bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment patterns for locoregional esophageal carcinoma according to race/ethnicity, histology, and insurance.
Authors: Cox D. D. , Fedewa S. , Chen A. , Virgo K. S. , Ward E. M. 
Published: February 2017

128 Background: Esophageal carcinoma (EC) is a disease with a poor prognosis. There has been a rise in incidence of EC in many western countries, including the United States. African Americans (AA) have a higher mortality rate from EC than any other ethnic group in the U.S. We investigated if there were differences in treatment and clinical characteristics in AA patients with locoregional EC compared to whites. Methods: We used the National Cancer Data Base (NCDB), a national hospital-based cancer of registry to study 20,056 adults diagnosed with locoregional EC from 2004-2007. Treatment and outcome data were obtained from the NCDB. Multivariate log binomial models were used to estimate relative risk ratios (RR) and 95% confidence intervals (CI) of receiving surgery, surgery plus systemic treatment vs. surgery alone, and margin status among patients undergoing surgery. Results: Compared to whites, AA were younger, more likely to have proximal tumors and squamous cell carcinoma, and to be uninsured. AA patients had a lower likelihood of surgery compared to whites (RR = 0.71, 95% CI = 0.66-0.77). Patients who were uninsured, Medicaid insured or younger Medicare patients had a lower likelihood of surgery. Other important predictors of surgical treatment included age, tumor location, size and histology type. Facility level factors impacted surgical treatment as well. Among patients receiving surgery, there were no differences in receipt of systemic treatment by race/ethnicity and insurance status. Younger Medicare patients and uninsured patients were more likely to have positive margins while there was no difference by race/ethnicity. Conclusions: AA patients were less likely than whites with locoregional EC to receive surgery, however, there were no treatment disparities among AA receiving surgery. Tumor characteristics, patient, provider and/or institutional factors that may influence lower receipt of surgical treatment and survival among AA should be further explored. No significant financial relationships to disclose.
Treatment outcome and safety of docetaxel as the third-line chemotherapy in advanced gastric cancer after progression or after failure of FOLFOX and FOLFIRI-based sequential chemotherapy.
Authors: Hwang I. , Kang J. , Park B. , Park S. , Jang M. , Kim S. 
Published: February 2017

133 Background: We performed multicenter retrospective study to evaluate the activity and the safety of a docetaxel as the third-line chemotherapy in advanced gastric cancer (AGC) patients who had undergone oxaliplatin (FOLFOX) and irinotecan (FOLFIRI)-based chemotherapy regimens. Methods: Thirty-eight patients with AGC previously treated were eligible for this study. Patients received docetaxel 30 mg/m2 +/- cisplatin 30 mg/m2 IV on day 1, 8 or docetaxel 60 mg/m2 +/- cisplatin 60 mg/m2 IV on day 1 every 3 weeks until disease progression, and responses were assessed after every two cycles according to RECIST criteria and toxicity was evaluated by NCI-CTC. Results: Thirty-two out of 38 patients were evaluable for response. A total of 95.1 cycles of chemotherapy (median 2, range 0.5–7) were administered. Relative dose intensities of docetaxel and cisplatin were 93.4% and 87.8%, respectively. The overall response rate was 15.6% and the disease control rate was 50%. With a median follow-up duration of 3.1 months (range 0.3-14.3 months), 36 patients had disease progression, and 34 patients had died at the time of analysis. The median progression-free survival was 1.8 months (95% CI, 1.3–2.3 months). The median overall survival was 3.1 months (95% CI, 2.3–3.9 months). Grade 3 or 4 hematologic toxicities included neutropenia in thirteen patients (38.3%), febrile neutropenia in four patients (11.7%). and thrombocytopenia in one patient (2.9%). Other grade 3 or 4 toxicities included neuropathy in three patients (8.8%) and mucositis in two patients (5.9%). There were three treatment-related deaths (8.8%) caused by infection associated with neutropenia. Conclusions: Salvage docetaxel chemotherapy in AGC patients failed in oxaliplatin and irinotecan-based treatment is not recommend routinely. However, selected patients with good performance status and sufficient albumin levels may have derived some survival benefits from salvage chemotherapy. No significant financial relationships to disclose.
Gastric HER2 testing study (GaTHER): Evaluation of gastric cancer testing accuracy in Australia.
Authors: Kumarasinghe M. P. , Morey A. , Bilous M. , Fox S. B. ,   GaTHER Study Group
Published: February 2017

15 Background: Amplification and/or overexpression of human epidermal growth factor receptor 2 (HER2) has been reported in 6%-33% of advanced gastric cancers (GC), and trastuzumab, an anti-HER2 monoclonal antibody, has been shown to provide a survival benefit in HER2-positive disease. Thus accurate testing will be critical to ensure HER2 utility as a predictive marker in GC. HER2 in situ hybridisation (ISH) testing is currently undertaken for all breast cancer in Australia as part of a national program, however pathologists have limited experience with GC tissue. This study evaluated testing methods and determined inter-laboratory reproducibility of HER2 scoring in GC across 9 Australian reference laboratories. Methods: A tissue microarray (TMA) comprising 100 pre-screened gastric or gastro-oesophageal junction (GOJ) adenocarcinoma samples with a range of HER2 positivity was prepared from 1-mm cores. Each laboratory assessed TMA HER2 status by both immunohistochemistry (IHC) (n=9) and ISH [chromogenic (n=3), silver (n=6), fluorescent (n=1)], using its validated testing methods and applying GC scoring criteria. Inter-laboratory agreement on HER2 ISH scoring, using both HER2 copy number and HER2:chr17 ratio, and agreement on IHC scoring (ToGA method), was calculated (kappa statistics). Results: There was only moderate agreement between laboratories on IHC scoring (κ = 0.46). Agreement on CISH/SISH scoring was good/very good when HER2 copy number, stratified into negative, equivocal and positive for amplification, was used (κ = 0.68-0.86), but was reduced when HER2:chr17 ratio was used (κ = 0.59-0.70). Agreement between CISH/SISH and FISH using HER2 copy number was excellent (κ = 0.88-0.91) but was again reduced when HER2:chr17 ratio was used (κ = 0.84-0.86). Good/very good agreement between IHC and FISH (κ = 0.85) or CISH/SISH (κ = 0.72-0.87) was also achieved when HER2 copy number was used. Conclusions: Good concordance across laboratories can be achieved with FISH, or single-probe CISH or SISH, scored using HER2 copy number, with use of chr17 probe in chromogenic assays best restricted to equivocal cases. HER2 IHC alone is not recommended for determining HER2 status in gastric and GOJ cancers. [Table: see text]
First interim results of the global investigation of therapeutic decisions in hepatocellular carcinoma (HCC) and of its treatment with sorafenib (GIDEON) study: Use of sorafenib (Sor) by oncologists and nononcologists in the management of HCC.
Authors: Venook A. P. , Lencioni R. , Marrero J. A. , Kudo M. , Nakajima K. , Ye S. 
Published: February 2017

157 Background: GIDEON is an ongoing, global, prospective, non-interventional registry study of patients (pts) with unresectable HCC (uHCC) receiving Sor under real-life practice settings. From January 2009 to September 2010, over 2,200 pts have been enrolled from 32 countries. Per protocol, the first planned interim analysis was triggered when 500 enrolled pts were followed for at least 4 mos; the primary safety and efficacy results were reported in October 2010. A preplanned subset analysis of treatment patterns across MD specialities is reported here. Methods: Demographics, medical, disease and treatment history are recorded at enrolment; Sor dose, concomitant treatments, performance status, liver function are noted at follow-up. Standard efficacy measures and adverse events (AEs) are captured. Preplanned subanalysis by MD specialty was conducted. Results: Of the 141 treating MDs, 69 (49%) were hepatologists/gastroenterologists (Hep/GIs), 55 (39%) were medical oncologists (Oncs) and 17 (12%) were other specialties. Descriptive statistics of differences in pts' HCC stage, Sor treatment and AEs by the main specialties are shown for the 479 pts evaluable for safety (Table). Conclusions: Interim data from the GIDEON study suggests differential use of Sor by MD specialties. It appears that Oncs tend to treat with lower doses of Sor and for a somewhat shorter duration than Hep/GIs. If these data persist, it will be important to explore the reasons for these differences in Sor usage between Oncs and Hep/GIs and potential impact on patient outcomes. [Table: see text] No significant financial relationships to disclose.
Efficacy of oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX4) versus doxorubicin in advanced HCC: Updates on the EACH study.
Authors: Thongprasert S. , Qin S. , Lim H. , Bhudhisawasdi V. , Yin X. , Gang W. , Kim B. , Jian Z. , Yang T. , Rau K. 
Published: February 2017

160 Background: In Asia, where hepatitis B is very common, patients often present with locally advanced or metastatic hepatocellular carcinoma (HCC), and their prognosis is poor. The EACH study was designed to evaluate the efficacy and safety of FOLFOX4 vs. doxorubicin as palliative systemic chemotherapy in advanced HCC. Methods: The open-label, randomized, multicenter phase III study was conducted in 371 patients in China, Taiwan, Korea and Thailand, who had locally advanced or metastatic HCC and were ineligible for resection. Patients were randomized 1:1 to receive either FOLFOX4 (oxaliplatin 85 mg/m2 i.v. d1; LV 200 mg/m2 i.v. h0–h2 d1 and d2; 5FU 400 mg/m2 i.v. bolus h2, then 600 mg/m2 over 22 hours d1 and d2 q2w) or doxorubicin (50 mg/m2 i.v. q3w). The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), response rate (RR) by RECIST and safety. Data from final and follow-up analyses of the intent-to-treat (ITT) population and selected subgroup analyses are presented. Results: At the final analysis, median OS with FOLFOX4 (N = 184) was 6.40 months (95% CI: 5.30, 7.03) vs. 4.97 months (95% CI: 4.23, 6.03) with doxorubicin [N = 187; p = 0.0695 using a stratified log-rank test; statistical significance (p = 0.0425) was achieved at the post hoc follow-up analysis conducted 7 months later]. Median PFS with FOLFOX4 was 2.93 months (95% CI: 2.43, 3.53) vs. 1.77 months with doxorubicin (95% CI: 1.63, 2.30; p = 0.0002). The RR was 8.2% vs. 2.7% of patients with FOLFOX4 and doxorubicin, respectively (p = 0.0233), and the disease control rate (DCR) was 52.2% vs. 31.6% (p < 0.0001). In the Chinese sub-population, OS, PFS, RR and DCR were significantly improved with FOLFOX4 vs. doxorubicin at both the final and follow-up analyses. In the other subgroups analyzed, the OS and PFS benefits of FOLFOX4 vs. doxorubicin were generally consistent. Conclusions: In the ITT population, median OS was greater with FOLFOX4 than doxorubicin throughout the study and statistical significance was achieved after continued follow-up. FOLFOX4 can benefit patients with advanced HCC, as it significantly increases median OS, PFS, RR and DCR compared with doxorubicin. [Table: see text]
An miRNA assay for the classification of benign and neoplastic lesions in pancreatic fine-needle aspirates.
Authors: Labourier E. , Lloyd M. , Andruss B. , Adai A. , Schwarzbach A. 
Published: February 2017

163 Background: Improved diagnosis of pancreatic ductal adenocarcinoma (PDAC) versus benign pancreatic lesions is an urgent clinical need. We previously reported a laboratory-developed test based on the differential expression of two miRNAs, miR-196a and miR-217, with a sensitivity and specificity of 95% in formalin-fixed, paraffin-embedded (FFPE) specimens with ≥60% tumor content. Here, we report the development and validation of an miRNA-based research test optimized for low % tumor specimens and fine needle aspirates (FNA). Methods: RNA was extracted using methods developed and validated by the Asuragen Services Laboratory from frozen, FFPE or FNA pancreatic specimens. One to three endoscopic ultrasonography-guided FNAs were collected, stored, and shipped in RNARetain, an RNA stabilization solution formulated in 1 mL single-use vials. Expression levels of up to 12 miRNAs were interrogated using TaqMan qRT-PCR assays. Results: A set of 211 specimens, including 94 PDAC, 96 chronic pancreatitis, and 21 normal, was used to develop a miRNA classifier to discriminate benign and low tumor content PDAC. Training on 95 FFPE specimens showed that expression analysis of miR-196a, -210, and -375 improved by 2- to 3-fold the detection rate of PDAC in specimens with 5-88% tumor. The classifier performance was further verified on 4 independent sets of specimens (n=116): frozen with high tumor content (80-100%), FFPE with high tumor content (60-95%), FFPE with low tumor content (10-60%), and FNA. The signature is now being evaluated in a multisite prospective study using FNAs collected in RNARetain; 110 specimens have been analyzed to date and we will report the relative performance of the 2- and 3-miRNA classifiers. Conclusions: Benign lesions and PDAC can be accurately classified based on the expression level of a few miRNAs in specimens with 5-100% tumor and in FNA. Testing of preoperative FNAs collected in RNARetain as part of routine clinical evaluation could in the future improve the differential diagnosis of PDAC and potentially reduce the rate of indeterminate or false-negative calls. [Table: see text]
Potential predictors of pancreatic cancer: A population-based screen.
Authors: Ragulin-Coyne E. , Smith J. K. , Ng S. , McDade T. P. , Shah S. A. , Tseng J. F. 
Published: February 2017

164 Background: Pancreatic cancer (PC) is the fourth leading cause of cancer-related death in the U.S. Unfortunately, PC is usually diagnosed at late stages. We hypothesized that certain diagnoses may precede PC diagnosis and assist in early identification of pancreatic cancer patients. Methods: SEER-Medicare 1991-2005 was used to identify PC patients. PC and prePC diagnoses were identified using ICD9 codes. We then examined pre-pancreatic cancer (prePC) diagnoses and compared the frequency of those diagnoses by PC stage at time of cancer diagnosis. Stepwise logistic regression was used to assess potential PrePC diagnoses. Risk factors were compared by stage at diagnosis using Kruskal-Wallis test, stratified univariate analysis and logistic regression. Time to diagnosis was calculated for each PrePC diagnosis. Results: 19,801 PC patients were identified. Significant (p<0.05) prePC diagnoses included acute pancreatitis, chronic pancreatitis, cyst/pseudocyst, other pancreatic disease, bile duct obstruction, diabetes, weight loss, jaundice, abdominal pain, hepatomegaly. Median time (months) and interquartile range percentiles (25th-75th) before PC diagnosis were as follows: acute pancreatitis 0.97 (0.33-8.6), chronic pancreatitis 1.56 (0.37-11), cyst/pseudocyst 0.83 (0.3-3.5), other pancreatic disease 0.47 (0.2-1.2), bile duct obstruction 0.4 (0.17- 0.83), diabetes 30.6 (11.3-59.8), weight loss 1.16 (0.43-5.1), jaundice 0.43 (0.2-0.8), abdominal pain 16 (1.07-55.5), hepatomegaly 1.06 (0.33-1.07). Patients diagnosed at AJCC stage 0 had a mean of 3.53 prePC diagnoses (±SD 1.42); stage IA, 2.80 (1.68); stage IB, 2.42 (1.57); stage IIA, 2.44 (1.63); stage IIB, 2.46 (1.64); stage III, 2.33 (1.59); and Stage IV, 1.79 (1.40) (p<0.001). Conclusions: PC patients who presented at later stages were less likely to have prePC claims identified prior to PC diagnosis compared with patients diagnosed at earlier stages. This analysis of potential prePC diagnoses suggests that access to care and earlier identification of PC related conditions may factor into the stage at which this lethal disease is identified. Further studies need to be conducted to identify and analyze additional predictors of PC and better screen individuals at risk. No significant financial relationships to disclose.
Preparation technique for cytologic study of EUS-guided FNA samples when onsite cytopathologist is absent: Cell block, smear, or both?
Authors: Nguyen N. Q. , Lim K. , Ruszkiewicz A. 
Published: February 2017

176 Background: Smearing EUS-guided fine-needle aspiration (FNA) samples, with or without cell block, is most commonly performed for cytologic study in centers without onsite cytology. The diagnostic yield of such technique is often low (35%-50%) and may be related to loss of diagnostic material during the smearing process. Cell block technique captures not only aspirated cells but also small tissue fragments, improving diagnostic yield and enabling additional ancillary studies. This study aimed to compare the diagnostic yield of cell block alone against conventional smear (±cell block) technique in the EUS-guided FNA evaluation of pancreatic solid mass without onsite cytological assessment. Methods: Data on the diagnostic yield of cell block alone technique performed over the last 12 months were prospectively collected and were compared to the yield of conventional smear ± cell block technique. A positive diagnostic yield was defined by the presence of adenocarcinoma and/or FNA findings consistent with the final surgical diagnosis. Results: Data were available for 96 patients, of which 66 had cell block alone and 30 had smear +/-cell block preparation. The diagnostic yield of cell block alone was significantly higher that that of smear +/- cell block (53/66 vs 13/30; P=0.003). The addition of cell block after smearing did not improve the diagnostic yield (smear: 42% vs. both: 45%, p=0.88). Of patients who had smear +/-cell block, the diagnostic yield was significantly higher when the smearing was performed by cytopathologist as compared to that by nurse (10/16 vs. 3/14, p=0.02). There was a direct relationship between the rate of diagnostic yield and the number of FNA passes performed. The yield was highest when 4 or more FNA passes was performed (85%) as compared to that of 3 passes (63%, p=0.049) and 2 or less passes (38%, p<0.0001). Conclusions: In the absence of onsite cytology services, the diagnostic yield from cell block alone was high (80%) and was superior to smear technique whether cell block was added to the evaluation of smears. In order to obtain adequate tissue material to maximise the diagnostic yield EUS-guided FNA of pancreatic mass, at least 4 FNA passes should be performed. No significant financial relationships to disclose.
Detection of viable human circulating tumor cells using telomerase-specific GFP-expressing bioengineered adenovirus in patients with gastric cancer: A feasibility study.
Authors: Fujiwara T. , Uno F. , Hashimoto Y. , Shirakawa Y. , Nagasaka T. , Kagawa S. , Urata Y. 
Published: February 2017

18 Background: The presence of circulating tumor cells (CTC) in the peripheral blood is associated with short survival and, therefore, the detection of CTC is clinically useful as prognostic factors of disease outcome and/or surrogate markers of treatment response. Recent technical advances in immunocytometric analysis and quantitative real-time PCR have made possible to detect a few CTC in the blood; however, there is no sensitive assay for detecting viable CTC. We developed a new approach to visually detect live CTC among millions of peripheral blood leukocytes using telomerase-specific replication-selective adenovirus expressing green fluorescent protein (GFP). Methods: We constructed a GFP-expressing attenuated adenovirus, in which the telomerase promoter regulates viral replication (OBP-401, TelomeScan). The detection method for viable human CTC in the peripheral blood involves a three-step procedure including the lysis of red blood cells, the subsequent addition of OBP-401 to the cell pellets, and the automated scan under the fluorescent microscope. We analyzed fresh blood samples collected from 37 patients with histologically confirmed gastric cancer. We further assessed the CTC dynamics in patients who were undergoing chemotherapy or surgery to demonstrate the clinical potential of our approach for monitoring treatment responses. Results: OBP-401 increased the signal-to-background ratio as a tumor-specific probe, because the fluorescent signal can be amplified only in viable human tumor cells by viral replication. Although the CTC level varied widely, ranging from 0 to 47 in 5-ml samples, 26 gastric cancer patients (70.3%) had more than one CTC; there was, however, no apparent relationship between CTC counts and TNM stages. Patients who had a recurrence of gastric cancer had decreased CTC counts after systemic chemotherapy. In the patients who underwent surgery, the CTC level dropped after complete resection. Conclusions: This GFP-expressing virus-based method is simple and allows precise enumeration of CTC, which might be useful for monitoring the efficacy of local and systemic treatments. [Table: see text]
Clinical significance of elevation of the serum IL-6 level in patients with advanced pancreatic cancer.
Authors: Mitsunaga S. , Ikeda M. , Nakachi K. , Ohno I. , Shimizu S. , Takahashi H. , Okuyama H. , Inagaki M. , Furuse J. , Ochiai A. ,   Chugai Pharmaceutical Co. Ltd.
Published: February 2017

181 Background: IL-6, one of the pro-inflammatory cytokines, is a recognized mediator of cachexia and cancer cell invasion. It has been reported that elevation of the serum IL-6 level may be associated with deterioration of the clinical condition and tumor progression in advanced pancreatic cancer (PC) patients. The aim of this study was to clarify the clinical features of increased serum IL-6 levels in patients with advanced PC receiving chemotherapy. Methods: Patients with treatment-naïve unresectable PC and no obvious infectious conditions were eligible for this study. Serum levels of IL-6 were measured by an electrochemiluminescence assay. Symptoms were rated numerically from 0 to 10 using the Japanese version of the M. D. Anderson Symptom Inventory. Tumor volume was calculated as the sum of the long diameters of the tumors. The measurements were performed before chemotherapy and at one month after the start of chemotherapy. Results: A total of 87 patients (male/female: 41/46; ECOG performance status: 0/1/2: 59/26/1; media age: 66 years) were enrolled; all patients were administered systemic chemotherapy (gemcitabine [GEM]/GEM+S-1/GEM+other/S-1: 52/11/9/15). The median serum level of IL-6 was 1.3 pg/mL before chemotherapy (at baseline) and 1.8 pg/mL at one-month after the start of chemotherapy. The median change of IL-6 from the baseline was +0.18 pg/mL. Patients with increase of the serum IL-6 level by more than 0.18 pg/mL were assigned to the elevated IL-6 group (n=42; median change in IL-6: +1.66 pg/mL). The elevated IL-6 group showed more sadness (p=0.019), numbness (p=0.008), and gain of body weight (p=0.016) at the baseline as compared to the non-IL-6-elevated group (n=42; median change in IL-6: -0.27 pg/mL). Comparison of the elevated and non-IL-6-elevated groups revealed a greater degree of increase in the tumor volume (p=0.015), deterioration of nausea (p=0.046) and vomiting (p=0.028), neutrophilia (p=0.004), and elevation of the serum C-reactive protein (p=0.011) in the elevated IL-6 group than in the non-IL-6-elevated group. Conclusions: Elevation of the serum IL-6 level may be associated withsymptom deterioration, increase of the tumor mass, and inflammatory reaction in patients with advanced PC. No significant financial relationships to disclose.