Application of neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy in curative surgery for esophageal cancer:A metaanalysis

BACKGROUND The effectiveness of neoadjuvant therapy in esophageal cancer(EC)treatment is still a subject of debate.AIM To compare the clinical efficacy and toxic side effects between neoadjuvant chemoradiotherapy(nCRT)and neoadjuvant chemotherapy(nCT)for locally advanced EC(LAEC).METHODS A comprehensive search was conducted using multiple databases,including PubMed,EMBASE,MEDLINE,Science Direct,The Cochrane Library,China National Knowledge Infrastructure,Wanfang Database,Chinese Science and Technology Journal Database,and Chinese Biomedical Literature Database Article.Studies up to December 2022 comparing nCRT and nCT in patients with EC were selected.RESULTS The analysis revealed significant differences between nCRT and nCT in terms of disease-free survival.The results indicated that nCRT provided better outcomes in terms of the 3-year overall survival rate(OSR)[odds ratio(OR)=0.95],complete response rate(OR=3.15),and R0 clearance rate(CR)(OR=2.25).However,nCT demonstrated a better 5-year OSR(OR=1.02)than nCRT.Moreover,when compared to nCRT,nCT showed reduced risks of cardiac complications(OR=1.15)and pulmonary complications(OR=1.30).CONCLUSION Overall,both nCRT and nCT were effective in terms of survival outcomes for LAEC.However,nCT exhibited better performance in terms of postoperative complications.

Optimal extent of lymphadenectomy improves prognosis and guides adjuvant chemotherapy in esophageal cancer: A propensity scorematched analysis

BACKGROUND The optimal extent of lymphadenectomy in esophageal squamous cell carcinoma(ESCC)patients remained debatable.AIM To explore the ideal number of cleared lymph nodes in ESCC patients undergoing upfront surgery.METHODS In this retrospective,propensity score-matched study,we included 1042 ESCC patients who underwent esophagectomy from November 2008 and October 2019.Patients who underwent neoadjuvant therapy were excluded.We collected pa-tients’clinicopathological features and information regarding lymph nodes,in-cluding the total number of resected lymph nodes(NRLN),and pathologically diagnosed positive lymph nodes(RPLN).SPSS and R software were used for statistical analysis.RESULTS Among the included 1042 patients,two cohorts:≤21(n=664)and>21 NRLN(n=378)were identified.The final prognostic model included four variables:T stage,N,venous thrombus,and the number of removed lymph nodes.Among them,NRLN>21 was determined as an independent prognosticator after surgery for esophageal cancer(hazards regression=0.66,95%confidence interval:0.50-0.87,P=0.004).A nomogram was created based on the regression coefficients of the variables in the final model.In the training cohort,the predictive model dis-played an uncorrected five-year overall survival C-index of 0.659,with a bootstrap-corrected C-index of 0.654.In the subgroup analysis,adjuvant chemotherapy was beneficial in the subgroup with NRLN>21 and RPLN≤0.16 and NRLN≤21 and RPLN>0.16.CONCLUSION NRLN>21 was an independent prognostic factor after ESCC surgery.The combination of NRLN and RPLN may provide a reference for adjuvant chemotherapy use in potential beneficiaries.

Effectiveness of 5-flurouracil-based neoadjuvant chemotherapy in locally-advanced gastric/gastroesophageal cancer:A meta-analysis

AIM:To investigate the effectiveness of 5-flurouracilbased neoadjuvant chemotherapy(NAC) for gastroesophageal and gastric cancer by meta-analysis.METHODS:MEDLINE and manual searches were performed to identify all published randomized controlled trials(RCTs) investigating the efficacy of the flurouracilbased NAC for gastroesophageal and gastric cancer,and RCTs of NAC for advanced gastroesophageal and gastric cancer vs no therapy before surgery.Studies that included patients with metastases at enrollment were excluded.Primary endpoint was the odds ratio(OR) for improving overall survival rate of patients with gastroesophageal and gastric cancer.Secondary endpoints were the OR of efficiency for down-staging tumor and increasing R0 resection in patients with gas-troesophageal and gastric cancer.Safety analyses were also performed.The OR was the principal measurement of effect,which was calculated as the treatment group(NAC plus surgery) vs control group(surgery alone) and was presented as a point estimate with 95% confidence intervals(CI).All calculations and statistical tests were performed using RevMan 5.1 software.RESULTS:Seven RCTs were included for the analysis.A total of 1249 patients with advanced gastroesophageal and gastric cancer enrolled in the seven trials were divided into treatment group(n = 620) and control group(n = 629).The quality scores of the RCTs were assessed according to the method of Jadad.The RCT quality scores ranged from 2 to 7(5-point scale),with a mean of 3.75.The median follow-up time in these studies was over 3 years.The meta-analysis showed that NAC improved the overall survival rate(OR 1.40,95%CI 1.11-1.76;P = 0.005),which was statistically significant.The 3-year progression-free survival rate was significantly higher in treatment group than in control group(37.7% vs 27.3%)(OR 1.62,95%CI 1.21-2.15;P = 0.001).The tumor down-stage rate was higher in treatment group than in control group(55.76% vs 41.38%)(OR 1.77,95%CI 1.27-2.49;P = 0.0009) and the R0 resection rate of the gastroesophageal and gastric cancer was higher in treatment group than in control group(75.11% vs 68.56%)(OR 1.38,95%CI 1.03-1.85;P = 0.03),with significant differences.No obvious safety concerns about mortality and complications were raised in these trials.There were no statistically significant differences in perioperative mortality(5.08% vs 4.86%)(OR 1.05,95%CI 0.57-1.94;P = 0.87 fixed-effect model) and in the complication rate between the two groups(13.25% vs 9.66%)(OR 1.40,95%CI 0.91-2.14;P = 0.12 fixed-effect model).Trials showed that patients from Western countries favored NAC compared with those from Asian countries(OR 1.40,95%CI 1.07-1.83).Monotherapy was inferior tomultiple chemotherapy(OR 1.40,95%CI 1.07-1.83).Intravenous administration of NAC was more advantageous than oral route(OR 1.41,95%CI 1.09-1.81).CONCLUSION:Flurouracil-based NAC can safely improve overall survival rate of patients with gastroesophageal/gastric cancer.Additionally,NAC can down the tumor stage and improve R0 resection.

Positron emission tomography complete metabolic response as a favorable prog-nostic predictor in esophageal cancer following neoadjuvant chemotherapy with docetaxel/cis-platin/5-fluorouracil

BACKGROUND 18F-fluorodeoxyglucose-positron emission tomography(PET)/computed tomography is useful in diagnosing lymph node and distant metastases of esophageal cancer.However,its value for predicting survival is controversial.AIM To evaluate the value of PET complete metabolic response(CMR)as a prognostic predictor for esophageal cancer.METHODS Between June 2013 and December 2017,58 patients with squamous cell esophageal cancer who underwent neoadjuvant chemotherapy(NAC)in Oita University were enrolled in this retrospective cohort study.Tumors were clinically staged using fluorodeoxyglucose-PET/computed tomography before and after NAC.After NAC,maximal standardized uptake value≤2.5 was defined as PET-CMR,and maximal standardized uptake value>2.5 was defined as non-PET-CMR.We compared short-term outcomes between the PET-CMR group and non-PET-CMR group and evaluated prognostic factors by univariate and multivariate analyses.RESULTS The PET-CMR group included 22 patients,and the non-PET-CMR group included 36 patients.There were no significant differences in intraoperative and post operative complications between the two groups.Five-year relapse-free survival and overall survival in the PET-CMR group were significantly more favorable than those in the non-PET-CMR group(38.6 mo vs 20.8 mo,P=0.021;42.8 mo vs 25.1 mo,P=0.011,respectively).PET-CMR was a significant prognostic factor in terms of relapse-free survival by univariate analysis(hazard ratio:2.523;95%confidence interval:1.034–7.063;P<0.041).Particularly,PET-computed tomography negative N was an independent prognostic factor of relapse-free survival and overall survival by multivariate analysis.CONCLUSION PET-CMR after NAC is considered a favorable prognostic factor for esophageal cancer.Evaluation by PET-computed tomography could be useful in clinical decision making for esophageal cancer.

The influence of neoadjuvant chemotherapy on immunity function in elderly patients with the stages of Ⅱ and Ⅲ esophageal cancer

Objective: We aimed to study the influence of neoadjuvant chemotherapy on immunity function in elderly patients with the stages of II and III esophageal cancer. Methods: Thirty-seven elderly patients (age ranged from 60 to 75 years) with the stages of II and III esophageal cancer underwent 2 cycles chemotherapy preoperatively with single-drug regimen (docetaxel, 35 mg/m2 once a week, on days 1, 8 and 15, at interval of 2 weeks for one cycle). Surgery were performed three weeks later. Blood samples were drawn separately on the day of admission, 1 day before operation, 7 day and 1 month after operation, and we conducted the Flow Cytometry to detect the levels of CD3+, CD4+, CD8+,CD4+/CD8+ and NK cells. Results: There were no significant differences in the levels of CD3+, CD4+, CD8+, CD4+/CD8+ and NK cells between before and after chemotherapy (P > 0.05). On day 7 after operation, the levels of CD3+, CD4+, CD4+/CD8+ and NK cells were degraded and CD8+ increased significantly (P < 0.05). One month after operation, the levels of CD3, CD4+, CD4+/CD8 and NK cells were higher than normal, and CD8 was depressed significantly (P < 0.05). Conclusion: Neoadjuvant chemotherapy has no significant impact on cellular immune function in elderly patients with the stages of II and III esophageal cancer, it is an effective and safe treatment.

MicroRNA signatures in chemotherapy resistant esophageal cancer cell lines

AIM: To investigate expression of microRNA (miRNA) and potential targets in chemotherapy resistant esophageal cancer cell lines.

Intensity-modulated radiation therapy with concurrent chemotherapy for locally advanced cervical and upper thoracic esophageal cancer

AIM： To evaluate the dosimetry, efficacy and toxicity of intensity-modulated radiation therapy （IMRT） and concurrent chemotherapy for patients with locally advanced cervical and upper thoracic esophageal cancer. METHODS： A retrospective study was performed on 7 patients who were definitively treated with IMRT and concurrent chemotherapy. Patients who did not receive IMRT radiation and concurrent chemotherapy were not included in this analysis. IMRT plans were evaluated to assess the tumor coverage and normal tissue avoidance. Treatment response was evaluated and toxicities were assessed. RESULTS： Five- to nine-beam IMRT were used to deliver a total dose of 59.4-66 Gy （median： 64.8 Gy） to the primary tumor with 6-MV photons. The minimum dose received by the planning tumor volume （PTV） of the gross tumor volume boost was 91.2%-98.2% of the prescription dose （standard deviation [SD]： 3.7%-5.7%）. The minimum dose received by the PTV Of the clinical tumor volume was 93.8%-104.8% （SD： 4.3%-11.1%） of the prescribed dose. With a median follow-up of 15 rno （range： 3-21 too）, all 6 evaluable patients achieved complete response. Of them, 2 developed local recurrences and 2 had distant metastases, 3 survived with no evidence of disease. After treatment, 2 patients developed esophageal stricture requiring frequent dilation and 1 patient developed tracheal-esophageal fistula. CONCLUSION： Concurrent IMRT and chemotherapy resulted in an excellent early response in patients with locally advanced cervical and upper thoracic esophageal cancer. However, local and distant recurrence and toxicity remain to be a problem. Innovative approaches are needed to improve the outcome.

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.

Induction chemotherapy with albumin-bound paclitaxel plus lobaplatin followed by concurrent radiochemotherapy for locally advanced esophageal cancer

BACKGROUND Albumin-bound paclitaxel(ABP)has been used as second-and higher-line treatments for advanced esophageal cancer,and its efficacy and safety have been well demonstrated.Lobaplatin(LBP)is a third-generation platinum antitumor agent;compared with the first two generations of platinum agents,it has lower toxicity and has been approved for the treatment of breast cancer,small cell lung cancer,and chronic granulocytic leukemia.However,its role in the treatment of esophageal cancer warrants further investigations.AIM To investigate the efficacy and safety of induction chemotherapy with ABP plus LBP followed by concurrent radiochemotherapy(RCT)for locally advanced esophageal cancer.METHODS Patients with pathologically confirmed advanced esophageal squamous cell carcinoma(ESCC)at our hospital were enrolled in this study.All patients were treated with two cycles of induction chemotherapy with ABP plus LBP followed by concurrent RCT:ABP 250 mg/m^(2),ivgtt,30 min,d1,every 3 wk;and LBP,30 mg/m^(2),ivgtt,2 h,d1,every 3 wk.A total of four cycles were scheduled.The dose of the concurrent radiotherapy was 56-60 Gy/28-30 fractions,1.8-2.0 Gy/fraction,and 5 fractions/wk.RESULTS A total of 29 patients were included,and 26 of them completed the treatment protocol.After the induction chemotherapy,the objective response rate(ORR)was 61.54%,the disease control rate(DCR)was 88.46%,and the progressive disease(PD)rate was 11.54%;after the concurrent RCT,the ORR was 76.92%,the DCR was 88.46%,and the PD rate was 11.54%.The median progression-free survival was 11.1 mo and the median overall survival was 15.83 mo.Cox multivariate analysis revealed that two cycles of induction chemotherapy followed by concurrent RCT significantly reduced the risk of PD compared with two cycles of chemotherapy alone(P=0.0024).Non-hematologic toxicities were tolerable,and the only grade 3 non-hematologic toxicity was radiation-induced esophagitis(13.79%).The main hematologic toxicity was neutropenia,and no grade 4 adverse event occurred.CONCLUSION Induction chemotherapy with ABP plus LBP followed by concurrent RCT is effective in patients with locally advanced ESCC,with mild adverse effects.Thus,this protocol is worthy of clinical promotion and application.

Validity of studies suggesting preoperative chemotherapy for resectable thoracic esophageal cancer:A critical appraisal of randomized trials

BACKGROUND In 2015,Kidane published a Cochrane review and meta-analysis to summarise the impact of preoperative chemotherapy versus surgery alone on survival for resectable thoracic esophageal cancer.The authors concluded that preoperative chemotherapy improved overall survival(OS).AIM The aim of this article was to assess the validity of the three most powerful studies included in the Cochrane review and the meta-analysis supporting the advantage of preoperative chemotherapy and to investigate the impact of an exclusion of these three studies on the result of the meta-analysis.METHODS OS was selected as the endpoint of interest.Among the ten included papers which analysed this endpoint,we identified the three publications with the highest weights influencing the final result.The validity of these papers was analysed using the CONSORT checklist for randomized controlled trials.We performed a new meta-analysis without the three studies to assess their impact on the general result of the original meta-analysis.RESULTS The three analysed studies revealed several inconsistencies.Inappropriate answers were found in up to one third of the items of the CONSORT checklist.Missing information about sample-size calculation and power,unclear or inadequate randomisation,and missing blinded set-up were the most common findings.When the three criticized studies were excluded in the meta-analysis,preoperative chemotherapy showed no benefit in OS.CONCLUSION The three most powerful publications in the Cochrane review show substantial deficits.After the exclusion of these studies from the meta-analysis,preoperative chemotherapy does not seem to result in an advantage in survival.We suggest a more critical appraisal regarding the validity of single studies.

Chemotherapy predictors and a time-dependent chemotherapy effect in metastatic esophageal cancer

BACKGROUND Chemotherapy has long been shown to confer a survival benefit in patients with metastatic esophageal cancer.However,not all patients with metastatic disease receive chemotherapy.AIM To evaluate a large cancer database of metastatic esophageal cancer cases to identify predictors of receipt to chemotherapy and survival.METHODS We interrogated the National Cancer Database(NCDB)between 2004-2015 and included patients with M1 disease who had received or did not receive chemotherapy.A logistic regression model was used to examine the associations between chemotherapy and potential confounders and a Cox proportional hazards model was employed to examine the effect of chemotherapy on overall survival(OS).Propensity score analyses were further performed to balance measurable confounders between patients treated with and without chemotherapy.RESULTS A total of 29182 patients met criteria for inclusion in this analysis,with 21911(75%)receiving chemotherapy and 7271(25%)not receiving chemotherapy.The median follow-up was 69.45 mo.The median OS for patients receiving chemotherapy was 9.53 mo(9.33-9.72)vs 2.43 mo(2.27-2.60)with no chemotherapy.Year of diagnosis 2010-2014[odds ratio(OR):1.29,95%confidence interval(CI):1.17-1.43,P value<0.001],median income>$46000(OR:1.49,95%CI:1.27-1.75,P value<0.001),and node-positivity(OR:1.35,95%CI:1.20-1.52,P<0.001)were independent predictors of receiving chemotherapy,while female gender(OR:0.86,95%CI:0.76-0.98,P=0.019),black race(OR:0.76,95%CI:0.67-0.93,P=0.005),uninsured status(OR:0.41,95%CI:0.33-0.52,P<0.001),and high Charlson Comorbidity Index(CCI)(OR for CCI≥2:0.61,95%CI:0.50-0.74,P<0.001)predicted for lower odds of receiving chemotherapy.Modeling the effect of chemotherapy on OS using a time-dependent coefficient showed that chemotherapy was associated with improved OS up to 10 mo,after which there is no significant effect on OS.Moreover,uninsured status[hazard ratio(HR):1.20,95%CI:1.09-1.31,P<0.001],being from the geographic Midwest(HR:1.07,95%CI:1.01-1.14,P=0.032),high CCI(HR for CCI≥2:1.16,95%CI:1.07-1.26,P<0.001),and higher tumor grade(HR for grade 3 vs grade 1:1.28,95%CI:1.14-1.44,P<0.001)and higher T stage(HR for T1 vs T4:0.89,95%CI:0.84-0.95,P<0.001)were independent predictors of worse OS on multivariable analyses.CONCLUSION In this large,retrospective NCDB analysis,we identified several socioeconomic and clinicopathologic predictors for receiving chemotherapy and OS in patients with metastatic esophageal cancer.The benefit of chemotherapy on OS is timedependent and favors early initiation.Focused outreach in lower income and underinsured patients is critical as receipt of chemotherapy is associated with improved OS.

Impact of palliative therapies in metastatic esophageal cancer patients not receiving chemotherapy

BACKGROUND Palliative therapy has been associated with improved overall survival(OS)in several tumor types.Not all patients with metastatic esophageal cancer receive palliative chemotherapy,and the roles of other palliative therapies in these patients are limited.AIM To investigate the impact of other palliative therapies in patients with metastatic esophageal cancer not receiving chemotherapy.METHODS The National Cancer Database was used to identify patients between 2004-2015.Patients with M1 disease who declined chemotherapy and had known palliative therapy status[palliative therapies were defined as surgery,radiotherapy(RT),pain management,or any combination thereof]were included.Cases with unknown chemotherapy,RT,or nonprimary surgery status were excluded.Kaplan-Meier estimates of OS were calculated.Cox proportional hazards regression models were employed to examine factors influencing survival.RESULTS Among 140234 esophageal cancer cases,we identified 1493 patients who did not receive chemotherapy and had complete data.Median age was 70 years,most(66.3%)had a Charlson Comorbidity Index(CCI)of 0,and 37.1%were treated at an academic center.The majority(72.7%)did not receive other palliative therapies.On both univariate and multivariable analyses,there was no difference in OS between those receiving other palliative therapy(median 2.83 mo,95%CI:2.53-3.12)vs no palliative therapy(2.37 no,95%CI:2.2-2.56;multivariable P=0.290).On univariate,but not multivariable analysis,treatment at an academic center was predictive of improved OS[Hazard ratio(HR)0.90,95%CI:0.80-1.00;P=0.047].On multivariable analysis,female sex(HR 0.81,95%CI:0.71-0.92)and non-black,other race compared to white race(HR 0.72,95%CI:0.56-0.93)were associated with reduced mortality,while South geographic region relative to West region(HR 1.23,95%CI:1.04-1.46)and CCI of 1 relative to CCI of 0(HR 1.17,95%CI:1.03-1.32)were associated with increased mortality.Higher histologic grade and T-stage were also associated with worse OS(P<0.05).CONCLUSION Palliative therapies other than chemotherapy conferred a numerically higher,but not statistically significant difference in OS among patients with metastatic esophageal cancer not receiving chemotherapy.Quality of life metrics,inpatient status,and subgroup analyses are important for examining the role of palliative therapies other than chemotherapy in metastatic esophageal cancer and future studies are warranted.

Impact of tumour histological subtype on chemotherapy outcome in advanced oesophageal cancer

To investigate the impact of histology on outcome in advanced oesophageal cancer treated with first-line fluoropyrimidine-based chemotherapy. METHODSIndividual patient data were pooled from three randomised phase III trials of fluoropyrimidine-based chemotherapy ± platinum/anthracycline in patients with advanced, untreated gastroesophageal adenocarcinoma or squamous cell carcinoma (SCC) randomised between 1994 and 2005. The primary endpoint was overall survival of oesophageal cancer patients according to histology. Secondary endpoints were response rates and a toxicity composite endpoint. RESULTSOf the total 1836 randomised patients, 973 patients (53%) were eligible (707 patients with gastric cancer were excluded), 841 (86%) had adenocarcinoma and 132 (14%) had SCC. There was no significant difference in survival between patients with adenocarcinoma and SCC, with median overall survivals of 9.5 mo vs 7.6 mo (HR = 0.85, 95%CI: 0.70-1.03, P = 0.09) and one-year survivals of 38.8% vs 28.2% respectively. The overall response rate to chemotherapy was 44% for adenocarcinoma vs 33% for SCC (P = 0.01). There was no difference in the frequency of the toxicity composite endpoint between the two groups. CONCLUSIONThere was no significant difference in survival between adenocarcinoma and SCC in patients with advanced oesophageal cancer treated with fluoropyrimidine-based chemotherapy despite a trend for worse survival and less chemo-sensitivity in SCC. Tolerance to treatment was similar in both groups. This analysis highlights the unmet need for SCC-specific studies in advanced oesophageal cancer and will aid in the design of future trials of targeted agents.

Effect of Docetaxel and Cisplatin Chemotherapy Combined with Intensitymodulated Radiotherapy in the Treatment of Postoperative Recurrence of Esophageal Cancer and Its Effect on Serum Tumor Markers

Objective: To investigate the effect of docetaxel and cisplatin combined with intensity-modulated radiotherapy in thetreatment of postoperative recurrence of esophageal cancer and the content of tumor markers in serum. Methods: According tosimple randomization method, 60 patients with postoperative recurrence of esophageal cancer admitted from February 2018 toSeptember 2019 were divided into control group (n = 30 cases) and observation group (n = 30 cases). All patients received IMRT.Fluorouracil + cisplatin was used in the control group and docetaxel + cisplatin was used in the observation group. After 2 coursesof continuous treatment, the therapeutic effect, serum tumor marker content and adverse reactions were compared between thetwo groups. Results: After treatment, the effective rate of observation group was higher than control group, and the difference wasstatistically significant (P < 0.05).The contents of carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) andcarbohydrate antigen 19-9 (CA19-9) in observation group were lower than those in control group, and the difference was statisticallysignificant (P < 0.05). The incidence of adverse reactions in the observation group was lower than that in the control group, and thedifference was statistically significant (P < 0.05). Conclusion: Docetaxel and cisplatin combined with intensemodulated radiotherapyfor postoperative recurrence of esophageal cancer can improve the therapeutic effect, inhibit the malignant degree of tumor, andreduce the incidence of adverse reactions.

Epinephrine use during chemotherapy to treat severe tracheal stenosis secondary to advanced esophageal cancer:A case report and review of the literature

Dyspnea from tracheal stenosis due to compression by a tumor is an emergency that complicates therapy in oncology.We report a case of advanced esophageal cancer in a 56-year-old male who developed severe dyspnea due to airway compression by mediastinal lymph node enlargement.We used epinephrine by subcutaneous injection and aerosol inhalation to temporarily relieve dyspnea while the patient received bevacizumab and chemotherapy.The dyspnea had subsided considerably after 5 days,and the mediastinal lymph nodes were significantly reduced after 2 cycles of chemotherapy.However,the patient died of massive tracheal hemorrhage 2 months later.

Recent progress of chemotherapy and biomarkers for gastroesophageal cancer

Key cytotoxic drugs of chemotherapy for gastroesophageal cancer include fluoropyrimidine, platinum, taxanes and irinotecan. Concurrent chemoradiotherapy is one of the main treatment strategies, especially for esophageal cancer. As molecular target agents, the anti-HER2 antibody trastuzumab for HER2-positive gastric cancer and the anti-angiogenesis agent ramucirumab combined with paclitaxel have been proven to improve the survival of gastric cancer patients. Recently, anti-PD-1 antibodies have become available as second- or later-line chemotherapy. Microsatellite instability is also useful as a biomarker to select patients suitable for immunotherapy. Furthermore, genome-wide analysis has improved our understanding of the biological features and molecular mechanisms of gastroesophageal cancer and will provide optimized treatment selection.

Palliative chemotherapy for gastroesophageal cancer in old and very old patients: A retrospective cohort study at the National Center for Tumor Diseases, Heidelberg

AIM:To investigate the outcome of palliative chemotherapy in old patients with gastroesophageal cancer at the National Center for Tumor Diseases,Heidelberg.METHODS:Using a prospectively generated database,we retrospectively analyzed 55 patients≥70years under palliative chemotherapy for advanced gastroesophageal cancer at the outpatient clinic of the National Center for Tumor Diseases Heidelberg,Germany between January 2006 and December2013.Further requirements for inclusion were(1)histologically proven diagnosis of gastroesophageal cancer;(2)advanced(metastatic or inoperable)disease;and(3)no history of radiation or radiochemotherapy.The clinical information included Eastern Cooperative Oncology Group performance status(ECOG PS),presence and site of metastases at diagnosis,date of previous surgery and perioperative chemotherapy,start and stop date of first-line treatment,toxicities and consecutive dosage reductions of first-line treatment,response to first-line therapy,date of progression,usage of second-line therapies and date and cause of death.Survival times[progression-free survival(PFS),overall survival(OS)and residual survival(RS)]were calculated.Toxicity and safety were examined.Prognostic factors including ECOG PS,age and previousperioperative treatment were analyzed.RESULTS:Median age of our cohort was 76 years.86%of patients received a combination of two cytotoxic drugs.76 percent of patients had an oxaliplatin-based first-line therapy with the oxaliplatin and 5-fluorouracil regimen being the predominantely chosen regimen(69%).Drug modifications due to toxicity were necessary in 56%of patients,and 11%of patients stopped treatment due to toxicities.Survival times of our cohort are in good accordance with the major phaseⅢtrials that included mostly younger patients:PFS and OS were 5.8 and 9.5 mo,respectively.Survival differed significantly between patient groups with low(≤1)and high(≥2)ECOG PS(12.7 mo vs 3.8 mo,P<0.001).Very old patients(≥75 years)did not show a worse outcome in terms of survival.Patients receiving secondline treatment(51%)had a significantly longer RS than patients with best supportive care(6.8 vs 1.4 mo,P=0.001).Initial ECOG PS was a strong prognostic factor for PFS,OS and RS.CONCLUSION:Old patients with non-curable gastroesophageal cancer should be offered chemotherapy,and ECOG PS is a tool for balancing benefit and harm upfront.Second-line treatment is reasonable.

Synchronous rectal and esophageal cancer treated with chemotherapy followed by two-stage resection

We report a case of 61-year-old male who had synchronous advanced rectal cancer involving the urinary bladder massively associated with multiple liver metastases, and esophageal cancer successfully treated by neoadjuvant chemotherapy followed by two-stage resection. Although complete resection of each of the lesions was considered possible by performing anterior pelvic exenteration, liver resection, and esophagectomy, it might be impossible for the patient to endure the stress of all of these operative procedures at once. Therefore, we planned to perform staged treatment with prioritizing consideration. First, we instituted chemotherapy with the FOLFOX(oxaliplatin + fluorouracil + leucovorin) plus cetuximab regimen, which could adequately control both rectal and esophageal cancer. After 6 cycles of chemotherapy, high anterior resection combined with cystoprostatectomy and lateral segmentectomy plus partial hepatectomy was performed followed by staged esophagectomy with three-field lymph node dissection. It was possible to use oxaliplatin and cetuximab safely as neoadjuvant therapy not only for advanced rectal cancer but for esophageal cancer, and it was effective.

Effect of cetuximab combined with paclitaxel + cisplatin neoadjuvant chemotherapy on esophageal cancer cell proliferation and invasion

Objective:To study the effect of cetuximab combined with paclitaxel + cisplatin neoadjuvant chemotherapy on esophageal cancer cell proliferation and invasion.Methods:A total of 62 patients with esophageal cancer who were treated in the hospital between January 2015 and December 2016 were collected and divided into control group and observation group according to random number table, with 31 cases in each group. Control group of patients received paclitaxel + cisplatin neoadjuvant chemotherapy + surgery, and observation group of patients accepted cetuximab combined with paclitaxel + cisplatin neoadjuvant chemotherapy + surgery. The differences in proliferation and invasion gene expression in the tumor tissue were compared between two groups of patients before and after chemotherapy.Results:Before chemotherapy, differences in proliferation and invasion gene expression in tumor tissue were not statistically significant between two groups of patients. After chemotherapy, pro-proliferation genes FOXA1, ABCE1, USP39 and Nestin mRNA expression in tumor tissue of observation group were significantly lower than those of control group;anti-proliferation genes PETN, KLF4, TSLC1 and AnnexinA2 mRNA expression were significantly higher than those of control group;pro-invasion genesγ-synuclein, CXCR4 and Snail mRNA expression were significantly lower than those of control group;anti-invasion genes CIAPIN1, Fez and Lrig1 mRNA expression were significantly higher than that of control group.Conclusions:Cetuximab combined with paclitaxel + cisplatin neoadjuvant chemotherapy can effectively inhibit the malignant degree of esophageal cancer cells and inhibit its proliferation and invasion.

Effects of VEP neoadjuvant chemotherapy before esophageal cancer surgery on the malignant biological behaviors of tumor cells

Objective: To study the effects of VEP neoadjuvant chemotherapy before esophageal cancer surgery on the malignant biological behaviors of tumor cells. Methods: Patients who were diagnosed with locally advanced esophageal cancer in Dangyang People's Hospital between March 2015 and March 2017 were selected as the research objects and randomly divided into the VEP group who received preoperative VEP (etoposide + 5-fluorouracil + cisplatin) chemotherapy and the control group who accepted routine preoperative preparation. The serum contents of tumor markers were determined at diagnosis and 1 d before surgery;the expression of proliferation genes and invasion genes in tumor tissue were determined after surgical resection. Results: One day before surgery, serum CEA, CA125, CYFRA21-1 and SCC-Ag levels of VEP group were significantly lower than those at diagnosis, and serum CEA, CA125, CYFRA21-1 and SCC-Ag levels of control group were not significantly different from those at diagnosis;after surgical resection, PTEN, Smac and PTPN14 mRNA expressions in the tumor tissue of VEP group were significantly higher than those of control group whereas CyclinB1, CDK1, Grp94, MMP2, β-catenin, Slug, Vimentin and N-cadherin mRNA expressions were significantly lower than those of control group. Conclusions: VEP neoadjuvant chemotherapy before esophageal cancer surgery can reduce the growth of tumor cells and inhibit the proliferation and invasion of tumor cells in the lesion.