Gastric cancer remains a major health challenge worldwide, with nearly 1 million new cases annually contributing to more than 650 000 deaths. Epidemiologically, gastric cancer shows substantial geographical variation in incidence, with higher rates in Asia, South America, and eastern Europe, and a rapid increase in early-onset cases among people younger than 50 years. Key risk factors for gastric cancer include Helicobacter pylori infection, diet, obesity, smoking, and genetic predisposition. Early detection through comprehensive diagnostic procedures is crucial for optimising treatment outcomes. Standard treatment approaches for locally advanced gastric cancer include surgical resection, particularly D2 lymphadenectomy, complemented by chemotherapy and radiotherapy. There is increasing implementation of minimally invasive surgical techniques for operable disease and integration of immune checkpoint inhibitors and targeted therapies for advanced stages. Emerging therapies, such as novel targeted treatments and next-generation immunotherapies, show promise in improving survival and quality of life. Future directions in the management of gastric cancer focus on precision medicine, continued advancement in immunotherapy, novel early detection methods, and a multidisciplinary approach to care. These strategies aim to enhance the overall effectiveness of treatment and prognosis worldwide.Copyright © 2025 Copyright © 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. Published by Elsevier Ltd.. All rights reserved.

The benefit of surgical resection of liver metastases from gastric cancer has not been well established. The aim of this study was to evaluate the rationale for hepatic resection in patients with hepatic metastases from gastric cancer.Among 10 259 patients diagnosed with gastric adenocarcinoma in the Yonsei University Health System from 1995 to 2005, we reviewed the records of 58 patients with liver-only metastases from gastric cancer who underwent gastric resection regardless of hepatic surgery.The overall 1-year, 3-year, and 5-year survival rates of 41 patients who underwent hepatic resection with curative intent were 75.3%, 31.7%, and 20.8%, respectively, and three patients survived >7 years. Of the 41 patients, 22 had complete resection and 19 had palliative resection. Between the curative and palliative resections, survival rates after curative intent were not different. The number of liver metastasis (solitary or multiple) was a marginally significant prognostic factor for survival.Surgery for liver metastases arising from gastric adenocarcinoma is reasonable if complete resection seems feasible after careful preoperative staging, even if complete resection is not actually achieved. Hepatic resection should be considered as an option for gastric cancer patients with hepatic metastases.

The epidemiology of metastatic gastric cancer is unexplored because cancer registries seldom cover metastatic involvement apart from "present or not". We used a novel approach by utilizing Swedish registers to assess metastatic spread in gastric cancer. To our knowledge, this is the first nationwide description of metastases in gastric cancer.The most common sites of metastasis were liver (in 48% of metastatic cancer patients), peritoneum (32%), lung (15%), and bone (12%). Metastases to the lung, nervous system, and bone were more frequent in cardia cancer and men, whereas non-cardia cancer more frequently metastasized within the peritoneum. Signet ring adenocarcinomas more frequently metastasized within the peritoneum, bone and ovaries, and less frequently to the lungs and liver compared with generic adenocarcinoma. The liver and the peritoneum were commonly single metastases while lung metastases occurred frequently together with liver metastases. The median survival in metastatic gastric cancer was 3 months, worst among those with bone and liver metastases (2 months).A total of 7,559 patients with gastric cancer were identified. Metastatic patterns and survival depending on sex, age, stage, anatomical location (cardia and non-cardia), and histological type were assessed.The patterns of metastasis differ notably depending on histological type. Cardia cancer exhibits a completely different metastatic behavior than non-cardia cancer. Awareness of the differing patterns may guide in tailored diagnosis of metastases. Survivors from cardia cancer would benefit from increased surveillance of extraperitoneal metastases. Bone metastases should be considered in patients with signet ring adenocarcinoma if symptoms emerge.

It has been widely accepted that radical resection is the primary consideration to improve the survival rate for gastric cancer, but it is still controversial whether surgery could bring any substantial survival benefit to gastric cancer patients with synchronous liver metastasis. We retrospectively analyzed pathological and clinical data of 39 gastric patients with liver metastasis who underwent gastric-hepatic radical resection to explore the related prognostic factors. In the whole group of 39 patients, 1-, 2-, 3- and 5-year RFS rates were 30.8, 12.8, 10.3 and 7.7 %; 1-, 2-, 3- and 5-year overall survival (OS) rates were 56.4, 25.6, 17.9 and 10.3 %, respectively. Compared with patients without surgery, operative ones had a statistically significant long-term survival rate. With univariate analysis, lymph node metastasis (N stage), soft tissue invasion and number of liver metastases were significant prognostic factors associated with OS time of synchronous liver metastasis after radical gastrectomy (P < 0.05). What is more, N stage and number of liver metastases were independent factors associated with OS in multivariate analysis. For gastric adenocarcinoma with liver metastases, surgery maybe a superior option if complete resection of gastric and hepatic lesions is feasible and careful postoperative supporting treatment could be received at the same time, especially ones who had less number of liver metastases.

Resection of liver metastases from gastric cancer (GC) is rarely performed, and the outcome after hepatic surgery has not been systematically evaluated in the literature. The aim of this study was to perform a systematic review of outcome and prognostic factors for survival after liver metastasectomy for GC.We performed a meta-analysis of published studies that focused on long-term outcomes (5-year overall survival [OS]) after surgical management of liver metastases from GC, and included more than 10 patients each. Pooled hazard ratios (HRs) were calculated for variables considered as potential prognostic factors for OS in at least three publications.Twenty-three studies comprising a total of 870 patients were considered in this analysis. The pooled weighted median OS was 22 months (95%CI 17.6-27.2). The pooled 5-year OS after liver resection was 23.8% (95%CI 19-29.3%). The pooled 5-year OS rates for metachronous and synchronous metastases were 30% (95%CI 24.7-35.8%) and 22.6% (95%CI 14-34.4%), respectively. Parameters associated with poor survival were (i) multiple metastases, and (ii) large size of metastases.Hepatic resection of GC liver metastases is associated with an acceptable 5-year OS, in particular after surgery of metachronous lesions, and could be offered to selected patients.© 2015 Wiley Periodicals, Inc.

Users of clinical practice guidelines and other recommendations need to know how much confidence they can place in the recommendations. Systematic and explicit methods of making judgments can reduce errors and improve communication. We have developed a system for grading the quality of evidence and the strength of recommendations that can be applied across a wide range of interventions and contexts. In this article we present a summary of our approach from the perspective of a guideline user. Judgments about the strength of a recommendation require consideration of the balance between benefits and harms, the quality of the evidence, translation of the evidence into specific circumstances, and the certainty of the baseline risk. It is also important to consider costs (resource utilisation) before making a recommendation. Inconsistencies among systems for grading the quality of evidence and the strength of recommendations reduce their potential to facilitate critical appraisal and improve communication of these judgments. Our system for guiding these complex judgments balances the need for simplicity with the need for full and transparent consideration of all important issues.

This article is the first of a series providing guidance for use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system of rating quality of evidence and grading strength of recommendations in systematic reviews, health technology assessments (HTAs), and clinical practice guidelines addressing alternative management options. The GRADE process begins with asking an explicit question, including specification of all important outcomes. After the evidence is collected and summarized, GRADE provides explicit criteria for rating the quality of evidence that include study design, risk of bias, imprecision, inconsistency, indirectness, and magnitude of effect. Recommendations are characterized as strong or weak (alternative terms conditional or discretionary) according to the quality of the supporting evidence and the balance between desirable and undesirable consequences of the alternative management options. GRADE suggests summarizing evidence in succinct, transparent, and informative summary of findings tables that show the quality of evidence and the magnitude of relative and absolute effects for each important outcome and/or as evidence profiles that provide, in addition, detailed information about the reason for the quality of evidence rating. Subsequent articles in this series will address GRADE's approach to formulating questions, assessing quality of evidence, and developing recommendations.Copyright © 2011 Elsevier Inc. All rights reserved.

To assess the usefulness of contrast-enhanced intraoperative ultrasound (CE-IOUS) during surgery for colorectal liver metastases (CRLM) when gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) is performed as a part of preoperative imaging work-up.EOB-MRI is expected to supersede CE-IOUS, which is reportedly indispensable in surgery for CRLM.One hundred consecutive patients underwent EOB-MRI, contrast-enhanced computed tomography (CE-CT), and contrast-enhanced ultrasound within 1 month before surgery for CRLM. Conventional IOUS and subsequent CE-IOUS using perflubutane were performed after the laparotomy. All the nodules identified in any of the preoperative or intraoperative examinations were resected and were submitted for histological examination, in principle.Preoperative imaging examinations identified 242 nodules; 25 additional nodules were newly identified using IOUS, 22 additional nodules were newly identified during CE-IOUS, and a histological examination further identified 4 nodules. Among the 25 nodules newly identified using IOUS, all 21 histologically proven CRLMs and 3 of the 4 benign nodules were correctly diagnosed using CE-IOUS. Among the 22 nodules newly identified using CE-IOUS, 17 nodules in 16 patients were histologically diagnosed as CRLMs. The planned surgical procedure was modified on the basis of IOUS and CE-IOUS findings in 12 and 14 patients, respectively. The sensitivity, positive-predictive value, and accuracy of CE-IOUS were 99%, 98%, and 97%, respectively. Those values of EOB-MRI (82%, 99%, 83%, respectively) were similar to CE-CT (81%, 99%, 81%, respectively).CE-IOUS is useful in hepatic resection for CRLM, even if EOB-MRI and CE-CT are performed.

To evaluate the feasibility of early metabolic change assessed by PET in predicting clinical response to chemotherapy and investigate its prognostic value in patients with advanced gastric cancer.A total of 64 patients with advanced gastric cancer were prospectively enrolled and examined by PET with (18)F-fluorodeoxyglucose (FDG) and (18)F-fluoro-3'-deoxy-3'-L-fluorothymidine (FLT) at baseline and 14 days after treatment initiation. PET findings were analyzed for the correlation with best clinical response of patients, disease control status, and survival after identifying the threshold of metabolic change percentage by ROC analysis.For FDG-PET, the total uptake value reduction percentage (δ-SUV) of 40% was the cut-off point with the maximum of sensitivity (70%) and specificity (83%) to predict clinical responding and that of prediction for disease control status was 30%, with the highest sensitivity (58%) and specificity (100%). The δ-SUV of FLT-PET played no predictive role for clinical response (AUC = 0.62; P= 0.134) and disease control (AUC = 0.66; P= 0.157). The univariate Cox regression analysis revealed no significant prognostic impact. FDG uptake reduction in liver metastases could predict both clinical response (P= 0.010) and disease control status (P= 0.002) at thresholds of 35% and 15%, respectively. Those with greater FDG uptake reduction in liver lesions had a longer overall survival (P= 0.004).Early metabolic change in FDG-PET might be a predictive marker for response and disease control in advanced gastric cancer. Early FDG uptake change in liver metastases might be a useful prognostic factor and needs further exploration.©2015 American Association for Cancer Research.

Despite recent clinical trials, the sensitivity and resistance of metastatic gastric cancer to anti-HER2 and anti-EGFR therapy are still unclear.To clarify the HER2 and EGFR expression status in the metastatic sites, we immunohistochemically compared HER2 and EGFR expression between primary and metastatic tumors from 52 gastric cancer patients with liver metastases and 85 patients with peritoneal metastases.The HER2 positivity rate of primary and metastatic tumors in patients with liver metastases, especially with intestinal-type histology (70.6 and 80.0 %, respectively), was significantly higher than in primary and metastatic tumors (22.4 and 16.4 %, respectively) in patients with peritoneal metastases. HER2 positivity of the primary tumor and liver metastases showed good concordance (87.5 %) in patients with liver metastases. In contrast, the EGFR positivity rate of metastatic tumors (70.1 %) in patients with peritoneal metastases was significantly higher than that of metastatic tumors (37.5 %) in patients with liver metastases. HER2 and EGFR expression tended to be mutually exclusive, and HER2/EGFR double-positive cases were rare in patients with liver or peritoneal metastases. In four such patients with HER2/EGFR double-positive primary tumors, the HER2- and EGFR-positive areas were separate, and corresponding liver metastasis was only positive for HER2 and peritoneal metastasis only positive for EGFR.These results indicate that HER2 and EGFR are preferentially expressed in the liver and peritoneal metastases, respectively, which would be potential targets for anti-HER2 and anti-EGFR molecular therapy in metastatic gastric cancer patients.

Clinical studies support the efficacy of programmed cell death 1 (PD-1) targeted therapy in a subset of patients with metastatic gastric cancer (mGC). With the goal of identifying determinants of response, we performed molecular characterization of tissues and circulating tumor DNA (ctDNA) from 61 patients with mGC who were treated with pembrolizumab as salvage treatment in a prospective phase 2 clinical trial. In patients with microsatellite instability-high and Epstein-Barr virus-positive tumors, which are mutually exclusive, dramatic responses to pembrolizumab were observed (overall response rate (ORR) 85.7% in microsatellite instability-high mGC and ORR 100% in Epstein-Barr virus-positive mGC). For the 55 patients for whom programmed death-ligand 1 (PD-L1) combined positive score positivity was available (combined positive score cut-off value ≥1%), ORR was significantly higher in PD-L1(+) gastric cancer when compared to PD-L1(-) tumors (50.0% versus 0.0%, P value <0.001). Changes in ctDNA levels at six weeks post-treatment predicted response and progression-free survival, and decreased ctDNA was associated with improved outcomes. Our findings provide insight into the molecular features associated with response to pembrolizumab in patients with mGC and provide biomarkers potentially relevant for the selection of patients who may derive greater benefit from PD-1 inhibition.

Mismatch repair (MMR) deficiency (MMRD) and microsatellite instability (MSI) are prognostic for survival in many cancers and for resistance to fluoropyrimidines in early colon cancer. However, the effect of MMRD and MSI in curatively resected gastric cancer treated with perioperative chemotherapy is unknown.To examine the association among MMRD, MSI, and survival in patients with resectable gastroesophageal cancer randomized to surgery alone or perioperative epirubicin, cisplatin, and fluorouracil chemotherapy in the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial.This secondary post hoc analysis of the MAGIC trial included participants who were treated with surgery alone or perioperative chemotherapy plus surgery for operable gastroesophageal cancer from July 1, 1994, through April 30, 2002. Tumor sections were assessed for expression of the MMR proteins mutL homologue 1, mutS homologue 2, mutS homologue 6, and PMS1 homologue 2. The association among MSI, MMRD, and survival was assessed.Interaction between MMRD and MSI status and overall survival (OS).Of the 503 study participants, MSI results were available for 303 patients (283 with microsatellite stability or low MSI [median age, 62 years; 219 males (77.4%)] and 20 with high MSI [median age, 66 years; 14 males (70.0%)]). A total of 254 patients had MSI and MMR results available. Patients treated with surgery alone who had high MSI or MMRD had a median OS that was not reached (95% CI, 11.5 months to not reached) compared with a median OS among those who had neither high MSI nor MMRD of 20.5 months (95% CI, 16.7-27.8 months; hazard ratio, 0.42; 95% CI, 0.15-1.15; P = .09). In contrast, patients treated with chemotherapy plus surgery who had either high MSI or MMRD had a median OS of 9.6 months (95% CI, 0.1-22.5 months) compared with a median OS among those who were neither high MSI nor MMRD of 19.5 months (95% CI, 15.4-35.2 months; hazard ratio, 2.18; 95% CI, 1.08-4.42; P = .03).In the MAGIC trial, MMRD and high MSI were associated with a positive prognostic effect in patients treated with surgery alone and a differentially negative prognostic effect in patients treated with chemotherapy. If independently validated, MSI or MMRD determined by preoperative biopsies could be used to select patients for perioperative chemotherapy.

Claudin 18.2 (CLDN18.2) is contained within normal gastric mucosa epithelial tight junctions; upon malignant transformation, CLDN18.2 epitopes become exposed. Zolbetuximab, a chimeric monoclonal antibody, mediates specific killing of CLDN18.2-positive cells through immune effector mechanisms.The FAST study enrolled advanced gastric/gastro-oesophageal junction and oesophageal adenocarcinoma patients (aged ≥18 years) with moderate-to-strong CLDN18.2 expression in ≥40% tumour cells. Patients received first-line epirubicin + oxaliplatin + capecitabine (EOX, arm 1, n = 84) every 3 weeks (Q3W), or zolbetuximab + EOX (loading dose, 800 mg/m then 600 mg/m Q3W) (arm 2, n = 77). Arm 3 (exploratory) was added after enrolment initiation (zolbetuximab + EOX 1000 mg/m Q3W, n = 85). The primary endpoint was progression-free survival (PFS) and overall survival (OS) was a secondary endpoint.In the overall population, both PFS [hazard ratio (HR) = 0.44; 95% confidence interval (CI), 0.29-0.67; P < 0.0005] and OS (HR = 0.55; 95% CI, 0.39-0.77; P < 0.0005) were significantly improved with zolbetuximab + EOX (arm 2) compared with EOX alone (arm 1). This significant PFS benefit was retained in patients with moderate-to-strong CLDN18.2 expression in ≥70% of tumour cells (HR = 0.38; 95% CI, 0.23-0.62; P < 0.0005). Significant improvement in PFS was also reported in the overall population of arm 3 versus arm 1 (HR = 0.58; 95% CI, 0.39-0.85; P = 0.0114) but not in high CLDN18.2-expressing patients; no significant improvement in OS was observed in either population. Most adverse events (AEs) related to zolbetuximab + EOX (nausea, vomiting, neutropenia, anaemia) were grade 1-2. Grade ≥3 AEs showed no substantial increases overall (zolbetuximab + EOX versus EOX alone).In advanced gastric/gastro-oesophageal junction and oesophageal adenocarcinoma patients expressing CLDN18.2, adding zolbetuximab to first-line EOX provided longer PFS and OS versus EOX alone. Zolbetuximab + EOX was generally tolerated and AEs were manageable. Zolbetuximab 800/600 mg/m is being evaluated in phase III studies based on clinical benefit observed in the overall population and in patients with moderate-to-strong CLDN18.2 expression in ≥70% of tumour cells.Copyright © 2021. Published by Elsevier Ltd.

Entrectinib is a potent inhibitor of tropomyosin receptor kinase (TRK) A, B, and C, which has been shown to have anti-tumour activity against NTRK gene fusion-positive solid tumours, including CNS activity due to its ability to penetrate the blood-brain barrier. We present an integrated efficacy and safety analysis of patients with metastatic or locally advanced solid tumours harbouring oncogenic NTRK1, NTRK2, and NTRK3 gene fusions treated in three ongoing, early-phase trials.An integrated database comprised the pivotal datasets of three, ongoing phase 1 or 2 clinical trials (ALKA-372-001, STARTRK-1, and STARTRK-2), which enrolled patients aged 18 years or older with metastatic or locally advanced NTRK fusion-positive solid tumours who received entrectinib orally at a dose of at least 600 mg once per day in a capsule. All patients had an Eastern Cooperative Oncology Group performance status of 0-2 and could have received previous anti-cancer therapy (except previous TRK inhibitors). The primary endpoints, the proportion of patients with an objective response and median duration of response, were evaluated by blinded independent central review in the efficacy-evaluable population (ie, patients with NTRK fusion-positive solid tumours who were TRK inhibitor-naive and had received at least one dose of entrectinib). Overall safety evaluable population included patients from STARTRK-1, STARTRK-2, ALKA-372-001, and STARTRK-NG (NCT02650401; treating young adult and paediatric patients [aged ≤21 years]), who received at least one dose of entrectinib, regardless of tumour type or gene rearrangement. NTRK fusion-positive safety evaluable population comprised all patients who have received at least one dose of entrectinib regardless of dose or follow-up. These ongoing studies are registered with ClinicalTrials.gov, NCT02097810 (STARTRK-1) and NCT02568267 (STARTRK-2), and EudraCT, 2012-000148-88 (ALKA-372-001).Patients were enrolled in ALKA-372-001 from Oct 26, 2012, to March 27, 2018; in STARTRK-1 from Aug 7, 2014, to May 10, 2018; and in STARTRK-2 from Nov 19, 2015 (enrolment is ongoing). At the data cutoff date for this analysis (May 31, 2018) the efficacy-evaluable population comprised 54 adults with advanced or metastatic NTRK fusion-positive solid tumours comprising ten different tumour types and 19 different histologies. Median follow-up was 12.9 months (IQR 8·77-18·76). 31 (57%; 95% CI 43·2-70·8) of 54 patients had an objective response, of which four (7%) were complete responses and 27 (50%) partial reponses. Median duration of response was 10 months (95% CI 7·1 to not estimable). The most common grade 3 or 4 treatment-related adverse events in both safety populations were increased weight (seven [10%] of 68 patients in the NTRK fusion-positive safety population and in 18 [5%] of 355 patients in the overall safety-evaluable population) and anaemia (8 [12%] and 16 [5%]). The most common serious treatment-related adverse events were nervous system disorders (three [4%] of 68 patients and ten [3%] of 355 patients). No treatment-related deaths occurred.Entrectinib induced durable and clinically meaningful responses in patients with NTRK fusion-positive solid tumours, and was well tolerated with a manageable safety profile. These results show that entrectinib is a safe and active treatment option for patients with NTRK fusion-positive solid tumours. These data highlight the need to routinely test for NTRK fusions to broaden the therapeutic options available for patients with NTRK fusion-positive solid tumours.Ignyta/F Hoffmann-La Roche.Copyright © 2020 Elsevier Ltd. All rights reserved.

Gastric cancer is the fifth most common cancer and the third most common cause of cancer death globally. Risk factors for the condition include Helicobacter pylori infection, age, high salt intake, and diets low in fruit and vegetables. Gastric cancer is diagnosed histologically after endoscopic biopsy and staged using CT, endoscopic ultrasound, PET, and laparoscopy. It is a molecularly and phenotypically highly heterogeneous disease. The main treatment for early gastric cancer is endoscopic resection. Non-early operable gastric cancer is treated with surgery, which should include D2 lymphadenectomy (including lymph node stations in the perigastric mesentery and along the celiac arterial branches). Perioperative or adjuvant chemotherapy improves survival in patients with stage 1B or higher cancers. Advanced gastric cancer is treated with sequential lines of chemotherapy, starting with a platinum and fluoropyrimidine doublet in the first line; median survival is less than 1 year. Targeted therapies licensed to treat gastric cancer include trastuzumab (HER2-positive patients first line), ramucirumab (anti-angiogenic second line), and nivolumab or pembrolizumab (anti-PD-1 third line).Copyright © 2020 Elsevier Ltd. All rights reserved.

Gastric cancer (GC) is still one of the most aggressive cancers with a few targetable alterations and a dismal prognosis. A liquid biopsy allows for identifying and analyzing the DNA released from tumor cells into the bloodstream. Compared to tissue-based biopsy, liquid biopsy is less invasive, requires fewer samples, and can be repeated over time in order to longitudinally monitor tumor burden and molecular changes. Circulating tumor DNA (ctDNA) has been recognized to have a prognostic role in all the disease stages of GC. The aim of this article is to review the current and future applications of ctDNA in gastric adenocarcinoma, in particular, with respect to early diagnosis, the detection of minimal residual disease (MRD) following curative surgery, and in the advanced disease setting for treatment decision choice and therapeutic monitoring. Although liquid biopsies have shown potentiality, pre-analytical and analytical steps must be standardized and validated to ensure the reproducibility and standardization of the procedures and data analysis methods. Further research is needed to allow the use of liquid biopsy in everyday clinical practice.

To analyze the diagnostic and prognostic value of combined detection of CA125, AFP, and CEA for gastric cancer. Ninety-eight gastric cancer patients treated in our hospital from January 2020 to November 2022 were retrospectively selected and classified into the gastric cancer group according to screening criteria, while 80 patients diagnosed with benign gastric lesions during the same period were classified into the benign group. Serum levels of CA125, AFP, CEA, and their positive rates were significantly higher in the gastric cancer group compared to the benign group (P&amp;lt;0.05). The AUCs for CA125, AFP, CEA, and their combined detection in diagnosing gastric cancer were 0.815, 0.813, 0.911, and 0.919, respectively (P&amp;lt;0.001). In patients with stage III-IV, the levels of CA125, AFP, and CEA were higher than those in stage I-II (P&amp;lt;0.05). The AUCs for serum CA125, AFP, CEA, and their combined detection in TNM staging of gastric cancer were 0.751, 0.834, 0.911, and 0.931, respectively (P&amp;lt;0.001). Poorly differentiated patients had higher levels of CA125, AFP, and CEA compared to moderately to well-differentiated patients (P&amp;lt;0.05). The AUCs for serum CA125, AFP, CEA, and their combined detection in diagnosing differentiation degree were 0.819, 0.883, 0.746, and 0.986, respectively (P&amp;lt;0.001). Patients with metastasis had higher levels of CA125, AFP, and CEA compared to those without metastasis (P&amp;lt;0.05). The AUCs for serum CA125, AFP, CEA, and their combined detection in diagnosing metastasis were 0.716, 0.825, 0.863, and 0.892, respectively (P&amp;lt;0.001). The levels of CA125, AFP, and CEA of patients in the death group were higher than those in the survival group (P&amp;lt;0.05). The AUCs for serum CA125, AFP, CEA, and their combined detection in predicting clinical outcomes of gastric cancer patients were 0.713, 0.809, 0.922, and 0.926, respectively (P&amp;lt;0.001). Cox regression analysis indicated that TNM staging, peritoneal metastasis, and elevated CEA levels were independent risk factors for poor prognosis (mortality) in patients with gastric cancer (P&amp;lt;0.05). Serum levels of CA125, AFP, and CEA in patients with gastric cancer were significantly elevated and were correlated with the degree of differentiation and TNM staging. Combined detection had diagnostic efficacy in assessing metastasis and clinical outcomes.

Post hepatectomy liver failure (PHLF) remains a significant cause of morbidity and mortality after major liver resection. Although the etiology of PHLF is multifactorial, an inadequate functional liver remnant (FLR) is felt to be the most important modifiable predictor of PHLF. Pre-operative evaluation of FLR function and volume is of paramount importance before proceeding with any major liver resection. Patients with inadequate or borderline FLR volume must be considered for volume optimization strategies such as portal vein embolization (PVE), two stage hepatectomy with portal vein ligation (PVL), Yttrium-90 radioembolization, and associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). This paper provides an overview of assessing FLR volume and function, and discusses indications and outcomes of commonly used volume optimization strategies.Copyright © 2018 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Liver volumetry is a critical component of safe hepatic surgery, in order to minimize the risk of postoperative liver failure. Liver volumes can be calculated routinely using the time-consuming gold standard method of manual volumetry. The current work sought to evaluate an alternative automatic technique based on a novel 3D virtual planning software, and to compare it to the manual technique.A prospective study of patients undergoing liver resection was conducted. Every patient had a pre and 2-day postoperative CT-scan. For each patient, total, remnant and resected volumes were calculated manually and automatically. Planes of resection were verified by a hepatobiliary surgeon and compared with postoperative volumes. Paired t-tests and correlation coefficients were calculated.A major hepatectomy was carried out in 36/43 patients. The automatic TLV (1,759 mL) and the manual TLV (1,832 mL) were significantly different (p < 0.001), but extremely highly correlated (r = 0.989). The percentages of preoperative RLV (manual 58.5%, automatic 58.9%) were similar, with an excellent correlation of 0.917. The preoperative RLV were matched with the 2-day postoperative RLV showing a significant difference (p = 0.0301). The resected volumes using both techniques (871 and 832 mL) were compared with the resected specimen volume (670 mL), showing a significant difference (p < 0.001) but a high degree of correlation (r = 0.874).The 3D virtual surgical planning software is accurate and reliable in determining the total liver and future remnant liver volumes. This technique demonstrates a good correlation with the manual technique. Future work will be required to confirm these findings and to evaluate the clinical value of the three-dimensional planning platform.

Locally advanced gastric cancer with extensive lymph node metastasis is usually considered unresectable and so treated by chemotherapy. This trial explored the safety and efficacy of preoperative chemotherapy followed by extended surgery in the management of locally advanced gastric adenocarcinoma.Patients with gastric cancer with extensive lymph node metastasis received two or three 28-day cycles of induction chemotherapy with irinotecan (70 mg/m(2) on days 1 and 15) and cisplatin (80 mg/m(2) on day 1), and then underwent gastrectomy with curative intent with D2 plus para-aortic lymphadenectomy. Primary endpoints were 3-year overall survival and incidence of treatment-related death.The study was terminated because of three treatment-related deaths when 55 patients had been enrolled (mortality rate above 5 per cent). Two deaths were due to myelosuppression and one to postoperative complications. Clinical response and R0 resection rates were 55 and 65 per cent respectively. The pathological response rate was 15 per cent. Median overall survival was 14.6 months and the 3-year survival rate 27 per cent.This multimodal treatment of locally advanced gastric cancer provides reasonable 3-year survival compared with historical data, but at a considerable cost in terms of morbidity and mortality.(c) 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Human epidermal growth factor receptor 2 (HER2) is likely overexpressed and/or amplified in locally advanced gastric cancer with extensive (bulky N2 or paraaortic) lymph node metastasis, and patients may benefit from treatment with anti-HER2 antibodies. This study evaluated the frequency of HER2 overexpression and amplification in The Japanese Gastric Cancer Association (JGCA)-N3 and JGCA-bulky N2 tumors and the correlation between HER2 status and survival.HER2 status was assessed using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in tumor tissue samples from 89 patients with gastric adenocarcinoma enrolled in the phase II JCOG0001 and JCOG0405 trials. HER2 positivity was defined as IHC3+ or IHC2+ with confirmatory FISH results.Of the 89 tumor samples, 24 (27 %) showed HER2 positivity, including 16 scored as IHC3+ and 8 as IHC2+ and FISH positive. Multivariate analysis showed that the HER2 positivity rate was significantly higher in evaluable differentiated tumors than in undifferentiated tumors [18/44 (40.9 %) vs. 5/42 (11.9 %)]. Although the apparent OS curve of HER2 positive was superior to that of HER2 negative patients, HER2 status was not a statistically significant prognostic factor in multivariate analysis.The HER2 positivity rate was relatively high in patients with JGCA-bulky N2 and JGCA-N3 gastric adenocarcinoma, suggesting that HER2 evaluation is essential to select the therapeutic regimen for neoadjuvant chemotherapy for this group of patients.

Although patients with gastric cancer liver metastases (GCLM) may achieve survival benefits after radical surgery, there is controversy regarding the surgical indications and choice of surgical methods. This study aims to investigate the impact of hepatic resection (HR) on the prognosis of patients with GCLM who have undergone radical resection of the primary tumor.This study conducted a retrospective analysis of 120 patients with GCLM who have undergone resection of the primary tumor. The patients were divided into an HR group and a non-hepatic resection (NHR) group. Propensity score matching (PSM) was analyzed and patients' prognoses were followed up and compared.The PSM analysis included a total of 88 patients. The HR group had a median overall survival (OS) time of 35.0 months [95% confidence interval (CI): 30.7-39.3], with 1-, 2-, and 3-year survival rates of 88.0%, 81.5%, and 46.8% respectively. The NHR group had a median OS time of 16.0 months (95% CI: 10.5-21.5), with 1-, 2-, and 3-year survival rates of 56.8%, 30.8%, and 22.4% respectively. The median OS time was statistically different between the two groups. Extrahepatic metastasis (hazard ratio =2.777; 95% CI: 1.598-5.223; P=0.002) and HR (hazard ratio =0.154; 95% CI: 0.040-0.594; P=0.007) were significant factors for OS. In the HR group, laparoscopic surgery (P=0.004) and extrahepatic recurrence (P=0.008) were significant factors for intrahepatic recurrence-free survival (IHRFS).HR can significantly improve the prognosis of GCLM with resected primary tumors. Laparoscopic surgery is preferred as the surgical approach. Patients with extrahepatic recurrence have a shorter IHRFS.Copyright © 2025 AME Publishing Company. All rights reserved.

First-line chemotherapy for advanced or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastro-oesophageal junction adenocarcinoma has a median overall survival (OS) of less than 1 year. We aimed to evaluate first-line programmed cell death (PD)-1 inhibitor-based therapies in gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma. We report the first results for nivolumab plus chemotherapy versus chemotherapy alone.In this multicentre, randomised, open-label, phase 3 trial (CheckMate 649), we enrolled adults (≥18 years) with previously untreated, unresectable, non-HER2-positive gastric, gastro-oesophageal junction, or oesophageal adenocarcinoma, regardless of PD-ligand 1 (PD-L1) expression from 175 hospitals and cancer centres in 29 countries. Patients were randomly assigned (1:1:1 while all three groups were open) via interactive web response technology (block sizes of six) to nivolumab (360 mg every 3 weeks or 240 mg every 2 weeks) plus chemotherapy (capecitabine and oxaliplatin every 3 weeks or leucovorin, fluorouracil, and oxaliplatin every 2 weeks), nivolumab plus ipilimumab, or chemotherapy alone. Primary endpoints for nivolumab plus chemotherapy versus chemotherapy alone were OS or progression-free survival (PFS) by blinded independent central review, in patients whose tumours had a PD-L1 combined positive score (CPS) of five or more. Safety was assessed in all patients who received at least one dose of the assigned treatment. This study is registered with ClinicalTrials.gov, NCT02872116.From March 27, 2017, to April 24, 2019, of 2687 patients assessed for eligibility, we concurrently randomly assigned 1581 patients to treatment (nivolumab plus chemotherapy [n=789, 50%] or chemotherapy alone [n=792, 50%]). The median follow-up for OS was 13·1 months (IQR 6·7-19·1) for nivolumab plus chemotherapy and 11·1 months (5·8-16·1) for chemotherapy alone. Nivolumab plus chemotherapy resulted in significant improvements in OS (hazard ratio [HR] 0·71 [98·4% CI 0·59-0·86]; p<0·0001) and PFS (HR 0·68 [98 % CI 0·56-0·81]; p<0·0001) versus chemotherapy alone in patients with a PD-L1 CPS of five or more (minimum follow-up 12·1 months). Additional results showed significant improvement in OS, along with PFS benefit, in patients with a PD-L1 CPS of one or more and all randomly assigned patients. Among all treated patients, 462 (59%) of 782 patients in the nivolumab plus chemotherapy group and 341 (44%) of 767 patients in the chemotherapy alone group had grade 3-4 treatment-related adverse events. The most common any-grade treatment-related adverse events (≥25%) were nausea, diarrhoea, and peripheral neuropathy across both groups. 16 (2%) deaths in the nivolumab plus chemotherapy group and four (1%) deaths in the chemotherapy alone group were considered to be treatment-related. No new safety signals were identified.Nivolumab is the first PD-1 inhibitor to show superior OS, along with PFS benefit and an acceptable safety profile, in combination with chemotherapy versus chemotherapy alone in previously untreated patients with advanced gastric, gastro-oesophageal junction, or oesophageal adenocarcinoma. Nivolumab plus chemotherapy represents a new standard first-line treatment for these patients.Bristol Myers Squibb, in collaboration with Ono Pharmaceutical.Copyright © 2021 Elsevier Ltd. All rights reserved.

Gastric and gastroesophageal junction cancers are diagnosed in more than 1 million people worldwide annually, and few effective treatments are available. Sintilimab, a recombinant human IgG4 monoclonal antibody that binds to programmed cell death 1 (PD-1), in combination with chemotherapy, has demonstrated promising efficacy.To compare overall survival of patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction cancers who were treated with sintilimab with chemotherapy vs placebo with chemotherapy. Also compared were a subset of patients with a PD ligand 1 (PD-L1) combined positive score (CPS) of 5 or more (range, 1-100).Randomized, double-blind, placebo-controlled, phase 3 clinical trial conducted at 62 hospitals in China that enrolled 650 patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma between January 3, 2019, and August 5, 2020. Final follow-up occurred on June 20, 2021.Patients were randomized 1:1 to either sintilimab (n = 327) or placebo (n = 323) combined with capecitabine and oxaliplatin (the XELOX regimen) every 3 weeks for a maximum of 6 cycles. Maintenance therapy with sintilimab or placebo plus capecitabine continued for up to 2 years.The primary end point was overall survival time from randomization.Of the 650 patients (mean age, 59 years; 483 [74.3%] men), 327 were randomized to sintilimab plus chemotherapy and 323 to placebo plus chemotherapy. Among the randomized patients, 397 (61.1%) had tumors with a PD-L1 CPS of 5 or more; 563 (86.6%) discontinued study treatment and 388 (59.7%) died; 1 patient (<0.1%) was lost to follow-up. Among all randomized patients, sintilimab improved overall survival compared with placebo (median, 15.2 vs 12.3 months; stratified hazard ratio [HR], 0.77 [95% CI, 0.63-0.94]; P = .009). Among patients with a CPS of 5 or more, sintilimab improved overall survival compared with placebo (median, 18.4 vs 12.9 months; HR, 0.66 [95% CI, 0.50-0.86]; P = .002). The most common grade 3 or higher treatment-related adverse events were decreased platelet count (sintilimab, 24.7% vs placebo, 21.3%), decreased neutrophil count (sintilimab, 20.1% vs placebo, 18.8%), and anemia (sintilimab, 12.5% vs placebo, 8.8%).Among patients with unresectable locally advanced or metastatic gastric and gastroesophageal junction adenocarcinoma treated with first-line chemotherapy, sintilimab significantly improved overall survival for all patients and for patients with a CPS of 5 or more compared with placebo.ClinicalTrials.gov Identifier: NCT03745170.

PD-1 inhibitors combined with chemotherapy have shown efficacy in gastric or gastro-esophageal junction cancer. We compared the efficacy and safety of pembrolizumab plus chemotherapy with placebo plus chemotherapy in participants with locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma.KEYNOTE-859 is a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial, done at 207 medical centres across 33 countries. Eligible participants were aged 18 years and older with previously untreated histologically or cytologically confirmed locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) to receive pembrolizumab or placebo 200 mg, administered intravenously every 3 weeks for up to 35 cycles. All participants received investigator's choice of fluorouracil (intravenous, 800 mg/m per day) administered continuously on days 1-5 of each 3-week cycle plus cisplatin (intravenous, 80 mg/m) administered on day 1 of each 3-week cycle or capecitabine (oral, 1000 mg/m) administered twice daily on days 1-14 of each 3-week cycle plus oxaliplatin (intravenous, 130 mg/m) administered on day 1 of each 3-week cycle. Randomisation was done using a central interactive voice-response system and stratified by geographical region, PD-L1 status, and chemotherapy in permuted block sizes of four. The primary endpoint was overall survival, assessed in the intention-to-treat (ITT) population, and the populations with a PD-L1 combined positive score (CPS) of 1 or higher, and PD-L1 CPS of 10 or higher. Safety was assessed in the as-treated population, which included all randomly assigned participants who received at least one dose of study intervention. Here, we report the results of the interim analysis. This study is registered with ClinicalTrials.gov, NCT03675737, and recruitment is complete.Between Nov 8, 2018, and June 11, 2021, 1579 (66%) of 2409 screened participants were randomly assigned to receive pembrolizumab plus chemotherapy (pembrolizumab group; n=790) or placebo plus chemotherapy (placebo group; n=789). Most participants were male (527 [67%] of 790 participants in the pembrolizumab plus chemotherapy group; 544 [69%] of 789 participants in the placebo plus chemotherapy group) and White (426 [54%]; 435 [55%]). Median follow-up at the data cutoff was 31·0 months (IQR 23·0-38·3). Median overall survival was longer in the pembrolizumab group than in the placebo group in the ITT population (12·9 months [95% CI 11·9-14·0] vs 11·5 months [10·6-12·1]; hazard ratio [HR] 0·78 [95% CI 0·70-0·87]; p<0·0001), in participants with a PD-L1 CPS of 1 or higher (13·0 months [11·6-14·2] vs 11·4 months [10·5-12·0]; 0·74 [0·65-0·84]; p<0·0001), and in participants with a PD-L1 CPS of 10 or higher (15·7 months [13·8-19·3] vs 11·8 months [10·3-12·7]; 0·65 [0·53-0·79]; p<0·0001). The most common grade 3-5 adverse events of any cause were anaemia (95 [12%] of 785 participants in the pembrolizumab group vs 76 [10%] of 787 participants in the placebo group) and decreased neutrophil count (77 [10%] vs 64 [8%]). Serious treatment-related adverse events occurred in 184 (23%) participants in the pembrolizumab group and 146 (19%) participants in the placebo group. Treatment-related deaths occurred in eight (1%) participants in the pembrolizumab group and 16 (2%) participants in the placebo group. No new safety signals were identified.Participants in the pembrolizumab plus chemotherapy group had a significant and clinically meaningful improvement in overall survival with manageable toxicity compared with participants in the placebo plus chemotherapy group. Therefore, pembrolizumab with chemotherapy might be a first-line treatment option for patients with locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma.Merck Sharp and Dohme.Copyright © 2023 Elsevier Ltd. All rights reserved.

To evaluate the efficacy and safety of tislelizumab added to chemotherapy as first line (primary) treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma compared with placebo plus chemotherapy.

Gastric cancer, including gastroesophageal junction cancer, is one of the most commonly diagnosed cancers worldwide, with high mortality. Sugemalimab is a fully human anti–programmed death-ligand 1 (PD-L1) antibody. The combination of sugemalimab and chemotherapy showed promising antitumor activity and safety in a phase 1b study among patients with treatment-naive, unresectable, locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma. This combination was further evaluated in the GEMSTONE-303 phase 3 trial.

Zolbetuximab, a monoclonal antibody targeting claudin-18 isoform 2 (CLDN18.2), has shown efficacy in patients with CLDN18.2-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma. We report the results of the SPOTLIGHT trial, which investigated the efficacy and safety of first-line zolbetuximab plus mFOLFOX6 (modified folinic acid [or levofolinate], fluorouracil, and oxaliplatin regimen) versus placebo plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma.SPOTLIGHT is a global, randomised, placebo-controlled, double-blind, phase 3 trial that enrolled patients from 215 centres in 20 countries. Eligible patients were aged 18 years or older with CLDN18.2-positive (defined as ≥75% of tumour cells showing moderate-to-strong membranous CLDN18 staining), HER2-negative (based on local or central evaluation), previously untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma, with radiologically evaluable disease (measurable or non-measurable) according to Response Evaluation Criteria in Solid Tumors version 1.1; an Eastern Cooperative Oncology Group performance status score of 0 or 1; and adequate organ function. Patients were randomly assigned (1:1) via interactive response technology and stratified according to region, number of organs with metastases, and previous gastrectomy. Patients received zolbetuximab (800 mg/m loading dose followed by 600 mg/m every 3 weeks) plus mFOLFOX6 (every 2 weeks) or placebo plus mFOLFOX6. The primary endpoint was progression-free survival assessed by independent review committee in all randomly assigned patients. Safety was assessed in all treated patients. The study is registered with ClinicalTrials.gov, NCT03504397, and is closed to new participants.Between June 21, 2018, and April 1, 2022, 565 patients were randomly assigned to receive either zolbetuximab plus mFOLFOX6 (283 patients; the zolbetuximab group) or placebo plus mFOLFOX6 (282 patients; the placebo group). At least one dose of treatment was administered to 279 (99%) of 283 patients in the zolbetuximab group and 278 (99%) of 282 patients in the placebo group. In the zolbetuximab group, 176 (62%) patients were male and 107 (38%) were female. In the placebo group, 175 (62%) patients were male and 107 (38%) were female. The median follow-up duration for progression-free survival was 12·94 months in the zolbetuximab group versus 12·65 months in the placebo group. Zolbetuximab treatment showed a significant reduction in the risk of disease progression or death compared with placebo (hazard ratio [HR] 0·75, 95% CI 0·60-0·94; p=0·0066). The median progression-free survival was 10·61 months (95% CI 8·90-12·48) in the zolbetuximab group versus 8·67 months (8·21-10·28) in the placebo group. Zolbetuximab treatment also showed a significant reduction in the risk of death versus placebo (HR 0·75, 95% CI 0·60-0·94; p=0·0053). Treatment-emergent grade 3 or worse adverse events occurred in 242 (87%) of 279 patients in the zolbetuximab group versus 216 (78%) of 278 patients in the placebo group. The most common grade 3 or worse adverse events were nausea, vomiting, and decreased appetite. Treatment-related deaths occurred in five (2%) patients in the zolbetuximab group versus four (1%) patients in the placebo group. No new safety signals were identified.Targeting CLDN18.2 with zolbetuximab significantly prolonged progression-free survival and overall survival when combined with mFOLFOX6 versus placebo plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Zolbetuximab plus mFOLFOX6 might represent a new first-line treatment in these patients.Astellas Pharma, Inc.Copyright © 2023 Elsevier Ltd. All rights reserved.

There is an urgent need for first-line treatment options for patients with human epidermal growth factor receptor 2 (HER2)-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma. Claudin-18 isoform 2 (CLDN18.2) is expressed in normal gastric cells and maintained in malignant G/GEJ adenocarcinoma cells. GLOW (closed enrollment), a global, double-blind, phase 3 study, examined zolbetuximab, a monoclonal antibody that targets CLDN18.2, plus capecitabine and oxaliplatin (CAPOX) as first-line treatment for CLDN18.2-positive, HER2-negative, locally advanced unresectable or mG/GEJ adenocarcinoma. Patients (n = 507) were randomized 1:1 (block sizes of two) to zolbetuximab plus CAPOX or placebo plus CAPOX. GLOW met the primary endpoint of progression-free survival (median, 8.21 months versus 6.80 months with zolbetuximab versus placebo; hazard ratio (HR) = 0.687; 95% confidence interval (CI), 0.544-0.866; P = 0.0007) and key secondary endpoint of overall survival (median, 14.39 months versus 12.16 months; HR = 0.771; 95% CI, 0.615-0.965; P = 0.0118). Grade ≥3 treatment-emergent adverse events were similar with zolbetuximab (72.8%) and placebo (69.9%). Zolbetuximab plus CAPOX represents a potential new first-line therapy for patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or mG/GEJ adenocarcinoma. ClinicalTrials.gov identifier: NCT03653507.© 2023. The Author(s).

Microsatellite instability-high (MSI-H) advanced gastric or esophagogastric junction cancer (AGC), accounting for 5%-6% of all AGC cases, has shown an enhanced responsiveness to immunotherapy. We performed a single-arm phase II study to evaluate the combination of nivolumab (NIVO) and low-dose (LD) ipilimumab (IPI) for first-line treatment of MSI-H AGC.Patients with MSI-H AGC received NIVO (240 mg once every 2 weeks) and IPI (1 mg/kg once every 6 weeks). The primary end point was overall response rate (ORR) assessed by blinded independent central review. Secondary end points included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety, and biomarker analysis. MSI-H status was confirmed with an MSI-IVD Kit (Falco).Twenty-nine patients were enrolled. The ORR was 62.1% (95% CI, 42.3 to 79.3), with a complete response rate of 10.3%. The DCR was 79.3% (95% CI, 60.3 to 92.0). Treatment-related adverse events (TRAEs) of any grade occurred in 93.1% of patients, with those of grade ≥3 manifesting in 37.9% of patients. At the data cutoff (median follow-up of 9.0 months), treatment had been discontinued in 21 patients, with such discontinuation being due to TRAEs in 12 (41.4%) patients. However, after exclusion of one patient with progressive disease, the remaining 11 patients showed long-term antitumor efficacy after treatment discontinuation (range of response duration, 0.9+ to 15.6+ months). The median PFS was 13.8 months (95% CI, 13.7 months to not reached [NR]) and the median OS was NR (95% CI, 13.7 months to NR), with a 12-month OS rate of 79.5%.NIVO plus LD-IPI showed robust and durable antitumor efficacy as a first-line treatment for MSI-H AGC. Although TRAEs often led to treatment discontinuation, treatment efficacy was subsequently sustained in most patients.

As minimally invasive techniques advances, minimally invasive surgery (MIS) has emerged as an alternative modality for advanced gastric cancer. In this study, we compared the short- and long-term surgical outcomes of MIS and conventional open surgery for gastric cancer liver metastasis (GCLM) in terms of safety, feasibility, and efficacy.This retrospective study used data from a prospective database at the Chinese People's Liberation Army General Hospital. From January 2006 to June 2016, 53 gastric cancer patients with synchronous liver metastasis accepted radical gastrectomy combined with either or both hepatectomy and radiofrequency ablation for liver metastases. The 53 patients enrolled in the study were divided into two groups: a conventional open surgery group (n = 42) and an MIS group (n = 11). Propensity score matching (PSM) analysis was performed to overcome possible bias.With PSM performed at a 1:3 ratio, 11 patients who received MIS were compared with 33 open surgery cases. Mean operation time was significantly longer for the MIS group compared with the open surgery group (301 vs. 236 min, P = 0.032), while the open surgery group had a larger estimated blood loss than the MIS group (421 vs. 196 ml, P = 0.019). Time to first flatus and postoperative complications, including Clavien-Dindo classification, were similar in the two groups. However, patients undergoing MIS had a significantly shorter time to first sips of water (P = 0.020) and soft diet (P = 0.020) compared with open surgery counterparts. Long-term outcomes were comparable between groups (P = 0.090) after adjustment by PSM analysis.MIS achieved superior short-term outcomes and comparable long-term outcomes compared with open surgery in GCLM patients. For experienced surgeons, both laparoscopic and robotic methods of MIS are reasonable approaches for the management of highly selected GCLM patients.

The objectives of this systematic review and pooled analysis were to examine long-term survival, morbidity, and mortality following thermal ablation of gastric cancer hepatic metastases and to identify prognostic factors that improve survival.

The optimal treatments for gastric cancer with liver metastases (GCLM) remain controversial. This study aimed to evaluate the efficacy of hepatectomy, RFA and TACE as local treatments for GCLM.From 2001 to 2015, 119 consecutive patients who received multidisciplinary treatments based on curative gastrectomy and local treatments (hepatectomy, RFA and TACE) for liver metastases were enrolled in this retrospective cohort study. Patients were divided into Group A (46, hepatectomy) and Group B (73, either or both RFA and TACE). Propensity score matching analysis was employed.The propensity model revealed that hepatectomy was associated with significantly longer OS compared with either or both RFA and TACE (P=0.021). The 1-, 3- and 5-year OS rates were 80.5%, 41.5% and 24.4%, respectively in Group A; and 85.4%, 21.9% and 12.2%, respectively in Group B. Subgroup analyses indicated that hepatectomy was associated with significantly longer long-term survival compared with TACE (P=0.033) and RFA (P=0.010). TACE had a similar efficacy as RFA (P=0.518), but with significantly lower costs (P=0.014) in for patients with metachronous GCLM.Hepatectomy is the optimal local treatment for GCLM when surgical R0 resection is intended. TACE attained a similar prognosis as RFA with relatively high cost-effectiveness, particularly for patients with metachronous GCLM.

We previously demonstrated the safety and efficacy of low-dose, short-interval target vessel regional chemotherapy (TVRC(LDSI)) delivered through the hepatic artery with transarterial embolization (TAE) in patients with advanced gastric cancer (AGC). The present study aimed to compare the efficacy of TAE + TVRC(LDSI) with that of standard TAE + TVRC in AGC patients with liver metastases who failed to respond to first- or second-line systemic chemotherapy.This study recruited a total of 58 GC patients with liver metastases after failure of first- or second-line systemic chemotherapy. Twenty-eight patients were assigned to the TAE + TVRC(LDSI) group and 30 patients to the TAE + TVRC group. The primary end point was overall survival (OS(TVRC)), which was defined as the time from the initiation of TVRC until the last follow-up or death.OS(TVRC), time to progression (TTP) until appearance of intra- and extrahepatic metastases, and overall TTP and treatment periods in the TAE + TVRC(LDSI) group were all significantly longer than in the TAE + TVRC group (all p < 0.001).TAE + TVRC(LDSI) had a higher efficacy and safety, which was reflected by OS rates, progression-free survival rates, longer duration of treatment and milder side effects compared to standard TAE + TVRC.© 2015 S. Karger AG, Basel.

The most frequent pattern of recurrence is remnant liver after hepatectomy for gastric cancer liver metastases (GLM). The evidence of adjuvant hepatic artery infusion chemotherapy (HAIC) after hepatectomy for GLM is lacking. The aim of this study was to evaluate the efficacy of adjuvant HAIC after hemihepatectomy for GLM.Between 2001 and 2012, 14 patients who underwent hemihepatectomy for GLM were included in this study. Adjuvant HAIC to the remnant hemiliver was the FEM regimen (333 mg/m 5-fluorouracil each week, 30 mg/m epirubicin once every 4 weeks, and 2.7 mg/m mitomycin-C once every 2 weeks) and was administered for 6 months after hemihepatectomy. Clinicopathological prognostic factors for survival were analyzed using a prospectively collected database.Nine patients had solitary GLM, and 5 patients had multiple GLM before surgery. The median period from hemihepatectomy to HAIC was 30 days. The 6-month HAIC completion rate was 79% (n = 11/14). Reasons of HAIC failure included liver dysfunction (n = 1), catheter infection (n = 1), and development of multiple recurrence (n = 1). The median follow-up was 29 (range 8-166) months. Recurrences were detected in 8 patients (57%). The site of recurrences included lung (n = 1), lymph nodes (n = 1), peritoneal dissemination (n = 1), brain (n = 1), pleural (n = 1), and multiple sites (n = 3). The overall 5-year survival rate was 43%. The pathological T4 classification and the preoperative CEA ≥5 ng/mL were significant prognostic factors for overall survival.Adjuvant HAIC after hemihepatectomy for GLM prevents remnant liver recurrence and may contribute to long-term survival.Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

For patients with liver metastases from gastric cancer (LMGC), combination chemotherapy with fluoropyrimidines and platinum agents has been recognized as standard treatment. However, the prognosis of hepatic progression after first-line treatment failure remains poor. When hepatic progression occurs, hepatic arterial infusion (HAI) chemotherapy may be helpful for preventing disease progression.To retrospectively assess the feasibility and efficacy of HAI chemotherapy using 5-fluorouracil, epirubicin, and mitomycin C (FEM) for patients with LMGC after failure of systemic S-1 plus cisplatin.We reviewed the records of patients who received HAI chemotherapy using FEM for LMGC that progressed during systemic S-1 plus cisplatin treatment while extrahepatic disease was decreased or did not appear. HAI chemotherapy was given as second-line therapy using 5-fluorouracil (330 mg/m(2) weekly), epirubicin (30 or 40 mg/m(2) every 4 weeks), and mitomycin C (2.7 mg/m(2) biweekly).Fourteen patients were analyzed. Toxicity of HAI chemotherapy was generally mild. The objective response rate was 42.9%, including a complete response rate of 14.3%. Median times to hepatic and extrahepatic progression were 9.2 and 7.4 months, respectively. Of 12 patients with documented progression after HAI chemotherapy, 10 patients (83.3%) received additional treatment, including irinotecan or taxanes. Overall, median survival was 12.7 months.Our findings suggest that HAI chemotherapy using FEM is a feasible and effective treatment for patients with LMGC after failure of systemic S-1 plus cisplatin. HAI chemotherapy employed in the second-line setting is useful for achieving long-term disease control of LMGC.© The Foundation Acta Radiologica 2015.

Radiation segmentectomy is a dynamic image-guided therapy for hepatic malignancies that uses yttrium 90 transarterial radioembolization to deliver high radiation doses to targeted hepatic segments, achieving high and sustained response rates.

Background: The purpose of this retrospective study was to determine whether RFA could provide an alternative treatment modality for selected patients who are not candidates for hepatic resection.Methods: A total of 18 consecutive patients with liver metastases alone from gastric cancer treated with radiofrequency ablation (RFA, n = 11) or hepatic resection (HR, n = 7) at Seoul St. Mary's Hospital, Korea, between January 2000 and September 2014, were enrolled.Results: The median OS and DFS in the RFA group were 40.5 +/- 22.3 and 10.3 +/- 1.07 months, respectively. There was no significant difference between the RFA and HR groups in terms of baseline characteristics except for performance status. Mean survival and DFS times of all patients were 60.1 +/- 9.4 and 40.9 +/- 10.2 months, respectively. Mean OS times in the HR and RFA groups were 67.5 +/- 15.4 and 51.1 +/- 9.8 months (P = 0.671), respectively, and the mean DFS time in the HR group (74.1 +/- 14.2 months) was longer than that in the RFA group (26.9 +/- 9.2 months), but the difference was not significant (P = 0.076).Conclusions: In patients who are not candidates for surgical treatment, RFA may be an alternative to HR.

Indications and efficacy of surgical treatment for liver metastases from gastric cancer (LMGCs) remain controversial. This retrospective study was designed to clarify the benefits of surgical treatment and identify prognostic factors.Between December 1997 and December 2015, 34 consecutive patients underwent hepatic resection and surgical microwave ablation for synchronous or metachronous LMGCs at our institution. We analyzed their cumulative overall survival (OS) and recurrence-free survival (RFS) rates and clinical parameters to identify predictors of prognosis.Of the 34 patients, 14 underwent hepatic resection, 13 underwent surgical microwave ablation, and 7 underwent hepatic resection combined with surgical microwave ablation. Their OS rates were 1-year: 84.4%, 3-year: 38.6%, and 5-year: 34.7%; and their RFS rates were 1-year: 38.5%, 3-year: 28.0%, and 5-year: 28.0%. OS did not significantly vary among the surgical procedures. In multivariable analysis, positive of both CEA and CA19-9 were independent predictors of poor survival (hazard ratio [HR] 4.51; P = 0.049) and early recurrence (HR 5.70; P = 0.047).Both hepatic resection and surgical microwave ablation for LMGCs are effective and can improve survival in selected patients.Copyright © 2017. Published by Elsevier Taiwan LLC.

Liver metastases occur in approximately 4%-14% of gastric cancer patients and are associated with high mortality. However, no standardized treatment approach is available for these patients. We aimed to assess the clinical outcomes of patients with gastric cancer liver metastases (GCLM) who underwent percutaneous cryoablation.We retrospectively enrolled 19 patients with 27 metastatic hepatic tumors who underwent cryoablation for liver metastases after gastrectomy for primary gastric cancer. Complications, overall survival (OS), local tumor progression-free survival (PFS), recurrence rates, and quality of life were assessed.After cryoablation therapy, the median OS for all 19 patients was 16.0 months (range, 5-50 months), and the 1-, 2-, and 3-year OS rates were 78.9%, 43.4%, and 21.7%, respectively. The median local tumor PFS was 8.0 months (range, 3-24 months), and the local tumor PFS rates at 6 and 12 months were 59.2% and 23.2%, respectively. Overall, patients' quality of life improved after cryoablation therapy (P < 0.05). Complications in this study were mild; no severe complications caused by technique were detected.Cryoablation provided good local control, improved patients' quality of life and had a low complication rate. Our research showed that cryoablation may be an effective palliative treatment for GCLM.Copyright © 2018 Elsevier Inc. All rights reserved.

Liver metastases from gastric cancer (LMGC) is a non-curable, fatal disease with a 5-year survival rate of <10%. Although various local treatments have been applied, their clinical utility has not been established. The purpose of this study was to investigate the safety and effectiveness of proton beam therapy (PBT) for the treatment of patients with LMGC. A total of nine patients (seven men, two women; aged 56-78 years) with LMGC who received PBT between 2002 and 2012 were retrospectively reviewed. Patients who had tumors confined to the liver were investigated, and patients who had extrahepatic tumors were excluded. Six of the patients had solitary tumors, and three patients had multiple tumors. The total irradiation dose was 64-77 Gy relative biological effectiveness (RBE), and three patients received concurrent chemotherapy. The overall and progression-free survival (OS and PFS) rates, local control (LC) rate, and adverse effects were investigated. All patients completed treatment without interruption, and late adverse effects of higher than Grade 3 were not observed. The OS rates at 1, 3 and 5 years were 100%, 78% and 56%, respectively (median, 5.5 years); the PFS rates were 67%, 40% and 40% (median, 2.6 years); and the LC rates were 89%, 71% and 71%. PBT was demonstrated to be a safe treatment, and the OS and PFS rates were not inferior to those for other types of local treatment. Therefore, PBT should be considered as an effective local treatment option for patients with LMGC.© The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

The purpose of this study was to explore the efficacy and safety of high intensity focused ultrasound (HIFU) in gastric cancer with liver metastasis (GCLM) patients who were contraindicated for either hepatectomy or radiofrequency ablation (RFA).This is a prospective, observational study on GCLM patients with 1-3 liver metastases. The primary gastric lesions were thoroughly resected and any case that exhibited extra-hepatic metastasis was excluded. A 1:2:2 propensity score-matching analysis was performed using a logistic regression model on the HIFU group, best supportive care (BSC) group, and palliative chemotherapy (PC) group. The primary endpoints include progression-free survival (PFS) and overall survival (OS).Forty patients were finally included, there were 8 cases in HIFU group, 16 cases in BSC group, and 16 cases in PC group. The median follow-up time for the entire cohort was 10 months. The median PFS was 16.5 months in HIFU group, 2 months in BSC group, and 5 months in PC group. The median OS was 27.5 months in the HIFU group, 7 months in the BSC group, and 11.5 months in the PC group. Additionally, no grade 3 or higher adverse events occurred in the HIFU group.The results of this study showed that HIFU treatment could improve the long-term prognosis of GCLM patients without a significant increase in the occurrence of adverse events. Compared with PC and BSC, HIFU is the preferred treatment option when GCLM patients without extra-hepatic metastasis are unable to undergo either surgery or RFA.© 2021. The Author(s).

Approximately 15-20% of advanced gastric and gastro-oesophageal junction cancers overexpress HER2. In DESTINY-Gastric01, the HER2-targeted antibody-drug conjugate trastuzumab deruxtecan improved response and overall survival versus chemotherapy in patients from Japan and South Korea with locally advanced or metastatic HER2-positive gastric or gastro-oesophageal junction cancer whose disease progressed after two lines of previous therapy including trastuzumab. Here, we report primary and updated analyses of the single-arm, phase 2 DESTINY-Gastric02 trial, which aimed to examine trastuzumab deruxtecan in patients living in the USA and Europe.DESTINY-Gastric02 is a single-arm, phase 2 study in adult patients from 24 study sites in the USA and Europe (Belgium, Spain, Italy, and the UK). Eligible patients were aged at least 18 years and had an Eastern Cooperative Oncology Group performance status of 0 or 1, pathologically documented unresectable or metastatic gastric or gastro-oesophageal junction cancer, progressive disease on or after first-line therapy with a trastuzumab-containing regimen, with at least one measurable lesion per Response Evaluation Criteria in Solid Tumours (version 1.1), and centrally confirmed HER2-positive disease on a postprogression biopsy. Patients were given 6·4 mg/kg of trastuzumab deruxtecan intravenously every 3 weeks until disease progression, withdrawal by patient, physician decision, or death. The primary endpoint was confirmed objective response rate by independent central review. The primary endpoint and safety were assessed in the full analysis set (ie, participants who received at least one dose of study drug). Here, we report the primary analysis of this study, with a data cutoff of April 9, 2021, and an updated analysis, with a data cutoff of Nov 8, 2021. This trial is registered with ClinicalTrials.gov, NCT04014075, and is ongoing.Between Nov 26, 2019, and Dec 2, 2020, 89 patients were screened and 79 were enrolled and subsequently treated with trastuzumab deruxtecan (median age 60·7 years [IQR 52·0-68·3], 57 [72%] of 79 were male, 22 [28%] were female, 69 [87%] were White, four [5%] were Asian, one [1%] was Black or African American, one [1%] was Native Hawaiian or Pacific Islander, one had missing race, and three [4%] were other races). At the primary analysis (median follow-up 5·9 months [IQR 4·6-8·6 months]), confirmed objective response was reported in 30 (38% [95% CI 27·3-49·6]) of 79 patients, including three (4%) complete responses and 27 (34%) partial responses, as assessed by independent central review. As of data cutoff for the updated analysis (median follow-up 10·2 months [IQR 5·6-12·9]), a confirmed objective response was reported in 33 (42% [95% CI 30·8-53·4]) of 79 patients, including four (5%) complete responses and 29 (37%) partial responses, as assessed by independent central review. The most common grade 3 or worse treatment-emergent adverse events were anaemia (11 [14%]), nausea (six [8%]), decreased neutrophil count (six [8%]), and decreased white blood cell count (five [6%]). Drug-related serious treatment-emergent adverse events occurred in ten patients (13%). Deaths determined to be associated with study treatment occurred in two patients (3%) and were due to interstitial lung disease or pneumonitis.These clinically meaningful results support the use of trastuzumab deruxtecan as second-line therapy in patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer.Daiichi Sankyo and AstraZeneca.Copyright © 2023 Elsevier Ltd. All rights reserved.

Outcomes are poor in patients with HER2-negative, advanced gastric or gastro-oesophageal junction adenocarcinomas. In this study, we investigated efficacy and safety of the first-in-class, afucosylated, humanised IgG1 anti-fibroblast growth factor receptor 2 isoform IIb (FGFR2b) monoclonal antibody bemarituzumab with modified 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) in patients with FGFR2b-selected gastric or gastro-oesophageal junction adenocarcinoma.In the randomised, double-blind, placebo-controlled phase 2 trial (FIGHT), patients aged 18 years and older with HER2 non-positive, FGFR2b-selected gastric or gastro-oesophageal junction adenocarcinoma, and an Eastern Cooperative Oncology Group performance status of 0-1 were recruited from 144 clinical sites across 17 countries. Patients with previous treatment with any selective inhibitor of the FGF-FGFR pathway were excluded. Eligible patients were randomly assigned (1:1), using permuted-block randomisation (block size of four) and a central interactive voice-web-based response system, stratified by geographical region, previous treatment with curative intent, and administration of mFOLFOX6 while being screened for FGFR2b status, to either bemarituzumab (15 mg/kg of bodyweight) or matched placebo intravenously every 2 weeks. All patients also received mFOLFOX6 (oxaliplatin 85 mg/m, leucovorin 400 mg/m, and 5-fluorouracil as a 400 mg/m bolus followed by 2400 mg/m over approximately 46 h) intravenously every 2 weeks. Patients were given treatment until disease progression (defined by Response Evaluation Criteria in Solid Tumours [RECIST] version 1.1), unacceptable toxicity, withdrawal of consent, or death. The primary endpoint was progression-free survival in the intention-to-treat population (defined as all patients randomly assigned to treatment). Safety was assessed in all patients who received at least one dose of assigned treatment. This study is registered with ClinicalTrials.gov, NCT03694522, and is now complete.Between Nov 14, 2017, and May 8, 2020, 910 patients were screened and 155 were randomly assigned to the bemarituzumab (n=77) or placebo group (n=78). Median age was 60·0 years (IQR 51·0-67·0), 44 (28%) participants were women, 111 (72%) were men, 89 (57%) were Asian, and 61 (39%) were White. At the time of the primary analysis and at a median follow-up of 10·9 months (IQR 6·3-14·2), median progression-free survival was 9·5 months (95% CI 7·3-12·9) in the bemarituzumab group and 7·4 months (5·8-8·4) in the placebo group (hazard ratio [HR] 0·68 [95% CI 0·44-1·04; p=0·073). Common grade 3 or worse adverse events were decreased neutrophil count (23 [30%] of 76 in the bemarituzumab group vs 27 [35%] of 77 in the placebo group), cornea disorder (18 [24%] vs none), neutropenia (ten [13%] vs seven [9%]), stomatitis (seven [9%] vs one [1%]), and anaemia (six [8%] vs ten [13%]). Serious treatment-emergent adverse events were reported in 24 (32%) patients in the bemarituzumab group and 28 (36%) in the placebo group. Serious mFOLFOX6 treatment-related adverse events occurred in nine (12%) patients in the bemarituzumab group and in 15 (19%) patients in the placebo group. All-grade corneal events (adverse events of special interest) occurred in 51 (67%) patients in the bemarituzumab group and eight (10%) in the placebo group; grade 3 corneal events were reported only in 18 (24%) patients in the bemarituzumab group. Treatment-related deaths occurred in three patients in the bemarituzumab group (two due to sepsis, one due to pneumonia) and none in the placebo group.In this exploratory phase 2 study, despite no statistically significant improvement in progression-free survival, treatment with bemarituzumab showed promising clinical efficacy. Confirmatory phase 3 trials of bemarituzumab plus mFOLFOX6 powered to demonstrate statistical significance are being investigated in patients with previously untreated, FGFR2b-overexpressing, advanced gastric or gastro-oesophageal junction adenocarcinoma.Five Prime Therapeutics.Copyright © 2022 Elsevier Ltd. All rights reserved.

Claudin18.2 (CLDN18.2) is highly expressed with the development of various malignant tumors, especially gastrointestinal cancers, and is emerging as a new target for cancer treatment. Satricabtagene autoleucel (satri-cel)/CT041 is an autologous chimeric antigen receptor (CAR) T cell targeting CLDN18.2, and the interim results of the CT041-CG4006 trial were reported in June 2022. Here we present the final results of this single-arm, open-label, phase 1 trial, which evaluated the safety and efficacy of satri-cel in patients with CLDN18.2-positive advanced gastrointestinal cancers. This trial included a dose-escalation stage (n = 15) and a dose-expansion stage in four different cohorts (total n = 83): cohort 1, satri-cel monotherapy in 61 patients with standard chemotherapy-refractory gastrointestinal cancers; cohort 2, satri-cel plus anti-PD-1 therapy in 15 patients with standard chemotherapy-refractory gastrointestinal cancers; cohort 3, satri-cel as sequential treatment after first-line therapy in five patients with gastrointestinal cancers; and cohort 4, satri-cel monotherapy in two patients with anti-CLDN18.2 monoclonal antibody-refractory gastric cancer. The primary endpoint was safety; secondary endpoints included efficacy, pharmacokinetics and immunogenicity. A total of 98 patients received satri-cel infusion, among whom 89 were dosed with 2.5 × 10, six with 3.75 × 10 and three with 5.0 × 10 CAR T cells. Median follow-up was 32.4 months (95% confidence interval (CI): 27.3, 36.5) since apheresis. No dose-limiting toxicities, treatment-related deaths or immune effector cell-associated neurotoxicity syndrome were reported. Cytokine release syndrome occurred in 96.9% of patients, all classified as grade 1-2. Gastric mucosal injuries were identified in eight (8.2%) patients. The overall response rate and disease control rate in all 98 patients were 38.8% and 91.8%, respectively, and the median progression-free survival and overall survival were 4.4 months (95% CI: 3.7, 6.6) and 8.8 months (95% CI: 7.1, 10.2), respectively. Satri-cel demonstrates therapeutic potential with a manageable safety profile in patients with CLDN18.2-positive advanced gastrointestinal cancer. ClinicalTrials.gov identifier: NCT03874897.© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.

Claudin-18 isoform 2 (CLDN18.2) has emerged as a promising therapeutic target in gastric or gastro-oesophageal junction cancer. Satricabtagene autoleucel (satri-cel; also known as CT041), an autologous CLDN18.2-specific chimeric antigen receptor (CAR) T-cell therapy, showed encouraging activity in previously treated patients with advanced gastric or gastro-oesophageal junction cancer in phase 1 clinical trials. In this Article, we report the primary results from the phase 2 pivotal trial (CT041-ST-01) investigating the efficacy and safety of satri-cel for gastric or gastro-oesophageal junction cancer.In this open-label, multicentre, randomised controlled trial conducted in China, patients with CLDN18.2-positive (immunohistochemistry expression intensity ≥2+ and positive tumour cells ≥40%) advanced gastric or gastro-oesophageal junction cancer, who were refractory to at least two previous lines of treatment, were randomly allocated (2:1) to receive satri-cel or treatment of physician's choice (TPC). In the satri-cel group, satri-cel was infused up to three times at a dose of 250 × 10 cells. For the TPC group, one of the standard-of-care drugs (nivolumab, paclitaxel, docetaxel, irinotecan, or rivoceranib [apatinib]) was given, per the physician's decision. Those who had disease progression or drug intolerance in the TPC group could receive subsequent satri-cel, if eligible. The primary endpoint was progression-free survival, assessed by an independent review committee, in the intention-to-treat population. This study is registered with ClinicalTrials.gov (NCT04581473), and is closed to new patients.Between March 22, 2022, and July 29, 2024, 266 patients were screened, of whom 156 were randomly allocated to the satri-cel group (n=104) or TPC group (n=52). 88 (85%) patients in the satri-cel group and 48 (92%) patients in the TPC group received study drug. In the satri-cel group, 28 (27%) patients had previously received three or more lines of treatment and 72 (69%) patients had peritoneal metastasis. In the TPC group, ten (19%) patients had previously received three or more lines of treatment and 31 (60%) patients had peritoneal metastasis. The median follow-up time for progression-free survival was 9·07 months (95% CI 6·21-13·01) in the satri-cel group and 3·45 months (2·89-not estimable) in the TPC group, based on the reverse Kaplan-Meier method. In the intention-to-treat population, median progression-free survival was 3·25 months (95% CI 2·86-4·53) in the satri-cel group and 1·77 months (1·61-2·04) in the TPC group (hazard ratio 0·37 [95% CI 0·24-0·56]; one-sided log-rank p<0·0001). In the safety analysis set (all patients who received at least one dose of study drug), grade 3 or higher treatment-emergent adverse events occurred in 87 (99%) of 88 patients in the satri-cel group and 30 (63%) of 48 patients in the TPC group. The most common grade 3 or worse treatment-emergent adverse events related to treatment were decreased lymphocyte count (86 [98%] of 88 patients), decreased white blood cell count (68 [77%] patients), and decreased neutrophil count (58 [66%] patients) in the satri-cel group. Cytokine release syndrome occurred in 84 (95%) of 88 patients in the satri-cel group.This is the first randomised controlled trial of CAR T-cell therapy in solid tumours globally. Satri-cel treatment resulted in a significant improvement in progression-free survival, with a manageable safety profile. These results support satri-cel as a new third-line treatment for advanced gastric or gastro-oesophageal junction cancer patients.CARsgen Therapeutics.Copyright © 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.

Thymosin α1 (Tα1), a thymosin‐related 28‐mer synthetic amino‐terminal acetylated peptide, has gained increasing interest in recent years, due to its pleiotropy. The peptide has been used worldwide as an adjuvant or immunotherapeutic agent to treat disparate human diseases, including viral infections, immunodeficiencies, and malignancies. The peptide can enhance T cell, dendritic cell (DC), and antibody responses, modulate cytokine and chemokine production, and block steroid‐induced apoptosis of thymocytes. Its central role in modulating DC function and activating multiple signaling pathways that contribute to different functions may offer a plausible explanation for its pleiotropic action. Additionally, the ability of Tα1 to activate the indoleamine 2,3‐dioxygenase enzyme—which confers immune tolerance during transplantation and restrains the vicious circle of chronic inflammation—has been a turning point, suggesting a potential, specific function in immunity. Accordingly, Tα1 has recently been shown to promote immune reconstitution and improve survival of recipients of HLA‐matched sibling T cell–depleted stem cell transplants in a phase I/II clinical trial. Thus, Tα1 continues to live up to its promises.

To investigate the clinical efficacy of comprehensive treatment focusing on transarterial chemoembolization (TACE) for postoperative liver metastasis in patients with gastric cancer and analyze the factors influencing prognosis.A retrospective study was conducted on 116 patients who developed liver metastasis after gastric cancer surgery and were admitted to Gansu Provincial Cancer Hospital between January 2018 and February 2020. The observation group, consisting of 62 patients, received TACE with fluorouracil (FU) + irinotecan (CPT-11) + oxaliplatin (OXA) and moderate lipiodol embolization. The control group, consisting of 54 patients, received systemic S-1 and Oxaliplatin regimen (SOX) alone. The clinical efficacy and incidence of adverse reactions were compared between the two groups. Liver function indicators, tumor markers, and immunoglobulin changes were analyzed in both groups. The 2-year survival rate of patients was analyzed using the Kaplan-Meier (K-M) curve. Lasso-Cox regression was used to identify independent prognostic factors affecting the 2-year survival rate. A Nomogram model was constructed to predict outcomes.The overall clinical efficacy (P = 0.001) and objective response rate (ORR) (P = 0.001) were significantly lower in the control group compared to the observation group. No significant differences were found in ALT and AST changes between the two groups (P > 0.05). Post-treatment, CEA and CA19-9 levels were significantly lower, and IgG and IgM levels were significantly higher in the observation group (P < 0.001). There was no significant difference in the incidence of adverse reactions (P > 0.05). Lasso-Cox regression identified treatment plan, pathological differentiation, degree of liver metastasis, and pre-treatment CEA as independent prognostic factors for 2-year survival. Based on these, a Nomogram model was constructed. In the training group, the model had AUC values over 0.8 for 1- and 2-year survival rates, and in the validation group, the AUC was 0.765 and 0.687, respectively, indicating good predictive performance.Compared to the conventional SOX regimen, comprehensive treatment focusing on TACE embolization for postoperative liver metastasis in gastric cancer is more effective and can improve survival rates.AJTR Copyright © 2024.