scholarly journals Аngiogenesis in Uveal Melanoma

2021 ◽  
Vol 18 (3) ◽  
pp. 495-502
Author(s):  
V. G. Likhvantseva ◽  
O. A. Anurova ◽  
M. V. Vereshchagina ◽  
V. E. Ovanesyan
Keyword(s):  
Uveal Melanoma ◽  
Unit Area ◽  
Antiangiogenic Therapy ◽  
Survival Rates ◽  
Malignant Neoplasm ◽  
Distant Metastases ◽  
Vascular Density ◽  
Intraocular Tumors ◽  
Effective System ◽  
Malignant Solid Tumor

Uveal melanoma (UM) is less than 0.5 % in the spectrum of human tumors, and less than 5 % among all types of melanoma, therefore, it is considered to be rare. At the same time, UM is recognized as the most common intraocular malignant neoplasm. Its share among all intraocular tumors is 60 %. Radical local treatments are considered effective, but the frequency of distant metastases is unacceptably high, and the life expectancy of patients with metastatic stage of the disease is short and on average is 4–5 months. Survival rates have remained stable for the past 40 years, reflecting the lack of current effective system strategies. The tumor metastasizes in a haematogenic way, so it is not surprising that angiogenesis is constantly in the focus of scientific developments. The importance of studying angiogenesis in UM is due to the ability to predict based on the quantitative indicators of vessels inside the tumor and to search for potential targets of antiangiogenic therapy in the future. The authors used two methods of studying angiogenesis in UM: morphological with quantitative vascular counting and immunohystochemical method (IHC) with markers of endothelial cells CD34 and CD31, VIII factor, VEGF molecules, bFGF, thrombospondin and others. IHC-staining of vessels in UM allowed to visualize vessels that were not visible due to intense pigmentation of tumors or compression of vessels by tumor cells. Comparison of data obtained by the two methods demonstrated the advantages of IHS analysis over classical morphological methods. It was found that UM, as a malignant solid tumor, differs high averages of vessels per unit area. The highest rates are recorded in epitheloid melanoma, which is associated with a higher rate of growth, and more frequent metastasis, compared to similar rates in revere cell melanoma. The number of vessels per unit area in the viewing area in UM decreases with age, which explained the development of metastases in more distant after enucleation time in elderly patients. Differences in vascular density in tumors of different localization were revealed and described: they were the maximum in pre-equatorial tumors, and minimal — in iris tumors.

A randomized phase II study of adjuvant sunitinib or valproic acid in high-risk patients with uveal melanoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22059-e22059
Author(s):  
Takami Sato ◽  
Marlana M. Orloff ◽  
Matias Emanuel Valsecchi ◽  
Ayako Shimada ◽  
Inna Chervoneva ◽  
...  
Keyword(s):  
Valproic Acid ◽  
High Risk ◽  
Uveal Melanoma ◽  
Adjuvant Treatment ◽  
Survival Rates ◽  
Distant Metastases ◽  
Toxicity Assessment ◽  
Primary Tumors ◽  
Systemic Metastasis ◽  
Melanoma Patients

e22059 Background: Uveal melanoma is the most common primary intraocular cancer in adults. Despite successful treatment of primary tumors, up to 50% of patients later die of distant metastases. Currently, no effective adjuvant treatment is available. Presence of both monosomy 3 and 8q amplification (M3 + 8q amp) or DecisionDx-UM Class 2 in the primary uveal melanoma characterizes a group of patients with high metastatic death rates with reported 2-year survival rates ranging from 50% to 78%. This study aims to decrease or delay the death from metastatic uveal melanoma. Methods: Uveal melanoma patients with high risk for systemic metastasis defined as any of the following were eligible: A) M3 + 8q amp; B) Class 2. Patients must show no evidence of systemic metastasis and they need to be enrolled within 6 months of initial treatment of primary uveal melanoma. Patients were randomized to receive either sunitinib 25 mg daily or valproic acid (VPA) 750 mg daily as adjuvant treatment for 6 consecutive months. Improvement of 2-year overall survival (OS) rate from historical reference (70%) to 85% was the primary endpoint. The secondary endpoints included 1) systemic relapse-free survival (RFS) rate at 18 months, 2) ability to complete adjuvant treatment and, 3) toxicity assessment. The study was not powered to compare the efficacy between each arm. Results: A total of 90 patients were enrolled in this study. Two patients were excluded from the study including one in the sunitinib arm (did not start treatment after randomization) and one in the VPA arm (refused to stop VPA at 6 months). Nine of 45 patients in the sunitinib arm and 4 of 43 patients in the VPA arm could not complete the 6-month treatment due to toxicity (sunitinib n = 6, VPA n = 2) or systemic progression (sunitinib n = 3, VPA n = 2). The rest of patients completed the 6-month course of study treatments and all patients were followed at least for 2 years. With a median follow-up of 40.2 months, the 2-year OS rates of the sunitinib and VPA group were 95.6% (90% CI 86.5-98.6) and 90.7% (90% CI 80.1 - 95.8), respectively. The 18-month RFS rates of the sunitinib and VPA group were 75.6% (90% CI 63.1 - 84.3) and 62.8% (90% CI 49.4 - 73.5), respectively. Conclusions: Although the study is still ongoing, adjuvant sunitinib and VPA were considered to be safe and tolerable treatments for high-risk uveal melanoma. Sunitinib showed a tendency for a better outcome, thus a Cohort 2 was created to investigate the safety and potential improvement of 18-month RFS rate with 12 months of treatment with sunitinib. Clinical trial information: NCT02068586.

scholarly journals Sinonasal mucosal melanoma: treatment strategies and survival rates for a rare disease entity

2021 ◽  
Author(s):  
Alexandros Andrianakis ◽  
Peter Kiss ◽  
Markus Pomberger ◽  
Axel Wolf ◽  
Dietmar Thurnher ◽  
...  
Keyword(s):  
Rare Disease ◽  
Survival Data ◽  
Survival Rates ◽  
Delayed Diagnosis ◽  
Distant Metastases ◽  
Primary Treatment ◽  
Mucosal Melanoma ◽  
Disease Entity ◽  
Improve Outcome ◽  
Initial Symptoms

Summary Background Sinonasal mucosal melanoma (SNMM) is a rare disease entity comprising 0.4–1.3% of all melanomas. Surgery with free margins has been the primary treatment over decades. Neither the addition of radiotherapy nor chemotherapy could significantly improve outcome rates of this devastating malignancy. This study presents our clinical experience with SNMM over a 19-year period and summarizes the current body of literature on SNMM. Methods This retrospective analysis included 12 patients with SNMM treated from 2001 to 2019 at an academic center. Additionally, a literature review of the last 29 years on treatment and survival data of SNMM was conducted. Results Main initial symptoms were epistaxis and nasal obstruction. Of the patients 9 underwent endoscopic surgery, 6 received adjuvant therapy. 3 patients who did not undergo surgery, received chemoradiotherapy, radiotherapy alone, and chemotherapy alone, respectively. At the time of diagnosis 2 patients had distant metastases and 4 patients developed distant metastases during the course of the disease. Mean overall survival (OS) was 30.6 months, 3‑year and 5‑year OS were 25%, and 18.2%, respectively. Conclusion Unspecific symptoms and hidden anatomic locations lead to delayed diagnosis and increased rates of metastatic dissemination. Distant metastasis is the main treatment failure in SNMM. Surgery with free margins remains the primary treatment for SNMM. Adjuvant radiotherapy might improve local control in individual cases but efficient systemic therapy is needed to improve outcome rates. To evaluate and define more effective targeted treatment options and improve outcome rates, homogeneous data and prospective multicentric analysis are needed.

scholarly journals Molecular Insights and Emerging Strategies for Treatment of Metastatic Uveal Melanoma

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2761
Author(s):  
Fabiana Mallone ◽  
Marta Sacchetti ◽  
Alessandro Lambiase ◽  
Antonietta Moramarco
Keyword(s):  
Clinical Trials ◽  
Uveal Melanoma ◽  
Treatment Options ◽  
Survival Rates ◽  
Metastatic Tumor ◽  
Clinical Use ◽  
Future Perspectives ◽  
Diagnosis And Prognosis ◽  
Novel Treatment ◽  
Combinational Therapies

Uveal melanoma (UM) is the most common intraocular cancer. In recent decades, major advances have been achieved in the diagnosis and prognosis of UM allowing for tailored treatments. However, nearly 50% of patients still develop metastatic disease with survival rates of less than 1 year. There is currently no standard of adjuvant and metastatic treatment in UM, and available therapies are ineffective resulting from cutaneous melanoma protocols. Advances and novel treatment options including liver-directed therapies, immunotherapy, and targeted-therapy have been investigated in UM-dedicated clinical trials on single compounds or combinational therapies, with promising results. Therapies aimed at prolonging or targeting metastatic tumor dormancy provided encouraging results in other cancers, and need to be explored in UM. In this review, the latest progress in the diagnosis, prognosis, and treatment of UM in adjuvant and metastatic settings are discussed. In addition, novel insights into tumor genetics, biology and immunology, and the mechanisms underlying metastatic dormancy are discussed. As evident from the numerous studies discussed in this review, the increasing knowledge of this disease and the promising results from testing of novel individualized therapies could offer future perspectives for translating in clinical use.

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.

scholarly journals Clinical features of a Chinese female nongestational choriocarcinoma cohort: a retrospective study of 37 patients

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Yuming Shao ◽  
Yang Xiang ◽  
Fang Jiang ◽  
Boju Pan ◽  
Xirun Wan ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Clinical Laboratory ◽  
Age Of Onset ◽  
Survival Rates ◽  
Malignant Neoplasm ◽  
Complete Response ◽  
College Hospital ◽  
Medical College ◽  
Gestational Choriocarcinoma ◽  
Therapeutic Outcomes

Abstract Background Choriocarcinoma is a rare malignant neoplasm, which is classified as either gestational choriocarcinoma or nongestational choriocarcinoma. The purpose of this study was to examine the clinical characteristics of Chinese female nongestational choriocarcinoma patients and discuss our experience in treating this rare disease. Results We conducted a single-center retrospective study on a sample of 37 nongestational choriocarcinoma patients who were diagnosed and treated at Peking Union Medical College Hospital from March 1982 to March 2020. Their demographic, clinical, laboratory, and therapeutic data were collected. Detailed information was available for all 37 individuals in our sample. The primary lesions included 34 in the ovaries, 2 in the pituitary and 1 in the stomach. The median age of onset was 22 years, and the median follow-up period spanned 41 months. The lungs (40.5%) were the most commonly observed metastatic site. All subjects were treated with surgery and multidrug chemotherapies, and a median of 4.0 courses was required to achieve complete remission. The overall complete response rate, relapse rate, and 3-year and 5-year survival rates were 81.1%, 16.7%, 80.0%, and 75.5%, respectively. Conclusions Nongestational choriocarcinoma can be managed well using surgery and multidrug chemotherapies, but the overall outcome of nongestational choriocarcinoma is still worse than that of gestational choriocarcinoma. Mixed nongestational choriocarcinoma seems to have similar therapeutic outcomes as pure tumors.

Differential Expression of Fourteen Proteins between Uveal Melanoma from Patients Who Subsequently Developed Distant Metastases versus Those Who Did Not

2012 ◽  
Vol 53 (8) ◽  
pp. 4634 ◽  
Author(s):  
Annett Linge ◽  
Susan Kennedy ◽  
Deirdre O'Flynn ◽  
Stephen Beatty ◽  
Paul Moriarty ◽  
...  
Keyword(s):  
Differential Expression ◽  
Uveal Melanoma ◽  
Distant Metastases

scholarly journals Increased Non-Homologous End Joining Makes DNA-PK a Promising Target for Therapeutic Intervention in Uveal Melanoma

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1278 ◽  
Author(s):  
Doherty ◽  
Bryant ◽  
Valluru ◽  
Rennie ◽  
Sisley
Keyword(s):  
Uveal Melanoma ◽  
Messenger Rna ◽  
Therapeutic Option ◽  
Survival Rates ◽  
The Cancer Genome Atlas ◽  
End Joining ◽  
Expression Of Genes ◽  
Effective Therapeutic Option ◽  
Non Homologous End Joining ◽  
Induced Apoptosis

Uveal melanoma (UM) is the most common primary intraocular tumour in adults, with a mean survival of six months following metastasis. The survival rates have not improved in over 30 years. This study has shown that sister chromatid exchange (SCE) is low in UM which is likely due to a reduced expression of FANCD2. As FANCD2 can function to suppress non-homologous end joining (NHEJ), this study therefore investigated NHEJ in UM. The activation of the catalytic subunit of the NHEJ pathway protein DNA-dependent protein kinase (DNA-PK) was measured by analysing the foci formation and the ligation efficiency by NHEJ determined using a plasmid-based end-joining assay. Using small-interfering RNA (siRNA) knock-down, and chemical inhibitors of DNA-PK, the survival of primary UM cultures and two cell lines were determined. To assess the homologous recombination capacity in response to the inhibition of DNA-PK, a SCE analysis was performed. In addition, to support the findings, the messenger RNA (mRNA) expression of genes associated with NHEJ was analysed using the Cancer Genome Atlas (TCGA)-UM RNAseq data (n = 79). The NHEJ activity and DNA-PKcs activation was upregulated in UM and the inhibition of DNA-PK selectively induced apoptosis and sensitized to ionising radiation and inter-strand cross-linking agents. The inhibition of the NHEJ protein DNA-PK is lethal to UM, indicating a potentially effective therapeutic option, either alone or as a sensitizer for other treatments.

scholarly journals Multicenter External Validation of the Liverpool Uveal Melanoma Prognosticator Online: An OOG Collaborative Study

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 477 ◽  
Author(s):  
Alda Cunha Rola ◽  
Azzam Taktak ◽  
Antonio Eleuteri ◽  
Helen Kalirai ◽  
Heinrich Heimann ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
External Validation ◽  
Collaborative Study ◽  
Survival Rates ◽  
Choroidal Melanoma ◽  
External Data ◽  
Calibration Methods ◽  
Anonymized Data ◽  
Using Data ◽  
Disseminated Disease

Uveal melanoma (UM) is fatal in ~50% of patients as a result of disseminated disease. This study aims to externally validate the Liverpool Uveal Melanoma Prognosticator Online V3 (LUMPO3) to determine its reliability in predicting survival after treatment for choroidal melanoma when utilizing external data from other ocular oncology centers. Anonymized data of 1836 UM patients from seven international ocular oncology centers were analyzed with LUMPO3 to predict the 10-year survival for each patient in each external dataset. The analysts were masked to the patient outcomes. Model predictions were sent to an independent statistician to evaluate LUMPO3’s performance using discrimination and calibration methods. LUMPO3’s ability to discriminate between UM patients who died of metastatic UM and those who were still alive was fair-to-good, with C-statistics ranging from 0.64 to 0.85 at year 1. The pooled estimate for all external centers was 0.72 (95% confidence interval: 0.68 to 0.75). Agreement between observed and predicted survival probabilities was generally good given differences in case mix and survival rates between different centers. Despite the differences between the international cohorts of patients with primary UM, LUMPO3 is a valuable tool for predicting all-cause mortality in this disease when using data from external centers.

scholarly journals Low-dose aspirin confers a survival benefit in patients with pathological advanced-stage oral squamous cell carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sheng-Dean Luo ◽  
Shao-Chun Wu ◽  
Wei-Chih Chen ◽  
Ching-Nung Wu ◽  
Tai-Jan Chiu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Oral Cavity ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cox Regression ◽  
Survival Rates ◽  
Distant Metastases ◽  
Good Prognosis ◽  
High Rate

AbstractOral squamous cell carcinoma (OSCC) remains one of the most challenging clinical problems in the field due to its high rate of locoregional and distant metastases. However, studies that assess the association between aspirin use and survival in patients with OSCC are limited. Moreover, patients that recruited from those studies might have tumors that arose from different anatomic regions of the head and neck, including the oral cavity, oropharynx, etc. Since tumors within these distinct anatomic regions are unique in the context of epidemiology and tumor progression, we sought to evaluate the association of aspirin use with squamous cell carcinomas located within the oral cavity only. In this 10-year cohort study, we evaluated aspirin use and survival rates in relation to clinical characteristics as well as duration of aspirin use in patients with OSCC. Our findings suggest that OSCC patients with aspirin use for more than 180 days showed improved overall and disease-specific survival rates. Aspirin also improves survival in patients across various stages of OSCC. Cox regression models indicated that aspirin use was associated with a good prognosis. In conclusion, this evidence indicates that aspirin may be potentially used as an adjuvant therapy for OSCC.

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