bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinicopathologic features of patients with KRAS wild-type pancreatic adenocarcinoma.
Authors: Salem Mohamed E. , Al-hajeili Marwan R. , Dyson Gregory , Stanski Natalja , Jain Tania , Mahaseth Hemchandra , Choi Minsig , Shields Anthony Frank , Philip Philip Agop 
Published: February 2017

192 Background: Pancreatic adenocarcinoma (PC) has the highest frequency of KRAS gene mutations among human cancers. A better understanding of disease biology may help improve targeted therapies for this disease. There is limited data about clinical, pathological features and treatment outcomes in patients (Pts) with wild type KRAS tumors (KRASwt). Methods: Retrospective review of 71 pts with histologically confirmed PC between 2009 and 2012 was undertaken. The KRAS codon 12 and 13 and BRAF codon 600 mutations were assessed in diagnostic tumor tissues (TrimGen Mutector II Shifted Termination Assay). Differences were evaluated with t-test and Fisher exact test. Results: KRAS mutations were identified in 50 tumors (70%), while 21 tumors (30%) had KRASwt genotype. Almost all (96%) mutations occurred at codon 12, there were no mutations in codon 13, and none of the KRASwt tumors harbored BRAF mutations. Pts with KRASwt tumors were mostly white (76%), females (57%), and did not have diabetes mellitus (80%). At diagnosis, pts with KRASwt tumors had a tendency to present at younger age (median age of 60 vs. 66 y; P = 0.1) and with lower CA19-9 values (median CA19-9: 392 vs. 3371 U/mL; P=0.042). Head of the pancreas was the primary site of disease in the majority of pts with KRAS wt tumors (58%), while body or tail was the primary site of disease in the majority of pts with KRAS mutant tumors (53%). There was no difference in the histologic differentiation. Although the majority of pts with KRAS wt (55%) and mutant tumors (57%) presented with distant metastases or locally advanced disease (40% and 39%; respectively), liver involvement was seen in only 55% of pts with KRAS wt tumors vs 92% in the pts with mutant tumors (p=0.016). In univariable analysis, age was an independent predictor of overall survival (HR 1.14, p=0.037) in pts with KRAS wt tumors, while level of bilirubin at presentation was a predictor of overall survival (HR 1.86 (0.77, 4.53); P <0.0001) in pts with KRAS wttumors who had distant metastasis. Conclusions: The frequency of pts with PC who had KRASwt tumors was higher than previously described. Pts with KRASwt tumors may have a disease that is biologically different than those with mutated KRAS. Further prospective characterization is warranted.
Comparison of a new prognostic system and five current staging systems in predicting the survival rate of patients with advanced hepatocellular carcinoma.
Authors: Chen Zhan-Hong , Li Xing , Dong Min , Ma Xiao-Kun , Wu Xiang-Yuan 
Published: February 2017

193 Background: Prognosis of patients with advanced HCC is very poor, median overall survival varies from 3 to 6 months. Life expectancy more than 3 months is one inclusion criteria for molecular targeted drugs in clinical tirals. We have established a new prognostic system called SYSU system (variables and risk classification criteria are listed below, reported in MASCC 2013) and now we want to compare this new prognostic system and 5 current staging systems in predicting the survival rate of patients with advanced HCC. Methods: From September 2008 to June 2010, a total of 253 patients with advanced HCC who were not amendable to locoregional therapy were analyzed. The median follow-up is 38.5 months and the median survival is 7 months. Data were collected to classify patients according to our new system(SYSU system), Barcelona Clinic Liver Cancer staging for hepatocellular carcinoma (BCLC), Advanced Liver Cancer Prognostic System (ALCPS), Chinese University Prognostic Index staging system for HCC (CUPI), OKUDA score system and French scoring system(GETCH) at diagnosis. OS and 3-month OS were the end points used in the analysis. Results: When predicting 3-month survival, ROC analysis show AUC of SYSU system, ALCPS, CUPI,OKUDA, GETCH and BCLC is 0.822,0.821,0.777,0.756,0.688 and 0.621. AUC of SYSU system and ALCPS is similar and they are significantly better than the other four staging system (p<0.05). When predicting overall survival, likelihood ratio test show χ2 of SYSU system, ALCPS, CUPI,OKUDA, GETCH and BCLC is 97.7,85, 50.5, 46.4,22.6 and 8.4 and AIC of SYSU system, ALCPS, CUPI,OKUDA, GETCH and BCLC is 1939,1952,1986,1990,2014 and 2028. Our SYSU system has best performance in terms of discriminatory ability, homogeneity and monotonicity. Conclusions: Our SYSU system is the best score system in prediction of OS and 3-month OS among the 6 systems analyzed for Chinese advanced HCC patients. [Table: see text]
MicroRNA-27b as a prognostic marker in pancreatic neuroendocrine tumor.
Authors: Kang Bong Kyun , Hwang In kyeom , Lee Yoon Suk , Kim Jaihwan , Hwang Jin-Hyeok 
Published: February 2017

251 Background: Pancreatic neuroendocrine tumors (PNETs) are heterogeneous group of tumors with a wide spectrum of behavioral characteristics. PNET generally behaves in an indolent fashion. However, when metastasis occurs, it is difficult to be treated. Little is known about prognostic biomarker in PNET. The aim of this study was to elucidate prognostic biomarker in PNET using nanostring microRNA (miRNA) array technology. Methods: We had already selected several candidate miRNAs (miR-27b, miR-122, miR-142-5p, miR-196a, miR-223, miR-590-5p, miR-630 and miR-944), which indicated 3 folds expression differences between primary tumor and metastatic tumor on the basis of nanostring-based microarray in two PNET patients. Further 39 PNET patients were enrolled for clinical validation (recurrence group includes patients who had metastasis subsequently; no-recurrence group includes the others) of 8 miRNAs. Surrounding pancreas and tumor miRNA were isolated separately from formalin-fixed paraffin-embedded tissues. Expression of candidate miRNAs was measured by quantitative real-time PCR using U6 as an internal control. Mann-Whitney U test and Spearman rank correlation analysis were used for statistical evaluation at p < 0.05 level. Results: miR-27b expression was elevated in recurrence group compared to no-recurrence group (p = 0.019). And also, miR-27b expression was statistically significant correlated positively with CA 19-9 level (p = 0.015). The Hierarchical cluster analysis of eight miRNAs showed miR-27b linked functionally to miR-142-5p and miR-196a. Furthermore, miR-196 expression was associated with Ki-67 index with a statistical significance (p = 0.035). Conclusions: The miR-27b would be a prognostic marker of recurrence in resected PNET and link to miR-142-5p and miR-196a, which correlated with Ki-67 index. Further experimental investigation would be required to demonstrate the role of these miRNAs in PNET.
Capecitabine plus temozolomide (CAP-TEM) in patients with advanced neuroendocrine neoplasms (NEN): An Italian multicenter retrospective analysis.
Authors: Spada Francesca , Fumagalli Caterina , Antonuzzo Lorenzo , Messerini Luca , Radice Davide , Di Rocco Roberta , Galdy Salvatore , Barucca Viola , PISA Eleonora , Barberis Massimo , Di Costanzo Francesco , Fazio Nicola 
Published: February 2017

281 Background: A combination of capecitabine (CAP) and temozolomide (TEM) has been successfully used as first-line treatment in low-grade pancreatic neuroendocrine neoplasms (PNEN). We reviewed activity and toxicity of the same regimen in patients with advanced NEN with different primary and grading. Methods: Clinical data of patients who had received oral CAP 1500 mg/m2/day over 14 days bid plus oral TEM 150-200 mg/m2/day on days 10-14 of each 28-day cycle, were retrospectively reviewed. The methylenguanilmetiltransferase (MGMT) methylation-status (MGMT-gene >5% = responders) and TS-polymorphisms (2R/2R, 2R/3R = responders, 3R/3R = non-responders) in tumor-tissue/peripheral-blood were evaluated by pyrosequencing. Results: Since March 2012, 29 patients were selected. The primary tumor was: pancreas in 14 patients (48%), gastrointestinal (GI) in 5 (17%), unknown in 2 (7%), lung in 8 (28%). According to 2010 WHO classification, Ki67 was <2% (G1) in 3%, 3-20% (G2) in 45% patients, >20% (G3) in 21% with two "low G3" (Ki67 21-30%), and unknown in 3%. Among lung: 7% typical and 21% atypical (Travis’ classification). 72% patients (21/29) were progressive on different therapies: peptide-receptor-radiotherapy (38%), chemotherapy (38%), everolimus (14%). Partial-response (PR) occurred in 14% (4/29) of patients (95% CI: 4-32), stable-disease (SD) in 59% (17/29) (95% CI: 39-77) mainly PNET. The two "low G3" responded. Disease control rate (PR+SD): 72% (95% CI: 53-87). Median TTP: 9 months (95% CI: 5.6-N.E.). Thrombocytopenia was the most frequent grade 3 toxicity, always temporary. All 4 PR patients had genotype 2R/3R-2R/2R investigated for the 28 base-pair (bp) variable number of tandem repeats (VNTR) in the 5'UTR of the TS-gene, and MGMT-gene inactivation by epigenetic silencing. Conclusions: This analysis suggests that CAP-TEM chemotherapy could be active and well tolerated in pretreated patients with advanced NEN of different origins and grading. This warrants a prospective investigation in a more homogeneous population (G2 and “low-G3” GEP NEN or lung carcinoids), in order to validate the predictive value of MGMT methylation-status and TS-polymorphisms.
Independent predictors of overall survival and recurrence in biphenotypic hepatocellular cancer.
Authors: Amin Manik , Chen Ling , Vachhajarani Neeta , Brunt Elizabeth , Doyle Maria Majella , Tan Benjamin R. 
Published: February 2017

291 Background: Biphenotypic hepatocellular cancer (BPHCC), which is a combined hepatocellular cancer (HCC) and cholangiocarcinoma (CC), is a rare form of primary liver cancer, whose long term prognosis is extremely poor as compared to either HCC or CC alone. Little is known about the recurrence rates and predictors of recurrence in BPHCC. Our objective was to 1) identify both overall survival and recurrence rates after primary resection or systemic and liver directed therapies and 2) to evaluate the independent predictors of survival and recurrence. Methods: Our Hepatobiliary Registry identified 65 patients with BPHCC from February 1999 till April 2013 at Siteman Cancer Center, Washington University, St. Louis MO. We conducted univariate Kaplan-Meier survival analysis and multivariable Cox proportional hazards regression to identify factors independently associated with overall survival. We also conducted multivariable logistic regression analysis to identify factors independently associated with recurrence. Results: Of the 65 patients in our study, 18 (28 %) with prior resection, 2 (3 %) after OLT, 45 (69 %) ineligible for surgery, 40 (62 %) were treated with chemotherapy, 17 (26%) with liver directed therapies. Overall survival was 39.2 % at 1 year. Independent factors associated with survival were: smoking (HR 2.84, 95% CI 1.29-6.23, p = 0.0089), tumor thrombus (HR 5.45, 95% CI 2.05-14.50, p = 0.0007), any liver directed treatment (HR 3.01, 95% CI 1.21-7.48, p = 0.0175), multiple satellite lesions (HR 3.17, 95% CI 1.71-8.58, p = 0.025) and prior tumor resection (HR 2.65, 95% CI 1.16-6.03, p = 0.020). Risk of recurrence was independently predicted by male sex (OR 3.98, 95% CI 1.30-12.15, p = 0.015) and multiple satellite lesions (OR 15.42, 95% CI 2.68-88.62, p = 0.0076). Conclusions: Patients with biphenotypic cancers have a devastating overall survival. Tumor thrombus and satellite lesions were the strongest predictors of poor survival; satellite lesions also strongly predicted recurrence. In this rare form of cancer, this is the largest study to identify factors associated with overall survival and recurrence. These factors should help guide clinical care of patients with BPHCC.
Outcomes of neoadjuvant chemotherapy with FOLFOX/FOLFIRINOX and chemoradiotherapy in borderline resectable pancreatic cancer: Single-institution experience.
Authors: Son Chang O , Pai Sachin Gopalkrishn , Satti Suma , Dornelles Adriana , Bolton John S. , Conway W. Charles , Fuloria Jyotsna 
Published: February 2017

327 Background: The clinical benefit of neoadjuvant treatment in locally advanced pancreatic adenocarcinoma (borderline/unresectable) has not been well established. However, the challenge of managing locally advanced pancreatic adenocarcinoma has led to the incorporation of neoadjuvant treatment into clinical practice. FOLFIRINOX has been increasingly used as neoadjuvant chemotherapy, but may not be well tolerated especially in older patients due to adverse effect profile. In our institution, we have used FOLFOX as an alternative for older patients and patients with poor performance status based on our retrospective observation of FOLFOX in metastatic/advanced pancreatic adenocarcinoma. Methods: We conducted a retrospective analysis of locally advanced pancreatic cancer patients from January 1, 2011 to February 28, 2013 treated with neoadjuvant chemotherapy (FOLFOX/FOLFIRINOX) with the intention of future resection. In addition patients also received neoadjuvant chemo-radiotherapy. Imaging studies, operative notes and Pathology reports were reviewed. Results: 27 patients were analyzed, 10 received FOLFIRINOX and 17 received FOLFOX regimen. Mean age of patients were 57.28 ± 11.68 SD and 68.66± 11.21 SD in the two groups respectively. Patients received 4.2 ± 0.92 SD and 3.59 ±1.06 SD cycles of chemotherapy in FOLFIRINOX and FOLFOX groups respectively. Mean duration of follow up was similar in both groups. 5 patients on FOLFOX and 1 patient on FOLFIRINOX had disease progression thereby precluding surgery. The Rate of R0 resections was 64.7 % and 60% (P 0.27) in the two groups respectively. Overall survival was not statistically significant between the two groups. (Kaplan Meier survival graphs will accompany final presentation). Conclusions: In our study, FOLFIRINOX was administered in younger patients. However the R0 resection rates were similar in both the groups. FOLFOX may be acceptable neoadjuvant chemotherapy of choice in patients with borderline functional status. Randomized trials are needed to define this better.
Clinical outcomes and prognostic factors of adjuvant treatment in resectable biliary tract cancer.
Authors: Hong Ji Hyung 
Published: February 2017

370 Background: The survival outcomes and prognostic factors of adjuvant treatment after resection for biliary tract cancer (BTC) has not been clearly established. We analyzed the clinical outcomes and prognostic factors of patients with resected BTCs between adjuvant treatment and non-adjuvant treatment group. Methods: A total 189 patients of BTC were treated with surgery followed by adjuvant chemotherapy or concurrent chemoradiotherapy between Jan. 2008 and Jan. 2013. We retrospectively analyzed the clinical characteristics and recurrence and survival outcomes with following variables: histologic grade, resected margin status, lymphatic/vascular/perineural invasion, T and N stage, treatment modality. Results: Median age at diagnosis was 64 years (range: 32-85). Of the total 189 patients, R0 resection was done in 152 patients (80.4%). Among the 73 patients with adjuvant treatment, forty-one patients (21.6%) were treated with adjuvant 5-FU based systemic chemotherapy and 31 patients with chemoradiotherapy (16.5%). Recurrence rate were 39.7%. Median disease free survival (DFS) time was 58.1 months (95% CI, 38.9-77.3) and median overall survival (OS) time was 87.8 months (95% CI, 79.5-96.0). Adjuvant treatment showed the tendency to improve DFS with 39.0 months (95% CI, 8.9-69.1) in the adjuvant group compared with 57.0 months (95% CI, 39.5-74.5) in the non-adjuvant group, however, without statistical significance (p=0.113). Between the recurrent and non-recurrent group, perineural invasion, lymphatic invasion and poorly differentiated histology showed statistical significant difference, respectively (65.3% vs 35% ; p <.001, 28% vs 14.9% ; p = .028, and 8.1% vs 7.1% ; p = .011). Presence of perineural invasion showed association with RFS (HR= 1.543; 95% CI 1.133-2.102, p=.006). There was no other significant correlation in R1 resection, poor histologic grade, lymphatic and vascular invasion, chemotherapy regimen, and treatment modality with survival outcome. Conclusions: Perineural invasion could be a potential prognostic factor for recurrence. Further prospective study should be warranted to confirm this data.
Preoperative (preop) chemosensitivity testing as predictor of treatment benefit in adjuvant stage III colon cancer (CC): Interim analysis of the PEPITA study.
Authors: Hendlisz Alain , Deleporte Amélie , Van Laethem Jean-Luc , Vergauwe Philippe , Van Den Eynde Marc , Deboever Guido , Janssens Jos , Demolin Gauthier , Holbrechts Stephane , Clausse Marylene , Vermeij Joanna , D'Hondt Lionel A. , Laurent Stéphanie , Efira André , Gomez Galdon Maria , Buggenhout Alexis , Paesmans Marianne , Garcia Camilo , Piccart-Gebhart Martine J. , Flamen Patrick ,   Belgian Group for Digestive Oncology (BGDO)
Published: February 2017

385 Background: Adjuvant chemotherapy (CT) improves stage III CC outcome but is not effective for all patients (pts). PePiTA’s main hypothesis is that absence of metabolic response (MR) of the primary tumor after 1 preop CT course predicts absence of benefit from adjuvant CT (at 3-year DFS). This strategy's aim is to spare pts from useless toxicities, improve healthcare resource allocation, and guide translational research. This interim analysis was performed for safety and feasibility of MR assessment (MRA). Methods: Pts ≥ 18 years, with PS ≤ 1, diagnosed with CC considered for curative resection are eligible, after signed consent. Baseline PET is repeated after 1 CT cycle, followed by surgery. PET quality insurance and MRA are performed centrally and the result is blinded for investigators. Results: From 2010 to 2013, 114 pts—M/F (55%/45%), median age 66 (26-81), ECOG 0/1(92%/8%)—were included in 15 Belgian centers. 11 pts were excluded from analysis: 2 hyperglycemia at baseline PET; 2 withdrew consent; 6 PET-revealed stage IV CC; and 1 second cancer. Preop CT was associated with 5% grade (gr) 3-4 neutropenia, 1% gr 3 diarrhea, 1% gr 3 hypokaliemia, 1% peritonitis and 1% gr 3 thromboembolic events. Colectomies were performed in all pts after a median of 20 days (interquartile interval 18-21): 32 right (31%), 69 left (67%), and 2 procedures not detailed. Pathology showed stages 0 (1%), I (13%), II (34%), III (47%), IV (7%), without lymph node downstaging. Postoperative morbidity is 9% (95%CI 5-16%) and includes fistulas (4%), transient ischemic attack (1%), ileus (2%), and evisceration (1%), but no death. Technical or methodological reasons prevented MRA in 19/103 pts. Median SUVmax was 14.4 (4.9-47.8) at baseline, and 10.9 (0-39.3) on day 14. 2 pts presented with complete MR. For the others, median delta SUVmax was -22% (-60 to +31%). MR was observed in 60% of pts, and was absent in 40%, with equal distribution for stages II and III (p = 1.00). Conclusions: 1 course of CT is feasible before curative surgery for CC, without inducing excessive toxicity, delay or surgical morbidity. MRA indicated metabolic signs of chemoresistance in 40% of the primary tumors. Clinical trial information: NCT00994864.
Neoadjuvant therapy for rectal cancer: Mature results from NSABP protocol R-04.
Authors: Allegra Carmen Joseph , Yothers Greg , O'Connell Michael J , Roh Mark S. , Beart Robert W. , Petrelli Nicholas J. , Lopa Samia H. , Sharif Saima , Wolmark Norman 
Published: February 2017

390 Background: The primary aims were to: 1) compare capecitabine (Cape) and continuous intravenous infusion (CVI) 5-FU combined with pelvic radiation therapy (RT) given preoperatively for patients (pts) with stage II or III rectal cancer; 2) determine whether the addition of oxaliplatin (Ox) would improve pt outcomes. Preliminary results focusing on pathologic complete response, sphincter-sparing surgery, surgical downstaging, and toxicity were presented at ASCO 2011 (Roh: J Clin Oncol 29: 2011 Ab 3503). Methods: Pts with clinical stage II or III rectal cancer undergoing preoperative RT (4,500cGy in 25 fractions over 5 wks + boost of 540cGy-1080cGy in 3-6 daily fractions) were randomly assigned to one of four chemotherapy regimens in a 2x2 design: CVI 5-FU (225mg/m2 5 days/wk), with or without intravenous Ox (50mg/m2 /wk x 5) or oral Cape (825 mg/m2 BID 5 days/wk), with or without Ox (50mg/m2/wk x 5). The primary endpoint of local-regional (L-R) tumor control included L-R tumor recurrence, less than an R0 resection (complete surgical resection), and no surgery. Results: From July 2004 to August 2010, 1608 patients were randomly assigned and 99.2% were eligible. There were no significant differences in L-R tumor control, DFS, or OS between regimens for either the 5-FU-Cape (L-R p=0.98) or the Ox-none (L-R p=0.70) comparisons. The addition of Ox was associated with significantly more grade 3-4 diarrhea (p<0.0001). Analysis of the primary endpoint showed 3-yr rates of L-R tumor control ranged from 87.4%-88.2%. 3-yr rates of L-R recurrence among pts who underwent R0 resection ranged from 2-4 % for stage II pts, and from 4-11% for stage III pts. 16% of stage II and 26% of stage III pts developed distant metastases by 5 yrs. From 84% to 97% of pts received >80% of the ideal chemotherapy dose in combination with preoperative RT. Conclusions: CVI 5-FU or oral Cape combined with RT produced similar outcomes and toxicity profiles. Because use of oral Cape avoids the need for central venous catheters and ambulatory infusion pumps, it can be considered a new standard of care in this setting. The addition of Ox provided no improvement in outcomes but did add significant toxicity. Clinical trial information: NCT00058474.