bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of proteomic profiles of normal mucosa, Barrett’s esophagus (BE), and esophageal adenocarcinoma (EAC) obtained from humans and the Levrat’s rat model of BE/EAC.
Authors: Gibson Michael K. , Zaidi Ali H , Zeng Xuemei , Davison Jon M. , Foxwell Tyler , Hoppo Toshitaka , Komatsu Yoshihiro , Nason Katie Sue , Rotoloni Christina , Bhatt Astha , Kosovec Juliann , Smith Cornelia , Bigbee William L , Luketich James D. , Jobe Blair A 
Published: March 2020

e14689 Background: EAC from BE is increasing, and prognosis is poor. Representative models are critical to understanding BE/EAC and developing therapies. We refined the Levrat’s model of BE/EAC and showed that a SMO inhibitor prevented BE/EAC (Proc ASCO 2012). To validate the rat model as representative of human and explore differentially expressed proteins/pathways, we evaluated the proteomic profiles of nl/BE/EAC from humans and rats. Methods: GE reflux was induced in 6-8 wk old male Sprague–Dawley rats by the Levrat’s procedure--approved by the IACUC. Incidence of BE/EAC at 28 wks was 90%/70%. Human nl/BE/EAC samples were obtained from the PENG database--IRB approved. Histology confirmed by a single pathologist (JD). Following LCM from paraffin, digests were analyzed in triplicate by nanoflow LC-MS/MS with a hybrid linear ion trap-Orbitrap Velos mass spectrometer followed by online nanoflow LC. Mass spectral data representing ~ 20-30,000 CID spectra were searched, and a quantitative estimate of relative abundance was obtained. Kruskal-Wallis non-parametric ANOVA was employed, and clusters were compared within and between humans and rats. Results: Data is available for rat tissues, 10 samples each for nl/BE/EAC. Heirarchical clustering of 410 features yielded 3 statistically significantly distinct groups corresponding to normal, BE and EAC (ANOVA p < 0.001). Pair-wise comparison between groups yielded statistically significant (p < 0.05) differential protein expression as follows: nl vs BE~550; nl vs EAC~450; BE vs EAC~150. For EAC, proteins were differentially expressed in pathways including: protein degradation/synthesis, cell death, growth and proliferation (NF-kB, EIF4A, Akt, b-tubulin). Analysis of human tissues and comparison to rat will be presented at the meeting. Conclusions: Proteomic evaluation of normal/BE/EAC tissues from the Levrat’s model of BE/EAC yielded distinct protein patterns for nl/BE/EAC. Proteins differentially expressed in EAC vs normal/EAC are involved in cancer related pathways. Differentially expressed proteins may provide targets for therapy, which could be tested in the Levrat’s model.
Practice patterns in the treatment of locally advanced resectable esophageal carcinoma: A national survey of Canadian thoracic surgeons.
Authors: Buduhan Gordon 
Published: March 2020

e14695 Background: Many institutions have adopted a multimodality strategy for treating locally advanced resectable esophageal cancer including surgery, chemotherapy and radiation. While many neoadjuvant protocols have been studied, there is no well defined standard treatment. In order to determine current practices and clinician opinions regarding treatment of esophageal cancer, a survey study of practicing Canadian thoracic surgeons was performed. Methods: Members of the Canadian Association of Thoracic Surgeons were contacted by email; those who currently treat esophageal cancer were asked to complete an online survey. Three separate emails were sent to maximize participation. Results: The response rate was 54% (56 /104). Of the respondents, 85% exclusively practiced general thoracic surgery, 87% worked at a University-affiliated hospital. We presented a hypothetical patient with bulky, resectable distal esophageal adenocarcinoma with enlarged paraesophageal lymph nodes (T3N1M0). 54% stated that neoadjuvant chemoradiation followed by surgery was their institution’s treatment of choice, while 33% used neoadjuvant chemotherapy plus surgery. When asked to choose the best treatment for this patient based on available evidence, 33% chose neoadjuvant chemoradiation, 33% favored neoadjuvant chemotherapy, 31% were undecided. Regarding neoadjuvant chemotherapy vs. chemoradiation, 63% strongly agreed or agreed there was insufficient evidence to decide whether or not one treatment was superior to the other. 73% strongly agreed or agreed to support a future randomized trial of preoperative chemotherapy vs. preoperative chemoradiation for esophageal cancer patients. Conclusions: Most Canadian thoracic surgeons use either neoadjuvant chemotherapy or chemoradiation followed by surgery for locally advanced resectable esophageal cancer. There is wide variation in practice patterns with no clear standard approach. 63% feel there is insufficient evidence to decide whether or not one treatment is superior to the other, and the majority support a future trial of neoadjuvant chemotherapy vs. chemoradiation. A pilot study is being planned to determine feasibility.
Role and strategies of radiofrequency ablation in treating advanced hepatocellular carcinoma.
Authors: Chen Min Hua , Yang Wei , Wu Jie , Wu Wei , Yan Kun 
Published: March 2020

e14701 Background: To investigate the application value and strategies of ultrasound-guided percutaneous radiofrequency ablation (RFA) in treating advanced hepatocellular carcinoma (HCC) which is common in china. Methods: A total of 655 patients with unresectablely advanced HCC underwent percuatenous RFA therapy and 92 patients with 136 tumors among them were enrolled into the study. According to the 6th UICC/AJCC-TNM system, 82 and 10 patients were in stage III and IV, respectively. The tumor size ranged from 1.5 to 8.0 cm (mean±SD, 4.5±1.6 cm). 59 patients had solitary tumor and the remaining 33 patients had multiple tumors. The Child-Pugh classification of A, B and C were 58,32 and 2 patients, respectively. Established strategies included: (1) select RFA indications based on the contrast-enhanced ultrasound (CEUS) results; (2) design radical protocols based on invasive range showed by CEUS; (3) multiple overlapping ablations based on mathematical protocol; (4) two or three bipolar RFA electrodes with three dimensional localization; (5) color US guided percutaneous ablation of tumor feeding artery (including TACE) + RFA for HCC with rich supply. The patients underwent follow-up using enhanced CT at one month, and then every three months after RFA. The ablation was considered a success if no abnormal enhancement or wash-out was detected in the treated area on the CT scan at one month. All patients after RFA received liver protection treatments. Overall survival was estimated by Kaplan-Meier analysis. Results: Early complete tumor necrosis rate after initial RFA was 90.4% (123/136 tumors). Serious complications were developed in two patients (2.2%) and no treatment-related death occurred. 3~129 months were followed up. Local recurrence rate was 15.4 %(21/136 tumors). The 1-, 3-, 5-year overall survival rates were 83.3 %, 48.3 %, 21.9%, respectively, and the median survival time was 35 months. Conclusions: RFA treatment of advanced HCC proved to be feasible. Paying attention to apply treatment strategies and liver protection therapies in RFA can effectively improve the survival.
Single institutional series of neuroendocrine tumours managed in the Australian capital territory.
Authors: Malik Laeeq , Chua Yu Jo , Butt Nadeem , Yip Desmond 
Published: March 2020

e14703 Background: Neuroendocrine tumours (NETs) have been regarded as indolent tumors with significantly variable clinical behavior. Limited information is available on long-term clinical outcome and clinically applicable prognostic factors.We performed a retrospective review of NETS managed in the Australian Capital Territory (ACT) over a 12-year period,with examination of epidemiology and various prognostic clinicopathologic factors. Methods: This multicenter analysis included patients in ACT and surrounding New South Wales treated with histologically proven neuroendocrine tumor (lung carcinoids excluded). The cases were identified from hospital databases. Data was analysed according to epidemiological, clinical and histopathological characteristics. Results: The cohort of 107 patients showed slight male predominance. Median age at diagnosis was 62 years and tumour size of 1.2 cm. The most common primary tumour site was jejunum/ileum (32%) followed by rectum (22%) and pancreas (11.2 %). Most patients had localised disease at initial diagnosis (n- 73/107 (68%). Distant metastases were seen in 32% (n-34/107) on initial staging with liver being most common site. Most patients were symptomatic at diagnosis while 22.4% cases were found incidentally. Second malignancies in particular of gastrointestinal origin were diagnosed in 33.6% (n-36/107). Surgical debulking was the most common treatment (59.8%) while 18% had multi-modality therapy. At a median followup of 25 months from diagnosis, 76 patients (78%) were still alive. Median time to first relapse was 15 months. 5 year survival rate was 75% for NETs originating from jejunum/ilieum on Kaplan-Meier analysis. Increasing age, tumor size, male gender, high histological grade, high Ki 67 index, raised plasma chromogranin A and urine 5 HIAA at the time of diagnosis were associated with shorter 5-year survival. Conclusions: The epidemiologic characteristics and long-term outcome in our series was comparable to reported studies from other centers. This analysis confirmed some important prognostic factors that could be considered for risk stratification and therapeutic management in patients with NETs.
Efficacy and tolerability of FOLFOX6 as first-line treatment for advanced gastric and esophagogastric junction cancers (AGC): A single-center experience.
Authors: Abdul Rahman Rozana , Teo MinYuen , McDonnell Felicity , McDermott Raymond S. 
Published: March 2020

e14705 Background: There are a number of options for first line treatment for AGC. We sought to review the efficacy and tolerability of FOLFOX (F) in AGC, and compare outcomes with anthracycline-based (A) ctx-treated patients (pts). Methods: Pts with AGC treated with F and A (EOX and ECF) were identified from institutional database. Pt. demographics, disease characteristics and treatment details were extracted from medical charts and pharmacy database. Progression-free survival (PFS) and overall survival (OS) were calculated from commencement of ctx to radiographic evidence of progression and death, respectively, estimated with the Kaplan-Meier method. Comparisons were made via log-rank method. Other descriptive statistics calculated via t-test or chi-square methods as appropriate. Results: Between July 05 and December 11, 27 pts were treated with F. Twenty-one (77.8%) were male and median age was 68yrs (range: 42 – 77). ECOG performance status was 0 -1 in 24 pts (88.9%) and 2 in 3 (11.1%). Median Charlson score prior to metastatic disease was 2 (range: 0 – 3). Three had relapsed disease and another three had locally-advanced disease. Sites of metastatic disease were liver (12), peritoneum (12), non-regional nodes (2) and lungs (2). Median number of cycles of F was 5 (range: 1 - 12), 51.8% of pts completed ≥10 cycles, while the rest discontinued treatment due to disease progression (33%) and toxicities (14.8%). 21 pts (77.8%) required dose reduction and 17 (63%) experienced treatment delay. Fourteen (51.8%), 6 and 2 pts had 2nd, 3rd and 4th line of ctx, respectively. Median PFS was 7.2 mos and median OS is 9.7 mos. Sixteen pts were treated with A. Pts were significantly younger (p=0.002) but other characteristics were similar. Median PFS with A was 6.6 mos and median OS was 9.2 mos. The hazard ratio (F vs A) for PFS was 1.11 (95% CI 0.56 to 2.18, p = 0.77) and for OS was 0.73 (95% CI 0.36 to 1.51, p = 0.40). Conclusions: Despite an older pts cohort with co-morbidities, high percentage of treatment delays and dose reductions, our data suggest that significant percentage of pts were able to complete ≥10 cycles of F and subsequent therapies. Outcomes are comparable to our A cohort and published data.
Evaluation of neoadjuvant chemotherapy for esophageal cancer.
Authors: Kawasaki Hitoshi , Hakamada Kenichi 
Published: March 2020

e14709 Background: Neoadjuvant chemotherapy (CT) followed by surgery has become the standard treatment in patients with clinical stage II/III thoracic esophageal cancer. This study evaluated our experience with this treatment approach. Methods: We evaluated 39 patients that underwent an esophagectomy after neoadjuvant concurrent 5-fluorouracil/cisplatin CT, and investigated the clinical and pathological results of neoadjuvant CT. Results: The 3-year overall survival (OS) rate was 70%. Clinical CR, PR, SD and PD were observed in 0, 22, 14 and 3 patients, respectively, and response rate was 56.4%. The 3-year OS of clinical CR group was significantly better than that of clinical PD group. The OS of clinical CR group was not significantly different from that of clinical SD group. Down-staging was observed in 13 cases (33%), but OS was not significantly different between down-staging group and non-down-staging group. Pathological complete response was observed in 1 case (3%). According to lymph node metastasis, down-grading was observed in 11 cases (28%) (responder). The OS was significantly better in responders compared with those in non-responders (100% vs. 50%, p=0.024). Conclusions: Neoadjuvant chemotherapy can be a good option in treatment of clinical stage II/III thoracic esophageal cancer. Especially in this study, the patients with pathological lymph node response are expected to have better outcome in survival.
The prognostic significance of Cerb-B2 determination in gastric cancer.
Authors: Fradique Antonio CALDEIRA 
Published: March 2020

e14713 Background: The Cerb-B2/HER2 marker, is a glycoprotein encoded by the ERBB2 oncogene, belongs to the family of epidermal growth factor receptors (EGFR), which has based its application on tests of new therapeutic modalities (target therapy). Apart from this interest has been invoked its value as a marker of tumor aggressiveness, due to his role as a regulator of cell proliferation and migration and consequent invasiveness and metastization. However, the results as to the meaning prognosis of this molecular marker are controversial and with variations depending on the geographical zone. Results: From a total of 50 pts. with advanced resectable gastric cancer that underwent surgery with D2 lymphadenectomy, 38 pts. had a total gastrectomy, and 12 pts. had subtotal gastrectomy. A mean of 35.7 lymph nodes/pt were resected at surgery. In 68% of pts. positive lymph node metastases were present. Tumor HER2-neu overexpression was observed in 16 pts (32%), several other parameters of tumor aggressiveness were also present, without any statistical significance or relevance. Methods: To determine if the Cerb-B2 played a prognostic role in gastric cancer, a total of 50 pts. with advanced resectable gastric cancer, were submitted to gastrectomy with D2 lymphadenectomy. In all cases assessment for tumor HER2-neu overexpression was performed using immunohistochemistry (IHC). FISH was used as a confirmation method in tumors with 2+ expression by IHC. A correlation was made between the tumor HER2-neu expression and the following parameters: tumor location, size, histological type, depth of invasion, lymph node metastases and clinical staging. Results: From a total of 50 pts. with advanced resectable gastric cancer that underwent surgery with D2 lymphadenectomy, 38 pts. had a total gastrectomy, and 12 pts. had subtotal gastrectomy. A mean of 35.7 lymph nodes/pt were resected at surgery. In 68% of pts. positive lymph node metastases were present.Tumor HER2-neu overexpression was observed in 16 pts (32%), several other parameters of tumor aggressiveness were also present, without any statistical significance or relevance. Conclusions: The determination of Cerb-B2 / HER2 expression has not shown prognostic significance in this study.
Effect of nab-paclitaxel combination chemotherapy on response and survival in pancreatic cancer.
Authors: Dean Andrew Peter , Cooray Prasad 
Published: March 2020

e14718 Background: Pancreatic cancer has traditionally had few effective chemotherapy options. Recent discovery of the over-expression of SPARC (Secreted Protein Acidic Rich in Cysteine) on the majority of pancreatic cancers suggests possible utility of nab-paclitaxel, (a novel albumin-bound form of paclitaxel) as a treatment option. A small prospective study (ASCO 2009) supported this theory. We sought to retrospectively evaluate the treatment efficacy of nab-paclitaxel with gemcitabine or carboplatin in patients with pancreatic cancer to assess concordance with the previous small prospective study. Methods: Data was collected retrospectively from the medical records of pancreatic cancer patients who presented to the private clinic of two treating oncologists (n = 63) from June 2009 to December 2011 and were treated with nab- paclitaxel in combination with either gemcitabine or carboplatin. Patients were assessed on the basis of changes in serum tumour marker (CA19-9, CEA or CA15-3) and changes in tumour size on radiological imaging. Results: 39 (70%) patients had a biochemical response with a greater than 20% drop in tumour markers. Of these, 30 (94%) showed greater than 70% drop with all responders showing reduction in markers within 6 weeks of starting. The number of patients with biochemically defined disease control was 48 (86%). 36 patients were deceased by the end of the series with median overall survival being 12.9 months. The median survival time from starting nab-paclitaxel for these patients was 7.9 months. Very long survival times (up to 28.1 months following commencement nab-paclitaxel) were also observed in 2 patients at the time of data analysis. The overall disease control rate radiologically was 76.79% (43 of 56). Of the 43 responders, 10 were complete responders, 22 showed partial radiological response and 11 had stable disease. Conclusions: This retrospective case series demonstrates a near doubling of overall median survival time and also an improved response rate in patients on nab-paclitaxel treatment as compared to historical data of other treatment options for pancreatic carcinoma. It further supports Von Hoff’s data from ASCO 2010. Further prospective data is eagerly awaited.
Correlation of SMAD4 mutational status and local or metastatic progression in patients with pancreatic cancer.
Authors: Derbel Olfa , de la Fouchardière Arnaud , Peron Julien , Rivoire Michel , Desseigne Françoise , Meeus Pierre , Peyrat Patrice , Heudel Pierre , Stella Mattia , Racadot Severine , DE LA Fouchardiere Christelle 
Published: March 2020

e14730 Background: Pancreatic cancer remains resistant to many key cytotoxic chemotherapeutic agents and novel targeted therapies. The molecular heterogeneity of this cancer may account for therapy failures to date, although the growing arsenal of novel targeted agents could translate into patient survival. A better understanding of the cellular and molecular features of advanced disease will afford new opportunities for investigation, therapeutic intervention and clinical management of patients afflicted with pancreatic cancer. Methods: This study examined the expression profiles of Smad4 in 45 samples of surgically resected pancreatic cancer. Of these 45 patients, 32 underwent pancreaticoduodenectomy. The clinicopathological parameters, the histologic features were determined and correlated to the stage at initial diagnosis, patterns of failure (locally advanced v metastatic disease) and the status SMAD4 genes. Results: Among the 45 patients, 40% of patients died with metastatic disease and 15 % died with locally advanced evolution. SMAD4 genetic status was determined in 25 patients and seems to be correlated with a high grade histologic features and progression to metastasis. Complementary data about correlation between the mutational status of SMAD4 and survival will be presented during congress. Conclusions: SMAD4 gene inactivation seems to be associated with poorer prognosis and disease progression. Prospective validation of SMAD4 as a predictive biomarker may personalize treatment strategies for patients with pancreatic cancer.
Survival outcomes of patients with unresectable hepatocellular carcinoma in a national population-based study: SEER versus tertiary cancer center.
Authors: Lawal Taoreed O. , El-Rayes Bassel F. , Kim Hyun Sik 
Published: March 2020

e14736 Background: To evaluate long-term survival in patients with unresectable hepatocellular carcinoma (HCC) in large national population-based database and to assess the impact of subspecialized care on similarly matched patients at a tertiary cancer center. Methods: Using the Surveillance, Epidemiology and End Results (SEER) registry, patients diagnosed between 2004 and 2008 with advanced unresectable HCC not amendable to radiation therapy or cancer-directed surgery were extracted. Additionally, similar matched patients receiving drug eluting bead transarterial chemoembolizaton (DEB TACE) for unresectable HCC were included in the study. Demographic, clinical, and procedural data were collected. Patients were stratified based on Contract Health Service Delivery Areas (CHSDA) and the rural- urban continuum. The Kaplan Meier method was used for survival analysis, and survival curves were compared using the log rank test in SPSS. Results: 14,369 patients were studied and demographics were as follows: mean age at time of diagnosis was 63.97 years (SD 12.5); 76.1% were male; 66.7% were Caucasian; 13.3% were African-American; and 19.4% were Asian or American Indian. The overall median observed survival from diagnosis of the 136 patients receiving DEB TACE was significantly higher when compared to the 404 Atlanta patients and the 12,012 SEER patients (median OS = 22 vs 4 vs 4 months respectively, p< 0.05). When compared to CHSDA, the median overall survival for patients receiving DEB TACE was 5 times longer than all other geographical areas (22 months vs 3, 4, 3, 4, and 4 in Alaska, East, Northern Plains, Pacific Coast, and the Southwest, respectively, p<0.05). Metropolitan, urban, and rural areas demonstrated similar survival outcomes and patients receiving DEB TACE had superior survival (22 vs 3-4 months, p<0.05). Conclusions: This study suggests that DEB TACE is viable treatment option that confers significantly beneficial survival results when compared to similar patients nationwide diagnosed with advanced unresectable HCC in the same 5-year time frame regardless of population demographics and health service delivery area.