bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient-tailored FOLFIRINOX in the first-line treatment of patients (pts) with advanced pancreatic cancer (PC).
Authors: Ulusakarya Ayhan , Teyar Nahla , Karaboue Abdoulaye , Haydar Mazen , Krimi Sarra , Biondani Pamela , Gumus Yusuf , Almohamad Watek , Morere Jean-Francois 
Published: January 2019

499 Background: FOLFIRINOX is an effective reference regimen in the 1st line treatment of advanced PC, despite its high level of toxicity. We report recent data from pts treated with this regimen at Paul Brousse university hospital. Methods: From January to December 2016, 37 pts with advanced PC received patient-tailored FOLFIRINOX as 1st line intent to treat chemotherapy. The first 1 to 3 courses were administered without irinotecan if initial serum bilirubin was ≥ 1.5 x upper limit of normal. Oxaliplatin was stopped for severe sensory neuropathy. Initial dose reductions were made according to pt profile (e.g., age, comorbidity) and later due to toxicity. The treatment was continued until surgery or disease progression. Endpoints were time to progression (TTP), overall survival (OS), objective response rate (ORR) and secondary complete resection (R0R1). Results: There were 22 male (59%) and 15 female pts (41%) aged 44 to 81 years (median: 64). They had locally-advanced (18 pts, 49%) and metastatic PC (19 pts, 51%). PC was head, body, tail located in 24 (65%), 8 (22%) and 5 pts (14%) respectively. Biliary stent was placed in 22 pts (59%). Pts had a performance status (PS) of 0 (60%) or 1 (40%). Median treatment duration was 20 weeks for oxaliplatin, 22 weeks for irinotecan, 23 weeks for 5FU. At the cut-off on April 27th 2017, protocol was ongoing for 11 pts (30%). Median number of cycles was 9 (2-20). Median dose intensity was 29 mg/m2/w for oxaliplatin, 57 mg/m2/w for irinotecan and 886 mg/m2/w for 5FU. We observed 4 CR (11%), 12 PR (32%), 12 SD (32%) and 5 PD (14%). Four pts were not evaluable. ORR was 43%, disease control rate 75%, 11 pts (30%) underwent R0R1 resection. After a median follow-up of 8 months (1 - 16), median TTP and OS were not reached. TTP was associated with body location (HR = 3.5 [95% CL, 1.1-11.0], p = 0.033) and disease stage (HR = 10.5 [2.2-49.5], p = 0.003), a trend was observed with biliary stent placement (HR = 0.4 [0.1-1.1], p = 0.067). Conclusions: Modified FOLFIRINOX with patient-tailored dose adaptations seems to offer better results in pts with advanced PC compared with classic FOLFIRINOX. This strategy deserves prospective evaluation to further improve clinical outcomes in the management of advanced PC.
Lenvatinib plus checkpoint inhibitors in patients (pts) with advanced intrahepatic cholangiocarcinoma (ICC): Preliminary data and correlation with next-generation sequencing.
Authors: Lin Jianzhen , Shi Weiwei , Zhao Songhui , Hu Jinwei , Hou Zheng , Yao Ming , Chrin Gungwei , Pan Jie , Hu Ke , Zhao Lin , Javle Milind , Wang Kai , Zhao Haitao 
Published: January 2019

500 Background: Lenvatinib (Len) is a multikinase inhibitor targeting VEGFR 1-3, FGFR 1-4 and other kinases. Pembrolizumab (Pem) and nivolumab (Nivo) are antibodies inhibiting programmed cell death 1 (PD-1) and reactivate T-cell cytotoxic effect. Len plus PD-1 inhibitors have shown promising results in treating various solid tumors. The role of this combination in ICC is undefined. Methods: 14 ICC pts (median age 49 years, range 34-68; 7 males and 7 females) with treatment of enrolled in a single center, observational study of Len plus Pem/Nivo. Objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) were measured according to RECIST 1.1. Next generation sequencing (NGS) with deep coverage on 450 cancer genes and whole exome sequencing were performed in 7 pts to detect all classes of genomic alterations, tumor mutational burden (TMB) and microsatellite instability (MSI) status. Results: All 14 pts had > = 2 prior anticancer therapy with clinical stage IV. ORR was 21.4% with 3 pts achieved partial response (PR), DCR was 92.9% and clinical benefit rate (ORR + durable stable disease > = 5 months) was 64.3%. Median PFS was 5.9 months (95% CI: 4.2-6.2). The most common adverse events (AEs) included hypertension, aminotransferase elevation and fatigue. The grade-3 AEs were occurred at 14% while no grade-4 AE was observed. The most altered genes in the 7 sequenced tumors were IDH1 (3 pts), ARID1A (3 pts), PIK3CA (3 pts), TP53 (2 pts) and BAP1 (2 pts). 4 out of the 7 pts had high TMB ( > 12 mut/Mb) and all responded to Len plus Pem/Nivo with 2 PR. One pt with low TMB and FGFR2 mutation had a response of 27% decreased target lesion. Two low TMB pts were progressed, including one with FGFR2 rearrangement. A responder harbored a 399 bp deletion on MLH1, and was identified as MSI-H. More data will be presented. Conclusions: Our study preliminarily indicates that combining Len with PD-1 inhibitors results in promising efficacy in advanced ICC. High TMB from 450-gene NGS panel was strongly associated with a better therapeutic response.
Economic analysis of transarterial chemoembolization (TACE) versus stereotactic body radiotherapy (SBRT) for the treatment of hepatocellular carcinoma (HCC).
Authors: Nugent Francis W. , Packard Amy , Hunter Klaudia , Qamar Amir , Stuart Keith E. , Gunturu Krishna , Flacke Sebastian , Molgaard Christopher , Iqbal Shams , Gordon Fredric 
Published: January 2019

508 Background: For HCC patients undergoing liver transplantation (LT), local treatment as a "bridge" is standard to decrease tumor burden. The most common treatment is TACE, but the best and cheapest bridging modality is unclear. We prospectively compared SBRT to TACE as a bridge for HCC patients undergoing LT. We then compared the cost of the two strategies. Methods: From 9/2014-1/2017, 31 patients within Milan Criteria with C-P Class A/B cirrhosis were randomized to TACE vs. SBRT. TACE patients received 2 treatments one month apart utilizing DEBDOX beads (n = 17) and were hospitalized for symptom management. Patients receiving SBRT (n = 14) received outpatient treatment comprising 5 fractions of radiation using fiducials. Using EPSI, the institutional cost accounting and clinical data base, all patients treated were analysed. Financial and cost data was used to calculate the average contribution margin (total payment minus direct cost) for each type of treatment and then multiplied for each patient by the number of treatments involved. Results: See table. Conclusions: SBRT costs less than TACE to treat HCC. Given reduced reimbursement for hospitalizations post-TACE, additional opportunity costs may be available at given institutions depending on bed availability. Clinical trial information: NCT02182687. [Table: see text]
Analyzing the efficacy and safety of immunotherapy in pancreatic ductal adenocarcinoma (PDA): A systematic review and meta-analysis.
Authors: Babiker Hani M. , Zahid Umar , Howe Carol L. , Scott Aaron James , Riaz Irbaz Bin , Elliott Cynthia M , Acharya Utkarsh H , Recio Boiles Alejandro , Elquza Emad , Mahadevan Daruka 
Published: January 2019

512 Background: The tumor microenvironment in PDA is heterogeneous and immunosuppressive given the presence of regulatory T cells and exhausted effector T cells. Despite the upsurge of effective immunotherapeutic agents (IA) in other tumor types, the role in PDA remains unknown. We conducted a meta-analysis of IA in PDA. Methods: Following PRISMA guidelines, we searched PubMed/MEDLINE, Elsevier/Embase, Wiley/Cochrane Library and ClinicalTrials.gov. Articles were selected per the following criteria: (1) Study participants had a diagnosis of PDA; (2) An IA was used in the trial. Titles, abstracts and full text articles were reviewed by 2 independent reviewers; disagreements were resolved by a third. Data extraction and analysis were performed by 3 independent reviewers. Descriptive analysis, mean, median, confidence interval and forest plots were used for statistical analysis. Results: We found 20,792 studies through the database, 16,105 remained after duplicates were removed and 15,889 were excluded due to irrelevance. Strict inclusion criteria were applied to the full text of 216 articles. The most common reason for exclusion were conference abstracts (44%) and ongoing trials (16%). Fifty-four trials (39 metastatic (met), 12 adjuvant (Ad) and 3 neoadjuvant (nAd) met criteria for further analysis. Age range was 27-86 (median 61) and 52.3% were males. IA included cytokine therapy (33%), peptide vaccines (22%), dendritic cell vaccine (13%), oncolytic viruses (9%), CTLA-4 inhibitors (2%) and others. IA in met-PDA had a median overall survival (mOS) of 8.1 months (ms) and a disease control rate (DCR) of 55.4% (95% CI, 51.85-58.95). There was no statistical difference in DCR among IA subtypes (range 49-60%) (p = 0.22). The mOS of Ad-PDA trials was 25 ms (historically comparable to gemcitabine, p = 0.75) and 18 ms for nAd-PDA. The most common Gr1/2 toxicities were skin reactions, fever, and chills and Gr3/4 were cytopenias, diarrhea, and mucositis. One death occurred due to neutropenic sepsis. Conclusions: IA demonstrates modest efficacy in the treatment of met-PDA albeit exhibits a favorable toxicity profile. Many trial results are available only in abstract format and some are ongoing.
Metastatic gastroenteropancreatic neuroendocrine tumors treated with somatostatin analogues: Ten years experience in a third level hospital in Mexico City.
Authors: Pimentel Alberto , Dip Borunda Abdel Karim , Bueno Rosario Luis Jonathan , Martinez Gloria Martinez , Pluma Miguel Angel , Quintana Miguel , Silva Juan ALEJANDRO , Rivera Samuel 
Published: January 2019

514 Background: Gastroenteropancreatic neuroendocrine tumors (GEP NET´s) are infrequent tumors, with a variety of symptoms depending of the kind of peptide they secrete as well as the affected organs. Long acting somatostatin analogues have shown an adequate rate of symptom control in functional tumors, they also have demonstrated antiproliferative effect, which is translated in a significant improvement of progression free and overall survival Methods: In this retrospective analysis of patients with metastatic GEP NET treated with long acting somatostatin analogues as first line, treated between 2005 and 2015, we evaluated clinical and pathological features, symptoms, disease control and survival adjusted with OMS classification Results: Our cohort included 95 patients with a mean age of 53 years. Primary affected sites were midgut (29.4%), followed by pNET (17.%), stomach (14.7%), and primary unknown in 14%. 20% of cases were functional tumors with diarrhea as the most common symptom in 70% and flushing in 50%. Considering the whole cohort the most prevalent symptom was abdominal pain in the 50% of cases. The OMS classification showed low grade tumors in 65% and 35% intermediate grade. Most common metastatic organ sites were; liver only 35%, liver and other 30%, peritoneum 10% and lymph nodes in 6%, non-specified sites in 19%. Somatostatine analogues used in first line were octreotide in 80% and lanreotide in 20%. Survival results demonstrated a progression free survival for the whole cohort of 84months. No differences between lanreotide and octreotide were observed. Conclusions: This study represents the first Mexican cohort of patients with GEP NET’s treated with somatostatin analogues with a long follow up.
Management of carcinoid syndrome (CS): A systematic review of systemic treatment options.
Authors: Wolin Edward M. , Benson Al Bowen 
Published: January 2019

516 Background: CS is a major cause of symptom burden (diarrhea/flushing) in patients (pts) with neuroendocrine tumors and is associated with shortened survival and severe complications such as carcinoid heart disease. We performed a systematic review of clinical evidence for CS systemic treatments. Methods: PubMed, Embase, and Cochrane databases were searched. Large ( > 60 pt) prospective clinical trials investigating the efficacy/safety of systemic treatment options for pts with CS were eligible for inclusion. Data extracted included study design, pt population, interventions, prior treatments, permitted concomitant medications, study endpoints/statistical analyses, and efficacy/safety outcomes. Results: Six large prospective clinical trials (total 953 pts) were identified from 144 search results. Significant heterogeneity existed in pt populations, control groups (placebo vs active comparator), duration of therapy, study endpoints, and efficacy/safety data reporting. Interventions assessed were long-acting and subcutaneous octreotide (OCT & OCT SC), lanreotide (LAN), telotristat ethyl (TE)+somatostatin analogues (SSA), pasireotide (PAS), and everolimus (EVE)+OCT. Symptom response was variably assessed by the frequency of diarrhea/flushing and/or receipt of rescue short-acting SSA in 5/6 studies; a significant improvement in at least one of these measures occurred in 4 studies (OCT and OCT SC; LAN; TE+SSA). Failure to meet symptom response criteria ranged from 29-82% in the studies. Reported reductions in CgA and/or 5-HIAA reached statistical significance in 3 studies (LAN; EVE+OCT; TE+SSA). Interventions were generally well tolerated. Two phase 3 trials focused specifically on management of CS symptoms refractory to SSA; strategies included switching to PAS or an increased dose of OCT (40 mg q28d) for refractory diarrhea/flushing, or receipt of TE with continued SSA for refractory diarrhea. Conclusions: SSA provide substantial symptom relief for pts with CS. For refractory symptoms, TE can be added, SSA dose increased, and metastasis debulking can be used (with surgery, hepatic artery embolization, ablation, and PRRT). The addition of biologic agents to SSA can further improve CS management.
Quantitative PET-MRI for early treatment response assessment in pancreatic ductal adenocarcinoma.
Authors: Consunji Martin Valera , Behr Spencer , Ko Andrew H. , Tempero Margaret A. , Cinar Pelin , Wang Zhen J. 
Published: January 2019

520 Background: There is an unmet need for improved non-invasive markers to assess early treatment response in pancreatic ductal adenocarcinoma (PDAC). Assessing early treatment response using tumor size on anatomic imaging or serum carbohydrate antigen 19-9 (CA19-9) level is unreliable. In contrast, metabolic and functional imaging is a promising new tool that may differentiate responders from non-responders early on during therapy. Therefore, the objective of this pilot study was to explore the potential of integrated positron emission tomography-magnetic resonance imaging (PET-MRI) to provide imaging biomarkers of early (4 weeks post treatment initiation) response in patients with advanced PDAC. Methods: 13 patients with biopsy-proven locally advanced or metastatic PDAC underwent integrated 18F-fluorodeoxyglucose PET-MRI through the abdomen prior to, and again at 4 weeks post, treatment initiation. Patients also had computed tomography (CT) imaging of the chest, abdomen, and pelvis and serum CA19-9 levels measured, as per standard of care. Patients were classified as responders or non-responders according to RECIST (Response Evaluation Criteria In Solid Tumors) on delayed CT, at 8-12 weeks interval post treatment initiation. Changes in metabolic tumor volume (MTV) and total lesion glycolysis (TLG) from PET, and apparent diffusion coefficient (ADC) from diffusion-weighted MRI at 4 weeks were compared between responders and non-responders. Results: Of the 13 patients, there were 7 responders (partial response by RECIST) and 6 non-responders (progressive or stable disease by RECIST). After 4 weeks of therapy, responders had a significantly greater decrease in MTV (p = 0.003) and TLG (p = 0.006) compared to non-responders. Responders also had a significantly greater increase in mean and minimum ADC (p = 0.004 and p = 0.024, respectively) compared to non-responders. Change in tumor size at 4 weeks was not significantly different between responders and non-responders (p = 0.11). Conclusions: Integrated PET-MRI can provide early assessment of treatment response in patients with advanced PDAC.
Phase I study of chemoradiotherapy using gemcitabine plus nab-paclitaxel for unresectable locally advanced pancreatic cancer.
Authors: Yamada Suguru , Fujii Tsutomu , Takano Nao , Takami Hideki , Suenaga Masaya , Niwa Yukiko , Hayashi Masamichi , Iwata Naoki , Kanda Mitsuro , Kobayashi Daisuke , Tanaka Chie , Nakayama Goro , Sugimoto Hiroyuki , Koike Masahiko , Fujiwara Michitaka , Kodera Yasuhiro 
Published: January 2019

523 Background: Gemcitabine plus nab-paclitaxel (GnP) treatment is recommended for metastatic pancreatic adenocarcinoma (PDAC), and has been widely spread in our clinics. However, the usefulness for the patients with locally advanced PDAC is still controversial. We designed the phase I study to assess the toxicity and decide the recommended dose based on dose-limiting toxicity (DLT) of concurrent chemoradiotherapy using GnP for unresectable locally advanced (UR-LA) PDAC. Methods: UR-LA PDAC patients were enrolled in this clinical trial. The patients received the GnP on days 1, 8 and 15 every 28 days, and the cycles were repeated until PD. The patients were scheduled to receive gemcitabine (mg/m2) and nab-paclitaxel (mg/m2) at 5 dose levels: 400/75 (level 0), 600/75 (level 1), 600/100 (level 2), 800/100 (level 3) and 800/125 (level 4). Radiation therapy was delivered as a total dose of 50.4 Gy in 28 fractions, 1.8Gy per day. DLT was defined as grade 4 leucopenia or neutropenia ≥ 3 days, grade 3 neutropenia with fever ≥ 38℃, grade 3 or 4 thrombopenia, grade 3 non-hematological toxicity and > 14 days delay of treatment. Response and disease control rate, safety, adverse events, PFS and OS were evaluated. Results: Twelve patients were enrolled in this study. Treatment was well tolerated, and every 12 patients completed radiotherapy of 50.4 Gy. Our recommended dose was level 3, gemcitabine 800 mg/m2 and nab-paclitaxel 100 mg/m2. One patient experienced the DLT. The response rate was 41.7% and disease control rate was 75% (PR: 5, SD: 4, PD: 3). Median OS was 9.0 months. Among 12 patients, 6 (50%) patients underwent conversion surgery, and the pathological CR was observed in 2 patients. Conclusions: The concurrent chemoradiotherapy using GnP for UR-LA PDAC can be delivered safely and the high rate of conversion surgery was observed in our clinical trial. Based on this results, we will proceed the phase-II study. Clinical trial information: UMIN000020475.
Identification of a novel molecule target for the diagnosis, prediction, and treatment of hepatic metastasis of gastric cancer.
Authors: Kanda Mitsuro , Tanaka Haruyoshi , Miwa Takashi , Kobayashi Daisuke , Tanaka Chie , Takami Hideki , Hayashi Masamichi , Iwata Naoki , Niwa Yukiko , Yamada Suguru , Nakayama Goro , Sugimoto Hiroyuki , Koike Masahiko , Fujiwara Michitaka , Kodera Yasuhiro 
Published: January 2019

53 Background: Hepatic metastasis of gastric cancer has become a growing issue, because effective treatment and specific biomarkers are not available. The aim of this study was to identify a molecule mediating hepatic metastasis, which serves as a diagnostic marker, and to determine its potential as a therapeutic target. Methods: Stable knockdown gastric cancer cells were established using genome editing technique and cell activities were compared to control cells in vitro and in vivo. Tissue expression levels of the candidate molecule were evaluated in 300 patients with gastric cancer and correlated to clinicopathological parameters including patterns of metastasis and recurrences. Results: Global expression analysis revealed that synaptotagmin VII (SYT7) was overexpressed in gastric cancer tissues with hepatic metastasis. Gastric cancer cell lines differentially expressed high levels of SYT7 that positively correlated with those of SNAI1 and TGFB3, and inversely with RGS2. Stable knockout of SYT7 inhibited the proliferation of gastric cancer cells, indicated by increased apoptosis, and decreased cell migration, invasion, and adhesion abilities. The tumorigenicity of SYT7 knockout cells was moderately reduced in a mouse subcutaneous model and more strikingly decreased in a hepatic metastasis model. The protein expression levels of BCL2 and HIF1A were decreased in tumors formed by SYT7 knockout cells, and SYT7 levels in primary gastric cancer tissues were significantly associated with hepatic recurrence, metastasis, and adverse prognosis. Conclusions: SYT7 serves as a target for treating hepatic metastasis of gastric cancer as well as a diagnostic tool.
A randomized phase 2 study of nivolumab monotherapy versus nivolumab combined with ipilimumab in patients with metastatic or unresectable gastrointestinal stromal tumor (GIST).
Authors: Singh Arun S. , Chmielowski Bartosz , Hecht J. Randolph , Rosen Lee S. , Wang Xiaoyan , Brackert Sandra , Adame Carlos R. , Linares Paulina J , Schink Elena , Marubio Lisa Marie , Eilber Frederick C. 
Published: January 2019

55 Background: The therapy with tyrosine kinase inhibitors changed the prognosis of patients with advanced GIST. Unfortunately, most of the tumors become resistant to therapy and patients succumb to the disease. New therapies for this patient population are needed. Here we report interim analyses of safety and efficacy in advanced GIST patients treated with immunotherapy. Methods: Patients with advanced/metastatic GIST progressing on at least imatinib were enrolled on a randomized, parallel group, unblinded phase 2 trial of either nivolumab(nivo) (240 mg Q2wks) or nivo (240 mg Q2wks) with ipilimumab(ipi) (1mg/kg Q6wks) for up to 2 years. The primary endpoint was the objective response rate (ORR) of nivo alone or nivo + ipi by RECIST 1.1 criteria. Patients were randomized 1:1 and the response was assessed every 8 weeks. With a sample size of 20 per group, an exact binomial test with a nominal 0.050 one-sided significance level will have 82% power to detect the difference between the null hypothesis response rate 1.5% and the alternative response rate of 15%. Secondary objectives are to ascertain the PFS, CBR, RR by Choi criteria and safety. Blood and biopsies are also being collected. Results: To date, 14 patients (median # of prior therapies: 4) have started on trial and 8 remain on treatment. In the nivo only arm, 3/7 patient had SD for a CBR of 42.8 %. The median PFS of the nivo arm was 8 weeks. In the nivo + ipi arm, 1/5(20%) patients had a PR and 1/5 have SD for a CBR of 40%; 2 patients were censored. The median PFS of the nivo + ipi arm was 8.43 weeks. 1 patient in the nivo arm had grade 3 fatigue and 1 patient in the nivo + ipi arm had grade 3 diarrhea. Pretreatment biopsies have been obtained in all patients and blood has been collected on all patients for correlative analysis. Conclusions: In a heavily pretreated GIST population, durable responses and disease control were observed. To date, the drugs have been well tolerated and no new safety signals have been observed in this disease state. Clinical trial information: NCT02880020.