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A Model Shows Utility in Predicting Postoperative Recurrence and Distant Metastasis in Curatively Resected Esophageal Squamous Cell Cancer.

ABSTRACT: After curative treatment of esophageal squamous cell cancer (ESCC), patients are at high risk for recurrence. The objective of this study was to develop an index with a high sensitivity and specificity to predict ESCC patients' recurrence and prognosis. A retrospective analysis was conducted on consecutive patients with EC who underwent esophagectomy. In total, 1417 patients were included in the current investigation. In total, 770 patients were included in the current study's exploratory group. Alcohol consumption, TNM classification, number of lymph node station metastases, and number of lymph node metastases were significantly correlated with recurrence. Multivariate logistical regression analysis resulted in the development of an equation for predicting recurrence and prognosis (REEC). When using the REEC value to predict recurrence, the cutoff value was 1.095, the area under the curve (AUC) values of the REEC were 0.68 ( p < 0.001) in the Exploratory Group and 0.65 ( p < 0.001) in the Validation Group, and the sensitivity and specificity were 76.68% and 51.18%, respectively. When using the REEC value to predict prognosis, the cutoff value was 1.215, the AUC values of the REEC were 0.65 ( p < 0.001) in the Exploratory Group and 0.64 ( p < 0.001) in the Validation Group, and the sensitivity and specificity were 73.12% and 50.67%, respectively. In the Exploratory Group, when the REEC value was >1.095, patients had a longer median overall survival (OS) and median disease-free survival (DFS) than those whose REEC value was < 1.095 (70.01±2.01 months versus 50.92±2.85 months and 75.66±1.35 months versus 53.68±2.81 months, respectively, p < 0.001). The differences were confirmed to still exist in the Validation Group (48.12±1.47 vs 32.68±2.53 months and 55.61±1.32 vs 35.68±2.73 months respectively, p < 0.001).This study reported an index that can predict esophageal cancer recurrence and prognosis, and its use can benefit patients.

SUBMITTER: Wang W

PROVIDER: S-EPMC6545664 | biostudies-literature | 2019 Jan-Dec

REPOSITORIES: biostudies-literature

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A Model Shows Utility in Predicting Postoperative Recurrence and Distant Metastasis in Curatively Resected Esophageal Squamous Cell Cancer.

Wang Weidong W Chen Yongqiang Y Zhang Xuewen X Xi Kexing K Feng Xiaoli X Zhang Lanjun L

Cancer control : journal of the Moffitt Cancer Center 20190101 1

After curative treatment of esophageal squamous cell cancer (ESCC), patients are at high risk for recurrence. The objective of this study was to develop an index with a high sensitivity and specificity to predict ESCC patients' recurrence and prognosis. A retrospective analysis was conducted on consecutive patients with EC who underwent esophagectomy. In total, 1417 patients were included in the current investigation. In total, 770 patients were included in the current study's exploratory group. ...[more]

PMID: 31146546

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Project description:BackgroundEsophageal squamous cell carcinoma (ESCC) still remains intractable disease with few therapeutic options. Programmed death-ligand 1 (PD-L1), which is essential for immune evasion, is involved in the pathogenesis of ESCC and thus is a potential therapeutic target. PIK3CA, KRAS, and BRAF mutations, microsatellite instability (MSI) caused by deficient mismatch repair (dMMR), and human papillomavirus (HPV) can potentially upregulate PD-L1 expression, which might contribute to the clinical outcome of patients with ESCC.MethodsWe investigated the significance of the present druggable markers [PD-L1, PIK3CA, KRAS, and BRAF mutations, MSI caused by deficient dMMR, and HPV] in 64 curatively resected ESCCs, using immunohistochemistry (PD-L1 and MMR protein expression), direct sequencing (KRAS, BRAF, and PIK3CA mutations), real-time PCR (HPV infection), and MSI using quasi-monomorphic markers.ResultsPD-L1 expression, PIK3CA mutation, and MSI/dMMR were detected in 35.9, 12.5, and 17.2% of ESCCs, respectively. HPV was rarely detected (1.6%) (high-risk HPV68), whereas KRAS and BRAF mutations were not detected in ESCCs. PD-L1-positive tumors were not correlated with PIK3CA mutation or MSI/dMMR (all P > 0.05). PD-L1, PIK3CA mutation, and MSI/dMMR characterized the patients associated with light smoking, female and younger age, and younger age and well-differentiated tumors, respectively (all P < 0.05). In multivariate analysis, only PD-L1-positivity was an independent favorable prognostic factor for overall survival (OS) and disease-free survival (DFS) (P = 0.023, P = 0.014). In the PD-L1-negative ESCCs, PIK3CA mutation had a poor prognostic impact on both OS and DFS (P = 0.006, P = 0.002).ConclusionsPIK3CA mutation may be an alternative prognostic biomarker in PD-L1-negative curatively resected ESCCs that can be optional to identify high-risk patients with worse clinical outcome who require more intensive therapy and follow-up.

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.

Dataset Information

A Model Shows Utility in Predicting Postoperative Recurrence and Distant Metastasis in Curatively Resected Esophageal Squamous Cell Cancer.

Publications

A Model Shows Utility in Predicting Postoperative Recurrence and Distant Metastasis in Curatively Resected Esophageal Squamous Cell Cancer.

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