scholarly journals Risk-stratification of HPV-positive women with low-grade cytology by FAM19A4/miR124-2 methylation and HPV genotyping

2021 ◽  
Author(s):  
Stèfanie Dick ◽  
Frederique J. Vink ◽  
Daniëlle A. M. Heideman ◽  
Birgit I. Lissenberg-Witte ◽  
Chris J. L. M. Meijer ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Positive Result ◽  
Substantial Reduction ◽  
Low Grade ◽  
Discriminative Power ◽  
Methylation Analysis ◽  
Hpv Genotyping ◽  
Hpv Screening ◽  
Triage Test ◽  
Direct Referral

Abstract Background The introduction of primary HPV screening has doubled the number of colposcopy referrals because of the direct referral of HPV-positive women with a borderline or mild dyskaryosis (BMD) cytology (ASC-US/LSIL) triage test. Further risk-stratification is warranted to improve the efficiency of HPV-based screening. Methods This study evaluated the discriminative power of FAM19A4/miR124-2 methylation, HPV16/18 genotyping and HPV16/18/31/33/45 genotyping in HPV-positive women with BMD (n = 294) in two Dutch screening trials. Absolute CIN3+ risks and colposcopy referrals within one screening round were calculated. Results Methylation analysis discriminated well, yielding a CIN3+ risk of 33.1% after a positive result and a CIN3+ risk of 9.8% after a negative result. HPV16/18 and HPV16/18/31/33/45 genotyping resulted in a 27.6% and 24.6% CIN3+ risk after a positive result, and a 13.2% and 9.1% CIN3+ risk after a negative result. Colposcopy referral percentages were 41.2%, 43.2%, and 66.3% for FAM19A4/miR124-2 methylation, HPV16/18 and HPV16/18/31/33/45 genotyping, respectively. The CIN3+ risk after a negative result could be lowered to 2.8% by combining methylation and extended genotyping, at the expense of a higher referral percentage of 75.5%. Conclusion The use of FAM19A4/miR124-2 methylation and/or HPV genotyping in HPV-positive women with BMD can lead to a substantial reduction in the number of direct colposcopy referrals.

scholarly journals Clinical use of the SelectMDx urinary-biomarker test with or without mpMRI in prostate cancer diagnosis: a prospective, multicenter study in biopsy-naïve men

2021 ◽  
Author(s):  
Rianne J. Hendriks ◽  
Marloes M. G. van der Leest ◽  
Bas Israël ◽  
Gerjon Hannink ◽  
Anglita YantiSetiasti ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Stratification ◽  
Specific Antigen ◽  
Low Grade ◽  
Diagnostic Study ◽  
High Grade ◽  
Net Benefit ◽  
Conditional Strategy ◽  
Detection Rates ◽  
Guided Biopsy

Abstract Background Risk stratification in men with suspicion of prostate cancer (PCa) requires reliable diagnostic tests, not only to identify high-grade PCa, also to minimize the overdetection of low-grade PCa, and reduction of “unnecessary” prostate MRIs and biopsies. This study aimed to evaluate the SelectMDx test to detect high-grade PCa in biopsy-naïve men. Subsequently, to assess combinations of SelectMDx test and multi-parametric (mp) MRI and its potential impact on patient selection for prostate biopsy. Methods This prospective multicenter diagnostic study included 599 biopsy-naïve patients with prostate-specific antigen level ≥3 ng/ml. All patients underwent a SelectMDx test and mpMRI before systematic transrectal ultrasound-guided biopsy (TRUSGB). Patients with a suspicious mpMRI also had an in-bore MR-guided biopsy (MRGB). Histopathologic outcome of TRUSGB and MRGB was used as reference standard. High-grade PCa was defined as ISUP Grade Group (GG) ≥ 2. The primary outcome was the detection rates of low- and high-grade PCa and number of biopsies avoided in four strategies, i.e., (1) SelectMDx test-only, (2) mpMRI-only, (3) SelectMDx test followed by mpMRI when SelectMDx test was positive (conditional strategy), and (4) SelectMDx test and mpMRI in all (joint strategy). A positive SelectMDx test outcome was a risk score of ≥−2.8. Decision curve analysis (DCA) was performed to assess clinical utility. Results Prevalence of high-grade PCa was 31% (183/599). Thirty-eight percent (227/599) of patients had negative SelectMDx test in whom biopsy could be avoided. Low-grade PCa was not detected in 35% (48/138) with missing 10% (18/183) high-grade PCa. Yet, mpMRI-only could avoid 49% of biopsies, not detecting 4.9% (9/183) of high-grade PCa. The conditional strategy reduces the number of mpMRIs by 38% (227/599), avoiding biopsy in 60% (357/599) and missing 13% (24/183) high-grade PCa. Low-grade PCa was not detected in 58% (80/138). DCA showed the highest net benefit for the mpMRI-only strategy, followed by the conditional strategy at-risk thresholds >10%. Conclusions SelectMDx test as a risk stratification tool for biopsy-naïve men avoids unnecessary biopsies in 38%, minimizes low-grade PCa detection, and misses only 10% high-grade PCa. Yet, using mpMRI in all patients had the highest net benefit, avoiding biopsy in 49% and missing 4.9% of high-risk PCa. However, if mpMRI availability is limited or expensive, using mpMRI-only in SelectMDx test positive patients is a good alternative strategy.

scholarly journals A urine-based DNA methylation assay to facilitate early detection and risk stratification of bladder cancer

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Weimei Ruan ◽  
Xu Chen ◽  
Ming Huang ◽  
Hong Wang ◽  
Jiaxin Chen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bladder Cancer ◽  
Risk Stratification ◽  
Early Stage ◽  
Operative Risk ◽  
Low Grade ◽  
Single Center ◽  
Detection Model ◽  
Methylation Assay ◽  
Muscle Invasive

Abstract Background Current non-invasive tests have limited sensitivities and lack capabilities of pre-operative risk stratification for bladder cancer (BC) diagnosis. We aimed to develop and validate a urine-based DNA methylation assay as a clinically feasible test for improving BC detection and enabling pre-operative risk stratifications. Methods A urine-based DNA methylation assay was developed and validated by retrospective single-center studies in patients of suspected BC in Cohort 1 (n = 192) and Cohort 2 (n = 98), respectively. In addition, a prospective single-center study in hematuria patient group (Cohort 3, n = 174) was used as a second validation of the model. Results The assay with a dual-marker detection model showed 88.1% and 91.2% sensitivities, 89.7% and 85.7% specificities in validation Cohort 2 (patients of suspected BC) and Cohort 3 (patients of hematuria), respectively. Furthermore, this assay showed improved sensitivities over cytology and FISH on detecting low-grade tumor (66.7–77.8% vs. 0.0–22.2%, 0.0–22.2%), Ta tumor (83.3% vs. 22.2–41.2%, 44.4–52.9%) and non-muscle invasive BC (NMIBC) (80.0–89.7% vs. 51.5–52.0%, 59.4–72.0%) in both cohorts. The assay also had higher accuracies (88.9–95.8%) in diagnosing cases with concurrent genitourinary disorders as compared to cytology (55.6–70.8%) and FISH (72.2–77.8%). Meanwhile, the assay with a five-marker stratification model identified high-risk NMIBC and muscle invasive BC with 90.5% sensitivity and 86.8% specificity in Cohort 2. Conclusions The urine-based DNA methylation assay represents a highly sensitive and specific approach for BC early-stage detection and risk stratification. It has a potential to be used as a routine test to improve diagnosis and prognosis of BC in clinic.

The role of cardiopulmonary exercise testing in a contemporary heart failure population

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
P Garcia Bras ◽  
A Valentim Goncalves ◽  
J Reis ◽  
T Pereira Da Silva ◽  
R Ilhao Moreira ◽  
...  
Keyword(s):  
Heart Failure ◽  
Risk Stratification ◽  
Exercise Testing ◽  
Predictive Power ◽  
Cardiopulmonary Exercise Testing ◽  
Composite Endpoint ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Discriminative Power ◽  
Cardiopulmonary Exercise

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Cardiopulmonary exercise testing (CPET) is used for risk stratification in patients with chronic heart failure (CHF). However, there is a lack of information regarding CPET prognostic power in patients under new HF therapies such as sacubitril/valsartan, Mitraclip, IV iron or SGLT2 inhibitors. The aim of this study was to evaluate the prognostic value of CPET parameters in a contemporary subset of patients with optimal medical and device therapy for CHF. Methods Retrospective evaluation of patients with CHF submitted to CPET in a tertiary center. Patients were followed up for 24 months for the composite endpoint of cardiac death, urgent heart transplantation or left ventricular assist device. CPET parameters, including peak oxygen consumption (pVO2) and VE/VCO2 slope, were analysed and their predictive power was measured. HF events were stratified according to cut-off values defined by the International Society for Heart and Lung Transplantation (ISHLT) guidelines: pVO2 of ≤12 mL/Kg/min and VE/VCO2 slope of >35. Results CPET was performed in 204 patients, from 2014 to 2018. Mean age was 59 ± 13 years, 83% male, with a mean left ventricular ejection fraction of 33 ± 8%, and a mean Heart Failure Survival Score of 8.6 ± 1.3. The discriminative power of CPET parameters is displayed in the Table. In patients with pVO2 ≤12 mL/Kg/min, the composite endpoint occurred in 18% of patients. A pVO2 value of ≤12 mL/Kg/min had a positive predictive power of 18% while pVO2 >12 had a negative predictive power of 93%. Regarding VE/VCO2 slope >35, the composite endpoint occurred in 13% of patients. A VE/VCO2 slope value of >35 had a positive predictive power of 13% while VE/VCO2 slope <35 had a negative predictive power or 94%. Conclusion Using ISHLT guideline cut-off values for advanced HF therapies patient selection, there was a reduced number of HF events (<20%) at 24 months in patients under optimal CHF therapy. While pVO2 and VE/VCO2 slope are still valuable parameters in risk stratification, redefining cut-off values may be necessary in a modern HF population. Discriminative power of CPET parameters Parameters HR; 95% CI AUC p-value Peak VO2 0.824 (0.728-0.934) 0.781 0.001 Percent of predicted pVO2 0.942 (0.907-0.978) 0.774 0.002 VE/VCO2 slope 1.068 (1.031-1.106) 0.756 0.008 Cardiorespiratory optimal point 1.118 (1.053-1.188) 0.746 0.004 PETCO2 maximum exercise 0.854 (0.768-0.950) 0.775 0.003 Ventilatory Power 0.358 (0.176-0.728) 0.796 0.002 HR Hazard ratio, AUC: Area under the curve, PETCO2: end-tidal CO2 pressure

scholarly journals LGG-50. INTEGRATED MOLECULAR AND CLINICAL ANALYSIS OF 1,000 PEDIATRIC LOW-GRADE GLIOMAS UNCOVERS NOVEL SUBGROUPS FOR CLINICAL RISK STRATIFICATION

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii375-iii376
Author(s):  
Uri Tabori ◽  
Scott Ryall ◽  
Michal Zapotocky ◽  
Julie Bennett ◽  
Liana Nobre ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Clinical Presentation ◽  
Mapk Pathway ◽  
Clinical Analysis ◽  
Genetic Alterations ◽  
Low Grade ◽  
Who Grade ◽  
Low Grade Gliomas ◽  
Younger Age ◽  
Risk Categories

Abstract Pediatric low-grade gliomas (pLGG) are primarily driven by genetic alterations in the RAS/MAPK pathway, most commonly involving BRAF of NF1. Despite their molecular convergence, pLGG often show unexplained variability in their clinical outcome. To address this, we molecularly characterized a cohort of >1,000 clinically annotated pLGG. 84% of cases harbored a detectable driver mutation. The remaining 16% of patients nonetheless showed RAS/MAPK pathway up-regulation at the RNA level. The clinical presentation and outcome of pLGG appeared highly variable and linked to the alteration type: re-arrangement or SNV. Re-arrangement-driven tumors were diagnosed at a younger age (6.6 versus 10.9 years, p<0.0001), enriched for WHO grade I histology (88% versus 66%, p<0.0001), infrequently progressed (27% versus 46%, p<0.0001), and rarely resulted in death (3 versus 13%, p<0.0001) as compared to SNV-driven tumors. These included the rarest molecular drivers of pLGG, for which we now have the clinicopathologic features of including MYB, MYBL1, FGFR2 fusions, FGFR1-TACC1, FGFR1 SNVs, IDH1 p.R132H, and H3.3 p.K27M. Utilizing this information, we suggest novel risk categories of pLGG that effectively predicted patient outcome. Low-risk tumors progressed infrequently and rarely succumbed to their disease (10-year PFS of 71% and OS of 98%). Intermediate-risk pLGG had a 10-year PFS and OS of 35% and 90%, respectively. High risk pLGG almost invariably progressed (10-year PFS of 0%) and these patients often succumbed to their disease (10-year OS of 41%). These data highlight the biological and clinical differences between pLGG subtypes and offers molecular based risk stratification to these cancers.

Microfluidic Assaying of Circulating Tumor Cells and its Correlation with Muscle Invasiveness and Tumor Grade of Urothelial Bladder Cancer

2021 ◽  
Author(s):  
Guanghou Fu ◽  
Kok Suen Cheng ◽  
Anqi Chen ◽  
Zhijie Xu ◽  
Xiaoyi Chen ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Risk Stratification ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Tumor Grade ◽  
Invasive Bladder Cancer ◽  
Low Grade ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

Abstract Background: Bladder cancer is characterized by its frequent recurrence and progression. Effective treatment strategies need to be based on an accurate risk stratification, in which muscle invasiveness and tumor grade represent the two most important factors. Traditional imaging techniques provide preliminary information about muscle invasiveness but are lacking in terms of accuracy. Although as the gold standard, pathological biopsy is only available after the surgery and cannot be performed longitudinally for long-term surveillance. Methods: In this work, we developed a microfluidic approach that interrogates circulating tumor cells (CTCs) in the peripheral blood of bladder cancer patients to reflect the risk stratification of the disease. Results：In a cohort of 48 bladder cancer patients comprising 33 non-muscle invasive bladder cancer (NMIBC) cases and 15 muscle invasive bladder cancer (MIBC) cases, the CTC count was found to be considerably higher in the MIBC group compared with the NMIBC group (4.67 vs. 1.88 CTCs/3 mL, P=0.019), and was significantly higher in high-grade bladder cancer patients verses low-grade bladder cancer patients (3.69 vs. 1.18 CTCs/3mL, P=0.024). Conclusions: This microfluidic assay of CTCs is believed to be a promising complementary tool for the risk stratification of bladder cancer.Trial registration: This research was conducted under the approval of the Ethics Committee of the First Affiliated Hospital at Zhejiang University School of Medicine with the Registration No. 2015-218.

scholarly journals 1158 – Risk Stratification of Barrett's Esophagus with Low-Grade Dysplasia Using Volumetric Laser Endomicroscopy

2019 ◽  
Vol 156 (6) ◽  
pp. S-249
Author(s):  
Allon Kahn ◽  
Amrit Kamboj ◽  
Prasad G. Iyer ◽  
Kenneth K. Wang ◽  
Cadman L. Leggett
Keyword(s):  
Risk Stratification ◽  
Barrett’S Esophagus ◽  
Barrett's Esophagus ◽  
Low Grade ◽  
Low Grade Dysplasia
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