Impact of circulating tumor cell (CTC) nucleus size on outcomes with abiraterone acetate (AA) therapy in men with metastatic castration-resistant prostate cancer (mCRPC).

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 253-253
Author(s):  
David Michael Gill ◽  
Neeraj Agarwal ◽  
Andrew W. Hahn ◽  
Eric Johnson ◽  
Austin Poole ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Proportional Hazards Model ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Significant Trend ◽  
Cox Proportional Hazards Model ◽  
Nuclear Size ◽  
Nucleus Size ◽  
Castration Resistant Prostate Cancer ◽  
The Impact

253 Background: CTC enumeration but not CTC morphology has been reported to predict outcomes to treatment in men with mCRPC. Recently Chen JF et. al (Cancer, 2015) showed an association with nuclear size and incidence of visceral disease in metastatic prostate cancer. In this study, we investigate the impact of CTC nucleus size on outcomes in men treated with AA for mCRPC. Methods: In a cohort of men with mCRPC treated with first-line AA, who had CTCs identified by CellSearch (CS) analysis prior to initiating treatment, we retrospectively quantified the nuclear size of CTCs by ImageJ/Fiji 1.46 software and correlated with progression free survival (PFS) on AA. We analyzed with univariate in addition to pre-specified multivariable analysis adjusted for Gleason score and baseline log PSA to assess independent predictive value of CTC nuclear size on PFS. Median PFS was calculated by Kaplan-Meier analysis and p-values were determined from Cox proportional hazards model. Results: 22 men treated with AA for mCRPC were included. Median nucleus size was 23.8 µm. Patients were divided in to 2 cohorts: small nuclear cohort (CTC nucleus size < 23.8 µm) vs large nuclear cohort (CTC nucleus size ≥23.8 µm). There was a non-significant trend towards worsened PFS (5.8 versus 6.8 months) in the larger nuclear size arm (Table). Conclusions: In this cohort of men with CRPC treated with AA, there is a non-significant trend towards decreased PFS associated with larger CTC nucleus size. Data are hypothesis generating and require further interrogation in a larger cohort. [Table: see text]

Association of very small nuclear circulating tumor cell (vsnCTC) with clinical outcomes in metastatic castration-resistant prostate cancer.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 168-168
Author(s):  
Jasmine Jiemei Wang ◽  
Pai-Chi Teng ◽  
Yu Jen Jan ◽  
Jie-Fu Chen ◽  
Galen Cook-Wiens ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Nuclear Size ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Pre Treatment

168 Background: Circulating tumor cells (CTCs) have arisen as contemporary noninvasive prognostic biomarkers for prostate cancer (PC). Previously, a subgroup of PC CTCs, with particularly small nuclei (<8.5 μm), were found to be correlated with the presence of visceral metastases. This subgroup was named very-small-nuclear CTCs (vsnCTCs). We proposed vsnCTCs as a putative biomarker of a lethal subtype in metastatic castration resistant PC (mCRPC). Methods: In this study, 76 patients with mCRPC were recruited for overall survival (OS) analysis. Of the 76 patients, 47 had available pre-treatment blood specimens prior to the initiation of androgen receptor signaling inhibitor (ARSI, e.g. abiraterone and enzalutamide) or taxane therapy. Using the NanoVelcro CTC Assay, CTCs were captured and subjected to immunofluorescence staining. CTCs were identified as DAPI+/CK+/CD45- with a round or oval nucleus. Additionally, CTC nuclear size was measured and defined as the square root of the product of the long axis and the short axis. Kaplan-Meier analysis and Cox proportional hazards model were conducted. Results: Patients with vsnCTC (i.e., vsnCTC+) had a significantly shortened OS compared with patients without vsnCTC (i.e., vsnCTC-). The median OS was 34 (vsnCTC+, n=49) vs. 149 (vsnCTC-, n=27) weeks (log-rank HR=2.6 with 95% CI 1.5 to 4.5, p=0.0006). Progression free survival (PFS) analysis was performed for the 47 patients with pre-treatment blood samples. The median PFS was 14 (vsnCTC+, n=29) vs. 26 (vsnCTC-, n=18) weeks (log-rank HR=2.2 with 95% CI 1.2 to 3.9, p=0.0069). We also found that the hazard ratio of overall survival increased significantly as the CTC nuclear size decreased using the p spline plot. Conclusions: Our study showed that nuclear size reduction has importance in CTCs in a fashion similar to its utility in tissue. This study points toward the importance of the vsnCTC in patients with mCRPC, as vsnCTC+ patients represented a group at risk for faster clinical progression who are at the highest risk for morality. We posit that the vsnCTC represents a new hallmark of an aggressive subtype of mCRPC. This has potential importance in optimizing therapeutic choices.

Impact of new systemic therapies on overall survival (OS) of patients (pts) with metastatic castration resistant prostate cancer (mCRPC) in a hospital-based registry.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 203-203
Author(s):  
Edoardo Francini ◽  
Kathryn P. Gray ◽  
Grace Shaw ◽  
Carolyn Evan ◽  
Anis Hamid ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Proportional Hazards Model ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards Model ◽  
Castration Resistant Prostate Cancer ◽  
New Therapies ◽  
Risk Of Death ◽  
Radium 223 ◽  
Ecog Ps

203 Background: From 2004 to 2009, mCRPC treatment options were limited to docetaxel (D), mitoxantrone, first generation anti-androgens (AA), estrogens, steroids, and ketoconazole, with only D showing OS benefit. Since 2010, five new therapies prolonged OS and were approved for mCRPC: sipuleucel-T, cabazitaxel, abiraterone acetate, enzalutamide, and radium 223. We sought to assess the aggregate impact of new therapies on OS. Methods: We used the DFCI CRIS database to identify cohorts of pts who developed mCRPC between 2004-2007 (cohort A) and 2010-2013 (cohort B). Therapies for mCRPC in each cohort were annotated. Given the median follow-up (FU) was 10.6 years (yrs) in cohort A and 4.6 yrs in cohort B, we evaluated OS, defined as time from mCRPC per PCWG3 criteria to death from all causes or last follow-up visit within 5 yrs (truncated OS). Kaplan-Meier method estimated the time to events distribution with median (95% CI). Cox proportional hazards model evaluated effects of treatment groups on disease outcomes with estimates of hazard ratio (95% CI). Results: Of the 583 pts identified, 317 (54%) were in cohort A and 266 (46%) in cohort B. Pts in cohort B had a significantly longer median OS (p<0.001), a 5-yr OS of 26% vs. 10%, and a 31% reduced risk of death compared to cohort A (HR=0.69; 95% CI, 0.57-0.83) (see Table). On multivariable analysis, adjusting for prior local Rx, ECOG PS, and the number of agents received, longer OS is confirmed associated with cohort B vs. A and also with ECOG PS status 0 vs. 1, number of agents received 5-12 vs. ≤3. Conclusions: Using the DFCI prostate cancer database, therapies approved for mCRPC since 2010 showed a modest impact on OS, with a median improvement of 6 months. There was a more substantial effect on long term survivors with 2.6 fold increase of 5-yr OS. [Table: see text]

Association of radiation therapy with overall survival in patients undergoing surgery for T3N0M0 adenocarcinoma of the rectum.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 528-528
Author(s):  
David Mitchell Marcus ◽  
Dana Nickleach ◽  
Bassel F. El-Rayes ◽  
Jerome Carl Landry
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Locally Advanced ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Entire Cohort ◽  
The Impact

528 Background: The standard treatment for locally advanced rectal cancer is neoadjuvant chemoradiation followed by surgery, but many physicians question the benefit of multimodality therapy in patients with stage T3N0M0 disease. We aimed to determine the impact of radiation therapy (RT) on overall survival (OS) in this group of patients. Methods: We used the Surveillance, Epidemiology, and End Results database to identify patients undergoing surgery for T3N0M0 adenocarcinoma of the rectum from 2004 to 2010. The Kaplan-Meier method was used to compare OS for patients receiving RT vs. no RT, along with for pre-op vs. post-op RT among patients that received RT. Multivariable analysis (MVA) using a Cox proportional hazards model was performed to assess the association of RT with OS after adjusting for patient age, gender, race, tumor grade, carcinoembryonic antigen, type of surgery, and circumferential margin status. The analysis was repeated separately on patients that underwent total colectomy (TC) vs. sphincter-sparing surgery. Results: The cohort included 8,679 patients, including 4,705 who received RT and 3,974 who did not. Median age was 66 years. Five year OS was 76.5% in patients who received RT, compared to 60.0% in patients who did not receive RT (p <0.001). Five year OS was 76.9% for patients receiving pre-op RT vs. 75.7% in patients receiving post-op RT (p = 0.247). In patients undergoing TC, five year OS was 74.7% for patients receiving RT, compared to 47.5% in patients not receiving RT (p <0.001). In patients undergoing sphincter-sparing surgery, five year OS was 77.7% in patients receiving RT, compared to 62.9% in patients not receiving RT (p <0.001). Use of RT was significantly associated with OS on MVA, both in the entire cohort (HR 0.70 [95% CI 0.60-0.81]; p<0.001) and in subsets of patients undergoing TC (HR 0.55 [95% CI 0.38-0.79]; p=0.001) and sphincter-sparing surgery (HR 0.70 [95% CI 0.59-0.84]; p<0.001). Conclusions: The use of RT is associated with superior OS in patients undergoing surgery for T3N0M0 adenocarcinoma of the rectum. This benefit is demonstrated in both the pre-op and post-op settings and applies to patients undergoing both TC and sphincter-sparing surgery.

Glucocorticoid receptor (GR) expression in circulating tumor cells (CTCs) to prognosticate overall survival (OS) for metastatic castration-resistant prostate cancer (mCRPC) patients (pts) treated with androgen receptor signaling inhibitors (ARSi).

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 194-194 ◽  
Author(s):  
David Wise ◽  
James Kelvin ◽  
Ryon Graf ◽  
Nicole A. Schreiber ◽  
Brigit McLaughlin ◽  
...  
Keyword(s):  
Protein Expression ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Predictive Biomarker ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Castration Resistant Prostate Cancer ◽  
Hazards Model ◽  
Kaplan Meier ◽  
The Impact

194 Background: Upregulation of GR protein expression in metastatic biopsies from pts with CRPC has previously been shown to correlate with resistance to enzalutamide and has been validated as a therapeutic target in pre-clinical studies. We sought to determine whether upregulated GR protein expression in CTCs from pts with progressing mCRPC predicted clinical outcomes following treatment with enzalutamide (E) or abiraterone (A). Methods: Pre-therapy blood samples from 54 pts with progressing mCRPC were subjected to CTC analysis using the Epic Sciences platform. Samples were examined to identify CK+ (CK+, CD45- cells, with intact nuclei, morph distinct) CTCs for GR protein expression. GR+ CTCs were defined as having expression greater than the 95th percentile of GR expression in the GR negative LNCAP cell line. Kaplan-Meier analysis was used to test the impact of GR+ CTCs on OS following treatment with A or E. A Cox proportional hazards model with CTC number and GR positivity was used in a multivariate analysis. Results: 37 out of 54 pts (69%) had detectable and viable CK+ CTCs. 28 out of 37 pts (76%) had CTCs with upregulated GR staining with a median of 6 GR+/CK+ cells/ml per patient (range 0.7 – 244 cells/ml). The OS of patients with GR+ CTCs treated with ARSi was significantly worse than that of patients without detectable GR+ CTCs (11.4 mo. vs NA, p < 0.01), an effect independent and additive to the presence of viable CTCs, a previously described prognostic biomarker (see Table). Conclusions: GR protein upregulation in CTCs can be detected in a significant percentage of pts with progressing mCRPC and the presence of GR+ CTCs predicts worse OS in response to ARSi. The data supports previously reported pre-clinical data proposing a pathogenic role for GR in mediating resistance to ARSi therapy. Detection of GR in patient CTCs may be a useful predictive biomarker to guide GR-directed therapies. [Table: see text]

Nuclear size of circulating tumor cells in advanced prostate cancer to reveal a potential biomarker for clinical outcomes and androgen receptor indifference.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 167-167
Author(s):  
Jasmine Jiemei Wang ◽  
Karen Angelica Cavassani ◽  
Pai-Chi Teng ◽  
Jie-Fu Chen ◽  
Yu Jen Jan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cell Lines ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Nuclear Size ◽  
Potential Biomarker

167 Background: Circulating tumor cells (CTCs) have arisen as contemporary noninvasive prognostic biomarkers for prostate cancer (PCa). Previously, a subgroup of PCa CTCs, with particularly small nuclei ( < 8.5 μm), were found to be correlated with the presence of visceral metastases. This subgroup was named very-small-nuclear CTCs (vsnCTCs). We hypothesized vsnCTCs as a putative biomarker of a lethal subtype associated with androgen receptor (AR) indifference and nuclear shape instability in metastatic castration resistant PCa (mCRPC). Methods: CTCs in blood from 76 patients with mCRPC were analyzed using NanoVelcro CTC assay for CTC nuclear size measurement and CTC RNA profiling of AR-indifferent pathways. Overall survival (OS) and progression free survival (PFS) of androgen receptor signaling inhibitor (ARSI), taxanes and other therapy were correlated with CTC nuclear size using Kaplan-Meier analysis and Cox proportional hazards model. Emerin fluorescence intensity and localization from patients with and without vsnCTC were compared. RNA profiles of CTCs were scored using Prostate Cancer Subtype (PCS) classification system. The CTC-PCS scores from patients with and without vsnCTC were compared using Mann-Whitney test. To investigate the underlying biology of vsnCTC phenotype, the nuclear size, the nuclear sizes of ARSI-resistant and lineage plasticity PCa cell lines were measured and correlated with the expression levels of RNA related to ARSI-indifferent pathways and nuclear envelope protein Emerin. Results: Patients with vsnCTC (i.e., vsnCTC+) had significantly shortened OS and PFS compared with patients without vsnCTC (i.e., vsnCTC-). The median OS was 34 (vsnCTC+, n = 49) vs. 149 (vsnCTC-, n = 27) weeks (HR = 2.6 with 95% CI 1.5 to 4.5, p < 0.001). The median PFS was 12 (vsnCTC+, n = 32) vs. 26 (vsnCTC-, n = 18) weeks (HR = 2.2 with 95% CI 1.3 to 4.0, p = 0.004). CTC nuclear sizes were significantly smaller in patients with prior ARSI therapy. CTC-RNA analysis revealed that vsnCTC+ patients had a significant higher CTC-PCS1 Z score(n = 19) compared with vsnCTC- patients(n = 26)(p = 0.01). In the cell line models, nuclear sizes were significantly smaller in cell lines with ARSI-resistance(p = 0.002) and lineage plasticity (p = 0.006). Emerin expression is significantly lower in vsnCTC+ patients(p = 0.009) and ARSI-resistant cell lines(p = 0.03). Conclusions: This study casts light on the importance of the vsnCTC in patients with mCRPC, as vsnCTC+ patients represented a group at risk for faster clinical progression who are at the highest risk for mortality. This has potential importance in optimizing therapeutic choices. We posit that the vsnCTC represents a new hallmark of an aggressive subtype of mCRPC and is related to the cellular mechanism of AR-indifference and Emerin dysregulation, which promotes lethal progression of metastatic PCa.

Real-world clinical adverse events (AEs) among nonmetastatic castration-resistant prostate cancer (nmCRPC) patients treated with novel anti-androgen (AA) therapies: A retrospective database study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18675-e18675
Author(s):  
Stephen J. Freedland ◽  
Sreevalsa Appukkuttan ◽  
Jianying Yao ◽  
Yuxian Du ◽  
Jacqueline Parkin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Median Time ◽  
Real World ◽  
Proportional Hazards Model ◽  
Incidence Rates ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Clinical Event ◽  
Adult Males ◽  
Castration Resistant Prostate Cancer

e18675 Background: Novel AA agents, such aspalutamide (Apa), enzalutamide (Enza) and darolutamide (Daro) are approved for the treatment of nmCRPC. In clinical trials, they were associated with AEs such as fatigue, fractures and falls. This study aimed to describe the real-world incidence of AEs among nmCRPC patients who initiated treatment with AA agents. Methods: Claims from Optum Clinformatics Data Mart, a large single-payer claims database were used to retrospectively identify adult males with prostate cancer (PC), evidence of castration, absence of metastases codes and >1 claim for AA therapies Apa and Enza (index date) from Jan 2017 through Dec 2019. Daro, a more recently approved AA, was not included due to lack of data. Incidence of central nervous system (CNS) (including but not limited to fatigue, falls and cognitive impairment) and any AE (fracture, rash, hypertension among others) were estimated and Kaplan-Meier analyses were used to quantify the median time from therapy initiation to clinical event occurrence. Multivariable Cox-proportional hazards model was used to identify clinical event predictors. A washout of previous AE events in the 1-year baseline was applied to identify true incident events. Results: A total of 605 patients (156 Apa and 449 Enza) were included in the study. The majority were ≥65 yrs (94.0%), white (56.0%), resided in the south (47.1%), and had Medicare insurance (86.4%). Almost all were medically castrated (99.0%) and mean Charlson Comorbidity Index (CCI) Score was 2.28. Incidence rates of all clinical events and CNS-related events were high (71.2% and 46.1%, respectively) with no major differences between Apa and Enza (Table). The median time from Apa or Enza treatment initiation to any clinical event was 71 and 64 days, respectively, and 282 and 209 days for CNS-related events, respectively. Significant predictors of having any events included age >75 yrs and high CCI score. Similar predictors were found for any CNS events. Conclusions: More than 70% of Apa and Enza treated nmCRPC patients had at least 1 clinical AE. Given the lack of a control cohort, further study is needed to assess whether these events are related to AAs or represent inherent risks of these events in the underlying population of largely older men with advanced PC. Future studies are warranted with all approved agents including Daro. [Table: see text]

Association of PI-RADS categories and PSA density with active surveillance progression in patients with prostate cancer.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 293-293
Author(s):  
Alex Z. Wang ◽  
Luke P. O'Connor ◽  
Nitin Yerram ◽  
Johnathan Zeng ◽  
Sherif Mehralivand ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Active Surveillance ◽  
Proportional Hazards Model ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Time Interval ◽  
Gleason Grade ◽  
Psa Density ◽  
Definitive Therapy

293 Background: Active surveillance (AS) is now considered a well-accepted alternative for low-favorable intermediate risk prostate cancer over definitive therapy. Few studies have incorporated the use of multi-parametric MRI (mpMRI) into the treatment paradigm. In this study we investigate imaging findings that are predictive of a patient dropping off AS. Methods: Our institutional database was queried for all patients who met criteria for active surveillance from 11/2003 to 5/2017. Criteria for inclusion included ≥ 2 mpMRIs, ≥ 2 prostate biopsies, and a diagnosis of Gleason Grade group (GG) 1 or higher. Patients were excluded if they received any other therapy for the treatment of their prostate cancer such as radiation, chemotherapy, focal therapy, or immunologic therapy. Patient demographics, mpMRI, biopsy and most recent follow-up data were recorded. Factors, including PSA density (PSAD), PSA, lesion size, and PI-RADS category, associated with AS progression were evaluated in Cox Proportional Hazards Model. Results: An analysis of a total of 212 patients were performed during the study time interval. 88 patients were dropped from AS during this time and of those patients the median amount of time before removal was 4.70 years (range, 0.7-10.5). On univariable analysis, PI-RADS category (HR, 1.302 for every increase in 1 unit of the PI-RADS category; 95% CI, 1.046-1.62, p = 0.01) and PSAD (HR, 4.98 for every increase in 0.001 ng/mL/cc; 95% CI, 2.127-11.66; p < 0.001) were found to be associated with being removed from AS. On multivariable analysis, both PI-RADS score (HR, 1.281 for every increase in 1 unit of the PI-RADS category; 95% CI, 1.025-1.6; p = 0.003) and PSAD (HR, 4.188 for every increase in 0.001 ng/mL/cc; 95% CI, 1.640-10.7; p < 0.001) remained associated with being removed from AS. Conclusions: PI-RADS categories and PSAD predict the risk of a patient to drop off active surveillance. AS. Patients with these criteria should be considered high risk in any current AS protocol.[Table: see text]

Effects of statin, aspirin, or metformin use on recurrence free and overall survival in patients with biliary tract cancer (BTC).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 303-303 ◽  
Author(s):  
Mairead Geraldine McNamara ◽  
Priya Aneja ◽  
Lisa W Le ◽  
Anne M Horgan ◽  
Elizabeth McKeever ◽  
...  
Keyword(s):  
Overall Survival ◽  
Proportional Hazards Model ◽  
Performance Status ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Cancer Center ◽  
Entire Cohort ◽  
The Impact

303 Background: BTCs include intrahepatic (IHC), hilar, distal bile duct (DBD), and gallbladder carcinoma (GBC). Statins, aspirin and metformin may have antineoplastic properties. The impact of their use on overall survival and the recurrence free survival of patients who had curative resection of BTC has not been evaluated. Methods: Baseline demographics and use of statins, aspirin or metformin at diagnosis were evaluated in 913 patients with BTC from 01/87 - 07/13 treated at Princess Margaret Cancer Center, Toronto. Their prognostic significance for recurrence free and overall survival was determined using a Cox proportional hazards model. Results: The median age at diagnosis for the entire cohort was 65.7 years (range 23.7-93.7). 795 patients had a performance status < 2 and 461 (50.5%) were male. The primary site was GBC in 310 (34%) patients, DBD in 212 (23%), IHC in 200 (22%) and hilar in 191 (21%). Curative surgical resection was performed in 355 (39%) patients. Among the entire cohort of 913 patients, 151 (16.5%) reported statin use at diagnosis. Atorvastatin was the statin used in 55% of patients. 146 (16%) reported aspirin use and 81 (9%) reported metformin use at diagnosis. Age (p=0.05, p<0.01), and stage (p<0.001, p<0.001) were prognostic on multivariable analysis for recurrence free and overall survival respectively. GBC (p=0.01), DBD (p<0.01) primary and performance status ≥ 2 (p < 0.0001) were also prognostic for overall survival. Recurrence free and overall survival among statin users and nonusers was similar (Hazard Ratio (HR) 1.07, 95% confidence interval (CI) 0.78-1.48, p=0.68) and (HR 0.84 (95% CI 0.67-1.05, p=0.12) respectively. Recurrence free and overall survival among aspirin users and nonusers was similar (HR 0.91, 95% CI 0.64-1.29, P=0.58) and (HR 0.98 (95% CI 0.80-1.22, P=0.88) respectively. Recurrence free and overall survival among metformin users and nonusers was also similar (HR 0.71, 95% CI 0.43-1.17, p=0.18) and (HR 0.81 (95% CI 0.60-1.08, p=0.14) respectively. Conclusions: In this large retrospective cohort of BTC patients, statin, aspirin or metformin use was not associated with improved recurrence free or overall survival.

Age at Exposure to Parental Suicide and the Subsequent Risk of Suicide in Young People

Crisis ◽  
2018 ◽  
Vol 39 (1) ◽  
pp. 27-36 ◽  
Author(s):  
Kuan-Ying Lee ◽  
Chung-Yi Li ◽  
Kun-Chia Chang ◽  
Tsung-Hsueh Lu ◽  
Ying-Yeh Chen
Keyword(s):  
Young People ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Birth Registry ◽  
Data Set ◽  
Parental Suicide ◽  
The Impact ◽  
Age At Exposure

Abstract. Background: We investigated the age at exposure to parental suicide and the risk of subsequent suicide completion in young people. The impact of parental and offspring sex was also examined. Method: Using a cohort study design, we linked Taiwan's Birth Registry (1978–1997) with Taiwan's Death Registry (1985–2009) and identified 40,249 children who had experienced maternal suicide (n = 14,431), paternal suicide (n = 26,887), or the suicide of both parents (n = 281). Each exposed child was matched to 10 children of the same sex and birth year whose parents were still alive. This yielded a total of 398,081 children for our non-exposed cohort. A Cox proportional hazards model was used to compare the suicide risk of the exposed and non-exposed groups. Results: Compared with the non-exposed group, offspring who were exposed to parental suicide were 3.91 times (95% confidence interval [CI] = 3.10–4.92 more likely to die by suicide after adjusting for baseline characteristics. The risk of suicide seemed to be lower in older male offspring (HR = 3.94, 95% CI = 2.57–6.06), but higher in older female offspring (HR = 5.30, 95% CI = 3.05–9.22). Stratified analyses based on parental sex revealed similar patterns as the combined analysis. Limitations: As only register-­based data were used, we were not able to explore the impact of variables not contained in the data set, such as the role of mental illness. Conclusion: Our findings suggest a prominent elevation in the risk of suicide among offspring who lost their parents to suicide. The risk elevation differed according to the sex of the afflicted offspring as well as to their age at exposure.

Histologic Evaluation Using the Robarts Histopathology Index in Patients With Ulcerative Colitis in Deep Remission and the Association of Histologic Remission With Risk of Relapse

2022 ◽  
Author(s):  
Jin Park ◽  
Soo Jin Kang ◽  
Hyuk Yoon ◽  
Jihye Park ◽  
Hyeon Jeong Oh ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Proportional Hazards Model ◽  
Characteristic Curve ◽  
Multivariable Analysis ◽  
Fecal Calprotectin ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Clinical Relapse ◽  
Endoscopic Remission ◽  
Risk Of Relapse

Abstract Background This study prospectively evaluated the risk of relapse according to the status of histologic activity in patients with ulcerative colitis (UC) who achieved deep remission. Methods Patients with UC in clinical remission (partial Mayo score ≤1) and endoscopic remission (ulcerative colitis endoscopic index of severity ≤1) were enrolled. Rectal biopsies were performed in patients, and histologic remission was defined as a Robarts histopathology index of ≤3. Receiver-operating characteristic curve analysis was conducted to determine fecal calprotectin cutoff values for histologic remission. The cumulative risk of relapse was evaluated using the Cox proportional hazards model. Results Among the 187 patients enrolled, 82 (43.9%) achieved histologic remission. The best cutoff value of fecal calprotectin for predicting histologic remission was 80 mg/kg (area under the curve of 0.646, sensitivity of 74%, and specificity of 61%). Among 142 patients who were followed up for &gt;3 months, 56 (39.4%) showed clinical relapse during a median of 42 weeks. The risk of relapse was lower in patients with histologic remission than in those with histologic activity (P = .026). In multivariable analysis, histologic remission (hazard ratio [HR], 0.551; 95% confidence interval [CI], 0.316-0.958; P = .035), elevated C-reactive protein levels (HR, 3.652; 95% CI, 1.400-9.526; P = .008), and history of steroid use (HR, 2.398; 95% CI, 1.196-4.808; P = .014) were significantly associated with clinical relapse. Conclusions In patients with UC who achieved clinical and endoscopic remission, histologic remission was independently associated with a lower risk of clinical relapse.

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