Recurrent Esophageal Carcinoma Research Articles

Survival outcomes of esophageal cancer patients with recurrence after curative treatments

BackgroundLittle is known about predictive factors for survival outcomes of esophageal carcinoma (EC) patients who developed recurrence after undergoing multimodal therapies. We aimed to investigate long-term outcomes and identify prognostic factors in patients with relapsed EC, focusing especially on those with oligometastasis (OM).MethodsEC patients who developed recurrence after curative treatments (radical esophagectomy or definitive chemoradiotherapy (dCRT)) between 2010 and 2017 were reviewed. Multivariate Cox hazards models were applied to determine independent predictors of poor post-recurrence survival (PRS).ResultsIn total, 178 patients were included. The median PRS was 12.9 months. Of the 178 patients, 98 had OM and 80 non-OM (NOM) disease. The survival outcomes of patients with OM were significantly better than those of patients with NOM (P < 0.01). Surgical treatments provided significantly better survival outcomes than CRT or chemo-/radiotherapy alone (3-year overall survival (OS); 78.1% vs. 42.5% vs. 28.9%, P < 0.01), mainly due to prolonging survival after the recurrence (3-year PRS 62.9% vs. 16.7% vs. 16.2%, P < 0.01). Multivariable analysis focusing on patients with OM revealed cStage III-IV disease (P < 0.01), high GPS at the time of recurrence (P = 0.02) and non-curative treatments (P < 0.01), to be independently associated with poor PRS. In contrast, in patients with NOM, no independent predictors for poor PRS were identified.ConclusionsThe survival outcomes of patients with relapsed EC remain poor. Surgical treatments could provide survival benefits for patients with recurrent EC, especially for patients with OM.

Clinical outcomes of doxorubicin-eluting CalliSpheres\xae beads-transarterial chemoembolization for unresectable or recurrent esophageal carcinoma

BackgroundThe clinical outcomes of drug-eluting beads transarterial chemoembolization (DEB-TACE) with doxorubicin-loaded CalliSpheres® beads for patients with unresectable or recurrent esophageal carcinoma have not been reported. The aim of this study is to study the clinical outcomes of DEB-TACE for patients with unresectable or recurrent esophageal carcinoma.MethodsThis retrospective study enrolled 21 patients (15 men; mean age 68.7 ± 9.7; range 46–86 years) with unresectable or recurrent esophageal carcinoma received DEB-TACE between July 2017 and September 2020. Patient characteristic data, imaging findings, complications and DEB-TACE procedure were reviewed. The primary endpoints, disease control rate (DCR) and objective response rate (ORR), were calculated. The secondary endpoints were overall survival rate and progression-free survival (PFS).ResultsTwenty-two sessions of DEB-TACE were performed in 21 patients. The technical success rate was 100%; without sever adverse events or procedure-related deaths. All patients received transarterial chemotherapy infusion with raltitrexed or oxaliplatin. The median follow-up period was 3.6 months (interquartile range, IQR 1.5–9.4 months). ORR and DCR were 42.9 and 85.7%, 28.6 and 71.4%, 20.0 and 40.0% respectively at 1-, 3-, and 6-months after DEB-TACE. The median PFS was 6.0 months, and the 3-, 6- and 12-month PFS rates were 68.2%, 45.5 and 0.0%, respectively. The median overall survival was 9.4 months, and the 3-, 6- and 12-month overall survival rates were 75.5%, 55.0 and 13.8%, respectively.ConclusionsTo our knowledge, this is the first study reports outcomes of DEB-TACE with doxorubicin-loaded CallSpheres bead treatment in the management of patients with unresectable or recurrent esophageal carcinoma. According to our results, this is a safe and feasible treatment modality that may be considered among the options for the treatment of these patients.

512 OUTCOME OF MULTIMODAL TREATMENT FOR SOLITARY LYMPH NODE RECURRENCE OF ESOPHAGEAL CARCINOMA AFTER CURATIVE RESECTION

Abstract Patients with esophageal squamous cell carcinoma (ESCC) often display recurrence in the solitary lymph nodes after surgery. The optimal treatment strategy for these patients has not been established. The aim of the present study was to evaluate the outcome of intensive treatment for recurrent lymph node metastasis retrospectively. Methods Of the 19 patients with solitary recurrent lymph node metastasis after curative esophagectomy between 2006 and 2015, 7 had cervical lymph node, 7 had mediastinal lymph node, and 5 had abdominal lymph node recurrence. Multimodal treatment was performed in the patients: 2 patients underwent lymphadenectomy with adjuvant therapy, and 15 received definitive chemoradiotherapy and repeated chemotherapy. The remaining 2 patients received chemotherapy. Results Survival of lymphadenectomy group tended to be better than that of other groups (p = 0.1388), and survival of the lymphadenectomy and the chemoradiotherapy groups was significantly better than that of the patients who received chemotherapy (p = 0.0209). Partial response (PR), stable disease, and progressive disease were obtained in 8 (53%), 1 (7%), and 6 (40%) patients who received chemoradiotherapy, respectively. Among chemoradiotherapy groups, patients with a therapeutic effect (PR) on radiation therapy had significantly better prognosis (p = 0.0175). Conclusion Multimodal treatment including lymphadenectomy and chemoradiotherapy could improve survival of the patients with solitary lymph node recurrence of esophageal carcinoma after curative resection.

Role of 18F-FDG PET/CT in restaging of esophageal cancer after curative-intent surgical resection.

The aim of the study was to evaluate diagnostic performance of FDG PET-CT in suspected recurrence of carcinoma esophagus after curative-intent surgical resection and impact of FDG PET-CT on intended management. This was retrospective study of patients with clinical or radiological suspicion of recurrent esophageal carcinoma who were referred for PET-CT from January 2006 to December 2017. Diagnostic performance of PET-CT was evaluated for disease recurrence and its impact on management decisions. PET-CT findings were confirmed with tissue diagnosis. When tissue diagnosis was not available clinical and radiological follow-up was used as reference standard. Relevant clinical data were available in 68 patients which were considered for analysis. In 91% (62/68) patients FDG PET-CT findings were suggestive of disease recurrence. Histopathological confirmation was available in 43 patients, whereas in remaining patients recurrence was confirmed by radiological and clinical follow-up. Forty percent (28/68) patients were detected with distant metastases. Sensitivity, specificity, positive and negative predictive values of FDG PET-CT was found to be 98.4, 80, 98 and 80% with accuracy of 97%. Change in management was observed in 41% (28/68) of patients from salvage radiotherapy/surgery to palliative chemotherapy/best supportive care based on evidence of distant metastases seen on FDG PET-CT. FDG PET-CT is highly sensitive in detection of recurrent disease in esophageal cancer patients after surgical resection. It can detect distant metastases in high proportion of patients thus changing the intent of management from radical salvage to palliative chemotherapy/best supportive care.

Nimotuzumab, an EGFR‑targeted antibody, promotes radiosensitivity of recurrent esophageal squamous cell carcinoma.

Local tumor recurrence is one of the main causes for the failure of esophageal cancer treatment following radiotherapy. Previous studies have demonstrated that epidermal growth factor receptor(EGFR)‑targeted therapy combined with radiotherapy is expected to become an effective means to control tumor recurrence. The aim of the present study was to investigate the effect and mechanism of nimotuzumab (an EGFR‑targeted antibody) in the treatment of recurrent esophageal carcinoma. The radiation responses of two esophageal squamous carcinoma cell lines, EC109 and TE‑1, with or without nimotuzumab, were first evaluated by CCK‑8 assay. Colony formation and apoptosis were used to measure anti‑proliferation effects. It was demonstrated that nimotuzumab arrested the cell cycle at the G2phase invitro. Western blotting and immunofluorescence analysis were used to determine signaling pathway changes. It was observed that nimotuzumab inhibited phosphorylation of EGFR in EC109 cells. Furthermore, recurrent tumor models were established and it was identified that the degree of tumor hypoxia was positively associated with EGFR overexpression. In EC109 cell xenografts, nimotuzumab combined with radiation led to a significant delay in recurrent tumor growth compared with that of radiation alone (P<0.001 for 0Gy pre‑irradiation, P=0.005 for 20Gy pre‑irradiation, P=0.005 for 10Gy pre‑irradiation). These results suggest that nimotuzumab combined with radiation may be an effective means to control recurrent esophageal squamous cell carcinoma with EGFR overexpression.

Efficacy of traction, using a clip-with-thread, for esophageal endoscopic submucosal dissection for esophageal lesions with fibrosis in an ex vivo pig training model.

Endoscopic submucosal dissection (ESD) of recurrent esophageal carcinoma is technically difficult to perform due to submucosal fibrosis that develops after definitive chemoradiation therapy. Therefore, our aim was to evaluate the usefulness of clip-with-thread traction for ESD of esophageal lesions with submucosal fibrosis. Four endoscopists excised 16 lesions by ESD in an ex vivo pig training model. Mock lesions (30 mm in diameter) were created, including a 10-mm area of submucosal fibrosis in the center of each lesion. Each endoscopist performed two ESDs with traction (ESD-T) and two without traction (ESD-N). The primary outcome was the time required for submucosal dissection. Secondary outcomes were the rate of en bloc (complete) resection and perforation during the procedure, and the total amount of solution injected. All esophageal ESDs were completed. The median dissection time was significantly shorter for the ESD-T group (median 12.5 min, interquartile range 10.2-14.5) when comparing to the ESD-N group (median 18.0 min, interquartile range 14.6-19.2) (P=0.040). The en bloc resection rate was 100% in both groups, with a rate of complete resection of 87.5% and a rate of perforation of 37.5% for both groups. The median amount of solution injected was not significantly different between the ESD-T (18.0 ml) and ESD-N (20.5 ml) groups (P=0.526). Clip-with-thread traction improved the performance of ESD for lesions with submucosal fibrosis. However, the method might not reduce the risk of perforation, which remains an important clinical issue to resolve.

Percutaneous endoscopic gastrostomy with jejunal extension for a post-esophagectomy gastric conduit.

Percutaneous endoscopic gastrostomy (PEG) is a minimally invasive procedure providing nutritional benefits to malnourished patients. Although a past history of celiotomy is not a contradiction for PEG construction, this procedure is rarely undertaken in post-esophagectomy patients, for two reasons: anatomically limited gastric spaces and high susceptibility to pulmonary aspiration. To overcome these limitations, we developed an original method of introducing PEG with jejunal extension for esophagectomized patients with retrosternal gastric pull-up reconstruction. The procedures were as follows: (1) confirmation of endoscopic transillumination of the antrum; (2) test puncture of the antral wall and subsequent gastropexy using a double-needle device; (3) insertion of a needle jejunostomy catheter into the antrum; (4) direct catheter cannulation to the pylorus and introduction of a feeding tube into the jejunum. We successfully carried out this procedure in three male patients (70-78years old): two suffering from repetitive aspiration pneumonia and one with extensive recurrence of esophageal carcinoma. The operative times ranged 15-50min. There were no PEG-associated complications. Of note, none of the patients experienced aspiration pneumonia after PEG construction. Our novel method appears to be a promising approach to managing esophagectomized patients because of its feasibility and the potential to prevent postoperative pulmonary aspiration.

Prognostic analysis of recurrent esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgical treatment

Objective To evaluate the clinical efficacy and prognostic factors of recurrent esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgery. Methods From December 2011 to December 2015, 152 cases of recurrent thoracic esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgery were retrospectively analyzed. The overall survival (OS) after treatment failure, clinical efficacy and prognostic factors of different salvage treatments were analyzed. OS was calculated by Kaplan-Meier method. Prognostic analysis was performed by using multivariate Cox regression model. Results The median interval of the first recurrence was 10.6(2.0 to 69.1) months. The median OS after recurrence was 8.0(0.8 to 43.3) months. The 1-, 2-and 3-year OS rates after recurrence were 36.0%, 15.1% and 5.2%, respectively. The median OS of patients with locoregional recurrence alone, distant metastasis alone and locoregional recurrence combined with distant metastasis was 11.3(1.8 to 43.3) months, 6.7(1.2 to 28.6) months and 5.1(0.8 to 22.9) months, respectively. Multivariate analysis demonstrated that neoadjuvant chemotherapy (P=0.009), ypTNM stage (P=0.012), comprehensive treatment after recurrence (P=0.000) and locoregional recurrence (P=0.026) were independently correlated with the OS of patients with recurrent esophageal squamous cell carcinoma. Conclusions Neoadjuvant therapy, ypTNM stage, recurrence pattern and post-recurrence treatment are the independent risk factors for clinical prognosis of patients with recurrent esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgery. Clinical prognosis of patients with recurrent esophageal squamous cell carcinoma after neoadjuvant therapy is not satisfactory. After recurrence, combined treatment mode should be adopted according to the site of recurrence and neoadjuvant treatment mode to maximize the benefits of salvage treatment. Key words: Esophageal neoplasm, recurrent/ neoadjuvant treatment; Locoregional recurrence; Distant metastasis; Prognosis

P223 BILATERAL RECURRENT LARYNGEAL NERVE LYMPHADENECTOMY DURING THORACOSCOPIC ESOPHAGECTOMY IN PRONE POSITION

Abstract Aim To present a video of a complete bilateral recurrent laryngeal nerve lymphadenectomy performed during minimally invasive esophagectomy using thoracoscopic video-assisted surgery in the prone position. Background and Methods Surgical treatment for esophageal cancer needs detailed lymphadenectomy. Indeed, the number of surgically dissected lymph nodes is important for staging accuracy and also determines patient’s prognosis, including those along the recurrent laryngeal nerve. However, recurrent laryngeal nerve dissection remains difficult and increases the appearance of postoperative complications. This is a video of a bilateral recurrent laryngeal nerve lymphadenectomy during thoracoscopic esophagectomy performed in the prone position in a female patient with esophageal cancer. Results A 75 year-old female was diagnosed with recurrent squamous cell middle third esophageal carcinoma. The patient had first been diagnosed eleven years ago, receiving chemoradiotherapy as a radical treatment. The patient achieved a complete response after treatment, which remained for eleven years. Eleven years later, during routine follow-up, tumor recurrence was identified in the middle third of the esophagus. After presentation in a Multidisciplinary Group the patient underwent minimally invasive McKeown esophagectomy. First, a video-assisted thoracoscopic surgery was performed in the prone position to mobilize the thoracic esophagus and complete a detailed mediastinal lymph node dissection, including infra-carinal lymph nodes, bilateral bronchial lymph nodes and also bilateral recurrent laryngeal nerve lymph nodes. Afterwards, the abdominal esophagus and lymph node dissection is performed using a laparoscopic approach, and also a left cervicotomy in the supine position. An assistance laparotomy was made to externalize the specimen and make the gastric conduit. A manual end-to end esophago-gastric anastomosis was executed and finally, a feeding jejunostomy tube was placed. The patient presented a benign postoperative course, introducing enteral nutrition and oral intake developing no complications, such as dysphonia, nor dysphagia and was discharged on the 8th postoperative day. The postoperative barium swallow radiography showed no leaks nor other complications and pathology report confirmed tumor free resection margins. Conclusion Detailed mediastinal lymph node dissection and exhaustive bilateral recurrent laryngeal nerve lymphadenectomy can be safely performed by minimally invasive surgery, as is shown in the video. The technique shown is feasible, achieves a complete lymph-node dissection and avoids postoperative complications such as dysphonia and recurrent laryngeal nerve palsy.

Diagnostic value of surveillance 18F-fluorodeoxyglucose PET/CT for detecting recurrent esophageal carcinoma after curative treatment.

Esophageal carcinoma recurs within two years in approximately half of patients who receive curative treatment and is associated with poor survival. While 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is a reliable method of detecting recurrent esophageal carcinoma, in most previous studies FDG PET/CT scans were performed when recurrence was suspected. The aim of this study was to evaluate FDG PET/CT as a surveillance modality to detect recurrence of esophageal carcinoma after curative treatment where clinical indications of recurrent disease are absent. A total of 782 consecutive FDG PET/CT studies from 375 patients with esophageal carcinoma after definitive treatment were reviewed. Abnormal lesions suggestive of recurrence on PET/CT scans were then evaluated. Recurrence was determined by pathologic confirmation or other clinical evidence within two months of the scan. If no clinical evidence for recurrence was found at least 6months after the scan, the case was considered a true negative for recurrence. The diagnostic sensitivity and specificity of PET/CT for detecting recurrent esophageal carcinomas were 100% (64/64) and 94.0% (675/718), respectively. There were no significant differences in the diagnostic performance of PET/CT for detecting recurrence according to initial stage or time between PET/CT and curative treatments. Unexpected second primary cancers were detected by FDG PET/CT in seven patients. Surveillance FDG PET/CT is a useful imaging tool for detection of early recurrence or clinically unsuspected early second primary cancer in patients with curatively treated esophageal carcinoma but without clinical suspicion of recurrence.

Successful multidisciplinary treatment including repeated metastasectomy for recurrent squamous cell esophageal carcinoma: a case report

BackgroundRecurrences after radical esophagectomy are common. The prognosis for recurrent esophageal cancer is generally poor. Recurrences usually occur between 1 and 3 years of surgery, with the duration of median survival after recurrence ranging from 5 to 10 months. The number of sites and involved organs vary among patients. Consequently, a standard therapeutic strategy has not been established, and the role of surgery in the management of recurrence is unclear.Case presentationA 67-year-old man presented with dysphagia 6 months previously and was diagnosed with esophageal squamous cell carcinoma (ESCC) in the upper thoracic region (T2M0M0, stage IB), for which he underwent thoracoscopy-assisted esophagectomy and lymphadenectomy. Adjuvant chemotherapy was not prescribed. Three years after the operation, he developed a solitary metastasis in the left lung, requiring segmentectomy followed by chemotherapy with combined cisplatin (CDDP) and 5-fluorouracil (5-FU). The following year, a metastatic lesion was recognized in the right lung, invading the chest wall, for which he underwent partial lobectomy with local chest wall resection. Multiple mediastinal and abdominal lymph node (LN) metastases were detected in the right lung a year later, which necessitated chemoradiation to a dose of 50.4 Gy with concomitant CDDP and 5-FU. Post-treatment computed tomography (CT) showed a good response. Positron emission tomography (PET)-CT revealed a reduction in the metastatic LNs with no fluoro-deoxy-glucose (FDG) uptake. The following year, metastases were detected in the left cervical LNs. Owing to the limited extent of metastases, resection was followed by chemoradiation to a dose of 50 Gy with CDDP and 5-FU. The following year, metastases were detected in the mediastinal LNs; chemotherapy was administered with nedaplatin and docetaxel. The follow-up CT and PET-CT demonstrated complete disappearance of the tumor, and the patient is currently surviving without recurrence for 11 years from the first curative operation.ConclusionsThis case demonstrates that aggressive multidisciplinary treatment including surgery and radiation to achieve local control could be a meaningful treatment strategy in cases with limited and slowly occurring recurrences.

Clinical efficacy and safety of re-radiotherapy combined with tegafur gimeracil oteracil potassium capsule in treatment of local recurrent esophageal carcinoma

Objective To investigate the clinical efficacy and safety of re-radiotherapy combined with TS-1 (tegafur gimeracil oteracil potassium capsule) in treatment of local recurrent esophageal carcinoma. Methods A total of 63 esophageal carcinoma patients who recurred after the first course radiation treatment admitted to Jiangdu People′s Hospital of Yangzhou during January 1, 2012 to June 30, 2015 were retrospec-tively analyzed. Twenty-seven of them treated with re-radiotherapy combined with TS-1 were deemed as the research group and 36 of them treated with radiotherapy alone were deemed as the control group based on diffe-rent treatment. Then the clinical efficacy and adverse reactions of the two groups were compared. Results The objective response rates were 77.8% (21/27) and 50.0% (18/36) respectively in the research group and control group, and the difference was statistically significant (χ2=5.048, P=0.025). The median survival time in the two groups were 21.6 months and 13.7 months, the 1-year (74.1%) and 2-year (44.4%) survival rates of the research group were both higher than those of the control group (52.8% and 30.6%, respectively), and the difference was statistically significant (χ2=6.086, P=0.013). The major adverse effects of the research group and control group during the treatment were radiation oesophagitis (92.6% vs. 80.5%), radiation pneumonia (18.5% vs. 19.4%), myelosuppression (96.3% vs. 77.8%) and gastrointestinal reactions (25.9% vs. 19.4%). Most of them were 1-2 grade, and there were no statistically significant differences (χ2=0.975, P=0.323; χ2=0.009, P=0.926; χ2=2.941, P=0.086; χ2=0.375, P=0.540). Conclusion The treatment of re-radiotherapy combined with TS-1 for local recurrent esophageal carcinoma can improve the efficacy and prolong survival period, and the adverse reactions are tolerable. Key words: Esophageal neoplasms; Radiotherapy, intensity-modulated; Recurrence; Tegafur gimeracil oteracil potassium capsule

Predictors of Survival After Treatment of Oligometastases After Esophagectomy

Recurrent esophageal carcinoma (EC) has a dismal prognosis. However, prior studies showed that selected patients with isolated recurrence may benefit from definitive therapy. The aim of this study was to identify the predictors of postrecurrence survival (PRS) in patients with isolated EC recurrence who were treated with curative intent. A retrospective review of a prospective database (1988 to 2015) was performed to identify all recurrent EC patients after curative esophagectomy. Demographic and clinicopathologic data were reviewed. The probability of PRS was estimated with the Kaplan-Meier method. Predictors of PRS after definitive therapy for isolated EC recurrence were determined by the multivariable Cox proportional hazards model. Of the 640 curative esophagectomies, 241 patients (37.7%) experienced recurrences (median follow-up 50 months). Fifty-six patients (9%) received definitive treatment of isolated EC recurrence (31 were treated surgically with or without chemotherapy-radiotherapy [CTRT] and 25 received definitive CTRT alone). Median time to recurrence (TTR) was 19 months. The 1- and 3-year PRSs were 78% and 38% (median survival 26 months). On multivariable analysis; TTR was the only significant independent predictor for survival after recurrence (hazards ratio 0.98, 95% confidence interval: 0.96 to 0.99, p= 0.034). No pronounced difference was found in disease-free survival or in PRS between recurrent patients treated with operation with or without CTRT and patients who received definitive CTRT. A select subgroup of patients with isolated EC recurrence can be treated with curative intent. TTR was the best predictor for PRS.

Re-irradiation of locoregional esophageal cancer recurrence following definitive chemoradiotherapy: A report of 6 cases.

There is currently no consensus on salvage therapy for recurrent esophageal cancer. Salvage surgery is a well-established option for attaining long-term survival; however, it is associated with a high risk of perioperative morbidity and mortality. A total of 6 patients who underwent re-irradiation for recurrence of locoregional esophageal cancer following definitive chemoradiotherapy were investigated. The median interval between initial radiotherapy and re-irradiation was 17.4 months (range, 6.4-59.2 months). Re-irradiation salvage therapy was mostly administered with concurrent chemotherapy, which consisted of several cycles of nedaplatin on day 1 and oral S-1 administration on days 1-14. The median survival after re-irradiation was 13.6 months (range, 1.9-33.3 months). A total of 3 patients who completed hyperfractionated radiation therapy survived for >1 year. One patient has had no signs of recurrence or late radiation toxicity for >2 years. Severe acute hematological adverse events (AEs) occurred in 3 patients, including 1 case of grade 4 leukopenia. One severe late AE occurred in 1 patient, who developed grade 3 dysphagia and became permanently dependent on percutaneous endoscopic gastrostomy tube feeding. Salvage radiotherapy is considered to be a good treatment option for inoperable locoregional recurrent esophageal cancer. The results of the present study demonstrated that re-irradiation, with or without chemotherapy, for recurrent esophageal carcinoma after definitive chemoradiotherapy was tolerable and yielded reasonably satisfactory results.

Theory and practice of involved-field radiotherapy for esophageal squamous cell carcinoma

Chemoradiotherapy is a major treatment for inoperable esophageal carcinoma (EC). However, there is still controversy over the target volume for radiation, particularly nodal target volume. EC is characterized by a high rate of lymph node metastasis, and its metastatic pattern is not always predictable. Elective nodal irradiation (ENI) will increase the radiation field, which may increase the incidence of adverse events. Some investigators used involved-field irradiation (IFI) to reduce treatment-related toxicities without compromising survival. Studies have demonstrated that regional and distant micrometastases can be controlled, to some extent, by chemotherapy, incidental irradiation, and the abscopal effects of radiation. With either ENI or IFI, EC recurrence is usually found in the primary tumor and at distant sites, without survival difference. These data suggest that IFI is feasible in EC patients. Key words: Esophageal neoplasms/radiotherapy; Involved-field irradiation; Clinical target volume

Enhanced radiosensitizing by sodium glycididazole in a recurrent esophageal carcinoma tumor model.

Re-irradiation is challenging for esophageal cancer patients with local-regional recurrence after initial radiotherapy. The purpose of this study is to establish a recurrent esophageal tumor model and investigate radiosensitizing effects of sodium glycididazole (CMNa). Tumor models were established by pre-irradiation (0 Gy, 10 Gy or 20 Gy) to the right hind leg of the nude mice 24 hours before tumor transplantation (ECA109 human esophageal carcinoma cells). Tumor growth curves were analyzed. Hypoxic microenvironment was exhibited in tumor frozen slides stained for pimonidazole, Hoechst 33342, hematoxylin-eosin and CD34. Mice bearing primary (0 Gy pre-irradiation) and recurrent (10 Gy pre-irradiation) tumors were randomized into control (no treatment), radiation (30 Gy in 3 weekly fractionations), or radiation combined with CMNa (1 mmol/kg i.p. injected 60 min before radiation) respectively. The data showed tumors from 10 Gy and 20 Gy pre-irradiated sites grew significantly slower than those in the 0 Gy pre-irradiated group. The recurrent xenograft tumors showed increased necrotic fractions, decreased micro-vascular density, increased pimonidazole-positive fraction, and decreased Hoechst-positive fraction. In the primary xenograft tumors, CMNa adding to radiation did not lead to significant tumor growth delay than radiation alone. However, for the recurrent tumor model, the growth rate was remarkably reduced as CMNa combined with radiation as comparison with radiation alone. In conclusion, the recurrent esophageal xenograft model with tumor bed effect was successfully established characterized by slow growth, increased hypoxia fraction and decreased blood flow. Significant radiosensitization by CMNa was demonstrated in the recurrent model.

High TRAF6 Expression Is Associated With Esophageal Carcinoma Recurrence and Prompts Cancer Cell Invasion.

Esophageal cancer is one of the most common types of cancer, and it has a poor prognosis. The molecular mechanisms of esophageal cancer progression remain largely unknown. In this study, we aimed to investigate the clinical significance and biological function of tumor necrosis factor receptor-associated factor 6 (TRAF6) in esophageal cancer. Expression of TRAF6 in esophageal cancer was examined, and its correlation with clinicopathological factors and patient prognosis was analyzed. A series of functional and mechanism assays were performed to further investigate the function and underlying mechanisms in esophageal cancer. Expression of TRAF6 was highly elevated in esophageal cancer tissues, and patients with high TRAF6 expression have a significantly shorter survival time than those with low TRAF6 expression. Furthermore, loss-of-function experiments showed that knockdown of TRAF6 significantly reduced the migration and invasion abilities of esophageal cancer cells. Moreover, the pro-oncogenic effects of TRAF6 in esophageal cancer were mediated by the upregulation of AEP and MMP2. Altogether, our data suggest that high expression of TRAF6 is significant for esophageal cancer progression, and TRAF6 indicates poor prognosis in esophageal cancer patients, which might be a novel prognostic biomarker or potential therapeutic target in esophageal cancer.

Clinical efficacy of radiotherapy combined with sodium glycididazole in the treatment of recurrent oesophageal carcinoma

Purpose: To assess the clinical efficacy and side effects of radiotherapy combined with sodium glycididazole in the treatment of recurrent esophageal carcinoma.Methods: Ninety patients with locally recurrent oesophageal carcinoma who were admitted to the Oncology Department at Taian City Central Hospital, Shandong, China, were randomly divided into a treatment group (treated with radiotherapy and sodium glycididazole) and a control group (treated with radiotherapy alone) in a randomized study. Short-term curative effects, median progression-free survival (PFS), and side effects were compared between the two groups.Results: The cure rate in the treatment group was 86.70 %, whereas that in the control group was 51.10 % (p &lt; 0.05). Median PFS in the treatment group was 9.9 months versus 5.3 months in the control group (p &lt; 0.05). Side effects in both groups included alopecia, headache, nausea, vomiting and leucopaenia, at level one or two. In this regard, the difference between the two groups was statistically insignificant (p &gt; 0.05).Conclusion: Radiotherapy combined with sodium glycididazole shows a higher short-term curative effect in the treatment of recurrent oesophageal carcinoma than radiotherapy alone.Keywords: Alopecia, Leucopaenia, Oesophageal carcinoma, Radiotherapy, Sodium glycididazole

Roles of squamous cell cancer antigen, cytokeratin 21-1 fragment, and carcinoembryonic antigen in the diagnosis and prognosis of postoperative locoregional recurrence in esophageal carcinoma

Background: Locoregional recurrence (LR) is the major cause for poor response after radical resection in patients with esophageal carcinoma (EC). Therefore, early diagnosis and positive treatment is crucial for the extension of overall survival in EC patients. We aim to investigate the feasibility of squamous cell cancer antigen (SCC-Ag), cytokeratin 21-1 fragment (CYFRA21-1), and carcinoembryonic antigen (CEA) in the diagnosis of postoperative LR in patients with EC, and the correlation between their expression and the prognosis of the disease. Methods: Sixty-two EC patients with postoperative LR were included, and thirty normal individuals served as normal control. Serum SCC-Ag, CYFRA21-1and CEA were determined before and one month after treatment. SCC-Ag level was evaluated using chemiluminescent microparticle immunoassay. CYFRA21-1 was determined using the chemiluminescence assay. CEA was determined using the direct chemiluminescence assay. The patients received radiotherapy and/or chemoradiotherapy. The survival rates were measured using Kaplan-Meier method, and was tested using Logrank analysis. Multiple logic regression analysis was used for the analysis of prognostic factors. Results: Remarkable elevation was noticed in serum SCC-Ag (t=4.79, P 0.05). The SCC-Ag and CYFRA21-1 other than CEA were related to the pathological staging of EC patients with postoperative LR. The median overall survival was 12.0 months (95% CI, 8.98–15.02). The survival rates at 1, 2, 3 and 5 years were 46.1%, 19.7%, 12.3%, and 8.2%, respectively. The serum SCC-Ag and CYFRA21-1 were decreased after radiotherapy and/or chemoradiotherapy in patients with postoperative LR (t=3.24, P 0.05). Among the EC patients with postoperative LR before radiotherapy or chemoradiotherapy, the survival of patients negative for SCC-Ag and CYFRA21-1 showed significantly longer disease-free interval compared to those for these markers (χ 2 =5.92, P<0.05; χ 2 =4.92, P<0.05). Among the EC patients with postoperative LR after radiotherapy or chemoradiotherapy, the survival of patients negative for SCC-Ag showed signifcantly longer disease-free interval compared to that with positivity for this marker (χ 2 =5.30, P<0.05). Multiple logic regression analysis indicated no independent risk factors for the postoperative LR of patients with EC. Conclusions: Our results indicate that serum SCC-Ag and CYFRA21-1 contribute to the diagnosis of postoperative LR in EC patients. Besides, radiotherapy and/or chemotherapy is beneficial to the extension of survival in these patients.

Roles of squamous cell cancer antigen, cytokeratin 21-1 fragment, and carcinoembryonic antigen in the diagnosis and prognosis of postoperative locoregional recurrence in esophageal carcinoma

Background: Locoregional recurrence (LR) is the major cause for poor response after radical resection in patients with esophageal carcinoma (EC). Therefore, early diagnosis and positive treatment is crucial for the extension of overall survival in EC patients. We aim to investigate the feasibility of squamous cell cancer antigen (SCC-Ag), cytokeratin 21-1 fragment (CYFRA21-1), and carcinoembryonic antigen (CEA) in the diagnosis of postoperative LR in patients with EC, and the correlation between their expression and the prognosis of the disease.