bluuebunny/crossref_metadata_2025_split huggingface dataset:
Camrelizumab (Camre) plus taxane-based chemotherapy (CT): Clinical outcomes and dynamic monitoring of CEA as a predictive biomarker of response in patients with recurrent or advanced esophageal squamous cell carcinoma (ESCC).
Authors: Kong Cheng , Xu Jianhua , Jiang Ming , Zhu Xiangzhi , Ye Jinjun , Yu Shaorong , Zhu Jun 
Published: May 2020

e16524 Background: Keynote-181 study reported anti-PD-1 antibody pembrolizumab as monotherapy had shown superior efficacy compared to CT for previously treated patients (pts) with advanced ESCC. The combination of anti-PD-1 antibody and CT may be a feasible approach to provide antitumor activity superior to either agent alone. However, the available data about the combination strategy is limited. Methods: We retrospectively reviewed the records of pts treated at our center to identify pts seen between 7/2019 and 12/2019 with recurrent or metastatic ESCC who received treatment with Camre (anti-PD-1 antibody) plus taxane-based CT. The primary endpoints were objective response rate (ORR) and disease control rate (DCR) per RECIST 1.1. Secondary endpoint included toxicity. The carcinoembryonic-antigen (CEA) dynamics and clinical associations were also evaluated in the selected pts. Results: A total of 14 pts were identified. The median age was 66 years (44-80). Most pts were male (12/14, 85.7%) with metastatic disease (10/14, 71.4%). The CT regimens contained nab-paclitaxel in 4 pts, nab-paclitaxel plus nedaplatin in 2, liposomal paclitaxel in 2, liposomal paclitaxel plus nedaplatin in 6. Camre in combination with CT were repeated every 3 to 4 weeks for up to 4 cycles. Two pts also received maintenance therapy of Camre for 4 and 6 cycles. Five pts (35.7%) exhibited a best overall response of PR, 6 (42.9%) SD, and 3 (21.4%) PD. The ORR and DCR were 35.7% (5/14) and 78.6% (11/14), respectively. All the SD determination as the best response met the minimum interval of 8 weeks from baseline. Toxicity profile was mild with mainly grade 1, expected toxicities. The most common grade 3/4 adverse events were leucopenia (2/14, 14.3%) and neutropenia (2/14, 14.3%). CEA baseline levels were normal in 6 cases, elevated in 8. It was observed that CEA levels closely paralleled overall measurable tumor burdens in all the CEA-elevated pts. A patient with equivocal radiographic pseudoprogression even had CEA dynamics that correlated with eventual clinical outcome. Conclusions: We identified a group of pts of recurrent or metastatic ESCC treated with Camre plus taxane-based CT and achieving a favorable DCR to therapy with a tolerable toxicity profile. This combination regimen warrants further exploration in a prospective clinical trial. CEA dynamics may be a useful tool to monitor disease evolution in this setting.
Study of efficacy and tolerability of paclitaxel and carboplatin as a concurrent chemotherapeutic radiation sensitizer regimen in patients of esophageal cancer: Prospective observational study from tertiary center in northern India.
Authors: Goyal Pankaj. , Chaudhari Krushna A. , Batra Ullas , Jain Parveen , Agrawal Chaturbhuj , Talwar Vineet , Goyal Sumit , Bothra Sneha , Domadia Kshitij , Babu Venkata Pradeep , Doval Dinesh Chandra 
Published: May 2020

e16526 Background: Neo-adjuvant chemotherapy followed by surgery is the standard of care in non metastatic oesophageal cancers. After the overall survival benefit observed in Cross trial, Paclitaxel and Carboplatin based neo-adjuvant chemoradiation has become the preferred treatment modality. There is paucity of data of its efficacy and tolerability in Indian patients. So this prospective study was done to assess the same. Methods: We enrolled 64 patients aged 18-75 years with histologically confirmed, potentially resectable squamous-cell carcinoma of the esophagus or esophagogastric junction from Aug 2017 to Jan 2019. On days 1, 8, 15, 22, and 29, carboplatin AUC 2 and paclitaxel 50 mg/m2 intravenously and a total radiation dose of 41.4 Gy was given in 23 fractions of 1.8 Gy each by external-beam radiation. Pathological complete response rate, Clinical response based on PET-CT scan and tolerability of paclitaxel and carboplatin as a concurrent chemotherapeutic radiation sensitizer regimen was studied. Results: 23 out 64 patients underwent surgery while others were either lost to follow up or they refused for surgery. Of these 23, 87.5% could complete all 5 planned cycles of chemotherapy. Complete pathological response was found in 73.9% patients. Statistically significant correlation was found between pathological and PET-CT based response (p-0.044). 4 patients showed distant progression on PET-CT based evaluation after neoadjuvant chemo radiotherapy before surgery. The most common major hematologic toxic effects were leukopenia (14%) and neutropenia (12.5%). Febrile neutropenia and grade 3 anemia was observed 2 and 4 patients respectively. The most common major non-hematologic toxic effects were vomiting (4.6%), nausea (3.1%), bronchoesophageal fistula(3.1%). Post operative mortality was seen in 1(4.3%) patient. Grade 3 pulmonary complications, atrial fibrillation and anastomotic leak was observed in 1 patient each. Conclusions: Concurrent chemoradiotherpy with weekly paclitaxel and caboplatin is well tolerated in Indian patients. High complete resection rate and PCR rate can be achieved with this regime with manageable adverse effect profile. Response evaluation with PET-CT after completion of preoperative therapy has correlation with pathological complete response.
Does radical surgery for gastric cancer after 70 years prolong survival?
Authors: Chanez Brice , Guiramand Jérome , Niziers Vincent , Dermeche Slimane , Rochigneux Philippe , Ries Pauline , Rousseau Fréderique , Loir Elika , Gilabert Marine 
Published: May 2020

e16527 Background: Gastric cancer (GC) occurs in 50% of case after 70 years old (y/o). Radical surgery or perioperative treatments have to be balanced with safety management in those potential frail patients. Methods: We perfomed a retrospective review of our single institution database to address the outcome of patient (pts) > 70y/o who underwent radical surgery for GC with or without neoadjuvant and adjuvant treatment. Results: From 2005 to 2019, 60 eligible patients (pts) have undergone radical surgery for resectable GC. Median age at diagnosis was 74.2y/o [70.3-92.8] and 82% were male. Initial echoendoscopy staged 12% of T1/T2 tumor versus 70% of T3/T4, whereas 60% were found with lymph node spreading (N+). 80% of pts were given neoadjuvant treatment: chemoradiation (58%), chemotherapy (45%) or radiation alone (1%). 1/4 pt received perioperative chemotherapy. Only one patient had post-operative radiation with FOLFOX and none had adjuvant radiation alone. Surgery procedure was total (27%) or sub-total (5%) gastrectomy, polar-oesogastrectomy with thoracotomy (18%) or without thoracotomy (50%). Post-operative mortality within 3 months was 5% (n = 3) including 2 pts in the first 30 days. For the global cohort, median overall survival (mOS) was 44.75 months and median progression free survival (mPFS) was 21.2 months. Patients who frontly underwent radical surgery (n = 15, 25%) had small disease with 13% pT0 and 60% of pT1 on final pathology. Only 27% had pT2/T3 but all had vascular and/or peri-nervous emboli. Two of them (13%) were pN+. The mOS was 60 months and mPFS 60 months in this cohort and 33% of pts end/was lost of follow up. Only one metastatic relapse was identifies and no local relapse. Six pts died (40%): 2 in the 30-days post surgery (13%), 3 (30%) from other cause than GC and 1 (7.5%) because of GC distant relapse. The cohort treated with neoadjuvant chemotherapy (n = 45, 75%) was given platinum and anthracycline-based regimen in 73% and 16% of cases, respectively. 1% received fluoropyrimidine +/- irinotecan. 53% associated radiation to neoadjuvant chemotherapy. After neoadjuvant treatment completion, 47% of downstaging (including 18% of pCR), 33% of stable stage and 15.5% of upstaging was observed and 40% of initial usN+ was pN0. After perioperative treatment, mOS was 31 months and mPFS was 18.9 months. Overall 44% experienced local and/or distant relapse. Conclusions: Age above 70y/o should not systematically exclude patient from neoadjuvant or perioperative treatment and radical surgery, which is feasible in selected population displaying long term result in focal and distant disease control.
Effects of alkaline water intake on gastritis and miRNA expression (miR-7, miR-155, miR-135b and miR-29c) in the Amazon population.
Authors: Chaves Juliana Ramos , de Souza Carolina Rosal Teixeira , Modesto Antonio André Conde , Moreira Fabiano Cordeiro , Teixeira Eliel Barbosa , Sarraf Jonathan Souza , Allen Thaís Suellen Ramos , Araújo Taíssa Maíra Thomaz , Khayat Andre Salim , Werneck De Carvalho Luis Eduardo 
Published: May 2020

e16544 Background: It is known that abnormal expression of miRNAs in the gastric cancer (GC) contributes to its carcinogenesis. Therefore, ingestion of commercial (usual) water on a daily basis may be a contributing factor for the occurrence of alterations in the gastric mucosal. In this study, it was evaluated the expression of the miRNAs miR-29c, miR-7, miR-155, and miR-135b in the gastric tissue of patients with gastritis before and after the consumption of alkaline water (pH range from 8.0 to 10.0), as well as the clinic pathological characteristics. Methods: 50 subjects from the Amazon region, diagnosed with gastritis that routinely used commercial (usual) water with a pH lower than 5.0, were enrolled to change the consume water to a pH of 8.5 to 10.0 for 5 months. Results: Endoscopic findings of gastritis were such different (less severe disease), p = 0.024; in 43% diagnosed with moderate gastritis upfront esophagogastroduodenoscopy (EGD) presented mild gastritis after the consumption of alkaline water, according to study methods; there were no worsening gastritis and there were a significant increase in the expression of miR-135b (p = 0.039) and miR-29c (p = 0.039). Conclusions: Modified pH range water (from 8.0 to 10.0) ingested for 5 months was able lead to a less severe gastritis according to the Sidney classification system, suggesting that this lifestyle change represented a clinical benefit in patients with gastritis on the Amazon region. In addition, higher expression of miR-135b and miR-29c was observed after the consumption of alkaline water for 5 months. [Table: see text]
Knockdown of KREMEN2 inhibits tumor proliferation and metastasis in gastric cancer.
Authors: Chen Beibei , Wang Saiqi , Huang Jinxi , Li Jitian , Zhang Jianying , Xu Weifeng , Lv Huifang , Nie Caiyun , Wang Jianzheng , Liu Yingjun , Chen Xiaobing 
Published: May 2020

e16555 Background: KREMEN2 is an important regulator of classical Wnt/β-catenin signaling pathway. However, the relationship between KREMEN2 and gastric cancer is not clear. The aim of this study was to explore the regulatory role of KREMEN2 in the tumorigenesis and metastasis of gastric cancer. Methods: We measured the protein level of KREMEN2 in 156 gastric adenocarcinoma, 40 metastatic gastric adenocarcinoma, 8 marginal and 4 normal tissues using tissue microarray. The differences in KREMEN2 expression were tested with Mann-Whitney U test. The relationship between KREMEN2 expression and pathologic data was determined with Pearson’s correlation analysis. The mRNA and protein level in cultured cell lines were detected by qRT-PCR and western blotting, respectively. Lentivirus was transfected by repressing KREMEN2. Cell viability was determined by the MTT assay. Apoptosis and cell cycle distribution were detected using flow cytometry. The cell migration was investigated by wound healing and transwell assay. Antibody array was performed to explore the underlying molecule mechanism. In vivo, Xenograft assay was established using nude mice to explore the role of KREMEN2 in gastric cancer cell and bioluminescence was observed via an in vivo imaging system. Results: It was demonstrated that, compared to para-cancerous tissues, KREMEN2 was significantly up-regulated in gastric cancer tissues, and was positively correlated with the pathological grade of gastric cancer patients. Given that KREMEN2 is abundantly expressed in most tested gastric cancer cell lines, KREMEN2 knockdown cell models were established and further used to construct mice xenograft model. After knocking down KREMEN2, the proliferation of gastric cancer cells was inhibited both in vivo and in vitro. At the same time, knockdown of KREMEN2 induced apoptosis, cell cycle arrest at G2/M phase and inhibition of migration in gastric cancer cells in vitro. Mechanistically, we found that knockdown of KREMEN2 suppressed PI3K/Akt pathway. Conclusions: Therefore, we revealed that the overexpression of KREMEN2 in gastric cancer may promote the carcinogenesis and metastasis of gastric cancer by activating the PI3K/Akt pathway.
Prognostic similarities between gastric adenosquamous carcinoma and typical gastric adenocarcinoma: A large population-based and propensity score-matched study.
Authors: Zhao Feng , Wang Jili , Cheng Xiaofei , Li Xinke , Lu Zhongjie , Chen Xin , Yan Senxiang 
Published: May 2020

e16559 Background: Gastric adenosquamous carcinoma (ASC) is an extremely rare form of stomach malignancy. To date, the limited knowledge of its biology and outcomes stems from mostly small, single institution experiences. We analyzed the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2016 to explore the treatment of ASC together with its prognostic factors to gain relatively large and consolidated insights. Methods: Propensity score matching (PSM) and Kaplan–Meier analyses were used to compare the prognosis between gastric ASC and typical gastric adenocarcinoma (AC). We assessed overall survival (OS) after patient stratification according to summary stage and treatment choice. Cox hazards regression analysis was performed to determine independent predictors of overall survival (OS). Results: A total of 171 gastric ASC were included (mean 65.20 ± 11.71 years-of-age). Patients with gastric ASC had similar OS to matched individuals with typical gastric AC (p = 0.915). In terms of treatment, 45.6% of gastric ASC patients underwent surgery, and 37.4% received radiotherapy (RT), and 64.3% received chemotherapy. Patients who underwent surgery had longer OS than those who did not receive surgery (p < 0.001), patients who received radiation therapy had longer OS than those who did not receive RT (p < 0.001), and patients who received chemotherapy had longer OS than those who did not receive chemotherapy (p < 0.001). A multivariate Cox analysis for OS showed that distant stage (HR, 3.334, 95% CI 1.544-7.199; p < 0.01) was independent prognostic factors for gastric ASC. Conclusions: Analysis of its outcomes indicates that gastric ASC is not a more malignant tumor as previously suspected. Gastric ASC shows a similar prognosis to typical gastric AC. Surgery, RT, and chemotherapy was associated with prolonged OS. Distant stage was associated with poor OS.
Clinical impact of oral intake on second-line treatment of advanced gastric cancer.
Authors: Ogata Takatsugu , Narita Yukiya , Kumanishi Ryosuke , Nakazawa Taiko , Matsubara Yuki , Nozawa Kazuki , Kato Kyoko , Honda Kazunori , Masuishi Toshiki , Bando Hideaki , Kadowaki Shigenori , Ando Masashi , Tajika Masahiro , Muro Kei 
Published: May 2020

e16560 Background: Trifluridine/tipiracil, an oral drug, was approved in Japan for patients (pts) with advanced gastric cancer (AGC). Insufficient oral intake (INSUF) is one of the most common complications. We evaluated the clinical characteristics and impact of oral intake during 2nd line chemotherapy (CT). Methods: We retrospectively evaluated AGC pts receiving 2nd line CT from January 2012 to December 2018 at a single institution. We defined “INSUF” as a requirement for daily intravenous fluids or hyperalimentation and “improvement of oral intake (IMP)” as no such requirement for > 1 week. Exacerbation (EXA) was defined as a change from “sufficient oral intake (SUF)” to INSUF. Results: We enrolled 495 pts, of which 67 (13%) and 428 (87%) pts had INSUF and SUF at the start of 2nd line CT, respectively. Patient characteristics are summarized in the Table. There was no difference in the cytotoxic drugs of 2nd line CT. The causes of INSUF were peritoneal metastases (79%), cachexia (15%), and primary complications (3%). The objective response rates of INSUF and SUF pts were 9% and 26%, respectively. INSUF pts had poorer progression-free survival (PFS) (1.7 vs. 3.7 months [M]; adjusted HR [aHR], 1.51; p < 0.001) and overall survival (3.2 vs. 10.1 M; aHR, 2.01; p < 0.001) than SUF pts. At the end of 2nd line CT, 147 (32%) and 314 (68%) pts had INSUF and SUF, respectively. In SUF pts, the factors correlated with EXA were poor ECOG PS (odds ratio [OR], 5.26; p < 0.001), massive or moderate ascites (OR, 2.04; p = 0.031), palliative operation history (OR, 2.90; p = 0.007), and ramucirumab use (OR, 0.50; p = 0.034). Median PFS was shorter after CT in pts with EXA than in those without (1.7 vs. 4.2 M; aHR, 2.05; p < 0.001). Among INSUF pts, 11 pts (16%) achieved IMP; the rate of IMP did not differ according to regimen. Median PFS was shorter in pts without IMP than in pts with IMP (1.1 vs. 3.3 M; aHR, 4.97; p = 0.001). Subsequent CT was administered to 29% and 71% of INSUF and SUF pts, respectively. Conclusions: INSUF at the start of 2nd line CT was a poor prognostic factor. For appropriate use of oral drugs, CT should be changed in SUF pts with factors associated with EXA. [Table: see text]
Factors related to the incidence of esophageal stenosis after treatment of advanced esophagus cancer.
Authors: Freitas Carla Simone Moreira de , Bastos Tiago Magalhães , Alberti Luiz Ronaldo , Bastos Lívia Maria Nicoletti Ariano , Soares Aleida Nazareth 
Published: May 2020

e16561 Background: Esophageal stenosis after curative treatment of esophageal cancer (CE) by radiochemotherapy has a high incidence, causing great impact to the patient’s health. Identifying risk factors for this type of pathology may provide earlier diagnosis and more effective follow-up for patients with CE undergoing curative radiotherapy. The objective of this study was to determine the risk factors for esophageal stenosis in patients with complete regression of the tumor lesion after advanced CE treatment with radiotherapy associated or not with chemotherapy. The choice of the theme is justified because there are no studies on esophageal stenosis after radiotherapy associated or not with chemotherapy in esophageal cancer in the west. Methods: Retrospective observational study with 103 patients of both sexes who presented total regression of esophageal squamous cancer, confirmed by endoscopy and biopsies, after treatment with or without chemotherapy. The relationship between the sexes, age, tumor staging, involvement of the esophageal circumference, tumor location, isolated use of radiotherapy or associated chemotherapy, and tumor extension with or without stenosis and its degree after treatment with total regression of the tumor. Results: Most patients are male (58.3%). There was a direct relationship between the degree of circumference involvement and the degree of stenosis and a significant association between tumor location and degrees of stenosis (p < 0.001). The higher the degree of posttreatment stenosis, the higher the percentage of more advanced tumors (p < 0.001). Regarding tumor extension, the greater the degree of stenosis after treatment, the greater the proportion of tumors larger than 60 mm (p < 0.001). T3 tumors increase in 23.77 chance of post-treatment stenosis compared to T2 tumors. T4 tumors, increase the chance of presenting post-treatment stenosis 23.94 times compared to T2 tumors. Conclusions: Our data show that impaired esophageal circunference, tumor extension, advanced stages, and pretreatment tumor stenosis are factors related to esophageal stenosis following treatment with advanced radiochemotherapy for esophageal cancer.
Weight loss after minimally-invasive esophagectomy for esophageal cancer.
Authors: Squires Malcolm Hart , Benbow Jennifer H , Trufan Sally Jeanne , Mann Della , Burchins Emily M , Byrne Meredith M , Hill Joshua , Gower Nicole Lee , Salo Jonathan C. 
Published: May 2020

e16565 Background: Nutritional deficiencies are common in esophageal cancer patients after esophagectomy. Patients frequently present with weight loss due to obstruction. Cancer therapies (chemoradiation and esophagectomy) further compromise nutrient intake through alterations in appetite, gastrointestinal function, and the catabolic effects of therapy. We aimed to understand and identify risk factors associated with post-esophagectomy weight loss. Methods: Patients undergoing minimally-invasive esophagectomy via laparoscopic and thoracoscopic techniques with intra-thoracic anastomosis between January 2015 and July 2019 were identified. Post-operative weight loss at 3- and 6-months post-surgery was calculated as percent change from preoperative weight. Univariate and multivariable generalized linear method (GLM) analysis was performed. Results: 176 patients (145 male, 31 female) underwent esophagectomy, with a median age of 64 [IQR 57-71] and median 3-month postoperative weight loss of 7.9% [IQR 1.5-12.3%]. The majority of patients were Caucasian (89%), histologically diagnosed adenocarcinoma (90%), and received neoadjuvant chemoradiation (71%). Median preoperative BMI was 28.3 [IQR 25.5-32.5]. Preoperative enteral feeding tubes were placed in 86 patients (49%). Five patients (2.8%) were converted to open surgery (laparotomy) and anastomotic leaks occurred in 12 (6.8%) patients. The median length of stay was 9 days [IQR 8-13]. Among a subset of 147 patients with data available, the median 6-month postoperative weight loss was 10% [IQR 5.3-15.0%]. On multivariable analysis, greater preoperative BMI and anastomotic leak were associated with increased weight loss at 3 and 6 months post-esophagectomy. Conclusions: Significant postoperative weight loss is common among minimally-invasive esophagectomy patients. Higher preoperative BMI and postoperative anastomotic complications are significantly associated with increased postoperative weight loss at 3 and 6 months. Need for preoperative feeding tube and conversion to open surgery were further associated with postoperative weight loss. [Table: see text]