scholarly journals Clinical Outcomes after International Referral of Uveal Melanoma Patients for Proton Therapy

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6241
Author(s):  
Marina Marinkovic ◽  
Lennart J. Pors ◽  
Vincent van den Berg ◽  
Femke P. Peters ◽  
Ann Schalenbourg ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Visual Impairment ◽  
Uveal Melanoma ◽  
Proton Therapy ◽  
Distant Metastasis ◽  
Proportional Hazards ◽  
Tumour Size ◽  
Cox Proportional Hazards ◽  
Tumour Control ◽  
Melanoma Patients

Objective: To assess oncological and ophthalmological outcomes after international referral of uveal melanoma patients for proton therapy. Materials and Methods: This is a retrospective study among Dutch uveal melanoma patients who were treated in Switzerland with 60.0 CGE proton therapy (in 4 fractions) from 1987 to 2019. All patients were ineligible for brachytherapy due to tumour size and/or proximity to the optic nerve. Time-to-event analyses were performed using Kaplan–Meier’s methodology and Cox proportional hazards models. Results: There were 103 patients (104 eyes) with a median largest tumour diameter of 19 mm (range 6–26 mm). Tumours were localised centrally (11%), mid-peripherally (65%) or peripherally (34%). Median follow-up was 7 years. Five-year local control, distant metastasis-free survival and eye preservation rates were 94%, 70% and 81% respectively. At five years, severe, moderate and mild visual impairment was observed in respectively 79%, 4% and 6% of the patients. Larger tumour volumes and more central tumour localisation were associated with severe visual impairment. After correction for these factors, dose to the macula, optic disc and retina, but not optic nerve was significantly associated with severe visual impairment. Conclusion: International referral for proton therapy yielded good tumour control and eye preservation rates, but risk of distant metastasis and severe visual impairment were substantial, possibly due to the selection of advanced tumour stages and/or central localisation. Dose to the macula may be more relevant than dose to the optic nerve for preservation of visual acuity, which is relevant for the treatment planning of proton therapy.

The prognostic value of B7-H6 in esophageal squamous cell carcinoma

2019 ◽  
Author(s):  
Shu Yang ◽  
Huan Zhou ◽  
Jun Dong ◽  
Liyi Guo ◽  
Xicheng Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Lymphatic Metastasis ◽  
Proportional Hazards ◽  
Tumour Size ◽  
Cox Proportional Hazards ◽  
Proportional Hazards Regression ◽  
Kaplan Meier

Abstract Background B7-h6, a member of the B7 family molecules, participates in the clearance of tumor cells by binding to NKp30 on NK cells. The expression of B7-H6 in esophageal squamous cell carcinoma and the clinical significance is unknown. The goal of this study was to determine the expression of B7-H6 in esophageal squamous cell carcinoma and the clinical significance of B7-H6 expression. Patients and methods We retrospectively collected clinical data from 145 patients diagnosed with esophageal squamous cell carcinoma between January 2007 and December 2008. These patients had all previously undergone surgical treatment for esophageal cancer, were clearly diagnosed, and had not received chemotherapy or radiotherapy. In addition, pathological tissue samples from the 145 patients were collected to detect the expression of B7-H6 by immunohistochemistry. The chi-square (χ2) test was used to analyse the relationships between B7-H6 and clinicopathological characteristics. The prognosis of the patients were analysed by Cox proportional hazards regression analysis and Kaplan-Meier analysis. Results B7-H6 was present in 133/145 (91.72%) of the esophageal squamous cell carcinoma samples and all localized in the cytoplasm. The expression level of B7-H6 was correlated with T stage (P=0.036) and lymphatic metastasis status (P=0.044). According to the results of the ROC curve analysis, H-score =90 was selected as the cut-off value. The 145 patients were divided into two groups, the high B7-H6 expression (H-score>90) group and the low B7-H6 expression (H-score≤90) group. Cox proportional hazards regression analysis indicated that tumour size (P=0.021), B7-H6 expression (P=0.025) and lymphatic metastasis status (P=0.049) were independent prognostic factors for esophageal squamous cell carcinoma. Kaplan-Meier analysis with the log-rank test demonstrated that the patients with high B7-H6 expression (P = 0.003), lymphatic metastasis (P <0.001) or a tumour size ≥ 3.0 cm (P = 0.001) had significantly worse survival than those with low B7-H6 expression, no lymphatic metastasis or a tumour size < 3.0 cm respectively. Conclusion B7-H6 is widely expressed in esophageal squamous cell carcinoma and high expression of B7-H6 can be used as a predictor of poor prognosis.

Effect of HPV Status on Survival of Oropharynx Cancer with Distant Metastasis

2020 ◽  
Vol 163 (2) ◽  
pp. 372-374 ◽  
Author(s):  
Adam W. Kaplon ◽  
Thomas J. Galloway ◽  
Mihir K. Bhayani ◽  
Jeffrey C. Liu
Keyword(s):  
Distant Metastasis ◽  
Survival Data ◽  
Regression Models ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
National Cancer Database ◽  
Proportional Hazards Regression ◽  
Kaplan Meier ◽  
Hpv Status ◽  
Oropharynx Squamous Cell Carcinoma

Human papillomavirus (HPV)–positive oropharynx squamous cell carcinoma (OPSCC) is known to have improved survival over HPV-negative disease. However, it is largely unknown whether HPV status similarly affects survival in patients presenting with distant metastatic disease. We queried the National Cancer Database for OPSCC with distant metastasis. Kaplan-Meier curves and Cox proportional hazards regression models controlling for relevant demographics were used to evaluate overall survival. In total, 768 OPSCC cases were available for analysis with HPV and survival data: 50% of cases were HPV negative and 50% were HPV positive. The 1- and 2-year survival for HPV-negative disease was 49% and 27%, respectively, as compared with 67% and 42% in the HPV-positive cohort. HPV positivity was associated with improved median survival in treated and untreated patients. Age, comorbidities, and HPV status were predictive of improved survival on multivariate analysis. HPV-positive OPSCC has improved survival in the setting of distant metastatic presentation as compared with HPV-negative disease and shows greater responsiveness to treatment.

scholarly journals Disparity in outcomes of melanoma adjuvant immunotherapy by demographic profile

2020 ◽  
Vol 7 (2) ◽  
pp. MMT43
Author(s):  
Alexandra Ikeguchi ◽  
Michael Machiorlatti ◽  
Sara K Vesely
Keyword(s):  
Survival Benefit ◽  
Proportional Hazards ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Demographic Factors ◽  
Cox Proportional Hazards ◽  
Adjuvant Immunotherapy ◽  
Node Positive ◽  
Melanoma Patients ◽  
The Impact

Background: Randomized comparisons have demonstrated survival benefit of adjuvant immunotherapy in node-positive melanoma patients but have limited power to determine if this benefit persists across various demographic factors. Materials & methods: We assessed the impact of demographic factors on the survival benefit of adjuvant immunotherapy in a database of 38,189 node-positive melanoma patients using the Kaplan–Meier method and Cox proportional hazards models. Results: All assessed demographic factors other than race significantly impacted survival of node-positive melanoma patients in univariate analysis. In multivariable analysis, only the age group interacted with immunotherapy. Conclusion: Analysis of this large database of unselected node-positive melanoma patients demonstrated a positive survival benefit of immunotherapy across all demographic factors assessed and the impact was greater for patients 65 years of age and older.

Prognostic relevance of neutrophil to lymphocyte ratio (NLR) before anti-PD1 therapy in metastatic melanoma patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21045-e21045
Author(s):  
Daniel Vilarim Araujo ◽  
Rafael Vanin de Moraes ◽  
Victor Aurelio Ramos Sousa ◽  
Mauro Daniel Spina Donadio ◽  
Aline Fusco Fares ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Metastatic Melanoma ◽  
Proportional Hazards ◽  
Checkpoint Inhibitors ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Continuous Variable ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Melanoma Patients

e21045 Background: Biomarkers to select the patients most likely to benefit from checkpoint inhibitors are urged. NLR is a simple way of measuring systemic inflammation and is an independent predictor of survival before Anti-CTLA4 therapy. We hypothesized if NLR is also a predictor of survival before Anti-PD1 therapy. Methods: We performed a retrospective review of the medical records of all consecutive metastatic melanoma patients who received Nivolumab treatment from January/2014 – February/2017, including 53 patients prospectively collected from an Expanded Access Program. Of 86 patients, 83 patients were included for demographic and efficacy analysis, and 74 had information about baseline pre-treatment NLR. We analyzed NLR as a continuous variable and categorised ≥ 5 vs. < 5. Kaplan-Meier method was used for survival analysis. Long-rank test compared categories and Cox proportional hazards regression model was used to assess the prognostic significance of baseline NLR in univariate and multivariable analysis. Results: Median PFS for the entire population was 6,407 months (3,28 – 9,52) and median OS was not reached (NR) with a median FU of 10,74 months. The median NLR ratio was 3,11 (0,87 – 19). 18 patients (24,3%) had a ≥ 5 NLR vs. 56 (75,7%) < 5. Median PFS for NLR ≥ 5 was: 2,3 (1,75 – 2,84) vs. 12,02 (5,11 – 18,93) for < 5 (HR = 3,11; IC95% 1,52 – 6,27; p = 0,001). Median OS ≥ 5: 3,05 (2,06 – 4,04) vs. NR for < 5 (HR = 5,88; IC95% 2,60 – 13,29; p = 0,001). NLR categorised remained statistically significant in multivariate analysis for PFS and NLR as a continuous variable remained statistically significant for both PFS and OS in multivariate analysis (Table 1). Conclusions: Baseline NLR is a rapid, simple, and cost-free predictor of survival before Anti-PD1 therapy. These results should be validated in a larger cohort of patients. [Table: see text]

scholarly journals Visual impairment and risk of dementia in two population-based prospective cohorts: UK Biobank and EPIC-Norfolk

2021 ◽  
Author(s):  
Thomas J Littlejohns ◽  
Shabina Hayat ◽  
Robert Luben ◽  
Carol Brayne ◽  
Megan Conroy ◽  
...  
Keyword(s):  
Visual Impairment ◽  
Proportional Hazards ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Uk Biobank ◽  
Cox Proportional Hazards Models ◽  
Hazard Ratios ◽  
Promising Target ◽  
Increased Risk

Abstract Visual impairment has emerged as a potential modifiable risk factor for dementia. However, there are a lack of large studies with objective measures of vison and with more than ten years of follow-up. We investigated whether visual impairment is associated with an increased risk of incident dementia in UK Biobank and EPIC-Norfolk. In both cohorts, visual acuity was measured using a “logarithm of the minimum angle of resolution” (LogMAR) chart and categorised as no (≤0.30 LogMAR), mild (&gt;0.3 - ≤0.50 LogMAR), and moderate to severe (&gt;0.50 LogMAR) impairment. Dementia was ascertained through linkage to electronic medical records. After restricting to those aged ≥60 years, without prevalent dementia and with eye measures available, the analytic samples consisted of 62,206 UK Biobank and 7,337 EPIC-Norfolk participants, respectively. In UK Biobank and EPIC-Norfolk. respectively, 1,113 and 517 participants developed dementia over 11 and 15 years of follow-up. Using multivariable cox proportional-hazards models, the hazard ratios for mild and moderate to severe visual impairment were 1.26 (95% Confidence Interval [CI] 0.92-1.72) and 2.16 (95% CI 1.37-3.40), in UK Biobank, and 1.05 (95% CI 0.72-1.53) and 1.93 (95% CI 1.05-3.56) in EPIC-Norfolk, compared to no visual impairment. When excluding participants censored within 5 years of follow-up or with prevalent poor or fair self-reported health, the direction of the associations remained similar for moderate impairment but were not statistically significant. Our findings suggest visual impairment might be a promising target for dementia prevention, however the possibility of reverse causation cannot be excluded.

scholarly journals Characteristics and Prognostic Factors of Patients With Osteosarcoma Older Than 60 Years From the SEER Database

2019 ◽  
Vol 26 (1) ◽  
pp. 107327481988889 ◽  
Author(s):  
Yue Pan ◽  
Daqi Chen ◽  
Taobo Hu ◽  
Guohua Lv ◽  
Zhehao Dai
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Distant Metastasis ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Disease Stage ◽  
Data Set ◽  
Primary Tumor Site ◽  
Histologic Subtype ◽  
Axial Location

Osteosarcoma is predominant in the adolescent and the elderly population, but few studies have described the characteristics and prognostic factors of patients older than 60 years. In this study, the Surveillance, Epidemiology, and End Results registry database was used to identify all patients diagnosed with primary osteosarcoma from 1973 to 2014. We utilized Cox proportional hazards regression analysis to evaluate the association between patient overall survival and relevant characteristics, including gender, race, disease stage, treatment methods, primary tumor site, differentiation grade, and histologic subtype. In the data set, a total of 1139 patients with osteosarcoma older than 60 years old were identified. The overall rate of distant metastatic cases was 28.6%. Osteosarcoma occurred equally in men and women (49.5% vs 50.5%). Of all, 41.3% of tumors were located in axial location (pelvis, spine, and ribs), 34.1% of tumors were located in extremity (long or short bones of the upper or lower extremity), and 24.6% in other location (mandible, skull, and other atypical locations). Male (hazard ratio [HR] = 1.201; 95% confidence interval [CI]: 1.056-1.366), axial location (HR = 1.342; 95% CI: 1.157-1.556), distant metastasis (HR = 2.369; 95% CI: 2.015-2.785), non-surgery perform (HR = 2.108; 95% CI: 1.814-2.451) were independent risk factors for 5-year overall survival. This study revealed distinct clinicopathological features of patients with osteosarcoma older than 60 years. Male gender, tumor in axial site, nonsurgery perform, and distant metastasis indicated worse prognosis survival. Performing surgery is still an effective and reliable treatment method for patients older than 60 years.

HER3-EGFR score to predict clinical outcomes in triple-negative breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11612-11612
Author(s):  
Angela Ogden ◽  
Shristi Bhattarai ◽  
Andrew R. Green ◽  
Mohammed A. Aleskandarany ◽  
Emad A. Rakha ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Distant Metastasis ◽  
Prognostic Value ◽  
Proportional Hazards ◽  
Distant Metastases ◽  
Cox Proportional Hazards ◽  
Erbb Family ◽  
Increased Risk ◽  
Canonical Pathways ◽  
The Individual

11612 Background: Limited preclinical evidence suggests that the ErbB family member HER3 may have prognostic value in TNBC. However, HER3 is a pseudokinase that cannot homodimerize, so in order to signal it must bind to other ErbB family members such as HER2 or EGFR. EGFR is frequently overexpressed in TNBC; consequently, it may be necessary to consider HER3 levels in the context of EGFR levels in TNBC to derive clinically meaningful insights. Methods: Towards this end, we tested the prognostic value of a combined immunohistochemical HER3-EGFR score (the sum of the individual H-scores, with the median used as a cutpoint) in a multi-institutional study of n = 510 TNBC patients using Cox proportional hazards regression. We also compared the HER3-EGFR-high and low groups in terms of 105 immunohistochemical biomarkers using Mann-Whitney U tests as well as Ingenuity canonical pathways using gene expression data from RNA-seq. Results: Among chemotherapy-treated TNBC patients, high HER3-EGFR score conferred a 2.30-fold increased risk of dying from breast cancer and a 1.78-fold increased risk of distant metastasis (p = 0.006 and p = 0.041, respectively) after adjusting for age and stage. Individual HER3 and EGFR H-scores were not associated with outcomes in simple or multivariable models. We also found that tumors from chemotherapy-treated TNBC patients with high HER3-EGFR scores exhibited higher immunohistochemical expression of luminal cytokeratins, DNA damage response proteins, and P-cadherin compared with tumors from chemotherapy-treated TNBC patients with low scores (q < 0.25). The top canonical pathway whose components were overexpressed in HER3-EGFR-high TNBCs was Hepatic Fibrosis (p = 0.008), which is linked to distant metastasis, and the top upstream regulator was HNF4A (p = 0.012), a transcription factor for ERBB3 with isoforms that promote liver and gut tumorigenesis. Conclusions: Collectively, our study reveals that HER3-EGFR score may identify chemotherapy-treated TNBC patients at increased risk for distant metastases and death whose tumors may be characterized by fibrotic processes. Our immunohistochemical test thus identifies high-risk TNBCs who may benefit from agents that inhibit HER3-EGFR signaling.

Plasma proteomic analyses and treatment predictive biomarker candidates in melanoma patients receiving immune checkpoint blockade or targeted therapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9574-9574 ◽  
Author(s):  
Hanna Eriksson ◽  
Haris Babacic ◽  
Janne Lehtio ◽  
Maria Pernemalm
Keyword(s):  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Proportional Hazards ◽  
Checkpoint Inhibitors ◽  
Mapk Pathway ◽  
Predictive Biomarkers ◽  
Cox Proportional Hazards ◽  
Protein Levels ◽  
Treatment Type ◽  
Melanoma Patients

9574 Background: The introduction of immune checkpoint inhibitors (ICIs) or therapies targeting the MAPK-pathway (MAPKis) has significantly improved clinical outcomes in metastatic melanoma patients. Still, a large proportion of the patients become resistant to therapy and there is a need for treatment predictive biomarkers. The aim of this study was to analyze the treatment predictive biomarkers based on the plasma proteome of patients with metastatic melanoma treated with ICIs or MAPKis. Methods: We analyzed serial plasma samples from 48 patients with metastatic melanoma collected; 24 patients were treated with ICIs and with MAPKis, respcetively. A non-biased, high-resolution isoelectric focusing of peptides-liquid chromatography-mass spectrometry (HiRIEFLC-MS/MS)-based method, and with proximity ligation assays (PEA) targeting 92 immuno-oncology-related proteins were used.We analyzed the change in protein levels during treatment with a paired t-test, and their association with progression free survival (PFS) with Cox proportional hazards models. Results: HiRIEFLC-MS/MS detected 1,835 proteins.We detected statistically-significant log2-fold-changes in 109 protein levels out of 1,160 proteins tested (not corrected for multiple testing). PDCD-1 had the highest log2-fold change (FC = 1.27) after treatment (p = 0.02). After stratifying for treatment type, PDCD-1 levels increased in patients treated with ICIs (FC = 2.13, p= 0.0008), but not in MAPKis-treated patients. PEA analyses confirmed this observation. The PEA panel showed association between 44 proteins and shorter PFS (pcoefficient <0.05, pLRT<0.05, qLRT<0.05), among them: LGALS1, CSF1, VEGFA, CASP8, CCL2, TNFSF14, ANGPT2, IL10, IL6, and ADGRG1. Of these, increase in plasma levels during treatment of LGALS1, CCL2 and ADGRG1 were associated with longer PFS. HiRIEF LC-MS/MS detected 69 proteins associated with PFS (pcoefficient< 0.05, pLRT< 0.05, qLRT < 0.05). Conclusions: By using HiRIEFLC-MS/MS, we could detect putative treatment predictive proteins in plasma from patients with metastatic melanoma treated with ICIs or MAPKis. Our findings require further validation.

scholarly journals Differentiated Thyroid Cancer in Navarra (Spain): Historic Cohort Results (1987–2003)

ISRN Oncology ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
María Pilar Salvador Egea ◽  
Ana Aranzazu Echegoyen Silanes ◽  
Eduardo Layana Echezuri ◽  
Emma Anda Apiñariz ◽  
Ana Puras Gil ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Differentiated Thyroid Cancer ◽  
Proportional Hazards ◽  
Statistical Significance ◽  
Tumour Size ◽  
Stage Iv ◽  
Follicular Carcinoma ◽  
Risk Groups ◽  
Cox Proportional Hazards ◽  
Node Metastases

Introduction. Navarra has the highest incidence of differentiated thyroid cancer in Spain. The aim of this study was to review its management carried out by the Navarra's multidisciplinary Thyroid Disease Unit, from 1987 to 2003. Material and Methods. 325 patients were studied to find the incidence, prevalence, and prognostic factors. Statistical analysis comprised univariate and multivariate Cox proportional hazards regression models for survival and tumor recurrence. Results. The average annual incidence was 3.6 per 100,000 inhabitants, with a final prevalence of 82.4 per 100,000. Regarding survival and recurrence, statistical significance was observed for stage IV, follicular carcinoma, capsular and prethyroid muscles invasion, and T4 group. Only survival was related to tumour size larger than 40 mm. Only recurrence was related to lymph node metastases and radioiodine dose higher than 100 mCi. Conclusions. Attendance of patients in a functional unit setting has allowed us to classify them into three risk groups.

scholarly journals Lactate Dehydrogenase Prior to Transarterial Hepatic Chemoperfusion Predicts Survival and Time to Progression in Patients with Uveal Melanoma Liver Metastases

2020 ◽  
Author(s):  
Johannes Ludwig ◽  
Johannes Haubold ◽  
Till-Alexander Heusner ◽  
Sebastian Bauer ◽  
Jens T. Siveke ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Liver Metastases ◽  
Uveal Melanoma ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Serum Lactate Dehydrogenase ◽  
Gamma Glutamyl Transferase ◽  
Glutamyl Transferase

Purpose To assess serum lactate dehydrogenase (LDH) as a pretreatment prognostic factor in patients with uveal melanoma liver metastases treated with transarterial hepatic chemoperfusion (THC). Materials and Methods 56 patients (48 % male, median age: 63.5 years) underwent a median of 4 THC sessions. Kaplan-Meier for median overall survival (OS) and time to hepatic progression (TTP; 95 %CI) in months and Cox proportional hazards model for uni- (UVA) & multivariate analyses (MVA) for hazard ratio (HR) evaluation were calculated. Results The median OS was 9.4 months. The pretreatment LDH value before 1st THC was the strongest OS predictor with 19.8 months for normal (≦ 280 units per liter (U/L)), 9.7 for intermediate (> 280–< 1000 U/L), and 3.84 months for high (≧ 1000 U/L) LDH. LDH significantly predicted a median TTP with 8 months, 4 months, and 1 month for normal, intermediate, and high LDH, respectively. UVA revealed intermediate (16.5) and high (77.3) LDH, bilirubin > the upper limit of normal (ULN) (2.89), alkaline phosphatase > 1.5 ULN (6.8), leukocytes > ULN (4.2), gamma-glutamyl transferase (GGT) > ULN (7), extrahepatic metastases (1.8) and liver lesions ≥ 5 cm (3.6) as significant predictors for worse OS. MVA confirmed intermediate (5) and high (27.1) LDH, bilirubin (5.7), GGT (2.9), and tumor size ≥ 5 cm (3.7) as significant independent predictors for worse OS. Patients with decreasing vs. increasing LDH > 10 % between 1st and 2nd THC (median: 38 days) survived longer (14.6 vs. 4.3 months) and progressed later (7 months vs. 1 month). Conclusion Elevated pretreatment serum LDH is an essential and robust OS and TTP predictor, potentially allowing for the identification of patients benefiting most from transarterial hepatic chemoperfusion. Key Points: Citation Format

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