bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ang-2 polymorphisms in relation to outcome in advanced HCC patients receiving sorafenib.
Authors: Marisi Giorgia , Scartozzi Mario , Faloppi Luca , Foschi Giuseppe Francesco , Lauletta Gianfranco , Valgiusti Martina , Aprile Giuseppe , Fornaro Lorenzo , Iavarone Massimo , Ercolani Giorgio , Frassineti Giovanni Luca , Amadori Dino , Casadei Gardini Andrea 
Published: September 2018

e15666 Background: Angiopoietin-2 (Ang-2) is a crucial angiogenic factor. By binding to its receptor Tie2, Ang-2 cooperates with the VEGF pathway to maintain normal physiological functions. In the presence of VEGF, Ang-2 destabilizes blood vessels and promotes vascular sprouting. In cancers, Ang-2 is linked to not only angiogenesis but also invasive and metastatic phenotypes. Although sorafenib exerts no significant activity against Tie2, the predictive value of Ang-2 has been explored in 2 studies. Llovet et al conducted a large biomarker study based on SHARP study. The authors found that a high baseline plasma Ang-2 level was an independent factor for poorer OS but not for reduced sorafenib efficacy. Polymorphism analysis seems to have more advantages than protein or gene expression analysis. Gene expression analysis is performed on biological material collected at a specific time in the natural history of the disease. It is also subject to the influence of a number of laboratory biases. Conversely, polymorphism analysis can be performed at any time during the course of the disease, is not substantially influenced by laboratory biases and is less expensive. In our study we analysed the role of ANG-2 polymorphisms in relation to clinical outcome in patients with hepatocellular carcinoma treated with sorafenib. Methods: We analyzed 135 patients with hepatocellular carcinoma treated with sorafenib. Peripheral blood samples or FFPE tumor tissues were available for DNA extraction and genotyping analysis. Nine Ang-2 polymorphisms were analyzed by direct sequencing or Real Time PCR method. Results: With regard to Ang4 rs55633437 was observed that patients carrying the allele GG were associated with a better PFS and OS. The variants GG were associated with a median OS of 16.9 months vs 6.5 months of variants GT and TT (p = 0.016). The variants GT and TT were associated with a median PFS of 2.94 months vs 4.67 months of variants GG (p = 0.03). These data were confirmed by multivariate analysis Conclusions: Ang4 rs55633437 could represent prognostic markers in patients with advanced hepatocellular carcinoma treated with sorafenib.
Predictive factors of carcinoid syndrome among patients with gastrointestinal neuroendocrine tumors (GI NETs).
Authors: Cai Beilei , Broder Michael , Chang Eunice , Yan Tingjian , Metz David C. 
Published: September 2018

e15690 Background: Carcinoid syndrome (CS) is associated with a significant symptom burden and deleterious impacts on quality of life. Patients may experience delays in CS diagnosis of 5 to 7 years from initial onset of symptoms, as symptoms may be mistaken for other diseases, such as irritable bowel syndrome or menopause. The current study attempts to detect factors predictive of CS prior to CS diagnosis among patients with GI NETs. Methods: Using a US administrative claims database (IMS PharMetrics) and a retrospective case-control study design, patients (≥18 years) who were newly diagnosed with GI NETs without CS (controls) were exactly matched to patients with CS (cases) based on NET diagnosis date (month and year) at a 3-to-1 ratio. For CS patients, the study index date was the first CS diagnosis date. Each control patient was assigned to have the same index month and year as the matched case patient. The most frequently observed conditions other than symptoms/diagnoses known to be associated with CS during the 1 year prior to the index date were assessed. These conditions were entered into a forward-stepwise logistic regression model to derive predictive factors. Similar methods were applied to another administrative claims database (Truven Health Analytics MarketScan) to validate these predictors. Results: In the development database 1,004 patients with GI NETs were identified, among whom 251 (25%) had CS and 753 (75%) were controls. In both databases, three factors prior to CS diagnosis were found consistently associated with higher risks for CS, including liver disorder [odds ratio (95% CI): 3.38 (2.07 - 5.51)], enlargement of lymph nodes [2.13 (1.10 - 4.11)], and abdominal mass [3.79 (1.87 - 7.69)]. Conclusions: By assessing patients with GI NET from two independent US claim databases, this study suggested that patients diagnosed with CS were 2-3 times more likely to be diagnosed with liver disorder, enlargement of lymph nodes, or abdominal mass, than those without CS during the one year prior to CS diagnosis. Future studies using patients’ medical charts are warranted to validate and interpret the findings. These findings, when validated, may aid physicians to diagnose CS patients earlier.
Prevalence of co-morbidities in elderly patients with distant stage neuroendocrine tumors.
Authors: Dasari A. , Shen Chan , Chu Yiyi , Halperin Daniel M. , Xu Ying , Zhou Shouhao , Shih Tina , Yao James C. 
Published: September 2018

e15699 Background: The median age of diagnosis of neuroendocrine tumors (NETs), an indolent tumor characterized by hormone production (carcinoid syndrome, CS) when metastatic is 63 years. Patients (pts) in this age group have multiple co-morbidities. However, their prevalence among elderly pts with metastatic NET is unknown. Methods: The Surveillance, Epidemiology and End Results (SEER)-Medicare database was used to identify 2,388 elderly patients with distant stage NET (Age: < 70: 631; 70-79: 1200; > 80: 557; Race: white: 83.4%, black: 8.6%) diagnosed between 1/03 and 12/11 identified by ICD-O-3 codes with continuous Medicare Parts A and B enrollment during the one year after NET diagnosis. We examined the prevalence of common co-morbidities in the elderly population: dementia, heart conditions including ischemic heart disease (IHD), hypertension (HTN) & congestive heart failure, chronic obstructive pulmonary disease, chronic kidney disease, hyperlipidemia, diabetes, arthritis, and two additional relevant comorbidities: osteoporosis (OP) and non-rheumatic tricuspid valve (TV) disorders. Pts were considered to have a condition if they had ≥ 1 inpt or ≥ 2 outpt visits indicative of the condition. We compared the prevalence in the NET group with that in a propensity score matched non-cancer group using chi-square test. Within the NET group, we also examined the association between pt characteristics and the presence of the conditions using a logistic regression model. Results: Compared to the matched non-cancer control group, NET pts were significantly (P < 0.01) more likely to have HTN (74% vs. 66%), OP (14% vs. 11%) & TV disorders (1.72% vs. 0.98%) and less likely to have dementia (7.3% vs 17.4%), IHD (23.2% vs 29%) and diabetes (30.3% vs 33.5%). CS was noted in 25.7% of the NET group and logistic regression showed that these pts with were significantly more likely to have TV disorders (AOR = 2.52, 95% CI: 1.24-5.14) and osteoporosis (AOR: 1.34, 95% CI: 1.01-1.81). Conclusions: This population-based study showed that elderly NET pts have significantly different prevalence of co-morbidities compared to non-cancer controls. The impact of these conditions on survival and therapeutic decisions is being evaluated.
Prognostic factors and effects of adjuvant therapy after pancreatoduodenectomy for ampullary adenocarcinoma: Mayo Clinic experience.
Authors: Jin Zhaohui , Hartgers Mindy L. , Sanhueza Cristobal T. , Johnson Benny , Shubert Christopher R. , Nagorney David M. , Smoot Rory L. , Truty Mark J. , Kendrick Michael L. , Smyrk Thomas C. , Mahipal Amit 
Published: September 2018

e15703 Background: The aim of this study is to identify prognostic factors and effects of adjuvant therapy for patients with ampullary adenocarcinoma who had pancreatoduodenectomy. Methods: A cohort of 123 consecutive patients underwent pancreatoduodenectomy for ampullary adenocarcinoma from January 1, 2006, through August 31, 2016 at Mayo Clinic in Rochester, MN. Only patients with ampullary carcinoma by pathology review were included and were histologically classified as pancreaticobiliary or intestinal subtypes. Median follow-up duration was 41.0 months. Patient survival and its correlation with patient and tumor variables were tested by univariate and multivariate analysis. Results: Pancreatoduodenectomy was curative-intent in 120 out of 123 patients. All 123 patients underwent radical surgery, 32 patients (26.0%) had laparoscopic pancreatoduodenectomy. Among 123 patients, there were 76 men (61.8%).Median age at diagnosis was 67.2 years. 54 patients (45%) without metastatic disease upon surgery had adjuvant therapy (35 patients had chemotherapy only while 19 patient also had radiation). Median overall survival (OS) was 91.8 months. Poor performance status at disease diagnosis (ECOG > = 1), old age ( > = 70 years), primary tumor infiltration (T), lymph node metastasis (N), and advanced disease stage (TNM) had a significant negative impact on survival (p < 0.05 by univariate analysis). Gender, diabetes at disease diagnosis, laparoscopic surgery approach, number of lymph nodes removed, number of positive lymph nodes, and tumor size did not influence survival. In multivariate analysis, ECOG score > = 1, adjuvant treatment, primary tumor infiltration (T) and lymph node metastasis (N) remained statistically significant. Adjuvant therapy was independently associated with improved disease free survival (P = 0.0388) and overall survival (p = 0.030) for patients with advanced disease (stage IIB and above). Conclusions: Poor performance status and advanced disease stage are associated with decreased survival in patients with ampullary adenocarcinoma. Patients with advanced disease should be considered for adjuvant chemotherapy.
Epigenetic regulation of cancer self-renewal differs between endocrine tumors.
Authors: Faleiro Ines , De Mello Ramon Andrade , Apolonio Joana Dias , Roberto Vania Palma , Tabori Uri , Castelo-Branco Pedro 
Published: September 2018

e15717 Background: Cancer cells achieve limitless self-renewal capacity mainly through telomerase reactivation. Methylation of a specific region in the h TERT promoter, termed TERT Hypermethylated Oncologic Region (THOR), has been associated with telomerase reactivation, increased telomerase activity and patient outcome in several cancers. Methods: In this study, we assessed the methylation status of THOR using The Cancer Genome Atlas (TCGA) data on cohorts of two endocrine cancers with distinct cell proliferation rates: the highly proliferative pancreatic adenocarcinoma (n = 194 patients) and the more indolent thyroid carcinoma (n = 571 patients). Results: THOR was significantly hypermethylated in malignant cancer when compared to benign adjacent tissue in pancreatic cancer (p < 0.0001), but not in thyroid cancer. In pancreatic cancer, THOR hypermethylation could also distinguish normal tissue from early stage I disease and it associated with worst patient prognosis. Conclusions: These preliminary findings indicate that THOR can discriminate aggressive tumors from non-aggressive ones, and evidenced the diagnostic and prognostic value of THOR in pancreatic cancer.
Efficacy and tolerability of second-line nab-paclitaxel and gemcitabine (NG) after failing first-line FOLFIRINOX in patients (pts) with advanced pancreatic cancer (APC): A single-institution experience.
Authors: Zhang Hanbo , Kellett Curtis , Lambert Pascal J , Kim Christina 
Published: September 2018

e15723 Background: APC is incurable and has a poor prognosis. First line chemotherapy options include 5-fluorouracil, irinotecan and oxaliplatin (FOLFIRINOX) or NG. However, the optimal second-line regimen is unclear. In pts who progress on FOLFIRINOX and maintain a good performance status, NG may be a reasonable second line option. As such, we sought to: 1) describe the clinical and pathologic features of pts who received second line NG compared to pts who received second line gemcitabine (GEM) or best supportive care (BSC); 2) Evaluate the toxicity profile of NG in the second line setting; 3) determine whether a survival benefit exists with second line NG. Methods: Pts ≥18 diagnosed with APC from 2012-2016 and treated with palliative chemotherapy at CancerCare Manitoba (CCMB) were identified from the Manitoba Cancer Registry. CCMB pharmacy records identified pts who received FOLFIRINOX followed by second line NG, GEM or BSC. A retrospective analysis was performed to identify pts and treatment characteristics, toxicity, dose reductions, dose delays and survival. Results: 146 pts received first line FOLFIRINOX. Of those who progressed and were offered second line therapy, 30 (50%) received NG, 8 (16%) received GEM and 22 (37%) chose BSC. Median age at diagnosis was 61 (35-84), 47% were female, 73% had metastatic disease and 63% had primaries in the head of pancreas. Grade 3 and 4 neutropenia was more common with NG compared to GEM (27% vs. 6.7%). There were more dose reductions and dose delays with NG compared to GEM (76.7% vs. 25% and 63.3% vs. 12.5% respectively). The median progression free survival was 3.61 months in the NG group, compared with 2.51 months in the GEM group (hazard ratio 2.48; 95% CI 1.08-5.65; P = 0.03). The median OS was 5.69 months in the NG group compared to 3.82 months the GEM group (hazard ratio 2.611; 95% CI, 1.11-6.38). Conclusions: In a select group of pts with APC who progress after first line FOLFIRINOX, there is a role for second line NG. Although many pts required dose reductions and delays, second line NG was associated with a survival benefit compared to GEM, with manageable toxicity.
Radioembolization with yttrium-90 resin microspheres for liver metastases of pancreatic adenocarcinoma: A retrospective multicenter analysis.
Authors: Kim Alexander Y. , Frantz Shelby , Akhter Nabeel , Zhang Jian 
Published: September 2018

e15745 Background: Patients with chemotherapy-treated metastatic pancreatic cancer typically survive for 7 to 11 months. Liver metastases from the pancreas are common and can reduce survival. Radioembolization of these metastases with Y-90 resin microspheres (Y-90 resin) may reduce tumor burden and improve prognosis, but data are limited. We report early data from a multicenter database of patients with pancreatic adenocarcinoma treated with Y-90 resin. Methods: Retrospective patient, treatment, and outcome data were entered by each site (Georgetown, U Maryland). Outcomes included overall survival (OS, determined with Kaplan-Meier analyses), response rate (RECIST), and adverse events (AEs; CTCAE v4.0). Results: Data from the first 24 patients (79% male, mean age 63 y [range 51-77 y]) were analyzed. ECOG status was 0 (n = 10), 1 (n = 13), and 2 (n = 1). Median (IQR) time from diagnosis to Y-90 resin was 10.2 (6.1) mo. Nine patients had extrahepatic disease. Median (IQR) dose delivered to the right (n = 14), left (n = 2), or whole (n = 8) liver was 1.36 (0.42) GBq. Y-90 resin was given concurrently with first-line chemotherapy in 12/21 patients (57%), with a minimum of 4 mo between the onset of chemotherapy and Y-90 resin treatment. Median OS was 6.0 mo (95% CI: 3.9, 12.5) from Y-90 resin and 16.7 mo (95% CI: 13.3, 26.1) from diagnosis. Five patients experienced a partial response. Most AEs were grade 1 or 2. Three patients had grade 3 AEs (abdominal distension or pain, fatigue, ascites, odynophagia, oral sores, biliary duct dilation), and 4 had grade 3 laboratory values (white blood cells, bilirubin, alkaline phosphatase, albumin). Two patients experienced grade 4 AEs, 1 with peripheral neuropathy and 1 with elevated ALT & AST suggesting post-radioembolization hepatitis. Conclusions: Overall, Y-90 resin was safe, with few serious AEs. Survival in this retrospective study was promising, given the generally poor prognosis for pancreatic adenocarcinoma; however, further investigation is needed.
The efficacy of addition of chemoradiotherapy to achieve resectability in locally-advanced pancreatic cancer remaining unresectable after neoadjuvant chemotherapy.
Authors: Mukherjee Sarbajit , Weir Joshua , Morton Jordan , Herman Terence S. , Khalid Bilal , Postier Russell , Hatoum Hassan 
Published: September 2018

e15761 Background: Although the efficacy of neoadjuvant chemotherapy (NACT) in achieving resectability in locally advanced pancreatic cancer (LAPC) has been 20-31%, many cases remain unresectable. The aim of this study is to evaluate the efficacy of adding chemo radiotherapy (CRT) to achieve resectability in LAPC that remained unresectable after NACT. Methods: Between January 2008 and December 2016, 38 patients with LAPC (borderline resectable or unresectable pancreatic cancer, BRPC or URPC) received NACT and remained unresectable; subsequently, all patients received CRT in an attempt to achieve resectability with curative-intent. The primary objective of this retrospective single institution study is to assess resection rate (RR) in these patients. The secondary objective is to assess overall survival (OS). Results: A total of 38 patients (22 male, 16 female) who were identified as BRPC (50%) or URPC (50%) at presentation as defined by multidisciplinary tumor board using pancreatic protocol CT scan received NACT and remained unresectable. The median age was 64 (56-70.5) years. The primary site was head of pancreas in 66% versus other sites in 34% . The T-stage distribution was T1 (2.6%), T2 (2.6%), T3 (34.2%) and T4 (60.6%). N0 and N1 were 63.1% and 36.9% respectively. The types of NACT included FOFIRINOX (39.5%), Gemcitabine-based (58%) and unknown (2.5%). The median number of NACT cycles was 4 (2.25-4). All patients received subsequent CRT. Only the primary tumor was targeted with a median dose of 5040 (4950-5400) cGy and a median number of fractions 18(18-28). Chemo used concurrently with radiation was 5-FU (52.5%), Xeloda (39.5%), Gemcitabine (5.5%) and unknown (2.5%). Of note, 36.8 % patients achieved resectablity (14/38). The R0 and R1 resections were 11 (28.9%) and 3 (7.9%) respectively. 52.6% patients received adjuvant chemotherapy. The OS was 17 (6-24) months in the R0 group versus 8 (7-9) months in the R1 group. For the whole group, median OS was 11.5 (7-18.25) months. Conclusions: The addition of CRT to NACT in LAPC may improve resectability leading to an OS that approximates the OS in those patients who had upfront resectable disease.
A comparison of percutaneous and endoscopic-guided celiac plexus block/neurolysis in pancreatic cancer patients.
Authors: Kambhampati Swetha , Sugar Elizabeth A. , Herman Joseph M. , Erdek Michael A. , Shin Eun Ji , Laheru Daniel A. 
Published: September 2018

e15767 Background: Celiac plexus block (CPB) and celiac plexus neurolysis (CPN) are options for pain control in pancreatic cancer. Conventionally they are performed percutaneously (PC) with fluoroscopic or CT guidance. However endoscopic ultrasound (EUS) guidance is being increasingly used. The aim of this retrospective study is to compare PC-guided and EUS-guided CPB/CPN for pain control. Methods: Our retrospective cohort study included pancreatic cancer patients who underwent CPN/CPB for pain control from 2008 to 2015 at Johns Hopkins. Patients were assessed immediately post-procedure and at 1 month. Patients were selected using CPT and ICD diagnosis code guided searches of the EHR. Pain intensity was assessed using a Numeric Rating Scale (NRS). A response was defined as a decrease in NRS scores by = > 3 points. The validated FACT-Hep score was used to assess quality of life (QOL). Opiate usage was converted into morphine dosage equivalents. Wilcox rank-sum and Fisher’s exact test were used to compare the EUS and PC cohorts. Results: Of 107 patients, 46 (43%) had EUS-CPN, 57 (53%) PC-CPN, and 4 (4%) PC-CPB. 10 patients had procedural complications (7% EUS and 11% PC, p = 0.51) with the most common being chronic diarrhea. The baseline median NRS score was 7 with significantly higher scores for those receiving EUS compared to PC (9 vs 7, p < 0.001). Immediately post-procedure, more PC patients (87%) had a response when compared to EUS patients (72%), although it did not reach statistical significance (p = 0.08). By one month, there was no difference in response rates. (43% CPN vs 34% EUS, p = 0.42) FACT-Hep score declined significantly in all patients with a median drop of 8 points at 1 month and no difference between PC and EUS (9 vs 8, p = 0.46). There was no difference in opiate usage at 1 month (88% PC vs 93% EUS, p = 0.51). Conclusions: Both EUS and PC-guided CPN were effective at reducing post-procedural pain in pancreatic cancer patients but their effectiveness waned by 1 month. EUS did have slightly fewer complications although PC did have slightly higher rates of response post-procedurally. QoL declined and opiate usage was unchanged in both groups. Both procedures had temporary efficacy and need further evaluation.
PANOVA: A phase II study of TTFields (150 kHz) concomitant with standard chemotherapy for front-line therapy of advanced pancreatic adenocarcinoma—Updated efficacy results.
Authors: Benavides Manuel , Guillen Carmen , Rivera Fernando , Gallego Javier , Lopez-Martin Jose A. , Küng Marc 
Published: September 2018

e15790 Background: TTFields are a non-invasive, regional antimitotic treatment modality, which has been approved for the treatment of glioblastoma by the FDA. TTFields predominantly act by disrupting the formation of the mitotic spindle during metaphase. TTFields were effective in multiple preclinical models of pancreatic cancer. PANOVA was the first trial testing TTFields in pancreatic cancer patients. Results from the first arm of the study, testing TTFields in combination with gemcitabine, have demonstrated superiority in efficacy compared to historical controls (Rivera F. et al, J Clin Oncol 34, 2016 (suppl 4S; abstr 269). Methods: Twenty advanced pancreatic cancer patients were enrolled in the second arm of PANOVA and treated with TTFields in combination with gemcitabine concomitant to nab-paclitaxel. All patients had unresectable tumors, an ECOG performance score of 0-1 and no prior therapy. The primary endpoint was the incidence and severity of adverse events. Results: The median age was 68.2 (range – 58-81) and most patients (65%) had an ECOG score of 1. Twelve patients (60%) had distant metastases. Ten patients (50%) had serious AEs during the study period. Eleven patients (55%) had treatment-related skin toxicity, of which 5 had grade 3 toxicity. No TTFields-related serious AEs were reported. The median PFS was 12.7 months (95% CI 5.4, NA): 9.3 months in patients with metastatic disease, and not reached in locally-advanced patients. PFS rate at 6 months was 65%: 50% in metastatic disease and 87.5% in locally advanced patients. Of the evaluable tumors, 40% had partial response and another 47% stable disease. The median OS was not reached, and the 1-year survival rate was 72% (62.5% in metastatic disease and 87.5% in locally advanced disease). Conclusions: TTFields concomitant to gemcitabine and nab-paclitaxel are safe for advanced pancreatic cancer patients, with promising clinical outcome which doubled historical data. A phase III trial is planned, testing the efficacy of TTFields combined with gemcitabine and nab-paclitaxel in locally-advanced pancreatic cancer patients. Clinical trial information: NCT01971281.