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Background: For patients with esophageal squamous cell carcinoma (ESCC) treated with surgery alone, the incidence of local-regional recurrence remains unfavorable. Postoperative radiotherapy (PORT) has been associated with increased local-regional recurrence-free survival (LRFS), although its application is limited by concerns of PORT-related toxicities. Methods: Among 3591 patients with ESCC analyzed in this study, 2765 patients with T3-4N0 and T1-4N1-3 lesions and specific local-regional status information were analyzed in a subsequent analysis of adjuvant radiation dose (aRTD) effect. Application of the restricted cubic spline regression model revealed a non-linear relationship between aRTD and survival/radiotoxicity. Linear regression analysis (LRA) was performed to evaluate correlations between LRFS and overall survival (OS)/ disease-free survival (DFS). Results: For patients staged T1–2N0, T1–2N1–3, T3–4N0, and T3–4N1–3, 5-year OS in PORT and non-PORT groups were 77.38% vs. 72.91%, p = 0.919, 52.35% vs. 46.60%, p = 0.032, 73.41% vs. 61.19%, p = 0.005 and 38.30% vs. 25.97%, p < 0.001. With aRTD escalation, hazard ratios (HRs) of OS/DFS declined until aRTD exceeded 50Gy, then increased, whereas that of LRFS declined until aRTD exceeded 50 Gy, then remained steady. HR of treatment-related mortality was stable until aRTD exceeded 50 Gy, then increased. LRA revealed strong correlations between LRFS and OS/DFS (r = 0.984 and r = 0.952, respectively). An absolute 1% advancement in LRFS resulted in 0.32% and 0.34% improvements in OS and DFS. Conclusions: An aRTD of 50Gy was well-tolerated, with favorable survival resulting from PORT-related LRFS improvement in patients staged T3–4N0 or T1-4N1–3. Further stratification analyses based on tumor burden would help determine potential PORT-beneficiaries.

Background Retrospective studies have shown that adjuvant treatment improves survival of patients with stage IIB–III esophageal squamous cell carcinoma, but there is no evidence from prospective trials so far. Materials and Methods Patients with pathological stage IIB–III esophageal squamous cell carcinoma were randomly assigned to receive surgery alone (SA), postoperative radiotherapy (PORT), or postoperative concurrent chemoradiotherapy (POCRT). PORT patients received 54 Gy in 27 fractions; the POCRT group received 50.4 Gy in 28 fractions, plus concurrent chemotherapy with paclitaxel (135–150 mg/m2) and cisplatin or nedaplatin (50–75 mg/m2) every 28 days. The primary endpoint was disease-free survival (DFS), and the secondary endpoint was overall survival (OS). Results A total of 172 patients were enrolled (SA, n = 54; PORT, n = 54; POCRT, n = 64). The 3-year DFS was significantly better in PORT/POCRT patients than in SA patients (53.8% vs. 36.7%; p = .020); the 3-year OS was also better in PORT/POCRT patients (63.9% vs. 48.0%; p = .025). The 3-year DFS for SA, PORT, and POCRT patients were 36.7%, 50.0%, 57.3%, respectively (p = .048). The 3-year OS for SA, PORT, and POCRT patients were 48.0%, 60.8%, 66.5%, respectively (p = .048). Conclusion PORT/POCRT (especially POCRT) may significantly improve DFS and OS in stage IIB–III esophageal squamous cell carcinoma. Implications for Practice The results of this phase III study indicated that postoperative radiotherapy/postoperative concurrent chemoradiotherapy (PORT/POCRT) could significantly improve disease-free survival and overall survival in stage IIB–III esophageal squamous cell carcinoma compared with surgery alone with acceptable toxicities. In-field and out-of-field recurrences were comparable between the POCRT and PORT groups, which demonstrates the rationality and safety of the radiation field used in this study. The postoperative regimens in this trial might be accepted as standard treatment options for pathological stage IIB–III esophageal cancer. Larger sample size prospective randomized trials to identify the value are warranted.

A kind of designing scheme of high voltage generator for medical diagnostic X-ray equipment is proposed. A X-ray HV generator, which has output voltage from 60kV to 160kV and tube current from 1mA to 10mA, is developed successfully by applying the technology of LC series resonant soft-switching, high voltage doubling and rectifying, full bridge inverter and pulse width modulation. The topologic structure and simulating result are listed detailed, including high frequency inverter circuit, doubling and rectifying circuit and the controlling system. At last, the experimental data and waveform of the X-ray high voltage generator are presented, verifying the validity of the design scheme.

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.

Effective tools evaluating the prognosis for patients with esophageal cancer undergoing surgery is lacking. The current study aimed to develop a nomogram to predict overall survival (OS) and provide evidence for adjuvant therapy for patients with esophageal carcinoma after esophagectomy. The study retrospectively reviewed patients with pathologic T1N +/T2-4aN0-3, M0 thoracic esophageal squamous cell carcinoma after radical esophagectomy, with or without adjuvant therapy, in one institution as the training cohort (n = 2281). A nomogram was established using Cox proportional hazard regression to identify prognostic factors for OS, which were validated in an independent validation cohort (n = 1437). Area under curve (AUC) values of receiver operating characteristic curves were calculated to evaluate prognostic efficacy. In the training cohort, the median OS was 50.46 months, and the 5-year OS rate was 47.08%. Adjuvant therapy, sex, tumor location, grade, lymphovascular invasion, removed lymph nodes, and T and N categories were identified as predictive factors for OS. The nomogram showed favorable prognostic efficacy in the training and validation cohorts (5-year OS AUC: 0.685 and 0.744, respectively), which was significantly higher than that of the American Joint Committee on Cancer (AJCC) staging system. The nomogram distinguished OS rates among six risk groups, whereas AJCC could not separate the OS of 2A and 1B, 3C and 3B, or 3A and 2B. Patients with a nomogram score of 72 to 227 were predicted to achieve a 5-year OS increase of 10% or more from adjuvant therapy. The nomogram could effectively predict OS and aided decision making in adjuvant therapy for patients with thoracic esophageal squamous cell carcinoma after esophagectomy.

The optimal strategy was not established for patients who initially responded to gefitinib although re-administration of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has been proven to be an option. Gefitinib and erlotinib were compared as salvage treatment after gefitinib failure. Thirty-eight lung adenocarcinoma patients were analyzed retrospectively as they received the second EGFR-TKIs treatment with either gefitinib or erlotinib. All of them had obtained disease control from initial gefitinib. Sixteen patients received gefitinib (G-G group) and 22 patients received erlotinib (G-E group). Of all patients, progress free survival (PFS) and overall survival (OS) were three and 12 months, respectively, and the disease controlled rate (DCR) of the second EGFR-TKIs treatment was 52.6%. One patient (6.3%) had partial remission (PR) and 10 (62.5%) had stable disease (SD), in the G-G group, whereas, three (13.6%) had PR and six (27.2%) had SD, in the G-E group. There was no statistical significance observed, although the DCR in the G-G group was higher than that in G-E group (68.8% vs. 40.8%, P= 0.09). Adverse events of both gefitinib and erlotinib were mild and administered. The median PFS and OS in G-G and G-E groups were similar (PFS four vs. three months; OS 22 vs. 12 months). In multivariate analysis, patients with SD in initial gefitinib treatment had significantly longer OS (P= 0.04). Gefitinib as well as erlotinib could be an option for patients who benefited from prior gefitinib treatment. Patients with SD in initial gefitinib obtained a significantly longer OS than those with PR.

Wencheng Zhang,1 Qingsong Pang,1 Cihui Yan,2 Qifeng Wang,3 Jingsong Yang,3 Shufei Yu,3 Xiao Liu,3 Zhiyong Yuan,1 Ping Wang,1 Zefen Xiao3 1Department of Radiation Oncology, 2Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China; 3Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China Purpose: The purpose of this study was to investigate the potential effect of activation of epidermal growth factor receptor (EGFR) signaling pathway on the expression of programmed death-ligand 1 (PD-L1) in esophageal squamous cell carcinoma (ESCC) cells with EGFR overexpression. Methods: Flow cytometry and Western blot methods were used to assess PD-L1 expression on ESCC cells when EGFR signaling pathway was activated by epidermal growth factor (EGF) with or without EGFR-specific inhibitor AG-1478, and then EGFR signaling array was applied to analyze the potential signaling pathways involved. Results: This study found that PD-L1 expression increased significantly in an EGFR-dependent manner by the activation of EGFR signaling and decreased sharply when EGFR signaling was blocked. The upregulated expression of PD-L1 was not associated with EGFR-STAT3 signaling pathway, but may be affected by EGFR–PI3K–AKT, EGFR–Ras–Raf–Erk, and EGR–PLC-γ signaling pathways. Conclusion: The expression of PD-L1 can be regulated by EGFR signaling activation in ESCC, which indicates an important role for EGFR-mediated immune escape and potential molecular pathways for EGFR-targeted therapy and immunotherapy. Keywords: epidermal growth factor receptor, programmed death-ligand 1, esophageal squamous cell carcinoma, immune checkpoint

Background: The optimal strategy was not established for patients who initially responded to gefitinib although re-administration of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has been proven to be an option. Gefitinib and erlotinib were compared as salvage treatment after gefitinib failure. Methods: Thirty-eight lung adenocarcinoma patients were analyzed retrospectively as they received the second EGFR-TKIs treatment with either gefitinib or erlotinib. All of them had obtained disease control from initial gefitinib. Sixteen patients received gefitinib (G-G group) and 22 patients received erlotinib (G-E group). Results: Of all patients, progress free survival (PFS) and overall survival (OS) were three and 12 months, respectively, and the disease controlled rate (DCR) of the second EGFR-TKIs treatment was 52.6%. One patient (6.3%) had partial remission (PR) and 10 (62.5%) had stable disease (SD), in the G-G group, whereas, three (13.6%) had PR and six (27.2%) had SD, in the G-E group. There was no statistical significance observed, although the DCR in the G-G group was higher than that in G-E group (68.8% vs. 40.8%, P= 0.09). Adverse events of both gefitinib and erlotinib were mild and administered. The median PFS and OS in G-G and G-E groups were similar (PFS four vs. three months; OS 22 vs. 12 months). In multivariate analysis, patients with SD in initial gefitinib treatment had significantly longer OS (P= 0.04). Conclusions: Gefitinib as well as erlotinib could be an option for patients who benefited from prior gefitinib treatment. Patients with SD in initial gefitinib obtained a significantly longer OS than those with PR.

Programmed death-ligand 1 (PD-L1) expression either indicates immune inhibitory status or concurrent immune response. Although the relationship between PD-L1 and clinical outcomes has been studied widely in recent years, its role in prognosis of esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we assessed the significance of PD-L1 in ESCC and its association with epidermal growth factor receptor (EGFR) and radiation response. We found that PD-L1 was present both on the surface of tumor cells and tumor-infiltrating immune cells. Patients with tumor-infiltrating immune cell PD-L1 expression had better survival. PD-L1 expression on immune cells was an independent prognostic factor for patients with ESCC. PD-L1 expression either on tumor-infiltrating immune cells or tumor cells was negatively associated with EGFR expression. EGFR/PD-L1 pairs could separate the survival between EGFR low/PD-L1 positive and EGFR high/PD-L1 negative groups. In ESCC cell lines with EGFR high expression, PD-L1 expression was induced significantly when EGFR signaling was activated by radiation and was dramatically inhibited by an EGFR tyrosine kinase inhibitor. In conclusion, tumor-infiltrating immune cell PD-L1 expression is an independent prognostic factor for ESCC, and the association between EGFR and PD-L1 is vital to determining survival. It is important to consider radiotherapy-induced imbalance of pro-tumor and anti-tumor immune response. A combination of radiotherapy and PD-L1-targeted therapy could be a promising therapeutic strategy for ESCC patients.

// Shufei Yu 1, 4 , Wencheng Zhang 2 , Wenjie Ni 1 , Zefen Xiao 1 , Xin Wang 1 , Zongmei Zhou 1 , Qinfu Feng 1 , Dongfu Chen 1 , Jun Liang 1 , Dekang Fang 3 , Yousheng Mao 3 , Shugeng Gao 3 , Yexiong Li 1 , Jie He 3 1 Department of Radiation Oncology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China 2 Department of Radiation Oncology, Tianjing Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin 300000, China 3 Department of Thoracic Surgery, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China 4 Department of Oncology, Beijing Chao-yang Hospital, Beijing 100000, China Correspondence to: Zefen Xiao, email: xiaozefen2013@163.com Keywords: esophageal carcinoma, esophagectomy, overall survival, nomogram, recursive partitioning analysis Received: April 20, 2016 Accepted: July 10, 2016 Published: July 28, 2016 ABSTRACT We have developed statistical models for predicting survival in patients with stage IIB–III thoracic esophageal squamous cell carcinoma (ESCC) and assessing the efficacy of adjuvant treatment. From a retrospective review of 3,636 patients, we created a database of 1,004 patients with stage IIB–III thoracic ESCC who underwent esophagectomy with or without postoperative radiation. Using a multivariate Cox regression model, we assessed the prognostic impact of clinical and histological factors on overall survival (OS). Logistic analysis was performed to identify factors to include in a recursive partitioning analysis (RPA) to predict 5-year OS. The nomogram was evaluated internally based on the concordance index (C-index) and a calibration plot. The median survival time in the training dataset was 30.9 months, and the 5-year survival rate was 33.9%. T stage, differentiated grade, adjuvant treatment, tumor location, lymph node metastatic ratio (LNMR), and the presence of vascular carcinomatous thrombi were statistically significant predictors of 5-year OS. The C-index of the nomogram was 0.70 (95% CI 0.67–0.73). RPA resulted in a three-class stratification: class 1, LNMR ≤ 0.15 with adjuvant treatment; class 2, LNMR ≤ 0.15 without adjuvant treatment and LNMR > 0.15 with adjuvant treatment; and class 3, LNMR > 0.15 without adjuvant treatment. The three classes were statistically significant for OS ( P < 0.001). Thus, the nomogram and RPA models predicted the prognosis of stage IIB–III ESCC patients and could be used in decision-making and clinical trials.

Objective To evaluate the prognostic factors affecting survival in esophageal squamous cell Carcinoma (ESCC) patients with pathologic T0 (ypT0) underwent preoperative radiotherapy. Patients and methods Two hundred and ninety-six patients with ESCC who had received preoperative radiotherapy from 1980 to 2007 were retrospectively analyzed. One hundred patients were ypT0 after preoperative radiotherapy. Univariate and multivariate analyses were performed to evaluate the predictive impact of residual lymph node status on overall survival (OS) and progression-free survival (PFS). Results Among the originally analyzed 296 patients, 100 (33.7 %) patients had ypT0, including 78 patients (78 %) with ypT0N0, and 22 patients (22 %) with ypT0N1. The 5-year OS of the total patients was 42.4 %. Patients with ypT0N0 have significant improved 5-year OS and PFS than ypT0N1 patients (OS: 50.7 % vs 13.6 %, P = 0.004; PFS: 49.6 % vs 13.6 %, P = 0.003). In multivariate analysis, residual lymph node status was also an independent prognostic factors for OS (HR: 0.406, 95 % CI: 0.240–0.686, P = 0.001) and PFS (HR: 0.427, 95 % CI: 0.248–0.734, P = 0.002). Conclusion Our results indicate that patients with ypT0N0 after preoperative radiotherapy had significantly better OS and PFS than patients with ypT0N1 in ESCC. Residual nodal metastasis of ESCC patients with pathological complete response of the primary tumor after neoadjuvant radiotherapy does influence prognosis.

e18504 Background: To evaluate the efficacy and safety of irinotecan in combination with platinum against refractory or relapsed small cell lung cancer. Methods: In this retrospective study, we analyzed the data of 1,140 patients who diagnosed small cell lung cancer at our hospital between 2009 and 2012. Of all the patients, 34 were treated with irinotecan and nedaplatin (irinotecan 60mg/m2 on days 1,8 nedaplatin 85mg/m2 day 1,every 3 weeks), and 20 patients were treated with irinotecan and cisplatin (irinotecan 60mg/m2 on days 1,8 cisplatin 75mg/m2day 1,every 3 weeks ) as the second line treatment. Prognostic factors of overall survival (OS) were estimated by Kaplan-Meier and Cox's Regression-proportional hazards model. Results: Of 54 eligible patients, median progression free survival (PFS) was 21weeks, and median OS was 58 weeks. Median PFS was 23 weeks for irinotecan plus nedaplatin and 19 weeks for irinotecan plus cisplatin (P=0.410). Median OS was 62 weeks and 58 weeks, respectively (P=0.714).The response rate (RR) was 29% and 33.3%, respectively (HR 0.818,95%CI 0.234to2.855; P=0.753). In multivariate analysis, younger age, extensive stage while diagnosed, brain metastasis, treated with 3 cycles of irinotecan in combination with platinum or less, and PS≥1 were all associated with a statistically significant increase in the mortality harzard. Toxicity profile was slightly different for each of the arms: hematologic toxicity was higher with nedaplatin, and diarrhea was higher with cisplatin. Conclusions: Irinotecan plus platinum is effective and tolerable for refractory and relapsed small cell lung cancer. [Table: see text]