RESUMO
BACKGROUND: Although the incidence of adenocarcinoma of the esophagogastric junction (AEG) has been increasing since the past decade, the proportion of AEG cases in two previous clinical trials (ACTS-GC and CLASSIC) that investigated the efficacy of adjuvant chemotherapy was relatively small. Therefore, whether AEG patients can benefit from adjuvant chemotherapy remains unclear. METHODS: Patients who were diagnosed with pathological stage II/III, Siewert II/III AEG, and underwent curative surgery at three high-volume institutions were assessed. Clinical outcomes were analyzed by using Kaplan-Meier curves, log-rank test, and Cox regression model. Propensity score matching (PSM) was used to reduce the selection bias. RESULTS: A total of 927 patients were included (the chemotherapy group: 696 patients; the surgery-only group: 231 patients). The median follow-up was 39.0 months. The 5-year overall survival was 63.1% (95% confidence interval [CI]: 59.0-67.6%) for the chemotherapy group and 50.2% in the surgery-only group (hazard ratio [HR] = 0.69, 95% CI: 0.54-0.88; p = 0.003). The 5-year, disease-free survival was 35.4% for the chemotherapy group and 16.6% for the surgery-only group (HR = 0.66, 95% CI: 0.53-0.83; p < 0.001). After PSM, the survival benefit of adjuvant chemotherapy for AEG was maintained. Multivariate analysis for overall survival and disease-free survival further demonstrated the survival benefit of adjuvant chemotherapy, with HRs of 0.63 (p < 0.001) and 0.52 (p < 0.001), respectively. CONCLUSIONS: Postoperative adjuvant chemotherapy was associated with improved overall survival and disease-free survival in patients with operable stage II or III AEG after D2 gastrectomy.
Assuntos
Adenocarcinoma , Neoplasias Gástricas , Humanos , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Junção Esofagogástrica/cirurgia , Junção Esofagogástrica/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Gastrectomia , Quimioterapia AdjuvanteRESUMO
BACKGROUND: Mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) status serves as a predictor of a poor response to adjuvant chemotherapy among stage 2 colon cancer patients. This study aimed to investigate the efficacy of adjuvant chemotherapy in dMMR/MSI-H gastric cancer (GC). METHODS: Clinical studies comparing adjuvant chemotherapy and surgery alone in dMMR/MSI-H GCs through June 2021 were retrieved to assess the survival of patients managed with both treatments. Two approaches were used to pool the hazard ratio (HR) of survival: (1) if Kaplan-Meier curves and number of patients at risk were provided, individual patient data were extracted. Cox models were used to calculate the HR with its 95% confidence interval (CI); (2) for study-level data, pooled HR was estimated using fixed/random-effects models. RESULTS: Seven clinical studies were assessed. For dMMR/MSI-H versus mismatch repair-proficient (pMMR)/microsatellite stable (MSS)/microsatellite instability-low (MSI-L) status, the estimated 5-year disease-free survival (DFS) rate was 74.2% versus 51.5% (HR, 0.44; 95% CI, 0.32-0.62; P < 0.001) and the estimated 5-year OS rate was 60.5% versus 49.1% (HR, 0.71; 95% CI, 0.60-0.85; P < 0.001). The study-level data showed pooled HRs of 0.42 for DFS (95% CI, 0.31-0.57; P < 0.001) and 0.65 for OS (95% CI, 0.38-1.11; P = 0.114). For adjuvant chemotherapy versus observation of dMMR/MSI-H, the estimated 5-year DFS rate was 76.1% versus 73.3% (HR, 0.72; 95% CI, 0.45-1.15; P = 0.171) and the estimated 5-year OS rate was 73.5% versus 59.7% (HR, 0.62; 95% CI, 0.46-0.83; P = 0.001). Significant survival differences also were observed at study level. CONCLUSIONS: The study findings confirm the benefit of adjuvant chemotherapy for dMMR/MSI-H GC patients.
Assuntos
Instabilidade de Microssatélites , Neoplasias Gástricas , Neoplasias Encefálicas , Quimioterapia Adjuvante , Neoplasias Colorretais , Reparo de Erro de Pareamento de DNA , Humanos , Estadiamento de Neoplasias , Síndromes Neoplásicas Hereditárias , Prognóstico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genéticaRESUMO
BACKGROUND: The benefit of adjuvant chemotherapy (AC) for patients with stage II gastric cancer remains controversial. This study aimed to explore the indications for adjuvant chemotherapy in patients with stage II gastric cancer by constructing an individual prediction model. PATIENTS AND METHODS: In this Chinese multicenter study, a total of 1012 patients with stage II gastric cancer after D2 radical gastrectomy were retrospectively analyzed. All patients were randomly assigned to a training cohort (n = 674) or a validation cohort (n = 338). A nomogram was constructed according to the training cohort. Concordance index (C-index), the area under the receiver operating characteristic (ROC) curves (AUC), calibration curves, and decision curve analysis (DCA) were applied to evaluate the performance of the nomogram. ROC curves and stratified survival were used to determine the patients' cutoff score for a benefit from adjuvant chemotherapy. An additional 338 patients were used as a validation cohort to validate the feasibility of using this nomogram to guide individualized therapy for patients with stage II gastric cancer. RESULTS: Univariate and multivariate analyses illustrated that age, sex, tumor location, size, carcinoembryonic antigen (CEA), hemoglobin (HB), and T stage were independent prognostic factors for overall survival (OS), and they were used to establish a nomogram. The cutoff value was determined by ROC curve analysis, and patients were divided into a high-risk group (< 239 points) and a low-risk group (≥ 239 points). There was no significant difference in the OS of low-risk patients in either the training cohort or the validation cohort. However, the OS of high-risk patients in the AC group was better than that of patients in the surgery-only group. CONCLUSIONS: This prediction model can be applied to guide treatment of patients with stage II gastric cancer. High-risk patients (< 239 points) are likely to benefit from AC after D2 radical gastrectomy.
Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Estudos Retrospectivos , Gastrectomia/efeitos adversos , Quimioterapia Adjuvante , Nomogramas , ChinaRESUMO
OBJECTIVE: The benefit of adjuvant chemotherapy is still controversial for stage II gastric cancer patients. This study aims to identify prognostic factors to guide individualized treatment for stage II gastric cancer patients. METHODS: We retrospectively reviewed 1121 stage II gastric cancer patients who underwent D2 radical gastrectomy from 2007 to 2017 in the Sixth Affiliated Hospital of Sun Yat-sen University, FuJian Medical School Affiliated Union Hospital and Sun Yat-sen University Cancer Center. Propensity score matching was used to ensure that the baseline data were balanced between the adjuvant chemotherapy group and surgery-only group. Kaplan-Meier survival and multivariate Cox regression analyses were carried out to identify independent prognostic factors. RESULTS: In univariate analysis, after propensity score matching, age, tumor location, tumor size, CEA, T stage and N stage were associated with overall survival (OS). Multivariate analysis illustrated that age ≥ 60 years old, linitis plastica and T4 were independent risk factors for OS, but lower location and adjuvant chemotherapy were protective factors. CONCLUSION: Stage II gastric cancer patients with adverse prognostic factors (age ≥ 60, linitis plastica and T4) have poor prognosis. Adjuvant chemotherapy may be more beneficial for these patients.
Assuntos
Neoplasias Gástricas , China , Gastrectomia , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Análise de SobrevidaRESUMO
BACKGROUND: The present study aims to report the surgical outcome and long-term survival of conversion surgery and clarify its role in advanced gastric cancer. PATIENTS AND METHODS: A total of 95 primary advanced gastric adenocarcinoma patients who underwent systemic chemotherapy and conversion surgery were reviewed retrospectively. The survival of conversion surgery was analyzed by Cox regression and the Kaplan-Meier method. Surgical outcomes were analyzed according to the Clavien-Dindo classification. RESULTS: The median survival time (MST) of the 95 patients was 26.8 months, and the postoperative MST was 19.3 months. The MSTs of the patients in categories 1, 2, 3, and 4 were 28.8, 25.5, 43.6, and 11.3 months, respectively. The MSTs of the patients who underwent R0 resection (47 cases) and R1/2 resection (48 cases) were 49.3 months and 21.9 months, respectively. The MST of patients treated with total gastrectomy was shorter (21.9 months) than that of patients who underwent proximal (55.0 months) or distal (46.3 months) gastrectomy. Patients who received more than 6 cycles of induction chemotherapy had a longer MST than patients who received 3-5 cycles or 1-2 cycles (MST: 55.0 months versus 21.1 months versus 21.7 months). The incident postoperative complications and postoperative mortality rates were 10.5% and 1.1%, respectively. CONCLUSIONS: Advanced gastric cancer patients may obtain a survival benefit from conversion surgery, except category 4. Performing a sufficient number of cycles of induction chemotherapy (usually ≥ 6 cycles) is recommended. Surgical oncologists should perform R0 resection and avoid total gastrectomy.
Assuntos
Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Terapia Combinada , Gastrectomia , Humanos , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: We aimed to assess whether disease-free survival (DFS) could serve as a reliable surrogate endpoint for overall survival (OS) in adjuvant trials of pancreatic cancer. METHODS: We systematically reviewed adjuvant randomized trials for non-metastatic pancreatic cancer after curative resection that reported a hazard ratio (HR) for DFS and OS. We assessed the correlation between treatment effect (HR) on DFS and OS, weighted by sample size or precision of hazard ratio estimate, assuming fixed and random effects, and calculated the surrogate threshold effect (STE). We also performed sensitivity analyses and a leave-one-out cross validation approach to evaluate the robustness of our findings. RESULTS: After screening 450 relevant articles, we identified a total of 20 qualifying trails comprising 5170 patients for quantitative analysis. We noted a strong correlation between the treatment effects for DFS and OS, with coefficient of determination of 0.82 in the random effect model, 0.82 in the fixed effect model, and 0.80 in the sample size weighting; the robustness of this finding was further verified by the leave-one-out cross-validation approach. Sensitivity analyses with restriction to phase 3 trials, large trials, trials with mature follow-up periods, and trials with adjuvant therapy versus adjuvant therapy strengthened the correlation (0.75 to 0.88) between DFS and OS. The STE was 0.96 for DFS. CONCLUSIONS: Therefore, DFS could be regarded as a surrogate endpoint for OS in adjuvant trials of pancreatic cancer. In future similar adjuvant trials, a hazard ratio for DFS of 0.96 or less would predict a treatment impact on OS.
Assuntos
Biomarcadores Tumorais/genética , Biomarcadores/análise , Quimioterapia Adjuvante/mortalidade , Neoplasias Pancreáticas/mortalidade , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de SobrevidaAssuntos
Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Junção Esofagogástrica/patologia , Quimioterapia Adjuvante , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: The present meta-analysis was to explore the surgical and oncological outcomes of bursectomy for advanced gastric cancer (AGC). METHODS: Relevant studies that evaluated the role of bursectomy for AGC were comprehensively examined to perform a meta-analysis. The primary outcomes were overall survival (OS) and disease-free survival (DFS). The secondary outcomes were the number of harvested lymph nodes (LNs), operation time, operative bleeding, hospital stay, postoperative complication and mortality. RESULTS: A total of seven studies comprising 2633 cases (1176 cases in the bursectomy group and 1457 cases in the non-bursectomy group) were finally included. There was no significant difference in OS (HR 0.95, P = 0.647) and DFS (HR 0.99, P = 0.936) between the two groups. Even for patients with serosa-penetrating tumours, OS was comparable between the two groups (HR 0.87, P = 0.356). The operation time of the bursectomy group was longer (weighted mean difference, WMD 32.76 min, P = 0.002). No significant difference was found between the two groups in terms of the number of dissected LNs (WMD 5.86, P = 0.157), operative bleeding (WMD 66.99 ml, P = 0.192) and hospital stay (WMD - 0.15 days, P = 0.766). The overall postoperative complication (relative risk, RR 1.08, P = 0.421) and mortality (RR 0.44, P = 0.195) were similar between two groups. CONCLUSIONS: This meta-analysis indicated that bursectomy is time-consuming without increasing the number of harvested LNs. Although bursectomy can be safely performed without increasing complications and mortality, it does not prolong the OS and DFS of AGC patients, including patients with serosa-penetrating tumours. Therefore, bursectomy should not be recommended as a standard procedure for AGC.
Assuntos
Gastrectomia/métodos , Tempo de Internação/estatística & dados numéricos , Complicações Pós-Operatórias , Neoplasias Gástricas/cirurgia , Humanos , Prognóstico , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: The current study sought to perform a meta-analysis to compare the preoperative staging of endoscopic ultrasonography (EUS) and multidetector computed tomography (MDCT) in gastric carcinoma. METHODS: Articles published between January 1, 2000, and April 1, 2016, that compared EUS with MDCT were included, and data were presented as 2 × 2 tables. The sensitivities, specificities and summary receiver operating characteristic (ROC) curves for T and N staging were calculated using a bivariate mixed effects model. Data were weighted by generic variance and then pooled by random-effects modeling. RESULTS: Eight studies comprising 1736 patients were included in this meta-analysis. For T1 staging, the sensitivity value for EUS (82%) was significantly higher than that for MDCT (41%) (relative risk (RR): 2.06, 95% confidence interval (CI) 1.07-3.94; P = 0.030). For lymph node involvement, the sensitivity value for EUS (91%) was also significantly higher than that for MDCT (77%) (RR 1.14, 95% CI 1.05-1.23; P = 0.001). However, the specificity values of both EUS and MDCT were quite low, at 49 and 63%, respectively. No significant differences in T2-4 staging between EUS and MDCT were noted. CONCLUSION: This meta-analysis indicates that EUS may be superior to MDCT in preoperative T1 and N staging. Additionally, the low specificity values of EUS and MDCT for N staging merits attention.
Assuntos
Endossonografia/métodos , Tomografia Computadorizada Multidetectores/métodos , Neoplasias Gástricas/patologia , Humanos , Estadiamento de Neoplasias , PrognósticoRESUMO
OBJECTIVE: The aim of this study was to explore whether palliative gastrectomy is suitable for gastric cancer patients with peritoneal metastasis, and for patients in whom the type of peritoneal metastasis should be selected to receive palliative gastrectomy. METHODS: A total of 747 patients diagnosed with gastric adenocarcinoma with peritoneal metastasis at our centers between January 2000 and April 2014 were retrospectively analyzed. After propensity score matching, the clinicopathologic characteristics and clinical outcomes of patients with peritoneal dissemination were analyzed. RESULTS: After propensity score matching, the median overall survival (OS) of patients in the gastrectomy group was longer than that for patients in the non-gastrectomy group (11.87 vs. 9.27 months; p = 0.020). Patients who received first-line chemotherapy had a significantly longer median OS than those who did not (11.97 vs. 7.03 months; p < 0.001); among these patients, those undergoing more than eight periods of first-line chemotherapy benefited the most (p < 0.001). Subgroup analyses revealed that patients classified as P1 who were undergoing chemotherapy benefited from gastrectomy (p = 0.024), and patients without multisite metastasis also benefited from gastrectomy with regard to OS (p = 0.007). In the multivariate survival analysis, multisite distant metastasis was the independent poor prognostic factor (p < 0.001), while palliative gastrectomy (p = 0.006) and a period of first-line chemotherapy (p < 0.001) were good prognostic factors. Morbidity rates in the gastrectomy and non-gastrectomy groups were 10.4 and 1.0 %, respectively (p = 0.003); however, no difference in mortality was noted between the two groups (p = 0.590). CONCLUSIONS: Palliative gastrectomy can prolong the survival of P1 patients without multisite distant metastasis when combined with more than five periods, and particularly more than eight periods, of first-line chemotherapy.
Assuntos
Adenocarcinoma/terapia , Antineoplásicos/uso terapêutico , Gastrectomia , Cuidados Paliativos , Neoplasias Peritoneais/secundário , Neoplasias Gástricas/terapia , Adenocarcinoma/secundário , Feminino , Gastrectomia/efeitos adversos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Taxa de SobrevidaRESUMO
Perioperative chemotherapy is the standard treatment for locally advanced gastric or gastro-esophageal junction cancer, and the addition of programmed cell death 1 (PD-1) inhibitor is under investigation. In this randomized, open-label, phase 2 study (NEOSUMMIT-01), patients with resectable gastric or gastro-esophageal junction cancer clinically staged as cT3-4aN + M0 were randomized (1:1) to receive either three preoperative and five postoperative 3-week cycles of SOX/XELOX (chemotherapy group, n = 54) or PD-1 inhibitor toripalimab plus SOX/XELOX, followed by toripalimab monotherapy for up to 6 months (toripalimab plus chemotherapy group, n = 54). The primary endpoint was pathological complete response or near-complete response rate (tumor regression grade (TRG) 0/1). The results showed that patients in the toripalimab plus chemotherapy group achieved a higher proportion of TRG 0/1 than those in the chemotherapy group (44.4% (24 of 54, 95% confidence interval (CI): 30.9%-58.6%) versus 20.4% (11 of 54, 95% CI: 10.6%-33.5%)), and the risk difference of TRG 0/1 between toripalimab plus chemotherapy group and chemotherapy group was 22.7% (95% CI: 5.8%-39.6%; P = 0.009), meeting a prespecified endpoint. In addition, a higher pathological complete response rate (ypT0N0) was observed in the toripalimab plus chemotherapy group (22.2% (12 of 54, 95% CI: 12.0%-35.6%) versus 7.4% (4 of 54, 95% CI: 2.1%-17.9%); P = 0.030), and surgical morbidity (11.8% in the toripalimab plus chemotherapy group versus 13.5% in the chemotherapy group) and mortality (1.9% versus 0%), and treatment-related grade 3-4 adverse events (35.2% versus 29.6%) were comparable between the treatment groups. In conclusion, the addition of toripalimab to chemotherapy significantly increased the proportion of patients achieving TRG 0/1 compared to chemotherapy alone and showed a manageable safety profile. ClinicalTrials.gov registration: NCT04250948 .
Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Adenocarcinoma/patologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Anticorpos Monoclonais Humanizados/efeitos adversos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
AIM: To investigate the clinical significance of the postoperative serum carcinoembryonic antigen (CEA) levels in gastric cancer patients who underwent D2 radical gastrectomy and to identify the prognostic factors for patients with marginally elevated postoperative CEA levels. METHODS: We performed a retrospective study of 480 patients who were histologically diagnosed with gastric cancer and who underwent D2 radical surgery at the Sun Yat-sen University Cancer Center between January 2004 and December 2009. The follow-up lasted until June 2011. Chi-squared tests and Kaplan-Meier methods were employed to compare the adverse events and prognoses. RESULTS: In this group of gastric cancer patients, the postoperative serum CEA level (P = 0.002) was an independent prognostic factor; the same was true for the histological T and N staging (P < 0.001 and P = 0.045, respectively). In the group of marginally elevated postoperative CEA level gastric cancer patients, univariate analysis demonstrated that tumor position (P = 0.042); histological grade (P = 0.002); and Boarrmann type (P = 0.003) were significant prognostic factors. Multivariate analysis showed that the tumor position (P = 0.003) and histological grade (P = 0.007) were independent prognostic factors for these patients. CONCLUSION: Our study showed that patients with normal postoperative CEA levels have a better prognosis. Furthermore, for marginally elevated postoperative CEA level gastric cancer patients, the tumor position and histological grade were two important factors for predicting the prognosis and the need for aggressive therapy.
Assuntos
Adenocarcinoma/cirurgia , Antígeno Carcinoembrionário/sangue , Gastrectomia , Neoplasias Gástricas/cirurgia , Adenocarcinoma/sangue , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Feminino , Seguimentos , Gastrectomia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Estadiamento de Neoplasias , Período Pós-Operatório , Estudos Retrospectivos , Neoplasias Gástricas/sangue , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVES: CD44 and CD133 have been reported as putative stem cell markers. However, the clinicopathologic significance of CD44 and CD133 expression in patients with gastric carcinoma (GC) has not been clearly elucidated. METHODS: Immunohistochemistry (IHC) was performed to investigate the CD44 and CD133 expression in gastric carcinomas and normal mucosal tissues. Receiver operating characteristic (ROC) curve analysis, spearman's rank correlation, Kaplan-Meier plots, and Cox proportional hazards regression model were used to analyze the data. RESULTS: The highly expressed CD44 and CD133 were observed in 27/152 (17.7%) and 64/152 (42.1%) of GCs and in 4/60 (6.7%) and 15/60 (25.0%) normal gastric mucosal tissues, respectively (P < 0.05, Fisher's exact test). High expression of CD44 was significantly correlated with tumor poorer differentiation, presence of distant metastasis, advanced TNM stage, and tumor relapse; and high expression of CD133 was positively associated with tumor invasion depth, presence of distant metastasis and advanced TNM stage. More importantly, high-expressed CD44 and CD133 were both associated with shorter survival as evidenced by univariate and multivariate analysis. CONCLUSIONS: Our study introduces high expression of CD44 and CD133 as adverse independent prognostic factors in GC patients. The combined CD44 and CD133 expression may become a useful tool for identifying patients with different clinical outcomes.
Assuntos
Antígenos CD/análise , Biomarcadores Tumorais/análise , Glicoproteínas/análise , Receptores de Hialuronatos/análise , Células-Tronco Neoplásicas , Peptídeos/análise , Neoplasias Gástricas/química , Neoplasias Gástricas/patologia , Antígeno AC133 , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Fenótipo , Prognóstico , Curva ROCRESUMO
BACKGROUND: Circulating tumor DNA (ctDNA) is a promising biomarker for predicting relapse in multiple solid cancers. However, the predictive value of ctDNA for disease recurrence remains indefinite in locoregional gastric cancer (GC). Here, we aimed to evaluate the predictive value of ctDNA in this context. METHODS: From 2016 to 2019, 100 patients with stage II/III resectable GC were recruited in this prospective cohort study (NCT02887612). Primary tumors were collected during surgical resection, and plasma samples were collected perioperatively and within 3 months after adjuvant chemotherapy (ACT). Somatic variants were captured via a targeted sequencing panel of 425 cancer-related genes. The plasma was defined as ctDNA-positive only if one or more variants detected in the plasma were presented in at least 2% of the primary tumors. RESULTS: Compared with ctDNA-negative patients, patients with positive postoperative ctDNA had moderately higher risk of recurrence [hazard ratio (HR) = 2.74, 95% confidence interval (CI) = 1.37-5.48; P = 0.003], while patients with positive post-ACT ctDNA showed remarkably higher risk (HR = 14.99, 95% CI = 3.08-72.96; P < 0.001). Multivariate analyses indicated that both postoperative and post-ACT ctDNA positivity were independent predictors of recurrence-free survival (RFS). Moreover, post-ACT ctDNA achieved better predictive performance (sensitivity, 77.8%; specificity, 90.6%) than both postoperative ctDNA and serial cancer antigen. A comprehensive model incorporating ctDNA for recurrence risk prediction showed a higher C-index (0.78; 95% CI = 0.71-0.84) than the model without ctDNA (0.71; 95% CI = 0.64-0.79; P = 0.009). CONCLUSIONS: Residual ctDNA after ACT effectively predicts high recurrence risk in stage II/III GC, and the combination of tissue-based and circulating tumor features could achieve better risk prediction.
Assuntos
DNA Tumoral Circulante , Neoplasias Gástricas , Humanos , Quimioterapia Adjuvante , DNA Tumoral Circulante/genética , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Estudos Prospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/cirurgia , Estudos de CoortesRESUMO
PURPOSE: To investigate the significance of palliative gastrectomy for different types of metastatic gastric cancer patients displaying peritoneal dissemination, hepatic metastasis, distant lymph node metastasis occurring locally during late-stage disease, and multi-organ metastases. METHODS: We performed a retrospective study of 862 patients who were histologically diagnosed as late-stage gastric cancer who could not undergo radical surgery at the Sun Yat-sen University Cancer Center between January 1993 and December 2008. The follow-up lasted until December 2010. Chi-square tests and Kaplan-Meier methods were employed to compare the adverse events and prognoses. RESULTS: In the peritoneal dissemination and multi-organ metastases groups, palliative gastrectomy has no survival benefit (P = 0.705, 0.331, respectively). In the patients with distant lymph-node metastases, liver metastasis and locally late-stage gastric cancer patients, palliative gastrectomy was a prognostic factor (P < 0.001, P < 0.001, P = 0.010, respectively). Multivariable analysis demonstrated that palliative gastrectomy was an independent prognostic factor for distant lymph-node metastases, liver metastasis, and local late-stage gastric cancer patients. Palliative gastrectomy combined with hepatectomy proved to be an independent prognostic factor to improve the overall survival of patients with liver metastases who underwent palliative gastrectomy (P = 0.008). CONCLUSION: For late-stage gastric cancer patients, palliative gastrectomy should be considered for locally late-stage, distant lymph node metastasis, and resectable liver metastasis patients. Especially among patients with liver metastasis, transfer medicine is essential for potentially curable patients to obtain access to radical surgery to improve the prognosis.
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Gastrectomia , Cuidados Paliativos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Peritônio/patologia , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVES: Beclin 1 plays a critical role in the regulation of autophagy, apoptosis, differentiation and the development and progression of cancer. The clinicopathological significance of Beclin 1 expression in patients with gastric carcinoma (GC) has not been yet elucidated. METHODS: Immunohistochemistry (IHC) was performed to investigate the Beclin 1 expression in GCs and normal mucosal tissues. Receiver operating characteristic curve analysis, spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the data. RESULTS: The highly expressed Beclin 1 was observed in 90/155 (58.1%) of GCs, in 24/60 (40.0%) adjacent mucosal tissues and in 13/30 (43.3%) of normal gastric mucosa tissues (P = 0.036). Decreased expression of Beclin 1 in cancer cells was significantly correlated with poor differentiation, nodal and distant metastasis, advanced TNM stage, and tumor relapse. More importantly, Decreased expression of Beclin 1 was associated with shorter survival as evidenced by univariate and multivariate analysis. CONCLUSIONS: Our findings provide a basis for the concept that decreased expression of Beclin 1 in GC may be important in the acquisition of a metastatic phenotype, suggesting that decreased Beclin 1 expression, as examined by IHC, is an independent biomarker for poor prognosis of patients with GC.
Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Proteínas de Membrana/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína Beclina-1 , Carcinoma/metabolismo , Carcinoma/mortalidade , Carcinoma/patologia , Estudos de Casos e Controles , Mucosa Gástrica/metabolismo , Genes Supressores de Tumor , Humanos , Imuno-Histoquímica , Metástase Linfática , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Recidiva Local de Neoplasia , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Neoplasias Gástricas/patologia , Adulto JovemRESUMO
Crosstalk between pyroptosis and tumor immune microenvironment (TIME) in cancer has yet to be elucidated. Herein, we aimed to explore the role of pyroptosis and its association with TIME in gastric cancer. Unsupervised clustering was performed to identify the pyroptosis-related clusters. Pyroptosis risk score was constructed using LASSO Cox regression. Clinicopathological and genetic data of pyroptosis clusters and pyroptosis risk scores were explored. Reproducibility of pyroptosis risk score in predicting response to immunotherapy and screening potential antitumor drugs was also investigated. Three pyroptosis clusters with distinct prognosis, immune cell fractions and signatures, were constructed. A low-pyroptosis risk score was characterized by increased activated T-cell subtype and M1 macrophage, decreased M2 macrophage, higher MSI status, and TMB. Meanwhile, low-score significantly correlated with PD-L1 expression, antigen presentation markers, and IFN-γ signature. The 5-year AUCs of PRS were 0.67, 0.62, 0.65, 0.67, and 0.67 in the TCGA, three external public and one real-world validation (SYSUCC) cohorts. Multivariable analyses further validated the prognostic performance of the pyroptosis risk scoring system, with HRs of 2.43, 1.83, 1.78, 2.35, and 2.67 (all p < 0.05) in the five cohorts. GSEA indicated significant enrichment of DNA damage repair pathways in the low-score group. Finally, the pyroptosis risk scoring system was demonstrated to be useful in predicting response to immunotherapy, and in screening potential antitumor drugs. Our study highlights the crucial role of interaction between pyroptosis and TIME in gastric cancer. The pyroptosis risk scoring system can be used independently to predict the survival of individuals and their response to immunotherapy.