bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence and prognostic significance of HER2 overexpression in gastric cancer (GC): A monoinstitutional retrospective analysis.
Authors: De Vita Ferdinando , Orditura Michele , Fabozzi Alessio , Laterza Maria Maddalena , Ventriglia Jole , Savastano Beatrice , Giordano Guido , Petrillo Angelica , Marano Luigi , Di Martino Natale , Morgillo Floriana , Martinelli Erika , Troiani Teresa , Ciardiello Fortunato 
Published: February 2017

160 Background: HER2 overexpression in GC is reported in 20% of cases; it is considered a negative prognostic factor with a positive predictive value of response to trastuzumab. We reviewed our case records analyzing its clinical significance. Methods: We retrospectively collected the data for patients (pts.) with histologically confirmed GC and tumor specimens. Results: From June 2011 to December 2012 we analyzed HER2 status in 76 pts with metastatic GC. (M/F 50/26, median age 64 years, ECOG performance status 0/1/2 = 59/12/5, G1/G2/G3 = 6.6%/22.4%/71%). In 36.8% of pts. gastric body was the primary tumor site. HER-2 overexpression was observed in 13 pts (17.1%). HER2-positive group had the following characteristics: M/F = 10/3, median age 63 years; Lauren’s histotype: 75% intestinal and 25% diffuse; G1/G2/G3 = 15.4%/30.8%/53.8%; T3-T4 tumors and N+ disease were observed in 46.1% respectively; the primary tumor site was: proximal 38.4%, distal 61.6%. 46.1% of pts with metastatic disease received a first line CT with a median progression free survival (mPFS) of 5 months (range, 3-7) and a median overall survival (mOS) of 9 months (range, 3-23). In HER2-negative group, (N= 63, M/F = 40/23, median age 64 years), 92.1% of pts. Lauren’s histotype: 45.5% intestinal and 54.5% diffuse; G1/G2/G3 = 4.8%/20.6%/74.6%; metastatic disease: 55.5%. T3-T4 tumors were assessed in 65.1% of pts and N+ disease in 61.9%. The primary tumor location was: proximal 38.1%, distal 61.9%. 57.1% with advanced disease received a first line CT with a mPFS of 5.5 months (range, 2-30) and a mOS of 10 months (range, 2-67). No statistically significant differences for mPFS (p: 0.08) and mOS (p: 0.06) were observed between HER2 positive and HER2 negative metastatic patients. Conclusions: According to our experience, HER2 overexpression doesn’t seem to correlate with a worse prognosis. In particular, it is not correlated with a worse histology and higher stage at diagnosis. Furthermore, no differences in terms of mPFS and mOS were observed between HER2 positive and HER2 negative metastatic pts.
A comparison of proton and photon radiotherapy in reducing cardiac exposure for patients receiving radiation therapy for distal and esophagogastric junction cancer.
Authors: Ling Ted Chen-Tai , Slater Jerry Monroe , Mifflin Rachel , Nookala Prashanth , Grove Roger , Ly Anh , Patyal Baldev , Slater Jerry D. , Yang Gary 
Published: February 2017

167 Background: Recent studies indicate that radiation exposure to heart may have a greater impact on perioperative cardiac morbidities than do other clinical factors. The purpose of this study is to investigate dose distributions of proton and photon treatment plans in patients (pts) with distal and esophagogastric junction (GEJ) carcinoma, focusing specifically on dose reduction to cardiac structures. Methods: Ten pts between 2010 and 2013 were included in this study. Three separate plans were generated for each patient: 3D proton plan, 3D photon plan, and Intensity modulated radiotherapy (IMRT) photon plan. The clinical target volume (CTV) consisted of the pre-operative extent of tumor plus a 10mm manual expansion in all directions. The planning target volume (PTV) was generated by a further expansion on the CTV ranging from 10-15mm. A dose of 50.4Gy given in 28 fractions was delivered to the PTV. All plans were optimized to allow 90% isodose coverage of at least 95% of the PTV. Dose-volume histograms were calculated and analyzed in order to compare plans between the three modalities. ANOVA and two-tailed paired t-tests were performed for all data parameters. Results: The 3D proton plans showed decreased dose to partial volumes of the entire heart, arteries, valves, atria, and ventricles in comparison to both the IMRT and 3D photon plans (see Table). The IMRT plans showed decreased dose delivered to the LAD artery, pericardium, and atria in comparison to the 3D photon plans (see Table). Conclusions: For pts receiving radiation therapy for distal esophageal and GEJ cancer, proton plans are technically feasible with adequate coverage while resulting in lower dose to cardiac structures. This may result in decreased cardiac toxicity and less complications in a multimodality setting. [Table: see text]
Skeletal muscle loss after total gastrectomy, exacerbated by adjuvant chemotherapy.
Authors: Fujitani Kazumasa , Yamaoka Yusuke , Tsujinaka Toshimasa , Yamamoto Kazuyoshi , Hirao Motohiro , Sekimoto Mitsugu 
Published: February 2017

168 Background: Skeletal muscle loss is associated with physical disability, nosocomial infections, postoperative complications, and decreased survival. Preventing the loss of skeletal muscle mass after gastrectomy may lead to improved outcomes. The aims of this study were to assess changes in skeletal muscle mass after total gastrectomy (TG) and to clarify the clinical factors affecting significant loss of skeletal muscle after TG. Methods: One hundred and two patients undergoing TG for primary gastric cancer underwent abdominal computed tomography (CT) before and 1 year after TG to precisely quantify postoperative changes in skeletal muscle and adipose tissue. Univariate and multivariate logistic regression analyses identified clinical factors contributing to significant loss of skeletal muscle after TG. Results: At 1 year after TG, the mass of both skeletal muscle and adipose tissue was reduced by 6.20±6.80% and 65.8±36.1% of the preoperative values, respectively, and 26 patients (25.5%) showed a significant loss of skeletal muscle of more than 10%. Adjuvant chemotherapy with S-1 for ≥6 months (hazard ratio 26.75, 95% confidence interval 3.511 to 203.9) was identified as the single independent risk factor for a significant loss of skeletal muscle. Conclusions: Skeletal muscle loss was exacerbated by extended adjuvant chemotherapy after TG. Further research should identify appropriate nutritional interventions for maintaining skeletal muscle mass and leading to improved outcomes.
Survival difference in octogenarians with resectable gastric GIST: Surgery versus nonsurgical management.
Authors: Chauhan Dhaval , Burnett Atuhani S. , Rajab Taufiek Konrad , Ernst Philip , McCain Donald A. , Mokashi Suyog A. 
Published: February 2017

171 Background: Surgical resection of gastric GIST (Gastro-Intestinal Stromal Tumor) in octogenarians is a morbid procedure. There is limited data in literature about the survival of octogenarians after resection of gastric GIST. In this study we focused on the outcome in terms of survival in octogenarians with resectable gastric GIST. Methods: 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. Results: The mean survival in the patient group undergoing surgery was 31.30 months and the mean survival in the patients opting for non-surgical management was 33.89 months. The survival benefit in avoiding surgery in this population was 2.59 months with a p-value of <0.0001 and a confidence interval of 1.35 to 3.83 months. Conclusions: The mean survival in the patient group undergoing surgery was 31.30 months and the mean survival in the patients opting for non-surgical management was 33.89 months. The survival benefit in avoiding surgery in this population was 2.59 months with a p-value of <0.0001 and a confidence interval of 1.35 to 3.83 months.
Neutrophil-to-lymphocyte ratio for predicting palliative chemotherapy outcomes in advanced pancreatic cancer patients.
Authors: Xue Peng , Kanai Masashi 
Published: February 2017

186 Background: Several previous studies reported neutrophil-to-lymphocyte ratio (NLR) could be a promising prognostic factor for patients with cancer. We aimed to determine the prognostic value of NLR in patients with advanced pancreatic cancer (APC) following palliative chemotherapy. Methods: We retrospectively reviewed 253 consecutive APC patients receiving palliative chemotherapy between January 2006 and December 2012. We classified the patients according to the pretreatment NLR values (≤5 or >5) into two groups and investigated the difference in treatment outcomes, including time to treatment failure (TTF) and overall survival (OS); and also analyzed the impact of NLR kinetics after one cycle of chemotherapy on the treatment outcomes. Results: A total of 213 patients had pretreatment NLR values of ≤5 (group A), while 40 patients had an NLR of >5 (group B). TTF and OS were significantly shorter in group B than in group A (3.1 vs. 6.0 months and 8.8 vs. 12.8 months, respectively). After adjustment for putative prognostic factors, including distant metastasis, status of recurrent/unresectable disease, pretreatment carbohydrate antigen 19-9 levels, carcinoembryonic antigen levels, and C-reactive protein levels, using the Cox regression model, elevated pretreatment NLR remained an independent poor prognostic factor for OS (hazard ratio, 1.95; 95% confidence interval, 1.29–2.95; P <0.01). In addition, patients in group B whose NLR dropped to ≤5 before the second cycle of chemotherapy showed longer TTF and OS compared with those whose NLR remained at >5. Conclusions: Our results support the idea that NLR can be a promising prognostic and predictive marker for APC patients receiving palliative chemotherapy.
Postoperative CA19-9 and Glasgow prognostic score to predict early recurrence and poor prognosis in pancreatic cancer patients undergoing adjuvant chemotherapy after surgery.
Authors: Katayama Yusuke , Morinaga Soichiro , Murata Ippei , Asari Masahiro , Numata Koji , Sawazaki Sho , Godai Teni , Higuchi Akio , Shiozawa Manabu , Rino Yasushi , Masuda Munetaka , Akaike Makoto 
Published: February 2017

198 Background: Despite proven benefit of adjuvant chemotherapy in pancreatic cancer patients, earlyrecurrenceoccursinaconsiderablerate. Therefore, outcomeprediction in these patients remains a challenge. The aim of this study was to determine whether Glasgow Prognostic Score (GPS) and CA19-9 could predict early recurrence in patients undergoing adjuvant chemotherapy after surgery. Methods: 67 pancreatic ductal adenocarcinoma (PDAC) patients underwent curative resection and received adjuvant chemotherapy with gemcitabine after surgery at Kanagawa Cancer Center between 2007 and 2012.The GPS, CA19-9(measured prior to adjuvant therapy) and other clinicopathological factors were retrospectively reviewed. The GPS was calculated from CRP and albumin as follows: patients with both an elevated CRP level (>0.5mg/dl) and hypoalbuminemia (<3.5g/dl) were allocated a score of 2, patients with only one of these biochemical abnormalities were allocated a score of 1, and patients with neither of these abnormalities were allocated a score of 0. Patients were divided to high and low CA19-9 group with cutoff points of 180 U/ml, on the basis of several RCT trials. Univariate and multivariate analyses were performed to identify clinicopathological variables associated with early recurrence (within 6 months after surgery), disease free survival (DFS), and overall survival (OS). Results: Postoperative elevated GPS and CA19-9 were independent risk factors for early recurrence. Positive/negative predictive value (PPV/NPV) were 0.86/0.54 in GPS and 0.84/0.69 in CA19-9 respectively, and in combination use, the PPV/NPV increased to 0.88/0.82. Additionally, the elevated GPS and CA19-9 were independently associated with worse DFS (GPS GHR1.95, 95%CI 1.03-3.69, p=0.042)(CA19-9 GHR5.03, 95%CI 2.05-12.3, p<0.001)and OS (GPS; HR5.29, 95%CI 2.14-13.1, p<0.01, CA19-9 GHR4.79, 95%CI 1.99-11.5, p<0.001). Conclusions: Our results show the potential utility of GPS and CA19-9 as a predictor of early recurrence and prognostic factor in pancreatic cancer.
Long-term outcomes of endoscopic resection for early gastric cancer: Appropriate surveillance strategy based on the incidence and patterns of local, metachronous, and extragastric recurrence.
Authors: Kim Eun Ran , Kim Jae J. , Min Byung-Hoon , Min Yang Won , Lee Jun Haeng , Kim Jae Gyu , Rhee Poong-Lyul 
Published: February 2017

2 Background: Endoscopic resection (ER) has been accepted as standard treatment of EGC. However, data about long-term outcomes especially related with recurrence have not yet been enough and appropriate surveillance strategy is not established. We evaluated the patterns and risk factors of recurrence, through evaluating the long-term outcomes of ER for treatment of EGCs comparing conventional and expanded indication criteria. Methods: We performed a retrospective review of prospectively and consecutively collected database of 1,855 EGCs in 1,803 patients [1,409 lesions in the conventional indication (CI) and 446 lesions in expanded indication (EI)] underwent ER for EGCs from April 2000 to June 2011. Results: Local recurrence was occurred from five tumors (0.35%) in the CI group and one tumor (0.22%) in the EI group. The median local recurrence interval was 13.5 months (range 2-34 months). 48 (3.1%) patients developed metachronous EGCs during follow up period. The median duration until metachronous recurrence was occurred, was 27.3 months (range, 12.25-115.29 months). There was not significantly different between metachronous group and non-metachronouos group except sex and histologic differentiation. Extragastric recurrence of tumor occurred from two patients in each of the CI and EI group. The extragastric recurrence interval was 62 months in the CI group and 48 months in the EI group. At that time, endoscopic examination showed no evidence of local recurrence around ESD scar area. Conclusions: The expanded indication of ER for EGCs showed acceptable long-term outcomes. More than 5 years of close follow up is needed and CT should be performed together with endoscopy for surveillance of recurrence after ER for EGC in the conventional indication group as well as the expanded indication group.
Genome-wide DNA methylation profiling of gastrointestinal neuroendocrine tumors to identify hypermethylation of mTOR, Wnt, and Notch pathways in GI NET pathogenesis.
Authors: Karpathakis Anna , Dibra Harpreet , Morris Tiffany , Oukrife Dahmane , Pipinikas Christodoulos P , Pearce Kerra , Francis Joshua , Pericleous Marinos , Mandair Dalvinder , Feber Andrew , Toumpanakis Christos , Luong Tu Vinh , Meyerson Matthew , Caplin Martyn E , Beck Stephan , Thirlwell Christina 
Published: February 2017

212 Background: Aberrant DNA methylation is known to play an important role in the pathogenesis of many human cancers, however little is known about its role in gastrointestinal neuroendocrine tumours (GI NET) development. We report the first unbiased genome-wide DNA methylation analysis of a large cohort of GI NETs, aiming to identify key methylation variable positions (MVPs) specific to GI NETs which may contribute to tumorigenesis and metastatic progression. Methods: Illumina Infinium Human Methylation 450 Array analysis was performed on 56 cases of GI NET DNA extracted from macrodissected tumour (n=67) and normal (n=29) specimens. Tumours were gastrointestinal primaries (n=39) or metastases (liver, mesenteric, omental or lymph node, n=28) of low (n=35), intermediate (n=17) or high grade (n=3)(unknown grade n=12). Data analysis was performed using the "ChAMP" custom pipeline and pathway analyses were performed using "GREAT," "WebGestalt," and "GSEA" web tools. A Bonferroni adjusted significance threshold value of p<0.05 was used throughout. Results: In order to identify and validate a GI NET specific methylation signature our cohort was divided into a discovery set (31 cases) and validation set (25 cases). Comparison of primary GI NET tumours with normal small bowel identified a total of 77,916 MVPs, including 1,666 sites hypermethylated by over 30% in tumour compared to normal tissue. Application of the profile to the validation set correctly identified 85% of samples. Tumours demonstrated global hypomethylation relative to normal tissue. Gene ontology analysis identified methylation of multiple cancer related pathways (including the Wnt, mTOR and Notch pathways) as a feature of hepatic metastases of GI NET primaries. Increasing RASSF1 promoter hypermethylation was associated with higher tumour grade. Conclusions: This study is the first comprehensive analysis of the epigenetic profile of GI NETs and identifies potential novel biomarkers and therapeutic targets. We are currently performing integrated analysis of epigenomic, genomic and transcriptomic data to further define the pathways involved in GI NET pathogenesis.
Profiling of a global cohort of 1,250 neuroendocrine tumors to identify multiple potential drug targets.
Authors: Astsaturov Igor A. , Cohen Steven J. , Engstrom Paul F. , Gatalica Zoran , Bender Ryan P. , Basu Gargi Dan , Millis Sherri Z. 
Published: February 2017

214 Background: Identification of new drug targets may extend treatment options for NET, regardless of histologic classification or primary organ site. Methods: 1,250 cases of infradiaphragmatic neuroendocrine tumors (all grades and sites) were identified among >50,000 cases profiled in a CLIA certified laboratory. Biomarker profiling utilized multiple platforms: gene sequencing (next generation sequencing, Sanger or pyrosequencing), gene copy number by in-situ hybridization, and protein expression by immunohistochemistry. The results are shown relative to the total number of tests performed. Results: Overall, drug therapy-relevant alterations were identified in 1,130 of 1,250 (90%) of cases. Low or absent (0 or 1+ by IHC) MGMT, a biomarker of sensitivity to alkylating agents, was found in 130/219 pancreatic cases (59%), and in 450/991 (45%) of non-pancreatic NET. Low or absent (0 or 1+ by IHC) expression of RRM1, a biomarker of gemcitabine sensitivity, was found in 813/1,100 of NET (74%) and low or absent thymidine synthase, TS, a biomarker of fluoropyrimidine sensitivity, was shown for 793/1,096 (72%) of NET by IHC. Sequencing of tumors showed oncogenic mutations in BRAF (4/369 (V600E in 3 and G596R in 1), CTNNB1 (2/150), KIT (3/281), EGFR (1/178), FGFR2 (1/150), GNAS (1/150), HRAS (2/150), PIK3CA (6/343), RB (2/150) VHL (1/150), KRAS (10/125), NRAS (2/274), and APC (2/150) and amplifications of EGFR (46/686) and MET (4/236). Ki67 status and correlation between the site of origin and biomarkers will be presented. Therapies guided by mechanism-based biomarkers produced durable responses in documented cases: partial response (PR) >1 year to imatinib in a patient with KIT-mutant metastatic NET, and in cases of MGMTlow/TSlowtreated with streptozocine or temizolomide plus fluoropyrimidine chemotherapy, thus supporting the clinical relevance of target profiling in NET. Conclusions: Comprehensive multiplatform profiling of a large series (n=1,250) of NET, despite low frequency of individual biomarkers, identified clinically relevant targets in the majority of patients. Our results provide the basis for future clinical trials to assess the efficacy of biomarker-based therapy for NET.
Clinical deployment of automatic treatment planning for pancreas SBRT patients.
Authors: Moore Joseph A. , Yang Wuyang , Evans Kim , Dholakia Avani Satish , Koong Albert , Chang Daniel Tandel , Goodman Karyn A. , Herman Joseph M. , McNutt Todd R. 
Published: February 2017

219 Background: To clinically utilize an SQL relational database of prior treated patients to generate objectives for future treatment plans. A database approach allows for more rapid planning by starting with a better initial solution and improves safety by providing good known achievable dose values for the initial optimization. The use of a database allows for trending of dose, structure and toxicity data. Methods: A database of fifty-three patients from three institutions is populated with dose and structure data via an automatic script within the treatment planning system. For each new patient, overlap volume histograms (OVHs) are generated to describe the relationship between targets and critical structures. To aid in database consistency, a renaming interface is used which maps known alternative structure names to common names in the database. To ensure all required structures are present, the user is prompted with the names of missing structures. This interface allows selection of machine, energy and commonly used beam sets. The database is queried for all prior patients with the same or closer relationship between the target and each critical structure. The dose objectives reported are the lowest achievable dose from all patients as difficult or harder to plan as determined by OVH. Queried dose objectives are automatically loaded into the treatment planning system and optimized. A protocol quality tool is developed to quickly assess how well plans adhere to specified protocols. Results: Twenty-seven SBRT patients have been planned and clinically approved using the automatic planning tool and future patients continue to be added to the database. OVH computation required approximately 2 minutes, while typical plan optimization required 2.5 minutes. If auto-planned patients require even one fewer optimization to achieve an acceptable plan, total planning time is reduced. Safety is improved by reducing the number of protocol violations from 35% to 6% for one objective. Conclusions: Automatic treatment planning allows for rapid planning while reducing normal tissue dose to known achievable values. The continued addition of patients to the database allows for improvement of the automatically selected planning objectives.
Analysis of prognostic factors in locally advanced and metastatic pancreatic cancer treated with gemcitabine or gemcitabine and S-1 chemotherapy using individual patient data from three randomized studies.
Authors: Nakai Yousuke , Okusaka Takuji , Ikari Takaaki , Isayama Hiroyuki , Furuse Junji , Ishii Hiroshi , Imai Shogo , Okamura Shota , Hamada Chikuma 
Published: February 2017

223 Background: Both gemcitabine (GEM) and S-1, an oral fluoropyrimidine, are shown efficacy for advanced and resected pancreatic cancer (PC). However PC has one of the poorest outcomes in various cancers. In this pooled analysis, the prognostic factors in locally advanced and metastatic PC were evaluated using individual patient data from three randomized studies (Phase III: GEST, randomized phase II: JACCRO PC-01 and GEMSAP). Methods: Patients (pts) were treated with GEM alone or GEM and S-1 (GS) chemotherapy for advanced PC. Evaluated prognostic factors were standard laboratory data, tumor marker (CA19-9, CEA), clinical and pathological indices and treatment related outcomes e.g. efficacy and safety. To identify the optimal cutoff value to divide continuous data into binomial data, maximized log likelihood value for the model were evaluated and the validity of the model was evaluated by the martingale residuals. The Cox proportional hazards model was performed for overall survival. Results: 770 pts were included in this analysis (389 pts were treated by GEM and 381 pts were GS) and 738 events for survival were observed (95.8%). In continuous data, baseline WBC, AST, CA19-9 and CRP were detected as independent prognostic factors and the cutoff values were identified. The results of multivariate analysis and cutoff value were shown in the table. Conclusions: In our analysis, treatment, extent of disease, target lesion, WBC, AST, CA19-9 and CRP were detected as independent prognostic factors and cutoff values were estimated in continuous data. The further examination is necessary, but these data may help future studies. [Table: see text]