scholarly journals A Signature-Based Classification of Gastric Cancer That Stratifies Tumor Immunity and Predicts Responses to PD-1 Inhibitors

2021 ◽  
Vol 12 ◽  
Author(s):  
Song Li ◽  
Jing Gao ◽  
Qian Xu ◽  
Xue Zhang ◽  
Miao Huang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Progression Free Survival ◽  
Activated T Cells ◽  
Independent Manner ◽  
Cyclin E1 ◽  
Cancer Management ◽  
T Cell Infiltration ◽  
Immune Signatures ◽  
Potential Efficacy ◽  
Caspase 7

Gastric cancer is a leading cause of cancer-related deaths with considerable heterogeneity among patients. Appropriate classifications are essential for prognosis prediction and individualized treatment. Although immunotherapy showed potential efficacy in a portion of patients with gastric cancer, few studies have tried to classify gastric cancer specifically based on immune signatures. In this study, we established a 3-subtype cluster with low (CLIM), medium (CMIM), and high (CHIM) enrichment of immune signatures based on immunogenomic profiling. We validated the classification in multiple independent datasets. The CHIM subtype exhibited a relatively better prognosis and showed features of “hot tumors”, including low tumor purity, high stromal components, overexpression of immune checkpoint molecules, and enriched tumor-infiltrated immune cells (activated T cells and macrophages). In addition, CHIM tumors were also characterized by frequent ARID1A mutation, rare TP53 mutation, hypermethylation status, and altered protein expression (HER2, β-catenin, Cyclin E1, PREX1, LCK, PD-L1, Transglutaminase, and cleaved Caspase 7). By Gene Set Variation Analysis, “TGFβ signaling pathway” and “GAP junction” were enriched in CLIM tumors and inversely correlated with CD8+ and CD4+ T cell infiltration. Of note, the CHIM patients showed a higher response rate to immunotherapy (44.4% vs. 11.1% and 16.7%) and a more prolonged progression-free survival (4.83 vs. 1.86 and 2.75 months) than CMIM and CLIM patients in a microsatellite-independent manner. In conclusion, the new immune signature-based subtypes have potential therapeutic and prognostic implications for gastric cancer management, especially immunotherapy.

scholarly journals Intratumoral CXCR5+CD8+T associates with favorable clinical outcomes and immunogenic contexture in gastric cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jieti Wang ◽  
Ruochen Li ◽  
Yifan Cao ◽  
Yun Gu ◽  
Hanji Fang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
T Cells ◽  
Epstein Barr Virus ◽  
Effector Memory ◽  
Feature Identification ◽  
Barr Virus ◽  
T Cell Infiltration ◽  
Epstein Barr ◽  
Gastric Cancer Patients

AbstractStudies that examined an association between CD8+T and prognosis in gastric cancer are inconsistent, and a distinct population of CXCR5+CD8+T associated with better overall survival has been reported among various malignancies. Here, we show that the abundance of intratumoral CXCR5+CD8+T cells is associated with better overall survival in patients with gastric cancer. Patients with TNM II + III gastric cancer with higher intratumoral CXCR5+CD8+T cell infiltration are more likely to benefit from adjuvant chemotherapy. Microsatellite-unstable and Epstein–Barr virus positive tumors are enriched with CXCR5+CD8+T cells. Gastric cancer infiltrating CXCR5+CD8+T cells represent a specific subtype of stem-like CD8+T with effector memory feature. Identification of the clinical significance and phenotype of gastric cancer infiltrating CXCR5+CD8+T provides a roadmap for patient stratification and trials of targeted therapies.

scholarly journals HIFU for the treatment of gastric cancer with liver metastases with unsuitable indications for hepatectomy and radiofrequency ablation: a prospective and propensity score-matched study

BMC Surgery ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Bin Zhou ◽  
Ning He ◽  
Jiaze Hong ◽  
Tong Yang ◽  
Derry Minyao Ng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Radiofrequency Ablation ◽  
Propensity Score ◽  
Adverse Events ◽  
Liver Metastases ◽  
Hepatic Metastasis ◽  
Focused Ultrasound ◽  
Progression Free Survival ◽  
High Intensity Focused Ultrasound ◽  
Entire Cohort

Abstract Background The purpose of this study was to explore the efficacy and safety of high intensity focused ultrasound (HIFU) in gastric cancer with liver metastasis (GCLM) patients who were contraindicated for either hepatectomy or radiofrequency ablation (RFA). Methods This is a prospective, observational study on GCLM patients with 1–3 liver metastases. The primary gastric lesions were thoroughly resected and any case that exhibited extra-hepatic metastasis was excluded. A 1:2:2 propensity score-matching analysis was performed using a logistic regression model on the HIFU group, best supportive care (BSC) group, and palliative chemotherapy (PC) group. The primary endpoints include progression-free survival (PFS) and overall survival (OS). Results Forty patients were finally included, there were 8 cases in HIFU group, 16 cases in BSC group, and 16 cases in PC group. The median follow-up time for the entire cohort was 10 months. The median PFS was 16.5 months in HIFU group, 2 months in BSC group, and 5 months in PC group. The median OS was 27.5 months in the HIFU group, 7 months in the BSC group, and 11.5 months in the PC group. Additionally, no grade 3 or higher adverse events occurred in the HIFU group. Conclusion The results of this study showed that HIFU treatment could improve the long-term prognosis of GCLM patients without a significant increase in the occurrence of adverse events. Compared with PC and BSC, HIFU is the preferred treatment option when GCLM patients without extra-hepatic metastasis are unable to undergo either surgery or RFA.

scholarly journals Efficacy and Safety of FLOT regimen vs. DCF, FOLFOX, and ECF regimens as Perioperative Chemotherapy Treatments for Resectable Gastric Cancer Patients

2021 ◽  
Author(s):  
Pegah Farrokhi ◽  
Alireza Sadeghi ◽  
Mehran sharifi ◽  
Payam Dadvand ◽  
Rachel Riechelmann ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Cox Regression ◽  
Progression Free Survival ◽  
R0 Resection ◽  
P Value ◽  
Perioperative Chemotherapy ◽  
Resectable Gastric Cancer ◽  
Gastric Cancer Patients

AbstractAimThis study aimed to evaluate and compare the efficacy and toxicity of common regimens used as perioperative chemotherapy including ECF, DCF, FOLFOX, and FLOT to identify the most effective chemotherapy regimen with less toxicity.Material and MethodsThis retrospective cohort study was based on 152 eligible gastric cancer patients recruited in a tertiary oncology hospital in Isfahan, Iran (2014-2019). All resectable gastric cancer patients who had received one of the four chemotherapy regimens including ECF, DCF, FOLFOX, or FLOT, and followed for at least one year (up to five years) were included. The primary endpoint of this study was Overall Survival (OS), Progression-Free Survival (PFS), Overall Response Rate (ORR), and R0 resection. We also considered toxicity according to CTCAE (v.4.0) criteria as a secondary endpoint. Cox -regression models were used applied to estimate OS and PFS time, controlled for relevant covariates.ResultsOf included patients, 32(21%), 51(33.7%), 37(24.3%), and 32(21%) had received ECF, DCF, FOLFOX and FLOT, respectively. After the median 25 months follow-up, overall survival was higher with the FLOT regimen in comparison with other regimens (hazard ratio [HR] = 0. 052). The median OS of the FLOT regimen was not reachable in Kaplan-Meier analysis and the median OS was 28, 26, and 23 months for DCF, FOLOFX, and ECF regimens, respectively. On the other hand, a median PFS of 25, 17, 15, and 14 months was observed for FLOT, DCF, FOLFOX, and ECF regimens, respectively (Log-rank = 0. 021). FLOT regimen showed 84. 4% ORR which was notably higher than other groups (p-value<0. 01).ConclusionsFor resectable gastric cancer patients, the perioperative FLOT regimen seemed to lead to a significant improvement in patients’ OS and PFS in comparison with ECF, DCF, and FOLFOX regimens. As such, the FLOT regimen could be considered as the optimal option for managing resectable gastric cancer patients.

Matched therapies for advanced gastric cancer based on genotype: A real-world study in China.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16098-e16098
Author(s):  
Qin Liu ◽  
Ju Yang ◽  
Nandie Wu ◽  
Song Liu ◽  
Yipeng Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Disease Control ◽  
Advanced Gastric Cancer ◽  
Real World ◽  
Systemic Therapy ◽  
Objective Response ◽  
Progression Free Survival ◽  
Braf V600e ◽  
Tumor Biopsy ◽  
Kit Mutation

e16098 Background: Systemic therapy options for patients with advanced gastric cancer (GC) are limited. We here presented the efficacy results for advanced GC patients matched to targeted therapies or immunotherapies based on the identification of tumor tissue genotypes. Methods: We selected 30 patients diagnosed between 2014 and 2020 with advanced GC at Nanjing Drum Tower Hospital, the affiliated Hospital of Nanjing University Medical School identified with actionable alterations and received ≥1 matched therapies. Tumor biopsy specimens from the patients were analyzed using NGS and/or selected immunohistochemistry and fluorescence in situ hybridization. Results: In these 30 patients, median age at diagnosis was 63 years (range 28-83) and 6 (20%) were female. In total, 11 (37%) harbored c-MET amplification/overexpression (received savolitinib or crizotinib, cohort A), 9 (30%) harbored HER2 mutation/overexpression (received RC48-ADC or trastuzumab, cohort B), 6 (20%) dMMR/MSI-H/TMB-H (received sintilimab, pembrolizumab, tislelizumab or nivolumab, combined with antivascular or not, cohort C), 2 (7%) KIT mutation/amplification (received imatinib or anlotinib, cohort D), 1 (3%) BRAF V600E mutation (received vemurafenib, cohort E) and 1 (3%) EGFR mutation (received afatinib, cohort F). Except for three patients in cohort C, all patients received at least one previous line systemic therapy. In cohort A, three of 11 patients had an objective response (1 complete response and 2 partial responses, objective response rate (ORR) 27%), disease control rate (DCR) was 45%, median progression-free survival (mPFS) was 2.1 months, and median overall survival (mOS) was 3.7 months. In cohort B, ORR was 44% (4/9), DCR was 78% (7/9), mPFS and mOS was 3.1 months and 5.5 months, respectively. In cohort C, ORR was 17% (1/6), DCR was 67% (4/6), mPFS and mOS was 1.9 months and 6.8 months, respectively. In cohort D, no patient had objective response or disease control. In cohort E, the one patient had PR. Stable disease was observed in the patient in cohort F. In all cohorts, ORR was 30% (9/30), DCR was 60% (18/30), mPFS and mOS was 2.7 months and 5.8 months, respectively. Conclusions: Overall, 30 patients with advanced GC were treated with matched therapies according to specific genotype. These real-world outcomes suggested that matched therapies for advanced GC has promising efficacy, supporting the adoption of genotyping in treatment determination.

Cost-effectiveness analysis of gastric cancer management using perioperative chemotherapy versus adjuvant chemoradiation therapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16079-e16079
Author(s):  
Vishnu Prasath ◽  
Patrick L. Quinn ◽  
Joseph B. Oliver ◽  
Omar Mahmoud ◽  
Mohammed Jaloudi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cost Effectiveness ◽  
Treatment Strategy ◽  
Chemoradiation Therapy ◽  
Adjuvant Chemoradiotherapy ◽  
Complication Rates ◽  
Perioperative Chemotherapy ◽  
Adjuvant Chemoradiation ◽  
Cancer Management ◽  
Life Years

e16079 Background: The most commonly used treatment options for gastric cancer include complete resection with adequate margins with either perioperative chemotherapy (PCT) or adjuvant chemoradiotherapy (CRT). While both treatment strategies have shown superiority over surgical resection alone, it is not clear which treatment strategy is more optimal. Methods: Our decision tree model was built to analyze the survival and costs associated with the two major management methods: perioperative chemotherapy and adjuvant chemoradiation therapy. Costs were obtained from Medicare reimbursement rates using a third-party payer perspective. Our model’s effectiveness was represented using quality-adjusted life years (QALYs). Our analysis tested the robustness of our conclusions by utilizing one-way, two-way, and probabilistic sensitivity analyses. Results: PCT was the preferred treatment strategy for diagnosed gastric cancer over CRT, with a cost of $54,326.10 and 4.08 QALYs. CRT was the costliest economic strategy with a cost of $77,987.52 and 4.28 QALYs and an ICER of 115,907.48. We set a threshold of $100,000 per QALYs gained which CRT surpassed making PCT the preferred treatment modality. Over 100,000 simulations, 51.4% of simulations favored PCT. CRT became favored when CRT non-curative procedure rates rose 3% higher than PCT non-curative procedure rates and when PCT complication rates rose 15% higher than CRT complication rates. Conclusions: In our simulated patients with diagnosed gastric cancer, the most cost-effective treatment strategy was PCT. We see cost-effectiveness alternating to favor CRT with changes in non-curative procedure rates and adjuvant therapy complication rates.[Table: see text]

EFFICACY OF PERFUSION THERMOCHEMOTHERAPY IN GASTRIC CANCE MANAGEMENT BASED ON RESULTS OF PROSPECTIVE RANDOMIZED STUDY

2021 ◽  
pp. 87-91
Author(s):  
М.Yu. Reiitovich ◽  
Keyword(s):  
Gastric Cancer ◽  
Survival Rate ◽  
Peritoneal Dissemination ◽  
Radical Surgery ◽  
Randomized Study ◽  
Progression Free Survival ◽  
Prospective Randomized Study ◽  
Free Survival ◽  
Borrmann Type

The article analyses the results of a prospective randomized study of a cohort of 154 radically operated patients with stage IIB-IIIC gastric cancer (Borrmann type 111 IV). 76 patients were administered intraoperative perfusion thermochemotherapy (HIPEC). It was noted that enhancing radical surgery procedure by complementing it with HIPEC in managing this prognostically unfavorable group of patients resulted in a decrease in the frequency of progression cases (p = 0.009), metachronous peritoneal dissemination — (p < 0.001), and 5-year cumulative carcinomatosis incidence — 70.7 ± 6.8 % to 23.6 ± 5.2 % (p < 0.001) thereby building a groundwork for improving 5-year adjusted survival rate from 27.0 ± 6.7 % to 45.1 ±6.4 % (p = 0.05), progression-free survival — from 16.3 ± 5.5 % to 42.1 ± 6.3 % (p < 0.001), and dissemination-free survival — from 19.4 ± 5.9 % to 45.2 ± 6.3 % (p = 0.001).

Cell Cycle Activity Correlates with Increased Anti-Tumor Immunity in Diverse Cancers

2020 ◽  
Author(s):  
Shanmei Jiang ◽  
Yin He ◽  
Mengyuan Li ◽  
Xiaosheng Wang
Keyword(s):  
Cell Cycle ◽  
Tumor Immunity ◽  
Cancer Biology ◽  
Cancer Genomics ◽  
Immune Checkpoint Blockade ◽  
Cytolytic Activity ◽  
The Cancer Genome Atlas ◽  
T Cell Infiltration ◽  
Immune Signatures ◽  
Positive Correlations

Abstract Objectives The cell cycle pathway regulating cell proliferation is overactivated in various cancers. Immune evasion is another important mechanism for tumor cell hyperproliferation. Nevertheless, the relationship between cell cycle and tumor immunity remains not fully understood. Materials and Methods Using the cancer genomics datasets for 10 cancer cohorts from the Cancer Genome Atlas (TCGA) program, we investigated the association between cell cycle activity (CCA) and anti-tumor immune signatures. We also explored the association between CCA and PD-L1 expression in these cancer cohorts. Moreover, we investigated the association between CCA and immunotherapy response in several cancer cohorts receiving immunotherapy. Results CCA likely exhibited positive associations with anti-tumor immune signatures (CD8+ T cell infiltration and immune cytolytic activity) in these cancer cohorts. The strong positive associations of CCA with DNA damage repair pathways and with tumor mutation load may explain the positive associations between CCA and anti-tumor immune signatures. Moreover, CCA displayed significant positive correlations with PD-L1 expression. Finally, we found that the enhanced CCA tended to be associated with unfavorable clinical outcomes in the TCGA cancer cohorts, though such association was not observed in the cancer cohorts receiving immune checkpoint blockade therapy. Conclusions CCA has significant positive associations with both anti-tumor immune signatures and tumor immune-suppressive signatures in diverse cancer types. Our findings provide new insights into cancer biology and potential clinical implications for cancer immunotherapy.

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