L-BLP25 in Patients With Colorectal Carcinoma After Curative Resection of Hepatic Metastases
Ontology highlight
ABSTRACT:
DISEASE(S): Rectum Carcinoma,Neoplasm Metastasis,Carcinoma,Colorectal Neoplasms,Colon Carcinoma
PROVIDER: 2114967 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Primary objectives: Comparative evaluation of recurrence-free survival time and three year overall survial between the treatment groups L-BLP25 plus cyclophosphamide versus placebo vaccination and saline infusion
Primary endpoints: Recurrence-Free Survival (RFS) time and three year overall survival based on standard imaging.
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Project description:Neoadjuvant (NA) stereotactic ablative radiotherapy (SAbR) may improve outcomes in pancreatic cancer. We compared outcomes and molecular characteristics of patients who had surgery after neoadjuvant chemotherapy, with and without SAbR. We compared clinical data from surgically resected patients treated with either NA chemotherapy or NA chemotherapy plus SAbR. Recurrence-free and overall survival (RFS/OS) were analyzed using stepwise-AIC-optimized multivariable Cox modeling and log-rank tests. When available, we used transcriptomic analyses (GSEA, CIBERSORTx, and SCISSOR) to link clinical outcomes to gene expression patterns. We reviewed 133 patients treated with NA chemotherapy and 48 with NA chemotherapy + SAbR, including RNA sequencing data from 29 and 14 patients, respectively. Before surgery, the SAbR group had more advanced disease with arterial involvement, yet still achieved similar OS and RFS. Patients treated with SAbR had better post-treatment pathology linked to improved OS and RFS. RNA sequencing showed that patients with nodal involvement had enriched MYC targets and worse distant RFS. Those with arterial involvement had worse locoregional RFS with chemotherapy alone, but not in the SAbR group. GSEA highlighted immune-related changes in myeloid and T cell activation, suggesting treatment-related functional changes. SCISSOR analysis revealed cytotoxic CD8 and NK/NKT cell signatures correlating with better local control, while Treg signatures were linked to worse LRFS. Patients treated with NA chemotherapy + SAbR showed better pathologic outcomes, improved local control, and comparable survival, along with a distinct immune response. Further evaluation of SAbR in the neoadjuvant setting, combined with enhanced chemotherapy and novel treatment combinations, may lead to even greater clinical benefits.
2025-03-06 | GSE277386 | GEO
Project description:Background: Circular RNAs (circRNAs) have attracted increasing attention in recent years for their potential application as disease biomarkers due to their high abundance and stability. In this study, we attempted to screen circRNAs that can be used to predict postoperative recurrence and survival in patients with gastric cancer (GC). Methods: High-throughput RNA sequencing was used to identify differentially expressed circRNAs in GC patients with different prognoses. The expression level of circRNAs in the training set (n=136) and validation set (n=167) was detected by quantitative real-time PCR (qRT-PCR). Kaplan–Meier estimator, receiver operating characteristic (ROC) curve and cox regression analysis were used to evaluate the prognostic value of circRNAs on recurrence-free survival (RFS) and overall survival (OS) in GC patients. CeRNA network prediction, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed for the circRNAs with prognostic significance. Results: A total of 259 differentially expressed circRNAs were identified in GC patients with different RFS. We found two circRNAs (hsa_circ_0005092 and hsa_circ_0002647) that highly expressed in GC patients with good prognoses, and subsequently established a predictive model for postoperative recurrence and prognosis evaluation, named circPanel. Patients with circPanellow might have shorter recurrence-free survival (RFS) and overall survival (OS). We also performed circRNA-miRNA-mRNA network prediction and functional analysis for hsa_circ_0005092 and hsa_circ_0002647. Conclusions: CircPanel has the potential to be a prognostic biomarker in GC patients with greater accuracy than a single circRNA and certain traditional tumor markers (e.g., CEA, CA19-9 and CA724).
2021-08-12 | GSE181769 | GEO
Project description:We analyzed whole transcriptome sequencing in tumors from 23 patients with stage III or IV melanoma from a pilot trial of the anti-GD2 immunocytokine, hu14.18-IL2, in melanoma patients at high risk for recurrence to identify predictive immune and/or tumor biomarkers. Patients with advanced resectable melanoma were randomized to receive the first of 3 monthly-courses of hu14.18-IL2 immunotherapy either before (Group A) or after (Group B) complete surgical resection of all known disease. Tumors were evaluated by histology, immunohistochemistry and whole transcriptome sequencing. We report here that tumor infiltrating lymphocyte (TIL) levels directly correlate with relapse-free-survival (RFS) and overall-survival (OS). Resected tumors from Group A, but not Group B, patients demonstrated a direct correlation between TIL levels and survival. TIL levels directly correlated with a previously Estimated RNAseq-determined Immune Signature (EIS). This EIS correlated with RFS and OS, particularly in Group A tumors. Group A tumors demonstrated decreased cell cycling RNA gene transcripts, but increased RNA gene transcripts associated with repair and growth. Additionally, we found several direct correlations of immune signatures and immune related RNA transcripts as well as many inverse correlations of tumor growth-associated transcripts with RFS and OS, particularly in Group A tumors. Most of these correlations were not seen in Group B tumors. We interpret these data to signify that both immunologic and tumoral cell processes, as measured by RNAseq analyses, are associated with long term survival after hu14.18-IL2 therapy and could potentially be prognosticated using neoadjuvant treatment resection specimens obtained after initiating immunotherapy.
2020-07-01 | GSE133713 | GEO
Project description:Patients with cytogenetically normal acute myeloid leukemia (CN-AML) show heterogeneous treatment outcomes. We used gene expression profiling to develop a gene signature that predicts overall survival (OS) in CN-AML. Based on data from 163 patients treated in the German AMLCG 1999 trial and analyzed on oligonucleotide microarrays, we used supervised principal component analysis to identify 86 probe sets (representing 66 different genes) which correlated with OS, and defined a prognostic score based on this signature. When applied to an independent cohort of 79 CN-AML patients, this continuous score remained a significant predictor for OS (hazard ratio [HR], 1.85; P=0.002), EFS (HR, 1.73; P=0.001), and RFS (HR, 1.76; P=0.025). It kept its prognostic value in multivariate analyses adjusting for age, FLT3 ITD and NPM1 status. In a validation cohort of 64 CN-AML patients treated on CALGB study 9621, the score also predicted OS (HR, 4.11; P<0.001), EFS (HR, 2.90; P<0.001), and RFS (HR, 3.14, P<0.001) and retained its significance in a multivariate model for OS. In summary, we present a novel gene expression signature that offers additional prognostic information for patients with CN-AML. Experiment Overall Design: Analysis of 163 samples of bone morrow or peripheral blood mononuclear cells from adult patients with untreated acute myeloid leukemia
2008-10-26 | E-GEOD-12417 | biostudies-arrayexpress
Project description:Patients with cytogenetically normal acute myeloid leukemia (CN-AML) show heterogeneous treatment outcomes. We used gene expression profiling to develop a gene signature that predicts overall survival (OS) in CN-AML. Based on data from 163 patients treated in the German AMLCG 1999 trial and analyzed on oligonucleotide microarrays, we used supervised principal component analysis to identify 86 probe sets (representing 66 different genes) which correlated with OS, and defined a prognostic score based on this signature. When applied to an independent cohort of 79 CN-AML patients, this continuous score remained a significant predictor for OS (hazard ratio [HR], 1.85; P=0.002), EFS (HR, 1.73; P=0.001), and RFS (HR, 1.76; P=0.025). It kept its prognostic value in multivariate analyses adjusting for age, FLT3 ITD and NPM1 status. In a validation cohort of 64 CN-AML patients treated on CALGB study 9621, the score also predicted OS (HR, 4.11; P<0.001), EFS (HR, 2.90; P<0.001), and RFS (HR, 3.14, P<0.001) and retained its significance in a multivariate model for OS. In summary, we present a novel gene expression signature that offers additional prognostic information for patients with CN-AML. Keywords: clinical outcome
2008-08-22 | GSE12417 | GEO
Project description:Allogenic hematopoietic cell transplantation (alloHCT) is a well-established curative modality for adults with high-risk ALL; yet large data describing alloHCT outcomes in Philadelphia (Ph)-like ALL is lacking. We retrospectively analyzed archived DNA samples from consecutive adults with B-cell Ph-negative ALL who underwent alloHCT in complete remission (CR) (n= 127) at our center between 2006 and 2020. Identification of fusions associated with Ph-like were performed using accumulative results from RNAseq, conventional cytogenetics, FISH, and whole genome array studies. Fusions associated with Ph-like were detected in 56 (44%) patients, of whom 38 were carrying CRLF2r; and the rest (n=18) were non-CRLF2r. Compared to other non-Ph-like (n=71), patients with fusions associated with Ph-like ALL were more frequently Hispanic (P=0.008), less frequently carried high-risk cytogenetics (P<0.001), and more likely to receive blinatumomab prior to HCT (P=0.019). With the median follow-up of 3.5 years, patients with Ph-like ALL fusions had comparable post-transplant outcomes compared to other B-cell ALL: 3-year relapse-free survival (RFS) [41% vs. 44%, P=0.36], overall survival (OS) [51% vs. 50%, P=0.59] and relapse [37% vs. 31%, P=0.47]. In multivariable analysis, age (P= 0.023), disease status at the time of transplant (P<0.001), and donor type (P=0.015) influenced OS. RFS (primary endpoint) was significantly influenced by disease status (P<0.001) and conditioning regimen intensity (P=0.014). Relapse rate was associated with disease status (P=0.028) and conditioning regimen intensity (P=0.028). In conclusion, our data suggest that alloHCT consolidation results in similarly favorable survival outcomes in adult patients with Ph-like fusions and other high-risk B-cell ALL.
2022-08-01 | E-MTAB-11954 | biostudies-arrayexpress
Project description:BACKGROUND & AIMS: Sorafenib is the standard systemic therapy for advanced hepatocellular carcinoma (HCC). In early-stage HCC, survival benefits of resection/local ablation are compromised by high recurrence rates (70% at 5-years). In this setting, the phase-3 STORM-trial did not achieve its primary end-point of improving recurrence-free-survival (RFS) comparing sorafenib to placebo as adjuvant treatment. Herein we present results of the biomarker companion study BIOSTORM in which we define predictors of recurrence prevention with sorafenib and prognostic factors with B-level of evidence. METHODS: Tumor tissue from 188 patients randomized to receive sorafenib (83) or placebo (105) in the STORM trial was collected. Analyses included gene-expression profiling, targeted exome sequencing (18 known onco-drivers), immunohistochemistry (pERK, pVEGFR2, Ki67), FISH (VEGFA) and immunome. A gene signature capturing improved RFS in sorafenib-treated patients was generated. All 70 RFS events were recurrences, thus time-to-recurrence equaled RFS. Predictive and prognostic value was assessed using Cox regression models and interaction test. RESULTS: BIOSTORM recapitulates clinical and pathological characteristics of STORM patients. None of the biomarkers tested that are known to be related to angiogenesis and proliferation, or previously proposed gene-signatures, or mutations predicted sorafenib benefit. A newly generated 146-gene signature identifying 30% of patients captured benefit to sorafenib in terms of RFS (p-of-interaction=0.04). These sorafenib responders were significantly enriched in CD4+ T, B, and cytolytic Natural Killer cells, and showed absence of activated macrophages and other components of adaptive immunity. Hepatocytic pERK (HR=2.41; p=0.012) and microvascular invasion (HR=2.09; p=0.017) were independent prognostic factors. CONCLUSIONS: In BIOSTORM, hepatocytic pERK and microvascular invasion predicted poor RFS. No mutation, gene amplification or previously proposed gene-signatures predicted sorafenib benefit. A newly generated multi-gene signature associated with improved RFS on sorafenib warrants further validation. KEYWORDS: sorafenib; tyrosine-kinase inhibitor; trial enrichment; stratification.
2018-08-21 | GSE109211 | GEO
Project description:We conducted a multicentre pilot study on patients with localized HCC following complete radiological response to surgical resection. Patients received 250 mg oral gefitinib once daily as adjuvant therapy, up to a maximum of 6 months. The clinical endpoints included recurrence-free survival (RFS) and overall survival (OS), and correlative genetic analyses were conducted from whole exome sequencing data (n=33). All statistical analyses were carried out on an intention-to-treat basis. The study is registered with ClinicalTrials.gov (NCT00282100).
| EGAS00001004371 | EGA
Project description:RNA sequencing of 32 FFPE tissue samples, including 11 recurrent and 21 non-recurrent tumor specimens demonstrated higher KRT1 gene expression in the recurrence group than in non-recurrent cases. Patients with KRT1-positive immunostaining exhibited trends of worse overall survival (OS) and recurrence-free survival (RFS). In vitro studies showed that KRT1 knockdown suppressed tumor cell invasion, cell migration, and expression of epithelial-mesenchymal transition (EMT)-related genes in human head and neck squamous cell carcinoma (HNSCC) cell lines. Additionally, KRT1 knockdown enhanced tumor cell apoptosis and exhibited synergistic effects with conventional radiation and chemotherapy treatments. KRT1 may serve as a biomarker for predicting advanced laryngeal cancer recurrence and assist with selecting patients to receive concurrent chemoradiotherapy (CCRT).
2025-04-01 | GSE293443 | GEO