Harnessing biomarkers of response to improve therapy selection in esophago-gastric adenocarcinoma.
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ABSTRACT:
SUBMITTER: Fong CY
PROVIDER: S-EPMC8265282 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The incidence of esophageal and junctional adenocarcinoma has increased 6-fold in the west in the last 30 years and 5 year survival remains <14%. We aimed to characterize genome-wide aberrations in esophageal adenocarcinoma to further understand disease pathogenesis and ultimately identify groups with differential survivals with implications for clinical management. Oligo-array-based high-resolution analysis of copy number changes in 89 fresh frozen esophageal adenocarcinoma resection sections with long-term clinical follow-up data was performed. Good quality array comparative genomic hybridization profiles were obtained from 56/89 of the samples (63%). Our analyses confirmed known genomic aberrations in esophageal adenocarcinoma and identified 3 novel genomic regions with copy number changes. A modified T test with adjusted Bonferroni correction identified 17 genes with significantly different log2 ratios (p<4x10-7), including 6 novel genes, that characterize a group with a poorer survival.
2011-02-01 | GSE20154 | GEO
Project description:BackgroundThe efficacy and safety of preoperative chemoradiation therapy (CRT) for advanced esophago-gastric adenocarcinoma are still in question, and the prognosis of these patients is poor.MethodsWe systematically searched electronic databases from January 1990 to July 2014. The primary outcome was overall survival. The secondary outcomes were a R0 resection rate, positive rate of lymph node metastasis, postoperative recurrence rate, pathological complete response (pCR) rate and perioperative mortality. Overall survival was measured with a hazard ratio (HR), while other secondary outcomes were measured with an odds ratio (OR).ResultsSeven randomized controlled trials (RCTs) including 1085 patients were searched and, of these, 869 had adenocarcinoma. Patients receiving preoperative CRT had a longer overall survival (HR 0.74; 95% confidence interval (CI) 0.63-0.88), higher likelihood of R0 resection and greater chance of pCR, while they had a lower likelihood of lymph node metastasis and postoperative recurrence. The difference of perioperative mortality was non-significant. In addition, the result of the comparison between preoperative CRT and preoperative chemotherapy (CT) in two RCTs was non-significant.ConclusionPatients with resectable esophago-gastric adenocarcinoma can gain a survival advantage from preoperative CRT. However, limited to the number of RCTs, the effect of adding radiotherapy to preoperative CT separately is still uncertain and more high-quality prospective trials are needed.
| S-EPMC4415228 | biostudies-literature
Project description:The incidence of esophageal and junctional adenocarcinoma has increased 6-fold in the west in the last 30 years and 5 year survival remains <14%. We aimed to characterize genome-wide aberrations in esophageal adenocarcinoma to further understand disease pathogenesis and ultimately identify groups with differential survivals with implications for clinical management. Oligo-array-based high-resolution analysis of copy number changes in 89 fresh frozen esophageal adenocarcinoma resection sections with long-term clinical follow-up data was performed. Good quality array comparative genomic hybridization profiles were obtained from 56/89 of the samples (63%). Our analyses confirmed known genomic aberrations in esophageal adenocarcinoma and identified 3 novel genomic regions with copy number changes. A modified T test with adjusted Bonferroni correction identified 17 genes with significantly different log2 ratios (p<4x10-7), including 6 novel genes, that characterize a group with a poorer survival. Total RNA isolated from human tissue sections was used to make fluorescently labeled cRNA that was hybridized to DNA oligonucleotide. Briefly, 4 µg of total RNA was used to synthesize dsDNA through reverse transcription. cRNA was produced by in vitro transcription and labeled postsynthetically with Cy3 or Cy5. Two populations of labeled cRNA, a reference population and an experimental population, were compared with each other by competitive hybridization to microarrays. Two hybridizations were done with each cRNA sample pair using a fluorescent dye reversal strategy. Human microarrays contained oligonucleotide probes corresponding to approximately 21,000 genes. All oligonucleotide probes on the microarrays were synthesized in situ with inkjet technology (Agilent Technologies, Palo Alto, CA). After hybridization, arrays were scanned and fluorescence intensities for each probe were recorded. Ratios of transcript abundance (experimental to control) were obtained following normalization and correction of the array intensity data. Gene expression data analysis was done with the Rosetta Resolver gene expression analysis software (version 7.0, Rosetta Biosoftware, Seattle, WA).
2011-02-01 | E-GEOD-20154 | biostudies-arrayexpress
Project description:Cancer immunotherapy uses the immune system and its components to mount an anti-tumor response. During the last decade, it has evolved from a promising therapy option to a robust clinical reality. Many immunotherapeutic modalities are already approved by the Food and Drug Administration (FDA) for treating cancer patients and many others are in the pipeline for approval as standalone or combinatorial therapeutic interventions, several also combined with standard treatments in clinical studies. The two main axes of cancer immunotherapeutics refer to passive and active treatments. Prominent examples of passive immunotherapy include administration of monoclonal antibodies and cytokines and adoptive cell transfer of ex vivo "educated" immune cells. Active immunotherapy refers, among others, to anti-cancer vaccines [peptide, dendritic cell (DC)-based and allogeneic whole cell vaccines], immune checkpoint inhibitors and oncolytic viruses, whereas new approaches that can further enhance anti-cancer immune responses are also widely explored. Herein, we present the most popular cancer immunotherapy approaches and discuss their clinical relevance referring to data acquired from clinical trials. To date, clinical experience and efficacy suggest that combining more than one immunotherapy interventions, in conjunction with other treatment options like chemotherapy, radiotherapy and targeted or epigenetic therapy, should guide the way to cancer cure.
| S-EPMC4971375 | biostudies-literature
Project description:Tumor-infiltrating lymphocytes (TILs) are correlated to prognosis of several kinds of cancer. Most studies focused on T cells, while the role of tumor-associated B cells (TABs) has only recently gained more attention. TABs contain subpopulations with distinct functions, potentially promoting or inhibiting immune responses. This study provides a detailed analysis of TABs in gastro-esophageal adenocarcinoma (EAC). Flow cytometric analyses of single cell suspensions of tumor samples, mucosa, lymph nodes and peripheral blood mononuclear cells (PBMC) of EAC patients and healthy controls revealed a distinct B cell compartment in cancer patients. B cells were increased in tumor samples and subset-analyses of TILs showed increased proportions of differentiated and activated B cells and an enrichment for follicular T helper cells. Confocal microscopy demonstrated that TABs were mainly organized in tertiary lymphoid structures (TLS), which resemble lymphoid follicles in secondary lymphoid organs. A panel of 34 tumor-associated antigens (TAAs) expressed in EAC was identified based on public databases and TCGA data to analyze tumor-specific B cell responses using a LUMINEXTM bead assay and flow cytometry. Structural analyses of TLS and the detection of tumor-specific antibodies against one or more TAAs in 48.1% of analyzed serum samples underline presence of anti-tumor B cell responses in EAC. Interestingly, B cells were decreased in tumors with expression of Programmed Death Ligand 1 or impaired HLA-I expression. These data demonstrate that anti-tumor B cell responses are an additional and underestimated aspect of EAC. Our results are of immediate translational relevance to emerging immunotherapies.
| S-EPMC6287776 | biostudies-literature
Project description:Patients with chronic small bowel obstruction and malignant ascites from diffuse peritoneal carcinomatosis have limited options for gastrointestinal decompression as part of end-of-life palliation. Insertion of a percutaneous gastrostomy tube is relatively contraindicated in patients with ascites. Alternatively, nasogastric tube placement often leads to significant discomfort to patients and necessitates hospitalization during their last days of life. Here, we demonstrate how placing a percutaneous cervical esophago-gastric tube can allow adequate gastrointestinal decompression for terminal patients with malignant small bowel obstruction. This palliative measure allows them to remain in the comfort of their own homes after the procedure.
| S-EPMC5187358 | biostudies-literature
Project description:Esophageal and gastric adenocarcinomas are frequently diagnosed at an advanced stage and have a dismal prognosis. Even in patients with potentially curative cancer, nearly 50% will develop recurrent disease despite aggressive treatments. A number of biomarkers currently guide treatment decisions for patients with esophageal and gastric adenocarcinoma and include human epidermal growth factor receptor 2 (HER2) amplification, mismatch repair deficiency/microsatellite instability (dMMR/MSI-H) and program death-ligand 1 (PD-L1) expression. This review will focus on the function, testing and FDA-approved targeted therapies for HER2, dMMR/MSI-H and PD-L1. In addition, a number of novel targets in esophageal and gastric cancer are being studied in clinical trials. Neurotrophic-tropomyosin receptor kinase (NTRK), claudin-18 (CLDN18)/Rho GTPase activating protein 26 (ARHGAP26) gene fusion, fibroblast growth factor receptor (FGFR), lymphocyte-activation gene 3 (LAG3) and T cell immunoglobulin and mucin-domain containing-3 (TIM3) will be briefly reviewed. Despite several biomarkers used in the selection of treatment therapies, treatment outcomes remain poor. Future research efforts will focus on the identification of new biomarkers, moving existing biomarkers into earlier lines of therapy, and evaluating new combinations of existing biomarkers and therapies.
| S-EPMC7530320 | biostudies-literature
Project description:PurposeThe Finnish National Esophago-Gastric Cancer Cohort (FINEGO) was established with the aim of identifying factors that could contribute to improved outcomes in oesophago-gastric cancer. The aim of this study is to describe the patients with gastric cancer included in FINEGO.ParticipantsA total of 10 457 patients with gastric cancer or tumour diagnosis in the Finnish Cancer Registry or the Finnish Patient Registry during 1987-2016 were included in the cohort, with follow-up from Causes of Death Registry until 31 December 2016. All of the participants were at least 18 years of age, and had undergone either resectional or endoscopic mucosal surgery with curative or palliative intent.Findings to dateOf the 10 457 patients, 90.1% were identified to have cancer in both cancer and patient registries. In all, the median age was 70 at the time of surgery, 54.5% of the patients were men and 64.4% had no comorbidities. Education data were available for 31.1% of the patients, of whom the majority had had <12 years of formal education. Of the 7798 with cancer staging data available, 41.1% had a local cancer. Adenocarcinoma was the most common (94.2%) histological type. Almost all patients underwent open gastrectomy and 214% in hospitals with annual volume of more than 30 gastrectomies per year. A total of 8561 deaths occurred during the study period, of which 6474 were due to oesophago-gastric cancers. The 5-year survival was 34.6% and 5-year cancer-specific survival was 39.7%.Future plansThe data in FINEGO can be currently used for registry-based research but is being expanded by data extraction from patient records and scanning of histological samples from the Finnish biobanks. Initially, we are planning on studies on the national trends in treatment and mortality, and studies on the demographic factors and their influence on survival.
| S-EPMC7569918 | biostudies-literature
Project description:Background and aimsThis study sought to determine the value of patient-derived organoids (PDOs) from esophago-gastric adenocarcinoma (EGC) for response prediction to neoadjuvant chemotherapy (neoCTx).MethodsEndoscopic biopsies of patients with locally advanced EGC (n = 120) were taken into culture and PDOs expanded. PDOs' response towards the single substances of the FLOT regimen and the combination treatment were correlated to patients' pathological response using tumor regression grading. A classifier based on FLOT response of PDOs was established in an exploratory cohort (n = 13) and subsequently confirmed in an independent validation cohort (n = 13).ResultsEGC PDOs reflected patients' diverse responses to single chemotherapeutics and the combination regimen FLOT. In the exploratory cohort, PDOs response to single 5-FU and FLOT combination treatment correlated with the patients' pathological response (5-FU: Kendall's τ = 0.411, P = 0.001; FLOT: Kendall's τ = 0.694, P = 2.541e-08). For FLOT testing, a high diagnostic precision in receiver operating characteristic (ROC) analysis was reached with an AUCROC of 0.994 (CI 0.980 to 1.000). The discriminative ability of PDO-based FLOT testing allowed the definition of a threshold, which classified in an independent validation cohort FLOT responders from non-responders with high sensitivity (90%), specificity (100%) and accuracy (92%).ConclusionIn vitro drug testing of EGC PDOs has a high predictive accuracy in classifying patients' histological response to neoadjuvant FLOT treatment. Taking into account the high rate of successful PDO expansion from biopsies, the definition of a threshold that allows treatment stratification paves the way for an interventional trial exploring PDO-guided treatment of EGC patients.
| S-EPMC10777586 | biostudies-literature
Project description: Not available
| S-EPMC8094513 | biostudies-literature