bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors contributing to cure in T2 pancreatic cancer.
Authors: Maetani S. , Doi R. , Imamura M. 
Published: February 2017

234 Background: It is crucial to determine whether cancer therapy achieves cure or merely prolongs time to death from cancer (failure time). Unfortunately, conventional survival tests such as log-rank test and Cox regression fail to distinguish between cure and prolonged failure time, both making a great difference in survival benefit. In 1994, Gamel extended the Boag model to three regressions, allowing us to study whether prognostic factors have significant effect on cure rate or failure time. Using the Gamel-Boag regressions, we study curative effects of clinicopathological factors in pancreatic cancer. Methods: Follow-up data from 452 patients who underwent pancreatectomy for T2 ductal cell cancer were analyzed. The prognostic factors to be studied were converted to binary variables, which include sex, age (<=60 or >60 years), tumor size (<=2 or >2 cm) lymphnode metastasis, and six types of invasions, i.e., serosal, retroperitoneal, portal vain, common bile duct and duodenal invasions. By calculating coefficients of the three regressions and their confidence intervals, we evaluated whether each (or combinations) of these variables are associated with increased cure rate or prolonged failure time. Results: Tthere were 11 relapse-free 5-year survivors. Except for tumor size (TS) and lymphnode metastasis (N), no factors were significantly associated with increased cure rate or prolonged failure time. The only factor found to significantly affect cure was TS; the estimated cure rate being 44% for patients with TS <= 2 cm and 4% otherwise (p=0.0001). This effect was not influenced by N and other factors. Only N significantly accelerated failure time; the median failure time being 11.9 months when N was negative and 6.7 months otherwise (p<0.0001). Thus, both TS and N affected the prognosis significantly but in different ways. By contrast the Cox regression showed that both TS and N were significantly associated with hazard reduction (p=0.003 and p<0.001, respectively), which, however, did no reveal a qualitative difference in survival outcome between TS and N. Conclusions: In T2 pancreatic cancer, a highly significant increase in cure rate is found when TS≤2 cm. This increase is not affected by N or tumor extension to nonpancreatic tissues. No significant financial relationships to disclose.
NPC-1C: A novel, therapeutic antibody to treat pancreas and colorectal cancers.
Authors: Diaz L. A. , Azad N. S. , Laheru D. , Le D. T. , Devoe C. E. , Cosgrove D. , Zheng L. , Arlen P. M. , Bristol J. A. 
Published: February 2017

235 Background: NPC-1C (ensituximab) is a chimeric monoclonal antibody being developed as a novel biologic treatment for pancreatic and colorectal cancers. This antibody was selected from a panel of hybridomas generated from mice immunized with semi-purified membrane-associated proteins derived from biologically screened, pooled human allogeneic colon cancer tissues. The NPC-1C epitope appears to be expressed specifically by human colon and pancreatic tumor tissues and cell lines. Methods: Antitumor activity was established in vitro by measuring ADCC with a standard 4-hour 111-Indium release assay on pancreatic and colorectal cancer cell lines. In vivo antitumor efficacy of NPC-1C was tested using pre-established subcutaneous human pancreatic tumor xenograft models. Results: In vitro, the NPC-1C antibody exhibits ADCC activity specifically against human colon and pancreatic tumor cells, but not against control tumor cell lines. The in vivo data showed significant, and reproducible, antitumor action, including some complete tumor regressions. The clinical application for this antibody was bolstered by several examples of human tumor tissues stained with biotin-conjugated NPC-1C that showed a strong correlation of NPC-1C staining against pancreatic and colon tumors. Approximately 45% of tumors stained strongly positive. The staining pattern was typical of elaborated mucin expression, but also showed cytoplasmic and cell membrane staining. Conclusions: A phase I open label, multicenter dose escalation clinical trial with NPC-1C is currently accruing patients with advanced pancreatic and colorectal cancer who are refractory to standard therapy. The primary objectives of the phase I clinical trial are to determine the safety and tolerability of escalating doses of NPC-1C monoclonal antibody therapy and to assess pharmacokinetics and select immune responses to the antibody at each dose level. Secondary objectives are to evaluate evidence of clinical benefit and to explore the immunologic correlates associated with administration of NPC-1C. Results from this trial will determine the minimum standard dosage levels to be used in further trials. [Table: see text]
A multinational phase II study of liposome irinotecan (PEP02) for patients with gemcitabine-refractory metastatic pancreatic cancer.
Authors: Ko A. H. , Tempero M. A. , Shan Y. , Su W. , Lin Y. , Dito E. , Ong A. , Yeh G. , Chen L. 
Published: February 2017

237 Background: PEP02 is a novel nanoparticle liposome formulation of irinotecan (CPT-11) that has improved pharmacokinetics and tumor biodistribution of both CPT-11 and its active metabolite-SN38 compared to the free form drug. PEP02 has showed encouraging safety and efficacy in various tumor types, including significant antitumor activity in a human pancreatic cancer L3.6pl orthotopic nude mouse xenograft model. In previous phase I studies, PEP02 either alone or in combination with 5-FU/LV demonstrated prolonged disease control in 5 of 7 (71%) patients (pts) with gemcitabine (GEM)-refractory advanced pancreatic cancer (PC). This phase II study aims to evaluate PEP02 monotherapy as 2nd-line treatment in pts with metastatic, GEM-refractory PC. Methods: Pts were eligible if they had metastatic pancreatic adenocarcinoma, KPS ≥ 70, and progressed following one line of GEM-based therapy. Treatment consisted of PEP02 120 mg/m2 administered as a 90-minute infusion every 3 weeks. A Simon's 2-stage design was used with 16 pts in the first stage and 39 pts in total; primary objective was 3-month survival rate (OS3-month). Results: Between March 2009 and August 2010, 37 pts were enrolled at 3 centers in the U.S. and Taiwan. Characteristics for the first 31 evaluable pts: 13 M/18 F; age 39-82 yrs; 19 Asian/12 Caucasian, KPS 100/90/80/70: 5/14/4/8. Mean number of treatment cycles is 5 (range, 1-22). Disease control rate (minor response + stable disease >2 cycles) is 52%. 8 of 24 pts (33%) with elevated baseline CA19-9 have had >50% biomarker decline. To date, 23/31 pts (74%) have survived > 3 months, with 4 pts still alive after 1 year. Reasons for study discontinuation: 74% progressive disease, 9% drug-related toxicity, 17% other. Preliminary safety data is available for the first stage. Most common G3/4 adverse events included: fatigue (31%), neutropenia (25%), nausea/vomiting (19%), and diarrhea (13%). Conclusions: This study has already met its primary endpoint (predicted OS3-month >65%). PEP02 appears to have both activity and tolerable side effects for pts with metastatic, GEM-refractory PC, and represents a promising option for this pt population with few standard options. [Table: see text]
Prognostic value of duodenal invasion length in patients with gastric cancer.
Authors: Oshima N. , Tokunaga M. , Tanizawa Y. , Bando E. , Kawamura T. , Kondo J. , Kinugasa Y. , Kanemoto H. , Uesaka K. , Terashima M. 
Published: February 2017

24 Background: Duodenal invasion (DI) has been considered as a poor prognostic factor of gastric cancer patients. Not all the patients would be able to undergo curative operation. Neoadjuvant chemotherapy (NAC) may improve the rate of curative operation of these patients. In this study, we investigated whether the length of duodenal invasion preoperative diagnosis can be one of factor to decide indication of NAC. Methods: A total of 118 gastric cancer patients with clinically evident DI, who underwent laparotomy at our center, were enrolled in this study. 42 patients with DI length 20 mm or longer were categorized into long invasion group (LI), 76 patients with DI length shorter than 20 mm were categorized into short invasion group (SI). Clinicopathologic features, rate of direct invasion and lymph nodes involvement, R0 resection, and survival rate were compared between two groups. Results: Resection rate was significantly different between two groups: SI group (85.5%; 65/76), LI group (69.0%; 29/42). Direct invasion to adjacent organs was significantly more frequently observed in LI group (21%; 6/29) than SI group (4 %; 3/65, p = 0.02). In LI group, pancreas invasion was observed in all patients except for one patient. Multivariate analysis to predict the adjacent organ invasion revealed that CT diagnosis (p = 0.005) and invasion length (p = 0.01) were selected as risk factors of direct invasion to adjacent organs. There was no significant difference of nodal involvement between LI group (83%; 24/29) and SI group (83%; 54/65 p = 0.99). The 5-year survival rate was 19% in LI group and 43% in SI group (p = 0.23). The number of patients who underwent R0 resection was more frequently in SI group (75.4%; 49/65) than SI group (69.1%; 16/29). The factors of R1 or R2 resection were metastasis of peritoneum or direct invasion to adjacent organs. Conclusions: In patients with long duodenal invasion, direct invasion to the pancreas was more frequently observed, and resulted in low curative resection rate and poor survival. Preoperative chemotherapy may improve the curative resection rate and survival in these patients. Prospective study is warranted to evaluate the efficacy of NAC for these patients. No significant financial relationships to disclose.
Minimally invasive surgery for resectable pancreatic cancer in the United States: From staging tool to treatment strategy.
Authors: Smith J. K. , Witkowski E. R. , Murphy M. M. , Ng S. , Shah S. A. , Tseng J. F. 
Published: February 2017

243 Background: Debate exists regarding the use of laparoscopy in pancreatic malignancy. The goal of this study was to examine recent laparoscopy use in pancreatic resections for cancer in the US. We hypothesized that there would be two noticeable trends in the use of laparoscopy – the first reflecting staging laparoscopy, the second associated with advancement of laparoscopic pancreatectomy. Methods: The Nationwide Inpatient Sample (NIS), 1998-2007, was used to identify patients ≥ 18 years old with pancreatic cancer who underwent pancreatic resection with or without associated laparoscopy. Patterns of laparoscopy use and correlated outcomes were examined. Results: Among 47599 patients (nationally weighted) who underwent resection for pancreatic cancer, 2640 (5.5%) had procedures that included laparoscopy. Yearly trend analyses demonstrated a peak in laparoscopy in 2003 followed by decreased use, then steady increase after 2005. Laparoscopy at time of resection was not significantly associated with decreased complications (p=0.09), but was associated with lower mortality compared to open resection alone (3.2% vs. 5.9%, p = 0.008). On multivariate analysis, independent predictors of increased complications included older age, male sex, higher comorbidity (Charlson) score, urban location, and non-teaching hospital. For increased risk of death, predictors were older age, male sex, Charlson >2, non-teaching hospital, and non-use of laparoscopy. Conclusions: Trends in the use of laparoscopy during pancreatic resections for cancer suggest initial increased use in the early 2000's following published staging recommendations, with a subsequent decrease contemporaneous with improving imaging techniques. A recent upward trend is likely associated with increased attempts at minimally-invasive resection. The use of laparoscopy is not associated with any difference in complication rate following surgery and is associated with improved perioperative survival. The effects of patient factors, selection, and volume status on minimally invasive pancreatectomy outcomes warrant further investigation. No significant financial relationships to disclose.
An interim analysis of a phase II study of the combination of TACE and sorafenib in patients with unresectable hepatocellular carcinoma in National Cancer Center Korea (COTSUN KOREA, NCT00919009).
Authors: Park J. , Kim H. , Shim J. , Woo S. , Choi J. , Nam B. 
Published: February 2017

253 Background: Transarterial chemoembolization (TACE) is the palliative treatment for patients with unresectable HCC. TACE-induced ischemic injury is known to increase circulating VEGF and related with poor prognosis.The aim of this study is to evaluate efficacy and safety of combined TACE with sorafenib, VEGFR inhibitor in unresectable HCC patients. Methods: This study is a non-randomized, open-labeld, single-arm, phase II investigator-initiated clinical study. Estimated number of subjects was 50 under the assumption of 3.2 months of median time to progression (TTP) with TACE alone. All patients are Child-Pugh class A or superb B. Sorafenib begins to be administered on 3 days after the first session of TACE and will be subsequently administered up to 24 weeks. Efficacy of TACE was evaluated after 4 weeks from TACE by dynamic CT. Repeated TACE is performed “on demand” in case of PR or SD according to CT/MRI evaluation. Results: A total of 50 patients were enrolled for this interim analysis. Male was 84% and mean age was 61.5years. Causes of underlying chronic liver disease were HBV in 28 patients (65.1%). Patients were categorized into modified UICC stage II (15, 30.0%), III (24, 48.0%) and IVA (11, 22.0%). Median follow-up period was 5.3 months (range, 1.0–13.1). The size of index lesions was ranged from 1.0 cm to 13.1 cm, and number of lesions was between 1 and 5. Number of TACE sessions was 1.0 (range, 1–4). Common adverse events (AE) during sorafenib therapy were elevation of serum AST/ALT (96.8%), hypocalcemia (90.0%), thrombocytopenia (84.0%), and hyperbilirubinemia (76.0%). Hand-foot skin reaction was most frequently observed among AE of NCI CTCAE grade 3 or higher (40.0%), followed by elevation of serum ALT (38.0%). Dose reduction of sorafenib was needed most commonly due to hand-food skin reaction (n=29). Median TTP was 5.1 months (range, 3.8–6.3). Conclusions: Adverse events were approved as acceptable by independent monitoring system. Preliminary evidence of antitumor activity was also observed. This trial can be safely performed with close monitoring in inoperable and/or unresectable HCC patients. No significant financial relationships to disclose.
Activity of a novel dual PI3-kinase/mTOR inhibitor NVP-BEZ235 to enhance antitumor activities of gemcitabine and EMAP II in pancreatic cancer.
Authors: Awasthi N. , Yen P. L. , Schwarz M. A. , Schwarz R. 
Published: February 2017

255 Background: Gemcitabine (Gem, G) has limited benefits as single agent or in combination for pancreatic ductal adenocarcinomas (PDACs). The phosphatidylinositol-3-kinase (PI3K)/AKT and mammalian target of rapamycin (mTOR) signaling pathways are frequently dysregulated in diverse human cancers including PDAC. NVP-BEZ235 (BEZ, B) is a novel dual PI3K/mTOR inhibitor that has been shown to have antitumor activity in multiple tumor types. Endothelial monocyte activating polypeptide II (EMAP, E) is an antiendothelial and antiangiogenic agent that enhances Gem and docetaxel activity in PDAC. We tested the combination benefits of BEZ and Gem in addition to EMAP in experimental PDAC. Methods: In vitro cell proliferation and protein expression were analyzed by WST-1 assay and Western blotting. In vivo animal survival experiments were performed in NOD-SCID PDAC xenografts. Results: Cultured cells of PDAC (AsPC-1), endothelial (HUVECs), and fibroblast origin (WI-38) all expressed AKT and mTOR protein. BEZ inhibited in vitro cell proliferation of AsPC-1 and HUVECs cells, with some additive effects in combination with Gem or EMAP, after 72 hours of incubation. In AsPC-1, treatment of BEZ (100 nM), Gem (100 nM) and EMAP (1 μM) caused 34, -7, -16, 62, 51, 3, and 59 percent inhibition in proliferation in the B, G, E, B+G, B+E, G+E and B+G+E groups. In HUVECs, percent inhibition in proliferation was 35, 33, 15, 55, 35, 31 and 53 in the B, G, E, B+G, B+E, G+E and B+G+E groups, respectively. Compared to controls (median survival: 16 days), an animal survival increase after BEZ and EMAP therapy alone (both 21 days) and Gem therapy alone (28 d) was observed. Further increases in survival occurred in combination therapy groups B+G (30 d, p=0.007), B+E (27 d, p=0.02), G+E (31 d, p=0.001) and B+G+E (33 d, p=0.004). Conclusions: Bez has experimental PDAC antitumor activity in vitro and in vivo that is further enhanced by combination of Gem and EMAP. These findings demonstrate advantages of combination therapy strategies targeting multiple pathways in pancreatic cancer treatment. No significant financial relationships to disclose.
Downstaging in pancreatic cancer: A matched analysis of patients resected following systemic treatment of initially locally unresectable disease.
Authors: Bickenbach K. A. , Gonen M. , Brennan M. F. , D'Angelica M. I. , DeMatteo R. P. , Fong Y. , Jarnagin W. R. , Allen P. J. 
Published: February 2017

257 Background: Patients with locally unresectable pancreatic cancer (AJCC stage III) have a median survival of 10–14 months. Standard treatment for these patients is systemic therapy with or without radiation. The objective of this study was to evaluate outcome of patients who respond to this treatment and undergo resection. Methods: Using a prospectively collected database (2000-2009), we identified patients who were initially deemed unresectable due to vascular invasion and had sufficient response to non-operative treatment to undergo resection (initial stage III). Overall survival (OS) was compared between this group and a matched group of patients who were resected during the same time period without receiving preoperative treatment (stage I and II). Case-matching was performed using a previously validated pancreatic cancer nomogram. Results: A total of 36 patients with initial stage III disease were identified who underwent resection after treatment with chemotherapy or radiation therapy. Initial unresectability was determined by operative exploration (n=15, 42%) or by cross-sectional imaging (n=21, 58%). All patients received chemotherapy prior to resection and 58% of patients received radiation. Resection consisted of pancreaticoduodenectomy (n=31, 86%), distal pancreatectomy (n=4, 11%), and total pancreatectomy (n=1, 3%). Pathology revealed T3 lesions in 27 patients (73%), nodal positivity in 6 patients (16%), and a negative margin in 30 patients (83%). There were no operative mortalities. Median follow-up was 13 months (range 2 to 44 months). The median OS in this series was 25 months from resection and 30 months since treatment initiation. There was no difference in OS from time of resection between the initial stage III patients and matched patients who presented with resectable disease (p=0.35). Conclusions: In this study, patients who were able to undergo resection following treatment of initial stage III pancreatic cancer experienced similar survival as those who presented with stage I and II disease. Resection is indicated in this highly select group of patients. No significant financial relationships to disclose.
Evaluation of the Charlson comorbidity index to predict outcome after esophagectomy in older patients.
Authors: Kothari A. , Bretl T. , Weigel T. 
Published: February 2017

27 Background: Esophagectomy remains a preferred treatment for several neoplastic and non-neoplastic conditions; however it is often avoided in elderly patients with several co-morbid conditions. Several centers endorse the use of the Charlson comorbidity index to predict surgical outcomes in high risk patients. To date, this standard measure of co-morbidity has not been used to predict surgical outcomes following esophagectomy in elderly (age ≥70) patients. Methods: We reviewed data from an IRB-approved, prospectively maintained thoracic surgery database over a three-year period (March, 2006 – March, 2009). We compared incidence of post-operative events, total length of stay, 30-day mortality, rate of readmission, and calculated Charlson comorbidity indices (CCI) for all patients. A validated electronic application was used to calculate CCI based on patient age, BMI, substance use, malignancy, and co-morbid diseases (CV, respiratory, GI, endocrine, inflammatory, psychiatric, neurologic, and immunologic). Results: There were 75 patients below the age of 70 and 41 patients ≥ 70 years old who underwent esophagectomy over the 3-year period studied. Patients over the age of 70 had a significantly higher CCI (5.02) than patients under the age of 70 (3.19, p < 0.05). However, the 30 day mortality in patients ≥ 70 (0.0%) and under 70 (2.3%) was not significantly different between groups (p = 0.33). There was no difference in median length of hospital stay (7 days vs. 7 days, p = 0.95) and rate of readmission (7.5% vs. 9.3%, p = 0.74) when comparing patients ≥ 70 and < 70 years old, respectively. Patients ≥ 70 had a significantly lower incidence of complications than patients under the age of 70 (34.1% vs. 60.0%, p < 0.05). Conclusions: Patients ≥ 70 years old had higher Charlson comorbidity indices than patients < 70 years old, however surgical outcomes in both groups following esophagectomy were similar. In this population, CCI may not be a valid tool for measuring surgical risk perhaps due to the inclusion of age in the index. Future study will focus on the development of a co-morbidity index which can predict outcomes following esophagectomy and is not biased by age. No significant financial relationships to disclose.