Multi-Omics Analysis Reveals the Role of Changes in Platelet Activation Pathways in the Survival Outcome of Patients with Esophageal Squamous Cell Carcinoma.

Objective: The objective of this study was to integrate metabolomics and transcriptomics data to identify key diagnostic and prognostic markers for esophageal squamous cell carcinoma (ESCC). Plasma samples were collected from 85 ESCC patients at different stages and 50 healthy volunteers for non-targeted metabolomic analysis. Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed for non-targeted metabolomic analysis. Subsequently, we integrated the metabolomic data with transcriptomic data from the Gene Expression Omnibus (GEO) and prognosis data from The Cancer Genome Atlas Program (TCGA) to perform pathway analysis. Our focus was on pathways that involve both metabolites and upstream genes, as they often exhibit higher accuracy. Results: Through the integration of metabolomics and transcriptomics, we identified significant alterations in the platelet activation pathway in ESCC. This pathway involves the participation of both metabolites and genes, making it a more accurate reflection of pathological changes associated with the disease. Notably, metabolite arachidonic acid (AA) and chemokine receptor type 2(CXCR2) were significantly downregulated in ESCC, while genes collagen type I alpha 1(COL1A1), collagen type I alpha 2(COL1A2), collagen type III alpha 1(COL3A1), type 3 inositol 1,4,5-trisphosphate receptor (ITPR3), and insulin-like growth factor II mRNA binding protein 3(IGF2BP3) were significantly upregulated, indicating the presence of tumor-induced platelet activation in ESCC. Further analysis of prognosis data revealed that high expression of COL1A1, IGF2BP3, and ITPR3 was associated with a favorable prognosis for ESCC, while high CXCR2 expression was linked to an adverse prognosis. In addition, we combined COL1A1, ITPR3, IGF2BP3, CXCR2, and AA to form a diagnostic biomarker panel. The receiver operating characteristic curve (ROC) demonstrated excellent diagnostic capability (AUC=0.987). Conclusion: Our study underscores the significant role of platelet activation pathways and related genes in the diagnosis and prognosis of ESCC patients. These findings offer promising insights for improving the clinical management of ESCC.

The clinical impacts of the prognostic nutritional index for the esophageal cancer patients who received curative treatment.

BACKGROUND: We investigated the impact of the prognostic nutritional index (PNI) on esophageal cancer survival and recurrence after curative treatment. METHODS: This study included 120 patients who underwent curative surgery followed by the adjuvant treatment for esophageal cancer between 2008 and 2018. The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified. RESULTS: The PNI of 49 was regarded to be the optimal critical point of classification considering the 1-year, 3-year, and 5-year survival rate. The OS rates at three and five years after surgery were 47.4% and 36.0% in the PNI low group, respectively, and 62.5% and 56.5% in the PNI high group, which amounted to a statistically significant difference ( P = 0.020). The RFS rates at three and five years after surgery were 31.0% and 24.8% in the PNI low group, respectively, and 50.9% and 42.8% in the PNI high group, which amounted to a statistically significant difference ( P = 0.020). A multivariate analysis demonstrated that the PNI was a significant independent risk factor for the OS and a marginally significant independent risk factor forRFS. CONCLUSION: The PNI was a risk factor for survival in patients who underwent curative treatment for esophageal cancer. It is necessary to develop the effective plan of the perioperative care and the surgical strategy according to the PNI.

Role of Nutritional Status in the Treatment Outcome for Esophageal Squamous Cell Carcinoma.

Undernourishment is reported to impair treatment response, further leading to poor prognosis for cancer patients. We aimed to investigate the role of nutritional status on the prognosis of squamous cell carcinoma (SCC) of the esophagus, and its correlation with anticancer immune responsiveness. We retrospectively reviewed 340 esophageal-SCC patients who completed curative treatment and received a nutrition evaluation by the Patient-Generated Subjective Global Assessment (PGSGA) score at the beginning and completion of neoadjuvant treatment at our hospital. The correlation between the nutritional status and various clinicopathological parameters and prognosis were examined. In addition, the role of nutritional status in the regulation of the anticancer immune response was also assessed in cancer patients and in a 4-nitroquinoline 1-oxide (4NQO)-induced esophageal tumor model. Our data revealed that malnutrition (patients with a high PGSGA score) was associated with advanced stage and reduced survival rate. Patients in the group with a high PGSGA score were correlated with the higher neutrophil-to-lymphocyte ratio, higher proportion of myeloid-derived-suppressor cells (MDSC) and increased IL-6 level. Furthermore, surgical resection brought the survival benefit to patients in the low PGSGA group, but not for the malnourished patients after neoadjuvant treatment. Using a 4NQO-induced tumor model, we found that nutrition supplementation decreased the rate of invasive tumor formation and attenuated the immune-suppressive microenvironment. In conclusion, malnutrition was associated with poor prognosis in esophageal-SCC patients. Nutritional status evaluated by PGSGA may be useful to guide treatment decisions in clinical practice. Nutritional supplementation is suggested to improve prognosis, and it might be related to augmented anticancer immune response.

Cost-Utility Analysis of Continuation Versus Discontinuation of First-Line Chemotherapy in Patients With Metastatic Squamous-Cell Esophageal Cancer: Economic Evaluation Alongside the E-DIS Trial.

OBJECTIVES: Continuous chemotherapy has been used to treat patients with metastatic esophageal squamous cell carcinoma (mESCC), despite weak evidence supporting a clinical benefit, associated side effects for the patients, and unjustified medical costs. In the French setting, we conducted a cost-utility analysis alongside the randomized E-DIS trial (NCT01248299), which compared first-line fluorouracil/platinum-based chemotherapy continuation (CT-CONT) to CT discontinuation (CT-DISC) in progressive-free patients after an initial 6-week treatment phase. METHODS: A partitioned survival analysis was performed using patient-level data collected during the trial for survival outcomes, quality of life (EQ-5D-3L), and medical costs. The mean quality-adjusted life-years (QALYs) and medical costs were estimated over an 18-month period to assess the incremental net monetary benefit and incremental cost-effectiveness ratio. Uncertainty was handled using the nonparametric bootstrap and univariate analysis. Sixty-seven patients with mESCC were randomized and included in the cost-utility analysis. RESULTS: On average, CT-CONT slightly decreased the number of QALYs (-0.038) and increased the cost per patient (+ €1177). At a willingness-to-pay threshold of €50 000/QALY, the incremental net monetary benefit was negative (-€3077 [95% confidence interval: -6564; 4359]), and the incremental cost-effectiveness ratio was -30 958€/QALY (CT-CONT dominated). The probability of the CT-CONT treatment option being cost-effective at a willingness-to-pay threshold of €50 000/QALY, compared to CT-DISC, was 29%. CONCLUSIONS: CT-DISC may be considered as an alternative therapeutic option to CT-CONT in patients with mESCC who have stable disease after an initial chemotherapy treatment phase. A continuous chemotherapy could indeed reduce the number of QALYs because of the disutility associated with the continuous treatment.

The marginal causal effect of opium consumption on the upper gastrointestinal cancer death using parametric g-formula: An analysis of 49,946 cases in the Golestan Cohort Study, Iran.

Upper gastrointestinal (UGI) cancer, including esophageal and gastric, is one of the most common cancers in the world. Hence, the determination of risk factors of UGI helps to reduce the economic and social burden of this cancer in communities. In Iran, the consumption of opium because of its neighborhood with Afghanistan are considerable. In this study, we examine the causal effect of opium use on the time to UGI cancer death. Based on the Golestan Cohort Study (GCS) in northeastern of Iran, about 50000 adults were enrolled to the study for four years (2004-2008) and followed annually until July 2018. We used "parametric g-formula" to study the causal effect of opium use on the time to death due to UGI. In this study, the information of 49946 individuals due to missingness were analyzed. So the median of follow-up time was 144 months and the prevalence of opium use was 17% (about 8489 persons). During the follow-up period, 593 (1.2%) death from upper gastrointestinal cancer were reported. The study showed that the effect of opium use on the time to UGI death was statistically significant (adjusted risk-ratio based on parametric g-formula = 1.31, 95% CI: [1.04, 1.65]). Additionally, the Population Attributable Fraction (PAF) in UGI cancer deaths of opium use was estimated 5.3% (95% CI: [0.6%, 11.3%]). Our results showed a causal effect of opium use on the intensity of upper gastrointestinal cancer death.

Esophageal adenocarcinoma with any component of signet ring cells portends poor prognosis and response to neoadjuvant therapy.

BACKGROUND: Multiple investigations have shown inferior outcomes for esophageal cancer patients with signet ring cell (SRC) histology. Traditionally, SRC adenocarcinoma has been defined by ≥50% of the tumor composed of SRC. We hypothesized that patients with SRC even <50% would show resistance to standard multimodality therapy with poorer long-term outcomes. METHODS: Patients treated with trimodality therapy for adenocarcinoma from 2006 to 2018 were evaluated for SRC on pretreatment biopsy specimens. Available hematoxylin and eosin slides containing SRC tumors were re-reviewed by an esophageal pathologist to quantify the percent composition of SRC. RESULTS: SRC histology was identified on at least 1 pathologic specimen in 106 of 819 (13%) patients. Rates of pathologic complete response (pCR) among usual-type and SRC tumors were 25% (177/713) and 10% (11/106), respectively (P = .006). The pretreatment SRC components did not independently affect the rate of pCR (1%-10% SRC: 4% [2/46] pCR; 11%-49% SRC: 25% [7/28] pCR; 50%-100% SRC: 7% [2/30] pCR). Kaplan-Meier analysis demonstrated worse survival among patients with any degree of SRC present on pretreatment biopsy, as compared with usual-type esophageal adenocarcinoma (P < .0001). Cox multivariable analysis failed to identify a relationship between increasing SRC component and poorer survival. CONCLUSIONS: We present the only known evaluation of the percentage of SRC component in esophageal carcinoma. Our data support the hypothesis that esophageal adenocarcinoma with any component of SRC are more resistant to chemoradiation with poorer survival. Pathologic reporting of esophageal adenocarcinoma should include any component of SRC. Alternative therapies in patients with any SRC component may be indicated.

Wide Area Transepithelial Sampling with Computer-Assisted Analysis (WATS3D) Is Cost-Effective in Barrett's Esophagus Screening.

BACKGROUND: Wide area transepithelial sampling with three-dimensional computer-assisted analysis (WATS3D) is an adjunct to the standard random 4-quadrant forceps biopsies (FB, "Seattle protocol") that significantly increases the detection of Barrett's esophagus (BE) and associated neoplasia in patients undergoing screening or surveillance. AIMS: To examine the cost-effectiveness of adding WATS3D to the Seattle protocol in screening patients for BE. METHODS: A decision analytic model was used to compare the effectiveness and cost-effectiveness of two alternative BE screening strategies in chronic gastroesophageal reflux disease patients: FB with and without WATS3D. The reference case was a 60-year-old white male with gastroesophageal reflux disease (GERD). Effectiveness was measured by the number needed to screen to avert one cancer and one cancer-related death, and quality-adjusted life years (QALYs). Cost was measured in 2019 US$, and the incremental cost-effectiveness ratio (ICER) was measured in $/QALY using thresholds for cost-effectiveness of $100,000/QALY and $150,000/QALY. Cost was measured in 2019 US$. Cost and QALYs were discounted at 3% per year. RESULTS: Between 320 and 337 people would need to be screened with WATS3D in addition to FB to avert one additional cancer, and 328-367 people to avert one cancer-related death. Screening with WATS3D costs an additional $1219 and produced an additional 0.017 QALYs, for an ICER of $71,395/QALY. All one-way sensitivity analyses resulted in ICERs under $84,000/QALY. CONCLUSIONS: Screening for BE in 60-year-old white male GERD patients is more cost-effective when WATS3D is used adjunctively to the Seattle protocol than with the Seattle protocol alone.

Platinum versus immunotherapy for unresectable esophageal cancer: A protocol for systematic review and meta analysis.

BACKGROUND: Esophageal cancer is one of the most common malignant tumors, with early metastasis, highly malignant characteristics. Morbidity ranks 7th among all malignant tumors, and mortality ranks 6th. Esophageal adjuvant therapy can significantly improve overall survival in unresectable esophageal cancer patients. With the breakthrough and progress of immunotherapy, the possibility of curing esophageal cancer has greatly increased. Some clinical trials have reported that compared with traditional platinum-based chemotherapy, the use of programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors alone can benefit patients and effectively prolong their overall survival. We compare the efficacy of single immunotherapy with traditional platinum-based chemotherapy in a systematic review and meta-analysis to provide a reliable basis for clinicians. METHODS: We will search PubMed, Medline, Embase, Web of Science, Cancerlit, Google Scholar, and the Cochrane Central Register of Controlled Trials for related studies published before December 1, 2019 without language restrictions. Two review authors will search and assess relevant studies independently. Randomized controlled trials (RCTs) or quasi-RCTs, and prospective cohort studies will be included. We will perform subgroup analysis in sex, age, ethnicity, and tumor stage of esophageal cancer patients. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: The results of this systematic review and meta-analysis will provide a basis for clinicians to formulate the best chemotherapy regimen for patients, as well as a research clue for clinical researchers in this field. The results of this study will expand the treatment options for esophageal patients, but due to the nature of the disease and intervention, large sample clinical trials are not abundant, so we will include some high-quality small sample trials, which may cause high heterogeneity. INPLASY REGISTRATION NUMBER: INPLASY2020110012.

Protocol for a systematic review and meta-analysis of Kang-ai injection for patients with oesophageal cancer.

BACKGROUND: Oesophageal cancer (OC) is the sixth leading cause of cancer death worldwide. Despite the improvement of therapeutic methods in recent years, the prognosis of OC remains unsatisfactory. Kang-ai injection, a kind of traditional Chinese herbal medicine, has been widely applied as a promising adjunctive drug for OC. In this study, we aimed to summarize the efficacy and safety of Kang-ai injection for patients with advanced OC through the meta-analysis, in order to provide scientific reference for the design of future clinical trials. METHODS: Relevant randomized controlled trials and high-quality prospective cohort studies were searched from PubMed, Web of Science, Medline, Cochrane Library, Google Scholar, Excerpt Medica Database, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, China Scientific Journal Database and Wanfang Database. Papers in English or Chinese published from their inception to August 2020 will be included without any restrictions.Study selection and data extraction will be performed independently by 2 investigators. The clinical outcomes including overall response rate, disease control rate, overall survival, disease-free survival, quality of life, immune function and adverse events, were systematically evaluated. Stata 14.0 and Review Manager 5.3 were used for data synthesis, subgroup analysis, sensitivity analysis, meta regression, and risk of bias assessment. RESULTS: The results of this study will be published in a peer-reviewed journal, or presented the findings at a relevant conference. CONCLUSION: Our study will draw an objective conclusion of the effects of Kang-ai injection combined with conventional treatment for advanced OC and provide a helpful evidence for clinicians to formulate the best postoperative adjuvant treatment strategy for OC patients. INPLASY REGISTRATION NUMBER: INPLASY202080019.

Survival of esophageal and gastric cancer patients with adjuvant and palliative chemotherapy-a retrospective analysis of a register-based patient cohort.

PURPOSE: The survival of esophageal and gastric cancer patients treated with chemotherapy is rarely assessed outside of clinical trials. Therefore, we compared the effectiveness of various curative or palliative chemotherapy regimens on the survival of esophageal and gastric cancer patients in a "real world" clinical setting. METHODS: We identified a cohort of 966 incident esophageal and gastric cancer patients in Stockholm/Gotland County (a low-risk Western population) during 2008-2013. Patients who received chemotherapy with curative intention (n = 279) and palliative intention (n = 182) were analyzed separately. Using Cox proportional hazards regression models, we estimated hazard ratios (HRs) with 95% confidence intervals (CIs) and adjusted for the potential confounding factors: age, sex, TNM stage, radiotherapy, comorbidity, marital status, education, income, and country of birth. RESULTS: In esophageal cancer patients with curative treatment intention, we observed a higher hazard for death among patients who received carboplatin-fluorouracil compared to patients who received cisplatin-fluorouracil, corresponding to a HR of 2.18 (95% CI 1.09-4.37). Conversely, in patients with cancer in the gastroesophageal junction who had a curative treatment intention at diagnosis, we observed a reduced hazard for death among those who received fluorouracil-oxaliplatin, compared to patients who received cisplatin-fluorouracil (HR 0.28; 95% CI 0.08-0.96). CONCLUSION: Among patients with esophageal cancer who received treatment with curative intention, cisplatin-fluorouracil was associated with better survival compared to carboplatin-fluorouracil, while patients with gastroesophageal junction cancer who were treated with cisplatin-fluorouracil had worse survival compared to fluorouracil-oxaliplatin.

Micronutrient Deficiencies Following Minimally Invasive Esophagectomy for Cancer.

Over the past decades, survival rates for patients with resectable esophageal cancer have improved significantly. Consequently, the sequelae of having a gastric conduit, such as development of micronutrient deficiencies, become increasingly apparent. This study investigated postoperative micronutrient trends in the follow-up of patients following a minimally invasive esophagectomy (MIE) for cancer. Patients were included if they had at least one postoperative evaluation of iron, ferritin, vitamins B1, B6, B12, D, folate or methylmalonic acid. Data were available in 83 of 95 patients. Of these, 78.3% (65/83) had at least one and 37.3% (31/83) had more than one micronutrient deficiency at a median of 6.1 months (interquartile range (IQR) 5.4-7.5) of follow-up. Similar to the results found in previous studies, most common deficiencies identified were: iron, vitamin B12 and vitamin D. In addition, folate deficiency and anemia were detected in a substantial amount of patients in this cohort. At 24.8 months (IQR 19.4-33.1) of follow-up, micronutrient deficiencies were still common, however, most deficiencies normalized following supplementation on indication. In conclusion, patients undergoing a MIE are at risk of developing micronutrient deficiencies as early as 6 up to 24 months after surgery and should therefore be routinely checked and supplemented when needed.

Higher lymph node harvest in patients with a pathologic complete response after neoadjuvant therapy for esophageal cancer is associated with improved survival.

BACKGROUND AND OBJECTIVES: Lymph node harvest during esophagectomy has been associated with improved survival for esophageal cancer but the value of enhanced lymph node harvest following complete pathologic response (pCR) is debated. This study investigated if increasing lymph node harvest in esophageal cancer patients with a pCR after neoadjuvant therapy and esophagectomy is associated with improved survival. METHODS: We queried the National Cancer Data Base for patients with esophageal cancer between 2004 and 2014 who underwent neoadjuvant chemotherapy or chemoradiation therapy followed by esophagectomy found to have pCR. Multivariable Cox modeling was utilized to evaluate the impact of increasing lymph node counts on overall survival (OS). RESULTS: A total of 1373 patients met inclusion criteria. A National Comprehensive Cancer Network compliant lymphadenectomy of ≥15 nodes was associated with improved survival (66.7% vs 51.1%; P < .001). Cox modeling showed that the first node cutoff to demonstrate a statistically significant improvement in OS was ≥7 nodes (hazard ratio [HR], 95% confidence interval [CI]: 0.81, 0.68-0.97; 5-year OS: 54.2%) with a trend of decreasing and statistically significant HRs until ≥25 nodes (HR, 95% CI: 0.52, 0.37-0.72; 5-year OS: 68.4%). CONCLUSIONS: High negative node counts after neoadjuvant therapy and esophagectomy are associated with improved survival in patients with pCR.

USP9X mRNA expression predicts clinical outcome for esophageal squamous cell carcinoma treated with cisplatin-based therapy.

INTRODUCTION: Combination therapy with cisplatin is the conventional first-line treatment in patients with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC). Ubiquitin-specific protease 9X (USP9X) has been shown to be associated with resistance to chemotherapy drugs in several cancers. The purpose of this study was to explore the predictive effects of USP9X on advanced ESCC patients treated with cisplatin-based regimens. MATERIALS AND METHODS: The subjects were 69 advanced ESCC patients who received first-line cisplatin-based chemotherapy or chemoradiotherapy. The quantitative real-time PCR was performed to measure USP9X mRNA expression. The correlation of USP9X expression with clinical parameters and tumor response was analyzed. The Kaplan-Meier method and Cox analysis were employed to analyze differences in overall survival (OS). RESULTS: USP9X mRNA expression was positively associated with the TMN stage at initial diagnosis. Patients with low USP9X mRNA expression had a significantly higher objective response rate (57.1% vs. 17.6%, P=0.001) and longer median OS (25.0 vs. 14.0 months, P<0.001) than those with high expression in all patients or in different treatment subgroups (all P<0.05). Multivariate analysis showed that low mRNA expression of USP9X emerged as an independent prognostic factor indicating prolonged OS (hazard ratio 0.50, 95% CI 0.34-0.73; P<0.001). CONCLUSION: These findings suggest that high USP9X mRNA expression predicts poor clinical efficacy and survival to cisplatin-based therapy in patients with advanced ESCC.

The Influence of the Perioperative Nutritional Status on the Survival Outcomes for Esophageal Cancer Patients with Neoadjuvant Chemotherapy.

BACKGROUND: Studies have shown a variety of nutritional indices to be prognostic predictors for esophageal cancer patients. However, which nutritional index should be used and when it should be measured during the perioperative period remain unclear. This study attempted to clarify the details surrounding predictive nutritional evaluation by assessing the longitudinal data of serologic indices in perioperative esophageal cancer patients. METHODS: The study included 141 esophageal cancer patients who underwent neoadjuvant chemotherapy after radical esophagectomy at Tohoku University Hospital from April 2008 to December 2017. The nutritional status was retrospectively assessed during the perioperative period, and the prognostic factors related to survival were analyzed. RESULTS: Use of the controlling nutritional status (CONUT) score showed that malnutrition occurred only from 14 days after surgery in most cases. Use of the prognostic nutritional index (PNI) showed that the ratio of malnutrition increased gradually from presurgery to 14 days after surgery. The timing of malnutrition that affected survival was 14 days after surgery with the CONUT score and presurgery and 4 months after surgery with the PNI. A multivariable analysis of independent prognostic factors predicting survival identified malnutrition 14 days after surgery with the CONUT score and a low PNI before surgery, invasion depth of the primary lesion, and node metastasis. CONCLUSIONS: Malnutrition occurring during the perioperative state of esophageal cancer was shown to be a survival prognostic factor. Development of an optimal nutritional intervention is recommended for esophageal cancer patients to prevent malnutrition both before and after surgery.

Surgery Is Associated With Survival Benefit in T4a Esophageal Adenocarcinoma: A National Analysis.

BACKGROUND: The National Comprehensive Cancer Network guidelines recommend consideration of surgery for clinical T4a esophageal adenocarcinoma. There are limited data on the outcomes of patients with T4a adenocarcinoma treated with surgery vs definitive chemoradiation, however. METHODS: The National Cancer Database was used to identify patients from 2010-2015 with clinical T4aN0-3M0 esophageal adenocarcinoma, and grouped by receipt of surgery (with or without perioperative therapy) or definitive, concurrent chemoradiation. Patients receiving incomplete definitive therapy or with missing survival information were excluded. Overall survival was evaluated with Kaplan-Meier and Cox proportional hazard analyses. RESULTS: Of 182 patients in the study, 85 (47%) underwent esophagectomy and 97 (53%) underwent chemoradiation. In the surgery cohort, 79 patients (93%) received perioperative chemotherapy. Unadjusted and multivariable analyses demonstrated a significant survival benefit associated with surgery compared with definitive chemoradiotherapy (adjusted hazard ratio 0.32; 95% confidence interval 0.21, 0.50). A 1:1 propensity score-matched analysis of 63 patient pairs also revealed a significant overall survival benefit with surgery compared with chemoradiotherapy alone (hazard ratio 0.26; 95% confidence interval 0.16, 0.43). CONCLUSIONS: In this national analysis, surgery for cT4a esophageal adenocarcinoma was associated with improved outcomes when compared with definitive chemoradiation. Surgery should be considered for medically fit patients with cT4aN0-3M0 esophageal adenocarcinoma.

A propensity-score matching analysis comparing long-term survival of surgery alone and postoperative treatment for patients in node positive or stage III esophageal squamous cell carcinoma after R0 esophagectomy.

BACKGROUND: Surveillance was recommended for patients after R0 esophagectomy by National Comprehensive Cancer Network (NCCN) guidelines. However, local failure was high in locally advanced patients (48-78%). The present study aimed to determine whether adjuvant treatment improved survival for stage IIb-III thoracic esophageal squamous cell carcinoma (TESCC). METHODS: A retrospective review of patients diagnosed as esophageal carcinoma at the Chinese Academy of Medical Sciences Cancer hospital, between January 2004 and December 2011, was performed. A database compiling 975 patents with node positive or stage III thoracic esophageal carcinoma after R0 surgery with or without postoperative radiation/chemoradiation was created. A 1:1 matched study group was generated by the Greedy method after propensity score matching (PSM) analysis. Survival curves were calculated by the Kaplan-Meier method and compared with the log-rank test. Univariate and multivariate analyses were using the Cox proportional hazards regression model. RESULTS: 975 patients were enrolled in the study, 510 patients (52.3%) did not receive any postoperative treatment after R0 surgery and 465 patients had either postoperative chemoradiation or radiotherapy. Median follow-up was 69.2 months. After PSM, 222 well-balanced patients in each group demonstrated the same results. The 3-year, 5-year survival rates and median survival in surgery group (33.0%, 26.4%, 24.3 months) were inferior to those in postoperative treatment group (48.3%, 37.1% and 34.3 months), (P = 0.002). Compared with radiotherapy, postoperative chemoradiation did not improve DFS and OS (P = 0.692; P = 0.368). N stage and adjuvant treatment are independent prognostic factors. CONCLUSIONS: Adjuvant treatment could improve survival for patients with stage IIb-III TESCC.

Impact of Perioperative Chemotherapy on Prognosis of Patients with Esophageal Carcinoma Undergoing Pulmonary Metastasectomy.

PURPOSE: To evaluate prognosis of patients with esophageal carcinoma undergoing pulmonary metastasectomy, and help determine appropriate therapeutic strategies. METHODS: We retrospectively studied 16 patients (15 men and one woman; median age 66.5 years) with esophageal carcinoma, who underwent curative resection of pulmonary metastases. Clinical characteristics and surgical outcomes were analyzed. RESULTS: In all, 11 patients underwent wedge resection, three segmentectomy, and two lobectomies. The average operating time and blood loss were 147 min and 103 mL, respectively. There were no perioperative deaths or severe complications. Five-year overall survival rate was 40.2% and 2-year disease-free survival rate was 35.2%. All recurrences occurred within 2 years. Univariate and multivariate analyses revealed that absence of adjuvant chemotherapy after therapy for esophageal carcinoma was a significant predictor of poor prognosis and recurrence, respectively (p <0.05). The prognosis of seven patients who underwent esophagectomy with adjuvant chemotherapy was better than that of the other nine patients (p = 0.0166). CONCLUSION: Pulmonary metastasectomy in patients with esophageal carcinoma was only one choice of multimodal treatment, and perioperative chemotherapy was important for long-term survival after pulmonary metastasectomy. Pulmonary metastasectomy was effective in patients undergoing esophagectomy with adjuvant chemotherapy.

EORTC-1203-GITCG - the "INNOVATION"-trial: Effect of chemotherapy alone versus chemotherapy plus trastuzumab, versus chemotherapy plus trastuzumab plus pertuzumab, in the perioperative treatment of HER2 positive, gastric and gastroesophageal junction adenocarcinoma on pathologic response rate: a randomized phase II-intergroup trial of the EORTC-Gastrointestinal Tract Cancer Group, Korean Cancer Study Group and Dutch Upper GI-Cancer group.

BACKGROUND: 10-20% of patients with gastric cancer (GC) have HER2+ tumors. Addition of trastuzumab (T) to cisplatin/fluoropyrimidine-based chemotherapy (CT) improved survival in metastatic, HER2+ GC. When pertuzumab (P) was added to neoadjuvant T and CT, a significant increase in histopathological complete response rate was observed in HER2+ breast cancer. This study aims to investigate the added benefit of using both HER2 targeting drugs (T alone or the combination of T + P), in combination with perioperative CT for localized HER2+ GC. METHODS: This is a prospective, randomized, open-label, phase II trial. HER2 status from patients with resectable GC (UICC TNM7 tumor stage Ib-III) will be centrally determined. Two hundred and-fifteen patients from 52 sites in 14 countries will be centrally randomized (1:2:2 ratio) to one of the following treatment arms: 1. Standard: CT alone. CT regimens will be FLOT (5-FU, leucovorin, oxaliplatin, taxotere) CapOx (capecitabine, oxaliplatin) or FOLFOX (5-FU, leucovorin, oxaliplatin) according to investigator's choice in Europe, and cisplatin/capecitabine in Asia. 2. Experimental arm 1: CT as in control group, plus T (8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks) at day 1, independent of CT chosen for 3 cycles of 3 weeks before and after surgery. 3. Experimental arm 2: CT plus T as in experimental arm 1, plus P (840 mg every 3 weeks) on day 1. Adjuvant treatment with T or T + P will continue for 17 cycles in total. Stratification factors are: histology (intestinal/non-intestinal); region (Asia vs Europe); location (GEJ vs non-GEJ); HER2 immunohistochemistry score (IHC 3+ vs IHC 2+/FISH+) and chemotherapy regimen. Primary objective is to detect an increase in the major pathological response rate from 25 to 45% either with CT plus T alone, or with CT plus the combination of T and P. DISCUSSION: Depending on the results of the INNOVATION trial, the addition of HER2 targeted treatment with either T or T and P to CT may inform future study designs or become a standard in the perioperative management HER2+ GC. TRIAL REGISTRATION: This article reports a health care intervention on human participants and was registered on July 10, 2014 under ClinicalTrials.gov identifier: NCT02205047 ; EudraCT: 2014-000722-38.

The prognostic value of pre-treatment prognostic nutritional index in esophageal squamous cell carcinoma: A meta-analysis.

BACKGROUND: Prognostic nutritional index (PNI) is an easily obtained index inflecting both one's nutritional and inflammatory status. Its clinical role in esophageal squamous cell carcinoma (ESCC) remains still in debate. The aim of this meta-analysis was to assess the prognostic value and the clinical-pathological features of pre-treatment PNI in ESCC patients. METHODS: A comprehensive search of online databases (PubMed, Embase, Web of Science) was performed. Studies explored the relationship between pre-treatment PNI and long-term survival of ESCC patients were regarded eligible for this meta-analysis. Outcomes were extracted and synthesized. Hazard ratio (HR) and relative ratio (RR) with 95% confidence interval (CI) were used to evaluate the prognostic value of PNI on long-term survival and association with clinical-pathological features, respectively. The heterogeneity levels and publication bias between studies were also estimated. RESULTS: Nine observational studies involving 2276 patients were considered eligible for this meta-analysis. The pooled results showed that low PNI score was significantly correlated with poorer overall survival (OS) of esophageal cancer (pooled HR = 1.418 95%CI: 1.200-1.676, P = .000), poorer recurrence free survival (HR = 1.880 95%CI: 1.207-2.929, P = .005) but not cancer specific survival (CSS) (HR = 1.948 95%CI: 0.544-6.977, P = .306). The PNI value was not related with patient age, sex, depth of tumor invasion, nodular metastasis, and differential grade but the TNM stage (III/IV vs 0/I/II, RR = 1.276, 95% CI 1.146-1.420). CONCLUSIONS: Low pre-treatment PNI was significantly related with OS and recurrence free survival but not CSS for ESCC. PNI was a reliable prognostic factor of ESCC, and higher stage ESCC have higher incidence of low PNI.

High-dose versus standard-dose radiation therapy for cervical esophageal cancer: Retrospective single-institution study.

BACKGROUND: To evaluate the role of definitive radiotherapy using higher-than-standard-dose radiation of 50 Gy for carcinoma of the cervical esophagus (CCE). METHODS: We reviewed 79 patients with stage I-III CCE, treated between 2000 and 2012. Patients received 5-fluorouracil/cisplatin-based chemotherapy concurrently and were divided into high-dose (≥59.4 Gy, n = 44) and standard-dose (<59.4 Gy, n = 35) groups. RESULTS: The median follow-up was 35 months for surviving patients. The high-dose group had significantly better 3-year local (90.0% vs 60.4%, P = .001) and locoregional (70.4% vs 45.3%, P = .04) control. Progression-free (45.4% vs 37.5%, P = .32) and overall (58.4% vs 49.1%, P = .69) survival rates were not different. High-dose radiation was an independent prognostic factor for locoregional control (P = .04). No differences in late toxicities (esophageal stenosis or tracheoesophageal fistula) were observed. CONCLUSION: High-dose radiation for CCE improves local and locoregional control, without increasing severe toxicities.