bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes of second line treatment in patients with advanced and metastatic biliary cancers.
Authors: Westin Gustavo Figueiredo Marcondes , Alsidawi Samer , Chandrasekharan Chandrikha , Briggler Andrew M. , Huffman Brendon , Pallante Angeline , Hubbard Joleen Marie , Alberts Steven R. , Halfdanarson Thorvardur Ragnar 
Published: March 2017

420 Background: Advanced biliary cancers respond poorly to chemotherapy and have a dismal survival. Currently gemcitabine-cisplatin (GC) is the standard of care for patients with advanced disease. The efficacy of second line treatment options is not well-defined. We retrospectively evaluated outcomes of patients undergoing second line treatment for advanced biliary cancers at Mayo Clinic. Methods: After obtaining approval from the institutional board review (IRB), we identified 42 patients with advanced and metastatic biliary cancers that progressed after first line (GC) and received second line treatment from 2007-2014. All patients had adequate follow up data. JMP software was used for statistical analysis. Kaplan-Meier method and log-rank tests were used for survival analysis, and multivariate cox proportional hazards model was used to evaluate the prognostic effect of pertinent clinical variables. All tests were two sided and a P value of < 0.05 was considered significant. Results: The median age at diagnosis was 61.5 (range 26-87). The most common regimens used for second line settings were 5-FU-based (69%) followed by gemcitabine-based regimens (19%). The overall response rate (ORR) was 9.1%, while the disease control rate (DCR; stable disease and partial response) was 33%. The median overall survival (mOS) for the entire cohort from first line was 16.8 months (95% CI 12.7-21.7) and the progression-free survival (PFS) was 9.16 months (95% CI 7.3-14.7). From second line start the mOS was 10.4 months (95%; CI 7.3-23.7), and PFS was 2.8 months (95% CI 2.3-4.0). 73% of patients who received second line therapy were alive at 6 months and 50% at 12 months. 25 patients received third line treatment after progression. An univariate and multivariate analysis were performed including age, sex, stage at diagnosis, regimen used, CA19-9 and total body weight loss > 5%, but no significant prognostic factors were identified. Conclusions: Patients with biliary cancers who progress after first line treatment have poor prognosis, but may benefit from second line regimens. 5-FU based regimens were the most commonly used in the second line setting, and 73% of patients who received second line therapy were alive at 6 months.
Utility of endoscopic ultrasound-guided biopsy for genomic analysis of pancreatic exocrine malignancies.
Authors: Larson Brent K , Deng Nan , Tuli Richard , Hendifar Andrew Eugene 
Published: March 2017

423 Background: Endoscopic ultrasound-guided fine needle biopsy (EUS FNB) and aspiration (FNA) are the gold standard for diagnosis of pancreatic malignancies. Oncologists increasingly use tumor genomic analysis to assist with management decisions for these malignancies. While the diagnostic use of FNB/A is known, adequacy of FNB/A tissue for next-generation sequencing (NGS) has not been evaluated. This study examined adequacy of FNB/A and other biopsy types for features that might predict inadequacy for NGS using an Illumina HiSeq platform. Methods: 76 consecutive biopsies (54 EUS FNBs, 8 radiology-guided biopsies, 7 EUS FNAs, 5 endoscopic forceps biopsies, and 2 biopsies of unknown type) of pancreatic exocrine malignancies (74 pancreatic ductal adenocarcinomas, 1 acinar cell carcinoma and 1 ampullary adenocarcinoma) submitted for NGS were assessed for adequacy. Adequacy was compared to other tumor/biopsy features. Subgroup analysis was performed on FNB/As. Analysis was performed via Spearman correlation. Results: 22/76 (29%) samples were inadequate, including 16/54 (30%) FNBs and 4/7 FNAs (57%). 17 were inadequate due to low tumor cellularity, 4 due to tissue size, and 1 due to both. Recorded needle gauges were 18 (n = 2), 19 (n = 2), 22 (n = 42), and 25 (n = 3). Larger needles were associated with adequacy in all samples (p = 0.0047) and in FNB samples (p = 0.05). Samples from metastases were more associated with adequacy than those from the pancreas (p = 0.0357). Radiology-guided biopsies were more likely to be adequate than EUS-guided FNB/As, though this trend did not reach significance (p = 0.0558). Tumor size (range: 1.3-8.7 cm), needle manufacturer (n = 3), number of passes (range: 1-5), biopsy size (range: 0.008-0.336 cm3), endoscopist (n = 4), and tumor location in the pancreas (head/uncinate/body/tail) were not associated with adequacy. Conclusions: These results suggest that metastatic lesions accessible by radiology-guided core biopsy may be preferable to EUS FNB/A for obtaining tissue for NGS. EUS-guided FNB were more likely to be successful using a larger gauge needle.
Randomized phase II study of S-1 monotherapy versus gemcitabine plus S-1 in gemcitabine-refractory advanced pancreatic cancer.
Authors: Ueno Makoto , Ohkawa Shinichi , Kobayashi Noritoshi , Sugimori Kazuya , Kawaguchi Yoshiaki , Kobayashi Satoshi , Taguri Masataka , Yamanaka Takeharu , Mine Tetsuya 
Published: March 2017

429 Background: Gemcitabine is one of the standard chemotherapeutic agents for pancreatic cancer in a first-line setting. In a second-line setting, there are various unmet needs. After gemcitabine chemotherapy, S-1 is mainly used and sometimes gemcitabine plus S-1 (GS) is used. Cytotoxic effect of gemcitabine had been reported to have the potential to be enhanced when used with fluorouracil. This randomized study aimed to evaluate the efficacy and safety of gemcitabine plus S-1 in gemcitabine-refractory advanced pancreatic cancer. Methods: This phase II study consisted of patients (pts) who were randomly allocated into the GS group (gemcitabine 1,000 mg/m2 on days 1 and 8 plus S-1 60, 80, or 100 mg/d according to body-surface area on days 1 through 14 of a 21-day cycle) or the S-1 group (S-1 80, 100, or 120 mg/d according to body-surface area on days 1 through 28 of a 42-day cycle) at a 1:1 ratio. The primary endpoint was the evaluation of progression-free survival (PFS). The sample size of 90 pts was chosen based on the randomized phase II selection design reported by Simon et al.(1985). The design suggests a correct selection probability of 75% with two-sided significance level of 0.10 if median PFS is 3.3 mo and 2.0 mo in GS and S-1 groups. Results: From Jan 2012 to March 2015, randomized 51 pts were examined (GS: 26, S-1: 25). This study was discontinued due to slow accrual. The median PFS of GS group was 2.0 mo while the S-1 group was 2.1 mo. The hazard ratio was 1.06 [95%CI 0.60-1.86]; (p=0.844). The median survival times were 3.8 mo in GS group and 5.5 mo in S-1 group, respectively. The hazard ratio was 1.02 [95%CI 0.57-1.81]; (p=0.96). The response rates were 4.2% and 4.3%. The disease control rates were 33.4% and 30.4%. Although bone marrow suppression is higher in GS group, the toxicities were manageable in both groups. Grade 3/4 toxicities (GS/S-1 %) included: neutropenia, 53.8/8; hemoglobin, 30.8/28.0; thrombocytopenia, 7.7/4.0; nausea, 0/8.0; anorexia 11.5/16.0, fatigue 7.7/0 and diarrhea, 3.8/4.0. Conclusions: Gemcitabine plus S-1 is not more effective than S-1 in gemcitabine-refractory advanced pancreatic cancer. Clinical trial information: 000007173.
Minimally invasive hepatectomy conversions: An analysis of outcomes.
Authors: Silva Jack P , Berger Nicholas G , Tsai Susan , Christians Kathleen K. , Clarke Callisia , Mogal Harveshp , Gamblin T. Clark 
Published: March 2017

430 Background: Surgical approach has been described as a factor influencing morbidity in patients undergoing hepatectomy. Minimally invasive surgery (MIS) converted to open has previously been included in an open hepatectomy cohort of the National Surgical Quality Improvement Program (NSQIP) dataset for analysis. This study sought to compare MIS conversion to open hepatectomy cases and analyze factors leading to conversion. Methods: The NSQIP data set was queried for patients undergoing hepatectomy for liver disease between January 1, 2014 and December 31, 2014. Cases were divided into three cohorts: completely MIS (laparoscopic or robotic), open, or planned MIS converted to open approach according to the dataset definitions. Demographic, clinical-pathologic, and perioperative variables were described and short-term postoperative outcomes were compared between groups. Results: A total of 2,884 patients were identified. Open approach was performed most commonly (80.96%, n = 2,335), followed by minimally invasive (15.05%, n = 434) and MIS converted to open (3.99%, n = 115). Patients undergoing conversion were more likely to have higher BMI, hypertension, and hepatocellular carcinoma. Conversion patients suffered from significantly higher morbidity (p < 0.001) compared to MIS, but had comparable outcomes to open procedures. Conclusions: MIS hepatectomy has been shown to have lower morbidity but similar mortality to open hepatectomy. Conversion procedures appear to have similar outcomes to open procedures, with greater morbidity compared to MIS. Differences in morbidity from previous studies may be partially attributed to the inclusion of conversions in the open hepatectomy cohort.
Stereotactic body radiotherapy for pancreatic cancer: Analysis of toxicity.
Authors: Perni Subha , Kim Pan , Yanagihara Theodore , Jani Ashish , Chin Christine , Yan Ping , Wolthius Brian , Elliston Carl , Gidea-Addeo Daniela , Horowitz David Paul 
Published: March 2017

436 Background: Pancreatic ductal adenocarcinoma (PDAC) carries a poor prognosis, with significant morbidity and mortality from local progression. Radiotherapy can be administered for local control, with stereotactic body radiotherapy (SBRT) increasingly being utilized. We aim to compare the toxicity of SBRT with intensity-modulated radiotherapy (IMRT) in this setting. Methods: A retrospective analysis of patients with PDAC receiving IMRT or SBRT at our institution between April 2011 and November 2015 was performed. 81 patients were identified. Clinical notes were reviewed for treatment details and acute and late toxicities. Late toxicity data was available for 62 patients. Toxicity was assessed using Common Terminology Criteria for Adverse Events version 4.0. Radiology reports were reviewed to assess for the presence of recurrence and/or progression. Results: Median follow-up from RT was 29 months (95% CI 22-36 months), and median survival from RT was 25 months (95% CI 22-34 months). IMRT patients received 37.5-54 Gy in 15-30 fractions. SRBT patients received 19.8-39.6 Gy in 3-6 fractions. 45% of IMRT and 29% of SBRT patients had local failure (p = 0.1329). IMRT patients were significantly more likely to have Grade ≥2 acute gastrointestinal (GI) toxicity than SBRT patients (RR 1.70; 95% CI 0.98-2.96, p = 0.0489), although one SBRT patient had to have treatment stopped due to extrahepatic stricture. There were no significant differences in late GI toxicity (67% Grade 2 or higher vs. 57%, respectively, p = 0.4244), although one IMRT patient died due to late GI bleeding.IMRT patients were more likely to lose weight during RT(Median -0.03% vs. -0.004%, p = 0.0001) and have moreEmergency Department (ED) visits after RT (Range 0-8 vs. 0-3, p = 0.0019). There were no significant differences in dermatitis, fatigue, or hematologic toxicity. Conclusions: Patients with locally advanced PDAC treated with IMRT versus SBRT had significantly more acute gastrointestinal toxicity, median weight loss, and ED visits after RT, but no significant differences in late gastrointestinal toxicity, dermatitis, fatigue, or hematologic toxicity. SBRT is a relatively tolerable and more convenient alternative for patients with pancreatic cancer.
A phase 1b study of ruxolitinib (Rux) + gemcitabine (G) ± nab-paclitaxel (N) in patients (pts) with advanced solid tumors.
Authors: Bauer Todd Michael , Patel Manish R. , Wood Tina Evans , George Thomas J. , Dawkins Fitzroy W. , Brill Kimberli J. , Du Yining , Hurwitz Herbert 
Published: March 2017

439 Background: Aberrant activation of the JAK-STAT pathway has been associated with increased malignant cell proliferation and survival. Rux, a potent JAK1/2 inhibitor, was evaluated in combination with G±N in advanced solid tumors. Methods: This was an open-label study of Rux + G, without N (regimen A) or with N (regimen B) in advanced solid tumors. The objective of the dose-finding phase (reported here) was to identify MTDs of Rux + G and Rux + G/N. See Table for evaluated cohorts. Results: Among 42 pts enrolled, median age was 62.5 years, 81% had pancreatic cancer (PC), 50% had 1 prior regimen and 12% had 2 prior regimens. Discontinuations were mainly due to radiological or clinical disease progression (86% of pts). Median treatment durations: 55.5 d (A) and 97.5 d (B). 4 pts in B had DLTs: Grade (Gr) 3 pneumonia (n = 1, SAE), Gr 3 neutropenia (n = 1) and Gr 4 thrombocytopenia (n = 2). Table summarizes AEs. The most common Gr 3/4 hem AEs (lab) were anemia (88% A, 85% B) and thrombocytopenia (81% A, 89% B). SAEs occurring in ≥ 2 pts were abdominal pain (n = 4, A), sepsis (n = 2, A), dehydration, anemia and asthenia (n = 2 each, B). Rux + G was tolerated with standard doses of G. Rux + G/N was tolerated with reduced doses of G/N or concomitant GCSF. These combinations were not pursued further, therefore MTDs were not defined. ORRs were 2/16 (13%) in A and 10/26 (39%) in B. ORRs in PC pts: 8/34 (24%); 2/14 (14%) in A and 6/20 (30%) in B. Conclusions: Rux + G or Rux + G/N at the doses investigated were generally safe and well tolerated in pts with advanced PC and other solid tumors. ORRs were noted in multiple tumor types including PC. Clinical trial information: NCT01822756. [Table: see text]
Inverse probability of treatment weighting analysis of upfront surgery versus neoadjuvant chemoradiotherapy followed by surgery for pancreatic adenocarcinoma with arterial abutment.
Authors: Fujii Tsutomu , Yamada Suguru , Murotani Kenta , Takami Hideki , Hayashi Masamichi , Kanda Mitsuro , Nakayama Goro , Sugimoto Hiroyuki , Koike Masahiko , Fujiwara Michitaka , Kodera Yasuhiro 
Published: March 2017

440 Background: Combined arterial resection during pancreatectomy can be a challenging treatment, and outcome would be more favorable if the tumor becomes technically removable from the artery. Neoadjuvant chemoradiotherapy (NACRT) is expected to achieve locoregional control and enable margin-negative resection. To investigate the effects of NACRT in patients with pancreatic adenocarcinoma (PDAC) which were deemed borderline resectable through preoperative imaging due to abutment of the major artery, including the superior mesenteric artery (SMA) or common hepatic artery (CHA), but were still considered to be technically removable. Methods: Comparisons were make between 71 patients who underwent upfront surgery and 21 patients who underwent NACRT followed by surgery in the strategy to preserve the artery, using unmatched and inverse probability of treatment weighting analysis (UMIN000017115). Results: Fifty patients in the upfront surgery group and 18 in the NACRT group underwent curative resection (70% vs 86%, respectively; P = 0.1609). The results of the propensity score weighted logistic regressions indicated that the incidences of pathological lymph node metastasis and a pathological positive resection margin were significantly lower in the NACRT group (odds ratio, 0.006; P < 0.0001 and odds ratio, 0.007; P = 0.0005, respectively). Among the propensity-score matched patients, the estimated 1- and 2-year survival rates in the upfront surgery group were 66.7% and 16.0%, respectively, and those in the NACRT group were 80.0% and 65.2%, respectively. Conclusions: It was suggested that chemoradiotherapy followed by surgery provided clinical benefits in patients with PDACs in contact with the SMA or CHA. Clinical trial information: 000017115.
Activity of RX-3117, an oral antimetabolite nucleoside, in patients with pancreatic cancer: Preliminary results of stage 1 of the phase 1a/2b.
Authors: Rasco Drew W. , Peterson Christine , Benaim Ely , Merchan Jaime R. 
Published: March 2017

445 Background: RX-3117 is an oral smallmolecule antimetabolite, cyclopentyl pyrimidyl nucleoside that is activated by uridine cytidine kinase 2. RX-3117 has shown efficacy in xenograft models of gemcitabine resistant pancreatic, bladder and colorectal cancer. Data from stage 1 of the Phase 1b/2a clinical study of RX3117 as a single agent in subjects with metastatic pancreatic cancer is described below. Methods: Stage 1 of the Phase 1b/2a study (NCT02030067) is designed to evaluate safety, tolerability and efficacy following treatment with 700 mg administered orally once-daily for 5 consecutive days with 2 days off per week for 3 weeks with 1 week off in each 4 week cycle in a 2-stage Simon design. Eligible subjects (aged ≥ 18 years) were those with relapsed/refractory metastatic pancreatic cancer. The primary endpoint is a ≥ 20% (2 out of 10 subjects) rate of progression free survival (PFS) benefit (i.e., proportion of subjects with stable disease for at least 4 months) and/or a 10% (1 of 10 subjects) with a partial response rate or better. Results: As of Sep 2016, 8 out of 10 subjects have been enrolled (4 females, 4 males), the mean age was 70 years, ECOG performance status was 1 and 5 subjects had received more than 4 prior therapies. Two subjects met the primary endpoint of stable disease with a duration of 140-168 days at the time of this submission. The most frequent adverse events were moderate to severe anemia, mild to moderate fatigue, abdominal pain and diarrhea. Conclusions: This ongoing trial shows an early efficacy signal where RX-3117 is active against advanced pancreatic cancer. As the primary endpoint has been achieved, the study will now move to stage 2 where an additional 40 subjects with advanced pancreatic cancer will be enrolled. Clinical trial information: NCT02030067.
Does hepatectomy approach influence transfusion? An analysis of the National Surgical Quality Improvement Program database.
Authors: Silva Jack P , Berger Nicholas G , Tsai Susan , Christians Kathleen K. , Clarke Callisia , Mogal Harveshp , Gamblin T. Clark 
Published: March 2017

447 Background: Transfusion is one of the causes of morbidity in hepatectomy, and is a predictor of mortality and cancer recurrence. This study sought to analyze the role of surgical approach in the incidence of transfusion in a large national dataset. Methods: The National Surgical Quality Improvement Program database identified patients undergoing hepatectomy between January 1, 2014 and December 31, 2014. Demographic information, surgical approach, perioperative characteristics, and short-term postoperative outcomes were compared for patients with and without perioperative red blood cell transfusion. Transfusions occurring from surgical start time to 72 hours postoperatively were included in the dataset. Results: A total of 3,064 patients were included in this study. Patients with right lobectomy and trisegmentectomy were more likely to receive transfusion compared to left and partial lobectomies (p < 0.001). Rate of transfusion was highest in unplanned minimally invasive conversion to open hepatectomy compared to open hepatectomy and minimally invasive surgery (25.2% vs. 21.2% vs. 6.7% respectively, p < 0.001). Patients requiring transfusion were more likely to suffer from other morbidity (47.1% vs. 19.6%, p < 0.001), had a longer median length of stay (7 vs. 5 days, p < 0.001), higher readmission rates (14.2% vs. 9.4%, p = 0.001), and higher 30-day mortality (4.9% vs. 0.8%, p < 0.001) compared to patients not receiving blood transfusions. Conclusions: Transfusion is the most common morbidity-defining complication associated with hepatectomy. Perioperative outcomes are significantly improved if no transfusion was needed. Further work should focus on avoiding unplanned conversion and minimizing blood loss.
Management of recurrent pancreatic cancer after surgical resection: Systematic review, evidence mapping, and meta-analysis.
Authors: Lee Jong-Chan , Hwang Jin-Hyeok , Kim Jaihwan , Kim Hyoung Woo , Lee Jongchan 
Published: March 2017

448 Background: Although almost patients with surgically resected pancreatic cancer (PC) experience recurrence, the optimal treatment option of recurrent PC is still unclear. Numerous studies have been reported about this issue, but all the scattered evidences are too small and heterogeneous to reach a conclusion. The aim of this systematic review is to perform ‘evidence mapping’ and subgroup meta-analysis. Methods: In regards to local recurrence and metastatic recurrence respectively, four treatment options including re-operation (ReOP), chemotherapy (CTx), radiotherapy (RT), best supportive care (BSC) were searched from Medline, Embase, Cochrane library, Scopus and Web of Science from 1976 to April 30, 2016. To visualize the mapping of evidence, we established a web-based mapping tool ( http://plotting-e-map.com ) and used it. In the treatment options with selected study types, subgroup meta-analyses were conducted using overall survival as a primary endpoint. Results: Among detected 12,040 studies, a total of 162 studies were included. In locally recurrent PC, overall 126 studies (39 of ReOP, 40 of CTx, 37 of RT, and 10 of BSC) were included. Median overall survival (OS) of each treatment option was 16.1 months (95% CI 4.9–22.1, I2 52%) for ReOP, 14.9 month (95% CI 7.5–18.9, I2 63%) for CTx, 13.8 months (95% CI 5.6–17.0, I2 59%) for RT. In metastatic recurred PC, overall 36 studies (10 of ReOP, 22 of CTx, no RT, 4 of BSC) were included. Median OS’s were 8.3 months (95% CI 3.6–11.2, I2 56%) for Re-OP, and 6.8 months (95% CI 4.1–9.5, I2 33%) for CTx. Conclusions: During recent 40 years, evidences showed that re-operation for highly selected patients with locally and metastatic recurrent PC could be a considerable therapeutic option. However, since the heterogeneity among the studies is relatively high, more prospective and comparative studies about re-operation with multimodality treatment are needed.
Consensus treatment guidelines for urgent symptoms in cholangiocarcinoma (CC) patients (pts) with biliary stents or catheters using the modified RAND/UCLA Delphi process.
Authors: Iyer Renuka V. , Acquisto Susan G. , Bridgewater John A. , Choti Michael A. , Hong Theodore S. , Kis Bela , Mead Peter A , Parikh Neehar D. , Roberts Lewis R. , Roberts Rebecca , Sicklick Jason K. , Siegel Richard S. , Whisenant Jonathan R. , Cherepanov Dasha , Broder Michael S. , Valle Juan W. 
Published: March 2017

452 Background: CC pts with biliary stents or catheters often present with fever and/or jaundice requiring urgent treatment for which there is no uniform guideline. We aimed to develop an expert panel consensus on this topic using the modified RAND/UCLA Delphi process to rate treatment appropriateness. Methods: We recruited 13 physician experts from relevant specialty, geography, and practice settings. Patient scenarios were developed based on a literature review, and therapies were rated by the experts before and after a face-to-face discussion. The appropriateness of various therapies was rated on a 1-9 scale and classified as appropriate, inappropriate, or uncertain. Scenarios with > 2 ratings of 1-3 (inappropriate) and > 2 ratings of 7-9 (appropriate) were considered to have disagreement and were not assigned an appropriateness rating. Results: Panelists were from all US regions (92%) and the UK (8%); had practiced for a mean 16.5 years (4-33 years) and reported seeing an average of 120 unique CC patients a year (0-900 pts). Panelists rated 288 clinical scenarios. Experts decided that ongoing treatment with chemotherapy did not influence decision-making. Disagreement decreased from 37.5% before the meeting to 10.4% after. Consensus statements are summarized in table 1. Conclusions: The Delphi process produced consensus guidelines to fill an unmet need in urgent management of ascending cholangitis in pts with CC. Studies of the impact of these guidelines on cost of care and pt outcomes are warranted. (Support: The Cholangiocarcinoma Foundation)[Table: see text]