bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro and in vivo evaluation of sunitinib eluting beads.
Authors: Bize Pierre E. , Jordan Olivier , Fuchs Katrin , Dormond Olivier , Duran Rafael , Doelker Eric , De Baere Thierry , Denys Alban 
Published: February 2017

246 Background: Chemoembolization is used to treat liver malignancies. However recurrence occurs frequently, possibly because of neoangiogenesis triggered by ischemia caused by the embolic agent. In this context, the combination of an embolic agent with an anti-angiogenic drug seems appealing. This study characterizes the in vitro loading and release profile of sunitinib eluting beads of different sizes and their pharmacokinetic profile in a rabbit model. Methods: 70-150 μm and 100-300 μm drug eluting beads (DC Bead, Biocompatibles UK) were loaded by incubation in a sunitinib hydrochloride solution. Drug was quantified by spectrophotometry at 430 nm. Drug release was measured over one-week periods and normalized using an internal standard in 30% ethanol in NaCl 0.9%. New-Zealand white rabbits were used. Eight animals received 0.2 ml of 100-300 μm DC Bead loaded with 6 mg of sunitinib in the hepatic artery (group 1) and 4 animals received 6 mg of sunitinib p.o. (group 2). Half of the animals were sacrificed after 6 hours and half after24 hours. Liver enzymes were measured at 0, 6 and 24 hours in both groups. Plasmatic sunitinib concentration was determined by tandem mass spectroscopy (LC MS/MS) at 0, 1, 2, 3, 4, 5, 6 and 24 hours. At sacrifice, the livers were harvested and sunitinib concentration in liver tissue was assessed by LC MS/MS. Results: High drug loading was obtained for both microsphere bead sizes. Particle shrinking was observed with adsorption of sunitinib. Almost complete release of sunitinib was detected under physiological conditions, with very similar release for 70-150 μm and 100-300 μm (t50%=1.2 h) DC Bead. Conclusions: Sunitinib eluting beads are well tolerated by rabbits when administered in the hepatic artery. No unexpected toxicity was observed. Very high drug concentration can be obtained at the site of embolization with minimal systemic passage.
Efficacy and safety of FOLFIRINOX in patients with pancreatic metastatic cancer.
Authors: Metges Jean-Philippe , Ramée Jean François , Faroux Roger , Douillard Jean Yves , Porneuf Marc , Cumin Isabelle , Etienne Pierre-Luc , Gourlaouen Alain , Geslin Guillaume , Achour Nacredine , Delalande Anne Helene , Soulie Patrick , Le Bihan Gerard , Le Roux Catherine , Miglianico Laurent , Deguiral Philippe , Campion Loic , Riche Christian , Grude Francoise 
Published: February 2017

248 Background: Efficacy and safety of a combination chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) is one of the gold standard in metastatic pancreatic cancer as first-line therapy for patients with PS 0-1, good haematological and renal function and a subnormal bilirubin level. Pending approval, this treatment has been allowed in Brittany (B) and Pays de la Loire (PL) respecting these criteria. Methods: Observatory of Cancer B/PL is a network of 50 private/public cancer centers focused on good practice for cancer drugs use. Our aim is to evaluate the use of FOLFIRINOX between July 2010 and June 2013 in B/PL. Sex, age, successive chemotherapeutic regimens, toxicities, response rate, progression free survival (PFS) and overall survival (OS) have been studied. Results: Data of 79 patients, treated in 2010 (37%), in 2011 (54%) or early 2012 (9%) have been studied (44 men, median age 62 years [37-74]). 64 patients were metastatic when cancer was diagnosed. Principal site of metastases was liver (73%). 17 primary tumors were resected and 15 patients received an adjuvant chemotherapy (gemcitabine (n=14)).The median number of treatment cycles was 9 [1-24]. Objective response was observed in 29 patients (37%), disease stabilization in 18 patients (23%) and progression in 18 patients (23%). During treatment, 75% of patients had a dose adjustment and 30 % had one or more dose delays. 22 patients presented grade III/IV toxicity (almost neurotoxicity or haematologic). 42 patients had a second line of treatment (mainly gemcitabine) and 7 patients a third line. The median PFS and OS were respectively 174 days IC95% [125-216] and 309 days IC 95% [229-376]. Conclusions: Our preliminary results are relatively convenient with those of Conroy et al in 2011. A higher rate of response (37% vs 32%) has been found. Concerning PFS and OS, our results are clearly worst with 174 vs 195 days and 309 vs 338 days. Our results confirm the aggressiveness of this schedule with 75% of the patients requiring a dose adjustement. Analysis of all pancreatic metastatic patients treated by FOLFIRINOX in B/PL by the Observatory of Cancer allows to assess its good use in the real life.
Effect of body mass index in patients undergoing resection for gastric cancer: A single-center U.S. experience.
Authors: Wong Joyce , Rahman Shams , Saeed Nadia , Lin Hui-Yi , Almhanna Khaldoun , Shridhar Ravi , Hoffe Sarah , Meredith Kenneth 
Published: February 2017

25 Background: With the rise of obesity in the U.S., the impact of body mass index (BMI) on surgical outcomes and survival in gastric cancer remains undetermined. Methods: An IRB-approved, prospectively-maintained institutional database of patients referred for surgical evaluation of gastric cancer was reviewed. Patients were stratified according to BMI: <18.5 (underweight), 18.5-25 (normal weight), 25.1-30 (overweight), and >30 (obese). Clinicopathologic factors and overall survival (OS) were analyzed using polytomous regression, Pearsons correlation and Kaplan Meier when appropriate. Results: From 1997-2012, 222 patients underwent exploration for gastric adenocarcinoma. Of these, 186 (84%) patients had BMI recorded: 9 (5%) with BMI<18.5, 72 (39%) 18.5-25, 62 (33%) 25.1-30, and 43 (23%) >30. 135 (73%) ultimately underwent resection. Operative factors including American Society of Anesthesiology (ASA) score and blood loss were not significantly associated with BMI. Increased BMI was associated with longer operative time, P=0.02. Pathologic factors including proximal tumor location, perineural invasion (PNI), lymphovascular invasion (LVI), positive surgical margins, and positive lymph nodes (LN+) were all associated with a worse OS. Although increased BMI was associated with a lower total lymph node count, P=0.004, the number of LN+ was not associated with BMI. Tumor location, PNI, LVI, margin status, and final pathologic stage were not significantly associated with BMI. Additionally, the use of neoadjuvant or adjuvant chemotherapy was not associated with BMI. Median OS for the group was 22 months. When stratified by BMI, median OS was improved with increased BMI: 21 months for <18.5, 13 months for 18.5-25, 28 months for 25-30, and 34 months for >30, P=0.02. Similarly, disease free survival (DFS) improved with increasing BMI: 2 months for <18.5, 7 months for 18.5-25, 15 months for 25.1-30, and 15 months for >30, P=0.02. Conclusions: Although BMI may impact the technical difficulty of resection for gastric cancer, increasing BMI is not associated with more aggressive disease. In this experience, increased BMI does not adversely impact OS or DFS.
Clinical efficacy of adjuvant surgery following systemic treatments in patients with initially unresectable pancreatic cancer: Results of a project study for pancreatic surgery by the Japanese Society of Hepato-Biliary-Pancreatic Surgery.
Authors: Hirano Satoshi , Satoi Sohei , Yamaue Hiroki , Kato Kentaro , Takahashi Shinichiro , Hirono Seiko , Takeda Shin , Eguchi Hidetoshi , Sho Masayuki , Wada Keita , Shinchi Hiroyuki , Kwon A-Hon , Kinoshita Taira , Nakao Akimasa , Nagano Hiroaki , Nakajima Yoshiyuki , Sano Keiji , Miyazaki Masaru , Takada Tadahiro 
Published: February 2017

255 Background: Medical oncologists or pancreatic surgeons have identified candidates for surgical resection in patients with initially unresectable pancreatic cancer who favorably responded to multimodal treatment. Additional surgical resection during multimodal treatment, is called “adjuvant surgery”. A multicenter survey was conducted to explore the clinical efficacy of adjuvant surgery for initially unresectable pancreatic cancer with a long-term favorable response to systemic treatments. Methods: Clinical data, including the primary endpoint of overall survival were retrospectively compared between 58 initially unresectable pancreatic cancer patients that underwent adjuvant surgery with a favorable response to non-surgical cancer treatments over 6 months after the initial treatment (adjuvant surgery group) and 101 patients who did not undergo adjuvant surgery (control group). Results: The median observation periods were 51 months (20-122) in the control group, and 54 months (26-125) in the adjuvant surgery group, respectively. The actuarial survival rate at 1, 3, and 5 years after initial treatment in adjuvant surgery group (95, 53, and 34%) was significantly better than that in control group (88, 18, and 10%, p<0.0001). The propensity score analysis to provide adjustment of significant differences in the clinical backgrounds between the two groups revealed that adjuvant surgery was a significant independent prognostic variable with an adjusted hazard ratio (95% confidential interval) of 0.569 (0.36-0.89). Subgroup analysis according to the time from initial treatment to surgical resection showed a significant favorable difference in the overall survival in patients who underwent adjuvant surgery over 240 days after the initial treatment. Conclusions: The adjuvant surgery can occupy an important position in the multimodal therapy for patients with initially unresectable pancreatic cancer. The overall survival rate from the initial treatment is extremely high, especially in patients who received systemic treatments for more than 240 days.
A retrospective study of gemcitabine and cisplatin combination therapy as second-line treatment for advanced biliary tract cancer.
Authors: Sasaki Takashi , Isayama Hiroyuki , Nakai Yousuke , Takahara Naminatsu , Akiyama Dai , Yagioka Hiroshi , Kogure Hirofumi , Matsubara Saburo , Ito Yukiko , Yamamoto Natsuyo , Sasahira Naoki , Hirano Kenji , Toda Nobuo , Tada Minoru , Koike Kazuhiko 
Published: February 2017

258 Background: The data of second-line treatment for advanced biliary tract cancer is still limited. We have previously reported feasibility study of gemcitabine and cisplatin combination therapy for refractory biliary tract cancer (Sasaki T et al, Invest New Drugs 2011). In this feasibility study, only 20 pts were enrolled, and both second-line and third-line treatments were involved. Therefore, we conducted a retrospective study of gemcitabine and cisplatin combination therapy as second-line treatment to clarify the treatment outcome of this combination therapy. Methods: Pts with advanced biliary tract cancer who were refractory to gemcitabine containing regimen were enrolled in this study. Gemcitabine 1,000 mg/m2 and cisplatin 25 mg/m2were administered intravenously on days 1 and 8 repeated every 3 weeks. Results: Fifty-nine pts were enrolled in this study. Patient characteristics were: median age 68 (range 25-84); male/female 32/27; performance status 0/1/2 (15/38/6). The primary tumor site was; 24 pts in gallbladders, 18 pts in intrahepatic bile ducts, 15 pts in extrahepatic bile ducts, and 2 pts in ampulla of Vater. The numbers of the pts with locally advanced, metastatic, and recurrent cases were 8, 44, and 7, respectively. Four pts received gemcitabine monotherapy and 55 pts received gemcitabine and S-1 combination therapy as first-line treatment. Response rate and disease control rate were 1.7% and 56.0%, respectively. The median time-to-progression and median overall survival were 3.9 months (95%CI, 2.6 – 5.0 months) and 6.4 months (95%CI, 4.9 – 8.0 months), respectively. Conclusions: Gemcitabine and cisplatin combination therapy showed a moderate efficacy for the treatment of advanced biliary tract cancer as second-line treatment.
Assessment of HER2 status from an epidemiology study in tumor tissue samples of gastric and gastro-esophageal junction cancer: Results from the french cohort of the HER-EAGLE study.
Authors: Monges Genevieve , Terris Benoit , Chenard Marie-Pierre , Penault-Llorca Frederique , Beauclair Sophie , Bibeau Frederic , Emile Jean-François , Volant Alain , Doucet Laurent 
Published: February 2017

26 Background: HER2 is an important prognostic and also a predictive biomarker for trastuzumab response in gastric cancer. Therefore, HER2 status should be tested in all gastro-esophageal junction (GEJ) and gastric cancer (GC) patients. ToGA phase III study showed a benefit in overall survival of trastuzumab added to standard chemotherapy in patients with HER2-positive advanced GEJ/GC. The objective of the HER-EAGLE study was to assess the incidence of HER2 positivity in GEJ/GC cancer. Methods: HER-EAGLE was an international epidemiological, non-interventional study assessing HER2 status by IHC/ISH in tumor samples from any stage in patients with GEJ/GC. Samples were obtained by excision or core biopsy and routinely analyzed via validated Ventana or Dako methods and scoring criteria used in ToGA: HER2-positive if IHC 3+ or IHC 2+ (FISH/SISH confirmed; HER2/CEP17 ratio ≥ 2.0); HER2-negative if IHC 0 or IHC 1+ or IHC 2+ if FISH/SISH negative ratio < 2.0. Overall and subgroup estimates calculated with 95% CI. Data from the French cohort are presented. Results: The HER-EAGLE French cohort included 267 patients (68.6% males) from 7 centers (May 2007 to March 2012), with 150 biopsies (56.2%) and 117 excisions (43.8%). Tumor locations were 65.9% stomach and 34.1% GEJ, and adenocarcinoma types were according to Lauren classification: 170 intestinal (63.7%), 72 diffused (27%), 22 mixed (8.2%) and 3 not available (1.1%). HER2 status was: 36 cases IHC 3+ (13.5%), 51 IHC 2+ (19.1%) whereof 18 ISH positive (35.3%), 35 IHC 1+ (13.1%) and 145 IHC 0 (54.3%). Overall HER2 positivity (IHC 3+ or IHC 2+/ISH+) was 20.2%. Heterogeneity for HER2 staining was observed in 81 samples (30.3%). No statistical difference was found according to cancer stage. HER2 positivity was higher in GEJ (31.9%) than in GC (14.2%), p<0,001, and higher in intestinal (28.2%) compared to diffused adenocarcinomas (5.6%), p<0,001. Conclusions: HER-EAGLE French cohort results confirmed the feasibility of HER2 testing in GEJ/GC in routine practice. The incidence of HER2 overexpression was similar to the literature review, and it was higher in GEJ and intestinal adenocarcinomas type.
Outcome and patterns of care in advanced biliary tract carcinoma (ABC): Experience from two tertiary institutions in the United Kingdom.
Authors: Huggett Matthew T. , Passant Helen , Hurt Chris , Pereira Stephen P. , Bridgewater John A. , Mukherjee Somnath 
Published: February 2017

272 Background: The ABC-02 trial has defined the standard therapy for patients with advanced biliary tract cancer (ABC), however outcome in an unselected patient population in the UK has not been described. We report the outcome of a series of patients with ABC from two large UK cancer networks. Methods: We retrospectively reviewed all cases of ABC presenting to two UK cancer networks over a 9-year period. Patients with a diagnosis recorded under anatomical site (liver, gallbladder or biliary tree) or histological diagnosis (cholangiocarcinoma or adenocarcinoma, liver), were included. Any patients who had surgery with curative intent were excluded. Overall survival (OS) and factors influencing OS were assessed. For the analysis, chemotherapy regimens were considered as: (i) gemcitabine (G)-based vs. non-G-based, (ii) platinum (P)-based vs. non-P-based and (iii) fluoropyrimidine (F)-based vs. non-F-based. Results: 402 patients were available for analysis. The median OS was 6.2 months. On univariate analysis, age ≥ 70 years (p=0.047), advanced disease stage (p<0.001), gall bladder primary (p=0.033), poor performance status (p<0.001) and lack of chemotherapy (p<0.001) were associated with worse outcome. Survival was superior in the 36.4% of patients who received palliative chemotherapy (12.5 versus 4.3 months; p<0.001). In patients receiving chemotherapy, on multivariate analysis males had higher mortality than females (HR=1.71; p=0.006) and stage 4 disease had a higher mortality (HR=2.62; p=0.002) than stage 1-2 disease. Patients who did not receive F-based regimens (HR=5.12; p=0.022) or G-based regimens (HR=5.01; p=0.021) had a higher mortality, whereas the effect of P-containing regimens was of borderline significance (HR=2.23; p=0.086). Sites, age, and multi-agent regimens were not significant. Conclusions: This is the first retrospective series from the UK and one of the largest population-based studies in ABC and confirms the benefit of palliative chemotherapy in an unselected group of patients. F-based regimens appear to be as effective as G-based treatments.
Efficacy and clinical outcomes of radiotherapy with or without chemotherapy in inoperable or post-operative high-risk cholangiocarcinoma.
Authors: Kalyani Nikhil Dhirendra , Engineer Reena , Chaudhari Suresh , Dharia Tejas , Shetty Nitin , Chopra Supriya , Shrivastava Shyam K 
Published: February 2017

273 Background: The purpose of this work was to determine efficacy, toxicity, and patterns of recurrence after radiotherapy (endobilliary and/or external RT) with or without chemotherapy in patients with unresectable or post operative high risk extrahepatic bile duct cancer (EHBDC) and hilar cholangiocarcinoma (Klatskin tumours). Methods: From Aug 2005 to July 2012, 67 patients with non-metastatic EHBDC and hilar cholangiocarcinoma were treated with radiotherapy (endobilliary and / or EBRT) with or without chemotherapy at our institution. Sixty one patients had unresectable disease while remaining six patients were post operative patients. Twenty two patients received only endobilliary RT, 20 patients received only EBRT, while 25 patients received both. Concurrent Gemcitabine during EBRT was given in 10 patients. Histopathological diagnosis was available in 50 patients (75%). Median dose for EBRT and endobilliary RT was 45 Gy (range: 25 Gy to 57 Gy) and 14 Gy (range: 12 Gy to 20 Gy) respectively. Results: Median age was 54 years (range 23-76 years) and there were 37 men and 30 women. Median follow up for whole group was 6 months (range 1-28 months). Seven patients had complete response, 22 patients had partial response, 4 patients had stable disease, while 6 patients had progressive disease after EBRT. Twenty five patients were alive at last follow up. The median overall survival was 7 months and one year survival was 30% for whole group. Patients receiving EBRT (with or without endobilliary) had better survival as compared to patients receiving only endobilliary RT (median survival 13 months Vs 5 months, p=0.001). The main sites of distant disease progression were liver and peritoneum. Eighteen patients had developed cholangitis while 3 patients developed hematemesis due to duodenitis. Conclusions: Radiation in unresectable cholangiocarcinoma is feasible with acceptable clinical outcome and toxicity. Patients receiving EBRT has better outcome as compared to those receiving only endobilliary RT.
Molecular profiles of gastric cancer: The UCSD experience.
Authors: McGee Devon Marcus , Shen John P. , Fanta Paul Timothy , Lowy Andrew M. 
Published: February 2017

29 Background: Gastric cancer is the 2nd leading cause of cancer mortality globally. A small number of studies reported that low TS and ERCC1 mRNA levels are associated with improved survival, and may be important as prognostic factors. Methods: Intratumoral gene expression levels were assessed using laser-captured micro-dissection and quantitative Real-Time PCR on formalin fixed paraffin embedded tumor samples from 22 gastric adenocarcinomas. A retrospective chart review was performed to measure clinical parameters. Primary objectives were to determine the range of expression of TS, ERCC1, and HER2, and to investigate if these biomarkers are predictive of survival. Results: TS, ERCC1, and HER2 median expression levels using RT-PCR were 3.56, 1.54, and 0.085, respectively. Median OS was 62 months. Subjects with low TS trended towards improved survival (92 months vs. 34 months, p: 0.17), as did subjects with low ERCC1 (92 months vs. 55 months, p: 0.44). There was no association between HER2 expression and OS. All subjects had HER2 levels below 0.55. With regard to treatment, 90.9% of patients received platinum-based chemotherapy and 4.5% received HER2-guided therapy. Conclusions: Our results are consistent with prior reports that associate low TS and low ERCC1 with improved OS, and may imply prognostic significance. Although these trends did not reach statistical significance, they are consistent with prior studies. Further molecular studies are needed to better assess the utility of these markers as prognostic indicators. There was no clear trend between HER2 levels and OS, most likely because all subjects had low HER2 levels. However, as accurate determination of HER2 expression is becoming increasingly important in the management of gastric cancer patients, further research into the degree of concordance between RT-PCR assessment and FISH assessment of HER2 gene amplication is warranted. Overall, more molecular studies are needed to better stratify this disease into subtypes, and identify new drug targets for chemo-resistant subtypes.
Small bowel carcinoid: Location isn’t everything.
Authors: Hari Danielle M. , Reich Heidi M Hari , Leung Anna Mary , Lee Ji Hey Hey , Sim Myung-Shin , Wolin Edward M. , Amersi Farin F. 
Published: February 2017

292 Background: Contemporary data has revealed that small bowel carcinoid (SBC) accounts for the majority of gastrointestinal carcinoids. However, data remains limited regarding prognostic factors that impact survival for SBC patients. Using a population-based analysis, we investigate the significance of the primary site of disease for SBC. Methods: The Surveillance, Epidemiology, and End Results database was queried for histologically confirmed SBC between the years 1988 and 2009. Patients were excluded if adequate demographic and staging information was unknown. Overall and disease survival curves (OS and DSS respectively) were analyzed using the Kaplan-Meier method and compared using Log rank testing. Log rank and multivariate Cox regression analysis was used to identify predictors of survival using age, year of diagnosis, race, gender, tumor histology/size/location, TNM stage, number of lymph nodes (LNs) examined and percent of LNs with metastases. Results: Of the 3,834 patients analyzed, the mean age was 62.13 years and 51.2% were male. Median follow up was 50 months. The 10-year OS (63%) and DSS (91%) for duodenal primaries was statistically significant when compared to jejunal (53%, 74%), ileal (50%, 68%) and overlapping primaries (50%, 78%), (p = 0.0290 and < 0.0001, respectively). However, more the 90% of duodenal primaries had stage I and II disease only. On multivariate Cox regression analysis, after adjusting for multiple factors, primary site location was not a significant predictor of survival (p = 0.948 for OS and = 0.625 DSS) while TNM stage, age, tumor size and number of LNs examined portend improved OS and DSS. Conclusions: This population-based study of SBC over the past 30 years refutes the concept that the location of the SBC influences survival. A key element to consider is that more than 90% of duodenal primaries present at early stages. Further screening and diagnostic methods to detect other SBC primary sites could significantly impact survival.