scholarly journals Treatment Outcome of Patients with Myelodysplastic Syndromes (MDS) in Regular Care: Incidence of IPSS Risk Groups and Different Therapies in the German Outpatient MDS Registry

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5601-5601 ◽  
Author(s):  
H. Tilman Steinmetz ◽  
Isolde Böttger ◽  
Bernd Lathan ◽  
Annette Sauer ◽  
Enno Moorahrend ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Research Funding ◽  
Risk Groups ◽  
Outpatient Setting ◽  
Observation Time ◽  
Epigenetic Therapy ◽  
International Prognostic Scoring System ◽  
Course Of Disease ◽  
Regular Care

Abstract The international prognostic scoring system (IPSS) for MDS patients (pts) receiving supportive care predicts a median overall survival of 68.4 months (mo), 42 mo, 14.4 mo and 4.8 mo according to the subgroups low, Int-1, Int-2, and high-risk, respectively. In July 2009, we established the German outpatient MDS registry with the aim to describe diagnostic procedures, treatment and course of disease of MDS pts in the community outpatient setting. In this analysis we evaluate the incidence of the IPSS subgroups, the frequencies of different therapies and the outcome, respectively. Methods: Newly diagnosed pts with MDS confirmed by bone marrow biopsy who gave informed consent were registered in an online database (IoStudy®). Baseline characteristics and diagnostics as well as a quarterly update of the course of disease were documented. Results: From July 2009 to March 2014 (56 mo) 1368 pts from 78 institutions were registered. Mean age was 73.5 years (y) (min-max 26.5 - 94.3 y, median 74.5 y) and 41% were women. 1,262 pts (92.3%) were evaluable for follow-up with a mean observation time (OT) of 21.7 mo (median: 19 mo). At diagnosis, IPSS risk classification was available in 898/1,262 (71%) pts. OT, overall survival (OS), number of pts (N) with epigenetic and iron-chelation therapy (ICT) over the entire term and the need of transfusions (tx) per quarter (Q) are given according to risk groups and treatment in the table. The figure shows the estimated Kaplan-Meyer-Plot for the IPSS risk groups. 180/1,315 pts (13.7%) received ICT, whereas 1,035 did not (86.3%). Median OS was 51 (95% confidential interval (CI) 44.7-57.3) and 49 mo (95% CI 43.7-54.3) (p = 0,281) for those with and without ICT, respectively. Conclusion: In the community outpatient setting in Germany, epigenetic therapy is used in a relative high proportion of pts with int-2 risk (57.1%) and high risk MDS (63.5%) at diagnosis, as well as in a substantial minority of patients with low-risk (6.7%) and int-1 risk (28.9%) MDS at progression. In the higher risk groups, transfusion need decreased more than 10% over time and overall survival was substantially longer than predicted by the IPSS. This may be considered as an empirical evidence for the efficacy of the new therapeutic options in regular care. Supported by Celgene, Munich, and Novartis, Erlangen, Germany Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Steinmetz: Novartis: Consultancy, Research Funding; Celgene: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Severin:Novartis: Research Funding; Celgene: Research Funding. Germing:Celgene: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau. Schmitz:Novartis: Consultancy, Research Funding; Celgene: Consultancy, Research Funding, Speakers Bureau. Gattermann:Celgene: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau.

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 WT1 mRNA Expression in the Peripheral Blood of Patients with MDS Yields Additional Prognostic Information within the IPSS-R Risk Categories "Very Low", "Low" and "Intermediate"

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1827-1827
Author(s):  
Christina Rautenberg ◽  
Sabrina Pechtel ◽  
Norbert Gattermann ◽  
Rainer Haas ◽  
Ulrich Germing ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Peripheral Blood ◽  
Research Funding ◽  
Risk Groups ◽  
Prognostic Information ◽  
Expression Status ◽  
Very High ◽  
Risk Categories ◽  
Who 2008

Abstract Introduction: The revised version of the International Prognostic Scoring System, (IPSS-R), is an accepted standard for assessing the prognosis of patients with MDS. Its usefulness may be further improved by integrating molecular findings. However, such efforts are impeded by limited access to molecular diagnostics, lack of standardized methodology, and a relatively low frequency of individual gene mutations in MDS. The Wilms' Tumor-1 (WT1) gene is overexpressed on mRNA level in the peripheral blood (PB) in about 50% of patients with MDS. The aim of this analysis was to determine whether PB WT1 expression status yields additional prognostic information. Methods: For this purpose, PB WT1 mRNA expression was measured in 91 newly diagnosed patients with MDS (WHO: MDS del5q, n=7; RARS, n=1; RCUD, n=4; RCMD, n=37; RAEB-I, n=16; RAEB-II, n=23; MDS/MPN unclassifiable, n=3 / IPSS-R: very low risk, n=3; low risk, n=28; intermediate risk, n=27; high risk, n=13; very high risk, n=20), using the Ipsogen® WT1 ProfileQuant® Kit. This standardized, commercially available assay uses a validated cut-off level of 50 WT1 copies/104ABL copies for discrimination between normal and overexpression of WT1 in PB. MDS patients in our study cohort were stratified accordingly (normal WT1 expression with <50 WT1 copies versus overexpression with >50 WT1 copies). WT1 expression status was correlated with clinical parameters and outcome. Results: Overall, 53 MDS patients (58%) showed WT1 overexpression, which correlated significantly with WHO 2008 disease category and IPSS-R risk groups, as indicated by both the absolute WT1 levels (correlation with WHO 2008 type, p=0.0028, and IPSS-R, p=0.0075) and the frequency of WT1-overexpressing patients within the respective MDS subgroup (correlation with WHO 2008 type, p=0.0029, and IPSS-R, p=0.0027). Regarding the entire cohort, patients with elevated WT1 expression had a significantly lower progression-free survival (PFS) and overall survival (OS) compared to those with normal WT1 expression (p<0.0001 and p=0.0306). Furthermore, within the IPSS-R risk groups 'very low', 'low' and 'intermediate', PFS differed significantly between patients showing normal vs. elevated WT1 expression status (IPSS-R very low/low: median PFS 30.1 months vs. not reached, for WT1 high vs normal, respectively, p=0.0127; IPSS-R intermediate: median PFS 14.4 months vs. 59.5 months, for WT1 high vs. normal, respectively p=0.0240). These differences in PFS retained their prognostic significance in multivariate analysis after adjusting for IPSS-R (HR 0.306; 95% CI 0,156-0,598, p=0.001). However, they did not translate into a difference in overall survival, which was probably due to a relevant number of patients proceeding to allogeneic stem cell transplantation. Given the large proportion of patients displaying WT1 overexpression in the IPSS-R high and very high risk groups, it was not surprising that no significant prognostic subdivision by WT1 expression level was seen in these risk categories. Conclusion: Our results show that PB WT1 expression offers additional prognostic information in patients belonging to the IPSS-R risk groups 'very low', 'low' and 'intermediate'. Assessment of WT1 expression status at diagnosis is a relatively time and cost efficient method that can be performed without patient discomfort and may help to identify MDS IPSS-R low and intermediate patients at risk for early progression. Disclosures Rautenberg: Celgene: Honoraria. Germing:Janssen: Honoraria; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Kobbe:Roche: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Celgene: Honoraria, Other: Travel Support, Research Funding. Schroeder:Celgene: Consultancy, Honoraria, Research Funding.

The Disease Risk Index Is a Robust Tool for Allogeneic Hematopoietic Stem Cell Transplantation Risk Stratification: An Independent Validation Study on a Large Cohort of the European Society for Blood and Marrow Transplantation (EBMT)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 988-988 ◽  
Author(s):  
Roni Shouval ◽  
Joshua Fein ◽  
Myriam Labopin ◽  
Nicolaus Kroger ◽  
Rafael F. Duarte ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Hematological Malignancies ◽  
Disease Risk ◽  
Risk Index ◽  
Risk Groups ◽  
Advisory Committees ◽  
Very High

Abstract Background: Allogeneic stem cell transplantation is a potentially curative procedure to a long list of hematological malignancies, but involves substantial risk of morbidity and mortality. Means for accurately predicting outcome and assessing risk are thus greatly needed. The Disease Risk Index (DRI) is a prognostic tool developed and validated by Armand et al. across a wide range of hematological malignancies (Blood 2012, Blood 2014) on cohorts of American patients. The Index stratifies patients into 4 distinct risk groups (low, intermediate, high, very high) and has yet to be validated in an international cohort. We sought to evaluate the validity of the DRI in a large cohort of European patients. Methods: This was a retrospective validation study on an independent cohort of patients undergoing allogeneic HSCT and reported the European Society for Blood and Marrow Transplantation (EBMT). Patients included had a hematological malignancy and underwent allogeneic transplantation between the years of 2000 and 2015. Risk groups were coded in accordance with the refined DRI (Blood, 2014). Outcomes were evaluated 4 years after the allogeneic HSCT. Overall survival (OS) was calculated with the Kaplan-Meier method. The log-rank test was used for comparisons of Kaplan-Meier curves. Cumulative incidence curves for nonrelapse mortality (NRM) and relapse with or without death were constructed reflecting time to relapse and time to NRM, respectively, as competing risks. The difference between cumulative incidence curves in the presence of a competing risk was tested with the Gray method. The prognostic effect of the DRI strata was estimated using a Cox proportional hazard model for OS and a Fine and Gray model for NRM and relapse. Results: A total of 89,061 patients from 423 transplantation centers were included in the analysis. Median age was 48.3 (IQR 36.2-57.5). The most frequent indication for transplantation was AML (39,530 patients) followed by ALL (16,206) and MDS (9,750); other indications spanned the spectrum of hematological malignancies. The majority of patients were in 1st or 2nd complete remission (54%). The median follow-up period was 3.6 years. Approximately 63% of patients were classified as intermediate risk by DRI, suggesting that this group could be further partitioned. The 4 year overall survival (95% CI) of the low, intermediate, high, and very high risk groups was 60.8% (59.9-61.8), 51.3% (50.8‐51.8), 27.0% (26.1‐27.8), 18.4% (17.1-19.8) (Figure 1). The same groups corresponded with increasing cumulative incidence of relapse; 8.9% (8.3-9.4), 19.3% (18.9-19.7), 39.0% (37.8-39.6), 45.1% (43.4-46.7), respectively. The DRI groups also showed increasing hazard between strata in the overall survival setting; intermediate risk was associated with a hazard ratio of 1.32, high risk 2.67 and very high risk 3.71 relative to low risk. Relapse showed a similar pattern. NRM was less strongly stratified by DRI (Table 1). The DRI groups maintained a similar risk, regardless of whether the transplantation was performed prior or after 2008. DRI was the strongest determinant of overall survival and relapse when introduced to a multivariable model with additional covariates. AUC for the index at 4 years was 62.5 for OS, 58.5 for NRM and 68.2 for relapse. Conclusions: We have validated the Disease Risk Index in a massive European data set. The groupings suggested by the DRI corresponded with distinct risk groups for overall mortality and relapse. Overall, our results indicate the international applicability of this robust prognostic tool. Figure 1. Kaplan-Meyer survival curves for overall survival, stratified by DRI Figure 1. Kaplan-Meyer survival curves for overall survival, stratified by DRI Table 1 Table 1. Disclosures Bader: Medac: Consultancy, Research Funding; Riemser: Research Funding; Neovii Biotech: Research Funding; Servier: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Bonini:Molmed SpA: Consultancy; TxCell: Membership on an entity's Board of Directors or advisory committees. Dreger:Gilead: Consultancy; Janssen: Consultancy; Novartis: Speakers Bureau; Gilead: Speakers Bureau; Novartis: Consultancy; Roche: Consultancy. Kuball:Gadeta B.V,: Membership on an entity's Board of Directors or advisory committees. Montoto:Roche: Honoraria; Gilead: Research Funding.

Azacitidine for Treatment of Therapy Related Myelodysplastic Syndrome

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1712-1712
Author(s):  
Rami S. Komrokji ◽  
Najla H Al Ali ◽  
E Alrawi ◽  
Eric Padron ◽  
Janelle Perkins ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Scoring System ◽  
Research Funding ◽  
Who Classification ◽  
De Novo ◽  
Risk Groups ◽  
Refractory Anemia ◽  
Cancer Center ◽  
P Value

Abstract Abstract 1712 Background: Therapy related MDS (t-MDS) is a rising challenge, it accounts for about 10%-15% of MDS cases. Outcome of t-MDS is generally poor. Azacitidine is currently standard of care for higher risk MDS based on AZA-001 randomized clinical trial demonstrating survival advantage. Efficacy of azacitidine in t-MDS is not well studied. We investigated the outcome of t-MDS patients treated with azacitidine at the Moffitt Cancer Center (MCC). Methods: This was a retrospective review of t-MDS cases treated at Moffitt Cancer Center (MCC) with azacitidine. Patients were identified through MCC MDS database and individual charts were reviewed. The primary objective was overall survival (OS) from time of azacitidine starting date. Patients were included if at least received one cycle of azacitidine. Disease status was defined by both the French American British (FAB) and the World Health Organization (WHO) classification systems, and risk was scored by the International Prognostic Scoring System (IPSS), and MD Anderson Scoring System (MDAS). Response to azacitidine was defined per the International Working Group (IWG 2006) criteria. All analyses were conducted using SPSS version 15.0. (SPSS Inc, Chicago, IL). Descriptive statistics were used for baseline characteristics and responses. Kaplan-Meier estimates were used to calculate overall survival (OS). Results: Between July 2004 and April 2010, 76 patients with t-MDS/AML were treated with azacitidine. The median duration of follow up was 58 months. The median age was 64.5 years (36–84). Majority of patients were Caucasians race 87% (n=66) and 55% (n=42) were male gender. The underlying malignancy was hematological malignancy in 38 patients (50%), solid tumor in 34 patients (45%), and 4 patients (5%) had both. Prior treatment for primary malignancy included chemotherapy in 44 patients (58%), chemoradiation in 23 patients (30%), and 9 patients (12%) received radiation therapy only. Fourteen patients received prior autologous SCT. According to WHO classification 2.6% (2) were Refractory anemia (RA), 3.9% (3) Refractory anemia with ring sideroblasts (RARS), 30.3% (23) refractory anemia with multilineage cytopenia (RCMD), 28.9% (22) refractory anemia with excess blasts I (RAEB-I), 25% (19) refractory anemia with excess blasts II (RAEB-II), 1.3% (1) CMML, 6.6% (5) AML, and 1.3 % (1) unknown. The IPSS risk was low in 1.3% (1), intermediate-1 (int-1) 19.7% (15), int-2 57.9% (44), high risk 17.1% (13) and unknown 3.9% (3). Based on MDAS the risk groups were 1.3% (1) low, 7.9% (6) int-1, 26.3% (20) int-2, 63.2% (48) high risk, and 1.3% (1) unknown. The cytogenetic risk groups were in 13.2% (10) good, 10.5% (8) intermediate, 72.4% (55) poor, and 1.3% (1) unknown. The median number of azacitidine cycles was 4 (Range 1–18). The response rates (IWG 2006 criteria) were 11.8% (9) CR, 2.6% (2) marrow CR, 10.5% (8) PR, 18.4% (14) HI, 14.5% (11) Stable disease (SD), 21.1 % (16) progressive disease (PD), and 17.1% (13) unknown. The overall response rate (CR+mCR+PR+HI) was 43.4 % (33). Among all patients 34.2% (26) had HI-E, 23.7% (18) had HI-N, and 32.9% (25) HI-P. The median OS was 14.9 months (95%CI 12.2–17.7) from start of azacitidine treatment. Twenty patients underwent allogeneic stem cell transplant (allo SCT). The median OS survival for patients who underwent allo SCT was 22.2 months compared to 13.6 months for those who did not. (p-value 0.015, log rank test). The median OS for patients who achieved SD or better best response with azacitidine therapy was 17.2 months compared to 8.3 months for patients with PD (p-value 0.014). Conclusion: Azacitidine is active in t-MDS; response rates are comparable to de novo MDS patients. Overall survival for t-MDS treated with azacitidine is slightly inferior to de novo MDS treated on AZA-001 study in general but similar to those with poor karyotype on the same study. Disclosures: Komrokji: Celgene: Honoraria, Research Funding, Speakers Bureau. Lancet:Celgene: Research Funding. List:Celgene: Consultancy.

scholarly journals A prognostic model based on seven immune-related genes predicts the overall survival of patients with hepatocellular carcinoma

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Qian Yan ◽  
Wenjiang Zheng ◽  
Boqing Wang ◽  
Baoqian Ye ◽  
Huiyan Luo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
High Risk ◽  
Risk Score ◽  
Immune Cells ◽  
Prognostic Model ◽  
Risk Groups ◽  
Low Risk ◽  
Prognostic Performance ◽  
Immune Related Genes

Abstract Background Hepatocellular carcinoma (HCC) is a disease with a high incidence and a poor prognosis. Growing amounts of evidence have shown that the immune system plays a critical role in the biological processes of HCC such as progression, recurrence, and metastasis, and some have discussed using it as a weapon against a variety of cancers. However, the impact of immune-related genes (IRGs) on the prognosis of HCC remains unclear. Methods Based on The Cancer Gene Atlas (TCGA) and Immunology Database and Analysis Portal (ImmPort) datasets, we integrated the ribonucleic acid (RNA) sequencing profiles of 424 HCC patients with IRGs to calculate immune-related differentially expressed genes (DEGs). Survival analysis was used to establish a prognostic model of survival- and immune-related DEGs. Based on genomic and clinicopathological data, we constructed a nomogram to predict the prognosis of HCC patients. Gene set enrichment analysis further clarified the signalling pathways of the high-risk and low-risk groups constructed based on the IRGs in HCC. Next, we evaluated the correlation between the risk score and the infiltration of immune cells, and finally, we validated the prognostic performance of this model in the GSE14520 dataset. Results A total of 100 immune-related DEGs were significantly associated with the clinical outcomes of patients with HCC. We performed univariate and multivariate least absolute shrinkage and selection operator (Lasso) regression analyses on these genes to construct a prognostic model of seven IRGs (Fatty Acid Binding Protein 6 (FABP6), Microtubule-Associated Protein Tau (MAPT), Baculoviral IAP Repeat Containing 5 (BIRC5), Plexin-A1 (PLXNA1), Secreted Phosphoprotein 1 (SPP1), Stanniocalcin 2 (STC2) and Chondroitin Sulfate Proteoglycan 5 (CSPG5)), which showed better prognostic performance than the tumour/node/metastasis (TNM) staging system. Moreover, we constructed a regulatory network related to transcription factors (TFs) that further unravelled the regulatory mechanisms of these genes. According to the median value of the risk score, the entire TCGA cohort was divided into high-risk and low-risk groups, and the low-risk group had a better overall survival (OS) rate. To predict the OS rate of HCC, we established a gene- and clinical factor-related nomogram. The receiver operating characteristic (ROC) curve, concordance index (C-index) and calibration curve showed that this model had moderate accuracy. The correlation analysis between the risk score and the infiltration of six common types of immune cells showed that the model could reflect the state of the immune microenvironment in HCC tumours. Conclusion Our IRG prognostic model was shown to have value in the monitoring, treatment, and prognostic assessment of HCC patients and could be used as a survival prediction tool in the near future.

scholarly journals Proposal of a Novel Latin American International Prognostic Index (LATAM-IPI) for Diffuse Large B-Cell Lymphoma (DLBCL) By the Grupo Para El Estudio De Linfoproliferativos En Latino-America (GELL)

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 25-27
Author(s):  
Luis Villela Villela ◽  
Ana Ramirez-Ibarguen ◽  
Brady E Beltran ◽  
Camila Peña ◽  
Denisse A. Castro ◽  
...  
Keyword(s):  
High Risk ◽  
Board Of Directors ◽  
Research Funding ◽  
Scoring Systems ◽  
Risk Groups ◽  
Training Set ◽  
Extranodal Involvement ◽  
Advisory Committees ◽  
Internal Validation ◽  
Biological Variables

Introduction. There are different scoring systems to differentiate risk groups in patients with DLBCL treated with chemoimmunotherapy. Those systems have used the same 5 variables (age, performance status, LDH, stage, extranodal involvement) for 27 years. However, LATAM data have not been included in the development of previous scoring systems. It is important to mention that novel biological variables, such as albumin, beta-2-microglobulin (B2M) and platelet/lymphocyte ratio (PLR), have been reported and could improve discrimination (Villela et al. Blood 2019; 134Suppl_1: 1613). Therefore, we carried out a large, multinational study to develop and validate a LATAM-IPI score. Methods. This is a retrospective cohort of 1030 patients with a diagnosis of DLBCL treated with standard chemoimmunotherapy with curative intent between 2010 and 2018. Data were obtained from 8 LATAM countries: Argentina, Colombia, Chile, Guatemala, Mexico, Paraguay, Peru, and Venezuela. The five classic IPI variables (age, ECOG, extranodal involvement, LDH, stage) were analyzed and albumin and PLR were added (Villela et al. Blood 2019; 134Suppl_1: 1613). B2M was not included because it was not requested regularly in all countries. Development of LATAM-IPI: The training set consisted of 85% of the sample, randomly selected, and the remaining 15% was reserved for internal validation. Using the training set, the univariate and multivariate association between clinical prognostic factors and OS was analyzed fitting Cox proportional-hazard models. Outcomes. Clinical characteristics of the training (n=878) and internal validation (n=151) cohorts are shown in Table 1. There were no statistical differences in baseline characteristics between the cohorts. The median follow-up for the whole cohort was 36 months (IQR: 11-57). When exploring the classic IPI variables on the training set, all variables were associated with high risk of mortality [age 65-74, Hazard Ratio (HR) 1.24, 95% CI 0.96 to 1.58, p=0.08; age ≥75, HR 1.71, 95% CI 1.28 to 2.28, p=0.0003), ECOG (≥ 2, HR=2, 95% CI 1.61 to 2.53; p&lt;0.0001), EN (≥2, HR=1.53, 95% CI 1.18 to 1.97; p=0.0012), stage (III/IV, HR=2.1, 95% CI 1.64 to 2.69; p&lt;0.0001) and LDH (ratio 1.1-2.9, HR=1.55, 95% CI 1.22 to 1.97; p=0.0003; ratio ≥3, HR= 2.68, 95% CI 1.93 to 3.7, p&lt;0.0001). Similarly, the biological variables Albumin (≤3.5 mg/dL, HR 2.37, 95% CI 1.9 to 2.95, p&lt;0.0001) and PLR (≥273, HR= 1.52, 95% CI 1.23 to 1.87; p=0.0001) were associated with high risk of death. Next, these variables were evaluated by multivariate analysis. The independent variables were albumin (&lt;3.5 mg/dL, HR 1.84, 95% CI 1.45 to 2.3, p&lt;0.0001, 1 point), LDH (ratio 1.1 to 2.9, HR 1.30, 95% CI 1.02 to 1.67, p=0.03, 1 point; ratio ≥3, HR=1.84, 95% CI 1.31 to 2.5, p=0.0004, 2 points), advanced stage (HR 1.65, 95% CI 1.27 to 2.13, p=0.0001, 1 point), age (≥75, HR= 1.51, 95% CI 1.15 to 1.98, p=0.003, 1 point), and ECOG (≥2, HR 1.40, 95% CI 1.10 to 1.77, p=0.005). Now, for the development of LATAM-IPI, the groups were distributed as follows: 0 points, low; 1-3 points, intermediate; 4-6 points, high risk. There were no differences in the distribution of the risk groups between training and validation sets (Table 2). In the learning cohort, the 5-year OS rates for low, intermediate and high risk were 81%, 63% and 33%, respectively (p&lt;0.0001). In the validation cohort, the 5-year OS rates for low, intermediate and high risk were 81%, 63% and 44%, respectively (p=0.02) (Figure 1). Conclusions: Using multinational learning and validation cohorts including over 1,000 DLBCL patients treated with standard chemoimmunotherapy in LATAM, we developed a novel LATAM-IPI score using age ≥75 years, ECOG ≥2, advanced stage, LDH ratio (1.1-29 and ≥3) and albumin &lt;3.5 mg/dl. Next steps are to disseminate our results with other involved researchers in LATAM to prospectively assess and reproduce our results. We expect this score will help to further define the prognosis of DLBCL patients in LATAM. Disclosures Villela: amgen: Speakers Bureau; Roche: Other: advisory board, Speakers Bureau. Idrobo:Janssen: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau; Tecnofarma: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau. Gomez-Almaguer:Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Castillo:Janssen: Consultancy, Research Funding; TG Therapeutics: Research Funding; Kymera: Consultancy; Abbvie: Research Funding; Beigene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding.

Thirty-Five Year Follow-up Analysis of Follicular Lymphoma Patients Treated through the Nebraska Lymphoma Study Group: Prognostic Factor Analysis and Outcomes

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 7-8
Author(s):  
Amulya Yellala ◽  
Elizabeth R. Lyden ◽  
Heather Nutsch ◽  
Avyakta Kallam ◽  
Kai Fu ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Follicular Lymphoma ◽  
Treatment Regimen ◽  
Research Funding ◽  
Study Group ◽  
Secondary Malignancies ◽  
Lymphoma Study Group

Background Follicular lymphoma (FL) is the second most common type of non-Hodgkin lymphoma (NHL) and most common of the clinically indolent NHLs. Although often considered an incurable disease, overall survival has increased significantly with refinement in diagnostic techniques and the addition of rituximab. The course of FL is quite variable and presence of symptoms, organ dysfunction, cytopenias, aggressiveness of tumor are all taken into consideration when deciding individual treatment. In this study, we evaluated a large patient cohort with FL treated over a 35 year period for progression free survival (PFS), overall survival (OS) based on FLIPI score, tumor grade, and treatment regimen and also looked at causes of late failures. Methods We evaluated 1037 patients (pts) from the Nebraska Lymphoma Study Group that were diagnosed with FL between the years of 1983-2020. Descriptive statistics were stratified according to age, histological subtype, treatment regimen, FLIPI category, presence and type of secondary malignancy. PFS was calculated from the time of diagnosis to progression or death and OS was the time from diagnosis to death from any cause. PFS and OS were plotted as Kaplan-Meier curves with statistically significant p&lt;0.05. Results The median age at diagnosis and treatment was 61 years (yrs, range 17-91). A total of 9.1% were characterized as FLIPI high risk, 37.8% intermediate risk, and 33.6% low risk, 19.5% unavailable. Among the histological grade, 23.1% had FL- grade 1, 30.2% FL-2, 27.3% FL-3A, 2.5 % FL-3B and 16.9 % Composite Lymphoma. Anthracycline + rituximab was given in 24.5% of pts, whereas 43.8% of pts received an anthracycline based regimen without rituximab, 9.8% received rituximab without an anthracycline and 10.6% received neither of these agents. 6.75% (70 pts) were later found to have secondary malignancies of which 11 pts had myelodysplastic syndrome, 10 pts had acute leukemia and 9 pts had lung cancer. With a median follow up of 9.2 yrs and a maximum of 36 yrs, 29.7% (308 pts) had not relapsed. The median PFS across all groups was 4.6 yrs (Fig 1) and OS was 12.1 yrs. Median OS was significantly longer in patients that received rituximab at 16.1 yrs as compared to patients that did not receive rituximab at 9.89 yrs (Fig 2). PFS was 8.6 yrs, 3.6 yrs and 2.1 yrs and OS was 15.1 yrs, 11.7 yrs and 4.9 yrs in FLIPI low, intermediate and high risk groups respectively (p=&lt;0.001) (Fig 3), suggesting that survival was influenced by FLIPI score. Median PFS in FL-3B and FL-3A was 9.2 yrs and 5.2 yrs respectively which is longer than 4.7 yrs and 4.2 yrs for FL-1 and FL-2 (p=0.24). OS in FL-3A and FL-3B subgroups was 10.8 yrs while it was 11.6 yrs and 14.3 yrs in FL-2 and FL-1 (P=0.081). PFS is significantly longer at 10.6 yrs in pts treated with both anthracycline and rituximab containing regimen as compared to 5.3 yrs in pts treated with rituximab alone and 3.05 yrs in pts that had only anthracycline based regimen (p=&lt;0.001) (Fig 4). The median OS also was significantly higher in the combination regimen group at 18.8 yrs as compared to 11.3 yrs in rituximab only group and 9 yrs in anthracycline based regimen group (p=&lt;0.001). When pts with FL-3A and FL-3B were grouped together and stratified according to treatment regimen, the group that received anthracycline and rituximab combination has highest PFS and OS at 13.3 yrs and 18.8 yrs (p&lt;0.001). when pts with FL-3A were analyzed separately and stratified by treatment regimen, the results of PFS and OS were similar and statistically significant. However, of the 24 pts in FL-3B group, analysis revealed that PFS and OS was longer in anthracycline based regimen only group, however results were not statistically significant. Among the pts that relapsed/died after 10 years (n=190), the cause of death was relapsed lymphoma in 13.7%, unknown in 55.8%, secondary malignancies in 4.2%, treatment related in 2.6% and not related to disease in 23.7%. A total of 278 pts survived &gt; 10 yrs, and of these pts, 119 (30%) had not relapsed at the last follow up. Conclusion The addition of rituximab to standard anthracycline based chemotherapy has resulted in significant improvements in the PFS and OS rates of FL. These results also support the prognostic value of the FLIPI in patients treated in the rituximab era. Late relapses after 10 yrs from disease can occur, but 11.5% of patients had not relapsed with long term follow up. Secondary malignancies are also an important consideration in the long term survivors. Disclosures Lunning: Acrotech: Consultancy; TG Therapeutics: Research Funding; Novartis: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Curis: Research Funding; Beigene: Consultancy, Honoraria; Aeratech: Consultancy, Honoraria; Bristol Meyers Squibb: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Legend: Consultancy; Verastem: Consultancy, Honoraria; ADC Therapeutics: Consultancy. Armitage:Trovagene/Cardiff Oncology: Membership on an entity's Board of Directors or advisory committees; Samus Therapeutics: Consultancy; Ascentage: Consultancy. Vose:Bristol-Myers Squibb: Research Funding; Karyopharm Therapeutics: Consultancy, Honoraria; Seattle Genetics: Research Funding; Allogene: Honoraria; AstraZeneca: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Honoraria, Research Funding; Wugen: Honoraria; Novartis: Research Funding; Celgene: Honoraria; Incyte: Research Funding; Roche/Genetech: Consultancy, Honoraria, Other; Verastem: Consultancy, Honoraria; Miltenyi Biotec: Honoraria; Loxo: Consultancy, Honoraria, Research Funding; Janssen: Honoraria; Epizyme: Honoraria, Research Funding; AbbVie: Consultancy, Honoraria.

Postoperative PET/CT for detection of early recurrence (ER) after surgery for squamous cell carcinomas (SCC) of the oral cavity (OC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6060-6060
Author(s):  
Yao Yu ◽  
Heiko Schöder ◽  
Jung Kang ◽  
Sean Matthew McBride ◽  
C. Jillian Tsai ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
High Risk ◽  
Postoperative Radiotherapy ◽  
Prospective Trial ◽  
Disease Free Survival ◽  
Distant Metastases ◽  
Risk Groups ◽  
Free Survival ◽  
Pet Ct

6060 Background: Patients with ER after surgery and prior to postoperative radiation (RT) for SCC of the OC have aggressive biology and poor prognosis. After the introduction of a PET/CT simulator in our department, we incorporated post-operative PET/CT as part of RT planning. We hypothesized PET/CT would improve detection of macroscopic disease before postoperative RT. Methods: We reviewed the medical records of patients treated with postoperative radiotherapy between 2005 and 2019 for OC SCC. Clinicopathologic risk factors were recorded. Intermediate risk factors (IRFs) included pT3-4 disease, nodal disease, perineural invasion (PNI), lymphovascular invasion (LVI), and close ( < 5mm) surgical margins (SM); extranodal extension (ENE) and positive SM were considered high-risk factors (HRF). Patients were stratified into risk groups based upon the number and type of risk factors: 0-1 IRFs, 2 IRFs, ≥3 IRFs, and any HRF. Patients were considered to have ER if they had biopsy confirmed recurrence, or if the imaging or exam was sufficiently suspicious, after discussion with the head and neck team, to warrant treatment to definitive doses of RT (70 Gy). Results: Our cohort included 391 patients with SCC of the OCC who were treated with postoperative radiotherapy. 61% of patients were male, 35% had pT3-4 disease, 36% had pN2a-3 disease, 53% had PNI, 20% had LVI, 30% had ENE, and 14% had positive SM. The most common sites were oral tongue (46%), alveolar ridge (18%), and buccal mucosa (13%). 237 (61%) patients underwent postoperative PET/CT planning, and 165 patients (41%) were planned with CT only. Patients screened with post-operative PET/CT were more likely to be diagnosed with ER (46/237, 19.4%) than those simulated with CT only (6/154, 3.9%, p < 0.0001). Among patients simulated with PET/CT, 7%, 9%, 14%, and 35% of patients were diagnosed with ER for patients with 0-1 IRFs, 2 IRFs, ≥3 IRFs, and any HRF, respectively. Median follow-up was 4.1 years (95% CI 3.6 – 4.5). Among 52 patients with ER, 24 (49.0%) had local, 41 (83.7%) had regional, and 5 (10.2%) had distant recurrence. 17 (33%) of ER were biopsy proven. For patients with ER, 3-year freedom from locoregional recurrence, distant-metastasis free survival, and overall survival were 45.2% (95% CI 32% - 64%), 55% (95% CI 42% – 72%), and 43% (95% CI 30% - 61%), respectively. For patients without ER, use of postoperative PET/CT was associated with improved disease-free survival (HR 0.68, 95% CI 0.46 – 0.98, p = 0.041) and overall survival (HR 0.59, 95% CI 0.38 – 0.91, p = 0.019). Conclusions: Postoperative PET/CT may increase detection ER compared to CT simulation alone and improve risk stratification. Patients with ER are at high risk of locoregional failure, distant metastases, and mortality, despite salvage therapy. A prospective trial is underway at our institution to systemically study the role of PET/CT for detection of ER.

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 Risk stratification in pediatric low-grade glioma and glioneuronal tumor treated with radiation therapy: an integrated clinicopathologic and molecular analysis

2020 ◽  
Vol 22 (8) ◽  
pp. 1203-1213 ◽  
Author(s):  
Sahaja Acharya ◽  
Jo-Fen Liu ◽  
Ruth G Tatevossian ◽  
Jason Chiang ◽  
Ibrahim Qaddoumi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
High Risk ◽  
Risk Stratification ◽  
Risk Groups ◽  
Low Risk ◽  
Glioneuronal Tumor ◽  
Low Grade ◽  
Diffuse Astrocytoma ◽  
Prognostic Features

Abstract Background Management of unresectable pediatric low-grade glioma and glioneuronal tumor (LGG/LGGNT) is controversial. There are no validated prognostic features to guide use of radiation therapy (RT). Our study aimed to identify negative prognostic features in patients treated with RT using clinicopathologic and molecular data and validate these findings in an external dataset. Methods Children with non-metastatic, biopsy-proven unresectable LGG/LGGNT treated with RT at a single institution between 1997 and 2017 were identified. Recursive partitioning analysis (RPA) was used to stratify patients into low- and high-risk prognostic groups based on overall survival (OS). CNS9702 data were used for validation. Results One hundred and fifty patients met inclusion criteria. Median follow-up was 11.4 years. RPA yielded low- and high-risk groups with 10-year OS of 95.6% versus 76.4% (95% CI: 88.7%–98.4% vs 59.3%–87.1%, P = 0.003), respectively. These risk groups were validated using CNS9702 dataset (n = 48) (4-year OS: low-risk vs high-risk: 100% vs 64%, P &lt; 0.001). High-risk tumors included diffuse astrocytoma or location within thalamus/midbrain. Low-risk tumors included pilocytic astrocytoma/ganglioglioma located outside of the thalamus/midbrain. In the subgroup with known BRAF status (n = 49), risk stratification remained prognostic independently of BRAF alteration (V600E or fusion). Within the high-risk group, delayed RT, defined as RT after at least one line of chemotherapy, was associated with a further decrement in overall survival (P = 0.021). Conclusion A high-risk subgroup of patients, defined by diffuse astrocytoma histology or midbrain/thalamus tumor location, have suboptimal long-term survival and might benefit from timely use of RT. These results require validation.

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