Chemotherapy For Gastric Cancer Research Articles

ASO Visual Abstract: Downstaging Effect Rather Than the Full Intended Cycles of the Perioperative Chemotherapy Determines the Value of Adjuvant Chemotherapy in Gastric Cancer.

ASO Visual Abstract: Downstaging Effect Rather Than the Full Intended Cycles of the Perioperative Chemotherapy Determines the Value of Adjuvant Chemotherapy in Gastric Cancer.

Tolerability of perioperative chemotherapy for gastric cancer in real clinical practice

Background. The choice of the optimal scheme of perioperative chemotherapy of locally advanced gastric cancer is an urgent problem in real clinical practice. Aim. To analyze therapy tolerability in this cohort of patients. Materials and methods. Perioperative chemotherapy of gastric cancer was performed in 90 patients in the Chemotherapy Department of the Oncology Center №1 of the Yudin City Clinical Hospital from January 2021 to February 2024. Results. The incidence of severe complications at the preoperative stage was 41.9% for the FOLFOX regimen and 40.7% for the FLOT regimen, at the adjuvant stage – 17.4 and 43.2%, respectively. Operative treatment was successfully performed in 79 (87.8%) patients, and the full scope of combined treatment of locally advanced gastric cancer was completed in 59 (65%) patients. 80.8% of pathomorphologic responses in the FOLFOX group and 67.9% in the FLOT group were TRG3-4, with complete response noted in only one patient. Conclusion. High toxicity rates in elderly and comorbid patients on the FOLFOX regimen require the development of an individualized approach to the treatment of this group of patients.

Trastuzumab plus chemotherapy versus chemotherapy alone in HER2-positive gastric cancer treatment in Iran: a cost-effectiveness analysis

BackgroundCombining Trastuzumab with chemotherapy for HER2-positive gastric cancer shows treatment promise but may raise costs. We aimed to evaluate the cost-effectiveness of combining Trastuzumab with chemotherapy for HER2-positive gastric cancer treatment in Iran.MethodsWe employed a partitioned survival model (PSM) to evaluate the cost-effectiveness of trastuzumab plus chemotherapy versus chemotherapy alone. The PSM framework included three distinct health states: progression-free, post-progression, and death. Clinical data, including overall survival and progression-free survival rates, were derived from the ToGA trial, a randomized controlled study. A bottom-up approach was used to calculate costs by considering drug costs, adverse event management costs and other disease management costs separately for the progression-free and post-progression states. The analysis was conducted from the Iranian healthcare system’s perspective, considering direct medical costs. We performed a cost-effectiveness analysis to determine the optimal strategy by comparing the incremental cost-effectiveness ratio (ICER) to Iran’s cost-effectiveness threshold, set at one to three times the GDP per capita. Additionally, we conducted sensitivity analyses to assess the robustness of our findings.ResultsBoth FOLFOX-based regimens were strongly dominated. In comparison, the CAPOX regimen cost $2,811.11 for 0.75 QALYs. Adding Trastuzumab to CAPOX increased the cost to $6,128 and improved effectiveness to 0.92 QALYs, resulting in an ICER of $19,089.94 per QALY, which is between 2 and 3 times the GDP per capita in 2022.ConclusionThe addition of trastuzumab to chemotherapy regimens improved clinical outcomes in HER2-positive gastric cancer patients. From an economic perspective, the CAPOX regimen is the most cost-effective option when considering a cost-effectiveness threshold of up to two times Iran’s GDP per capita. However, when the threshold increases to three times the GDP per capita, the CAPOX + Trastuzumab regimen becomes the preferred choice. These findings provide valuable insights for healthcare policymakers in Iran.

Predictors of tolerability for postoperative adjuvant S1 plus docetaxel chemotherapy for gastric cancer: a multicenter retrospective study.

Adjuvant docetaxel plus S1 (DS) chemotherapy after gastrectomy with D2 lymph node dissection is the standard treatment for stage III gastric cancer in Japan; however, some patients are unable to receive adequate drug administration because of the deterioration of their conditions. This study aimed to investigate the correlation between tolerability for postoperative adjuvant DS chemotherapy and prognosis, and the factors affecting tolerability. This retrospective study involved patients with stage III gastric cancer who underwent curative resection between 2018 and 2021 from a multicenter database. Patients with a cumulative dose of docetaxel and S1 greater than 120 and 8400mg/m2, respectively, were considered tolerable. The prognostic impact and factors predicting tolerability were analyzed. Of the 103 patients, the tolerable group comprised of 63 (61%) patients and had a significantly better 3-year recurrence-free survival than the intolerable group (83% vs. 64%, P = 0.02). Among the preoperative factors, only performance status (PS, P = 0.04) was significantly correlated with tolerability in the univariate analysis. Among the postoperative factors, PS (P = 0.001) and perioperative weight loss rate (P = 0.02) were significantly correlated with tolerability in the univariate analysis. The multivariate analysis showed significant differences in the PS (odds ratio [OR]: 4.94, 95% confidence interval [CI] 1.79-14.98, P = 0.002) and weight loss rate (OR: 1.10, 95% CI 1.01-1.21, P = 0.03). Tolerance to postoperative adjuvant DS chemotherapy has a significant prognostic impact. Postoperative PS and perioperative weight loss rates were independent predictors of tolerability.

Advantages of adjuvant chemotherapy using S-1 following minimally invasive gastrectomy for gastric cancer versus open surgery: a propensity score-matched analysis.

It is essential to ensure optimal adherence to adjuvant chemotherapy regimens following gastric cancer surgery. However, treatment intensity for S-1 as adjuvant chemotherapy has not as yet been compared between minimally invasive (MI) and open (Open) surgery. We retrospectively compared dose modification of adjuvant S-1 between MI and Open surgery in patients undergoing R0 gastrectomy for gastric or esophago-gastric junction cancer at the Cancer Institute Hospital Tokyo, Japan, during the period from 2012 to 2022, and receiving S-1 for pStage II or S-1 plus docetaxel for pStage III as adjuvant chemotherapy. Propensity score matching (PSM) was conducted to adjust for possible confounders. In total, 323 patients were initially included. After PSM, 158 patients remained, 79 in each group. The adjuvant chemotherapy completion rates were similar in the two groups. However, the proportion of patients who required S-1 dose reduction was significantly lower in the MI than in the Open group (43.0% vs. 65.8%, p = 0.004). In addition, the MI group had significantly fewer patients requiring suspension of S-1 than the Open group (46.8% vs. 64.6%, p = 0.025). Moreover, the frequency of adverse events of grade ≥ 3 was significantly lower in the MI than in the Open group (17.7% vs. 31.7%, p = 0.042). In adjuvant chemotherapy for gastric cancer, minimally invasive surgery may offer better treatment intensity for oral S-1 administration than open surgery.

Circ_0006089 facilitates gastric cancer progression and oxaliplatin resistance via miR-217/NRP1

BackgroundOxaliplatin (OXA) is a vital tool in the chemotherapy of gastric cancer (GC) patients. Circular RNAs (circRNAs) are a group of non-coding RNAs that have been associated with tumorigenesis. Nevertheless, the function of circRNAs in OXA resistance of GC is unknown. MethodsCirc_0006089/miR-217/NRP1 were elucidated through qRT-PCR in GC OXA-tolerant tissues and cell lines. OXA half-inhibitory concentration (IC50) was quantified by MTT assay. RNA pull-down and luciferase reporter tests were applied to characterize the interaction between circ_0006089 and miR-217, miR-217 and NRP1 in GC cells. ResultsThe findings disclosed that circ_0006089 and NRP1 was heightened whereas miR-217 was dramatically declined in OXA-tolerant GC tissues and cell lines. OXA resistance was reduced and the proliferation, migration and invasion ability of OXA cells were diminished after silencing circ_0006089. In addition, circ_0006089 raised OXA resistance by sponging miR-217. Further studies revealed that miR-217 bound to NRP1 and weakened OXA resistance. In addition, it was found that circ_0006089 accelerated GC progression and OXA resistance by upregulating NRP1 expression via sponging miR-217. ConclusionCirc_0006089 regulated OXA resistance in GC cells through miR-217/NRP1 axis, implying it was a promising biomarker for GC therapy.

Understanding the patient-spouse communication experience during chemotherapy for gastric cancer: A qualitative study

Purpose This study examines how patients with gastric cancer and their spouses communicate about the illness, assessing the impact of positive or negative communication on their psychological adaptation and the intimacy of their relationship as a couple. Method Employing The Relationship Intimacy Model of Couple Adaptation to Cancer, this study used purposive sampling with the principle of maximum variation to select participants. Sixteen pairs of patients with gastric cancer and their spouse caregivers, hospitalized in the oncology department of a tertiary hospital in Jingjiang City, Jiangsu Province, from March to July 2023, were chosen for semi-structured face-to-face interviews. The recorded data were transcribed within 24 h following each interview and supplemented with field notes. Directed content analysis was employed for the qualitative content analysis. Results The interview data revealed three themes and six subthemes. Theme 1: The impact of negative patient-spouse communication, with the subthemes being (i) a decline in couples’ relationship intimacy and (ii) reduced psychological adaptation. Theme 2: The impact of positive patient-spouse communication, with the subthemes being (i) enhanced couples’ relationship intimacy and (ii) increased psychological adaptation. Theme 3: The impact of protective concealment, with the subthemes being (i) declined couples’ relationship intimacy and psychological adaptation, and (ii) increased couples’ relationship intimacy and psychological adaptation. Throughout the chemotherapy period, patients with gastric cancer and their spouses experienced both positive and negative forms of patient-spouse communication. This underscores the significance of acknowledging protective concealment within couples. Moreover, the study highlights how the dynamics of couples’ relationship intimacy and psychological adaptation are influenced by both positive and negative communication patterns surrounding the illness. Conclusions For patients with gastric cancer and their spouses, it is crucial for nurses to emphasize the importance of spousal disease communication during chemotherapy. Efforts should be made to mitigate one-sided, conflictual communication and avoidance behaviors, and to adopt appropriate communication strategies in terms of content and timing to deeply promote couple communication. Additionally, there is a need to focus on the physical and psychological stress of protective concealment in couples.

LOXL1 promotes gastric cancer progression by β-catenin-cyclinD mediated proliferation.

Although much progress has been made in chemotherapy or target therapy for advanced gastric cancer, the prognosis is still poor. It is necessary to screen biomarkers for early diagnosis and prognosis prediction. However, the prognostic value of LOX family in gastric cancer and the underlying molecular mechanisms for promoting the progression of gastric cancer remains unclear. Among five members of LOX family, LOXL1 was the unique independent prognostic risk factor. The nomogram established based on the expression of LOXL1 and other clinical parameters could predict the overall survival rate of gastric cancer. Knockdown (KD) of LOXL1 decreased cell proliferation and led to G1 phase arrest in gastric cells. According to GSEA analysis that LOXL1 was positively correlated with the WNT signaling pathway, in vitro experiment proved that LOXL1-KD reduced the phosphorylation level of β-catenin and the expression of the downstream G1 phase checkpoint CCND1.In Conclusion, LOXL1 has been identified as a potential risk prognostic biomarker for gastric cancer by promoting gastric cancer proliferation via WNT/β-catenin/cyclinD1 pathway.

Impact of Pre-operative Lymphocyte and Albumin Combination on Adjuvant Chemotherapy and Prognosis of Gastric Cancer.

Cancer-associated systemic inflammatory response is a pivotal indicator of tumor progression and prognosis in various cancers. "Lymphocyte × albumin (LA)" is a prognostic inflammatory marker in rectal cancer. This study examined the correlation between LA, complete adjuvant chemotherapy (ACT), and prognosis in patients with gastric cancer (GC) who underwent radical gastrectomy. We retrospectively evaluated 108 patients with stage II/III GC who underwent radical gastrectomy at our institute between January 2015 and December 2021. Survival was assessed using Kaplan-Meier and Cox regression analyses. Factors associated with complete ACT were identified using logistic regression analysis. Of the 108 patients with GC, 60 (55.6%) and 41 (38.0%) initiated and completed ACT, respectively. In multivariate analysis, the pre-operative LA was an independent factor for complete ACT [hazard ratio (HR)=0.35, 95% confidence interval (CI)=0.121-0.995; p=0.049]. In addition, age, pre-operative creatinine clearance, neutrophil-to-lymphocyte ratio, modified Glasgow prognostic score, and poor overall survival were significantly associated with low LA (<7,474). LA was an independent prognostic factor for overall survival in univariate analysis (HR=2.29, 95%CI=1.020-5.145; p=0.045) but not in multivariate analysis (HR=2.00, 95%CI=0.882-4.552; p=0.097). Pre-operative LA is a useful marker for predicting complete ACT and prognosis of patients with GC following radical gastrectomy.

Downstaging Effect Rather than the Full Intended Cycles of Perioperative Chemotherapy Determines the Value of Adjuvant Chemotherapy in Gastric Cancer.

Perioperative chemotherapy is the standard treatment modality for locally advanced gastric cancer. However, the efficacy and indication of adjuvant chemotherapy in patients who have already received neoadjuvant chemotherapy remain unclear. This study aims to explore the association between adjuvant chemotherapy with patient prognosis in those who have received neoadjuvant chemotherapy plus D2 gastrectomy in a real-world setting, and whether this association is affected by the duration of neoadjuvant treatment. A total of 174 patients with cT3-4N+ gastric cancer who had received neoadjuvant chemotherapy plus D2 radical gastrectomy were included in the study. Kaplan-Meier curves and log-rank tests were used to assess and compare the survival outcomes between patients who received adjuvant therapy and those who did not. Patients who were younger age, had a lower American Society of Anesthesiologists (ASA) grade, did not experience postoperative complication, and received fewer than six cycles of neoadjuvant chemotherapy were more likely to receive adjuvant chemotherapy, rather than those with advanced ypTNM stage or poor tumor regression grade. Patients who received adjuvant therapy had a better overall survival (OS) (2-year OS rate 86.2% versus 64.1%, p=0.002). Adjuvant therapy was associated with longer survival in patients who remained ypTNM stage III despite receiving at least six cycles of neoadjuvant chemotherapy. However, there was no significant longer survival observed in patients with ypTNM stages 0-II receiving adjuvant chemotherapy, even when they received less than six cycles of neoadjuvant chemotherapy. Patients with locally advanced gastric cancer may still need adjuvant chemotherapy, even after receiving neoadjuvant chemotherapy. The value of adjuvant chemotherapy after neoadjuvant chemotherapy depends more on the actual downstaging effect achieved after neoadjuvant chemotherapy, rather than the completion of "full intended" cycles of perioperative treatment.

Exploring the Efficacy of Hyperthermic Intraperitoneal Perfusion Chemotherapy in Gastric Cancer: Meta-analysis Based on Randomized Controlled Trials.

Based on randomized clinical trials, this meta-analysis evaluated the efficacy and safety of intent-to-cure or prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of gastric cancer. PubMed, Cochrane Library, Medline, and Embase databases were all systemically searched from 2004 to 2023. The quality of the study was assessed by using the Cochrane risk of bias method. The certainty of the evidence was determined by using the GRADE evaluation. In this study, 12 articles with a total of 1181 patients were analyzed based on the inclusion criteria. The findings revealed that HIPEC had a higher survival rate (risk ratio [RR] 0.60; 95% confidence interval [CI] [0.43, 0.86], P = 0.005, RR 0.82; 95% CI [0.70, 0.97], P = 0.02, RR 0.83; 95% CI [0.71, 0.96], P < 0.01, and RR 0.63 [0.54, 0.73], P < 0.00001) after 1, 2, 3, and 5 years compared with the control group. The RR was statistically significant for 1, 2, 3, and 5 years. Furthermore, the observed overall recurrence rate for the HIPEC group was lower than control group and statistically significant (RR 0.59; 95% CI [0.50, 0.68], P < 0.0001). Higher disease-free survival rate (RR 1.42; 95% CI [1.07, 1.89], P < 0.01) was observed in the HIPEC group and statistically significant. Gastric cancer patients treated with HIPEC have shown promising outcomes with regard to survival, recurrence, disease-free survival, and adverse reactions. However, multicenter trials with larger sample sizes consisting of different ethnicities is suggested.

7799 Nesidioblastosis Concurrent with Anatomically Confirmed Metastatic Gastric Cancer

Abstract Disclosure: Y. Cho: None. K. Jo: None. J. Han: None. S. Moon: None. E. Kim: None. Background: Nesidioblastosis is a rare condition that should be considered in cases of pancreatogenic hyperinsulinemic hypoglycemia without evidence of insulinoma on imaging. We present the first case of nesidioblastosis concomitant with anatomically confirmed metastatic gastric cancer of the pancreas. Case Report A 57-year-old male presented with recurrent episodes of loss of consciousness and hypoglycemia, with a glucose level of 26 mg/dl upon arrival at the emergency room. Despite a history of advanced gastric cancer and previous chemotherapy, the patient had not been diagnosed with diabetes and was not taking medications associated with hypoglycemia. Four months prior, he underwent total gastrectomy. The fasting plasma glucose levels was 38 mg/dl, accompanied by C-peptide levels of 6.10 ng/mL, insulin levels exceeding 1000 uIU/ml, and proinsulin levels at 8.8 pmol/L. The insulin antibody level was more than 100%, and the highest cortisol level reached 15.60 ug/dL during the rapid ACTH stimulation test. The patient's postprandial 2-hour glucose level reached 233 mg/dl during the 75g glucose tolerance test. Imaging studies, including whole-body PET CT and abdominal CT, showed no evidence of suspected metastatic lesions, and the pancreas appeared normal on MRI. Endoscopic ultrasound could not be performed due to anatomical changes following the surgery. A selective arterial calcium stimulation test demonstrated a substantial over twofold increase in insulin concentrations in the gastroduodenal artery, splenic artery, and superior mesenteric artery. The patient received methylprednisolone 125 mg once daily but insulin levels remained elevated, exceeding 1000 uIU/ml, requiring continuous dextrose infusion. Octreotide therapy was initiated, resulting in an improvement in insulin levels to 589 uIU/ml, although discontinuation of dextrose fluid remained unfeasible. After consultation with the surgeon, a open subtotal pancreatectomy was performed, allowing discontinuation of dextrose on the second post-surgery day, with improved glucose and insulin levels. Histological examination showed three clusters of atypical cells with perineural infiltration. Immunostaining indicated negative synaptophysin and positive CK20, suggesting possible gastric cancer metastasis, consistent with prior gastrectomy findings. Moreover, an increased number of variable-sized Langerhans islets exhibited positive insulin and glucagon immunostaining within the islets, indicative of nesidioblastosis. Conclusion: Nesidioblastosis should be considered in cases of unexplained post-surgery hypoglycemia following metastatic gastric cancer treatment. Furthermore, given the potential link with metastatic gastric cancer, which may elude detection via imaging alone, aggressive surgical intervention should be contemplated as a nesidioblastosis treatment strategy. Presentation: 6/3/2024

SY24-KL1 Perioperative chemotherapy for gastric and gastroesophageal junction cancer, European perspective

SY24-KL1 Perioperative chemotherapy for gastric and gastroesophageal junction cancer, European perspective

P11-3 Efficay and safety of chemotherapy plus nivolumab for advanced gastric cancer with ascites

P11-3 Efficay and safety of chemotherapy plus nivolumab for advanced gastric cancer with ascites

The Tumour Immune Microenvironment Drives Survival Outcomes and Therapeutic Response in an Integrated Molecular Analysis of Gastric Adenocarcinoma.

We performed an integrated analysis of molecular classification systems proposed by The Cancer Genome Atlas (TCGA), the Asian Cancer Research Group (ACRG) and the Tumour Microenvironment Score (TME) to identify which classification scheme(s) are most promising to pursue in subsequent translational investigations. Supervised machine learning classifiers were created using 10-fold nested cross-validation for TCGA, ACRG and TME subtypes and applied to 2,202 gastric cancer patients from 11 separate publicly available datasets. Overall survival was assessed with a multivariable Cox proportional hazards model. A propensity score matched analysis was performed to evaluate the subgroup effect of adjuvant chemotherapy on molecular subtypes. A public external cohort comprised of metastatic gastric cancer treated with immunotherapy was used to externally validate the molecular subtypes. Classification models for TCGA, ACRG and TME achieved an accuracy ± standard deviation of 89.5% ± 0.04, 84.7% ± 0.04 and 89.3% ± 0.02, respectively. We identified the TME score as the only significantly prognostic classification system (HR 0.54 [95% CI 0.39, 0.74], global Wald test p<0.001). In our subgroup analysis, patients who received adjuvant chemotherapy achieved greater survival with increasing TME score (HR 0.47 [95% CI 0.29, 0.74], interaction p<0.05). The combination of TME High and microsatellite instability (MSI) scores significantly outperformed MSI as a univariable predictor of immunotherapy response. We conclude that the Tumour Microenvironment Score is a predominate driver of prognosis as well as chemotherapy and immunotherapy-related outcomes in gastric cancer. This paper provides a foundation for additional analyses and translational work.

Huang-Jin-Shuang-Shen Decoction promotes CD8+ T-cell-mediated anti-tumor immunity by regulating chemokine CXCL10 in gastric cancer

BackgroundResearch on immunotherapy for gastric cancer is currently receiving significant attention, with particular emphasis on the role of CD8+ T cells in anti-tumor immune responses. In recent years, the importance of the chemokine CXCL10 in promoting anti-tumor immunity has been increasingly recognized because it plays a crucial role in recruiting CD8+ T cells to the tumor microenvironment. The Huang-Jin-Shuang-Shen (HJSS) Decoction, a Chinese medicine, has been used as an adjuvant drug for gastric cancer chemotherapy. Its mechanism of action may be related to the activation of anti-tumor immunity. PurposeTo assess the role of the HJSS Decoction in regulating the immune microenvironment of gastric cancer and elucidate its mechanism. Study design/methodsUltra-high performance liquid chromatography Q Exactive-mass spectrometry was used to analyze the main components of the HJSS Decoction and evaluate the therapeutic effect of the HJSS Decoction synergized with 5-fluorouracil (5-FU) on gastric cancer. The proportions of CD8+ T cells and killing markers were determined using flow cytometry. Mechanisms of action and targets were screened using network pharmacology. The level of CXCL10 was detected using enzyme-linked immunosorbent assay and western blot, and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) related signaling pathway was detected in vitro. The target function was validated by siRNA transfection. ResultsThe combination of HJSS Decoction and 5-FU demonstrated a synergistic effect in impeding the progression of subcutaneous gastric cancer. This was achieved through the facilitation of apoptosis and suppression of proliferation. Furthermore, HJSS Decoction exhibited the ability to enhance the population of CD8+ T cells and augment their cytotoxic capabilities, both in laboratory settings and in living organisms. Notably, HJSS Decoction upregulated the expression of CXCL10, and mechanistically, it activated the NFκB-related signaling pathway to initiate subsequent transcription of chemokines. ConclusionThe present study aimed to investigate the pharmacological mechanism of the HJSS Decoction and its potential clinical application in inhibiting gastric cancer in mice. HJSS Decoction can cooperate with 5-FU to inhibit gastric cancer, and the optimal dose is medium. HJSS Decoction exerts anti-tumor immunity by activating the NFκB-related signaling pathway and promoting the expression of CXCL10, which in turn recruits CD8+ T cells into the tumor immune microenvironment. Overall, these findings provide valuable evidence for the potential clinical application of HJSS Decoction.

Impact of web-based positive psychological intervention on emotions, psychological capital, and quality of life in gastric cancer patients on chemotherapy.

Gastric cancer is a malignant digestive tract tumor that originates from the epithelium of the gastric mucosa and occurs in the gastric antrum, particularly in the lower curvature of the stomach. To evaluate the impact of a positive web-based psychological intervention on emotions, psychological capital, and quality of survival in gastric cancer patients on chemotherapy. From January 2020 to October 2023, 121 cases of gastric cancer patients on chemotherapy admitted to our hospital were collected and divided into a control group (n = 60) and an observation group (n = 61) according to the admission order. They were given either conventional nursing care alone and conventional nursing care combined with web-based positive psychological interventions, respectively. The two groups were compared in terms of negative emotions, psychological capital, degree of cancer-caused fatigue, and quality of survival. After intervention, the number of patients in the observation group who had negative feelings toward chemotherapy treatment was significantly lower than that of the control group (P < 0.05); the Positive Psychological Capital Questionnaire score was considerably higher than that of the control group (P < 0.05); the degree of cancer-caused fatigue was significantly lower than that of the control group (P < 0.05); and the Quality of Life Scale for Cancer Patients (QLQ-30) score was significantly higher than that of the control group (P < 0.05). Implementing a web-based positive psychological intervention for gastric cancer chemotherapy patients can effectively improve negative emotions, enhance psychological capital, and improve the quality of survival.

Histopathological response to chemotherapy and survival of mucinous type gastric cancer.

Data on the clinicopathological characteristics of mucinous gastric cancer (muc-GC) are limited. This study compares the clinical outcome and response to chemotherapy between patients with resectable muc-GC, intestinal (int-GC) and diffuse (dif-GC) gastric cancer. Patients from the D1/D2 study or the CRITICS trial were included in exploratory surgery-alone (SAtest) or chemotherapy test (CTtest) cohorts. Real-world data from the Netherlands Cancer Registry on patients treated between with surgery-alone (SAvalidation), and receiving preoperative chemotherapy with or without postoperative treatment (CTvalidation) were used for validation. Histopathological subtypes were extracted from pathology reports filed in the Dutch Pathology Registry and correlated with tumor regression grade (TRG) and relative survival (RS). In SAtest (n = 549) and SAvalidation (n = 8062) cohorts, muc-GC patients had a five-year RS of 39% and 31%, similar to or slightly better than dif-GC (43% and 29%, p = .52 and p = .011), but worse than int-GC (55% and 42%, p = .11 and p < .001). In CTtest (n = 651) and CTvalidation (n = 2889) cohorts, muc-GC showed favorable TRG (38% and 44% (near-)complete response) compared to int-GC (26% and 35%) and dif-GC (10% and 28%, p < .001 and p = .005). The 5-year RS in CTtest and CTvalidation cohorts for muc-GC (53% and 48%) and int-GC (58% and 59%) was significantly better compared to dif-GC (35% and 38%, p = .004 and p < .001). Recognizing and incorporating muc-GC into treatment decision-making of resectable GC can lead to more personalized and effective approaches, given its favorable response to preoperative chemotherapy in relation to int-GC and dif-GC and its favorable prognostic outcomes in relation to dif-GC.

MEF2A, a gene associated with mitochondrial biogenesis, promotes drug resistance in gastric cancer

Chemotherapeutic resistance is a major obstacle to the effectiveness of cisplatin-based chemotherapy for gastric cancer (GC), leading to treatment failure and poor survival rates. However, the underlying mechanisms are not fully understood. Our study demonstrated that the transcription factor myocyte enhancer factor 2A (MEF2A) plays a role in chemotherapeutic drug resistance by regulating the transcription of PGC1α and KEAP1, promoting mitochondrial biogenesis. It was found that increased MEF2A expression is linked with poor prognosis, cisplatin insensitivity, and mitochondrial function in GC. MEF2A overexpression significantly decreases GC cell sensitivity in vitro and in vivo, while MEF2A knockdown enhances the sensitivity to cisplatin. Mechanistically, MEF2A activates the transcription of PGC1α, leading to increased mitochondrial biogenesis. In addition, MEF2A inhibits KEAP1 transcription, reduces NRF2 ubiquitination degradation, and activates the KEAP1/NRF2 signaling pathway, which modulates the reactive oxygen species level. The present study identifies MEF2A as a new critical oncogene involved in GC chemoresistance, suggesting a novel therapeutic target for GC.

Prognostic Impact of Tumor Growth Rate During Second-line Chemotherapy in Patients With Gastric Cancer.

Despite the remarkable developments in chemotherapy for gastric cancer (GC), rapid tumor growth is sometimes experienced during chemotherapy. This study investigated the association of tumor growth rate (TGR) during second-line chemotherapy with the prognosis of patients with GC. We retrospectively reviewed 29 patients with GC treated with nab-paclitaxel plus ramucirumab as second-line chemotherapy between 2017 and 2019 at Osaka Metropolitan University. Of them, 13 cases with target lesions were classified into two groups according to TGR using a cutoff value of 0.25. Clinicopathological factors and survival outcomes were compared between the high TGR (n=5) and low TGR (n=8) groups. The median duration of first-line chemotherapy was significantly longer in the high TGR group than in the low TGR group [median 298 days vs. 72.5 days, p=0.030]. Progressive disease (PD) was observed in 60% of patients with high TGR, whereas stable disease (SD) was observed in 75% patients with low TGR. The median survival time (MST) after starting chemotherapy was 488 days in the low TGR group but was not reached in the high TGR group (log rank p=0.215). The MST after PD was 145 days in the low TGR group but was not estimated in the high TGR group (log rank p=0.345). Based on the absence of significant differences in survival outcomes between the high and low TGR groups, sequential late-line chemotherapy might be considered important, even for patients with high TGR.