Outcome Of Esophageal Cancer Patients Research Articles

60: Outcomes of Esophageal Cancer Patients Treated with Trimodality Therapy in a Community Hospital

60: Outcomes of Esophageal Cancer Patients Treated with Trimodality Therapy in a Community Hospital

Stage-directed individualized therapy in esophageal cancer.

Esophageal cancer is the eighth most common cancer worldwide, and the incidence of esophageal carcinoma is rapidly increasing. With the advent of new staging and treatment techniques, esophageal cancer can now be managed through various strategies. A good understanding of the advances and limitations of new staging techniques and how these can guide in individualizing treatment is important to improve outcomes for esophageal cancer patients. This paper outlines the recent progress in staging and treatment of esophageal cancer, with particularly attention to endoscopic techniques for early-stage esophageal cancer, multimodality treatment for locally advanced esophageal cancer, assessment of response to neoadjuvant treatment, and the role of cervical lymph node dissection. Furthermore, advances in robot-assisted surgical techniques and postoperative recovery protocols that may further improve outcomes after esophagectomy are discussed.

Postoperative infectious complications-driven recurrence after radical resection for esophageal cancer

Few reports have reported the long-term outcome of esophageal cancer patients suffering from postoperative infectious complications. Here, we investigated the impact of postoperative infectious complications in patients who had undergone curative resection for esophageal cancer. The study population comprised 97 patients who underwent radical resection for esophageal cancer with curative intent between 2001 and 2008. Postoperative infectious complications were defined as surgical site infections and pneumonia. We compared clinical features, tumor histology, recurrence, and overall survival between patients with postoperative infections and those who did not. Of the 97 patients studied, 37 had postoperative infectious complications. The disease-free and overall survival rates of the entire cohort did not significantly differ between patients with and without postoperative infectious complications. Univariate analysis revealed that among patients with stage III esophageal cancer, those with postoperative infectious complications demonstrated significantly shorter disease-free survival than those without. Multivariate analysis demonstrated that postoperative infectious complications were independent prognostic indicators for disease-free survival of stage III esophageal cancer patients. Our findings suggest that postoperative infectious complications in stage III esophageal cancer patients have a negative impact on disease-free survival.

Effect of nutritional counseling combined with oral nutritional supplements on clinical outcome of esophageal cancer patients under radiotherapy treatment

Objective To investigate the effect of nutritional counseling combined with oral high-fat, high-protein nutritional supplement (Ensource) on nutritional status and clinical outcomes of esophageal cancer patients under radiotherapy treatment. Methods Totally 80 esophageal cancer patients under radiotherapy treatment who were able to take oral feeding and with Nutritional Risk Screening 2002 (NRS 2002) score ≥3 were selected and divided into a study group (n=41, nutritional counseling combined with oral nutritional supplements) and a control group (n=39, nutritional counseling) with a random number table. Energy intake, nutritional status, and incidences of radiotherapy complications of the two groups before and after radiotherapy were compared. Results Energy intakes in the study group increased significantly during radiotherapy compared with the control group [(2 445±686) kJ vs.(1 747±456)kJ, P=0.003]; and the level of prealbumin and transferrin were increased significantly compared with before radiotherapy [(17.35±5.83)mg/L vs. (20.15±6.02)mg/L, P=0.008; (213.74±52.66)mg/L vs. (264.19±43.78)mg/L, P=0.002]. Besides, compared with the control group, incidence of radiation esophagitis (Grade Ⅲ) and radiation skin injury (Grade Ⅲ) in the study group decreased significantly (24% vs. 38%, P=0.000; 27% vs. 41%, P=0.000). Conclusion Nutritional counseling combined with oral nutritional supplements in esophageal cancer patients could help improve the patients' nutritional profile and decrease the incidence of complications related with radiotherapy. Key words: Nutritional counseling; Oral nutritional supplement; Cancer-specific full nutritional formula; Esophageal cancer; Radiotherapy

Postoperative Infectious Complications are Associated with Adverse Oncologic Outcomes in Esophageal Cancer Patients Undergoing Preoperative Chemotherapy.

For some types of cancer, postoperative complications can negatively influence survival, but the association between these complications and oncological outcomes is unclear for patients with esophageal cancer who receive preoperative treatments. Data were retrospectively analyzed for patients who underwent curative resection following preoperative chemotherapy for esophageal squamous cell carcinoma from 2001 to 2011. Clinicopathological parameters and cancer-specific survival (CSS) were compared between patients with and without severe postoperative complications, grade III or higher, using the Clavien-Dindo classification. Of 255 patients identified, 104 (40.8%) postoperatively developed severe complications. The most common complication was atelectasis in 61 (23.9%), followed by pulmonary infection in 22 (8.6%). Three-field lymphadenectomy, longer operation time, and more blood loss were significantly associated with a higher incidence of severe complications. Multivariate analysis of CSS revealed severe complications [hazard ratio (HR)=1.642, 95% confidence interval (95% CI) 1.095-2.460, p=0.016] as a significant prognostic factor along with pT stage [HR=2.081, 95% CI 1.351-3.266, p<0.001] and pN stage [HR=3.724, 95% CI 2.111-7.126, p<0.001], whereas postoperative serum C-reactive protein value was not statistically significant. Among all complications, severe pulmonary infection was the only independent prognostic factor [HR=2.504, 95% CI 1.308-4.427, p=0.007]. The incidence of postoperative infectious complications, in particular pulmonary infection, is associated with unfavorable prognosis in patients with esophageal cancer undergoing preoperative chemotherapy.

The role of PD-L1 in the radiation response and prognosis for esophageal squamous cell carcinoma related to IL-6 and T-cell immunosuppression.

The aim of this study was to assess the significance of programmed cell death 1 ligand 1 (PD-L1) in esophageal squamous cell carcinoma (ESCC) and its association with IL-6 and radiation response. Weretrospectively enrolled 162 patients with ESCC, and examined the correlation between PD-L1 levels and clinical outcomes in esophageal cancer patients. Furthermore, the human esophageal SCC cell line CE81T and TE2 were selected for cellular experiments to investigate the role of PD-L1 in T cell functions and radiation response. Here we demonstrated that PD-L1 expression was significantly higher in esophageal cancer specimens than in non-malignant epithelium. In clinical outcome analysis, this staining of PD-L1 was positively linked to the clinical T4 stage (p=0.004), development of LN metastasis (p=0.012) and higher loco-regional failure rate (p=0.0001). In addition, the frequency of PD-L1 immunoreactivity was significantly higher in IL-6-positive esophageal cancer specimens. When IL-6 signaling was inhibited in vitro, the level of PD-L1 is significantly down-regulated. PD-L1 is a significant predictor for poor treatment response and shorter survival. As demonstrated through in vitro experiments, Irradiation increased PD-L1 expression in human esophageal cancer cells. The inhibition of T cell functions including proliferation and cytotoxicity against tumor cells might be the mechanisms responsible to the role of PD-L1 in radiation response. In conclusion, PD-L1 is important in determining the radiation response and could predict the prognosis of patients with esophageal SCC. Therefore, we suggest inhibition of PD-L1 as a potential strategy for the treatment of esophageal SCC.

An Interdisciplinary Nutrition Support Team Improves Clinical and Hospitalized Outcomes of Esophageal Cancer Patients with Concurrent Chemoradiotherapy.

Background:The prevalence of malnutrition is very high in patients with cancer. The purpose of this study was to investigate whether or not a nutrition support team (NST) could benefit esophageal cancer patients undergoing chemoradiotherapy (CRT).Methods:Between June 2012 and April 2014, 50 esophageal cancer patients undergoing concurrent CRT were randomly assigned into two groups: The NST group and the control group. The nutritional statuses of 25 patients in the NST group were managed by the NST. The other 25 patients in the control group underwent the supervision of radiotherapy practitioners. At the end of the CRT, nutritional status, the incidence of complications, and completion rate of radiotherapy were evaluated. Besides, the length of hospital stay (LOS) and the in-patient cost were also compared between these two groups.Results:At the completion of CRF, the nutritional status in the NST group were much better than those in the control group, as evidenced by prealbumin (ALB), transferrin, and ALB parameters (P = 0.001, 0.000, and 0.000, respectively). The complication incidences, including bone marrow suppression (20% vs. 48%, P = 0.037) and complications related infections (12% vs. 44%, P = 0.012), in the NST group were lower and significantly different from the control group. In addition, only one patient in the NST group did not complete the planned radiotherapy while 6 patients in the control group had interrupted or delayed radiotherapy (96% vs. 76%, P = 0.103). Furthermore, the average LOS was decreased by 4.5 days (P = 0.001) and in-patient cost was reduced to 1.26 ± 0.75 thousand US dollars person-times (P > 0.05) in the NST group.Conclusions:A NST could provide positive effects in esophageal cancer patients during concurrent CRT on maintaining their nutrition status and improving the compliance of CRF. Moreover, the NST could be helpful on reducing LOS and in-patient costs.

Perioperative Blood Transfusion, Age at Surgery, and Prognosis in a Database of 526 Upper Gastrointestinal Cancers

Aims: It is demonstrated that older animals have significantly weaker responses to new alloantigen stimulation than young animals, but the effect on prognosis of perioperative blood transfusion in relation to patient age is unknown. This study is retrospective review to investigate the relationship between perioperative blood transfusion, age at surgery, and clinical outcome in upper gastrointestinal cancer patients. Methods: We analyzed data of 526 upper gastrointestinal cancer patients who underwent curative resection from 2005 to 2010. Results: In esophageal cancer patients, patients with blood transfusion experienced significantly shorter overall survival (OS; univariate HR 2.50, p = 0.0006) and disease-free survival (DFS; univariate HR 1.71, p = 0.016) than patients without. Similar results were observed in gastric cancer patients (OS; univariate HR 3.35, p = 0.0001 and DFS; univariate HR = 3.18, p < 0.0001). Furthermore perioperative blood transfusion may be an independent prognostic factor in esophageal cancer patients (multivariate HR = 2.07, p = 0.026). Interestingly, age at surgery significantly affected the influence of blood transfusion on patient outcome in esophageal cancer patients (p for interaction = 0.022). Conclusion: The negative effect of perioperative blood transfusion was particularly evident among younger patients with esophageal cancer.

Clinical Outcomes for Esophageal Cancer Patients Treated With Intensity Modulated Radiation Therapy Compared to 3-D Conformal Radiation Therapy: An Analysis of the National Cancer Data Base

Clinical Outcomes for Esophageal Cancer Patients Treated With Intensity Modulated Radiation Therapy Compared to 3-D Conformal Radiation Therapy: An Analysis of the National Cancer Data Base

CD44, SHH and SOX2 as novel biomarkers in esophageal cancer patients treated with neoadjuvant chemoradiotherapy

Background and purposeNeoadjuvant chemoradiotherapy (nCRT) improves survival in esophageal cancer (EC) patients, but the response to treatment is heterogeneous and little is known regarding prognostic and predictive markers in these patients. CD44, SOX2 and SHH have been implicated in resistance to CRT, possibly through an association with a cancer stem cell phenotype. Material and methods101 EC patients treated with nCRT and surgery were included. Sufficient pre-treatment biopsy material was present in 71 patients, of which 53 patients were non-complete responders on nCRT (nCR). Protein expression was examined using immunohistochemistry (IHC). Prognostic factors were determined using Cox regression analysis for disease free survival (DFS) and cause specific survival (CSS) in the complete cohort, the pre-treatment biopsies group and post-treatment nCR group. ResultsLow CD44 expression in the nCR group was an independent prognostic factor for both DFS and CSS (DFS HR 2.81, p=0.002 and CSS HR 3.48, p=0.002). Absent SOX2 expression in pretreatment biopsies was related to systemic recurrence (p=0.029) while low SHH in pretreatment biopsies was an independent prognostic factor for a poor DFS (HR 2.27, p=0.036). No relation between marker expression and response to nCRT was observed. ConclusionsLow expression of CD44 and SHH are associated with a poor survival outcome in EC patients treated with nCRT.

CD44, a cancer stemness marker, to predict poor clinical outcome of esophageal cancer patients after neoadjuvant chemoradiotherapy.

e15068 Background: The major causes of treatment failure in cancer are the development of metastases and drug resistance. Recently, extensive studies have shown hyaluronan (HA) - CD44 interactions ...

Postoperative Complications Do Not Affect Long‐Term Outcome in Esophageal Cancer Patients: Reply

Postoperative Complications Do Not Affect Long‐Term Outcome in Esophageal Cancer Patients: Reply

Evaluation of α-1-acid glycoprotein as a prognostic factor of survival in patients with stage II-III esophageal carcinoma treated with neoadjuvant docetaxel, cisplatin, and fluorouracil chemotherapy followed by surgery.

100 Background: Serum α-1-acid glycoprotein (AAG) level was an independent predictor of response and a prognostic factor of survival in patients with non-small cell lung cancer treated with docetaxel chemotherapy. However, it has not been determined whether AAG is associated with the outcomes of esophageal cancer patients who have been treated with a combination of docetaxel, cisplatin and 5-fluorouracil (DCF) as neoadjuvant therapy. Methods: This retrospective study included a cohort of 39 patients with clinical stage II/III esophageal cancer, based on the International Union Against Cancer TNM classification system 7th edition, who were treated with neoadjuvant DCF followed by surgery. DCF consisted of docetaxel (70mg/m2) and cisplatin (70mg/m2) on day 1, and continuous infusion of 5-fluorouracil (750mg/m2/day) on days 1-5, with this regimen repeated every 3 weeks up to three cycles. Patients were divided into groups by median value of baseline AAG levels. Patient characteristics, preoperative clinical stage, chemotherapy effect, and survival were compared between the high and low AAG groups. Results: The clinical stage IIA, IIB, IIIA, IIIB and IIIC were 4, 4, 14, 17 and 0, respectively. The completion rate of three cycles of chemotherapy was 76.9% (30/39). All patients underwent surgery and the R0 resection rate was 97.4% (38/39). The best overall response rate of DCF was 48.7% with a pathological complete response of 5.1%. The 2-year progression-free survival and overall survival (OS) rates were 60.5% and 76.9%, respectively. The median serum AAG was 95 g/L, ranging from 57 to 228 g/L. A trend of lower response rate (35.0% vs. 57.9%; P = 0.20) and shorter OS (median not reached; hazard ratio [HR] 2.08; P = 0.24) was observed in patients with a high AAG level (AAG &gt; 95 g/L) compared with a low AAG level (AAG ≦ 95 g/L). Multivariate analysis showed an AAG level hazard ratio of 1.60 (P = 0.59) for OS. Conclusions: There was a trend toward improved response and survival with low serum AAG level, for patients with esophageal cancer who received neoadjuvant DCF chemotherapy.

The correlation between high body mass index and survival in patients with esophageal cancer after curative esophagectomy: evidence from retrospective studies.

To investigate the predictive value of high body mass index (H-BMI) on the survival of patients with esophageal cancer (EC) after curative esophagectomy. Studies were systematically identified to investigate the relationship between overweight and obese (H-BMI) and clinical outcomes in EC patients treated with curative esophagectomy. Measured clinical outcomes were disease-free survival (DFS) and overall survival (OS). The pooled hazard ratio (HR) with 95% confidence interval (CI) was estimated. Subgroup analyses were performed according to tumour type and body mass index (BMI). Fourteen studies with 4823 cases were included in the final pooled quantitative analysis. In EC patients overall, H-BMI was associated with improved DFS (HR, 0.83; 95% CI: 0.75-0.90) and OS (HR, 0.79; 95 % CI: 0.73-0.85), as compared with normal BMI. The results were consistent with those who were overweight. Among patients with esophageal adenocarcinoma (EAC), a better prognosis, as reflected by OS, was observed with H-BMI (HR, 0.81; 95% CI: 0.73-0.89). The same results were also observed in EAC patients who were obese and overweight. In contrast, among patients with esophageal squamous cell carcinoma (ESCC), H-BMI was associated with a worse prognosis, as reflected by DFS (HR, 2.26; 95% CI: 1.29-3.24). H-BMI has distinctly different impacts on the postoperative survival of EAC and ESCC patients. H-BMI is a potential predictor for better prognosis in EC patients overall, and particularly in EAC patients, treated with curative esophagectomy. However, in ESCC patients, H-BMI is a potential predictor for a worse prognosis of postoperative survival.

Analysis of Intensity-Modulated Radiation Therapy (IMRT), Proton and 3D Conformal Radiotherapy (3D-CRT) for Reducing Perioperative Cardiopulmonary Complications in Esophageal Cancer Patients.

Background. While neoadjuvant concurrent chemoradiotherapy has improved outcomes for esophageal cancer patients, surgical complication rates remain high. The most frequent perioperative complications after trimodality therapy were cardiopulmonary in nature. The radiation modality utilized can be a strong mitigating factor of perioperative complications given the location of the esophagus and its proximity to the heart and lungs. The purpose of this study is to make a dosimetric comparison of Intensity-Modulated Radiation Therapy (IMRT), proton and 3D conformal radiotherapy (3D-CRT) with regard to reducing perioperative cardiopulmonary complications in esophageal cancer patients. Materials. Ten patients with esophageal cancer treated between 2010 and 2013 were evaluated in this study. All patients were simulated with contrast-enhanced CT imaging. Separate treatment plans using proton radiotherapy, IMRT, and 3D-CRT modalities were created for each patient. Dose-volume histograms were calculated and analyzed to compare plans between the three modalities. The organs at risk (OAR) being evaluated in this study are the heart, lungs, and spinal cord. To determine statistical significance, ANOVA and two-tailed paired t-tests were performed for all data parameters. Results. The proton plans showed decreased dose to various volumes of the heart and lungs in comparison to both the IMRT and 3D-CRT plans. There was no difference between the IMRT and 3D-CRT plans in dose delivered to the lung or heart. This finding was seen consistently across the parameters analyzed in this study. Conclusions. In patients receiving radiation therapy for esophageal cancer, proton plans are technically feasible while achieving adequate coverage with lower doses delivered to the lungs and cardiac structures. This may result in decreased cardiopulmonary toxicity and less morbidity to esophageal cancer patients.

Synuclein-gamma predicts poor clinical outcome in esophageal cancer patients.

The synuclein gamma (SNCG) protein, a member of neuronal protein family synuclein, has been considered as a promising potential biomarker as an indicator of cancer stage and survival in patients with cancer. The present study was conducted to evaluate the prognostic value of SNCG in patients with esophageal carcinoma (EC). SNCG levels were assessed immunohistochemically in cancer tissues from 73 EC patients. Median age was 57 (range, 29-78) years old. Forty-seven percent of the patients were male. Thirty-seven percent of the patients had upper or middle localized tumor whereas 59% had epidermoid carcinoma. More than half of the patients (61%) had undergone operation where 57% received adjuvant treatment including chemotherapy or chemotherapy plus radiotherapy. Median overall survival was 11.3 ± 1.8months (95% confidence interval (CI): 7.7-14.9months). SNCG positivity was significantly associated with the histological type of EC and inoperability (for SNCG positive vs. negative group; epidermoid 80 vs. 53%; p = 0.05 and inoperable 59 vs.32%; p = 0.04, respectively). Lymph node metastasis, inoperability and receiving no adjuvant treatment had significantly adverse effect on survival in the univariate analysis (p = 0.01, p < 0.001, and p = 0.001, respectively). SNCG positivity had significantly adverse effect on survival in both univariate and multivariate analysis (p = 0.02 and p = 0.01, respectively). Our results are the first to suggest that SNCG is a new independent predictor for poor prognosis in EC patients in the literature.

Preoperative chemoradiation versus preoperative chemotherapy alone for esophageal cancer: Higher response rates but equivalent survival.

4071 Background: Controversy exists over the optimal neoadjuvant therapy in patients with locally advanced esophageal cancer (EC). While most groups favor neoadjuvant chemoradiation (nCRT), some advocate preoperative chemotherapy (nCT) without radiation. The objective of this study was to compare outcomes in EC patients undergoing either regimen, followed by surgery. Methods: We reviewed a prospectively collected database of EC patients undergoing esophagectomy following nCT or nCRT (1989-2013). Choice of therapy was at the discretion of the multidisciplinary team. Demographic data, clinical and pathologic staging, and survival (KM) were compared. Results: From 600 patients, 261 patients were identified with EC treated with nCRT (n=63) or nCT (n=199) followed by surgery. Patients were well matched for age, gender, PS, histology, and clinical stage. Following therapy, more nCRT patients had a complete clinical response (36% vs. 14%, p<0.001) by post-induction endoscopy and CT/PET. At surgery, 88% and 92% o...

Esophageal cancer in Iran; a population-based study regarding adequacy of cancer surgery and overall survival

Prognosis of esophageal cancer (EC) is poor. Population-based studies regarding EC survival and adequacy of cancer surgery (ACS) from developing countries are lacking. We aimed to evaluate EC patients' survival and ACS in a population-based setting for the first time from Iran. We randomly selected 409 cases from all 3048 newly diagnosed EC patients who were registered in the nationwide cancer registry in calendar year 2005-2006 and followed them until 2009. An expert panel in Cancer Institute of Iran reviewed adequacy of esophageal cancer surgery on a national basis. Overall three-year survival rate was 17%. The median (95% CI) survival time of all patients and cases who underwent surgery alone were 8.5 (6.9-10.1) and 6.0 (3.1-8.9) months, respectively. The hospital mortality was 27.8% among the operated patients. Only 6.8% of cases had documented free circumferential resection margin and merely 4.0% of patients experienced resection of more than 15 lymph nodes during surgery. In Iran, the overall survival of EC patients with different treatment modalities are slightly less than those reported from high-income countries, but cases with surgery alone as the main treatment had worse outcome compared with their counterparts in developed countries. Surgery with curative intent has not been performed in most cases in Iran. It seems current clinical outcome of EC patients could be improved with surgical quality improvement and/or more use of chemoradiation in Iran.

Nomogram Score of Pathologic Complete Response to Neoadjuvant Chemoradiation Predicts for Survival Outcomes in Esophageal Cancer Patients Treated With Definitive Chemoradiation

Pathologic complete response (pCR) after neoadjuvant chemoradiation is a known good prognostic factor compared to esophageal cancer patients without a pCR. Previously, we described a nomogram predictor for pCR in the trimodality-treated esophageal cancer patients. For this study, we hypothesized that the nomogram pCR score can predict for clinical outcomes in patients treated with chemoradiation alone.

Association of low serum levels of transforming growth factor β1 (TGF-β1) and high levels of vascular endothelial growth factor-A (VEGF-A) following neoadjuvant chemoradiotherapy with poor outcome in esophageal cancer patients receiving combined modality therapy: A preliminary analysis using proximity ligation assay.

80 Background: Currently, serum biomarkers do not influence the treatment of esophageal cancer. The purpose of this project is to investigate, using the proximity ligation assay (PLA), serum biomarkers that predict treatment response and survival outcome for patients with locally advanced esophageal cancer (LAEC) undergoing neoadjuvant concurrent chemoradiotherapy (CCRT) followed by radical esophagectomy. Methods: From 2004 to 2011, 79 patients with LAEC receiving CCRT of taxane-based chemotherapy and 40 Gy followed by curative surgery were enrolled in this study. Serum samples were collected before and within one month after CCRT. Fifteen biomarkers (Axl, BMP2/4, EGFR, FAM84B, Gas6, Her2, IGFBP3, MMP1, MMP13, OPN, PDGFR-α, Periostin, SPARC, TGF-β1, VEGF-A) were analyzed using PLA. Pathological responses were classified into complete response (CR), microscopic residual (MicroR), or macroscopic residual (MacroR). Associations between serum level of each biomarker and pathological response, disease-free survival (DFS), and overall survival (OS) were evaluated by ANOVA and Log-rank tests. Results: Of 79 patients, 30 had CR (38%), 37 had MicroR (47%) and 12 had MacroR (15%). With a median follow-up of 54.5 months, the median OS and DFS were 34 and 43 months, respectively. Among evaluated biomarkers, TGF-β1 was the most significant one associated with pathological response (p=0.009, two-way ANOVA), with higher post-CCRT TGF-β1 levels predicting better response (p=0.035, one-way ANOVA). Patients with higher post-CCRT TGF-β1 levels (≥3rd quartile) had significantly better DFS (median not reached vs. 27 months, p=0.03). Patients with both lower levels of post-CCRT TGF-β1 and higher levels of VEGF-A had significantly worse DFS (13 months, p=0.001) and OS (18 months, p=0.035). Conclusions: Post-CCRT serum TGF-β1 and VEGF-A levels by PLA may be used to predict pathological response and survival outcome for esophageal cancer patients receiving combined modality therapy.