scholarly journals Validation of Androgen Receptor loss as a risk factor for the development of brain metastases from ovarian cancers

2020 ◽  
Author(s):  
Gloria Mittica ◽  
Margherita Goia ◽  
Angela Gambino ◽  
Giulia Scotto ◽  
Mattia Fonte ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Brain Metastases ◽  
Validation Cohort ◽  
Univariate Analysis ◽  
Early Assessment ◽  
Small Series ◽  
Combining Data ◽  
Significant Difference ◽  
Predictive Role ◽  
Independent Cohort

Abstract Background Central nervous system (CNS) spreading from epithelial ovarian carcinoma (EOC) is an uncommon but increasing phenomenon. We previously reported in a small series of 11 patients a correlation between Androgen Receptor (AR) loss and localization to CNS. Aims of this study were: to confirm a predictive role of AR loss in an independent validation cohort; to evaluate if AR status impacts on EOC survival. Results We collected an additional 29 cases and 19 controls as validation cohort. In this independent cohort at univariate analysis, cases exhibited lower expression of AR, considered both as continuous (p<0.001) and as discrete variable (10% cut-off: p<0.003; Immunoreactive score: p<0.001). AR negative EOC showed an odds ratio (OR) = 8.33 for CNS dissemination compared with AR positive EOC. Kaplan-Meier curves of the combined dataset, combining data of new validation cohort with the previously published cohort, showed that AR<10% significantly correlates with worse outcomes (p=0.005 for Progression Free Survival (PFS) and p=0.002 for brain PFS (bPFS) respectively). Comparison of AR expression between primary tissue and paired brain metastases in the combined dataset did not show any statistically significant difference. Conclusions We confirmed AR loss as predictive role for CNS involvement from EOC in an independent cohort of cases and controls. Early assessment of AR status could improve clinical management and patients’ prognosis.

scholarly journals Validation of Androgen Receptor loss as a risk factor for the development of brain metastases from ovarian cancers

2020 ◽  
Author(s):  
Gloria Mittica ◽  
Margherita Goia ◽  
Angela Gambino ◽  
Giulia Scotto ◽  
Mattia Fonte ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Brain Metastases ◽  
Validation Cohort ◽  
Univariate Analysis ◽  
Early Assessment ◽  
Kaplan Meier ◽  
Small Series ◽  
Significant Difference ◽  
Predictive Role ◽  
Independent Cohort

Abstract Background Central nervous system (CNS) spreading from epithelial ovarian carcinoma (EOC) is an uncommon but increasing phenomenon. We previously reported in a small series of 11 patients a correlation between Androgen Receptor (AR) loss and localization to CNS. Aims of this study were: to confirm predictive role of AR loss in an independent validation cohort; to evaluate if AR status impacts on EOC survival. Results We collected other 29 cases and 19 controls as validation cohort. In this independent cohort at univariate analysis, cases exhibited lower expression of AR, considered both as continuous ( p <0.001) and as discrete variable (10% cut-off: p <0.003; Immunoreactive score: p <0.001). AR negative EOC showed an odds ratio (OR) = 8.33 for CNS dissemination compared with AR positive EOC. Kaplan-Meier curves of the whole dataset showed that AR<10% significantly correlates with worse outcomes (p=0.005 for PFS and p=0.002 for brain PFS (bPFS) respectively). Comparison of AR expression between primary tissue and paired brain metastases in the whole dataset did not show any statistically significant difference. Conclusions AR’s deficiency confirms its predictive role for CNS involvement from EOC in an independent cohort of cases and controls. Early assessment of AR status could improve clinical management and patients’ prognosis.

Gene predictors for extrathoracic metastases (EM) in advanced bronchioloalveolar carcinoma (BAC) of the lung obtained from formalin-fixed, paraffin-embedded tissue (FFPE)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7622-7622
Author(s):  
G. J. Weiss ◽  
W. A. Franklin ◽  
C. Zeng ◽  
Z. V. Tran ◽  
C. D. Coldren ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Gene Profiling ◽  
Smoking History ◽  
Bronchioloalveolar Carcinoma ◽  
Clinical Factors ◽  
Benign Tissue ◽  
Small Series ◽  
Significant Difference

7622 Background: Advanced BAC is typically a more indolent tumor confined to the lungs, thus raising the question of the role for bilateral lung transplantation (BLT). In a small series, BLT produced a 5-year survival rate of 50%. Determining biological predictors of EM could identify the most ideal candidates for curative BLT. Methods: We retrospectively reviewed patient records from 1/1/98–10/1/06. RNA was extracted from FFPE tissue. RNA was amplified using Arcturus kits and profiled by Affymetrix X3P chips, which contain 47,000 transcripts and 61,000 probe sets. Chi-square and t-tests were used to compare clinical characteristics. Log-rank and Cox hazards modeling were used to determine clinical factors that predict either overall survival or time to EM. Logistic regression modeling was used to examine clinical factors predicting rate of EM. Hybridization signals and detection calls were generated in BioConductor, using gcrma and affy tools, and normalized to benign tissue. Univariate analysis was performed to identify genes of interest. Results: Patients with advanced BAC/adenocarcinoma with BAC features at diagnosis, (TanyNanyM1 [lung only]; n=20), and matched cohort of locally-advanced adenocarcinoma (TanyN2–3M0) and pure adenocarinoma with pulmonary metastases only, (TanyNanyM1 [lung only]), were identified (n=45). There was no significant difference for age, gender, smoking history, survival, or EM between the 2 groups. Arrays have been performed on 12 samples (4 BAC, 5 lung adenocarcinoma, 2 benign lung, and 1 benign lymph node). Preliminary analysis shows 27 genes were significantly up- and down-regulated vs. benign tissue (p<0.01). Seven of these genes were highly altered and may differentiate risk for EM. Conclusions: Gene expression profiling may discern risk for EM not readily apparent from clinical characteristics and could serve to identify advanced BAC patients with low risk for EM that may benefit from BLT. Gene profiling of 12 additional tumor samples is ongoing and results will be updated. We plan future validation of candidate genes in collaboration with cooperative groups or other multi-center sites. Supported by a grant from Cancer League of Colorado. No significant financial relationships to disclose.

Influence of genetic variants of genes potentially associated with colorectal brain metastases on overall survival.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 487-487
Author(s):  
Stefan Stremitzer ◽  
Anna Sophie Berghoff ◽  
Nico Benjamin Volz ◽  
Wu Zhang ◽  
Dongyun Yang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Genetic Variants ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Univariate Analysis ◽  
Nucleotide Polymorphisms ◽  
Primary Tumor Site ◽  
Prognostic Effect ◽  
Significant Difference

487 Background: Brain metastases (BM) in colorectal cancer (CRC) are rare, developing in only 0.3-9% of the patients, and considered a late-stage manifestation of the disease. The aim of this study was to investigate whether genetic variants of genes involved in BM-related pathways, such as integrin, invasion- and adhesion-mediating, angiogenic and tumor suppressing pathways, are associated with outcome. Methods: Genomic DNA was extracted from formalin-fixed paraffin embedded resected BM from 70 patients with histologically proven CRC. Single nucleotide polymorphisms (SNP) in seven genes (CXCR4, MMP9, ST6GALNAC5, ITGAV, ITGB1, ITGB3, KLF4) were analyzed by direct Sanger DNA sequencing and evaluated for association with overall survival (OS) from resection of BM. Only SNPs with an allele frequency of ≥ 10% were analyzed. Results: In univariate analysis, rs17577 (MMP9) and rs4642 (ITGB3) showed a significant difference in OS [(G/G 7.4 months, G/A 5.1 months; HR (95% CI) 1.83 (0.95-3.53), p = 0.0440) and (A/A 9.4 months, A/G 4.8 months, G/G 4.3 months; HR (95% CI) 0.81 (0.44-1.49) and 2.14 (0.98-4.67), p = 0.0354), respectively]. In multivariate analysis adjusted for baseline characteristics [primary tumor site (right colon, left colon, rectal), chemotherapy before BM (yes/no), BM location (supratentorial, infratentorial, both), Karnofsky performance status (<80, 80-100)], rs2236599 (KLF4), and rs10171481 (ITGAV) are significant in OS [(G/G 7.4 months, G/A or A/A 4.8 months; HR (95% CI) 3.19 (1.55-6.53), p = 0.0016) and (A/A 5.7 months, A/G 4.4 months, G/G 15.5 months; HR (95% CI) 0.61 (0.29-1.29) and 0.25 (0.10-0.60), p = 0.0082), respectively]. Conclusions: This study suggests for the first time a prognostic effect of the SNPs involved in the BM pathway. Further analyses are needed to confirm these findings.

Outcomes after radiation therapy for brain metastases from gastrointestinal primaries.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 647-647
Author(s):  
Keith Robert Unger ◽  
Brian Timothy Collins ◽  
John Marshall ◽  
Michael J. Pishvaian ◽  
Ruth He ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Brain Metastases ◽  
Disease Control ◽  
Disease Progression ◽  
Systemic Therapy ◽  
Univariate Analysis ◽  
Intracranial Disease ◽  
Small Series ◽  
Gi Cancers ◽  
The Brain

647 Background: There is limited data regarding outcomes of patients with colorectal cancer (CRC) and other gastrointestinal (GI) cancers metastatic to the brain. The aim of this study is assess intracranial disease control in GI patients treated with radiation therapy (RT) and the likelihood of receiving systemic therapy following the diagnosis of metastatic disease to the brain. Methods: From 1/2007 to 6/2013, 24 consecutive patients with adenocarcinoma of a GI primary were treated with RT for brain metastases. Patients were excluded if they had prior RT to the brain. The majority of patients had CRC (n = 15). Ten patients had resection of at least one brain tumor prior to radiation therapy. Patients were treated with the following RT modalities: stereotactic radiosurgery alone (n = 12), whole brain RT (n = 7), both (n = 1), and partial brain RT (n = 1). Survival and control rates were analyzed by the Kaplan-Meier method. Results: Twenty-one patients had died at the time of analysis and the median overall survival was 5.4 months (range, 0.5 – 58 months). Radiographic follow up was available in 20 patients and 60% (12/20) had intracranial disease progression. The 6- and 12-month control rates for the treated tumors were 60% and 30%, respectively. Seven patients received salvage radiation therapy following intracranial disease progression. Fifty-eight percent (14/24) did not receive further systemic therapy. On univariate analysis, only prior surgical resection predicted for improved survival (3.8 vs. 7.8 months, p = 0.018), while number of lesions, performance status, primary site, chemotherapy after RT, and RT modality were not significant. Conclusions: Survival and intracranial disease control following RT for brain metastasis from GI cancers are poor and many patients do not receive further systemic therapy. In this small series, outcomes are worse than published series for other disease sites metastatic to the brain and further research is warranted.

Brain metastasis in a series of NSCLC: Egyptian experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18001-e18001
Author(s):  
Salah Eldeen Elmesidy ◽  
Mahmoud Abdelsalam ◽  
Husam Zawam
Keyword(s):  
Lung Cancer ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Cancer Patients ◽  
Univariate Analysis ◽  
Developing Brain ◽  
Smoking History ◽  
Lung Cancer Patients ◽  
Significant Difference

e18001 Background: Incidence of cerebral metastasis is increasing among lung cancer patients. Many factors have been reported associated with increase risk of brain metastasis. The aim of this retrospective analysis is to investigate the predictive factors for the development of brain metastasis in lung cancer patients. Methods: We retrospectively analyzed histologically proven lung cancer patients radiologically diagnosed of having brain metastases who presented to Kasr Al-Eini Center for Oncology (NEMROCK) in the period from 2004 till 2010, with follow up period of 6 months at least. The following factors were analyzed: age, gender, PS, smoking history, tumor size & grade preceding development of brain metastasis. Results: Our study included 403 patients. 67 patients (16.6%) experienced brain metastasis during the course of their disease. 40 (10%) patients had brain metastasis among other sites of distant spread at first presentation which represent 88.9% of patients presented with metastatic disease. In a median follow-up of 17.1 months (6-77) the time to develop brain metastasis (TTBM) for the whole group was 5 months (range 2-22 months) (95% CI : 4.3-7.7). The most important factor affecting the TTBM was the use of chemotherapy before developing brain metastasis with a median TTBM of 5.9 months (95%CI : 3.2-6.8) among those who received chemotherapy compared to 2 months among the patients who didn't receive chemotherapy (P= <0.0001). The second factor was PS at time of initial diagnosis (P= 0.027). The median OS after brain metastasis was 6 months (95% CI : 4.26-7.74). On univariate analysis, PS and use of chemotherapy after developing brain metastases showed statistically significant difference affecting OS. Conclusions: We concluded that PS as well as use of chemotherapy are the 2 main factors associated with shorter time to develop brain metastasis. PS and use of chemotherapy after developing brain metastases showed longer OS after developing brain metastases. Keywords: NSCLC, Brain metastasis, Egypt

Venous tortuosity as a novel biomarker of rupture risk in arteriovenous malformations: ARI score

2021 ◽  
pp. neurintsurg-2021-018181
Author(s):  
Alejandra Mosteiro ◽  
Leire Pedrosa ◽  
Ramón Torne ◽  
Ana Rodríguez-Hernández ◽  
Sergi Amaro ◽  
...  
Keyword(s):  
Arteriovenous Malformations ◽  
Operating Characteristic ◽  
Validation Cohort ◽  
Predictive Accuracy ◽  
Univariate Analysis ◽  
Evaluation Tool ◽  
Simple Index ◽  
Risk Of Rupture ◽  
Brain Avms ◽  
Independent Cohort

BackgroundRisk of rupture in arteriovenous malformations (AVMs) varies considerably among series. Hemodynamic factors, especially within the venous side of the circuit, seem to be responsible but are not yet well defined. We analyzed tortuosity in the draining vein as a potential new marker of rupture in AVMs, and propose a simple index to predict AVM bleeding.MethodsA retrospective analysis of the venous angioarchitecture of brain AVMs was carried out at our center from 2013 to 2021, with special attention to venous tortuosity. After univariate analysis, the features of interest were combined to construct several predictive models using multivariate logistic regression. The best model proposed was the new AVM rupture index (ARI), which was then validated in an independent cohort.Results68 AVMs were included in the first step and 32 in the validation cohort. Venous tortuosity, expressed as at least one curve >180°, was a significant predictor of rupture (p=0.023). The proposed bleeding index consisted of: venous tortuosity (any curve of >180°), single draining vein, and paraventricular/infratentorial location. It seems to be a robust evaluation tool, with an area under the receiver operating characteristic (AUROC) curve of 0.806 (95% CI 0.714 to 0.899), consistently replicated in the independent sample (AUROC 0.759 (95% CI 0.607 to 0.911)), and with an inter-rater kappa coefficient of 0.81 .ConclusionsVenous tortuosity may serve as a predictor of bleeding in AVMs that warrants further investigation. This likely new marker was one of the three elements of the proposed ARI. ARI outperformed the predictive accuracy of previous scores, and remained consistent in an independent cohort.

Gamma knife radiosurgery for intracranial metastatic melanoma: a 6-year experience

2002 ◽  
Vol 97 ◽  
pp. 494-498 ◽  
Author(s):  
Jorge Gonzalez-martinez ◽  
Laura Hernandez ◽  
Lucia Zamorano ◽  
Andrew Sloan ◽  
Kenneth Levin ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Brain Metastases ◽  
Metastatic Melanoma ◽  
Gamma Knife Radiosurgery ◽  
Tumor Control ◽  
Karnofsky Performance Scale ◽  
Content Type ◽  
Significant Difference ◽  
The Mean ◽  
Fine Print

Object. The purpose of this study was to evaluate retrospectively the effectiveness of stereotactic radiosurgery for intracranial metastatic melanoma and to identify prognostic factors related to tumor control and survival that might be helpful in determining appropriate therapy. Methods. Twenty-four patients with intracranial metastases (115 lesions) metastatic from melanoma underwent radiosurgery. In 14 patients (58.3%) whole-brain radiotherapy (WBRT) was performed, and in 12 (50%) chemotherapy was conducted before radiosurgery. The median tumor volume was 4 cm3 (range 1–15 cm3). The mean dose was 16.4 Gy (range 13–20 Gy) prescribed to the 50% isodose at the tumor margin. All cases were categorized according to the Recursive Partitioning Analysis classification for brain metastases. Univariate and multivariate analyses of survival were performed to determine significant prognostic factors affecting survival. The mean survival was 5.5 months after radiosurgery. The analyses revealed no difference in terms of survival between patients who underwent WBRT or chemotherapy and those who did not. A significant difference (p < 0.05) in mean survival was observed between patients receiving immunotherapy or those with a Karnofsky Performance Scale (KPS) score of greater than 90. Conclusions. The treatment with systemic immunotherapy and a KPS score greater than 90 were factors associated with a better prognosis. Radiosurgery for melanoma-related brain metastases appears to be an effective treatment associated with few complications.

Gamma knife radiosurgery for renal cell carcinoma brain metastases

2002 ◽  
Vol 97 ◽  
pp. 489-493 ◽  
Author(s):  
Laura Hernandez ◽  
Lucia Zamorano ◽  
Andrew Sloan ◽  
James Fontanesi ◽  
Simon Lo ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Brain Metastases ◽  
Cell Carcinoma ◽  
Gamma Knife ◽  
Median Survival ◽  
Renal Cell ◽  
Univariate Analysis ◽  
Gamma Knife Radiosurgery ◽  
Content Type ◽  
Fine Print

Object. The purpose of this study was to clarify the effectiveness of gamma knife radiosurgery (GKS) in achieving a partial or complete remission of so-called radioresistant metastases from renal cell carcinoma (RCC) and to propose guidelines for optimal treatment Methods. During a 5-year period, 29 patients (19 male and 10 female) with 92 brain metastases from RCC underwent GKS. The median tumor volume was 4.7 cm3 (range 0.5–14.5 cm3). Fourteen patients (48%) also underwent whole-brain radiotherapy (WBRT) before GKS, and two patients (6.8%) after GKS. The mean GKS dose delivered to the 50% isodose at the tumor margin was 16.8 Gy (range 13–30 Gy). All cases were categorized according to the Recursive Partitioning Analysis (RPA) classification for brain metastases. Univariate analysis was performed to determine significant prognostic factors and survival. The overall median survival was 7 months after GKS treatment. Age, sex, Karnofsky Performance Scale score, and controlled primary disease were not predictors of survival. Combined WBRT/GKS resulted in median survival of 18, 8.5, and 5.3 months for RPA Classes I, II, and III, respectively, compared with the median survival 7.1, 4.2, and 2.3 months for patients treated with WBRT alone. Conclusions. These results suggest that WBRT combined with GKS may improve survival in patients with brain metastases from RCC. Furthermore, this improvement in survival was seen in all RPA classes.

scholarly journals Cohort study of the overall survival of patients with pancreatic cancer in a hospital of specialties of Quito-Ecuador in the period 2007–2017

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Andrés Moreno Roca ◽  
Luciana Armijos Acurio ◽  
Ruth Jimbo Sotomayor ◽  
Carlos Céspedes Rivadeneira ◽  
Carlos Rosero Reyes ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cohort Study ◽  
Survival Time ◽  
Univariate Analysis ◽  
Rank Test ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Icd 10 ◽  
The Difference ◽  
Clinical Records

Abstract Objectives Pancreatic cancers in most patients in Ecuador are diagnosed at an advanced stage of the disease, which is associated with lower survival. To determine the characteristics and global survival of pancreatic cancer patients in a social security hospital in Ecuador between 2007 and 2017. Methods A retrospective cohort study and a survival analysis were performed using all the available data in the electronic clinical records of patients with a diagnosis of pancreatic cancer in a Hospital of Specialties of Quito-Ecuador between 2007 and 2017. The included patients were those coded according to the ICD 10 between C25.0 and C25.9. Our univariate analysis calculated frequencies, measures of central tendency and dispersion. Through the Kaplan-Meier method we estimated the median time of survival and analyzed the difference in survival time among the different categories of our included variables. These differences were shown through the log rank test. Results A total of 357 patients diagnosed with pancreatic cancer between 2007 and 2017 were included in the study. More than two-thirds (69.9%) of the patients were diagnosed in late stages of the disease. The median survival time for all patients was of 4 months (P25: 2, P75: 8). Conclusions The statistically significant difference of survival time between types of treatment is the most relevant finding in this study, when comparing to all other types of treatments.

scholarly journals 387. Markers for Mortality in COVID-19 Patients with Atrial Fibrillation or Flutter

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S262-S262
Author(s):  
Kok Hoe Chan ◽  
Bhavik Patel ◽  
Iyad Farouji ◽  
Addi Suleiman ◽  
Jihad Slim
Keyword(s):  
Atrial Fibrillation ◽  
Logistic Regression ◽  
Cohort Study ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Prognostic Markers ◽  
Univariate Analysis ◽  
Laboratory Data ◽  
Significant Difference ◽  
New Onset

Abstract Background Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection can lead to many different cardiovascular complications, we were interested in studying prognostic markers in patients with atrial fibrillation/flutter (A. Fib/Flutter). Methods A retrospective cohort study of patients with confirmed COVID-19 and either with existing or new onset A. Fib/Flutter who were admitted to our hospital between March 15 and May 20, 2020. Demographic, outcome and laboratory data were extracted from the electronic medical record and compared between survivors and non-survivors. Univariate and multivariate logistic regression were employed to identify the prognostic markers associated with mortality in patients with A. Fib/Flutter Results The total number of confirmed COVID-19 patients during the study period was 350; 37 of them had existing or new onset A. Fib/Flutter. Twenty one (57%) expired, and 16 (43%) were discharged alive. The median age was 72 years old, ranged from 19 to 100 years old. Comorbidities were present in 33 (89%) patients, with hypertension (82%) being the most common, followed by diabetes (46%) and coronary artery disease (30%). New onset of atrial fibrillation was identified in 23 patients (70%), of whom 13 (57%) expired; 29 patients (78%) presented with atrial fibrillation with rapid ventricular response, and 2 patients (5%) with atrial flutter. Mechanical ventilation was required for 8 patients, of whom 6 expired. In univariate analysis, we found a significant difference in baseline ferritin (p=0.04), LDH (p=0.02), neutrophil-lymphocyte ratio (NLR) (p=0.05), neutrophil-monocyte ratio (NMR) (p=0.03) and platelet (p=0.015) between survivors and non-survivors. With multivariable logistic regression analysis, the only value that had an odds of survival was a low NLR (odds ratio 0.74; 95% confidence interval 0.53–0.93). Conclusion This retrospective cohort study of hospitalized patients with COVID-19 demonstrated an association of increase NLR as risk factors for death in COVID-19 patients with A. Fib/Flutter. A high NLR has been associated with increased incidence, severity and risk for stroke in atrial fibrillation patients but to our knowledge, we are first to demonstrate the utilization in mortality predictions in COVID-19 patients with A. Fib/Flutter. Disclosures Jihad Slim, MD, Abbvie (Speaker’s Bureau)Gilead (Speaker’s Bureau)Jansen (Speaker’s Bureau)Merck (Speaker’s Bureau)ViiV (Speaker’s Bureau)

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