Cobalt plaque versus enucleation for uveal melanoma. Comparison of survival rates Adams, K. S., Abramson, D. H., Ellsworth, R. M., Haik, B.GG., Bedford, M., Packer, S., Seddon, J. Albert, D., and Polivogianis, L. (Manhattan Eye, Ear and Throat Hosp., Dept. Ophthalmol., 210 E. 64th St., New York, NY 10021). Br. J. Ophthalmol. 72:494, 1988

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.

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Phenotype and outcome of pulmonary arterial hypertension patients carrying a TBX4 mutation

European Respiratory Journal ◽

10.1183/13993003.02340-2019 ◽

2020 ◽

Vol 55 (5) ◽

pp. 1902340 ◽

Cited By ~ 3

Author(s):

Pierre Thoré ◽

Barbara Girerd ◽

Xavier Jaïs ◽

Laurent Savale ◽

Maria-Rosa Ghigna ◽

...

Keyword(s):

New York ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Survival Rates ◽

Heart Association ◽

Lung Parenchyma ◽

Functional Class ◽

Class Iii ◽

High Resolution Computed Tomography ◽

Pulmonary Arterial

IntroductionTBX4 mutation causes small patella syndrome (SPS) and/or pulmonary arterial hypertension (PAH). The characteristics and outcomes of PAH associated with TBX4 mutations are largely unknown.MethodsWe report the clinical, functional, radiologic, histologic and haemodynamic characteristics and outcomes of heritable PAH patients carrying a TBX4 mutation from the French pulmonary hypertension (PH) network.Results20 patients were identified in 17 families. They were characterised by a median age at diagnosis of 29 years (0–76 years) and a female to male ratio of three. Most of the patients (70%) were in New York Heart Association (NYHA) functional class III or IV with a severe haemodynamic impairment (median pulmonary vascular resistance (PVR) of 13.6 (6.2–41.8) Wood units). Skeletal signs of SPS were present in 80% of cases. Half of the patients had mild restrictive or obstructive limitation and diffusing capacity of the lung for carbon monoxide (DLCO) was decreased in all patients. High-resolution computed tomography (HRCT) showed bronchial abnormalities, peri-bronchial cysts, mosaic distribution and mediastinal lymphadenopathies. PAH therapy was associated with significant clinical improvement. At follow-up (median 76 months), two patients had died and two had undergone lung transplantation. One-year, three-year and five-year event-free survival rates were 100%, 94% and 83%, respectively. Histologic examination of explanted lungs revealed alveolar growth abnormalities, major pulmonary vascular remodelling similar to that observed in idiopathic pulmonary arterial hypertension (IPAH) and accumulation of cholesterol crystals within the lung parenchyma.ConclusionPAH due to TBX4 mutations may occur with or without skeletal abnormalities across a broad age range from birth to late adulthood. PAH is usually severe and associated with bronchial and parenchymal abnormalities.

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

Cancers ◽

10.3390/cancers11091278 ◽

2019 ◽

Vol 11 (9) ◽

pp. 1278 ◽

Cited By ~ 5

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.

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

Cancers ◽

10.3390/cancers12020477 ◽

2020 ◽

Vol 12 (2) ◽

pp. 477 ◽

Cited By ~ 7

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.

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

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e22059 ◽

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.

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Comparison of Survival Rates for Patients With Uveal Melanoma After Treatment With Proton Beam Irradiation or Enucleation

American Journal of Ophthalmology ◽

10.1016/0002-9394(85)90357-5 ◽

1985 ◽

Vol 99 (3) ◽

pp. 282-290 ◽

Cited By ~ 103

Author(s):

Johanna M. Seddon ◽

Evangelos S. Gragoudas ◽

Daniel M. Albert ◽

Chung Cheng Hsieh ◽

Lela Polivogianis ◽

...

Keyword(s):

Proton Beam ◽

Uveal Melanoma ◽

Survival Rates ◽

Beam Irradiation ◽

Proton Beam Irradiation

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Craniopharyngiomas in Children

Neurosurgery ◽

10.1227/00006123-198209000-00008 ◽

1982 ◽

Vol 11 (3) ◽

pp. 382-389 ◽

Cited By ~ 107

Author(s):

Peter W. Carmel ◽

Joao L. Antunes ◽

Chu H. Chang

Keyword(s):

New York ◽

Survival Rates ◽

Initial Therapy ◽

Aspiration Biopsy ◽

Total Removal ◽

Actuarial Survival ◽

Postoperative Death ◽

Cyst Aspiration ◽

Radiotherapy Alone ◽

Subtotal Removal

Abstract Forty-three children with craniopharyngiomas were operated upon at The Neurological Institute of New York between 1952 and 1977. The removal was thought to be total in 14 children and subtotal in 20, and cyst aspiration/biopsy was performed in 9 cases. Radiation was given as part of the initial therapy in 6 children after subtotal removal and to 8 others after aspiration/biopsy. There was 1 postoperative death. All children with tumors thought to have been removed totally are alive. The 10-year actuarial survival rates are 52% for subtotal removal alone and 87% for subtotal removal plus radiation. Tumors have recurred by 10 years in half of those thought to be totally removed, in more than 90% of those subtotally removed, and in less than 25% of those at risk after subtotal removal and radiation therapy. Tumors recurred in 22 children, and 17 underwent reoperation. Total removal was obtained in 4 cases, and 5 had radiation after subtotal removal. Radiotherapy alone was used in 2 cases. Recurrences usually occurred within 2 years. However, after “total” removal recurrences were quite delayed. Our data indicate that total removal allows excellent survival rates and that some of these children are potentially cured. The attempt at total removal did not inflict a severe hypothalamic or visual burden on these children. Where total removal is not possible, further therapy, either radiation or reoperation, will be required. Radiation dramatically decreased recurrence and improved survival after subtotal removal.

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Abstract 16632: Clinical Characteristics and In-Hospital Outcomes of Covid-19 Patients With Ecg St Segment Elevation: A System Wide Analysis

Circulation ◽

10.1161/circ.142.suppl_3.16632 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Avneet SINGH ◽

Perwaiz Meraj ◽

Arvind Reddy ◽

Eitezaz Mahmood ◽

Ibrahim Ali ◽

...

Keyword(s):

New York ◽

Hospital Mortality ◽

Clinical Characteristics ◽

Survival Rates ◽

Female Gender ◽

Stepwise Logistic Regression ◽

Stepwise Logistic Regression Analysis ◽

St Segment Elevation ◽

Kaplan Meier ◽

St Segment

Myocardial injury is seen in approximately 20% of COVID-19 patients and ST elevation myocardial infarction may be the presenting clinical manifestation. Recent data suggest that the ST-segment elevation (STE) may be due to myopericarditis. We assessed the clinical characteristics, electrocardiographic patterns, incidence, management and outcomes of COVID-19 pts with STE. Methods: We analyzed 23,406 ECGs (10,018 pts) admitted to 13 New York City area hospitals between March 1 and April 30, 2020. Results: After manual adjudication, 51 (0.5%) had focal STE, 22 (0.2%) had diffuse STE and 9,945 did not have STE. Baseline clinical characteristics were similar among the three groups, albeit a higher percentage of pts with low ejection fraction in the diffuse STE group. Cardiac catheterization was performed on 10 pts. Three pts did not have obstructive disease. Pts with focal STE were more likely to require inotropes and die during index hospitalization. Kaplan-Meier estimated overall survival rates were 31%, 33% and 6% in patients without STE, focal and diffuse STE, respectively (p < 0.0001) (Figure). By stepwise logistic regression analysis, focal STE was the strongest predictor of death (OR=7.0; CI 3.8-13.0, p<0 .0001) followed by age > 65 years (OR=3.5; CI 3.1-3.9; p<0.0001) and diffuse STE (OR=2.9; CI 1.1-7.2; p<0.0001). Female gender was associated with a decreased risk (OR 0.72; CI, 0.65-0.79; p<0.0001). Conclusions: In this large retrospective analysis of 10,018 COVID-19 pts, we observed that: 1) a very small percentage (0.7%) presented with STE; 2) 70% had focal STE and 30% had diffuse STE; 3) a minority underwent coronary angiography; 4) in-hospital mortality rates were very high for pts with STE, and even more so for those with focal STE (63% vs 46%) and; 5) focal STE was the strongest predictor of in-hospital mortality and female gender was a predictor of survival.

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