bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase 2, randomized trial of GVAX pancreas and CRS-207 immunotherapy versus GVAX alone in patients with metastatic pancreatic adenocarcinoma: Updated results.
Authors: Le Dung T. , Wang-Gillam Andrea , Picozzi, Jr Vincent , Greten Tim F. , Crocenzi Todd S. , Springett Gregory M. , Morse Michael , Zeh Herbert , Cohen Deirdre Jill , Fine Robert Lance , Onners Beth , Uram Jennifer N. , Laheru Dan , Murphy Aimee , Skoble Justin , Lemmens Ed , Grous John J. , Dubensky Thomas , Brockstedt Dirk G. , Jaffee Elizabeth M. 
Published: February 2017

177^ Background: Immunotherapy for pancreatic ductal adenocarcinoma (PDA) is likely to require synergistic combinations. One approach is to use heterologous prime boost vaccinations to capitalize on immunostimulatory features of distinct vectors. GVAX is irradiated, GM-CSF-secreting allogeneic pancreatic cell lines given intradermally to elicit a broad antigenic response. Low-dose cyclophosphamide (CY) is given prior to GVAX to inhibit regulatory T-cells. CRS-207 is live-attenuated Listeria monocytogenes (Lm) which expresses mesothelin and stimulates innate and adaptive immunity. In mouse tumor models, Lm/GVAX vaccines are synergistic and in the Phase 1 study of CRS-207, 3 PDA patients who had received prior GVAX lived ≥15 months (mos). Methods: Metastatic PDA patients (ECOG 0-1; adequate organ function) who received or refused ≥1 prior chemotherapy were randomized 2:1 to receive either 2 doses of CY/GVAX followed by 4 doses of CRS-207 (Arm A) or 6 doses of CY/GVAX (Arm B) every 3 weeks. Courses could be repeated. The primary endpoint was to compare overall survival (OS) between the arms. Secondary endpoints were safety, clinical and immune responses. One-sided p-values are reported. Results: 90 patients (Full Analysis Set [FAS]; A: 61, B: 29), of which 51% had received ≥2 chemotherapy regimens for metastatic PDA, were treated. After a median follow-up of 7.8 mos, median OS in FAS was 6.1 vs 3.9 mos (A vs B; HR=0.54, p=0.011). Median OS in patients who received ≥3 doses (per protocol [PP] set: 2 doses of CY/GVAX and ≥1 dose of CRS-207 in A or ≥3 doses of CY/GVAX in B) was 9.7 vs 4.6 mos (A vs B; HR=0.44, p=0.0074). The treatment effect was particularly evident in patients who received ≥2 prior regimens for metastatic PDA with median OS of 5.1 vs 3.7 mos (A vs B; HR=0.34, p=0.001). OS in the PP set was 8.2 vs 4.0 mos (A vs B; HR=0.23, p=0.0003). CA19-9 stabilization was seen in 32% vs 13% of patients (A vs B; p=0.06). Toxicities included local reactions after GVAX and transient fevers, rigors and lymphopenia after CRS-207. Conclusions: CY/GVAX followed by CRS-207 shows extended survival with manageable toxicity in previously-treated metastatic PDA and warrants further study. Clinical trial information: NCT01417000.
Pre-SBRT metabolic tumor volume and total lesion glycolysis to predict survival in patients with locally advanced pancreatic cancer receiving stereotactic body radiation therapy.
Authors: Dholakia Avani Satish , Chaudhry Muhammad Ali , Leal Jeffrey P. , Chang Daniel Tandel , Raman Siva P. , Su Zheng , Hacker-Prietz Amy , Pai Jonathan , Griffith Mary E , Wahl Richard L. , Tryggestad Erik , Pawlik Timothy M. , Laheru Daniel A. , Wolfgang Christopher Lee , Koong Albert , Herman Joseph M. 
Published: February 2017

189 Background: Though prior studies have demonstrated the prognostic value of pre- and post-treatment positron emission tomography (PET) parameters in other malignancies, the role of PET in pancreatic cancer is yet to be established. We analyzed the prognostic utility of PET for patients with locally advanced pancreatic cancer (LAPC) undergoing fractionated stereotactic body radiotherapy (SBRT). Methods: Thirty-two patients with LAPC received up to 3 doses of gemcitabine, followed by SBRT 6.6 Gy in 5 daily fractions, 33 Gy total, on a prospective clinical trial. All patients received a baseline PET scan prior to SBRT (pre-SBRT PET). Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum and peak standardized uptake values (SUVmax and SUVpeak) on pre-SBRT PET scans were calculated using an in-house software. Disease measurability was assessed at a threshold based on the liver standard uptake value (SUV) using the equation Livermean + (2 * Liversd). Median values of PET parameters were used as cutoffs when assessing their prognostic potential through univariate and multivariate Cox regression analyses. Results: Of the 32 patients in this study, the majority were male (N=19, 59%), 65 years or older (N=21, 66%), and had tumors located in the pancreatic head (N=27, 84%). Twenty-seven patients (85%) received induction gemcitabine prior to SBRT per protocol. Median overall survival for the entire cohort was 18.8 months (95% CI, 15.7-22.0). An MTV of 26.8 cm3 or greater (HR 4.46, 95% CI 1.64 to 5.88, p < 0.003) and TLG of 70.9 cm3 or greater (HR 3.08, 95% CI 1.18 to 8.02, p < 0.021) on pre-SBRT PET scan were associated with inferior overall survival on univariate analysis. Both pre-SBRT MTV (HR 5.13, 95% CI 1.19 to 22.21, p=0.029) and TLG (HR 3.34, 95% CI 1.07 to 10.48, p=0.038) remained independent prognostic factors for overall survival in separate multivariate analyses. Conclusions: Pre-SBRT MTV and TLG yield prognostic information on overall survival in patients with LAPC and may assist in tailoring therapy. Clinical trial information: NCT01146054.
A novel method combining gene and protein platforms on one slide for the detection of HER2 in gastric cancer: Final results.
Authors: Werner Dominique , Battmann Achim , Steinmetz Kristina , Jones Tobin , Lamb Tiffany , Martinez Michele , Al-Batran Salah-Eddin 
Published: February 2017

19 Background: The evaluation of gene amplification and/or protein overexpression of HER2 in gastric cancer is a prerequisite to establish an adequate treatment strategy. Gastric tumors are heterogeneous and separate evaluations lead to uncertainties in localizing distinct clones and are time consuming. The aim of this study was to evaluate the feasibility of gene-protein platform in comparison to single staining methods. Methods: Immunohistochemistry (IHC) plus silver in situ hybridization (SISH) (IHC/SISH) and the new gene-protein platform (gene/protein) method for HER2 were performed in randomly collected 100 cases of gastric carcinoma. Evaluation was performed by two observers, in discrepant cases a third observer was consulted to make a decision by consensus. Results of IHC and SISH were compared with gene/protein staining. Rüschoff criteria were applied. Tumors showing HER2 expression 3+ or amplification were considered HER2 positive. Results: 96 of 100 samples were eligible. Amplification was observed in 14.6% by both, conventional SISH and gene/protein platform. 70.8% by IHC and gene/protein had no expression (0) and 10.4%/11.5% (IHC vs. gene/protein) had weak (1+) HER2 expression. Moderate expression (2+) was observed in 9.4% by IHC and 7.3% by gene/protein. Rate of overexpression (3+) was similar in IHC (9.4%) and gene/protein (10.4%). There were complete concordances (100%; κ=1) in IHC assessment of cases with score 0 and SISH amplified tumors. High concordance are shown in score 1+ (98.96%; κ=0.947) and 3+ (96.88%; κ=0.825) cases. Concordance in cases with score 2+ was found in 95.83% (κ=0.728) of the observations. After third observation, there were 5 discordant cases with most discrepancies in assessment of IHC score 2+ or 3+. Conclusions: Gene-protein platform has been tested for first time in gastric carcinoma. Results showed that this novel platform can be a feasible alternative to single methods. Discrepancies in cases with moderate HER2 expression are a result of observer variability.
Prevalence of detectable HBV DNA in cancer patients with resolved HBV infection (HBsAg (-) HBcAb (+) and its evolution after cytotoxic chemotherapy.
Authors: Shah Taral Ramesh , Zheng Huo Xiang , Gohari Pouyan , Shulimovich Maxim , Huang Yiwu , Xu Yiqing 
Published: February 2017

194 Background: Reactivation of hepatitis B virus (HBV) has been widely reported in HBsAg+ cancer patients undergoing chemotherapy, mainly in patients with lymphoma and breast cancer who received Rituximab and Adriamycin based chemotherapy. Reactivation of HBV has also been reported in a few patients who had previous exposure and resolved HBV infection (HBsAg-, HBcAb+). However there is no consensus as to whether prophylactic antiviral therapy should be used for this group, or whether the presence HBsAb plays a further protective role. Methods: We retrospectively and prospectively identified cancer patients undergoing chemotherapy who have HBsAg-, HBcAb+ status. Their HBV DNA levels and serial liver functions were followed. We aimed to evaluate the prevalence of detectable HBV DNA and HBV seroconversion rate after chemotherapy. Results: Between 11/2011 to 6/2013, 124 patients were screened and 51 (41%) had pretreatment HBsAg-, HBcAb+ status. Forty two (82%) patients were of Asian descent; 18 (35%) were males and 33 (65%) were females. Median age was 60 years with a range of 28 to 84 years. Forty seven patients (92%) received chemotherapy for solid malignancies while 4 (8%) received rituximab. Only one patient (2%) had detectable HBV DNA prior to treatment and received baraclude for prophylaxis. Fifteen patients (29%) had HBsAg-, HBcAb+, HBsAb- status, 36 (71%) had HBsAg-, HBcAb+, HBsAb+ status. Serial LFTs were followed over a median chemotherapy duration of 4 months (1 to 18 months). 2 had transient increase; 13 showed persistent but stable elevation related to tumor in the liver; 4 patients were tested for HBV DNA at LFT elevation and were negative. No patient had persistent or worsening LFT related to HBV reactivation. Conclusions: The prevalence of HBsAg-,HBcAb+ cancer patients is very high in South Brooklyn, NY, predominantly in Asian patients. Prevalence of detectable baseline HBV DNA is extremely low, even in isolated HbcAb positive patients and there was no seroconversion of HBV during chemotherapy, irrespective of HBsAb status. Prophylactic antiviral therapy is unnecessary.
A California population-based study on long-term survivors of hepatocellular carcinoma.
Authors: Subramaniam Somasundaram , Yang Juan , Lichtensztajn Daphne , Clarke Christina A 
Published: February 2017

195 Background: Hepatocellular carcinoma (HCC) is becoming increasingly common in the United States and long-term survival remains dismal, with only 15% of patients surviving more than 5 years. Little is known about the demographic and clinical characteristics of patients who survive. Methods: Using data from the California Cancer Registry, a member of the National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) program, we identified all patients diagnosed with hepatocellular carcinoma between 1988 and 2007. Patients were included if they had pathological, clinical, laboratory or radiological confirmation of diagnosis. Patient’s demographic information including socio-economic status, summary stage, tumor characteristics and treatment details were included in the analysis. Hazard ratios (HR) for survival were calculated using Cox proportional hazards regression modeling. Results: We identified 19,855 patients with a median age of diagnosis of 63. Patients were predominantly male (74.4%). The majority of patients were Non-Hispanic Whites (38.1%) followed by Asian and Pacific Islander (API) (30.4%) and Hispanics (23.2%). Of the entire cohort, 3546 (17.9%) survived at least 3 years. Amongst long-term survivors, when classified by summary stage, 2552 (72%) were localized, 556 (15.7%) regional, 217 (6.1%) remote and 221 (6.2%) unknown. In a multivariate model, variables associated with survival were resection or transplant (HR 0.31), liver-directed therapies (0.53), chemotherapy (0.64), academic status of treating hospital (0.74), API race (0.832), highest socio-economic status quintile (0.88), female gender (0.93) and Hispanic race (0.94). When stratified by summary stage, API race, receipt of surgery, receipt of liver-directed therapies and treatment in an academic hospital remained significantly associated with long-term survival across all stages. Conclusions: Patients who survive for 3 years after a diagnosis of HCC have distinct demographic and clinical characteristics from patients who do not survive.
Characterization of patients with high serum level of IL-6 in advanced pancreatic cancer.
Authors: Miura Tomofumi , Mitsunaga Shuichi , Shimizu Satoshi , Ohno Izumi , Takahashi Hideaki , Okuyama Hiroyuki , Kuwahara Akiko , Ikeda Masafumi 
Published: February 2017

197 Background: IL-6 is a key mediator of cancer cachexia. The degree of cachexia affects serum IL-6 level in pancreatic cancer (PC) and is varied according to disease progression. The study population to characterize advanced PC patients with high IL-6 level needs the homogeneity in disease status. This study was aimed to identify IL-6-related factors in patients who were scheduled to undergo first-line chemotherapy for treatment-naïve advanced PC. Methods: Patients with treatment-naïve advanced PC were eligible for inclusion in this study. Patients with obvious infection or biliary drainage were excluded. Serum IL-6 levels and clinical parameters (e.g. symptoms, body composition) were prospectively collected. A high IL-6 level was defined as a value greater than the median value in all of the analyzed patients, and analyses were performed to identify risk factors for high IL-6 levels. Results: Eighty patients were analyzed. A multivariate analysis determined that the following parameters were associated with high IL-6: the presence of liver metastasis [Odds ratio (OR): 4.8, p < 0.01], fatigue (OR 3.4, p = 0.02), high carcinoembryonic antigen (CEA) levels (OR: 6.9, p = 0.03), anemia (OR: 9.5, p = 0.01), and high C-reactive protein (CRP) levels (OR: 12.4, p = 0.02). A decreased skeletal muscle mass tended to be frequently observed in patients with high IL-6 levels. Conclusions: High serum IL-6 related the presence of liver metastasis, severe fatigue, high CEA, high CRP and anaemia. Additionally, skeletal muscle loss might be the IL-6 related factor.
Clinical features of young patients (below age 40) with pancreatic ductal adenocarcinoma.
Authors: Ohmoto Akihiro , Morizane Chigusa , Kubo Emi , Shimada Kazuaki , Okusaka Takuji , Yachida Shinichi 
Published: February 2017

199 Background: The median age of pancreatic ductal adenocarcinomas (PDAC) patients is approximately 70 years. We investigated clinical features of PDAC occurring in young patients (< 40 years) in order to determine if any difference exists in comparison to older patients. Methods: We reviewed a single-institution database of 785 patients with pathologically proven PDAC between 2001 and 2012. We examined the clinical features in patients with PDAC below 40 years of age and compared it to those in older patients (≥ 40 years). Results: Of these 785 patients, a total of 10 patients (1.3%) under the age of 40 were identified, with a range of 28 to 37 years. Clinical features in young and older patients have been summarized (table). There are no differences between groups in terms of sex, smoking, tumor location, UICC stage, a family history of PDAC and a family history of any cancer. In the young patients group, three of them were diagnosed with localized diseases, two others with locally advanced diseases, and five others with metastatic diseases. Two of the three patients with localized diseases underwent curative operation. The five patients with metastatic diseases received chemotherapy, and only one patient achieved a partial response treated with FOLFIRINOX regimen. Two of the patients were long-term survivors, having survived over three years. Six of the patients had a family history of other cancers in first-degree relatives. Unexpectedly and most importantly, only one patient had a family history of PDAC. Conclusions: Cases of patients with PDAC below 40 years of age are rare. The clinical features in young patients were generally similar to those in older patients. Almost all young patients had no family history of PDAC, which suggests that hereditary genetic factors have a weak relationship with cases of onset of PDAC at a young age in Japan. [Table: see text]
Pancreas cancer: Influence of gender and other demographic and clinical parameters on survival.
Authors: Blank Patricia Renee , Szucs Thomas D. 
Published: February 2017

200 Background: Research suggests that lower excess mortality risk for females compared to men do exist for several cancer types. The primary aim of this study was to investigate whether gender affects pancreas cancer (PC) prognosis. In addition, the relationship of gender and survival adjusted for clinical and demographic factors was assessed. Methods: The SEER database (version 1973-2009) was used to identify patients with primary histological confirmed PC (≥18 years, 80,689 males and 82,356 females) in the United States. The analysis was stratified by five different stages according to the categories of the American Joint Committee on Cancer (in situ, locally invasive, regional, distant, unstaged). The crude effect of gender was assessed in the total sample and in age-stratified Kaplan-Meier Curves (<55 years) in all five stages, respectively. Univariate and multivariate Cox proportional hazard models were run within the local stage at diagnosis. The predictors included in the models were demographic and clinical factors based on a prior clinical and scientific knowledge. Two-sided p-values of 0.05 were assumed as statistical significant. Results: In total, 128,645 PC-related deaths were reported with a median follow-up time of 13 months (censored patients). Kaplan-Meier curves showed a significant difference in survival among men and female in the locally invasive group (median survival in male and female: 7 months; 1-year survival: 35.5% and 35.1% among female and men, respectively; Log-Rank: p=0.0072). The remaining strata had non-significant differences (p= <.0001), except the unstaged group. The local recurrence group had a 5.6% (95%CI: 1.4%, 9.9%, p=0.0081) higher rate of dying among men compared to female. Among the population <55 years, the gender difference was significant across all disease stages, except the in situ group. Histology grade, age, race, and marital status was associated with survival from PC in the multivariate analysis. Conclusions: The present study indicates that male patients with PC have a worse prognosis than female patients. However, these results need validation and further studies are needed in the research on the prognostic value of gender in PC survival.
The role of surgical resection for hepatocellular carcinoma in octogenarians: A population-based analysis.
Authors: Akinbiyi Takintope , Burnett Atuhani S. , Ernst Philip , Cevasco Marisa , McCain Donald A. , Mokashi Suyog A. 
Published: February 2017

202 Background: Hepatocellular carcinoma (HCC) is a significant source of morbidity and mortality amongst the elderly population. In appropriately selected patients, surgery is known to confer a survival advantage. Octagenarians, however, given their remaining life expectancy may receive limited benefit from surgery. Nevertheless, insufficient information is available in the literature on the survival benefit of surgery in octagenarians with HCC. Methods: Octogenarians with HCC were selected from the Surveillance, Epidemiology, and End Results (SEER) database between 1998 and 2009. We evaluated patients who underwent surgical resection and those that declined to assess the impact surgery has on overall survival in this population. Results: A total of 8,614 with HCC were identified in the SEER database, of which surgery was recommended for 3,529 (41%). A total of 1,002 patients (28%) underwent surgery and 2,497 (71%) declined. Although there was a trend towards improved survival in the surgery group (7.91 months) vs the non-surgical group (7.03 months), there was no statistically significant difference in survival between the two groups (p = 0.09). Conclusions: Our study demonstrates that octagenarians as a whole do not experience a survival benefit from surgical resection for HCC. Subgroup analysis, however, may ultimately identify benefit in specific disease stages or patients with fewer comorbidities.
Clinical significance of serum protein and mRNA level of insulin-like growth factor-1 (IGF-1) in patients with hepatocellular carcinoma.
Authors: Karabulut Senem , Aykan Nuri Faruk , Yildiz Ibrahim , Kilic Leyla , Sen Fatma , Vatansever Sezai 
Published: February 2017

203 Background: The hepatocellular carcinoma (HCC) is one of the most common malignant tumors and the absolute positive and negative markers for HCC are still lacking, and even those characterized by very high sensitivity and specificity do not have an universal diagnostic usefulness. The aim of this study was to assess the usefulness of serum protein and circulating mRNA of insulin-likegrowth factor-1 (IGF-1) as a diagnostic and prognostic tool in HCC. Methods: Fifty-four HCC patients were enrolled into this study. Age and sex matched 20 healthy controls were also included in the study. Serum IGF-1 levels were determined by the solid-phase sandwich ELISA method. Serum IGF-1 mRNA levels were determined by quantitative RT-PCR. Results: The median age at diagnosis was 60 years, range 16–88 years; 48 patients were men. All of patients had cirrhotic history. Fourty-six percent (n=25) of patients had Child-Pugh Score A, 30% (n=16) had Score B or C. All of the patients were preformed with local therapies but none of them treated with sorafenib. The baseline serum IGF-1 mRNA levels were significantly higher in HCC patients than in the control group (p=0.04). while for IGF-1 protein no significant difference was observed (p=0.18). History of HBV infection and untreated patients for HCC had higher serum IGF-1 mRNA levels (p=0.03, and p=0.03, respectively). Poor performance status (p<0.001), viral etiology of cirrhosis (p=0.03), large tumor size (p=0.01), lower serum hemogloblin levels (p=0.03), and not be treated for HCC (p=0.001) related to worse survival. However, neither serum IGF-1 nor serum IGF-1 mRNA had significantly adverse effect on survival (p=0.53, and p=0.42, respectively). Conclusions: Serum circulating IGF-1 mRNA had diagnostic value, both serum protein and mRNA levels of IGF-1 had no prognostic value in patients with HCC.