The association of a 17-gene genomic prostate score with adverse surgical pathology and recurrence following surgery for localized prostate cancer (PCa): A comparison of African American and Caucasian patients.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 86-86
Author(s):  
Jennifer Cullen ◽  
Inger L. Rosner ◽  
Timothy C. Brand ◽  
Amina Ali ◽  
Yongmei Chen ◽  
...  

86 Background: Molecular assays can improve risk assessment for newly diagnosed PCa, but it is imperative to characterize assay performance in different racial groups, since tumor biology and clinical outcomes may vary. A racially diverse cohort of men (20% AA) with PCa in the Center for Prostate Disease Research multi-center national database was used to determine the association of GPS with outcomes in men treated with radical prostatectomy (RP) for localized PCa. Methods: Biopsy specimens from 431 men treated with RP for NCCN very low, low or intermediate risk PCa at 2 U.S. military medical centers were tested with a 17-gene RT-PCR assay to validate the association between GPS (scale 0-100) and 1) biochemical recurrence (BCR) following RP, and 2) adverse pathology (AP) at RP. BCR was defined as 2 successive PSA levels > 0.2 ng/mL. AP was defined as high-grade (primary Gleason pattern 4 or any pattern 5) and/or pT3 disease. Cox proportional hazards and logistic regression models were used. Results: GPS was obtained in 402 cases (93%), including 82 AA men. A broad range of GPS results was observed in both AA and CA men; GPS distributions were similar between AA (median GPS = 30.3; inter-quartile range (IQR): 23-38) and CA (median GPS = 30.3; IQR: 23-40); no correlation was observed between GPS and race (r = -0.04, p = 0.45). No differences in expression of individual genes or gene groups in the assay were observed between the two groups. In univariable analysis, PSA, biopsy GS and NCCN risk group were associated with BCR and AP, but race was not. The associations between GPS and clinical outcomes were similarly strong and statistically significant in both AA and CA men - BCR HR/20 GPS units = 3.0 (95% CI: 2.0-4.3) for CA vs. 3.5 (95% CI: 1.0-11.7) for AA; AP OR/20 units = 4.0 (95% CI: 2.6-6.6) for CA vs. 2.9 (95% CI: 1.2-7.6) for AA (p < 0.05 for all). Conclusions: In this cohort of patients treated in a health care system with equal access, clinical outcomes and the tumor biology measured by GPS were similar between AA and CA patients. GPS is a significant predictor of BCR and AP in men treated with RP for localized PCa in both AA and CA men.

2021 ◽  
Vol 147 (5) ◽  
pp. 1407-1419
Author(s):  
Manuela Limam ◽  
Katarina Luise Matthes ◽  
Giulia Pestoni ◽  
Eleftheria Michalopoulou ◽  
Leonhard Held ◽  
...  

Abstract Background Colorectal cancer (CRC) is among the three most common incident cancers and causes of cancer death in Switzerland for both men and women. To promote aspects of gender medicine, we examined differences in treatment decision and survival by sex in CRC patients diagnosed 2000 and 2001 in the canton of Zurich, Switzerland. Methods Characteristics assessed of 1076 CRC patients were sex, tumor subsite, age at diagnosis, tumor stage, primary treatment option and comorbidity rated by the Charlson Comorbidity Index (CCI). Missing data for stage and comorbidities were completed using multivariate imputation by chained equations. We estimated the probability of receiving surgery versus another primary treatment using multivariable binomial logistic regression models. Univariable and multivariable Cox proportional hazards regression models were used for survival analysis. Results Females were older at diagnosis and had less comorbidities than men. There was no difference with respect to treatment decisions between men and women. The probability of receiving a primary treatment other than surgery was nearly twice as high in patients with the highest comorbidity index, CCI 2+, compared with patients without comorbidities. This effect was significantly stronger in women than in men (p-interaction = 0.010). Survival decreased with higher CCI, tumor stage and age in all CRC patients. Sex had no impact on survival. Conclusion The probability of receiving any primary treatment and survival were independent of sex. However, female CRC patients with the highest CCI appeared more likely to receive other therapy than surgery compared to their male counterparts.


Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1453
Author(s):  
Chiara Fabbroni ◽  
Giovanni Fucà ◽  
Francesca Ligorio ◽  
Elena Fumagalli ◽  
Marta Barisella ◽  
...  

Background. We previously showed that grading can prognosticate the outcome of retroperitoneal liposarcoma (LPS). In the present study, we aimed to explore the impact of pathological stratification using grading on the clinical outcomes of patients with advanced well-differentiated LPS (WDLPS) and dedifferentiated LPS (DDLPS) treated with trabectedin. Patients: We included patients with advanced WDLPS and DDLPS treated with trabectedin at the Fondazione IRCCS Istituto Nazionale dei Tumori between April 2003 and November 2019. Tumors were categorized in WDLPS, low-grade DDLPS, and high-grade DDLPS according to the 2020 WHO classification. Patients were divided in two cohorts: Low-grade (WDLPS/low-grade DDLPS) and high-grade (high-grade DDLPS). Results: A total of 49 patients were included: 17 (35%) in the low-grade cohort and 32 (65%) in the high-grade cohort. Response rate was 47% in the low-grade cohort versus 9.4% in the high-grade cohort (logistic regression p = 0.006). Median progression-free survival (PFS) was 13.7 months in the low-grade cohort and 3.2 months in the high-grade cohort. Grading was confirmed as an independent predictor of PFS in the Cox proportional-hazards regression multivariable model (adjusted hazard ratio low-grade vs. high-grade: 0.45, 95% confidence interval: 0.22–0.94; adjusted p = 0.035). Conclusions: In this retrospective case series, sensitivity to trabectedin was higher in WDLPS/low-grade DDLPS than in high-grade DDLPS. If confirmed in larger series, grading could represent an effective tool to personalize the treatment with trabectedin in patients with advanced LPS.


2020 ◽  
Vol 5 (4) ◽  
pp. 598-616 ◽  
Author(s):  
Austin C Doctor

Abstract Why do rebel organizations splinter into competing factions during civil war? To explain this outcome, I leverage variation in rebel leadership. I argue that rebel leaders draw on their pre-war experiences—i.e., their military and political experiences—to manage their organizations during conflict. These experiences bear unique patterns of rebel management and, thus, corresponding risks of fragmentation. Empirical evidence comes from a two-stage research design and original data featuring over 200 rebel leaders from 1989 to 2014. In the first stage, I estimate the probability of group fragmentation with a series of logistic regression models. In the second stage, I use Cox proportional-hazards models to estimate leadership effects on the rate of group fragmentation. Results indicate that variation in rebel leadership corresponds with unique risks of fragmentation. In particular, the results suggest that leaders with real military experience are best equipped to maintain group cohesion. This study offers insight into the processes by which rebel groups splinter into armed factions. In addition, it makes an important contribution to the broader discussion on the roles of structure and agency in shaping the dynamics of civil war.


Author(s):  
Joshua R Ehrlich ◽  
Bonnielin K Swenor ◽  
Yunshu Zhou ◽  
Kenneth M Langa

Abstract Background Vision impairment (VI) is associated with incident cognitive decline and dementia. However, it is not known whether VI is associated only with the transition to cognitive impairment, or whether it is also associated with later transitions to dementia. Methods We used data from the population-based Aging, Demographics and Memory Study (ADAMS) to investigate the association of visual acuity impairment (VI; defined as binocular presenting visual acuity &lt;20/40) with transitions from cognitively normal (CN) to cognitive impairment no dementia (CIND) and from CIND to dementia. Multivariable Cox proportional hazards models and logistic regression were used to model the association of VI with cognitive transitions, adjusted for covariates. Results There were 351 participants included in this study (weighted percentages: 45% male, 64% age 70-79 years) with a mean follow-up time of 4.1 years. In a multivariable model, the hazard of dementia was elevated among those with VI (HR=1.63, 95%CI=1.04-2.58). Participants with VI had a greater hazard of transitioning from CN to CIND (HR=1.86, 95%CI=1.09-3.18). However, among those with CIND and VI a similar percentage transitioned to dementia (48%) and remained CIND (52%); there was no significant association between VI and transitioning from CIND to dementia (HR=0.94, 95%CI=0.56-1.55). Using logistic regression models, the same associations between VI and cognitive transitions were identified. Conclusions Poor vision is associated with the development of CIND. The association of VI and dementia appears to be due to the higher risk of dementia among individuals with CIND. Findings may inform the design of future interventional studies.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18565-e18565
Author(s):  
Olga Kantor ◽  
Monica L. Wang ◽  
Kimberly Bertrand ◽  
Mariana Chavez-MacGregor ◽  
Rachel A. Freedman ◽  
...  

e18565 Background: The persistent racial and socioeconomic status (SES) disparities in breast cancer outcomes are partially attributed to propensity towards more aggressive cancers or presentation at higher stages among these groups. Chronic stressors related to race and SES are another major mechanism underlying these inequities. This study aims to examine the effect of race and SES within the AJCC 8th-edition staging system, which incorporates anatomic extent of disease and tumor biology. Methods: The SEER breast cancer database linked with county-level census data was used to identify patients with invasive breast cancer from 2010-2015. The database includes a composite SES-index which was analyzed in quintiles. Cox proportional-hazards regression was used to estimate disease-specific survival (DSS). Results: 259,852 patients were included: 176,369 (67.9%) non-Hispanic white, 28,510 (11.0%) Black, 29,737 (11.4%) Hispanic, and 22,887 (8.8%) Asian. Black race, lower SES, public insurance, lower education, and increased poverty were associated with decreased DSS. Adjusted survival analysis for patient, SES, tumor, and treatment characteristics demonstrated that patients of black race had inferior DSS within each stage. Fully adjusted models also showed patients residing in lower SES counties had inferior DSS [Table]. Conclusions: Racial and SES disparities in breast cancer-specific mortality were evident across all stages of disease. Future efforts to improve breast cancer outcomes should systematically assess and address racial and socioeconomic factors as fundamental drivers of inequitable outcomes. Adjusted 5-year DSS Estimates, Stratified by Race and SES.[Table: see text]


Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Filomena Gomes ◽  
Peter W Emery ◽  
Christine E Weekes

INTRODUCTION Several studies have shown a paradoxical association between body mass index (BMI) and mortality after stroke. However, the association between BMI, waist circumference (WC) and mortality and stroke recurrence is unclear. This study aimed to determine the associations between BMI, WC and mortality and stroke recurrence at 6 months post stroke. METHODS Patients were recruited from consecutive admissions at 2 hyper-acute stroke units in London and were classified into 4 categories of BMI (underweight, normal weight, overweight and obese) and quartiles of WC. Outcomes were obtained for each patient through a national database that contains details of all hospital admissions. Chi-square tests were used to compare mortality and stroke recurrence rates. Cox Proportional Hazards Models were used to compare mortality risk and survival curves between different BMI categories and WC quartiles. RESULTS Of 543 recruited patients, 51% were males and 87% had an ischaemic stroke, with a mean age of 74.7 years (range 22-99). There were significant inverse associations between BMI and WC and risk of mortality at 6-months post-stroke (see table) ( p=0.001 and p=0.04, respectively). After adjusting for possible confounders (age, ethnicity, gender, severity and type of stroke, stroke risk factors), these associations were attenuated ( p=0.06 for BMI and p=0. 11 for WC). No significant differences were found in stroke recurrence rates between BMI groups (underweight 3.7%, normal weight 3.8%, overweight 4.5%, obese 2.8%; p=0.91) or WC quartiles (Q1 2.8%, Q2 5.1%, Q3 3.5%, Q4 3.6%; p=0.83). CONCLUSION After a stroke, being obese and having a larger waist circumference was associated with reduced mortality but did not affect the risk of a recurrent stroke.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Kenjiro Ishigami ◽  
Syuhei Ikeda ◽  
KOSUKE DOI ◽  
Yasuhiro Hamatani ◽  
Akiko Fujino ◽  
...  

Introduction: Anemia has been reported to be associated with poor prognosis in patients with atrial fibrillation (AF). Concomitant thrombocytopenia (TP) may or may not affect the prescription of antithrombotic drugs and clinical outcomes in these patients. Methods: The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto. We defined TP as platelet counts less than 150,000/μL and anemia as hemoglobin less than 11 g/dL. Among 666 patients with anemia, we compared the clinical backgrounds and outcomes of those with TP (n=183) and those without (n=483). Results: Compared with patients without TP, patients with TP were more likely to have chronic kidney disease (75.4% vs. 61.8%, p=0.001), and less likely to have hypertension (58.5% vs. 67.0%, p=0.0393), and less likely to have dyslipidemia (27.3% vs. 38.3%, p=0.0079). Age, sex, body weight, CHADS 2 score, CHA 2 DS 2 -VASc score, HAS-BLED score, and previous major bleeding were comparable between the groups. Furthermore, prescription of anti-thrombotic drugs was comparable (Figure A). On Kaplan-Meier analysis, the incidence of all-cause death was higher in TP group (hazard ratio [HR] 1.52; 95% confidence interval [CI] 1.20-1.91, p<0.05) (Figure B-1). There was no significant difference in other adverse events between patients with and without TP (major bleeding: HR 1.11; 95% CI 0.41-3.31, p=0.8, hospitalization for heart failure: HR 1.11; 95% CI 0.74-1.61, p= 0.61 and stroke or systemic embolism: HR 0.91; 95% CI 0.43-1.78, p=0.80) (Figure B-2, 3, 4). Multivariate Cox proportional hazards regression analysis adjusting for potential confounders revealed that TP was an independent determinant of all-cause death (adjusted HR: 1.41, 95% CI; 1.11-1.78, p=0.006). Conclusions: Concomitant TP in AF patients with anemia did not affect the prescription of antithrombotic drugs, and was independently associated with all-cause death in the Fushimi AF Registry.


2018 ◽  
Vol 69 (8) ◽  
pp. 1288-1295 ◽  
Author(s):  
Haley J Appaneal ◽  
Aisling R Caffrey ◽  
Kerry L LaPlante

Abstract Background Metronidazole may still be an appropriate therapeutic option for mild Clostridium difficile infection (CDI) in select patients, but data are limited to guide clinicians in identifying these patients. Methods Our 2-stage study included a national cohort of Veterans with a first episode of mild CDI (2010–2014). First, among those treated with metronidazole, we identified predictors of success, defined as absence of all-cause mortality or recurrence 30 days posttreatment, using multivariable unconditional logistic regression. Second, among a subgroup of patients with characteristics predictive of success identified in the first stage, we compared clinical outcomes among those treated with metronidazole compared with vancomycin, using Cox proportional hazards models for time to 30-day all-cause mortality, CDI recurrence, and failure. Results Among 3656 patients treated with metronidazole, we identified 3282 patients with success and 374 patients without success (failure). Younger age was the only independent predictor of success. Age ≤65 years was associated with an odds of success 1.63 times higher (95% confidence interval [CI], 1.29–2.06) than age >65 years. Among 115 propensity score–matched pairs ≤65 years of age, no significant differences were observed between metronidazole and vancomycin (reference) for all-cause mortality (hazard ratio [HR], 0.29 [95% CI, .06–1.38]), CDI recurrence (HR, 0.62 [95% CI, .26–1.49]), or failure (HR, 0.50 [95% CI, .23–1.07]). Conclusions Among patients ≤65 years of age with initial mild CDI, clinical outcomes were similar with metronidazole and vancomycin. These data suggest that metronidazole may be considered for the treatment of initial mild CDI among patients 65 years of age or younger.


Neurosurgery ◽  
2019 ◽  
Vol 87 (1) ◽  
pp. 63-70
Author(s):  
Haruhisa Fukuda ◽  
Daisuke Sato ◽  
Yoriko Kato ◽  
Wataro Tsuruta ◽  
Masahiro Katsumata ◽  
...  

Abstract BACKGROUND Flow diverters (FDs) have marked the beginning of innovations in the endovascular treatment of large unruptured intracranial aneurysms, but no multi-institutional studies have been conducted on these devices from both the clinical and economic perspectives. OBJECTIVE To compare retreatment rates and healthcare expenditures between FDs and conventional coiling-based treatments in all eligible cases in Japan. METHODS We identified patients who had undergone endovascular treatments during the study period (October 2015-March 2018) from a national-level claims database. The outcome measures were retreatment rates and 1-yr total healthcare expenditures, which were compared among patients who had undergone FD, coiling, and stent-assisted coiling (SAC) treatments. The coiling and SAC groups were further categorized according to the number of coils used. Retreatment rates were analyzed using Cox proportional hazards models, and total expenditures were analyzed using multilevel mixed-effects generalized linear models. RESULTS The study sample comprised 512 FD patients, 1499 coiling patients, and 711 SAC patients. The coiling groups with ≥10 coils and ≥9 coils had significantly higher retreatment rates than the FD group with hazard ratios of 2.75 (1.30-5.82) and 2.52 (1.24-5.09), respectively. In addition, the coiling group with ≥10 coils and SAC group with ≥10 coils had significantly higher 1-year expenditures than the FD group with cost ratios (95% CI) of 1.30 (1.13-1.49) and 1.31 (1.15-1.50), respectively. CONCLUSION In this national-level study, FDs demonstrated significantly lower retreatment rates and total expenditures than conventional coiling with ≥ 9 coils.


2005 ◽  
Vol 23 (36) ◽  
pp. 9312-9318 ◽  
Author(s):  
Matthew P. Goetz ◽  
James M. Rae ◽  
Vera J. Suman ◽  
Stephanie L. Safgren ◽  
Matthew M. Ames ◽  
...  

Purpose Polymorphisms in tamoxifen metabolizing genes affect the plasma concentration of tamoxifen metabolites, but their effect on clinical outcome is unknown. Methods We determined cytochrome P450 (CYP)2D6 (*4 and *6) and CYP3A5 (*3) genotype from paraffin-embedded tumor samples and buccal cells (living patients) in tamoxifen-treated women enrolled onto a North Central Cancer Treatment Group adjuvant breast cancer trial. The relationship between genotype and disease outcome was determined using the log-rank test and Cox proportional hazards modeling. Results Paraffin blocks were obtained from 223 of 256 eligible patients, and buccal cells were obtained from 17 living women. CYP2D6 (*4 and *6) and CYP3A5 (*3) genotypes were determined from 190, 194, and 205 patient samples and in 17 living women. The concordance rate between buccal and tumor genotype was 100%. Women with the CYP2D6 *4/*4 genotype had worse relapse-free time (RF-time; P = .023) and disease-free survival (DFS; P = .012), but not overall survival (P = .169) and did not experience moderate to severe hot flashes relative to women heterozygous or homozygous for the wild-type allele. In the multivariate analysis, women with the CYP2D6 *4/*4 genotype still tended to have worse RFS (hazard ratio [HR], 1.85; P = .176) and DFS (HR, 1.86; P = .089). The CYP3A5*3 variant was not associated with any of these clinical outcomes. Conclusion In tamoxifen-treated patients, women with the CYP2D6 *4/*4 genotype tend to have a higher risk of disease relapse and a lower incidence of hot flashes, which is consistent with our previous observation that CYP2D6 is responsible for the metabolic activation of tamoxifen to endoxifen.


Sign in / Sign up

Export Citation Format

Share Document