| BackgroundPeritoneal dissemination(PD)is one of the most common type of recurrence and metastasis after radical surgery for gastric cancer,which seriously affects the prognosis and survival of patients with gastric cancer.Currently,although there are clinical preventive strategies for PD,including hyperthermic intraperitoneal chemotherapy(HIPEC)and extensive intraoperative peritoneal lavage plus intraperitoneal chemotherapy(EIPL-IPC),its application also accompanied by high complications.Thus,prediction or early detection of PD could help identify the GC patients who need intensive therapy to prevent PD.However,current commonly used clinical methods such as cytology of peritoneal lavage fluid(PLF)cannot accurately determine the high-risk patients for early intervention to prevent PD.ObjectiveTo develop a NGS-based and personalized tumor-specific mutation detection technique,and to evaluate the proportion of free cancer cells in PLF for the prediction of PD in gastric cancer patients.MethodsA total of 131 patients with clinical stage Ⅰ-Ⅲ gastric adenocarcinoma treated at at the National Cancer Center in China from June 2017 to October 2021 were prospectively enrolled.Whole exome sequencing was performed on tumor tissues and matched white blood cells(WBC)of enrolled gastric cancer patients.After comparison,tumor-specific somatic mutations were obtained by removing the same mutations detected in WBC from the detected tumor tissue mutations.We selected about 20 detection sites from tumorspecific mutations of each patient,and applied the "Mutation Capsule" technology to conduct personalized primer design,and detected the PLF sample obtained during operation of gastric cancer patients.The fraction of cancer cells was calculated according to the number of selected mutation sites,mutation frequency in tumor tissue,sequencing depth in PLF,mutation frequency of each mutation in PLF sample,to predict PD of patients after radical surgery.ResultsTotally,131 gastric cancer patients(mean[SD]age,60[9.1]years;94[72%]male)were eligible for the MRD analysis on PLF samples.Minimal residual cancer cells were detectable(≥0.01%cancer cell fraction in PLF sample)in fifty-one(39%)patients,covering all the 32 patients that occurred PD in the 46 months’ follow up.Positive for peritoneal free cancer cell model in PLF was associated with significantly higher risk of PD occurrence(hazard ratio[HR],32.68;95%CI,15.09-70.77;P<0.0001)and significantly shorter overall survival(OS)(HR=6.30,95%CI 2.44-16.26,P<0.0001).In pathologically high-risk(T4)patients,the PLF mutation profiling model exhibited even better specificity of 86%and positive predictive value(PPV)of 81%,while keeping 100%sensitivity in the prediction of PD.In addition,univariate and multivariate analyses showed that peritoneal free cancer cell model was an independent prognostic factor for RFS in gastric cancer patients,which was superior to pathological and cytology.ConclusionsOur study showed that mutation-based and personalized analysis of PLF based on next-generation sequencing can effectively predict PD in patients with gastric cancer,and this method has a higher prediction efficiency for patients with T4 stage.Based on this method,it is worth further exploration to identify the high-risk group to develop PD at T4 stage for early intervention.Background Currently,the surgery based comprehensive treatment strategy has become the standard treatment for locally advanced gastric cancer(LAGC),and neoadjuvant therapies(NAT)and adjuvant therapies(ACT)have been recommended by most guidelines.However,there are limited studies that compare the outcomes between patients with LAGC treated with and without NAT.Moreover,the benefit of adding radiation therapy to neoadjuvant therapy for LAGC remains controversy.Objective The primary aim of this study was to compare the long-term survival between patients of LAGC treated with and without NAT.The secondary aim was to compare the short?term and long-term outcomes between neoadjuvant chemotherapy(nCT)and neoadjuvant chemoradiation(nCRT).Methods This study retrospectively analyzed the clinical treatment information,pathology and prognosis of LAGC patients treated at the China National Cancer Center between October2006 and December 2018.All patients included were divided into two groups,NAT followed by surgery(NAT-Surgery)and adjuvant chemotherapy following surgery(Surgery-ACT).Subgroup analysis comparing between patients underwent either neoadjuvant chemotherapy(nCT)or neoadjuvant chemoradiation(nCRT)was conducted.Short-term outcomes included toxicity induced by neoadjuvant therapies,post-operative complications,safety of surgery and pathological response rate.Long-term outcomes included overall survival(OS),disease free survival(DFS)and local recurrence free survival(LRFS).A ratio of 1:1 propensity score matching(PSM)was implemented to reduce selection bias.Propensity scores were estimated using a logistic regression model and including the following characters: age,gender,year of diagnosis,tumor location,grade,clinical T-stage,clinical N-stage,clinical TNM stage(AJCC,8th edition).The Kaplaa-Meier method was used to analyze the survival data,the log-rank test to compare the survival rates.The OS was calculated from the date of surgery to the date of death or last contact.The DFS was defined as the time from surgery to the date of recurrence or metastasis.The LRFS was defined as the time from surgery to the date of local recurrence.A P < 0.05 was considered to be statistically significant.Results In totals 2779 patients were included in this study(494 of NAT-Surgery group and2285 of Surgery-ACT group).After PSM,the baseline of two groups,NAT-Surgery group and Surgery-ACT group,was balanced with each group contains 389 patients.With a median follow-up duration of 47.0 months(range of 0.6-137.8 months),the median OS in NAT-Surgery group was 52.0 months and the median OS in Surgery-ACT group was 26.4months,the patients in NAT-Surgery group had a significantly longer OS than patients in Surgery-ACT group(P<0.001).Subgroup analysis revealed that grade 3 or 4 adverse events were more frequently observed in nCRT group during neoadjuvant treatment(52.0%in nCRT group vs.34.0% in nCT group,P=0.010).While postoperative morbidity,estimated blood loss,surgical time,intraoperative blood transfusion and length of postoperative hospital stay were comparable between the two groups.Pathological complete response(pCR)being achieved in 17.0% after nCRT versus 4.0% after nCT(P<0.001).Patients of the nCRT group obtained better disease-free survival(DFS,P=0.024)and local-recurrence-free survival(LRFS,P=0.014)than patients in nCT group,while there was no significant difference in OS between the two groups.Conclusions Neoadjuvant treatments improved survival among patients with LAGC over surgery followed by adjuvant chemotherapy.The addition of radiotherapy to neoadjuvant chemotherapy results in higher pCR rate,better PFS and LRFSs with comparable surgical safety and postoperative morbidity to nCT alone.While adding radiation to neoadjuvant chemotherapy dose not significantly affect the OS.Background Initially unresectable gastric cancer,which represents advanced gastric cancer that cannot be resected with a curative intent at first diagnose,including local invasion,distant metastasis such as peritoneal dissemination,liver metastasis and extra-regional lymph node metastasis.Recently,with the development of multidisciplinary comprehensive therapy for gastric cancer,some patients underwent surgical treatment aimed at RO resection after received systemic chemotherapy,which is called conversion therapy.However,there is still a lack of large-scale studies on conversion therapy for gastric cancer to evaluate the long-term survival outcomes,and there is no evidence for whether postoperative adjuvant chemotherapy is necessary and what factors can predict the prognosis of these patients.Objective The primary aim of this study was to evaluate the long-term outcomes of patients who underwent conversion therapy,including progression free survival(PFS)and overall survival(OS),and prognostic factors.Moreover,We also examined the patients5 survival according to different preoperative chemotherapy regimens to aid in the selection of optimal adjuvant treatment for patients with initially unresectable gastric cancer.Methods This study retrospectively analyzed the clinical treatment information,pathology and prognosis of initially unresectable gastric cancer patients treated at the China National Cancer Center between May 2006 and May 2017.The Kaplan-Meier method was used to analyze the surviv 1 data,the log-rank test to compare the survival rates.The OS was calculated from the date of chemotherapy initiation to the date of death or last contact.The PFS was calculated form the date of chemotherapy initiation to the date of recurrence or metastasis or the date of death or last contact.Multivariate regression analysis of prognosis was performed by COX model.A P< 0.05 was considered to be statistically significant.Results For all the 122 patients,the median age was 56 years(range 28-78),and there were 88males(72.1%).After a median follow-up of 63.6 months(range 4.9-121.3 months),the respective 3-and 5-year OS rate of all the 122 patients were 61.0% and 52%,with a median OS of 63.6 months(95% Cl,36.0-89.2 months).The 3-and 5-year PFS rates were 34.0%and 26.0%,respectively.The median PFS was 19.2 months(95% Cl,14.4-26.4 months).During follow-up,the recurrence was observed in 49(40.1%)patients who underwent conversion surgery.According to the multivariate COX regression analysis,receipt of postoperative adjuvant chemotherapy(POAC)was the only significant independent predictor of a favorable OS(HR 0.40;95% Cl 0.18-0.85,P=0.017).Log-rank analysis showed that POAC group experienced a survival advantage in terms of PFS when compared with observation group(HR 0.53,95%CI 0.31-0.92,P=0.009).Conclusions Conversion therapy may provide long-term survival for patients with initially unresectable gastric cancer.Postoperative adjuvant chemotherapy might be recommended for patients who underwent conversion therapy. |
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