scholarly journals The Impact of Comorbidities on Clinical Outcome of Patients with Myelodysplastic Syndromes: A Real-Life Survey

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4668-4668
Author(s):  
Enrico Balleari ◽  
Chiara Salvetti ◽  
Andrea Bacigalupo ◽  
Gianluca Forni ◽  
Marco Gobbi ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Lower Risk ◽  
Risk Group ◽  
Real Life ◽  
High Risk Group ◽  
Low Risk ◽  
Survival Analyses ◽  
Intermediate Group ◽  
Comorbidity Index

Abstract Introduction: Myelodysplastic syndromes (MDS) are a highly heterogeneous group of clonal disorders, with very different prognosis in given individuals, overall survival (OS) ranging from more than 10 years (y) for the more indolent conditions to only few months (m) for the forms approaching AML; beside of the well-established disease-related prognostic systems (classical IPSS or its revised form [IPSS-R], the prognostic implication of comorbidities is emerging as a relevant patient-related factor influencing clinical outcome. Aim of our study was to evaluate the clinical impact of comorbidities in a series of MDS patients whatever treated in a “real-life” setting. Methods: this retrospective cohort study involved the MDS patients consecutively registered between Jan 2011 and Dec 2013 into the Registro Ligure delle Mielodisplasie database, a regional registry established within the framework of the Italian Network of regional MDS registries. Data of 318 patients (pts) with available complete assessment of comorbidities at diagnosis were included into the study. The clinical characteristics and comorbidities were all considered into the analysis. Comorbidities were evaluated according to both hematopoietic cell transplantation-specific comorbidity index (HCT-CI) and MDS-specific comorbidity index (MDS-CI). All survival analyses were made from the date of diagnosis to last follow-up, death, or progression to AML. Unless specified, survival analyses were Cox models using continuous variables accounting for interactions. Results: Our cohort mainly consisted of older (median age 75y (range 40-98) “lower-risk” MDS pts: according to IPSS stratification, 151 (54.7%) pts were classified as low-risk, 86 (31.2%) as intermediate-1, 32 (11.6%) as intermediate-2 and 7 (2.5%) were in the high-risk group. One or more comorbidity of any grade of severity was seen in 177 (55.7%) pts at diagnosis. The more common comorbidity was cardiac (26.5%). At least a single comorbidity was present in 61.2% of pts older than 75y and in 50.6% of younger pts (p=0.07). Cardiovascular disorders were more frequent among older (32.9% for >75y vs 15.1% for ≤ 75y, p<0.001), and among males (28.7% vs 17.1% for females, p=0.02). According to HCT-CI risk stratification, 141pts (44.3%) were in the low-risk group, 94 (29.6%) in the intermediate-risk group, and 83 (26.1%) in the high-risk group, while according to MDS-CI, 197 (61.9%) pts had a low-risk score, 99 (31.1%) were intermediate, and 22 (6.9%) were in the high-risk group. MDS-CI score was higher among males (43.8% vs 30.7% for females, p=0.02). It was also higher among subjects >75 y (48% vs. 28.9% for < 75 y (p=0.001). A lower comorbidity score impacted on the clinical choice for active forms of therapy, while pts with an higher burden of comorbidities were preferentially treated with supportive care, even if difference did not reach significance (p=0.07). Overall survival and risk of non-leukemic death (NLD) were analyzed (median f.u. 26.9 m (range 1-220). HCT-CI did not significantly correlated with OS nor NLD (p= 0.1 and p= 0.07, respectively), while MDS-CI was found to be of prognostic significance both for OS (mean 136.6 (95%CI 116-157) m for the low-risk group, 81.3 (95%CI 61-102) m for the intermediate group and 48.1 (95%CI 30-66) m for the high-risk group, p=0.001) and for NLD (mean 159.6 (95%CI 139-180) m for the low-risk group, 96.5 (95%CI 72-121) m for the intermediate group and 49 (95%CI 31-67) m for the high-risk group (p<0.001). The correlation was significant (p<0.001) in IPSS or IPSS-R “lower-risk” (low and intermediate-1 risk or very-low, low and intermediate groups, respectively) but not in IPSS nor IPSS-R “higher-risk” (intermediate-2 and high or high and very-high groups, respectively) pts. In multivariate analysis, the prognostic impact of MDS-CI remained independent of baseline IPSS (p=0.01) or IPSS-R (p=0.03). Conclusions: a comprehensive evaluation of comorbidities according to a tailored tool such is MDS-CI helps to predict survival in patients with MDS and should be incorporate to current prognostic scores in order to better define clinical management of these patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals An autophagy-related long non-coding RNA signature for patients with colorectal cancer

2021 ◽  
Author(s):  
Dongyan Zhao ◽  
Xizhen Sun ◽  
Sidan Long ◽  
Shukun Yao
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
High Risk ◽  
Cox Regression ◽  
Risk Group ◽  
Expression Profiles ◽  
High Risk Group ◽  
Low Risk ◽  
Gene Set Enrichment Analysis ◽  
Cox Regression Analysis

AbstractAimLong non-coding RNAs (lncRNAs) have been identified to regulate cancers by controlling the process of autophagy and by mediating the post-transcriptional and transcriptional regulation of autophagy-related genes. This study aimed to investigate the potential prognostic role of autophagy-associated lncRNAs in colorectal cancer (CRC) patients.MethodsLncRNA expression profiles and the corresponding clinical information of CRC patients were collected from The Cancer Genome Atlas (TCGA) database. Based on the TCGA dataset, autophagy-related lncRNAs were identified by Pearson correlation test. Univariate Cox regression analysis and the least absolute shrinkage and selection operator analysis (LASSO) Cox regression model were performed to construct the prognostic gene signature. Gene set enrichment analysis (GSEA) was used to further clarify the underlying molecular mechanisms.ResultsWe obtained 210 autophagy-related genes from the whole dataset and found 1187 lncRNAs that were correlated with the autophagy-related genes. Using Univariate and LASSO Cox regression analyses, eight lncRNAs were screened to establish an eight-lncRNA signature, based on which patients were divided into the low-risk and high-risk group. Patients’ overall survival was found to be significantly worse in the high-risk group compared to that in the low-risk group (log-rank p = 2.731E-06). ROC analysis showed that this signature had better prognostic accuracy than TNM stage, as indicated by the area under the curve. Furthermore, GSEA demonstrated that this signature was involved in many cancer-related pathways, including TGF-β, p53, mTOR and WNT signaling pathway.ConclusionsOur study constructed a novel signature from eight autophagy-related lncRNAs to predict the overall survival of CRC, which could assistant clinicians in making individualized treatment.

The FLIPI2 SCORE Predicts PROGRESSION-FREE SURVIVAL (PFS) and OVERALL SURVIVAL (OS) IN AN INDEPENDENT SERIES of Follicular LYMPHOMA: A Single Institution EXPERIENCE

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3128-3128 ◽  
Author(s):  
María José Terol ◽  
Ana Isabel Teruel ◽  
Paula Amat ◽  
Danella Elaluf ◽  
Mar Tormo ◽  
...  
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
Risk Group ◽  
Progression Free Survival ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Free Survival ◽  
Intermediate Group ◽  
Independent Series

Abstract Abstract 3128 Background: follicular lymphoma is an incurable, long-lasting disease with an heterogeneous outcome. Several prognostic systems have been proposed, and recently a new one, the FLIPI2 score based on five parameters has been published. However, in order to confirm its prognostic utility, further studies at other centers are highly recommendable. Aim: to validate the new FLIPI2 score in independent series of follicular lymphoma patients diagnosed at our institution between February 1990 and July 2010. Patients and methods. We considered 180 patients consecutively diagnosed with follicular diagnosis in the period described and from whom all variables required were available. The variables included were: beta2microglobulin higher than the upper normal value, longest diameter of the largest involved node longer than 6 cm, bone marrow infiltration, hemoglobin level lower than 120 g/L and age older than 60 years (one point if present). Three risk groups were identified: low risk (0 points), intermediate risk (1 -2) and high risk (3 or more) Progression-free survival was measured from date of treatment until date of progression or death from any cause. Continuous variables were summarized as median and range, categorical variables reported as counts, and PFS and OS carried out using the Kaplan-Meier method and curves compared by the log-rank test. Results: median age was 55 years (range, 24 to 77), male sex 92 (51%), Ann Arbor Stage I-II: 32(18%), III-IV: 143 (82%), age > 60 y 70 (39%), Hb < 120 g/L 38 (21%), β2microglobulin > UNV: 45 (25%), LDH > UNV: 34 (19%), bone marrow infiltration 82 (48%), longer diameter of the largest involved node > 6 cm 64 (36%). 47 patients (26%) received rituximab-containing regimens and 124 received conventional chemotherapy regimens (pre-rituximab era). Median follow-up of the series was 66.9 months (range,1.3-221). Using the FLIPI score (n=162) 58 patients (36%) were in the low risk group, 54 (33%) were in the intermediate group and 50 (31%) in the high risk group. Using the FLIPI2 (n=180) 36 patients (20%) were in the low risk group, 103 (57%) in the intermediate group and 41 (23%) in the high risk group. According to FLIPI 5y- PFS rate was 79% for the low risk group, 63% for the intermediate group and 32% for the high risk group, p < 0.001. According to FLIPI2 score, 5y-PFS rate was 82% for the low risk, 54% for the intermediate and 43% for the high risk groups, p=0.017. Concerning OS, applying the FLIPI, 5y-OS rate for the low, intermediate and high risk groups were 94%m 84% and 64%, respectively, p=0.003. Using the FLIPI2, 5y-OS for the low, intermediate and high risk groups were 96%, 80% and 67% respectively, p=0.006. Conclusions: in our experience the FLIPI2 score is a reproducible prognostic index in patients with follicular lymphoma although the FLIPI score seems to discriminate better between groups than the FLIPI2 score. Disclosures: No relevant conflicts of interest to declare.

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 Treatment Outcome and a Practical 10-Point Prognostic Index in Adult Patients with Non-M3 Acute Myeloid Leukemia: A Retrospective, Multicenter Study in Malaysia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2606-2606
Author(s):  
Tze Shin Leong ◽  
Sen Mui Tan ◽  
Lee Ping Chew ◽  
Tee Chuan Ong ◽  
Siew Lian Chong ◽  
...  
Keyword(s):  
Overall Survival ◽  
Treatment Outcome ◽  
High Risk ◽  
Relapse Rate ◽  
Survival Benefit ◽  
Risk Group ◽  
Prognostic Index ◽  
High Risk Group ◽  
Low Risk ◽  
Intermediate Risk

Background: Literature on Acute Myeloid Leukemia (AML) survival and prognostic factors were often derived from strict trial studies from developed country. A simple yet practical prognosis index has not been developed and tested in resource limited setting such as Malaysia. We described the treatment outcome and designed a 10 point prognostic index to predict survival of adult AML (non-M3) in real clinical practice in Malaysia. Methods: Data were retrospectively collected and analyzed from all adults with AML diagnosed and treated from 2007 to 2017 in three main hematology centers in Malaysia, Ampang Hospital, Sarawak General Hospital and Miri General Hospital. Treatment pattern and survival outcome were described. Multivariable analysis using Cox regression statistics were performed to identify significant prognostic variables affecting overall survival. Each variable were assigned points based on hazard ratios. A sum of the points led to a maximum score of 10. Patients were then categorized into low (0 point), intermediate (1 to 3 points) or high-risk group (4 points or above). Results: Demographics and treatment outcome of patients are shown in Table 1 & 2. There were 1277 adult patients, diagnosed with AML where 86.5% (n= 1106) of them were non M3 AML. Out of these, 908 patients (82.2%) received intensive chemotherapy treatment. Median age of diagnosis was 45 years. The remission post induction rate was 64.3% with induction death, refractory and relapse rate of 8.8%, 20.0% and 27.7% respectively. Median overall survival (OS) and Event Free Survival (EFS) time was 15 months and 12 months. The 3-year OS and EFS was 32.9% and 28.5% respectively. At the time of analysis, 66.1% of patients were dead (n=600) with disease progression being the main cause of death (n=416, 45.8%). Three year overall OS for patients who underwent allogeneic stem cell transplant (n=301, 33.1%) versus patients without transplantation were 53.7 % versus 22.0 % (HR 2.597, p <0.001). Cumulative incidence of relapsed and non-relapse mortality for transplant patients, shown in Figure 1 were 27.5% and 22.1%. Multivariate analysis in Table 3 showed that age 60 years old and above, male gender, white cell count more than 100 x 109 /L ,relapsed less than 12 months of treatment, refractory state after induction and high risk genetic group (based on EuropeanLeukemiaNet/Medical Research Council risk stratification by genetics) are prognostic factors associated with worse OS and EFS. The information was used to develop a 10 point prognostic index based on calculation described in Table 3. Overall survival decreased with each additional index point. When stratified according to risk group, the 3 year OS for low risk, intermediate risk and high risk group was 53.3%, 34.3% and 4.9% respectively. This is shown in Table 4 & Figure 2. Relapse rate was also lower in the low-risk group (8.8%), compared to intermediate-risk group (19.2%) and high-risk group (35.2%). Comparing transplant and non transplant cohort shown in Figure 3, there was no survival benefit in the low-risk group (58.6% vs 49.2%, p=0.122) but significant survival benefit in both intermediate-risk group (56.6% vs 23%, p<0.001) and adverse-risk group (13% vs 7%, p=0.002). Discussion/Conclusion: This is one of few survival studies that involved patients of different ethic groups in Asia (Malay, Chinese, Indian and native Borneo Sarawakians). Our results are comparable to data from large population based database such as US SEER and EURO CARE. This is the first prognostic index incorporating genetics, baseline characteristics and dynamic response, eg. refractory and/or relapsed post induction in non M3 AML. The results reaffirmed the importance of these factors in determining the clinical outcome and prognosis of patients with AML. When stratified using our 10 point prognostic index, our cohort of patients who is in low risk group has lower relapse rate and did not have significant survival benefit from allogeneic transplant compare to stratification using only the ELN/MRC genetic classification.(Table 5 & 6). In resource limited setting, measurable residual disease (MRD) monitoring and advanced genetic testing are difficult financially. This prognostic scoring index is an economical and practical alternative to guide physicians on treatment after induction therapy. However, it still needs to be validated by a larger cohort of patients in a prospective study. Disclosures No relevant conflicts of interest to declare.

An Immune-Related Gene Pairs Signature Predicts Overall Survival in Melanoma

2021 ◽  
Author(s):  
Ding Pan ◽  
Qi-Feng Ou ◽  
Pan-Feng Wu ◽  
Fang Yu ◽  
Ju-Yu Tang
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Related Gene ◽  
Immune Genes ◽  
Gene Pairs ◽  
Immune Related Gene ◽  
Public Data

Abstract Background:The incidence rate and mortality rate of melanoma have been increasing in recent decades. Increasing evidence has depicted the correlation between melanoma prognosis and immune signature. Therefore, the aim of this study is to develop a robust prognostic immune-related gene pairs (IRGPs) signature for estimating overall survival (OS) of melanoma.Methods:Gene expression profiling and clinical information of melanoma patients were derived from two public data sets, divided into training and validation cohorts. Immune genes significantly associated with prognosis were selected. Results:Among 1,646 immune genes, a 25 IRGPs signature was built which was significantly associated with OS in the training cohort (P=1.80×10−22; hazard ratio [HR] =9.50 [6.04, 14.93]). In the validation datasets, the IRGPs signature significantly divided patients into high- vs low- risk groups considering their prognosis (P=2.47×10−4; HR =2.99 [1.66, 5.38]) and was prognostic in multivariate analysis. Functional analysis showed that several biological processes, including keratinization and pigment phenotype-related pathways, enriched in the high-risk group. Macrophages M0, NK cells resting and T cells gamma delta were significantly higher in the high-risk group compared with the low-risk group. Conclusions:We successfully constructed a robust IRGPs signature with prognostic values for melanoma, providing new insights into post-operational treatment strategies.

Sunitinib in metastatic clear cell renal cancer (CCRC): A real life Chilean single institution experience.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16562-e16562
Author(s):  
Luis J. Orlandi ◽  
Pedro Pablo Galaz ◽  
Robert Melo Holloway ◽  
Belkys Melina Linares ◽  
Vicente Larrain Garcia
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Real Life ◽  
Stage Iv ◽  
High Risk Group ◽  
Good Choice ◽  
Low Risk ◽  
Entire Group ◽  
Access Methods ◽  
Secondary Reactions

e16562 Background: The introduction of biologic and immunologic therapy has produced a profound change in the management of metastatic CCRC but there is no definitive indication on drug selection and therapeutic sequences based on efficacy, toxicity, costs and access. Methods: We report 50 consecutive stage IV CCRC patients treated at our Institution from 12/2007 to 11/2020 with sunitinib at recommended dosage. Median age at stage IV diagnoses was 62.5 months (39 to 79). Sex distribution was 5 women (10%) and 45 (90%) men. Under MSKCC criteria 35 patients were medium + high risk (70%) and 15 (30%) low risk. Results: On an intent to treat basis the complete + partial response rate was 56% (28/50) for the entire group , 45.7% (16/35) for the high-risk group and 80% (12/15) for the low-risk group. Actuarial 5 year survival was 24% for the entire group, 11.4% for the high-risk group and 53.3% for the low -risk group. We explored the effect of metastases-free time on survival. We found that 15 patients were metastatic at the moment of initial diagnoses versus 26 patients who developed metastatic disease at 12+ months after primary tumor diagnoses. Mean survival was 32.7 months (1 - 97) for the first group and 49.5 months (6 - 156) for the second group (p<0.5). Subsequent therapies consisted of pazopanib (25 patients), axitinib (17 patients), everolimus (9 patients), nivolumab (6 patients) and cabozantinib (1 patient). Secondary reactions consisted of emesis (20%), diarrhea (16%), asthenia (14%), skin dispigmentation (12%), mucositis (10%), disgeusia (10%), dermatitis (10%), neutropenia (8%), hand and foot syndrome (4%). Conclusions: Sunitinib is a good choice in low-risk metastatic CCRC and we adopted this regimen as standard therapy in this group of patients at our Institution.

scholarly journals A Prognostic Model for Hepatocellular Carcinoma Patients Based on Signature Ferroptosis-related Genes

2021 ◽  
Author(s):  
Sizhe Wan ◽  
Yiming Lei ◽  
Mingkai Li ◽  
Bin Wu
Keyword(s):  
Overall Survival ◽  
T Cells ◽  
High Risk ◽  
Risk Score ◽  
Cox Regression ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Tnm Stage ◽  
Functional Enrichment

Abstract BackgroundWith the increasing number of HCC patients, it is necessary to accurately predicting the prognosis of these patients. Ferroptosis has been confirmed to be closely related to HCC progression. However, there is still a challenge in predicting the survival of HCC patients through ferroptosis-related genes.MethodThe RNA-seq data and corresponding clinical data of HCC from TCGA database were downloaded to establish a prognosis model, and data of ICGC and GSE14520 as the validation set. The risk score was constructed with 5 genes identified by univariate and LASSO Cox regression analysis. Then, risk score, TNM stage and cirrhosis were included to construct a nomogram, through univariate and multivariate Cox regression analysis.Results5 genes were identified from 70 ferroptosis-related DEGs to construct a gene signature to predict HCC patient survival from TCGA cohort. PCA and heatmap results show that there are obvious differences in patients with different score groups. Then, we included risk score, TNM stage and cirrhosis to construct a nomogram to further predict the overall survival of the patients. Survival analysis indicates that overall survival of the low- risk group is significantly higher than that of the high-risk group. Similarly, the data in the GSE14520 cohort also confirmed good performance for the nomogram. Furthermore, KEGG and GO functional enrichment analyses indicates the difference in overall survival between groups is closely related to immune-related pathways. Finally, through analyzing the immune status of all patients, we found that compared with patients in the low-risk group, “Macrophages M0”, “T cells CD8”, and “T cells regulatory” of the high-risk group were significantly higher.ConclusionThe nomogram based on ferroptosis-related genes has a good performance for the prognosis of HCC patients. The model may provide a reference for evaluation of HCC patients by targeting ferroptosis.

Risk Stratification Using a New Prognostic Model for Patients with Secondary Acute Myeloid Leukemia - Results of the DSIL-AML96 Trial.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2652-2652
Author(s):  
Friedrich Stölzel ◽  
Walter E. Aulitzky ◽  
Heinrich Bodenstein ◽  
Martin Bornhäuser ◽  
Michael Kramer ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Prognostic Model ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Allogeneic Hsct ◽  
Secondary Acute Myeloid Leukemia ◽  
Acute Myeloid

Abstract Abstract 2652 Poster Board II-628 Background: Secondary acute myeloid leukemia (sAML) following a myelodysplastic syndrome (mdsAML) or deriving as therapy-related AML (tAML) is regarded as an entity with a poor prognosis and patients are normally treated as high risk AML. However due to progress in elucidating the impact of molecular and cytogenetic markers and therefore combining biological and clinical data for prognosis and treatment outcome the aim of this analysis was to provide a prognostic scoring system for this entity by including clinical and laboratory data from patients being treated in the prospective AML96 trial of the DSIL study group. Patients and methods: A total of 318 patients with sAML (mdsAML = 239 and tAML = 79) were treated within the AML96 trial with a median follow-up for patients alive of 5.66 years (95% CI 4.426 – 6.895). All patients received double induction chemotherapy. Consolidation therapy contained high-dose cytosine arabinoside and for patients ' 60 years of age the option of autologous or allogeneic hematopoietic stem cell transplantation (HSCT) according to donor availability. Prognostic factors for survival were analyzed in the whole group of sAML patients in a multivariate Cox regression model for overall survival (OS) stratified by treatment groups (chemo-consolidation vs. allogeneic HSCT). Model selection was performed by backward selection applying the Likelihood-Ratio-Test. Results: Complete remission (CR) rate for all patients was 30.8% (n = 96). CR rate was lower in patients with mdsAML compared to patients with tAML (25.9% vs. 44.3%, p=.003). Patients with mdsAML were older and had a higher percentage of CD34+ blasts at diagnosis but to a lower extend aberrant karyotypes than patients with tAML. OS and disease free survival (DFS) at three years for all patients was 15.8% and 20.6%, respectively. While disease status (mdsAML vs. tAML) had no independent influence on survival, the dichotomized prognostic factors platelet count in the peripheral blood at diagnosis [HR = 0.535 (95% CI .415 – .689), p=<.000] as well as the NPM1 mutational status in the bone marrow at diagnosis [HR = 0.572 (95% CI .351 – .933), p=.025] were detected as independent predictors for overall survival. By combining these two variables, a prognostic model for OS with two risk groups for patients with sAML could be established with the low risk group being NPM1 positive or having platelets of >50 Gpt/l at diagnosis and the high risk group being NPM1 negative and having platelets of '50 Gpt/l at diagnosis. Three year OS for patients who received chemo-consolidation in the low risk group was 19.9% [95% CI = .128 - .270] and for patients in the high risk group 5.1% [95% CI = .014 - .088], p<.001. For patients who underwent allogeneic HSCT in first CR belonging to the low risk group the three year OS was 53.8% [95% CI = .346 - .730] and for patients in the high risk group 15.4% [95% CI = .000 - .35], p<.001. Conclusions: For patients with sAML we provide a new prognostic model for risk stratification: 1) NPM1+ or Platelets >50 Gpt/l defining a low risk group and 2) NPM1- and Platelets ' 50 Gpt/l defining a high risk group. Disclosures: No relevant conflicts of interest to declare.

Identification of Eight Surface Molecules with Survival Predictive Power in B Cell Chronic Lymphocytic Leukemia (B-CLL): A Proposal for a Scoring System.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2797-2797
Author(s):  
Valter Gattei ◽  
Paolo Sonego ◽  
Stefania Russo ◽  
Riccardo Bomben ◽  
Michele Dal Bo ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Predictive Power ◽  
Risk Group ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Intermediate Risk ◽  
Z Score ◽  
Surface Molecules

Abstract Studies of gene expression profiling of B-CLL cells revealed a phenotype related to experienced B cells, although only a subset of B-CLLs has IgVH mutations. With the aim to identify the immunophenotypic profile associated with a different prognosis, we investigated by flow cytometry the expression of 36 surface molecules (cell-adhesion molecules, integrins, complement activity regulators, myeloid, T and B markers) in 125 B-CLLs, all characterized for IgVH mutations and survival. To recognize the surface molecules with survival predictive power, univariate Cox proportional-hazards analysis was applied to antigen expression values with overall survival as dependent variable. Once identified the antigens whose expression correlated with a z score of ±2.5 (P&lt;0.005) or greater, the maximally selected log-rank statistics were applied to define the optimal cut-off values yielding the best separation of two subgroups with different survival. According to this approach, the following eight antigens were selected (cut-off values in parenthesis): CD55 (30%), CD62L (30%), CD49c (40%), CD11c (20%), CD54 (50%), CD25 (15%), CD79b (65%), CD38 (30%). The first six antigens had negative z score and therefore were identified as favorable prognosticators, while CD79b and CD38 had positive z score, hence were associated with shorter overall survival (negative prognosticators). To build-up a scoring system, we assigned score “1” to each positive prognosticator when its expression was above the designated cut-off (score “0” if below), and score “0” to each negative prognosticator when its expression was above the cut-off (score “1” if below). A total score ranging from 0 to 8 points was therefore obtained in 102/125 cases in which the expression of all the eight markers was available. Three risk groups were identified: i) high-risk (29 cases), score 0–3; ii) intermediate-risk (38 cases), score 4–6; iii) low-risk (35 cases), score 7–8. These three groups differed greatly for survival probabilities (p=5x10–13 by the log-rank test). All patients belonging to the low-risk group were alive throughout the follow-up duration, whereas mean survivals for intermediate- and high-risk groups were 173 months (p=0.032) and 61 months (p=2.0x10–9), respectively. Several relationship between risk groups and other variables was studied: i) patients included in high- and intermediate-risk groups had the same male to female (M:F) ratio (1.4), while the M:F ratio of patients included in low-risk group (group 3) was lower (0.7); ii) Rai’s stage distribution was comparable in the three groups, with the exception of stage “0”, which was significantly less frequent in the high-risk group (p=0.04); iii) if % IgVH mutations (2% cut-off) was checked, mutated to unmutated (M:UM) ratios were 4.8, 2.6 and 0.8 in low-, intermediate- and high-risk groups, respectively (p=0.006); iv) as compared to high-risk group, low- and intermediate-risk groups were characterized by a higher number of B-CLL cases with a IgVH mutational status consistent with antigen-driven selection (20/24 and 17/26 vs. 7/13). In conclusion, the present study introduces a novel predictive tool based on the expression of eight surface molecules, easily investigable, which can stratifies populations of B-CLL patients in three distinct risk categories.

Development and validation of a novel ten-gene prognostic signature for hepatocellular carcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16665-e16665
Author(s):  
Taicheng Zhou ◽  
Zhihua Cai ◽  
Ning Ma ◽  
Wenzhuan Xie ◽  
Chan Gao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
High Risk ◽  
Cox Regression ◽  
Risk Group ◽  
Gene Signature ◽  
High Risk Group ◽  
Low Risk ◽  
Gene Set Enrichment Analysis ◽  
Prognosis Prediction

e16665 Background: Hepatocellular carcinoma (HCC) remains a major challenge for public health worldwide and long-term outcomes remained dismal despite availability of curative treatment. We aimed to construct a multi-gene model for prognosis prediction to inform clinical management of HCC. Methods: RNA-seq data of paired tumor and normal tissue samples of HCC patients from the TCGA and GEO database were used to identify differentially expressed genes (DEGs). DEGs shared by both cohorts along with patients’ survival data of the TCGA cohort were further analyzed using univariate Cox regression and LASSO Cox regression to build a prognostic 10-gene signature, followed by validation of the signature via ICGC cohort and identification of independent prognostic predictors. A nomogram for prognosis prediction was built and Gene Set Enrichment Analysis (GSEA) was performed to further understand the underlying molecular mechanisms. Results: Of 571 patients (70.93% men and 29.07% women; median age [IQR], 65 [56-72] years), a signature of 10 genes was constructed using the training cohort. In the testing and validation cohorts, the signature significantly stratified patients into low- vs high-risk groups in terms of overall survival across and within subpopulations with stage I/II and III/IV disease and remained as an independent prognostic factor in multivariate analyses (hazard ratio range, 0.13 [95% CI, 0.07-0.24; P < 0 .001] to 0.38 [95% CI, 0.2-0.71; P < 0.001]) after adjusting for clinicopathological factors. Prognosis was significantly worse in the high-risk group than in the low-risk group across cohorts (P < 0.001 for all). The 10-gene signature achieved a higher accuracy (C-index, 0.84; AUCs for 1-, 3- and 5-year OS, 0.84, 0.81 and 0.85, respectively) than 8 previously reported multigene signatures (C-index range, 0.67 to 0.73; AUCs range, 0.68 to 0.79, 0.68 to 0.80 and 0.67 to 0.78, respectively) for estimation of survival in comparable cohorts. A nomogram incorporating tumor stage and signature-based risk group showed better predictive performance for 1- and 3- year survival than for 5 year survival. Moreover, GSEA revealed that the pathways related to cell cycle regulation were more prominently enriched in the high-risk group while the low-risk group had higher enrichment of metabolic process. Conclusions: Taken together, we established a robust 10-gene signature and a nomogram to predict overall survival of HCC patients, which may help recognize high-risk patients potentially benefiting from more aggressive treatment.

Sign in / Sign up

Export Citation Format

Share Document