Locally Advanced Gastric Cancer Research Articles

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

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

Diagnostic Potential of miR-143-5p, miR-143-3p, miR-551b-5p, and miR-574-3p in Chemoresistance of Locally Advanced Gastric Cancer: A Preliminary Study

Gastric cancer (GC) is one of the most frequently diagnosed cancers in the world. Although the incidence is decreasing in developed countries, the treatment results are still unsatisfactory. The standard treatment for locally advanced gastric cancer (LAGC) is gastrectomy with perioperative chemotherapy. The association of selected microRNAs (miRNAs) with chemoresistance was assessed using archival material of patients with LAGC. Histological material was obtained from each patient via a biopsy performed during gastroscopy and then after surgery, which was preceded by four cycles of neoadjuvant chemotherapy (NAC) according to the FLOT or FLO regimen. The expression of selected miRNAs in the tissue material was assessed, including miRNA-21-3p, miRNA-21-5p, miRNA-106a-5p, miRNA-122-3p, miRNA-122-5p, miRNA-143-3p, miRNA-143-5p, miRNA-203a-3p, miRNA-203-5p, miRNA-551b-3p, miRNA-551b-5p, and miRNA-574-3p. miRNA expression was assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The response to NAC was assessed using computed tomography of the abdomen and chest and histopathology after gastrectomy. The statistical analyses were performed using GraphPad Prism 9. The significance limit was set at p < 0.05. We showed that the expression of miR-143-3p, miR-143-5p, and miR-574-3p before surgery, and miR-143-5p and miR-574-3p after surgery, decreased in patients with GC. The expression of miR-143-3p, miR-143-5p, miR-203a-3p, and miR-551b-5p decreased in several patients who responded to NAC. The miRNA most commonly expressed in these cases was miRNA-551b-5p. Moreover, it showed expression in a patient whose response to chemotherapy was inconsistent between the histopathological results and computed tomography. The expression of miR-143-3p, miR-143-5p, miR-203a-3p, and miR-551b-5p in formalin-fixed paraffin-embedded tissue (FFPET) samples can help differentiate between the responders and non-responders to NAC in LAGC. miR-143-3p, miR-143-5p, and miR-574-3p expression may be used as a potential diagnostic tool in GC patients. The presence of miR-551b-5p may support the correct assessment of a response to NAC in GC via CT.

Comparative assessment of the capability of machine learning-based radiomic models for predicting omental metastasis in locally advanced gastric cancer

The study aims to investigate the predictive capability of machine learning algorithms for omental metastasis in locally advanced gastric cancer (LAGC) and to compare the performance metrics of various machine learning predictive models. A retrospective collection of 478 pathologically confirmed LAGC patients was undertaken, encompassing both clinical features and arterial phase computed tomography images. Radiomic features were extracted using 3D Slicer software. Clinical and radiomic features were further filtered through lasso regression. Selected clinical and radiomic features were used to construct omental metastasis predictive models using support vector machine (SVM), decision tree (DT), random forest (RF), K-nearest neighbors (KNN), and logistic regression (LR). The models’ performance metrics included accuracy, area under the curve (AUC) of the receiver operating characteristic curve, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). In the training cohort, the RF predictive model surpassed LR, SVM, DT, and KNN in terms of accuracy, AUC, sensitivity, specificity, PPV, and NPV. Compared to the other four predictive models, the RF model significantly improved PPV. In the test cohort, all five machine learning predictive models exhibited lower PPVs. The DT model demonstrated the most significant variation in performance metrics relative to the other models, with a sensitivity of 0.231 and specificity of 0.990. The LR-based predictive model had the lowest PPV at 0.210, compared to the other four models. In the external validation cohort, the performance metrics of the predictive models were generally consistent with those in the test cohort. The LR-based model for predicting omental metastasis exhibited a lower PPV. Among the machine learning algorithms, the RF predictive model demonstrated higher accuracy and improved PPV relative to LR, SVM, KNN, and DT models.

Neoadjuvant Docetaxel, Oxaliplatin, and S-1 Plus Surgery and Adjuvant S-1 for Resectable Advanced Gastric Cancer: Updated Overall Survival Outcomes From Phase III PRODIGY.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The phase III PRODIGY study demonstrated that neoadjuvant chemotherapy with docetaxel, oxaliplatin, and S-1 (DOS) followed by surgery and adjuvant S-1 chemotherapy (CSC) improved progression-free survival (PFS) compared with surgery followed by adjuvant S-1 (SC) for patients with resectable locally advanced gastric cancer (LAGC) with clinical T2-3N+ or T4Nany disease. The primary end point was PFS. Overall survival (OS) was the secondary end point. We herein report the long-term follow-up outcomes, including OS, from this trial. A total of 238 and 246 patients were randomly assigned to the CSC and SC arms, respectively, and were treated (full analysis set). As of the data cutoff (September 2022), the median follow-up duration of the surviving patients was 99.5 months. Compared with SC, CSC significantly increased the OS (adjusted hazard ratio [HR], 0.72; stratified log-rank P = .027) with an 8-year OS rate of 63.0% and 55.1% for the CSC and SC arms, respectively. CSC also significantly improved the PFS (HR, 0.70; stratified log-rank P = .016). In conclusion, neoadjuvant DOS chemotherapy, as part of perioperative chemotherapy, prolonged the OS of Asian patients with LAGC relative to patients treated with surgery and adjuvant S-1. It should be considered one of the standard treatment options for patients with LAGC in Asia.

Short- and Long-Term Advantages of Laparoscopic Gastrectomy for Elderly Patients with Locally Advanced Cancer

Minimally invasive surgery has provided several clinical advantages in locally advanced gastric cancer (LAGC) care, although a consensus on its application criteria remains unclear. Surgery remains a careful choice in elderly patients, who frequently present with frailty, comorbidities, and other disabling diseases. This study aims to assess the possible advantages of laparoscopic gastric resections in elderly patients presenting with LAGC. This retrospective study analyzed a single-center series of elderly patients (≥75 years) undergoing curative resections for LAGC between 2015 and 2020. A comparative analysis of open versus laparoscopic approaches was conducted, focusing on postoperative complications, length of hospital stay (LOS), and long-term survival. A total of 62 patients underwent gastrectomy through an open or a laparoscopic approach (31 pts each). The study population did not show statistically significant differences in demographics, operative risk, and neoadjuvant chemotherapy. The laparoscopic group reported significantly minimized overall complications (45.2 vs. 71%, p = 0.039) and pulmonary complications (0 vs. 9.7%, p = 0.038) as well as a shorter LOS (8 vs. 12 days, p = 0.007). Lymph node harvest was equal between the groups, although long-term overall survival presented significantly better after laparoscopic gastrectomy (p = 0.048), without a relevant difference in terms of disease-free and disease-specific survivals. Laparoscopic gastrectomy proves effective in elderly LAGC patients, offering substantial short- and long-term postoperative benefits.

Short- and Long-Term Advantages of Laparoscopic Gastrectomy for Elderly Patients with Locally Advanced Cancer.

Minimally invasive surgery has provided several clinical advantages in locally advanced gastric cancer (LAGC) care, although a consensus on its application criteria remains unclear. Surgery remains a careful choice in elderly patients, who frequently present with frailty, comorbidities, and other disabling diseases. This study aims to assess the possible advantages of laparoscopic gastric resections in elderly patients presenting with LAGC. This retrospective study analyzed a single-center series of elderly patients (≥75 years) undergoing curative resections for LAGC between 2015 and 2020. A comparative analysis of open versus laparoscopic approaches was conducted, focusing on postoperative complications, length of hospital stay (LOS), and long-term survival. A total of 62 patients underwent gastrectomy through an open or a laparoscopic approach (31 pts each). The study population did not show statistically significant differences in demographics, operative risk, and neoadjuvant chemotherapy. The laparoscopic group reported significantly minimized overall complications (45.2 vs. 71%, p = 0.039) and pulmonary complications (0 vs. 9.7%, p = 0.038) as well as a shorter LOS (8 vs. 12 days, p = 0.007). Lymph node harvest was equal between the groups, although long-term overall survival presented significantly better after laparoscopic gastrectomy (p = 0.048), without a relevant difference in terms of disease-free and disease-specific survivals. Laparoscopic gastrectomy proves effective in elderly LAGC patients, offering substantial short- and long-term postoperative benefits.

Evaluation of oxaliplatin and tigio combination therapy in locally advanced gastric cancer.

Locally advanced gastric cancer (LAGC) is a common malignant tumor. In recent years, neoadjuvant chemotherapy has gradually become popular for the treatment of LAGC. To investigate the efficacy of oxaliplatin combined with a tigio neoadjuvant chemotherapy regimen vs a conventional chemotherapy regimen for LAGC. Ninety patients with LAGC were selected and randomly divided into control and study groups with 45 patients in each group, according to the numerical table method. The control group was treated with conventional chemotherapy, and the study group was treated with oxaliplatin combined with tigio-neoadjuvant chemotherapy. The primary outcome measures were the clinical objective response rate (ORR) and surgical resection rate (SRR), whereas the secondary outcome measures were safety and Karnofsky Performance Status score. The ORR in the study group was 80.00%, which was significantly higher than that of the control group (57.78%). In the study group, SRR was 75.56%, which was significantly higher than that of the control group (57.78%). There were 15.56% adverse reactions in the study group and 35.56% in the control group. These differences were statistically significant between the two groups. The combination of oxaliplatin and tigio before surgery as neoadjuvant chemotherapy for patients with LAGC can effectively improve the ORR and SRR and is safe.

Exploration of neoadjuvant chemotherapy and post-tumor microenvironment for advanced gastric cancer (GC) or gastroesophageal junction cancer (EGJ).

e16099 Background: Neoadjuvant chemotherapy (NAC) is still the main strategy for operable local advanced gastric cancer (GC) or gastroesophageal junction cancer (EGJ). Keynote585 and Matterhorn studies had demonstrated the improvement of pathologic complete response rate (PCR), however, the overall survival benefit remains unclear. Little is known why patients’ response differently to NAC in terms of chemotherapy regiment and post neoadjuvant tumor microenvironment (TME). Methods: We retrospectively analyzed the resectable GC or EGJ patients who had been treated with neoadjuvant chemotherapy followed by surgery during 2019.11.26-2023.8.18 in the Chinese PLA general hospital. Patients with complete survival data were enrolled in the final evaluation. The association between clinical features or chemotherapy regiment and outcomes including TGR grade (NCCN criteria) and survival data were explored. Furthermore, tumor-microenvironment by means of multiplex fluorescence staining(mIHC) (CD8, CD68, CD56, PD1, PDL1, PANCK) after SOX neoadjuvant chemotherapy was analyzed. Results: 184 patients were offered neoadjuvant chemotherapy and underwent surgery. Due to follow-up lost, 141 patients with complete survival data were included in this analysis finally. Average age was 61, majority of patients were male. 85 patients received Sox and 33 received Xelox and 12 patients with docetaxel and S1(DS) and 11 patients were administered with triplets (FOLT and DOS). The median cycle of neoadjuvant treatment was 4(range from 1-7). Large proportion of patients were performed Laparoscopic. 31 patients suffered from post surgery complication. Above all, 1-year DFS and 2-year DFS, 3-year DFS rate were 72.6%, 54.8%, 49.0% respectively. 2-year OS and 3-year OS rate were 76.9%, 64.5%. PCR rate was 6.38% (n=9), which is consistent with other previous studies. 9 patients achieved TRG 0 and 26 had TRG 1. There is no statistical difference between triplets and double regiment of NEC for TRG0-1 group (45.5% vs 23.1%, p=0.099). The addition of docetaxel to oxaliplatin based therapy had not improved the TRG0-1 population compared with docetaxel-free regiment (30.4% VS 23.7%, p=0.496). YN0 is a predictor of longer survival in contrast YN+( 1-year DFS, 89.4% vs 62.8%, p=0.000).In the mIHC analyses, the density of CD8 positive and CD8+PD1- in the TGR0-1 group is higher than those cells in the TGR 2-3 group(P<0.05). TGR0-1 group had lower density of PDL1+,CD68+PDL1+ and CD68+PDL1- cells in contrast to TGR 2-3 group(P<0.05).Other multi-dimensional analyses were ongoing to be further disclosure. Conclusions: Neoadjuvant chemotherapy led to nearly 7% PCR rate for patients with local advanced GC. YN0 after NAC is a predictor of longer survival. CD8 positive and CD8+PD1- might be the determinant immune cells for better anticancer-response when exposed to chemotherapy.

Correlation Analysis Between Tumor Deposit and Clinicopathologic Characteristics and Prognosis of Gastric Cancer: A Multicenter Retrospective Study.

The mechanism underlying the formation of gastric tumor deposits (TDs) is unclear. We aimed to explore the risk factors for the formation and prognostic value of TDs. This retrospective analysis included 781 locally advanced gastric cancer (LAGC) patients from four medical institutions in China, from June 2014 to June 2018. The risk factors for TD formation and prognostic value were determined through univariate and multivariate analyses. Univariate analysis revealed that TD positivity was closely related to tumor diameter, Borrmann classification, differentiation degree, pT stage, pN stage, pTNM stage, and nerve and vascular invasion (p < 0.05). Multivariate logistic regression revealed that tumor diameter ≥ 5cm (odds ratio [OR] 1.836, 95% confidence interval [CI] 1.165-2.894, p = 0.009) and vascular invasion (OR 2.152, 95% CI 1.349-3.433, p = 0.001) were independent risk factors for TD positivity. Multivariate Cox analysis revealed that TD positivity (OR 1.533, 95% CI 1.101-2.134, p = 0.011), tumor diameter ≥ 5 cm (OR 1.831, 95% CI 1.319-2.541, p<0.001), pT4a stage (OR 1.652, 95% CI 1.144-2.386, p = 0.007), and vascular invasion (OR 1.458, 95% CI 1.059-2.008, p = 0.021) were independent risk factors for GC prognosis. The 5-year overall and disease-free survival of the TD-positive group showed significant effects among patients in the pT4a and pN3b stages (p < 0.05). TDs are closely related to tumor diameter and vascular invasion in LAGC patients, and TD positivity is an independent prognostic factor for LAGC patients, especially those at pT4a and pN3b stages.

Deep learning nomogram for predicting neoadjuvant chemotherapy response in locally advanced gastric cancer patients.

Developed and validated a deep learning radiomics nomogram using multi-phase contrast-enhanced computed tomography (CECT) images to predict neoadjuvant chemotherapy (NAC) response in locally advanced gastric cancer (LAGC) patients. This multi-center study retrospectively included 322 patients diagnosed with gastric cancer from January 2013 to June 2023 at two hospitals. Handcrafted radiomics technique and the EfficientNet V2 neural network were applied to arterial, portal venous, and delayed phase CT images to extract two-dimensional handcrafted and deep learning features. A nomogram model was built by integrating the handcrafted signature, the deep learning signature, with clinical features. Discriminative ability was assessed using the receiver operating characteristics (ROC) curve and the precision-recall (P-R) curve. Model fitting was evaluated using calibration curves, and clinical utility was assessed through decision curve analysis (DCA). The nomogram exhibited excellent performance. The area under the ROC curve (AUC) was 0.848 [95% confidence interval (CI), 0.793-0.893)], 0.802 (95% CI 0.688-0.889), and 0.751 (95% CI 0.652-0.833) for the training, internal validation, and external validation sets, respectively. The AUCs of the P-R curves were 0.838 (95% CI 0.756-0.895), 0.541 (95% CI 0.329-0.740), and 0.556 (95% CI 0.376-0.722) for the corresponding sets. The nomogram outperformed the clinical model and handcrafted signature across all sets (all P < 0.05). The nomogram model demonstrated good calibration and provided greater net benefit within the relevant threshold range compared to other models. This study created a deep learning nomogram using CECT images and clinical data to predict NAC response in LAGC patients undergoing surgical resection, offering personalized treatment insights.

Integrating Tumor and Nodal Radiomics to Predict the Response to Neoadjuvant Chemotherapy and Recurrence Risk for Locally Advanced Gastric Cancer.

To develop and evaluate machine learning models using tumor and nodal radiomics features for predicting the response to neoadjuvant chemotherapy (NAC) and recurrence risk in locally advanced gastric cancer (LAGC). Early and accurate response prediction is vital to stratify LAGC patients and select proper candidates for NAC. A total of 218 patients with LAGC undergoing NAC followed by gastrectomy were enrolled in our study and were randomly divided into a training cohort (n = 153) and a validation cohort (n = 65). We extracted 1316 radiomics features from the volume of interest of the primary lesion and maximal lymph node on venous phase CT images. We built 3 radiomics signatures for distinguishing good responders and poor responders based on tumor radiomics (TR), nodal radiomics (NR), and a combination of the two (TNR), respectively. A nomogram was then developed by integrating the radiomics signature and clinical factors. Kaplan- Meier survival curves were used to evaluate the prognostic value of the nomogram. The TNR signature achieved improved predictive value, with AUCs of 0.755 and 0.744 in the training and validation cohorts. Our proposed nomogram model (TNRN) showed a good performance for GR prediction in the prediction efficacy, calibration ability, and clinical benefit, with AUCs of 0.779 and 0.732 in the training and validation cohorts, superior to the clinical model. Moreover, the TNRN could accurately classify the patients into high-risk and low-risk groups in both training and validation cohorts with regard to postoperative recurrence and metastasis. The TNRN performed well in identifying good responders and provided valuable information for predicting progression-free survival time (PFS) in patients with LAGC who underwent NAC.

Analysis of Patient Outcomes following Curative R0 Multiorgan Resections for Locally Advanced Gastric Cancer: A Systematic Review and Meta-Analysis.

Background: This systematic review examines the efficacy of multiorgan resection (MOR) in treating locally advanced gastric cancer (LAGC), focusing on survival outcomes, postoperative morbidity, and mortality. Methods: We conducted a comprehensive search of studies in PubMed, Scopus, and Embase up to November 2023, based on the PRISMA guidelines. The inclusion criteria focused on clinical trials, observational studies, case-control studies, and qualitative research, involving patients of any age and gender diagnosed with LAGC undergoing MOR aimed at R0 resection, with secondary outcomes focusing on survival rates, postoperative outcomes, and the effects of adjuvant and neoadjuvant therapies. Exclusion criteria ruled out non-human studies, research not specifically focused on LAGC patients undergoing MOR, and studies lacking clear, quantifiable outcomes. The quality assessment was performed using the Newcastle-Ottawa Scale. The final analysis included twenty studies, involving a total of 2489 patients across a time span from 2001 to 2023. Results highlighted a significant variation in median survival times ranging from 10 to 27 months and R0 resection rates from 32.1% to 94.3%. Survival rates one-year post-R0 resection varied between 46.7% and 84.8%, with an adjusted weighted mean of 66.95%. Key predictors of reduced survival included esophageal invasion and peritoneal dissemination, the presence of more than six lymph nodes, and tumor sizes over 10 cm. Nevertheless, the meta-analysis revealed a significant heterogeneity (I2 = 87%), indicating substantial variability across studies, that might be caused by differences in surgical techniques, patient demographics, and treatment settings which influence survival outcomes. Results: The review underlines the important role of achieving R0 resection status in improving survival outcomes, despite the high risks associated with MOR. Variability across studies suggests that local practice patterns and patient demographics significantly influence results. Conclusions: The findings emphasize the need for aggressive surgical strategies to improve survival in LAGC treatment, highlighting the importance of achieving curative resection despite inherent challenges.

Impact of body composition, grip strength, and physical performance on clinical outcomes for locally advanced gastric cancer during neoadjuvant chemotherapy: A prospective cohort study

ObjectiveNeoadjuvant chemotherapy (NC) is critical in treating locally advanced gastric cancer (LAGC). However, the effect of body composition, grip strength, and physical performance during neoadjuvant chemotherapy remains uncertain. This study aimed to investigate the impact of these factors on perioperative clinical outcomes in LAGC patients undergoing NC. MethodsA total of 162 consecutive patients receiving NC at two centers were prospectively registered between June 2022 and September 2023. The data on body composition parameters, grip strength, and physical performance during NC were collected, compared, and analyzed. The primary outcome was the tumor response after completion of NC. ResultsOverall, we included 92 LAGC patients. No significant changes were observed in body composition, grip strength, and physical performance after NC. The change in skeletal muscle index and grip strength were both significantly lower in the patients with poor tumor response. According to the Youden index, the cutoff values of △SMI and △grip strength were −2.0 and −2.8, respectively. Based on these two parameters, the area under the curve to predict tumor response was 0.817 (P < 0.001). Furthermore, visceral fat index (VFI) loss >6.9 and 5-time chair stand test increase >2.4 independently predicted postoperative complication (OR: 3.82, 95% CI: 1.138–12.815, P = 0.030; OR: 5.01, 95% CI: 1.086–23.131, P = 0.039, respectively). ConclusionsFor LAGC patients receiving NC, changes in SMI, VFI, grip strength, and physical status can predict perioperative clinical outcomes. These patients should be given special nutritional intervention.

The safety and efficacy of neoadjuvant immunochemotherapy following laparoscopic gastrectomy for gastric cancer: a multicenter Real-world clinical study.

The safety and efficacy of neoadjuvant immunochemotherapy (nICT) for locally advanced gastric cancer (LAGC) remain controversial. Patients with LAGC who received either nICT or neoadjuvant chemotherapy (nCT) at 3 tertiary referral teaching hospitals in China between January 2016 and October 2022 were analysed. After propensity-score matching (PSM), comparing the radiological response, pathological response rate, perioperative outcomes, and early recurrence between the two groups. After PSM, 585 patients were included, with 195 and 390 patients comprising the nICT and nCT groups, respectively. The nICT group exhibited a higher objective response rate (79.5% versus [vs.] 59.0%; P<0.001), pathological complete response rate (14.36% vs. 6.41%; P=0.002) and major pathological response rate (39.49% vs. 26.15%; P=0.001) compared with the nCT group. The incidence of surgical complications (17.44% vs. 16.15%, P=0.694) and proportion of perioperative textbook outcomes (80.0% vs. 81.0%; P=0.767) were similar in both groups. The nICT group had a significantly lower proportion of early recurrence than the nCT group (29.7% vs. 40.8%; P=0.047). Furthermore, the multivariable logistic analysis revealed that immunotherapy was an independent protective factor against early recurrence (odds ratio 0.62 [95% CI 0.41-0.92]; P=0.018). No significant difference was found in neoadjuvant therapy drug toxicity between the two groups (51.79% vs. 45.38%; P=0.143). Compared with nCT, nICT is safe and effective, which significantly enhanced objective and pathological response rates, and reduced the risk for early recurrence among patients with LAGC. Clinical Trials.gov.

Clinical significance of immune checkpoint inhibitors in neoadjuvant therapy for gastric cancer

Multiple prospective clinical studies have demonstrated that chemotherapy combined with immune checkpoint inhibitors (ICIs) can prolong the survival of patients with far-advanced gastric cancer. For patients with locally advanced gastric cancer (LAGC), preoperative neoadjuvant chemotherapy combined with immunotherapy has also achieved some encouraging results which benefit some patients, achieve clinical downstage, attenuate hidden metastases, increase R0 resection rate and reduce postoperative recurrence rate, etc. How to apply ICIs or combine immunotherapy with other therapies correctly in the course of neoadjuvant comprehensive treatment for patients with LAGC is still a very challenging and difficult problem. There are three basic principles in immunotherapy to be grasped: (1) Based on high-level clinical practice guidelines; (2) Based on the results of high-quality evidence-based medical research; and (3) Based on molecular pathology and tumor biomarkers. Perioperative immunotherapy for gastric cancer can be correctly applied if these three principles are organically integrated. Referring to the results of domestic and international clinical research in recent years, the three basic principles are demonstrated in this article for readers.

Prognostic significance of a pathological response in metastatic lymph nodes of patients with gastric cancer who underwent neoadjuvant chemotherapy followed by surgery.

To grade the pathological response of lymph nodes (LNs) to neoadjuvant chemotherapy (NAC) in patients with locally advanced gastric cancer (LAGC) and investigate its prognostic significance. This retrospective study included 196 patients who underwent NAC, followed by radical gastrectomy for LAGC between January 2010 and October 2019. Pathological responses were evaluated based on the proportion of residual tumor cells within the tumor area in the primary tumor (PT) and LNs and included the following categories: 1a (0%), 1b (< 10%), 2 (10-50%), and 3 (> 50%). Among 166 patients with clinically node-positive disease, 38/27/39/62 were classified as having LN regression grade (LRG) 1a/1b/2/3, respectively. Compared to LN non-responders (LRG 2 or 3), LN responders (LRG 1a or 1b) had significantly higher 5-year overall survival (72.5% vs. 19.0%, P < 0.001) and recurrence-free survival rates (67.8% vs. 22.2%, P < 0.001), irrespective of PT response. Furthermore, a multivariate analysis revealed that the LN response was an independent risk factor for the overall survival (hazard ratio [HR] 0.417, 95% confidence interval [CI] 0.181-0.962, P = 0.040) and recurrence-free survival (HR 0.490, 95% CI 0.242-0.991, P = 0.047), but not the PT response (P > 0.05). The pathological LN response may be a reliable prognostic prediction tool in patients with LAGC who received NAC.

Surgical options and survival prognosis in geriatric patients beyond average lifespan with locally advanced gastric cancer: a propensity score-matched analysis.

The appropriateness of laparoscopic gastrectomy (LG) for super-geriatric patients with locally advanced gastric cancer (LAGC) is inconclusive, and the prognostic factors are also yet to be elucidated. Herein, we aimed to investigate the surgical and oncological outcomes of LG versus open gastrectomy (OG) for geriatric patients with LAGC who have outlived the average lifespan of the Chinese population (≥ 78years). This is a monocentric, retrospective, comparative study. A 1:1 propensity score matching (PSM) was performed to minimize selection bias and ensure well-balanced characteristics. The primary endpoint of interest was 3-year overall survival, while secondary endpoints included procedure-related variables, postoperative recovery indices, and complications. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify unfavorable prognostic factors. Of 196 eligible individuals, 107 underwent LG and 89 underwent OG, with a median age (interquartile range [IQR]) of 82 [79, 84] years. PSM yielded 61 matched pairs, with comparable demographic and tumor characteristics. The LG group had a significantly lower overall complication rate than the OG group (31.1% vs. 49.2%, P = 0.042), as well as shorter duration of postoperative hospital stay [12 (11, 13) vs. 13 (12, 15.5) d, P < 0. 001], less intraoperative blood loss [95 (75, 150) vs. 230 (195, 290) mL, P < 0.001], but a longer operative time [228 (210, 255.5) vs. 196 (180, 219.5) min, P < 0.001]. The times to first aerofluxus, defecation, liquid diet, and half-liquid diet were comparable. Kaplan-Meier analyses revealed no significant difference in 3-year overall survival between the groups, either in the entire cohort or in subgroups with different TNM staging. Moreover, Age-adjusted Charlson Comorbidity Index scores of > 6 [hazard ratio (HR) 4.003; P = 0.021] and pathologic TNM stage III (HR 3.816, P = 0.023) were independent unfavorable prognostic factors for long-term survival. LG performed by experienced surgeons offers the benefits of comparable or better surgical and oncological safety profiles than OG for super-geriatric patients with LAGC.

Adjuvant treatment for locally advanced gastric cancer: an Asian perspective.

Standard adjuvant treatment for locally advanced gastric cancer (LAGC) is regionally different. Whereas perioperative chemotherapy is the standard in Western populations, D2 gastrectomy followed by adjuvant chemotherapy has been the standard in East Asia. Recently, the pivotal phase 3 PRODIGY and RESOLVE studies have demonstrated survival benefits of adding neoadjuvant chemotherapy to surgery followed by adjuvant chemotherapy over up-front surgery followed by adjuvant chemotherapy in Asian patients. Based on these results, neoadjuvant chemotherapy is considered one of the viable options for patients with LAGC. In this review, various aspects of neoadjuvant chemotherapy will be discussed for its optimal application in Asia. Candidates for neoadjuvant chemotherapy should be carefully chosen in consideration of the inaccurate aspects of radiological clinical staging and its potential benefit over up-front surgery followed by a decision on adjuvant chemotherapy according to the pathological stage. Efforts should continuously be made to optimally apply neoadjuvant chemotherapy to patients with LAGC, considering various factors, including a more accurate radiological assessment of the tumor burden and the optimization of post-operative chemotherapy. Future neoadjuvant trials involving novel agents for Asian patients should be designed based on proven Asian regimens rather than adopting Western regimens.

Assessment of Laparoscopic Indocyanine Green Tracer-guided Lymphadenectomy After Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer: A Randomized Controlled Trial.

To assess the effectiveness of indocyanine green (ICG)-guided lymph node (LN) dissection during laparoscopic radical gastrectomy after neoadjuvant chemotherapy (NAC) in patients with locally advanced gastric cancer (LAGC). Studies on ICG imaging use in patients with LAGC on NAC are rare. Patients with gastric adenocarcinoma (clinical T2-4NanyM0) who received NAC were randomly assigned to receive ICG-guided laparoscopic radical gastrectomy or laparoscopic radical gastrectomy alone. Here, we reported the secondary endpoints including the quality of lymphadenectomy (total retrieved LNs and LN noncompliance) and surgical outcomes. Overall, 240 patients were randomized. Of whom, 236 patients were included in the primary analysis (118 in the ICG group and 118 in the non-ICG group). In the ICG group, the mean number of LNs retrieved was significantly higher than in the non-ICG group within the D2 dissection (48.2 vs 38.3, P < 0.001). The ICG fluorescence guidance significantly decreased the LN noncompliance rates (33.9% vs 55.1%, P = 0.001). In 165 patients without baseline measurable LNs, ICG significantly increased the number of retrieved LNs and decreased the LN noncompliance rate ( P < 0.05). For 71 patients with baseline measurable LNs, the quality of lymphadenectomy significantly improved in those who had a complete response ( P < 0.05) but not in those who did not ( P > 0.05). Surgical outcomes were comparable between the groups ( P > 0.05). ICG can effectively improve the quality of lymphadenectomy in patients with LAGC who underwent laparoscopic radical gastrectomy after NAC.

Predicting pathologic response to neoadjuvant chemotherapy in locally advanced gastric cancer: The establishment of a spectral CT-based nomogram from prospective datasets

BackgroundTo establish a spectral CT-based nomogram for predicting early neoadjuvant chemotherapy (NAC) response for locally advanced gastric cancer (LAGC). MethodsThis study prospectively recruited 222 cases (177 male and 45 female patients, 9.59 ± 9.54 years) receiving NAC and radical gastrectomy. Triple enhanced spectral CT scans were performed before NAC initiation. According to post-operative tumor regression grade (TRG), patients were classified into responders (TRG = 0 + 1) or non-responders (TRG = 2 + 3), and split into a primary (156) and validation (66) dataset at 7:3 ratio chronologically. We compared clinicopathological data, follow-up information, iodine concentration (IC), normalized ICs (nICs) in arterial/venous/delayed phases (AP/VP/DP) between responders and non-responders. Independent risk factors of response were screened by multivariable logistic regression and adopted for model construction. Model was visualized by nomograms and its capability was determined through receiver operating characteristic (ROC) curves. Log-rank survival analysis was conducted to explore associations between TRG, nomogram and patients’ survival. ResultsThis work identified Borrmann classification, ICDP, and nICDP were independent risk factors of response outcomes. A spectral CT-based nomogram was built accordingly and achieved an area under the curve (AUC) of 0.797 (0.692–0.879) and 0.741(0.661–0.811) for the primary and validation dataset, respectively, higher than AUC of individual parameters alone. The nomogram was related to disease-free survival in the validation dataset (Hazard ratio (HR): 5.19 [1.18–12.93], P = 0.02). ConclusionsThe spectral CT-based nomogram provides an efficient tool for predicting the pathologic response outcomes of GC after NAC and disease-free survival risk stratification.