Gastric Cancer最新文献

Background: Although many studies have developed logistic regression models for predicting complications using preoperative and intraoperative data, none have applied comprehensive perioperative information with machine learning (ML) to enable time-sequential predictions.

Methods: This study included patients undergoing gastric cancer surgery between 2013 and 2019 at two hospitals. Comprehensive perioperative data were collected. Four ML models were developed: the postoperative day (POD) 1 and POD 3 models predicted complications occurring from POD 2 and POD 4, while the 24-h and 8-h models predicted complications within the 24 and 8 h, respectively, after collection of the most recent biochemical data and vital signs. Model performance was assessed using the area under the receiver operating characteristic curve (AUC) with repeated validation for generalizability.

Results: Among 4139 patients, 782 (18.9%) experienced complications (Clavien-Dindo grade ≥ II). The 8-h model achieved the highest AUC (0.737) for overall complications. The POD 3 model outperformed the POD 1 model, with AUCs exceeding 0.8 for pancreatic fistula (0.869) and intra-abdominal abscess (0.821). The 8-h and the 24-h model both achieved AUCs above 0.8 for specific infectious complications. The 8-h model demonstrated the following AUCs: 0.889 for pancreatic fistula, 0.842 for intra-abdominal abscess, 0.826 for pneumonia, and 0.824 for anastomotic leakage, surpassing all POD-based models. In each 8-h model, C-reactive protein, pulse rate, and intraoperative blood loss consistently emerged as significant variables.

Conclusion: Hour-based ML models incorporating comprehensive perioperative data predict post-gastric cancer surgery complications with high accuracy and time-sequential capability, potentially aiding clinical decision-making and improving outcomes.

Background: Emerging studies suggest obesity may improve PD-1/PD-L1 inhibitor efficacy, correlating with prolonged survival, known as the 'obesity paradox'. However, the impact of this paradox and obesity-related chronic inflammation on immunotherapy for advanced gastric cancer (AGC) has not received sufficient research.

Methods: Between January 2018 and December 2021, patients receiving neoadjuvant therapy were categorized into two groups: combined immunotherapy (ICIs, n = 173) and neoadjuvant chemotherapy (NAC, n = 126). Visceral (VATI) and subcutaneous adipose tissue index (SATI) were obtained from pre-treatment CT images. The systemic immune-inflammation index (SII) was calculated as platelet count multiplied by the neutrophil-to-lymphocyte ratio.

Results: The median age of patients was 64 years (IQR 56-69), with 219 (73.2%) males and 80 (26.8%) females. In the ICIs group, the VATI-High group showed significantly higher 3-year overall survival (OS) (p = 0.010) and disease-free survival (DFS) (p = 0.029). Similar results were observed in the SATI analysis (p < 0.05). Conversely, OS (p = 0.040) and DFS (p = 0.039) were significantly lower in the SII-High group. Both VATI and SATI were independent protective factors for OS and DFS, but the effect disappeared after adjustment for SII. SII was associated with poorer OS and DFS, even after adjustment for VATI and SATI. No significant differences were observed in the analysis of the NAC group.

Conclusions: Elevated adiposity indices (VATI/SATI) and low SII correlate with survival benefit in ICI-treated AGC patients, and importantly, this paradoxical survival benefit is dependent on SII status. In contrast, no such benefit is observed in chemotherapy-alone cohorts.

Background: Gastric cancer (GC) is the fourth most common cause of cancer-related mortality and the fifth most common cancer worldwide. Despite efforts, the identification of biomarkers and new therapeutic approaches for GC remains elusive. Recent studies have begun to reveal the role of N6-adenosine methylation (m⁶A) in the regulation of gene expression.

Methods: The expression of the reader YT521-B homology domain-containing family 3 (YTHDF3) in GC was assessed in 331 patients using immunohistochemistry. GC cell lines depleted of YTHDF3 using CRISPR-Cas9 were evaluated for migration, metastasis, orientation of the mitotic spindle, and response to paclitaxel. The association between YTHDF3 and EZRIN (EZR) mRNA was shown using RNA sequencing, immunofluorescence, real-time PCR, and RNA immunoprecipitation. The single-base elongation- and ligation-based qPCR amplification (SELECT) method was used to map m⁶A in the EZR transcript.

Results: YTHDF3 was significantly overexpressed in GC, and high levels of YTHDF3 were predictive of the response to chemotherapy. In GC cell lines, YTHDF3 was the most highly expressed reader protein. YTHDF3 depletion impaired cytoskeleton organization, cell migration and metastasis, and orientation of the mitotic spindle, leading to an increased response to paclitaxel. EZR was one of the downregulated targets in the YTHDF3 knockout cell models and was associated with the observed phenotype.

Conclusion: YTHDF3 contributes to cell motility and response to paclitaxel in GC cell lines, at least in part through EZR regulation. The YTHDF3-EZR regulatory axis is a novel molecular player in GC, with clinical relevance and potential therapeutic utility.

Over the past three decades, the implementation of the complete mesocolic excision (CME)/total mesorectal excision (TME) technique in colorectal cancer surgery has significantly reduced local recurrence rates and improved tumor-related survival outcomes. However, due to the morphological complexities of the gastric mesentery and its presence is still controversy, the concept of mesogastric excision(MGE) has yet to gain widespread acceptance in gastric cancer surgery. Nowadays, surgeons have begun to identify a dissectible loose connective-tissue layer between the lymph nodes and landmark structures through magnified images obtained during laparoscopic or robotic gastrectomy. We agree with the authors that MGE serves as a standardized concept in gastric cancer surgery.

Background: Nivolumab plus chemotherapy demonstrated clinically significant improvement in quality-adjusted survival versus chemotherapy alone as first-line treatment for advanced non-HER2-positive gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma (GC/GEJC/EAC) in the CheckMate 649 post-hoc quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis at 1-year minimum follow-up. We report Q-TWiST analysis results at 4-year minimum follow-up.

Methods: Q-TWiST methodology was applied post-hoc to CheckMate 649 study data from all randomized patients, patients with PD-L1 combined positive score (CPS) ≥ 1, and patients with PD-L1 CPS ≥ 5. Relative Q-TWiST gains ≥ 10% were predefined as clinically important and ≥ 15% as clearly clinically important.

Results: Among all randomized patients, patients with PD-L1 CPS ≥ 1, and patients with PD-L1 CPS ≥ 5, mean (95% CI) absolute Q-TWiST gains of 3.4 (1.8-5.1), 4.2 (2.4-6.1), and 5.4 (3.0-7.7) months with nivolumab plus chemotherapy versus chemotherapy were observed, respectively. These translated to clearly clinically important relative Q-TWiST gains of 20.5%, 26.1%, and 33.4% in each population; relative Q-TWiST gains benefit remained clearly clinically important in all subgroups (15.7%, 20.3%, and 26.4%) after expanding the analysis to include grade 2 adverse events. Greater Q-TWiST gains were observed with nivolumab plus chemotherapy across most subgroups in all randomized patients and patients with PD-L1 CPS ≥ 1 and across all subgroups in patients with PD-L1 CPS ≥ 5.

Conclusion: Clearly clinically important benefit in quality-adjusted survival with first-line nivolumab plus chemotherapy versus chemotherapy was observed across all evaluated PD-L1 CPS expression levels in patients with advanced GC/GEJC/EAC from CheckMate 649 with 4-year minimum follow-up.

Trial registration: ClinicalTrials.gov identifier, NCT02872116.

Background: Perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) is the standard of care for locally advanced oesophagogastric adenocarcinoma (LA-OGA) in Western countries. However, completing treatment is challenging for patients, particularly in the postoperative setting. This study investigated the impact of adjuvant chemotherapy (ACT) administration and treatment completion on survival outcomes in patients receiving FLOT.

Methods: Charts of LA-OGA patients treated from 2017 to 2023 were retrospectively reviewed. Survival was analysed using Kaplan-Meier and restricted mean survival time (RMST) analyses, with propensity score matching (PSM) adjustments. Subgroup analyses were stratified by pathological nodal status and tumour regression grade (Mandard TRG). The primary endpoint was 3-year overall survival (OS).

Results: The study included 233 patients, among whom 62.4% completed the full perioperative FLOT regimen and 21% did not receive ACT. After PSM adjustment, 3-year OS for patients who completed and those who did not complete perioperative therapy was 69% and 57%, respectively (p = 0.09). The 3-year OS was 81% and 52% for patients who did and did not receive ACT, respectively (p = 0.01). In multivariate analysis, completion of perioperative FLOT was independently associated with improved OS (p = 0.04). Survival improvement with ACT was observed in the ypN-positive subgroup but not in the ypN-negative subgroup.

Conclusions: Perioperative FLOT administration is recommended as the standard of care for LA-OGA. The survival impact of ACT might be influenced by pathological lymph node metastasis.

Peritoneal metastasis (PM) is a major challenge in advanced gastric cancer (GC) with poor prognosis. Normothermic intraperitoneal and systemic treatment (NIPS) has become a promising therapeutic approach. This consensus aims to provide practical recommendations for NIPS treatment for gastric cancer with peritoneal metastasis (GCPM). The GRADE standards were used to rank evidence, and the Delphi method was employed for expert voting. 30 experts from China, Japan, South Korea, and Singapore participated in the development of this consensus. 28 experts participated in the voting process, which produced 29 statements covering diagnostic approaches, patient selection criteria, treatment regimens, management of intraperitoneal port placement, and conversion surgery considerations, and post-surgical treatment strategies in NIPS therapy. Based on current evidence and expert experience, these statements aim to improve the clinical outcomes of NIPS therapy for GCPM patients.

Background: TFF2 is a promising yet underexplored biomarker for gastric cancer. We aimed to investigate the relationship between serum TFF2 and gastric cancer, including early gastric cancer, and its interactions with other factors.

Methods: A cross-sectional, population-based study was conducted involving 3986 participants from Wuwei Cohort. The serum levels of TFF2, TFF1, TFF3, PG I, PG II, and Hp IgG were measured. Logistic regression and restricted cubic splines assessed associations and dose-response relationships.

Results: Gastric cancer prevalence rose across serum TFF2 tertiles, from 1.6 to 5.0% (p for trend < 0.001). TFF2 demonstrated the strongest association with gastric cancer, with participants in the highest tertile showing over a fourfold increased risk (OR 4.02, 95% CI 2.25-7.19, p < 0.001) after adjusting for traditional risk factors and other biomarkers. The association remained robust for early gastric cancer, exhibiting over a threefold risk (OR 3.31, 95% CI 1.80-6.08, p < 0.001). RCS analyses confirmed dose-response relationships (p for non-linearity < 0.05). The joint analyses showed that participants in the highest tertiles of both TFF1 and TFF2, or in the lowest tertile of TFF1 and highest tertile of TFF2, had at least an eightfold increased risk of gastric cancer and early gastric cancer compared to those with both biomarkers in the lowest tertile.

Conclusion: Serum TFF2 is a more reliable biomarker for gastric cancer, including early gastric cancer, in the general population. Its strong dose-response association with gastric cancer outcomes and the synergistic effects with TFF1 highlight its potential to improve risk prediction and guide future research.

Background: Since the FLOT4 gastric cancer (GC) trial, the use of adjuvant chemotherapy has been perceived as limited and its added value questioned. We wanted to objectify this perception and reassess the value of adjuvant chemotherapy in a real-world setting.

Methods: In our retrospective cohort study we analyzed real-world data from 147 patients with GC or cancer of the gastroesophageal junction (AEG) who received perioperative FLOT. Data originated from clinical care at the university hospital, local hospitals and medical practices. Clinicopathologic data, survival outcomes, and targetable biomarkers were analyzed.

Results: Median overall survival (OS) and tumor specific survival (TSS) were 19.4 ± 2.9 and 19.9 ± 3.1 months, respectively. 84.4% completed all cycles of neoadjuvant chemotherapy. The pathological complete response rate was 11.8%. Adjuvant chemotherapy was initiated in only 42.9%. Survival rates of patients with marked tumor regression (TRG1) were not improved by adjuvant chemotherapy. Conversely, patients with partial histopathologic response (TRG2) showed a marked trend and those with minimal histopathologic response (TRG3) showed a significantly longer survival with any number of adjuvant chemotherapy cycles (OS: 22.3 ± 2.6 months versus 8.7 ± 2.4 months, p = 0.005; TSS: 22.3 ± 4.5 months versus 8.7 ± 2.4 months, p = 0.016). Targetable biomarkers PD-L1, Claudin 18.2, HER2 and microsatellite instability were detected in 53.4%, 26.2%, 7.8%, and 3.9% of the TRG2/3 patient subset, respectively.

Conclusions: In the real-world setting, adjuvant chemotherapy proved to be a critical turning point of the FLOT regimen. It should be sought-even in a reduced form-in patients with TRG2/3.

Background: In 2021, anamorelin, a ghrelin receptor agonist, was approved in Japan for cancer cachexia in select cancers, including gastric cancer. However, evidence regarding its efficacy and predictive factors in patients with gastric cancer remains lacking.

Methods: This prospective observational study encompassed 229 patients with unresectable, advanced, or recurrent gastric cancer and cancer cachexia who received anamorelin from 2021 to 2023 at 25 institutions affiliated with Osaka University. Body weight change at 12 weeks was the primary endpoint. Appetite, food intake, treatment compliance, and adverse events comprised the secondary endpoints. Multivariable logistic regression analyses were employed for identifying weight gain predictors.

Results: Of the 229 patients (median age, 73 years), 126 completed the 12-week follow-up. The median anamorelin administration duration was 62 days. The mean weight significantly increased from baseline to 4, 8, and 12 weeks (up to + 0.88 kg, p < 0.001). Moreover, appetite and food intake improved. Multivariable analysis identified baseline body mass index (BMI) < 20 kg/m² and neutrophil-to-lymphocyte ratio (NLR) < 4.0 as independent predictors of significant weight gain at 12 weeks. Treatment was generally well tolerated, with a 41% completion rate; 59% of the participants discontinued mainly owing to disease progression.

Conclusion: In patients with gastric cancer-related cachexia, anamorelin was associated with significant increases in body weight and improvements in appetite. Lower BMI and lower systemic inflammation (NLR < 4.0) were predictive of better response.