bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-omic molecular profiling of pancreatic neuroendocrine tumors.
Authors: Patel Rishi , Bender R Joseph , Li Quanlin , Pan Dana , Tuli Richard , Pishvaian Michael J. , Hendifar Andrew Eugene 
Published: September 2018

e15685 Multi-omic Molecular profiling of Pancreatic Neuroendocrine Tumors Authors: Rishi R Patel, Joseph Bender, Quanlin, Dana Pan, Lynn Matrisian, David Halverson, Emanuel Petricoin, Subha Madhavan, Richard Tuli, Michael Pishvaian, Andrew Hendifar; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA Background: Pancreatic Neuroendocrine Tumors (pNETs) are a rare malignancy with an incidence of 2 per 1,000,000. In 2016, the Pancreatic Cancer Action Network and Perthera initiated the Know Your Tumor (KYT) initiative in an effort to improve coordination across clinical spectrums in regards to multi-omic molecular profiling and clinical outcomes data pertaining to pancreatic tumors. We used data collected as part of the KYT effort to describe demographic, clinical and genomic data for pNETs. Methods: From 2015 - 2016, 15 patients with pNET were enrolled in the KYT program, which helped facilitate tissue acquisition, clinical data collection, and multi-omic molecular profiling. Using the data collected, we performed Fisher’s Exact to assess for statistical significance between genetic alterations and histology. Results: 11/15 of our patients were female. 8/15 had metastatic disease at the time of diagnosis, while 5/15 had locally advanced disease at the time of diagnosis. 29 genetic alterations were pathogenic. KMT2D and MEN1 were jointly found in 6/15 of our patients. 5/15 with pathogenic alterations in p53, 2/15 with DAXX, 5/15 with alteration in RB1, and 2/15 with alterations in PTEN and TSC2. 2 patients had pathologic alterations in mismatch repair genes, MLH1 and MSH1. Two genes had a statistically significant relationship to pNET histology. Alterations in MEN1 (p = 0.0097) and SPTA1 (p = 0.0333) were associated with high grade tumors (p = 0.0097). Of note, both of the patients under the age of 35 shared an alteration in ATR, which none of the other enrollees expressed. Conclusions: In PNETS, multi-omic profiling through the KYT program identified targetable alterations in several key pathways. Outcome data will be explored.
Periprocedural management of patients undergoing liver resection or liver-directed therapy for neuroendocrine tumor metastases.
Authors: Kwon Daniel , Mulvey Claire , Paciorek Alan T , Chan Hilary , Meng Lingzhong , Zhang Li , Nakakura Eric K. , Fidelman Nicholas , Bergsland Emily K. , Van Loon Katherine 
Published: September 2018

e15689 Background: Carcinoid crisis is a life-threatening event caused by release of vasoactive substances from neuroendocrine tumors (NETs). Octreotide is often used in the periprocedural setting as prophylaxis against carcinoid crisis; however, there is no standardized protocol for its use. We aimed to describe the periprocedural management of patients with metastatic NETs who underwent liver-directed procedures at UCSF. Methods: We identified 54 patients with NETs with hepatic metastases who underwent either liver resection/ablation (n = 30) or liver-directed embolization (n = 24) between 2012 and 2016. Anesthesia records and clinical data were abstracted. Carcinoid crisis was defined by physician documentation. Hemodynamic instability was defined as ≥10 minutes of systolic blood pressure < 80 mmHg or > 180 mmHg or heart rate > 120. Pearson chi-squared tests were used to test associations with three outcomes: crisis, instability, or none. Results: Three (6%) patients were documented to have developed carcinoid crisis. Another 14 (26%) patients developed hemodynamic instability. Of 16 patients who received preprocedural octreotide, 1 (6%) had a carcinoid crisis and 5 (31%) developed hemodynamic instability. History of carcinoid syndrome, degree of hepatic involvement, and use of pre or intraprocedural octreotide were not associated with carcinoid crisis or at least hemodynamic instability. Patients undergoing embolization were less likely to develop hemodynamic instability versus those undergoing liver resection (17% vs 43%, Pearson chi-squared p = 0.04). Conclusions: Occurrence of documented carcinoid crisis was low in this high-risk population. However, a significant proportion of patients developed hemodynamic instability, suggesting that carcinoid crisis is a spectrum diagnosis and may be clinically under-recognized. Use of octreotide was not associated with risk of carcinoid crisis or hemodynamic instability; however, this analysis was limited by our modest sample size at a single institution. There remains a need to establish an objective definition of carcinoid crisis and to inform standardization of periprocedural use of octreotide for at-risk patients.
Association of weight change with telotristat ethyl in the treatment of carcinoid syndrome.
Authors: Weickert Martin O , Kaltsas Gregory , Hörsch Dieter , Lapuerta Pablo , Pavel Marianne , Valle Juan W. , Caplin Martyn E. , Bergsland Emily K. , Kunz Pamela L. , Anthony Lowell Brian , Grande Enrique , Oberg Kjell E. , Warner Richard R. P. , Lombard-Bohas Catherine , Welin Staffan , Fleming Rosanna , Kittur Ashwin , Arnold Karie , Yang Qi Melissa , Kulke Matthew H. 
Published: September 2018

e15692 Background: In the Phase 3 TELESTAR study, the oral tryptophan hydroxylase inhibitor telotristat ethyl (TE) significantly reduced bowel movement (BM) frequency compared with placebo (pbo) over a 12-week Double-blind Treatment (DBT) period in patients with carcinoid syndrome (CS). Weight loss has previously been associated with uncontrolled CS and may result in reduced survival, so it is important to examine weight changes in patients with neuroendocrine tumors (NETs). Methods: We conducted an analysis, prespecified in the statistical analysis plan, of the incidence of weight change of ≥3% at Week 12 in TELESTAR. Patients with metastatic NETs, CS, and ≥4 BMs per day were randomly assigned to receive pbo, TE 250 mg 3x/day (tid), or TE 500 mg tid for 12 weeks, in addition to somatostatin analog therapy. Results: There were 45 patients in each group. Mean baseline age was 63.5 years, with 5.8 BMs/day and mean body mass index 24.87 kg/m2. Weight gain ≥3% at Week 12 was observed in 2/39 (5.1%), 7/41 (17.1%), and 13/40 (32.5%) patients on pbo, TE 250 tid, and TE 500 mg tid, respectively. The Cochrane–Armitage test for trend in weight gain incidence across groups yielded p = 0.0017. Among the 20 patients with a ≥3% weight gain on TE, 10 patients experienced a reduction of at least 30% in BM frequency at Week 12 (maximum reduction 75%). Weight loss ≥3% at Week 12 was observed in 5 (12.8%), 4 (9.8%), and 6 (15.0%) patients on pbo, TE 250 tid, and TE 500 mg tid. Adverse events of vomiting, decreased appetite, cachexia, and performance status decreased were reported during the DBT period among those with weight loss but not those with weight gain. Conclusions: The incidence of weight gain was dose-related on TE and was greater than that on pbo. It was possibly related to a reduction in diarrhea severity, and it may be a relevant aspect of TE efficacy among patients with functioning metastatic NETs. Clinical trial information: NCT01677910.
Association between duration of somatostatin analogs (SSAs) use and quality of life in patients with carcinoid syndrome in the United States based on the FACT-G instrument.
Authors: Halperin Daniel M. , Huynh Lynn , Beaumont Jennifer L , Cai Beilei , Totev Todor , Bhak Rachel , Duh Mei Sheng , Vekeman Francis , Neary Maureen , Cella David 
Published: September 2018

e15693 Background: Carcinoid syndrome (CS) results from the secretion of bioactive amines by functional neuroendocrine tumors. The only FDA-approved agents to treat carcinoid syndrome symptoms (CSS) are SSAs. This study assessed the association of duration of SSA use and quality of life (QoL) among patients with CSS usingthe validated Functional Assessment of Cancer Therapy-General (FACT-G) instrument. Methods: Patients with CSS in the US were recruited by NCAN for a two-part online, anonymous survey (~6 months apart). The first survey was fielded between July-October 2016 and results are reported here. Eligible patients were ≥18 years old with CSS and received either SSA or non-SSA treatment for CSS control. The survey consisted of demographic, clinical and QoL questions, including FACT-G. Descriptive and multivariable regression analyses, adjusting for demographic and clinical characteristics, were performed to assess predictors of FACT-G QoL scores. Duration of SSA use was categorized into quartiles ( < 2.7, 2.7-4.42, 4.43-8.0, and > 8.0 years). Results: Among 117 patients who completed the first survey, 76.9% were female and 87.2% Caucasian with a mean age of 58.0 years. A predominant number of patients (98.3%) received SSAs in the past month. The mean ± SD FACT-G total score was 67.6 ± 20.0 (possible range: 0-108), lower than that of the general US population (80.1 ± 18.1). The mean ± SD duration of SSA use was 6.1 ± 4.7 years. Descriptive analysis suggested that patients receiving SSA treatment for > 8 years had higher (better) FACT-G subscale and total scores than reference group < 2.7 years. Multivariable models showed that FACT-G total score was 11.3 points ( P= 0.033) higher for patients treated with SSA > 8 years compared to those treated for < 2.7 years. Similar patterns were observed for two FACT-G subscales - Physical Well Being and Functional Well Being. Conclusions: The duration of SSA use was positively associated with QoL benefit among CS patients. This may be explained by long-term effectiveness of SSAs or selection bias favoring patients with more indolent disease. Future studies will be needed to distinguish between these possibilities.
Microarray analysis of cytokine expression in the gastrointestinal stromal tumors with different malignant potential.
Authors: Zhang Bo 
Published: September 2018

e15701 Background: Nowadays, a variety of prognostic criteria, which established merely based on clinicopathologic features, have been proposed, validated and widely used in practice. Numerous studies have confirmed tumor location, size and mitotic index were closely associated with the prognoses of GISTs. However, no method has yet been proven sufficient power to discriminate malignant potential and to predict biological behavior in all cases. In fact, the changes in cytokine level may result in alteration of tumor's microenvironment, which is considered to be related in the course of malignization for many tumors. Methods: The expression profile of cytokine in 4 patients with gastric GISTs (low malignant potential in 2 cases: 2x2cm, 3/50HPF; 2x1.8cm, 2/50HPF. high malignant potential in 2 cases: 12x10cm, 14/50HPF; 15x12cm, 16/50HPF), along with matched normal gastric tissue was evaluated by microarray. Results: The majority of cytokines expression between adjacent tissue of low and high malignant potential GISTs was similar. The high malignant potential GISTs exhibiting a notable upregulation of 41 cytokines, whereas a total of 23 cytokines with decreased expression in comparison to those with low malignant potential, after considering the expression level of cytokines among matched normal tissue. The cytokines expressed differentially including SPARCL1, MMP13 and FAP have been proven enormously valuable for assessing the prognoses of many tumors. Conclusions: Abnormally expressed cytokines in GISTs may play a vital role in promoting tumor progression, and detection of these cytokines proteins is useful to understand GISTs- malignization mechanisms and is also helpful to evaluate risk of recurrence in the treatment of GISTs patients.
Effect of palliative surgery, chemotherapy, and radiation in stage IV pancreatic cancer.
Authors: Vuong Brooke , Dehal Ahmed , Graff-Baker Amanda N , Chang Shu-Ching , Foshag Leland , Bilchik Anton , Goldfarb Melanie R 
Published: September 2018

e15707 Background: Despite significant advances in multi-modality treatment for pancreatic adenocarcinoma (PC), prognosis for stage IV PC remains poor. While reducing suffering and optimizing quality of life are the primary goals of palliative therapies, these interventions may extend overall survival. We examined the impact on survival when aggressive palliative treatments including surgery, chemotherapy, or radiation were employed in end-of-life care. Methods: The 2004-2014 National Cancer Data Base (NCDB) was queried to identify patients with stage IV PC that did not undergo primary surgical resection. Univariate (Kaplan Meier and log-rank) and multivariable (Cox proportional hazard) analyses were used to assess the associations between patient characteristics, use of palliative therapies, and overall survival. Results: Of 72,736 patients identified with metastatic stage IV PC, 2,097 (3%) underwent surgical palliation (ST), 5,615 (8%) received palliative chemotherapy (CT), 940 (1%) received palliative radiation (RT), 1,163 (2%) received multimodality treatment (MMT), and 62,921 (87%) had no aggressive palliative intervention (NT). The choice of palliative therapy, if any, was influenced by all demographic and tumor variables except for gender (all p < 0.001). Median OS was greatest after CT (5.09 months, p < 0.001) compared to any other modality (NT: 3.45months, ST: 3.71months, RT: 3.25months, MMT: 4.47months). This remained true regardless of age, gender, race/ethnicity, insurance, and facility type. After adjusting for all demographic and tumor factors, use of CT decreased the annual risk of death by 20% (HR = 0.8; 95%CI [0.77, 0.82]) and MMT by 10% (HR = 0.9; 95%CI [0.84, 0.96]). Employment of RT increased risk of death by 9% (HR = 1.09; 95%CI [1.01, 1.17]) and ST did not affect OS (HR = 1.01; 95%CI [0.96,1.06]). Conclusions: Despite advances in palliative treatments, Stage IV PC arries a dismal prognosis. Palliative RT may shorten survival. Equivalent survival for ST versus NT suggests that this may be beneficial in the appropriate patient. Palliative CT independently improved survival by approximately 6 weeks and should be considered in patients that want to extend survival and can tolerate the toxicity.
BP-C1 in the treatment of primary inoperable pancreatic cancer.
Authors: Larsen Stig Einride , Ibrahim Tarek M.M. 
Published: September 2018

e15708 Background: The aim was to estimate the efficacy and tolerability of intramuscular administration of a new benzene-poly-carboxylic acids complex with cis-diammineplatium (II) (BP-C1) in treatment of primary inoperable pancreatic cancer patients Methods: The study was an open, single center, non-randomized trial with security sequential design. The study sample consists of 12 patients with a mean age 61.8 years, BMI 23.9 and disease duration 1.8 months. The patients received daily intramuscular injection of 0.035 mg/kg bw BP-C1 for 32 days. NCI Bethesda (CTC-NCI) and EORTC QOL-C30 were recorded at screening, after every 16 days of treatment and 28 days follow-up. CT-scans performed at screening, after 32-days BP-C1 treatment and follow-up. The RECIST criteria used for tumor evaluation and the sum diameters of the three largest lesions measured. Patient classified as responding to treatment if Stable Disease (SD) or better was obtained. Results: The number of target lesions was unchanged from screening to Day 32. The sum lesion diameters declined from 47.3 mm at screening to 46.3 after 32 days of BP-C1. During follow-up, the sum diameters declined significantly (p = 0.03) to 14.0 mm. After 32 days of treatment, three patients classifies as Progressive Disease (PD) and nine as SD: A responds rate of 75% (95% CI: 42.8 – 94.5%). After 28 days follow-up, five patients classifies as PD, three as SD and four as PR: A responds rate of 58.3% (95% CI: 27.7 – 84.8%). “Discomfort last week” and “Physical activity problem” declined significantly (p < 0.01) and “Health and life quality” increases significantly (p < 0.01) from screening to Day 16 and Day 32. Sum CTC score increase non-significantly from 9.8 at screening to 12.3 and 13.4 after 16 and 32 days of treatment, respectively. During follow-up, the score decreased to 8.8. Thirty AE recorded. Ten classified as “Unrelated”, seven as “Possibly”, 12 as “Probably” and one as “Definite” related to the trial treatment. Of the 20 AE, which might be related to the treatment, 12 classifie as “Mild”, six as “Moderate”, one as “Severe “and one as “Life-threatening”. Conclusions: BP-C1 reduce the cancer growth, improve quality-of-life and well tolerated with only few mild to moderate AE.
Comparison of standard versus reduced-dose pegfilgrastim on clinical outcomes and chemotherapy dose intensity in patients with advanced pancreatic cancer receiving cytotoxic combination chemotherapy (NAPPCG) in an outpatient oncology infusion clinic.
Authors: Hicks Krystal , Odeh Adam 
Published: September 2018

e15710 Background: Pegfilgrastim use has been shown to reduce the incidence of febrile neutropenia when given at recommended dosage (6 mg) following myelosuppressive chemotherapy. Despite lack of supportive data, many prescribers have adopted the practice of utilizing reduced dosages (3-4 mg) of pegfilgrastim, often citing bone pain as reason for dose reduction. We sought to explore the impact of reduced-dose pegfilgrastim on chemotherapy dose intensity in patients with pancreatic cancer treated with the triplet combination of nab-paclitaxel, cisplatin and gemcitabine (NabPlagem) at our facility. Methods: A retrospective analysis was conducted on all patients who received NabPlagem chemotherapy in combination with pegfilgrastim during the period of 1/1/16 - 9/30/16. Patients who received at least 2 cycles were considered evaluable. Chemotherapy was administered on Days 1 and 8 of a 21-day cycle with pegfilgrastim administered Days 2 and 9. Chemotherapy doses were considered full-intensity if no reduction made from original treatment schema (i.e. 125 mg/m2 nab-paclitaxel, 25 mg/m2 cisplatin and gemcitabine 1000 mg/m2) with no doses delayed or omitted from treatment plan. Results: A total of 54 chemotherapy cycles were administered, with patients receiving between 5-13 cycles. Of these 54 cycles, 14 were given with reduced-dose pegfilgrastim (26%) and 40 at full dosage (74%). In the patients receiving full dose pegfilgrastim, treatment delays and omissions were observed in 5% cycles (n = 2), with no dose reductions required. Full dose-intensity was obtained in 90% cycles (36/40). In comparison, treatment delays and omissions were observed in 14% cycles given with reduced-dose pegfilgrastim. Dose reductions were required in 10/14 cycles (71%). Full dose-intensity was observed in 28.5% cycles (4/14). Conclusions: Based on this data, dosage of pegfilgrastim dose is an important factor in maintaining dose-intensity of chemotherapy, and full dosing (6 mg) should be preferred dosing schedule when used with myelosuppressive chemotherapy.
A phase IIb of eryaspase in combination with gemcitabine or FOLFOX as second-line therapy in patients with metastatic pancreatic adenocarcinoma (NCT02195180).
Authors: Hammel Pascal , Bachet Jean-Baptiste , El-Hariry Iman , Portales Fabienne , Mineur Laurent , Metges Jean-Philippe , De La Fouchardiere Christelle , Louvet Christophe , El Hajbi Farid , Faroux Roger , Guimbaud Rosine , Tougeron David , Volet Julien , Lecomte Thierry , Tournigand Christophe , Rebischung Christine , Berlier Willy , Gupta Anu , Cros Jerome , Andre Thierry 
Published: September 2018

e15718 Background: L-asparaginase (L-ASP) hydrolyses asparagine (ASN) leading to depletion of this amino acid. While normal cells are protected from ASN requirement due to their ability to produce ASN,.leukemic lymphoblasts and most cancer cells have a very low level or even lack of L-asparagine synthetase (ASNS), and thus depend on serum ASN for their proliferation and survival. L-ASP depletes serum ASN, which in turn inhibits the protein synthesis, resulting in cell cycle arrest and apoptosis in susceptible cancer cells, especially pancreatic cancer cells Eryaspase, which is L-ASP encapsulated in red blood cells, recently showed an encouraging activity and improved safety profile compared to L-ASP in patients (pts) with relapsed ALL. Knowing that up to 70% of pancreatic adenocarcinomas (PC) have low or null ASNS expression (Bachet Pancreas 2015), prompted us to evaluate the efficacy and safety of eryaspase in combination with chemo in PC. Methods: This open label, multicenter phase II randomized study (2:1) enrolled pts with second-line metastatic PC. Pts eligible to gemcitabine or FOLFOX regimen (according to first line chemo) were randomized to chemo +/- eryaspase (100 IU/Kg D3 and D17 of 4-wk regimen) until disease progression Primary end point: progression free survival in pts with ASNS negative tumors (0/1+). ASNS expression was measured using immunohistochemistry and optical density. Key secondary endpoints: PFS in ASNS positive pts (2+/3+), overall survival, biomarkers ( KRASmutation, cell free DNA), and safety. Results: 141 pts were enrolled. Treatment was generally well tolerated, with no safety concerns based on IDMC reviews. ASNS expression was negative in 69%, and positive in 31% of the pts At the time of submission, PFS and OS analysis and the correlation of ASNS expression with clinical outcomes were not yet available but will be presented at the meeting. Conclusions: This is the largest set of PC pts tested for the expression of ASNS and treated in second line with an asparaginase combined with chemotherapy. The ASNS expression levels may be a potential therapeutic target and therefore predictive of response to eryaspase for the treatment of advanced PC. Clinical trial information: NCT02195180.
Prognostic influence of waiting time in management of pancreatic ductal adenocarcinoma.
Authors: Suzuki Rei , Takagi Tadayuki , Hikichi Takuto , Ohira Hiromasa 
Published: September 2018

e15726 Background: Since pancreatic ductal adenocarcinoma (PDAC) showed aggressive progression, we hypothesized that waiting time in management might have prognostic influence on patients’ prognosis. Methods: Data on PDAC patients who underwent either chemotherapy or surgical resection in our hospital (2006 – 2016) were collected. Waiting time was classified into two groups as detection-to-diagnosis waiting time (WT1) and diagnosis-to-treatment waiting time (WT2). Median disease free survival (DFS) and overall survival (OS) were calculated by Kaplan-Meier method and utilized as cut-off points to divide patients into 2 groups (short- and long-survival group). Clinical characteristics including age, sex, tumor size, location of tumor, stage of disease, the levels of serum tumor markers, waiting times, use of adjuvant chemotherapy and resectability were compared between the two survival groups. Results: In total, 149 patients were included. Seventy-two patients who underwent chemotherapy (median OS: 9.7 months) were divided into long survival group (n = 42) and short survival group (n = 30). We did not find significant differences in both WT1 (20.0 days vs. 19.0 days, P = 0.98) and WT2 (17.0 days vs. 18.5 days, P = 0.93), while proportion of patients with locally advanced disease ( P = 0.02) and combination chemotherapy ( P = 0.003) was significantly associated with long survival. Among 79 patients underwent surgical resection, median DFS after pancreatic resection was 16.4 months and OS was 35.0 months. The patients were divided into short DFS (n = 47) versus long DFS (n = 30) and short OS (n = 57) versus long OS (n = 20). We did not find significant differences in both WT1 (short vs. long DFS: 21.0 days vs. 21.0 day, P = 0.65, short vs. long OS: 21.0 days vs. 23.0 days, P = 0.45) and WT2 (short vs. long DFS: 46.0 days vs. 44.5 days, P = 0.45, short vs. long OS: 46.0 vs. 41.0 days, P = 0.36). Both advanced T- and N-stage was significantly associated with poor DFS ( P = 0.049, P = 0.03, respectively) while only advanced T-stage was significantly associated with poor OS ( P = 0.02). Conclusions: Our findings suggested that both detection-to-diagnosis waiting time and diagnosis-to-treatment waiting time might not influence on prognosis of patients with PDAC.