bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determinants of bile acids.
Authors: LaFleur Bonnie , Tong Weiqun , Liu Junmei , Lance M Peter , Thompson Patricia 
Published: February 2017

632 Background: Several epidemiological studies have demonstrated an association between bile acids (BA) and colorectal cancer. Despite this evidence, there are limited studies that examine the determinants of bile acids in humans. We conducted a secondary, cross-sectional analysis on 735 adenoma formers from a phase III adenoma prevention trial of ursodeoxycholic acid (URSO) who provided a fecal sample at their baseline visit. Methods: Fecal measures of primary bile acids cholic acid (CA) and chenodoxycholic acid (CDCA), as well as secondary bile acids, deoxycholic acid (DCA), lithocholic (LCA) were the outcome variables of interest. Dietary, non-dietary, medication use, genetic variation in the CYP7A1 gene (as single nucleotide polymorphisms (SNPs) and haplotypes), and physical activity, and characteristics of baseline adenoma were evaluated as correlates of fecal BAs. We used maximum likelihood methods to incorporate left-censoring in the BAs that had concentrations below the detection limit (BDL). These log-normal parametric survival models were used to fit potential predictors of fecal BA levels, stratifying by sex. The Akaike information criterion (AIC) was used to choose the best predictive model from each BA outcome. Model accuracy was assessed using leave-one-out cross validation and a likelihood-based measure of R2 and the Brier score. Results: LDL and cholesterol were predictors for primary bile acid CDCA in men and women, as was the use of pain medication (use of medication lowered BA levels). Genetic variation in CYP7A1 (as haplotypes and individual SNP's) was a significant determinant of CA level in both men and women. BMI was an important predictor for both men and women for DCA and CA. Presentation with tubular-villous histology was associated with LCA levels whereas proximal adenoma was an important predictor for CA levels, in men and women. Conclusions: This secondary analysis of a uniquely large dataset validates previous studies that suggest lifestyle and genetic factors influence colonic exposure to carcinogenic BAs. These findings also importantly highlight gender-specific differences in BA determinants that may explain colorectal cancer incidence differences between men and women.
IMPACT study: A phase II-III clinical study with the immunomodulator MGN1703 in patients with advanced colorectal carcincoma.
Authors: Tschaika Marina , Schmoll Hans-Joachim , Riera-Knorrenschild Jorge , Nitsche Dieter , Trojan Jorg , Kröning H. , Maiwirth Fritz Albert , Reiser Marcel , Schroff Matthias , Weith Ekaterina , Schmidt Manuel , Wittig Burghardt 
Published: February 2017

633 Background: The synthetic DNA-based immunomodulator MGN1703 acts as an agonist of toll-like receptor 9. Based on promising data from a phase I study in patients with metastatic solid tumors including those with CRC, a phase II-III study was initiated in patients with advanced CRC having disease control after first-line therapy. The objective of the study is to assess efficacy and safety of the MGN1703 treatment in comparison to placebo. Methods: The IMPACT study is designed as a randomized double-blind placebo-controlled phase II-III study, which is conducted in patients with advanced CRC showing disease control after first-line therapy with standard chemotherapy regimen. The treatment is administered subcutaneously twice weekly in a ratio 2:1 (60 mg MGN1703 or placebo). The study is conducted in Germany, Austria, France, UK, Czech Republic and Russia, and 129 patients will be recruited into the study. The efficacy and safety of the study treatment will be evaluated based on extensive immunological tests, radiological assessment, safety laboratory results and assessments of the quality of life. The study treatment will be continued until tumor progression, intolerable toxicity, exclusion criteria or withdrawal of consent. Results: The majority of adverse events were assessed as not drug-related by the investigator. The remaining AEs include mild night sweat (not assessable), mild fever (at three occasions, possible related), and mild arthralgia (certain related) in one patient each. Three SAE have been reported so far of which one was assessed as probably drug-related – atypical pneumonia. Only in single patients local reactions such as mild redness and swelling at injection site were reported. No laboratory or clinical signs of autoimmunity or dose-limiting toxicities were reported, so far. Conclusions: With these preliminary safety results of the ongoing clinical study in patients with advanced CRC it could be shown that ttreatment with MGN1703 at the dosage of 60 mg is well tolerated and safe. Reported adverse events assessed as possibly drug-related belong to expected study drug reactions known for immune modulating drugs. These events were not accompanied by any signs of autoimmunity.
Low preoperative platelets to predict postoperative liver dysfunction in patients with metastatic colorectal cancer undergoing liver resection.
Authors: Starlinger Patrick , Herberger Beata , Tamandl Dietmar , Stremitzer Stefan , Brostjan Christine , Gruenberger Birgit , Gruenberger Thomas 
Published: February 2017

634 Background: Despite improving median survival of metastatic colorectal cancer (mCRC) patients, chemotherapy (CTx) compromises liver function. Therefore, selection of patients who are of high risk to develop liver dysfunction (LD) after surgery is important. As platelets are of major importance in liver regeneration, we investigated the impact of preoperative platelet counts on the incidence of postoperative LD and its correlation to postoperative morbidity and mortality. Methods: Patients treated with liver resection for mCRC between January 2000 and December 2010 were eligible. LD was defined as bilirubin > 5 mg/dL or prothrombin time <50% within the first postoperative week. The association of preoperative platelets < 150 x 103/ml with LD, 90 days mortality and surgical complications was analyzed. Results: 518 patients with metastatic CRC cancer underwent liver resection, of whom 68% had received neoadjuvant CTx. 21% of all patients developed LD. Postoperative complications occurred in 13.5%. 10 patients died within 90 days after liver resection (1.9%). The incidence of LD and complications was significantly higher in patients with preoperative platelets < 150 x 103/ml (P=0.010, P=0.047). 90 days mortality was nearly 3 times higher in patients with reduced preoperative platelets (9.8% vs. 3.7%). Neoadjuvant CTx was associated with an increased rate of platelets < 150 x 103/ml (with CTx 25%, without CTx 17%; P=0.051), LD (with CTx 23%, without CTx 15%; P=0.029) and postoperative mortality (with CTx 5.3%, without CTx 2.5%). Conclusions: Patients with platelets < 150 x 103/ml have an increased incidence of postoperative LD, major complications and 90 days mortality. Using this simple routine parameter, it might be possible to select patients that could be better served with alternative treatments such as radiofrequency ablation. Furthermore, reduced platelet counts and the incidence of LD were more frequent in patients after neoadjuvant CTx resulting in an increased 90 days mortality. This suggests that patients after extensive CTx accompanied by low platelets are of high risk to suffer from postoperative complications and surgical treatment should be reconsidered.
Patient versus clinician symptom reporting during chemoradiation for rectal cancer.
Authors: Flores Libertad T. , Bennett Antonia V , Law Ethel B , Hajj Carla , Griffith Mindy P , Goodman Karyn A. 
Published: February 2017

646 Background: Pelvic radiotherapy with concurrent 5-fluorouracil based chemotherapy (chemoradiation) is a component of standard therapy for patients with T3/T4 or node-positive rectal cancer. Chemoradiation can be associated with significant acute gastrointestinal toxicity. This study sought to retrospectively compare patient and clinician reports of acute symptoms experienced by rectal cancer patients receiving chemoradiation. Methods: The charts of 199 rectal cancer patients who received chemoradiation from 11/06 to 2/11 were reviewed. Clinicians assessed toxicity weekly using Common Terminology for Clinical Adverse Event (CTCAE) version 3.0. Patient-reported outcomes (PROs) were collected weekly, in clinic, beginning 9/09 using the 7-item Bowel Problems Scale. 197 patients had at least one clinician assessment or PRO and were eligible for this study. Patient and clinician assessments were compared among a subgroup of 65 patients (paired group) who had at least one patient and clinician assessment on the same date using descriptive statistics. Agreement between patient and clinician assessments was evaluated by Cohen’s kappa coefficient. Results: Characteristics were well-balanced between all rectal patients and the paired group, with the exception of the use of intensity modulated radiotherapy (IMRT). IMRT has been used increasingly over time, and IMRT was therefore used in a larger proportion of the paired group versus all patients (77% vs. 51%, respectively). Diarrhea and proctitis were reported more often by patients than clinicians throughout treatment. Uncorrected agreement for diarrhea and proctitis was 82% and 72%, respectively. Corrected for chance, Cohen’s kappa was .64 for diarrhea, indicating moderate agreement, and .22 for proctitis, indicating only slight agreement. Conclusions: Our findings suggest a discrepancy between clinician and patient symptom reports. Further study is warranted to discern potential benefits of including PROs in prospective studies, and to find whether PROs can help clinicians set patient expectations, and/or enhance communication for optimal symptom management.
Effect of chemoradiotherapy (CRT) for rectal cancer on the lymph nodes (LNs): Exploration of the number of retrieved LNs, number of metastatic LNs, and the size of LNs.
Authors: Okada Kazutake , Sadahiro Sotaro , Suzuki Toshiyuki , Tanaka Akira , Okamura Hiroko , Kamijo Akemi 
Published: February 2017

651 Background: For accurate staging of colon cancer, 12 or more LNs are recommended to be explored. Although the total number of LNs in rectal cancer was reported to be decreased after CRT, the number of LNs to be explored is not yet clear. We investigated the number of retrieved LNs, number of metastatic LNs, and the LN sizes within the radiation field in comparison with those outside the radiation field, to clarify the influence of CRT. Methods: The subjects were 211 patients with cStage II/III rectal adenocarcinoma who underwent radical surgery between 1991 and 2010. Of these, 111 patients underwent surgery alone (S group) and 100 patients also received preoperative CRT (40 or 45Gy) with concurrent oral UFT or S-1 (RT-group). The numbers of LNs were reviewed by pathological chart, and HE-stained specimens were examined with a digitizer to evaluate the LN sizes (short-axis, long-axis and area). Results: A total of 2049 LNs were retrieved, of which 230 were metastatic LNs. The average number of retrieved LNs was significantly higher in the S group (16±11) than that in the RT group (9±7) (P < 0.0001). The number of LNs inside the radiation field was significantly higher in the S group (6±6) than that in the RT group (4±4) (P = 0.001), whereas outside the radiation field, there was no significant difference between the two groups (5±4 in the S group vs. 5±4 in the RT group). The short-axis of the retrieved LNs was significantly larger in the S group (within the radiation field: 3.5±2.1 mm in the S group vs. 3.0±1.9 mm in the RT group, P < 0.0001; outside the radiation field: 4.3±2.6 in the S group vs. 3.8±2.4 in the RT group, P = 0.05). Conclusions: Preoperative CRT significantly decreased the total number of LNs compared to the surgery alone, attributable to the decrease in the number of LNs inside the radiation field. CRT reduced the size of the LNs and the degree of reduction was larger in the nodes within the radiation field than in those outside. And it was suggested that CRT also had an effect on the LNs outside the radiation field.
The prognostic signficance of pretreatment leukocytosis in patients with anal cancer treated with radical chemoradiotherapy or radiotherapy.
Authors: Banerjee Robyn , Roxin George , Eliasziw Misha , Joseph Kurian , Buie Donald , Doll Corinne 
Published: February 2017

656 Background: There are emerging data showing prognostic significance of pre-treatment leukocytosis (elevated white blood cell count) in cervical cancer patients. However the prognostic impact of leukocytosis in anal cancer patients has not been previously reported. The purpose of this study was to determine the association of pre-treatment leukocytosis on outcome in patients with anal cancer treated with radical chemoradiotherapy (CRT) or radiotherapy (RT). Methods: 126 patients with anal cancer, treated with radical CRT (91.3%) or RT (8.7%) from 2 major Canadian cancer centers (University of Calgary, n=65 and University of Alberta, n=61), between 2000 and 2008 were evaluated. Demographic, clinical, hematologic and treatment factors were retrieved from retrospective review of the patients’ records. The association of clinical factors and hematologic status with overall survival (OS) and disease-free survival (DFS) was analyzed using Cox proportional hazards regression models. Results: Median follow-up was 24 months. Median tumor size was 4 cm. Mean age was 59 years and M:F was 29:97. Pre-treatment leukocytosis (WBC count greater than 10^9/L) was identified in 16% (20/126) of patients. After adjusting for gender, tumor size and stage in a multivariate analysis, leukocytosis remained significantly associated with worse 2-year OS [HR 2.9 (95% CI 1.1-7.9), p=0.036] and worse DFS [HR 2.2 (95% CI1.1-4.8), p=.045]. The patient group with both pre-treatment hemoglobin (Hgb) less than 125 g/L (lowest quartile) and leukocytosis had very poor outcomes, 2-year OS 61% versus 89% for patients without these factors; more than doubling the hazard for DFS [HR2.7 (95% CI 1.1-6.8), p=0.033] and for OS [4.5 (95% CI 1.5-13.2), p=.006]. Conclusions: Pre-treatment leukocytosis is associated with worse OS and DFS in patients with anal cancer treated with radical CRT or RT. Patients with both low Hgb and leukocytosis had very poor outcomes. These hematologic parameters represent potential biomarkers for prognosis and treatment response, and warrant further investigation to uncover the underlying biologic mechanisms and therapeutic strategies in this patient group.
Phase II intermittent (or stop and go) l-OHP administration of first-line bevacizumab (BV) plus mFOLFOX6 or CapeOX therapies in Japanese patients with mCRC: The interim report of T-CORE0901.
Authors: Gamoh Makio , Kato Shunsuke , Niitani Tomohito , Murakawa Yasuko , Sakayori Masato , Isobe Hideki , Shimodaira Hideki , Akiyama Shoko , Yoshida Kozue , Yoshioka Takashi , Ishioka Chikashi ,   Tohoku Clinical Oncology Research and Education Society
Published: February 2017

664 Background: Cumulative sensory neurotoxicity of l-OHP used in standard 1st-line FOLFOX / CapeOX +/− BV therapies in mCRC results in impairment of patient's quality of life (QoL) and discontinuation of the treatment. CONcePT trial revealed that intermittent l-OHP use in BV plus FOLFOX7 is safe, keeping efficacy comparing with BV plus FOLFOX7 in which l-OHP is administered until time to treatment failure. But it is unknown that intermittent l-OHP administration is also safe and effective in Japanese pts with mCRC Methods: This trial aims to enroll 65 of Japanese pts with mCRC. Either BV+FOLFOX or BV+CapeOX is selected by decision of physician in charge. In BV+FOLFOX arm, pts receive 6 cycles of BV plus mFOLFOX6 (5 mg/kg of BV, 85 mg/m2 of l-OHP, 200 mg/m2 of I-LV, 400 mg/m2 of 5-FU by rapid IV infusion on day1, and 2,400 mg/m2 of 5-FU 46 hr by continuous IV infusion as a 2 weeks course) and 6 cycles of BV plus sLV5FU2. In BV+CapeOX arm, pts recieve 4 cycles of BV plus CapeOX (7.5 mg/kg of BV, 120 mg/m2 of l-OHP and capecitabine 1,000mg/m2 twice daily, day1 to 14 as a 3weeks course) and 4 cycles of BV+capecitabine. The primary endpoint is progression free survival (PFS) and secondary endpoints are tumor response (RR), overall survival (OS), time to treatment failure (TTF) and frequency of neurotoxicity. Results: According the protocol, interim analysis about efficacy and safety was performed at the time the 13th pts was received the treatment for 7 months. Median progression free survival is 290+ days (95% CI 119 - 558 days) and PFS of 9 cases were more than 7 months, which is threshold value. No serious adverse effects were observed in 13 cases. The efficacy and safety evaluation committee recommended continuing the study and the current accrual is 47 cases. Conclusions: This is the interim report of T-CORE0901 trial and the study remains open to accrual with projected enrollment completion in 2012.
Predictive factors of early and late local toxicities in anal cancer treated by radiotherapy in combination with or without chemotherapy.
Authors: Doyen Jerome , Benezery Karen , Ortholan Cecile , Gérard Jean-Pierre , Hannoun-Levi Jean-Michel , Follana Philippe , Francois Eric 
Published: February 2017

667 Background: Treatment of anal cancer is based on combined radiotherapy and chemotherapy (CT). Some patients present early (<2 months) and late (>2 months) toxicities of grade 3 or greater which can strongly impair quality of life. We aimed to identify predictive factors of toxicities in 106 patients treated in a single center between January 2000 and February 2010. Methods: Retrospective analysis of our databases reported severe local toxicities (grade 3 or higher) during treatment of proven localized epidermoid carcinoma of the anal cancer. The following factors were screened as potential predictive factors: gender, age, irradiation dose, HIV status, type of boost (external vs brachytherapy), circumferential extension, type of chemotherapy, invasion of anal margin, clinical T and N stage, and clinical stage. Results: With a median follow-up of 54.1 months (46.8-61.4) early severe local toxicities occurred in 42 patients (pts) (39.6%) whereas late severe toxicities happened in 21 pts (19.8%). Both early and late toxicities were dominated by proctitis (diarrhea and/or rectal bleeding) (7 pts, 6.6% and 6 pts, 5.6% respectively) and recto-anal epithelial toxicities (27 pts, 25.4% and 17 pts, 16% respectively). Two patients got colostomia because of treatment toxicities (1,8%). Predictive factors of increased early toxicities were as follows: clinical stage III/IV (p=0.04), no brachytherapy boost (p=0.008) and type of CT (no CT, 5.9%, CT, 48.8% p=0.001). Brachytherapy boost and presence of CT retained their independency in multivariate analysis (respectively, p=0.001 and p=0.05). Only HIV positivity (p=0.02) was identified as a predictive factor of late toxicities. HIV positivity (p=0.02), invasion of anal margin (p=0.01) and circumferential extension > 33% (p=0.007) correlated with epithelial ulcer. Invasion of anal margin (p<0.001) and circumferential extension (p=0.02) were identified as independent factors in multivariate analysis. Conclusions: In this cohort absence of brachytherapy boost and CT correlated with more severe early local toxicities whereas HIV positivity was the only predictor of local late toxicities.
Feasibility of dignity therapy in patients with stage IV colorectal cancer receiving chemotherapy.
Authors: Vergo Maxwell Thomas , Nimeiri Halla Sayed , Mulcahy Mary Frances , Von Roenn Jamie H. , Benson Al Bowen , Emanuel Linda 
Published: February 2017

671 Background: Dignity Therapy (DT) is a structured psychotherapeutic interview which allows people to create a permanent document to validate their existence and leave a legacy. It focuses on life review, meaningful relationships, and words of comfort to loved ones. In terminal patients no longer receiving chemotherapy, this intervention improved the majority of patients’ sense of dignity, purpose, and meaning, and also reduced depression and self reported suffering (Chochinov, J Clin Oncol, 2005). This study evaluates the feasibility of DT in patients receiving active chemotherapy. Methods: Outpatients ≥ 18 years of age with metastatic colorectal cancer recently starting second line chemotherapy were recruited. DT was administered, the interview transcribed, and the transcription edited into a proof version. This version was read to the patient and given to them after it was finalized. Main outcome was feasibility as measured by enrollment rate, discontinuation rate, and satisfaction after completing therapy. Other secondary measures included assessments for terminal illness acknowledgement (TIA), symptoms, peacefulness, quality of life, and finally preferences in a hypothetical end-of-life scenario. Results: Overall, there has been a 91% enrollment rate (10 out of 11 approached), 0% discontinuation, and a 100% rate of being satisfied or very satisfied (7 patients). 3 patients were removed due to non-compliance, sedation, or lost data. Of those who completed therapy, > 70% felt it was helpful or very helpful and strongly or very strongly felt it increased their sense of dignity, purpose, and meaning as well as the potential to help their family in the future. Symptoms remained stable over time. Exploratory endpoints included a 33% increase in TIA (p=0.23), no increase in peacefulness (p=0.44), less aggressive goals of care (p=0.28), and decreased distress. Conclusions: DT is a highly satisfying and meaningful intervention for advanced colorectal cancer patients receiving chemotherapy. Given its feasibility, an ongoing randomized wait-list control study should help answer if DT effects TIA, end-of-life goals of care, or distress levels in this population. Funding: ACS-IRG 93-037-15.