Long-term efficacy and predictors of pembrolizumab-based regimens in patients with advanced esophageal cancer in the real world.

BACKGROUND: Pembrolizumab combined with chemotherapy has been proven effective as first-line therapy in patients with advanced esophageal cancer. Few trials have assessed the safety and efficacy of this treatment in patients with locally advanced disease. AIM: To analyze long-term outcomes of pembrolizumab in locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) in the real world. METHODS: Patients with advanced ESCC admitted to our center from October 2019 to October 2021 were enrolled in this study. Clinical staging of the patients was based on the 8th edition of the American Joint Committee on Cancer TNM staging system. The patients received different treatments based on clinical stage. In brief, patients with locally advanced and resectable ESCC received neoadjuvant therapy combined with surgery. For those who were not candidates for resection, radical concurrent chemoradiotherapy plus pembrolizumab was more preferable. Patients with metastatic ESCC or who were unsuitable for radiotherapy underwent chemotherapy in combination with pembrolizumab. Long-term survival outcomes such as overall survival (OS), progression-free survival, disease-free survival, long-term adverse effects (AEs), immune maintenance therapy and predictors of immune checkpoint inhibitors (ICIs) efficacy were evaluated. RESULTS: A total of 55 patients with advanced ESCC were enrolled in this retrospective, observational study. The median age was 61 years (range 44-74), with 47.3% (26/55) of the patients in stage IV and 45.5% of the patients had the tumor (25/55) located in the middle third of the esophagus. The median OS in all patients was not reached. The 12-mo OS rate among all patients was 78.8% and the 18-mo OS rate was 72.7%. 9 patients died due to tumor progression and 7 patients died due to treatment-related complications. The therapeutic effect evaluated at the interim evaluation was significantly reflected in the long-term outcome. Patients with complete response or partial response in all patients (P = 0.005) and in the chemoradiotherapy plus pembrolizumab group (P = 0.007) obtained a better prognosis than non-responders. A total of 20 patients (20/55, 36%) received immune maintenance therapy. Baseline peripheral blood biomarkers of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and neutrophil-to-(leukocyte-neutrophil) ratio did not predict the efficacy of ICIs. CONCLUSION: Pembrolizumab combined with chemotherapy or radiotherapy resulted in favorable long-term survival in patients with locally advanced or metastatic ESCC, with safe and manageable long-term AEs.

Changes in the nutritional status of nine vitamins in patients with esophageal cancer during chemotherapy.

BACKGROUND: Many studies have investigated the relationships between vitamins and esophageal cancer (EC). Most of these studies focused on the roles of vitamins in the prevention and treatment of EC, and few studies have examined the changes in vitamin nutritional status and their influencing factors before and after chemotherapy for EC. Chemotherapy may have a considerable effect on EC patients' vitamin levels and hematological indicators. AIM: To research the nutritional status of multiple vitamins in EC patients during chemotherapy and to assess its clinical significance. METHODS: EC patients admitted to our center from July 2017 to September 2020 were enrolled in this study. Serum concentrations of nine vitamins (A, D, E, B9, B12, B1, C, B2 and B6), hemoglobin, total protein, albumin, blood calcium, blood phosphorus concentrations and body mass index (BMI) were measured in all EC patients. The changes in nine vitamins, hematological indicators and BMI were compared before and after two cycles of chemotherapy. The possible influential factors were analyzed. RESULTS: In total, 203 EC patients receiving chemotherapy were enrolled in this study. Varying degrees of vitamin A, D, C and B2 deficiency and weight loss were found in these patients, and the proportions of vitamin B2 and vitamin C deficiencies increased significantly after chemotherapy (both P < 0.05). Serum concentrations of vitamins A, C, B2 and B6 and BMI before and after chemotherapy were statistically significant (all P < 0.05). Multivariate analysis showed that vitamin A levels significantly differed between male and female EC patients, whereas vitamin D concentration significantly differed in EC patients in different stages (all P < 0.05). Correlations were observed between the changes in serum concentrations of vitamin A and C before and after two cycles chemotherapy and the change in BMI (P < 0.05). Hemoglobin, total protein, serum albumin and blood calcium concentrations significantly decreased in EC patients after chemotherapy (all P < 0.05), while the blood phosphorus level significantly increased after chemotherapy (P < 0.05). Using the difference in vitamin concentrations as the independent variables and the difference in BMI as the dependent variable, logistic regression analysis revealed statistically significant differences for vitamin A, vitamin D and vitamin C (F = 5.082, P = 0.002). CONCLUSION: Vitamin A, D, C and B2 were mainly deficient in patients with EC during chemotherapy. Multivitamin supplementation may help to improve the nutritional status, chemotherapy tolerance and efficacy.

[Relationship between serum homocysteine and metabolic syndrome: a cross-sectional study].

OBJECTIVE: To explore the relationship between serum homocysteine and metabolic syndrome (MS). METHODS: A cohort with 1680 people involved in a community-based population in Beijing was investigated. Metabolic syndrome was defined by NCEP-ATPIII criteria. Multivariate logistic regression analysis was used to estimate the odds ratios (OR) of MS. Multiple linear regression analysis was performed to analyze the association between Hcy and characteristic variables. RESULTS: Homocysteine was higher in MS population compared to those without MS (17.99 µmol/L vs. 17.18 µmol/L, P=0.007) after adjusted for age and sex. Levels of homocysteine increased with the presence of MS components (from 0 to 4 or 5) (16.71, 16.94, 17.62, 18.20, 17.82 µmol/L respectively, P=0.044 for linear trend). Among the components, groups with larger waist circumference, higher blood pressure and triglycerides showed significantly higher Hcy level than their counterparts. RESULTS: from multiple logistic regression analysis revealed that the highest Hcy quartile (Hcy IV) was significantly associated with MS. Compared with the lowest Hcy quartile (Hcy I), the adjusted odds ratio of having MS in HcyIV was 1.379 (1.005-1.892) after adjusting for age, sex, levels on creatinine/estimated glomerular filtration rate (eGFR)/low-density lipoprotein cholesterol (LDL-C) and uric acid, smoking, alcohol intake and exercise. In the partial correlation analyses, Hcy was positively associated with body mass index (BMI), waist circumsternece, blood pressure, LDL-C, triglycerides (TG), uric acid, serum creatinine, eGFR, but inversely associated with high-density lipoprotein cholesterol (HDL-C) and independently with age and sex. In multiple linear regression analysis, age, male sex, BMI, LDL-C, creatinine and uric acid were found to be independently associated with Hcy level. CONCLUSION: There was an association noticed between the MS using NCEP-ATPIII criteria and the highest quartile level of Hcy in this study. Factors as age and being male, the levels of BMI, LDL-C, creatinine and uric acid were independently associated with the Hcy level.

[HER-2 and ER expression in prediction of chemo-sensitivity of taxane for advanced breast cancer].

OBJECTIVE: To investigate the predictive value of HER-2 and ER expression for chemosensitivity of taxane in the treatment of advanced breast cancer. METHODS: Of 268 advanced breast cancer patients treated: 71 were by paclitaxel alone, 32 by docetaxel alone, 110 by paclitaxel combined with anthracylines or gemcitabine or platins and 55 by docetaxel-based combinations. HER-2 and ER expression of all patients treated by taxane underwent immunohistochemical (IHC) assay. RESULTS: Univariate analysis showed: the response rate (RR) in HER-2 overexpression group was 56.7%, and in HER-2 weak expression group 33.3% (P = 0.003). The response rate in ER positive group and ER negative group was 33.3% and 48.9%, respectively, with a significant difference (P = 0.015). The RR was 67.6% in ER negative but HER-2 overexpression group. However, in ER positive but HER-2 weak expression group and the other groups, the RR were around 35% (P < 0. 01). Multivariate analysis showed that overexpression of HER-2 was the only significant factor to predict the chemosensitivity of taxane (P = 0. 007), but the ER, Karnofsky performance score (KPS), anthracylines, metastatic sites were not the statistically significant chemo-sensitivity predictive factors for taxane. CONCLUSION: ER negative and/or HER-2 overexpression, especially latter, may be associated with good response in advanced breast cancers treated by taxane.