bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relief of bowel-related symptoms with telotristat etiprate in octreotide refractory carcinoid syndrome: Preliminary results of a placebo-controlled, multicenter study.
Authors: O'Dorisio Thomas M. , Phan Alexandria T. , Langdon Robert M. , Marek Billie J. , Ikhlaque Nadeem , Bergsland Emily K. , Freiman Joel , Law Linda , Banks Phillip Lee , Frazier Kenneth , Jackson Jessica , Zambrowicz Brian , Kulke Matthew 
Published: February 2017

312 Background: Diarrhea associated with carcinoid syndrome (CS) has been attributed to tumor production of serotonin. Telotristat etiprate, (LX1032, LX1606), is an oral inhibitor of peripheral serotonin synthesis. This study explored the safety, tolerability, and efficacy of telotristat etiprate in carcinoid patients with octreotide-refractory diarrhea. Methods: Carcinoid patients with >4 bowel movements (BM)/day on octreotide were randomized 3:1 to receive telotristat etiprate or placebo. Patients enrolled in sequential, escalating dose cohorts of 150, 250, 350, or 500 mg tid, followed by a 500 mg tid expansion cohort. Patients were followed for toxicity, 24-hr urinary 5-HIAA (u5-HIAA) secretion, BM frequency, and self-reported relief of bowel-related symptoms. Subjects were asked “In the past 7 days, have you had adequate relief of your carcinoid syndrome bowel complaints such as diarrhea, urgent need to have a bowel movement, abdominal pain or discomfort?” Responses (yes or no) were analyzed as categorical variables. Results: 16 patients enrolled in the 4 escalating dose cohorts and 7 in the expansion cohort; 18 on telotristat etiprate and 5 on placebo. Median age was 62 yrs with a mean 6.2 BMs/day (range 4-10). AEs included primarily mild-moderate diarrhea, nausea, and abdominal discomfort. In treated subjects, adequate relief was reported as follows: Week 1 – 6/18 (33.3%), Week 2 – 5/16 (31.3%), Week 3 - 5/15 (33.3%), and Week 4 – 6/12 (50.0%). No placebo subjects reported improvement at any timepoint. Biochemical response (>50%reduction in u5-HIAA) and BM response (>30% reduction in daily BM for 2 weeks) were associated with reporting of adequate relief. For evaluable telotristat etiprate-treated patients, 9/16 (56%) experienced a biochemical response and 5/18 (28%) experienced a clinical (BM) response; no placebo subjects achieved either biochemical or clinical response. Conclusions: Treatment with telotristat etiprate was associated with decreases in u5-HIAA and BM frequency, and with self-reported relief of bowel related symptoms. Treatment in an extension phase with open-label telotristat etiprate is ongoing.
Percutaneous transhepatic biliary drainage (PTBD) in patients (pts) with advanced solid malignancies: Clinical outcomes and prognostic factors.
Authors: Crosara Marcela Alves Teixeira , Mak Milena P. , Marques Daniel Fernandes , Capareli-Azevedo Fernanda C. , Hoff Paulo Marcelo 
Published: February 2017

315 Background: Obstructive jaundice (OJ) is a cumbersome complication in pts with advanced digestive malignancies, and PTBD is often used to relieve symptoms and allow chemotherapy (CT) administration. Methods: From July 2008 to August 2011, a total of 71 pts with OJ due to advanced solid malignancies underwent PTBD in our institution. Baseline characteristics, procedure complications and outcome were retrospectively collected. The primary goal was to estimate overall survival (OS) after PTBD. Results: Patients’ median age was 60 years old, 52% were male, 72% had an ECOG performance status (PS) of 1-2 and 10% were in supportive care (SC). Most had metastatic disease at diagnosis (59.2%) and primary gastrointestinal tumors (biliary tract 42.3%, gastric 18.3%, colorectal 11.3%, pancreas 16.9% and 11.3% other sites). Mean hospital stay was 16.6 days (2-90), with bilirubin value decreased (BVD) in 80% of pts. The rate of cholangitis following PTBD was 66.2% and 60.6% of pts had readmissions related to procedure complications. Only 51.6% of pts not in SC were eligible for CT after PTBD. Median OS was 2.9 months (95% CI: 0.62-5.2). Prognostic factors on univariate analysis were ECOG ≤2 (13 versus 0.72 months p<0.0001); BVD (6.7 versus 0.33 months p<0.0001); CT after PTBD (13.7 versus 1.2 months p<0.0001). SC was a negative prognostic factor (0.8 versus 4.5 months p<0.0001). On the multivariate analysis, palliative CT after procedure was related to better OS (HR 0,16 CI: 0.05-0.48 p<0.001). Conclusions: Malignant OJ is a late, and often final event in cancer pts. Thorough evaluation is needed before determining pts eligibility to PTBD, due to its high complication and hospitalization rates. In the current analysis, pts with PS >2 and who are not candidates for further CT had a dismal prognosis, and should probably not be offered PTBD.
Margin distance as an independent predictor of survival after R0 resection for pancreatic adenocarcinoma.
Authors: Van Buren George , Zeh Herbert , Krasinskas Alyssa M , Gooding William E. , Steve Jennifer , Lee Kenneth K , Magge Deepa , Daouadi Mustapha , Bartlett David L. , Moser Arthur J , Zureikat Amer H 
Published: February 2017

321 Background: Microscopic tumor at the surgical margin is a predictor of recurrence and poor survival for pancreatic ductal adenocarcinoma (PDA). However, the impact of distance between the surgical margin and microscopic tumor on survival remains controversial. We hypothesized that margin distance (MD) would correlate with disease free survival (DFS) and overall survival (OS) in R0 resected PDA. Methods: Retrospective analysis of 191 resections for PDA. Margin distance was measured (0-1, 1-2, 2-4, 4-10, and > 10 mm) and categorized by location. Parameters including age, gender, BMI, TNM, AJCC stage, lymph node (LN) ratio, vascular and perineural invasion, vein resection, and adjuvant therapy were analyzed. Primary endpoints were DFS and disease specific OS. Univariate analysis was used to estimate factors associated with outcomes. The log rank test was applied to selected group comparisons. Results: 149 (78%) R0 outcomes were analyzed. 118 (79%) patients received adjuvant chemotherapy, 31 of whom also received XRT. Univariate analysis demonstrated reduced DFS (HR = 1.65, 95% CI = 1.13 – 2.48, p = .009) and OS (HR = 1.52 95% CI =.98 – 2.35, p = .059) among patients with margins ≤ 2mm compared to margins > 2mm. In addition LN status, LN ratio, tumor size, AJCC stage, vascular invasion, perineural invasion and adjuvant chemotherapy were found to influence OS on univariate analysis. Adjuvant XRT had no measurable effect on DFS or OS. Following adjustment for covariates in a multivariate model, margin distance >2mm did not correlate with DFS (HR = 1.14, 95%CI = .73 – 1.78, p = .57) or OS (HR = 1.13 95% CI = .69 – 1.85, p = .63), whereas adjuvant chemotherapy and presence of vascular invasion significantly affected OS (P=0.0006 and P=0.008 respectively). The retroperitoneal margin was the margin most commonly in close proximity to tumor (43% of Whipple), although there was no correlation between the closest margin and DFS (p=0.94) or OS (p=0.94). Conclusions: Margin distance is not an independent predictor of DFS or OS after R0 resection for PDA. Irrespective of margin distance, adjuvant chemotherapy, but not XRT, was associated with improved OS.
The role of fusion positron emission tomography/computed tomography (PET/CT) scan in patients with resectable pancreatic neoplasms.
Authors: Razzaque Saqib , Ashraf Noman , Weber Jill M. , Pimiento Jose Mario , Malafa Mokenge Peter , Kim Richard D. 
Published: February 2017

322 Background: The role of fusion positron emission tomography/computed tomography scans (PET/CT) in staging of patients with pancreatic neoplasms (PN) is poorly defined. Currently PET/CT is not recommended as part of staging workup in patients with potentially resectable PN. Methods: Using a comprehensive cancer PET registry we identified 107 patients with PN who were potentially resectable based on the initial preoperative staging CT scans and endoscopic ultrasound (EUS), from January 2006 - December 2010. Subsequently all these patients had PET/CT performed prior to surgery. Patients with borderline resectable or locally advanced disease were excluded from the analysis. Statistical analyses were performed included sensitivity, specificity, positive predictive value, and negative predictive value. Statistical analyses were performed with STATA IC (Stata Statistical Software, Release 10.0; Strata Corp., College Station, TX). Results: PET/CT altered management and prevented futile surgery in 6.5 % patients by identifying metastases not detected by other modalities. One patient was found to have metastasis to the supraclavicular lymph node, five had occult hepatic lesions and another had peri-esophageal lymph nodes. All sites were biopsied and metastases confirmed by pathology. The sensitivity and specificity of PET/CT scan in detecting metastatic disease in this patient population was 42.1% and 83.3% respectively. Our study indicated a positive predictive value of PET/CT to be 40% and negative predictive value 84.5%, with a false positive rate of 16.6%. Conclusions: PET/CT was instrumental in preventing futile laprotomy in 6.5 % patients. Larger studies utilizing PET/CT in the initial preoperative staging workup are warranted.
The role of LDH serum levels in predicting global outcome in patients with HCC undergoing TACE: Implications for clinical management.
Authors: Bianconi Maristella , Faloppi Luca , Scartozzi Mario , Giampieri Riccardo , Maccaroni Elena , Bittoni Alessandro , Del Prete Michela , Loretelli Cristian , Belvederesi Laura , Svegliati Baroni Gianluca , Cascinu Stefano 
Published: February 2017

326 Background: In many tumor types serum LDH levels proved to represent an indirect marker of tumour hypoxia, neo-angiogenesis and worse prognosis. However data about HCC are lacking particularly in the clinical setting of patients undergoing transarterial-chemoembolization (TACE) in whom hypoxia and neo-angiogenesis may represent a molecular key to treatment failure. Aim of our analysis was to evaluate the role of lactate dehydrogenase (LDH) pre-treatment levels in determining clinical outcome for patients with HCC receiving TACE. Methods: One-hundred and fourteen patients were available for our analysis. For all patients LDH values were collected within one month before the procedure. For study purposes we divided our patients into two groups, according to LDH serum concentration registered before TACE (first group: LDH ≤ 450U/l 84 patients; second group: LDH > 450U/l 30 patients). Patients were, also, classified according to the variation in LDH serum levels pre- and post-treatment (increased: 62 patients vs decreased 52 patients). Results: Patients proved homogeneous for all clinical characteristics analyzed. In patients with LDH values below 450 U/l median time to progression (TTP) was 16.3 months, whereas it was of 10.1 months in patients above the cut-off (p=0.0085). Accordingly median overall survival (OS) was 22.4 months and of 11.7 months (p=0.0049). In patients with decreased LDH values after treatment median TTP was 12.4 months, and median OS was 22.1 months, whereas TTP was 9.1 months and OS was 9.5 in patients with increased LDH levels (TTP: p=0.0087; OS: p<0.0001). Conclusions: In our experience, LDH seemed able to predict clinical outcome in terms of TTP and OS for HCC patients undergoing TACE. Given the correlation between LDH levels and tumour angiogenesis we can speculate that patients with high LDH pretreatment levels may be optimal candidates for clinical trial exploring a multimodality treatment approach with TACE and anti-VEGF inhibitors in order to improve TTP and OS.
Maintenance therapy with capecitabine in patients with resected pancreatic adenocarcinoma after adjuvant therapy.
Authors: Yang Xuezhong , Wu Christina Sing-Ying , Hwang Jimmy J. , Weinberg Benjamin , Pishvaian Michael J. , He Aiwu Ruth , Marshall John 
Published: February 2017

333 Background: The 5-year disease free survival of pancreatic adenocarcinoma (PAC) with surgery alone is below 10%, and adjuvant chemotherapy increases that to about 20%. The original GITSG adjuvant study demonstrating a survival benefit compared to surgery could be attributed to the use of 2-years of weekly IV bolus 5FU, and not chemoradiation. This hypothesis has not been tested since that trial. In theory, the prolonged exposure to therapy could maintain pressure on dormant cancer cells that may remain in G0 arrest, by attacking them as they infrequently enter G1/S phase. To evaluate this hypothesis, we retrospectively evaluated our patient (pts) who were treated with maintenance capecitabine (cape). Methods: Pts in the Georgetown University Hospital/Lombardi Cancer Center electronic medical record database since Oct 2007 were sought for PAC that were resected with curative intent, received standard adjuvant chemotherapy with or without chemoradiation, and received maintenance cape for at least 2 months. Results: Among 214 PAC pts that have been treated at our institution in this time, 21 pts met these criteria. Among the 21 pts, 1 was lost to follow up after moving overseas, and 20 pts were eligible for this analysis. 13 of the 20 pts had lymph node involvement at resection. Cape was usually given 1000mg orally twice a day, Monday through Friday following adjuvant therapy, for an indefinite period, most often two years. Pts received cape for median duration of 12.5 months (2 to 24 months), and the median followup duration was 33 months (16 to 78 months). The median overall survival (OS) for the 20 analyzed patients was 48 months. The 2 year OS was 94%, and 5 year OS was 40%. The median recurrence free survival (RFS) was 39 months. The 2 year RFS was 67%, and the 5 year RFS was 25%. Common toxicities were mild hand-and-foot syndrome and fatigue. 4 pts discontinued cape due to toxicities: febrile neutropenia, severe fatigue, weight loss and diarrhea respectively. Conclusions: Cape maintenance therapy following adjuvant chemotherapy in resected PAC is associated with a promising higher overall survival and PFS compared to historical data, and this approach should be further studied in a randomized controlled study.
Demographic and prognostic factors in ampullary adenocarcinoma: A retrospective review of 74 sequential cases undergoing multidisciplinary management between 1997 and 2009.
Authors: Marsh Robert de Wilton , Bentrem David J. , Baker Marshall , Stocker Susan , Brown Eric , Talamonti Mark S. 
Published: February 2017

334 Background: Ampullary adenocarcinoma represents 1% of GI cancers but accounts for almost 30% of Whipple operations at major centers. Prognosis falls between that of pancreatic and duodenal cancer, but demographic and prognostic factors are not fully delineated. A better understanding of the biology of this disease is essential both for patient care and for the optimal design of future studies. Methods: Retrospective review, with patient consent, of an IRB approved comprehensive common surgical database at two academic institutions. This database included all cases operated on for ampullary adenocarcinoma between 1997 and 2009. Demographics and factors thought to have potential relevance for prognosis by literature review were examined, where available, via Kaplan Meier and/or Cox models. Results: 74 cases were identified: 50 had conventional and 22 pylorus preserving Whipple procedures with 2 unresectable cases. Demographics: 38 males, 36 females; 64 Caucasian, 6 African American and 4 others; age 23-83, median 63.08 years. Tumor characteristics: Tis -1, T1-10, T2-22, T3-27, T4-12, Unknown-2; N0-35, N1-38, Unknown-1; pre-existing adenomas in 37 (50%). Tumor markers: CEA 2/34 and CA 19-9 16/37 tested were abnormal. Adjuvant therapy given (chemo and/or chemoRT): 33/74. Status: 34 patients alive and 41 deceased with a median follow-up of 22 months. Factors associated with poor outcome: Perineural invasion (PNI) p = 0.02; Pre-existing adenoma p = 0.001; Weight loss of 10 lbs or more p = 0.01; RBC transfusion in the OR p = 0.001. Factors not statistically prognostic: T stage, lymph nodal status, lymphovascular invasion, jaundice, CEA or CA 19-9 values and absence of adjuvant therapy. Pancreaticobiliary versus intestinal subtype could not be assessed as this was rarely reported. Conclusions: This dataset describes the demographics of patients sequentially treated for ampullary adenocarcinoma over 12 years, and identifies PNI, weight loss, pre-existing adenoma and transfusion in the OR as adverse factors. These prognostic factors (and potentially histologic subtype) should be considered in patient care and future study design.
Radiation in the management of pancreatic neuroendocrine tumors.
Authors: Maidment Bertram W. , Ellison Trevor , Herman Joseph M. , Sharma Navesh K , Laheru Dan , Regine William , Wild Aaron Tyler , Olino Kelly , Hruban Ralph H. , Cameron John L , Alexander H. Richard , Hanna Nader , Hausner Petr Frantisek , Zheng Lei , Choti Michael A. , Schulick Richard D. , Wolfgang Christopher Lee , Edil Barish H 
Published: February 2017

335 Background: Radiation therapy (RT) has not historically been incorporated into multidisciplinary management of pancreatic neuroendocrine tumors (PNTs). We provide a two-institution series of patients with PNTs who were treated with external beam RT either neoadjuvantly to attempt down-staging for surgery, or in the setting of post-surgical recurrence. Our objective was to assess treatment response and outcomes in this cohort of patients. Methods: We identified eleven patients with a pathologic diagnosis of PNT from 2006-2011 who received external beam RT to the primary tumor or resection bed. Each institution’s electronic medical record was used to evaluate patient demographics, disease characteristics, treatment regimens and tolerance, radiographic response, and survival. Results: Our series consists of eleven patients (6 men, 5 women) with a mean age of 57 years (range 37-72 years). All had biopsy proven PNT and were clinically T3 (n=3) or T4 (n=8), M0. Five patients were clinically node positive. All patients received RT to the primary tumor or resection bed to a median dose of 50.4 Gy. Seven patients received concurrent chemotherapy with capecitabine at a median dose of 1000mg/m2 bid. Nine patients were treated definitively for locally advanced disease, two of whom subsequently underwent surgical resection. Two patients were treated to palliate post-resection recurrence. Initial radiographic response to RT included 2 complete responses (CR), 2 partial responses (PR), 4 stable disease, 3 progressive disease (PD). Two patients were classified as PD due to the development of distant metastases less than 2 months after completing RT. Two grade 3 toxicities were documented (one early, one late). At a median follow-up of 30.4 months, three patients had died with evidence of PD, two had died without evidence of PD, three were alive with metastases, and three were alive without evidence of disease progression (1 stable, 1 PR, 1 CR). From the start of RT, median overall survival was 32.1 months; progression free survival was 14.6 months. Conclusions: RT may have the potential to convert PNTs from locally-advanced to resectable. RT may also increase local control of PNTs. Consideration should be given to the use of RT in prospective trials of PNT treatment.
Toxicity study of gemcitabine, oxaliplatin, and bevacizumab followed by 5-fluorouracil, oxaliplatin, bevacizumab, and radiotherapy in patients with locally advanced pancreatic cancer.
Authors: Sohal Davendra , Metz James M. , Sun Weijing , Harlacker Kathleen , Giantonio Bruce J. , Rosato Ernest F. , Ginsberg Gregory , Kochman Michael , Teitelbaum Ursina R. , Redlinger Colleen , Feldman Michael D , Drebin Jeffrey A. , O'Dwyer Peter James 
Published: February 2017

337 Background: Patients with advanced pancreatic cancer experience higher response rates (though not always improved survival) with combinations of either platinum compounds or bevacizumab in combination with gemcitabine. In patients with locally advanced pancreatic cancer, improved response affects local control and surgical options. Methods: We piloted a three-drug combination of gemcitabine/oxaliplatin/5-FU/bevacizumab Q2w for four cycles, followed by oxaliplatin (85 mg/m2/q2w) and bevacizumab (5 mg/kg q2w) added to infusional 5-FU and radiation, in patients with pancreatic cancer that was unresectable or borderline resectable. Results: Nineteen patients have been treated, of whom 17 received the entire treatment. Median age was 60, with 12 women and 7 men. Stages were: one IIA, one IIB, and 17 III. Sixteen were unresectable and 3 borderline resectable by protocol-specified criteria. Major toxicities during chemotherapy were: grade 3 neutropenia (5/19); grade 2 neutropenia (7/19), anemia (2/19), thrombocytopenia (2/19). During chemoradiation major toxicities were: grade 3 nausea (3/19), vomiting (3/19), leukopenia (2/19); grade 2 nausea (5/19), leukopenia (4/19). One patient had grade 3 pulmonary embolism that led to withdrawal from the study. One patient had progressive pain early on; no other disease progression was noted during treatment. Five patients (3 inoperable, 2 borderline) went on to have surgery. Median survival was 14 months (range 3 to 40+). For the 5 patients who had surgery, median survival was 17.1 months (range 9.5 to 40+). Conclusions: We conclude that this regimen is well-tolerated by patients with locally advanced pancreatic cancer, and that the therapeutic results support further evaluation. Additional correlative studies are underway to identify characteristics associated with a favorable outcome.
Whole-liver irradiation with hepatic arterial floxuridine/leucovorin/streptozotocin followed by hepatic arterial floxuridine/leucovorin and chemo-embolization with mitomycin C for patients with metastatic neuroendocrine tumors.
Authors: Shilkrut Mark , Hanasoge Sheela , Normolle Daniel Paul , Ben-Josef Edgar , Ensminger William D. , Lawrence Theodore Steven , Feng Mary Uan-Sian 
Published: February 2017

339 Background: Neuroendocrine tumors metastatic to liver are incurable with limited treatments. We conducted a phase I trial combining hepatic arterial (HA) chemotherapy, chemoembolization and dose-escalated whole liver radiotherapy (WLRT) to determine if the maximum safe dose of 32 Gy in 2 Gy fractions could be achieved. Methods: Patients (pts) with liver metastases from neuroendocrine tumors who failed somatostatin analog therapy were eligible. First, floxuridine (FUDR, 3 mg/m2/d) and leucovorin (LV, 300 mg/m2/d) were given by continuous hepatic artery infusion for 12 days; streptozotocin (500 mg/m2/d) was given over 3 h on days 5, 8 and 10. Concurrent WLRT was prescribed in 2 Gy/day with doses escalated from 24 Gy to 32 Gy using the time-to-event continual reassessment method for dose allocation with a target rate of dose-limiting grade (gr.) ≥ 3 radiation-induced liver disease (RILD) of 10%. 8 weeks later, for pts without RILD and other gr. ≥ 4 toxicities, continuous 72-h infusion with HA FUDR (3 mg/m2/d) and LV (300 mg/m2/d) was given, followed by chemoembolization with mitomycin C (20 mg) and polyvinyl alcohol foam. Results: 19 pts were enrolled in the trial. 8 pts received 24 Gy, 2 - 26 Gy, 1 - 28 Gy, 2 - 30 Gy and 6 - 32 Gy. 8 pts received only the first part of the treatment, 11 completed the entire protocol. No pts developed dose-limiting RILD; 5 - had gr. 3-4 increased liver function tests (LFT), 4 - had other gr. 4 toxicities after the first part of the treatment, primarily chemotherapy and embolization-related; 3 - had gr. 3 increased LFT, and 1 - had other gr. 4 toxicities after the second part of the treatment. 4 pts (21%) had partial response, 14 (74%) - stable disease and one pt (5%) receiving only part 1 had progressive disease. Median progression free survival for all pts was 20.6 (8.4-45.4) months (m); 15.4 (3.4-67.8) m for pts who received the first part of the treatment only, and 27.9 (8.4 – infinite) m for pts who received both parts of treatment. Conclusions: This study showed that chemotherapy can be safely combined with a full dose of WLRT and subsequent chemoembolization without producing RILD.