bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patterns of local failure after definitive radiotherapy in patients with esophageal squamous cell carcinoma: Implications for the longitudinal clinical target volume design.
Authors: Cheng Bo , Meng Xue 
Published: May 2019

e15504 Background: The correlation between the clinical target volume (CTV) margin and esophageal squamous cell carcinoma (ESCC) recurrence pattern is not completely clear. Our aim was to retrospectively evaluate the recurrence patterns in ESCC patients who received definitive radiotherapy (RT) with different CTVs, and determine the optimum longitudinalmargin. Methods: Patients with histologically proven ESCC (N = 134) were classified into the following three groups according to the initial expanding margin of CTV at the recurrence side: CTV1 with longitudinal margin ≥ 3cm (N = 73), CTV2 with 2-3cm (N = 37), and CTV3 with < 2cm (N = 24). The recurrence patterns were analyzed relative to the CTV margins, as well as the radiation dose, tumor stage, comorbidities etc. Results: The recurrence sites were significantly different between the CTV1 and CTV3 (p < 0.001), but not between the CTV1 and CTV2 groups (p = 0.052). In addition, 42 (91.3%) of the 46 patients that received low-dose (55-60Gy) RT showed recurrence at the site of the primary tumor, an obviously greater proportion compared to those who underwent a high-dose ( > 60Gy) treatment (77.3%, p = 0.018). Drinking was also a clear contributing factor (p = 0.025). Age, smoking, comorbidities,tumor location, stage and treatment mode were not significant prognostic factors for ESCC recurrence. Conclusions: CTV with a 2-3cm longitudinal expansion to the gross tumor volume (GTV) is acceptable for radical RT for ESCC, and recurrence at the primary tumor site is associated with low radiation dose ( < 60Gy).
Dosimetric and radiobiological comparison of external beam radiotherapy using simultaneous integrated boost technique for esophageal cancer in different location.
Authors: Wang Lu , Yu Jinming 
Published: May 2019

e15505 Background: Based on dosimetry and radiobiology to compare treatment plans for esophageal cancer (EC) in different location using intensity modulated radiotherapy (IMRT), volumetric modulated arc radiotherapy (VMAT) and helical tomotherapy(HT) with simultaneous integrated boost (SIB) technique. Methods: A total of 20 patients including 5 cases respectively located in the cervix, upper, middle and lower thorax were generated for IMRT, VMAT and HT plans. The dose volume histogram statistics, conformity index (CI), homogeneity index (HI), tumor control probability (TCP) and normal tissues control probability (NTCP) were analyzed to evaluate treatment plans. Results: HT showed significantly improvement over IMRT and VMAT in terms of CI(0.93±0.03), HI(0.07±0.03) and TCP(88.08±0.82%) in cervical EC(p<0.05). IMRT greatly developed TCP(88.29±1.79%;85.11±0.79%), and offered superior CIs (0.87±0.04;0.90±0.01) and HIs(0.10±0.01; 0.06±0.01) compared with VMAT and HT in upper and middle thoracic EC(p<0.05). Meanwhile, the V30(33.30±6.49%), mean dose (2559.00±219.64cGy) and NTCP(0.50±0.61%) of heart for IMRT were significantly reduced than other two techniques in middle thoracic EC. Patients with lower thoracic EC yielded the similar CIs and HIs(all p>0.05) for the 3 techniques, but VMAT showed the lowest NTCP of lungs (0.01±0.01%) with improved TCP (84.84±1.13%). Conclusions: HT was a good option with little lung and heart involvement as it achieved superior dose conformality and uniformity. IMRT was a perfect strategy with large thoracic involvement. It significantly improved tumor local control and reduced heart dose and complications with acceptable dose to lungs. VMAT was preferred with a smaller target volume but surrounded by more heart and less lungs. Individually choosing optimal technique for EC in different location will be warranted.
A phase Ib study of oraxol in combination with ramucirumab in patients with gastric or esophageal cancers who failed previous chemotherapy.
Authors: Hung Yi-Ping , Chao Yee , Chen Ming Huang , Cutler David , Kramer Douglas , Chan Wing Kai , Kwan Rudolf , Hung Noelyn Anne , Hung Tak , Tenner Laura LaNiel 
Published: May 2019

e15518 Background: Oraxol consists of oral paclitaxel (PTX) administered with the novel P-glycoprotein inhibitor HM30181A which enables the oral absorption of PTX. Ramucirumab (RAM) + intravenous weekly PTX is FDA approved 2nd line treatment of gastric cancer. Oraxol (oral PTX) 200mg/m2 days 1-3, weekly results in similar exposure to weekly 80/m2 intravenous PTX. This phase 1 clinical trial is to determine the maximum tolerated dose (MTD) of Oraxol + RAM. Methods: Eligible patients (pts) have gastric or esophageal cancers and failed prior fluoropyrimidine or platinum containing chemotherapies. Dose escalation followed the standard 3+3 design: Cohort 1: Oraxol 200mg/m2 days 1-3, weekly. Cohort 2: Oraxol 250mg/m2 days 1-3, weekly. Cohort 3: Oraxol 300mg/m2 days 1-3, weekly. Dose of RAM is standard 8 mg/kg IV every 2 weeks. Pts were monitored for dose limiting toxicity (DLT) by week 4. Adverse events (AEs) were assessed per CTCAE v4.03 and response by RECIST v1.1. Results: Cohort 1: One febrile neutropenia (DLT) observed in 6 pts. Partial response (PR) = 2/6, stable disease (SD) = 1/6 and progressive disease (PD) = 3/6 pts. Cohort 2: One grade-3 neutropenia with treatment delay (DLT) in 7 pts. PR = 3/6 and PD = 3/6 in 6 evaluable pts. Cohort 3: One febrile neutropenia (DLT) in 3 pts and study is ongoing. All pts had complete recovery of their DLT. PK showed increase of plasma PTX exposure with dose. Conclusions: The MTD for Oraxol has not been reached yet in combination with RAM. Preliminary results showed that Oraxol + RAM is tolerable and have encouraging anti-tumor activity in gastric or esophageal cancers pts who failed prior chemotherapies. Final results of this study will be presented. Clinical trial information: NCT02970539.
Investigation to metastasis of regional lymph node station and prediction to long-term survival following esophagectomy in thoracic esophageal cancer with stage T1 to T3.
Authors: Li Yin , Qin Jianjun , Li Xiaofei , Fu Xiangning , Liu Lunxu , Liu Yang , Xu Lin , Liu Deruo , Hu Jian , Zhao Heng , Sun Wei , Yang Haiying 
Published: May 2019

e15519 Background: The Lymph node metastasis (LNM) trends toward inferior outcomes for the esophageal cancer (EC) patients after radical operation. However, it is not well known for status to metastasis of regional lymph node (RLN) and impacts of RLN metastasis on long-term survival following esophagectomy, especially in squamous cell carcinoma. Methods: Data was extracted from the Collaborative Prospective Esophageal Cancer Database (designed by LinkDoc Technology Co, Ltd.) for patients with stage T1-3 thoracic tumors who underwent radical esophagectomy between 1 January 2010 and 30 June 2017 across ten hospitals with high volume of surgeries in China. The rate of LNM in every lymph node station was defined as the number of patients with LNM in the station divided by the number of patients with examination of lymph node (ELN) in the station. The hazard ratios (RLN metastasis versus no RLN metastasis) for postoperative survival were analyzed by method of multivariate cox’s proportional hazard models, and confounders such as age, sex, histological grade, stage T, tumor size and neoadjuvant therapy were adjusted. Results: Total 6485 patients (mean age: 61.80±8.13) were included, composing of 75.2% male and 24.8% female. For tumor types, there were 95.5% squamous cell carcinoma, 2% adenocarcinoma and 2.5% others. The rates of RLN metastasis and hazard ratios are in the table. Conclusions: Besides lymph node station 8, LNM was commonly found at station 1,2,4,16,17 and 20 in thoracic stage T1-3 EC. The RLN metastasis predicted inferior postoperative long-term survival. [Table: see text]
Expression of CD44 and CD133 in tumor сells of metastatic and non-metastatic gastric cancer.
Authors: Sagakyants Aleksandr B. , Kit Oleg I. , Ulianova Elena P. , Zlatnik Elena Yu. , Novikova Inna A. , Shulgina Oksana G. , Gevorkyan Yuriy A. , Soldatkina Natalya V. , Samoylenko Nikolay S. , Vladimirova Liubov Yu 
Published: May 2019

e15531 Background: High incidence and mortality rates of gastric cancer cause a constant search for the most informative and effective methods of diagnosis and treatment assessment. In this regard, studying the expression of markers with the stem phenotype in primary tumor tissues in patients with gastric cancer with and without metastases is of undoubted interest. Methods: The study included 20 gastric cancer patients aged 30-80 years: group 1 – gastric cancer T3-4аN0-3M0 (G2) without metastasis (58.9±9.7 years); group 2 – gastric cancer T3-4аN0-3M1 (G2) with peritoneal metastasis (53.4±11.9 years). Immunohistochemical study was performed on paraffin-embedded tumor tissue sections using mouse monoclonal antibodies to CD44 (156-3С11 Thermo Scientific) at a 1:2500 dilution and rabbit polyclonal antibodies to CD133 (Cloud-Clone Corp.) at a 1:700 dilution; the Thermo Scientific autostainer was used for staining. Membrane staining and staining intensity were assessed: 0, 1+ weak, 2+ moderate, 3+ strong staining. Positive expression was defined as ≥10% cut-off for CD44 and ˃5% for CD133. Results: Positive expression of CD44+ was detected in 67% (13) in group 2 vs. 20% (4) in group 1. In the metastatic group, the number of cells that stained positive for CD44 expression ranged from 9 to 15%, on average 10.0±3.08%, without metastases – from single cells to 13%, on average 6.0±2.3%. A chi-square test showed statistically significant association in the groups (8.256 at p = 0.004). Positive CD133+ expression in tumor tissues was registered in 100% (20) in group 2 and 80% (16) in group 1. The range of positively stained cells in group 2 was from 10 to 40%, on average 21.3±11.6%, in group 1 - from single cells to 14%, on average 10.0±2.4%. A chi-square test showed statistically significant association in the groups (4.444 at p = 0.036). Conclusions: Immunohistochemical study of the selected tumor cell markers in gastric cancer revealed some characteristics of their expression depending on the presence of metastases. The results can be the basis for further research for the most complete characterization of a heterogeneous tumor population in gastric cancer and the role of individual cells in the tumor growth, progression and metastasis.
Apatinib inhibits tumor progression and promotes antitumor efficacy of cytotoxic drugs in esophageal squamous cell carcinoma.
Authors: Chi Yanyan , Wang Feng , Meng Xiangrui , Shan Zhengzheng , Sun Yan , Fan Qingxia 
Published: May 2019

e15554 Background: Apatinib, a highly selective inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2), inhibits the angiogenesis of tumors. The function and mechanism of Apatinib in esophageal squamous cell carcinoma (ESCC) remains unknown. Methods: The expression of VEGFR-2 in ESCC cell lines (KYSE450, EC1, KYSE410, KYSE70) were detected by western blot. KYSE450 and EC1 cell lines were treated with Apatinib, or combined with cytotoxic drugs: paclitaxel (TAX), 5-fluorouracil (5-FU) or cisplatin (DDP) respectively. Cell proliferation was then measured using CCK-8 assay; cell apoptosis was analyzed by flow cytometry; cell migration and invasion were evaluated by wound healing and transwell assays. The expression of VEGFR-2, Bcl2, MMP-2/MMP-9, p-Akt and p-mTOR in KYSE450 and EC1 cell lines were determined by western blot. Esophageal cancer xenografts model was established and used to evaluate the antitumor effects of combination of Apatinib and cytotoxic drugs in vivo. Immunohistochemistry was used to detect the expression of Ki67, VEGFR-2 and CD31 in tumor tissues of esophageal cancer xenografts model. Results: We found that Apatinib efficiently inhibited cell growth, metastasis and activity of the Akt/mTOR pathway in ESCC cells. Western blot analysis showed that Apatinib significantly increased Bax protein levels, decreased VEGFR-2, Bcl2, MMP-2/MMP-9, p-Akt and p-mTOR protein levels in ESCC cells. Moreover, Apatinib enhanced chemosensitivity of cytotoxic drugs TAX, 5-FU and DDP by upregulating expression of Bax protein, and downregulating expression of VEGFR-2, Bcl2, MMP-2/MMP-9 protein in vitro. Compared with single agent groups, the combination of Apatinib with each chemotherapeutic drug significantly repressed tumor growth and angiogenesis through blocking the expression of Ki67, VEGFR-2 and CD31 in vivo. Conclusions: Taken together, Apatinib suppressed cell growth, migration and invasion, and promoted antitumor effect of chemotherapeutic agents in ESCC.
Tumor copy number alteration (CNA) burden as a prognostic factor for overall survival in Chinese gastric cancers.
Authors: Han Bo , Ren Dandan , Mao Beibei , Song Xue , Yang Wanning , Zhang Henghui , Gao Feng 
Published: May 2019

e15555 Background: Gastric cancer (GC) is associated with high morbidity and mortality rates in the world with poor prognosis and limited treatment options. The level of copy number alteration (CNA), termed CNA burden, is reported as a pan-cancer prognostic factor associated with recurrence and death. The current study aims to investigate association between CNA burden in primary tumor tissue and overall survival (OS) of Chinese patients with GC after surgical resection. Methods: The present study included 78 patients who had received surgical resection and adjuvant chemotherapy with poorly differentiated GC. The primary outcome was OS. Tumor specimens were obtained from surgery and submitted for next generation sequencing (NGS) with matched normal tissue samples. A 1408-gene panel was used to identify genome profiles. Data were analyzed using Cox proportional hazards models and Kaplan-Meier survival analysis. Results: The most frequently altered genes were TP53 (47%), PIK3CA (10%), PTEN (9%), NOTCH1 (8%) and RNF43 (6%), and copy numbers of TRPS1 (65%), COL1A2 (50%), CSMD3 (45%), ZFHX4 (45%), NAV3 (36%) varied most frequency in current cohort. Greater tumor CNA burden correlated with an increase in death from disease compared to a lower tumor CNA burden ( p= 0.0066). In addition, there were statistically significant differences in OS between different clinical staging ( p= 0.0011). Moreover, the Cox proportional hazard model showed that CNA burden was an independent prognosis factor in GC. Finally, we performed an independent signature that includes CNA burden and clinical staging to predict survival of GC. Conclusions: This study indicates that tumor CNA burden is an independent predictive survival biomarker for Chinese gastric cancers. CNA burden combined with clinical staging is a better predictor for postoperative survival prediction of gastric cancer.
Comparison of tumor characteristics and survival between esophageal and other gastroenteropancreatic neuroendocrine neoplasms.
Authors: Taherian Mehran , Samankan Shabnam , Groman Adrienne , Yendamuri Saikrishna S. , Bhalla Amarpreet 
Published: May 2019

e15556 Background: Neuroendocrine neoplasms (NEN) of esophagus are extremely rare. Limited information is available on survival of these tumors. The objective of this study was to define the clinicopathologic predictors of overall survival (OS) in esophageal NEN, and to compare them with the other gastroenteropancreatic NEN (GEP-NEN). Methods: Esophageal NEN were selected from the National Cancer Database (2004–2013). Multivariable analysis and Kaplan–Meier method were performed. The prognostic factors for GEP-NEN were derived from literature including WHO classification and AJCC TNM classification. Results: Of 802 selected patients with esophageal NEN, 97.5% were NEC and only 2.5% typical NET. The median age for NET was 58 vs. 66 for NEC (p = 0.007). NET more commonly presented in females (60%) compared to NEC wherein 68% patients were male. Most of the NEC were grade III/IV and > 4 cm, while most NET were grade I/II and < 4 cm. They most frequently metastasized to the liver. 10.7% of patients with esophageal NEN underwent esophagectomy while 86.5% had no surgery; 68.5% had adjuvant and 6.6% neoadjuvant therapy. Multivariable analysis showed that tumor > 4 cm (hazard ratio (HR) 1.45; P = 0.013), stage III and IV (HR 2.27; p = 0.030, and HR 4.02; P < 0.001, respectively) were associated with significantly worse OS, while esophagectomy (HR 0.30; P = 0.019) and neoadjuvant therapy (HR 0.35; p = 0.006) were predictors of better OS. The 5-year OS rate was 12% for all esophageal NEN (95% CI, 10-15): 89% for NET and 9% for NEC. Pancreatic NET are generally > 2 cm and NEC have an average size of 4 cm. The factors associated with worse prognosis in pancreatic NEN include positive surgical resection margins, lymph node metastases, advanced TNM stage, vascular invasion and distant metastasis. The 5-year OS for patients with pancreatic NET and NEC is 65% and 16%, respectively. NET of ileum are < 2 cm in 47% of cases, and the 5-year OS is about 60%. Tumor stage is the most important predictor of survival. The malignant potential is retained for ileal NET > 1 cm. Only Stage III vs. Stage IV has a better OS. The G3 NEC and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) have poor OS and variable median survival time reported up to 40 months. Conclusions: Using the largest dataset of esophageal NEN to date, the major independent predictors of OS include tumor size, stage, esophagectomy, and chemotherapy. The majority of esophageal NEN are NEC. Their OS is similar or slightly higher in comparison to ileal NEC but poor in comparison to similar tumors presenting in the pancreas.
The genetic profiles of esophageal squamous cell carcinoma (ESCC) in Hebei, a northern province of China.
Authors: Zuo Jing , Jia Yimeng , Wang Yudong , Fan Zhisong , Wang Long , Su Yu , Liu Fengling , Jiang Da 
Published: May 2019

e15558 Background: Esophageal squamous cell carcinoma (ESCC) is a common malignancy without effective therapy. Methods: DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) sections from 29 ESCC samples. A panel of 520 genes was sequenced with NGS to identify genomic alterations at an average sequencing depth of 1000×. Results: In total, 421 genomic alterations were identified. We identified 230 single nucleotide variants (SNVs) and 35 insertions and deletions (indels) , 147 CNAs, 9 deletions and 0 translocations. The most frequently mutated genes were TP53 (97%), NOTCH1 (31%), CDKN2A (21%), NFKBIA (21%). Most frequent CN gains were observed in FGF3/4/19/CCND1(41%) which were co-occurrence in cBioPortal.By performing targeted NGS in 29 ESCC samples, we found a median TMB of 5.6/Mb (range: 0.8 to 42.9/Mb).TMB-high was located according to TMB > = 10, where 17.2% of the samples were TMB-H.C·G > T·A transversions were the most common mutations, followed by G·C > A·T transitions,The patients with NFKBIA mutation were all significantly older (p = 0.05), and the patients with FGF3/4/19/CCND1 amplification were mostly moderately differentiated, and the patients without high differentiation, suggesting a higher degree of malignancy (p = 0.03). CDKN2A, FGF3/4/19/CCND1 amplification, and NFKBIA mutated were associated with a smaller invasion depth, respectively (p = 0,p = 0.03,p = 0.05). Patients with wild type KMT2D had earlier stage, and all N0 stages were wild type for KMT2D (p = 0.03).Notably, high activity of DNA damage,Cell cycle and Notch signaling pathway might be particularly promising strategies for ESCC.In potential therapeutic target analysis, CDKN2A(20.7%) and PIK3CA (13.8%) were the validated and candidate therapeutic targeted genes. Conclusions: Collectively, our data provide comprehensive insights into the mutational signatures of ESCC and identify markers for early diagnosis and potential therapeutic targets.
Management of synchronous Krukenberg tumors from gastric cancer: A single-center experience.
Authors: Yu Pengfei , Huang Ling , Du Yian , Cheng Xiangdong 
Published: May 2019

e15563 Background: Whether metastasectomy improves prognosis of gastric cancer patients with ovarian metastases (Krukenberg tumors) is not clear. In this study, we examined the survival benefit of metastasectomy combined with chemotherapy for treatment of synchronous Krukenberg tumors from gastric cancer and identified the prognostic factors. Methods: The subjects of this study were patients diagnosed as synchronous Krukenberg tumors of gastric origin in the period between December 2004 and December 2015. Patients were classified in accordance with treatment modality: metastasectomy group (metastasectomy combined with chemotherapy) and non-metastasectomy group (chemotherapy alone). Clinicopathological characteristics together with treatment records were investigated in detail and their relationship with survival outcomes was examined. Results: Out of a total of 103 patients, 54 (52.4%) underwent metastasectomy of Krukenberg tumors while 49 (47.6%) patients had chemotherapy alone. Overall survival (OS) in the metastasectomy group was significantly longer than that in the non-metastasectomy group (18.9 months vs. 12.4 months, respectively; P < 0.001). Metastasectomy (hazard ratio [HR] 0.486; 95% confidence interval [CI] 0.323–0.729; P < 0.001), signet ring cells (HR 1.938; 95% CI 1.182–3.175; P = 0.009), peritoneal carcinomatosis (HR 1.934; 95% CI 1.230–3.049; P = 0.004), expression of estrogen receptor-β (ER-β) (HR 0.404; 95% CI 0.251–0.648; P < 0.001), and progesterone receptor (PR) (HR 0.496; 95% CI 0.301–0.817; P < 0.001) were independent predictors of OS. Conclusions: Metastasectomy combined with chemotherapy showed an association with survival benefit in patients with synchronous Krukenberg tumors from gastric cancer. Metastasectomy, expression of ER-β and PR, peritoneal carcinomatosis, and signet ring cells were independent predictors of survival. Further prospective studies are warranted.