scholarly journals The Revised Myeloma Comorbidity Index (R-MCI) As a Promising Approach for Predicting Overall (OS)- and Progression-Free (PFS) Survival and Optimizing Therapy Strategies in Multiple Myeloma (MM) Patients (pts) - Comparative Analysis of 5 Comorbidity Indices (CI), Including Retro- and Prospective Applicability

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3474-3474
Author(s):  
Katja Schoeller ◽  
Gabriele Ihorst ◽  
Sophia Scheubeck ◽  
Max Holler ◽  
Sandra M. Woerner ◽  
...  
Keyword(s):  
High Risk ◽  
Research Funding ◽  
Risk Group ◽  
Risk Groups ◽  
Low Risk ◽  
Chi Square ◽  
Mayo Score ◽  
The Difference ◽  
Therapy Strategies ◽  
Group Distribution

Introduction: MM is considered an incurable disease. Due to the improvement in long-term survival of MM pts with innovative therapy strategies, the necessity of including comorbidities and biological fitness status to treatment options has significantly increased over the last years. However, elderly pts still remain to benefit to lesser extends revealing lower PFS and OS rates, show more treatment-induced side effects and a lower quality of life. Therefore, it is inevitable to include an objective frailty assessment into MM guidelines to avoid under- and overtreatment. Since no CI has been widely established yet, selection process should include the capability of assessing a retro- and prospective baseline for comparing CI results among available data sets. This analysis compared 5 internationally well-discussed CIs regarding OS and PFS prediction and tested if these CIs can be reliably assessed retro- and prospectively. Methods: This prospective study was performed for 347 consecutive pts treated at our center, analyzing OS and PFS for the R-MCI, IMWG-, CCI, Mayo- and MRP-scores: the factors that are included in each individual score are shown in Table 1. For each CI, pts were divided into 3 risk groups (low-, intermediate-, high-risk), except for the CCI with possible designation into low- and high-risk group only. Based on these risk groups, OS and PFS were estimated by Kaplan Meier Method and compared via log rank test. Additionally we compared this above mentioned prospective cohort with a prior study including 749 pts treated at our center (Haematologica 2017;102:910-21). For this cohort we now performed a retrospective analysis with 4 of the latter CIs to analyze differences in risk group distribution within these two cohorts via Chi Square tests. Since there was missing laboratory data for the UK-MRP-score in the retrospective cohort, it was excluded from the latter analysis. Results: Pts' characteristics were typical for tertiary centers with a median age of 65 years (yrs). Median Follow-up was 36 months, median OS was not reached and PFS was 34 months. All 5 CIs could divide pts into risk groups with significantly different OS (p<0.05). The difference in 3yr OS for high- and low-risk group using the R-MCI was 43% and via IMWG- and Mayo-score 37% and 70% respectively. Minor distinction for OS prediction was achieved by CCI and MRP with only 25% and 20% difference. For the MRP, the 3-yr-OS rate for frail (59%) exceeded that of intermediate pts (50%), moreover, this group comprised only low numbers (n=8). In analogy, the difference in 3yr PFS amounted to 48% for the R-MCI vs. 40% and 59% for IMWG- and Mayo-scores, respectively. Here again the CCI and MPR showed lowest PFS differences with only 20% and 27% between high- and low-risk groups (Table 1). Comparing the pro- and retrospective analyses via Chi-Square tests, only the R-MCI showed comparable results for the risk group distribution in both cohorts (p=0.26) with 26% vs. 27%, 60% vs. 55% and 14% vs. 18% in low-risk, intermediate-risk and high-risk groups, respectively (Table 1). Respective results for IMWG and CCI scores showed that significantly more patients were defined as low-risk in the retrospective than in prospective cohorts with 41% vs. 30% for the IMWG and 65% vs. 47% for the CCI, respectively (p<0.001). The results for the Mayo-score revealed that 13% of the retrospective cohort were classified as high-risk as compared to 8% of the prospective cohort (p=0.0209). Conclusions: To our knowledge this is the first large prospective comparative analysis of 5 internationally discussed CIs. Our results show an excellent separation into risk groups with different OS and PFS via R-MCI, IMWG and Mayo-scores, whereas via CCI and Mayo-score to a much lesser extent. The results of this analysis reinforce the multifunctionality and convenience of using one MM-CI, like the robustly tested and repeatedly validated R-MCI. Further unique features of the R-MCI are the pro- and retrospective applicability in daily clinics, a user-friendly homepage and the future perspective of extended use, e.g. for tailoring therapies, which is currently investigated and which results will be shown at the meeting. Disclosures Wäsch: Takeda: Consultancy; Pfizer: Consultancy; Amgen: Other: travel, Research Funding; Sanofi: Consultancy; Gilead: Other: travel, Research Funding; Novartis: Consultancy; Celgene: Other: travel, Research Funding; Sanofi: Other: Travel, Research Funding; Gilead: Consultancy; Jazz: Other: travel, Research Funding; Amgen: Consultancy.

Combining Information Regarding Chromosomal Aberrations t(4;14), Del(17p13) and the Copy Number of 1q21 with the International Staging System Classification Allows Stratification of Myeloma Patients Undergoing Autologous Stem Cell Transplantation: Results From the HOVON-65/GMMG HD4 Trial

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 332-332
Author(s):  
Kai Neben ◽  
Henk M. Lokhorst ◽  
Anna Jauch ◽  
Uta Bertsch ◽  
Thomas Hielscher ◽  
...  
Keyword(s):  
High Risk ◽  
Board Of Directors ◽  
Research Funding ◽  
Prognostic Value ◽  
Risk Group ◽  
Staging System ◽  
Risk Groups ◽  
Low Risk ◽  
Advisory Committees ◽  
International Staging System

Abstract Abstract 332 PURPOSE : In Multiple Myeloma (MM), the combination of serum beta-2-microglobulin level with serum albumin concentration has been proposed as an outcome predictor in the International Staging System (ISS). More recently, subgroups of MM defined by genetic and cytogenetic abnormalities have been associated with unique biologic, clinical, and prognostic features. PATIENTS AND METHODS: We analyzed the prognostic value of 12 chromosomal abnormalities by fluorescent in situ hybridization (FISH) in a series of 354 MM patients treated within the HOVON-65/GMMG-HD4 trial. Patients with newly diagnosed MM were randomized to receive either three cycles of VAD (arm A; vincristine, adriamycin, dexamethasone) or PAD (arm B; bortezomib, adriamycin, dexamethasone). All patients underwent autologous stem cell transplantation (ASCT) followed by maintenance therapy with thalidomide 50 mg daily (arm A) or bortezomib 1.3 mg/m2 once every 2 weeks (arm B), respectively. In addition, a second cohort of patients was analyzed as a control group (n=462), undergoing ASCT at the University of Heidelberg between September 1994 and December 2010. RESULTS: For the entire group of patients treated within the HOVON-65/GMMG-HD4 trial, we identified 233 patients with 2 copies (67.7%), 95 patients with 3 copies (27.6%) and 16 patients (4.7%) with more than three copies of the chromosomal region 1q21. In addition to del(17p13) and t(4;14), we added +1q21 (>3 copies) to the group of high-risk aberrations, since the outcome of these patients was almost as poor as it was observed for patients with del(17p13). Subsequently, we analyzed whether combining the ISS score with information on the presence of high-risk aberrations could improve the prognostic value with regard to patients' outcome. A combination of the presence or absence of del(17p13), t(4;14), or +1q21 (>3 copies) with the ISS score allowed patients to be stratified into three distinct groups: low-risk [absence of del(17p13)/t(4;14)/+1q21 (>3 copies) and ISS I], high-risk [presence of del(17p13)/t(4;14)/+1q21 (>3 copies) and ISS II/III], and intermediate-risk (all remaining patients). Most of the patients belonged to the low- (33%) and intermediate-risk (49%) groups, whereas 18% were allocated to the high-risk group. The median PFS times for the low-, intermediate-, and high-risk groups were 41.9 months, 31.1 months (HR=1.7; p=0.0018) and 18.7 months (HR=3.6; p<0.0001), respectively. The 3yr-overall survival (OS) decreased from 94% in the low-risk group to 80% (HR=4.6; p=0.0001) and 43% (HR=12.8; p<0.0001) in the intermediate- and high-risk groups, respectively. These results were confirmed in the independent cohort of patients: From date of first ASCT, the median PFS times for the low-, intermediate-, and high-risk groups were 43.3 months, 23.0 months (HR=1.5; p=0.015) and 13.8 months (HR=2.4; p=0.0003), respectively. The 4yr-OS decreased from 84% in the low-risk group to 71% (HR=2.1; p=0.0043) and 49% (HR=3.84; p<0.0001) in the intermediate- and high-risk groups, respectively. CONCLUSION: In our series, the ISS/FISH-based score/algorithm predicted PFS and OS much better than the ISS alone. Our results with molecular cytogenetic techniques may already have implications for the risk-adapted clinical management of patients with MM particularly in younger patients. Disclosures: van de Velde: Ortho Biotech Oncology Research & Development: Employment. Sonneveld:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Membership on an entity's Board of Directors or advisory committees.

The Combination of SKY92 and ISS Provides a Powerful Tool to Identify Both High Risk and Low Risk Multiple Myeloma Cases, Validation in Two Independent Cohorts

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2970-2970 ◽  
Author(s):  
Martin van Vliet ◽  
Joske Ubels ◽  
Leonie de Best ◽  
Erik van Beers ◽  
Pieter Sonneveld
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Research Funding ◽  
Prognostic Markers ◽  
Risk Group ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Kaplan Meier ◽  
Standard Risk

Abstract Introduction Multiple Myeloma (MM) is a heterogeneous disease with a strong need for robust markers for prognosis. Frequently occurring chromosomal abnormalities, such as t(4;14), gain(1q), and del(17p) etc. have some prognostic power, but lack robustness across different cohorts. Alternatively, gene expression profiling (GEP) studies have developed specific high risk signatures such as the SKY92 (EMC92, Kuiper et al. Leukemia 2012), which has shown to be a robust prognostic factor across five different clinical datasets. Moreover, studies comparing prognostic markers have indicated that the SKY92 signature outperforms all other markers for identifying high risk patients, both in single and multivariate analyses. Similarly, when assessing the prognostic value of combinations of various prognostic markers, the SKY92 combined with ISS was the top performer, and also enables detection of a low risk group (Kuiper et al. ASH 2014). Here, we present a further validation of the low and high risk groups identified by the SKY92 signature in combination with ISS on two additional cohorts of patients with diverse treatment backgrounds, containing newly diagnosed, previously treated, and relapsed/refractory MM patients. Materials and Methods The SKY92 signature was applied to two independent datasets. Firstly, the dataset from the Total Therapy 6 (TT6) trial, which is a phase 2 trial for symptomatic MM patients who have received 1 or more prior lines of treatment. The TT6 treatment regime consists of VTD-PACE induction, double transplant with Melphalan + VRD-PACE, followed by alternating VRD/VMD maintenance. Affymetrix HG-U133 Plus 2.0 chips were performed at baseline for n=55 patients, and OS was made available previously (Gene Expression Omnibus identifier: GSE57317). However, ISS was not available for this dataset. Secondly, a dataset of patients enrolled at two hospitals in the Czech Republic, and one in Slovakia (Kryukov et al. Leuk&Lymph 2013). Patients of all ages, and from first line up to seventh line of treatment were included (treatments incl Bort, Len, Dex). For n=73 patients Affymetrix Human Gene ST 1.0 array, OS (n=66), and ISS (n=58) was made available previously (ArrayExpress accession number: E-MTAB-1038). Both datasets were processed from .CEL files by MAS5 (TT6), and RMA (Czech), followed by mean variance normalization per probeset across the patients. The SKY92 was applied as previously described (Kuiper et al. Leukemia 2012), and identifies a High Risk and Standard Risk group. In conjunction with ISS, the SKY92 Standard Risk group is then further stratified into low and intermediate risk groups (Kuiper et al. ASH 2014). Kaplan-Meier plots were created, and the Cox proportional hazards model was used to calculate Hazard Ratios (HR), and associated 1-sided p-values that assess whether the SKY92 High Risk group has worse survival than SKY92 Standard Risk group (i.e. HR>1). Results Figure 1 shows the Kaplan Meier plots of the SKY92 High Risk and Standard Risk groups on the TT6 and Czech cohorts. On the TT6 dataset, the SKY92 signature identifies 11 out of 55 patients (20%) as High Risk. In both datasets, the SKY92 High Risk group has significantly worse overall survival, HR=10.3, p=7.4 * 10-6 (TT6), and HR=2.6, p=2.2 * 10-2 (Czech). In addition, the combination of SKY92 with ISS on the Czech dataset identifies a low risk group of 14 out of 61 patients (23%), with a five year overall survival estimate of 100% versus 28.7% in the SKY92 High Risk group (HR=inf). Robustness of the SKY92 signature is further demonstrated by the fact that it validates on both datasets, despite different microarray platforms being used. Conclusions The SKY92 high risk signature has been successfully validated on two independent datasets generated using different microarray platforms. In addition, on the Czech data, the low risk group (SKY92 Standard Risk combined with ISS 1) has been successfully validated. Together, this signifies the robust nature of the SKY92 signature for high and low risk prediction, across treatments, and with applicability in newly diagnosed, treated, and relapsed/refractory MM patients. Figure 1. Kaplan-Meier plots showing a significantly poorer overall survival in patients identified as SKY92 High Risk (red curves), relative to SKY92 Standard Risk, on both the TT6 (left), and Czech (middle) datasets, as well as a low risk group by SKY92 & ISS1 on the Czech dataset (green curve, right). Figure 1. Kaplan-Meier plots showing a significantly poorer overall survival in patients identified as SKY92 High Risk (red curves), relative to SKY92 Standard Risk, on both the TT6 (left), and Czech (middle) datasets, as well as a low risk group by SKY92 & ISS1 on the Czech dataset (green curve, right). Disclosures van Vliet: SkylineDx: Employment. Ubels:SkylineDx: Employment. de Best:SkylineDx: Employment. van Beers:SkylineDx: Employment. Sonneveld:Celgene: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Karyopharm: Research Funding; SkylineDx: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Research Funding.

scholarly journals Cardiac Troponin-I And CK-MB for Risk Stratification in Acute Myocardial Infarction (First Attack): A Comparative Study

2013 ◽  
Vol 4 (1) ◽  
pp. 10-15 ◽  
Author(s):  
S Joarder ◽  
M Hoque ◽  
M Towhiduzzaman ◽  
AF Salehuddin ◽  
N Islam ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
High Risk ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Risk Group ◽  
Risk Groups ◽  
Low Risk ◽  
The Mean ◽  
The Difference

Myocardial infarction is associated with release of two important enzymes. The enzymatic diagnosis is mainly based on the measurement of CK-MB and troponin-I. Cardiac troponin- I(cTnI) is known to have higher specificity and analytic sensitivity than CK-MB for detection of myocardial injury & risk stratification. These are used both as diagnostic and prognostic marker. This prospective observational study included 60 patients of 40-65 years age range, diagnosed as acute myocardial infarction. The mean ages were 50± 8 years and 53±8 years respectively. Male and female patients included were 86.7% and 13.3%; BMI was 25.3±1.5. The two important cardiac markers troponin-I and CK-MB were studied in 60 patients, admitted in the hospital with acute MI. Blood samples to estimate these markers were collected from the patients after admission at 6-9 hours, 9-24 hours and after 24 hours and their mean values with ±SD were calculated, evaluated and compared between the two groups of patients with low and high risk MI. The patients with low risk MI were those who recovered early and the high risk patients improved later in comparison to low risk group. Out of 60 patients, 37 had troponin-I level>1.5 ng /ml. Among them 29 developed high risk MI and 8 recovered earlier than high risk group. 23 patients had troponin-I <1.5 ng /ml, out of whom 10 were high and 13 were low risk. The difference of troponin-I levels between high and low risk groups of patients was statistically significant (p<0.01). On the other hand CK-MB level was >7 ng /ml in 33 patients. Out of them 22 patients developed high and 11 patients were low risk but 18 patients out of 27 who had CK-MB <7 ng /ml became high and 9 patients were low risk. The difference of outcome in respect to higher and lower values of CK-MB between the two groups was not statistically significant (p>0.05). Both troponin-I and CK-MB were estimated in all 60 patients on three occasions. The mean troponin-I levels were statistically significant between the high and the low risk groups on all occasions. On the contrary, the values of CK-MB were not statistically significant on two occasions but was significant (p < 0.01) on one occasion when it was estimated at 9 - 24 hour. Serum cTnI is better and more characteristic biomarker than CK-MB for risk prediction and prognosis evaluation in AMI patients. DOI: http://dx.doi.org/10.3329/bjmb.v4i1.13776 Bangladesh J Med Biochem 2011; 4(1): 10-15

scholarly journals Possibility of a Risk-Adapted Treatment Strategy for Untreated Aggressive Adult T-Cell Leukemia-Lymphoma (ATL) Based on the ATL Prognostic Index: A Supplementary Analysis of the JCOG9801 Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1645-1645
Author(s):  
Kosuke Toyoda ◽  
Kunihiro Tsukasaki ◽  
Ryunosuke Machida ◽  
Tomohiro Kadota ◽  
Takuya Fukushima ◽  
...  
Keyword(s):  
High Risk ◽  
Research Funding ◽  
Risk Group ◽  
Prognostic Index ◽  
Risk Groups ◽  
Low Risk ◽  
Intermediate Risk ◽  
Adult T Cell Leukemia ◽  
Ann Arbor ◽  
Ecog Ps

Abstract Introduction The JCOG9801 study, a randomized phase III trial of the Japan Clinical Oncology Group (JCOG), compared CHOP every two weeks (CHOP-14) with VCAP-AMP-VECP (mLSG15) for patients with untreated aggressive adult T-cell leukemia-lymphoma (ATL) [J Clin Oncol 2007;25:5458-64]. Based on a higher complete response (CR) rate and marginally better overall survival (OS), we concluded that mLSG15 could be a sufficiently effective regimen at the expense of higher toxicity profiles. However, there was an insufficient mLSG15 effect among patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or those aged ≥56 years, suggesting that mLSG15 is not always a definitive treatment for all patients with aggressive ATL. Thus, identifying patients who should receive mLSG15 is essential. We aimed to conduct a supplementary analysis of patients enrolled in the JCOG9801 study using the ATL prognostic index (ATL-PI) that has been recently advocated for acute- and lymphoma-types of ATL [J Clin Oncol 2012;30:1635-40]. Methods We adopted the "age-adjusted" ATL-PI that was established for ATL patients aged ≤70 years as patients aged between 15 and 69 years were eligible in the JCOG9801 study. Having eliminated "age", this index comprised 4 factors, namely Ann Arbor stage (III or IV), ECOG PS (>1), serum albumin (<3.5 g/dL), and soluble interleukin-2 receptor (sIL-2R; >20,000 U/mL). We excluded patients lacking any factors of the age-adjusted ATL-PI and those with unfavorable chronic type based on the age-adjusted ATL-PI model from patients enrolled in JCOG9801. Subsequently, we categorized the remaining patients into three groups, namely low, intermediate, and high risk, and compared mLSG15 and CHOP-14 in terms of OS, treatment CR rate, and toxicity in each risk group. Results Of 118 enrolled JCOG9801 patients, we included 105 patients in this supplementary analysis based on the above criteria, of which 51 and 54 were treated with mLSG15 and CHOP-14, respectively. According to the age-adjusted ATL-PI, these patients were classified as follows: low (n=44, 41.9%), intermediate (n=54, 51.4%), and high (n=7, 6.7%) risks. Regarding patient characteristics, between the two treatment arms, there were no remarkable differences in age, sex, ECOG PS, ATL subtypes, Ann Arbor stage, presence of B symptoms, presence of bulky mass (≥5 cm), and serum albumin, serum calcium, and sIL-2R levels. The mLSG15 arm included 21 (41.2%), 25 (49.0%), and 5 (9.8%) patients in the low-, intermediate-, and high-risk groups, respectively, whereas the CHOP-14 arm included 23 (42.6%), 29 (53.7%), and 2 (3.7%) patients, respectively. We excluded the high-risk group from our analysis due to the small number of patients. mLSG15 did not show any superior trend for OS compared to CHOP-14 in the low-risk group (hazard ratio [HR]: 0.957; 95% confidence interval [CI]: 0.491-1.868) (Figure A). In contrast, in the intermediate-risk group, better prognosis for OS was observed with mLSG15 (HR: 1.538; 95% CI: 0.841-2.811) than with CHOP-14 (Figure B). Similarly, the CR rate, including the unconfirmed CR rate, did not differ between both arms of the low-risk group (mLSG15 vs. CHOP-14, 47.6% vs. 43.5%), while in the intermediate-risk group, mLSG15 showed a higher CR rate than CHOP-14 (44.0% vs. 13.8%). Regarding toxicity profiles, grade 4 thrombocytopenia was more frequently observed in the mLSG15 arm of both risk groups than in the CHOP-14 arm (66.7% vs. 4.5% in the low-risk group; 68.0% vs. 24.1% in the intermediate-risk group only). There was a higher incidence of grade 4 neutropenia in the mLSG15 arm than in the CHOP-14 arm (100.0% vs. 75.9%) only in the intermediate-risk group. All three treatment-related deaths were documented in the mLSG15 arm of the intermediate-risk group. Conclusions Given the very poor prognosis of ATL, our findings suggest that despite higher toxicities, mLSG15 is more suitable for the intermediate-risk group of age-adjusted ATL-PI, whereas its benefits appear modest in the low-risk group. This supplementary analysis is exploratory; therefore, a further prospective study of aggressive ATL is necessary to confirm these results. Disclosures Tsukasaki: Daiich-Sankyo: Consultancy; Ono Pharma: Consultancy; HUYA: Consultancy, Research Funding; Chugai Pharma: Honoraria, Research Funding; Eisai: Research Funding; Celgene: Honoraria; Mundy Pharma: Honoraria; Kyowa-hakko/Kirin: Honoraria; Seattle Genetics: Research Funding. Fukushima:NEC corporation: Research Funding. Maruyama:Bristol-Myers Squibb: Honoraria; Solasia Pharma: Research Funding; Pfizer: Research Funding; Nippon Boehringer Ingelheim: Research Funding; Novartis: Research Funding; Otsuka: Research Funding; Astellas Pharma: Research Funding; Abbvie: Research Funding; Mundipharma International: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Biomedis International: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Kyowa Hakko Kirin: Honoraria, Research Funding; Fujifilm: Honoraria, Research Funding; Ono Pharmaceutical: Honoraria, Research Funding; MSD: Honoraria, Research Funding; Chugai Pharma: Honoraria, Research Funding; Dai-ichi-Sankyo: Honoraria; Dai-Nippon-Sumitomo: Honoraria; Asahi Kasei Pharma: Honoraria; AstraZeneca: Research Funding; Amgen Astellas BioPharma: Research Funding; Zenyaku Kogyo: Honoraria, Research Funding; GlaxoSmithKline: Research Funding. Nagai:SymBio Pharmaceuticals Limited: Research Funding; Otsuka Pharmaceutical Co., Ltd.: Research Funding; Kyowa Hakko Kirin Co., Ltd.: Honoraria, Research Funding; Janssen Pharmaceutical K.K.: Honoraria, Research Funding; Chugai Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Solasia Pharma K.K.: Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Bayer Yakuhin Ltd.: Research Funding; Abbvie G. K.: Research Funding; Celgene Corporation: Honoraria, Research Funding; Takeda Pharmaceutical Co., Ltd.: Honoraria, Research Funding; AstraZeneca plc.: Research Funding; Roche Ltd.: Honoraria; Esai Co., Ltd.: Honoraria, Research Funding; HUYA Bioscience International: Research Funding; Ono Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Sanofi K. K.: Honoraria; Zenyaku Kogyo Co., Ltd.: Honoraria, Research Funding; Mundipharma K.K.: Honoraria, Research Funding; Gilead Sciences Inc.: Honoraria, Research Funding.

Short-term risk stratification using CADILLAC risk score in patients with ST elevation myocardial infarction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Satou ◽  
H Kitahara ◽  
K Ishikawa ◽  
T Nakayama ◽  
Y Fujimoto ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
High Risk ◽  
Adverse Events ◽  
Risk Score ◽  
Risk Group ◽  
Risk Groups ◽  
Low Risk ◽  
Short Term ◽  
Recurrent Myocardial Infarction ◽  
St Elevation

Abstract Background The recent reperfusion therapy for ST-elevation myocardial infarction (STEMI) has made the length of hospital stay shorter without adverse events. CADILLAC risk score is reportedly one of the risk scores predicting the long-term prognosis in STEMI patients. Purpose To invenstigate the usefulness of CADILLAC risk score for predicting short-term outcomes in STEMI patients. Methods Consecutive patients admitted to our university hospital and our medical center with STEMI (excluding shock, arrest case) who underwent primary PCI between January 2012 and April 2018 (n=387) were enrolled in this study. The patients were classified into 3 groups according to the CADILLAC risk score: low risk (n=176), intermediate risk (n=87), and high risk (n=124). Data on adverse events within 30 days after hospitalization, including in-hospital death, sustained ventricular arrhythmia, recurrent myocardial infarction, heart failure requiring intravenous treatment, stroke, or clinical hemorrhage, were collected. Results In the low risk group, adverse events within 30 days were significantly less observed, compared to the intermediate and high risk groups (n=13, 7.4% vs. n=13, 14.9% vs. n=58, 46.8%, p&lt;0.001). In particular, all adverse events occurred within 3 days in the low risk group, although adverse events, such as heart failure (n=4), recurrent myocardial infarction (n=1), stroke (n=1), and gastrointestinal bleeding (n=1), were substantially observed after day 4 of hospitalization in the intermediate and high risk groups. Conclusions In STEMI patients with low CADILLAC risk score, better short-term prognosis was observed compared to the intermediate and high risk groups, and all adverse events occurred within 3 days of hospitalization, suggesting that discharge at day 4 might be safe in this study population. CADILLAC risk score may help stratify patient risk for short-term prognosis and adjust management of STEMI patients. Initial event occurrence timing Funding Acknowledgement Type of funding source: None

scholarly journals Immune‐related Long Noncoding RNA Signature for Patients with Cervical Cancer

2020 ◽  
Author(s):  
Jianfeng Zheng ◽  
Jinyi Tong ◽  
Benben Cao ◽  
Xia Zhang ◽  
Zheng Niu
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
Risk Score ◽  
Immune Cell ◽  
Risk Group ◽  
Risk Groups ◽  
Low Risk ◽  
Gene Set Enrichment Analysis ◽  
Training Set ◽  
Score Model

Abstract Background: Cervical cancer (CC) is a common gynecological malignancy for which prognostic and therapeutic biomarkers are urgently needed. The signature based on immune‐related lncRNAs(IRLs) of CC has never been reported. This study aimed to establish an IRL signature for patients with CC.Methods: The RNA-seq dataset was obtained from the TCGA, GEO, and GTEx database. The immune scores（IS）based on single-sample gene set enrichment analysis (ssGSEA) were calculated to identify the IRLs, which were then analyzed using univariate Cox regression analysis to identify significant prognostic IRLs. A risk score model was established to divide patients into low-risk and high-risk groups based on the median risk score of these IRLs. This was then validated by splitting TCGA dataset(n=304) into a training-set(n=152) and a valid-set(n=152). The fraction of 22 immune cell subpopulations was evaluated in each sample to identify the differences between low-risk and high-risk groups. Additionally, a ceRNA network associated with the IRLs was constructed.Results: A cohort of 326 CC and 21 normal tissue samples with corresponding clinical information was included in this study. Twenty-eight IRLs were collected according to the Pearson’s correlation analysis between immune score and lncRNA expression (P < 0.01). Four IRLs (BZRAP1-AS1, EMX2OS, ZNF667-AS1, and CTC-429P9.1) with the most significant prognostic values (P < 0.05) were identified which demonstrated an ability to stratify patients into low-risk and high-risk groups by developing a risk score model. It was observed that patients in the low‐risk group showed longer overall survival (OS) than those in the high‐risk group in the training-set, valid-set, and total-set. The area under the curve (AUC) of the receiver operating characteristic curve (ROC curve) for the four IRLs signature in predicting the one-, two-, and three-year survival rates were larger than 0.65. In addition, the low-risk and high-risk groups displayed different immune statuses in GSEA. These IRLs were also significantly correlated with immune cell infiltration. Conclusions: Our results showed that the IRL signature had a prognostic value for CC. Meanwhile, the specific mechanisms of the four-IRLs in the development of CC were ascertained preliminarily.

A Novel Risk Classification Model Predicts Overall Survival and Locoregional Surgery Benefit in Colorectal Patients with Distant Metastasis at the Initial Diagnosis

2020 ◽  
Author(s):  
Mo Chen ◽  
Tian-en Li ◽  
Pei-zhun Du ◽  
Junjie Pan ◽  
Zheng Wang ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Distant Metastasis ◽  
Cox Regression ◽  
Risk Group ◽  
Risk Groups ◽  
Risk Classification ◽  
Low Risk ◽  
Classification Model ◽  
Intermediate Risk

Abstract Background and aims: In this research, we aimed to construct a risk classification model to predict overall survival (OS) and locoregional surgery benefit in colorectal cancer (CRC) patients with distant metastasis.Methods: We selected a cohort consisting of 12741 CRC patients diagnosed with distant metastasis between 2010 and 2014, from the Surveillance, Epidemiology and End Results (SEER) database. Patients were randomly assigned into training group and validation group at the ratio of 2:1. Univariable and multivariable Cox regression models were applied to screen independent prognostic factors. A nomogram was constructed and assessed by the Harrell’s concordance index (C-index) and calibration plots. A novel risk classification model was further established based on the nomogram.Results: Ultimately 12 independent risk factors including race, age, marriage, tumor site, tumor size, grade, T stage, N stage, bone metastasis, brain metastasis, lung metastasis and liver metastasis were identified and adopted in the nomogram. The C-indexes of training and validation groups were 0.77 (95% confidence interval [CI] 0.73-0.81) and 0.75 (95% CI 0.72-0.78), respectively. The risk classification model stratified patients into three risk groups (low-, intermediate- and high-risk) with divergent median OS (low-risk: 36.0 months, 95% CI 34.1-37.9; intermediate-risk: 18.0 months, 95% CI 17.4-18.6; high-risk: 6.0 months, 95% CI 5.3-6.7). Locoregional therapies including surgery and radiotherapy could prognostically benefit patients in the low-risk group (surgery: hazard ratio [HR] 0.59, 95% CI 0.50-0.71; radiotherapy: HR 0.84, 95% CI 0.72-0.98) and intermediate risk group (surgery: HR 0.61, 95% CI 0.54-0.68; radiotherapy: HR 0.86, 95% CI 0.77-0.95), but not in the high-risk group (surgery: HR 1.03, 95% CI 0.82-1.29; radiotherapy: HR 1.03, 95% CI 0.81-1.31). And all risk groups could benefit from systemic therapy (low-risk: HR 0.68, 95% CI 0.58-0.80; intermediate-risk: HR 0.50, 95% CI 0.47-0.54; high-risk: HR 0.46, 95% CI 0.40-0.53).Conclusion: A novel risk classification model predicting prognosis and locoregional surgery benefit of CRC patients with distant metastasis was established and validated. This predictive model could be further utilized by physicians and be of great significance for medical practice.

scholarly journals MO048MULTICENTRE PROSPECTIVE VALIDATION OF THE URINARY PEPTIDOME-BASED CLASSIFIER CKD273 AS A PREDICTOR OF RENAL FUNCTION DECLINE IN SUBJECTS WITH TYPE 2 DIABETES

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Morten Lindhardt ◽  
Nete Tofte ◽  
Gemma Currie ◽  
Marie Frimodt-Moeller ◽  
Heiko Von der Leyen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Renal Function ◽  
High Risk ◽  
Risk Group ◽  
Cox Model ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Renal Function Decline

Abstract Background and Aims In the PRIORITY study, it was recently demonstrated that the urinary peptidome-based classifier CKD273 was associated with increased risk for progression to microalbuminuria. As a prespecified secondary outcome, we aim to evaluate the classifier CKD273 as a determinant of relative reductions in eGFR (CKD-EPI) of 30% and 40% from baseline, at one timepoint without requirements of confirmation. Method The ‘Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy In TYpe 2 diabetic patients with normoalbuminuria trial’ (PRIORITY) is the first prospective observational study to evaluate the early detection of diabetic kidney disease in subjects with type 2 diabetes (T2D) and normoalbuminuria using the CKD273 classifier. Setting 1775 subjects from 15 European sites with a mean follow-up time of 2.6 years (minimum of 7 days and a maximum of 4.3 years). Patients Subjects with T2D, normoalbuminuria and estimated glomerular filtration rate (eGFR) ≥ 45 ml/min/1.73m2. Participants were stratified into high- or low-risk groups based on their CKD273 score in a urine sample at screening (high-risk defined as score &gt; 0.154). Results In total, 12 % (n = 216) of the subjects had a high-risk proteomic pattern. Mean (SD) baseline eGFR was 88 (15) ml/min/1.73m2 in the low-risk group and 81 (17) ml/min/1.73m2 in the high-risk group (p &lt; 0.01). Baseline median (interquartile range) urinary albumin to creatinine ratio (UACR) was 5 (3-8) mg/g and 7 (4-12) mg/g in the low-risk and high-risk groups, respectively (p &lt; 0.01). A 30 % reduction in eGFR from baseline was seen in 42 (19.4 %) subjects in the high-risk group as compared to 62 (3.9 %) in the low-risk group (p &lt; 0.0001). In an unadjusted Cox-model the hazard ratio (HR) for the high-risk group was 5.7, 95 % confidence interval (CI) (3.9 to 8.5; p&lt;0.0001). After adjustment for baseline eGFR and UACR, the HR was 5.2, 95 % CI (3.4 to 7.8; p&lt;0.0001). A 40 % reduction in eGFR was seen in 15 (6.9 %) subjects in the high-risk group whereas 22 (1.4 %) in the low-risk group developed this endpoint (p&lt;0.0001). In an unadjusted Cox-model the HR for the high-risk group was 5.0, 95 % CI (2.6 to 9.6; p&lt;0.0001). After adjustment for baseline eGFR and UACR, the HR was 4.8, 95 % CI (2.4 to 9.7; p&lt;0.0001). Conclusion In normoalbuminuric subjects with T2D, the urinary proteomic classifier CKD273 predicts renal function decline of 30 % and 40 %, independent of baseline eGFR and albuminuria.

scholarly journals Immune-Related Four-lncRNA Signature for Patients with Cervical Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Jianfeng Zheng ◽  
Benben Cao ◽  
Xia Zhang ◽  
Zheng Niu ◽  
Jinyi Tong
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
Immune Cell ◽  
Risk Group ◽  
Pearson Correlation ◽  
Characteristic Curve ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Gynecological Malignancy

Cervical cancer (CC) is a common gynecological malignancy for which prognostic and therapeutic biomarkers are urgently needed. The signature based on immune-related lncRNAs (IRLs) of CC has never been reported. This study is aimed at establishing an IRL signature for patients with CC. A cohort of 326 CC and 21 normal tissue samples with corresponding clinical information was included in this study. Twenty-eight IRLs were collected according to the Pearson correlation analysis between the immune score and lncRNA expression ( p < 0.01 ). Four IRLs (BZRAP1-AS1, EMX2OS, ZNF667-AS1, and CTC-429P9.1) with the most significant prognostic values ( p < 0.05 ) were identified which demonstrated an ability to stratify patients into the low-risk and high-risk groups by developing a risk score model. It was observed that patients in the low-risk group showed longer overall survival (OS) than those in the high-risk group in the training set, valid set, and total set. The area under the curve (AUC) of the receiver operating characteristic curve (ROC curve) for the four-IRL signature in predicting the one-, two-, and three-year survival rates was larger than 0.65. In addition, the low-risk and high-risk groups displayed different immune statuses in GSEA. These IRLs were also significantly correlated with immune cell infiltration. Our results showed that the IRL signature had a prognostic value for CC. Meanwhile, the specific mechanisms of the four IRLs in the development of CC were ascertained preliminarily.

Validation of Postpartum Hemorrhage Admission Risk Factor Stratification in a Large Obstetrics Population

2020 ◽  
Author(s):  
Halley Ruppel ◽  
Vincent X. Liu ◽  
Neeru R. Gupta ◽  
Lauren Soltesz ◽  
Gabriel J. Escobar
Keyword(s):  
Risk Factors ◽  
Risk Assessment ◽  
High Risk ◽  
Blood Loss ◽  
Postpartum Hemorrhage ◽  
Risk Group ◽  
Risk Groups ◽  
Low Risk ◽  
Hemorrhage Risk ◽  
Present On Admission

Abstract Objective This study aimed to evaluate the performance of the California Maternal Quality Care Collaborative (CMQCC) admission risk criteria for stratifying postpartum hemorrhage risk in a large obstetrics population. Study Design Using detailed electronic health record data, we classified 261,964 delivery hospitalizations from Kaiser Permanente Northern California hospitals between 2010 and 2017 into high-, medium-, and low-risk groups based on CMQCC criteria. We used logistic regression to assess associations between CMQCC risk groups and postpartum hemorrhage using two different postpartum hemorrhage definitions, standard postpartum hemorrhage (blood loss ≥1,000 mL) and severe postpartum hemorrhage (based on transfusion, laboratory, and blood loss data). Among the low-risk group, we also evaluated associations between additional present-on-admission factors and severe postpartum hemorrhage. Results Using the standard definition, postpartum hemorrhage occurred in approximately 5% of hospitalizations (n = 13,479), with a rate of 3.2, 10.5, and 10.2% in the low-, medium-, and high-risk groups. Severe postpartum hemorrhage occurred in 824 hospitalizations (0.3%), with a rate of 0.2, 0.5, and 1.3% in the low-, medium-, and high-risk groups. For either definition, the odds of postpartum hemorrhage were significantly higher in medium- and high-risk groups compared with the low-risk group. Over 40% of postpartum hemorrhages occurred in hospitalizations that were classified as low risk. Among the low-risk group, risk factors including hypertension and diabetes were associated with higher odds of severe postpartum hemorrhage. Conclusion We found that the CMQCC admission risk assessment criteria stratified women by increasing rates of severe postpartum hemorrhage in our sample, which enables early preparation for many postpartum hemorrhages. However, the CMQCC risk factors missed a substantial proportion of postpartum hemorrhages. Efforts to improve postpartum hemorrhage risk assessment using present-on-admission risk factors should consider inclusion of other nonobstetrical factors.

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