scholarly journals Quantifying the ki-67 heterogeneity profile in prostate cancer.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 73-73
Author(s):  
Mitchell Kamrava ◽  
Shane Mesko ◽  
Robyn Banerjee ◽  
Jiaoti Huang ◽  
D. Jeffrey Demanes ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Prostate Biopsy ◽  
Risk Groups ◽  
Tumor Diameter ◽  
Ki 67 ◽  
High Risk Patients ◽  
Prostate Biopsies ◽  
Positive Biopsy ◽  
Risk Patients

73 Background: Ki-67 is a robust predictive/prognostic marker in prostate cancer however tumor heterogeneity may compromise its clinical utility when Ki-67 is determined off of prostate biopsy samples. We examined the variation of Ki-67 in prostate biopsy samples by NCCN risk groups and the location of the highest Ki-67 relative to the most dominant lesion on multiparametric (MP) MRI. Methods: An IRB approved retrospective analysis was done on 77 consecutive men whose prostate biopsies revealed cancer. Using a MRI/US fusion device (Artemis), biopsy cores were obtained systematically and when MRI indicated a lesion, by targeting. Ki-67 staining was determined by a manual semi-quantitative method and reported as % of positive cells. The highest Ki-67 per patient was used to determine inter-prostatic variation. Ki-67 range (highest Ki-67 minus lowest Ki-67 value) was used to determine intra-prostatic variation on a subset of 47 patients with ≥2 positive biopsy cores. Ki-67 range was also used to evaluate intra-lesion variation on 31 MP MRI defined lesions with > 1 targeted positive biopsy core. The relationship of the dominant lesion (lesion with the largest tumor diameter) to the highest Ki-67 in the entire prostate was examined for 10 patients with ≥2 distinct lesions on MP MRI. Analysis of variance (ANOVA) was used to evaluate differences between the means of NCCN-defined risk groups. Results: Inter-prostatic Ki-67 mean±standard deviation (SD) values for low, intermediate and high risk patients were 5.1% ± 3.8%, 7.4% ± 6.8%, and 12.0% ± 12.4% (ANOVA p=0.01). Intra-prostatic mean±SD Ki-67 ranges in low, intermediate, and high risk patients were 2.6% ± 3.4%, 4.6% ± 6.4%, 9.5% ± 10.6% (ANOVA p = 0.0246). Intra-lesion mean±SD Ki-67 ranges in low, intermediate and high risk patients were 1.0%±1.0%, 4.0%±4.29%, and 6.7%±11.51% (ANOVA p=0.39). The dominant lesion harbored the highest Ki-67 30% of the time. Conclusions: High risk patients have significantly higher inter- and intra-prostatic Ki-67 heterogeneity profiles than men with low/intermediate risk disease. The highest Ki-67 is often not located in the dominant MRI defined lesion. This data can inform future biopsy strategies when integrating Ki-67 into clinical practice.

scholarly journals Importance of repeat laterally directed sextant prostate biopsy for detection of prostate cancer in high-risk patients

Medicina ◽  
2007 ◽  
Vol 43 (11) ◽  
pp. 843
Author(s):  
Kęstutis Vaičiūnas ◽  
Stasys Auškalnis ◽  
Aivaras Matjošaitis ◽  
Antanas Mickevičius ◽  
Ramūnas Mickevičius ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Prostate Biopsy ◽  
Specific Antigen ◽  
Antigen Level ◽  
Ultrasound Guided ◽  
High Risk Patients ◽  
Prostate Biopsies ◽  
Risk Patients ◽  
Detect Prostate Cancer

Our purpose was to evaluate the relevance of repeat laterally directed sextant prostate biopsy for detection of prostate cancer in high-risk patients. Material and methods. Our study included 195 men at high risk for prostate cancer (elevated prostatespecific antigen level and/or abnormal prostate detected by digital rectal examination). We consulted the patients in outpatient department of Kaunas University of Medicine Hospital during 2003–2007. We performed transrectal ultrasound-guided laterally directed sextant prostate biopsy in every patient. For the patients with benign histological findings and increased risk of prostate cancer, laterally directed sextant biopsies were repeated. Results. Prostate cancer was detected in 30.3% of patients (59/195) on the first prostate biopsy, in 13.1% (11/84) on the second prostate biopsy, in 10.3% (4/39) on the third, and in 7.7% (1/13) on the forth biopsy. After all biopsies, prostate cancer was detected in 38.5% (75/195) of patients, and it differed significantly from the percentage of prostate cancer cases detected on the first biopsy (30.3%, P=0.04). We detected 78.7% (59/75) of all prostate cancer cases by the first laterally directed sextant prostate biopsy. The rest 21.3% (16/75) of cases we detected by repeat biopsies. The second laterally directed sextant prostate biopsy revealed additional 14.6% (n=11) of prostate cancer cases and increased the detection of prostate cancer to 93.3% (70/75). At the time of the first prostate biopsy, prostate cancer was diagnosed most frequently when patients had both risk factors: elevated prostate-specific antigen level and abnormal digital prostate examination; prostate cancer was diagnosed in 45.3% of these patients. The odds ratio to detect prostate cancer by the first biopsy in patients with elevated prostate-specific antigen level and abnormal digital prostate examination was 3.7, and odds ratio to detect prostate cancer by repeat biopsies was 4.7. Conclusions. Repeat ultrasound-guided laterally directed sextant prostate biopsies reveal more cases of prostate cancer as compared to the first prostate biopsy. The majority of prostate cancer cases (93.3%) are detected by the first and second laterally directed sextant prostate biopsies. After the first negative prostate biopsy, we recommend to repeat prostate biopsy in high-risk patients.

A validation/evaluation of five postoperative prognostic tools for prostate cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5117-5117
Author(s):  
B. A. Inman ◽  
B. C. Leibovich ◽  
S. A. Siddiqui ◽  
I. Frank
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Radical Prostatectomy ◽  
Prediction Interval ◽  
Risk Groups ◽  
Lower Probability ◽  
High Risk Patients ◽  
Psa Failure ◽  
Pubmed Search ◽  
Risk Patients

5117 Background: Prognostic nomograms, scoring tools, and risk tables are rapidly accumulating in the prostate cancer (PCa) literature. It is not always clear to whom these tools should apply and how well they predict the outcomes they were designed to forecast. There is need for independent evaluation of these tools. Methods: We used the Mayo Clinic Radical Prostatectomy Registry, a prospective database of radical prostatectomy (RP) outcomes, to assess tools designed to predict RP outcomes. The validation set included 13,313 RP patients from 1990–2005. There were 3,256 PSA failures, 566 metastases, and 1,599 deaths (301 were due to PCa). We assessed the discrimination, calibration and overall accuracy of prediction tools identified through a structured Pubmed search. Results: Tools varied greatly in terms of complexity, width of prediction interval, and method of presentation. Several tools included non-standard variables and were therefore unevaluable, despite an extensive dataset, leaving the 1999 and 2005 Kattan nomograms, the 1998 and 2001 CDPR scores, and the 2001 GPSM score for analysis. Discrimination (quantitated by the c index) was better for PCa-specific survival and metastases than for PSA failure ( Table ). Kaplan-Meier plots demonstrated clustering of risk groups in most tools, most severely in the higher risk groups of the Kattan nomograms. The calibration plots of most tools (excepting GPSM) had a serious discordance between observed and predicted outcomes in the lower probability ranges. This meant that most tools gravely overestimated the probability of RP failure in high-risk patients, by up to 4- fold. Conclusions: The tools showed moderate discriminatory ability for PSA failure but performed much better for non-surrogate outcomes. Most tools (excepting GPSM) were miscalibrated in high risk patients and dramatically underestimated the efficacy of surgery in this cohort. Prognostic tools may not be as accurate as previously reported. [Table: see text] No significant financial relationships to disclose.

Abstract P275: Demographic and Clinical Profile of Patients with Risk Factors for Coronary Heart Disease (CHD) Defined by National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III Guidelines

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
David M Kern ◽  
Sanjeev Balu ◽  
Ozgur Tunceli ◽  
Swetha Raparla ◽  
Deborah Anzalone
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Risk Groups ◽  
Lipid Lowering ◽  
High Risk Patients ◽  
Low Hdl ◽  
Risk Patients ◽  
Artery Disease ◽  
Very High ◽  
Statin Use

Introduction: This study aimed to compare the demographic and clinical characteristics of patients with different risk factors for CHD as defined by NCEP ATP III guidelines. Methods: Dyslipidemia patients (≥1 medical claim for dyslipidemia, ≥1 pharmacy claim for a statin, or ≥1 LDL-C value ≥100 mg/dL [index date]) aged ≥18 y were identified from the HealthCore Integrated Research Environment from 1/1/2007-7/31/2012. Patients were classified as low risk (0 or 1 risk factor): hypertension, age ≥45 y [men] or ≥55 y [women], or low HDL-C), moderate/moderately high risk (≥2 risk factors), high risk (having CHD or CHD risk equivalent), or very high risk (having ACS or other established cardiovascular disease plus diabetes or metabolic syndrome). Demographics, comorbidities, medication use and lipid levels during the 12 months prior, and statin use during the 6 months post-index date were compared across risk groups (very high vs each other risk group). Results: There were 1,524,351 low-risk (mean age: 47 y; 45% men), 242,357 moderate-risk (mean age: 58 y; 59% men), 188,222 high-risk (mean age: 57 y; 52% men), and 57,469 very-high-risk (mean age: 63 y; 61% men) patients identified. Mean Deyo-Charlson comorbidity score differed greatly across risk strata: 0.20, 0.33, 1.26, and 2.22 from low to very high risk (p<.0001 for each). Compared with high-risk patients, very-high-risk patients had a higher rate of ischemic stroke: 5.4% vs 4.1%; peripheral artery disease: 17.1% vs 11.6%; coronary artery disease: 8.5% vs 8.2%; and abdominal aortic aneurysm: 2.3% vs 2.0% (p<.05 for each). Less than 1% of the total population had a prior prescription for each non-statin lipid-lowering medication (bile acid sequestrants, fibrates, ezetimibe, niacin, and omega-3). Very-high-risk patients had lower total cholesterol (very-high-risk mean: 194 mg/dL vs 207, 205, and 198 mg/dL for low-, moderate-/moderately-high-, and high-risk patients, respectively) and LDL-C (very-high-risk mean: 110 mg/dL vs 126, 126, and 116 mg/dL for the other risk groups; p<.0001 for each); higher triglycerides (TG) (very-high-risk mean: 206 mg/dL vs 123, 177, and 167 mg/dL for the other groups; p<.0001 for each); and lower HDL-C (very-high-risk mean: 45 mg/dL vs 57 [p<.0001], 45 [p=.006], and 51 mg/dL [p<.0001]). Statin use was low overall (15%), but higher in the very-high-risk group (45%) vs the high- (29%), moderate-/moderately-high- (18%), and low- (12%) risk groups (p<.0001 for each). Conclusions: Despite a large proportion of patients having high lipid levels, statin use after a dyslipidemia diagnosis was low: ≥80% of all patients (and more than half at very high risk) failed to receive a statin, indicating a potentially large population of patients who could benefit from statin treatment. Prior use of non-statin lipid-lowering medications was also low considering the high TG and low HDL-C levels among high-risk patients.

Prostate Cancer Diagnosis in High Risk Patients – The Finasteride Challenge Trial

2008 ◽  
Vol 01 (03) ◽  
Author(s):  
Bernd J Schmitz-Dräger ◽  
Arndt Hartmann ◽  
Gert Hüsgens ◽  
Jack Groskopf ◽  
Jochen Gleissner ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Cancer Diagnosis ◽  
Prostate Cancer Diagnosis ◽  
High Risk Patients ◽  
Risk Patients

Survival in Patients with Newly Diagnosed Myeloma Undergoing Therapy with Lenalidomide and Dexamethasone: Impact of High-Risk Cytogenetic Risk Status on Outcome

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 95-95 ◽  
Author(s):  
Prashant Kapoor ◽  
Shaji Kumar ◽  
Rafael Fonseca ◽  
Martha Q. Lacy ◽  
Thomas E Witzig ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Stratification ◽  
Plasma Cell ◽  
Risk Groups ◽  
Newly Diagnosed ◽  
High Risk Patients ◽  
Risk Patients ◽  
The Impact ◽  
Standard Risk

Abstract Background: Multiple myeloma (MM) is a heterogeneous disease with very divergent outcomes that are dictated in a large part by specific cytogenetic abnormalities, as well as other prognostic factors such as the proliferative rate of marrow plasma cells. Prognostic systems incorporating these factors have shown clinical utility in identifying high-risk patients, and are increasingly being utilized for treatment decision-making. However, the prognostic relevance of these factors may change with the application of novel therapies. The objective of this study was to determine the impact of risk-stratification (incorporating plasma cell metaphase cytogenetics, interphase fluorescent in-situ hybridization (FISH) and the slide-based plasma cell labeling index (PCLI)) in a cohort of patients with newly diagnosed MM treated initially with lenalidomide + dexamethasone (Rev-Dex). Methods: From March 2004 to November 2007, 100 consecutive patients treated with Rev (25mg/day) on days 1 through 21 of a 4-week cycle in combination with dexamethasone as initial therapy for newly diagnosed myeloma, were identified. High-risk MM was defined as presence of any one or more of the following: hypodiploidy, monoallelic loss of chromosome 13 or its long arm (by metaphase cytogenetics only), deletion of p53 (locus 17p13) or PCLI ≥ 3% or immunoglobulin heavy chain (IgH) translocations, t(4;14) (p16.3;q32) or t(14;16)(q32;q23) on FISH. PFS and OS survival estimates were created using the Kaplan Meier method, and compared by log-rank tests. Results: The median estimated follow-up of the entire cohort (N=100) was 36 months. The median PFS was 31 months; the median OS has not been reached. The 2- and 3-year OS estimates were 93% and 83%, respectively. 16% patients were deemed high-risk by at least one of the 3 tests (cytogenetics, FISH or PCLI). Response rates (PR or better) were 81% versus 89% in the high-risk and standard risk groups, respectively, P=NS; corresponding values for CR plus VGPR rates were 38% and 45% respectively. The median PFS was 18.5 months in high-risk patients compared to 37 months in the standard-risk patients (n=84), P<0.001(Figure). Corresponding values for TTP were 18.5 months and 36.5 months, respectively, P=<0.001. OS was not statistically significant between the two groups; 92% 2-year OS was noted in both the groups. Overall, 95 patients had at least one of the 3 tests to determine risk, while 55 patients could be adequately stratified based on the availability of all the 3 tests, or at least one test result that led to their inclusion in the high-risk category. The significant difference in PFS persisted even when the analysis was restricted to the 55 patients classified using this stringent criterion; 18.5 months vs. 36.5 months in the high-risk and standard- risk groups respectively; P<0.001. In a separate analysis, patients who underwent SCT before the disease progression were censored on the date of SCT to negate its effect, and PFS was still inferior in the high-risk group (p=0.002). Conclusion: The TTP and PFS of high-risk MM patients are inferior to that of the standard-risk patients treated with Rev-Dex, indicating that the current genetic and proliferation-based risk-stratification model remains prognostic with novel therapy. However, the TTP, PFS, and OS obtained in high-risk patients treated with Rev-Dex in this study is comparable to overall results in all myeloma patients reported in recent phase III trials. In addition, no significant impact of high-risk features on OS is apparent so far. Longer follow-up is needed to determine the impact of risk stratification on the OS of patients treated with Rev-Dex. Figure Figure

scholarly journals Association between HIV status and Positive Prostate Biopsy in a Study of U.S. Veterans

2009 ◽  
Vol 9 ◽  
pp. 102-108 ◽  
Author(s):  
Wayland Hsiao ◽  
Katrina Anastasia ◽  
John Hall ◽  
Michael Goodman ◽  
David Rimland ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Hiv Infection ◽  
Prostate Biopsy ◽  
Medical Center ◽  
Digital Rectal Examination ◽  
Hiv Positive ◽  
Gleason Grade ◽  
Hiv Status ◽  
Prostate Biopsies ◽  
Positive Biopsy

HIV infection is associated with increased incidence of malignancies, such as lymphomas and testicular cancers. We reviewed the relationship between HIV infection and prostate cancer in a contemporary series of prostate biopsy patients. The study is a retrospective analysis of consecutive prostate biopsies performed at a VA Medical Center. The indications for performing a prostate biopsy included an abnormal digital rectal examination and/or an elevated PSA. Patients were categorized according to their HIV status, biopsy results, and various demographic and clinical characteristics. Univariate and multivariate analyses compared distributions of HIV status, and various clinical and demographic characteristics. The adjusted measures of association between HIV status and positive biopsy were expressed as odds ratios (ORs) and corresponding 95% confidence intervals (CI). The likelihood of positive biopsy was significantly higher among 18 HIV-positive patients compared to patients with negative HIV tests (adjusted OR = 3.9; 95% CI: 1.3–11.5). In analyses restricted to prostate cancer patients, HIV-positive patients were not different from the remaining group with respect to their prostate cancer stage, PSA level, PSA velocity, PSA density, or Gleason grade. There is an association between HIV infection and prostate biopsy positive for carcinoma in a population referred for urologic workup. Further confirmation of this association by prospective studies may impact the current screening practices in HIV patients.

scholarly journals Comparison of Oncological Outcomes Between Radical Prostatectomy and Radiotherapy by Type of Radiotherapy in Elderly Prostate Cancer Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiao-Xiao Guo ◽  
Hao-Ran Xia ◽  
Hui-Min Hou ◽  
Ming Liu ◽  
Jian-Ye Wang
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Radical Prostatectomy ◽  
External Beam Radiotherapy ◽  
The Other ◽  
Oncologic Outcomes ◽  
Intermediate Risk ◽  
High Risk Patients ◽  
Significant Difference ◽  
Risk Patients

ObjectiveWe aimed compare the oncologic outcomes of radical prostatectomy (RP) with those of external beam radiotherapy (EBRT), brachytherapy (BT), or EBRT + BT (EBBT) in elderly patients with localised prostate cancer (PCa).MethodsLocalised PCa patients aged ≥70 years who underwent RP, EBRT, BT, or EBBT between 2004 and 2016 were identified from the Surveillance, Epidemiology, and End Results database. Multivariable competing risks survival analyses were used to estimate prostate cancer-specific mortality (CSM) and other-cause mortality (OCM). Subgroup analyses according to risk categories were also conducted.ResultsOverall, 14057, 37712, 8383, and 5244 patients aged ≥70 years and treated with RP, EBRT, BT, and EBBT, respectively, were identified. In low- to intermediate-risk patients, there was no significant difference in CSM risk between RP and the other three radiotherapy modalities (all P &gt; 0.05). The corresponding 10-year CSM rates for these patients were 1.2%, 2.3%, 2.0%, and 1.8%, respectively. In high-risk patients, EBRT was associated with a higher CSM than RP (P = 0.003), whereas there was no significant difference between RP and BT or RP and EBBT (all P &gt; 0.05). The 10-year CSM rates of high-risk patients in the RP, EBRT, BT, and EBBT groups were 7.5%, 10.2%, 8.3%, and 7.6%, respectively. Regarding OCM, the risk was generally lower in RP than in the other three radiotherapy modalities (all P &lt; 0.001).ConclusionsAmong men aged ≥70 years with localised PCa, EBRT, BT, and EBBT offer cancer-specific outcomes similar to those of RP for individuals with low- to intermediate-risk disease. In patients with high-risk disease, EBBT had outcomes equally favourable to those of RP, but RP is more beneficial than EBRT. More high-quality trials are warranted to confirm and expand the present findings.

scholarly journals Protocol for a multinational risk-stratified randomised controlled trial in paediatric Crohn’s disease: methotrexate versus azathioprine or adalimumab for maintaining remission in patients at low or high risk for aggressive disease course

BMJ Open ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. e034892
Author(s):  
Rachel E Harris ◽  
Marina Aloi ◽  
Lissy de Ridder ◽  
Nicholas M Croft ◽  
Sibylle Koletzko ◽  
...  
Keyword(s):  
High Risk ◽  
Randomised Controlled Trial ◽  
Controlled Trial ◽  
Risk Groups ◽  
Low Risk ◽  
High Risk Patients ◽  
Link Type ◽  
Risk Patients ◽  
Randomised Controlled ◽  
Paediatric Crohn’S Disease

IntroductionImmunomodulators such as thiopurines (azathioprine (AZA)/6-mercaptopurine (6MP)), methotrexate (MTX) and biologics such as adalimumab (ADA) are well established for maintenance of remission within paediatric Crohn’s disease (CD). It remains unclear, however, which maintenance medication should be used first line in specific patient groups.AimsTo compare the efficacy of maintenance therapies in newly diagnosed CD based on stratification into high and low-risk groups for severe CD evolution; MTX versus AZA/6MP in low-risk and MTX versus ADA in high-risk patients. Primary end point: sustained remission at 12 months (weighted paediatric CD activity index ≤12.5 and C reactive protein ≤1.5 fold upper limit) without relapse or ongoing requirement for exclusive enteral nutrition (EEN)/steroids 12 weeks after treatment initiation.Methods and analysisREDUCE-RISK in CD is an international multicentre open-label prospective randomised controlled trial funded by EU within the Horizon2020 framework (grant number 668023). Eligible patients (aged 6–17 years, new-onset disease receiving steroids or EEN for induction of remission for luminal ± perianal CD are stratified into low and high-risk groups based on phenotype and response to induction therapy. Participants are randomised to one of two treatment arms within their risk group: low-risk patients to weekly subcutaneous MTX or daily oral AZA/6MP, and high-risk patients to weekly subcutaneous MTX or fortnightly ADA. Patients are followed up for 12 months at prespecified intervals. Electronic case report forms are completed prospectively. The study aims to recruit 312 participants (176 low risk; 136 high risk).Ethics and disseminationClinicalTrials.gov Identifier: (NCT02852694), authorisation and approval from local ethics committees have been obtained prior to recruitment. Individual informed consent will be obtained prior to participation in the study. Results will be published in a peer-reviewed journal with open access.Trial registration numberNCT02852694; Pre-results.

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