scholarly journals Trastuzumab Specific Epitope Evaluation as a Predictive and Prognostic Biomarker in Gastric Cancer Patients

Biomolecules ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 782
Author(s):  
Jiwon Koh ◽  
Soo Kyung Nam ◽  
Youn Woo Lee ◽  
Jin Won Kim ◽  
Keun-Wook Lee ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Univariate Analysis ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Test Methods ◽  
Her2 Status ◽  
Her2 Receptor ◽  
Free Survival ◽  
Conventional Methods

While human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) antibodies bind to the intracellular domain, trastuzumab binds to the extracellular epitope of HER2 receptor: target of drug action. We aimed to evaluate clinical significance of the new IHC method assessing the target of trastuzumab in gastric cancer (GC) patients and compare with conventional methods. Sixty-nine trastuzumab-treated GC patients were enrolled from two different cohorts. Additionally, we enrolled 528 consecutive GC patients to evaluate prognostic implications of HER2 test methods. HER2 status was assessed by trastuzumab IHC, HER2 IHC (4B5), and HER2 silver in situ hybridization (SISH). HER2 IHC showed 3+ in 48/69 trastuzumab-treated patients (69.6%), however, trastuzumab IHC showed 3+ in 25 (36.2%). Patients with trastuzumab IHC ≥2+ had significantly better progression-free survival (PFS) and overall survival (OS) than their counterpart (p = 0.014). In univariate analysis, trastuzumab IHC ≥2+ and HER2 IHC 3+ were only significant predictive factors for OS in trastuzumab-treated patients. Of the 528 consecutive GCs, patients with trastuzumab IHC ≥2+ had shorter disease-free survival (DFS) and OS (p = 0.008 and 0.031, respectively), while conventional methods failed to reveal any significant survival differences. HER2 assessment by trastuzumab IHC was different from conventional HER2 test results. Trastuzumab IHC was suggested to be a significant predictive factor for trastuzumab responsiveness and prognostic factor for consecutive GCs.

scholarly journals The Impact of Mismatch Repair Status on Prognosis of Patients With Gastric Cancer: A Multicenter Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Wen-Long Guan ◽  
Yue Ma ◽  
Yue-Hong Cui ◽  
Tian-Shu Liu ◽  
Yan-Qiao Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Mismatch Repair ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Clinicopathological Characteristics ◽  
Her2 Status ◽  
Clinical Role ◽  
Record System ◽  
Free Survival ◽  
The Impact

BackgroundThe clinical role of deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) in gastric cancer (GC) is still controversial. We aimed to analyze the relationship between dMMR/MSI-H and clinicopathological features along with survival.MethodsPatients who were diagnosed with GC at the three big cancer centers in China from 2015 to 2020 were evaluated retrospectively. MMR/MSI status was assessed using immunohistochemistry/PCR. Clinical and pathological data were collected from the medical record system.ResultsA total of 196 patients with dMMR/MSI-H status were enrolled for analysis. The prevalence of MSI-H/dMMR in GC was 6.6%. Another 694 proficient MMR (pMMR) GC patients were enrolled for comparison. Compared with pMMR patients, dMMR/MSI-H patients were associated with older age, female predominance, distal location in the stomach, earlier TNM stage, intestinal subtype, better differentiation, and more negative HER2 status. The median overall survival (OS) of the dMMR/MSI-H group was better than that of the pMMR/microsatellite stability (MSS) group (not reached vs. 53.9 months, p = 0.014). Adjuvant chemotherapy had no impact in both disease-free survival (DFS) and OS of dMMR/MSI-H patients (p = 0.135 and 0.818, respectively). dMMR/MSI-H patients had poorer response and progression-free survival (PFS) of first-line chemotherapy, though they were statistically significant (p = 0.361 and 0.124, respectively).ConclusionsdMMR/MSI-H GC patients have specific clinicopathological characteristics and better prognosis than pMMR patients.

Is It The Time That We Can Depend on Bioscore as a New Staging System in Non-Metastatic Breast Cancer to Predict the Disease-Free Survival?

2021 ◽  
Author(s):  
Rehab Farouk Mohamed ◽  
Donia Hussein Abd El Hameed ◽  
Mohamed Alaa Eldeen Hassan
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Prognostic Value ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Her2 Status ◽  
Free Survival ◽  
Disease Free

Abstract Purpose: Novel molecular characterization of breast cancer with cellular markers has allowed a new classification that offers prognostic value. This study investigates the prognostic value of the Bioscore among non-metastatic breast cancer patients with respect to disease free survival (DFS).Methods: This study included 317 patients with non-metastatic surgically treated breast cancer; they were identified in the period from January 2015 to December 2018 at Clinical Oncology Department of Assiut University Hospital. Many variables were used; pathologic stage (PS), T stage (T), nodal stage (N), grade (G), estrogen receptor (ER), progesterone receptors (PR), and human epidermal growth factor receptor (HER2) status. Univariate & two multivariate analyses were performed to identify which of these variables are associated with disease-free survival (DFS). Results: The only significant factors in the Univariate analysis were PS3, T2, T3, T4, N3, G2, G3, ER -ve, PR -ve, and HER2 –ve. The factors which were significant in the first multivariate analysis; PS3, G3, ER –ve, and in the second one were; T2, T4, N3, G3, and ER –ve. Two sets of models were built to determine the utility of combining variables. Models incorporating G and E status had the highest C-index (0.72) for T+N + G + ER in comparison with (0.69) for (PS+ G + ER) and the lowest AIC (953.01) for T + N + G + E and (966.9) for PS + G + E. Conclusions: This study confirms the prognostic significance of bioscore in non-metastatic breast cancer in concerning DFS.

Salvage gastrectomy for unresectable advanced gastric cancer after combination chemotherapy with docetaxel, cisplatin, and S-1.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15113-e15113
Author(s):  
Kei Hosoda ◽  
Keishi Yamashita ◽  
Shinichi Sakuramoto ◽  
Hiroaki Mieno ◽  
Katsuhiko Higuchi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
Advanced Gastric Cancer ◽  
Univariate Analysis ◽  
Pancreatic Head ◽  
Progression Free Survival ◽  
Hematologic Toxicity ◽  
Primary Tumors ◽  
Free Survival

e15113 Background: The prognosis for patients with unresectable advanced gastric cancer treated with chemotherapy alone is extremely poor. We have evaluated the safety and efficacy of salvage gastrectomy following chemotherapy with docetaxel, cisplatin, and S-1 (DCS) in patients with unresectable advanced gastric cancer. Methods: We evaluated 30 patients with unresectable advanced gastric adenocarcinoma whose lesions were down-staged by DCS chemotherapy and who underwent salvage gastrectomy with lymph node dissection from 2006 to 2012, when visible lesions were judged resectable. We retrospectively reviewed their medical records to identify factors that would influence overall survival. Results: Of the 30 patients, 17 had extra-regional lymph node metastases, 5 had liver metastases, 9 had peritoneal dissemination and 6 had pancreatic head invasion prior to DCS chemotherapy. Of the 30 patients, 23, 3, and 4 underwent R0, R1, and R2 resection, respectively. No in-hospital deaths or reoperations occurred. Pathological evaluation of primary tumors revealed grades 3, 2, 1b, 1a, and 0 tumor regression in 4, 9, 7, 7, and 2 patients, respectively. Median progression-free survival was 19 months.Two-year progression-free survival and overall survival rates were 45% and 65%, respectively. Of 17 patients with target tumors, 15 had partial responses, making the overall response rate 88%. The most common grade 3/4 hematologic toxicity was neutropenia (56%); all treatment-related toxicities were resolved, and no patient died of toxicity-related causes. Univariate analysis showed that R1/2 surgery (p<0.001), diffuse type histology (p=0.054), histological grade 0/1a/1b following chemotherapy (p<0.033), ypN3 (p<0.001) and yply2/3 (p=0.003), were significantly prognostic of reduced overall survival. A multivariate proportional hazard model found that ypN3 (p=0.003) was the sole independent prognostic factor. Conclusions: Salvage gastrectomy after DCS chemotherapy was safe and effective in patients with unresectable advanced gastric cancer. Lymph node metastasis after chemotherapy was significantly prognostic of poor prognosis, suggesting the need for further treatment.

Association of dynamic changes of methylated SFRP2 in ctDNA with prognosis in advanced gastric cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15051-e15051
Author(s):  
Yan Haijiao ◽  
Kele Ge ◽  
Wenyu Chen ◽  
Xizheng Mao ◽  
Xiaodong Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Dynamic Change ◽  
Disease Free Survival ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Suppressor Gene ◽  
Stage Iii ◽  
Dynamic Monitoring ◽  
Free Survival ◽  
Potential Biomarker

e15051 Background: Secreted frizzled-related protein 2 (SFRP2) is a tumor suppressor gene and its hyper methylation could cause its inactivation and promote cancer development. However, whether methylated SFRP2 (mSFRP2) in ctDNA could serve as prognostic biomarker for patients with gastric cancer has not been thoroughly studied. Methods: Stage III or IV gastric cancer patients treated with systemic chemotherapy in the Third Affiliated Hospital of Soochow University from 2015 to 2017 were included. The mSFRP2 before and during chemotherapy were dynamically detected from ctDNA by digital polymerase chain reaction-based technologies. Results: In total, 121 patients were enrolled, with 63 in stage III and 58 in stage IV. Baseline median mSFRP2 was higher in stage IV than stage III (64 VS 18 copies/ng, P < 0.001). In stage III GC, the top 50% mSFRP2 population had shorter median disease-free survival (DFS, 11.0 months VS NR; HR, 13.05; 95% CI, 3.05-55.95;) and overall survival (OS, 17.0 months VS NR; HR, 7.80; 95% CI, 1.81-33.60). Similar results were observed in stage IV GC that the median progression-free survival (PFS, 4.0 VS 7.0 months; HR, 2.74; 95% CI, 1.58-4.78) and OS (12.0 VS 16.0 months; HR, 3.14; 95% CI, 1.67-5.92) was shorter in patients with top 50% mSFRP2. During the dynamic monitor along treatment, elevated mSFPR2 was associated with worse PFS (5.0 VS 7.0 months; HR, 2.17; 95% CI, 1.25-3.76) and OS (12.0 VS 15.5 months; HR, 3.51; 95% CI, 1.94-6.35) in stage IV patients. Conclusions: Our study shows the association between SFRP2 methylation and its dynamic change and prognosis in patients with gastric cancer. Our results provide a potential biomarker in ctDNA for prognosis and dynamic monitoring in patients with gastric cancer.

scholarly journals Prognostic significance of NDRG2 combined with EGFR-sensitizing mutations in lung adenocarcinoma

2020 ◽  
Author(s):  
Bo Yang ◽  
Linlin Ji ◽  
Yiling Feng ◽  
Xiao-Ping Li ◽  
Hong-Gang Zhou ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Lung Parenchyma ◽  
Clinicopathological Characteristics ◽  
Free Survival ◽  
Positive Correlations ◽  
Lung Puncture

Abstract Background: N-myc downstream-regulated gene 2 (NDRG2) plays a substantial role in lung adenocarcinoma (LUAD). Epidermal growth factor receptor (EGFR)-sensitizing mutation could significantly improve prognosis in patients with LUAD. Here, we aimed to elucidate the prognostic value of NDRG2 combined with EGFR-sensitizing mutations in patients with LUAD. Methods: Lung parenchyma specimens obtained during surgery or CT-guide percutaneous lung puncture biopsy for the NDRG2 protein and EGFR genomic testing were obtained. Associations between NDRG2/EGFR and clinicopathological characteristics of patients with LUAD were extracted from the Tianjin First Central Hospital in China between June 2013 and June 2014. Results: The expression of NDRG2 was significantly decreased in patients with LUAD. Expressions of NDRG2 and EGFR-sensitizing mutations showed positive correlations with survival. Expression of NDRG2 and EGFR-sensitizing mutations were associated with the longer overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS). Advanced stages were significantly associated with low expression of NDRG2. In multivariate analysis, compared with other patients, NDRG2 (+)/EGFR (+) was independently associated with prolonged OS and PFS. Conclusion: NDRG2 combined with EGFR-sensitizing mutations might be valuable markers to evaluate the prognosis of LUAD patients.

scholarly journals Anlotinib combined with SOX regimen (S1 (tegafur, gimeracil and oteracil porassium capsules) + oxaliplatin) in treating stage IV gastric cancer: study protocol for a single-armed and single-centred clinical trial

BMJ Open ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. e034685 ◽  
Author(s):  
Juan Wang ◽  
Dong Xue Wu ◽  
Lu Meng ◽  
Gang Ji
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Disease Free Survival ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Free Survival ◽  
Stage Iv Gastric Cancer ◽  
Before And After

IntroductionAnlotinib hydrochloride is a multi-targeted receptor tyrosine kinase inhibitor that targets angiogenesis-related kinases and has already showed good safety and efficacy in some solid tumours. However, evidence on the safety and feasibility of anlotinib in patients with stage IV gastric cancer is scarce.Methods and analysisThis study is a single-armed and single-centred clinical study being designed to include 150 patients of stage IV gastric cancer. The patients’ demographics, pathological characteristics, test results of blood, biochemistry and tumour markers before and after medication, disease-free survival and overall survival will be collected and analysed. The primary and main efficacy outcomes are objective response rate, progression-free survival, disease control rate and overall survival. The secondary efficacy outcome is safety indicator including the incidence of adverse drug reactions and adverse events after administration.Ethics and disseminationEthics approval has been obtained from the Ethics Committee at the First Affiliated Hospital (Xijing Hospital) of Fourth Military Medical University (KY20192111-F-1). The results of this study will be disseminated at several research conferences and as published articles in peer-reviewed journals.Trial registration numberChiCTR1900026291 (registration date: 29 September 2019).

scholarly journals High Galectin-7 and Low Galectin-8 Expression and the Combination of both are Negative Prognosticators for Breast Cancer Patients

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 953
Author(s):  
Anna Trebo ◽  
Nina Ditsch ◽  
Christina Kuhn ◽  
Helene Hildegard Heidegger ◽  
Christine Zeder-Goess ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Cell ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Her2 Status ◽  
Cancer Tissue ◽  
Breast Cancer Patients ◽  
Patient Age ◽  
Free Survival ◽  
Patient Âgé

Galectins are commonly overexpressed in cancer cells and their expression pattern is often associated with the aggressiveness and metastatic phenotype of the tumor. This study investigates the prognostic influence of the expression of galectin-7 (Gal-7) and galectin-8 (Gal-8) in tumor cell cytoplasm, nucleus and on surrounding immune cells. Primary breast cancer tissue of 235 patients was analyzed for the expression of Gal-7 and Gal-8 and correlated with clinical and pathological data and the outcome. To identify immune cell subpopulations, immunofluorescence double staining was performed. Significant correlations of Gal-7 expression in the cytoplasm with HER2-status, PR status, patient age and grading, and of Gal-8 expression in the cytoplasm with HER2-status and patient age and of both galectins between each other were found. A high Gal-7 expression in the cytoplasm was a significant independent prognosticator for an impaired progression free survival (PFS) (p = 0.017) and distant disease-free survival (DDFS) (p = 0.030). Gal-7 was also expressed by tumor-infiltrating macrophages. High Gal-8 expression in the cytoplasm was associated with a significantly improved overall survival (OS) (p = 0.032). Clinical outcome in patients showing both high Gal-7 and with low Gal-8 expression was very poor. Further understanding of the role of galectins in the regulation and interaction of tumor cells and macrophages is essential for finding new therapeutic targets.

scholarly journals Prognostic significance of NDRG2 combined with EGFR-sensitizing mutations in lung adenocarcinoma 

2020 ◽  
Author(s):  
Bo Yang ◽  
Linlin Ji ◽  
Yiling Feng ◽  
Xiao-Ping Li ◽  
Hong-Gang Zhou ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Lung Parenchyma ◽  
Diagnostic Value ◽  
Clinicopathological Characteristics ◽  
Free Survival ◽  
Lung Puncture

Abstract Background: N-myc downstream-regulated gene 2 (NDRG2) plays a substantial role in lung adenocarcinoma (LUAD). Epidermal growth factor receptor (EGFR)-sensitizing mutation could significantly improve prognosis in patients with LUAD. Here, we aimed to elucidate the prognostic value of NDRG2 combined with EGFR-sensitizing mutations in patients with LUAD. Methods: Lung parenchyma specimens obtained during surgery or CT-guide percutaneous lung puncture biopsy for the NDRG2 protein and EGFR genomic testing were obtained. Associations between NDRG2/EGFR and clinicopathological characteristics of patients with LUAD were extracted from the Tianjin First Central Hospital in China between June 2013 and June 2014. Results: The expression of NDRG2 was significantly decreased in patients with LUAD. Expressions of NDRG2 and EGFR-sensitizing mutations showed positive correlations with survival. ROC curve analyses showed that the diagnostic value of NDRG2 combined with EGFR in LUAD was significantly higher than that of each biomarker alone. Expression of NDRG2 and EGFR-sensitizing mutations were associated with the longer overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS). Advanced stages were significantly associated with low expression of NDRG2. In multivariate analysis, compared with other patients, NDRG2 (+)/EGFR (+) was independently associated with prolonged OS and PFS. Conclusion: NDRG2 combined with EGFR-sensitizing mutations might be valuable markers to evaluate the prognosis of LUAD patients.

scholarly journals Circulating Tumour Cells (CTCs) as Potential Biomarkers of Clinicopathological and Prognostic Significance in Gastric Cancer Patients: A Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Yiding Li ◽  
Guiling Wu ◽  
Wanli Yang ◽  
Xiaoqian Wang ◽  
Lili Duan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Cancer Staging ◽  
Diagnostic Value ◽  
Pooled Analysis ◽  
Clinicopathological Parameters ◽  
Free Survival

Abstract Background: Gastric cancer (GC) is a common highly recurrent malignant tumor that is associated with poor prognosis. Circulating tumor cells (CTCs) have drawn much attention because of their diagnostic value in diverse cancers, including GC. This study aimed to assess the relevance of CTCs in predicting the clinicopathological parameters and prognostic significance of GC. Methods: We systematically searched PubMed, Medline and Web of Science for relevant studies. Each database was searched from its date of inception through January 22, 2020. The odds ratios (ORs), hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated as effect values using the random-effects model. Results: In total, 52 articles that reported 68 studies comprising 4158 GC patients were included. The pooled results on TNM stage indicated that the III/IV group had a notably higher CTCs positivity rate than the I/II group (OR=2.73, 95% CI (1.95,3.82), I2=65%). The poorly differentiated group had a significantly higher CTCs positivity rate than the well/moderately differentiated group (overall: OR=1.91, 95% CI (0.77,4.71)), as well as the Lauren classification diffuse/hybrid type group and the intestinal group (overall: OR=1.77, 95% CI (0.70,4.44)). The bulk of analysis revealed that CTC positivity detected in GC patients was correlated with worse overall survival (OS) (HR =1.94, 95% CI (1.64,2.30), P≤0.001), progression-free survival (PFS) (HR =2.45, 95% CI (1.65,3.64), P≤0.001), and disease-free survival (DFS) (HR =2.78, 95% CI (1.89,4.10), P≤0.001). Then, we extracted data and analyzed the DCR of chemotherapy in patients with GC, and the pooled analysis demonstrated that the DCR of the CTC positivity was lower than that of the CTC negativity (RR =0.63, 95% CI (0.44,0.91))Conclusions: In conclusion, our study demonstrated that the CTCs positivity was correlated with the poor OS, PFS and DFS in GC patients and provided a scientific foundation for gastric cancer staging.

scholarly journals Low Pretreatment Albumin-to-Globulin Ratio Predicts Poor Prognosis in Gastric Cancer: Insight From a Meta-Analysis

2021 ◽  
Vol 10 ◽  
Author(s):  
Chengzhi Wei ◽  
Zhu Yu ◽  
Gonghe Wang ◽  
Yiming Zhou ◽  
Lei Tian
Keyword(s):  
Gastric Cancer ◽  
Poor Prognosis ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
China National Knowledge Infrastructure ◽  
Free Survival ◽  
Albumin To Globulin Ratio

BackgroundIn recent five years, reports regarding albumin-to-globulin ratio (AGR) and the survival of gastric cancer (GC) have emerged rapidly, yet their association remains controversial. This meta-analysis was aimed to provide an insight into the prognostic significance of pretreatment AGR in GC.MethodsPubMed, Embase, Cochrane library, Web of Science, WanFang, China National Knowledge Infrastructure (CNKI) and VIP databases were searched for relevant studies, from inception to September 30, 2020. Individual hazard ratios (HRs) with their 95% confidence intervals (CIs) were combined by Stata 12.0 software to evaluate the association between pretreatment AGR and overall survival (OS) and disease-free survival/progression-free survival (DFS/PFS).ResultsA total of 8,305 patients with GC from 12 studies were included for further analysis. Pooled analyses indicated that low AGR was closely associated with worse OS (HR = 1.531, 95% CI: 1.300–1.803, P &lt; 0.001) and worse DFS/PFS (HR = 2.008, 95% CI: 1.162–3.470, P = 0.012) in GC patients. Moreover, subgroup analyses demonstrated that the association between low AGR and worse OS remained constant despite variations in country, tumor stage, cut-off value, cut-off selection and treatment method.ConclusionAGR could act as an efficient prognostic indicator for GC, and that low pretreatment AGR predicts poor prognosis in GC.

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