bluuebunny/crossref_metadata_2025_split huggingface dataset:
Occurrence and characteristics of hospitalizations during first-line chemotherapy among individuals with metastatic colorectal cancer.
Authors: Fisch Michael Jordan , Grabner Michael , Mytelka Daniel S , Raval Amit D , Bowman Lee , Kern David M , Churchill Collin , Singer Joseph , Wetmore Stewart , Barron John , Eleff Michael 
Published: January 2019

691 Background: Choosing chemotherapy for metastatic colorectal cancer (mCRC) requires balancing clinical effectiveness and risk of complications. This study characterized real-world inpatient/ER hospitalizations (HOSP) during first-line chemotherapy among individuals with mCRC. Methods: We conducted a retrospective cohort study of adults with mCRC identified using claims data from the HealthCore Integrated Research Environment as initiating first-line chemotherapy from 12/23/2013 to 06/30/2016 (no minimum follow-up). Cohorts were analyzed in aggregate and for the most frequently observed first-line agents (5 overlapping subcohorts). HOSPs were identified from initiation of first-line chemotherapy to 30 days after the end of first-line chemotherapy or last available data. Results: A total of 717 individuals (mean age 55y; 58% male; 44%/39%/6%/12% with ECOG = 0/1/2+/missing; median follow-up 116 days) met study criteria. Metastasis was most commonly to the liver (51%) and 53% of patients had cancer-attributable morbidities. Chemotherapies included 5-FU (79%), oxaliplatin (67%), bevacizumab (58%), irinotecan (21%), and capecitabine (19%). Overall, 40% of patients had ≥1 HOSP [n = 285; total 415 events], ranging from 38% to 49% across the 5 chemotherapy-based subcohorts; 12% (n = 85) had > 1 HOSP. The median time to first HOSP for patients with an event was 52 days. The median length of inpatient stays was 4 days; Infections/neutropenia (21%), bowel-related complications (17%), cardiac and circulatory disorders (9%), malnutrition (5%), pain (5%) and renal disease (2%) were the most common issues associated with inpatient HOSPs. An increase in HOSPs was observed with worsening ECOG status: 0 (34%), 1 (46%), and 2+ (65%). In regression analyses, ECOG≥1 was associated with a 64%-72% increase (p < 0.01) in the odds of HOSPs compared to patients with ECOG = 0. Conclusions: Approximately 40% of mCRC patients had hospitalizations during the study period. Hospital stays were typically short and associated with infections, neutropenia, or bowel-related complications. Further research is needed to determine how many of these hospitalizations may be avoidable.
Matrix metalloproteinase-related gene polymorphisms to predict efficacy of regorafenib in patients with metastatic colorectal cancer.
Authors: Suenaga Mitsukuni , Schirripa Marta , Cao Shu , Zhang Wu , Yang Dongyun , Ning Yan , Bergamo Francesca , Zagonel Vittorina , Rossini Daniele , Borelli Beatrice , Okazaki Satoshi , Berger Martin D , Miyamoto Yuji , Gopez Roel , Barzi Afsaneh , Yamaguchi Toshiharu , Loupakis Fotios , Lenz Heinz-Josef 
Published: January 2019

692 Background: Matrix metalloproteinases (MMPs) are proteolytic enzyme for extracellular matrix and involved in regulation of tumor environment including angiogenesis. MMP-2 and MMP-9 were reported to be prognostic marker of anti-angiogenic therapy. We tested whether genetic polymorphisms in the MMP family predict clinical outcomes in patients with refractory mCRC receiving regorafenib. Methods: 228 patients with mCRC receiving regorafenib were included in this pooled analysis combining two different cohorts from Italy and Japan (median age, 62 years; male, 51.5%; median follow-up time, 26.2 months; Italian/Japanese, 150/79). Six single nucleotide polymorphisms (SNPs) of five genes in MMPs ( MMP2, MMP9, MMP14, TIMP2, CD44) were analyzed by PCR-based direct sequencing. Correlations between candidate SNPs and progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier curves and log-rank test. Disease control was compared by Fisher’s exact test. Multivariable analyses were conducted using the Cox proportional hazard regression model. Results: In univariate analysis, patients carrying the G/G variant in MMP2 rs1477017 had a significantly shorter OS compared to those with any A allele (4.4 vs. 7.8 months, HR 1.85, 95%CI: 1.13-3.03, P= 0.011). The findings were confirmed in multivariable analysis (HR 1.84, 95%CI: 1.11-3.07, P= 0.019). Although the frequency of the T/T variant in MMP9 rs2274755 was considerably low, the T/T variant was associated with shorter PFS and OS compared to any G allele in univariate analysis (1.7 vs. 2.1 months, HR 2.53, 95%CI: 1.17-5.46, P= 0.011; 3.9 vs. 7.6 months, HR 2.51, 95%CI: 1.11-5.72, P= 0.021) and multivariable analysis (HR 3.04, P= 0.009; HR 5.20, P< 0.001). No significant interaction was shown between the SNPs and cohorts. Disease control was significantly infrequent in patients carrying the T/T variant in MMP9 rs2274755 ( P= 0.046). Conclusions: Our data suggest that MMPs network potentially mediates tumor angiogenesis responding to regorafenib. The MMP2 and MMP9 SNPs may predict efficacy of regorafenib in patients with refractory mCRC. However, this preliminary finding warrants further validation.
Epithelial mesenchymal transition in an advanced BRAF mutation type colorectal cancer.
Authors: Hwang Jun-Eul , Bae Woo Kyun , Shim Hyun-Jeong , Cho Sang-Hee , Chung Ik-Joo 
Published: January 2019

693 Background: BRAF mutation is associated with poor survival in colorectal cancer. We aimed to generate genomic signature associated with BRAF mutation that possibly predict prognosis in colorectal cancer. Methods: A gene expression signature reflecting BRAF mutation was generated in TCGA cohorts (n = 207). The colorectal cancer patients were stratified into two groups according to this signature: BRAF mutation type colorectal cancer or BRAF wild type colorectal cancer. Prognostic significance of BRAF mutation-associated gene signature was tested in three independent cohorts (GSE 17536, GSE 14333, and GSE 39582). Results: The BRAF mutation signature was associated with poor prognosis in two independent cohorts (total n = 522). BRAF mutation type colorectal cancer was associated with poor disease-free survival (median: not reached, P = 0.0303) in GSE14333, and associated with poor overall survival (BRAF mutation vs. wild, P = 0.0355), poor disease-free survival (P = 0.00794), and poor disease-specific survival (P = 0.0341) in GSE 17536. In GSE 39582, BRAF mutation type colorectal cancer demonstrated the trend of poor overall survival according to increase of stage. In a multivariate analysis, BRAF mutation gene signature was independent poor prognostic factor for disease-free survival (hazard ratio 2.7; 95% CI 1.59-2.83: P = 0.001). Gene network analyses suggested epithelial-mesenchymal transition and colon cancer metastasis signaling are the possible explanations for poor prognosis of BRAF mutation type colorectal cancer. Conclusions: BRAF mutation signature is highly associated with poor prognosis in colorectal cancer, especially in advanced stage, and the molecules associated with epithelial-mesenchymal transition can be potential therapeutic targets in BRAF mutation type colorectal cancer.
COX2 and HLA immunohistochemical (IHC) staining in colorectal tumour samples from patients participating in the ASCOLT clinical trial of adjuvant aspirin therapy.
Authors: Segelov Eva , Sieber Oliver , Chia John Whay Kuang , Williams David S 
Published: January 2019

695 Background: ASCOLT is an international Phase III randomized control trial (NCT00565708) investigating the impact of adjuvant aspirin on recurrence and survival after curative resection of colorectal cancer (CRC). Retrospective data suggest that COX2 and HLA Class 1 antigen expression may predict for aspirin benefit (Reimers MS, JAMA internal medicine, 2014;174(5):732-739; and Chan AT, JAMA, 2009;302(6):649-658.) Translational studies aim to confirm putative biomarkers of aspirin sensitivity in this prospective trial. This study reports the IHC assessment of COX2 and HLA in representative samples. Methods: FFPE slides from consenting Australian patients were stained with COX2 and HLA Class 1 antibodies (Chan AT, JAMA, 2009;302(6):649-658.). Digital images were captured using Aperio software. IHC expression was scored by a pathologist (DW) blinded to sample identification. Intensity was assessed semi-quantitatively for each antibody in one area of dominant (primary) intensity and one of secondary intensity in each section. A scale was applied for staining intensity: 0=absent, 1=weak, 2=moderate and 3=strong; and for amount of tumor epithelium stained: 1= 5%-24%, 2= 25%-49%, 3=50%-74% 4= >75%. Normal epithelium, which typically has strong COX2 and HLA staining, was used as internal control. Only tumor epithelium was scored (not inflammatory cells). Results: 90 tumors were stained for both COX2 and HLA Class 1. All tumors showed diffuse staining for both markers, mostly strong, but with many tumors having regions with lesser degrees of expression (Table). Conclusions: COX2 expression was generally strong and HLA Class 1 was more likely to show regions of weak to moderate expression. No significant correlation was detected between COX2 and HLA expression levels. Further pathological analysis is underway and correlations will be made with outcome once trial data has matured in 2020. Clinical trial information: NCT00565708. [Table: see text]
Prognostic value of progranulin in patients with colorectal cancer underwent curative resection.
Authors: Koo Dong-Hoe , Do In-Gu , Oh Sukjoong , Kim Kyungeun , Sohn Jin Hee , Park Soo-Kyung , Yang Hyo-Joon , Jung Yoon Suk , Dong Il Park , Jung Kyung Uk , Kim Hyung Ook , Kim Hungdai , Serrero Ginette , Chun Ho-Kyung 
Published: January 2019

696 Background: Progranulin (PGRN), characterized as an autocrine growth and survival factor, is known to stimulate the tumorigenesis and proliferation of several cancer cell types. Evidence has emerged for a potential role of PGRN as biomarkers in some diseases, however, little is known about the prognostic role of PGRN in colorectal cancers (CRCs). Methods: A retrospective analysis was performed on patients with CRCs underwent curative resection between May 2013 and June 2015. PGRN expression in tumor cells was semiquantitatively categorized (no expression, 0; weak/focal, 1+; moderate/focal or diffuse, 2+; strong/diffuse, 3+). PGRN was considered positive when either tumor cells were shown with 2+ or 3+ staining intensity. Results: A total of 109 patients (28 stage I, 32 stage II, and 49 stage III) were analyzed. The median age was 67 years (range, 30–86) and 66 patients (61%) were male. Thirty-eight patients (35%) had high tumor PGRN expression (PGRN-positive), and there was a trend of elevated pre-operative CEA and CA19–9 in patients with PGRN–positive tumor compared to those with PGRN–negative tumor (CEA, 49% vs. 21%, P = 0.003; CA19–9, 21% vs. 7%; P = 0.077). The median follow-up duration for surviving patients was 28.9 months (interquartile range, 22.5–33.9). The 3–year RFS and OS were 83.7% (95% CI, 76.8–90.6) and 96.0% (95% CI, 92.3–99.7), respectively. Patients with PGRN–positive tumors had a worse recurrence free survival (RFS) with a 66.8% at 3–year (95% CI, 51.8–81.8) compared to PGRN–negative patients with a 92.4% at 3–year (95% CI, 86.2–98.6; P = 0.01). Multivariate analysis for RFS showed that PGRN–positive tumors (hazard ratio [HR] 4.61, 95% CI, 1.26–16.93; P = 0.021) and age ( > 66 years, HR 8.87, 95% CI, 1.94–40.53; P = 0.005), stage (III, HR 8.56, 95% CI, 2.02–36.27; P = 0.004) and perineural invasion (HR 4.64, 95% CI, 1.05–20.62; P = 0.043) were prognostic factors independently associated with poor RFS after adjusting for possible confounding factors including sex, MSI status, tumor location, KRAS status, and lympho-vascular invasion. Conclusions: PGRN overexpression was significantly associated with poor RFS in patients with CRCs underwent curative resection.
Prognostic value of DNA mismatch repair status and KRAS mutations in Korean colorectal cancer patients.
Authors: Hwang Soon Woo , Cho Young-Seok , Kyeong Ok Kim , Cha Jae Myung , Joo Young-Eun 
Published: January 2019

697 Background: The association of DNA mismatch repair (MMR) and KRAS mutation on clinical outcome of patients with colorectal cancer are frequently documented. However, development of more accurate prediction on clinical outcome using combination of both biomarkers remains a worthy area of investigation. The aim of this study was to evaluate the clinical relevance of KRAS mutation and MMR status in Korean patients with colorectal cancer (CRC). Methods: Clinical and pathological information for 1174 patients, who underwent surgery for colorectal cancer in 3 teaching hospitals from 2011 to 2013, were reviewed and recorded. Mutation analysis for exon 2 of KRAS gene was performed by Sanger sequencing. Expression of MMR proteins including MLH1 and MSH2 was evaluated by immunohistochemistry. Results: The overall frequencies of KRAS mutation was 34.9%. Mutations in KRAS codon 12 and codon 13 were detected in 26.7% and 8.2% of patients, respectively. Overall, 90 s (7.7%) tumors that had at least loss of expression for at least one MMR protein were defined as MMR protein deficient (MMR-D), and the remaining tumors were classified as MMR protein intact (MMR-I). According to KRAS mutation and MMR status, CRC was classified to 4 groups: Group 1, KRAS-mutated and MMR-I; Group 2, KRAS-mutated and MMR-D; Group 3, KRAS wild and MMR-I; and Group 4, KRAS wild and MMR-D. We found that patients in Group 4 had the best prognosis, and patients in Group 2 had the worst overall survival. KRAS mutation was independently associated with shorter time to recurrence and poorer overall survival. Conclusions: Combination status of KRAS mutation and MMR provide fundamental genetic signatures affecting tumor behavior, and may be used as a prognostic biomarker for CRC patient. These findings should be validated by further larger prospective study. [Table: see text]
Serological assessment of type ΧVΙ collagen in patients with colorectal cancer and ulcerative colitis.
Authors: Jensen Christina , Nielsen Signe Holm , Mortensen Joachim Høg , Kjeldsen Jens , Klinge Lone Gabriels , Krag Aleksander , Harling Henrik , Jørgensen Lars N , Karsdal Morten A , Willumsen Nicholas 
Published: January 2019

698 Background: Altered extracellular matrix (ECM) remodeling is an important part of the pathology of gastrointestinal (GI) disorders. In the intestine, type XVI collagen (col-16) plays a role in pathogenesis by affecting ECM architecture and induce cell invasion. Measuring col-16 in serum may therefore have biomarker potential in GI disorders such as colorectal cancer (CRC) and ulcerative colitis (UC). The aim of this study was to determine whether col-16 can serve as a biomarker for altered ECM remodeling in patients with CRC and UC. Methods: A monoclonal antibody was raised against the C-terminal end of col-16 (C16-C) and a competitive enzyme-linked immunosorbent assay (ELISA) was developed and technically validated. Levels of C16-C were measured in serum from patients with CRC (before (n = 50) and three months after (n = 23) tumor resections), UC (n = 39) and healthy controls (n = 50). Results: The C16-C ELISA was specific towards the C-terminal of col-16. C16-C was significantly elevated both in serum from patients with CRC (p = 0.0026) and UC (p < 0.0001) compared to controls. No difference was detected in levels of C16-C between patients with CRC at baseline and three months after tumor resections (p > 0.999). Levels of C16-C identified patients with a GI disorder with a positive predictive value of 0.9 and an odds ratio of 12 (95%CI = 4.5-29.5, p < 0.0001). Conclusions: The newly developed assay detected significantly elevated levels of C16-C in serum from patients with GI disorders compared to controls suggesting its potential as a biomarker in this setting. Future studies are needed to validate these findings.
Prognostic significance of SATB1 expression in metastatic colorectal cancer: A Nordic prospective cohort study.
Authors: Siesing Christina , Sorbye Halfdan , Dragomir Anca , Pfeiffer Per , Qvortrup Camilla , Ponten Fredrik , Nodin Bjorn , Glimelius Bengt , Eberhard Jakob , Jirstrom Karin 
Published: January 2019

707 Background: Special AT-rich sequence binding protein 1 (SATB1) is a transcription factor involved in global gene regulation. SATB1 expression has been associated with poor prognosis in numerous cancer forms, including colorectal cancer (CRC). The value of SATB1 expression in metastatic CRC (mCRC) has, however, not yet been described. The aim was to evaluate the expression and prognostic significance of SATB1 in mCRC. Methods: SATB1 expression was analysed by immunohistochemistry in tissue microarrays with tumors from a prospective cohort with 454 mCRC patients from three Nordic countries. Cox regression proportional hazards models were applied to assess the impact of SATB1 expression on overall survival (OS); in the entire cohort, and in strata per chemotherapy and mutational status. Results: Among the 454 evaluable cases, 144 (32%) were positive and 310 (68%) were negative for SATB1 expression. Positive SATB1 expression was significantly more frequent in cases with lung metastases (41% vs 29%, p = 0.018), but did not correlate with other sites of distant metastasis. SATB1 expression (positive vs negative) was not prognostic in the entire cohort. The prognostic value of SATB1 did not differ between patients receiving palliative treatment (n = 281) and untreated patients (n = 178), and did not differ in relation to type of chemotherapy. In patients with BRAF wild type tumors, SATB1 expression was significantly associated with prolonged OS, whereas the opposite was seen in BRAF mutated tumors (hazard ratio = 0.77 vs 1.60, p for interaction = 0.005). SATB1 expression was significantly associated with prolonged OS in patients with KRAS mutated tumors (hazard ratio = 0.68), but not in KRAS wild type tumors, and there was no significant prognostic interaction between SATB1 expression and KRAS status. The prognostic value of SATB1 expression did not differ by tumor location. Conclusions: The prognostic value of SATB1 expression in mCRC appears to depend on the mutational status of the tumors, in particular BRAF. The potential value of SATB1 expression as a predictive biomarker for targeted therapies merits further investigation.
Apatinib in combination with S-1 as first-line treatment in patients with advanced gastric cancer: A phase II clinical trial.
Authors: Zhang Chuantao , Liu Zimin , Zhou Na , Zhang Jianli , Zhu Jingjuan , Lv Hongying , Li Tianjun , Hou Helei , Liu Dong , Cong Jing , Jiang Man , Liu Kewei , Cui Zhumei , Zhou Yanbing , Zhang Xiaochun 
Published: January 2019

71 Background: Apatinib is a standard therapy for advanced gastric cancer in third-line setting. However, the efficacy and safety of apatinib plus S-1 as first-line therapy is unknown. Here, we conducted a single center study to evaluate the efficacy and safety of it. Methods: In this phase II trial, chemotherapy-naive patients with advanced gastric cancer were enrolled between August 24, 2016 and Sept 25, 2017, at a single centers in P.R. China. The patients enrolled were assigned to S-1 plus apatinib, S-1 (40 mg m-2 depending on patient's body surface area) was given orally, twice daily for 2 consecutive weeks, followed by a 1-week rest period, and apatinib 500 mg was given once daily, every 3-week cycle. The primary endpoint was overall survival(OS). Secondary endpoints were progression-free survival(PFS), time to progress (TTP), objective response rate (ORR) and safety. On disease progression, patients had the option to receive single-agent apatinib every 3 weeks.This trial is registered with ClinicalTrials.gov , number NCT02525237. Results: Thirty eligible patients, median age 63 years (range 40-76) and median performance status 1 (ECOG 0-2) ,were enrolled, 9 patients have no evaluation or withdrew consent. Therefore, of the 21 patients the median PFS and TTP were 5.34±1.83 months [1.76–8.92] and 1.34±0.08 months[1.18–1.51], respectively. Additionally, one(4.76%) patient had a complete response, one (4.76%)patients had partial responses, 11 patients had stable disease, and 9 patients had progress of disease. The objective response rate(ORR)and the disease control rate(DCR) were 9.52%(2/21) and 57.14%(12/21),respectively. Until Sept 25.2017,the primary endpoint(OS) had not been reached. We recorded grade 3 or 4 adverse events including elevated bilirubin and/or transaminase, fatigue, abdominal pain, thrombocytopenia,et al. There were no treatment-related deaths. Conclusions: First-line chemotherapy with S-1 plus apatinib in patients with advanced gastric cancer did not reach its primary objective. However, it holds promise of becoming a standard first-line treatment for patients with advanced gastric cancer. Clinical trial information: NCT02525237.
A 20-year comparison of definitive chemoradiation with 5-FU versus capecitabine in anal cancer patients treated at Stanford.
Authors: Pumpalova Yoanna S , Kozak Margaret M. , von Eyben Rie , Fisher George A. , Kunz Pamela L. , Chang Daniel Tandel , Haraldsdottir Sigurdis 
Published: January 2019

710 Background: Capecitabine is an established treatment alternative to intravenous 5-fluorouracil (5-FU) for chemoradiation in rectal cancer. Few studies have compared the two agents in anal cancer. The objective of this retrospective study was to compare outcomes and toxicities in non-metastatic anal cancer patients undergoing definitive radiotherapy (RT) at Stanford combined with capecitabine/mitomycin (CM) versus 5-FU/mitomycin (FM). Methods: We included all non-metastatic anal cancer patients treated with definitive chemoradiation at Stanford from 1997 – 2016. Patients who received cisplatin or induction chemotherapy were excluded. Patient charts were reviewed and cause of death determined from the cancer registry. Fisher’s exact test was used to compare nominal parameters, Mann-Whitney U test for continuous variables. Gray’s test for equality was used to compare recurrence and colostomy incidence, and Log-rank test to compare disease-specific and overall survival. Results: Sixty-eight patients were treated at Stanford. Twenty-nine received FM and RT, 12 received standard 5-FU and 17 received low-dose continuous 5-FU; 39 patients received CM and RT. Median age was 59.5 years, and 56% were female. There was no difference in the 3-year overall and disease-specific survival between the FM and CM groups (81.5% v 90.5% p = 0.262; 88.1% v 96.0% p = 0.229). Incidence of recurrence was equivalent between the two groups (13.8% v 10.6%, p = 0.927) but patients in the combined FM group recurred earlier (6.9 v 20 months, p = 0.004) and distant recurrences were only seen in the CM group. Colostomy rates were higher in the FM group (14.6% v 2.8%, p = 0.082); all colostomies in the FM group were in patients receiving continuous 5-FU. Toxicities were similar between the two groups. The most common grade 2 or higher toxicities were dermatitis (77%), anal pain (77%), diarrhea (54%), stomatitis (19%), and nausea (22%). Conclusions: Overall and disease-specific survival and recurrence rates were equivalent between FM and CM groups. Recurrence patterns differed with loco-regional recurrences and higher colostomy rates in the FM group, while most recurrences in the CM group were distant.