bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality indicator for esophagogastroduodenoscopy in screening gastric cancer.
Authors: Lee Yong Chan , Park Chan Hyuk , Chung Hyun Soo , Lee Hyuk , Park Jun Chul , Lee Sang Kil 
Published: February 2017

25 Background: The national gastric cancer screening program including endoscopy has been introduced in Korea in which the high incidence of gastric cancer have been reported. The good quality indicators of screening endoscopy for gastric cancer are mandatory to improve the detection rate. However, most quality indicators were focused on the standardization of an endoscopy unit rather than the individual assessment of endoscopists for cancer screening ability. We aimed to identify quality-assessment indicators associated with screening gastric cancer. Methods: The database records for 54,889 subjects who underwent esophagogastroduodenoscopy (EGD) for screening purpose at the Yonsei University Severance Hospital Health Promotion Center, Seoul, Korea between February 2006 and July 2013 were analyzed. All the endoscopists (n=66) involved in this study were experienced endoscopists who performed 1,000 or more EGDs. The detection rate of early gastric neoplasm according to endoscopists were assessed. The detection rates of various gastric lesions other than gastric epithelial neoplasms were also analyzed. The scoring formula for predicting the qualified endoscopists was proposed and analyzed. Results: Of the enrolled subjects, mean age was 48 years and the percentage of males was 59.7%. The percentage of gastric dysplasia, early gastric cancer, and advanced gastric cancer was 0.18%, 0.10%, and 0.04%, respectively. Most frequently detected lesions were gastric erosions (22.30%) followed by atrophic gastritis and intestinal metaplasia. In multivariate analysis, the detection rates of gastric subepithelial lesion or gastric diverticulum were independent associate factors with early gastric neoplasm detection. Cochran-Armitage trend test confirmed that higher quality score group was associated with significant higher early gastric neoplasm detection rate. Conclusions: The detection rates of gastric subepithelial lesion or gastric diverticulum are well correlated with early gastric neoplasm detection. the proposed quality score formula can be a good indicator assessing endoscopist's ability to detect early gastric neoplasm.
Metabolic landscape using 18F-FDG PET and its clinical significances in advanced biliary tract cancer.
Authors: Cho Kyoung - Min , Kim Tae Yong , Oh Do-Youn , Lee Kyung-Hun , Han Sae-Won , Im Seock-Ah , Kim Tae-You , Bang Yung-Jue 
Published: February 2017

252 Background: Metabolic landscape evaluated by 18F-FDG positron emission tomography (PET) in advanced biliary tract cancer (BTC) has not been studied. Furthermore, the clinical meanings of metabolic features have rarely been reported. We evaluated the metabolic features using 18F-FDG PET and its clinical significances in advanced BTC. Methods: We consecutively enrolled advanced BTC patientswho underwent PET prior to palliative chemotherapy between 2003 and 2013. We retrospectively evaluated the findings of PET such as SUVmax, lesion numbers, involved organ and pathologic findings and other clinical factors including response to chemotherapy, progression-free survival (PFS) and overall survival (OS). Results: A total of 106 patients were enrolled (intrahepatic cholangiocarcinoma (ICC):53, extrahepatic BTC :7, gallbladder cancer (GB Ca) :30, and ampulla of vater cancer (AoV Ca): 16 patients) ECOG PS 0-1 in 89 and PS 2 in11 patients. 52.8 % of patients received gemcitabine-based chemotherapy and 47.1% of patients received 5-FU-based chemotherapy. The SUVmax was median 7.8 (range 0-44). Fifty-four percent of patients showed higher SUVmax in metastatic lesion than primary site. The SUVmax was different according to primary origin (ICC: 9.10, extrahepatic BTC: 5.90, GB Ca : 9.10, AoV Ca :6.37, p=0.008) and histologic differentiation (well-differentiated: 4.95, moderately-differentiated :6.60, poorly-differentiated :14.50, p=0.004) Patients with a SUVmax of >7.5 had more poorly differentiated histology and more PET uptake-lesions (p < 0.05) than those with a SUVmax of <7.5. The OS and PFS of all patients were 8.3 (95% CI: 5.7 – 10.8 ) and 4.9 months (95% CI: 3.4 – 6.3), respectively. Patients with a SUVmax of <7.5 had a significantly longer OS (11.4 vs. 7.4 months, p = 0.007) and PFS (6.6 vs. 4.3 months, p = 0.024) than those with a SUVmax of >7.5. In multivariate analysis, SUVmax was also a significant prognostic factor for OS (p=0.012) and PFS (p=0.039). Conclusions: Metabolic landscapes of advanced BTC are different according to primary origin and histology. This metabolic feature such as SUVmax could be a potential prognostic factor for OS and PFS in advanced BTC.
Efficacy of platinum chemotherapy agents in the adjuvant setting for adenosquamous carcinoma of the pancreas.
Authors: Wild Aaron Tyler , Dholakia Avani Satish , Fan Katherine Yu-Ting , Kumar Rachit , Laheru Daniel A. , Zheng Lei , De Jesus-Acosta Ana , Ellsworth Susannah G. , Hacker-Prietz Amy , Voong K Ranh , Hruban Ralph H. , Tran Phuoc T. , Pawlik Timothy M. , Wolfgang Christopher Lee , Herman Joseph M. 
Published: February 2017

269 Background: Pancreatic adenosquamous carcinoma (PASC) accounts for only 1-4% of exocrine pancreatic cancers and carries a particularly poor prognosis. This retrospective study was performed to determine whether inclusion of a platinum agent as part of adjuvant therapy is associated with improved survival in patients with PASC. Methods: Records of all patients who underwent pancreatic resection at our institution from 1986-2012 were reviewed to identify those with PASC. Multivariable Cox proportional hazards modeling was used to assess for significant associations between patient characteristics and survival. Results: In total, 62 patients with PASC were identified among 5,627 cases (1.1%). Median age was 68 (interquartile range [IQR], 57-77) and 44% were female. Multivariate analysis revealed that among all patients (n=62) the following factors were independently predictive of survival: lack of adjuvant therapy (hazard ratio [HR]=3.558, p=0.0002), positive margin (HR=3.466, p=0.0003), lymph node involvement (HR=3.482, p=0.004), and age (HR=1.030, p=0.035). Among patients who underwent adjuvant therapy (n=39), those who received a platinum agent as part of the adjuvant therapy regimen experienced a longer median survival of 19.1 months (95% CI, 13.8-24.4) compared to 10.7 months (95% CI, 7.9-13.5) for patients who never received a platinum agent (p=0.011, log-rank test). Given this improvement in survival on univariate analysis, a second multivariable model was constructed to elucidate factors associated with survival among patients who received adjuvant therapy in order to confirm the univariate result while controlling for potential confounding risk factors. Backward elimination performed using this second multivariable model revealed that inclusion of a platinum agent in the adjuvant regimen (median survival HR=0.408, p=0.040) and larger tumor diameter (HR=1.259, p=0.047) were independent predictors of survival for this cohort. Conclusions: Addition of a platinum agent to adjuvant regimens for resected PASC should be considered as a means to improve survival among these high risk patients, though collaborative prospective investigation is needed.
Final result of a phase I study of combination of pasireotide (SOM 230) LAR plus gemcitabine in metastatic pancreatic cancer (MPC).
Authors: Suleiman Yaman , Springett Gregory M. , Siegel Erin M. , Shibata David , Fulp William J. , Kim Richard D. 
Published: February 2017

277 Background: Pasireotide is a cyclohexapeptide engineered to bind to multiple somatostatin (SST) receptor subtypes (SST 1, 2, 3, and 5) to mimic the action of natural somatostatin with 40-times higher affinity for SST1 and SST5 and 5-times higher affinity for SST3 compared to octreotide and is potent inhibitor of insulin-like growth factor-1 (IGF-1). SST receptors and IGF receptors are highly expressed in pancreatic cancer, therefore potentially making it a valuable target. Methods: A 3+3 dose escalation design was used; patients with previously untreated MPC were eligible for the trial. Patients received GEM 1000 mg/m2(30-min, once-weekly IV infusion for 3 out of 4 weeks) and SOM 230 LAR according to dose escalation. Two dose levels were planned, 40mg IM and 60 mg IM once a month. Cohort was expanded to 10 more patients at the highest tested dose to further access safety and efficacy. IGF-1, IGFBP (insulin-like growth factor binding protein)-1, and IGFBP-3 were measured at baseline and with each restaging. Results: 20 patients enrolled with this study were treated and 16 patients (median age 65.5 years; male/female 6:10) were evaluable for safety and efficacy. No dose limiting toxicities were observed with the two used doses, therefore cohort at 60mg was expanded to 10 patients to assess efficacy. 12 % (2/16) of patients had partial responses (PR), 56% (9/16) had stable disease (SD) as best response. Median PFS was 4.1 months (range 1 to 16 months) and median overall survival was 6.8 months. Most common grade 3 or 4 toxicities were hyperglycemia (n=5), increased bilirubin (n=2), neutropenia (n=1), thrombocytopenia (n=1) and fatigue (n=1). Median baseline IGF-1 level was lower in Pts with stable disease than in progressive disease (63 vs.71 ng/mL), the median drop in the level of IGF-1 between the first cycle and the last cycle was more prominent in the stable disease than progressive disease (16 vs. 28 ng/mL). Conclusions: Pasireotide in combination with gemcitabine was well-tolerated. The disease control rate (56% SD + 12% PR) in patients with MPC. Baseline IGF-1 level may potentially be a prognostic and predictive biomarker for pasireotide. These results are promising and warrant further evaluation. Clinical trial information: NCT01385956.
Phase II study of first-line trebananib plus sorafenib in patients with advanced hepatocellular carcinoma (HCC).
Authors: Abou-Alfa Ghassan K. , Blanc Jean-Frédéric , Miles Steven , Ganten Tom M. , Trojan Jorg , Cebon Jonathan S. , Liem Andre K. D. , Lipton Lara Rachel , Gupta Charu , Wu Benjamin , Litten Jason B. , Saltz Leonard 
Published: February 2017

286 Background: Trebananib is a first-in-class antiangiogenic therapy that sequesters Ang1 and Ang 2, preventing their interaction with the Tie 2 receptor. A previous study of the combination of trebananib with sorafenib in renal cell carcinoma showed an acceptable toxicity profile. Elevated Ang 2 levels have been associated with a poor prognosis in HCC. We thus evaluated the safety and efficacy of trebananib plus sorafenib in HCC. Methods: Patients with HCC, ECOG ≤ 2, Childs-Pugh A, and adequate organ function received IV trebananib at 10mg/kg weekly (cohort 1) or 15 mg/kg weekly (cohort 2) plus sorafenib 400 mg PO twice daily. Thirty patients were accrued to each cohort to provide a power of 80% with the 1-sided exact test for single proportion at α = 0.20 to show a ≥ 78% PFS rate at 4 months relative to 62% reported in the sorafenib historical control. Secondary endpoints included safety and tolerability, progression free survival, objective response rate, disease control rate, time to progression, and overall survival. Results: See table. Conclusions: Trebananib at 10 mg/kg and 15 mg/kg plus sorafenib were well tolerated in patients with advanced HCC. When compared with historical controls, study results did not show an improvement in PFS rate at four months. Clinical trial information: NCT00872014. [Table: see text]
Pre-90Y hepatic radiotherapy hemoglobin and liver functions to predict overall survival in unresectable, chemotherapy-refractory metastatic colorectal cancer.
Authors: Kennedy Andrew S. , Ball David , Cohen Steven J. , Cohn Michael , Coldwell Douglas M. , Drooz Alain , Ehrenwald Edward , Kanani Samir , Moeslein Fred M , Nutting Charles W. , Putnam Samuel G. , Rose Steven C. , Savin Michael , Schirm Sabine , Sharma Navesh K , Wang Eric 
Published: February 2017

292 Background: Patients with liver metastases from colorectal cancers (mCRC) can benefit from 90Y resin microsphere radioembolization (RE) administered via the hepatic arteries. This study investigated which standard laboratory tests may assist in improving treatment outcomes by identifying potentially correctable pre-radiation abnormalities prior to delivery of RE. Methods: A database containing retrospective review of 606 mCRC patients treated consecutively from July 2002 to December 2011 at 11 US institutions was used. Data collected included background characteristics, prior chemotherapy, surgery/ablation, radiotherapy, vascular procedures, 90Y treatment, subsequent adverse events and survival. Kaplan-Meier estimates compared survival of patients across lines (0–≥4) of chemotherapy. The following values were obtained within 10 days prior to treatment: hemoglobin, albumin, alkaline phosphatase, AST, ALT, total bilirubin and creatinine. CTCAE v3.0 grade was assigned to each parameter and analyzed for impact on survival by line of chemotherapy. Where applicable, Consensus Guidelines were used to establish the abnormal limits for RE. Results: 606 patients (370 Male; 236 Female) were studied with a median follow-up of 8.5 months (IQR 4.3–15.6) after RE. Fewer than 11% of patients were treated outside recommended guidelines, with grade 2 albumin (<3–2.0 g/dL) being the most common (10.5%) at time of RE. Abnormal parameters (grade >0) were associated with statistically significantly decreased median survivals (p<0.05) and this was consistent across most lines of prior chemotherapy. Compared to patients with grade 0, those with grade 2 albumin decreased median survival by 67%; for grade 2 total bilirubin, by 63%; and grade 1 hemoglobin, by 66%. Conclusions: Review of pre-RE laboratory parameters may aid in improving median survivals if correctable grade >0 values are addressed prior to radiation delivery. Hemoglobin <10 g/dL is a well-known negative factor in radiation response and is easily corrected. Improving other parameters is more challenging. These efforts are important in optimizing treatment response to liver radiotherapy.
Streptozocin-based chemotherapy in patients with advanced pancreatic neuroendocrine tumors.
Authors: Pavel Marianne E. , Dilz Lisa-Marie , Denecke Timm , Steffen Ingo , Prasad Vikas , Pape Ulrich-Frank , Pascher Andreas , Heetfeld Maximilian , Wiedenmann Bertram 
Published: February 2017

295 Background: The role of systemic chemotherapy for advanced pancreatic neuroendocrine tumours (pNETs) is controversially discussed. Objective response rates (RR) with streptozocin(STZ)-based chemotherapy range between 6% and 69%. Novel targeted drugs have recently been approved, however sequence of treatment remains unclear. We aimed to evaluate efficacy of STZ+5-FU chemotherapy in a large pNET cohort. Methods: Clinical data of 95 patients (pts) with advanced pNET who had been treated with STZ+5-FU between Aug 1998 and Sept 2013 were analyzed retrospectively. RR, time to tumour progression (TTP) and overall survival (OS) were assessed. Assessment of RR was judged by tumour board involving an experienced radiologist (TD). Results: Median age at start of chemotherapy was 60 years (range 32-80). 74 pts (77.9%) had non-functional pNETs. In 52 pts (54.7%) STZ+5-FU was 1st line systemic therapy. 11.6% had G1, 78.9% G2 and 6.3% G3 tumours. Baseline progression was evident in 75.8% of cases. Mean number of therapy cycles was 6 (range 1-18). Treatment was discontinued for toxicity in 15.8% of the cases. Partial response was seen in 43.2% of pts, stable disease in 32.6% and disease progression as best response in 18.9% of cases. Overall TTP was 13.7 months and was independent of prior systemic treatment (1st line vs. >1st line, 13.6 vs. 25.3 months, P= 0.54). Functionality had no impact on median TTP. There was no difference between pts with G1 and G2 NET (TTP 21.3 vs. 16.4 months, P=0.78). Median OS was 27.6 months (range 0.8-174 months). In pts with at least two extrapancreatic disease sites (34.7%) median OS was inferior compared to pts with one disease site involvement (37.3 vs. 70.5 months, P=0.02). Conclusions: The combination of STZ and 5FU was associated with a considerable objective response rate in advanced G1/G2 pNETs who had prior disease progression. Efficacy of treatment was not depending on therapy line or grading (G1 vs. G2). Objective response rate is higher than those observed with targeted drugs. This finding along with good tolerability of the treatment strengthens the durable value of this chemotherapy in the era of targeted drugs for the outcome of pts with pNETs.
Associations between K-ras mutation, smoking, and prognosis of pancreatic cancer.
Authors: Saito Kei , Nakai Yousuke , Isayama Hiroyuki , Sasaki Takashi , Takahara Naminatsu , Hamada Tsuyoshi , Miyabayashi Koji , Yamamoto Keisuke , Mizuno Suguru , Mohri Dai , Kogure Hirofumi , Yamamoto Natsuyo , Hirano Kenji , Ijichi Hideaki , Tateishi Keisuke , Tada Minoru , Koike Kazuhiko 
Published: February 2017

298 Background: Smoking is recognized as a risk factor for pancreatic cancer, but its associations with prognosis are not fully elucidated. Smoking was associated with poor outcomes in colon cancer, especially in patients with K-ras mutation (J Clin Oncol. 2013;31:2016-23). Therefore, we conducted this retrospective analysis of the associations of K-ras mutation, smoking and prognosis in patients with pancreatic cancer. Methods: Patients with pancreatic cancer who received surgery or chemotherapy at the University of Tokyo Hospital were retrospectively studied. The prognosis of patients with mutant and wild K-ras were compared. Overall survival was evaluated using Kaplan-Meier methods and compared by long-rank test. Cox regression models were used to calculate hazard ratios (HRs) to evaluate the prognostic factors in patients with pancreatic cancer with mutant K-ras or wild K-ras. Results: Between January 2009 and August 2013, K-ras mutation analysis was evaluated in 187 patients (47 surgical resection and 140 chemotherapy). K-ras mutation was detected in 74.3%. The rates of current-, ex- and never-smokers were 18.2%, 31.6% and 50.3%, respectively. In patients with mutant K-ras, the rate of male gender (46.0% vs. 29.0%), presence of distant metastasis (50.4% vs. 31.3%) and median CA19-9 (374 U/mL vs. 136 U/mL) were significantly higher than that in patients with wild K-ras. The rate of ever smokers (current- and ex-smokers) did not differ significantly (48.2% in mutant K-ras vs. 56.3% in wild K-ras, p=0.403). Median survival time (MST) was 16.7 (95%CI, 11.9-21.8) months in patients with mutant K-ras, compared with 20.3 (95%CI, 15.8-34.6) in patients with wild K-ras (p=0.193). Meanwhile, MST was 22.2 (95%CI, 16.9-27.9) vs. 14.8 (95%CI, 9.1-19.4) months in patients with and without smoking (p=0.024). After adjustment by age, gender, performance status, CA19-9 and treatment, HRs of smoking were 1.96 (95%CI, 1.06-3.68, p=0.032) in patients with mutant K-ras, but the association was not significant in patients with wild-K-ras (HR 1.35 [95%CI, 0.37-5.28], p=0.653). Conclusions: As previously reported in colon cancer, smoking was associated with poor prognosis in pancreatic cancer with K-ras mutation.
Phase I/II trial of gemcitabine (Gem) plus irinotecan (CPT-11) for metastatic pancreatic cancer (MPC).
Authors: Yamai Takuo , Ioka Tatsuya , Sueyoshi Hironari , Takada Ryoji , Fukutake Nobuyasu , Ashida Reiko , Katayama Kazuhiro 
Published: February 2017

301 Background: Treatment options for patients with metastatic pancreatic cancer are still limited. Recently, new strategies to prolong disease control are reported. We conducted phase I/II trial of GEM+CPT-11 combination chemotherapy for MPC to evaluate the effectiveness and safety. Methods: As phase I study, traditional 3 + 3 dose-escalation design was used to determine the maximum tolerated dose (MTD) and the recommended phase II dose. Four escalating dose levels of GEM/CPT-11 (800/60 mg/m2, 1000/60 mg/m2, 1000/80 mg/m2, and 1000/100 mg/m2) were studied. As results of this investigation, the recommended phase II dose was GEM 1000 mg/m2 and CPT-11 100 mg/m2, biweekly. Phase II eligibility included naïve MPC, PS0-2, Pathological diagnosis, no refractory ascites and pleural effusion, and adequate organ function. Primary endpoint was overall survival. Results: Eighteen patients were entered phase I study. The DLTs were anorexia, and nausea/vomiting. Severe neutropenia was rare. MTDs were determined GEM 1000 and CPT-11 100 mg/m2. After that, we investigated phase II trial in 40 patients. There were 6 partial response, 14 stable disease, 18 progressive disease and 2 in-evaluable. Response rate was 16%. The median overall survival was 7.5 months; progressive disease 4.0 months. Grade 3 to 4 toxicity included neutropenia (7%), anemia (7%), diarrhea (7%), ALT elevation (10%), pneumonitis(7%). There was no treatment-related death. Conclusions: This combination chemotherapy is not effective as first-line chemotherapy for metastatic pancreatic cancer. But this is safe and generally well tolerated. This chemotherapy could be effective of salvage chemotherapy with low toxicity after standard chemotherapy such as FOLFIRINOX.
Potential factors influencing initial sorafenib dose selection in hepatocellular carcinoma (HCC): U.S. regional analysis of GIDEON.
Authors: Piperdi Bilal , Cohn Allen Lee , El-Khoueiry Anthony B. , Geschwind Jean-Francois , Gholam Pierre Michel , Mantry Parvez , Martin Robert C. G. , McGuire Brendan , Miksad Rebecca A. , Sanyal Arun J. , Venook Alan Paul , Babajanyan Svetlana , Goldenberg Alec 
Published: February 2017

304 Background: GIDEON is a global, prospective, noninterventional study to evaluate sorafenib (SOR) safety under real-life practice conditions. Here we examine potential factors that may have had an impact on initial SOR dose (ID) selection in the U.S. cohort of GIDEON. Methods: Patients (pts) with unresectable HCC who were candidates for systemic therapy and for whom a decision was made to treat with SOR were eligible for inclusion. ID choice was at physician discretion. Baseline characteristics were analyzed for their potential impact on the choice of ID. Adverse events (AEs) were evaluated by ID. All results are descriptive. Results: 563 pts were valid for safety. 54% of pts received the recommended ID of 800 mg/d, 35% received 400 mg/d, and 11% other (includes 100, 200, 600 mg/d. dose). Among pts who had an ID <800 mg/d, 37% underwent a dose increase to 800 mg/d. ID did not appear to differ by baseline Child-Pugh or its components, BCLC stage, etiology, or body mass index. By ECOG performance status (PS), IDs of 800/<800 mg/day were given as follows: PS ≤1: 55%/45%; PS ≥2: 44%/56%. By age, corresponding values were 57%/42% for <75 yr; 33%/67% for ≥75 yr. The incidence of AEs was similar across dose levels (Table). Conclusions: Baseline liver function, tumor stage, and etiology did not seem to have an influence on ID selection. We observed a trend toward lower ID in pts with age ≥75 yr and PS ≥2. Despite differences in average daily dose and time on drug, the safety profile for each ID was similar and dose adjustments may have contributed. Additional analyses are being evaluated to assess these and other contributing factors. Clinical trial information: NCT00812175. [Table: see text]