Comparison of tumor regression grading systems for locally advanced gastric adenocarcinoma after neoadjuvant chemotherapy

BACKGROUND Current tumor regression grade(TRG)evaluations are based on various systems which brings confusion for oncologists and pathologists when interpreting results.The recent six-tier system(JGCA2017-TRG)recommended by the Japanese Gastric Cancer Association(JGCA)is worth investigating,as four-tier TRG systems are favored in various parts of the world.AIM To compare the predictive accuracies of five published TRG systems.METHODS Data were retrospectively collected from patients with locally advanced gastric cancer(LAGC)who underwent neoadjuvant chemotherapy followed by D2 Lymphadenectomy between January 2005 and January 2014 at our institution.Outcomes were overall survival(OS)and disease-free survival(DFS),which were evaluated separately using the following TRG systems:JGCA2017,JGCA,Becker,AJCC/CAP,and Mandard.RESULTS All five published TRG systems were independent predictors for OS and DFS.Concordance indices of the JGCA2017,JGCA,Becker,AJCC/CAP-TRG,and Mandard systems were 0.651/0.6480.652/0.649,0.693/0.695,0.688/0.685,and 0.674/0.675 for OS and DFS,respectively.The four-tier Becker system showed the highest c-index,which was significantly greater than that of the six-tier JGCA2017 and five-tier JGCA systems(P<0.05 in OS and DFS).When residual tumor percentages were reset as:“no residual tumor”,<10%,<100%,and“no response”,the rearranged cutoff values achieved a maximum c-index with 0.728 for OS and 0.737 for DFS,which was superior to the other five systems.CONCLUSION The newly introduced six-tier JGCA-TRG system cannot increase prognostic stratification.The four-tier Becker system is more suitable for LAGC patients.A population-based study is warranted to define the optimal criterion for TRG in LAGC patients.

Safety and efficacy of a programmed cell death 1 inhibitor combined with oxaliplatin plus S-1 in patients with Borrmann large type III and IV gastric cancers

BACKGROUND Gastric cancer(GC)is the fifth most common and the fourth most lethal malignant tumour in the world.Most patients are already in the advanced stage when they are diagnosed,which also leads to poor overall survival.The effect of posto-perative adjuvant chemotherapy for advanced GC is unsatisfactory with a high rate of distant metastasis and local recurrence.AIM To investigate the safety and efficacy of a programmed cell death 1(PD-1)inhibitor combined with oxaliplatin and S-1(SOX)in the treatment of Borrmann large type III and IV GCs.METHODS A retrospective analysis(IRB-2022-371)was performed on 89 patients with Borrmann large type III and IV GCs who received neoadjuvant therapy(NAT)from January 2020 to December 2021.According to the different neoadjuvant treatment regimens,the patients were divided into the SOX group(61 patients)and the PD-1+SOX(P-SOX)group(28 patients).RESULTS The pathological response(tumor regression grade 0/1)in the P-SOX group was significantly higher than that in the SOX group(42.86%vs 18.03%,P=0.013).The incidence of ypN0 in the P-SOX group was higher than that in the SOX group(39.29%vs 19.67%,P=0.05).The use of PD-1 inhibitors was an independent factor affecting tumor regression grade.Meanwhile,the use of PD-1 did not increase postoperative complications or the adverse effects of NAT.CONCLUSION A PD-1 inhibitor combined with SOX could significantly improve the rate of tumour regression during NAT for patients with Borrmann large type III and IV GCs.

Development of a clinical nomogram for prediction of response to neoadjuvant chemotherapy in patients with advanced gastric cancer

BACKGROUND The efficacy of neoadjuvant chemotherapy(NAC)in advanced gastric cancer(GC)is still a controversial issue.AIM To find factors associated with chemosensitivity to NAC treatment and to provide the optimal therapeutic strategies for GC patients receiving NAC.METHODS The clinical information was collected from 230 GC patients who received NAC treatment at the Central South University Xiangya School of Medicine Affiliated Haikou Hospital from January 2016 to December 2020.Least absolute shrinkage and selection operator logistic regression analysis was used to find the possible predictors.A nomogram model was employed to predict the response to NAC.RESULTS In total 230 patients were finally included in this study,including 154 males(67.0%)and 76 females(33.0%).The mean age was(59.37±10.60)years,ranging from 24 years to 80 years.According to the tumor regression grade standard,there were 95 cases in the obvious response group(grade 0 or grade 1)and 135 cases in the poor response group(grade 2 or grade 3).The obvious response rate was 41.3%.Least absolute shrinkage and selection operator analysis showed that four risk factors significantly related to the efficacy of NAC were tumor location(P<0.001),histological differentiation(P=0.001),clinical T stage(P=0.008),and carbohydrate antigen 724(P=0.008).The C-index for the prediction nomogram was 0.806.The calibration curve revealed that the predicted value exhibited good agreement with the actual value.Decision curve analysis showed that the nomogram had a good value in clinical application.CONCLUSION A nomogram combining tumor location,histological differentiation,clinical T stage,and carbohydrate antigen 724 showed satisfactory predictive power to the response of NAC and can be used by gastrointestinal surgeons to determine the optimal treatment strategies for advanced GC patients.

Value of Pretreatment Inflammation-nutrition Score to Predict Non-response to Neoadjuvant Chemotherapy in Locally Advanced Rectal Cancer

Objective To investigate the value of pretreatment inflammatory-nutritional biomarkers in predicting the pathological response of locally advanced rectal cancer(LARC)after neoadjuvant chemotherapy(nCT).Methods This retrospective study included eligible participants who underwent nCT followed by radical surgery.Pretreatment inflammatory nutritional biomarkers were calculated within one week prior to nCT.Correlations between biomarkers and pathological responses were analyzed.The cut-off values of the pretreatment biomarkers for predicting non-response were determined using receiver operating characteristic(ROC)curve analysis.The inflammation-nutrition score was calculated using the lymphocyte level,neutrophil-to-lymphocyte ratio(NLR),and prognostic nutritional index(PNI).Results A total of 235 patients were retrospectively recruited between January 2017 and September 2022.Lower lymphocyte levels,lymphocyte monocyte ratio(LMR),and PNI,and higher NLR and platelet-to-lymphocyte ratio(PLR)were observed in patients without response.Multivariate logistic regression analysis revealed that NLR could independently predict non-response to nCT in patients with LARC.The sensitivity and specificity of the inflammation-nutrition score for predicting nonresponse were 71.2%and 61.7%,respectively.Conclusion The pretreatment inflammation-nutrition score is a practical parameter for predicting nonresponse to nCT in patients with LARC.Patients with high scores were more likely to respond poorly to nCT.

Neutrophile-to-lymphocyte,lymphocyte-to-monocyte,and platelet-tolymphocyte ratios as prognostic and response biomarkers for resectable locally advanced gastric cancer

BACKGROUND Perioperative fluorouracil plus leucovorin,oxaliplatin,and docetaxel(FLOT)improves prognosis in locally advanced gastric cancer(LAGC).Neutrophil-to-lymphocyte(NLR),lymphocyte-tomonocyte(LMR),and platelet-to-lymphocyte(PLR)ratios are prognostic biomarkers but not predictive factors.AIM To assess blood ratios’(NLR,LMR and PLR)potential predictive response to FLOT and survival outcomes in resectable LAGC patients.METHODS This was a multicentric retrospective study investigating the clinical potential of NLR,LMR,and PLR in resectable LAGC patients,treated with at least one preoperative FLOT cycle,from 12 Portuguese hospitals.Means were compared through non-parametric Mann-Whitney tests.Receiver operating characteristic curve analysis defined the cut-off values as:High PLR>141 for progression and>144 for mortality;high LMR>3.56 for T stage regression(TSR).Poisson and Cox regression models the calculated relative risks/hazard ratios,using NLR,pathologic complete response,TSR,and tumor regression grade(TRG)as independent variables,and overall survival(OS)as the dependent variable.RESULTS This study included 295 patients(mean age,63.7 years;59.7% males).NLR was correlated with survival time(r=0.143,P=0.014).PLR was associated with systemic progression during FLOT(P=0.022)and mortality(P=0.013),with high PLR patients having a 2.2-times higher risk of progression[95% confidence interval(CI):0.89-5.26]and 1.5-times higher risk of mortality(95%CI:0.92-2.55).LMR was associated with TSR,and high LMR patients had a 1.4-times higher risk of achieving TSR(95%CI:1.01-1.99).OS benefit was found with TSR(P=0.015)and partial/complete TRG(P<0.001).Patients without TSR and with no evidence of pathological response had 2.1-times(95%CI:1.14-3.96)and 2.8-times(95%CI:1.6-5)higher risk of death.CONCLUSION Higher NLR is correlated with longer survival time.High LMR patients have a higher risk of decreasing T stage,whereas high PLR patients have higher odds of progressing under FLOT and dying.Patients with TSR and a pathological response have better OS and lower risk of dying.

Predictors of pathologic complete response in patients with residual flat mucosal lesions after neoadjuvant chemoradiotherapy for locally advanced rectal cancer

Objective:The accurate prediction of tumor response to neoadjuvant chemoradiotherapy(nCRT)remains challenging.Few studies have investigated pathologic complete response(ypCR)prediction in patients with residual flat mucosal lesions after treatment.This study aimed to identify variables for predicting ypCR in patients with residual flat mucosal lesions after nCRT for locally advanced rectal cancer(LARC).Methods:Data of patients with residual flat mucosal lesions after nCRT who underwent radical resection between 2009 and 2015 were retrospectively collected from the LARC database at Peking University Cancer Hospital.Univariate and multivariate analyses of the association between clinicopathological factors and ypCR were performed,and a nomogram was constructed by incorporating the significant predictors.Results:Of the 246 patients with residual flat mucosal lesions included in the final analysis,56(22.8%)had ypCR.Univariate and multivariate analyses showed that pretreatment cT stage(pre-cT)≤T2(P=0.016),magnetic resonance tumor regression grade(MR-TRG)1-3(P=0.001)and residual mucosal lesion depth=0 mm(P<0.001)were associated with a higher rate of ypCR.A nomogram was developed with a concordance index(C-index)of0.759 and the calibration curve showed that the nomogram model had good predictive consistency.The follow-up time ranged from 3.0 to 113.3 months,with a median follow-up time of 63.77 months.The multivariate Cox regression model showed that the four variables in the nomogram model were not risk factors for disease-free survival(DFS)or overall survival(OS).Conclusions:Completely flat mucosa,early cT stage and good MR-TRG were predictive factors for ypCR instead of DFS or OS in patients with LARC with residual flat mucosal lesions after nCRT.Endoscopic mucosal re-evaluation before surgery is important,as it may contribute to decision-making and facilitate nonoperative management or organ preservation.