Prognostic biomarker potential of quantifying endotrophin in serum from pancreas cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16804-e16804
Author(s):  
Nicholas Willumsen ◽  
Inna Chen ◽  
Neel Ingemann Nissen ◽  
Astrid Zedlitz Johansen ◽  
Julia S. Johansen ◽  
...  
Keyword(s):  
Pancreas Cancer ◽  
Cox Regression ◽  
Performance Status ◽  
Tumor Stage ◽  
Tumor Type ◽  
Cox Regression Analysis ◽  
Desmoplastic Reaction ◽  
Increased Risk ◽  
Metastatic Sites ◽  
Stage 1

e16804 Background: Pancreas cancer (PC) is the most stroma rich tumor type defined by increased collagen deposition and remodeling (desmoplasia/tumor fibrosis), which result in poor prognosis and lack of treatment response. The cleavage product of the type VI collagen alpha 3 (COL6a3) chain, also knowns as endothrophin, has been shown to signaling properties and affect several pro-tumorigenic events by augmenting desmoplasia, angiogenesis, inflammation and tumor growth. Here we evaluate the clinical utility of a biomarker (PRO-C6) quantifying endothrophin in serum from patients with PC. Methods: Serum PRO-C6 was measured by ELISA (Nordic Bioscience) in 814 PC patients (n = 15, 201, 164 and 434 for stage 1-4, respectively) and 87 patients with benign conditions from the clinical study BIOPAC (NCT03311776, Denmark). PC was histologically confirmed, and patients received standard of treatment (surgical resection or palliative chemotherapy). PRO-C6 was compared between PC and benign conditions and correlated to stage. Association between OS and PRO-C6 in PC patients was analyzed by Kaplan-Meyer curves and Cox regression analysis alone, and after adjusting for age, gender, BMI, diabetes, smoking, performance status, cachexia, CA19-9, stage and metastatic sites. Results: PRO-C6 was elevated in PC compared to benign disease (p = 0.009) and increased with tumor stage (p = 0.0006). When dividing PRO-C6 into quartiles (Q1-Q4) a stepwise decrease was detected in median OS time (Q1:380 days, Q2:264 days, Q3:236 days, Q4:176 days, p < 0.0001). Patients in Q4 had 85% increased risk of dying compared to Q1 (HR:1.85, p < 0.0001). High PRO-C6 (Q4) remained associated with poor OS after adjusting for co-variates (HR: 1.66, p = 0.0018). Conclusions: Pretreatment serum PRO-C6 (a measure of the COL6a3 chain/endothrophin) is associated with PC and has independent prognostic value. This suggests that endothrophin, and the desmoplastic reaction, plays a key role in PC and indicate that PRO-C6 may provide means for a theragnostic approach for stratifying and treating PC patients in the future. Clinical trial information: NCT03311776 .

scholarly journals Extramural Venous Invasion as Prognostic Factor of Recurrence in Stage 1 and 2 Colon Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-6
Author(s):  
E. E. van Eeghen ◽  
M. J. Flens ◽  
M. M. R. Mulder ◽  
R. J. L. F. Loffeld
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cox Regression ◽  
Venous Invasion ◽  
Prognostic Indicator ◽  
Hazard Ratio ◽  
Cox Regression Analysis ◽  
Increased Risk ◽  
Additional Value ◽  
Stage 1

Aim. Extramural venous invasion (EMVI) is a prognostic indicator in patients with colorectal cancer. However, its additional value in patients with stage 1 and 2 colorectal cancer is uncertain. In the present study, the incidence of EMVI and the hazard ratio for recurrence in patients with stage 1 and 2 colon cancer were studied. Methods. 184 patients treated for stage 1 and 2 colon cancer were included with a follow-up of at least 5 years. Chart review was performed and EMVI was assessed by two separate pathologists. EMVI was scored with additional caldesmon staining on the resection specimen. Primary outcomes were recurrence-free survival (RFS) measured through the Cox regression analysis and prevalence of EMVI. Results. There were 10 cases of EMVI and 3 cases of intramural venous invasion (IMVI) all occurring in patients with stage 2 disease corresponding to a prevalence of 9%. Thirty-one percent of the patients with venous invasion experienced recurrence versus 14% in patients without, corresponding with a hazard ratio of 2.39 (p=0.11). Conclusion. The present study demonstrates a trend towards an increased risk of recurrence in patients with stage 2 colon cancer with venous invasion. This warrants consideration of adjuvant chemotherapy despite the lack of lymph node metastases.

Study of genotypic variations and protein expression of the xCT subunit of cystine/glutamate transporter in pancreatic cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 210-210
Author(s):  
T. J. Huang ◽  
D. Li ◽  
Y. Li ◽  
S. P. Kar ◽  
S. Krishnan ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Protein Expression ◽  
Cox Regression ◽  
Performance Status ◽  
Glutamate Transporter ◽  
Supporting Evidence ◽  
Cox Regression Analysis ◽  
Risk Of Death ◽  
Increased Risk

210 Background: The plasma membrane xCT cystine-specific subunit of the cystine/glutamate transporter contributes to chemotherapy resistance in pancreatic cancer by regulating intracellular glutathione levels and protecting cancer cells against oxidative stress. We previously noted that the rs7674870 single nucleotide polymorphism (SNP) of xCT correlated with overall survival in pancreatic cancer and may be predictive of platinum resistance. There are no data regarding xCT protein expression in pancreatic cancer or the functional significance of this SNP. Methods: Paraffin-embedded core and surgical biopsy tumor specimens from 49 patients with metastatic pancreatic adenocarcinoma were analyzed by immunohistochemistry (IHC) using an xCT specific antibody (Novus Biologicals). xCT protein IHC expression scores (product of intensity and percentage of staining cells) were analyzed in relation to overall survival and genotype of the patients using the one factor ANOVA test, Kaplan-Meier plot, log-rank test, and Cox regression analysis. Overall survival was measured from the date of diagnosis to the date of death or last follow-up. Results: Positive xCT expression was detected in 38 (78%) of the 49 samples, and 9 (18%) patients had high levels of expression. High xCT expression was associated with lower overall survival as compared with low expression (5.1 months versus 8.8 months; p = 0.119). In a multivariate Cox regression model with adjustment for prognostic parameters of age, sex, performance status and CA19-9 level, high xCT expression was associated with a 2.1-fold increased risk of death (p = 0.096). Performance status also correlated with overall survival (p = 0.027). Preliminary analysis on the genotype-phenotype association (n = 12) indicated that xCT expression was higher with the TT genotype than the TC/CC genotype (p = 0.115), which is consistent with the previous observation that the TT genotype was associated with reduced survival. Conclusions: These data provide supporting evidence for a possible role of cystine/glutamate transporter xCT subunit in pancreatic cancer progression and survival. Further pharmacogenomic and clinicopathologic studies are ongoing. No significant financial relationships to disclose.

Analysis of prognostic factors in patients with advanced relapsed/refractory NSCLC: Cox regression analysis of a randomized phase III trial comparing docetaxel and paclitaxel poliglumex (PPX)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7040-7040 ◽  
Author(s):  
P. Bonomi ◽  
C. Langer ◽  
M. O’Brien ◽  
K. O’Byrne ◽  
B. Bandstra ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cox Regression ◽  
Performance Status ◽  
Stage Iv ◽  
Tumor Stage ◽  
Phase Iii ◽  
Line Treatment ◽  
Phase Iii Trial ◽  
Cox Regression Analysis ◽  
The Impact

7040 Background: A phase III trial compared PPX to docetaxel as 2nd-line treatment in pts with relapsed/refractory advanced NSCLC (STELLAR 2). While overall survival was similar between arms, the need for supportive measures to manage the effects of myelosuppression was significantly reduced in the PPX arm. The current analysis was performed to evaluate determinants of survival in the 2nd-line treatment of NSCLC. Methods: STELLAR 2 enrolled 849 pts, 427 on PPX and 422 on docetaxel; all patients were included in the analysis. Randomization between the study arms was stratified by tumor stage, performance status (PS), start of frontline chemotherapy (< 4 mo vs more than 4 mo), gender, and prior taxane therapy. Univariate and multivariate Cox regression analyses were performed to evaluate the impact of baseline characteristics on overall survival (OS). Results: At randomization, 29% of pts had received prior taxane, 14% were PS2, 80% had stage IV disease, and 31% had started frontline therapy within the prior 4 months. Risk factors significantly affecting survival as determined by multivariate analysis are listed in the table . These factors were consistent when treatment was added to the model. Prior exposure to taxane was not predictive of survival; tumor stage was a significant univariate predictor (p=0.0349), but had relatively less impact in the multivariate model. Conclusion: These analyses identified several factors associated with reduced survival benefit from standard second line therapy. Consequently, alternative treatment strategies may be necessary in patients with poor prognosis. For example, more tolerable agents may enhance the benefit/toxicity ratio in these patients. [Table: see text] [Table: see text]

scholarly journals Blood Pressure Classification of 2017 Associated With Cardiovascular Disease and Mortality in Young Chinese Adults

Hypertension ◽  
2020 ◽  
Vol 76 (1) ◽  
pp. 251-258 ◽  
Author(s):  
Shouling Wu ◽  
Yongjian Song ◽  
Shuohua Chen ◽  
Mengyi Zheng ◽  
Yihan Ma ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Cox Regression ◽  
Chinese Adults ◽  
Cox Regression Analysis ◽  
Increased Risk ◽  
All Cause Mortality ◽  
New Guidelines ◽  
Stage 1

The American College of Cardiology/American Heart Association introduced new guidelines for blood pressure (BP) classification in 2017. We explored associations between the newly defined categories and eventual cardiovascular disease (CVD) events, stroke, and all-cause mortality in young Chinese adults. In the community-based Kailuan Study, 16 006 participants aged 18 to 40 years and examined at baseline in 2006/2007 underwent 2-yearly follow-up examinations up to 2016 to 2017. Taking the highest BP reading recorded by manual sphygmomanometry at baseline in 2006 to 2007, we categorized the BP according to the new guidelines. Outcome parameters were CVD events, stroke, and all-cause mortality. During follow-up (mean: 10.9±0.63 years), we observed 458 events (CVD, 167; stroke, 119; and all-cause death, 172). After multivariable adjustment, hazard ratios for CVD events were for elevated BP 0.80 (95% CI, 0.28–2.30), stage 1 hypertension 1.82 (95% CI, 1.12–2.94), and stage 2 hypertension 3.54 (95% CI, 2.18–5.77) versus normal BP. Similar results were obtained for stroke and all-cause death. In Cox regression analysis with BP category entered as time-dependent covariate, stage 1 hypertension was not associated with increased risk ( P >0.10). In the subgroup of individuals taking antihypertensive medication during follow-up, none of the BP categories was significantly associated with the incidence of CVD events. During a mean follow-up of 10.9 years, the newly defined category of stage 1 hypertension in young untreated Chinese adults aged <40 years at baseline was associated with an increased risk for CVD, stroke, and all-cause mortality. This increased risk occurred, however, after progression to stage 2 hypertension. The data may help validating the new BP classification system for young adult Chinese.

scholarly journals Association between blood pressure levels and cardiovascular deaths: a 20-year follow-up study in rural China

BMJ Open ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. e035190 ◽  
Author(s):  
Mengying Wang ◽  
Tao Wu ◽  
Canqing Yu ◽  
Wenjing Gao ◽  
Jun Lv ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cox Regression ◽  
Heart Association ◽  
Outcome Variable ◽  
Cox Regression Analysis ◽  
Chinese Populations ◽  
Follow Up Study ◽  
Increased Risk ◽  
Stage 1

ObjectivesThe 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guideline recommended 130/80 mm Hg as blood pressure (BP) target goals. However, the generalisability of this recommendation to populations at large with hypertension remains controversial. We assessed the association between BP and cardiovascular diseases (CVDs) mortality using a 20-year follow-up study among Chinese populations.DesignProspective cohort study.Participants7314 participants were followed up for a median of 20 years in Fangshan District, Beijing, China.MethodsThe primary outcome variable was death from cardiovascular causes. The adjusted HR for CVDs mortality associated with baseline BP was calculated using Cox regression analysis.ResultsWe identified 350 deaths from CVDs (148 stroke, 113 coronary heart disease and 89 other CVDs) during follow-up. Hypertension (defined by systolic BP (SBP)/diastolic BP (DBP) ≥140/90 mm Hg) was significantly associated with mortality due to CVDs (HR=2.49, 95% CI=1.77 to 3.50) among people aged 35–59 years rather than people aged ≥60 years. In addition, there was no significant association between stage 1 hypertension defined by the 2017 ACC/AHA (SBP/DBP of 130–139/80-89 mm Hg) and CVDs mortality when compared with SBP/DBP of <120/80 in neither the participants aged <60 years (HR=0.90, 95% CI=0.54 to 1.50) nor participants aged ≥60 years (HR=1.47, 95% CI=0.94 to 2.29).ConclusionThe study revealed hypertension of SBP/DBP≥140/90 mm Hg was an important risk factor of CVDs mortality, especially among people aged 35–59 years. However, stage 1 hypertension under the definition of 2017 ACC/AHA was not associated with an increased risk of CVDs mortality. This study indicated that whether adopting the new hypertension definition needs further consideration in rural Chinese populations.

Sex differences in transaortic flow rate and association with all-cause mortality in patients with severe aortic stenosis

2021 ◽  
Author(s):  
Sahrai Saeed ◽  
Anastasia Vamvakidou ◽  
Spyridon Zidros ◽  
George Papasozomenos ◽  
Vegard Lysne ◽  
...  
Keyword(s):  
Sex Differences ◽  
Aortic Stenosis ◽  
Flow Rate ◽  
Cox Regression ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Cox Regression Analysis ◽  
Increased Risk ◽  
All Cause Mortality

Abstract Aims It is not known whether transaortic flow rate (FR) in aortic stenosis (AS) differs between men and women, and whether the commonly used cut-off of 200 mL/s is prognostic in females. We aimed to explore sex differences in the determinants of FR, and determine the best sex-specific cut-offs for prediction of all-cause mortality. Methods and results Between 2010 and 2017, a total of 1564 symptomatic patients (mean age 76 ± 13 years, 51% men) with severe AS were prospectively included. Mean follow-up was 35 ± 22 months. The prevalence of cardiovascular disease was significantly higher in men than women (63% vs. 42%, P &lt; 0.001). Men had higher left ventricular mass and lower left ventricular ejection fraction compared to women (both P &lt; 0.001). Men were more likely to undergo an aortic valve intervention (AVI) (54% vs. 45%, P = 0.001), while the death rates were similar (42.0% in men and 40.6% in women, P = 0.580). A total of 779 (49.8%) patients underwent an AVI in which 145 (18.6%) died. In a multivariate Cox regression analysis, each 10 mL/s decrease in FR was associated with a 7% increase in hazard ratio (HR) for all-cause mortality (HR 1.07; 95% CI 1.03–1.11, P &lt; 0.001). The best cut-off value of FR for prediction of all-cause mortality was 179 mL/s in women and 209 mL/s in men. Conclusion Transaortic FR was lower in women than men. In the group undergoing AVI, lower FR was associated with increased risk of all-cause mortality, and the optimal cut-off for prediction of all-cause mortality was lower in women than men.

scholarly journals Fast-Track Programs in Total Hip and Knee Replacement at Swedish Hospitals—Influence on 2-Year Risk of Revision and Mortality

2021 ◽  
Vol 10 (8) ◽  
pp. 1680
Author(s):  
Urban Berg ◽  
Annette W-Dahl ◽  
Anna Nilsdotter ◽  
Emma Nauclér ◽  
Martin Sundberg ◽  
...  
Keyword(s):  
Fast Track ◽  
Cox Regression ◽  
Cox Regression Analysis ◽  
Total Hip ◽  
Total Knee Replacements ◽  
Risk Of Death ◽  
Kaplan Meier ◽  
Increased Risk ◽  
Hip And Knee Arthroplasty ◽  
Total Knee

Purpose: We aimed to study the influence of fast-track care programs in total hip and total knee replacements (THR and TKR) at Swedish hospitals on the risk of revision and mortality within 2 years after the operation. Methods: Data were collected from the Swedish Hip and Knee Arthroplasty Registers (SHAR and SKAR), including 67,913 THR and 59,268 TKR operations from 2011 to 2015 on patients with osteoarthritis. Operations from 2011 to 2015 Revision and mortality in the fast-track group were compared with non-fast-track using Kaplan–Meier survival analysis and Cox regression analysis with adjustments. Results: The hazard ratio (HR) for revision within 2 years after THR with fast-track was 1.19 (CI: 1.03–1.39), indicating increased risk, whereas no increased risk was found in TKR (HR 0.91; CI: 0.79–1.06). The risk of death within 2 years was estimated with a HR of 0.85 (CI: 0.74–0.97) for TKR and 0.96 (CI: 0.85–1.09) for THR in fast-track hospitals compared to non-fast-track. Conclusions: Fast-track programs at Swedish hospitals were associated with an increased risk of revision in THR but not in TKR, while we found the mortality to be lower (TKR) or similar (THR) as compared to non-fast track.

scholarly journals High rate of second ACL injury following ACL reconstruction in male professional footballers: an updated longitudinal analysis from 118 players in the UEFA Elite Club Injury Study

2021 ◽  
pp. bjsports-2020-103555
Author(s):  
Francesco Della Villa ◽  
Martin Hägglund ◽  
Stefano Della Villa ◽  
Jan Ekstrand ◽  
Markus Waldén
Keyword(s):  
Acl Reconstruction ◽  
Cox Regression ◽  
Injury Rate ◽  
Acl Injury ◽  
High Rate ◽  
Football Players ◽  
Professional Football ◽  
Cox Regression Analysis ◽  
Career Length ◽  
Increased Risk

BackgroundStudies on subsequent anterior cruciate ligament (ACL) ruptures and career length in male professional football players after ACL reconstruction (ACLR) are scarce.AimTo investigate the second ACL injury rate, potential predictors of second ACL injury and the career length after ACLR.Study designProspective cohort study.SettingMen’s professional football.Methods118 players with index ACL injury were tracked longitudinally for subsequent ACL injury and career length over 16.9 years. Multivariable Cox regression analysis with HR was carried out to study potential predictors for subsequent ACL injury.ResultsMedian follow-up was 4.3 (IQR 4.6) years after ACLR. The second ACL injury rate after return to training (RTT) was 17.8% (n=21), with 9.3% (n=11) to the ipsilateral and 8.5% (n=10) to the contralateral knee. Significant predictors for second ACL injury were a non-contact index ACL injury (HR 7.16, 95% CI 1.63 to 31.22) and an isolated index ACL injury (HR 2.73, 95% CI 1.06 to 7.07). In total, 11 of 26 players (42%) with a non-contact isolated index ACL injury suffered a second ACL injury. RTT time was not an independent predictor of second ACL injury, even though there was a tendency for a risk reduction with longer time to RTT. Median career length after ACLR was 4.1 (IQR 4.0) years and 60% of players were still playing at preinjury level 5 years after ACLR.ConclusionsAlmost one out of five top-level professional male football players sustained a second ACL injury following ACLR and return to football, with a considerably increased risk for players with a non-contact or isolated index injury.

Tumor Stage After Neoadjuvant Chemotherapy Determines Survival After Surgery for Adenocarcinoma of the Esophagus and Esophagogastric Junction

2014 ◽  
Vol 32 (27) ◽  
pp. 2983-2990 ◽  
Author(s):  
Andrew R. Davies ◽  
James A. Gossage ◽  
Janine Zylstra ◽  
Fredrik Mattsson ◽  
Jesper Lagergren ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Surgical Resection ◽  
Esophagogastric Junction ◽  
Cox Regression ◽  
Tumor Regression ◽  
Clinical Stage ◽  
Tumor Stage ◽  
Response To Treatment ◽  
Cox Regression Analysis ◽  
Systemic Recurrence

Purpose Neoadjuvant chemotherapy is established in the management of most resectable esophageal and esophagogastric junction adenocarcinomas. However, assessing the downstaging effects of chemotherapy and predicting response to treatment remain challenging, and the relative importance of tumor stage before and after chemotherapy is debatable. Methods We analyzed consecutive resections for esophageal or esophagogastric junction adenocarcinomas performed at two high-volume cancer centers in London between 2000 and 2010. After standard investigations and multidisciplinary team consensus, all patients were allocated a clinical tumor stage before treatment, which was compared with pathologic stage after surgical resection. Survival analysis was conducted using Kaplan-Meier analysis and Cox regression analysis. Results Among 584 included patients, 400 patients (68%) received neoadjuvant chemotherapy. Patients with downstaged tumors after neoadjuvant chemotherapy experienced improved survival compared with patients without response (P < .001), and such downstaging (hazard ratio, 0.43; 95% CI, 0.31 to 0.59) was the strongest independent predictor of survival after adjusting for patient age, tumor grade, clinical tumor stage, lymphovascular invasion, resection margin status, and surgical resection type. Patients downstaged by chemotherapy, compared with patients with no response, experienced lower rates of local recurrence (6% v 13%, respectively; P = .030) and systemic recurrence (19% v 29%, respectively; P = .027) and improved Mandard tumor regression scores (P < .001). Survival was strongly dictated by stage after neoadjuvant chemotherapy, rather than clinical stage at presentation. Conclusion The stage of esophageal or esophagogastric junction adenocarcinoma after neoadjuvant chemotherapy determines prognosis rather than the clinical stage before neoadjuvant chemotherapy, indicating the importance of focusing on postchemotherapy staging to more accurately predict outcome and eligibility for surgery. Patients who are downstaged by neoadjuvant chemotherapy benefit from reduced rates of local and systemic recurrence.

Efficacy and toxicity hypofractionated radiotherapy for centrally located non-small cell lung cancer

2021 ◽  
pp. 1-4
Author(s):  
Tanzeel Janjua ◽  
Fei Sun ◽  
Katy Clarke ◽  
Pete Dickinson ◽  
Kevin Franks ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cox Regression ◽  
Early Stage ◽  
Performance Status ◽  
Small Cell ◽  
Small Cell Lung ◽  
Early Stage Lung Cancer ◽  
Cox Regression Analysis

Abstract Aim: Centrally located early-stage non-small cell lung cancer in patients who are unfit for surgery are treated with fractionated radiotherapy. We present the outcomes of a moderately hypofractionated accelerated dose regimen of 50 Gy in 15 fractions from a single centre in the UK. Materials and methods: Electronic case notes and radiotherapy records of lung cancer patients treated between January 2014 and December 2016 were retrospectively reviewed. Adult Comorbidity Evaluation-27 score was used to evaluate comorbidities. Mean lung doses and percentage of lung receiving more than 20 Gy were calculated for all patients. Survival outcomes were estimated using Kaplan–Meier curves. Results: Fifty-three patients were included in the study; the median follow-up was 20.2 months. 87% of patients had stage I disease. There was no 30-day post-treatment mortality. Ninety-day mortality rate after radiotherapy was 3.8%. Grade 2 pneumonitis was seen in five patients while no grade 3 or 4 pneumonitis was observed. The median progression-free survival (PFS) and overall survival (OS) were 18.5 months and 28.2 months, respectively. The estimated 1 and 2 years PFS were 62.3% and 41.3%, respectively, and OS were 77.4% and 56.6%, respectively. Worsening performance status was associated with worse survival on cox regression analysis. Disease relapsed in 36% of patients. 7.5% of patients with relapsed disease had infield recurrence. Findings: 50 Gy in 15 fractions radiotherapy for central early-stage lung cancer is a feasible choice that requires further randomised trials.

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