VentX promotes tumor specific immunity and efficacy of immune checkpoint inhibitors.

Immune suppression within tumor microenvironments (TME) have been implicated in limited efficacy of immune check point inhibitors (ICIs) against solid tumors. Down-regulated VentX expression in tumor associated macrophages (TAMs) underlies phagocytotic anergic phenotype of TAMs, which govern immunological state of TME. In this study, using a tumor immune microenvironment enabling model system (TIME-EMS) of non-small cell lung cancer (NSCLC), we found that PD-1 antibody modestly activates cytotoxic T lymphocytes (CTLs) within the NSCLC-TME but not the status of TIME. We showed that the restoration of VentX expression in TAMs reignites the phagocytotic function of TAMs, which in turn, transforms TIME, activates CTLs in a tumor-specific manner and promotes efficacy of PD-1 antibody against NSCLC but not toxicity on normal lung epithelial cells. Supported by in vivo data on NSG-PDX models of primary human NSCLC, our study revealed potential venues to promote the efficacy of ICI against solid tumors through VentX-based mechanisms.

Oncological outcomes of conversion therapy in gastric cancer patients with peritoneal metastasis: a large-scale retrospective cohort study.

BACKGROUND: Data on the long-term oncological outcomes of patients who undergo conversion surgery (CS) in gastric cancer (GC) patients with peritoneal metastasis (PM) are limited. METHODS: GC patients with PM who received intraperitoneal (ip) and systemic chemotherapy between April 2015 and January 2021 were enrolled. Multivariate analysis was performed to identify risk factors associated with survival. Clinicopathological and survival outcomes were compared between those with CS and those without CS (NCS). The paclitaxel (PTX) plus tegafur-gimeracil-oteracil potassium capsules (S-1) (PS) + ip PTX and oxaliplatin plus S-1 (SOX) + ip PTX groups were matched in a 1:1 ratio using propensity score matching. Oncological and survival data were collected and analyzed. RESULTS: A total of 540 patients who received ip chemotherapy via subcutaneous port and systemic chemotherapy were analyzed and 268 patients were enrolled, including 113 who underwent CS and 155 who did not. Overall survival (OS) were 27.0 months and 11.8 months in the CS and NCS groups (P < 0.0001), respectively. R0 resection was an independent prognostic factor for patients who underwent CS. The OS of patients with or without ovariectomy was 21.3 or 12.0 months (P < 0.0001). No difference of clinicopathological and survival outcomes was found between the PS + ip PTX and SOX + ip PTX groups. CONCLUSION: Conversion therapy is safe and adverse events were manageable. CS improves the survival of GC patients with PM after ip and systemic chemotherapy. R0 is an important prognostic factor. Furthermore, outcomes are comparable between the PS + ip PTX and SOX + ip PTX groups.

Sintilimab combined neoadjuvant intraperitoneal and systemic chemotherapy in gastric cancer with peritoneal metastasis.

Intraperitoneal chemotherapy combined with systemic chemotherapy is one of the therapeutic modalities currently used for the treatment of gastric cancer patients with peritoneal metastasis. This study was designed to evaluate the efficacy and safety of sintilimab plus S-1 combined intraperitoneal and intravenous paclitaxel. This is an open-label, single-center, phase II study including 36 gastric adenocarcinoma patients with peritoneal metastases diagnosed by laparoscopy. All enrolled patients received sintilimab, intraperitoneal and intravenous paclitaxel plus oral S-1 every 3 weeks. Conversion operation should be considered when a patient responds to the regimen and the peritoneal metastasis disappears. After gastrectomy, the protocol treatment is repeated until disease progression, unacceptable toxicity, investigator decision or patient withdrawal. The primary end point is the 1-year survival rate. Clinical Trial Registration: NCT05204173 (ClinicalTrials.gov).

Intra-abdominal fat volume estimation by multi-detector rows computed tomography: relevance in surgical fellowship training program in Shanghai: a retrospective study.

Background: Intra-abdominal fat volume (IFV) has been shown to have a negative impact on surgical outcomes in gastric cancer (GC) and other gastrointestinal surgeries. The purpose of this study is to look into the relationship between IFV and perioperative outcomes in GC patients using multi-detector rows computed tomography (MDCT) and assess the importance of implementing this observation in current surgical fellowship training programs. Methods: Patients with GC who underwent open D2 gastrectomy between May 2015 and September 2017 were included in the study. Based on MDCT estimation, patients were divided into high IFV (IFV ≥ 3,000 ml) and low IFV (IFV < 3,000 ml) groups. Perioperative outcomes for cancer staging, type of gastrectomy, intraoperative blood loss (IBL), anastomotic leakage, and hospital stay were compared between the two groups. This study was registered as CTR2200059886. Results: Out of 226 patients, 54 had early gastric carcinoma (EGC), while 172 had advanced gastric carcinoma (AGC). There were 64 patients in the high IFV group and 162 in the low IFV group. The high IFV group had significantly higher IBL mean values (p = 0.008). Therefore, having a high IFV was a risk factor for the occurrence of perioperative complications (p = 0.008). Conclusions: High IFV estimated by MDCT prior to GC surgery was associated with increased IBL and postoperative complications. Incorporating this CT-IFV estimation into surgical fellowship programs may aid aspiring surgeons in selecting patients during independent practice in their learning curve and surgical practice for the most appropriate approach for treating GC patients.

NF-κB-regulated VentX expression mediates tumoricidal effects of chemotherapeutics at noncytotoxic concentrations.

Limited therapeutic efficacy and severe side effects represent the central hurdles facing cancer chemotherapy. Immune suppression within tumor immune microenvironments (TIME) has been implicated in chemoresistance. In this study, using a TIME-enabling model system (TIME-EMS), we demonstrate that the chemotherapeutic agent doxorubicin has cytocidal effects on tumor cells at high dosage but induces changes in the immune landscape of the TIME at low noncytotoxic concentrations via NF-κB-mediated induction of homeobox protein VentX expression in tumor-associated macrophages (TAMs). We demonstrated that VentX-regulated TAMs drastically promote tumor chemosensitivity >10-fold but exert little effect on chemotoxicity to normal cells through activating cytotoxic T lymphocytes in a tumor-specific manner. Supported by the in vivo synergy of VentX-regulated TAMs and low-dosage noncytotoxic doxorubicin, our data suggest a cell-death-independent immune mechanism for improving the therapeutic index of chemotherapeutic agents.

Efficacy and Safety of Conversion Therapy by Intraperitoneal and Intravenous Paclitaxel Plus Oral S-1 in Gastric Cancer Patients With Peritoneal Metastasis: A Prospective Phase II Study.

Background: Neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) has shown promising results in gastric cancer (GC) with peritoneal metastasis. However, clinical practice experience of NIPS is still lacking in China. In this study, we investigate the efficacy and safety of NIPS in Chinese patients. Methods: Eligible patients received NIPS every 3 weeks. Gastrectomy was performed for patients who met the criteria of conversion surgery. The primary end point was 1-year overall survival (OS) rate. Secondary end points were the response rate, toxic effects, conversion surgery outcomes and median survival time (MST). Results: Sixty-seven patients were enrolled. The primary endpoint was achieved with 1-year OS rate reached 67.2% (95% CI, 56.8%-79.4%). Conversion surgery was performed in 42 patients (62.9%), and R0 resection was achieved in 23 patients (54.8%) with the MST of 31.3 months (95% CI, 24.3-38.3). And the MST was 19.3 months (95% CI, 16.4-22.2) for all patients. Toxicity and surgical complications were well-tolerated. Moreover, sex, R0 resection, pathological nodal stage and tumor regression grade (TRG) were independent prognostic factors for patients who underwent conversion surgery. Conclusion: The NIPS is effective and safe in treating GC patients with peritoneal metastasis. Male patients, patients who underwent R0 resection, patients with ypN0-1 or TRG 1 after conversion surgery are more likely to benefit from the NIPS. Clinical Trial Registration: http://www.chictr.org.cn/, identifier https://clinicaltrials.gov/ ().

Adjuvant Chemotherapy in pT2N0M0 Gastric Cancer: Findings From a Retrospective Study.

Background: There is no global consensus on adjuvant chemotherapy (ACT) for pT2N0M0 gastric cancer. We conducted a retrospective study to reveal the role of ACT in such patients. Methods: Patients with pT2N0M0 gastric cancer who underwent radical resection with D2 lymphadenectomy for primary gastric cancer between January 2012 and May 2016 were included. Kaplan-Meier and Cox regression were used to evaluate overall survival (OS), disease-specific survival (DSS) and predictors of prognosis. Stratified analysis based on high-risk factors was conducted. Results: Of enrolled 307 patients, 111 patients underwent surgery alone and 196 patients received ACT. Surgery alone (HR = 2.913, 95% CI: 1.494-5.682, p = 0.002) and total gastrectomy (HR = 2.445, 95% CI: 1.279-4.675, p = 0.007) were independently associated with decreased OS. With the median follow-up of 73.1 months, the 5-year OS rate was 87.9% and 5-year DSS rate was 91.8%. Patients receiving ACT showed a better 5-year OS rate (92.9 vs. 79.3%, p < 0.001) and DSS rate (96.8 vs. 83.0%, p < 0.001) than patients underwent surgery alone. Patients receiving monotherapy (n = 130) had a relatively poor prognosis compared to patients receiving dual-drug (n = 66) without a significant difference (92.3 vs. 93.9%, p = 0.637). In patients without high-risk factors based on the Chinese Society of Clinical Oncology (CSCO) Guidelines, ACT also provided survival benefit (96.0 vs 82.9%, p = 0.038). Conclusions: ACT was accompanied with higher 5-year OS and DSS rates of patients with pT2N0M0 gastric cancer. Patients with pT2N0M0 gastric cancer, regardless of high-risk factors based on the CSCO guidelines, might be considered candidates for ACT. In regard to the therapy regimen, monotherapy might be the optimal choice, considering the adverse events.

A phase III trial of neoadjuvant intraperitoneal and systemic chemotherapy for gastric cancer with peritoneal metastasis.

Although recent advances in systemic chemotherapy have improved the clinical outcomes of gastric cancer patients with peritoneal metastasis, the peritoneum still represents a common site of treatment failure and disease recurrence. Neoadjuvant intraperitoneal-systemic chemotherapy has been acknowledged as a more aggressive treatment for gastric cancer patients with peritoneal metastasis. In this multicenter phase III randomized controlled trial, 238 patients will be randomly separated into two groups in a 2:1 ratio after laparoscopic exploration. The experimental arm will receive the proposed neoadjuvant intraperitoneal-systemic chemotherapy regimen, whereas the control group will receive a Paclitaxel + S-1 (PS) chemotherapy regimen. The endpoints for the study are overall survival, response rate, gastrectomy radicality rate, progression-free survival and adverse events.

Recent advances in technology have improved the outcomes of stomach cancer patients. However, there are still many patients who die of cancer that has spread from another part of the body. Neoadjuvant intraperitoneal­systemic chemotherapy has been acknowledged as a more aggressive treatment for stomach cancer patients with peritoneal metastasis (cancer that has spread to the very thin layer of tissue on the inside of the abdomen that covers the stomach and other organs). In this study, 238 patients will be randomly separated into two groups in a 2:1 ratio after evaluation. The experimental group will receive the proposed neoadjuvant intraperitoneal­systemic chemotherapy regimen, whereas the control group will receive a Paclitaxel + S-1 (PS) chemotherapy regimen. The endpoints for the study are how long patients live, number of patients who respond to treatment, number of patients who undergo surgery, how long patients live without their disease getting worse and problems caused by treatment. Trial registration number: ChiCTR-IIR-16009802.

Addition of sintilimab to nanoparticle albumin-bound paclitaxel and S-1 as adjuvant therapy in stage IIIC gastric cancer.

The prognosis of stage III gastric cancer (GC) is not satisfying and the specific chemotherapy regimens for GC of stage IIIC based on the 8th edition of the UICC/AJCC TNM staging system are still inconclusive. Peritoneal recurrence is the common and severe relapse pattern. Nanoparticle albumin-bound paclitaxel (Nab-PTX) is safer and more effective than PTX in the peritoneal metastasis. Clinical trial has demonstrated the safety and efficacy of sintilimab in GC. A combination of Nab-PTX, S-1 and sintilimab could be a promising triplet regimen as adjuvant therapy for GC. The aim of this article is to describe the design of this prospective Dragon-VII trial, conducted to evaluate the safety and efficacy of the combination of Nab-PTX, S-1 and sintilimab. Clinical trial registration: NCT04781413.

Lay abstract The prognosis of stage IIIC gastric cancer is poor and the treatment for it is not satisfying. This is a clinical trial that aims to explore a more effective therapy in gastric cancer patients of stage IIIC. Patients with stage IIIC gastric cancer must meet all of the inclusion criteria and none of the exclusion criteria to be eligible for this trial. The eligible patients will be given eight cycles of combinatory therapy of albumin-bound paclitaxel, a chemotherapy (day 1 and day 8), and S-1, another chemotherapy (days 1 to 14), plus sintilimab, a type of immunotherapy called an immune checkpoint inhibitor (day 1) every 3 weeks and then sintilimab maintenance for up to 12 months.

A phase II study of perioperative treatment in gastric cancer with No.16a2/b1 lymph node metastasis: DRAGON-06 trial.

Although gastric cancer with para-aortic lymph node (PAN) metastasis is commonly regarded as unresectable, surgeons have explored the optimal treatment for patients with PAN metastases limited to No.16a2/b1 in the past few decades. Preoperative systemic therapy combined with D2 gastrectomy plus PAN dissection may improve the prognosis of these patients. In this multicenter phase II trial, 29 gastric cancer patients with PAN metastasis limited to No.16a2/b1 will receive preoperative treatment with nab-paclitaxel, oxaliplatin, S-1 (nab-POS: nab-paclitaxel, oxaliplatin, S-1) and sintilimab followed by D2 gastrectomy plus PAN dissection; and postoperative treatment with oral S-1, intravenous sintilimab and intraperitoneal paclitaxel. The end points for the study are 3-year overall survival, 3-year disease-free survival, pathological response rate, incidence of postoperative complications and adverse events.

Stomach cancer with metastases in the para-aortic lymph nodes is usually considered inoperable. Chemotherapy combined with resection of the stomach and more extensive lymph node dissection may prolong the life of these patients. In this multicenter study, 29 stomach cancer patients with para-aortic lymph node metastases will receive preoperative treatment with nab-paclitaxel, oxaliplatin, S-1 and sintilimab, followed by resection of the stomach combined with para-aortic lymph node dissection and use of continued oral, intravenous and intraperitoneal chemotherapy. The study's end points are 3-year overall survival, 3-year disease-free survival, pathological response rate, incidence of postoperative complications and adverse events. Clinical Trial Registration: ChiCTR2200061125 (ChiCTR.org.cn).

Oxaliplatin plus S-1 with intraperitoneal paclitaxel for the treatment of Chinese advanced gastric cancer with peritoneal metastases.

BACKGROUND: In this study, we tried to access the efficacy and safety of oxaliplatin plus S-1 with intraperitoneal paclitaxel (PTX) for the treatment of Chinese advanced gastric cancer with peritoneal metastases. PATIENTS AND METHODS: Thirty patients diagnosed with advanced gastric cancer underwent laparoscopic exploration and were enrolled when macroscopic disseminated metastases (P1) were confirmed. PTX was diluted in 1 l of normal saline and IP administered through peritoneal port at an initial dose of 40 mg/m2 over 1 h on day1,8, respectively. Oxaliplatin was administered intravenously at an initial dose of 100 mg/m2 on day1, and S-1 was administered orally at an initial dose of 80 mg/m2 for 14 days followed by 7 days rest, repeated by every 3 weeks. RESULTS: Of all these 30 patients, the median number of cycles was 6 (range 2-16) due to the limitation of hematotoxicity and peripheral neuropathy by oxaliplatin. There were 11 (36.7%) patients received conversion surgery. The median progression free survival (PFS) was 6.6 months (95% CI = 4.7-8.5 months) and the median overall survival (OS) was 15.1 months (95% CI = 12.4-17.8 months). The grade 3-4 hematological toxicities were leucopenia (23.3%), neutropenia (23.3%), anemia (16.7%), and thrombocytopenia (20%), respectively. The grade 3-4 non-hematological toxicities were tolerated, most of which were peripheral sensory neuropathy (40%) due to oxaliplatin, diarrhea (20%), nausea and vomiting (26.7%). CONCLUSIONS: SOX+ip PTX regimen was effective in advanced gastric cancer with peritoneal metastasis. Survival time was significantly prolonged by conversion surgery. Grade 3-4 toxicities were uncommon. Large scale clinical trial is necessary to get more evidence to identify its efficacy. TRAIL REGISTRATION: ChiCTR, ChiCTR-IIR-16009802 . Registered 9 November 2016.

Is D2 Lymphadenectomy Alone Suitable for Gastric Cancer With Bulky N2 and/or Para-Aortic Lymph Node Metastases After Preoperative Chemotherapy?

BACKGROUND: For gastric cancer (GC) with extensive lymph node metastasis (bulky N2 and/or para-aortic lymph node metastases), there is no standard therapy worldwide. In Japan, preoperative chemotherapy (PCT) followed by D2 gastrectomy plus para-aortic lymph node dissection (PAND) is considered the standard treatment for these patients. However, in China, the standard operation for GC patients with only bulky N2 metastases was D2 gastrectomy. Besides, after PCT, whether doing PAND improves survival or not is debatable for GC patients with para-aortic lymph node (PAN) metastases. Therefore, we conducted this study to investigate whether D2 lymphadenectomy alone is suitable for these patients after PCT. METHODS: We retrospectively collected data on patients from our electronic medical record system. GC patients with bulky N2 and/or PAN metastases who underwent D2 lymphadenectomy alone after PCT were enrolled. The survival outcomes and chemotherapy responses were analyzed and compared with the results of the JCOG0405 study. RESULTS: From May 2009 to December 2017, a total of 83 patients met all eligibility criteria and were enrolled. The median survival duration for all patients was 40.0 months. The 3-year and 5-year OS rates for all patients were 50.3% and 45.6%, respectively. For patients with only bulky N2 metastasis, the 3-year and 5-year OS rates were 77.1% and 71.6%, respectively, which were similar to the results of the JCOG0405 study (82.7% and 73.4%). For patients with only PAN metastases, the 3-year and 5-year OS rates were 50.0% and 50.0%, respectively, which seemed to be lower than those of the JCOG0405 study (64.3% and 57.1%). For patients with bulky N2 and PAN metastases, the 3-year and 5-year OS rates were 7.4% and 0.0%, respectively, which were lower than those of the JCOG0405 study (20.0% and 20.0%). CONCLUSION: The results of our study suggest that D2 lymphadenectomy alone is suitable for GC patients with only bulky N2 metastasis after PCT. However, D2 lymphadenectomy alone perhaps is not suitable for patients with bulky N2 and PAN metastases after PCT.

Neoadjuvant Chemotherapy Versus Direct Surgery for Locally Advanced Gastric Cancer With Serosal Invasion (cT4NxM0): A Propensity Score-Matched Analysis.

BACKGROUND: For locally advanced gastric cancer (LAGC) with serosal invasion (cT4NxM0), adjuvant chemotherapy (AC) after D2 gastrectomy is the standard therapy in Asia. However, perioperative chemotherapy (PCT) combined with D2 gastrectomy is mostly suggested in Europe and America. As a part of PCT, the value of neoadjuvant chemotherapy (NAC) is unclear. We investigated whether NAC could further improve survival and other outcomes for these patients. METHODS: Patients with cT4NxM0 gastric cancer who underwent D2 gastrectomy were analyzed. The patients were divided into two groups based on whether they received NAC: the neoadjuvant chemotherapy (NAC) and direct surgery (S) groups. After propensity score matching (1:1 ratio), survival and perioperative outcomes were analyzed between the two groups. RESULTS: A total of 902 patients met all the eligibility criteria and were enrolled. After propensity score matching, 221 matched pairs of patients were identified. The median overall survival (OS) and disease-free survival (DFS) of all patients were 75.10 and 43.67 months, respectively. The median OS of patients in the NAC and S groups were undefined and 29.80 months, respectively (P<0.0001). The median DFS of patients in the NAC and S groups were undefined and 22.60 months (P<0.0001). There were no significant differences in the radical degrees of operation between the two groups (P=0.07). However, there were significant differences in postoperative hospital stay (P<0.001) and complications (P=0.037) between the two groups. CONCLUSION: This study suggested NAC can further improve prognosis and prevent recurrence in LAGC (cT4NxM0) patients. NAC is feasible and safe for LAGC (cT4NxM0) patients, and does not increase the risk of perioperative surgery.

Risk factors predicting the occurrence of metachronous ovarian metastasis of gastric cancer.

BACKGROUND: Ovarian metastasis following radical gastrectomy, also known as metachronous ovarian metastasis (MOM), pose a significant threat to the long-term survival of female gastric cancer (GC) patients. However, a mechanism to identify and characterize operated patients at high risk of developing MOM remains unknown. This retrospective study aimed to identify risk factors for the occurrence of MOM based on the profiling of clinicopathological parameters and expression of sex hormone receptors (SHR) of operated GC patients with and without ovarian relapse. METHODS: The clinicopathological data of 1,055 female GC patients from two medical centers who underwent surgery between January 2011 and December 2015 were reviewed. A total of 378 patients with and without the occurrence of MOM met the eligibility criteria, including the availability of medical records, adequacy of lymph node dissection, completeness of clinicopathological data, sufficient follow-up time, and no administration of neoadjuvant chemotherapy were selected for further analysis. Expressions of estrogen receptor alpha (ERα), estrogen receptor beta (ERß), and progesterone receptor (PR) were detected by immunohistochemical staining on the surgical specimens of patients, and retrospective statistical analyses identified independent risk factors for the occurrence of MOM. A risk prediction model in the format of a polygenic hazard score (PHS) for the occurrence of MOM was established by introducing and modifying the previously validated polygenic risk score (PRS)/PHS. RESULTS: A Cox regression-based multivariate analysis identified premenopausal with an HR of 3.15 (95% CI, 1.66-5.98), more advanced pathological T stage with an HR of 3.79 (95% CI, 2.14-6.69), more advanced pathological N stage with an HR of 1.85 (95% CI, 1.35-2.54), and negative expression of ERß with an HR of 0.33 (95% CI, 0.15-0.7) as independent risk factors for the occurrence of MOM (P<0.01). Accordingly, a PHS for the occurrence of MOM was established, with 1-, 2-, and 3-year ovarian relapse rates for the high-risk group estimated at 17.8%, 33.7%, and 46.2%, respectively. CONCLUSIONS: Premenopausal status, depth of tumor invasion, number of positive lymph nodes, and negative expression of ERß were independent factors for the occurrence of MOM. More frequent follow-up examinations are recommended to provide timely diagnosis and medical intervention.

A Novel Inflammatory-Nutritional Prognostic Scoring System for Stage III Gastric Cancer Patients With Radical Gastrectomy Followed by Adjuvant Chemotherapy.

PURPOSE: The present study was designed to explore the prognostic value of preoperative inflammatory and nutritional biomarkers in stage III gastric cancer (GC) patients with adjuvant chemotherapy and to develop a novel scoring system called the inflammatory-nutritional prognostic score (INPS). METHODS: A total of 513 patients with pathological stage III GC undergoing radical gastrectomy followed by adjuvant chemotherapy from 2010 to 2017 were enrolled in the study. Clinicopathological characteristics and blood test parameters of individual patients were collected. The least absolute shrinkage and selection operator (LASSO) Cox regression model was used for feature selection to construct INPS. Survival curves were generated using the Kaplan-Meier method with log-rank tests. The nomogram was generated based on the result of the multivariate analysis using Cox's proportional hazards model. The model was assessed by the concordance index (C-index) and was internally validated by bootstraps. RESULTS: According to the results of Lasso Cox regression and K-M survival curves, INPS was determined as follows: a low body mass index (BMI) (<23 kg/m2), a low prealbumin (<180 mg/L), a high neutrophil-lymphocyte ratio (NLR) (≥2.7), a high platelet-lymphocyte ratio (PLR) (≥209.4), a low lymphocyte-monocyte ratio (LMR) (<2.8), and a low prognostic nutritional index (PNI) (<45.1); each were scored as 1, and the remaining values were scored as 0. The individual scores were then summed up to construct the INPS and further divided into 4 groups: Low Risk (INPS 0); Low-medium Risk (INPS 1); High-medium Risk (INPS 2-4); and High Risk (INPS 5-6). In multivariate analysis, INPS was an independent predictor of overall survival (OS) in stage III GC, with the 5-year OS rates of 70.8%, 57.4%, 41.5%, and 30.6%, respectively. The nomogram based on INPS and other independent predictors (gender, pT stage, pN stage, lymphovascular invasion, and CEA level) showed good predicting performance with a C-index of 0.707, which was superior to the TNM stage alone (C-index 0.645, p=0.008) and was internally validated with the corrected C-index of 0.693. CONCLUSION: Preoperative INPS was an independent prognostic factor of stage III GC patients with radical surgery followed by adjuvant chemotherapy. The nomogram based on INPS may serve as a simple and potential model in risk stratification and guiding treatment strategies in clinical practice.

Is adjuvant chemotherapy necessary for early gastric cancer?

OBJECTIVE: To quantify the potential benefit of adjuvant chemotherapy (ACT) with respect to survival, and to identify factors for predicting prognoses in early gastric cancer patients. METHODS: Patients with pT1 gastric cancer (GC) who underwent radical resection with D2 lymphadenectomy were retrospectively analyzed. Based on lymph node metastasis (LNM) status and treatment regimens, patients were classified into groups, and clinicopathological variables, overall survival (OS), and disease-specific survival (DSS) were compared. RESULTS: Of 1,050 enrolled patients, 151 patients (14.4%) had a positive LNM status. Submucosal invasion, undifferentiated state, tumor size > 2 cm, ulceration, and lymphovascular invasion were independent risk factors for LNM using multivariate analyses. The 5-year OS of all patients was 96.4%. HER2 positive, perineural invasion, and LNM were independent factors for worse survival. Patients with pT1N3 GC had a worse 5-year OS and DSS than pT1N0, pT1N1, and pT1N2 patients (P < 0.001). The 5-year OS and DSS for pT1N1 patients showed no significant difference between ACT and surgery only patients. For pT1N2 patients, the 5-year OS and DSS showed no significant difference between S-1 and Xelox treatments. For pT1N3 patients, 7 (36.8%) received S-1, while 12 (63.2%) received Xelox treatment. Patients receiving Xelox treatment showed a better 5-year OS (75.0% vs. 14.3%) and DSS (81.8% vs. 20.0%) than patients receiving S-1 (P < 0.05). CONCLUSIONS: Curative surgery only was adequate for patients with pT1N0 and pT1N1. Xelox showed no survival benefits for pT1N2 patients. Therefore, S-1 is the optimal choice for pT1N2 patients, when considering adverse effects. Xelox is recommended for pT1N3 patients.

Prediction Model of Tumor Regression Grade for Advanced Gastric Cancer After Preoperative Chemotherapy.

BACKGROUND: Preoperative chemotherapy (PCT) has been considered an important treatment for advanced gastric cancer (AGC). The tumor regression grade (TRG) system is an effective tool for the assessment of patient responses to PCT. Pathological complete response (TRG = 0) of the primary tumor is an excellent predictor of better prognosis. However, which patients could achieve pathological complete response (TRG = 0) after chemotherapy is still unknown. The study aimed to find predictors of TRG = 0 in AGC. METHODS: A total of 304 patients with advanced gastric cancer from July 2009 to November 2018 were enrolled retrospectively. All patients were randomly assigned (2:1) to training and internal validation groups. In addition, 124 AGC patients receiving PCT from December 2018 to June 2020 were included prospectively in the external validation cohort. A prediction model for TRG = 0 was established based on four predictors in the training group and was validated in the internal and external validation groups. RESULTS: Through univariate and multivariate analyses, we found that CA199, CA724, tumor differentiation and short axis of the largest regional lymph node (LNmax) were independent predictors of TRG = 0. Based on the four predictors, we established a prediction model for TRG = 0. The AUC values of the prediction model in the training, internal and external validation groups were 0.84, 0.73 and 0.82, respectively. CONCLUSIONS: We found that CA199, CA724, tumor differentiation and LNmax were associated with pathological response in advanced gastric cancer. The prediction model could provide guidance for clinical work.

A randomized controlled trial to evaluate omentum-preserving gastrectomy for patients with T1-T3 gastric cancer.

Although complete omentectomy is traditionally performed in patients with gastric cancer as part of radical gastrectomy to ensure the elimination of micrometastases, the prognostic value of omentectomy during gastrectomy remains unclear. Retrospective studies have shown that the incidence of metastases in the greater omentum is very low in T1-T3 gastric cancer. Thus radical gastrectomy with D2 lymphadenectomy and preservation of the greater omentum may be a proper curative treatment for gastric cancer patients with T1-T3 tumors. The aim of this article is to describe the design and rationale for this prospective, randomized controlled DRAGON-05 trial, conducted to evaluate the prognostic value of omentum-preserving gastrectomy for patients with T1-T3 gastric cancer. Clinical trial registration: ChiCTR2000040045 (ClinicalTrials.gov).

Prediction model of objective response after neoadjuvant chemotherapy in patients with locally advanced gastric cancer.

BACKGROUND: Neoadjuvant chemotherapy (NAC) plays an important role in the therapeutic strategy of locally advanced gastric cancer (LAGC). However, the response of LAGC after NAC varies among different patients. The objective response after NAC has proven to be an excellent indicator for benefiting from NAC, yet effective predictors of objective response are still lacking. The present study aimed to identify potential predictors of objective response in LAGC patients treated with NAC. METHODS: Clinicopathological data from 267 patients with LAGC who received NAC and met the inclusion criteria between July 2009 and December 2018 were retrospectively reviewed. Patients were randomly divided into the training and test sets at a 2:1 ratio. Univariate analysis was used to investigate whether any factors were correlated with objective response in the training set. Multivariate logistic regression analysis was applied to find independent predictors. A risk score model was then constructed based on the independent predictors, and its performance in predicting objective response was validated in the test set. RESULTS: Univariate analysis found that gender, age, short axis diameter of the largest regional lymph node (LNmax), serum total protein content, CEA detection value, tumor location, tumor differentiation, signet ring cell carcinoma component and Borrmann type were potential predictors for objective response. In multivariate logistic regression analysis, gender, LNmax and signet ring cell carcinoma component were independent predictors for objective response. Based on independent predictors, we developed a prediction model for objective response. CONCLUSIONS: We found gender, LNmax and signet ring cell carcinoma component were independent predictors for objective response. The prediction model is a good tool to predict the objective response for LAGC patients treated with NAC, which can be applied to guide clinical practice.