scholarly journals New risk model is able to identify patients with a low risk of progression in systemic sclerosis

RMD Open ◽  
2021 ◽  
Vol 7 (2) ◽  
pp. e001524
Author(s):  
Nina Marijn van Leeuwen ◽  
Marc Maurits ◽  
Sophie Liem ◽  
Jacopo Ciaffi ◽  
Nina Ajmone Marsan ◽  
...  
Keyword(s):  
Machine Learning ◽  
Systemic Sclerosis ◽  
High Risk ◽  
Disease Progression ◽  
Risk Model ◽  
Immunosuppressive Drugs ◽  
Low Risk ◽  
Expert Assessment ◽  
Risk Of Progression

ObjectivesTo develop a prediction model to guide annual assessment of systemic sclerosis (SSc) patients tailored in accordance to disease activity.MethodsA machine learning approach was used to develop a model that can identify patients without disease progression. SSc patients included in the prospective Leiden SSc cohort and fulfilling the ACR/EULAR 2013 criteria were included. Disease progression was defined as progression in ≥1 organ system, and/or start of immunosuppression or death. Using elastic-net-regularisation, and including 90 independent clinical variables (100% complete), we trained the model on 75% and validated it on 25% of the patients, optimising on negative predictive value (NPV) to minimise the likelihood of missing progression. Probability cutoffs were identified for low and high risk for disease progression by expert assessment.ResultsOf the 492 SSc patients (follow-up range: 2–10 years), disease progression during follow-up was observed in 52% (median time 4.9 years). Performance of the model in the test set showed an AUC-ROC of 0.66. Probability score cutoffs were defined: low risk for disease progression (<0.197, NPV:1.0; 29% of patients), intermediate risk (0.197–0.223, NPV:0.82; 27%) and high risk (>0.223, NPV:0.78; 44%). The relevant variables for the model were: previous use of cyclophosphamide or corticosteroids, start with immunosuppressive drugs, previous gastrointestinal progression, previous cardiovascular event, pulmonary arterial hypertension, modified Rodnan Skin Score, creatine kinase and diffusing capacity for carbon monoxide.ConclusionOur machine-learning-assisted model for progression enabled us to classify 29% of SSc patients as ‘low risk’. In this group, annual assessment programmes could be less extensive than indicated by international guidelines.

scholarly journals A Novel Epigenetic Machine Learning Model to Define Risk of Progression for Hepatocellular Carcinoma Patients

2021 ◽  
Vol 22 (3) ◽  
pp. 1075
Author(s):  
Luca Bedon ◽  
Michele Dal Bo ◽  
Monica Mossenta ◽  
Davide Busato ◽  
Giuseppe Toffoli ◽  
...  
Keyword(s):  
Machine Learning ◽  
Hepatocellular Carcinoma ◽  
High Risk ◽  
Progression Free Survival ◽  
Low Risk ◽  
Functional Enrichment ◽  
Free Survival ◽  
High Risk Patients ◽  
Risk Of Progression ◽  
Risk Patients

Although extensive advancements have been made in treatment against hepatocellular carcinoma (HCC), the prognosis of HCC patients remains unsatisfied. It is now clearly established that extensive epigenetic changes act as a driver in human tumors. This study exploits HCC epigenetic deregulation to define a novel prognostic model for monitoring the progression of HCC. We analyzed the genome-wide DNA methylation profile of 374 primary tumor specimens using the Illumina 450 K array data from The Cancer Genome Atlas. We initially used a novel combination of Machine Learning algorithms (Recursive Features Selection, Boruta) to capture early tumor progression features. The subsets of probes obtained were used to train and validate Random Forest models to predict a Progression Free Survival greater or less than 6 months. The model based on 34 epigenetic probes showed the best performance, scoring 0.80 accuracy and 0.51 Matthews Correlation Coefficient on testset. Then, we generated and validated a progression signature based on 4 methylation probes capable of stratifying HCC patients at high and low risk of progression. Survival analysis showed that high risk patients are characterized by a poorer progression free survival compared to low risk patients. Moreover, decision curve analysis confirmed the strength of this predictive tool over conventional clinical parameters. Functional enrichment analysis highlighted that high risk patients differentiated themselves by the upregulation of proliferative pathways. Ultimately, we propose the oncogenic MCM2 gene as a methylation-driven gene of which the representative epigenetic markers could serve both as predictive and prognostic markers. Briefly, our work provides several potential HCC progression epigenetic biomarkers as well as a new signature that may enhance patients surveillance and advances in personalized treatment.

The 70-Gene MyPRSR prognostic Risk Score Signature Predicts Increased Risk of Progression from MGUS to Multiple Myeloma Requring Treatment

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3275-3275 ◽  
Author(s):  
Ryan van Laar ◽  
Phillip Farmer ◽  
Richard A Bender ◽  
Aga Zielinski ◽  
Kenton Leigh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
High Risk ◽  
Gene Expression Profiling ◽  
Disease Progression ◽  
Risk Score ◽  
Expression Profiling ◽  
Medical Sciences ◽  
Risk Of Progression

Abstract Background: The 70-gene prognostic risk score (MyPRS), originally developed by the University of Arkansas for Medical Sciences, is the most validated genomic assay for prediction of event free and overall survival in asymptomatic, newly diagnosed and relapsed multiple myeloma. Gene expression profiling was performed on CD138+ plasma cells obtained from the bone marrow of individuals with the precursor condition, monoclonal gammopathy of undetermined significance (MGUS), who later progressed to MM. Analysis of the 70 gene risk score vs. the probability of progression to MM requiring therapy was performed. Method and Results: Between 2011 and 2015, MyPRS gene expression profiling of 266 individuals who initially presented with MGUS was performed. The mean length of time between MGUS diagnosis and disease progression or last follow-up was 6.9 years (standard deviation = 4.0 years). The mean length of time between MGUS gene expression profiling and either disease progression or date of last follow-up was 4.8 years (standard deviation = 2.9 years). Disease progression was defined as the development of CRAB criteria or bone marrow plasmacytosis exceeding 60%. 28 patients developed MM requiring therapy within two years of their MGUS GEP. Twelve individuals (5%) were classified as high risk using the previously established threshold for AMG (GEP70 >37.2 = high risk). Four high risk patients (33%) progressed to active MM within 2 years. 24/255 (9%) patients who were classified as low risk progressed to MM within the same length of time. A risk score histogram and binary fitted line plot of risk score vs. probability of progression to MM within 2 years were generated. Conclusion: Performing MyPRS gene expression profiling on patients diagnosed with MGUS provides personalized information on the individuals' risk of progression to MM requiring treatment. While the overall rate of progression is low, approximately 5% of individuals are at higher risk and may benefit from increased monitoring. The 70-gene signature appears useful for identifying high risk behavior in MGUS patients thereby allowing early intervention and possible inclusion in clinical trials. MyPRS provides a risk assessment at a single point in time unlike recently reported metrics (ASCO Abs. # 8004) which measure a change in Hgb and M protein over time, along with bone marrow plasmacytosis, in order to determine the risk of progression. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures van Laar: Signal Genetics, Inc.: Employment. Farmer:University of Arkansas: Employment. Bender:Signal Genetics, Inc.: Employment. Zielinski:Signal Genetics, Inc.: Employment. Leigh:Signal Genetics, Inc.: Employment. Brown:Signal Genetics, Inc.: Employment. Barlogie:Mount Sinai Hospital: Employment. Morgan:Univ of AR for Medical Sciences: Employment; Bristol Meyers: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Research Funding; Celgene: Consultancy, Honoraria, Research Funding.

Inclusion of Total BODY Computed Tomography (TB-CT) SCANS In the INITIAL WORK-up of Binet STAGE A CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) PATIENTS On CLINICAL Grounds: PRELIMINARY RESULTS of the Prospective, MULTICENTER O-CLL1- GISL STUDY

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2837-2837
Author(s):  
Massimo Gentile ◽  
Giovanna Cutrona ◽  
Sonia Fabris ◽  
Emanuela Anna Pesce ◽  
Francesco Maura ◽  
...  
Keyword(s):  
High Risk ◽  
Ct Scan ◽  
Disease Progression ◽  
Low Risk ◽  
Ct Scans ◽  
Intermediate Risk ◽  
Trisomy 12 ◽  
Initial Work ◽  
Binet Stage

Abstract Abstract 2837 Rai and Binet staging systems are not devoid of some limitations, including the lack of evaluation of thoracic and abdominal lymphadenopathies. The widely-used IWCLL guidelines do not incorporate use of TB-CT scan in the diagnostic algorithm. In the present study, we investigated whether TB-CT scans could up-stage Binet stage A CLL patients included in the prospective multicenter O-CLL01 GISL study (clinicaltrial.gov ID: NCT00917549), and whether this subgroup presented differences in prognostic markers and in progression-free survival (PFS). To date, 454 patients have been enrolled and TB-CT scans were available in 238 patients. The median age was 60 years (range, 33–71) and 136 (57%) were male. According to Rai, 180 patients were at low risk (stage 0) and 58 at intermediate risk (stages I-II). b2-microglobulin was elevated in 35.5% of cases. Seventy-eight patients (32%) were IgVH unmutated, 108 patients (45%) had a high ZAP-70 expression, 45 patients (19%) were CD38 positive (>30%). FISH data were available in 226/238 cases; the most frequent abnormality was del(13)(q14) (105 pts, 46.5%), followed by trisomy 12 (24 pts, 10.6%), del(11q22.3) (13 pts 5.5%), del(17p13) (4 pts 1.8%) while 80 cases (35.4%) cytogenetics were normal. Cytogenetic abnormalities were clustered in 3 risk groups [i.e. low (del(13q14) and normal), intermediate (trisomy 12) and high risk (del(11q22) and del(17p13)]. Two hundred six out of 238 patients had a minimum follow-up of 6 months and were evaluable for PFS. Considering TB-CT scan, 54 out of 238 analyzed (22.7%) patients converted into Binet stage B. Notably, 63% were male, b2-microglobulin was elevated in 50% of cases, 42.6% were IgVH unmutated, 48.1% had a high ZAP-70 expression, 27.8% were CD38 positive, and 17.6% showed a high-risk FISH. Binet B patients showed a statistically higher rate of cases with high risk cytogenetic abnormalities than Binet A patients (17.6% vs 4.6%; p=0.032). While, no statistically different distribution of gender, age, B2-microglobulin, IgVH mutational status, CD38 or ZAP-70 expression were observed between the two subgroups. After a median follow-up of 24 months 46/206 (22%) evaluable cases showed disease progression. Binet B patients showed a PFS significantly shorter than those with a normal TB-CT (2-years PFS probability, 85.6% vs 68.5%; p<0.0001). According to the Rai classification 102/180 (56.7%) low risk patients were re-defined as intermediate risk with the integration of TB-CT scan. This subset of patients showed a statistically higher rate of cases with elevated ZAP-70 (51.5% vs 35.9%; p=0.049) and CD38 (22.5% vs 10.3%; p=0.045) than patients at low risk. After a median follow-up of 25 months, 23/154 (15%) of evaluable cases showed disease progression. Patients with an intermediate risk Rai stage showed a PFS significantly shorter than those with a low risk (2-years PFS probability, 82% vs 96%; p=0.002). In this setting 70 cases met the diagnostic criteria of monoclonal B-lymphocytosis (<5 × 109/L B- lymphocytes in the blood). With the integration of TB-CT scan 30/70 (42.9%) monoclonal B-lymphocytosis patients were re-defined as intermediate risk according the Rai classification. No statistically different distribution of clinical and biological parameters were observed between cases who remained in the low risk stage and those who became at intermediate risk. After a median follow-up of 28 months 4/57 cases evaluable for PFS showed a disease progression (2 cases for each subgroup). Considering low risk Rai stage, no statistical difference in PFS was observed among nonCT-upstaged MBL, CT-upstaged MBL, nonCT-upstaged Rai 0, while CT-upstaged Rai 0 cases showed a statistically shorter PFS (p<.0001) than the other groups (Figure 1). Finally, TB-CT scan allowed the early identification of a second neoplasia in 2 cases (lung cancer 1 pt, renal cell carcinoma 1 pt). Our preliminary data indicate that the integration of TB-CT scans in the clinical staging allows for an effective clinical discrimination of Binet A CLL cases in approximately 23% of cases at more advanced stages, predicting a worse clinical outcome. However, the use of TB-CT scanning for upstaging is not beneficial for predicting PFS in MBL cases. A longer follow-up will demonstrate whether the inclusion of TB-CT scan in the initial work-up of patients with early-stage CLL will provide clinically relevant prognostic information.Figure 1.PFS in Rai 0 cases.Figure 1. PFS in Rai 0 cases. Disclosures: Di Raimondo: celgene: Honoraria. Foà:Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees.

A Clinicogenetic Risk Model (m7-FLIPI) Prospectively Identifies One-Half of Patients with Early Disease Progression of Follicular Lymphoma after First-Line Immunochemotherapy

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 333-333 ◽  
Author(s):  
Jurinovic Vindi ◽  
Robert Kridel ◽  
Annette M Staiger ◽  
Monika Szczepanowski ◽  
Heike Horn ◽  
...  
Keyword(s):  
High Risk ◽  
Research Funding ◽  
Risk Model ◽  
Low Risk ◽  
First Line ◽  
Free Survival ◽  
Therapy Initiation ◽  
Line Therapy ◽  
Progression Of Disease

Abstract Background: Follicular lymphoma (FL) is the second most common nodal lymphoma worldwide and remains incurable for most patients (pts). FL is recognized to be a highly heterogeneous disease and a subset of pts experience remarkable poor outcome. In a recent study, 19-26% of pts receiving first-line R-CHOP experienced progression of disease (POD) within 24 months after diagnosis and had a 5-year (yr) overall survival (OS) of only 34-50%, as compared to a 5-yr OS of 90-94% for pts without POD within 24 months (Casulo et al., J Clin Oncol 2015). Consequently, event-free survival at 12 (EFS12) and 24 months (EFS24) have been suggested as novel surrogate endpoints for poor overall survival in clinical trials and useful for patient counseling (Maurer et al., ASH 2014). We have previously shown that a clinicogenetic risk model (m7-FLIPI) that includes the mutation status of seven genes (EZH2, ARID1A, MEF2B, EP300, FOXO1, CREBBP, and CARD11), the FL International Prognostic Index (FLIPI), and the Eastern Cooperative Oncology Group (ECOG) performance status, improves risk stratification for failure-free survival (FFS) and OS in pts with FL receiving first-line immunochemotherapy (Pastore et al., Lancet Oncology 2015). An online tool is available at: http://www.glsg.de/m7-flipi. It would be advantageous to determine prognosis prior to front-line therapy rather than after POD. Thus, we aimed to investigate the predictive utility of the m7-FLIPI for early POD. Patients and Methods: Clinical and mutation data were available from two independent cohorts: 151 pts who received R-CHOP and IFN maintenance as part of a randomized trial of the German Low-Grade Lymphoma Study Group (GLSG), and 107 pts from a population-based registry of the British Columbia Cancer Agency (BCCA) who received R-CVP. Among the latter, 93 (87%) received R-maintenance by intention to treat. All pts had symptomatic, advanced stage or bulky disease considered ineligible for curative radiotherapy, and a biopsy specimen obtained </=12 months prior to the initiation of first-line therapy. POD was defined as progression, relapse, or death due to any cause. POD12 and POD24 were defined based on POD status at 12 and 24 months after therapy initiation, respectively. Logistic regression analysis was performed to assess if m7-FLIPI was predictive of early POD using the statistical software R (version 3.1.2). Results: In the GLSG cohort, median age was 57 yrs (range 27-77), 51% had high-risk FLIPI, and 5-yr failure-free survival (FFS) and OS rates were 66% and 83%, respectively (median follow-up for OS 7.7 yrs). In the BCCA cohort, median age was higher (62 yrs, 37-83), but high-risk FLIPI was similarly frequent (50%); 5-yr FFS and OS rates were 58% and 74%, respectively (median follow-up for OS 6.7 yrs). A total of 43 GLSG (28%) and 24 BCCA pts (22%) were classified as high-risk by m7-FLIPI, with a 5-yr OS of 65% and 42%, respectively. In the GLSG cohort, 8 (5%) and 29 pts (19%) had POD within 12 and 24 months, respectively, 4 and 10 pts were censored before POD12 and POD24 (table). High-risk m7-FLIPI pts were significantly more likely to experience early POD with an Odds Ratio (OR) of 20.80 (95% confidence interval (CI) 3.53-395.96; p=0.0052) for POD12 and 6.33 (95% CI 2.67-15.69; p<0.0001) for POD24. Likewise, in the BCCA cohort, 16 (15%) and 28 pts (26%) experienced POD12 and POD24, respectively (table). The OR for high-risk m7-FLIPI pts was 4.69 (95% CI 1.52-14.65; p=0.0068) for POD12, and 5.36 (95% CI 2.03-14.60; p=0.0008) for POD24. In the GLSG and BCCA cohorts, the m7-FLIPI had a sensitivity of 88% and 50%, a specificity of 75% and 82%, a positive predictive value (PPV) of 16 and 33%, and a negative predictive value (NPV) of 96% and 90% to predict POD12. For POD24, sensitivity was 62% and 46%, specificity 79% and 86%, PPV 42% and 54%, and NPV 82% and 82%, respectively. Conclusion: We conclude that patients classified as high-risk m7-FLIPI are highly enriched among those with early progression of disease. However, approximately one-half of patients with progression by 24 months after therapy initiation are classified as low-risk m7-FLIPI. Thus, further efforts are needed to refine the m7-FLIPI and thereby capture additional cases that may benefit from innovative first-line approaches. Table. Population m7-FLIPI N POD12 POD24 GLSG Total 151 8/147* 29/141* High-risk 43 7 18 Low-risk 108 1 11 BCCA Total 107 16/107 28/107 High-risk 24 8 13 Low-risk 83 8 15 *Pts censored were removed Disclosures Ansell: Bristol-Myers Squibb: Research Funding; Celldex: Research Funding.

MO040LONG-TERM FOLLOW-UP OF IGA NEPHROPATHY PATIENTS AT HIGH RISK OF PROGRESSION ACCORDING TO THE THERAPEUTIC APPROACH EMPLOYED: A MULTICENTER RETROSPECTIVE STUDY OF 947 PATIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Federico Alberici ◽  
Ivano Baragetti ◽  
Francesca Ferrario ◽  
Serena Ponti ◽  
Chiara Salviani ◽  
...  
Keyword(s):  
High Risk ◽  
Therapeutic Approach ◽  
Immunosuppressive Drugs ◽  
Free Survival ◽  
Risk Of Progression ◽  
Time Average ◽  
Group 2 ◽  
Group 1

Abstract Background and Aims IgA-nephropathy (IgA-N) is a frequent cause of CKD and ESRD. The optimal therapeutic approach and the role of glucocorticoids and immunosuppression is still debated. Aim of this study was to perform a survey across several Italian centers focusing on the long-term outcome of patients with IgA-N at high risk of progression stratified according to the therapeutic approach employed. Method All the consecutive patients affected by biopsy proven IgA-N, proteinuria &gt;1g/day and a follow-up longer than 24 months have been collected across 48 centers. The population has been divided in three groups according to the therapeutic approach: group-1 received ACEi or ARBs alone, group-2 a six months course of glucocorticoids while group-3 glucocorticoids and immunosuppressive drugs. Primary endpoints have been ESRD free-survival, halving of the eGFR free-survival and rate of non-responders (NR, proteinuria &gt;1 g/day). Secondary endpoints have been assessment of the prognostic role of the time average proteinuria (TAP) as well as of the time average slope of proteinuria (TASP) and rate of severe adverse events (SAEs). Results 947 patients have been included and followed for a median time of 60 months (IQR 24-96). Baseline eGFR and proteinuria in the three groups have been respectively 68.1 (95%CI 63.9-72.4)-67.8 (95%CI 65.3-70.3)-63.3 (95%CI 58.5-68.1) ml/min/1.73m2 (p=0.191) and 2.38 (95%CI 2-2.77)-2.65 (95%CI 2.49-2.82)-3.26 (95%CI 2.89-3.64) g/day (p&lt;0.001). Respectively 76/586 (13%) and 28/167 (17%) of the patients in group-2 and 3 required re-treatment with glucocorticoids alone or in combination with immunosuppressive drugs after a median of 24 months from the first cycle. ESRD free-survival has been longer in the group-2 (p=0.004) (figure, panel A); at subgroup analysis this was restricted to the patients with a eGFR&lt;50 ml/min (p=0.004) (figure, panel B) while only a trend was observed in the ones with eGFR ≥50 ml/min (p=0.0631). The halving of the eGFR free-survival has been longer in group-2 only when limiting the analyses to the subgroup with eGFR&lt;50 ml/min (p=0.026) (figure, panel C). The proportion of NR has been significantly lower in group-2 compared to group-1 throughout the first 36 months of follow-up (figure, panel D); of note being NR during the first 36 months increased the risk of developing ESRD during the follow-up (OR 4 95%CI 2.2-7.3, p&lt;0.0001). The TAP and TASP of the first 24 months have been higher in the patients developing ESRD (respectively, mean 2.48 95%CI 2.14-2.82 and 0.81 95%CI 0.70-0.92) compared to the other patients (mean 1.12 95%CI 1.2-1.32 and 0.59 95%CI 0.56-0.61) (p&lt;0.0001 for both comparisons). Of note the 24 months TASP of group-2 was lower compared to group-1 (respectively mean 0.56 95%CI 0.54-0.59 and 0.79 95%CI 0.71-0.87) (p&lt;0.0001). The rate of patients experiencing SAEs during the first 6 months of therapy in the three groups has been respectively 2%, 7% and 16%; of these withdrawn of the therapeutic approach employed has been necessary in 67%, 21% and 48%. During the whole follow-up the number of SAEs per 100 patients/years has been respectively 1.9-2.7 and 2.5 in the 3 groups. Conclusion In this large multicenter retrospective survey, the use of glucocorticoids in patients with IgA-N at high risk of progression has been associated to longer ESRD free-survival, longer time to the halving of the eGFR in the subgroup with eGFR &lt;50 ml/min, lower rate of non-response during the first 36 months of follow-up as well as lower TASP during the first 24 months. The overall rate of SAEs has been low but higher in the group receiving glucocorticoids alone or in combination with immunosuppressors.

scholarly journals Prostate Cancer Survival By Risk of Progression and Other Prognostic Factors in Mallorca, Spain

2021 ◽  
Author(s):  
Juan-José Montaño ◽  
Antoni Barceló ◽  
Paula Franch ◽  
Jaume Galceran ◽  
Alberto Ameijide ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Cancer Survival ◽  
Cox Regression ◽  
Strong Relationship ◽  
Low Risk ◽  
Medium Risk ◽  
Risk Of Progression ◽  
Very High

Abstract Objectives: 1) to find out the distribution of prostate cancer by risk of progression; 2) to determine the cause-specific survival by risk of progression in prostate cancer; 3) to identify the factors associated with the risk of dying from this cancer.Methods: Incident prostate cancer cases diagnosed between 2006 and 2011 were identified through the Mallorca Cancer Registry. Inclusion criteria: invasive cases with code C61.9 and any histology. Cases identified exclusively through death certificate were excluded. We collected: age; date and method of diagnosis; date of follow-up or death; T, N, M and stage according to the TNM 7th edition; Gleason score; PSA; histology according to the ICD-O 3rd edition 6 ; comorbidities and treatments. We calculated risk in 4 categories: low, medium, high and very high. End point of follow-up was 31 December 2014. Multiple imputation (MI) was performed to estimate cases with unknown risk of progression. Survival analysis was performed using the actuarial and Kaplan-Meier methods, as well as the Cox regression model.Results: We identified 2921 cases. After MI, 9.5% had low risk, 24.9% medium risk, 42.7% high risk and 22.9% very high risk. Five years after diagnosis, survival after MI was 89% globally, that being 100% for low risk cases, 96% for medium risk, 93% for high risk and 69% for very high risk. Cases with histology other than adenocarcinoma, with high and, especially, very high risk of progression, as well as with systemic, mixed and observation/unspecified treatments have worse prognosis. Treatment showed a strong relationship with age and life expectancy.Conclusions: Risk of progression and treatment were the main variables associated to survival in prostate cancer.

scholarly journals Ki67 Predicts Progression in Early CIN: Validation of a Multivariate Progression-Risk Model

2004 ◽  
Vol 26 (1-2) ◽  
pp. 13-20
Author(s):  
Arnold-Jan Kruse ◽  
Jan P. A. Baak ◽  
Emiel A. Janssen ◽  
Kjell-Henning Kjellevold ◽  
Bent Fianec ◽  
...  
Keyword(s):  
High Risk ◽  
Prognostic Value ◽  
Risk Model ◽  
Subjective Evaluation ◽  
Low Risk ◽  
Subjective Analysis ◽  
Risk Patients ◽  
Progression Risk ◽  
Quantitative Assessments

This study of early CIN biopsies (25 CIN1 and 65 CIN2) with long follow-up was done to validate, in a new group of patients, the value of Ki67 immuno-quantitative features to predict high CIN grade in a follow-up biopsy (often denoted to as “progression”), as described in a previous study. Each biopsy in the present study was classified with the previously described Ki67-model (consisting of the stratification index and the % positive nuclei in the middle third layer of the epithelium) as “low-risk” or “high-risk”, and matched with the follow-up outcome (progression-or-not). Furthermore, it was studied whether subjective evaluation of the Ki67 sections by experienced pathologists, who were aware of the prognostic quantitative Ki67 features, could also predict the outcome. Thirdly, the reproducibility of routine use of the quantitative Ki67-model was assessed. Fifteen cases progressed (17%) to CIN3, 2/25 CIN1 (8%) and 13/65 CIN2 (20%), indicating that CIN grade (as CIN1 or CIN2) is prognostic and that the percentage of CIN1 and CIN2 cases with progression in the present study is comparable to many previous studies. However, the quantitative Ki67 model had stronger prognostic value than CIN grade as none of the 40 “Ki67-model low-risk” patients progressed, in contrast to 15 (30%) of the 50 “Ki67-model high-risk” patients (p < 0.001). In multivariate analysis, neither CIN grade nor any of the other quantitative Ki67 features added to the abovementioned prognostic Ki67-model. Subjective analysis of the Ki67 features was also prognostic, although quantitative assessments gave better results. Routine application of the quantitative Ki67-model in CIN1 and CIN2 was well reproducible. In conclusion, the results confirm that quantitative Ki67 features have strong prognostic value for progression in early CIN lesions.

scholarly journals Myelodysplastic Syndromes with Isolated 20q Deletion: A New Clinical-Biological Entity?

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5516-5516
Author(s):  
Daniela De Benedittis ◽  
Luana Fianchi ◽  
Pasquale Niscola ◽  
Annalina Piccioni ◽  
Ambra Di Veroli ◽  
...  
Keyword(s):  
High Risk ◽  
Myelodysplastic Syndromes ◽  
Good Prognosis ◽  
Low Risk ◽  
Biological Entity ◽  
Entire Cohort ◽  
Prognostic Features ◽  
Erythroid Response ◽  
Risk Of Progression

Abstract Deletion of the chromosome 20 long arm (del20q) has been reported in 3-7% of patients with Myelodysplastic Syndromes (MDS). In particular, isolated del20q seems to be associated with good prognosis, low risk of progression to AML and prolonged survival: however, very few reports addressed this subset of MDS patients up to now. To highlight this issue, we collected data from all patients with MDS and isolated del20q diagnosed and followed by Centers of the Gruppo Romano-Laziale Sindromi Mielodisplastiche (GROM-L). On the whole, 53 patients were analysed: the main features at diagnosis of these patients are reported in the Table. Platelet (PLT) count was < 100 x 109/l in 28 patients (52.8%), Hb level was < 10.0 g/dl in 23 patients (43.3%) and neutrophil count was < 1.0 x 109/l in 12 patients (22.6%). As to risk prognostication, according to IPSS score 51 patients (96.2%) had low/intermediate-1 risk and 2 (3.8%) had intermediate-2/high risk: according to r-IPSS, 8 patients (15.1%) had very low risk, 20 (37.7%) low risk, 19 (35.9%) intermediate risk and 6 (11.3%) high risk. During follow-up, 14 patients (26.4%) did not need any therapy and were only observed, 36 (67.9%) were treated with Erythropoietin (EPO), 1 (1.9%) with hypomethylating agents, 2 (3.8%) with other treatments (TNF-α inhibitor, interferon). Among the 36 patients treated with ESA after a median interval from diagnosis of 5.0 months [interquartile range (IR) 1.2 - 27.6], 24 (66.6%) received α-EPO, 11 (30.5%) β-EPO and 1 (2.9%) darbopoietin. Two patients were too early (< 3 months of treatment) for response evaluation: among the 34 evaluable patients, 21 (61.7%) achieved stable erythroid response according IWG criteria (Hb increase > 1.5 g/dl in 18 patients and reduction > 50% of basal transfusion requirement in 3 patients) while 13 (38.2%) were resistant to EPO. Nine patients (17%) progressed to Acute Myeloid Leukemia (AML) after a median time from diagnosis of 16.8 months (IR 4.1 - 51.7). At the last follow-up, 21 patients (39.6%) died (13 from MDS/AML related causes and 8 from unrelated causes), 12 (22.6%) were lost to follow-up and 20(37.8%) were alive. Median Overall Survival (OS) of the entire cohort was 61.6 months (95%CI 42.2 - 81.0): the 10-year cumulative OS was 38.6% (95%CI 18.6 - 58.6) (Figure 1). In conclusion, as MDS represent a heterogeneous group of pathologies, many efforts are ongoing to identify patients with similar biological, clinical and prognostic features (eg 5q- syndrome, MDS with ring sideroblasts). From the scarce data in the literature and from our results, it is reasonable that also patients with isolated del20q may represent a distinct clinical and biological entity, with specific clinical and prognostic features (low PLT count, low number of marrow blasts, low IPSS and r-IPSS risk score, good response to EPO, long OS). The mechanisms underlying del20q are still unclear and warrant future molecular analysis. Disclosures Breccia: Novartis: Honoraria; BMS: Honoraria; Pfizer: Honoraria; Incyte: Honoraria.

scholarly journals Accuracy of upper endoscopies with random biopsies to identify patients with gastric premalignant lesions who can safely be exempt from surveillance

2021 ◽  
Vol 24 (3) ◽  
pp. 680-690
Author(s):  
Michiel C. Mommersteeg ◽  
Stella A. V. Nieuwenburg ◽  
Wouter J. den Hollander ◽  
Lisanne Holster ◽  
Caroline M. den Hoed ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
High Risk ◽  
Low Risk ◽  
Premalignant Lesions ◽  
High Risk Patients ◽  
European Guidelines ◽  
Progression Of Disease ◽  
Risk Patients ◽  
Progression Risk

Abstract Introduction Guidelines recommend endoscopy with biopsies to stratify patients with gastric premalignant lesions (GPL) to high and low progression risk. High-risk patients are recommended to undergo surveillance. We aimed to assess the accuracy of guideline recommendations to identify low-risk patients, who can safely be discharged from surveillance. Methods This study includes patients with GPL. Patients underwent at least two endoscopies with an interval of 1–6 years. Patients were defined ‘low risk’ if they fulfilled requirements for discharge, and ‘high risk’ if they fulfilled requirements for surveillance, according to European guidelines (MAPS-2012, updated MAPS-2019, BSG). Patients defined ‘low risk’ with progression of disease during follow-up (FU) were considered ‘misclassified’ as low risk. Results 334 patients (median age 60 years IQR11; 48.7% male) were included and followed for a median of 48 months. At baseline, 181/334 (54%) patients were defined low risk. Of these, 32.6% were ‘misclassified’, showing progression of disease during FU. If MAPS-2019 were followed, 169/334 (51%) patients were defined low risk, of which 32.5% were ‘misclassified’. If BSG were followed, 174/334 (51%) patients were defined low risk, of which 32.2% were ‘misclassified’. Seven patients developed gastric cancer (GC) or dysplasia, four patients were ‘misclassified’ based on MAPS-2012 and three on MAPS-2019 and BSG. By performing one additional endoscopy 72.9% (95% CI 62.4–83.3) of high-risk patients and all patients who developed GC or dysplasia were identified. Conclusion One-third of patients that would have been discharged from GC surveillance, appeared to be ‘misclassified’ as low risk. One additional endoscopy will reduce this risk by 70%.

scholarly journals Combination of Immune and Viral Factors Distinguishes Low-Risk versus High-Risk HIV-1 Disease Progression in HLA-B*5701 Subjects

2012 ◽  
Vol 86 (18) ◽  
pp. 9802-9816 ◽  
Author(s):  
Melissa M. Norström ◽  
Marcus Buggert ◽  
Johanna Tauriainen ◽  
Wendy Hartogensis ◽  
Mattia C. Prosperi ◽  
...  
Keyword(s):  
T Cell ◽  
High Risk ◽  
High Resolution ◽  
Disease Progression ◽  
T Cell Responses ◽  
Low Risk ◽  
Early Infection ◽  
Cell Responses ◽  
Cell Counts ◽  
Hiv 1

HLA-B*5701 is the host factor most strongly associated with slow HIV-1 disease progression, although rates can vary within this group. Underlying mechanisms are not fully understood but likely involve both immunological and virological dynamics. The present study investigated HIV-1in vivoevolution and epitope-specific CD8+T cell responses in six HLA-B*5701 patients who had not received antiretroviral treatment, monitored from early infection for up to 7 years. The subjects were classified as high-risk progressors (HRPs) or low-risk progressors (LRPs) based on baseline CD4+T cell counts. Dynamics of HIV-1 Gag p24 evolution and multifunctional CD8+T cell responses were evaluated by high-resolution phylogenetic analysis and polychromatic flow cytometry, respectively. In all subjects, substitutions occurred more frequently in flanking regions than in HLA-B*5701-restricted epitopes. In LRPs, p24 sequence diversity was significantly lower; sequences exhibited a higher degree of homoplasy and more constrained mutational patterns than HRPs. The HIV-1 intrahost evolutionary rate was also lower in LRPs and followed a strict molecular clock, suggesting neutral genetic drift rather than positive selection. Additionally, polyfunctional CD8+T cell responses, particularly to TW10 and QW9 epitopes, were more robust in LRPs, who also showed significantly higher interleukin-2 (IL-2) production in early infection. Overall, the findings indicate that HLA-B*5701 patients with higher CD4 counts at baseline have a lower risk of HIV-1 disease progression because of the interplay between specific HLA-linked immune responses and the rate and mode of viral evolution. The study highlights the power of a multidisciplinary approach, integrating high-resolution evolutionary and immunological data, to understand mechanisms underlying HIV-1 pathogenesis.

Sign in / Sign up

Export Citation Format

Share Document