bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase III study of S-1 plus cisplatin versus fluorouracil plus cisplatin in patients with advanced gastric or gastroesophageal junction adenocarcinoma.
Authors: Xu Rui-hua , Sun Guo-ping , Lu Hui-shan , Yun Peng Liu , Xu Jian-ming , Zhong Mei-zuo , Zhang He-long , Yu Shi-ying , Li Wei , Hu Xiao-hua , Wang Jie Jun , Cheng Ying , Zhou Jun-tian , Guo Zeng-qing , Guan Zhongzhen 
Published: March 2020

4025 Background: A combination of S-1 and cisplatin (DDP) has been shown to be effective and safe for the first-line treatment of advanced gastric cancer in Japan. This is the first randomized phase III trial to compare S-1 plus DDP with 5-fluorouracil (5-Fu) plus DDP in Asia. Methods: This is an open-label, multicenter, phase 3, randomized controlled study. Patients with gastric or gastro-oesophageal junction adenocarcinoma were eligible for inclusion. Patients were randomly assigned in a 1:1 ratio to receive S-1 plus DDP (experiment group) or 5-Fu plus DDP (control group) for 6 cycles. In the experiment group, the dose of S-1 was 80 mg/m2/day, po, twice daily on day 1-21 and DDP was 20mg/m2 iv on day 1-4, repeat every 5 weeks. In the control group, 5-Fu was given as 0.8g/m2/d CI 120h ,and the dose of DDP was the same with the experiment group, while repeat every 4 weeks. Allocation was by block randomization stratified by Eastern Cooperative Oncology Group performance status, sites of metastasis and prior gastrectomy. The primary endpoint was time to progression (TTP). Secondary end points included time to failure (TTF), overall survival (OS), and quality of life. Results: Totally 255 patients were enrolled into the study, of whom 236 were included in the analysis (n=120; n=116). Median TTP was 5.51 months (95% CI 4.59-6.26) in those assigned to experiment group compared with 4.62 months (95% CI 4.00-6.33) in the control group (hazard ratio [HR] 1.03; 95%CI 0.76-1.39, p=0.86). In the experiment and control groups, response rates were 22.5% vs 21.5%; P=0.86. Median OS was 10.00 months (95% CI 8.59-14.52) in the experiment group compared with 10.46 months (8.92-13.84) in the control group (HR 1.05; 95%CI 0.71-1.54, p=0.82). The most common adverse events in both groups were anemia (S-1 plus cisplatin, 80.17% vs 5-Fu plus cisplatin, 71.19%), leukopenia (71.90% vs 62.71%), neutropenia (68.60% vs 55.93%), nausea (50.41% vs 60.17%), thrombocytopenia (44.63% vs 26.27%), vomiting (42.98% vs 42.37%) and anorexia (38.02% vs 41.53%). Conclusions: S-1 plus DDP is an effective and tolerable option for patients with advanced gastric or gastro-oesophageal junction adenocarcinoma. Clinical trial information: NCT01198392.
Sorafenib (S) alone versus S combined with gemcitabine and oxaliplatin (GEMOX) in first-line treatment of advanced hepatocellular carcinoma (HCC): Final analysis of the randomized phase II GONEXT trial (UNICANCER/FFCD PRODIGE 10 trial).
Authors: Assenat Eric , Boige Valerie , Thézenas Simon , Pageaux Georges-Philippe , Peron Jean-Marie , Becouarn Yves , Dahan Laetitia , Merle Philippe , Blanc Jean-Frédéric , Bouche Olivier , Ramdani Mohamed , Mazard Thibault , Bleuse Jean-Pierre , Ychou Marc 
Published: March 2020

4028 Background: HCC is a vascular tumor with poor prognosis. Although S has been shown to improve survival, its ability to induce tumor shrinkage is very low. Given the activity of Gemcitabine and Oxaliplatin (GEMOX) in HCC, a phase II trial combining S with GEMOX was undertaken to define efficacy and safety profile. Methods: Patients with inoperable advanced and/or metastatic HCC (BCLCC B or C), with or without prior palliative chemoembolization, Child pugh score A, WHO performance status (PS) 0-1, were eligible for this two-stage, randomized phase II trial. Patients received S (400 mg BID) alone (arm A) or in combination with GEMOX every 2 weeks (gem. 1000 mg/m² [10 mg/m²/min] on D1; oxaliplatin, 100 mg/m² on D2) (arm B). Randomization was stratified according to CLIP score (0-1 vs. 2-3) and center. Primary endpoint was crude 4-mo Progression-Free Survival (PFS) rate (H0, < 50%; H1, ≥ 70%; α = 10%; 1- β= 90%). Results: From Dec 2008 to Oct. 2011, 94 pts were enrolled: median age, 64 yrs; male, 88%; PS 0 (69%) 1(31%), CLIP 0-1 (48%) 2-3 (52%), cirrhosis (63%), portal vein thrombosis (29%), extra liver metastasis (69%). These characteristics were well balanced in both arms. Median duration and dose intensity of S were 4 mo (1-27) and 81% in both arms, respectively. Median number of GEMOX cycles was 7 (1-12) in arm B. Main severe (grade 3-4) toxicity (arm A/B) consisted of neutropenia (grade 3-4: 0%/7%), fatigue (18%/24%), thrombocytopenia (0%/9%), diarrhea (grade 2-4: 10%/21%), peripheral neuropathy (grade 2-3: 0%/10%), and hand foot syndrome (grade 2-3: 13%/7%). For evaluable pts (n = 83), ORR was 9% / 16% and DCR was 70%/77% in arms A/B, respectively. For all pts (median follow-up, 17.6 mo), 4-mo PFS rate was 54%/61%, median PFS was 4.6 (3.9-6.2)/6.2 (3.8-6.8) mo, and median OS was 13.0 (10.4-22.2) /13.5 (7.5-19.1) mo in arms A/B, respectively. Conclusions: S plus GEMOX was feasible in HCC. This trial met its primary endpoint (4-mo PFS ≥ 50%) and ORR, median PFS and OS were encouraging data. Exploratory analyses are underway to identify subgroups of patients likely to derive most benefit from this combination. Clinical trial information: NCT00941967.
Prospective randomized phase II trial with gemcitabine versus gemcitabine plus sunitinib in advanced pancreatic cancer: A study of the CESAR Central European Society for Anticancer Drug Research-EWIV.
Authors: Richly Heike , Maute Luise , Heil Gerhard , Rüssel Jörn , Jäger Elke , Koeberle Dieter , Fuxius Stefan , Weigang-Koehler Karin , Aulitzky Walter , Woehrmann Bernhard , Hartung Gernot Georg , Moritz Berta , Burkholder Iris , Scheulen Max E. , Bergmann Lothar 
Published: March 2020

4035 Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most common malignant tumours, but PDAC is still associated with a poor prognosis in advanced disease with an overall 5-year survival of only about 15%. Therefore there is a need for new treatment strategies. To improve the standard therapy with gemcitabine we initiated a prospective randomized phase-II trial with gemcitabine (GEM) vs. gemcitabine plus sunitinib (SUNGEM) based on data of in vitro trials and phase-I data for the combination treatment. Methods: Patients (N=113) with locally advanced or metastatic PDAC were prospectively randomized to receive gemcitabine alone (GEM) at a dosage of 1000 mg/m² day 1, 8, 15 q28 or to a combination of gemcitabine and sunitinib (SUNGEM) at a dosage of GEM 1000 mg/m² d1+8 and sunitinib 50mg p.o. d1-14, qd21 (based on a phase-I trial). The primary endpoint was progression-free survival (PFS), secondary endpoints were overall survival (OS), time to progression (TTP), overall response rate (ORR) and toxicity. Results: The confirmatory analysis of PFS was based on the ITT population (N=106). The median PFS was 13.3 weeks (95 %-Cl: 10.4-18.1 weeks) in the GEM group and 11.6 weeks in the SUNGEM arm (95 %-Cl: 7.0-18.0 weeks) (one-sided logrank: p=0.74). The 6-month PFS rate was 26.8 % (95 %-Cl: 15.4-39.5 %) in GEM arm and 25.0 % in SUNGEM arm (95 %-Cl: 14.0-37.8 %). The overall response rate was 6.1 % (95 %-Cl: 0.7-20.2 %) in the GEM arm and was a slightly but not significantly higher for the SUNGEM arm with 7.1% (95%-Cl: 0.9 – 23.5%).The median time to progression (TTP) was 14.0 weeks (95 %-Cl: 12.4-22.3 weeks) for the GEM arm and 18.0 weeks (95 %-Cl: 11.3-19.3 weeks) for the SUNGEM arm (two-sided logrank: p=0.60). The median OS was 30.4 weeks (95 %-Cl: 18.1-37.6 weeks) for the SUNGEM and 36.7 weeks (95 %-Cl: 20.6-49.0 weeks) for the GEM arm (two-sided logrank: p=0.44). With regard to toxicities, at least one AE of grade 3 or 4 was reported in 78.8% in the SUNGEM arm and 72.2% in the GEM arm. Conclusions: The combination of gemcitabine plus sunitinib (SUNGEM) did not improve the PFS in locally advanced or metastatic PDAC compared to gemcitabine alone. Clinical trial information: NCT00673504.
A phase I trial of a local delivery of siRNA against k-ras in combination with chemotherapy for locally advanced pancreatic adenocarcinoma.
Authors: Golan Talia , Hubert Ayala , Shemi Amotz , Segal Amiel , Dancour Alan , Khvalevsky Elina Zorde , Ben-David Eliel , Raskin Stephen , Goldes Yuri , Inbar Yael , Lahav Maor , Domb Avi , Galun Eithan 
Published: March 2020

4037 Background:K-Ras mutation G12D is most prevalent in pancreatic adenocarcinoma (PDAC). siRNA against the K-RasG12D(siG12D) mutant had showed significant preclinical anti-tumor effects. siG12D LODER - miniature biodegradable polymeric matrix that encompasses anti-K-RasG12D siRNA drug, is placed with Endoscopic US biopsy and designed to continuously release the drug regionally over a period of 4 months. Methods: Open label phase I study of patients with locally advanced non-operable PDAC in the first-line setting. Patients were assigned to receive siG12D LODERs in dose escalation cohorts: 0.025mg, 0.75mg and 3.0mg. Gemcitabine 1000 mg/m2IV was given weekly, following siG12D LODER insertion. The RP2D (recommended phase II dose) was further examined in 3.0 mg dose cohort in combination with modified Folfirinox (Oxaliplatin 85mg/m2, Irinotecan 150mg/m2, Fluorouracil infusion 2,400mg/m2 46 hours, every 2 weeks). Follow up period was 8 weeks and survival follow up until death. Primary study objectives were to determine the dose-limiting toxicities (DLT) and maximum tolerated doses (MTD). Results:15 patients have been enrolled. 2 patients were omitted from study due to metastatic disease detected on day 1 post siG12D LODER implant imaging . Median age = 70 (range 52-85); male:female 8:7. Among 13 treated patients, the most frequent adverse events observed in the study were typically grade 1- 2 in severity; 4 patients experienced serious adverse events (SAE), one procedure related. No DLTs were observed. MTD was not reached. CT performed 8-10 weeks following the procedure showed stable disease in all patients. Reduction in tumor marker CA 19-9 was observed in 64% (7/11) of patients. The median survival of 13 patients was 16 months ( 8/13 patients still alive at analysis). Conclusions: The combination of siG12D LODER and chemotherapy is well tolerated. The combination has demonstrated promising efficacy in locally advanced PDAC with durable responses. Phamocodynamic endpoints are currently being examined in an expansion cohort in operable patients. A phase II randomized trial is planned in order to investigate efficacy of siG12D LODER in locally advanced non-operable PDAC. Clinical trial information: NCT01188785.
Extended neoadjuvant chemotherapy (CT) in borderline resectable pancreas cancer (BRPC).
Authors: Rose J Bart , Rocha Flavio G. , Lin Bruce S. , Alseidi Adnan , Biehl Thomas A. , Moonka Ravi , Ryan John A. , Traverso L. William , Helton Scott , Picozzi Vincent J. 
Published: March 2020

4043 Background: The optimal surgical (S) approach to BRPC is unknown. We evaluated an approach to BPRC using extended course chemotherapy (CT) without routine neoadjuvant chemoradiation (CRT). Clinical outcomes were evaluated on an "intent to treat" basis. Methods: Patients (pts) were identified from a prospectively-maintained database started in 2008. Pts required 1) Dx BRPC with non-tail primary per radiographic staging using AHPBA/NCCN guidelines 2) No prior therapy (Rx) 3) Negative staging/exploratory laparoscopy prior to S 4) All cancer Rx at VMMC prior to S. Pts received gemcitabine/docetaxel (G/D) as initial CT. Pts with systemic progression/comorbid complication prior to 24 wks were not offered local Rx; pts with localized cancer at 24 wks judged likely to achieve R0 resection were offered S; all other pts were offered fluoropyrimidine-based CRT. Results: Of 76 identified pts (median age 66), 12 (16%) are on initial CT and not fully evaluable. G/D as sole CT achieved 24 wk disease control in 46/64 (72%) pts and >50% decline in baseline CA 19.9 in 39/55 pts (71%). 53/64 fully evaluable pts (83%) completed 24 wks CT, 11/64 pts (17%) did not (4 systemic progression, 3 Rx- related, 4 intercurrent illness). 50/53 pts attempted local Rx (40 S, 10 CRT, 2 unfit, 1 refused). 30/40 pts (75%) had successful S (all R0), 10/40 pts (25%) had inoperable disease (4 local-subsequently received CRT, 6 systemic). 23/30 pts (77%) have received some form Rx post R0 resection. With median f/o of 20 mo, 23/44 (52%), 17/30 (57%), and 6/14 (43%) receiving any local Rx, S, and CRT-only remain progression free. 13/30 S pts recurred, 3 local (10%) and 10 systemic (33%). 1-yr, 2-yr, 3-yr, and median overall survivals (OS) for fully evaluable pts respectively are 82%, 50%, 36%, and 27 mo. Median OS for pts receiving CT-only (20 pts), CT+CRT (14 pts), and R0 pts are 12 mo, 17 mo, and >20 mo, respectively. 25/30 R0 pts remain alive (range 6-54 mo). Conclusions: 1) Extended neoadjuvant CT without routine neoadjuvant CRT is a feasible approach to BRPC. 2) G/D has significant activity in BRPC. 3) Pretreatment surgical staging combined with the above Rx yields a high probability of R0 resection. 4) OS for both resected and non-resected pt was superior to usual literature comparators.
Development and validation of a predictive model to assess an individual's risk of pancreatic cancer.
Authors: Nam Byung-Ho , Yu Ami , Woo Sang Myung , Yang Hye-Ryung , Joo Jungnam , Lee Woo Jin , Park Sang Jae 
Published: March 2020

4045 Background: Due to the very low survival of pancreatic cancer (PC), early detection is a critical strategy to improve the outcome of PC.Screening individuals with genetic syndromes associated with a high incidence of PC or families predisposed to PC is increasing. However, those populations account for only 10% of all PC cases. A different approach for developing an effective surveillance tool is needed to identify high-risk individuals without hereditary risks. The goal of this study was to develop and validate risk prediction models for filtering purposes as part of the sporadic PC surveillance activities. Methods: Based on an eight-year follow-up of a cohort study involving 1,289,933 men and 557,701 women in Korea who had biennial examinations in 1996-1997, gender-specific risk prediction models were developed using the Cox proportional hazards model. The models were validated using independent data of 500,046 men and 627,629 women who had biennial examinations in 1998-1999. The models’ performance was evaluated with respect to their discrimination and calibration abilities based on the C-statistic and the Hosmer-Lemeshow (H-L) type χ2-statistic. Results: Age, height, BMI, fasting glucose, urine glucose, smoking, and age at smoking initiation were included in the model for men. In the model for women, height, BMI, fasting glucose, urine glucose, smoking, and drinking habits were included. Smoking was the most significant risk factor for developing pancreatic cancer in both men and women. Model validation showed excellent model performance with C-statistics (95% confidence interval) of 0.813 (0.800−0.826) and 0.804 (0.788−0.820) for men and women, respectively. The H-L type χ2-statistics (P-values) were 7.478 (0.587) and 10.297 (0.327) for men and women, respectively. Five different risk groups could be identified with hazard ratios (HR) greater than 20 in the highest risk group compared to the lowest risk group in both the men and women. Conclusions: Gender-specific individualized risk prediction models for PC were developed and validated with a high level of performance. These models can be used to identify high-risk individuals who may benefit from increased surveillance of PC.
Circulating tumor cells in locally advanced pancreatic adenocarcinoma: The ancillary study Circe 07 of the LAP 07 trial.
Authors: Huguet Florence , Bidard Francois-Clement , Louvet Christophe , Mineur Laurent , Bouche Olivier , Chibaudel Benoist , Artru Pascal , Desseigne Francoise , Bachet Jean Baptiste , Gasmi Mohamed , Nguyen Suzanne , Wander Lionel , Mathiot Claire , Pierga Jean-Yves , Hammel Pascal ,   GERCOR
Published: March 2020

4046 Background: Pancreatic carcinoma is one of the leading causes of cancer-related mortality. At time of diagnosis, 30% of patients present with a locally advanced unresectable but non metastatic carcinoma (LAPC). Theoretically, patients with micrometastatic dissemination at diagnosis should benefit from systemic treatments, whereas radiation therapy should be favored in the others. Based on the hypothesis that circulating tumor cells (CTC) count is a surrogate of the cancer metastatic abilities, CTC detection rates and prognostic value were studied in a prospective cohort of LAPC patients. Methods: LAP07 international multicenter randomized study assesses in patients whose LAPC is controlled after 4 months of gemcitabine-based chemotherapy whether to administrate a chemoradiotherapy could increase overall survival versus continuation of chemotherapy alone. A subgroup of patients included in LAP 07 trial were prospectively screened for CTC before the start of the chemotherapy and after two months of treatment, using the CellSearch technique. Clinico-pathological characteristics and survival of patients were obtained prospectively and were correlated with CTC detection. Results: Seventy-nine patients were included in this ancillary study. One or more CTC/7.5ml were detected in 5% of patients before treatment and in 9% of patients after two months of chemotherapy (overall detection rate: 11% of patients). CTC positivity was associated with poor tumor differentiation (p=0.04), and with shorter overall survival in multivariable analysis (RR=2.5, p=0.01), together with anemia (p=0.005). Conclusions: The evaluation of micrometastatic disease using CTC detection appears as a promising tool which could help to personalize treatment modalities in LAPC patients. Clinical trial information: NCT00634725.
Is successful resection following neoadjuvant radiation therapy for borderline resectable pancreatic cancer dependent on improved tumor-vessel relationships?
Authors: Dholakia Avani Satish , Hacker-Prietz Amy , Wild Aaron Tyler , Raman Siva P. , Wood Laura D. , Laheru Daniel A. , Zheng Lei , De Jesus-Acosta Ana , Huang Peng , Le Dung T. , Schulick Richard D. , Edil Barish H. , Ellsworth Susannah G. , Pawlik Timothy M. , Iacobuzio-Donahue Christine A , Hruban Ralph H. , Cameron John L. , Fishman Elliot K. , Wolfgang Christopher Lee , Herman Joseph M. 
Published: March 2020

4057 Background: Margin-negative (R0) surgical resection is the only potentially curative therapy for pancreatic cancer. For patients deemed borderline resectable (BL), neoadjuvant chemoradiotherapy (NRT) increases the likelihood of subsequent R0 resection and improves overall survival. Prognostic factors for achieving resection following NRT have yet to be clearly identified. Methods: Fifty consecutive patients with BL-PDAC evaluated by a multidisciplinary tumor board who received NRT from 2007-2012 were retrospectively identified. Computed tomography (CT) scans pre- and post-radiation and surgical specimens were centrally reviewed. Results: 29 patients underwent resection following NCRT, while 21 remained unresectable. Between the two groups, age, gender, mean RT dose, and proportion of pancreatic head tumors were not significantly different. Smaller tumor volume and lack of the following factors was associated with selection for resection: superior mesenteric/portal vein encasement (p=0.01), superior mesenteric artery involvement (p=0.02), ascites (p=0.01), and questionable/overt metastases (p=0.01). Notably, celiac artery involvement/encasement, common hepatic artery encasement, and percentage change in tumor volume were not significant predictors of resection (all p>>0.05). Interestingly, tumor volume and degree of individual vessel involvement did not significantly change from scans before and after NCRT (all p>>0.05). Median OS was 22.9 vs.13.0 months in resected and unresected patients, respectively (p<0.001). Of resected patients, 93% had negative margins, 28% had positive nodes, 27% demonstrated <10% viable tumor, and 12% had pathologic complete response at surgery. Dpc4 expression was retained in 68% of specimens with viable tumor. Conclusions: Although the apparent radiographic extent of vascular involvement does not change significantly after NRT, subsequent R0 resection rates are high, nodal involvement is low, and outcomes are similar to resected patients who receive adjuvant therapy. Resection attempts should not be deferred solely based on lack of improvement in tumor-vessel interactions.
Customizing surveillance of patients with esophageal or esophagogastric junction adenocarcinoma (E-EGA) after trimodality therapy (TMT).
Authors: Taketa Takashi , Correa Arlene M. , Sudo Kazuki , Blum Mariela A. , Wadhwa Roopma , Skinner Heath D. , Komaki Ritsuko , Lee Jeffrey H. , Bhutani Manoop S. , Weston Brian , Liao Zhongxing X. , Rice David C. , Swisher Stephen , Hofstetter Wayne Lewis , Ajani Jaffer A. 
Published: March 2020

4085 Background: Follow-up strategy for E-EGA patients after TMT has varied and is debated often due to the lack of evidence. It is an expensive endeavor and the literature provides little guidance. Methods: Between 2000 and 2010, we identified 518 E-EGA patients who had TMT. We reviewed the timing/pattern of recurrence after TMT and grouped them as local-regional (LR) or metastatic (M). Results: The median follow-up time from date of surgery was 29.3 months (range, 0.8 to 149.2 months). 215 (41.5%) had a relapse (M=188 [87.5%] and LR=27 [12.5%]). Among LRs, regional node only in 16 (7.4%) and intra-luminal only occurred in 11 (5.1%). The frequency of relapses was highly associated with the surgical stage (p<0.001). >90% of all relapses occurred within 29.2 months of surgery. In addition, almost all intra-luminal only relapses occurred within 24 months (see Table). Conclusions: Our data suggest that it may be possible to customize surveillance of patients after TMT based on the surgical stage. Additionally, intra-luminal only relapse are rare and are unlikely after 24 months. Our data can contribute to the development of an evidence-based surveillance strategy. [Table: see text]