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Venous invasion as a risk factor for recurrence after gastrectomy followed by chemotherapy for stage III gastric cancer.

ABSTRACT: Although adjuvant chemotherapy with S-1 after curative gastrectomy has been performed as a standard treatment for Stage II and III gastric cancer (GC) in Japan, patients with Stage III GC still have a high incidence of recurrence and a poor prognostic outcome. The aim of this study was to investigate risk factors for recurrence in patients with Stage III GC despite of curative gastrectomy followed by adjuvant chemotherapy, suggesting an indicator for more intensive management.A total of 97 patients with pathological Stage III GC underwent adjuvant chemotherapy after curative gastrectomy between 2001 and 2014, were enrolled in this study. We retrospectively analyzed their hospital records from our hospital.The 5-year relapse-free survival (RFS) rates of patients with pStage III GC were 42.0%. Univariate and multivariate analyses for RFS revealed that venous invasion (v+) was an independent factor predicting a shorter RFS (v?+?vs. v-, 36.5% vs. 47.4%, P?=?0.034, HR 1.82, 95% CI: 1.01-3.37). Venous invasion also predicted a shorter overall survival (OS) (v?+?vs. v-, 33.7% vs. 50.4%, P?=?0.027). Regarding the patterns of recurrence, hematogenous recurrence was significantly occurred in patients with v?+?GC than those without (P?=?0.022).Stage III GC with venous invasion is a high-risk subgroup for hematogenous recurrence after curative surgery followed by adjuvant chemotherapy. More intensive and effective adjuvant chemo and/or molecular targeted therapy for Stage III GC patients with venous invasion should be considered to improve their outcomes.

SUBMITTER: Nishibeppu K

PROVIDER: S-EPMC5791734 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Venous invasion as a risk factor for recurrence after gastrectomy followed by chemotherapy for stage III gastric cancer.

Nishibeppu Keiji K Komatsu Shuhei S Ichikawa Daisuke D Imamura Taisuke T Kosuga Toshiyuki T Okamoto Kazuma K Konishi Hirotaka H Shiozaki Atsushi A Fujiwara Hitoshi H Otsuji Eigo E

BMC cancer 20180130 1

<h4>Background</h4>Although adjuvant chemotherapy with S-1 after curative gastrectomy has been performed as a standard treatment for Stage II and III gastric cancer (GC) in Japan, patients with Stage III GC still have a high incidence of recurrence and a poor prognostic outcome. The aim of this study was to investigate risk factors for recurrence in patients with Stage III GC despite of curative gastrectomy followed by adjuvant chemotherapy, suggesting an indicator for more intensive management. ...[more]

PMID: 29382310

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Project description:BACKGROUND:Mesothelin is overexpressed in many solid tumors, and recent studies have shown that mesothelin expression is associated with poor outcomes in several malignant tumors and may play a role in cancer progression. Clinical trials of mesothelin-targeted immunotherapies are currently under way, but the correlation between mesothelin expression and gastric cancer prognosis is still unclear. SUBJECTS, MATERIALS, AND METHODS:Mesothelin expression in tumor cells was evaluated immunohistochemically in 958 patients with advanced gastric cancer and interpreted according to the intensity and extent of staining. Samples were scored from 0 to 2, with high expression defined as a score of 2. Clinicopathological factors, overall survival (OS), recurrence-free survival (RFS), and sites of initial recurrence, including peritoneal recurrence, were evaluated. Staging was performed according to the American Joint Committee on Cancer 7th edition. RESULTS:High mesothelin expression was observed in 49.7% of patients and significantly associated with high pathologic T (p = .021) and peritoneal recurrence (p = .018). Multivariate survival analysis showed that high mesothelin expression was independently associated with poor RFS (p = .001), OS (p = .001), and peritoneal recurrence (p = .002) in addition to stage, lymphovascular invasion, and Lauren classification. In a subgroup analysis of peritoneal recurrence, high mesothelin expression was also an independent prognostic factor in stage III (p = .013) and diffuse/mixed type gastric cancer (p = .010). CONCLUSION:High mesothelin expression is correlated with poor outcomes. In addition, mesothelin expression, Lauren classification, and stage are meaningful predictive factors for peritoneal recurrence. Moreover, mesothelin was a significant predictor of a high risk of peritoneal recurrence in patients with stage III gastric cancer. IMPLICATIONS FOR PRACTICE:This study demonstrates that high mesothelin expression correlates with poor outcomes and is a significant predictor of peritoneal recurrence in patients with stage III gastric cancer. This study provides instrumental evidence for designing anti-mesothelin antibody-drug conjugate clinical trials in patients with diffuse-type gastric cancer to reduce their high risk of peritoneal carcinomatosis.

Project description:Simple Summary Adjuvant chemotherapy regimens tegafur/gimeracil/oteracil (S-1) and capecitabine plus oxaliplatin (CAPOX) have predominated, owing to evidence of their remarkable oncologic outcomes, however, there has been a lack of studies on the difference in efficacy between the two regimens. We conducted pairwise meta-analyses comparing the efficacy of S-1 and CAPOX regimens for overall survival (OS) and disease-free survival (DFS) in stage II or III gastric cancer patients. In all stages (stages II and III), the five-year OS was not different between the two regimens (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.78–1.17; p = 0.56). Additionally, the five-year DFS was not different at any stage (HR 1.00, 95% CI 0.85–1.18; p = 0.21). The present meta-analysis showed that five-year OS and DFS for stage II or III gastric cancer patients were comparable between the S-1 and CAPOX adjuvant chemotherapy regimens. Abstract Background: Adjuvant chemotherapy (AC) regimens tegafur/gimeracil/oteracil (S-1) and capecitabine plus oxaliplatin (CAPOX) have predominated, however, there has been a lack of studies on their differences in efficacy. Methods: We conducted pairwise meta-analyses comparing the efficacy of S-1 and CAPOX regimens for overall survival (OS) and disease-free survival (DFS) in stage II or III GC patients. Results: Three studies were enrolled and analyzed using a forest plot for meta-analysis. Two of them were propensity score matching studies, and the remaining one was a retrospective observational study. In all stages, the five-year OS was not different between the two regimens (HR 0.96, 95% CI 0.78–1.17; p = 0.56). Additionally, the 5-year DFS was not different at any stage (HR 1.00, 95% CI 0.85–1.18; p = 0.21). After omitting the retrospective observational study, the five-year OS (HR 1.40, 95% CI 0.53–3.73) and DFS (HR 1.41, 95% CI 0.57–3.44) of S-1 tended to be better in stage II, and the five-year OS (HR 0.81, 95% CI 0.56–1.16) and DFS (HR 0.85, 95% CI 0.63–1.13) of CAPOX tended to be better in stage III, without statistical significance. Conclusions: In the present meta-analysis, the five-year OS and DFS for stage II or III GC patients were comparable between S-1 and CAPOX regimens as AC.

Project description:BackgroundThe benefits of adjuvant chemotherapy for elderly patients with gastric cancer (GC) remain unknown because elderly patients are underrepresented in most clinical trials. This study aimed to evaluate the effectiveness and complications of adjuvant chemotherapy in patients > 65 years of age after laparoscopic D2 gastrectomy.MethodsThis was a single-center retrospective cohort study of elderly patients (> 65 years) with stage II/III GC who underwent curative laparoscopic D2 gastrectomy with R0 resection between 2004 and 2018. The adjuvant chemotherapy regimens included monotherapy (oral capecitabine) and doublet chemotherapy (oral capecitabine plus intravenous oxaliplatin [XELOX] or intravenous oxaliplatin, leucovorin, and 5-fluorouracil [FOLFOX]). The data were retrieved from a prospectively registered database maintained at the Department of General Surgery in Nanfang Hospital, China. The patients were divided as surgery alone and surgery plus adjuvant chemotherapy (chemo group). The overall survival (OS), disease-free survival (DFS), chemotherapy duration, and toxicity were examined.ResultsThere were 270 patients included: 169 and 101 in the surgery and chemo groups, respectively. There were 10 (10/101) and six (6/101) patients with grade 3+ non-hematological and hematological adverse events. The 1-/3-/5-year OS rates of the surgery group were 72.9%/51.8%/48.3%, compared with 90.1%/66.4%/48.6% for the chemo group (log-rank test: P = 0.018). For stage III patients, the 1-/3-/5-year OS rates of the surgery group were 83.7%/40.7%/28.7%, compared with 89.9%/61.2%/43.6% for the chemo group (log-rank test: P = 0.015). Adjuvant chemotherapy was significantly associated with higher OS (HR = 0.568, 95%CI: 0.357-0.903, P = 0.017) and DFS (HR = 0.511, 95%CI: 0.322-0.811, P = 0.004) in stage III patients.ConclusionsThis study suggested that adjuvant chemotherapy significantly improves OS and DFS compared with surgery alone in elderly patients with stage III GC after D2 laparoscopic gastrectomy, with a tolerable adverse event profile.

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Venous invasion as a risk factor for recurrence after gastrectomy followed by chemotherapy for stage III gastric cancer.

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Venous invasion as a risk factor for recurrence after gastrectomy followed by chemotherapy for stage III gastric cancer.

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