bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical implications of polymorphisms in UDP-glucuronosyl transferase (UGT) in patients with metastatic colorectal cancer (mCRC) who were treated with oxaliplatin, irinotecan, and S-1.
Authors: Kim Sun Young , Jang Mi Song I , Kim Hyun Mi , Baek Ji Yeon , Hong Yong Sang , Jung Kyung Hae 
Published: February 2017

503 Background: The three-drug regimen with oxaliplatin, irinotecan and fluoropyrimidine is an effective therapeutic option for patients with mCRC, but is associated with high rate of toxicity. Pharmacogenetic profile might be helpful for selection of proper patients for this intensive regimen. Methods: Forty-two patients were enrolled to our phase II trial and were given irinotecan 150mg/m2 plus oxaliplatin 85mg/m2 on D1 and S-1 80mg/m2/day on D1-14 every 21 days as their front-line therapy for mCRC. Genomic DNA was extracted from peripheral blood, where the presence of germline polymorphisms of UGT including UGT1A1*6, UGT1A1*28, UGT1A1*60, UGT1A6*2, and UGT1A7*3 were tested. Results: Patients with UGT1A1*6 allele had a tendency of more frequent grade 2-3 vomiting (p = 0.06) compared to those without UGT1A1*6. The presence of a haplotype containing UGT1A6*2 and UGT1A7*3 was associated with grade 2-3 vomiting (p = 0.014) and grade 2-3 diarrhea (p = 0.063). Higher objective response rate (18/20, 90%) was noted in patients without UGT1A*60 compared to those with UGT1A1*60 (11/22, 50%; p = 0.008). The absence of UGT1A1*60 was also associated with marginally improved progression-free survival (10.3 mo v 7.7 mo, p = 0.081) and overall survival (26.8 mo v 15.1 mo, p= 0.044) compared to the presence of the variant allele. Conclusions: UGT1A1*6 and a haplotype containing UGT1A6*2 and UGT1A7*3 may be associated with irinotecan-related gastrointestinal toxicities. Phenotypic association of UGT1A1*60 and efficacy of the three-drug regimen requires further investigation.
Estrogen as a prognostic factor on liver metastasis from colorectal cancer.
Authors: Zhang Sen , He Zhen Hua , Zhang Xue Lei , Wu Zhen Jie , Ouyang Jun 
Published: February 2017

506 Background: Estrogen plays an important role in some cancer. However, previous studies about the influence of estrogen on colorectal cancer (CRC) have been conflicting, especially rare reports on liver metastasis. This study tries to explore the prognostic impact of estrogen on CRC with liver metastasis. Methods: Eighty six patients with CRC including 43 synchronous liver metastases were studied. Estrogen receptor-beta (ER-beta) were assayed by immunohistochemistry (IHC) in liver metastasis tissues, colorectal cancer tissues and normal tissues. And the serum estrogens were detected by radioimmunoassay (RIA) in 30 patients with CRC including 14 synchronous liver metastases. After follow-up, the relationship between ERβ, estrogen and survival time were analyzed. Results: The positive rates of ER-beta in liver metastases tissues, CRC tissues and normal tissues were 39.5% (17/43), 39.5% (34/86) and 62.8% (54/86), respectively; and significant differences were found between liver metastasis (P=0.012) or CRC (P=0.002) with normal tissues. The 1-, 2-, 3-and 5-year survival rates for ER-beta positive patients were 97%, 79%, 71% and 51%, respectively comparing with 82%, 59%, 55% and 40%, respectively for ER-beta negative patients (P=0.190). In contrast, the 1-, 2-, 3- and 5-year survival rates in liver metastasis group were 77%, 37%, 31% and 23%, respectively; and 93%, 64%, 57% and 57%, respectively for ER-beta positive patients comparing with 67%, 19%, 14% and 7%, respectively for ER-beta negative patients (P=0.004). Serum estrogen levels in patients with liver metastases were significantly lower than those without liver metastasis (P=0.012) and Pearson Correlation showed that there was a moderate positive correlation between level of serum estrogen and survival time (P=0.006). Conclusions: CRC liver metastasis patients with positive ER-beta have a better survival, which indicates estrogen is a protective factor for CRC liver metastasis patients. But more study is needed to show estrogen would be a protective factor for CRC patients.
Association of peripheral blood guanylyl cyclase C (GCC) expressions with prognostic parameters and response to therapy in patients with colorectal cancer.
Authors: Camci Celalettin , Sevinc Alper , Sahin Akif , Kalender Mehmet Emin , Oztuzcu Serdar , Sever Ozlem nuray , Ozyazgan Esma , Demiryurek Abdullah Tuncay 
Published: February 2017

508 Background: Guanylyl cyclase C (GCC) is expressed exclusively in normal intestinal mucosal cells, primary and metastatic colorectal cancers (CRC). The aim of this study was to determine the possible association between the GCC expressions in peripheral blood, prognostic parameters and response to chemotherapy in CRC patients. Methods: Forty-nine metastatic CRC patients and 41 healthy controls with similar age and sex were included to this study. Peripheral blood GCC expressions are measured by the reverse transcriptase-polymerase chain reaction (RT-PCR) method. Results: No GCC expression was measured in healthy controls but GCC expressions of the patients were detectable. Although there was a significant reduction in GCC expressions in 30 patients with regression (from 5.46 ± 4.12 to 0.06 ± 0.03, p < 0.0001), marked increase in GCC expressions was observed in 19 patients with progression following chemotherapy (from 0.43 ± 0.19 to 1.38 ± 0.52, p = 0.0174). Significant correlation was found between the GCC expressions and carbohydrate antigen 19-9 (CA19-9) levels (p = 0.0041) in 30 patients with regression before chemotherapy. Marked correlation was also detected between the GCC expressions and carcinoembryonic antigen (CEA) levels (p = 0.0072) in 19 patients with progression before chemotherapy. Conclusions: The results of the present study suggest that peripheral blood GCC expressions along with CEA and CA19-9 can be used to determine the early respose to chemotherapy in patients with metastatic CRC. These findings imply that higher expression of GCC in peripheral blood seems to be an indicator of good therapeutic response to chemotherapy and remission. Monitoring the peripheral blood GCC expressions may allow employing different treatment options to metastatic CRC patients.
The single-nucleotide polymorphism T>C rs4353229 in CASP7 gene and mir-224 as new biomarkers of oxaliplatin-induced neurotoxicity in advanced colorectal cancer.
Authors: Villa Guzman José Carlos , Zarate Ruth , Boni Valentina , Gomez A. , De la Haba Juan R. , Bandres Eva , Garcia-Foncillas Jesus , Aranda Enrique 
Published: February 2017

513 Background: Oxaliplatin represents a central component of colorectal (CCR) cancer treatment. It is known that the ways in which oxaliplatin is neurotoxic include not only DNA damage, but also the modulation of specific molecules, such as caspases 3 and 7, involved in regulating the cellular equilibrium between apoptotic death and the cell cycle. MiRNAs are non-coding RNAs that can block mRNA traslation. Recent evidences indicate that variations in miRNA binding sites may contribute to the susceptibility to CCR. However, the effect of these SNPs on miRNA-target interaction remains to be determined. The SNP T>C rs4353229 in CASP7 gene is binding site of miR-224. We hypothesize that miR-224 and the SNP T>C rs4353229 could be new predictive biomarkers of oxaliplatin-induced neurotoxicity in advanced colorectal cancer. Methods: We examined the SNP T>C rs4353229 in CASP7 gene in 62 patients with advanced CCR. All patients had received first line of chemotherapy based in fluoropirimidines plus oxaliplatin. The Oxaliplatin-Specific Neurotoxicity Scale was utilized to assess oxaliplatin-related symptoms. Time to progresion (TTP) and objetive response rate (ORR) were calculated. Genomic DNA was extracted from peripheral blood and genotyped by allelic discrimination. We explored the possible correlation of rs4353229 with neurotoxicity, DCR and TTP using and Chi-cuadrado test and Kaplan-Meier model (log rank) respectively. Results: SNP distribution was 3,2% (ancestral homozygous CC), 46,7% (variant homocygous TT) and 43,7% (heterocygous CT). Median TTP was 10 months (IC95%: 7,4-12,5); regarding CASP7 polymorphism, there were not differences (p=0,41; log rank). ORR was 64,5% and there are not differences between CC, CT and TT patients (p=0,50). Fifteen patients experienced neurotoxicity grade III/IV (24,19%) and it was correlated significantly with ancestral homoygous CC patients (p=0,003). Conclusions: The SNP T>C rs4353229 in CASP7 gene and miR-224 may be new candidates predictor of oxaliplatin-induced neurotoxicity. Further characterization of CASP7 SNPs and miR-224 may open new avenues for the study of cancer and therapeutic interventions.
High-resolution melting analysis (HRMA) for KRAS mutational study in patients with metastatic colorectal cancer (mCRC pts).
Authors: De Stefano Alfonso , Malapelle Umberto , Carlomagno Chiara , Bianco Roberto , Marciano Roberta , Cimminiello Carolina , Colantuoni Maria , De Placido Sabino , Troncone Giancarlo 
Published: February 2017

515 Background: The use of anti EGFR monoclonal antibodies cetuximab and panitumumab is restricted to KRAS wild-type (WT) mCRC pts. Standard method for KRAS testing is direct sequencing. To overcome its limited sensitivity, novel techniques have been developed. However there is little concordance on the clinical significance of more sensitive tests. HRMA is very sensitive and economic and allows rapid detection of DNA sequence variations based on specific sequence-related melting profile. Here we report the evaluation of therapeutic effects of cetuximab in direct sequencing tested WT pts, according to their HRMA mutational status. Methods: We retrospectively evaluated 50 (35 males, 15 females) mCRC pts with WT KRAS status by direct sequencing. Median age was 61 years (range 29 – 77). Most (40%) pts had liver metastases and 24% had multi-organ disease. They received second- or third-line cetuximab-containing chemotherapy, with irinotecan (n=25) or with combination regimen (22 FOLFIRI and 3 FOLFOX). Twenty-eight pts were treated in second-line and 22 in third-line. KRAS mutation status was reassessed in all pts using HRMA. Results: All 50 pts were evaluated for tumor response, PFS and OS. In 4 (8%) pts, KRAS mutations were only identified by HRMA. The response rate of HRMA KRAS WT pts was 28.3%, with 1 complete (2.2%) and 12 partial (26.1%). No response was observed in HRMA KRAS MT (3/4 with a progression as best response). Stable disease rates were 30.4% (14/46 pts) and 25% (1/4 pts) in HRMA WT and MT cases respectively. Disease control rate (objective responses plus stable disease) was 58.7% in HRMA KRAS WT pts and 25% in HRMA KRAS MT. No significant correlation was found between HRMA-KRAS status and response rate (p=0.287) or disease control rate (p=0.219). However, median PFS (5.1 versus 2.5 months; HR=0.34, p=0.04) and median OS (11.3 versus 3.2 months; HR=0.11, p=0.03) were significantly longer for HRMA KRAS WT pts compared to HRMA KRAS MT. Conclusions: These data show a significant difference in clinical outcome between HRMA KRAS WT and MT pts receiving a cetuximab-containing second- or third-line treatment, suggesting that techniques more sensitive than direct sequencing could better select pts for cetuximab-based treatment.
Association of temporary blood pressure drop after bevacizumab administration with clinical course of advanced colorectal cancer.
Authors: Kanai Masashi , Ishiguro Hiroshi , Mori Yukiko , Kitano Toshiyuki , Nishimura Takafumi , Matsumoto Shigemi , Yanagihara Kazuhiro , Chiba Tsutomu , Toi Masakazu 
Published: February 2017

528 Background: Hypertension is a common adverse event of bevacizumab and recent data demonstrates that this event is associated with a better clinical course. However, a blood pressure drop after bevacizumab administration and its clinical significance have not yet been reported. Methods: Between August 2007 and October 2010, 85 patients with colorectal cancer underwent palliative chemotherapy using bevacizumab at Kyoto University Hospital. For these patients, we obtained data using both the designated database system (CyberOncology, CyberLaboratory Co. Ltd., Ibaragi, Japan) and the hospital’s electronic medical records system on blood pressure values at 0 min (before administration), at 90 min and 180 min after the initiation of bevacizumab during the first three cycles of bevacizumab treatment. Out of the 85 patients, there were 81 for whom two or more sets of blood pressure data from the first three cycles were available. Therefore, we retrieved data from a total of 162 bevacizumab administrations in 81 patients (data from 2 separate administrations per patient). Results: Twenty-five patients (30%) demonstrated an average temporary drop of 20 mm Hg or more in systolic blood pressure between 0 and 90 min. We classified these 25 patients as group A and the others as group B. In group A the mean blood pressure drop between 0 and 90 min was 25 and 30 mm Hg in the first and second monitoring, respectively, compared with 3 and 5 mm Hg in group B. There were no significant differences between the 2 groups in their baseline characteristics. Interestingly, median time to treatment failure (TTF) was significantly longer in group A compared to group B (291 vs. 162 days; hazard ratio, 0.53; 95% CI, 0.31 – 0.89; P = 0.02). Furthermore, the proportion of patients who required intervention with antihypertensive drugs during bevacizumab treatment was significantly higher in group A compared to group B (36% vs 4%; P < 0.01). Conclusions: Our current study suggests that a temporary blood pressure drop after bevacizumab administration could be a predictive marker for bevacizumab treatment.
Effectiveness and safety of second-line (2L) irinotecan- and oxaliplatin-based regimens after first-line (1L) bevacizumab (BV)-containing treatment (tx) for metastatic colorectal cancer (mCRC): Results from the ARIES observational cohort study.
Authors: Bekaii-Saab Tanios S. , Grothey Axel , Bendell Johanna C. , Kozloff Mark , Cohn Allen Lee , Mun Yong , Fish Susan , Flick Elizabeth Dawn , Dalal Darshan , Hurwitz Herbert 
Published: February 2017

535 Background: Prior ARIES analyses showed that BV-treated mCRC patients (pts) receiving chemotherapy (CT)/biologics + BV within 2 months (mo) after 1st progressive disease (PD) had longer post-progression survival (PPS) than pts receiving only CT/biologics. The present analysis evaluated whether this effect of BV was consistent when used with common 2L CT regimens— irinotecan- (iri-) and oxaliplatin- (ox-) based—in mCRC pts exposed to 1L BV in ARIES. Methods: ARIES enrolled mCRC pts receiving 1L CT + BV. No tx regimens or assessments were protocol specified. This analysis evaluated 1L BV-treated mCRC pts who had PD, survived ≥2 mo after PD, and received 2L iri- or ox-based tx. PPS was estimated by Kaplan-Meier methods. Cox regression was used to estimate hazard ratios (HRs), while adjusting for covariates (eg, 1L time to progression). Results: Of 1550 1L pts in ARIES, 1074 had 1st PD and survived ≥2 mo after PD. Of these 1074, 390 and 114 received 2L iri- and ox-based tx, respectively, ± BV ( table ). Baseline characteristics were generally similar between groups. The incidence of targeted adverse events (TAEs) was as expected and similar between the BV and No BV groups over time. In pts receiving 2L iri- or ox-based CT tx, PPS in BV-treated pts was longer compared to those not on BV. Analyses may be limited by small pt numbers in some groups. Conclusions: Consistent with prior ARIES analyses, the continued use of BV after 1st PD was associated with prolonged PPS regardless of the 2L CT backbone used. [Table: see text]
A 21-year analysis of lymph node trends in colon cancer: Do quality measures really matter?
Authors: Hari Danielle M. , Stojadinovic Alexander , Chiu Connie G. , Leung Anna M. , Sim Myung-Shin , Bilchik Anton J. 
Published: February 2017

539 Background: Lymph node (LN) number has been endorsed as a quality measure (QM) in colon cancer (CC) because of the impact on survival. However, the current mandate requiring > 12 LNs has been questioned. We evaluated whether compliance of this QM has improved and whether this has impacted overall survival (OS). Methods: The Surveillance, Epidemiology, and End Results (SEER) Database was queried to identify patients (pts) with pathologically confirmed, localized and regional CC (Stage I-III) diagnosed between 1988 and 2008. Interval trends in lymph node (LN) harvest and OS were evaluated over time (Year Strata (YS): 1988-1993, 1994-1998, 1999-2003 and 2004-2008). Results: For pts with local and regional CC, 181,035 had confirmed LN examinations. For Stages I-III, there has been a dramatic improvement in compliance for pts with > 12 LNs harvested over the recent two 5-yr periods (19, 21, 18% respectively, p<0.0001) whereas previously only a 5-7% increase occurred over time (see Table ). This rise in compliance had the greatest effect on the increased survival trend for stage II CC with minimal change for those with Stage I and Stage III CC. Irrespective of LN examined there has been a significant increase in OS for all stages over time (p<.0001). Conclusions: In the largest time-dependent assessment of lymph node examination in colon cancer, significant improvements in surgical quality measures have occurred over the past decade for Stage I, II and III. These measures have translated into improvements in overall survival particularly for Stage II disease. Lymph node yield alone is not an adequate quality measure for patients with stage I and III colon cancer. [Table: see text]
Association of NCCN guideline adherence with improved survival in high-risk stage II and stage III colon cancer.
Authors: Boland Genevieve Marie , Chiang Yj , Chagpar Ryaz , Xing Yan , Hu Chung-Yuan , Feig Barry W. , Chang George J. , You Y. Nancy , Cormier Janice N. 
Published: February 2017

543 Background: Evidence-based treatment guidelines have been proposed as a quality metric for cancer care. There is significant variability in the treatment of high-risk stage II (defined by tumor depth, histologic grade, margin status, and # of nodes retrieved) and stage III colon cancer patients in the National Cancer Database (NCDB). This study examines whether adherence to guidelines is associated with improved outcomes. Methods: Patients with colon adenocarcinoma (1998-2002) were identified from the NCDB. The stage-specific NCCN guidelines were used to classify patients into two groups based on adherence to guidelines (adherent or non-adherent). Overall survival (OS) and relative survival (RS) were calculated for both groups. Relative survival was used as a surrogate for disease-specific survival and calculated using the methods of Dickman et al. Results: A total of 77,350 patients were included in the analytic cohort. Stage-specific outcomes were compared and stage is an independent predictor of survival. As reported in our previous analyses, nonadherence as a result of omission of chemotherapy, was noted in 64.3% and 26.4% of high-risk stage II and stage III patients, respectively. Nonadherence was associated with decreased OS and RS with a hazard ratio for death of 1.43 (95% CI: 1.33, 1.54) for high-risk stage II and 1.89 (95% CI: 1.82, 1.95) for stage III (p < 0.001, Table) RS. Additionally, regression analysis demonstrated that gender, age, race, insurance, income, and type of facility were associated with differences in RS. Conclusions: Guideline-based practice, particularly for high-risk stage II and stage III colon cancer, is associated with improved survival outcomes. Therefore, these guidelines may be appropriate as a metric of performance comparable across various institutions. Additionally, factors associated with deviations from guidelines can be used to focus improvements in the access to and delivery of cancer treatment. [Table: see text]
What determines adjuvant chemotherapy use after neoadjuvant chemoradiotherapy for rectal cancer?
Authors: Chang George J. , Hu Chung-Yuan , You Y. Nancy , Eng Cathy , Rodriguez-Bigas Miguel A. , Skibber John Michael 
Published: February 2017

546 Background: The treatment standard for rectal cancer patients after neoadjuvant chemoradiotherapy (CXRT) and radical resection includes adjuvant chemotherapy (CT). The purpose of this study was to evaluate patient demographic and clinicopathologic characteristics in relation to adjuvant CT use. Methods: A retrospective cohort study of patients ≥ 65 years old with rectal cancer treated by neoadjuvant CXRT and radical resection in the Surveillance, Epidemiology, and End Results-linked Medicare database (1998-2007, Medicare Part A/B only) was performed. Multivariate logistic regression was used to assess CT utilization in relation to patient, tumor and treatment response characteristics. Results: Among 1344 patients who met study criteria, 748 (55.6%) received adjuvant CT with 5-fluorouracil (FU) including 189 (25.3%) who also received oxaliplatin (Ox). ypStage was the strongest determinant of both any post-operative CT (43.1% stage I, 51.3% stage II, 73.4% stage III). Other associated factors included age, comorbidity, marital status and surgery type. In addition, age, socioeconomic status, and grade were associated with Ox use. These effects persisted even after exclusion of patients with comorbidities. Conclusions: Although standard treatment guidelines for locally advanced rectal cancer include postoperative CT for all patients after neoadjuvant CXRT and radical resection, nearly 1 in 2 patients failed to receive adjuvant CT. Despite the absence of established evidence, treatment decisions appear to be influenced by the findings at surgical pathology. [Table: see text]
A randomized phase III trial exploring the use of long-acting release octreotide in the prevention of chemotherapy-induced diarrhea in patients with colorectal cancer: The LARCID trial.
Authors: Hoff Paulo Marcelo , Saragiotto Daniel Fernandes , Barrios Carlos H. , Del Giglio Auro , Coutinho Anelisa Kruschewsky , Andrade Aline C , Dutra Carolina , Forones Nora , Correa Mariangela , Portella Maria Socorro , Passos Vanessa Q. , Chinen Renata N , van Eyll Brigitte 
Published: February 2017

549 Background: Chemotherapy-induced diarrhea (CID) is a relatively common adverse event in the treatment of colorectal cancer patients. The LARCID trial evaluated the efficacy and safety of long-acting release octreotide (octreotide LAR) for the prevention of CID in this population. Methods: Colorectal cancer patients starting adjuvant or first-line treatment with a chemotherapy combination containing fluorouracil (5-FU), capecitabine and/or irinotecan were randomized to receive octreotide LAR, 30 mg intramuscularly every 4 weeks, (experimental arm) or the physician’s treatment of choice in case of diarrhea (control arm). Results: A total of 139 patients were randomized, most of which received 5-FU- and oxaliplatin-containing chemotherapy regimens. The rate of diarrhea was 76.1% in the experimental group (n=68) and 78.9% in the control group (n=71). Treatment with octreotide LAR did not prevent nor reduced the severity of CID. Treatment choices for diarrhea management included loperamide in the majority of cases. No benefit from octreotide LAR was identified in terms of need for diarrhea treatment, opioids, or intravenous hydration, nor in the rate of hospitalization, or quality-of-life. Conclusions: Octreotide LAR is not indicated for the prevention of CID.