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

BACKGROUND: Locally advanced gastric cancer (LAGC) is a common malignant tumor. In recent years, neoadjuvant chemotherapy has gradually become popular for the treatment of LAGC. AIM: To investigate the efficacy of oxaliplatin combined with a tigio neoadjuvant chemotherapy regimen vs a conventional chemotherapy regimen for LAGC. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Epidemiology and prognostic nomogram for locally advanced gastric signet ring cell carcinoma: A population-based study.

BACKGROUND: Gastric signet ring cell carcinoma (GSRC) represents a specific subtype of gastric cancer renowned for its contentious epidemiological features, treatment principles, and prognostic factors. AIM: To investigate the epidemiology of GSRC and establish an improved model for predicting the prognosis of patients with locally advanced GSRC (LAGSRC) after surgery. METHODS: The annual rates of GSRC incidence and mortality, covering the years 1975 to 2019, were extracted from the Surveillance, Epidemiology, and End Results (SEER) database to explore the temporal trends in both disease incidence and mortality rates using Joinpoint software. The clinical data of 3793 postoperative LAGSRC patients were collected from the SEER database for the analysis of survival rates. The Cox regression model was used to explore the independent prognostic factors for overall survival (OS). The risk factors extracted were used to establish a prognostic nomogram. RESULTS: The overall incidence of GSRC increased dramatically between 1975 and 1998, followed by a significant downward trend in incidence after 1998. In recent years, there has been a similarly optimistic trend in GSRC mortality rates. The trend in GSRC showed discrepancies based on age and sex. Receiver operating characteristic curves, calibration curves, and decision curve analysis for 1-year, 3-year, and 5-year OS demonstrated the high discriminative ability and clinical utility of this nomogram. The area under the curve indicated that the performance of the new model outperformed that of the pathological staging system. CONCLUSION: The model we established can aid clinicians in the early prognostication of LAGSRC patients, resulting in improved clinical outcomes by modifying management strategies and patient health care.

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

PURPOSE: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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 ≥ 5 cm (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). CONCLUSIONS: 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.

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

OBJECTIVE: Neoadjuvant 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. METHODS: A 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. RESULTS: Overall, 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). CONCLUSIONS: For 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.

Nomogram for predicting pathological response to neoadjuvant treatment in patients with locally advanced gastric cancer: Data from a phase III clinical trial.

PURPOSE: This study aimed to establish a nomogram using routinely available clinicopathological parameters to predict the pathological response in patients with locally advanced gastric cancer (LAGC) undergoing neoadjuvant treatment. MATERIALS AND METHODS: We conducted this study based on the ongoing Neo-CRAG trial, a prospective study focused on preoperative treatment in patients with LAGC. A total of 221 patients who underwent surgery following neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) at Sun Yat-sen University Cancer Center between June 2013 and July 2022 were included in the analysis. We defined complete or near-complete pathological regression and ypN0 as good response (GR), and determined the prognostic value of GR by Kaplan-Meier survival analysis. Eventually, a nomogram for predicting GR was developed based on statistically identified predictors through multivariate logistic regression analysis and internally validated by the bootstrap method. RESULTS: GR was confirmed in 54 patients (54/221, 24.4%). Patients who achieved GR had a longer progression-free survival and overall survival. Then, five independent factors, including pretreatment tumor differentiation, clinical T stage, monocyte count, CA724 level, and the use of nCRT, were identified. Based on these predictors, the nomogram was established with an area under the curve (AUC) of 0.777 (95% CI, 0.705-0.850) and a bias-corrected AUC of 0.752. CONCLUSION: A good pathological response after neoadjuvant treatment was associated with an improved prognosis in LAGC patients. The nomogram we established exhibits a high predictive capability for GR, offering potential value in devising personalized and precise treatment strategies for LAGC patients.

Perioperative or neoadjuvant chemotherapy for locally advanced gastric or gastroesophageal junction cancer: from independent evidence in the West, the East, and Japan to global collaboration.

The survival outcome of patients with locally advanced gastric or gastroesophageal junction (G/GEJ) cancer remains unsatisfactory, and improvements in survival and recurrence remain urgent issues for clinicians worldwide. Prior to the 2000s, locally advanced G/GEJ was a different disease between the West and the East regarding diagnosis, surgery, and prognosis. However, recent advances in medical oncology have set the stage for harmonization. Herein, this review highlights clinical trials of perioperative or neoadjuvant chemotherapy conducted during the past two decades to provide insights into future directions. We focused on pivotal clinical trials of perioperative or neoadjuvant chemotherapy for patients with locally advanced G/GEJ cancer. We paid special attention to the indication and oncological outcomes of perioperative or neoadjuvant chemotherapy. The attempts to investigate the optimal treatment strategy for locally advanced G/GEJ cancer over the past 20 years have resulted in a global consensus on the necessity of perioperative or neoadjuvant chemotherapy, although there have been different circumstances regarding treatment for G/GEJ cancer among the West, the East other than Japan, and Japan. Two randomized global phase III trials, the KEYNOTE-585 and MATTHERHORN, were successfully accomplished for a common indication. Furthermore, perioperative immunotherapy suggested a new indication with molecular biomarkers such as microsatellite status or PD-L1 status beyond the conventional tumor-lymph node-metastasis (TNM) staging system. Global studies provide the stage for discussing the future optimal indication of neoadjuvant chemotherapy, opening the door for future global collaborations to better treat patients with locally advanced G/GEJ cancer.

Neoadjuvant versus adjuvant radiotherapy for resectable locally advanced gastric cancer: A SEER population analysis.

Background: There is a lack of evidence on whether resectable locally advanced gastric cancer (LAGC) patients could benefit from neoadjuvant or adjuvant radiotherapy (RT). Methods: Patients with surgically diagnosed LAGC from 2004 to 2015 were retrieved from the SEER database. Kaplan-Meier method and the log-rank test were used to evaluate survival analysis between neoadjuvant and adjuvant RT. Univariate Cox regression was used to evaluate the hazard ratio (HR) and 95 % confidence interval (CI). Results: A total of 4790 LAGC patients who treated with surgery and RT were identified, including 3187 patients with intestinal subtype and 1603 patients with diffuse subtype. For patients with both intestinal and diffuse subtypes, median cancer-specific survival (mCSS) was better with adjuvant RT or neoadjuvant RT. Moreover, patients benefited more from adjuvant RT than neoadjuvant RT (intestinal subtype: mCSS 49 vs. 36 months, P < 0.001; diffuse subtype: mCSS 32 vs. 26 months, P = 0.050). Further analyses showed that patients with intestinal subtype and T1-2N+, T3N-, T3N+ subgroups, as well as patients with diffuse subtype and T1-2N+ and T3N+ subgroups benefited more from adjuvant RT than those with neoadjuvant RT. Patients in the diffuse subtype and T3N- subgroups also tended benifit from adjuvant RT and survive. There was no difference in survival between the T4N- and T4N + subgroups of the two subtypes. After propensity score matching, subgroup analysis identified an improved survival in favor of adjuvant RT in the age ≥65 years and female subgroups in diffuse subtypes and T4N+ patients. Conclusions: For patients with resectable LAGC in the T1-2N+, T3N-, T3N+ clinical subgroups, adjuvant RT yields more benefits than neoadjuvant RT or no RT, which is worthy of prospective clinical trial.

Value of 68Ga-FAPI-04 and 18F-FDG PET/CT in Early Prediction of Pathologic Response to Neoadjuvant Chemotherapy in Locally Advanced Gastric Cancer.

This prospective study investigated whether PET parameters from 18F-FDG and 68Ga-fibroblast activation protein inhibitor (FAPI)-04 PET/CT can predict a pathologic response to neoadjuvant chemotherapy (NAC) early in patients with locally advanced gastric cancer (LAGC). Methods: The study included 28 patients with LAGC who underwent 18F-FDG PET/CT and 68Ga-FAPI-04 PET/CT at baseline and after 1 cycle of NAC. PET parameters including SUV and tumor-to-background ratio (TBR), as well as the change rate of SUV and TBR, were recorded. Patients were classified as major or minor pathologic responders according to postoperative pathology findings. We compared the PET parameters between the 2 pathologic response groups and different treatment regimens and analyzed their predictive performance for tumor pathologic response. Results: Major pathologic responders had significantly lower 68Ga-FAPI change rates (percentage SUVmax [%SUVmax], percentage SUVpeak [%SUVpeak], and percentage TBR [%TBR]) than minor pathologic responders. Among the PET parameters, 68Ga-FAPI %SUVmax (area under the curve, 0.856; P = 0.009), %SUVpeak (area under the curve, 0.811; P = 0.022), and %TBR (area under the curve, 0.864; P = 0.007) were significant parameters for early prediction of pathologic response to NAC in LAGC; they had the same predictive accuracy of 89.29%, with the thresholds of decrease to at least 52.43%, 60.46%, and 52.96%, respectively. In addition, 68Ga-FAPI %SUVmax and %TBR showed significant differences between the different treatment regimens. Conclusion: In this preliminary study, 68Ga-FAPI-04 PET change rate parameters were preferable to 18F-FDG in predicting pathologic response to NAC at an early stage in LAGC. 68Ga-FAPI %SUVmax and %TBR may be better predictors of therapeutic response between different treatment regimens. These findings may help optimize the treatment for patients with LAGC.

Effect of sarcopenia on short-term and long-term outcomes of older patients with locally advanced gastric cancer: a multicenter study.

OBJECTIVE: To assess the effect of preoperative sarcopenia on the short-term and long-term outcomes in older patients with locally advanced gastric cancer (LAGC). METHODS: Clinicopathological data of older patients with LAGC who underwent radical surgery were retrospectively analyzed. Sarcopenia was defined as a skeletal muscle index of less than 36.4 cm2/m2 for men and less than 28.4 cm2/m2 for women. Comparing the postoperative complications and survival between sarcopenia and non-sarcopenia groups using multicenter data. RESULTS: A total of 406 older patients with LAGC were included in the analysis, including 145 (35.7%) with sarcopenia and 261 (64.3%) with non-sarcopenia. Multivariate logistic regression analysis showed that sarcopenia was an independent risk factor for postoperative complications with CD grade ≥ II (OR 1.616; P < 0.05). Kaplan-Meier survival curve analysis showed that the 5-year overall survival (OS) and 5-year recurrence-free survival (RFS) in the sarcopenia group were lower than those in the non-sarcopenia group (P both < 0.05). Multivariate Cox regression analyses showed that sarcopenia was an independent prognostic factor for 5-year OS and RFS (P both < 0.05). The 5-year recurrence rate in the sarcopenia group was 57.2%, which was significantly higher than that in the non-sarcopenia group (46.4%; P = 0.036). Recurrence pattern analysis showed that the incidence of distant metastases in patients with sarcopenia (42.8%) was significantly higher than non-sarcopenia (31.4%; P = 0.022). CONCLUSION: Sarcopenia serves as a valuable predictor of both short-term and long-term outcomes in older patients with LAGC. Therefore, the significance of assessing preoperative nutritional status and implementing thorough postoperative follow-up for older LAGC patients with sarcopenia should be emphasized.

DNA mismatch repair deficiency and outcomes of patients with locally advanced gastric cancer treated with preoperative docetaxel, oxaliplatin, and S-1 plus surgery and postoperative S-1 or surgery plus postoperative S-1: a sub-analysis of the phase 3 PRODIGY trial.

BACKGROUND: The benefit of adjuvant chemotherapy for locally advanced gastric cancer (LAGC) patients with DNA mismatch repair (MMR) deficiency (D-MMR) is controversial due to concerns about its potential detrimental effect. The PRODIGY trial showed the survival benefit of adding preoperative docetaxel, oxaliplatin, and S-1 (DOS) to surgery plus postoperative S-1 for LAGC patients. In this sub-analysis, we evaluated the benefit of preoperative DOS according to MMR status. METHODS: Among patients enrolled in the PRODIGY trial treated with either preoperative DOS followed by surgery and postoperative S-1 (CSC arm), or surgery and postoperative S-1 (SC arm) at Asan Medical Center (n = 249), those in the full analysis set with available tissue to assess MMR status were included in the present analysis. RESULTS: A total of 231 patients (CSC arm, n = 108; SC arm, n = 123) were included (median age, 58 years [range, 27-75]), and 21 patients (CSC arm, n = 8 [7.4%]; SC arm, n = 13 [10.6%]) had D-MMR tumors. Progression-free survival and overall survival tended to be superior in the CSC arm than in the SC arm among D-MMR patients (HR 0.48 [95% CI 0.09-2.50]; log-rank P = 0.37 and HR 0.55 [95% CI 0.11-2.86]; log-rank P = 0.46, respectively), as well as among proficient MMR (P-MMR) patients (HR 0.68 [95% CI 0.46-1.03]; log-rank P = 0.07 and HR 0.75 [95% CI 0.49-1.14]; log-rank P = 0.17, respectively). CONCLUSION: Preoperative DOS followed by surgery and postoperative S-1 may be considered a treatment option for LAGC patients regardless of MMR status.

Efficacy and safety of laparoscopic vs open gastrectomy after neoadjuvant therapy for locally advanced gastric cancer.

BACKGROUND: Laparoscopic gastrectomy (LG) is widely accepted as a minimally invasive approach for the treatment of early gastric cancer. However, its role in locally advanced gastric cancer (LAGC) after neoadjuvant therapy (NAT) remains controversial. This study aimed to compare the efficacy and safety of LG vs open gastrectomy (OG) after NAT for the treatment of LAGC. AIM: To compare the efficacy and safety of LG vs OG after NAT for LAGC. METHODS: We conducted a prospective study of 76 patients with LAGC who underwent NAT followed by LG (n = 38) or OG (n = 38) between 2021 and 2023. The primary endpoint was overall survival (OS), and the secondary endpoints were disease-free survival (DFS), surgical complications, and quality of life (QOL). RESULTS: The two groups had comparable baseline characteristics, with a median follow-up period of 24 mo. The 3-year OS rates in the LG and OG groups were 68.4% and 60.5%, respectively (P = 0.42). The 3-year DFS rates in the LG and OG groups were 57.9% and 50.0%, respectively (P = 0.51). The LG group had significantly less blood loss (P < 0.001), a shorter hospital stay (P < 0.001), and a lower incidence of surgical site infection (P = 0.04) than the OG group. There were no significant differences in other surgical complications between the groups, including anastomotic leakage, intra-abdominal abscess, or wound dehiscence. The LG group had significantly better QOL scores than the OG group regarding physical functioning, role functioning, global health status, fatigue, pain, appetite loss, and body image at 6 months postoperatively (P < 0.05). CONCLUSION: LG after NAT is a viable and safe alternative to OG for the treatment of LAGC, with similar survival outcomes and superior short-term recovery and QOL. LG patients had less blood loss, shorter hospitalizations, and a lower incidence of surgical site infections than OG patients. Moreover, the LG group had better QOL scores in multiple domains 6 mo postoperatively. Therefore, LG should be considered a valid option for patients with LAGC who undergo NAT, particularly for those who prioritize postoperative recovery and QOL.

Comprehensive survival nomograms for locally advanced gastric cancer: a large population-based real-world study.

Background: This study aimed to construct and verify nomograms predicting overall survival (OS) and cancer-specific survival (CSS) for locally advanced gastric cancer (LAGC) based on a therapeutic selection, demographic factors, and pathological features. Methods: The data used for the analysis were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Nomograms were constructed based on the Cox regression model. Results: The entire cohort comprised 21,757 patients with histologically confirmed LAGC, and was randomly distributed into training and verification groups at a ratio of 2:1 for building the prognostic predictive model. According to the multivariate analysis, 13 variables [i.e., age, marital status, race, tumor location, pathological grade, histological type, T and N stage, surgery, radiotherapy, chemotherapy, tumor size, and regional nodes examined (RNE)] were confirmed as independent predictors for both OS and CSS. All of the significant variables were used to create the nomograms for OS and CSS. Time-dependent receiver operating characteristic (ROC) curves, a decision curve analysis (DCA), the C-index, and calibration curves were applied to identify the discriminating superiority of the nomograms. Conclusions: The nomograms for OS and CSS in LAGC were built and validated based on the therapeutic selection and pathological and demographic variables using a national database. This study aims at helping clinicians make better clinical decisions and encouraging patients receive treatment actively.

Safety and Efficacy of Neoadjuvant Chemotherapy for Advanced Gastric Cancer in Elderly Patients.

BACKGROUND/AIM: Elderly patients with pathological stage II/III gastric cancer struggle to complete adjuvant chemotherapy. Neoadjuvant chemotherapy (NAC) for treating locally advanced gastric cancer (LAGC) has drawn attention; however, its indication for elderly patients who are vulnerable to chemotherapy is unclear. This study aimed to investigate the feasibility and efficacy of NAC for elderly patients with gastric cancer. PATIENTS AND METHODS: In this study, patients aged ≥75 years who underwent curative gastrectomy for LAGC or adenocarcinoma of the esophagogastric junction between April 2013 and November 2021 were included. Vulnerable patients, with poor Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of 2-3 were also included. The patients were classified into NAC+ (n=20) and NAC - (n=45) groups. The clinicopathological data of the patients were retrospectively investigated. RESULTS: The NAC+ group showed a higher R0 resection rate than the NAC- group (100% vs. 89.1%, p=0.3) and pathological downstaging was achieved in 12 (60%) cases, including five (25%) pathological complete responses. The incidence of adverse events during postoperative chemotherapy was 35%, and the rate of postoperative complications greater than Clavien-Dindo Grade II was comparable between the two groups (35% vs. 46.7%, p=0.43). The NAC+ group showed a higher three-year overall survival rate (75% vs. 36%, p=0.015). CONCLUSION: NAC was feasible and effective for elderly patients including vulnerable patients with LAGC or adenocarcinoma of the esophagogastric junction. It can be considered as treatment option, with a high down staging rate and better survival.

Comparison between upfront surgery and neoadjuvant chemotherapy in patients with locally advanced gastric cancer: A systematic review.

BACKGROUND: Gastric cancer (GC) is a major health concern worldwide. Surgical resection and chemotherapy is the mainstay treatment for gastric carcinoma, however, the optimal approach remains unclear and should be different in each individual. Chemotherapy can be administered both pre- and postoperatively, but a multidisciplinary approach is preferred when possible. This is particularly relevant for locally advanced GC (LAGC), as neoadjuvant chemotherapy (NAT) could potentially lead to tumor downsizing thus allowing for a complete resection with curative intent. Even though the recent progress has been impressive, European and International guidelines are still controversial, thus attenuating the need for a more standardized approach in the management of locally advanced cancer. AIM: To investigate the effects of NAT on the overall survival (OS), the disease-free survival (DFS), the morbidity and the mortality of patients with LAGC in comparison to upfront surgery (US). METHODS: For this systematic review, a literature search was conducted between November and February 2023 in PubMed, Cochrane Library and clinicaltrials.gov for studies including patients with LAGC. Two independent reviewers conducted the research and extracted the data according to predetermined inclusion and exclusion criteria. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses was used to form the search strategy and the study protocol has been registered in the International Prospective Register of Systematic Reviews. RESULTS: Eighteen studies with 4839 patients with LAGC in total were included in our systematic review. Patients were separated into two groups; one receiving NAT before the gastrectomy (NAT group) and the other undergoing upfront surgery (US group). The OS ranged from 41.6% to 74.2% in the NAT group and from 30.9% to 74% in the US group. The DFS was also longer in the NAT group and reached up to 80% in certain patients. The complications related to the chemotherapy or the surgery ranged from 6.4% to 38.1% in the NAT group and from 5% to 40.5% in the US group. Even though in most of the studies the morbidity was lower in the NAT group, a general conclusion could not be drawn as it seems to depend on multiple factors. Finally, regarding the mortality, the reported rate was higher and up to 5.3% in the US group. CONCLUSION: NAT could be beneficial for patients with LAGC as it leads to better OS and DFS than the US approach with the same or even lower complication rates. However, patients with different clinicopathological features respond differently to chemotherapy, therefore currently the treatment plan should be individualized in order to achieve optimal results.

Neoadjuvant PD-1 inhibitor plus apatinib and chemotherapy versus apatinib plus chemotherapy versus chemotherapy alone in patients with locally advanced gastric cancer.

Programed cell death protein-1 (PD-1) inhibitor, apatinib, and chemotherapy show synergistic antitumor effect in gastric cancer. This study aimed to evaluate this combination as a neoadjuvant therapy in locally advanced gastric cancer (LAGC). In this retrospective study, data from 179 LAGC patients who underwent neoadjuvant therapy with a PD-1 inhibitor plus apatinib and chemotherapy (PAC group, n=56), apatinib and chemotherapy (AC group, n=50), or chemotherapy alone (C group, n=73) were analyzed. The PAC group displayed a numerically higher radiologic objective response rate than the AC group (73.2% vs. 60.0%, P=0.149) and significantly higher than the C group (73.2% vs. 35.6%, P<0.001). Tumor resection rates between the PAC and AC groups were not significantly different (100.0% vs. 94.0%, P=0.102) but were higher in the PAC group compared to the C group (100.0% vs. 89.0%, P=0.010). Pathological evaluations revealed comparable R0 resection rates across all groups (P=0.873) and a non-significantly higher pathological complete response rate in the PAC group compared to the AC group (26.8% vs. 17.0%, P=0.236), while significantly higher than the C group (26.8% vs. 7.7%, P=0.005). Moreover, the PAC group exhibited a longer progression-free survival compared to the AC (P=0.036) and C (P<0.001) groups, an extended disease-free survival compared to the C group (P=0.002), and improved overall survival compared to the AC (P=0.028) and C (P=0.002) groups. Adverse events were generally comparable, with the highest incidence of peripheral neuropathy observed in the PAC group (26.8%, P=0.020). PD-1 inhibitor plus apatinib and chemotherapy may represent an effective neoadjuvant regimen for LAGC management, necessitating further validation.

Association between Pre-Treatment Biological Indicators and Compliance to Neoadjuvant/Perioperative Chemotherapy in Operable Gastric Cancer.

BACKGROUND AND AIMS: Perioperative treatment is currently the gold standard approach in Europe for locally advanced gastric cancer (GC). Unfortunately, the phenomenon of patients dropping out of treatment has been frequently observed. The primary aims of this study were to verify if routine blood parameters, inflammatory response markers, sarcopenia, and the depletion of adipose tissues were associated with compliance to neoadjuvant/perioperative chemotherapy. METHODS AND STUDY DESIGN: Blood samples were considered before the first and second cycles of chemotherapy. Sarcopenia and adipose indices were calculated with a CT scan before starting chemotherapy and before surgery. Odds ratios (OR) from univariable and multivariable models were calculated with a 95% confidence interval (95% CI). RESULTS: A total of 84 patients with locally advanced GC were identified between September 2010 and January 2021. Forty-four patients (52.4%) did not complete the treatment according to the number of cycles planned/performed. Eight patients (9.5%) decided to suspend chemotherapy, seven patients (8.3%) discontinued because of clinical decisions, fourteen patients (16.7%) discontinued because of toxicity and fifteen patients (17.9%) discontinued for miscellaneous causes. Seventy-nine (94%) out of eighty-four patients underwent gastrectomy, with four patients having surgical complications, which led to a suspension of treatment. Sarcopenia was present in 38 patients (50.7%) before chemotherapy began, while it was present in 47 patients (60%) at the CT scan before the gastrectomy. At the univariable analysis, patients with basal platelet to lymphocyte ratio (PLR) ≥ 152 (p = 0.017) and a second value of PLR ≥ 131 (p = 0.007) were more frequently associated with an interruption of chemotherapy. Patients with increased PLR (p = 0.034) compared to the cut-off were associated with an interruption of chemotherapy, while patients with increased monocytes between the first and second cycles were associated with a lower risk of treatment interruption (p = 0.006); patients who underwent 5-fluorouracil plus cisplatin or oxaliplatin had a higher risk of interruption (p = 0.016) compared to patients who underwent a 5-fluorouracil plus leucovorin, oxaliplatin and docetaxel (FLOT) regimen. The multivariable analysis showed a higher risk of interruption for patients who had higher values of PLR compared to the identified cut-off both at pretreatment and second-cycle evaluation (OR: 5.03; 95% CI: 1.34-18.89; p = 0.017) as well as for patients who had a lower PLR than the identified cut-off at pretreatment evaluation and had a higher PLR value than the cut-off at the second cycle (OR: 4.64; 95% CI: 1.02-21.02; p = 0.047). Becker regression was neither affected by a decrease of sarcopenia ≥ 5% (p = 0.867) nor by incomplete compliance with chemotherapy (p = 0.281). CONCLUSIONS: Changes in PLR values which tend to increase more than the cut-off seem to be an immediate indicator of incomplete compliance with neoadjuvant/perioperative treatment. Fat loss and sarcopenia do not appear to be related to compliance. More information is needed to reduce the causes of interruption.

Using Normalized Carcinoembryonic Antigen and Carbohydrate Antigen 19 to Predict and Monitor the Efficacy of Neoadjuvant Chemotherapy in Locally Advanced Gastric Cancer.

Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are established prognostic biomarkers for patients with gastric cancer. However, their potential as predictive markers for neoadjuvant chemotherapy (NACT) efficacy has not been fully elucidated. METHODS: We conducted a retrospective analysis to determine values of CEA and CA19-9 prior to NACT (pre-NACT) and after NACT (post-NACT) in 399 patients with locally advanced gastric cancer (LAGC) who received intended NACT and surgery. RESULTS: Among the 399 patients who underwent NACT plus surgery, 132 patients (33.1%) had elevated pre-NACT CEA/CA19-9 values. Furthermore, either pre-NACT or post-NACT CEA /CA19-9 levels were significantly associated with prognosis (p = 0.0023) compared to patients with non-elevated levels. Moreover, among the patients, a significant proportion (73/132, 55.3%) achieved normalized CEA/CA19-9 following NACT, which is a strong marker of a favorable treatment response and survival benefits. In addition, the patients with normalized CEA/CA19-9 also had a prolonged survival compared to those who underwent surgery first (p = 0.0140), which may be attributed to the clearance of micro-metastatic foci. Additionally, the magnitude of CEA/CA19-9 changes did not exhibit a statistically significant prognostic value. CONCLUSIONS: Normalization of CEA/CA19-9 is a strong biomarker for the effectiveness of treatment, and can thus be exploited to prolong the long-term survival of patients with LAGC.

Case Report: Clinical application of continuous arterial infusion chemotherapy in neoadjuvant therapy for locally advanced gastric cancer.

Platinum-fluorouracil combination chemotherapy is the standard neoadjuvant treatment for locally advanced gastric cancer in China, but it does not improve the survival benefit of patients. In recent years, the application of immune checkpoint inhibitors and/or targeted drugs in neoadjuvant therapy for gastric cancer has achieved certain efficacy, but the survival benefit of patients is still not obvious. Intra-arterial infusion chemotherapy, as a method of regional therapy, has been widely used in the treatment of many advanced tumors and achieved remarkable curative effect. The role of arterial infusion chemotherapy in neoadjuvant therapy for gastric cancer is not clear. We describe two patients with locally advanced gastric cancer treated with continuous arterial infusion neoadjuvant chemotherapy. Two patients received continuous arterial infusion of chemotherapy drugs for 50 hours, the drugs were pumped into the main feeding artery of the tumor through the arterial catheter. A total of 4 cycles were followed, then undergone surgical resection. The postoperative pathological pCR of two patients was 100%, TRG was 0 grade, and no further anti-tumor therapy was required after operation, achieving clinical cure. During the treatment period, no serious adverse events occurred in either patient. These results suggest that continuous arterial infusion chemotherapy may be a new adjuvant therapy for locally advanced gastric cancer.

Multidisciplinary treatment for locally advanced gastric cancer: A systematic review and network meta-analysis.

Introduction: This study aimed to evaluate the efficacy of multidisciplinary treatment for patients with locally advanced gastric cancer (LAGC) who underwent radical gastrectomy. Patients and Methods: Randomised controlled trials (RCTs) comparing the effectiveness of surgery alone, adjuvant chemotherapy (CT), adjuvant radiotherapy (RT), adjuvant chemoradiotherapy (CRT), neoadjuvant CT, neoadjuvant RT, neoadjuvant CRT, perioperative CT and hyperthermic intraperitoneal chemotherapy (HIPEC) for LAGC were searched. Overall survival (OS), disease-free survival (DFS), recurrence and metastasis, long-term mortality, adverse events (grade ≥3), operative complications and R0 resection rate were used as outcome indicators for meta-analysis. Results: Forty-five RCTs with 10077 participants were finally analysed. Adjuvant CT had higher OS (hazard ratio [HR] = 0.74, 95% credible interval [CI] = 0.66-0.82) and DFS (HR = 0.67, 95% CI = 0.60-0.74) than surgery-alone group. Perioperative CT (odds ratio [OR] = 2.56, 95% CI = 1.19-5.50) and adjuvant CT (OR = 0.48, 95% CI = 0.27-0.86) both had more recurrence and metastasis than HIPEC + adjuvant CT, while adjuvant CRT tended to have less recurrence and metastasis than adjuvant CT (OR = 1.76, 95% CI = 1.29-2.42) and even adjuvant RT (OR = 1.83, 95% CI = 0.98-3.40). Moreover, the incidence of mortality in HIPEC + adjuvant CT was lower than that in adjuvant RT (OR = 0.28, 95% CI = 0.11-0.72), adjuvant CT (OR = 0.45, 95% CI = 0.23-0.86) and perioperative CT (OR = 2.39, 95% CI = 1.05-5.41). Analysis of adverse events (grade ≥3) showed no statistically significant difference between any two adjuvant therapy groups. Conclusion: A combination of HIPEC with adjuvant CT seems to be the most effective adjuvant therapy, which contributes to reducing tumour recurrence, metastasis and mortality - without increasing surgical complications and adverse events related to toxicity. Compared with CT or RT alone, CRT can reduce recurrence, metastasis and mortality but increase adverse events. Moreover, neoadjuvant therapy can effectively improve the radical resection rate, but neoadjuvant CT tends to increase surgical complications.