Validation of cAMP phosphodiesterase-4D7 (PDE4D7) for its independent contribution to risk stratification in a prostate cancer patient cohort with longitudinal biological outcomes.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5069-5069
Author(s):  
Jos Rijntjes ◽  
Marcia Alves de Inda ◽  
Dianne van Strijp ◽  
Eveline den Biezen-Timmermans ◽  
Anne van Brussel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Risk Stratification ◽  
Surgical Margin ◽  
Low Risk ◽  
Camp Phosphodiesterase ◽  
Historical Cohort ◽  
Clinical Risk ◽  
Psa Relapse ◽  
Biological Outcomes

5069 Background: In this study we present the retrospective validation of the prognostic prostate cancer biomarker PDE4D7 in predicting longitudinal biological outcomes in a historical cohort of radical prostatectomy patients. Methods: Biopsy punches from 550 patients were collected from a representative tumor area of FFPE surgical resections. RNA was extracted and PDE4D7 quantified by one-step RT-qPCR. PDE4D7 scores were calculated by normalization of PDE4D7 to the averaged expression of four reference genes. The independent prognostic value of the PDE4D7 scores were evaluated using uni- and multivariate Cox proportional hazard regression. Multivariate analyses were adjusted for clinical prognostic variables. Post-surgical outcomes tested were: PSA relapse, start of salvage treatment, progression to metastases, overall and prostate cancer specific mortality. Logistic regression was used to create a combined prognostic model of PDE4D7 with clinical risk and tested in outcome prediction. Results: The PDE4D7 score was significantly associated with time to PSA failure after prostatectomy (HR 0.53; 95% CI 0.41-0.67 for each unit increase; p < 1.0E-04). After adjustment for pathology Gleason, pT stage, surgical margin status, and seminal vesicle invasion the HR was 0.55 (95% CI 0.43-0.72; p < 1.0E-04). Patients with a high PDE4D7 score that were clinically classified as intermediate to high risk of progression were re-classified into a group with an average progression risk less than the average cohort risk of clinically very low risk patients. The maximum benefit, compared to Gleason score, was observed in the clinically intermediate favorable risk group. Combining clinical risk with PDE4D7 scores improved the overall risk stratification. Conclusions: The PDE4D7 score has potential to provide independent risk information and, in particular, to re-stratify patients with clinical intermediate to high risk characteristics to a very low risk profile.

scholarly journals Age dependence of modern clinical risk groups for localized prostate cancer – a population-based study

2019 ◽  
Author(s):  
Minh-Phuong Huynh-Le ◽  
Tor Åge Myklebust ◽  
Christine H. Feng ◽  
Roshan Karunamuni ◽  
Tom Børge Johannesen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Gleason Score ◽  
Risk Group ◽  
Risk Groups ◽  
Low Risk ◽  
Intermediate Risk ◽  
Clinical Risk ◽  
High Risk Disease ◽  
Clinical Risk Groups

AbstractBackgroundOptimal prostate cancer (PCa) screening strategies will focus on men most likely to have potentially-lethal, localized disease. Age-specific incidence rates (ASIRs) for clinical risk groups could guide risk-stratified screening.ObjectiveDetermine ASIRs and proportions of PCa diagnoses in Norway for modern risk-group and Gleason score categories.Design, Setting, and ParticipantsAll men diagnosed with PCa in Norway in 2014-2017 (n=20,356).Outcome Measurements and Statistical AnalysisPatients were assigned to clinical risk groups: low, favorable-intermediate, unfavorable-intermediate, high, regional, and metastatic, using Gleason score and clinical stage. Associations were assessed between age and (1) Gleason score (including Gleason 3+4 and 4+3) and (2) PCa risk group. Risk-group ASIRs were calculated by multiplying the overall Norwegian ASIR by the proportions observed for each category.ResultsOlder age was significantly associated with higher Gleason score and more advanced disease. For example, among men aged 55-59, 65-69, 75-79, and 85-89 years, the percentage with Gleason 8-10 disease was 16.5%, 23.4%, 37.2%, and 59.9%, respectively (p<0.001); the percentage with at least high-risk disease was 29.3%, 39.1%, 60.4%, and 90.6%, respectively. Corresponding percentages for low-risk PCa were 24.0%, 17.9%, 10.2%, and 4.1% (p<0.001). The respective maximum ASIRs (per 100,000 men) for low-risk, favorable-intermediate-risk, unfavorable-intermediate-risk, high-risk, regional, and metastatic disease were: 157.1, 183.8, 194.8, 408.3, 172.3, and 330.0; incidence for low-risk and favorable-intermediate-risk PCa peaked before age 70, while more advanced categories peaked after 70. At age 75-79 years, the ASIR of high-risk disease was approximately 6 times greater than at 55-59 years.ConclusionsRisk of clinically-significant, localized PCa increases with age. Healthy older men may be among those most likely to benefit from PCa screening.

Plasma Biomarker Profiling In Langerhans Cell Histiocytosis: Risk-Stratifying The Inflammatory Storm

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2854-2854
Author(s):  
Miguel Dario Cantu ◽  
Tricia L Peters ◽  
Karen Phaik-Har Lim ◽  
Albert Shih ◽  
Rikhia Chakraborty ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Stratification ◽  
Langerhans Cell Histiocytosis ◽  
Risk Groups ◽  
Langerhans Cell ◽  
Response To Therapy ◽  
Low Risk ◽  
Clinical Risk ◽  
Clinical Risk Groups ◽  
Single Lesion

Abstract Introduction Despite indistinguishable histology and the common feature of Birbeck granules in lesion biopsies, clinical presentation of patients with Langerhans Cell Histiocytosis (LCH) is highly variable, from single lesion cured by curretage, to multi-system disease requiring aggressive chemotherapy or stem cell transplant. Risk stratification for Langerhans Cell Histiocytosis has historically assigned clinical risk groups based on anatomic location and extent of LCH lesions, which is the basis for dose and duration of chemotherpy on recent Histiocyte Society trials. In this study, we test the hypothesis that distinct subgroups of patients with LCH may be identified by relative levels of circulating biomarkers. Methods Pre-therapy plasma was collected on 97 patients with LCH (82 Pediatric: 17 High-Risk, 23 Multisystem/Multifocal “Non-risk”, 42 Single Lesion “Non-risk”; 15 Adult: 5 High-Risk, 5 Multisystem/Multifocal “Non-risk”, 5 Single Lesion “Non-risk”) and 49 control subjects (32 Pediatric, 17 Adult). Quantitative levels of plasma proteins (158 analytes) was determined by multiplex analysis with Millipore MagPix kits and the Luminex plate reader. Data were analyzed with both unsupervised and supervised methodologies. Results Consensus clustering with non-negative matrix factorization (NMF) clusters identified three groups which were analyzed along with clinical categories. Significant clinical variables included age (adult samples clustered in NMF group 1) and LCH risk category (High-Risk LCH samples clustered in NMF group 3). Samples from patients with the BRAF-V600Emutation or relapse within 1 year did not cluster into any NMF group with signifiance. Additionally, supervised analysis identified specific molecules that were significantly differentially expressed between different clinical categories after multiple testing correction (FDR<0.10): Pediatric LCH vs Adult LCH (72 molecules significant, largest differences in MMP-3, MMP-2 and osteopontin); Pediatric Control vs Pediatric LCH (66 molecules significant, largest differences in SDF-1a, IL-20, MIP-1d, FGF-2 and sIL-4R); Pediatric Low-Risk vs Pediatric High-Risk (47 molecules significant, largest differences in sTNF-R11, sTNF-RI, I-309, sIL2Ra and osteopontin). While previous studies have analyzed expression differences of cytokines in LCH lesions and plasma, in this study the most striking differences are between control vs LCH samples are chemokine molecules. The largest differences between Low-Risk and High-Risk LCH patients include inflammatory cytokines and receptors. Conclusions Despite mounting evidence supporting pathogenesis of LCH as a myeloid neoplasia arising from immature dendritic cell precursors, these results are consistent with exuberant chemokine and cytokine expression in patients with active LCH, supporting a potential role for inflammation in pathogenesis. This study demonstrates the feasibility of identifying novel LCH sub-groups according to plasma protein profiles with unsupervised analysis, and significant differences can be detected in protein levels between clinical risk groups. Future studies will validate the clinical utility of plasma biomarkers in diagnosis, risk-stratification and determining response to therapy. Finally, feasibility of collecting plasma compared to viable lesions makes plasma studies ideal for prospective collection and analysis in cooperative group studies. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Diagnosis of transition zone prostate cancer by multiparametric MRI: added value of MR spectroscopic imaging with sLASER volume selection

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Neda Gholizadeh ◽  
Peter B. Greer ◽  
John Simpson ◽  
Jonathan Goodwin ◽  
Caixia Fu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Transition Zone ◽  
Sensitivity And Specificity ◽  
Cancer Detection ◽  
Diagnostic Performance ◽  
Spectroscopic Imaging ◽  
Multiparametric Mri ◽  
Low Risk ◽  
Intermediate Risk

Abstract Background Current multiparametric MRI (mp-MRI) in routine clinical practice has poor-to-moderate diagnostic performance for transition zone prostate cancer. The aim of this study was to evaluate the potential diagnostic performance of novel 1H magnetic resonance spectroscopic imaging (MRSI) using a semi-localized adiabatic selective refocusing (sLASER) sequence with gradient offset independent adiabaticity (GOIA) pulses in addition to the routine mp-MRI, including T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI) and quantitative dynamic contrast enhancement (DCE) for transition zone prostate cancer detection, localization and grading. Methods Forty-one transition zone prostate cancer patients underwent mp-MRI with an external phased-array coil. Normal and cancer regions were delineated by two radiologists and divided into low-risk, intermediate-risk, and high-risk categories based on TRUS guided biopsy results. Support vector machine models were built using different clinically applicable combinations of T2WI, DWI, DCE, and MRSI. The diagnostic performance of each model in cancer detection was evaluated using the area under curve (AUC) of the receiver operating characteristic diagram. Then accuracy, sensitivity and specificity of each model were calculated. Furthermore, the correlation of mp-MRI parameters with low-risk, intermediate-risk and high-risk cancers were calculated using the Spearman correlation coefficient. Results The addition of MRSI to T2WI + DWI and T2WI + DWI + DCE improved the accuracy, sensitivity and specificity for cancer detection. The best performance was achieved with T2WI + DWI + MRSI where the addition of MRSI improved the AUC, accuracy, sensitivity and specificity from 0.86 to 0.99, 0.83 to 0.96, 0.80 to 0.95, and 0.85 to 0.97 respectively. The (choline + spermine + creatine)/citrate ratio of MRSI showed the highest correlation with cancer risk groups (r = 0.64, p < 0.01). Conclusion The inclusion of GOIA-sLASER MRSI into conventional mp-MRI significantly improves the diagnostic accuracy of the detection and aggressiveness assessment of transition zone prostate cancer.

Identification of Molecular Biomarkers and Pathways for Risk Stratification in Human Papilloma Virus-Associated Cancers

2021 ◽  
Author(s):  
Eun Jung Kwon ◽  
Hye Ran Lee ◽  
Ju Ho Lee ◽  
Mihyang Ha ◽  
Yun Hak Kim ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Stratification ◽  
Expression Patterns ◽  
Risk Groups ◽  
Molecular Biomarkers ◽  
Low Risk ◽  
Receptor Interaction ◽  
Prognostic Impact ◽  
Tumor Microenvironments ◽  
Cell Immunity

Abstract Background: Human papillomavirus (HPV) is the major cause of cervical cancer (CC) etiology; its contribution to head and neck cancer (HNC) incidence is steadily increasing. As individual patients’ response to the treatment of HPV-associated cancer is variable, there is a pressing need for the identification of biomarkers for risk stratification that can help determine the intensity of treatment. Methods: We have previously reported a novel prognostic and predictive indicator (HPPI) scoring system in HPV-associated cancers regardless of the anatomical locations by analyzing the TCGA and GEO databases. In this study, we comprehensively investigated the association of group-specific expression patterns of common differentially expressed genes (DEGs) between high-risk and low-risk groups in HPV-associated CC and HNC, identifying a molecular biomarkers and pathways for the risk stratification. Results: Among the identified 174 DEGs, expression of the genes associated with extracellular matrix (ECM)-receptor interaction pathway (ITGA5, ITGB1, LAMB1, LAMC1) were increased in high-risk groups in both HPV-associated CC and HNC while expression of the genes associated with the T-cell immunity (CD3D, CD3E, CD8B, LCK, and ZAP70) were decreased vise versa. The individual genes showed statistically significant prognostic impact on HPV-associated cancers but not on HPV-negative cancers. The expression levels of identified genes were similar between HPV-negative and HPV-associated high-risk groups with distinct expression patterns only in HPV-associated low-risk groups. Each group of genes showed negative correlations, and distinct patterns of immune cell infiltration in tumor microenvironments. Conclusion: These results identify molecular biomarkers and pathways for risk stratification in HPV-associated cancers regardless of anatomical locations. The identified targets are selectively working in only HPV-associated cancers, but not in HPV-negative cancers indicating possibility of the selective targets governing HPV-infective tumor microenvironments.

The national impact of the COVID-19 pandemic on U.S. prostate cancer community care.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5061-5061
Author(s):  
Matthew R. Cooperberg ◽  
Paul Brendel ◽  
Daniel J. Lee ◽  
Rahul Doraiswami ◽  
Hariesh Rajasekar ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Language Processing ◽  
Care Delivery ◽  
Specific Antigen ◽  
Risk Groups ◽  
Low Risk ◽  
T Stage ◽  
Risk Stratum ◽  
The Impact

5061 Background: We used data from a specialty-wide, community-based urology registry to determine trends in outpatient prostate cancer (PCa) care during the COVID-19 pandemic. Methods: 3,165 (̃ 25%) of US urology providers, representing 48 states and territories, participate in the American Urological Association Quality (AQUA) Registry, which collects data via automated extraction from electronic health record systems. We analyzed trends in PCa care delivery from 156 practices contributing data in 2019 and 2020. Risk stratification was based on prostate-specific antigen (PSA) at diagnosis, biopsy Gleason, and clinical T-stage, and we used a natural language processing algorithm to determine Gleason and T-stage from unstructured clinical notes. The primary outcome was mean weekly visit volume by PCa patients per practice (visits defined as all MD and mid-level visits, telehealth and face-to-face), and we compared each week in 2020 through week 44 (November 1) to the corresponding week in 2019. Results: There were 267,691 PCa patients in AQUA who received care between 2019 and 2020. From mid-March to early November, 2020 (week 10 – week 44) the magnitude of the decline and recovery varied by risk stratum, with the steepest drops for low-risk PCa (Table). For 2020, overall mean visits per day (averaged weekly) were similar to 2019 for the first 9 weeks (̃25). Visits declined to week 14 (18.19; a 31% drop from 2019), recovered to 2019 levels by week 23, and declined steadily to 11.89 (a 58% drop from 2019) as of week 44, the cut off of this analysis. Conclusions: Access to care for men with PCa was sharply curtailed by the COVID-19 pandemic, and while the impact was less for men with high-risk disease compared to those with low-risk disease, visits even for high-risk individuals were down nearly one-third and continued to fall through November. This study provides real-world evidence on the magnitude of decline in PCa care across risk groups. The impact of this decline on cancer outcomes should be followed closely.[Table: see text]

scholarly journals Pre-hospital risk assessment in suspected non-ST-elevation acute coronary syndrome: A prospective observational study

2018 ◽  
Vol 9 (1_suppl) ◽  
pp. 5-12 ◽  
Author(s):  
Dominique N van Dongen ◽  
Rudolf T Tolsma ◽  
Marion J Fokkert ◽  
Erik A Badings ◽  
Aize van der Sluis ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
High Risk ◽  
Risk Stratification ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Heart Score ◽  
Coronary Syndrome ◽  
Risk Patients ◽  
St Elevation

Background: Pre-hospital risk stratification of non-ST-elevation acute coronary syndrome (NSTE-ACS) by the complete HEART score has not yet been assessed. We investigated whether pre-hospital risk stratification of patients with suspected NSTE-ACS using the HEART score is accurate in predicting major adverse cardiac events (MACE). Methods: This is a prospective observational study, including 700 patients with suspected NSTE-ACS. Risk stratification was performed by ambulance paramedics, using the HEART score; low risk was defined as HEART score ⩽ 3. Primary endpoint was occurrence of MACE within 45 days after inclusion. Secondary endpoint was myocardial infarction or death. Results: A total of 172 patients (24.6%) were stratified as low risk and 528 patients (75.4%) as intermediate to high risk. Mean age was 53.9 years in the low risk group and 66.7 years in the intermediate to high risk group ( p<0.001), 50% were male in the low risk group versus 60% in the intermediate to high risk group ( p=0.026). MACE occurred in five patients in the low risk group (2.9%) and in 111 (21.0%) patients at intermediate or high risk ( p<0.001). There were no deaths in the low risk group and the occurrence of acute myocardial infarction in this group was 1.2%. In the high risk group six patients died (1.1%) and 76 patients had myocardial infarction (14.4%). Conclusions: In suspected NSTE-ACS, pre-hospital risk stratification by ambulance paramedics, including troponin measurement, is accurate in differentiating between low and intermediate to high risk. Future studies should investigate whether transportation of low risk patients to a hospital can be avoided, and whether high risk patients benefit from immediate transfer to a hospital with early coronary angiography possibilities.

scholarly journals Establishment of an Ultrasound Malignancy Risk Stratification Model for Thyroid Nodules Larger Than 4 cm

2021 ◽  
Vol 11 ◽  
Author(s):  
Xuehua Xi ◽  
Ying Wang ◽  
Luying Gao ◽  
Yuxin Jiang ◽  
Zhiyong Liang ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Stratification ◽  
Diagnostic Performance ◽  
Thyroid Nodules ◽  
Low Risk ◽  
Validation Dataset ◽  
Intermediate Risk ◽  
Solid Mass ◽  
Incidence And Mortality ◽  
Risk Stratification Model

BackgroundThe incidence and mortality of thyroid cancer, including thyroid nodules &gt; 4 cm, have been increasing in recent years. The current evaluation methods are based mostly on studies of patients with thyroid nodules &lt; 4 cm. The aim of the current study was to establish a risk stratification model to predict risk of malignancy in thyroid nodules &gt; 4 cm.MethodsA total of 279 thyroid nodules &gt; 4 cm in 267 patients were retrospectively analyzed. Nodules were randomly assigned to a training dataset (n = 140) and a validation dataset (n = 139). Multivariable logistic regression analysis was applied to establish a nomogram. The risk stratification of thyroid nodules &gt; 4 cm was established according to the nomogram. The diagnostic performance of the model was evaluated and compared with the American College Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS), Kwak TI-RADS and 2015 ATA guidelines using the area under the receiver operating characteristic curve (AUC).ResultsThe analysis included 279 nodules (267 patients, 50.6 ± 13.2 years): 229 were benign and 50 were malignant. Multivariate regression revealed microcalcification, solid mass, ill-defined border and hypoechogenicity as independent risk factors. Based on the four factors, a risk stratified clinical model was developed for evaluating nodules &gt; 4 cm, which includes three categories: high risk (risk value = 0.8-0.9, with more than 3 factors), intermediate risk (risk value = 0.3-0.7, with 2 factors or microcalcification) and low risk (risk value = 0.1-0.2, with 1 factor except microcalcification). In the validation dataset, the malignancy rate of thyroid nodules &gt; 4 cm that were classified as high risk was 88.9%; as intermediate risk, 35.7%; and as low risk, 6.9%. The new model showed greater AUC than ACR TI-RADS (0.897 vs. 0.855, p = 0.040), but similar sensitivity (61.9% vs. 57.1%, p = 0.480) and specificity (91.5% vs. 93.2%, p = 0.680).ConclusionMicrocalcification, solid mass, ill-defined border and hypoechogenicity on ultrasound may be signs of malignancy in thyroid nodules &gt; 4 cm. A risk stratification model for nodules &gt; 4 cm may show better diagnostic performance than ACR TI-RADS, which may lead to better preoperative decision-making.

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