bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of body mass index dynamics on survival of patients with advanced pancreatic cancer receiving chemotherapy.
Authors: Choi Younak , Oh Do-Youn , Kim Tae-Yong , Lee Kyung-Hun , Han Sae-Won , Im Seock-Ah , Kim Tae-You , Bang Yung-Jue 
Published: March 2020

e15066 Background: The obesity is increasing worldwide. High body mass index (BMI) is linked with an increased risk of developing pancreatic cancer (PC). However, in patients with advanced PC (APC), especially those are receiving palliative chemotherapy (the majority of all PC patients), the impact of BMI and its change during disease course on survival has not been fully investigated. Methods: Consecutive patients with APC were enrolled during years 2003-2010, all treated with palliative chemotherapy. The BMI measured at the point of starting the first cycle of palliative chemotherapy was called as “BMI at diagnosis”. “Pre-cancer weight” which means the weight in good health was the sum of “weight at diagnosis” and “weight loss at diagnosis” that the patients’ self- reported at the first visit. “Pre-cancer BMI” was calculated using pre-cancer weight. We got weight data measured at every visit during chemotherapy to investigate BMI change during chemotherapy period. Clinical characteristics and outcomes were analyzed. Results: A total of 425 patients were enrolled (median age, 60.1 years). At diagnosis of APC, the BMI distribution of patients was as follows: <18.5 (45, 10.6%); 18.5-19.9 (67, 15.8%); 20.0-22.4 (156, 36.7%); 22.5-24.9 (107, 25.2%); 25.0-29.9 (49, 11.5%); and ≥30.0 (1, 0.2%). Clinical characteristics were balanced across BMI groups. Median overall survival (OS) was 8.1 months (95% CI, 7.2-9.1). Pre-cancer BMI and BMI at diagnosis had no impact on OS (p = 0.488, p = 0.348, respectively), although patients at BMI range of 22.5-24.9 achieved the longest OS (9.9 months; 95% CI, 8.5-11.3). BMI loss at diagnosis (pre-cancer BMI minus BMI at the diagnosis) and BMI loss during chemotherapy (both stipulated as BMI change ≥1) were associated with shortened OS (HR, 1.300; p = 0.012 and HR, 1.367; p= 0.010, respectively). Conclusions: In patients with APC undergoing palliative chemotherapy, both declines in BMI at diagnosis of APC and during chemotherapy are more hazardous for OS than pre-cancer BMI or BMI at diagnosis itself as absolute values. Further research evaluating strategies to maintain BMI during chemotherapy in this setting is thus warranted.
Comparing recist and Choi’s criteria to evaluate radiological response to chemotherapy in patients with advanced pancreatic cancer.
Authors: Vecchiarelli Silvia , Macchini Marina , Grassi Elisa , Ferroni Fabio , Ciccarese Federica , Calculli Lucia , Ricci Claudio , Casadei Riccardo , Pezzilli Raffaele , Biasco Guido , Di Marco Mariacristina 
Published: March 2020

e15069 Background: Assessment of response after chemotherapy (CTH) for pancreatic cancer (PC) is currently based on RECIST criteria. In 2007 Choi et al. published a new classification system.The purpose of this study was to evaluate the accuracy of these classification systems for radiological response to CTH in patients with advanced PC. Methods: From 2006 to 2012, 66 untreated patients with advanced PC underwent palliative CTH. Fourty (60 %) had a locally advanced PC and 26 (40%) a metastatic disease. All patients were treated with a GEM-based CTH or FOLFIRINOX. We assessed radiological response after three months of first-line therapy applying both RECIST criteria, which evaluate differences in CT size, and Choi’s criteria, which consider changes both in size and in density at CT. We evaluated the accuracy in restaging, comparing the class of response with overall survival (OS). OS was calculated with Kaplan-Meier method. The accuracy in restaging was assessed through log rank test and multivariate analysis with Cox Regression. Results: At restaging, using RECIST criteria, we registered 7 (10.6 %) patients with partial response (PR), 32 (48.5 %) with stable disease (SD), and 27 (40.9 %) with disease progression (PD). Instead Choi’s criteria assessed 19 PR (28.8 %), 12 SD (18.2%) and 35 PD (53.0%). Comparing each classification with OS, we observed that patients with different prognosis were better stratified with Choi’s criteria. Using RECIST criteria we found a borderline significant difference in OS between patients with PR (13.47 months), SD (13.67 months) and PD (9.97 months) (p=0.05). Instead we found a significant statistical difference in OS using Choi’s criteria between patient with PR (14 months), SD (16.37 months), PD (9.7 months; p=0.004). Multivariate analysis showed a statistically significant difference in OS between Disease Control Rate (DCR, PR+SD) and PD patients (14.47 vs. 9.67 months, p=0.02), only using Choi’s criteria. Conclusions: In our experience, Choi’s criteria seem to better assess radiological response of CTH in PC patients than RECIST criteria. Due to the small number of patients, larger prospective studies are needed.
Effect of the combination of the dual mTOR/pI3K inhibitor NVP-BEZ235 with gemcitabine on growth inhibition in pancreatic cancer cells in vitro and in vivo.
Authors: Maute Luise , Wicht Johannes , Zoernig Martin , Niederhagen Manuel , Bergmann Lothar 
Published: March 2020

e15070 Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignant tumours and is still associated with a very poor prognosis. Therefore new treatment strategies are needed. The PI3K/AKT and mTOR signaling pathways are frequently dysregulated in PDAC. Thus we investigated the effects of NVP-BEZ235, a novel dual PI3K/mTOR inhibitor, alone or in combination with gemcitabine first in vitro and after promising results also in vivo. Methods: We examined the effect of gemcitabine and NVP-BEZ235 (kindly provided by Novartis Pharma) on cell viability as single agents and in combination with sequential administrations in the four human pancreatic cancer cell lines MiaPaCa-2, Panc-1, AsPC-1 and BxPC-3. For in vivo experiments we used NOD SCID Mice, which were injected with BxPc3 into the right flank. Treatments consisted of Gemcitabine alone, NVP-BEZ235 alone, simultaneous application of both, first application of Gemcitabine followed by NVP-BEZ235 and NVP-BEZ235 followed by Gemcitabine. Results: Simultaneous incubation of gemcitabine and NVP-BEZ235 affected the PDAC cell lines significantly better than the single agent administration. But most effective was a sequential administration of gemcitabine followed by NVP-BEZ235. In vivo Gemcitabine and NVP-BEZ235 as single agents showed a slightly reduced tumor growth and the treatment in the sequence NVP-BEZ235 first, followed by Gemcitabine resulted in only a minimal reduction of tumor growth. The most effective results were obtained by simultaneous and even better in the sequence of Gemcitabine followed by NVP-BEZ235, respectively. Conclusions: The combination of gemcitabine with the dual PI3k/mTOR inhibitor NVP-BEZ235 enhanced the efficacy of PDAC treatment via down-regulation of the DDR related gene Survivin in vitro. This combination seems to be significantly more effective than single agent use in vitro and also in vivo. Furthermore we demonstrated that the sequence of administration of these agents could be a relevant issue. These promising results might offer a new and effective option for the treatment of pancreatic cancer in the future.
Association of decline in serum Ca19-9 after neoadjuvant therapy with improved survival among borderline resectable pancreatic cancer patients.
Authors: Tsai Susan , Mahmoud Anna , George Ben , Kelly Tracy R. , Ritch Paul S. , Erickson Beth , Evans Douglas B. , Christians Kathleen K. 
Published: March 2020

e15082 Background: Serum Ca19-9 (19-9) decline in response to therapy has been associated with an increased overall survival in metastatic pancreatic cancer patients (pts). However, the prognostic value of a 19-9 decline after neoadjuvant therapy in pts with localized disease is less well defined. Methods: We evaluated 73 pts with NCCN defined BRPC who received neoadjuvant therapy with induction chemotherapy (CRX) followed by chemoradiation (CRT). Staging with CT and 19-9 was obtained at three defined time points: baseline (bilirubin normal), after CRX, and following CRT (pre-surgical). Change in 19-9 (δ19-9) was defined as: (baseline 19-9- pre-surgical 19-9)/baseline 19-9. δ19-9 was classified as: absent (δ19-9<0) or minimal (0 <δ19-9<0.25), low (0.25<δ19-9<0.50), moderate (0.50<δ19-9<0.75), high (δ19-9> 0.75). Results: Of the 73 pts, 20 pts had normal/undetectable 19-9 and were excluded from the analysis. Of the remaining 53 pts, mean 19-9 levels at baseline, after CRX, and after CRT were 956, 164, and 139 U/mL, respectively. The mean change in 19-9 after CRX was 44%. Changes in 19-9 after CRX correlated with continued decline in 19-9 after CRT (Spearman rho = 0.81, p<0.001). δ19-9 was high in 38 (71%), moderate in 9 (17%), min/low in 1 (2%), and absent in 5 (9%). Of the 53 pts, 49 (92%) were considered for surgery after neoadjuvant therapy and 38 (72%) underwent pancreatectomy. In a multivariate logistic regression, higher δ19-9 was associated with a 5.4 fold increased odds of completing all neoadjuvant therapy including surgery as compared to pts with no change in 19-9 (absent δ19-9; HR 5.4, p=0.12). Patients with absent δ19-9 had a worse overall survival than pts with minimal to high δ19-9 (median survival 11.5 mo vs. 30.1 mo, p = 0.0002). In a multivariate Cox proportional hazard, a decline in pre-surgical 19-9 from baseline was associated with improved survival (HR 0.21, p =0.02). Conclusions: Following neoadjuvant therapy, a decline in 19-9 is associated with surgical resection and improved overall survival. An increase in 19-9 above baseline (the absent δ19-9 group) prior to surgery is a poor prognostic marker and such patients may benefit from additional systemic therapy.
Differences in the survival rate between premenopausal and post menopausal women with gastric cancer: U.S. SEER database.
Authors: Yousif Nasser Ghaly 
Published: March 2020

e15092 Background: Gastric cancer is the fourth most common malignancy in the world, The presence of estrogen receptor alpha (ER a) and estrogen receptor beta (ER b) have been reported in cell and tissue level in gastric cancer, but its impact on patients' survival remains unclear. The male predominance of gastric cancer suggests that female sex hormones may have a protective effect against gastric cancer. To understand the clinical impact of the estrogen pathway, we analyzed the national SEER database to compare the outcomes for gastric cancer in premenopausal vs.postmenopausal women. Methods: Data from the national SEER registry between the years of 1985-2009 was analyzed. Women between the ages 31-50 were chosen as representative of the pre-menopausal group (n=1291) and 51-70 year-old women represented the post-menopausal group (n=3089) as defined by the American College of Obstetricians and Gynecologists. To control the effect of age alone as a determinant of outcome, we compared the survival between men were similarly divided into two categories: younger men (n = 2114) aged 31- 50 years and older men (n = 5102) aged 51 - 70 years. Survival rates were analyzed by Kaplan-Meier method and compared by Z-test through SEER*Stat software version 7.0.9. Results: The cardiac gastric cancer site type and diffuse histological subtype had statistical significance difference between premenopausal and postmenopausal groups (49% vs.72%), (44% vs. 692%) respectively. The Kaplan-Meier curve shows the survival rate in premenopausal superior to postmenopausal women in diffuse gastric cancer P=0.01, while no statistically significant difference regarding mixed sub-types P>0.05 and control groups. Conclusions: The results suggest varying estrogen effects between localization and histological subtype of gastric cancer, the presence of estrogen in gastric cancer could have a protective effect against gastric cancer and support clinical strategies need to stimulate the ER pathway or use estrogen for the treatment of gastric cancer, and additional studies are warranted as well as experimental studies that can shed light on the mechanism underlying this potentially protective action.
Paclitaxel, carboplatin, and etoposide (TCE) in advanced poorly differentiated neuroendocrine carcinoma.
Authors: Mantovani Loeffler Luisa , Mauersberger Elias , Weimann Arved , Kuerschner Dorit , Schimmelpfennig Christoph , Wiechmann Volker , Bisanz Heike , Zeissig Gisela , Zeynalova Samira , Schmoll Hans-Joachim 
Published: March 2020

e15096 Background: Only limited data are available on treatment outcomes in poorly differentiated neuroendocrine carcinomas. We evaluated retrospectively a complete series of consecutive patients with poorly differentiated neuroendocrine carcinoma treated with a regimen containing TCE in a single center. Methods: 50 new consecutively diagnosed patients were treated between 01/2000 and 04/2012 at St. Georg Hospital Cancer Center Leipzig. Dosing: paclitaxel (175-200mg/m² d1), carboplatin (AUC 6 d1) and etoposide (50/100mg d1-10) q3w (Hainsworth et al. JCO 2006, 22, 3548-3554). In cases of response after three cycles patients have been treated until progression or toxicities. Patient initial characteristics: age 61 years (range 23-85); 34 male, 16 female; 8/50 limited disease, 29/50 liver metastases, 13/50 only extra hepatic metastasis; 12/50 hormon active tumors. Histological confirmation, immunhistochemical staining (synaptophysin, chromogranin A) and proliferationsrate were performed in all cases. Resection of primary tumor was performed in 20/50 pts. Median no. of cycles was 4 (range 1-12 courses). CT-Scans of all patients were reviewed according to RECIST to detect maximal response. Results: 7/50 (14%) had CR, 20/50 PR (with a median reduction of the sum of diameters to 49%); 12/50 (24%) had no change; 7/50 PD (14%); 4/50 (8%) were not evaluable for response because of early death (3 sepsis, 1 liver failure). Median progression free survival time was 4.0 months (95% CI 2.9-5.1). The median overall survival time was 14,8 months (95% CI 9,5 -20,3). Major toxicity was myelosuppression. As a consequence paclitaxel dose was reduced to 175 mg/m² in the last 40 pts of this series (80%). Conclusions: TCE treatment is effective and induces tumor control in a substantial subgroup of patients. This analysis confirms the data of Hainsworth et al. and shows in an unselected population nearly the same encouraging results. [Table: see text]
Impact of the 92-gene assay on cost of diagnosis of tumor type in metastatic cancer of uncertain origin.
Authors: Bentley Tanya G. , Schroeder Brock , Schnabel Catherine A. , Ortendahl Jesse , Hsiao Wendy C. , Erlander Mark G. , Broder Michael S. 
Published: March 2020

e15104 Background: Molecular classification of tumors has been incorporated into clinical algorithms for patients with metastatic cancers of uncertain origin. This study is a comprehensive cost analysis—characterizing standard of care for metastatic disease, cost implications of correct vs incorrect diagnosis, and cost effectiveness of implementing molecular classification into the diagnostic paradigm. Methods: A deterministic model was developed to project the cost and effectiveness of standard care for metastatic tumors of uncertain origin, compared with incorporating use of the 92-gene assay at 3 points: before immunohistochemical (IHC) analysis, or after 1, or 2 sets of IHC stains. For each strategy, total and incremental costs, life-years (LYs), quality-adjusted life years (QALYs), and incremental cost effectiveness ratios (ICERs) were projected, as well as the % of patients treated correctly vs incorrectly. Model inputs and costs were based on published literature, analyses of the SEER database, the Physicians’ Fee and Coding Guide 2012, and interviews with disease experts. Sensitivity analyses were performed on key inputs. Results: When standard care was compared with each 92-gene assay strategy, costs increased between $4,804 and $6,038 and QA-survival by 1.03-1.15 months. Using the 92-gene assay after 1 set of IHC stains was the most cost effective strategy ($50,273/QALY). Overall, the 92-gene assay increased the % of patients treated correctly and decreased the % of patients treated with empiric therapy compared with standard care. When compared with incorrect treatment, correct treatment provided an additional 5.4 QA-months of survival. Sensitivity analyses identified that costs of empiric treatment, the 92-gene assay, and lung cancer treatment had the greatest effect on outcomes. At a societal willingness-to-pay (WTP) threshold of $100,000, the 92-gene assay was cost effective 94% to 99% of the time. Conclusions: Use of the 92-gene assay is considered cost effective using current societal WTP thresholds, represents an efficient use of economic resources that improves patients' survival and quality of life, and could contribute to standardization of the costs of diagnosis.
EGFR family and c-Met expression profiles and prognostic significance in esophagogastric adenocarcinoma.
Authors: Chan Ellie , Alkhasawneh Ahmad , Duckworth Lizette Vila , Zuluaga-Toro Tania , Lu Xiaomin , Hughes Steven J. , George Thomas J. 
Published: March 2020

e15108 Background: Targeted therapy of HER2 overexpression in patients with esophagogastric adenocarcinoma (EGA) improves survival; however, the effect is transient due to the development of resistance. Targeting of EGFR alone in EGA was not active. cMet overexpression is suggested to be a possible resistance pathway for EGFR and HER-2 inhibition. We characterized the expression profile of the EGFR family of receptors and cMet as well as their prognostic significance in EGA. Methods: This retrospective analysis included all patients (pts) with EGA who underwent primary resection at the University of Florida from 2001 to 2011 without neoadjuvant therapy. Demographics, risk factors, tumor features, and outcome data were analyzed. Central blinded immunohistochemistry (IHC) was performed on paraffin embedded tumor specimens with EGFR, HER2, HER3, HER4 and cMet expression scored as low (0, 1+) or high expression (2+, 3+). Descriptive statistics, Fisher exact test, Cox regression and Kaplan-Meier methods were used for statistical analyses. Results: 52 pts (42 M/10 F) were analyzed with median age 66 years (37-83). Most tumors (58%) were stage I (T1N0). Receptors expression profiles and their associations are presented in the Table. High HER3-HER4 co-expression was found in 35% of cases (p = 0.002). Univariate analysis did not show significant correlation of age, tumor differentiation, BMI, tobacco use and receptor expression with survival. Stage was the only variable that correlated significantly with survival (p=0.02). Conclusions: This is the first study to our knowledge examining the EGFR family expression relationships and cMet in treatment naïve resected EGA tumors. Associations between receptor expression patterns are of clinical interest for rational development of multi-targeted inhibition. Although our data do not significantly show receptor status as a prognostic factor, some receptor expression associations suggest trends towards worse survival. Larger studies are warranted for further investigation. [Table: see text]
Salvage gastrectomy for unresectable advanced gastric cancer after combination chemotherapy with docetaxel, cisplatin, and S-1.
Authors: Hosoda Kei , Yamashita Keishi , Sakuramoto Shinichi , Mieno Hiroaki , Higuchi Katsuhiko , Moriya Hiomitsu , Katada Natsuya , Kikuchi Shiro , Watanabe Masahiko 
Published: March 2020

e15113 Background: The prognosis for patients with unresectable advanced gastric cancer treated with chemotherapy alone is extremely poor. We have evaluated the safety and efficacy of salvage gastrectomy following chemotherapy with docetaxel, cisplatin, and S-1 (DCS) in patients with unresectable advanced gastric cancer. Methods: We evaluated 30 patients with unresectable advanced gastric adenocarcinoma whose lesions were down-staged by DCS chemotherapy and who underwent salvage gastrectomy with lymph node dissection from 2006 to 2012, when visible lesions were judged resectable. We retrospectively reviewed their medical records to identify factors that would influence overall survival. Results: Of the 30 patients, 17 had extra-regional lymph node metastases, 5 had liver metastases, 9 had peritoneal dissemination and 6 had pancreatic head invasion prior to DCS chemotherapy. Of the 30 patients, 23, 3, and 4 underwent R0, R1, and R2 resection, respectively. No in-hospital deaths or reoperations occurred. Pathological evaluation of primary tumors revealed grades 3, 2, 1b, 1a, and 0 tumor regression in 4, 9, 7, 7, and 2 patients, respectively. Median progression-free survival was 19 months.Two-year progression-free survival and overall survival rates were 45% and 65%, respectively. Of 17 patients with target tumors, 15 had partial responses, making the overall response rate 88%. The most common grade 3/4 hematologic toxicity was neutropenia (56%); all treatment-related toxicities were resolved, and no patient died of toxicity-related causes. Univariate analysis showed that R1/2 surgery (p<0.001), diffuse type histology (p=0.054), histological grade 0/1a/1b following chemotherapy (p<0.033), ypN3 (p<0.001) and yply2/3 (p=0.003), were significantly prognostic of reduced overall survival. A multivariate proportional hazard model found that ypN3 (p=0.003) was the sole independent prognostic factor. Conclusions: Salvage gastrectomy after DCS chemotherapy was safe and effective in patients with unresectable advanced gastric cancer. Lymph node metastasis after chemotherapy was significantly prognostic of poor prognosis, suggesting the need for further treatment.
Expression of cyclin D1 and p21(WAF1/CIP1) in human gastric carcinoma and its clinicopathologic significance.
Authors: Michalaki Vasiliki , Theodosopoulos Theodosios , Kondi- Pafiti Agathi , Gennatas Constantine G. 
Published: March 2020

e15114 Background: The deregulation of cyclin, cyclin-dependent kinases (CDKs) and their inhibitors could have a crucial role in the development of diverse human cancers. Alterations in cell cycle regulators and subsequent deregulation of the cell cycle are frequently involved in tumorigenesis and/or tumor progression. The aim of our study was to detect the abnormal expression of cyclin D1 and p21(WAF1/CIP1)in gastric carcinoma and investigate its clinicopathologic significance. Methods: Proteins of cyclin D1 were detected by immunohistochemistry in 80 cases of advanced gastric carcinoma, and 30 cases of benign gastric diseases (chronic gastritis, atrophic gastritis, gastric metaplasia, and gastric dysplasia). From each patient formaldehyde–fixed paraffin sections were stained and examined by immunohistochemistry using monoclonal antibodies.All tumor cells with distinct nuclear staining were considered positive. Results: Sixty-five patients were male and forty five female. Normal gastric epithelium showed consistently positive immunostain for p21WAF1/CIP1. Loss of p21WAF1/CIP1 expression was noted in 65% of intestinal type adenocarcinoma and in 90% of diffuse type adenocarcinoma. Overexpression of cyclin D1 was detected in 90% of advanced gastric carcinomas. Among the various clinicopathological findings, overexpression of cyclin D1 was associated with lymph-node metastasis (P=0.003) and recurrence (P=0.044). Loss of p21WAF1/CIP1 expression was more frequent in diffuse type cancers (P=0.005) and was correlated with recurrence (P=0.002) and death (P=0.001). Conclusions: These findings suggest that overexpression of cyclin D1 is a frequent finding in gastric cancer and immunohistochemical analysis for cell cycle regulators, might be a useful prognostic indicator in gastric cancer.