Survival outcomes of management in metastatic gastric adenocarcinoma patients.
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ABSTRACT:
SUBMITTER: Hu HM
PROVIDER: S-EPMC8633380 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background It remains largely unclear how education level, an important socioeconomic factor, affects prognoses for patients with gastric adenocarcinoma (GAC). We aimed to demonstrate the associations between education level and clinical outcomes in patients with GAC. Methods We included a total of 30,409 patients diagnosed with GAC from the Surveillance, Epidemiology, and End Results 18 registry database. Education level, household income, unemployment rate, poverty rate, insurance status, and marital status were selected as sociodemographic variables for the comprehensive analysis. Cox and logistic regression models, Kaplan–Meier curves, and subgroup analyses were the primary statistical methods employed. Results A low level of education was correlated with less income, higher unemployment rates, and higher poverty rates (all p < 0.001). The multivariate Cox analysis indicated that a high education level was significantly associated with superior overall survival rates and cancer-specific survival rates in patients with GAC (both p < 0.001). We also corroborated favorable survival outcomes by high education level within almost every clinical and demographic subgroup. Furthermore, chemotherapy combined with surgery could markedly prolong the survival for all patients, including patients of stage IV cancer (both p < 0.001). By using multivariable logistic models, patients in counties with high education levels had a higher probability of chemotherapy receipt (p < 0.001). Contrarily, those in the counties with low levels of education were less likely to receive chemotherapy or undergo surgery (p < 0.001). Conclusions Education level was identified and confirmed as an independent predictor of treatment and survival for GAC patients. Efforts are needed to provide effective interventions for those whose educational status is adverse.
| S-EPMC9218109 | biostudies-literature
Project description:Trastuzumab is a human epidermal growth factor receptor 2 (HER2) inhibitor used to treat HER2+ metastatic gastric cancer (mGC). The present study aims to investigate the relationship between CDH1 mRNA expression and HER2-positivity in mGC using a multiplexed gene expression profile in two series of gastric cancer (GC): Series 1 (n = 38): HER2+ and HER2- mGC; Series 2 (n = 36) HER2- GC with and without metastasis. To confirm the results, the same expression profiles were analyzed in 354 GC from The Cancer Genome Atlas (TCGA) dataset. The difference in gene expression connected HER2 overexpression with canonical wingless-type (Wnt)/β-catenin pathway and immunohistochemical (IHC) expression loss of E-cadherin (E-CAD). CDH1 mRNA expression was simultaneously associated with the rs16260-A variant and an increase in E-CAD expression. Differences in retinoic acid receptor alfa (RARA), RPL19 (coding for the 60S ribosomal L19 protein), catenin delta 1 (CTNND1), and epidermal growth factor (EGF) mRNA levels-all included in the Wnt/β-catenin pathway-were found associated with overall survival (OS). RARA, CTNND1, and EGF resulted in independent OS prognostic factors. EGF was confirmed as an independent factor along with TNM stage in HER2-overpressed mGC from TCGA collection. Our study highlighted factors involved in the WNT/β-catenin pathway that interconnected E-CAD with HER2 overexpression and patient survival.
| S-EPMC8909509 | biostudies-literature
Project description:Gastric adenocarcinoma (GAC) is one of the most aggressive malignancies and has a dismal prognosis. Therefore, multimodality therapies to include surgery, chemotherapy, targeted therapy, immunotherapy, and radiation therapy are needed to provide advantage. For locally advanced GAC (>cT1B), the emerging strategies have included preoperative chemotherapy, postoperative adjuvant chemotherapy, and (occasionally) postoperative chemoradiation in various regions. Several novel therapies have been assessed in clinical trials, but only trastuzumab and ramucirumab (alone and in combination with paclitaxel) have shown overall survival advantage. Pembrolizumab has been approved by the US Food and Drug Administration on the basis of response rate only for patients with microsatellite instability (MSI-H) or if PD-L1 expression is positive (≥1% labeling index in tumor/immune cells in the presence of at least 100 tumor cells in the specimen). Nivolumab has been approved in Japan on the basis of a randomized trial showing significant survival advantage for patients who received nivolumab compared with placebo in the third or later lines of therapy. The cure rate of patients with localized GAC in the West is only about 40% and that for metastatic cancer is very poor (only 2-3%). At this stage, much more target discovery is needed through molecular profiling. Personalized therapy of patients with GAC remains a challenge.
| S-EPMC6117861 | biostudies-literature
Project description:BackgroundWe previously observed decreasing resection rates of non-metastatic gastric adenocarcinoma (GaC) in the US and some European countries. If and to what extent these trends affect the trends in overall survival (OS) of patients with non-metastatic GaC at the population level remain unclear. This large international population-based cohort study aimed to assess the impact of the previously observed decreasing resection rates on multivariable-adjusted trends in the long-term OS of patients with non-metastatic GaC.MethodsIndividual-level data of patients with non-metastatic GaC were obtained from the national cancer registries of the Netherlands, Belgium, Sweden, Norway, and Slovenia, and the US Surveillance, Epidemiology, and End Results database. We analyzed data for each country separately. Associations between year of diagnosis and OS were assessed using Cox proportional hazards regression model with adjustment for multiple prognostic variables, with and without including resection and chemotherapy as potential explanatory variables.ResultsA total of 66,398 non-metastatic GaC patients diagnosed in 2003-2016 were analyzed, with an accumulated follow-up of 172,357 person-years. Without adjustment for resection, OS was improved only slightly in the US [hazard ratio (HR)per year = 0.99; HR≥ vs. <2010 = 0.96], and no improvement was observed in the investigated European countries, with OS even worsening in Sweden (HRper year = 1.03; HR≥ vs. <2010 = 1.17). After adjusting for resection, the increasing OS trend became stronger in the US (HRper year = 0.98; HR≥ vs. <2010 = 0.88), and the temporal trend became insignificant in Sweden. In Slovenia (HRper year = 0.99; HR≥ vs. <2010 = 0.92) and Norway (HRper year = 0.97; HR≥ vs. <2010 = 0.86), improved OS over time emerged after resection adjustment. Improved OS in patients undergoing resection was observed in the US, the Netherlands, and Norway. Adjustment for chemotherapy did not alter the observed associations. Stratified analyses by tumor location showed mostly similar results with the findings in all patients with non-metastatic GaCs regarding the associations between year of diagnosis and survival.ConclusionsOS of patients with non-metastatic GaC mostly did not improve in selected European countries and was even worsened in Sweden, while it was slightly increased in the US in the early 21st century. Progress in OS of patients with non-metastatic GaC seems to have been impeded to a large extent by decreasing rates of resection.
| S-EPMC9257984 | biostudies-literature
Project description:BackgroundReal-world practice patterns, treatment sequencing, and outcomes in patients with metastatic pancreatic cancer remain unclear. Previous research indicates that the likelihood of patients with metastatic pancreatic cancer receiving or continuing cancer-directed therapy is low-a phenomenon called nihilism. This retrospective, descriptive analysis examined clinical characteristics, treatment patterns, and outcomes for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC).MethodsTreatment patterns were examined using electronic health records from the Flatiron Health database covering the period from January 1, 2014, to June 30, 2019. Real-world overall survival [rwOS]) was compared for a subgroup of patients receiving treatment and a matched subgroup not receiving treatment.ResultsOf 7666 patients, 5687 (74.2%) received at least one line of systemic therapy. A greater proportion of patients receiving treatment than not receiving treatment had an initial diagnosis of stage IV disease (68.8% vs 61.2%, respectively). Among patients receiving an initial therapy, fewer than half (38.2%; 2174/5687) received second-line treatment, mostly because they died, and only 34.3% (745/2174) of those receiving second-line treatment advanced to third-line treatment. The rwOS for patients receiving at least one line of systemic therapy was 8.1 months versus 2.6 months for matched patients not receiving treatment (hazard ratio, 0.41; 95% confidence interval, 0.38-0.45; 1470 patients per group).ConclusionsSystemic therapy provided significant clinical benefit for patients who were eligible and chose to receive it, particularly when treatment was consistent with guideline recommendations. The large proportion of patients initiating treatment suggests that nihilism with mPDAC is diminishing.
| S-EPMC7666752 | biostudies-literature
Project description:Incidence of young patients (aged 40 years or younger) diagnosed with gastric carcinoma has increased worldwide. Young GC diagnosis, have clinicopathological features that differ from elderly, and is correlated with bad prognosis factors. The purpose of this work is to describe the prevalence, clinic-pathological features, and prognosis of overall survival (OS) of young Latin-American patients with GC. Retrospective, observational study. Included patients treated at the National Cancer Institute [2004-2020]. Statistical analysis: χ2 and t-test, Kaplan-Meier, Log-Rank and Cox-Regression. Statistical significance differences were assessed when P was bilaterally <0.05. A total of 2,543 patients fulfilled the inclusion criteria. Young-patients were predominantly female (54%), with diffuse-type adenocarcinoma (68%), signet-ring-cell (72%), poor-differentiation (90%), and metastatic (79%). In OS analysis, patients with metastatic disease, showed differences regarding age, young patients reported a median-OS of 8 versus 13 months for elderly patients (P=0.001). Among young patients, differences were also observed regarding gender, young-female patients had a median-OS of 5 versus 11 months for young-man (P=0.001). This is one of the pioneer studies correlating age with gender and the prognostic features of bad prognosis in Latin-American population. Besides, supports the idea that a global effort is required to improve awareness, prevention, and early diagnosis of GC.
| S-EPMC10643594 | biostudies-literature
Project description:IntroductionPancreatic ductal adenocarcinoma (PDAC) is a genetically heterogeneous disease often diagnosed with synchronous metastatic disease involving the liver. Tumors with extra-abdominal spread that bypass the liver are thought to represent a unique molecular subgroup and those with isolated pulmonary metastatic disease are thought to have a more favorable clinical phenotype.MethodWe conducted a retrospective review of patients with pathologically confirmed PDAC treated between the years 2007 and 2020 at a Scripps Health hospital. The final study sample (N = 205) included patients with isolated pulmonary metastasis (IL), isolated liver metastasis or synchronous liver and lung metastasis (LL), or metastasis to any site other than the liver or lung (NLL). Primary endpoint was overall survival (OS). Progression-free survival (PFS) and recurrence-free survival (RFS) were analyzed as secondary endpoints. Each survival outcome was analyzed using Cox proportional hazards tests.ResultsNo statistically significant differences were seen between the three groups in OS, PFS, or RFS. Median OS for the IL group was 561 days, 341 days for the LL group, and 441 days for the NLL group. Median RFS was 748 days for the IL group, 574 days for the LL group, and 545 days for the NLL group. Median PFS was 307 for the IL group, 236 for the LL group, and 265 for the NLL group. When comparing only the IL and LL groups, a statistically significant difference in OS was seen favoring the IL group (HR1.59 LL vs IL [ref], CI 1.04-2.41, p = 0.031) CONCLUSION: Though statistically significant differences in survival outcomes were not seen in our population, there was a trend toward improved survival for patients with isolated lung metastases. When comparing only the IL to LL group, statistically significant overall survival favoring the IL group was seen. These findings highlight a potential prognostic indicator of metastatic PDAC.
| S-EPMC10225201 | biostudies-literature
Project description:BackgroundAlthough metastatic breast cancer (MBC) remains incurable, advances in therapies have improved survival. Using a contemporary dataset of de novo MBC patients, we explore how overall (OS) and cancer-specific survival (CSS) changed over time.MethodsAll patients with de novo MBC from 1988 to 2016 were selected from Surveillance, Epidemiology, and End Results (SEER) 18. Unadjusted OS and CSS were estimated by Kaplan-Meier method and stratified by disease characteristics. Cox proportional hazards models determined factors associated with survival.Results47,034 patients were included, with median OS of 25 months and CSS of 27 months. Survival steadily improved over time (1988: 1-year OS 62%, CSS 65%; 2015: 1-year OS 72%, CSS 74%). Patients with triple-negative breast cancer (TNBC) had the worst prognosis and were most likely to die from MBC [versus human epidermal growth factor receptor 2 (HER2)+ and hormone receptor (HR)+/HER2-]. Those with ≥ 4 sites of metastatic disease were also more likely to die from MBC with nearly identical OS and CSS (5-year OS 9%, CSS 9%), when compared with those with 1 site (5-year OS 31%, CSS 35%). After adjustment, improved CSS was associated with bone-only disease [hazard ratio (HR) 0.88, 95% confidence interval (CI) 0.83-0.94], while TNBC (versus HER2+: HR 3.12, 95% CI 2.89-3.36) and > 3 sites of metastatic disease (versus 1 site: HR 3.24, 95% CI 2.68-3.91) were associated with worse CSS (all p < 0.001).ConclusionsAccurate prognostic estimates are essential for patient care. As treatments for patients with MBC have expanded, OS and CSS have improved, and more patients, particularly with limited distant disease or favorable tumor subtypes, are also dying from non-MBC causes.
| S-EPMC8530869 | biostudies-literature
Project description:ObjectivesSurvival benefit of combination over single-agent chemotherapy for metastatic pancreatic ductal adenocarcinoma (PDAC) was demonstrated in younger patients in clinical trials. The authors aimed to evaluate whether this survival benefit of combination chemotherapy is present in elderly patients with metastatic PDAC.Materials and methodsThe authors identified elderly patients (age 65 y or older) with stage IV PDAC and extracted available clinical information from a prospectively maintained institutional pancreatic cancer registry from 2007 to 2016. The primary endpoint was overall survival. Cox proportional hazards regression was used for multivariable survival analyses. Survival outcomes for the entire cohort and by age group I (elderly, 65 to 75 y) and age group II (very elderly, older than 75 y) were assessed.ResultsA total of 606 patients were included with a median age of 73.8 years. Among them, 239 patients (39%) received combination chemotherapy and 152 patients (25.1%) received single-agent chemotherapy as first-line treatment. Combination chemotherapy was associated with significantly longer median overall survival compared with single-agent chemotherapy (10.9 vs. 7.5 mo, P<0.001) with hazard ratio 0.62 (95% confidence interval, 0.47-0.81; P=0.001) after adjusting for age, sex, comorbidity, Eastern Cooperative Oncology Group (ECOG) performance status, and carbohydrate antigen 19-9 level. Analyses by age groups indicated that very elderly patients (age group II) benefited from combination chemotherapy compared with single-agent chemotherapy with hazard ratio 0.56 (95% confidence interval, 0.31-1; P=0.049), comparable with the age group I (Page-treatment interaction=0.81).ConclusionElderly patients, even those older than 75 years, with metastatic PDAC benefited from combination chemotherapy.
| S-EPMC7395872 | biostudies-literature
Project description:ImportanceConsidering its low completion rate, the survival benefit associated with postoperative chemotherapy (PC) is unclear in patients with resectable gastric adenocarcinoma who received preoperative chemotherapy.ObjectiveTo determine whether preoperative chemosensitivity is associated with postoperative survival among patients with resectable gastric adenocarcinoma who receive PC.Design, setting, and participantsThis national, hospital-based cohort study used data from the National Cancer Database, which covers more than 70% newly diagnosed gastric adenocarcinomas in the US, between 2006 and 2017. Participants included patients with clinical stage II or III disease treated with preoperative chemotherapy and curative-intent resection, excluding radiotherapy. Preoperative chemosensitivity was defined as very sensitive (ypT0N0), sensitive (pathological TNM stage less than clinical, excluding ypT0N0), and refractory (pathological greater than or equal to clinical). Data were analyzed in April 2021.ExposuresReceipt of PC or not.Main outcomes and measuresOverall survival from surgical discharge.ResultsThis study included 2382 patients (1599 men [67%]; median [IQR] age, 63 [54-70] years). Most patients (1524 patients [64%]) received no PC. Most patients (1483 patients [62%]) had refractory disease, followed by sensitive disease (727 patients [31%]) and very sensitive disease (172 patients [7%]). Patients with older age (odds ratio [OR], 0.99; 95% CI, 0.97-1.00), comorbidity (OR, 0.71; 95% CI, 0.57-0.90), longer time from chemotherapy initiation to surgery (OR, 0.99; 95% CI, 0.97-1.00), less sensitivity to preoperative chemotherapy (very sensitive vs refractory OR, 0.58; 95% CI, 0.37-0.89; sensitive vs refractory OR, 0.96; 95% CI, 0.76-1.20), and longer surgical hospitalization (OR, 0.95; 95% CI, 0.93-0.97) had a significantly lower likelihood of receiving PC. PC was not associated with improved survival in the whole group (hazard ratio [HR], 0.88; 95% CI, 0.75-1.02). Patients with refractory disease had the worst survival compared with patients with sensitive disease (HR, 0.39; 95% CI, 0.32-0.46) and those with very sensitive disease (HR, 0.12; 95% CI, 0.07-0.20). Preoperative chemosensitivity was significantly associated with the survival benefit from PC (P for interaction = .03). PC was significantly associated with longer survival in patients with sensitive disease (5-year survival rate, 73.8% in the PC group vs 65.0% in the no PC group; HR, 0.64; 95% CI, 0.46-0.91), but not in those with very sensitive disease (5-year survival rate, 80.0% in the PC group vs 90.8% in the no PC group; HR, 2.45; 95% CI, 0.81-7.43) and those with refractory disease (5-year survival rate, 41.8% in the PC group vs 40.7% in the no PC group; HR, 0.93; 95% CI, 0.79-1.10).Conclusions and relevanceIn this cohort study, preoperative chemosensitivity was associated with survival among patients with resectable gastric adenocarcinoma who received PC. These findings may help inform future studies to personalize postoperative therapy.
| S-EPMC8605482 | biostudies-literature