bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prooxidant effect of α-tocopherol in pancreatic tumors.
Authors: Surikova Ekaterina I. , Frantsiyants Elena M. , Goroshinskaya Irina A. , Trifanov Vladimir S. , Aleynov Viacheslav A. , Nemashkalova Ludmila A. , Neskubina Irina V. , Chernyak Maksim N. , Sanamyants Sergey V. , Gabrichidze Petr N. , Kit Oleg I. , Zhukova Galina V. , Fomenko Yuriy A. , Petrov Dmitry S. 
Published: May 2020

e16698 Background: The coexistence of neuroendocrine tumors and pancreatic adenocarcinoma is rare, and treatment of such mixed tumors is challenging due to the differences in their natural course and response to systemic therapy. There is growing evidence that vitamins affect the biology of pancreatic tumors. The purpose of the study was to measure concentrations of retinol (RET), α-tocopherol (α-TCP) and diene conjugates (DC) in the blood of patients with pancreatic cancer in order to reveal its pathogenetic characteristics. Methods: Blood levels of RET and α-TCP (ELISA methods, Cloud-Clone Corp, USA), their ratio and DC concentrations (biochemical method) were measured before treatment if 42 patients with pancreatic cancer: adenocarcinoma (AC), T1-3N0-1M0, n = 9; AC with a neuroendocrine component (AC+NE) (up to 30%), n = 21; neuroendocrine tumors (NET), T1-3N0-1M0, n = 12. 22 healthy men of similar age were controls. All patients gave their voluntary informed consent for the study. Results: RET levels in all patient were statistically significantly lower than in controls: in AC by 3.8 times, in AC+NE by 1.9 times, in NET by 3.7 times (p = 0.0000). Concentrations of α-TCP in AC were 1.6 times (p = 0.0011) lower than in controls, in AC+NE were similar, and in NET α-TCP was 1.5 times higher than in controls (p = 0.0000). The ratio of α-TCP/RET in all patients significantly exceeded control values: in AC by 2.2 times, in AC+NE by 1.6 times, in NET by 5.7 times (p = 0.0000). Levels of DC in all patients were higher than in controls: in AC by 2.5, in AC+NE by 2.1, in NET by 2.7 times (p = 0.0001). Conclusions: Changes in serum levels of RET and α-TCP differ in patients with AC, NET and mixed tumors, which causes changes in the balance of vitamins and can contribute to a prooxidant effect, as evidenced by an increase in DC levels.
Phase II study of ONC201 in pheochromocytoma-paragangliomas (PC-PG), medullary thyroid carcinoma (MTC), and other neuroendocrine tumors.
Authors: Anderson Peter Meade , Zahler Stacey 
Published: May 2020

e16703 Background: ONC201 is an imipridone with specificity for the dopamine-like DRD2 receptor. Anti-cancer effects involve up-regulation of TRAIL/DR5, dual AKT/ERK pathway inhibition, and integrated stress response. Because TCGA analysis showed very high DRD2 expression in neuroendocrine tumors, especially pheochromocytoma-paragangliomas (PC-PG), an investigator initiated IND study of ONC201 in neuroendocrine tumors (CCF IRB17-808; CASE2716; IND132665; NCT03034200) was done. Methods: ONC201 dose was 625 mg po/wk. Metastatic PG-PG were enrolled in cohort A. Other neuroendocrine patients were entered in cohort B. Two additional patients had single patient IND. Because hypertension is an issue from catecholamine producing PC-PG, all PC-PG patients had combined alpha + beta blockade and bp was monitored in the clinical research unit after dose #1 ONC201. Additional data was obtained with daily home bp monitoring, often with a wireless cuff which connects into EPIC via MyChart. Labs, scans, and clinic visits were done at week 6, then every 3 months from initial ONC201 dose. Patients with clinical benefit remained on study and could get radiation for bone metastases. Results: Neuroendocrine tumors were treated with ONC201 included 10 PC-PG, 3 with MTC 13 with other varieties including sarcomas, adrenal cortical carcinoma (ACC), neuroblastoma, and GI neuroendocrine tumor (NET). ONC201 was exceptionally well tolerated. All patients were able to maintain or improve KPS while on study. No adverse effects on bp were seen. The only ONC201-related AE was temporary grade 1 neurocognitive dysfunction for ~36 hours after weekly ONC201 dosing in 2/10 PC-PG patients. 4/10 PC-PG patients remain on study at 28, 22, 22, and 4 month. 1 DSRCT patient achieved a PR at 3 months and has been treated 28 months. An ACC patient was initially responsive (PR), but rapidly progressed in liver; 1 GI NET patient had -10% reduction by RECIST at 3 months and remains on treatment. MTC may be responsive (1 no response, 2 stable and improving by RECIST at 3 months). Conclusions: ONC201 is very well tolerated with excellent quality of life and extended clinical benefit against neuroendocrine tumors. Although ONC201 has activity against neuroendocrine tumors, especially PC-PG, increased efficacy will likely require combination therapy. Clinical trial information: NCT03034200 . [Table: see text]
Molecular correlation of the activity of evofosfamide (EVO) in combination with sunitinib (SUN) in pancreatic Neuroendocrine Tumors (pNETs) in the SUNEVO GETNE Trial.
Authors: López-López Carlos , Alonso Gordoa Teresa , Benavent Marta , Capdevila Jaume , Teule Alex , Custodio Ana , Sevilla Isabel , Santos Maria , Lanillos J. , Rodríguez-Antona Cristina , Garcia-Carbonero Rocio , Grande Enrique 
Published: May 2020

e16706 Background: MEN1, DAXX, ATRX, and PI3K/AKT/mTOR pathway genes are frequently mutated in pNETs. Sunitinib is approved and widely used in the metastatic setting but unfortunately, no validated predictive biomarker has been identified to guide therapy yet. The SUNEVO phase II trial of the Spanish Task Force Group for Neuroendocrine and Endocrine Tumours (GETNE) trial combined the pro-drug of EVO under SUN-induced hypoxic conditions. Methods: We performed an exploratory analysis aimed to identify somatic mutations associated with the clinical benefit of pNET patients treated with SUN+EVO combination. Seventeen treatment-naïve pts with pNETS were included in the SUNEVO trial, and 4 (23.5%) achieved a partial response (by RECIST 1.1). Tumor DNA from 10 FFPE tumor samples were successfully sequenced with an enrichment panel (Nimblegen, Roche) including 42 cancer-related genes and TERT promoter region. Median coverage was 793x. Coding non-synonymous and loss-of-function variants were considered for the analysis. Final analysis included tumor samples from the 10 patients with NGS results. Results: Somatic mutations were found in MEN1 (70%), DAXX (30%), ATRX (20%), SETD2 (20%) and PTEN (10%). Mutations in the telomere maintenance genes DAXX and ATRX were concordant with mutual exclusivity. The loss of MEN1 was associated with a greater number of mutations (p = 0.019). Patients with complete and partial response showed heterogeneous genetic profiles. Conclusions: The molecular alterations of the patients in the SUNEVO trial were consistent with those previously described for metastatic pNETs. No clear association between molecular defects and treatment response was found. Clinical trial information: NCT02402062 .
Survey of challenges in access to diagnostics and treatment for neuroendocrine tumor (NET) patients (SCAN): Awareness of specialized techniques and latest interventions.
Authors: McDonnell Mark , Van Genechten Dirk , Kolarova Teodora , O'Toole Dermot , Singh Harjit , Chen Jie , Howe James R. , Singh Simron , Bouvier Catherine , Rodien-Louw Christine , Leyden Simone , Dureja Sugandha 
Published: May 2020

e16708 Background: SCAN measured global readiness to provide diagnostics and treatments for NET patients in terms of awareness, availability, quality and affordability. This analysis focused on patient and healthcare professional (HCP) awareness of NET diagnostics and treatments. Methods: During Sept-Nov 2019, NET patients and HCPs completed an online survey (available in 14 languages). Results: There were 2795 respondents from 68 countries across 6 continents (2359 patients/carers; 436 HCPs). Primary NETs were most often gastroenteropancreatic NETs (GEP NET; 71% [1408/1983]), particularly small intestinal (35% [690/1983]) or pancreatic (20% [402/1983]). Biopsy was the most well-known diagnostic option in the overall NET patient group (82% [1917/2325]), the GEP NET patient subgroup (83% [1156/1395]) and HCPs (94% [411/435]), followed by CT (all patients: 81% [1874/2325]; GEP NET: 80% [1118/1395]; HCPs: 86% [376/435]). More HCPs were aware of specialized diagnostics, such as 68Ga-DOTA PET CT (HCP 81% [353/435]) and chromogranin A (CgA; 79% [344/435]), than patients (all: 68% [1574/2325] & 62% [1451/2325], respectively; GEP NET: 69% [962/1395] & 67% [936/1395]). The vast majority of all patients (87% [1983/2275]), GEP NET patients (89% [1215/1363]) and HCPs (91% [392/431]) knew surgery was a treatment option. Somastatin analogues were recognised as a treatment option by 90% of HCPs (387/431), but only 75% of GEP NET patients (1019/1363) and 70% of all NET patients (1599/2275). Nearly a quarter of HCPs (22% [95/431]) and one-third of patients (all: 33% [755/2275]; GEP NET: 30% [409/1363]) had not heard of peptide receptor radionuclide therapy (PRRT). The majority of patients (all: 88% [2007/2273]; GEP NET: 89% [1213/1370]) and HCPs (93% [396/425]) were aware of conventional imaging, such as CT/MRI/ultrasound, being used for ongoing monitoring of NETs. Approximately a third of all NET patients and a quarter of HCPs were unware CgA (patients: 32% [723/2273]; HCPs: 22% [94/425]) or 68Ga-DOTA PET CT (patients: 29% [670/2273]; HCPs: 24% [102/425]) were ongoing monitoring tools. Similarly, CgA and 68Ga-DOTA PET CT were not recognized by 27% of GEP NET patients (364/1370 & 371/1370, respectively). Conclusions: Increased awareness of NET diagnostics and treatments, particularly newer, more specialized tools, amongst both HCPs and patients is required to ensure continued advancements and improvements in the global standard of care for NETs.
Distinct clinical characteristics in young-onset pancreatic neuroendocrine tumor: A propensity-adjusted analysis.
Authors: Goksu Suleyman Yasin , Ozer Muhammet , Kazmi Syed Mohammad Ali , Sanford Nina Niu , Aguilera Todd Anthony , Hsieh David , Sanjeevaiah Aravind , Verma Udit , Khosama Leticia , Maxwell Mary Claire , Bleeker Jonathan , Atiq Muslim , Beg Muhammad Shaalan 
Published: May 2020

e16710 Background: Pancreatic neuroendocrine tumor (PNET) is a rare disease. There is a lack of data on the association of age and sociodemographic characteristics on survival in patients with NET. Our study aimed to evaluate clinical, molecular differences, and survival outcomes in young-onset PNET (YOPNET) and late-onset PNET (LOPNET). Methods: We used the National Cancer Database to identify patients with YOPNET ( < 50 years) and LOPNET (≥50 years) who underwent definitive surgery diagnosed between 2004 and 2015. We calculated the survival outcomes using Kaplan Meier and Cox regression methods before and after 1:1 nearest neighbor propensity score matching. We used the AACR Genie cohort to compare mutation frequency with the Benjamini-Hochberg method between YOPNET and LOPNET. Results: A total of 6,259 patients with PNET were selected, of which 27% were YOPNET. Patients with YOPNET were more likely to be female, black, and Hispanic, have private insurance versus LOPNET (all p < .001). Patients with YOPNET had less comorbidity score, but greater tumor size ( > 4 cm) and higher stage (all p < .001). Patients with LOPNET were more likely to be treated in an academic/research facility ( p < .001). Patients with YOPNET were more likely to be located in the head of the pancreas ( p = .004). Patients with YOPNET had better overall survival (OS) as compared to patients with LOPNET which persisted after propensity score matching ( p < .001). This difference continued after adjusting for clinically significant variables (unmatched p = .008; matched p = .01) (Table). For genomic analysis, we identified 177 patients; 27% was YOPNET, and patients with YOPNET had a significantly lower rate of MEN1 mutation than patients with LOPNET (26% vs. 56%, p < .001). Rate of other mutations was not different. Conclusions: Patients with YOPNET who underwent surgery had better OS than LOPNET and were more likely to have higher stage and greater tumor size. YOPNET represents a disease with distinct clinical and molecular features. [Table: see text]
Patient-derived organoids as a potential tool for clinical decision in advanced gallbladder cancer.
Authors: Obreque Javiera , Vergara Luis , Suarez Felipe , Garcia Patricia , Marcelain Katherine , Toro Jessica , Rivas Solange , Rosa Lorena , Roa Juan Carlos , Nervi Bruno , Viñuela Eduardo , Aguayo Gloria , Muñiz-Muñoz Sabrina , Caire Nicole , Escalante Anrried , Mondaca Sebastian , Bizama Carolina 
Published: May 2020

e16717 Background: Human gallbladder cancer research lacks in vitro models that can recapitulate the pathophysiology of the original tumor and normal epithelia. Organoids cultures emulate the tumor heterogeneity and have been successively used as translational models to evaluate clinical response to anticancer drug. Here, we established and characterized patients derived organoids culture (PDOs) from human gallbladder cancer patients. Methods: Fresh tissues obtained from gallbladder cancer patients who underwent cholecystectomy were digested with Collagenase/Dispase, filtered and then suspension cells were mixed with Matrigel (1:1) for organoids establishment. Cultures were maintained at 37°C and 5% CO2. The organoids were characterized through histopathology evaluation, immunohistochemistry, and ultra-deed targeted sequencing (TruSeq protocol, Illumina, TSACP; 25 genes). In addition, we evaluated the response of organoids to gemcitabine, cisplatin and Fluorouracil (5-FU), using the CellTiter-Glo 3D luminescence assay. Results: We have successfully established PDOs cultures from six patients with gallbladder adenocarcinoma with a 60% efficiency (6/10). The PDOs recapitulated the histological features and maintained the expression of CK19, Ki67, P53 as compared with the epithelia of primary tumors. Moreover, the PDOs maintained the mutational status of major driver genes, including TP53 and PIK3CA. Finally, tumor organoids showed differential response to standard chemotherapy treatment. GBC-PDO2 and GBC-PDO4 showed high resistant to gemcitabine (IC50 > 10μM), which suggests that the personalized treatment is necessary for generate better response. Conclusions: the established gallbladder tumor organoids exhibited similar histological and genomic features in relation to their original epithelia. PDOs can be considered a valuable tool for future research aimed to understand gallbladder cancer biology and for developing personalized-medicine approaches for advanced gallbladder cancer patients. (Funding Source: FONDECYT #1171463, FONDECYT #1170893 and Fondef IT16I10051).
Intraoperative electrochemotherapy in locally advanced pancreatic cancer: Results and impact on quality of life. a single center experience.
Authors: Di Marco Mariacristina , Ricci Claudio , Carloni Riccardo , Grassi Elisa , De Lorenzo Stefania , Palloni Andrea , Abbati Francesca , Andrini Elisa , Di Federico Alessandro , Ricci Angela Dalia , Ingaldi Carlo , Serra Carla , Alberici Laura , De Raffele Emilio , Guido Alessandra , Minni Francesco , Rizzo Alessandro , Brandi Giovanni , Pantaleo Maria A. , Casadei Riccardo 
Published: May 2020

e16731 Background: Locally advanced pancreatic cancer (LAPC) is usually treated with chemoradiotherapy with poor results, thus additional therapies have been proposed. Of the latter, electrochemotherapy (ECT) represents a non-thermal ablation method, which combines the administration of chemotherapeutic drugs with permeabilizing electric pulses for cell membrane electroporation. The present study is the first to assess the short and long-term results, and the quality of life of the patients who underwent ECT for LAPC. Methods: Observational study of patients affected by LAPC who underwent intraoperative ECT after chemoradiotherapy. The inclusion criteria were: 1- patients with LAPC (defined according to the National Comprehensive Cancer Network 2019), 2- previous chemoradiotherapy and 3- absence of disease progression at restaging. Data at diagnosis and at restaging were collected for each patient. The Quality of life was evaluated using the Euro Quality of Life Group Association Questionnaire (EQ-5D-5L). The questionnaire was administered to all patients before and after ECT. Results: From May 25, 2018 to November 26, 2019 five patients underwent ECT: in 4 cases, the tumors were located in the head and, in one, in the body of the pancreas. Preoperative chemotherapy consisted mainly of 6 cycles of modified folfirinox, while the radiotherapy consisted of 54 Gy (27 fractions). At restaging, the serum value of CA 19-9 and tumor size were reduced; however, the vascular involvement did not change. No downstaging was recorded. Intravenous bleomycin 15,000IU/m2 was given as a bolus, the ECT procedure was performed using at least 4 needles with a mean duration time of 27 minutes, (range 15-40). No postoperative mortality or major complications were reported. The mean length of stay was 8 days (range 5-14). Four patients were alive and well at the end of the study while one patient died from disease progression. The mean follow-up was 20.8 months (range 9-34) from diagnosis and 9.4 months (range 2-19) from ECT. The quality of life was good (EQ-5D-5L scale > 50 in all cases) and there was improvement in pain/discomfort with respect to the pre-treatment period in 3 out of 5 patients. Conclusions: Electrochemotherapy can be considered a simple, feasible and safe palliative additional treatment in LAPC without progression after chemoradiotherapy, and it seems to allow a good quality of life and pain improvement.
Association of losartan use with outcomes in metastatic pancreatic cancer patients treated with chemotherapy.
Authors: Allen Jessica , Mehta Kathan , Anant Shrikant , Dandawate Prasad , Saeed Anwaar , Kasi Anup 
Published: May 2020

e16738 Background: A phase II trial has shown improved efficacy of neoadjuvant therapy when combined with losartan (by remodeling desmoplasia) in locally advanced pancreatic ductal adenocarcinoma (PDA). However, role of losartan is unknown in metastatic PDA. We examined the relationship between the use of the angiotensin II receptor antagonist, losartan, at time of diagnosis with clinical outcomes in metastatic PDA pts that received chemo. Methods: We retrospectively evaluated 114 metastatic PDA pts treated at our center between Jan 2000 and Nov 2019. We compared OS, PFS, objective response rate (ORR), and disease control rate (DCR) between pts using losartan at time of cancer diagnosis and a control group of pts not on losartan. A subanalysis was performed based on losartan dose: 100mg dose versus control pts. and based on chemo: FOLFIRINOX or gemcitabine+abraxane. Results: Table shows baseline demographics. No significant difference was found in OS [p = 0.455] or PFS [p = 0.919] in pts on losartan (median 274d, 83d) vs control (median 279d, 111d) [p = 0.466]. No significant difference was found in ORR [p = 0.621] or in DCR [p = 0.497]. No significant difference was found in OS [p = 0.771] or PFS [p = 0.064] in losartan pts (median 347d, 350d) vs control (median 333d, 101d) treated with FOLFIRINOX. No significant difference was found in OS [p = 0.916] or PFS [p = 0.341] in losartan (median 312d, 69d) vs control (median 221d, 136d) [p = 0.916] treated with gemcitabine+abraxane. No significant difference was found in OS [p = 0.727] or PFS [p = 0.790] in 100mg losartan pts (median 261d, 84d) vs control (median 279d, 111d). Conclusions: Pts on losartan at time of diagnosis had no significant difference in OS, PFS, ORR, DCR than control pts. However, a subanalysis of pts treated with FOLFIRINOX revealed a longer PFS with losartan than control but did not meet statistical significance, likely due to small sample size. To confirm if the benefit of losartan + FOLFIRINOX seen in neoadjuvant setting for locally advanced cancer also applies to metastatic cancer, our findings need to be validated in a larger cohort. [Table: see text]
Real-world use of liposomal irinotecan-based regimens among patients (pts) with metastatic pancreatic adenocarcinoma (mPDAC) in the United States (U.S.).
Authors: Kim George P. , Cockrum Paul , Surinach Andy , Koeller Jim M. 
Published: May 2020

e16740 Background: The goals of randomized control trials (RCTs) are to make causal inferences and precise treatment comparisons, not to describe large heterogeneous pt populations. RWE allows population-based healthcare decision makers to assess and manage therapeutic and economic options for their pts, including those who would and would not have met inclusion/exclusion criteria of a given RCT and are instead managed under usual care, irrespective of clinical trial protocols. In the pivotal phase 3 trial, NAPOLI-1, 117 pts were treated with liposomal irinotecan + 5-fluorouracil/folinic acid, median age 63 years; 66% were treated first- (1L) or second line (2L), and 91% had performance score ECOG 0 or 1. Pts in the trial had overall survival (OS) of 6.2 months (mos), time to treatment failure (TTF) 2.3 mos, and 27% experienced grades 3-4 neutropenia. The present study describes the patient characteristics and outcomes of pts with mPDAC treated with liposomal irinotecan in the US. Methods: This retrospective observational study used data from Flatiron Health EHR-derived de-identified database from over 280 cancer clinics. Patient characteristics, OS, TTF, and rates of neutropenia during treatment (tx) were assessed in adult pts diagnosed with mPDAC who received liposomal irinotecan based tx between November 1, 2015 and October 31, 2019. Results: 600 pts with mPDAC treated with a liposomal irinotecan based regimen were identified. Of these, 56% were initially diagnosed with stage IV disease, 53% were male, 21% had undergone a previous Whipple procedure, and 61% initiated liposomal irinotecan in the 1L or 2L metastatic setting. Median age at tx initiation was 68 (IQR: 62 – 75) years. 92% of pts were treated in the community setting. Among pts with available ECOG (n = 440), 77.5% were score 0-1. Grade 3/4 neutropenia was observed in 11% (n = 66). Overall, median OS was 5.0 mos [95%CI: 4.2–5.6]. mOS among pts treated in 1L (n = 88), 2L (n = 280), and third line plus (3L+, n = 232) were 6.9 mos [5.3–9.2], 5.4 mos [4.6–6.4], and 4.0 mos [3.4–4.5], respectively. Overall, median TTF was 1.9 mos [1.6–2.1]. TTF by line was 3.5 mos [2.3–4.8] in 1L, 2.1 mos [1.7–2.8] in 2L, and 1.4 mos [1.2–1.6] in 3L. Conclusions: This real-world cohort of pts with mPDAC were older, had worse performance status, and had more prior lines compared to the pivotal trial for liposomal irinotecan. Median OS, TTF, and neutropenia were similar to those previously reported. As expected, pts receiving liposomal irinotecan in earlier lines had higher median OS and TTF.