk, consistent with prior studies.

scholarly journals Epidemiology of uveal melanoma in Brazil

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Evandro Lucena ◽  
Daniel Cohen Goldemberg ◽  
Luiz Claudio Santos Thuler ◽  
Andreia Cristina de Melo
Keyword(s):  
Sex Education ◽  
Uveal Melanoma ◽  
Healthcare Access ◽  
Regional Distribution ◽  
Age Distribution ◽  
Treatment Strategies ◽  
Distant Metastases ◽  
Cancer Registries ◽  
Clinical Staging ◽  
Continuous Variables

Abstract Purpose To report the prevalence of uveal melanoma in a Hospital database in Brazil over the period of 16 years (2000 to 2016). Design Descriptive epidemiological study evaluating the Brazilian Hospital Based Cancer Registries. Participants/methods Uveal melanomas were identified based on ICD-O-3 codes C69.3 [choroid], C69.4 [ciliary body and iris], and C69.2 [retina]) derived from the Integrator Registry database. Kolmogorov–Smirnov Test was used for evaluation of normality of data, t-test and Chi square were used for categorical and continuous variables respectively using SPSS Software. Main outcome measures Age, sex, education, regional distribution, clinical staging at the diagnosis, time from diagnosis to treatment (≤ 60 days versus > 60 days) and first-course therapy (surgery, chemotherapy, radiotherapy or a combination of such). Results There were 2166 cases of uveal melanoma representing 5.4% of all cases of melanoma. Histological confirmation of uveal melanoma was available in all cases. Higher prevalence of 1139 cases (52.6%) in women than 1027 cases (47.4%) in men was observed. Age distribution revealed 1411 cases (65.1%) in the group between 41 and 69 years old. A total of 429 (19.8%) patients were classified as initial disease and 334 (15.4%) as advanced (regional or distant metastases). Staging as initial disease was more frequent (113–24.8%) in patients with > 8 school years than in patients with < 8 school years (179–17.6%) reflecting disparities in healthcare access between those two populations. No difference was noticed in terms of diagnosis, staging and treatment after the Brazilian “60 days law” (Federal Law 12.732/12) came into effect in 2013 regulating the maximum period that a patient with cancer has to wait until start the treatment. Conclusion Epidemiological data is critical for planning early treatment strategies and allocating medical resources. This study intended to understand the characteristics of uveal melanoma in Brazil.

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