bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expanded analyses of napoli-1: Phase 3 study of MM-398 (nal-IRI), with or without 5-fluorouracil and leucovorin, versus 5-fluorouracil and leucovorin, in metastatic pancreatic cancer (mPAC) previously treated with gemcitabine-based therapy.
Authors: Chen Li-Tzong , Von Hoff Daniel D. , Li Chung-Pin , Wang-Gillam Andrea , Bodoky Gyorgy , Dean Andrew Peter , Shan Yan-Shen , Jameson Gayle S. , Macarulla Teresa , Lee Kyung-Hun , Cunningham David , Blanc Jean-Frédéric , Hubner Richard , Chiu Chang-Fang , Schwartsmann Gilberto , Siveke Jens T , Braiteh Fadi S. , Moyo Victor M. , Belanger Bruce , Bayever Eliel 
Published: February 2017

234 Background: MM-398 is a nanoliposomal encapsulation of irinotecan. OS in the ITT population was significantly longer with MM-398+5FU/LV over 5FU/LV alone, and the most frequent grade 3+ AEs included neutropenia, fatigue, and GI effects (diarrhea and vomiting). Expanded, pre-specified analyses of the Phase 3 study are presented. Methods: Patients (n=417) with mPAC previously treated with gemcitabine-based therapy, were randomized 1:1:1 in an open-label study to receive: (A) MM-398 (120 mg/m2 IV over 90 min) q3w; (B) 5FU (2,000 mg/m2 over 24 h) plus racemic leucovorin (LV) (200 mg/m2 over 30 min) x 4w followed by 2w rest; or (C) combination of MM-398 (80 mg/m2 IV over 90 min) prior to 5FU (2,400 mg/m2 over 46 h) and racemic LV (400 mg/m2 over 30 min) q2w. The primary endpoint was OS. The Intent To Treat (ITT) population included all randomized patients; the Per Protocol (PP) population included patients who received at least 80% of the target dose in the first 6 weeks and did not violate any inclusion/exclusion criteria. Results: Analysis of the PP populations confirmed the favorable OS, which was also reflected by the PFS, ORR and CA19-9 levels, of the combination MM-398+5FU/LV arm over the control 5FU/LV arm. The MM-398 monotherapy arm did not show a statistically significant improvement in OS compared with the control arm. Analysis of subgroups, based on pretreatment characteristics including stage at diagnosis, time since initial histological diagnosis, prior lines of therapy, time since last prior therapy, and CA19-9 levels, consistently favored OS for the MM-398+5FU/LV arm over the 5FU/LV arm. Conclusions: Expanded analysis of the PP population and sensitivity analyses support the favorability of MM-398+5FU/LV over 5FU/LV, with a manageable safety profile. Clinical trial information: NCT01494506. [Table: see text]
New prognostic staging system from the multivariate survival analysis (MVA) of the patients with unresectable hepatocellular carcinoma (HCC) treated with doxorubicin drug eluting beads transarterial chemoembolization (DEB TACE).
Authors: Prajapati Hasmukh J. , Kim Hyun Sik 
Published: February 2017

236 Background: To develop the staging system from MVA in pts with unresectable HCC treated with DEB TACE. Methods: Consecutive unresectable and non-tranplantable pts with HCC, who received DEB TACE over the 88 months(m), were studied. 420 pts (mean age, 61.4 yrs) were included in the study. Survivals were analyzed according to different parameters from the time of the 1st DEB TACE. Kaplan Meier estimator by log rank test and Cox Proportional Hazard model were used for survival analysis. The staging system was constructed from the survival analyses. Results: The overall median survival (OS) was 20m. Pts with Child Pugh (CP) class A(54.5%), B(40.2%) and C(5.3%) had OSs of 28m, 12.9m and 4.1m respectively (p<0.0001). Pts with BCLC A(9.3%), B(21.2%), C(61.4%) and D(8.1%) had OSs of 37m, 30m, 17.2 and 4.4m respectively (p<0.0001). In HCC pts with venous thrombosis (VT) of large vein (main PV, right or left PV, HV, IVC) (72.7%) versus (vs) small vein (segmental/subsegmental PV) had OSs of 5.8m versus 17.3m accordingly (p=0.008). Pts with Alfa-feto protein (AFP) >400ng/dl had OS of 7.6m vs 24.3 m with AFP<400 (p<0.0001). On MVA, the significant independent PFs of survival were CP class, ECOG PS, number (no) of HCC, index HCC (iHCC) size, site of Portal or hepatic VT, extra-hepatic metastasis (mets), serum(s) creatinine, and s.AFP. Based on these PFs, the staging system was constructed, which is shown in table 1 and named as CIS (Clinical, Imaging and Serum examination) staging system. The OSs of stage I, II, III and IV were 40.4m, 24m, 10.6m, and 2.6m respectively (p<0.0001). Conclusions: We propose the new CIS prognostic staging system for advanced HCC from the MVA of survival after DEB TACE in pts with unresectable HCC. [Table: see text]
The management of small asymptomatic pancreatic neuroendocrine tumors: A matched case-control study.
Authors: Sadot Eran , Reidy Diane Lauren , Tang Laura H. , Gonen Mithat , D'Angelica Michael Ian , DeMatteo Ronald P. , Kingham T. Peter , Jarnagin William R. , Allen Peter J. 
Published: February 2017

239 Background: Overdiagnosis and overtreatment has become an evolving challenge for several cancer sub-types. We hypothesized that a substantial portion of incidentally diagnosed small pancreatic neuroendocrine tumors(PanNET) are overtreated as a result of overdiagnosis and that non-operative management may be reasonable for selected patients. Methods: Consecutive patients evaluated for incidentally discovered, sporadic, stage I-II PanNET were analyzed retrospectively. Diagnosis was determined either by pathology or unequivocal imaging characteristics. Patients selected for radiographic surveillance (RS) were matched with patients who underwent resection based on tumor size at initial imaging. Clinicopathological characteristics were compared between the groups. Results: During the study period (2000-2013), RS was recommended for 80 patients, and 79 matched patients underwent resection (resection group). Pathologic diagnosis was obtained in 42 (53%) of the 80 RS patients. Median initial tumor size was similar between the RS vs resection groups (1.2cm (0.8-1.7) vs 1.3 cm (1-1.9), respectively, p=0.4). The resection group was younger and had a longer median follow-up compared to the RS group (58 vs 65 years, p<0.001; 50 vs 29 months, p=0.006; respectively). At the time of last follow-up of the RS group, median tumor size had not changed (1.2cm, p=0.4), no patient had developed metastases, and no patient had experienced radiographic changes in the primary tumor that prompted resection. Within the resection group, low-grade (G1) pathology was recorded in 74 (95%) tumors, one patient had node positive disease, and five developed recurrence (6%). The postoperative complication rate was 36%. No patient in either group died from disease. Death from other causes occurred in 7 out of 159(4%) patients. Conclusions: In this study, no patient who was selected for observation developed metastases or died from disease after a median follow-up of almost 2.5 years.Radiographic surveillance for stable, small, incidentally discovered PanNETs is reasonable in selected patients.
A phase I/II multicenter study of the chimeric monoclonal antibody NEO102 (NPC-1C) in adults with refractory pancreatic (PC) and colorectal cancer (CC).
Authors: Beg Muhammad Shaalan , Morse Michael , Patel Sandip Pravin , Mavroukakis Sharon , Beatson Melony A. , Arlen Philip M. , Azad Nilofer Saba 
Published: February 2017

240 Background: NPC-1C (NEO102) is a novel chimeric monoclonal antibody that recognizes a variant form of MUC5AC expressed specifically by human pancreatic (P) and colorectal (CC) tumors. The mechanism of action is through Antibody-dependent cell-mediated cytotoxicity (ADCC). We are presenting results of dose escalation and preplanned expansion cohort of NEO-102. Methods: This is a Phase Ib/IIa, open label, multicenter clinical trial and expansion cohort of NEO102. Patients are preselected based on an Immunuhistochemistry (IHC) companion diagnostic assay. Antigen expression cut off was set at 20% expression. NEO102 was administered every 2 weeks IV with tumor assessments every 8 weeks. The primary objective was to determine safety and tolerability of NEO102. Secondary objectives include overall survival, clinical benefit, pharmacokinetics and explore the immunologic correlates. Results: Twenty-six patients (3 pancreatic and 23 colon cancer) are evaluable for toxicity and response. Median age is 55 (32 - 68) years, 14 are male. Two dose limiting toxicities were experienced at 4.0 mg/kg: grade 3 hyperbilirubinemia (n=4) and grade 3 anemia (n=1). The maximum tolerated dose (MTD) and recommended phase-2 dose (RP2D) was established at 3.0 mg/kg. Of 12 patients evaluated for response, 5 demonstrated stable disease by RECIST (42%; 4 CC, 1 P) after the first course (Day 57) and 1 PC had SD after the second course (Day 114). OS is 4.5+ months (1+ - 13.5+), median duration of treatment of 74+ days (36-133). Of those screened, 60-70% tumors were IHC positive. Immune correlates (including cytokine profile, HAMA) will be presented. Conclusions: Treatment with NEO102 is well tolerated with a manageable safety profile. RP2D is 3.0 mg/kg. Preliminary results with NEO102 have demonstrated signs of clinical activity based on stabilization of disease in heavily pretreated patients with PC and CC. A Phase II study of NEO102 monotherapy in pancreatic and colon cancer is now enrolling patients. In addition, a combination study using NEO102 with cytotoxic chemotherapy in metastatic pancreatic cancer is underway. Clinical trial information: NCT01040000.
Discussing treatment (Tx) and clinical trials for pancreatic cancer (PC): Learnings from the Pancreatic Cancer Action Network (PanCAN) survey.
Authors: Engebretson Anitra , Matrisian Lynn , Thompson Cara 
Published: February 2017

241 Background: In 2014, 46,420 patients (pts) in the US will be diagnosed with PC, and only 6.7% are expected to survive ≥ 5 years after diagnosis. Enrollment in clinical trials is recommended to improve pt outcomes. Methods: Funded by Celgene, PanCAN developed a 25-minute survey and distributed it online between 7/30/13 and 9/18/13 to pts with PC or caregivers whose loved ones were alive or had died of PC within the past 6 months. Results: Respondents included 184 pts (81 with metastatic PC) and 213 caregivers (145 for pts with metastatic PC). Pts and caregivers answered similarly with a few exceptions. Quality of life (QoL), extending survival, and symptom management were the 3 most important issues to all respondents. Caregivers placed statistically significantly more emphasis on QoL and managing symptoms vs pts (88% vs 71% and 68% vs 33%, respectively). A total of 196 respondents reported that Tx options were not offered at diagnosis, and 20% of these respondents stated that Tx options were never discussed with an MD. Most pts (95%) followed their doctors’ Tx recommendation, and 83% received chemotherapy. Almost half of respondents (49%) reported that their MD never discussed clinical trials; of those that did, oncologists (52%) were the primary source used to learn about possible clinical trial participation, followed by caregivers (16%) and loved ones (13%).Twelve percent of pts enrolled in clinical trials (> the US average of 4.6%; J Clin Oncol 31:3432-3438). Forty-eight percent of respondents were aware of the Pt and Liaison Services (PALS) program, a support service from PanCAN. PALS-aware respondents were more likely than others to report that the pt had undergone chemotherapy (89% vs 78%), surgery (64% vs 41%), or radiation (47% vs 32%) and more likely to state that the pt followed a Tx recommendation because it was the best/most realistic option (19% vs 11%). PALS-aware pts also participated more often in clinical trials (15% vs 9%). Conclusions: These results underscore the importance of discussing Tx options, clinical trials, and support services with pts. Such steps could increase Tx and enrollment in clinical trials, possibly improving QoL, survival, and symptom management.
The identification of the age effects in 1,287 patients with biliary tract cancer.
Authors: Umemoto Kumiko , Mitsunaga Shuichi , Watanabe Kazuo , Okuyama Hiroyuki , Hashimoto Yusuke , Takahashi Hideaki , Ohno Izumi , Shimizu Satoshi , Ikeda Masafumi 
Published: February 2017

244 Background: Age is a mirror for pathogenesis in some of biliary tract cancer (BTC) as liver fluke- or pancreaticobiliary maljunction-associated BTCs. However, the age effects including prognosis in BTC were not fully understood. The identification of the age effects might be helpful for the management of BTC. Methods: For the years 1992-2014, 1287 patients receiving initial treatment for BTC in our institution were reviewed. According to age at diagnosis of BTC, patients were divided into the five age groups as <50, 50-59, 60-69, 70-79, and ≥80. The relationships between overall survival time (OS) and the five age groups were analyzed using wilcoxon test to choose a prognostic cut-off of age. On the basis of a prognostic cut-off of age, the prognostic age classification was constructed. The multivariate analysis with logistic regression modeling was performed to determine the influence of gender, Eastern Cooperative Oncology Group performance status scale [ECOG-PS], primary site, and metastatic site on the prognostic age classification. Results: Median age was 67 years with male 59%. ECOG PS of 0 was 63.7%.The sites of primary tumor included intrahepatic (25.2%) and extrahepatic bile duct (34.0%), gallbladder (31.9%) and ampulla of Vater (8.9%). The prognostic cut-off of age was age less than 60 (21.8% of all). Median OS in younger patients (age<60, median OS: 7.9mo) was shorter than that in elder patients (age≥60, median OS 12.4mo, P<0.01). In univariate analysis, the prevalence of bone metastasis, distal lymph node metastasis and peritoneal dissemination was higher in younger BTC than elder patients. Multivariate analysis revealed that peritoneal dissemination was an independent younger BTC related-factor (OR=1.9, P<0.01). Conclusions: Younger BTC patients (age<60) showed poor prognosis and the high frequency of peritoneal dissemination, compared to elder BTC patients. The relationship between age and peritoneal dissemination of BTC might be a key to elucidate the age effect concomitant with poor prognosis.
Molecular profiling with the 92-gene assay and decision-impact on cancer treatment: Interim results from a prospective, multidisciplinary study.
Authors: Thomas Sachdev P. , Braiteh Fadi S. , Cherkis Karen Ann , Operana Theresa N. , Blatner Nichole Renee , Schroeder Brock , Schnabel Catherine A. 
Published: February 2017

249 Background: Metastatic lesions with unknown (CUP), unclear, or differential diagnoses pose significant challenges, particularly when presenting in the GI tract, leading to suboptimal treatment and outcomes. In clinical studies, molecular classification with the 92-gene assay demonstrated improved diagnostic accuracy compared to standard pathology techniques and improved survival in patients treated based on assay results. The current study assessed the utility of the 92-gene assay in diagnoses and treatment decision-making in clinical practice. Methods: Cases in which the 92-gene assay was ordered as part of routine clinical care were submitted into a study database via web-based, standardized, discipline-specific questionnaires. Utilization and impact of the assay were characterized for medical oncologists and pathologists. Physician-reported results from medical oncologists are included in this interim analysis of 134 cases. Results: Results from this registry-based reporting study showed that molecular profiling impacted treatment decisions in 53% of cases. Significantly, 46% of these cases reported a change in treatment regimen associated with integration of 92-gene assay results. Clinical scope included 18 tumor types with 52% having a molecular diagnosis of GI origin. The top 3 diagnoses were pancreaticobiliary, intestine, and gastroesophageal adenocarcinoma. The pre-assay working diagnosis was unknown in 41%, a differential diagnosis in 26%, and a single suspected site in 33% of cases. Conclusions: Findings from this study demonstrate that use of the 92-gene assay impacted treatment decisions and selection in a significant proportion of patients, and further define its role in clinical practice in the diagnosis and treatment planning of diagnostically-challenging metastatic cancer. [Table: see text]
Predictors of long-term survival with metastatic pancreatic cancer (mPC) in the gemcitabine era: The Fox Chase Cancer Center experience.
Authors: Vijayvergia Namrata , Dotan Efrat , Devarajan Karthik , Lewis Bianca , Cohen Steven J. 
Published: February 2017

253 Background: Although median survival (OS) for patients (pts) with mPC was ~6 months (m) in the gem era, a subset of pts lived significantly longer as long term survivors (LTS). We compared the patterns of care and outcomes of pts living < 12 m (Gp 1) and ≥ 12 m (Gp 2) to identify predictors for LTS. Methods: With IRB approval, we retrospectively analyzed medical charts of mPC pts treated at our center between 2000 and 2010. Gp 1 and Gp 2 were compared with respect to pt, tumor and treatment characteristics. Fisher’s exact and Mann-Whitney tests were used, respectively, to compare categorical and continuous variables, and the log-rank test to compare OS. All tests were two-sided and a Type I Error of 5% was used to determine statistical significance. Results: 579 mPC pts (median age 64 y, 56% males) were identified, 476 pts in Gp1 and 103 in Gp 2 (OS 4m vs 18 m, respectively). There was no significant difference in the age, site of pancreatic primary, comorbidities, tobacco use or stage at diagnosis between the two. 341 (72%) pts in Gp1 and 86 (83%) in Gp 2 had an initial PS <2 (p 0.06). Alcohol use was more prevalent in LTS [170 (36%) in Gp1 vs 50 (49%) in Gp2 (OR 1.8, p 0.008)]. 170 (36%) pts in Gp 1 and 55 (52%) in Gp 2 had serum albumin (alb) > 3.5 gm/dl (p< 0.001) and this predicted survival (OS 4m if Alb < 3.5 and 7m if Alb > 3.5, p <0.001). Use of chemotherapy in the metastatic setting (66% in Gp1 vs 93% in Gp 2) and number of agents used also predicted survival with 202 (42%) pts in Gp 1 and 79 (87%) in Gp 2 having received > one agent in the metastatic setting (p < 0.001). Liver metastases were more common as an initial site in Gp1 vs Gp2 [329 (70%) vs 48 (47%) respectively, p < 0.001]. In contrast, lung metastases were more common in Gp 2 [42 (9%) Gp 1 vs 20 (19%) in Gp 2, p< 0.001]. The median survival for pts with liver as initial metastatic site was worse than those with lung metastases (5m vs 7m, p < 0.001). Conclusions: Use of chemotherapy and increasing number of agents are associated with better survival in mPC, in line with the current practice of using combination chemotherapy. The site of initial metastasis and serum albumin also predict for survival. Clinical trial designs should consider the latter as stratification factors.
Interleukin-6 (IL-6) as an inflammatory biomarker in patients with hepatobiliary cancers.
Authors: Anwar Sidra , Miller Austin , Fetterly Gerald J. , Iyer Renuka V. 
Published: February 2017

257 Background: IL-6 is an inflammatory cytokine that modulates growth and differentiation of tumor cells. The role of IL-6 as a biomarker in this cancer subset population remains questionable. We aimed to study IL-6 levels in patients with hepatobiliary cancer and the associated patient characteristics. Methods: Stored serum from 91 patients with treatment-naïve hepatobiliary cancers (hepatocellular carcinoma, gallbladder cancer, intra- and extra-hepatic cholangiocarcinoma) were measured for IL-6 levels. Demographics and clinical parameters were collected from retrospective chart review. IL-6 was measured in stored serum from 91 controls, matched for age, gender and BMI. Associations between baseline covariates and IL6 measurements and differences in Overall Survival (OS) were assessed using Accelerated Failure Time (AFT) models. P-values <0.05 were considered statistically significant. All data analyses were generated using SAS/STAT software, Version 9.4. Results: A total of 91 cases+91 controls were analyzed: 68% males in each set. IL-6 levels were significantly higher in the cases than the controls [median: 15.2pg/ml vs 1.7pg/ml p<0.01]. Amongst cancer patients the following elements were associated with significantly higher levels of IL-6: cirrhosis (AF=3.18 p<0.01), uncontrolled pain (AF=1.97 p<0.01), worse ECOG status (p<0.01) and portal vein thrombosis (AF=1.57, p=0.03). A 3-fold increase in Alpha fetoprotein (AFP) corresponded with a 9% increase in IL-6 (AF=1.09, p=0.015). IL-6 appeared to be modestly higher in males [median: 4.47 vs 5.32 p=0.5]. IL-6 remained an independent predictor of OS after controlling for several possible confounders (AFP, Cirrhosis, portal vein thrombosis). Each 10-unit increase in IL-6 resulted in an 8% reduction in the time to death (AF=0.92 (95% CI:0.78 to 1.00) p=0.033). Conclusions: IL-6 levels are significantly elevated in hepatobiliary cancers, directly correlating with AFP. Higher IL-6 levels are associated with aggressive tumors and poorer survival. These findings suggests the potential prognostic/predictive value of IL-6 and should initiate early palliative care referrals. Anti-IL6 therapy could increase meaningful survival time for patients.
A comparison of the WHO 2004 and 2010 classification systems in pancreatic neuroendocrine tumors (PNET).
Authors: Sama Ashwin Reddy , Asija Aakanksha , Casey James , Andrel-Sendecki Jocelyn , Lewis Nancy , Lavu Harish , Winter Jordan Michael , Brody Jonathan Robert , Mitchell Edith P. , Yeo Charles , Prestipino Anthony , Pillai Madhavan V. 
Published: February 2017

267 Background: PNETs are rare tumors with multiple classification systems. We compared the WHO 2004 and 2010 classification systems for predicting mortality and metastasis. Variables associated with mortality were explored. Methods: Descriptive statistics were calculated for characteristics of 50 PNET patients. The relationship between the WHO 2004 and 2010 system was investigated using an exact Chi squared test. WHO grade categorization was explored by vital status, by the exact method, in order to determine if there was a difference in survivorship and metastasis by grading system. Associations between death and categorical variables were tested using exact methods and between death and continuous variables by the Wilcoxon test. Survival was explored using Cox Proportional Hazards regression (COX). Results: 62 % of patients were female and the median age was 60 years. Both grading systems were strongly associated with predicting mortality (table 1); all cases of mortality were in the higher grades. The 2010 grades do slightly better in predicting metastasis as metastases occur only in high grades (G2 and G3). Patients with lymphovascular or perineural invasion had significantly higher mortality. Mitotic Index was significantly different with a median of 0 in live patients versus 15 in deceased, p <0.001. This was similarly borne out in the survival analysis using COX, where for every one unit increase in Mitotic Index, there was about a one third increase in the hazard of death (p = 0.001). There was no significant difference in survival by tumor size, comorbidities, or margins. Conclusions: The WHO 2010 grading system is strongly associated with predicting mortality and performs better in predicting metastasis than the 2004 grading system. [Table: see text]