Clinical outcomes and ctDNA correlates for CAPOX BETR: A phase II trial of capecitabine, oxaliplatin, bevacizumab, trastuzumab in previously untreated advanced HER2+ gastroesophageal adenocarcinoma
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PROVIDER: PRJNA1133829 | ENA |
REPOSITORIES: ENA
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Project description:Background: miRNAs might be potentially useful biomarkers for prediction of response to chemotherapeutic agents, radiotherapy and survival. The aim of this retrospective study was to validate miRNA response predictors in a cohort of patients with gastroesophageal cancer in order to predict overall survival (OS) and disease-specific survival (DSS). Material and methods: The study population encompassed 53 patients treated with curative intended for loco-regional gastroesophageal cancer. miRNA expression was quantified from pre-therapeutic and diagnostic, formalin-fixed, paraffin embedded tumor specimens using Affymetrix GeneChip miRNA 1.0 Array. Based on growth inhibition of the NCI60 panel in the presence of cisplatin, epirubicine and capecitabine, a miRNA based response predictor was developed. The Cox proportional hazards model was applied to assess the correlations of the response predictor with OS and DSS. Results: A univariate analysis demonstrated a statistical significant improvement of OS for patients who had undergone surgical resection with prediction scores above the median prediction score (HR: 0.41 (95% CI: 0.17-0.96). Adjusting for surgery and stage, this predictor was identified to be independently associated with both OS (HR: 0.37 (95% CI: 0.16-0.87)) and DSS (HR: 0.32 (0.12-0.87)). Conclusion: The miRNA profile predictive for sensitivity to cisplatin, epirubicine and capecitabine was shown to be independently associated with OS and DSS in patients with gastroesophageal cancer. Tumor biopsies from 53 patients with gastroesophageal cancer *** Submitter has provided limited clinical information. Thus, this submission is incomplete. ***
2016-02-18 | E-GEOD-78049 | biostudies-arrayexpress
Project description:Background: miRNAs might be potentially useful biomarkers for prediction of response to chemotherapeutic agents, radiotherapy and survival. The aim of this retrospective study was to validate miRNA response predictors in a cohort of patients with gastroesophageal cancer in order to predict overall survival (OS) and disease-specific survival (DSS). Material and methods: The study population encompassed 53 patients treated with curative intended for loco-regional gastroesophageal cancer. miRNA expression was quantified from pre-therapeutic and diagnostic, formalin-fixed, paraffin embedded tumor specimens using Affymetrix GeneChip miRNA 1.0 Array. Based on growth inhibition of the NCI60 panel in the presence of cisplatin, epirubicine and capecitabine, a miRNA based response predictor was developed. The Cox proportional hazards model was applied to assess the correlations of the response predictor with OS and DSS. Results: A univariate analysis demonstrated a statistical significant improvement of OS for patients who had undergone surgical resection with prediction scores above the median prediction score (HR: 0.41 (95% CI: 0.17-0.96). Adjusting for surgery and stage, this predictor was identified to be independently associated with both OS (HR: 0.37 (95% CI: 0.16-0.87)) and DSS (HR: 0.32 (0.12-0.87)). Conclusion: The miRNA profile predictive for sensitivity to cisplatin, epirubicine and capecitabine was shown to be independently associated with OS and DSS in patients with gastroesophageal cancer.
2016-02-18 | GSE78049 | GEO
Project description:This study aims to compared ctDNA methylation status induced by ionizing to different ograns. SD rats were irradiated with local radaition to brain, lung or skin. Serum was collected and subjiected to ctDNA extraction. ctDNA were then treated by methylation-sensive bisulfite and sequencing.
2021-12-23 | GSE163763 | GEO
Project description:We aimed to characterize the genomic profiles of adenocarcinomas in the gastroesophageal junction in relation to cancers in the esophagus and the stomach. Profiles of gains/losses as well as gene expression profiles were obtained from 27 gastroesophageal adenocarcinomas using 32k high-resolution array-based comparative genomic hybridization (aCGH) and 27k oligo gene expression arrays and putative target genes were validated in an extended series. Adenocarcinomas in the distal esophagus and the gastroesophageal junction showed strong similarities with the most common gains at 20q13, 8q24, 1q21-q23, 5p15, 13q34, and 12q13, whereas different profiles with gains at 5p15, 7p22, 2q35, and 13q34 characterized gastric cancers. CDK6 and EGFR were identified as putative target genes in cancers of the esophagus and the gastroesophageal junction with upregulation in one quarter of the tumors. Gains/losses and gene expression profiles show strong similarity between cancers in the distal esophagus and the gastroesophageal junction with frequent upregulation of CDK6 and EGFR, whereas gastric cancer displays distinct genetic changes. These data suggest that molecular diagnostics and targeted therapies can be applied to adenocarcinomas of the distal esophagus and gastroesophageal junction alike. Three types of gastroesophageal adenocarcinomas; 7 distal esophageal (EA) tumors, 9 junctional (JA) and 7 proximal stomach cancers (GA) was genomically profiled using tiling 32k BAC-arrays. Two replicates of tumors IDs 1-EA-CGH (replicate 1-EA-CGH-2), 12-EA-CGH (replicate 12-EA-CGH-2) and 18-EA-CGH (replicate 18-EA-CGH-2). Reference samples consist of a pool of male DNA (Promega, Madison, WI, USA).
2010-06-24 | E-GEOD-22524 | biostudies-arrayexpress
Project description:Dasatinib inhibits src family kinases and has anti-angiogenic properties. We conducted a phase I study of dasatinib, capecitabine, oxaliplatin, and bevacizumab (CapeOx/bevacizumab), with an expansion cohort in metastatic colorectal cancer (CRC).Patients were enrolled in a dose escalation cohort to establish the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D). Using a "3?+?3" design, twelve patients with advanced solid tumors received dasatinib (50 mg twice daily or 70 mg daily), capecitabine (850 mg/m(2) twice daily, days 1-14), oxaliplatin (130 mg/m(2) on day 1) and bevacizumab (7.5 mg/kg on day1), every 3 weeks. Ten patients with previously untreated metastatic CRC were then enrolled in an expansion cohort. Activated src (src(act)) expression was measured by immunohistochemistry, using an antibody that selectively recognizes the active conformation of src (clone 28).Twenty-two patients were enrolled between June 2009 and May 2011. Two DLTs were observed in the 50 mg bid dasatinib cohort, and one DLT was observed in the 70 mg daily dasatinib cohort. The MTD and RP2D for dasatinib was 70 mg daily. The most common treatment-related adverse events were fatigue (20; 91 %) and diarrhea (18; 82 %). Biomarker analysis of src(act) expression demonstrated that the overall response rate (ORR) was 75 % (6/8) for patients with high src(act) expression (IHC???2), compared to 0 % (0/8) for patients with low srcact expression (IHC 0 or 1); (p?=?0.007).The RP2D of dasatinib is 70 mg daily in combination with CapeOx/bevacizumab. High levels of srcact expression may predict those patients most likely to benefit from dasatinib.
| S-EPMC4108590 | biostudies-literature
Project description:A 68-year-old male, who was undergoing XELOX plus trastuzumab therapy for gastric cancer, developed proteinuria, hematuria, and progressive increase in creatinine after 3 months. Subsequently, the patient also experienced hemoptysis, nasal bleeding. Chest CT examination shown pulmonary hemorrhage. The MRI of the nasopharynx ruled out nasopharyngeal cancer recurrence. The MPO and PR3 were elevated, and renal biopsy confirmed ANCA-related vasculitis, which affected the lungs, kidneys, and nasopharynx. Based on the review of the patient''s medical history and medication, it is believed that ANCA-related vasculitis was caused by XELOX plus trastuzumab chemotherapy, but it is difficult to confirm which specific drug caused it. After stopping XELOX plus trastuzumab chemotherapy, glucocorticoids and cyclophosphamide was given, the patient''s pulmonary hemorrhage and nasal bleeding stopped, and the lung lesions were absorbed. The renal function also improved. The patient later experienced pulmonary infection again, and tNGS indicated Legionella pneumophila and pulmonary tuberculosis infection. Despite anti-infection treatment, steroid dose was rapidly reduced. Ultimately, the patient gave up on treatment and eventually died.
| S-EPMC11001309 | biostudies-literature
Project description:We aimed to genetically characterize adenocarcinomas in the gastroesophagel junction in relation to cancers in the esophagus and the stomach. In total 27 tumors was genetically profiled using gene expression array. Adenocarcinomas located in the gastroesophageal junction showed strong similarites with tumors in the distal esophagus, whereas different profiles were generated for tumors in the proximal stomach. Three types of gastroesophageal adenocarcinomas; 10 distal esophageal (EA) tumors, 9 junctional (JA) and 8 proximal stomach cancers (GA) was undergone differentially analysis based on gene expression profiles. One replicate of tumor ID 27_JA (replicate ID 27_JA_2) and one replicate of tumor ID 3-GA (replicate ID 3-GA-2). Reference samples consist of the Stratagene Universal Reference (10 cellines), commercially obtained from Stratagene, La Jolla, CA, USA.
2010-05-29 | E-GEOD-22050 | biostudies-arrayexpress
Project description:We aimed to characterize the genomic profiles of adenocarcinomas in the gastroesophageal junction in relation to cancers in the esophagus and the stomach. Profiles of gains/losses as well as gene expression profiles were obtained from 27 gastroesophageal adenocarcinomas using 32k high-resolution array-based comparative genomic hybridization (aCGH) and 27k oligo gene expression arrays and putative target genes were validated in an extended series. Adenocarcinomas in the distal esophagus and the gastroesophageal junction showed strong similarities with the most common gains at 20q13, 8q24, 1q21-q23, 5p15, 13q34, and 12q13, whereas different profiles with gains at 5p15, 7p22, 2q35, and 13q34 characterized gastric cancers. CDK6 and EGFR were identified as putative target genes in cancers of the esophagus and the gastroesophageal junction with upregulation in one quarter of the tumors. Gains/losses and gene expression profiles show strong similarity between cancers in the distal esophagus and the gastroesophageal junction with frequent upregulation of CDK6 and EGFR, whereas gastric cancer displays distinct genetic changes. These data suggest that molecular diagnostics and targeted therapies can be applied to adenocarcinomas of the distal esophagus and gastroesophageal junction alike.
2010-06-24 | GSE22524 | GEO
Project description:We found that ERY974 shows only moderate antitumor efficacy in MKN45 non-inflamed tumor in huNOG mice. We also observed that ERY974 + capecitabine increases antitumour efficacy in non-inflamed MKN45 tumours. To identify a mechanism of combination effect, we compared RNA expression of MKN45 tumors treated with ERY974, capecitabine, or combination.
2022-08-21 | GSE211373 | GEO
Project description:Results: In subjects who completed treatment and surgery, the pCR and near-complete response rates were 15.8% in HER2-negative and 50% in HER2-positive subjects. When stratified by genomic subtype, subjects of the HER2-enriched subtype had the best response (66.7%), the luminal A (11%) and B (4.8%) subtypes the poorest. Of 147 patients tested for p53 mutations using the AmpliChip test, 78 variants were detected; 55 were missense. The response rate among TP53 mutated patients was 30%, significantly higher than the rate in TP53 wild-type patients (10%, P = .0032). Concordance between AmpliChip mutation status versus IHC staining was 65%, with AmpliChip status being predictive of response and IHC status being not being predictive. Conclusion: Capecitabine plus docetaxel in HER2-negative subjects, and with trastuzumab in HER2-positive subjects, provided a good response rate with fewer cycles. p53 mutational analysis using the AmpliChip p53 assay, and genomic subtyping using the PAM50 assay, were promising predictive tests of response. reference x sample
2011-03-18 | E-GEOD-22358 | biostudies-arrayexpress