bluuebunny/crossref_metadata_2025_split huggingface dataset:
The enhanced antitumor effect of combined triptolide and paclitaxel on pancreatic cancer cell lines.
Authors: Wang Wei , Lin Wenjie , Wang Qingda , Zhuang Xin , Luo Jinbing 
Published: February 2017

335 Background: Pancreatic cancer is a disease with dismal prognosis and its treatment options are limited. Recently albumin-bound paclitaxel (nab-paclitaxel) was approved by FDA for advanced pancreatic cancer patients. This study aims to explore the enhancement of therapeutic effect on human pancreatic cancer cell lines (AsPC-1 and PANC-1) via the combination of triptolide, derived from the herb Tripterygium wilfordii, and paclitaxel. Methods: Pancreatic cells were treated with paclitaxel or triptolide alone, and the combination of them. Cell proliferation was measured by sulforhodamine B (SRB). Apoptotic cells were assessed by flow cytometry and western blot for cleaved caspase-3, 8, 9 and PARP. To explore the role of nuclear factor kappaB (NF-kB) activity in pancreatic cancer cell lines, AsPC-1/IkBaM and PANC-1/IkBaM cells (NF-kB activity of cells was silenced by IkB-a mutation) were treated with triptolide plus paclitaxel and NF-kB activity were analyzed. Results: Triptolide demonstrated cytotoxicity on pancreatic cancer cell lines with the IC50 of 25-40nM. The combination of triptolide (IC30 concentration) and paclitaxel enhanced the cytotoxicity significantly . Combination index (CI) indicated that the effect of triptolide plus paclitaxel was synergistic. Furthermore, pancreatic cancer cells treated with triptolide plus paclitaxel exhibited increased apoptosis, as evidenced by stronger Annexin V/ PI staining, higher levels of pro-apoptotic proteins including cleaved caspases and activated PARP compared to cells treated with paclitaxel or gemcitabine alone. In the mechanism study, the combination of triptolide and paclitaxel did not demonstrate synergistic effect on AsPC-1/IkBaM and PANC-1/IkBaM cells. It indicated that the enhanced effect of triptolide plus paclitaxel was correlated with NF-kB activity. Conclusions: (1) the combination of triptolide and paclitaxel enhances the apoptosis in vitro, low concentration of triptolide showed synergistic effect with paclitaxel; (2) the antitumor effect of triptolide plus paclitaxel on pancreatic cancer is mediated by the induction of apoptosis and triptolide enhances paclitaxel-mediated apoptosis via suppression of NF-kB activity.
Outcomes of patients treated with capecitabine and temozolamide (CapTem) for advanced pancreatic neuroendocrine tumors (PNETs) and non-PNETs.
Authors: Peixoto Renata D'Alpino , Noonan Krista , Kennecke Hagen F. , Lim Howard John 
Published: February 2017

343 Background: Retrospective studies have demonstrated high response rates among patients with advanced PNETs treated with CapTem while responses are infrequently seen among non-PNETs. The objective of the study was to describe progression free survival (PFS) and overall survival (OS) among sequential NET patients treated with CapTem and to identify factors associated with response. Methods: Patients who initiated therapy with CapTem between 2009 and 2013 for advanced NETs and referred to one of 6 provincial cancer treatment centers were included. Patients received Cap 2000 mg/m2 day 1-14 and TMZ 200 mg/m2 on days 10-14 every 28 days. Their characteristics and outcomes were retrospectively analyzed. Results: In our cohort, 29 patients (16 male) with a median age of 59 (range 26 – 76) received palliative CapTem, 15 of them as first-line chemotherapy and 14 as subsequent lines. Primary tumors included pancreas (48.3%), small bowel (20.7%), lung (10.3%), unknown (10.3), rectum (6.9%) and appendix (3.4%). Median number of cycles was 3. For the entire cohort, median PFS and OS were 4.7 and 20.2 months, respectively. Although pancreatic NETs (PNETs) had shorter OS (18.8 months versus not reached, p=0.37), their PFS was longer than non-PNETs (4.9 versus 2.8 months, p=0.178). There was no difference in PFS between first or subsequent lines of therapy. Patients with Ki67 above 10% had a shorter PFS when compared to lower Ki67 (3.1 versus 5.5 months, p = 0.028). Three patients had to discontinue CapTem due to poor tolerance (2 intractable nauseas and 1 myocardial infarction). There were no treatment-related deaths. Conclusions: CapTem showed good activity among NETs, especially for PNETS, who derived the greatest benefit. Effectiveness was not exclusive to first-line therapy and seems better for well-differentiated tumors.
Living with hepatocellular carcinoma from the patient perspective: A longitudinal study.
Authors: Hansen Lissi , Vaccaro Gina M. , Rosenkranz Susan J. 
Published: February 2017

373 Background: Hepatocellular carcinoma (HCC) is a growing problem. For those diagnosed with terminal HCC, there is no curative treatment. Despite a high death rate, no longitudinal studies were found examining the illness experience of patients with HCC as they are approaching death. The aim of this study was to describe the experience of living with terminal HCC and how it may affect end of life care from the perspective of patients. Methods: This was a longitudinal, prospective mixed methods pilot study using quantitative and qualitative approaches. Semi-structured interviews were conducted with a convenience sub-sample of 14 patients with HCC once a month for a 6-month period. The interview guide included questions about living with HCC, pain and symptom management strategies, treatment decisions, and any current concerns of significance. Interview data were analyzed using qualitative description. Results: This poster reports on qualitative analysis of 45 interviews from the sub-sample. Eleven patients were male and 3 were female (mean age=61.5, range=54-68 years). Findings included 4 major themes: 1) illness perceptions, 2) uncertainty about treatments over time, 3) quality of life, and 4) coping strategies. Patients perceived HCC as isolating as compared to other cancers. Patients lacked information to prepare them for the journey ahead. They struggled with symptom management over time and chose to stop treatment, delay treatment in hope of improvement, or regretted starting treatment once underway. Conclusions: For patients, the impact of HCC and treatment side effects on quality of life was challenging and filled with uncertainty. From this first step, knowledge gained is serving as the foundation for a proposed larger scale study. The goal is to develop future interventions to address challenges (e.g., symptom management and treatment decision making) at the end of life for these understudied cancer patients.
Prevalence and incidence of comorbidities associated with gastric cancer.
Authors: Danese Mark D. , Gleeson Michelle L. , Langeberg Wendy J. , Ke Juan , Kelsh Michael A. 
Published: February 2017

39 Background: Understanding the burden of comorbidities in patients with gastric cancer may aid in treatment planning and evaluating the safety of new treatments. Methods: Using the Surveillance, Epidemiology, and End Results (SEER)–Medicare combined dataset, we identified 12,612 patients diagnosed with gastric cancer 2000–2007. A cohort of 12,612 cancer-free individuals was frequency-matched by Medicare enrollment year and county of residence. Subjects were ≥66 years-old at index date to allow for ≥1 full year of Medicare coverage. Prevalence the year before index date and 3- and 12-month incidence rates (per 100 person-years) after index date were estimated for 42 common comorbidities. Results: Comorbidities with the highest (≥8%) 3-month incidence in patients with gastric cancer are shown. Conclusions: Comorbidity prevalence before index date was modestly higher, and incidence rates after index date were much higher in gastric cancer patients than in cancer-free individuals. The potential reasons for this include the increased diagnostic testing, physician visits, and reporting of morbidities that occurs with the diagnosis of cancer, as well as the effects of cancer and its treatment. [Table: see text]
Incidence of diabetes among patients with colorectal cancer.
Authors: Singh Simron , Rochon Paula , Anderson Geoffrey , Earle Craig , Fischer Hadas , Austin Peter , Yun Lingsong , Lipscombe Lorraine 
Published: February 2017

393 Background: Emerging data show an increasingly recognized risk of colorectal cancer (CRC) in patients with type 2 diabetes (DM) likely due to common biologic pathways. Few data are available on DM incidence among patients with CRC. Our objective was to determine whether patients with CRC have a higher incidence of DM compared to those without CRC. Methods: We conducted a population-based retrospective cohort study in Ontario, Canada, using administrative databases comparing the incidence of DM among all CRC patients identified in the Ontario Cancer registry from Jan 1, 2002 to Dec 31, 2011 with an age-matched control population without CRC. We used Cox proportional hazard to study the association. We modeled the effect of CRC on the cause-specific hazard of developing DM and censored subjects at the time of a competing event. Subgroup analysis was performed on patients receiving chemotherapy vs. not, metastatic disease vs. not and colon vs. rectal cancer. Results: We identified 39,707 persons with CRC and 198,535 controls. The mean age was 68 and 48.6% were female. We found an overall DM incidence of 8.7% over a mean follow up time of 4.8 years. On multivariable analysis, the effect of CRC on the instantaneous hazard of the DM incidence varied over time, and thus we estimated instantaneous hazard ratios (IHR) for years 1-5 of follow up. The risk of DM among CRC patients was significantly higher than controls for at least five years post CRC diagnosis. The overall DM incidence was higher in patients with no metastasis (10.6% vs 8.6%, p<0.01), and lower in patients who received chemotherapy (8.0% vs 9.0%, p<0.01). Conclusions: This is among the first study to report an increased DM incidence among CRC survivors. This association may be due to common risk factors rather than a treatment effect, as the risk remains elevated for at least five years post diagnosis. The hazard may be underestimated, as patients with advanced cancer may not be formally diagnosed with DM. These results strengthen our understanding of the common biologic pathway of both diseases and have major implications for survivorship care in patients with CRC. [Table: see text]
Positron emission tomography/computed tomography for optimized colon cancer staging and follow-up.
Authors: Engelmann Bodil E. , Loft Annika , Kjær Andreas , Nielsen Hans J. , Berthelsen Anne Kiil , Binderup Tina , Brinch Kim , Brünner Nils , Høyer-Hansen Gunilla , Gerds Thomas A. , Kristensen Michael Holmsgaard , Kurt Engin Y. , Latocha Jan E. , Lindblom Gunnar , Sloth Carsten , Højgaard Liselotte 
Published: February 2017

408 Background: Optimal management of colon cancer requires detailed assessment of extent of disease. Diagnostic accuracy of 18F-fluorodeoxyglucose (FDG) positron emission tomography/ computed tomography (PET/CT) in primary colon cancer staging and for detection of recurrence was investigated. Methods: PET/CT for preoperative staging was performed on 66 prospectively included patients with primary colon cancer. Diagnostic accuracy for PET/CT and CT alone was analysed. Forty-two stage I-III colon cancer patients had PET/CT follow-up examinations every six months for two years. Serological levels of Tissue Inhibitor of Metalloproteinases (TIMP-1), Carcinoembryonic Antigen (CEA), and liberated domain I of urokinase Plasminogen Activator Receptor [uPAR(I)] and FDG-uptake related tumour gene expression were analysed. Results: Accuracy for T-, N- and M-staging by PET/CT were 82 % [95% Confidence Interval (CI) 70; 91], 66 % [CI 51; 78] and 89 % [CI 79; 96]; for CT 77 % [CI 64; 87], 60 % [CI 46; 73] and 69 % [CI 57; 80]. Cumulative relapse incidences for stage I – III colon cancer at 6, 12, 18 and 24 months were 7.1 % [CI 0; 14.9]; 14.3 % [CI 3.7; 24.9]; 19.0 % [CI 7.1; 30.9] and 21.4 % [CI 9.0; 33.8]. PET/CT diagnosed all relapses detected during the first two postoperative years. High preoperative TIMP-1 levels were associated with significant hazards towards both risk of recurrence and shorter overall survival. FDG-uptake in colon cancer showed significant correlation to hexokinase 2, the hypoxia marker carboanhydrase IX and the proliferation marker ki67. Conclusions: This study indicates PET/CT to be a valuable tool for staging and follow-up in colon cancer. TIMP-1 provided prognostic information potentially useful in selection of patients for intensive follow-up.
The cost of one added day of survival by targeted therapy in metastatic colorectal cancers.
Authors: Guirgis Helmy M. 
Published: February 2017

421 Background: Data was collected to assess the cost of one day of added survival over control in metastatic cancer. Aflibercept and regorafenib have been approved as last resort treatments in refractory colorectal cancer (mCRC). Objective: Study the impact of number of cycles on overall survival gain (OSg) in refractory and first-line mCRC. Methods: Average Wholesale Prices in United States dollars (US$) of evaluated drugs and ancillary costs were added. The total was divided by reported median OSg in days. Plans were designed to rate and score drugs. Results: See Table. The data was collected to share with physicians, patients, and authorities, not for drug comparison. Conclusions: The cost of one-day survival gain by aflibercept and regorafenib was relatively high. Increased number of cycles of targeted therapy increased cost/OSg and decreased ratings and scores. [Table: see text]
Targeted analysis of progressive metabolic perturbations in colorectal cancer in colorectal adenoma: Potential for a serum metabolomics-based colorectal cancer screening test.
Authors: Farshidfar Farshad , Weljie Aalim , Kopciuk Karen A. , Vogel Hans J. , Hilsden Robert , McGregor Elizabeth , Bathe Oliver F. 
Published: February 2017

426 Background: Colorectal cancer (CRC) could be resected and cured if detected at an early stage. A serum metabolomics-based screening test would represent a rapid and convenient means to identify adenoma and early CRC. However, changes in the metabolome with such minimal disease may be too subtle if the usual high throughput discovery approach were taken. We postulated that adenoma-associated metabolic changes could be better identified by targeting our analysis to metabolites that changed in a progressive manner with sequential stages of disease. Methods: Sera from patients with locoregional (LR CRC) and metastatic (mCRC) disease (stage I n=21, stage II n=30 , stage III n= 35, stage IVa n=67) and matched controls (n=121) were analyzed by gas chromatography-mass spectrometry (GC-MS). After normalization, batch correction and autoscaling, 249 features were selected. Metabolites that characterized CRC were filtered by identifying those metabolites that increased or decreased in a progressive manner with higher disease stage. Subsequently, sera from 31 adenoma patients and 31 matched controls, collected under standardized conditions prior to colonoscopy and polypectomy, were analyzed by GC-MS. "The variable importance” of metabolites identified in the first analysis were studied. Results: Products of fatty acid metabolism (dodecanoic acid, 2-amino butanoic acid, isocaproic acid, hexadecanoic acid) and urea were among metabolites that were altered more markedly in advanced disease stages. A number of metabolites that changed in this progressive fashion were found to change to a more subtle degree in adenoma. Conclusions: A targeted analysis of metabolites that change in a progressive fashion as CRC progresses represents a means to identify the subtle changes in the serum metabolome that accompany adenoma. This demonstrates the feasibility of developing a serum metabolomics-based screening test for CRC. In addition, extension of this selection approach can be used in other applications where minimal disease is challenging to detect with conventional statistical methods.
Retrospective review of FOLFIRI with or without bevacizumab (bev) for patients (pts) with metastatic colorectal cancer (mCRC): Reviewing a single-center standard clinical practice.
Authors: Maroun Jean Alfred , Marginean Horia 
Published: February 2017

434 Background: Use of bev with FOLFIRI proved, in clinical trials, to be well tolerated and clinically effective in mCRC pts. In this single-center retrospective review we assess outcomes of mCRC pts on standard first-line treatment with FOLFIRI alone and FOLFIRI bev in routine care. Methods: Patients treated with FOLFIRI at TOHCC from Jan 1, 2004 to Aug 10, 2010 on a first-line mCRC were followed until August 10, 2012. According to bev availability three groups of pts can be identified: treated with FOLFIRI bev and treated with FOLFIRI alone before and after bev availability (Sept 5, 2005). Results: Of 526 pts, 470 (89%) were eligible; 176 (37%) treated with FOLFIRI with bev and 294 (63%) with FOLFIRI alone—127 (43%) before and 167 (57%) after bev availability. At the start of FOLFIRI therapy there was no significant difference among the 3 groups: median age 62 (range 36-83), 61 (32-81), 64 (28-85) years, male 54%, 72%, 64%, respectively. Pts treated with FOLFIRI bev received a median 19 cycles (range 2-78) of FOLFIRI and a median of 15 cycles (range 2-63) of bev; 89 (51%) discontinued bev before FOLFIRI. Pts treated with FOLFIRI alone received a median 12 cycles (range 3-35) before bev availability and 13 cycles (2-48) after. Toxicity was responsible for at least 1 dose adjustment in 146 (83%) pts on FOLFIRI bev and 215 (73%) pts on FOLFIRI alone. Bev was held in 95 (54%) pts; once 35%, twice 25%. The median time off bev was 37 days. Median PFS was 17 months (95%CI 13-20) for patients treated with FOLFIRI bev. When we consider patients treated with FOLFIRI before bev availability median PFS was 13 mo (95%CI 10-17) and 14 mo (95%CI 10-16) when we consider pts post bev availability. Over a period of 3 years the survival rates in three groups of pts (FOLFIRI bev, FOLFIRI alone before bev availability, FOLFIRI alone post bev availability) were 1 year 90%, 77%, and 78%; 2 years 67%, 49%, and 56%; 3 years 54% , 31%, and 44%. Conclusions: Pts treated with FOLFIRI bev received more cycles of chemotherapy however with more dose adjustments. There is a relevant benefit in terms of PFS and a more substantial advantage in terms of 1, 2 and 3 years survival rates with the addition of bev to FOLFIRI.
PET scan as a prognostic marker in advanced colorectal cancer.
Authors: Kollepara Sri Lakshmi S. , Choi Minsig , Heilbrun Lance K. , Smith Daryn W. , Shields Anthony Frank , Philip Philip Agop 
Published: February 2017

442 Background: Clinical utility and ability to prognosticate using FDG-PET scan in metastatic colorectal cancer (mCRC) has not been well studied in previous literature. We hypothesized that standardized uptake value (SUV) in post treatment FDG-PET predicts clinical outcomes. Methods: We retrospectively reviewed mCRC patients who had pre and post treatment FDG - PET scans during 2005-2012 at Karmanos Cancer Institute. Primary end points of time to progression (TTP) and overall survival (OS) were compared between the two groups (follow up SUV = 0 vs. SUV > 0) using log-rank testing. Results: Study population consisted of 44 patients (median age of 58.1 years). Forty (91%) of these patients were treated first line and 34 (77 %) received an Oxaliplatin based regimen. Forty-one patients had both pre- and a post-treatment SUV. The 12 patients with post treatment SUV= 0 and the 29 patients with post-treatment SUV > 0 had median OS of 42 and 25.2 months, respectively; they had median TTP of 8.2 and 6.9 months, respectively. The patients with post treatment SUV= 0 had significantly longer OS (p = 0.0310) and weakly significantly longer TTP (p = 0.0628) compared to the patients with post-treatment SUV > 0. Conclusions: Systemic therapy decreased SUV on follow-up PET scans in the study population. Absence of FDG uptake on follow up PET scan was associated with longer OS and was suggestive of longer TTP in patients with metastatic colorectal cancer.
Predictors of radiotherapy-related gastrointestinal toxicity from anal cancer DP-IMRT: Secondary analysis of RTOG 0529.
Authors: Olsen Jeffrey R. , Moughan Jennifer , Myerson Robert J. , Abitbol Andre , Kunos Charles , Johnson Douglas , Schefter Tracey , Chen Yuhchyau , Fisher Barbara Jean , Michalski Jeff M. , Narayan Samir , Chang Albert , Crane Christopher H. , Kachnic Lisa A. 
Published: February 2017

460 Background: Radiation Therapy Oncology Group (RTOG) 0529 assessed feasibility of dose-painted intensity-modulated radiation therapy (DP-IMRT) to reduce the acute morbidity of chemoradiation with 5-fluorouracil (5FU) and mitomycin-C (MMC) for T2-4N0-3M0 anal cancer. This secondary analysis was performed to identify patient (pt) and treatment factors associated with acute and late gastrointestinal (GI) adverse events (AEs). Methods: RTOG 0529 treatment plans were reviewed to extract dose-volume data for tightly contoured small bowel (SB), loosely contoured anterior pelvic contents (APC), and uninvolved portions of colon outside the clinical target volume (UC). T-tests were performed to evaluate differences in the mean absolute volumes of each critical structure receiving doses ≥ 5 to 60 Gy (V5-V60) in 5 Gy increments between pts with and without ≥ grade (G) 2, acute and late GI AEs, and ≥G3 acute GI AEs using the NCI Common Terminology Criteria, version 3. Acute is defined as ≤ 90 days from the start of treatment and late is > 90 days. Additional factors (age, location, gender, race, Zubrod, grade, size, stage, prone vs supine position) were also evaluated in multivariate (MV) logistic regression (acute AEs) or Cox proportional hazards models (late AEs) to evaluate correlation with GI AEs. Results: Among 52 evaluable pts, ≥G2 acute, ≥G2 late, and ≥G3 acute GI AEs were observed in 35, 17, and 10 pts, respectively. Trends (p<0.05) towards statistically significant associations were observed between: ≥G2 acute GI AEs and SB dose (V20-V40); ≥G2 late GI AEs and APC dose (V60); ≥G3 acute GI AEs and APC dose (V5-V25), increasing age, tumor size >4cm, and worse Zubrod. SB and APC dose parameters remained correlated with GI AEs on MV analysis. Treatment in the prone vs supine position correlated with lower SB V10-V35 and APC V5-V20, although no significant differences in GI AEs were observed. Conclusions: Acute and late GI AEs from 5FU/MMC chemoradiation using DP-IMRT correlates with RT dose to the SB and APC. Further analysis is underway to determine critical structure cut-point parameters that may aid treatment plan optimization for anal cancer DP-IMRT. Supported by RTOG U10 CA21661, CCOP U10 CA3742 and ATC U24 CA 81647 NCI grants. Clinical trial information: NCT00423293.