Preoperative Chemoradiotherapy vs Chemotherapy for Adenocarcinoma of the Esophagogastric Junction: A Network Meta-Analysis.

Importance: The prognosis of patients with adenocarcinoma of the esophagus and esophagogastric junction (AEG) is poor. From current evidence, it remains unclear to what extent preoperative chemoradiotherapy (CRT) or preoperative and/or perioperative chemotherapy achieve better outcomes than surgery alone. Objective: To assess the association of preoperative CRT and preoperative and/or perioperative chemotherapy in patients with AEG with overall survival and other outcomes. Data Sources: Literature search in PubMed, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, and International Clinical Trials Registry Platform was performed from inception to April 21, 2023. Study Selection: Two blinded reviewers screened for randomized clinical trials comparing preoperative CRT plus surgery with preoperative and/or perioperative chemotherapy plus surgery, 1 intervention with surgery alone, or all 3 treatments. Only data from participants with AEG were included from trials that encompassed mixed histology or gastric cancer. Among 2768 initially identified studies, 17 (0.6%) met the selection criteria. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed for extracting data and assessing data quality by 2 independent extractors. A bayesian network meta-analysis was conducted using the 2-stage approach. Main Outcomes and Measures: Overall and disease-free survival, postoperative morbidity, and mortality. Results: The analyses included 2549 patients (2206 [86.5%] male; mean [SD] age, 61.0 [9.4] years) from 17 trials (conducted from 1989-2016). Both preoperative CRT plus surgery (hazard ratio [HR], 0.75 [95% credible interval (CrI), 0.62-0.90]; 3-year difference, 105 deaths per 1000 patients) and preoperative and/or perioperative chemotherapy plus surgery (HR, 0.78 [95% CrI, 0.64-0.91]; 3-year difference, 90 deaths per 1000 patients) showed longer overall survival than surgery alone. Comparing the 2 modalities yielded similar overall survival (HR, 1.04 [95% CrI], 0.83-1.28]; 3-year difference, 15 deaths per 1000 patients fewer for CRT). Similarly, disease-free survival was longer for both modalities compared with surgery alone. Postoperative morbidity was more frequent after CRT plus surgery (odds ratio [OR], 2.94 [95% CrI, 1.01-8.59]) than surgery alone. Postoperative mortality was not significantly more frequent after CRT plus surgery than surgery alone (OR, 2.50 [95% CrI, 0.66-10.56]) or after chemotherapy plus surgery than CRT plus surgery (OR, 0.44 [95% CrI, 0.08-2.00]). Conclusions and Relevance: In this meta-analysis of patients with AEG, both preoperative CRT and preoperative and/or perioperative chemotherapy were associated with longer survival without relevant differences between the 2 modalities. Thus, either of the 2 treatments may be recommended to patients.

Gastric cancer fibroblasts affect the effect of immunotherapy and patient prognosis by inducing micro-vascular production.

Introduction: Immunotherapy is critical for treating many cancers, and its therapeutic success is linked to the tumor microenvironment. Although anti-angiogenic drugs are used to treat gastric cancer (GC), their efficacy remains limited. Cancer-associated fibroblast (CAF)-targeted therapies complement immunotherapy; however, the lack of CAF-specific markers poses a challenge. Therefore, we developed a CAF angiogenesis prognostic score (CAPS) system to evaluate prognosis and immunotherapy response in patients with GC, aiming to improve patient stratification and treatment efficacy. Methods: We assessed patient-derived GC CAFs for promoting angiogenesis using EdU, cell cycle, apoptosis, wound healing, and angiogenesis analysis. Results: We then identified CAF-angiogenesis-associated differentially-expressed genes, leading to the development of CAPS, which included THBS1, SPARC, EDNRA, and VCAN. We used RT-qPCR to conduct gene-level validation, and eight GEO datasets and the HPA database to validate the CAPS system at the gene and protein levels. Six independent GEO datasets were utilized for validation. Overall survival time was shorter in the high- than the low-CAPS group. Immune microenvironment and immunotherapy response analysis showed that the high-CAPS group had a greater tendency toward immune escape and reduced immunotherapy efficacy than the low-CAPS group. Discussion: CAPS is closely associated with GC prognosis and immunotherapy outcomes. It is therefore an independent predictor of GC prognosis and immunotherapy efficacy.

[Treatment strategies of cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy for gastric cancer with peritoneal metastasis: a systematic review].

Peritoneal metastasis in gastric cancer is associated with rapid disease progression. Hyperthermic intraoperative peritoneal chemotherapy (HIPEC) done immediately after cytoreductive surgery (CRS) has become an important treatment for peritoneal metastasis in gastric cancer patients. However, different treatment options for HIPEC exist with potential influence on survival rates and prognosis in patients, exist. These treatment options include open or closed abdomen technique, perfusion solution, number of catheters, temperature, duration, and drug regimens. This paper aims to provide more evidence on standardization of HIPEC treatment options and technologies by systematically reviewing different drug regimens and technical approaches. The study included 2 randomized controlled trials, 3 phase I/II clinical trials, 2 prospective cohort studies, and 34 retrospective cohort studies, involving 1511 patients. The most common HIPEC option is to dissolve 50-75 mg/m2 of Cisplatin and 30-40 mg/m2 of Mitomycin C in 3-4 L saline solution at 42-43℃. After gastrointestinal anastomosis, 2-3 catheters are used in the HIPEC system with a perfusion flow rate of 500 ml/min. The duration is 60-90 minutes. Anastomotic leakage was low in studies where HIPEC was performed after gastrointestinal anastomosis. The utilization of open HIPEC and a two-drug regimen resulted in improved overall survival rates. The future development of HIPEC aims to enhance tumor-specific therapy by optimizing various aspects, such as identifying the safest and most effective chemotherapy regimens, refining patient selection criteria, and improving perioperative care.

Safety and efficacy of minimally invasive gastrectomy for older patients with gastric cancer after neoadjuvant chemotherapy and immunotherapy: a propensity score-matched analysis.

BACKGROUND: The effect of neoadjuvant immunotherapy on minimally invasive gastrectomy (MIG) in older patients with gastric cancer remains controversial. This study aimed to evaluate the safety, and efficacy of MIG for older patients who underwent neoadjuvant chemotherapy and immunotherapy (NICT). METHODS: The clinical data of 726 older patients aged over 65 years who underwent upfront MIG or MIG after NICT in the Department of General Surgery, Chinese PLA General Hospital First Medical Center between Jan 2020 and Nov 2023 were retrospectively analyzed. Propensity score-matched (PSM) analysis at a ratio of 1:2 was performed to reduce bias from confounding patient-related variables, short- and long-term outcomes were compared between the two groups. RESULTS: The baseline characteristics were comparable between 61 patients in the NICT-MIG group and 114 patients in the MIG group after PSM (P > 0.05). The major pathological response (MPR) rate and pathological complete response (pCR) rate were 44.2% and 21.3%, respectively, in the NICT-MIG group. Patients in the NICT-MIG group had longer operation times (P = 0.005) and postoperative days (P = 0.030) than those in the MIG group. No significant differences were found in intraoperative bleeding, number of retrieved lymph nodes, first flatus day, R0 resection rate, overall postoperative complication (POC) morbidity, severe POC morbidity, 2-year overall, and recurrence-free survival between the MIG and NICT-MIG groups (P > 0.05). Multivariate logistic analysis revealed that an estimated blood loss > 200 mL (P = 0.010) and a lymphocyte-to-monocyte ratio (LMR) ≤ 3.25 (P = 0.006) were independent risk factors for POCs after MIG in older patients. CONCLUSION: The safety, and efficacy of NICT-MIG were comparable to those of upfront MIG in older patients with GC. Patients with an estimated blood loss > 200 mL or an LMR ≤ 3.25 should be carefully evaluated for an increased risk of POCs in older patients who undergo MIG. TRIAL REGISTRATION: Chinese Clinical Trial Registry (Registration Number: ChiCTR2400086827).

Adjuvant Concurrent Chemoradiotherapy (CRT) plus Docetaxel-Cisplatin-Fluorouracil (DCF) versus CRT plus Fluorouracil-Folinic Acid (FUFA) in Stage III Gastric Cancer.

INTRODUCTION: Adjuvant chemoradiotherapy (CRT) is the optimal management strategy in resectable gastric cancer. There is a debate about the efficacy of more aggressive CRT plus chemotherapy regimens in adjuvant setting. This study aimed to compare the efficacy of adjuvant CRT plus docetaxel-cisplatin-fluorouracil (DCF) versus CRT plus fluorouracil-folinic acid (FUFA) in stage III gastric cancer. METHODS: Patients with a diagnosis of stage III gastric cancer treated with adjuvant therapy after curative resection were analyzed. Patients' disease characteristics and impacts of the regimens on median disease-free survival (DFS) and median overall survival (OS) were analyzed retrospectively. RESULTS: One hundred sixty-one patients (102 in FUFA arm and 59 in DCF arm) with a median age of 56.0 (29-79) were evaluated. In the DCF arm, there were more renal toxicities (31.6% vs 6.4% P < 0.001), emergency department admissions (64.9% vs 23.7%, P < 0.001), and dose reductions/treatment modifications in the DCF arm (51.6% vs 37.2, P < 0.001). The median follow-up was 23 months (1-124) in the FUFA arm and 26.0 months (1-77) in the DCF arm. The median DFS was 25.0 months (%95 CI, 12.7-37.2) in the DCF arm and 17.0 months (%95 CI, 2.6-31.3) in the FUFA arm, P = 0.66. The median OS was 28.0 months (%95 CI, 17.0-38.9) in the DCF arm and 25.0 months (%95 CI, 11.9-36.0) in the FUFA arm, P = 0.70. CONCLUSION: In conclusion, when compared with FUFA regimen, more aggressive therapy with DCF was more toxic and did not improve OS in adjuvant setting of stage III gastric cancer.

Complete and rapid response with the combination of immunotherapy and chemotherapy in a young adult patient with microsatellite instability-high metastatic gastric cancer.

ABSTRACT: Gastric cancer (GC) is an aggressive malignancy; 5.0% of GC patients are diagnosed before the age of 40. These patients are more aggressive and advanced stage at the diagnosis. Microsatellite instability-high (MSI-H) status is usually seen in relatively older patients. We report a 31-year-old male patient presenting with an intra-abdominal mass and spleen lesions that radiologically mimic a gastrointestinal stromal tumor (GIST). He underwent surgery. Histological examination revealed poorly differentiated adenocarcinoma starting from the deep gastric mucosa. After surgery, rapidly progressive disease was observed. The patient with MSI-H and combined positive score (CPS) of 65% was treated with a combination of immunotherapy and chemotherapy; complete response was observed in approximately 3 months. This is a very rare GC case in young adult age with MSI-H status and responds to treatment in a short time. Predictive markers for immunotherapy efficacy are still being discussed; this case supports the predictive role of high CPS score and MSI-H phenotype in demonstrating treatment efficacy.

[Clinical significance of combined therapy with immune checkpoint inhibitor in perioperative treatment for locally advanced gastric cancer or adenocarcinoma of gastroesophageal junction].

The clinical application of immune checkpoint inhibitor (ICI) offers novel treatment modality for locally advanced gastric cancer (LAGC) and adenocarcinoma of the gastroesophageal junction (AGEJ), with the crucial benefit of providing higher cure rates. These agents have become part of standard treatments in the perioperative setting for selected cases, such as tumor with MSI-H/dMMR, high expression of CPS (≥5) or EBV (+), MSI-H and MSS/TP53+ according to tumor immunohistochemical, genetic testing or molecular characterization. An in-depth understanding of the immune response mechanisms in "cold" and "hot" tumors enables us to better identify ICI beneficiary and further provide a rationale for converting nonresponsive "cold" tumors into responsive "hot" tumors, subsequently allowing nonresponders to benefit from ICI immunotherapy. Several recent clinical trials clearly demonstrated a synergistic and complementary effect of combining ICI with chemotherapy or chemoradiotherapy, as well as combining ICI with anti-HER2 or anti-VEGF/VEGFR and chemotherapy. Compared with chemotherapy alone, the combination treatment can significantly improve pCR, MRR or ypT0N0, and is expected to improve the prognosis. This article reviews the results of a series of clinical trials in recent years in the field of perioperative application of ICI with other modalities in LAGC/AGEJ, aiming at expanding upon the discussion of current standard neoadjuvant and adjuvant therapies for LAGC/AGEJ and exploring the feasibility of new perioperative combined immunotherapy in the future.

[Neoadjuvant immunotherapy ushers in a new era of gastric cancer treatment].

Recent advances in tumor immunology have made immunotherapy a new direction for neoadjuvant treatment of gastric cancer. Multiple clinical trials have confirmed that combining immunotherapy with chemotherapy and targeted therapy in the neoadjuvant treatment of gastric cancer can effectively improve treatment response and prolong patient survival time. This article aims to comment on the application of immunotherapy in the neoadjuvant treatment of gastric cancer, exploring its mechanisms, integration strategies with traditional treatments, safety, and personalized precision therapy in the hope of providing new insights and directions for the field of gastric cancer treatment.

[Significance and treatment strategies of pathologic complete response after neoadjuvant therapy for gastric cancer].

Neoadjuvant therapy, as an important part of comprehensive treatment for locally advanced gastric cancer, has been recommended by various guidelines. Partial locally advanced gastric cancer patients can achieve pathologic complete response (pCR) after neoadjuvant therapy, thus achieving relatively good prognosis. However, there is still controversy over whether complete remission in local pathology can translate into survival benefits, whether pCR is equivalent to cure, and whether subsequent adjuvant therapy is needed. Therefore, how to predict patients who can achieve pathologic complete response after neoadjuvant therapy and identify truly cured patients is the direction of future exploration.

[Rethinking the scope of lymphadenectomy after neoadjuvant immunotherapy for locally advanced gastric cancer].

Radical gastrectomy is the core of comprehensive treatment for patients with locally advanced gastric cancer,while reasonable and standardized lymphadenectomy is the key to radical gastrectomy.With the continuous development of treatment methods and therapeutic drugs for advanced gastric cancer, it is worth exploring whether the scope of lymphadenectomy needs to be changed. Neoadjuvant immunotherapy has brought a new breakthrough for locally advanced gastric cancer, increased pathological complete response rate, reduced clinical stage of tumors, and increased radical surgical resection rate, but it has not brought long-term benefits to patients. Lymph nodes play an important role in human anti-tumor immune response, and some basic studies suggest that preserving some normal lymph nodes may be more helpful to enhance the efficacy of immunotherapy. Thus, in the era of immunotherapy, the extent of lymph node dissection for locally advanced gastric cancer needs to balance continuous drug benefits, patient quality of life, and survival benefits, awaiting further high-quality clinical research for determination. Questions such as how to differentiate between normal and metastatic lymph nodes, how to rationally preserve normal lymph nodes, and whether preserving partial lymph node function can lead to greater benefits for patients from immunotherapy warrant further exploration.

[Advances in the application of intragastric flora in the diagnosis and treatment of gastric cancer].

Gastric cancer is one of the major causes of cancer-related deaths worldwide, and infection with Helicobacter pylori and EBV, smoking and a salt-heavy diet have been shown to be risk factors for the development of gastric cancer. Currently, numerous research has demonstrated that differences in the structure of the gastric flora can be exploited to distinguish the different stages of gastric mucosal lesions and to predict the progression of gastric cancer. Therefore, a new biomarker is presented for the diagnosis of gastric cancer based on the structural differences of the gastric flora. Gastric flora has also potential in the treatment of gastric cancer. The application of non-H. pylori flora to modulate immune cells may increase the sensitivity of tumour cells for chemotherapy, improve the efficacy of immune checkpoint inhibitors and significantly prolong the survival of patients. This review of advances in the application of gastric flora in the diagnosis and treatment of gastric cancer is aimed at providing a reference and basis for future research in this field.

Diffuse-Type Histology Is Prognostic for All Siewert Types of Gastroesophageal Adenocarcinoma.

PURPOSE: The optimal treatment for gastroesophageal junction adenocarcinoma (GEJA) remains controversial. We evaluated the treatment patterns and outcomes of patients with locally advanced GEJA according to the histological type. MATERIALS AND METHODS: We conducted a single-institution retrospective cohort study of patients with locally advanced GEJA who underwent curative-intent surgical resection between 2010 and 2020. Perioperative therapies as well as clinicopathologic, surgical, and survival data were collected. The results of endoscopy and histopathological examinations were assessed for Siewert and Lauren classifications. RESULTS: Among the 58 patients included in this study, 44 (76%) were clinical stage III, and all received neoadjuvant therapy (72% chemoradiation, 41% chemotherapy, 14% both chemoradiation and chemotherapy). Tumor locations were evenly distributed by Siewert Classification (33% Siewert-I, 40% Siewert-II, and 28% Siewert-III). Esophagogastrectomy (EG) was performed for 47 (81%) patients and total gastrectomy (TG) for 11 (19%) patients. All TG patients received D2 lymphadenectomy compared to 10 (21%) EG patients. Histopathological examination showed the presence of 64% intestinal-type and 36% diffuse-type histology. The frequencies of diffuse-type histology were similar among Siewert groups (37% Siewert-I, 36% Siewert-II, and 33% Siewert-III). Regardless of Siewert type and compared to intestinal-type, diffuse histology was associated with increased intraabdominal recurrence rates (P=0.03) and decreased overall survival (hazard ratio, 2.33; P=0.02). With a median follow-up of 31.2 months, 29 (50%) patients had a recurrence, and the median overall survival was 50.5 months. CONCLUSIONS: Present in equal proportions among Siewert types of esophageal and gastric cancer, a diffuse-type histology was associated with high intraabdominal recurrence rates and poor survival. Histopathological evaluation should be considered in addition to anatomic location in the determination of multimodal GEJA treatment strategies.

PERIOPERATIVE CHEMOTHERAPY, ADJUVANT CHEMOTHERAPY AND ADJUVANT CHEMORADIOTHERAPY IN THE SURGICAL TREATMENT OF GASTRIC CANCER IN A HOSPITAL OF THE BRAZILIAN UNIFIED HEALTH SYSTEM.

BACKGROUND: Despite the preference for multimodal treatment for gastric cancer, abandonment of chemotherapy treatment as well as the need for upfront surgery in obstructed patients brings negative impacts on the treatment. The difficulty of accessing treatment in specialized centers in the Brazilian Unified National Health System (SUS) scenario is an aggravating factor. AIMS: To identify advantages, prognostic factors, complications, and neoadjuvant and adjuvant therapies survival in gastric cancer treatment in SUS setting. METHODS: The retrospective study included 81 patients with gastric adenocarcinoma who underwent treatment according to INT0116 trial (adjuvant chemoradiotherapy), CLASSIC trial (adjuvant chemotherapy), FLOT4-AIO trial (perioperative chemotherapy), and surgery with curative intention (R0 resection and D2 lymphadenectomy) in a single cancer center between 2015 and 2020. Individuals with other histological types, gastric stump, esophageal cancer, other treatment protocols, and stage Ia or IV were excluded. RESULTS: Patients were grouped into FLOT4-AIO (26 patients), CLASSIC (25 patients), and INT0116 (30 patients). The average age was 61 years old. More than 60% of patients had pathological stage III. The treatment completion rate was 56%. The pathological complete response rate of the FLOT4-AIO group was 7.7%. Among the prognostic factors that impacted overall survival and disease-free survival were alcoholism, early postoperative complications, and anatomopathological status pN2 and pN3. The 3-year overall survival rate was 64.9%, with the CLASSIC subgroup having the best survival (79.8%). CONCLUSIONS: The treatment strategy for gastric cancer varies according to the need for initial surgery. The CLASSIC subgroup had better overall survival and disease-free survival. The INT0116 regimen also protected against mortality, but not with statistical significance. Although FLOT4-AIO is the preferred treatment, the difficulty in carrying out neoadjuvant treatment in SUS scenario had a negative impact on the results due to the criticality of food intake and worse treatment tolerance.

THE MOLECULAR CANCER SUBTYPES VERSUS THE INDUSTRY ARSENAL. WHICH ONE DRIVES GASTRIC CANCER TREATMENT?

Molecular medicine opened new horizons in understanding disease mechanisms and discovering target interventions. The wider availability of DNA and RNA sequencing, immunohistochemical analysis, proteomics, and other molecular tests changed how physicians manage diseases. The gastric cancer molecular classification proposed by The Cancer Genome Atlas Program divides gastric adenocarcinomas into four subtypes. However, the available targets and/or immunotherapies approved for clinical use seem to be dissociated from these molecular subtypes. Until a more reliable interpretation of the stupendous amount of data provided by the molecular classifications is presented, the clinical guidelines will rely on available actionable targets and approved therapies to guide clinicians in conducting cancer management in the era of molecular therapies.

The functions of cuproptosis in gastric cancer: therapy, diagnosis, prognosis.

Gastric cancer (GC) is the fifth most prevalent type of cancer in the whole world. Cuproptosis is discovered as a programmed cell death pathway and connected to cells' growth and death, as well as tumorigenesis. The relationship between cuproptosis and GC is still elusive. Two aspects of this study will elaborate the relationship between cuproptosis and immunotherapy as well as biomarkers in GC. Notably, the herein review is intended to highlight what has been accomplished regarding the cuproptosis for the diagnosis, immunotherapy, and prognosis in GC. The aim of this study is to offer a potential directions and the strategies for future research regarding cuproptosis inside the GC.

IL-4/IL-4R axis signaling drives resistance to immunotherapy by inducing the upregulation of Fcγ receptor IIB in M2 macrophages.

In recent years, immunotherapy, particularly PD-1 antibodies, have significantly enhanced the outcome of gastric cancer patients. Despite these advances, some patients do not respond well to treatment, highlighting the need to understand resistance mechanisms and develop predictive markers of treatment effectiveness. This study retrospectively analyzed data from 106 patients with stage IV gastric cancer who were treated with first-line immunotherapy in combination with chemotherapy. By comparing plasma cytokine levels between patients resistant and sensitive to PD-1 antibody therapy, the researchers identified elevated IL-4 expression in the resistant patients. Mechanical investigations revealed that IL-4 induces metabolic changes in macrophages that activate the PI3K/AKT/mTOR pathway. This alteration promotes ATP production, enhances glycolysis, increases lactic acid production, and upregulates FcγRIIB expression in macrophages. Ultimately, these changes lead to CD8+ T cell dysfunction and resistance to PD-1 antibody therapy in gastric cancer. These findings highlight the role of IL-4-induced macrophage polarization and metabolic reprogramming in immune resistance and verify IL-4 as potential targets for improving treatment outcomes in gastric cancer patients.

Influence of acupuncture and moxibustion on gastrointestinal function and adverse events in gastric cancer patients after surgery and chemotherapy: a meta-analysis.

OBJECTIVE: The impact of acupuncture and moxibustion on postoperative complications and adverse events (AEs) of chemotherapy in patients with gastric cancer (GC) has been investigated. Through a meta-analysis of existing randomized controlled trials (RCTs), this study sought to strengthen the evidentiary basis to help investigators further understand the effects of moxibustion and acupuncture on postoperative complications and AEs of chemotherapy among GC patients. METHODS: Embase, Web of Science, PubMed, The Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, and VIP Database for Chinese Technical Periodicals were searched to collect RCTs on effects of acupuncture and moxibustion on gastrointestinal function and AEs among GC patients undergoing surgery and chemotherapy. Outcome measures included postoperative gastrointestinal recovery (bowel sound recovery time, time to first flatus/defecation/feeding), the incidence of AEs (nausea and vomiting, abdominal distension, and diarrhea), myelosuppression (white blood cells, hemoglobin, and platelet), and immune function indicators (CD3+ and CD4+). To assess quality, the Cochrane Risk of Bias Tool was utilized. Review Manager 5.4 was implemented to do the meta-analysis. RESULTS: Fifteen eligible RCTs involved 1259 patients. Meta-analysis results showed that the experimental group had a significantly shorter bowel sound recovery time (MD = - 14.57, 95% CI = [- 18.97, - 10.18], P < 0.00001), time to first flatus (MD = - 17.56, 95% CI = [- 22.23, - 12.88], P < 0.00001), time to first defecation (MD = - 17.05, 95% CI = [- 21.02, - 13.09], P < 0.00001), and time to first feeding (MD = - 23.49, 95% CI = [- 28.81, - 18.17], P < 0.00001) than the control group. There were significant decreases in the incidence of nausea and vomiting (RR = 0.46, 95% CI = [0.21, 1.02], P = 0.05) and abdominal distension (RR = 0.45, 95% CI = [0.27, 0.75], P = 0.002) observed in the experimental group in comparison with the control group. The experimental group demonstrated a significant increase in white blood cell counts in comparison with to the control group (MD = 0.89, 95% CI = [0.23, 1.55], P = 0.008). The experimental group showed significantly higher levels of CD3+ (MD = 7.30, 95% CI = [1.86, 12.74], P = 0.009) and CD4+ (MD = 2.75, 95% CI = [1.61, 3.90], P < 0.00001) than the control group. CONCLUSION: Among GC patients, acupuncture and moxibustion can aid in gastrointestinal function recovery, reduce the incidence of AEs of surgery and chemotherapy, and improve immune function.

Establishing a model composed of immune-related gene-modules to predict tumor immunotherapy response.

At present, tumor immunotherapy has been widely applied to treat various cancers. However, the accuracy of predicting treatment efficacy has not yet achieved a significant breakthrough. This study aimed to construct a prediction model based on the modified WGCNA algorithm to precisely judge the anti-tumor immune response. First, we used a murine colon cancer model to screen corresponding DEGs according to different groups. GSEA was used to analyze the potential mechanisms of the immune-related DEGs (irDEGs) in each group. Subsequently, the intersection of the irDEGs in every group was acquired, and 7 gene-modules were mapped. Finally, 4 gene-modules including cogenes, antiPD-1 immu-genes, chemo immu-genes and comb immu-genes, were selected for subsequent study. Furthermore, a clinical dataset of gastric cancer patients receiving immunotherapy was enrolled, and the irDEGs were identified. A total of 34 vital irDEGs were obtained from the intersections of the vital irDEGs and the four gene-modules. Next, the vital irDEGs were analyzed by the modified WGCNA algorithm, and the correlation coefficients between the 4 gene-modules and the response status to immunotherapy were calculated. Thus, a prediction model based on correlation coefficients was built, and the corresponding model scores were acquired. The AUC calculated according to the model score was 0.727, which was non-inferior to that of the ESTIMATE score and the TIDE score. Meanwhile, the AUC calculated according to the classification of the model scores was 0.705, which was non-inferior to that of the ESTIMATE classification and the TIDE classification. The prediction accuracy of the model was validated in clinical datasets of other cancers.

Incorporating Molecular Data Into Treatment Decision Making in Gastroesophageal and Pancreaticobiliary Cancers: Timing and Strategies.

Gastroesophageal (GE) and pancreatobiliary (PB) cancers represent a significant clinical challenge. In this context, it is critical to understand the key molecular targets within these malignancies including how they are assayed for as well as the clinical actionability of these targets. Integrating biomarkers into the standard of care presents a critical avenue for refining treatment paradigms. This review aims to explore these complexities, offering insights into the optimal sequencing of chemotherapy and targeted therapies and their utility in the management of GE and PB cancers. The timely integration of promising investigational therapies into clinical practice has broader implications around strategies for future clinical trial designs, which would pave the way for advancements in the management of GE and PB cancers. This review provides guidance in navigating the evolving landscape of GE and PB cancer care, which ultimately will drive forward progress in the field and lead to improved patient outcomes.