Impact of distance to the hospital on mortality in metastatic colorectal cancer patients in chemotherapy
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Cancer
PROVIDER: 2656577 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:While patients with microsatellite instable, metastatic colorectal cancer (CRC) benefit from immune checkpoint blockade, chemotherapy with targeted therapies remains the only therapeutic option for microsatellite stable (MSS) tumors. The single arm, phase IB/II MEDITREME trial evaluates safety and efficacy of durvalumab plus tremelimumab in combination with mFOLFOX6 chemotherapy in first line, in 57 patients with RAS-mutant unresectable mCRC. Safety was primary objective of phase IB and no safety issue was observed. The primary objective of phase II was efficacy in terms of 3-month PFS in MSS patients, which was met with a 3 month PFS of 90.7% [95% CI: 79.2-96%]. For secondary objective, response rate was 64.5%, median PFS was 8.2 months [95% CI: 5.9–8.6] and overall survival was not reached in MSS patients. Higher tumor mutational burden and a lower degree of genomic instability in responder patients. Integrated transcriptomic analysis underlined that high immune signature, and low epithelio-mesenchymal transition were associated with better outcome. Immunomonitoring showed induction of neoantigen and NY-ESO1 and TERT blood tumor specific T cell response associated with better PFS. The combination of durvalumab-tremelimumab with mFOLFOX6 was tolerable with promising clinical activity in MSS mCRC.
2023-07-05 | GSE235917 | GEO
Project description:While patients with microsatellite instable, metastatic colorectal cancer (CRC) benefit from immune checkpoint blockade, chemotherapy with targeted therapies remains the only therapeutic option for microsatellite stable (MSS) tumors. The single arm, phase IB/II MEDITREME trial evaluates safety and efficacy of durvalumab plus tremelimumab in combination with mFOLFOX6 chemotherapy in first line, in 57 patients with RAS-mutant unresectable mCRC. Safety was primary objective of phase IB and no safety issue was observed. The primary objective of phase II was efficacy in terms of 3-month PFS in MSS patients, which was met with a 3 month PFS of 90.7% [95% CI: 79.2-96%]. For secondary objective, response rate was 64.5%, median PFS was 8.2 months [95% CI: 5.9–8.6] and overall survival was not reached in MSS patients. Higher tumor mutational burden and a lower degree of genomic instability in responder patients. Integrated transcriptomic analysis underlined that high immune signature, and low epithelio-mesenchymal transition were associated with better outcome. Immunomonitoring showed induction of neoantigen and NY-ESO1 and TERT blood tumor specific T cell response associated with better PFS. The combination of durvalumab-tremelimumab with mFOLFOX6 was tolerable with promising clinical activity in MSS mCRC.
2023-07-05 | GSE235919 | GEO
Project description:Background: Early prognostication is a major challenge after out-of-hospital cardiac arrest (OHCA). Aims: We hypothesized that a genome-wide analysis of blood gene expression could offer new prognostic tools and lines of research. Methods: Sixty-nine patients were enrolled from an ancillary study of the clinical trial NCT00999583 that tested the effect of erythropoietin (EPO) after OHCA. Blood samples were collected in comatose survivors of OHCA at hospital admission and 1 and 3 days after resuscitation. Gene expression profiles were analyzed (Illumina HumanHT-12 V4 BeadChip; >34,000 genes). Patients were classified into two categories representing neurologically favorable outcome (Cerebral Performance Category [CPC] = 1-2) vs unfavorable outcome (CPC>2) at Day 60 after OHCA. Differential and functional enrichment analyses were performed to compare transcriptomic profiles between these two categories. Results: Among the 69 enrolled patients, 33 and 36 patients were treated or not by EPO, respectively. Among them, 42% had a favorable neurological outcome in both groups. EPO did not affect the transcriptomic response at Day-0 and 1 after OHCA. In contrast, 76 transcripts differed at Day-0 between patients with unfavorable vs favorable neurological outcome. This signature persisted at Day-1 after OHCA. Functional enrichment analysis revealed a down-regulation of adaptive immunity with concomitant up-regulation of innate immunity and inflammation in patients with unfavorable vs favorable neurological outcome. The transcription of many genes of the HLA family was decreased in patients with unfavorable vs favorable neurological outcome. Concomitantly, neutrophil activation and inflammation were observed. Up-stream regulators analysis showed the implication of numerous factors involved in cell cycle and damages. A logistic regression including a set of genes allowed a reliable prediction of the clinical outcomes (Specificity=88%; Hit Rate=83%). Conclusions: A transcriptomic signature involving a counterbalance between adaptive and innate immune responses is able to predict neurological outcome very early after hospital admission after OHCA. This deserves confirmation in a larger population.
2019-03-21 | E-MTAB-7699 | biostudies-arrayexpress
Project description:BackgroundPreclinical studies showed that antibiotic exposure played a role in clinical outcomes in patients with chemotherapy via modulation of microbiota. However, it remains unknown whether antibiotic exposure during the bevacizumab therapy affects the clinical outcomes in metastatic colorectal cancer(mCRC) patients. This study aimed to examine the association between the antibiotic medication and the clinical outcomes in mCRC patients with bevacizumab therapy.MethodsThis retrospective cohort analysis included 147 mCRC patients treated with bevacizumab. The hazard ratio of death was estimated using three Cox proportional hazards models with (1) never vs ever; (2) never vs 1-6 days and 7-40 days;(3) increase per day, and further tested using propensity score matching (PSM) and landmark analysis. A smooth curve technique was used to explore the shape of dose-response relationship.ResultsCompared with the non-antibiotic group, antibiotic exposure was inversely associated with the mortality in the antibiotic group after adjustment for demographic and other potential confounders (a history of medication: HR, 0.650(95%CI: 0.360 to 1.173); an increase per day: HR, 0.967(CI: 0.924 to 1.011); 1-6 days: HR, 0.859(CI: 0.441 to 1.674); 7-40 days: HR, 0.474(CI: 0.225 to 0.999); P for trend = 0.040). A test for the interaction between sex was statistically significant (p = 0.016). A similar result was found as measured by landmark and PSM analysis. Significant negative dose-response relationship was shown by smooth curve analysis in the male patients but not female after adjustment for confounders(p = 0.028). No association was found between the antibiotic medication and adverse events of bevacizumab.ConclusionAntibiotic exposure could be inversely associated with the mortality in mCRC patients treated with bevacizumab.
| S-EPMC6736303 | biostudies-literature
Project description:BACKGROUND; Cisplatin-containing chemotherapy is the standard of care for patients with locally advanced and metastatic transitional cell carcinoma of the urothelium. The response rate is around 50% and tumor derived molecular prognostic markers are needed for estimation of response and survival. METHODS; Affymetrix GeneChip expression profiling was carried out using tumor material from 30 patients. A set of genes having an expression with high correlation to survival time after chemotherapy was identified. Two of these genes were selected for validation by immunohistochemistry (IHC) in tumor tissue from 149 cisplatin treated patients having complete follow-up data. RESULTS; Fifty-five differentially expressed genes correlated significantly to survival time. Two of these (Emmprin and Survivin) were validated using IHC, and multivariate analysis (n=145) identified Emmprin expression (hazard ratio 2.38; p<0.0001) and Survivin expression (hazard ratio 2.34; p<0.0001) as independent prognostic markers for poor outcome, together with the presence of visceral metastases (hazard ratio 2.72; p<0.0001). In the good prognosis group of patients without visceral metastases, both markers showed significant discriminating power as supplemental risk factors (p<0.0001). Within this group of patients, the subgroups of patients with no positive, one positive or two positive IHC stainings (Emmprin and Survivin) had estimated 5-year survival rates (+- SE) of 35.6+-?%, 6.3+-?%, and 0+?%, respectively. Response to chemotherapy could also be predicted with an OddsRatio of 4.60 (2.13-9.93) and 2.59 (1.25-5.38) for Emmprin and Survivin respectively. CONCLUSION; Emmprin and Survivin proteins were identified as strong independent prognostic predictors for response and survival after cisplatin-containing chemotherapy in patients with bladder cancer. Experiment Overall Design: Tumors from 30 patients with advanced bladder cancer used in the study. A SAM analysis was used for identifying genes co-varying with treatment response.
2008-06-13 | E-GEOD-5287 | biostudies-arrayexpress
Project description:Purpose: Neoadjuvant chemotherapy is one important therapeutic strategy for breast cancer with the drawback of resistance development. Chemotherapy has adverse effects that combined with resistance could contribute to lower overall survival. This work aimed to evaluate the molecular profile of patients who received neoadjuvant chemotherapy trying to discover differentially expressed genes (DEGs) that could be used as biomarkers of chemotherapy response and overall survival. Methods: Breast cancer patients who received neoadjuvant chemotherapy were enrolled in this study and according to their pathological response were assigned as sensitive or resistant. To evaluate DEGs, GO, KEGG and protein-protein interactions, RNAseq information from all patients was obtained by next generation sequencing. Results: A total of 1985 DEGs were found and KEGG analysis indicated a great number of DEGs in metabolic pathways, pathways in cancer, cytokine-cytokine receptor interactions, and neuroactive ligand-receptor interactions. A selection of 73 DEGs were used further for an analysis of overall survival using the METABRIC study. Seven of those DEGs were found to correlated with overall survival, of them the sub-expression of C1QTNF3, CTF1, OLFML3, PLA2R1, PODN and the over expression of TUBB and TCP1 were found in resistant patients and related to patients with lower overall survival. Conclusions: This work highlights differences at the level of gene expression in patients resistant and sensitive to neoadjuvant chemotherapy. Cellular components related to extracellular region and plasma membrane were mainly involved. Furthermore, 73 DEGs were able to discriminate patients resistant and sensitive to neoadjuvant chemotherapy, and 7 of them were able to predict overall survival.
2021-04-30 | GSE162187 | GEO
Project description:Purpose The analysis of breast cancer residual tumors after neoadjuvant chemotherapy (nCT) may be useful for identifying new biomarkers. MicroRNAs are known to be involved in oncogenic pathways and treatment resistance of breast cancer. Our aim was to determine the role of miR-18a, a member of the miR-17-92a cluster, in breast cancer behavior and outcome after nCT. Methods Pre- and post-nCT tumor miR-18a expression was retrospectively assessed by qRT-PCR in 121 patients treated with nCT and was correlated with survival outcomes and with clinical and pathological characteristics. Breast cancer-derived MCF-7 and MDA-MB-231 cell lines were transfected with miR-18a and anti-miR-18a to evaluate the biological effects of this molecule. In addition, whole-transcriptome expression analysis was performed. Results High miR-18a expression in post-nCT residual tumors was found to be associated with a significantly worse overall survival [hazard ratio (HR): 2.80, 95% confidence interval (CI): 1.01–7.76] and a strong trend towards a poorer disease-free survival (HR: 2.44, 95% CI: 0.99–5.02) compared to low miR-18a expressing post-nCT residual tumors. Clinical and experimental data were found to be in conformity with the proliferative effects of miR-18a, which showed a significant correlation with Ki67 and MYBL2 expression, both in pre- and post-nCT tumors and in public databases. In vitro analysis of the role of miR-18a in breast cancer-derived cell lines showed that a high expression of miR-18a was associated with a low expression of the estrogen receptor (ER), a decreased sensitivity to tamoxifen and an enrichment in luminal B and endocrine resistance gene expression signatures. Conclusions From our data we conclude that post-nCT miR-18a expression in breast cancer serves as a negative prognostic marker, especially in luminal tumors. Clinical, in vitro and in silico data support the role of miR-18a in breast cancer cell proliferation and endocrine resistance and suggest its potential utility as a biomarker for additional adjuvant treatment in patients without a pathologic complete response to neoadjuvant therapy.
2019-05-27 | GSE102121 | GEO
Project description:High-grade osteosarcoma is a malignant primary bone tumor with a peak incidence in puberty. Overall survival of patients with metastatic disease is approximately twenty percent. Mechanisms behind the development of metastases in osteosarcoma are unknown. To identify gene signatures that play a role in metastasis, we performed genome-wide gene expression profiling on pre-chemotherapy biopsies of osteosarcoma patients who developed metastases within 5yrs and patients who did not develop metastases within 5yrs.
2011-02-11 | GSE21257 | GEO
Project description:Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive cancer with a dismal prognosis and few effective therapeutic approaches. This study aimed to investigate the efficacy, safety, and predictive biomarkers of hepatic arterial infusion chemotherapy (FOLFOX-HAIC) in combination with lenvatinib and PD-1 inhibitor for patients with advanced iCCA. Locally advanced or metastatic iCCA patients receiving the triple combination therapy of lenvatinib, PD-1 inhibitor, and FOLFOX-HAIC were included in this retrospective study. Primary endpoint was the progression-free survival, evaluated using the RECIST criterion. The secondary endpoints included overall survival, objective response rate, and safety. Whole exome and RNA sequencing of tumor biopsy tissues were performed for biomarker exploration. Between May, 2019 and December 2022, a total of 46 patients were included in this study. The primary endpoint showed a median progression-free survival of 9.40 months (95% CI: 5.28-13.52), with a 6-month progression-free survival rate of 76.1%. The median overall survival was 16.77 months (95% CI, 14.20-19.33), with an objective response rate of 47.8% and disease control rate of 91.3% per RECIST. In addition, 4.3% and 8.7% of patients achieved complete response of all lesions and intrahepatic target lesions per mRECIST, respectively. The most common treatment-related adverse events were neutropenia, thrombocytopenia, elevated aspartate aminotransferase and alanine aminotransferase level. Furthermore, integrated analysis of genetic, transcriptomic, and immunohistochemistry data revealed that pre-existing immunity (high expression level of immune-related signatures and intra-tumoral CD8+ T cell density) in baseline tumour tissues was associated with superior clinical benefits. However, the evaluation of tumor mutation burden did not show potential predictive value in this triple combination. FOLFOX-HAIC in combination with lenvatinib and PD-1 inhibitor demonstrated a promising antitumor activity with manageable safety profiles in patients with advanced iCCA. Moreover, our study also revealed new perspectives on potential biomarkers for clinical efficacy.
2024-02-06 | GSE255058 | GEO
Project description:Aim To identify predictors for in-hospital mortality in patients with metastatic cancer in intensive care units (ICUs) and established a prediction model for in-hospital mortality in those patients. Methods In this cohort study, the data of 2,462 patients with metastatic cancer in ICUs were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. Least absolute shrinkage and selection operator (LASSO) regression analysis was applied to identify the predictors for in-hospital mortality in metastatic cancer patients. Participants were randomly divided into the training set (n = 1,723) and the testing set (n = 739). Patients with metastatic cancer in ICUs from MIMIC-IV were used as the validation set (n = 1,726). The prediction model was constructed in the training set. The area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were employed for measuring the predictive performance of the model. The predictive performance of the model was validated in the testing set and external validation was performed in the validation set. Results In total, 656 (26.65%) metastatic cancer patients were dead in hospital. Age, respiratory failure, the sequential organ failure assessment (SOFA) score, the Simplified Acute Physiology Score II (SAPS II) score, glucose, red cell distribution width (RDW) and lactate were predictors for the in-hospital mortality in patients with metastatic cancer in ICUs. The equation of the prediction model was ln(P/(1 + P)) = −5.9830 + 0.0174 × age + 1.3686 × respiratory failure + 0.0537 × SAPS II + 0.0312 × SOFA + 0.1278 × lactate − 0.0026 × glucose + 0.0772 × RDW. The AUCs of the prediction model was 0.797 (95% CI,0.776–0.825) in the training set, 0.778 (95% CI, 0.740–0.817) in the testing set and 0.811 (95% CI, 0.789–0.833) in the validation set. The predictive values of the model in lymphoma, myeloma, brain/spinal cord, lung, liver, peritoneum/pleura, enteroncus and other cancer populations were also assessed. Conclusion The prediction model for in-hospital mortality in ICU patients with metastatic cancer exhibited good predictive ability, which might help identify patients with high risk of in-hospital death and provide timely interventions to those patients.
| S-EPMC9922743 | biostudies-literature