bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pilot study of low-dose capecitabine plus trastuzumab as first-line treatment for patients older than 75 years with HER2-positive advanced gastric cancer.
Authors: Sym Sun Jin , Kim Young Saing , Park Inkeun , Ahn Hee Kyung , Hong Junshik , Park Jinny , Cho Eun Kyung , Lee Jae Hoon , Lee Woon Ki , Chung Min , Kim Hyung-Sik , Shin Dong Bok 
Published: February 2017

165 Background: Elderly patients often present with concomitant co-morbidities and age-associated physiologic problems, such as impaired organ function and functional changes that make the selection of optimal treatment difficult. We report the treatment outcome in 13 elderly patients with HER2-positve advanced gastric cancer who treated with low-dose capecitabine plus trastuzumab. Methods: Patients older than 75 years with gastric cancer were eligible for inclusion if their tumors showed overexpression of HER2 protein by immunohistochemistry (IHC) (3+) or gene amplification by FISH and IHC 2+. Capecitabine 1000 mg/m2was given orally twice a day for 14 days followed by a 1-week rest. Trastuzumab was given by intravenous infusion as a dose of 8 mg/kg on day 1 of the first cycle, followed by 6 mg/kg every 3 weeks. Chemotherapy was given every 3 weeks for eight cycles. Results: Between December 2011 and July 2013, 13 consecutive patients (IHC 3+;7, IHC 2+ and FISH+;6) with a median age of 79 years (range, 75-92 years) were enrolled in this study. ECOG PS was 0/1/2:1/7/5, respectively. A total of 54 cycles of capecitabine plus trastuzumab were administered (median, three cycles; range, 2-8 cycles). Of the 12 patients with measurable lesions, the overall response rate was 41.6% (95% CI, 13.7 to 69.5%). Disease control was achieved in 75.0% of patients. Median progression-free survival was 8.2 months (95% CI, 2.5-13.7 months) and median overall survival was 10.9 months (95% CI, 1.4-20.4 months). Grade 3-4 toxicities were stomatitis (7.6%) and anemia (7.6%). No treatment-related deaths and symptomatic congestive heart failure were observed. Conclusions: Our findings suggest that low-dose capecitabine plus trastuzumab is effective and well tolerated in elderly patients with advanced HER2-positive gastric cancer who are considered ineligible for combination chemotherapy. Prospective trials investigating this regimen in elderly patients with advanced gastric cancer are warranted. Clinical trial information: Gachon University IRB.
A novel biomarker panel examining response to adjuvant pancreatic cancer therapy in RTOG 9704.
Authors: Heestand Gregory M. , Murphy James Don , Moughan Jennifer , Regine William , Luo Jia , Graber Madeline Sydney , Kunz Pamela L. , Fisher George A. , Guha Chandan , Lin Bryan , Mowat Rex B. , Gaur Rakesh , Buyyounouski Mark K. , Chen Yuhchyau , Chang Daniel Tandel , Koong Albert 
Published: February 2017

176 Background: RTOG 9704 was an adjuvant pancreatic adenocarcinoma trial. Patients with resected stage I-III disease were randomized to receive 5-FU vs. gemcitabine (GEM) chemotherapy pre and post 5-FU chemoradiation. Prior to adjuvant therapy, patients had baseline serum samples drawn and archived for future study. Methods: To better understand the biology of pancreatic cancer, investigators involved with this project have evaluated numerous proteins of interest via literature review and gene expression data. By using the multiplex capabilities and high sensitivity detection of the proximity ligation assay (PLA), a probe panel was built from commercially available antibodies capable of quantifying 42 key proteins from 24 uL of patient serum. To determine if any of these proteins corresponded with survival or predicted response, the baseline serum specimens were obtained for assay with our PLA panel. Clinical endpoints were overall (OS) and disease-free survival (DFS). Univariate and multivariate statistical techniques were used. Using a Bonferroni correction, a p-value of <0.0012 was considered statistically significant. Results: Of the 451 eligible patients, 213 had samples available for study – 112 (53%) in the 5-FU arm and 101 (47%) in the GEM arm. As expected, decreased levels of CEA and CA 19-9 were prognostic for improved OS in all patients. Low levels of matrix metalloproteinase-7 (MMP-7) predicted an OS benefit from adjuvant GEM, but not 5-FU. Conclusions: PLA is a powerful tool for identifying potential biomarkers from archived, small volume serum samples. These data suggest that pancreatic cancer patients with low MMP-7 serum levels were most likely to benefit from adjuvant GEM. Supported by RTOG grants U10 CA21661, CCOP grant U10 CA37422, and RTOG Biospecimen Resource grant U24 CA114734 from the National Cancer Institute. [Table: see text]
Discriminant, identifiable plasma metabolites in pancreatic cancer–associated diabetes.
Authors: Urayama Shiro , Tolstikov Vladimir 
Published: February 2017

180 Background: Pancreatic cancer has been associated with development of glucose intolerance and dysregulation. Based on our previous report of strong potential for existence of metabolite biomarkers for PDAC detection, in this study, we have pursued initial characterization of plasma metabolites for discriminating PDAC cases among diabetic patients. Methods: IRB-approved prospectively collected database and corresponding plasma from UC Davis Pancreas Registry was searched for appropriate cases: PDAC patients with recent-onset diabetes (≤3yrs prior to the index PDAC diagnosis) (Grp 1) and non-PDAC patients with long history of diabetes mellitus (>3 yrs) (Grp 2). The plasma was processed and non-targeted GC/MS and targeted LC/MS were performed to assay for identifiable plasma metabolites. The data was processed and the peak intensity levels were normalized, scaled and identifiable metabolites were processed via metabolomics specific multivariate analysis and bootstrap methods as well as ROC evaluation (Metaboanalyst and ROCCET) for visualization and biomarker development. Results: We have identified 36 patients in Grp 1 and 22 patients for Grp 2. The metabolite specific multivariate and ROC analyses revealed specific features such as elaidic acid, uric acid, 2,3-propanediol, arachidonic acid, docosahexanoic acid, 5-oxo-EET, lysine, LysoPC(18:2), 9(10)-EpOME, LysoPC(16:0), sphingosine-1-phosphate and others as strong discriminators for recent-onset diabetic patients with pancreatic cancer. Such set yielded AUC of 0.964 with 15 features [CI=0.876-1]. Conclusions: We have demonstrated that an identifiable set of plasma metabolite biomarkers exists for discriminating diabetic patients with developing pancreatic cancer. These features could be utilized in a larger set of new-onset diabetic population for further validation in near-future study.
A joint United Kingdom (UK) and Hong Kong (HK) study to determine prognostic factors for hepatocellular carcinoma (HCC) undergoing curative and palliative treatment.
Authors: Chan Stephen Lam , Johnson Philip James , Mo Frankie , Berhane Sarah , Ma Brigette , Teng Mabel , Poon Darren M. C. , Morse Janet , Chan Anthony T. C. , Yeo Winnie 
Published: February 2017

181 Background: There have been few international studies that systematically evaluate the impact of geographical region on the prognosis of HCC. Methods: Prospective cohorts of patients (pt) were accrued in UK (n=567; 2006-2011) and HK (n=517; 2007-2012). Clinical data were documented at baseline; treatments were decided by multidisciplinary teams at both centers. Results: The median follow-up time of the UK and HK cohort was 27.9 and 29.8 months, respectively. The median overall survival (OS) of the whole UK and HK cohort was 22.9 months and 8.6 months. In the HK cohort, 425 underwent palliative treatment (TACE, systemic agents or supportive care) and 92 had curative treatment (surgery and locoablation); in the UK cohort, 338 had palliative treatment and 228 underwent curative treatment. In the curative group, the median OS was 54.8 months in the UK cohort but has not yet been achieved in the HK cohort. For the palliative group, the median OS was 12.7 and 5.5 months in the UK and HK cohort respectively. In the palliative group, geographical difference was an independent prognostic factor (HK vs. UK, HR=2.0; p<0.0001). Other prognostic factors were mainly tumorous features and Child’s liver function (Table). In the curative group, neither geographical difference nor Child’s score were prognostic factors. Conclusions: Separate prognostic factors exist for curative and palliative treatment. Geographical differences need to be considered during design of clinical trials on novel agents where palliative treatments are investigated but not for surgery or locoablation. [Table: see text]
Disconnect between earlier presentation patterns and application of curative treatments in HCC.
Authors: Ulahannan Susanna Varkey , Duffy Austin G. , Kish Jonathan K , McGlynn Katherine , Rahma Osama E. , Greten Tim F. , Altekruse Sean 
Published: February 2017

187 Background: In the U.S., a greater proportion of small hepatocellular carcinomas are being diagnosed. The extent to which patients with small HCCs are receiving potentially curative therapies is unclear. Methods: Receipt of liver transplantation, resection, radiofrequency ablation, and other or unspecified surgery/ablation as first therapy was examined among HCC cases in the NCI SEER18 cancer registries during the years 2000 to 2010. Survival of HCC by treatment modality was also examined. Results: The diagnosis of small tumors (≤5 cm) significantly increased between 2000 and 2010, surpassing diagnosis of larger tumors beginning in 2005. Among patients diagnosed during 2007-2010 with complete data available, 57% had small tumors and more than three quarters had a single tumor, however fewer than one third received surgical or ablative treatment. Incidence rates of resection, ablation and transplantation (therapies with curative intent) increased 17.6% per year between 2000 and 2005, then decreased by -2.9% per year through 2010. Resection was the leading treatment followed by radiofrequency ablation and transplantation. The number of patients treated with curative intent decreased as tumor size or tumor number increased; 42% of patients with single tumors ≤5 cm in size were treated with curative intent compared to 20% with single tumors >5 cm. While radiofrequency ablation was used to treat small tumors, resection was used to treat both small and large tumors. Patients who received transplants had the best five-year survival rate (71%), followed by patients who received resection (42%) and radiofrequency ablation (30%). Five-year survival of patients who did not receive surgery or ablation was 6%. Conclusions: Despite more patients being diagnosed with small tumors, the US-SEER database analysis demonstrates a recent decrease in the use of curative treatments. Treatment guidelines suggest that early diagnosis HCC cases are eligible for treatment with curative intent. Investigations of reasons for the limited treatment are recommended with the goal of improving outcomes.
Hepatitis B viral load to predict survival of HCC patients treated with sorafenib.
Authors: Lim Seungtaek , Han Kwang-Hyub , Choi Hye Jin 
Published: February 2017

188 Background: Sorafenib demonstrated survival prolongation in patients with advanced hepatocellular carcinoma (HCC). Until now, the effect of HBV DNA titer on prognosis of HCC patients treated with sorafenib has not been determined. Methods: From 2008 to 2012, 78 HBV-related HCC patients who received sorafenib at Severance hospital were included in our analysis. The prognostic effect of pretreatment HBV DNA level was examined by univariate and multivariate analysis. Results: The median overall survival was 5.2 months (95% confidence interval [CI]: 4.0-6.4) and median progression free survival was 3.5 months (95% CI: 2.3–4.7). Multivariate analysis revealed that a high baseline HBV DNA level (>2,000 IU/L) was an independent risk factor for worse overall survival (p=0.005; hazard ratio [HR], 2.85), and rapid disease progression in a subgroup who did not receive antiviral prophylaxis with sorafenib (p=0.008; HR, 87.4). Moreover, viral reactivation occurred more frequently in patients who did not receive prophylactic antiviral therapy with sorafenib compared to those who did (4/38 vs. 0/40; p=0.025). Conclusions: A higher HBV DNA level before sorafenib was associated with poorer prognosis and increased viral reactivation. This result suggests the role of prophylactic antiviral therapy in patients who received sorafenib. [Table: see text]
CYFRA 21-1 as a novel diagnostic serum biomarker in pancreatic cancer.
Authors: Kim Jung Hoon , Song Joon Cheol , Kwon Jung Hyun , Kim Dae Kyun , Jekarl Dong Wook , Jang Jeong Won , Yoon Young Chul 
Published: February 2017

191 Background: CYFRA 21-1 is a fragment of cytokeratin 19, a structure protein and part of intermediate filament proteins contributing to stability of epithelial cells. Serum concentration of CYFRA 21-1 is known to be elevated in many types of epithelial malignancies, and especially it has a prognostic and predictive value in patients with non-small cell lung cancer. We assessed serum CYFRA 21-1 and studied its clinical significance in patients with pancreatic cancer. Methods: The sera from 52 patients diagnosed with pancreatic cancer was collected between May 2012 and August 2013 at Incheon St. Mary’s hospital, Catholic University of Korea, School of Medicine and was measured for CYFRA 21-1 and CA 19-9. 48 patients had an advanced disease at presentation, 2 patients had a locally advanced disease, and 2 patients presented with a local disease. Control blood samples were obtained from 31 healthy individuals and 48 patients with nonmalignant hepatic or pancreatobiliary disease. We measured CYFRA 21-1 using two-step sandwich, chemiluminescent microparticle immunoassay, Architect i2000SR (Abbott Laboratories, Ltd., Il, USA). Results: Serum concentration of CYFRA 21-1 was significantly elevated in patients with pancreatic cancer compared with control group. (p=.000) CYFRA 21-1 ( >1.96 ng/ml as determined by the ROC curve) had a sensitivity, specificity, positive predictive value, and negative predictive value of 86.5%, 79.7%, 73.8%, 90% for the diagnosis of pancreatic cancer. Additionally, CA 19-9 ( >35 U/ml determined by our institute’s criteria) had a sensitivity, specificity, positive predictive value, and negative predictive value of 67.3%, 89.9%, 69.1%, 81.6%. The area under curve for CYFRA 21-1 and CA 19-9 was 86.3% and 81.5%, respectively. Conclusions: CYFRA 21-1 has a potential to become a novel serum biomarker for the diagnosis of pancreatic cancer. Serum concentration of CYFRA 21-1 in combination with CA 19-9 can be useful in clinical practice to diagnose pancreatic cancer.
Diagnostics of pancreatic duct hypertension by the serotonin-stimulating magnetic resonance cholangiopancreatography (MRCP): A preliminary study.
Authors: Kashintsev Alexey 
Published: February 2017

196 Background: Serotonin is a neurotransmitter which stimulates the pancreatic secretion. Pancreatic and periampullary tumors can cause the dilatation of the main pancreatic duct. Its partial stenosis can remain undiagnosed on conventional MRCP. Increasing secretion of pancreatic juice after stimulation by the serotonin can help to detect the location and length of a lesion. Methods: Eighteen patients with pancreatic cancer (n=14) and tumor of papilla Vateri (n=4) were included into the study. Median age was 64.9 years with range 45-84 years. Serotonin (0,01mg/kg) was administered perorally (n=2), intramuscularly (n=2), or intravenously with dilution (n=5) and without it (n=9). MRCP was performed before the drug application and 7 minutes later. Results: In cases where serotonin was administered perorally, intramuscularly or intravenously with dilution we did not receive any significant results. The positive results were obtained in 5 (55.6%) of 9 cases when MRCP was performed 7 minutes after intravenous administration of concentrated solution. The mean increase in width of the main pancreatic duct was 1.1 mm (range 0.9-1.9 mm). Conclusions: The method of serotonin stimulating MRCP can improve the diagnosis of pancreatic ductal hypertension. In these 5 cases, a presented technique allowed us to detect the size and localization of a lesion more precisely: tumor of a papilla (n=2), cancer of a pancreatic head (n=3) including one case with involvement of the pancreatic body. In cases of primary ductal dilatation more than 5 mm (n=3), we did not receive any positive results, so these patients were excluded from the study.
Conditional survival for intrahepatic cholangiocarcinoma: SEER database analysis.
Authors: Muzaffar Mahvish , Kaur Sandeep , Afroz Fir , Lone Maqbool , Khan Nazir Ahmad , Teli MA 
Published: February 2017

201 Background: Conditional survival can be useful for estimating survival probability for patients who have survived one or more years after the initial diagnosis. It reflects the possible change in risk profile over time especially for malignancies with poor outcome. Methods: The Surveillance, Epidemiology and End Results database was reviewed for intrahepatic cholangiocarcinoma. We reviewed data for all intrahepatic cholangiocarcinoma from year 2000-2010. Data of 8278 patients was extracted from SEER database. We sub stratified using factors like age <50 versus ≥50, gender, grade, stage, primary site surgery. SEER*Stat: Version *8.1.2 software was used to calculate conditional survival. Conditional survival is defined as the calculated probability of survival after having already survived a specified number of years from diagnosis. Results: The analysis showed that Conditional survival (CS) probability for intrahepatic cholangiocarcinoma increased from 33.25 to 85% at 5 years for all age groups conditional to surviving one year after diagnoses. For age group <50 years CS increased from 50.4% to 86.9%, while for age group >50yrs from 31.4% to 84.5%.The conditional survival for well differentiated histology increased from 60.7% to 81.0%, moderately differentiated from 53.8% to 87.7%, poorly differentiated from 37.1% to 83.6% .The conditional survival for localized stage increased from 50.7% to 88.8%, regional 40.6% to 77.7% and distant 19.0% to 65.6%.Majority of cases had missing data with regard to primary site surgery. 1707 cases had documented primary site surgery. Conditional survival for this group increased from 30.7% to 82.8% subject to surviving one year after diagnosis. Conclusions: There are several limitations associated with these results due to missing data in SEER. Nonetheless these results emphasize the trend of patient’s surviving more than 1 year after diagnosis have higher conditional survival probability. CS may provide more relevant prognostic information as compared to traditional survival estimates.
Molecular features of BRCA1/2 and PALB2 mutation associated pancreatic cancer (PAC).
Authors: Lowery Maeve Aine , Timms Kirsten , Abkevich Victor , Neff C , Gutin Alexander , Lanchbury Jerry S. , Tang Laura H. , O'Reilly Eileen Mary 
Published: February 2017

206 Background: Several clinical reports have indicated increased sensitivity to DNA damaging agents and PARP inhibitors in patients with PAC arising on a background of known BRCA1/2 or PALB2 germline mutation. While the mechanism of tumorigenesis in these cancer remains unclear, it appears likely that BRCA1/2germline mutations can predispose to PAC via 2 mechanisms, only one of which requires loss of the second allele. Determination as to whether biallelic inactivation of these genes is present in the tumor may have important therapeutic implications in predicting sensitivity to PARP inhibitors and other strategies targeting DNA repair. Methods: Following approval by the IRB and human bio specimen utilization committee at MSKCC, full exon sequencing of coding regions of 28 genes including BRCA1, 2 and PALB2 using exon capture by hybridization and next generation sequencing was performed on DNA extracted from 135 PAC samples. In addition, samples were analyzed for the presence of BRCA1 promotor methylation, KRAS hotspot mutations, and genome wide loss of heterozygosity (LOH) as an exploratory assessment of number and length of LOH as a marker of homologous repair deficiency / genomic instability. All patients underwent surgery for PAC at MSKCC after year 2000. Patients were selected on the basis of survival and included if they suffered a cancer-specific death within 1 year of resection or survived at least 30 months. Results: 7 tumors had mutations in BRCA2, 1 in BRCA1 and 1 in PALB2. Of 4 BRCA2 mutated samples evaluated for LOH at the BRCA2 locus, 2 demonstrated LOH while 2 did not. There was no LOH at PALB2 in the sample where a mutation was identified. Activating KRAS mutations were identified in BRCA2 mutated tumors with and without LOH. Methylation of the BRCA1promotor regions was not identified. Conclusions: The frequency of BRCA1/2 mutation carriers was as anticipated in this population. Biallelic loss of BRCA2 or PALB2 are not required for pancreatic tumorigenesis. The benefit of PARP inhibitors in BRCA1 / 2 mutated PAC may be limited to tumors with LOH of these genes. Inactivation of BRCA1 through promoter methylation is not identified in sporadic PAC.
Next-generation sequencing yields promising targets in advanced cholangiocarcinoma (CCA).
Authors: Shroff Rachna T. , Churi Chaitanya , Rashid Asif , Mishra Lopa , Zuo Mingxin , Kaseb Ahmed Omar , Janku Filip , Aloia Thomas A. , Vauthey Jean-Nicolas , Curley Steven A. , Javle Milind M. 
Published: February 2017

209 Background: The incidence of CCA is rising and the clinical efficacy of systemic therapy is suboptimal. Next generation sequencing (NGS) technology offers potential for targeted therapeutics against genetically heterogenous solid tumors including cholangiocarcinoma (CCA). Methods: DNA was extracted from biopsy specimens of 61 patients (pts) with CCA seen at MD Anderson Cancer Center Houston, TX. DNA sequencing was performed for 3,769 exons of 236 cancer-related genes plus 47 introns from 19 genes to an average depth of 1000X using the Illumina HiSeq 2000 platform (performed by Foundation Medicine, Cambridge, MA). Results: 174genomic alterations (GA) were identified from 61 pt samples with an average of 2.85 GAs/pt (range 0-10). GAs identified were mutations (75%), amplifications (16%), loss/deletions (7%) and others (2%). 6 (10%) tumors showed no GAs. Most frequent GAs were TP53 (34%), KRAS (30%), ARID1A (15%), PBRM1 (11%), BAP1 (8%), ERBB2 (8%), FBXW7 (8%), SMAD4 (8%) and IDH1 (8%). ERBB2 GAs included 4 mutations and 1 amplification. KRAS mutation was associated with a statistically significant reduction in overall survival (OS). Mean OS in pts with KRAS mutation was 32 weeks vs. 63 weeks in KRAS wt (t = -2.126, p = 0.039). Ingenuity Pathway Analysis indicated disruption in cell cycle, proliferation, development, death and DNA repair pathways. Targetable signaling pathways from this study are described in the Table. Targetable GAs were noted in 62% of pts. These are potentially targetable by inhibitors to ERBB2, FGF, mTOR, MEK, BRAF and PARP-1. Conclusions: These data are the single largest compilation of NGS analysis on CCA pts and demonstrate the range of GAs that are eligible for investigational targeted therapies. These results can be used as a basis to develop personalized treatments for CCA pts based on individual genetic profiles. [Table: see text]