Non-metastatic Gastric Cancer Research Articles

Abstract 4822: Disparities in receiving non-surgical therapy impact outcomes in non-metastatic gastric cancer in Louisiana

Abstract Background: Given the history of evolving medical therapies and advancements in cancer treatments over the last decades, resectable gastric cancer has presented multiple strategies for care. Previous literature indicates historically decreased use of multimodal therapies in minority populations. This study aims to evaluate Louisiana patient populations for rates of definitive treatment, inequities in access to care, and evaluating its impact on the outcomes of minorities and underserved population. Methods: Patients with non-metastatic primary invasive gastric cancer, with T2-4 or any T status with positive lymph nodes, were identified in the Louisiana Tumor Registry using ICD-O codes and AJCC staging system. Receipt of non-surgical therapy was modeled using logistic regression. Overall survival (OS) was modeled using a Cox proportional hazards model. Results: The study included 561 patients, of which 37.6% (n=211) did not receive surgical treatment and 16.2% (n=91) did not receive non-surgical therapy. A subset of the cohort received no definitive treatment, (6.8%, n=38). In a demographic only multivariable model, adjusting for age, sex, and race, age 70 and over [OR (95%CI) =0.18 (0.08-0.42), p<0.001] and female sex [OR (95%CI) =0.48 (0.28-0.85), p=0.011] was associated with decreased rates of non-surgical therapy. Black [OR (95%CI) = 0.54 (0.31-0.93), p=0.027] and Hispanic [OR (95%CI) = 0.38 (0.13-1.08), p=0.070] race was associated with decreased receipt of non-surgical therapies. However, after adjusting for domestic partner, insurance status, rurality, area poverty, and surgery status, racial disparities were no longer significant compared to whites: Black [OR (95% CI) = 0.59 (0.33-1.06), p=0.075]; Hispanic [OR (95% CI) = 0.52 (0.17-1.66), p=0.272]. In multivariable analyses, receipt of surgery [HR (95% CI) = 0.3 (0.23 - 0.38), p<0.001) and any non-surgical therapy [HR (95% CI) = 0.43 (0.31 - 0.60), p<0.001) were associated with increased overall survival. Conclusion: A significant number of patients did not receive all modalities of the multidisciplinary treatment that is recommended for patients with non-metastatic gastric adenocarcinoma. Black patients and females are less likely to receive non-surgical modalities for gastric cancer in Louisiana, which is, at least, partially driven by socioeconomic determinants. Identifying patients with these risk factors is a crucial step in allocating resources to increase access the care and improve outcomes. Citation Format: Conner D. Hartupee, Kyla Maupin, Denise M. Danos, Omeed Moaven. Disparities in receiving non-surgical therapy impact outcomes in non-metastatic gastric cancer in Louisiana [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4822.

Adjuvant and neoadjuvant chemotherapy for MSI early gastric cancer: a systematic review and meta-analysis.

Perioperative chemotherapy (CT) is an established therapeutic approach for patients diagnosed with stage IB-III gastric cancer (GC). This study aimed to investigate the efficacy of this approach in individuals with GC exhibiting high microsatellite instability (MSI-H). A systematic review was conducted, including studies that provided data on (neo)adjuvant CT outcomes in patients with MSI-H GC. Systematic searches were conducted in PubMed, Cochrane Central of Controlled Trials, and Embase databases. Data were aggregated using hazard ratios (HRs) to compare overall survival between CT and surgery. Data analysis from 23 studies, including 22,011 patients, revealed that the prevalence of MSI-H is 9.8%. Administration of adjuvant or perioperative CT did not significantly reduce the risk of death or relapse in patients with MSI-H GC (HR = 0.8, 95% CI 0.54-1.16; p = 0.24 and HR = 0.84, 95% CI 0.59-1.18; p = 0.31, respectively). Chemotherapy did not benefit patients diagnosed with MSI-H nonmetastatic GC but rather will be integrated with immune checkpoint inhibitors in the near future.

What determines complications and prognosis among patients subject to multivisceral resections for locally advanced gastric cancer?

BackgroundLocally advanced gastric cancer (GC) extending to the surrounding tissues may require a multivisceral resection (MVR) to provide the best chance of cure. However, little is known about how the extent of organ resection affects the risks and benefits of surgery.MethodsAn electronic database of patients treated between 1996 and 2020 in an academic surgical centre was reviewed. MVRs were defined as partial or total gastrectomy combined with splenectomy, distal pancreatectomy, or partial colectomy.ResultsSuspected intraoperative tumour invasion of perigastric organs (cT4b) was found in 298 of 1476 patients with non-metastatic GC, and 218 were subject to MVRs, including the spleen (n = 126), pancreas (n = 51), and colon (n = 41). MVRs were associated with higher proportions of surgical and general complications, but not mortality. A nomogram was developed to predict the risk of major postoperative morbidity (Clavien–Dindo’s grade ≥ 3a), and the highest odds ratio for major morbidity identified by logistic regression modelling was found for distal pancreatectomy (2.53, 95% CI 1.23–5.19, P = 0.012) and colectomy (2.29, 95% CI 1.04–5.09, P = 0.035). Margin-positive resections were identified by the Cox proportional hazards model as the most important risk factor for patients’ survival (hazard ratio 1.47, 95% CI 1.10–1.97). The extent of organ resection did not affect prognosis, but a MVR was the only factor reducing the risk of margin positivity (OR 0.44, 95% CI 0.21–0.87).ConclusionsThe risk of multivisceral resections is associated with the organ being removed, but only MVRs increase the odds of complete tumour clearance for locally advanced gastric cancer.

OGC O07 The prognostic role of positive peritoneal cytology in gastric cancer

Abstract Background Locally advanced non-metastatic gastric cancer is primarily managed with surgical resection and peri-operative oncological therapies. Positive peritoneal cytology is often considered to be indicative of disseminated malignancy. We have previously shown that conversion from positive (Cy+) to negative (Cy0) cytology with systemic therapy, and absence of macroscopic disease, improves survival. With the advent of novel chemo- and radiotherapy regimes as well as immunotherapy, we recognise a lack of current understanding of the role of peritoneal cytology as a prognostic factor. Our study aims to determine the role of positive peritoneal cytology as a prognostic factor in gastric cancer. Methods This is an international multi-centre retrospective cohort study including high-volume, gastric cancer tertiary referral centres. Adult patients without macroscopic metastatic disease who underwent peritoneal cytology, and subsequently multi-modality treatment including surgical resection between 2011 and 2021 were included. The primary outcome measure is overall survival at 1, 3 and 5 years. Secondary outcome measures include recurrence-free survival at 1, 3 and 5 years; 30-day and 90-day major postoperative morbidity; and subset survival analyses were performed in patients who converted to Cy0 in restaging laparoscopy after neoadjuvant therapy. Statistical analysis was performed using R software. Results This is an interim analysis of the data of 280 patients with a mean age of 64.9 (0.72). 231 patients received pre-operative chemotherapy. 51.0% underwent open gastrectomy (41.2% laparoscopic and 4.64% robotic). 55% of patients underwent a total gastrectomy. 25.9% patients had positive cytology on laparoscopy, while 9.71% had indeterminate cytology. There was significant variation in the sites of peritoneal washings (Figure 1). So far, only 1 patient has shown conversion from positive to negative cytology after oncological therapy. At 1 year, the mortality rate was 41.5% (figure 2), while the recurrence rate was 41.4%. Conclusions In this interim report, we demonstrate significant heterogeneity in the way peritoneal cytology is performed, and the peri-operative management of this cohort. The POPEC study closes to patient recruitment at the end of August 2023, and thus at AUGIS we plan to report on the final findings of this study with an anticipated sample size of over 1000 patients.

Gastric Radiotherapy in the UK – Current Practice and Opinion on Future Directions

Gastric radiotherapy (RT) is more commonly practiced in the US compared to the UK, where postoperative chemoradiotherapy (CRT) is reserved for selected high-risk patients, and preoperative CRT is not standard of care pending the results of phase 3 trials, TOPGEAR and CRITICSII. CRT for inoperable, non-metastatic gastric cancer is also not recommended in the UK, despite being listed in NCCN guidelines. Recent systematic review of definitive gastric CRT (dCRT) conducted by the authors found median overall survival of 11-26.4 months, clinical complete response rates of 8-45% and acceptable rates of ≥G3 toxicity, supporting further research. Given these promising findings and perceived low uptake of gastric RT in the UK, we set out to establish current UK practice, opinion and RT technique to inform the development of a UK gastric RT protocol and future clinical trials. A 19 question survey was developed. Following local ethical approval and pilot by 4 clinical oncologists, the final survey was distributed electronically on 13/12/22 to UK Consultant Clinical Oncologists specializing in esophago-gastric (OG) cancer. Responses were anonymous. Survey was closed 6/2/23 and data analyzed using JISC/spreadsheet software. A total of 43 clinicians completed the survey. For gastric cancer, 28.6%, 7.1% and 9.5% would agree/strongly agree with use of postoperative (postopRT), preoperative (preopRT) or definitive RT (dRT) respectively, compared to 26.2%, 45.2% and 46.6% for type III gastro-esophageal junction tumors. 93% had prescribed palliative gastric RT in the last 3 years compared to 40.5% postopRT, 16.7% dRT and 9.5% preopRT. Main reasons for infrequent use were; rarely indicated within standard UK practice 88.4%, lack of UK gastric RT protocol 53.5%, toxicity concerns 44.2%. 45Gy/25# was most commonly used for preopRT (66%) and postopRT (86%), and 50Gy/25# for dRT (58%). 96% use IMRT/VMAT, 85% CT simulation with IV/oral contrast, 69% gastric filling protocol and 54% 4DCT. When ranked out of 10 (1 = low 10 = high), clinician confidence in accurately delineating gastric volumes mean rank was 4.33 for postopRT, with 9% rating ≥8/10, and 4.52 for dCRT/preopRT with 17% rating ≥8/10. However, 48.8% were experienced in outlining upper abdominal nodes and 62.8% duodenum. 93% would find a detailed outlining protocol useful, 81.4% wanted some form of peer review, 76.7% a nodal atlas, and 74.4% a workshop with an expert. 77.6% would be supportive of a future clinical trial of dCRT, with 23.4% needing more supporting evidence. No-one would not support a future trial in this setting. Gastric RT is not often practiced in the UK, due to lacking evidence and toxicity concerns. Given the growing evidence and supportive OG community, it is time to consider a trial of dCRT in the UK, which must include detailed RT protocols, atlases and educational materials to improve clinician confidence and ensure good RT quality assurance.

Prognostic significance of post-preoperative tumor markers increments in patients with non-metastatic gastric cancer.

Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are the most common tumor markers detected before and after gastric cancer (GC) surgery. However, the impact of post-preoperative CEA/CA19-9 increments on prognosis of GC remains unclear. In addition, there is no research incorporating post-preoperative CEA/CA19-9 increments into the prognostic model. Patients who underwent radical gastrectomy for GC at the First Affiliated Hospital of Anhui Medical University and Anhui Provincial Hospital from January 2013 to December 2017 were enrolled and divided into the discovery and validation cohort. Prognostic value of post-preoperative CEA/CA19-9 increments and preoperative CEA/CA199 levels were assessed by Kaplan-Meier log-rank analysis and compared by time-dependent receiver operating characteristic (t-ROC) curves. Multivariate Cox regression analysis was applied to establish the nomogram. The performance of the prognostic model was validated by the concordance index (C-index), calibration curve, and ROC curve analysis. A total of 562 GC patients were included in this study. Overall survival (OS) rates decreased with an increasing number of incremental tumor markers after surgery. The t-ROC curves implied that the prognostic ability of the number of incremental post-preoperative tumor markers was superior to that of the number of positive preoperative tumor markers. Cox regression analysis suggested that the number of incremental post-preoperative tumor markers was an independent prognostic factor. The nomogram incorporated with the post-preoperative CEA/CA19-9 increments showed reliable accuracy. Incremental post-preoperative CEA/CA19-9 were indicator of poor prognosis of GC. The prognostic value of post-preoperative CEA/CA19-9 increments exceed that of preoperative CEA/CA19-9 levels.

Impact of Signet-Ring Cell Histology in the Management of Patients with Non-Metastatic Gastric Cancer: Results from a Retrospective Multicenter Analysis Comparing FLOT Perioperative Chemotherapy vs. Surgery Followed by Adjuvant Chemotherapy.

FLOT perioperative chemotherapy represents the standard of care in non-metastatic gastric cancer patients. Signet-ring cell positivity is associated with a worse prognosis in patients with gastric cancer treated with chemotherapy. Comparison between FLOT perioperative chemotherapy vs. surgery followed by adjuvant chemotherapy based on signet-ring cell positivity is lacking. The aim of the analysis was to compare perioperative FLOT with adjuvant chemotherapy in gastric cancer patients stratified by signet-ring cell positivity. We conducted a retrospective multicenter analysis based on disease-free survival (DFS) and overall survival (OS) in patients with gastric cancer who received perioperative chemotherapy with a FLOT regimen and compared their survival with a historical cohort of patients treated with adjuvant chemotherapy, matched by cT and cN stage and by tumor histological features. Seventy-six patients were enrolled and 24 (32%) were signet-ring cell positive. At a median follow-up time of 39 months, the median DFS was 26.3 months and the median OS was 37.3 months. Signet-ring cell positivity was associated with a shorter OS (median OS: 20.4 vs. 46.9 months, HR: 3.30, 95%CI: 1.56-6.99, p = 0.0018) and DFS (mDFS: 15.2 vs. 38.6 months, HR: 3.18, 95%CI: 1.55-6.54, p = 0.0016). This was confirmed by multivariate analysis for DFS (Exp(B): 2.55) and OS (Exp(B): 2.68). After propensity score matching, statistically significant shorter DFS (HR: 3.30, 95%CI: 1.50-7.35, p = 0.003) and OS (HR: 5.25, 95%CI: 2.18-12-68, p = 0.0002) were observed for patients with signet-ring cell positivity who received perioperative treatment vs. those who received surgery followed by adjuvant chemotherapy. Signet-ring positivity was associated with shorter DFS and OS in patients who received perioperative treatment with FLOT compared with surgery followed by adjuvant therapy. These data suggest that for patients with signet-ring cell histology, FLOT perioperative treatment might not always be the best choice of treatment, and further research should be focused on this group of patients.

Expression of PI3K-AKT-mTOR signaling pathway in gastric cancer

Background: The PI3K/AKT/m TOR pathway is activated in gastric cancer (GC). This pathway may be an appropriate target for GC therapy. Such therapy may involve inhibiting cell proliferation, enhancing apoptosis, and restoring the sensitivity of cancer cells to chemotherapy. Aim: To study the expression of the PI3K/AKT/mTOR pathway in Egyptian patients with GC. Methods: Enrolled Patients were divided into 2 groups, group 1 included 23 patients with lymph node metastatic (LNM) gastric cancer (GC) and group 2 included 10 patients with non-metastatic GC. Liver and renal biochemical tests, CBC, H. pylori testing, CEA, CA19-9 & metastatic radiological work up were done. Upper Gastrointestinal endoscopy was done to diagnose the site, size and morphology of GC and to take biopsy from the suspicious lesion, adjacent mucosa and all parts of the stomach. Enrolled patients had received surgical resection when appropriate. The harvested tumor tissue was processed for histopathology as well as Immunohistochemical staining (IHC) for detection of expression of PI3K/AKT/mTOR. IHC score for the expression of mTOR, AKT & PI3K (ranging from 0 to 12) was calculated as follows: Grade of stain intensity × Grade of coloration rate. A score ≥4 was considered positive. Results: The mTOR expression was positive in 54.5%, AKT expression was positive in 72.7% & PI3K expression was positive in 36.4% of cases. There was significantly higher expression of AKT in metastatic (87%) than non-metastatic GC (40%), p=0.010. AKT expression was significantly higher in LNM GC (median score was 12) than non-metastatic GC (median score was 2.5), p=0.028. AKT score at cutoff value of more than 3 was a statistically significant discriminator between LNM and non-metastatic GC, AUC=0.743, p=.014, sensitivity, 87% & specificity, 60%. Conclusion: The mTOR expression was positive in 54.5%, AKT expression was positive in 72.7% & PI3K expression was positive in 36.4% of GC cases. AKT expression score may discriminate between LN metastatic and non-metastatic gastric cancer

Advanced lung cancer inflammation index predicts the outcomes of patients with non-metastatic gastric cancer after radical surgical resection.

Advanced lung cancer inflammation index predicts the outcomes of patients with non-metastatic gastric cancer after radical surgical resection.

Survival analysis comparing neoadjuvant chemoradiotherapy versus perioperative chemotherapy for locoregional gastric cancer.

e16097 Background: Surgical resection is established as the only potentially curative approach for patients with early stage and regional gastric cancer. With a high risk of recurrence that ranges between 40% to 60% for stage II and III disease, combination therapies including chemotherapy and radiation that complement surgery were incorporated as standard of care for Stage >IB disease with clear survival benefit over surgery alone. While the National Comprehensive Cancer Network (NCCN) guidelines recommend neoadjuvant chemoradiation (NCR) or perioperative chemotherapy (PC) for clinical Stage T2 or higher, there has been no consensus on the optimal treatment approach for these patients. Our study sought to compare survival differences between the two therapies. Additionally, we analyzed predictive factors and shifting trends in the choice of treatment over the period of our study i.e., 2010 to 2017. Methods: The National Cancer Database was used to analyze patients with non-metastatic regional gastric cancer diagnosed from 2010 to 2017 staged as clinical T2 or higher. Demographic data and clinicopathological tumor characteristics were assessed using chi-square analysis to assess baseline differences between both groups. The primary outcome was to determine differences in overall survival (OS) using Kaplan Meier (KM) and Cox proportional hazards analysis. The secondary outcome was to evaluate patient related factors associated with the choice of treatment. Results: N = 7475 patients with non-metastatic clinical T2+ gastric cancer were included in the study (NCR: n = 5394, 72.16% vs. PC: n = 2081, 27.84%). The majority of patients were of male sex (75.9%) and within the 50-69 age group (64.5%) for both groups. T3 clinical staging was the most prevalent among both groups (78.0% and 70.3% respectively). Patients receiving PC had longer median OS (49.480 months) than those undergoing NCR (40.970 months). KM curve showed a higher cumulative survival with PC over NCR at 1-year, 3-year, and 5-year endpoints (0.93 vs. 0.85, 0.58 vs. 0.54, and 0.46 vs. 0.40, p<0.0001). Moreover, on multivariate cox regression analysis, OS was inferior in the NCR group (HR 1.57, p<0.001) compared to PC after adjusting for significant covariates. In a subgroup analysis for clinical T3 and T4 tumors, NCR remained associated with worse OS (HR 1.83, p <0.0001) compared to PC. Lastly, patients in the 70-79 and 80-100 age group preferred NCR over the PC approach (OR 0.737 and OR 0.50, p 0.035 and p 0.008, respectively) when compared to the younger population. Cochran-Armitage Trend Test revealed NCR (p <0.0001) and PC (p <0.0001) had an increased trend by year. Conclusions: In our study, PC showed clear survival benefits over NCR in patients with locoregional gastric cancer. Future large-scale clinical trials would aid in adding to our findings and setting guidelines for optimal management of these patients.

Understanding Factors Leading to Surgical Attrition for "Resectable" Gastric Cancer.

We used a novel combined analysis to evaluate various factors associated with failure to surgical resection in non-metastatic gastric cancer. We identified factors associated with the receipt of surgery in publicly available clinical trial data for gastric cancer and in the National Cancer Database (NCDB) for patients with stages I-III gastric adenocarcinoma. Next, we evaluated variable importance in predicting the receipt of surgery in the NCDB. In published clinical trial data, 10% of patients in surgery-first arms did not undergo surgery, mostly due to disease progression and 15% of patients in neoadjuvant therapy arms failed to reach surgery. Effects related to neoadjuvant administration explained the increased attrition (5%). In the NCDB, 61.7% of patients underwent definitive surgery. In a subset of NCDB patients resembling those enrolled in clinical trials (younger, healthier, and privately insured patients treated at high-volume and academic centers) the rate of surgery was 79.2%. Decreased likelihood of surgery was associated with advanced age (OR 0.97, p < 0.01), Charlson-Deyo score of 2+ (OR 0.90, p < 0.01), T4 tumors (OR 0.39, p < 0.01), N+ disease (OR 0.84, p < 0.01), low socioeconomic status (OR 0.86, p = 0.01), uninsured or on Medicaid (OR 0.58 and 0.69, respectively, p < 0.01), low facility volume (OR 0.64, p < 0.01), and non-academic cancer programs (OR 0.79, p < 0.01). Review of clinical trials shows attrition due to unavoidable tumor and treatment factors (~ 15%). The NCDB indicates non-medical patient and provider characteristics (i.e., age, insurance status, facility volume) associated with attrition. This combined analysis highlights specific opportunities for improving potentially curative surgery rates.

Does non-metastatic gastric cancer of the cardia warrant a different treatment strategy?

Multimodal treatment strategies with surgery as its centerpiece have been accepted as the standard of care in nonmetastatic cardia gastric cancer (CGC). There remains a lack of consensus regarding the optimal multimodal treatment strategy. We queried National Cancer Database from 2004 to 2016 to identify patients with resected nonmetastatic CGC who received perioperative chemotherapy (PEC), postoperative chemoradiation therapy (POCR), or postoperative chemotherapy (POC). A subgroup analysis was performed in optimally treated patients defined as initial chemotherapy within 45 days of diagnosis, resection within 45 days of diagnosis, negative margins, adjuvant chemotherapy within 90 days of resection, and standard radiation dose (45 Gy). Kaplan-Meier, Univariate analysis (UVA), and Multivariable analysis (MVA) were performed. We identified 2387 patients. Median survival was 38.8 months in the PEC group, 36 months in the POCR group, and 32.3 months in the POC group (p = 0.1025). On UVA, patients treated with PEC had an association with improved survival (HR, 0.83; p = 0.037) when compared with POC. On MVA, no significant difference was noted in overall survival (OS) between PEC, POCR, and POC, similar to subgroup analysis of optimally treated cohort. OS rate in nonmetastatic CGC is not significantly different between patients receiving PEC, POCR, or POC.

Current trends in perioperative treatment of resectable gastric cancer.

In the last few decades, the treatment strategy for locally advanced resectable gastric cancer (GC) has shifted to a multimodal approach, which potentially decreases recurrence risk and improves survival rates. Perioperative therapy leads to downstaging, increased curative resection rates, and prolonged disease-free and overall survival, by preventing micrometastases in patients with resectable GC. Application of neoadjuvant therapy provides information about tumor biology and in vivo sensitivity. A consensus regarding the therapeutic approach for non-metastatic GC does not exist, and many clinical trials aim to clarify this aspect. Advances in precision medicine and the role of immunotherapy have been the focus of research in GC treatment. Herein, the current status and possible future developments of perioperative therapy for locally advanced resectable GC are reviewed, based on the most recent randomized clinical trials.

Trends in best-case, typical and worst-case survival scenarios of patients with non-metastatic esophagogastric cancer between 2006 and 2020: A population-based study.

New treatment options and centralization of surgery have improved survival for patients with non-metastatic esophageal or gastric cancer. It is unknown, however, which patients benefitted the most from treatment advances. The aim of this study was to identify best-case, typical and worst-case scenarios in terms of survival time, and to assess if survival associated with these scenarios changed over time. Patients with non-metastatic potentially resectable esophageal or gastric cancer diagnosed between 2006 and 2020 were selected from the Netherlands Cancer Registry. Best-case (20th percentile), upper-typical (40th percentile), typical (median), lower-typical (60th percentile) and worst-case (80th percentile) survival scenarios were defined, and regression analysis was used to investigate the change in survival time for each scenario across years. For patients with esophageal cancer (N=24 352) survival time improved on average 12.0 (until 2011), 1.5 (until 2018), 0.7, 0.4 and 0.2months per year for the best-case, upper-typical, median, lower-typical and worst-case scenario, respectively. For patients with gastric cancer (N=9993) survival time of the best-case scenario remained constant, whereas the upper-typical, median, lower-typical and worst-case scenario improved on average with 1.0 (until 2018), 0.5, 0.2 and 0.2months per year, respectively. Subgroup analyses showed that, survival scenarios improved for nearly all patients across treatment groups and for patients with squamous cell carcinomas or adenocarcinomas. Survival improved for almost all patients suggesting that in clinical practice the vast majority of patients benefitted from treatment advances. The clinically most meaningful survival advantage was observed for the best-case scenario of esophageal cancer.

Conditional relative survival in nonmetastatic esophagogastric cancer between 2006 and 2020: A population-based study.

Conditional relative survival (CRS) is useful for communicating prognosis to patients as it provides an estimate of the life expectancy after having survived a certain time after treatment. Our study estimates the 3-year relative survival conditional on having survived a certain period for patients with esophageal or gastric cancer. Patients with nonmetastatic esophageal or gastric cancer diagnosed between 2006 and 2020 treated with curative intent (resection with or without [neo]adjuvant therapy, or chemoradiotherapy) were selected from the Netherlands Cancer Registry. CRS was calculated since resection or last day of chemoradiotherapy. The probability of surviving an additional 3 years (ie, 3-year CRS), if the patients survived 1, 3 and 5 years after diagnosis was 62%, 79%, 87% and 69%, 84%, 90% for esophageal and gastric cancer, respectively. The 3-year CRS after having survived 3 years for patients with esophageal cancer who underwent a resection (n=12 204) was 91%, 88%, 77% and 60% for pathological Stage 0, I, II and III, and for patients with esophageal cancer who received chemoradiotherapy (n=4158) was 51% and 66% for clinical Stage II and III, respectively. The 3-year CRS after having survived 3 years for patients with gastric cancer who underwent a resection (n=6531) was 99%, 90%, 73% and 59% for pathological Stage 0, I, II and III, respectively. Despite poor prognosis of patients with esophageal or gastric cancer, life expectancy increases substantially after patients have survived several years after treatment. Our study provides valuable information for communication of prognosis to patients during follow-up after treatment.

Development of a Signature Based on Eight Metastatic-Related Genes for Prognosis of GC Patients.

Gastric cancer (GC) has been a common tumor type with high mortality. Distal metastasis is one of the main causes of death in GC patients, which is also related to poor prognosis. The mRNA profiles and clinical information of GC patients were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. Univariate Cox and LASSO Cox analyses were used to screen the optimal metastasis-related genes (MRGs) to establish a prognostic Risk Score model for GC patients. The nomogram was used to visualize the Risk Score and predict the 1-, 3-, 5-year survival rate. The immune cell infiltration was analyzed by CIBERSORT and the ratio of immune-stromal component was calculated by the ESTIMATE algorithm. A total of 142 differentially expressed genes were identified between metastatic and non-metastatic GC samples. The optimal 8 genes, comprising GAMT (guanidinoacetate N-methyltransferase), ABCB5 (ATP-binding cassette subfamily B member 5), ITIH3 (inter-alpha-trypsin inhibitor heavy chain 3), GDF3 (growth differentiation factor 3), VSTM2L (V-set and transmembrane domain-containing 2 like), CIDEA (cell death inducing DFFA like effector a), NPTX1 (neuronal pentraxin-1), and UMOD (uromodulin), were further screened to establish a prognostic Risk Score, which proved to be an independent prognostic factor. Patients in high-risk group had a poor prognosis. There were significant differences in the proportion of 11 tumor-infiltrating immune cells between high-risk and low-risk subgroups. In addition, the StromalScore, ImmuneScore, and ESTIMATEScore in high-risk group were higher than those in low-risk group, indicating that the tumor microenvironment of the high-risk group was more complex. A Risk Score model based on eight metastasis-related genes could clearly distinguish the prognosis of GC patients. The poor prognosis of patients with high-Risk Score might be associated with the complex tumor microenvironments.

Advanced lung cancer inflammation index predicts the outcomes of patients with non-metastatic gastric cancer after radical surgical resection.

The prognostic value of the advanced lung cancer inflammation index (ALI) has been demonstrated in various tumors. However, the prognostic significance of ALI in non-metastatic gastric cancer (GC) remains unclear. This study aimed to identify the prognostic values of ALI in patients with non-metastatic GC who underwent radical surgical resection. Patients who underwent radical surgery for non-metastatic GC from January 2008 to September 2020 were enrolled in this study. The preoperative ALI was calculated as follows: body mass index × serum albumin/neutrophil to lymphocyte ratio. The primary outcomes were overall survival (OS) and cancer-specific survival (CSS). Cox regression analyses were performed to assess the association between ALI and survival. The potential of ALI was supported by sensitivity testing based on the propensity score matching (PSM) analysis. Low preoperative ALI was significantly correlated with male gender (P=0.037), older age (P=0.004), T3/4 stage (P=0.001), lymph node metastasis (P=0.030), Tumor Node Metastasis (TNM) stage classification progression (P=0.004), and vessel invasion (P=0.001). Patients with low ALI showed worse OS (P<0.001) and CSS (P=0.001) compared to those with high ALI. Multivariable analysis showed that ALI was an independent prognostic factor for both OS [hazard ratio (HR) =1.55; 95% confidence interval (CI), 1.11-2.16]; P=0.010] and CSS (HR =1.46; 95% CI, 1.01-2.10; P=0.043) in non-metastatic GC patients who underwent radical surgical resection. Further PSM analysis confirmed the prognostic value of ALI in the PSM cohort. The preoperative ALI is associated with survival outcomes in patients who have undergone radical surgical resection for non-metastatic GC. Low ALI appears to predict a worse prognosis.

Identification and validation of crucial lnc-TRIM28-14 and hub genes promoting gastric cancer peritoneal metastasis

BackgroundGastric cancer peritoneal metastasis (GCPM) is an important cause of cancer-related deaths worldwide. Long non-coding RNAs (lncRNAs) play a key role in the regulation of GCPM, but the underlying mechanisms have not been elucidated.MethodsHigh-throughput RNA sequencing (RNA-seq) was performed on four groups of clinical specimens (non-metastatic gastric cancer primary tumor, adjacent normal gastric mucosal tissue, gastric cancer primary tumor with peritoneal metastasis and adjacent normal gastric mucosal tissue). After sequencing, many lncRNAs and mRNAs were screened for further Weighted Gene Co-expression Network Analysis (WGCNA). GCPM-related hub lncRNAs and genes were identified by cytoHubba and validated by Quantitative real-time PCR (qRT-PCR), Receiver operating characteristic curve (ROC) analysis and Kaplan-Meier survival analysis. GO, KEGG and GSEA showed GCPM-related pathways. Correlation analysis revealed the potential relationship between hub lncRNAs and genes.ResultsBy analyzing lncRNA expression data by WGCNA, we found that blue module was highly correlated with GCPM (r = 0.44, p = 0.04) and six lncRNAs involved in this module (DNM3OS, lnc-MFAP2-53, lnc-PPIAL4C-4, lnc-RFNG-1, lnc-TRIM28-14 and lnc-YARS2-4) were identified. We then performed qRT-PCR validation of gastric cancer specimens and found that the expression of lnc-RFNG-1 and lnc-TRIM28-14 was significantly increased in gastric cancer tissues with peritoneal metastasis. Kaplan-Meier survival analysis showed shorter overall survival time (OS) for gastric cancer patients with high expression of lnc-TRIM28-14. Receiver operating characteristic curve (ROC) analysis showed that lnc-TRIM28-14 could improve the sensitivity and specificity of GCPM diagnosis. In addition, we identified three key mRNAs (CD93, COL3A1 and COL4A1) associated with gastric cancer peritoneal metastasis through WGCNA analysis and clinical specimen validation. Moreover, there was a positive correlation between lnc-TRIM28-14 and the expression of CD93 and COL4A1 in gastric cancer peritoneal metastasis, suggesting a regulatory relationship between them. Subsequent GO, KEGG and GSEA analysis suggested that ECM-receptor interaction and focal adhesion were the hub pathways of GCPM.ConclusionIn summary, lnc-RFNG-1, lnc-TRIM28-14, CD93, COL3A1 and COL4A1 could be novel tumor biomarkers and potential therapeutic targets for GCPM.

Treatment Outcome in Non-Metastatic Gastric Cancer “A Retrospective Study “

Treatment Outcome in Non-Metastatic Gastric Cancer “A Retrospective Study “

High Frequency of Microsatellite Instability among Non-Metastatic Gastric Cancer.

Background: Microsatellite instability (MSI) is considered a key factor in carcinogenesis and a genetic alteration pattern in many types of cancers such as gastric cancer (GC). Although the role of MSI in colorectal cancer (CRC) is well known, its prognostic impact on GC has not been clearly defined. The assessment of MSI in GC has notbeen documented in the Iranian population yet. Therefore, this study analyzed the association of MSI status with GC in Iranian patients. Materials and Methods: We compared the frequency of MSI at 5 loci from formalin-fixed paraffin-embedded (FFPE) gastrectomy specimens, between metastatic and non-metastatic cases of GC (N = 60). A panel of five quasi-monomorphic markers and a single dinucleotide marker with linker-based fluorescent primers was used. Results: MSI was observed in 46.6% of cases, including MSI-high (H) (33.3%) and MSI-Low (L) (13.3%). Moreover, the most unstable and stable markers in our study were NR-21 and BAT-26 accordingly. MSI-H and MSI were seen more frequently in non-metastatic tumors (p= 0.028 and p= 0.019, respectively). Conclusion: The current study showed MSI status more frequently in non-metastatic GC which may reflect a good prognostic factor in GC like CRC. Although, larger and more comprehensive studies are needed to confirm this statement. A panel consisting of NR-21, BAT-25, and NR-27 mononucleotide markers appears to be reliable and useful markers for detecting MSI in GC in Iranian patients.