Resected Gastric Cancer Patients Research Articles

Association between adjuvant component of perioperative chemotherapy and survival outcomes in resected gastric cancer (GC).

378 Background: Perioperative chemotherapy is the standard of care for resectable GC but many patients do not proceed to or complete adjuvant chemotherapy (AC). It remains unclear whether AC following neoadjuvant chemotherapy (NAC) improves survival. Methods: Patients with GC who received NAC and underwent curative-intent gastrectomy from 2006-2022 were identified from an institutional database. Patients with mismatch repair-deficient/microsatellite instability-high tumors, GEJ tumors, M1 disease, neoadjuvant radiotherapy, total neoadjuvant intent treatment, incomplete NAC (<66% of planned cycles), and incomplete data were excluded. A lymph node ratio (LNR) risk cutoff was determined using maximally selected rank statistics. Kaplan-Meier analysis with log-rank tests were used to compare overall survival (OS) and disease-free survival (DFS). Cox proportional hazards regression models were used to identify independent predictors of OS and DFS. All analyses were performed in R statistical software. Results: Of 340 patients included, 264 (78%) received AC. Most common reasons for incomplete AC were postoperative complications (20%), poor performance status (16%), minimal pathologic response to NAC (14%), patient choice (14%), and NAC toxicity (9%). Median follow-up was 6.4 years. In the overall cohort, there was no significant difference in OS (median 10 vs. 8.3 years; p=0.14) or DFS (7.0 vs. 7.5 years; p=0.12) between AC and non-AC groups. In node-negative (ypN-) patients (n=170), there was no association between receipt of AC and OS (12 vs. 10 years; p=0.6) or DFS (12 vs. 10 years; p=0.8). On univariable analysis, lack of AC receipt was not associated with shorter OS (p=0.3) or DFS (p=0.4). In the node-positive (ypN+) cohort (n=170), AC receipt was associated with significantly longer DFS (4.8 vs. 2.7 years; p=0.031) but not OS (5.5 vs. 2.8 years; p=0.071). However, on multivariate analysis, AC only showed a non-significant trend towards longer DFS (HR 0.77 [95% CI 0.49-1.19]; p=0.20). High-risk patients based on LNR (LNR>0.0684; n=112) who received AC (n=87; 78%) had longer OS (p=0.033) and DFS (p=0.014). No such differences were observed in the low risk LNR subgroup (LNR<0.0684; n=227). Conclusions: Following NAC, AC was not associated with improved survival in patients with ypN- GC. The association between AC and survival in ypN+ GC remains unclear but LNR may be used to identify patients with ypN+ disease who may benefit from AC. These observations require prospective validation but may have implications for clinical care and future trial design.

Patient access to perioperative chemotherapy with fluorouracil, leucovorin, oxaliplatin and docetaxel in patients with resectable gastric cancer in the Netherlands.

The FLOT4 trial demonstrated superior survival of perioperative chemotherapy with 5-fluorouracil, oxaliplatin, and docetaxel (FLOT) compared to anthracycline triplets for resectable gastric cancer. These results were presented at the American Society of Clinical Oncology (ASCO) congress in June 2017 and published in April 2019. However, adoption of novel treatments in clinical practice often encounters delays. This study assesses the patterns of perioperative chemotherapy utilization and FLOT uptake in clinical practice within the Netherlands. A retrospective cohort study was conducted with resectable gastric cancer patients (cT1-4a,XcNallcM0) between 2015-2020 from the Netherlands Cancer Registry. Descriptive statistics, Cochran-Armitage tests, Fisher's exact or unpaired T-tests, and Jonckheere-Terpstra tests were used to analyze chemotherapy trends and FLOT uptake across hospitals. Among 3290 included patients, 42.9% received neoadjuvant treatment. In 2015, 43.6% of patients received perioperative chemotherapy versus 43.5% in 2020 (p=0.63). 40 out of 62 hospitals (64.5%) adopted FLOT between the ASCO presentation and the full publication. FLOT increased from 42.9% before publication to 86.8% after publication (p<0.0001), while anthracycline triplet use decreased to 0.9% (p<0.0001). Higher hospital volume was associated with fewer days to adoption (p=0.04) but not with adoption of FLOT before publication (p=0.14). Timing of FLOT adoption varied among Dutch hospitals, leading to unequal patient access to effective treatments. Establishing (inter)national guidelines on provisional treatment adjustment pending publication is crucial to reduce variation in access. Moreover, rapid publication of final trial results is imperative to reduce variation in practice and ensure fair patient treatment.

Perioperative Anemia Is an Independent Prognostic Factor for Gastric Cancer Patients Who Receive Curative Treatment.

This study evaluated the clinical impact of anemia during the perioperative period on both short- and long-term oncological outcomes in resectable gastric cancer (GC) patients who received curative treatment. We conducted a retrospective review of medical records and collected data from consecutive patients with gastric cancer who underwent curative resection at Yokohama City University between 2015 and 2022. A total of 330 patients were evaluated in this study. In the present study, we set the cutoff value of preoperative hemoglobin at 11.0 g/dl. The 1-, 3-, and 5-year overall survival rates were 88.6%, 59.8%, and 47.0%, respectively, in patients with hemoglobin levels <11 g/dl, and 96.8%, 86.0%, and 80.0% in those with hemoglobin levels ≥11 g/dl. Based on univariate and multivariate analyses, the preoperative hemoglobin status was identified as an independent prognostic factor for both overall survival (hazard ratio=1.772, 95% confidence interval=1.109-2.831, p=0.017) and recurrence-free survival (hazard ratio=1.782; 95% confidence interval=1.166-2.723, p=0.008). In addition, perioperative anemia was also found to affect the clinical course of postoperative surgical complications and postoperative adjuvant chemotherapy. Perioperative anemia was identified as an independent prognostic factor in GC patients who received curative treatment. To improve the survival of patients with GC, it is necessary to provide care and management for perioperative anemia before curative treatment.

Comparison of treatment strategies based on clinical and pathological nodal status in resectable gastric adenocarcinoma.

To determine the optimal multimodal treatment strategy between perioperative chemotherapy (PEC), postoperative chemoradiation therapy (POCR), and postoperative chemotherapy (POC) in resected gastric cancer (GC) patients based on nodal status. In this retrospective analysis, the National Cancer Database was used to identify resected non-metastatic GC (2006-2016). Patients were stratified by clinical nodal status-negative (cLN-) and positive (cLN+). In patients with cLN- disease who underwent upfront resection and were upstaged to pathological LN+, overall survival (OS) was compared between POC and POCR. In patients with cLN- and cLN+ disease, OS was compared between PEC, POCR, and POC. Kaplan-Meier survival estimate, log-rank test, and multivariable Cox proportional hazards analysis were performed. We identified 7827 patients (cLN- 4828; cLN+ 2999). On multivariable analysis in patients with cLN- disease who underwent upfront resection (n = 4314) and were upstaged to pLN+ disease (70%), POCR (n = 2300, aHR 0.78, 95% CI 0.70-0.87, p < 0.001) was associated with improved OS compared to POC (n = 907). No significant difference was noted between POCR (n = 766, aHR 1.11, 95% CI 0.88-1.40, p = 0.39) and POC (n = 341) in patients with pLN- disease. On multivariable analysis in all patients with cLN- disease, POCR (n = 3066) was significantly associated with improved OS (aHR 0.84, 95% CI 0.75-0.92, p < 0.01) compared to POC (n = 1248). No significant difference was noted between POCR (aHR 1.0, 95% CI 0.70-1.01, p = 0.958) and PEC (n = 514). These results remained consistent in patients with cLN+ disease (POCR = 1602, POC = 720, PEC = 677). Postoperative chemoradiation is associated with improved survival in GC patients upstaged from clinically node-negative disease to pathologically node-positive disease. Negative clinical nodal disease status is not a reliable indicator of pathological nodal disease.

Comparison of Peritoneal Cytology Results Before and After Resection in Gastric Cancer Patients.

Peritoneal cytology is used to detect the peritoneal spread of gastric cancer and to assess survival rate. The aim of this study was to compare the risk factors, recurrence, and survival of gastric cancer patients with positive and negative peritoneal cytology before and after resection. Patients with gastric cancer who underwent elective surgery were retrospectively analysed. The study covered a period between September 2018 and September 2020. After applying the exclusion criteria, 57 patients were included in the study. For the purpose of this study, peritoneal cytology was taken from the same three intra-abdominal regions before and after resection from patients with operable gastric cancer. Of the 57 patients included in the study, 36 (63.2%) were male patients and 21 (36.8%) were female patients. Preoperative or postoperative malignant cytology was detected in 12 patients (21.1%). Tumour diameter was larger in patients with preoperatively detected malignant cytology than in the patients with postoperatively positive malignant cytology (66.67 mm vs. 44.44 mm) (p = 0.006). The recurrence rate was higher in patients with preoperative and postoperative positive cytology than in those with negative cytology (p = 0.019). The survival of patients with preoperative malignant cytology was worse than the survival of patients with preoperative benign cytology (p = 0.011). A significant correlation was found between lymphovascular invasion (+), perineural invasion (+), T4, Stage 3 disease, number of malignant lymph nodes, and preoperative cytology positivity (p <0.05). In our study, we found that the preoperative cytology positivity is associated with lymphovascular invasion positivity, perineural invasion positivity, T4 tumour, Stage 3 disease, and the number of malignant lymph nodes. Postoperative positive cytology was not associated with the same variables. Because of the significant associations in preoperative positivity, fluid samples should be obtained immediately after the abdomen is open and before the tumour is manipulated. If possible, fluid samples should be taken from different quadrants, but if the sample is to be taken from a single quadrant, it should be taken from the pelvis.

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&lt;0.05). TGR0-1 group had lower density of PDL1+,CD68+PDL1+ and CD68+PDL1- cells in contrast to TGR 2-3 group(P&lt;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.

Robotic gastrectomy was reliable option for overweight patients with gastric cancer: a propensity score matching study.

The role of minimally invasive surgery using robotics versus laparoscopy in resectable gastric cancer patients with a high body mass index (BMI) remains controversial. A total of 482 gastric adenocarcinoma patients with BMI ≥ 25 kg/m2 who underwent minimally invasive radical gastrectomy between August 2016 and December 2019 were retrospectively analyzed, including 109 cases in the robotic gastrectomy (RG) group and 321 cases in the laparoscopic gastrectomy (LG) group. Propensity score matching (PSM) with a 1:1 ratio was performed, and the perioperative outcomes, lymph node dissection, and 3-year overall survival (OS) and disease-free survival (DFS) rates were compared. After PSM, 109 patients were included in each of the RG and LG groups, with balanced baseline characteristics. Compared with the LG group, the RG group had similar intraoperative estimated blood loss [median (IQR) 30 (20-50) vs. 35 (30-59) mL, median difference (95%CI) - 5 (- 10 to 0)], postoperative complications [13.8% vs. 18.3%, OR (95%CI) 0.71 (0.342 to 1.473)], postoperative recovery, total harvested lymph nodes [(34.25 ± 13.43 vs. 35.44 ± 14.12, mean difference (95%CI) - 1.19 (-4.871 to 2.485)] and textbook outcomes [(81.7% vs. 76.1%, OR (95%CI) 1.39 (0.724 to 2.684)]. Among pathological stage II-III patients receiving chemotherapy, the initiation of adjuvant chemotherapy in the RG group was similar to that in the LG group [median (IQR): 28 (25.5-32.5) vs. 32 (27-38.5) days, median difference (95%CI) - 3 (- 6 to 0)]. The 3-year OS (RG vs. LG: 80.7% vs. 81.7%, HR = 1.048, 95%CI 0.591 to 1.857) and DFS (78% vs. 76.1%, HR = 0.996, 95%CI 0.584 to 1.698) were comparable between the two groups. RG conferred comparable lymph node dissection, postoperative recovery, and oncologic outcomes in a selected cohort of patients with BMI ≥ 25 kg/m2.

Development and validation of a preoperative CT-based risk scoring system for predicting recurrence-free survival in patients undergoing curative surgery for gastric cancer

PurposeThe objective of this study was to establish and validate a preoperative risk scoring system that incorporated both clinical and computed tomography(CT) variables to predict recurrence-free survival (RFS) in gastric cancer(GC) patients who underwent curative resection. MethodWe retrospectively included consecutive patients with surgically confirmed GC who underwent preoperative CT scans between October 2017 and January 2022. Multivariate Cox regression analysis was employed in the derivation set to identify clinical and CT variables associated with RFS and to construct a risk score. This risk score was subsequently validated in an independent test set. ResultsA total of 346 patients were included in the study, with 213 in the derivation set and 133 in the test set. Five variables, namely ctEMVI, ctBorrmann, visceral obesity, sarcopenia, and NLR, were independently associated with RFS. In the test set, the preoperative risk score exhibited a c-index of 0.741, which outperformed the predictive accuracy of pathological tumor staging (c-index of 0.673, p = 0.021) at various time points. The preoperative risk score effectively stratified patients into low and high-risk groups. ConclusionThe developed preoperative risk scoring system demonstrated the ability to predict RFS following curative resection in GC patients.

Clinicopathologic features and prognostic value of claudin 18.2 overexpression in patients with resectable gastric cancer

Claudin 18.2 has emerged as a promising therapeutic target in gastric cancer based on phase 3 studies. However, clinicopathologic features associated with claudin 18.2 overexpression have not been comprehensively studied specifically for patients with resectable gastric cancer. This retrospective study included 299 patients with stage I–III resectable gastric cancer who underwent curative surgical resection. Possible associations between claudin 18.2 overexpression (moderate-to-strong expression in ≥ 75% by the 43-14A clone) and clinicopathologic features and survival outcomes were analyzed. There were 90 (30.1%), 96 (32.1%), and 113 (37.8%) patients with stage I, II, and III disease, respectively. Claudin 18.2 overexpression was noted in 139 out of 299 patients (46.5%). Claudin 18.2 overexpression was associated with a younger age, a lower invasion depth limited to the mucosa/submucosa, and less frequent lymphovascular invasion. Claudin 18.2 overexpression was also associated with Borrmann type 4 among patients with advanced gastric cancer and the diffuse histological type. Claudin 18.2 overexpression was not an independent factor for survival outcomes. In conclusion, claudin 18.2 was overexpressed in almost half of resectable gastric cancer patients. Claudin 18.2 overexpression was associated with some clinicopathological characteristics, but was not an independent prognostic factor in a localized setting.

Does the ypTNM-stage adequately predict long-term survival rates in gastric cancer patients receiving neoadjuvant chemotherapy followed by radical resection?

Background Following neoadjuvant chemotherapy (NAC) for resectable gastric cancer, the prognostic adequacy of the UICC staging system needs to be investigated. In particular to explore whether the ypTNM curves for radically resected gastric cancer patients receiving NAC follow the stage-matched survival curves of radically resected chemo-naïve patients (pTNM). Further, to disclose any interaction between the TNM-response mode to NAC and stage-specific survival rates, i.e., whether survival for a particular pathological disease stage was dependent on whether this was reached through a downstaging or as stable disease following NAC. Material and methods Retrospective study on radically resected patients ≤ 75 years of age with gastric adenocarcinoma stages I-III diagnosed during 2001–2016. The patients constitute two population-based cohorts; the SURG-group with n = 121 patients treated before 2007 when NAC was introduced, and the NAC-group with n = 126 patients diagnosed since early 2007, receiving NAC and subsequent radical resection. Results Long-term survival rates were similar when specific ypTNM-stages were compared to their corresponding pTNM chemo-naïve counterparts. The dichotomised N0 vs. N + had a substantial impact on the long-term survival rates in both groups, however, no discrepancy in long-term survival rates between pN0 vs. ypN0, and pN + vs. ypN + was found. The pathological stage determined long-term survival rates irrespective of the baseline disease stage, as no interaction between the response mode and stage-specific survival rates was found. Conclusions Survival curves for specific ypTNM-stages following NAC did not differ from the corresponding survival curves of their chemo-naïve pTNM counterparts. The interpretation is that NAC affected the gastric cancer, lymph nodes, and micrometastases, in such a way that the final ypTNM-stage provided similar prognostic information as the chemo-naïve pTNM-stages. Survival rates were contingent on the final ypTNM-stages alone, and not influenced by the response mode to reach that particular disease stage, or predetermined by the original clinical TNM-stage.

The value of intravoxel incoherent motion diffusion-weighted imaging in predicting perineural invasion for resectable gastric cancer: a prospective study

To investigate the potential of intravoxel incoherent motion (IVIM) diffusion-weighted imaging to predict perineural invasion (PNI) preoperatively in resectable gastric cancer (GC). This study prospectively recruited 85 surgically resected GC patients (58 men, 27 women) aged 60.87±10.17 (39-81) years, who underwent IVIM sequence within 1 week before surgery. According to histopathological PNI diagnoses, patients were divided into PNI positive and negative groups. Conventional apparent diffusion coefficient (ADC) and the IVIM parameters, including true diffusion coefficient (D), pseudodiffusion coefficient (D∗), and pseudodiffusion fraction (f), were compared between the two groups. Morphological MRI features were also analysed. Multivariate logistic regression was used to screen independent predictors of PNI. Receiver-operating characteristic curve analyses were preformed to evaluate the efficacy. Spearman's correlation test was performed to analyse the relationship between MRI parameters and PNI. Tumour thickness and f in PNI-positive group were higher, whereas the ADC, D were lower than those in PNI-negative group (p<0.05). These four parameters correlated with PNI (p<0.05). The D, f, and tumour thickness were independent predictors of PNI. The area under the curve of ADC, D, f, thickness, and the combined parameter (D+f+thickness) were 0.648, 0.745, 0.698, 0.725, and 0.869, respectively. The combined parameter demonstrated higher efficacy than any other parameters (p<0.05). The ADC, D, and f can effectively distinguish PNI status in GC. The D, f, and thickness were independent predictors of PNI.

Toll-like receptors 1, 2, 4, 5, and 6 in gastric cancer.

Toll-like receptors (TLRs) are expressed on both immune cells and tumor cells, triggering both anti-tumor and pro-tumor responses. Therefore, TLRs have potential as prognostic biomarkers and immunotherapeutic targets. The aim of this study was to investigate TLR1, TLR2, TLR4, TLR5, and TLR6 expression and association with clinicopathological variables and survival in gastric cancer. Immunohistochemical study on cancer specimens from 564 resected gastric cancer patients was performed using tissue microarrays. The association between patient survival and TLR expression was calculated with Cox regression adjusted for confounding factors. Patients with high cytoplasmic TLR2 expression had significantly poorer 5-year survival than the low cytoplasmic TLR2 expression group in multivariate analysis (adjusted HR 1.38, 95% CI 1.11-1.71), and this estimate was similar in intestinal type (adjusted HR 1.33, 95% CI 0.98-1.80) and diffuse type (adjusted HR 1.48, 95% CI 1.06-2.05) histology subgroups. Patients with high cytoplasmic TLR6 expression group had significantly better 5-year survival compared with low cytoplasmic TLR6 expression group in multivariate analysis (adjusted HR 0.74, 95% CI 0.60-0.91). In the subgroup analysis of diffuse type of histology, the 5-year survival was better in high cytoplasmic TLR6 expression group in multivariable analysis (HR 0.62, 95% CI 0.46-0.83). In the intestinal type of histology subgroup, no significant differences between the groups were present. TLR1, TLR4, and TLR5 expression were not associated with 5-year survival. In conclusion, cytoplasmic TLR2 and TLR6 expression seem to have independent prognostic impact in gastric cancer, while TLR1, TLR4, and TLR5 do not.

Soluble PD-L1 as a diagnostic and prognostic biomarker in resectable gastric cancer patients.

In this study, we compared programmed death-ligand 1 (PD-L1) expression in primary tissue samples and its soluble form (sPD-L1) concentration in matched preoperative plasma samples from gastric cancer patients to understand the relationship between tissue and plasma PD-L1 expression and to determine its diagnostic and prognostic value. PD-L1 expression in tissue was assessed by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA), and sPD-L1 concentration in plasma was quantified by ELISA. The levels of the CD274 gene, which encodes for PD-L1 protein, were examined as part of bulk tissue RNA-sequencing analyses. Additionally, we evaluated the association between sPD-L1 levels and various laboratory parameters, disease characteristics, and patient outcomes. GC patients had significantly higher levels of sPD-L1 in their plasma (71.69pg/mL) compared to healthy controls (35.34pg/mL) (p < 0.0001). Moreover, sPD-L1 levels were significantly correlated with tissue PD-L1 protein, CD274 mRNA expression, larger tumor size, advanced tumor stage, and lymph node metastasis. Elevated sPD-L1 levels (> 103.5ng/mL) were associated with poor overall survival (HR = 2.16, 95%CI 1.15-4.08, p = 0.017). Furthermore, intratumoral neutrophil and dendritic cell levels were directly correlated with plasma sPD-L1 concentration in the GC patients. sPD-L1 was readily measurable in GC patients, and its level was associated with GC tissue PD-L1 expression, greater inflammatory cell infiltration, disease progression, and survival. Thus, sPD-L1 may be a useful minimally invasive diagnostic and prognostic biomarker in GC patients.

The value of lymph nodes ratios in the prognosis of resectable remnant gastric cancer through the retrospective propensity score matching analysis

PurposeCurrently, the characteristics and prognosis of remnant gastric cancer (RGC) are not fully understood yet. The present study aimed to describe the details of clinicopathological features of resectable RGC and investigated the factors affecting survival after the curative operation.MethodsFrom Jan. 2006 to Dec. 2015, a total of 118 resectable RGC patients (the RGC group) and 236 age-, sex- and TNM stages-matched resectable gastric cancer (GC) patients (the control group) were recruited retrospectively. Clinicopathological characteristics and overall survival were compared between the two groups.ResultsThe overall survival rate was 46.61% for RGC patients compared to 55.08% for control groups (P < 0.01), and the mean overall survival time of RGC patients was 40.23 ± 32.27 months, compared to 55.06 ± 34.29 months in the control group (P = 0.023 after matching). The overall survival (OS) of RGC patients with stage IIb was much worse than IIa (P < 0.001) and similar to IIIa (P = 0.463) and IIIb (P = 0.014). Multivariate Cox proportional hazards model analysis revealed that TNM stage (HR: 3.899, P < 0.001) and lymph nodes ratio (LNR) (HR: 2.405, P = 0.028) were independent prognostic significance to OS.ConclusionsThe OS of RGC was much worse than GC with similar TNM stages, and LNR might consider a highly reliable indicator to evaluate the prognostic in RGC.

A feasibility study of modified docetaxel, cisplatin, and capecitabine for advanced gastric cancer followed by gastrectomy.

To explore the feasibility of modified docetaxel, cisplatin, and capecitabine (mDCX) chemotherapy with a lower dose of docetaxel than previously reported for stage III resectable gastric cancer patients with a high risk of recurrence or for stage IV gastric cancer patients aiming for conversion surgery. Patients with stage III resectable HER2-negative gastric cancer with large type 3 or type 4 tumors or extensive lymph node metastasis (bulky N or cN3) and those who had stage IV HER2-negative gastric cancer with distant metastasis were enrolled to receive 30mg/m2 docetaxel and 60mg/m2 cisplatin on day 1, followed by 2000mg/m2 capecitabine per day for 2 weeks every 3 weeks. Five patients with stage III gastric cancer with a high risk of recurrence received three courses of mDCX, and four patients with stage IV gastric cancer received three or four courses of mDCX. In terms of grade 3 or worse adverse events, leukopenia was observed in one (11%) patient, neutropenia in two (22%) patients, anemia in one (11%) patient, anorexia in two (22%) patients and nausea in two (22%) patients. All six patients with measurable lesions achieved a partial response. All nine patients underwent subsequent surgeries. The histological responses of the nine patients revealed grade 3 in one (11%) patient, grade 2 in five (56%) patients, and grade 1a in three (33%) patients. Three of the nine patients survived without recurrence, and two of them survived for more than four years. mDCX seems to be feasible and may be helpful as neoadjuvant chemotherapy for patients at high risk of recurrence or as chemotherapy for patients who are likely to undergo conversion surgery.

Development and validation of a clinical cure marker based on negative lymph nodes for gastric cancer after gastrectomy.

To explore lymph node (LN)-related derived indicators as clinical cure markers for gastric cancer (GC) after gastrectomy. Data of resected GC patients were extracted from the SEER database and our own department. Propensity score matching (PSM) was used to balance the baseline differences between the clinical cure and the nonclinical cure groups. The area under the curve (AUC) and decision curve analysis (DCA) were used to choose the optimal marker, and survival analysis was used to validate the clinical value of the most effective marker. After PSM, the differences in age, sex, race, location, surgical type, and histologic type between the two groups were significantly reduced (all P > 0.05), and the AUCs of examined LNs (ELNs), negative LNs (NLNs), ESR (ELNs/tumor size), ETR (ELNs/T-stage), NSR (NLNs/tumor size), NTR (NLNs/T-stage), EPR (ELNs/PLNs) and NPR (NLNs/PLNs) were 0.522, 0.625, 0.622, 0.692, 0.706, 0.751, 7.43, and 7.50, respectively. When NTR was 5.9, the Youden index of 0.378 was the highest. The sensitivity and specificity were 67.5% and 70.3% in the training group and 66.79% and 67.8% in the validation group, respectively. DCA showed that NTR had the largest net clinical benefit, and patients with NTR greater than 5.9 had significantly prolonged overall survival in our own cohort. NLNs, NTR, NSR, ESR, ETR, NPR and EPR can be used as clinical cure markers. However, NTR was the most effective, and the best cutoff value was 5.9.

Clinicopathological characteristics and treatment outcome of resectable gastric cancer patients with small para-aortic lymph node.

Resectable gastric cancer (GC) patients with small para-aortic lymph node (smaller than 10mm in diameter, sPAN) were seldom reported, and existing guidelines did not provide definite treatment recommendation for them. A total of 667 consecutive resectable GC patients were enrolled. 98 patients were in the sPAN group, and 569 patients without enlarged para-aortic lymph node were in the nPAN group. Standard D2 lymphadenectomy was performed. Neoadjuvant and adjuvant chemotherapy were administrated according to the cTNM and pTNM stage, respectively. Clinicopathological features and prognosis were compared between these two groups. The median size of sPAN was 6 (range, 2-9) mm and the distribution was prevalent in No. 16b1. cN stage (p=0.001) was significantly related to the presence of sPAN. sPAN was both independent risk factor for OS (p=0.031) and RFS (p=0.046) of all patients. The prognosis of patients with sPAN was significantly worse than that of patients with nPAN (OS: p=0.008; RFS: p=0.007). Preoperative CEA and CA19-9 were independent risk factors for prognosis of patients with sPAN. Furthermore, patients in the sPAN group with normal CEA and CA19-9 exhibited acceptable prognosis (5-year OS: 67%; RFS: 64%), while those with elevated CEA or CA19-9 suffered significantly poorer prognosis (5-year OS: 17%; RFS: 17%) than patients in the nPAN group (5-year OS: 64%; RFS 62%) (both p < 0.05). Standard D2 lymphadenectomy should be considered a valid approach for GC patients with sPAN associate to normal preoperative CEA and CA19-9 levels. Patients with sPAN associated to elevated CEA or CA19-9 levels could benefit from a multimodal approach: neoadjuvant chemotherapy; radical surgery with D2 plus lymph nodal dissection extended to No. 16 station.

Time to first treatment and optimal adjuvant treatment strategy in patients with resectable gastric cancer pathologically upstaged to lymph node–positive disease.

473 Background: Treatment strategies in resectable gastric cancer (GC) patients include perioperative chemotherapy (PEC), postoperative chemoradiation therapy (POCR), and postoperative chemotherapy (POC). Treatment delay can lead to metastases with unfavorable outcomes. We aim to identify the distribution of patients upstaged to pathologically node positive disease (pLN+) stratified by time and the optimal treatment in this cohort. Methods: We analyzed resected GC patients in the National Cancer Database (2004-2016) with clinically node negative disease (cLN-). Time from diagnosis to first definitive therapy was stratified as ≤2, &gt;2 to ≤4, and &gt;4 weeks. The distribution of patients upstaged from cLN- to pLN+ disease, the concordance between cLN- and pathologically lymph node negative (pLN-) disease based on treatment strategy, and time to first definitive therapy was analyzed. POC and POCR were compared to evaluate their effect on overall survival (OS) in patients with cLN- upstaged to pLN+ disease. Kaplan-Meier test, log-rank test, multivariable Cox proportional hazards analysis (MVA) were performed. Results: Of the 4,828 gastric cancer patients with cLN- disease, 514 (10.65%) patients received PEC and 4,314 (89.35%) patients received upfront surgery followed by POCR/POC. Distribution of patients stratified by time between diagnosis to first definitive treatment - chemotherapy (PEC) or surgery (POC/POCR), for ≤2 weeks was 9.5% vs. 33%, &gt;2 - ≤4 weeks was 28.4% vs. 24.2% and &gt;4weeks was 62% vs 42.7%, respectively. Patients upstaged from cLN- to pLN+ disease in the PEC group was 43.37%(n=206), and 70%(n=2574) in the upfront surgery group (POC/POCR). Of the 206 (43.37%) patients upstaged from cLN- to pLN+ in the PEC cohort, the upstage rate was 7.77% when chemotherapy was started within 2 weeks of diagnosis, compared to 27.67% with &gt;2 to ≤4 weeks, and 64.56% with &gt;4 weeks. Of the 2,574 (70%) patients upstaged in the upfront surgery cohort (POCR/POC), 30.61% were upstaged in ≤2 weeks, 24.95% in &gt;2 to ≤4 weeks, and 44.44% in ≥4 weeks. On MVA, patients with cLN- disease that were pLN- (POCR=766, POC=341) had no significant difference in OS when treated with POCR (HR 1.11, p=0.39) compared to POC. Patients with pLN+ (POCR=2300, POC=907) disease had an association with improved OS when treated with POCR (HR 0.78, p&lt;0.001) compared to POC. Conclusions: When resectable gastric cancer patients undergoing upfront surgery are upstaged from clinically node negative to pathologically node positive disease, postoperative chemoradiation therapy may be the optimal treatment strategy compared to postoperative chemotherapy. Clinical nodal status may not be an optimal predictor of nodal disease.

Systemic inflammation score as a preoperative prognostic factor for patients with pT2–T4 resectable gastric cancer: a retrospective study

BackgroundSystemic inflammation has been reported to be associated with cancer progression and metastasis. Systemic inflammation score (SIS), calculated from preoperative serum albumin level and lymphocyte-to-monocyte ratio, has been shown to be a novel prognostic factor for several types of tumors. This study aimed to evaluate the prognostic value of the SIS in patients with pT2–4 resectable gastric cancer (GC).MethodsTotal 97 patients with pT2–4 GC who underwent curative surgery from 322 cases between 2009 and 2015 in Fukushima Medical University Hospital were included. We performed univariate and multivariate analyses to evaluate the usefulness of preoperative SIS and other prognostic factors for relapse-free survival (RFS) and overall survival (OS).ResultsThe higher SIS score was associated with undifferentiated cancer and recurrence. Univariate analysis of RFS identified deeper tumor invasion and higher SIS were significant risk factors and multivariate analysis revealed that both of them were independent prognostic factors for RFS. As for OS, age, tumor invasion, SIS and LNR were significantly correlated with RFS. In multivariate analysis, tumor invasion, SIS and LNR were independent prognostic factors for OS.ConclusionsSIS was an independent prognostic factor for RFS and OS in pT2–4 resectable gastric cancer patients who underwent curative gastrectomy.

Efficacy and safety of FLOT regimen vs DCF, FOLFOX, and ECF regimens as perioperative chemotherapy treatments for resectable gastric cancer patients; a report from the middle east.

This study aimed to compare the efficacy and toxicity of perioperative chemotherapy regimens including epirubicin, cisplatin, 5-fluorouracil (ECF), docetaxel, cisplatin, 5-fluorouracil (DCF), leucovorin, 5-fluorouracil, oxaliplatin (FOLFOX), and 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) to identify the most effective chemotherapy regimen with less toxicity. This retrospective cohort study (2014-2021) was based on 152 eligible resectable gastric cancer patients who had received one of the perioperative mentioned chemotherapy regimens and followed for at least two years. The primary endpoint of this study was overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and R0 resection. Of included patients, 21%, 33.7%, 24.3%, and 21% had received ECF, DCF, FOLFOX and FLOT, respectively. After the median 30-month follow-ups, OS was higher with the FLOT regimen in comparison with other regimens (hazard ratio = 0. 276). The median OS of the FLOT regimen was 39 months. Besides, the median OS was 28, 25, and 21 months for DCF, FOLOFX, and ECF regimens, respectively. Moreover, a median PFS of 24, 18, 17, and 14 months was observed for FLOT, DCF, FOLFOX, and ECF regimens, respectively (Log-rank < 0.001). FLOT regimen showed 84. 4% ORR which was notably higher than other groups. For resectable gastric cancer patients, the perioperative FLOT regimen led to a significant improvement in patients' OS and PFS versus ECF, DCF, and FOLFOX regimens. As such, the FLOT regimen could be considered the optimal option for managing resectable gastric cancer patients.