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.

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 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.

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.

scholarly journals Prognostic Parameters of Metastatic Adrenocortical Carcinoma

2007 ◽  
Vol 92 (1) ◽  
pp. 148-154 ◽  
Author(s):  
Guillaume Assié ◽  
Guillemette Antoni ◽  
Frédérique Tissier ◽  
Bernard Caillou ◽  
Gwenaelle Abiven ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Adrenocortical Carcinoma ◽  
Validation Cohort ◽  
Univariate Analysis ◽  
Mitotic Rate ◽  
Prognostic Parameters ◽  
High Power Field ◽  
Primary Tumors ◽  
Kaplan Meier ◽  
Two Parameters

Abstract Context: Prognostic parameters of metastatic adrenocortical carcinoma (ACC) are poorly characterized. Objective: The objective of the study was to describe the clinical presentation of metastatic ACC and determine prognostic factors for survival. Design: This was a retrospective cohort study (1988–2004). Setting: The study was conducted in an institutional practice. Patients: Participants included 124 consecutive patients with metastatic ACC, 70 from Gustave-Roussy Institute (main cohort) and 54 patients from the Cochin Hospital (validation cohort). Clinical data concerning all patients, histopathologic slides of primary tumors (44 in the main cohort and 40 in the validation cohort), and molecular biology data on 15 primary tumors (main cohort) were analyzed. Intervention: There was no intervention. Main Outcome: The main outcome was the specific survival after discovery of the first metastasis (Kaplan-Meier method). This included univariate analysis on the main cohort, confirmed on the validation cohort and then analyzed in a multivariate analysis. Results: In the main cohort, overall median survival was 20 months. In univariate analysis, the presence of hepatic and bone metastases, the number of metastatic lesions and the number of tumoral organs at the time of the first metastasis, a high mitotic rate (&gt;20 per 50 high-power field), and atypical mitoses in the primary tumor predicted survival (P = 0.05, 0.003, 0.046, 0.001, 0.01, and &lt; 0.001, respectively). The number of tumoral organs and a high mitotic rate were confirmed on the validation cohort (P = 0.009 and 0.03, respectively). These two parameters were confirmed in multivariate analysis (P = 0.0058 and 0.049). Conclusion: Metastatic ACC is a heterogeneous disease with poor outcome. The combination of the number of tumoral organs at the time of the first metastasis and the mitotic rate can predict different outcomes.

Gestational Age as a Predictor of Pregnancy Outcome After Repeat Cerclage

2021 ◽  
Author(s):  
Benshuo Cai ◽  
Xinni Na
Keyword(s):  
Survival Rate ◽  
Pregnancy Outcome ◽  
Gestational Age ◽  
Roc Curve ◽  
Univariate Analysis ◽  
Area Under The Curve ◽  
Roc Curve Analysis ◽  
Kaplan Meier ◽  
Significant Difference ◽  
The Mean

Abstract Background: The role of repeat cerclage (RC) as a remedy for patients with prolapsed membranes after prior cerclage remains controversial. We aimed to investigate whether gestational age (GA) could be used as a valuable factor for predicting pregnancy outcome following RC in women with prolapsed membranes after prior cerclage. Methods: We retrospectively investigated the clinical data of 29 patients who underwent RC resulting from prolapsed membrane after prior cerclage. Receiving operating characteristic (ROC) curve analysis and univariate analysis were performed to determine predictive factors. Patients were divided into two groups according to GA at RC, GA<24.2 weeks and GA≥24.2 weeks. Pregnancy outcomes were compared between groups.Results: The mean GA at prior cerclage was 16.5 weeks; mean GA at RC was 23.6 weeks. The mean GA at delivery was 27.8 weeks with a 69.0% neonatal survival rate. ROC curve and univariate analysis demonstrated that GA at RC was significantly predictive for neonatal survival (area under the curve: 0.928; p=0.000). Using a GA cut-off of ≥24.2 weeks at RC, the sensitivity and specificity of predicting neonatal survival were 93.75% and 61.54%, respectively. There was a significant difference in neonatal survival rate between the GA <24.2 weeks group and GA ≥24.2 weeks group (38.5% vs. 93.8%, p=0.003). Kaplan–Meier survival curves showed a lower incidence of neonatal death in the GA ≥24.2 weeks group (6.3%) compared with GA <24.2 weeks group (61.5%, p=0.023).Conclusions: GA could be a valuable factor for predicting pregnancy outcome post-RC in women with prolapsed membrane after prior cerclage.

scholarly journals RADI-37. CLINICAL RISK FACTORS FOR INTRACRANIAL HEMORRHAGE OF SOLID MELANOMA BRAIN METASTASES AFTER RADIOSURGERY

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i29-i29
Author(s):  
Catherine Okoukoni ◽  
Michael LeCompte ◽  
Ryan Hughes ◽  
Emory McTyre ◽  
Christina Cramer ◽  
...  
Keyword(s):  
Risk Factors ◽  
Brain Metastases ◽  
Intracranial Hemorrhage ◽  
Imaging Data ◽  
Free Survival ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Melanoma Brain Metastases ◽  
Impact Risk

Abstract PURPOSE: Melanoma brain metastases (MBM) are among the most common solid tumors associated with intracranial hemorrhage (ICH). Our objective is to investigate risk factors for post-radiosurgery intracranial hemorrhage (PRH). METHODS: We collected demographic, clinical, treatment, toxicity, survival, and imaging data for patients with solid MBM who underwent SRS between 2000 and 2016 at our institution. Bleed free survival (BFS) and overall survival (OS) analyses were performed using Kaplan–Meier methods. Logistic regression was used to identify PRH risk factors. RESULTS: From 2000 to 2016, 107 patients with a total of 548 solid MBM received SRS. Median patient age at time of SRS was 63.2 years. Median MBM volume was 2.8 cm3 (range 0.01–21.3 cm3). MBM were in the cortex (n = 431), cerebellum (n= 85), basal ganglia (n= 23), and brain stem (n= 9). MBM were treated to a median dose of 20 Gy (range 14–20 Gy). Seventeen patients received immunotherapy (IT) within 1 year of SRS, 7 patients received concurrent immunotherapy (XR-IT). Median follow-up and OS was 13.5 months and 10.8 months, respectively. Median BFS was 8.3 months. PRH occurred in 123 MBM (22%). MBM volume (p= 0.0001), total MBM volume (p= 0.0006), IT (p= 0.04), and XR-IT (p= 0.03) were associated with increased PRH. PRH cumulative incidence within 24 mo of SRS was increased in MBM &gt; 2.8 cm3 compared with patients with smaller MBM: 27.5% verse 5.3%, respectively. Age, sex, hypertension, MBM location, total MBM number, and marginal dose (p &gt; 0.05) did not significantly impact risk of PRH. No significant difference in 6, 12, or 24 mo actuarial OS rates were observed in patients with PRH (p &gt; 0.05). CONCLUSIONS: Patients with larger MBM volume and IT within 1 year of SRS have the greatest risk of PRH. PRH did not significantly impact OS in this study.

scholarly journals The prognosis of hepatoid adenocarcinoma of the stomach: a propensity score-based analysis

2020 ◽  
Author(s):  
Kai Zhou ◽  
Anqiang Wang ◽  
Sheng Ao ◽  
Jiahui Chen ◽  
Ke Ji ◽  
...  
Keyword(s):  
Propensity Score ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Survival Rates ◽  
Hepatoid Adenocarcinoma ◽  
Chi Square ◽  
Clinical Indicators ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Propensity Matching

Abstract Background To investigate whether there is a distinct difference in prognosis between hepatoid adenocarcinoma of the stomach (HAS) and non-hepatoid adenocarcinoma of the stomach (non-HAS) and whether HAS can benefit from radical surgery. Methods We retrospectively reviewed 722 patients with non-HAS and 75 patients with HAS who underwent radical gastrectomy between 3 November 2009 and 17 December 2018. Propensity score matching (PSM) analysis was used to eliminate the bias among the patients in our study. First, univariate analysis, including the chi-square and Mann-Whitney U tests, was used to investigate the relationship between all included clinical indicators and dependent variables, and some clinical indicators that might be meaningless were excluded. Then, clinical indicators with statistical and clinical significance were included in the logistic regression analysis to obtain more reliable results. The relationships between gastric cancer types and overall survival (OS) were evaluated by the Kaplan-Meier method and Cox regression models. Results Our data demonstrate that there is no statistically significant difference in the OS between HAS and non-HAS {K-M, P=log rank (Mantel-Cox), (before PSM P=0.490); (1:1 PSM P=0.345); (1:2 PSM P=0.195)}. Moreover, there were no significant differences in the 1-, 2-, or 3-year survival rates between patients with non-HAS and patients with HAS (before propensity matching, after 1:1 propensity matching, and after 1:2 propensity matching). Conclusion HAS is generally considered to be an aggressive gastric neoplasm, but its prognosis may not be as unsatisfactory as previously believed.

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

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