Objective: To explore the possible mechanism of radiotherapy regulating the expression of PD-L1 in esophageal carcinoma. Methods: Three esophageal cancer cell lines (Eca109, Kyse150, TE1) were irradiated with different doses of X-rays, and 6 Gy+ AG490 group was set. The mRNA expression of PD-L1 was detected by real-time quantitative polymerase chain reaction (RT-qPCR). The protein expressions of PD-L1, STAT3, p-STAT3 were detected by western blotting and the protein level of IL-6 was detected by ELISA. Results: The mRNA expressions of PD-L1 in Eca109, Kyse150 and TE1 were 2.86±0.30, 960.01±21.27 and 106.78±6.67, higher than 1.07±0.15 in normal esophageal cell line HET-1A (P<0.01). The protein expressions of PD-L1 in Eca109, Kyse150 and TE1 were 0.091±0.036, 1.533±0.079 and 0.914±0.035, higher than 0.063±0.01 in normal esophageal cell line HET-1A (P<0.01). After 48 hours of 6 Gy irradiation, the protein expression levels of PD-L1 in Eca109, Kyse150 and TE1 were 0.135±0.007, 1.66±0.06 and 1.32±0.06, higher than 0.09±0.01, 1.21±0.05 and 0.93±0.03 of the 0 Gy group (P<0.01), while the protein expression levels of p-STAT3 in Eca109, Kyse150 and TE1 were 1.44±0.26, 0.75±0.04 and 1.92±0.17, higher than 0.18±0.05, 0.48±0.02 and 0.36±0.06 of the 0 Gy group (P<0.01). IL-6 protein expression increased significantly after different doses of irradiation (P<0.01). After the IL-6/STAT3 signaling pathway was blocked by the specific inhibitor AG490, the expressions of PD-L1 of Eca109, Kyse150 and TE1 in the 6 Gy+ AG490 groups were 0.11±0.03, 1.07±0.08 and 0.96±0.11, without significant differences of 0.09±0.01, 0.96±0.05 and 0.85±0.09 of the 0 Gy group (P>0.05), while the protein expressions of p-STAT3 were 0.76±0.11, 0.59±0.06 and 0.96±0.12, without significant differences of 0.67±0.08, 0.54±0.06 and 0.84±0.11 of the 0 Gy group (P>0.05). Conclusion: Radiotherapy may regulate the expression of PD-L1 in esophageal cancer cells through IL-6 / STAT3 signaling pathway.
B7-H1 Antigen/metabolism* ; Cell Line, Tumor ; Cell Proliferation ; Esophageal Neoplasms/radiotherapy* ; Humans ; Interleukin-6/metabolism* ; RNA, Messenger ; STAT3 Transcription Factor/metabolism* ; Signal Transduction

Objective: To evaluate the long-term outcomes, failure patterns and prognostic factors of definitive radiotherapy in patients with cervical esophageal carcinoma (CEC). Methods: We retrospectively reviewed the clinical data of 148 CEC patients who treated with definitive radiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from January 2001 to December 2017. The median radiation dose was 66 Gy (59.4-70 Gy) and 33.1% of patients received concurrent chemotherapy. The Kaplan-Meier method was used to calculate survival rates. The log rank test was used for survival comparison and univariate prognostic analysis. The Cox model was used for multivariate prognostic analysis. Results: The median follow-up time was 102.6 months. The median survival time, 2- and 5-year overall survival (OS) were 22.7 months, 49.9% and 28.3%. The median, 2- and 5-year progression-free survival were 12.6 months, 35.8% and 25.8%. The 2- and 5-year locoregional recurrence-free survival were 59.1% and 50.8%. The 2- and 5-year distant metastases-free survival were 74.6% and 65.9%. Multivariate analysis showed that EQD(2)>66 Gy was the only independent prognostic indicator for OS (P=0.040). The median survival time and 5-year OS rate significantly improved in patients who received EQD(2)>66 Gy than those who received≤66 Gy (31.2 months vs. 19.2 months, 40.1% vs. 19.1%, P=0.027). A total of 87 patients (58.8%) developed tumor progression. There were 50 (33.8%), 23 (15.5%) and 39 (26.4%) patients developed local, regional recurrence and distant metastases, respectively. Eleven patients (7.4%) underwent salvage surgery, and the laryngeal preservation rate for entire group was 93.9%. Conclusions: Definitive radiotherapy is an effective treatment for cervical esophageal carcinoma with the advantage of larynx preservation. Local recurrence is the major failure pattern. EQD(2)>66 Gy is associated with the improved overall survival.
Humans ; Retrospective Studies ; Esophageal Neoplasms/pathology* ; Carcinoma/drug therapy* ; Prognosis ; Treatment Outcome ; Chemoradiotherapy/methods* ; Radiotherapy Dosage

BACKGROUND: To explore the effect of radiation on metastatic lymph nodes (LNs) after neoadjuvant chemoradiation therapy (nCRT), we examined the metastatic features of LNs according to their inclusion in the radiation field. METHODS: The patient group included 88 men and 2 women, with a mean age of 61.1±8.1 years, who underwent esophagectomy and lymphadenectomy after nCRT. Dissected LNs were compared in terms of clinical suspicion of metastasis, nodal station, and inclusion in the radiation field. RESULTS: LN positivity did not differ between LNs that were inside (in-field [IF]) and outside (out-field [OF]) of the radiation field (IF: 40 of 465 [9%], OF: 40 of 420 [10%]; p=0.313). In clinical N+ nodal stations, IF stations had a lower incidence of metastasis than OF stations (IF/cN+: 16 of 142 [11%], OF/cN+: 9/30 [30%]; p=0.010). However, in clinical N- nodal stations, pathological positivity was not affected by whether the nodal stations were included in the radiation field (IF/cN-: 24 of 323 [7%], OF/cN-: 31 of 390 [8%]; p=0.447). CONCLUSION: Radiation therapy for nCRT could downstage clinically suspected nodal metastasis. However, such therapy was ineffective when used to treat nodes that were not suspicious for metastasis. Because significant numbers of residual metastases were identified irrespective of coverage by the radiation field, lymphadenectomy should be performed to ensure complete removal of residual nodal metastases after nCRT.
Esophageal Neoplasms ; Esophagectomy ; Female ; Humans ; Incidence ; Lymph Node Excision ; Lymph Nodes ; Male ; Neoadjuvant Therapy ; Neoplasm Metastasis ; Radiotherapy

BACKGROUND/AIMS: Endoscopic resection is a standard treatment for stage T1a esophageal cancer, with esophagectomy or radical radiation therapy (RT) performed for stage T1b lesions. This study aimed to compare treatment outcomes of each modality for clinical stage T1 esophageal cancer. METHODS: In total, 179 patients with clinical T1N0M0-stage esophageal cancer treated from 2006 to 2016 were retrospectively evaluated. Sixty-two patients with clinical T1a-stage cancer underwent endoscopic resection. Among 117 patients with clinical T1b-stage cancer, 82 underwent esophagectomy, and 35 received chemoradiotherapy or RT. We compared overall survival (OS) and recurrence-free survival (RFS) rates for each treatment modality. RESULTS: The median follow-up time was 32 months (range, 1 to 120 months). The 5-year OS and RFS rates for patients with stage T1a cancer receiving endoscopic resection were 100% and 85%, respectively. For patients with stage T1b, the 5-year OS and RFS rates were 78% and 77%, respectively, for the esophagectomy group; 80% and 44%, respectively, for the RT alone group; and 96% and 80%, respectively, for the chemoradiation group. The esophagectomy group showed significantly higher RFS than the RT alone group (p=0.04). There was no significant difference in RFS between the esophagectomy and chemoradiation groups (p=0.922). Grade 4 or higher treatment-related complications occurred in four patients who underwent esophagectomy. CONCLUSIONS: Endoscopic resection appeared to be an adequate treatment for patients with T1a-stage esophageal cancer. The multidisciplinary approach involving chemoradiation was comparable to esophagectomy in terms of survival outcome without serious complications for T1b-stage esophageal cancer.
Chemoradiotherapy ; Esophageal Neoplasms ; Esophagectomy ; Follow-Up Studies ; Humans ; Radiotherapy ; Retrospective Studies

PURPOSE: The objective of this study was to compare dosimetric characteristics of three-dimensional conformal radiotherapy (3D-CRT) and two types of intensity-modulated radiotherapy (IMRT) which are step-and-shoot intensity modulated radiotherapy (s-IMRT) and modulated arc therapy (mARC) for thoracic esophageal cancer and analyze whether IMRT could reduce organ-at-risk (OAR) dose. MATERIALS AND METHODS: We performed 3D-CRT, s-IMRT, and mARC planning for ten patients with thoracic esophageal cancer. The dose-volume histogram for each plan was extracted and the mean dose and clinically significant parameters were analyzed. RESULTS: Analysis of target coverage showed that the conformity index (CI) and conformation number (CN) in mARC were superior to the other two plans (CI, p = 0.050; CN, p = 0.042). For the comparison of OAR, lung V5 was lowest in s-IMRT, followed by 3D-CRT, and mARC (p = 0.033). s-IMRT and mARC had lower values than 3D-CRT for heart V30 (p = 0.039), V40 (p = 0.040), and V50 (p = 0.032). CONCLUSION: Effective conservation of the lung and heart in thoracic esophageal cancer could be expected when using s-IMRT. The mARC was lower in lung V10, V20, and V30 than in 3D-CRT, but could not be proven superior in lung V5. In conclusion, low-dose exposure to the lung and heart were expected to be lower in s-IMRT, reducing complications such as radiation pneumonitis or heart-related toxicities.
Esophageal Neoplasms ; Heart ; Humans ; Lung ; Radiation Pneumonitis ; Radiotherapy ; Radiotherapy, Conformal ; Radiotherapy, Intensity-Modulated

PURPOSE: The purpose of this study was to evaluate the benefits of adjuvant treatment for curatively resected thoracic esophageal squamous cell carcinoma (ESCC) and determine the optimal adjuvant treatments. MATERIALS AND METHODS: One hundred ninety-five patients who underwent a curative resection for thoracic ESCC between 1994 and 2014 were reviewed retrospectively. Postoperatively, the patients received no adjuvant treatment (no-adjuvant group, n=68), adjuvant chemotherapy (AC group, n=62), radiotherapy (RT group, n=41), or chemoradiotherapy (CRT group, n=24). Chemotherapy comprised cisplatin and 5-fluorouracil administration every 3 weeks. The median RT dose was 45.0 Gy (range, 34.8 to 59.4 Gy). The overall survival (OS), disease-free survival (DFS), locoregional recurrence (LRR), and distant metastasis (DM) rates were estimated. RESULTS: At a median follow-up duration of 42.2 months (range, 6.3 to 215.2 months), the 5-year OS and DFS were 37.6% and 31.4%, respectively. After adjusting for other clinicopathologic variables, the AC and CRT groups had a significantly better OS and DFS compared to the no-adjuvant group (p < 0.05). The LRR rate was significantly lower in the RT and CRT groups than in the no-adjuvant group (p < 0.05), whereas no significant difference was observed in the AC group. In the no-adjuvant and AC groups, 25% of patients received high-dose salvage RT due to LRR. The DM rates were similar. The anastomotic stenosis and leakage were similar in the treatment groups. CONCLUSION: Adjuvant treatment might prolong survival after an ESCC resection, and RT contributes to a reduction of the LRR. Overall, the risks and benefits should be weighed properly when selecting the optimal adjuvant treatment.
Carcinoma, Squamous Cell* ; Chemoradiotherapy ; Chemotherapy, Adjuvant ; Cisplatin ; Constriction, Pathologic ; Disease-Free Survival ; Drug Therapy ; Epithelial Cells* ; Esophageal Neoplasms ; Fluorouracil ; Follow-Up Studies ; Humans ; Neoplasm Metastasis ; Radiotherapy* ; Recurrence ; Retrospective Studies ; Risk Assessment

Solitary renal metastasis of esophageal cancer is rarely encountered. Herein, we report the case of a 47-year-old man who developed a solitary renal metastasis after concurrent chemoradiotherapy followed by esophagectomy with esophagogastrostomy for esophageal squamous cell carcinoma, and treatment with nephrectomy and subsequent chemotherapy. Histopathological evaluation after operation revealed that the kidney mass was a metastatic lesion from esophageal cancer. He completed 15 cycles of palliative chemotherapy after nephrectomy and remained cancer-free for 36 months. Although lymph node metastasis occurred during regular follow-up, no evidence of lymph node metastasis was found on the imaging study after 9 cycles of chemotherapy with radiotherapy.
Carcinoma, Squamous Cell ; Chemoradiotherapy ; Drug Therapy ; Esophageal Neoplasms* ; Esophagectomy ; Follow-Up Studies ; Humans ; Male ; Lymph Nodes ; Middle Aged ; Neoplasm Metastasis* ; Nephrectomy ; Radiotherapy

PURPOSE: To evaluate the efficacy and safety of extended-field radiation therapy for patients with thoracic superficial esophageal cancer (SEC). MATERIALS AND METHODS: From May 2007 to October 2016, a total of 24 patients with thoracic SEC (T1a and T1b) who underwent definitive radiotherapy and were analyzed retrospectively. The median total radiotherapy dose was 64 Gy (range, 54 to 66 Gy) in conventional fractionation. All 24 patients received radiotherapy to whole thoracic esophagus and 23 patients received elective nodal irradiation. The supraclavicular lymph nodes, the celiac lymph nodes, and both of those nodal areas were included in 11, 3, and 9 patients, respectively. RESULTS: The median follow-up duration was 28.7 months (range 7.9 to 108.0 months). The 3-year overall survival, local control, and progression-free survival rates were 95.2%, 89.7%, and 78.7%, respectively. There were 5 patients (20.8%) with progression of disease, 2 local failures (8.3%) and 3 (12.5%) regional failures. Three patients also experienced distant metastasis and had died of disease progression. There were no treatment-related toxicities of grade 3 or higher. CONCLUSION: Definitive extended-field radiotherapy for thoracic SEC showed durable disease control rates in medically inoperable and endoscopically unfit patients. Even extended-field radiotherapy with elective nodal irradiation was safe without grade 3 or 4 toxicities.
Disease Progression ; Disease-Free Survival ; Esophageal Neoplasms* ; Esophagus ; Follow-Up Studies ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Radiotherapy ; Retrospective Studies

PURPOSE: To evaluate the efficacy and safety of extended-field radiation therapy for patients with thoracic superficial esophageal cancer (SEC). MATERIALS AND METHODS: From May 2007 to October 2016, a total of 24 patients with thoracic SEC (T1a and T1b) who underwent definitive radiotherapy and were analyzed retrospectively. The median total radiotherapy dose was 64 Gy (range, 54 to 66 Gy) in conventional fractionation. All 24 patients received radiotherapy to whole thoracic esophagus and 23 patients received elective nodal irradiation. The supraclavicular lymph nodes, the celiac lymph nodes, and both of those nodal areas were included in 11, 3, and 9 patients, respectively. RESULTS: The median follow-up duration was 28.7 months (range 7.9 to 108.0 months). The 3-year overall survival, local control, and progression-free survival rates were 95.2%, 89.7%, and 78.7%, respectively. There were 5 patients (20.8%) with progression of disease, 2 local failures (8.3%) and 3 (12.5%) regional failures. Three patients also experienced distant metastasis and had died of disease progression. There were no treatment-related toxicities of grade 3 or higher. CONCLUSION: Definitive extended-field radiotherapy for thoracic SEC showed durable disease control rates in medically inoperable and endoscopically unfit patients. Even extended-field radiotherapy with elective nodal irradiation was safe without grade 3 or 4 toxicities.
Disease Progression ; Disease-Free Survival ; Esophageal Neoplasms* ; Esophagus ; Follow-Up Studies ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Radiotherapy ; Retrospective Studies

An aortoesophageal fistula (AEF) is a rare and lethal disorder. However, aortic surgery is usually performed with extracorporeal circulation, and there is a high rate of surgical complications and mortality. This report describes a case of AEF caused by radiotherapy for esophageal cancer. A 59-year-old man was treated with preoperative chemoradiation, and developed a tracheoesophageal fistula (TEF) 3 months later (3 cycles of cisplatin and 5-fluorouracil). He complained of hemoptysis and hematemesis. Based on computed tomography and diagnostic endoscopic findings, he was diagnosed with an AEF and TEF, and initially underwent endovascular coiling, which failed. Because of bleeding, emergent thoracic endovascular aortic repair was performed. Esophageal resection and reconstruction were performed 45 days later to control mediastinal inflammation. The patient was followed up as an outpatient. He has had no recurrence of cancer or any further complications.
Cisplatin ; Esophageal Fistula ; Esophageal Neoplasms* ; Extracorporeal Circulation ; Fistula* ; Hematemesis ; Hemoptysis ; Hemorrhage ; Humans ; Inflammation ; Middle Aged ; Mortality ; Outpatients ; Radiotherapy ; Recurrence ; Tracheoesophageal Fistula