bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of the addition of algenpantucel-L immunotherapy to standard adjuvant therapy on survival in patients with resected pancreas cancer.
Authors: Hardacre J. M. , Mulcahy M. F. , Small W. , Talamonti M. , Obel J. C. , Rocha Lima C. S. , Safran H. , Lenz H. , Chiorean E. G. , Link C. J. 
Published: February 2017

236 Background: Pancreatic cancer portends a poor prognosis with ∼4% long-term survival. Among the estimated 20% of patients who have resectable disease, the 1-/3-/5-year survival rates approximate only 70%/30%/18%, even with adjuvant therapy. Better treatment options are needed and addition of algenpantucel-L (HyperAcute-Pancreas) to standard adjuvant therapy is proposed to improve prospects for survival. Algenpantucel-L is composed of irradiated, live, allogeneic human pancreatic cancer cells expressing the enzyme α-1,3 galactosyl transferase (α-GT), which is the major barrier to xenotransplantation from lower mammals to humans (e.g., hyperacute rejection). Up to 2% of circulating human antibodies are directed against the α-GT epitope of algenpantucel-L and are the proposed mechanism of initiating the anti-tumor immune response. Methods: Open-label, single arm, multi-institutional phase II study (NLG0205) to evaluate algenpantucel-L + standard adjuvant therapy (RTOG-9704, JAMA, 2008: gemcitabine + 5-FU-XRT) for pancreatic cancer patients undergoing R0/R1 resection. Disease-free (DFS) and overall survival (OS) are the primary and secondary endpoints, respectively. Results: 73 patients (70 evaluable, 15 month median follow up) received gemcitabine + 5-FU-XRT + algenpantucel-L (mean 12 doses, range 1-14). Demographics and prognostic factors: median age 62 years, 47% female, 81.4% lymph node positive, median tumor size 3.2 cm (range 2-15 cm; 26% > 4cm) and 24% post-operative CA 19-9 > 90. Kaplan-Meier estimated survival rates at 12 and 24 months are 91% and 54%, respectively, comparing favorably to 63% and 32% expected based on the nomogram described by Brennan et al (Ann Surg, 2004). Likewise, the current median DFS of 16 months compares favorably to the 11 months observed in RTOG 9704. OS data continues to mature, with 74% still censored. Algenpantucel-L was well tolerated with no likely/directly attributable grade 3 SAEs. The most common adverse events were injection site pain and induration. Conclusions: Addition of algenpantucel-L to standard adjuvant therapy for resected pancreatic cancer may improve survival. A phase III study began patient enrollment in May 2010. [Table: see text]
A randomized phase II study of gemcitabine (GEM) plus S-1 combination chemotherapy versus GEM monotherapy in patients (pts) with advanced biliary tract cancer (BTC).
Authors: Sasaki T. , Isayama H. , Ito Y. , Yasuda I. , Toda N. , Hanada K. , Matsubara S. , Maguchi H. , Yashima Y. , Kamada H. ,   Japanese Endoscopist & IVRists Group for Biliary Tract Cancer
Published: February 2017

250 Background: Our previous phase II study demonstrated that GEM/S-1 combination chemotherapy was tolerable and showed good efficacy in pts with advanced BTC (Sasaki et al, Cancer Chemother Pharmacol 2010). This randomized phase II study compared the response rate of GEM/S-1 combination chemotherapy and GEM monotherapy in pts with advanced BTC. Methods: Pts with advanced BTC who had at least one measurable lesion were randomized into two groups. GEM/S-1: GEM 1,000 mg/m2 (day 1, 15) and S-1 80 mg/m2 (day 1-14) repeated every 4 weeks. GEM: GEM 1,000 mg/m2 (day 1, 8, 15) repeated every 4 weeks. Treatment was continued until disease progression. The primary endpoint was objective response according to RECIST version 1.0. Results: From November 2008 to March 2010, 62 pts were enrolled from 13 institutions. Patient characteristics were: median age 72 (range 47-86); Male/Female 36/26; Performance status 0/1/2 (37/22/3). The primary tumor site was; 30 pts in gallbladders, 16 pts in intrahepatic bile ducts, and 16 pts in extrahepatic bile ducts. Seven pts had previous surgical resection. Response rates of GEM/S-1 and GEM were 16.7% and 9.4%, respectively. The median time-to-progressions of GEM/S-1 and GEM were 5.6 months and 4.1 months, respectively. Conclusions: GEM/S-1 combination chemotherapy is more active than GEM monotherapy in pts with advanced BTC. Updated time-to-progression and overall survival data will be presented at the meeting. No significant financial relationships to disclose.
Significance and reliability of pathologic marker Ki-67 in patients with neuroendocrine cancers.
Authors: Singh S. , Feinberg Y. , Rowsell C. , Law C. 
Published: February 2017

264 Background: Molecular markers, especially Ki-67, in neuroendocrine cancers (NETs) have become increasingly important. Debate exists as to the optimal role of ki-67 in the treatment of this uncommon cancer. This study was designed to examine the significance of ki-67 as a clinical predictor and its reliability in the treatment of NETs. Methods: A retrospectively assembled integrated database with prospectively collected data of patients undergoing multidisciplinary management for NETs between 2000 to 2009 was analysed. Clinical and outcomes data were collected. Ki-67 was then categorized to Group A (≤2%), B (3-15%) and C (>15%). We compared the original Ki-67 value to the reviewed value. We then used a kappa statistic to calculate the inter-rater agreement between the original and reviewed determination of Ki-67. Fisher's exact test was used to compare categorical variables. Survival was evaluated using the log-rank test. All analyses were carried out using SAS 9.1.3. Results: A total of 184 patients were seen at our clinic. Ki-67 correlated with metastases at presentation (36, 52, 63% for Groups A, B, C respectively, p<0.05), while influencing treatment with chemotherapy even in the absence of metastases (14, 29, 57% for Groups A, B, C respectively, p< 0.002). Ki-67 predicted overall survival (p=0.0005) in favor of Group A. 99 patients had an original Ki-67 reported from the referring center and then a review by an expert pathologist at the multidisciplinary clinic. In Group A, there was 94.4% agreement, with 3.7% of cases upgraded at review to Group B and 1.9% of cases upgraded to Group C. In Group B, there was 94.3% agreement, with 5.7% of cases downgraded to Group A, and 0% upgraded. In Group C, there was 90% agreement, with 10% of cases downgraded to Group B and none to Group A (kappa = 0.89). Conclusions: Our previous report had demonstrated that Ki-67 influenced decisions regarding treatment options. In our updated population of NETs patients, Ki-67 continued to predict biology, influence treatment, and predict survival. In addition we demonstrated high reproducibility of Ki-67. It appears that with modern techniques Ki-67 can be highly reproducible and reliable tool in improving outcomes in this patient population. No significant financial relationships to disclose.
Dose-escalated external beam radiotherapy in unresectable hepatocellular carcinoma.
Authors: Skinner H. D. , Sharp H. J. , Kaseb A. O. , Javle M. M. , Vauthey J. , Abdalla E. K. , Delclos M. E. , Das P. , Crane C. H. , Krishnan S. 
Published: February 2017

267 Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Data regarding the use of external beam radiotherapy is limited in patients from populations without endemic viral hepatitis. We examine the outcomes for patients treated with external beam radiotherapy in the modern era at a single institution. Methods: A total of 29 patients with localized HCC treated from 2000 to 2009 were reviewed. Patients with metastatic disease at the time of radiation were excluded. Median radiation dose was 50 Gy (range 30-75 Gy) with a median biologically effective dose (BED) of 80.6 (range 60-138.6). Median tumor size at the time of radiation was 5.2 cm (range 2-25 cm). Results: Median residual tumor following radiation was 80% (range 27%-278%), with a median residual α-fetoprotein of 47% (range 0.8%-8240%). Estimated one-year overall survival (OS) and in-field progression-free survival (PFS) rates for the study population were 56% and 79%, respectively. One year OS in patients treated to a BED <75 was 18% vs. 69% in patients treated to a BED ≥75 (p=0.002). One year in-field PFS rate (60% vs. 88%, p=0.023) and biochemical PFS duration (median 6.5 vs. 1.6 mos., p=0.001) were also significantly improved in patients treated to a BED ≥75. Grade 3 toxicity was seen in only 13.8% of patients. Conclusions: In a population without endemic viral hepatitis, unresectable HCC demonstrates significant response toexternal beam radiotherapy with minimal toxicity. Furthermore, our findings suggest that increased BED is associated with improved survival and local tumor control. No significant financial relationships to disclose.
Effect of extrahepatic disease on transarterial chemoembolization for metastatic carcinoid.
Authors: Arrese D. , Feria-Arias E. , Khabiri H. , Guy G. , Schmidt C. R. , Shah M. H. , Bloomston M. 
Published: February 2017

283 Background: Transarterial chemoembolization (TACE) is the locoregional therapy of choice for the management of patients with inoperable carcinoid liver metastases. Often, metastatic disease is not limited to the liver. The impact of extra-hepatic metastases on response and outcomes following TACE has not been described. Objective: We hypothesized that patients who have extra-hepatic disease would have similar tumor response and symptom control following TACE. Methods: We reviewed 198 patients that underwent TACE for inoperable carcinoid liver metastases. Two groups were identified, those with (N= 129) and without (N= 69) evidence of extra-hepatic disease at the time of TACE. Demographics, clinicopathologic characteristics, response to TACE, complications, and survival were compared. Results: The two groups were similar in demographics and histopathologic characteristics. Complications following TACE were similar. There was no difference between the groups with and without evidence of extrahepatic disease in symptomatic (76% vs 71%), biochemical (78% vs 90%) or radiographic response (35.0% vs 46%) to TACE. The group without extra-hepatic disease had a median survival of 88 vs 35 months with five-year survival of 65% vs 30% compared to patients with extra-hepatic disease at the time of TACE. Conclusions: Patients with extrahepatic metastatic disease from carcinoid tumor experienced shorter overall survival following TACE compared to those without extrahepatic disease. However, patients with extra- hepatic disease had similar symptomatic, biochemical and radiographic response to TACE compared to those with disease confined to the liver. Although the long-term prognosis for patients with extrahepatic disease is worse than those with liver-only metastasis, meaningful response to TACE is possible and should be considered. No significant financial relationships to disclose.
A randomized phase II study of gemcitabine (G) plus the cardiac glycoside huachansu (H) in the treatment of patients with locally advanced (LAPC) or metastatic pancreatic cancer (MPC).
Authors: Meng Z. , Liu L. , Shen Y. , Yang P. , Cohen L. , Huo Y. , Zhao Q. , Ng C. S. , Chang D. Z. , Garrett C. R. 
Published: February 2017

284 Background: Wild toad venom has been used for over 1,000 years as a traditional Chinese medicine; H, the extract of dried toad skin glands, is a potent cardiac glycoside without significant toxicity. H has demonstrated preliminary evidence of antitumor activity in phase I clinical trial evaluation (Cancer 2009, 115:5309-18). Methods: We conducted a randomized, single-blind, phase II clinical trial of G + H versus G + placebo in patients with LAPC or MPC. Plasma bufalin levels were performed in H-treated subjects. 80 evaluable subjects accrued from October 2007 to May 2010 and were treated with G 1,000mg/m2 (iv on days 1, 8, 15, q 28d) plus either H (20 mL/m2 iv daily for 21 days followed by 7 days off, q 28d) or placebo. Demographic data is demonstrated in the table below. Results: Grade 3/4 adverse events, objective radiographic response rates (ORR), time to progression (TTP), quality of life (QOL), and overall survival (OS) were similar in the two groups (Table). There was not a statistically significant difference in the average plasma bufalin levels in patients with a radiographic partial response (PR) or stable disease versus those with progressive disease (PD) (0.098 ± 0.093 ng/mL vs. 0.071 ± 0.048 ng/mL, p=0.679). Conclusions: H when added to G was well tolerated but did not improve OS, TTP, QOL, or ORR. Further investigation of a more potent oral formulation of H is planned. H provided by Shenzhen 999 Traditional Chinese Medicine & Development Co., Ltd. Supported by NIH U19CA121503-01. [Table: see text] No significant financial relationships to disclose.
Construction and validation of a practical prognostic index for patients with metastatic pancreatic adenocarcinoma.
Authors: Morizane C. , Okusaka T. , Morita S. , Tanaka K. , Ueno H. , Kondo S. , Ikeda M. , Nakachi K. , Mitsunaga S. , Yamaguchi T. 
Published: February 2017

285 Background: The aim of the present study was to determine prognostic factors in patients with metastatic pancreatic adenocarcinoma (PC) receiving systemic chemotherapy and to construct and validate a prognostic index for metastatic PC. Methods: The relationship between patient characteristics and outcome was examined by multivariate regression analyses of data from 409 consecutive patients with metastatic pancreatic adenocarcinoma who had been treated with a gemcitabine- containing regimen (GEM alone: 302 patients, GEM + cisplatin (CDDP): 39, GEM + 5-flurorouracil (5-FU): 27, GEM + S-1:41), and we stratified the patients into three risk groups according to the number of prognostic factors they had for a poor outcome. A validation data set obtained from 145 patients who had been treated with agents other than GEM (5-FU + CDDP, MTX+5- FU, docetaxel, UFT, S-1, CPT-11) was analyzed. The prognostic index was applied the each of the patients. Results: The multivariate regression analyses revealed that the presence of pain (hazard ratio (HR): 1.692), peritoneal dissemination (HR:1.756), liver metastasis (HR:1.423), and an elevated serum CRP level by > 1.0 mg/dl (HR:1.540) significantly contributed to a shorter survival time. The patients were stratified into three groups according to their number of risk factors and their outcomes of the three groups were significantly different. The median survival times (MSTs) of the low-, intermediate-, and high-risk groups were 11.1, 7.3, and 3.2 months, respectively. When the prognostic index was applied to the validation data set, the respective outcomes of the three groups were found to be significantly differed from each other. The MSTs of the low-, intermediate-, and high-risk groups were 8.6, 5.2, and 2.3 months, respectively. Conclusions: Pain, peritoneal dissemination, liver metastasis, and an elevated serum CRP value are important prognostic factors for patients with metastatic pancreatic adenocarcinoma. No significant financial relationships to disclose.
Immediate impact of the FOLFIRINOX phase III data reported at the 2010 ASCO Annual Meeting on prescribing plans of American oncology physicians for patients with metastatic pancreas cancer (MPC).
Authors: Bendell J. C. , Britton S. , Green M. R. , Willey J. , Lemke K. E. , Marshall J. 
Published: February 2017

286 Background: Since 2005 we at Xcenda, LLC have studied prescribing plans of American medical oncologists for first-line therapy in patients with MPC. In 2008 we reported the steady growth of prescribing plans for the gemcitabine-erlotinib (GE) combination from 23% in late 2005 to 46% in 2007. In 2007, gemcitabine (G) alone was the second most common regimen planned (27%) (Green MR. Proc GI ASCO 2008). No cytotoxic doublet consistently garnered >10% prescribing share in this clinical setting. At ASCO 2010 Conroy et al. (J Clin Oncol. 2010;28(15s): Abstract 4010) reported a survival advantage for the FOLFIRINOX regimen compared to package insert dose and schedule of G alone as first-line therapy in patients with MPC and excellent PS (0-1). Methods: Between 7/31 and 8/28/2010 we again used our extensively tested, live research vehicle, NMCR Challenging Cases, to assess current prescribing plans of over 370 American medical oncologists for first-line therapy in a patient with metastatic pancreas cancer and either PS 1 or PS 2. Results: The FOLFIRINOX data have produced an immediate change in the distribution of planned first-line prescribing with 18% share for the PS 1 scenario, largely substituted for previous use of GE for this setting (Table). In PS 2, plans for FOLFIRINOX are minimal with G alone followed by GE as the dominant selections. Conclusions: The recently reported phase III FOLFIRINOX data are impacting first-line prescribing plans for patients with MPC. We will continue to quantitate physician-prescribing plans to more fully understand the additional impact the FOLFIRINOX data may have on overall chemotherapy management of these patients. [Table: see text] [Table: see text]
Everolimus versus placebo in Japanese patients with advanced pancreatic neuroendocrine tumors (pNET): Japanese subgroup analysis of RADIANT-3.
Authors: Ito T. , Okusaka T. , Ikeda M. , Tajima T. , Kasuga A. , Fujita Y. , Furuse J. 
Published: February 2017

289 Background: Everolimus demonstrated a statistically and clinically significant improvement in PFS over placebo in a multi-national, randomized, placebo-controlled, phase III trial in patients with advanced low- or intermediate-grade pNET with disease progression within the prior 12 months (RADIANT-3) (Ann Oncol [2010] 21[suppl 6]: NP doi:10.1093/annonc/mdq340). Forty patients were enrolled from Japanese sites and randomized (n=23: everolimus; n=17: placebo) in that study. The purpose of this report is to investigate the efficacy and safety in the Japanese subgroup. Methods: Subgroup analysis for the Japanese patients was performed comparing the efficacy and safety between everolimus 10mg/d orally plus best supportive care (BSC) and matching placebo plus BSC. The primary efficacy endpoint was progression-free survival (PFS). The safety was evaluated based on the incidence of adverse events (AEs). Results: Treatment with everolimus resulted in a significant prolongation by 16.62 months in median PFS (19.45 months for everolimus, 2.83 months for placebo), with 81% reduction in the hazard ratio of progression/death (HR 0.19 [95% CI: 0.08, 0.48]; one-sided unstratified log-rank test: p<.001). The most common AE was stomatitis (73.9% everolimus vs 23.5% placebo); mostly grade 1/2. Grade 3/4 AEs occurred in 69.5% of the everolimus arm and 29.4% of the placebo arm, and amongst the most frequent included (% in everolimus vs % in placebo): neutropenia (17.4% vs 3%); anemia (8.7% vs 0%); pneumonitis (8.7% vs 0%); leukopenia (8.7% vs 0%). The remainder of grade 3/4 AEs was less than 3%. Median duration of exposure to everolimus was 57 weeks vs 47 weeks on placebo. Treatment discontinuation for AEs was 17% in the everolimus arm vs 0% in the placebo arm. Conclusions: Everolimus demonstrated a clinically meaningful improvement in PFS over placebo in Japanese patients. Everolimus was well tolerated in Japanese patients, and no new safety concerns were noted. This result suggests that everolimus can be a standard treatment for Japanese patients with advanced pNET. [Table: see text]
Correlation of clusterin with pancreatic endocrine tumors' size and stage.
Authors: Allam-Nandyala P. , Djeu J. , Coppola D. 
Published: February 2017

291 Background: Clusterin, a ubiquitous multifunctional cytoplasmic and secretory sulfated glycoprotein (sCLU), plays a role in prevention of apoptosis and it is overexpressed in a variety of tumors. The role of sCLU in pancreatic neuroendocrine tumors (PET) has not been investigated. In this study sCLU expression was evaluated in a subset of PET, and the results were correlated with the clinical pathological features of the tumors. Methods: sCLU expression was immunohistochemically evaluated in 106 cases of PET using the avidin-biotin-complex method and the tissue microarray analysis technology. The immunohistochemical reactions were qualitatively and semiquantitatively evaluated by 2 pathologists. Results: Strong sCLU reactivity was identified in 36/65 (51%) PETs. In 23/65 (35%) cases the sCLU score was 3 or less. sCLU expression scores significantly correlated with tumor size (p-value= 0.03) and with tumor stage (p-value= 0.02). The IHC score index did not correlate with tumor grade (p= 0.15). Conclusions: We report the novel expression of sCLU in PET. The correlation of sCLU with PET size and stage involves this molecule in pancreatic neuroendocrine tumorigenesis. sCLU may represent a new target of therapy for PET. No significant financial relationships to disclose.
PET-guided treatment in locally advanced adenocarcinoma of the esophagogastric junction (AEG): The MUNICON-II study.
Authors: Lordick F. , Meyer Zum Bueschenfelde C. , Herrmann K. , Geinitz H. , Schuster T. , Friess H. , Molls M. , Schwaiger M. , Peschel C. , Krause B. 
Published: February 2017

3 Background: Previous studies demonstrated that fluorodeoxyglucose (FDG)-PET can help to detect response early during neoadjuvant chemotherapy. The prognosis of metabolic non-responders is poor. Therefore, we initiated the prospective MUNICON-II study to determine the value of salvage neoadjuvant chemoradiation in early PET nonresponders. Methods: 56 patients (pts) with locally advanced AEG type I and II (cT3/4 Nx M0) were included. Tumor glucose uptake was assessed by FDG-PET before and 14 days after initiation of chemotherapy. PET nonresponse was defined as a decrease of the tumor FDG standard uptake value < 35%. Nonresponders received salvage preoperative chemoradiation consisting of external beam radiation 32 Gy (1.6 Gy/fr x 2/day) plus daily cisplatin 6mg/m2 and then proceeded to surgery. Metabolic responders continued with chemotherapy (platin/5-FU-based) for 3 months. Results: 33 pts had a PET response, 23 had a PET nonresponse. Resection was performed on 54 pts. R0 was achieved in 27 (82%) PET responders versus 16 (70%) nonresponders (p = 0.51). Major histologic remissions (< 10% residual tumor) were observed in 12 PET responders (36%) and 6 PET non responders (26%). After a median follow-up time of 38.0 mon, the median event-free survival (EFS) and the median overall survival (OS) were not yet reached in the PET responders, while EFS was 15.4 mon and OS was 18.3 mon in nonresponders. Conclusions: This study confirms the prognostic value of early metabolic response evaluation during neoadjuvant chemotherapy. Histopathologic responses were observed after salvage chemoradiation, but the clinical outcome of early PET non-responders to chemotherapy remains poor, indicating a dismal tumor biology in this group of pts. No significant financial relationships to disclose.