bluuebunny/crossref_metadata_2025_split huggingface dataset:
The introduction of bevacizumab for the treatment of metastatic colorectal cancer (CRC) in Ontario and its effect on hepatic metastectomy.
Authors: Leeper William Robert , Li Chang Hector Hugo , Welch Stephen , Driman David K , Quan Douglas 
Published: February 2017

303 Background: Where possible, the optimal treatment for CRC liver metastases is metastectomy. Perioperative chemotherapy may be associated with improved outcomes in this setting. The government of Ontario approved public funding of bevacizumab (Bev) for metastatic CRC in July 2008. For first-line treatment, funding of Bev has been limited to use in combination with FOLFIRI, an irinotecan-containing regimen. However, the best evidence in support of perioperative chemotherapy for CRC liver metastases involves the use of oxaliplatin, not irinotecan. We sought to analyze changes in prescribing patterns, histologic findings, and clinical outcomes since the funding approval for Bev in Ontario. Methods: A single centre, retrospective review was performed of all patients receiving metastectomy for CRLM between 2004 and 2010, and archival hematoxylin-eosin slides were reviewed. Results: A total of 121 patients underwent metastectomy for CRLM during the study period. Of these, 54 were treated with perioperative chemotherapy, 37 before and 16 after funding approval of Bev. A marked increase was seen in Bev and irinotecan-containing regimens since funding approval (p < 0.01). Pathologic examination of the surgical specimens did not reveal any increase in steatosis or steatohepatitis. However, there was a trend towards more R0 resections (p = 0.3) in the post-bev era. A significant reduction in the occurrence of post-operative hepatic dysfunction was observed in the post-Bev era (p = 0.04). Overall survival (OS) and disease-free survival (DFS) were similar. Conclusions: Public funding of Bev-FOLFIRI for metastatic CRC has led to an increased and yet incomplete utilization of this regimen for CRLM. Pathologic and clinical data do not suggest harm and may show early signs of benefit. Further research is needed to determine the optimal utilization of bev in the setting of CRLM. [Table: see text]
The use of peptide receptor radionuclide therapy in patients with metastatic low-grade neuroendocrine tumors.
Authors: Naraev Boris , Sharma Nancy , Engelman Eric Steven , Bushnell David L , O'Dorisio Thomas M. , Halfdanarson Thorvardur Ragnar 
Published: February 2017

308 Background: Peptide receptor radionuclide therapy (PRRT) is frequently used for patients (pts) with metastatic low grade neuroendocrine tumors (mNETs) in Europe, but it is not readily available in the USA. We report on 108 patients seen at the University of Iowa who underwent PRRT. Methods: Cases were identified by searching our institutional NET database. Early stage (AJCC 1-3) and high-grade tumors were excluded. Groups were compared using a Wilcoxon rank-sum test and survival calculated with the Kaplan-Meier method. Results: Men were 62% and women 38%; median age at diagnosis was 52 years (25 – 78). The origin of the primary tumor was small bowel (SBNET) 43.5%, pancreas (PNET) 27.8%, lung 4.6%, unknown primary 11.1%, other sites 13%. PRRT was performed at the University of Basel, Switzerland in 72%, University of Iowa, USA in 26%, and elsewhere in 2%. 97 patients received two treatments. 90Y was used in 86% and 177Lu in 13% for the first PRRT. The survival of patients is shown in the table 1. Radiographic responses (any) at 1-6 months after PRRT were observed in 62%, 11% had a mixed response and 18% progressed. A biochemical response (>50% reduction) in chromogranin A and pancreastatin was seen in 16% and 19% respectively but data was frequently missing. Conclusions: Patients with mNETs enjoy a relatively long survival. The OS from 1st PRRT was considerably less than OS after diagnosis, suggesting that PRRT is used late in the disease course. PRRT appears to be a valuable treatment option for mNETs, especially SBNETS, and its role earlier in the disease course warrants investigation. [Table: see text]
Assessment of gastric cancer malignancy based on CD133 and thrombospondin1 (THBS1) expression and the role of histone acetylation.
Authors: Sato Hirohiko , Shimada Mitsuo , Kurita Nobuhiro , Iwata Takashi , Nishioka Masanori , Morimoto Shinya , Yoshikawa Kozo , Miyatani Tomohiko , Goto Masakazu , Kashihara Hideya , Mikami Chie 
Published: February 2017

31 Background: Epigenetic modification by HDAC (histone deacetylase) plays important roles in the development and progression of cancer. It has been reported that CD133 positive cancer stem cells were induced through the HDAC → HIF-1α (Hypoxia Inducible Factor-1α) pathway, and Thrombospondin1 (THBS1) is associated with tumor angiogenesis. The aim of this study is to evaluate relationship between the HDAC, CD133, THBS1 and prognosis in gastric cancer. Methods: 65 patients of gastric cancer were enrolled in this study. HDAC1, CD133 and THBS1 expressions were evaluated in immunohistochemical (IHC) staining of surgical specimens. Relationship between the expressions of HDAC1, CD133, THBS1 and clinicopathological factors was investigated. Results: HDAC1-positive patients were 52% and had significantly poor prognosis compared with negative patients. There were more frequent liver metastasis and lymphatic invasion in positive patients. CD133-positive patients were 23.1% and had significantly poor prognosis compared with negative patients. There were more frequent depth wall invasion, distant metastasis, peritoneal recurrence. THBS1-positive patients were 26% and had significantly better prognosis compared with negative patients. In THBS1 positive patients, there was less lymph node metastasis, positive peritoneal cytology in ascites, distant metastasis and lymphatic invasion. CD133 expression is positively correlated with HDAC1. THBS1 expression revealed negative correlation with HDAC1. The survival rate of HDAC1 (+) / CD133 (+) group was significantly poor prognosis compared to the other group (HDAC1 (+) / CD133 (-), HDAC1 (-) / CD133 (+), HDAC1 (-) / CD133 (-)). HDAC1 (-) / THBS1 (+) group revealed significantly higher survival rate compared to the other group (HDAC1 (-) / THBS1 (+), HDAC1 (+) / THBS1 (+), HDAC1 (+) / THBS1 (-)). Conclusions: It was suggested that HDAC1 promoted CD133, suppressed THBS1 in gastric cancer and their interaction were increased the degree of malignancy.
Pharmacogenetic dosing by UGT1A1 genotype as first-line therapy for advanced small-bowel adenocarcinoma: A North Central Cancer Treatment Group (NCCTG) trial.
Authors: McWilliams Robert R. , Mahoney Michelle R. , Marchello Benjamin T. , Jatoi Aminah , Krewer Keith D. , Ames Matthew M. , Schneider Daniel Jay , Seeger Grant R. , Mowat Rex B. , Alberts Steven R. , Goetz Matthew P. 
Published: February 2017

314 Background: Small bowel adenocarcinoma (SB-ACA) is rare, having little prospective data guiding management. A prior phase I study evaluated UGT1A1 genotype specific dosing of oxaliplatin, irinotecan, and capecitabine. Our prospective, multicenter clinical trial assessing tumor response in pts having metastatic SB-ACA, used a similar dosing strategy. Methods: Genotypes were determined via central lab. Previously untreated pts were dosed by UGT1A1*28 genotypes 6/6, 6/7, and 7/7 receiving 100/85/85 mg/m2 oxaliplatin d1, 150/150/75 mg/m2 irinotecan d1, and 1600/400/200 mg/m2 capecitabine (BID) d2-15 of 21 days. The study design was such that 1 confirmed response in 16 pts expanded enrollment to 33 pts, with 7 required for demonstrating efficacy. Results: 28 pts (13-6/6, 10-6/7, 5-7/7) have been enrolled [75% male, mean age 62.5 (range 41-77)]. Location of primary included: duodenum (63%), jejunum (26%), and ileum (7%), with pts having >1 metastatic site (abdominal-41%, bone-7%, liver-56%, lung-30%, nodal-52%, subcutaneous-4%, other-19%). Gr 3+ treatment related toxicity was not significantly different by genotype (50%-6/6, 44%-6/7, 20%-7/7, p=0.48) and included (pts): diarrhea(5), vomiting(5), leukopenia(5), neutropenia(7), and nausea(6). 57% (13 of 23) pts achieved responses during therapy, with a confirmed response rate of 39% (95% CI 0-58%). 18 have died, with a median follow-up of 8.3 mos (range 0-43). Conclusions: UGT1A1 genotype directed dosing with oxaliplatin, irinotecan, and capecitabine appears to result in prolonged response in this population. Larger studies are needed to determine comparability to CapeOx alone or if response/toxicity differs among genotypes. Supported by NIH Grant CA25224, Sanofi-Aventis, and Pfizer. [Table: see text]
Does age count in pancreatic resection? An Irish experience.
Authors: Connell Louise Catherine , Mulvihill Erica , O'Keeffe Margaret , O'Reilly Seamus , Geoghegan Justin , O'Suilleabhain Criostoir , Power Derek Gerard 
Published: February 2017

348 Background: Radical resection offers the only potential cure in pancreas cancer. The majority of patients (pts) are >65 years(yrs) at presentation. Age alone is often a key factor in deciding to resect. The elderly represent 11.5% of the population of Ireland, with an anticipated growth of 26% in the over-65 age group by the end of 2011. Appropriate treatment for elderly potential candidates for pancreatic resection has become increasingly important. We assessed our national experience of pancreatic resection for elderly pts. Methods: Prospectively maintained institutional databases were retrospectively reviewed for all pts undergoing pancreatic resection from 2006 to 2011, in the 2 specialised pancreas cancer centres in Ireland. Demographic, laboratory, treatment and outcome data were obtained and analysed. Results: In a single institution,of the 69 pts who had surgery for pancreas neoplasm, 19 (28%) pts were ≥ 70 yrs. Surgical procedures included pancreaticoduodenectomy (n=16, 84%) and double biliary bypass (n=3,16%). Pathologies included adenocarcinoma (AC) (n=16,84%) and NET (neuroendocrine tumour)/IPMN(intraductal papillary mucinous neoplasms) (n=3, 16%). Number of R0 resections was 15 (15/16,94%). Median baseline ECOG was 1 (range, 0-2).There was no perioperative mortality. Median length of hospital stay was 13 days (range,9-50). Thirteen pts who underwent pancreatico-duodenectomy for AC (81%) received adjuvant chemotherapy (with expected toxicities). Ten pts, after pancreatico-duodenectomy and adjuvant therapy had at least 2 yrs follow-up with median overall survival of 21.5 mths (range,12-44). A further 3 pts aged ≥ 80 yrs underwent pancreaticoduodenectomy followed by adjuvant chemotherapy in the past 12 mths, with no peri-operative complications or significant acute chemotherapy-related toxicities. The data set from the second specialised pancreas cancer centre, with similar survival outcomes, is currently being added to provide overall national results. Conclusions: Age alone should not be a contraindication to pancreatic resection in elderly pts with pancreas cancer. This group can undergo pancreatic resection, with acceptable post-operative morbidity, mortality and overall outcome as evidenced by our national experience.
The utility of PET-CT in predicting malignant potential of GIST.
Authors: Yoshikawa Kozo , Shimada Mitsuo , Kurita Nobuhiro , Sato Hirohiko , Nishioka Masanori , Iwata Takashi , Morimoto Shinya , Miyatani Tomohiko , Goto Masakazu , Kashihara Hideya , Mikami Chie 
Published: February 2017

38 Background: The risk category of gastrointestinal stromal tumors (GIST) is usually determined by tumor size and mitotic count. Because of technical complexity and tumor heterogeneity in biopsy, accurate preoperative evaluation of malignant potential of GIST is very difficult. The aim of this study is to evaluate the utility of preoperative PET-CT examination for predicting the malignant potential of GIST. Methods: Ten patients with GIST who underwent preoperative PET-CT examination were enrolled. They were divided into two groups (low/intermediate-risk or high-risk) by risk category (tumor size, mitotic index). The relationships between the standardized uptake value (SUV) and GIST parameters including the size, mitotic index and Ki67 index were examined. Results: There was a significant correlation between the mitotic index and the SUV (p=0.029) but tumor size is not correlated with SUV. The SUV was significantly higher in the high-risk group (11.0 ± 3.04) than in the low/intermediate-risk group (2.1 ± 1.5). The Ki67 labeling index was also significantly higher in the high-risk group (8.63 ± 6.2) than in the low/intermediate-risk group (1.75 ± 0.52). There was a significant correlation between the Ki67 labeling index and the SUV (p=0.028). A mitotic index of 5/50 HPF was equivalent to an SUV of 4.3, and a Ki67 labeling index of 5 was equivalent to SUV of 6.3. SUV of 5 can predict the malignant potential between the high and low/intermediate risk. Conclusions: PET-CT can predict malignant potential. Cases with a high SUV, using a criterion of 5, might have malignant potential.
Clinical and technical validation of a genomic classifier (ColoPrint) for predicting outcome of patients with stage II colon cancer.
Authors: Tabernero Josep , Moreno Victor , Rosenberg Robert , Nitsche Ulrich , Bachleitner-Hofmann Thomas , Lanza Giovanni , van den Akker Jeroen , Roepman Paul , Simon Iris , Salazar Ramon 
Published: February 2017

384 Background: Between 25 and 35% of stage II colon cancer patients will experience a relapse of their disease and may benefit from adjuvant chemotherapy. ColoPrint is a gene expression classifier that can predict disease relapse in patients with early-stage colorectal cancer (Salazar et al. JCO 2011). Methods: ColoPrint was developed using gene expression data from whole genome microarrays and was validated in in-silico datasets and independent patient cohorts from 5 European hospitals. Fresh frozen tissues, clinical parameters, MSI-status and follow-up data for patients were available. Samples were hybridized to Agilent microarrays and the ColoPrint index was determined. Uni-and multivariate analysis was performed on the pooled stage II patient set (n=320) who had a median follow-up of 70 months. Reproducibility and precision studies were performed using clinical and control samples specific for each outcome level (high risk, low risk). Experiments were performed on 20 days with 2 runs per day by multiple technicians reflecting daily diagnostic conditions. Results: Performance of the prognostic classifier was confirmed in reproducibility and stability assays and stringent quality controls were established. In the clinical validation, ColoPrint classified two-third of patients (209/320) as low risk. The 3-year relapse-free survival was 94% for low risk patients and 79% for high risk patients with a HR of 2.74 (95% CI 1.54-4.88; p=0.006). MSI-status and the number of assessed lymph nodes were the only significant clinical parameters in the univariate analysis. Using parameters from the ASCO recommendation (T4, perforation, less than 12 LN assessed and/ or high grade) for the identification of high risk patients was not significant (HR 1.43, 95% CI 0.81-2.55; p= 0.22) and no clinical parameter added power to the ColoPrint classification in multivariate analysis. Conclusions: ColoPrint is available as a routine diagnostic test with a high precision and reproducibility. ColoPrint significantly improves the prognostic accuracy of pathologic factors and MSI and facilitates the identification of low risk patients with stage II disease who may be safely managed without chemotherapy.
Prognostic impact of hexokinase and glucose transporter expressions and clinicopathologic features related to F-18-FDG uptake in esophageal cancer.
Authors: Schreurs Liesbeth M , Pultrum Bareld B , Pavlov Kirill , Pruim Jan , Groen Henk , Hollema Harry , Plukker John Theodorus 
Published: February 2017

39 Background: Elucidation of prognostic predictors based on biological viability may be useful for a better detection of patients with a high risk of relapse or death from esophageal cancer. Methods: Maximum standardized uptake values (SUVmax) were measured in the preoperative 18F-FDG positron emission tomography (PET) scans of 47 patients who had a radical esophageal resection without previous treatment. Expression levels of hexokinase-II (HK-II), glucose transporter I (GLUT-I), hypoxia inducible factor-1α (HIF-Iα), vascular endothelial growth factor (VEGF), p53 and the proliferative activity (MIB-I score) were determined immunohistochemically on paraffin-embedded tumor tissue. Correlations and survival functions were calculated to identify independent correlations between FDG-uptake and prognostic expression levels. Results: High HK-II expression was significantly correlated with reduced SUVmax values (p= 0.002) and HK-II expression was significant higher among adenocarcinomas than squamous cell carcinomas (36/37 vs. 5/9, p= 0.004). The five years survival was significant better for patients with SUVmax≤ 3 in their primary tumors (75% vs. 25%) and a lymph node (LN) ratio ≤0.20 (40% vs. 6%). There were also significant disease free survival benefits for different expression rates of GLUT-I, p53 and MIB (log rank p= 0.03, p= 0.03 and p= 0.04 respectively) in patients with a lymph node ratio >0.20. Conclusions: FDG-uptake and LN ratio are strong prognostic predictors in patients with esophageal cancer. The level of GLUT-I and p53 expression and the MIB score may be useful prognostic markers that provide information about tumor aggressiviness in esophageal cancer.
Known colorectal cancer susceptibility loci and survival after colorectal cancer diagnosis.
Authors: Phipps Amanda , Garcia-Albeniz Xabier , Hutter Carolyn , White Emily , Fuchs Charles S. , Nan Hongmei , Peters Ulrike , Newcomb Polly A. , Chan Andrew T. 
Published: February 2017

394 Background: Beyond clinicopathologic stage, there are few established markers of prognosis in colorectal cancer (CRC). Recent genome-wide association studies have identified 17 germline single nucleotide polymorphisms (SNPs) significantly associated with incident CRC. However, it is unclear if these CRC susceptibility SNPs influence survival after CRC diagnosis. Although the functionality of many of these SNPs remains unknown, a few, including rs4939827 in SMAD7, map to genes with plausible biological mechanisms associated with both cancer risk and prognosis. We examined 17 CRC susceptibility SNPs in relation to survival after CRC diagnosis. Methods: We genotyped 2,611 men and women enrolled in five prospective cohort studies who were diagnosed with invasive CRC during study follow-up: the Physicians’ Health Study (N=281), Health Professionals Follow-up Study (N=268), Nurses’ Health Study (N=367), Vitamins and Lifestyle Study (N=281), and the Women’s Health Initiative (N=1414). Analyses were limited to Caucasians with known vital status, cause of death, and survival time. We used Cox proportional hazards regression to assess associations between each SNP and CRC-specific and overall survival in study-specific models adjusted for age, sex, and stage; SNPs were modeled additively to reflect associations per copy of the minor allele. Study-specific results were combined via fixed-effects meta-analysis. Results: The G allele in rs4939827 was associated with poorer CRC-specific survival [hazard ratio (HR)=1.16, p=0.02] and overall survival (HR=1.13, p=0.03) in CRC patients. The A alleles in rs10795668 and in rs4925386 were associated with a 1.14-fold increased risk of overall mortality (both p-values=0.03) but not CRC-specific mortality. Other evaluated SNPs were not associated with survival. Conclusions: Genetic variation in rs4939827 (SMAD7) is associated with CRC-specific and overall survival. These results suggest that SMAD7 may have a role in CRC progression, and provide proof-of-principle that common germline variation may provide prognostic information beyond traditional considerations such as stage.
DPD deficiency: Medicoeconomic evaluation of pretreatment screening of 5-FU toxicity.
Authors: Traoré Sory , Boisdron-Celle Michele , Hunault Gilles , Andre Thierry , Morel Alain , Guerin-Meyer Veronique , Capitain Olivier , Gamelin Erick 
Published: February 2017

410 Background: Deficiency of DPD activity is associated with severe toxicity or even death after the first two cycles 5-fluorouracil (5-FU) based of chemotherapy. The objective of this study was to assess the cost-effectiveness of a screening test before treatment of the deficiency of DPD activity combining two approaches (genetic and phenotype (UH2 / U)). The main measure of effectiveness was the number of avoided severe toxicities (grade 3-4), but the number of quality adjusted life days was the secondary endpoint. Methods: The analysis was based on retrospective data from a population of patients treated for colorectal cancer. 856 patients were screened (5-FUODPM Tox, ODPM, France) before being treated with adjusted doses (5-FUODPM Protocol, ODPM, France) versus a population of 886 patients treated according to standard doses (2400 mg/m²). The main point of view was society perspective and the time horizon was 2 cycles of chemotherapy. A multi-state Markov-type was used to estimate the mean cost and results for each of the two strategies. The cost of the strategy with screening was composed of the cost of the screening test and the cost of remaining toxicities, the cost of the standard strategy was just the cost of toxicities. The incremental cost-effectiveness ratio (ICER) was calculated: (COSTStandard - COSTWithScreening)/(EffStandard - EffWithScreening) COSTA : Cost of the strategy A, EffA : Effectiveness of the strategy A. Results: In the screened and adapted arm, the prevalence of severe toxicities at 1 cycle of chemotherapy was 0.5%, at 2 cycles was 0.9%. In the arm with standard doses, they were 5.80% and 6.90%, respectively. Any toxicity associated death was observed in the screened arm versus 1 death in the standard arm. The screening strategy was dominant, it allowed avoiding toxicities and saving money. The avoided cost per patient screened was 313 € for two cycles of treatment and a saving of 2780 € per toxicity avoided. The incremental net benefit (INB) per patient screened is 426 €. Conclusions: Pre-treatment screening test combining genetic and phenotype reduced the incidence of toxicities associated with 5-FU, it avoided deaths due to 5-FU and its additional cost was less than the cost of care of toxicity that it avoided.