bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of perioperative red blood cell transfusion on long-term survival after hepatectomy for colorectal liver metastases.
Authors: Hallet Julie I. , Tsang Melanie , Cheng Eva , Kulyk Iryna B. , Hanna Sherif , Law Calvin , Coburn Natalie G. , Karanicolas Paul Jack 
Published: February 2017

725 Background: Perioperative red blood cell transfusions (RBCT) are associated with postoperative morbidity and may increase cancer recurrence through immunologic mechanisms following resection of colorectal liver metastases (CRLM). We sought to explore the relationship between RBCTs and long-term survival following resection of CRLM in the contemporary surgical era. Methods: We conducted a retrospective review of a prospective database including all patients undergoing partial hepatectomy for CRLM from 2003-2012. Data regarding date of death was abstracted from a validated, population-based cancer registry. Primary outcome was overall survival (OS), compared based on RBCT (defined as time of surgery to 30 days following surgery) and on number of RBC units received using Kaplan-Meier curves. Cox regression analysis was performed to examine the association between RBCT and OS, while adjusting for prognostic factors including Fong score and period of treatment (2003-2007 vs. 2008-2012). Results: We included 483 patients operated for CRLM, of which 27.5% received RBCT. 90-day post-operative mortality was 4.8% and median follow-up was 33 (IQR: 20.1-54.8) months. Median survival in patients who received RBCT was 44.5 months compared with 93.5 months in patients who did not(p<0.0001). The difference persisted in subgroup analysis excluding patients who died within 90 days of surgery (62.3 vs. 93.5 months, p=0.023). After adjustment for Fong score and period of treatment, RBCT was independently associated with decreased OS (HR 2.15; 95% CI: 1.52-3.04). Conclusions: Perioperative RBCT is independently associated with decreased OS following hepatectomy for CRLM. Interventions to minimize and rationalize the use of RBCT for hepatectomy are warranted in order to mitigate this detrimental effect on long-term outcomes.
Resection of primary tumor in patients who present with stage IV colon cancer may result in improved survival.
Authors: Lewis Aaron , Nelson Rebecca A. , Lai Lily L. 
Published: February 2017

726 Background: Resection of the primary cancer in patients with metastatic disease has been shown to result in improved survival in cancers such as renal cell carcinoma. Currently, the impact primary tumor resection has on survival in stage IV colon cancer patients is unknown. Methods: The SEER dataset was queried for patients who presented with histologically confirmed, stage IV colon cancer from 1998-2011. We excluded patients with rectal cancer, multiple primary tumors, age <18 or >90 years, diagnosis upon autopsy/death record, mortality within 30 days of diagnosis, or resection of other tumor sites (regional or distant). Cox proportional hazard models were used to assess demographic and clinical factors predictive of disease specific and overall survival. To limit group differences, a 1:1 matched analysis was also performed on patients who underwent primary resection compared to patients who did not. Results: A total of 28,068 stage IV colon cancer patients were evaluated, of which 70.3% underwent resection. Among the variables studied, multivariate models showed that patients who underwent primary tumor resection were at lower risk of disease-specific and overall mortality, with hazard ratios (HR) of 0.44 (0.43-0.46) and 0.45 (0.43-0.47), respectively. In the matched analysis (n=5,410 in each group), patients who underwent resection of the primary tumor remained at decreased risk of disease-specific and overall mortality, HR 0.48 (0.45-0.52) and 0.49 (0.46-0.53), respectively. The median survival and 3-year survival after matching was 17 and 9 months and 23% and 6% in the resection and nonresection groups, respectively, p<0.0001. Conclusions: The majority (70.3%) of patients in the United States with stage IV colon cancer undergo resection of primary tumors. Analyses of SEER data suggests that resection of the primary tumor may result in improved DSS and OS in patients with stage IV colon cancer. A prospective, randomized trial is warranted to confirm a survival benefit.
Timeline analysis of adjuvant therapy timing in colorectal cancer to improve adherence to the 120-day quality measure.
Authors: Rashid Omar Maen , Coyne Karen A. , Ross Thomas W. , Shibata David 
Published: February 2017

729 Background: Multiple organizations, including ASCO, have developed accountability quality of cancer care measures that have been incorporated into accreditation, managed care contracts and quality monitoring. Institutional adherence to adjuvant chemotherapy (chemo) for stage III colon cancer (CC) provided within 120 days of diagnosis (Dx) is one such measure. We previously reported our institutional experience with reasons for non-adherence to this measure. We undertook an in-depth comparison of the clinical management timeline in adherent (A) and non-adherent (NA) cases to identify potential areas for process improvement to address this issue. Methods: All CC cases reported at a single institution from 2008–2012 were reviewed using ACS Commission on Cancer coding standards. Student t-test was used for statistical comparisons. Results: Of the 122 measure-eligible cases 16 (13.1%) were deemed NA. Of NA cases, 2(12.5%) were lost to follow up and 14(87.5%) received delayed chemo. In NA cases, the mean time from initial Dx to chemo was 159.5(+/-51) days vs. 68.7(+/-24.5) days in A cases (p=2x10-6). The Table reports the mean interval times between diagnosis, initial visit, surgery, medical oncology consultation, and receipt of chemo. The most significant differences between A and NA cases were in the pre-operative time period and related to obtaining the initial consultation and subsequent surgical treatment. Conclusions: Treatment timeline analysis revealed the most prominent delays were time to initial presentation and to surgical intervention. These areas could potentially be addressed by measure awareness, streamlining of scheduling and improved inter-provider communication. With the inevitable implementation of such measures, institutions may benefit from similar systematic evaluations for process improvement. [Table: see text]
Amphiregulin (AREG) expression and response to first-line panitumumab (pmab) plus FOLFIRI in metastatic colorectal cancer (mCRC).
Authors: Kohne Claus-Henning , Hofheinz Ralf , Mineur Laurent , Letocha Henry , Greil Richard , Thaler Josef , Twomey Brian , Oliner Kelly Smith , Boedigheimer Michael , Terwey Jan-Henrik , Karthaus Meinolf 
Published: February 2017

731 Background: Biomarker analyses have shown that patients (pts) with RAS wild-type (WT) mCRC can achieve overall survival (OS) benefits with first-line pmab plus chemotherapy. Other biomarkers may exist that could optimize pt selection. Epidermal growth factor receptor ligand (eg AREG) levels have been correlated with OS during anti-EGFR therapy. Here we investigate the relationship between AREG expression and treatment outcome in a single-arm first-line mCRC study of pmab + FOLFIRI. Methods: Qualified reverse transcription quantitative polymerase chain reaction (RT-qPCR) assays were used to measure AREG RNA expression in archival formalin-fixed, paraffin embedded tumor samples from mCRC pts in two pmab trials (STEPP and 314). The STEPP analysis was used to establish a cut-off point in AREG expression that identified the best responders. This cut-off was applied prospectively to samples previously analyzed for KRAS in the 314 trial. Using the KRASMT subgroup as a non-responding comparator, Cox proportional hazards (PH) models were used to evaluate AREG expression levels as a continuous covariate. Decision curves were used to estimate the progression-free survival (PFS) hazard ratio (HR) with increasing levels of baseline AREG expression. Results: In the 314 trial 100 pts had evaluable AREG levels. Among 50 KRAS WT pts, high AREG expression was associated with objective response (OR) (Table). The high AREG group had better PFS HRs (KRAS WT/KRAS MT: 0.30 [95% CI, 0.12–0.75]) compared with the low AREG group (PFS HR 0.49 [95% CI 0.21–1.1]). There was a significant biomarker-by-AREG expression interaction in the Cox PH model (p=0.03). Conclusions: Treatment decision curves based on the PH model suggest that most KRAS WT patients express AREG at levels where treatment benefit is predicted. Future analysis of samples from a RASWT population may provide further insights. Clinical trial information: NCT00508404. [Table: see text]
A phase II trial of panitumumab with irinotecan and S-1 (IRIS) as second-line treatment in patients with wild-type KRAS metastatic colorectal cancer.
Authors: Shimoyama Rai , Kimura Tetsuo , Takaoka Toshi , Sakamoto Kazuki , Kawamoto Shunji , Yoshizaki Koji , Negoro Yuji , Goda Fuminori , Tsuji Akihito , Nakayama Tsuyoshi , Miyamoto Hiroshi , Takayama Tetsuji , Niitsu Yoshiro 
Published: February 2017

732 Background: Panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) in second-line chemotherapy increased objective response rate and prolonged progression-free survival (PFS) versus FOLFIRI alone in patients with wild-type (WT) KRAS metastatic colorectal cancer (mCRC) (Peeters et al, J Clin Oncol 2010). This trial (UMIN000004659) evaluated tolerability and efficacy of combination therapy with irinotecan and S-1, an oral fluoropyrimidine (IRIS) plus panitumumab as second-line chemotherapy in patients with WT KRASmCRC. Methods: Main inclusion criteria were: patients with WT KRAS mCRC refractory to one prior chemotherapy regimen for mCRC, ECOG PS 0-2, and age ≥20 years. Patients received panitumumab (6 mg/m2) and irinotecan (100 mg/m2) on days 1 and 15 and S-1 (40-60 mg according to body surface area) twice daily for 2 weeks, repeated every 4 weeks. The primary endpoint was completion rate of protocol therapy (CRT). The secondary endpoints were response rate (RR), progression-free survival (PFS), and overall survival (OS). Results: Thirty-seven patients were enrolled in 9 centers. The overall CRT was 62.2% (23/37). Most frequent grade 3/4 toxicities were: skin rash (24%), diarrhea (16%), and appetite loss (11%). The overall RR was 32.4% (12/37). Of these, four patients underwent conversion surgery. Median PFS and OS were 9.5 months (95% CI: 3.5-15.4 months) and 20.1 months (95% CI: 16.7-23.2 months), respectively. Conclusions: IRIS plus panitumumab has acceptable toxicity profile and promising efficacy in patients with previously treated WT KRAS mCRC. This regimen can be an additional treatment option for second-line chemotherapy in WT KRAS mCRC. Clinical trial information: UMIN000004659.
Stereotactic body radiotherapy (SBRT) in difficult-to-treat areas (para-aortic lymphadenoapthy and pelvic recurrence) in oligometastatic colorectal carcinoma.
Authors: Bhattacharya Indrani Subarna , Woolf David , Hughes Robert , Harrison Mark 
Published: February 2017

733 Background: Oligometastatic (OM) colorectal carcinoma (defined as three or fewer sites of isolated metastatic disease) may occur in potentially difficult to treat areas (including para-aortic lymphadenopathy and pelvic recurrence). Proximity of critical structures and previous irradiation may prove treatment of OM disease challenging. The aim of this study was to identify local control, overall survival (OS), and progression free survival (PFS) of patients receiving SBRT for difficult to treat oligometastatic disease (para-aortic lymphadenopathy and pelvic recurrence). Methods: Data were prospectively collected for patients receiving SBRT between 1/9/10-31/3/14, including demographic details, SBRT date, date of local/distant progression, toxicity, and date of death. Data was collected until 1/6/14. All patients were discussed within a specialist SBRT MDT and planned for treatment utilizing the Cyberknife (Accurray) treatment system. Treatment doses included 24 Gy/3F (22.7%), 27 Gy/3F (27.3%), 30 Gy/3F (13.6%), 30 Gy/5F (4.5%), 33 Gy/3F (22.7%), 36 Gy/3F (9.1%). Total dose was determined by surrounding normal tissue toxicities. Results: 9 received SBRT for para-aortic lymphadenopathy and 13 for pelvic recurrence. Median age was 58 (38-81) years. 14 were male. Median follow-up was 8.0 (0.5-28.0) months. 59.1% patients were treated within a prior radiotherapy treatment volume. 31.8% patients were disease free after SBRT. 63.6% had distant relapse and 4.5% had local and distant relapse. Local control was 95%. Median time to relapse was 4.5 (1.2-37.2) months. OS was 72% at 1 year and 46% at 2 years. PFS was 36% at 1 year and 27% at 2 years. Significant toxicities included 1 patient with duodenal ulcer formation following para-aortic node SBRT. Conclusions: Our prospective series confirms excellent local control (95%) with SBRT for OM colorectal carcinoma in areas considered to be difficult to treat, and with limited toxicity.
Surrogacy of progression-free survival (PFS) for overall survival (OS) in rectal cancer trials with preoperative therapy: Literature-based meta-analysis.
Authors: Mizusawa Junki , Nakamura Kenichi , Kataoka Kozo , Eba Junko , Katayama Hiroshi , Shibata Taro , Fukuda Haruhiko 
Published: February 2017

734 Background: Disease-free survival (DFS) after adjuvant chemotherapy in colon cancer has been validated as a surrogate endpoint for OS. An analysis of individual patient data from two randomized controlled trials evaluating preoperative chemoradiotherapy for rectal cancer has already shown that PFS might be a surrogate endpoint for OS (Eur J Cancer, 2012). However, since the report was derived from only two trials, the further evaluation of surrogacy with a larger number of trials is desirable. This study was conducted to explore the trial level correlations between PFS and OS in resectable rectal cancer with preoperative therapy. Methods: A systematic literature search of randomized trials of preoperative chemoradiotherapy, radiotherapy or chemotherapy for rectal cancer reported from January 1990 to September 2014 was conducted using PubMed and the Cochrane library. Weighted linear regression using sample size of each trial as a weight was used to estimate coefficient of determination (R2) within PFS and OS. 95% confidence interval of R2 was estimated by bootstrap method. The primary analysis included trials in which the HR of PFS and OS were reported. A sensitivity analysis included the trials in which either HR or 5 years point estimates of PFS and OS was reported. In the sensitivity analysis, HR was estimated from the point estimates of PFS and OS assuming exponential distribution. Results: Of 1,048 articles, 14 trials (7,233 patients) were selected for the primary analysis and 18 (8,020) for the sensitivity analysis. Median numbers of enrolled patients were 332 (range 113-1,805) in primary analysis, and 296 (113-1,805) in sensitivity analysis. The primary analysis did not show the correlation between treatment effects on PFS and OS(R2 0.408; 95% CI [0.133-0.845]). The sensitivity analysis showed modest correlation between PFS and OS (R2 0.603; 95% CI [0.296-0.871]). Conclusions: The primary analysis showed that PFS was not suitable as a surrogate endpoint, which is contradictory to the previous report. Based on our results, OS is still preferable as the primary endpoint in the trials of preoperative therapy for resectable rectal cancer.
Colorectal cancer surgery in extreme elderly population.
Authors: Gallego Plazas Javier , Asensio Martinez Elena , Ore Martin , Cotes Almudena , Ricote Guillermo , Lozano Inmaculada , Ors Mamen , Magdaleno Alejandra , Baron Jose M. , Escudero Maria J , Navarro Jose M , Morcillo Miguel A 
Published: February 2017

738 Background: Colorectal cancer surgery in extreme elderly population ( ≥80 years) is a growing problem and a subject in question. Experiences and results in this scenario are limited. Methods: Medical records of patients ≥80 years old hospitalized in General Surgery Department in Vega Baja Hospital between January 1, 2008, and December 31, 2012, were retrospectively reviewed. Patients diagnosed with colorectal cancer (CRC) were selected. Data regarding comorbidity, treatment performed, complications, and survival were collected. Results: 95 patients (74 colon, 21 rectum) were identified: median age 83.9 years (80-93), 64.2% males. 93.7% of patients were operated on: median hospital and post-operative stay of 14.1 and 11 days, respectively; curative intention surgery 82.1%. 5.4% of patients were treated with interventionist procedures, and 2.1% of patients in a conservative way. 17.9% and 4.2% of patients came up with early and late complications, respectively. Early and late mortality occurred in 9.5% and 3.2% of patients, respectively. There was no statiscally significant association between number of comorbidities and morbi-mortality. Early complications were more frequently associated to bronchopathy (33%) or cardiopathy (25.9%), while late complications were to diabetes (15%), congnitive disorders (12.5%), and cardiopathy (7.4%). Late mortality ocurred more frequently associated to diabetes (5%) and cardiopathy (3.7%). Colon cancer was more frequently associated to early complications and early and late mortality, maybe explained with more unscheduled surgeries. By March 2014, with a median folluw up of 43.8 months, 37.9% of patients are alive free of relapse, 2.1% are alive with disease, 26.3% had died of cancer, 10.5% had died of surgery related complications, and 23.2% of patients had died of other causes. Conclusions: Certain comorbidities and not the addition of them were associated with morbidity and mortality due to CRC surgery. Personalizing CRC treatment in a extreme elderly population may result in extended survival in this increasing subgroup of patients.
Antitumorigenic effect of plumbagin by induction of SHP1 in human gastric carcinoma cell lines.
Authors: Koh Jin Sung , Park Jong-Jae , Joo Moon Kyung , Yoo Hyo Soon , Kim Jiwon , Jeoung Yong , Kim Ho , Choe Jung Wan , Lee Beom Jae , Kim Jae Seon , Bak Young-Tae 
Published: February 2017

74 Background: Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) is a plant-drived natural agent extracted from the root of Plumbago zeylanic. A recent study reported that plumbagin down-regulated the activity of Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway to show various anti-tumor effects. We aimed in this in vitrostudy to demonstrate the inhibition of JAK2-STAT3 pathway by plumbagin through inducing SH2-containing protein tyrosine phosphatase 1 (SHP1) expression in gastric cancer cell line. Methods: We performed Wetern blot to measure SHP1, phospho-JAK2/STAT3 level, and reverse transcriptase-polymerase chain reaction (RT-PCR) to evaluate target gene expression of STAT3. Several functional studies such as water soluble tetrazolium-1 (WST-1) assay, wound closure assay and matrigel invasion assay were also performed. Results: Plumbagin induced SHP1 expression and simultaneously down-regulated phospho-JAK2/STAT3 level via dose-and time-dependant manner in MKN28 cell, a gastric carcinoma cell line which has negative SHP1 expression. This effect was consistent when JAK2-STAT3 signaling was activated by interleukin-6, and ameliorated when cells were treated with prevanadate, a protein tyrosin phosphatase inhibitor. Furthermore, plumbagin significantly reduced gene expression of cyclin D1, VEGF1, survivin, MMP9, known target products of STAT3 activation in gastric cancinogenesis. The functional effect of plumbagin could be validated as inhibition of cell proliferation, migration and invasion, which are the results of activation of JAK2-STAT3 pathway in gastric cancer cells. Conclusions: Plumbagin is a potential negative regulator of cellular growth, migration and invasion by inhibiting both constitutive and inducible STAT3 activity through induction of SHP1 in gastric cancer cells.
Attitudes of patients towards cancer clinical trials.
Authors: Ayodele Olubukola , Akhtar Mateen , Eastwood Mathew Chad , Linkeviciute-Koneko Aiste , Keegan Niamh M. , Calacsan Flordeliza , O'Connor Miriam , Calvert Paula , Horgan Anne M. 
Published: February 2017

741 Background: Older patients (pts) with cancer are under-represented in clinical trials (CTs). To better understand the causes for low accrual rates, the pts perspective must be explored. Objectives: To determine the attitudes of Irish pts towards enrolment into cancer CTs and in particular, the differences between the attitudes of older and younger pts. Methods: Pts with a gastrointestinal cancer, receiving treatment or in follow-up in University Hospital Waterford were eligible. Pts completed a self-dministered questionnaire comprising three sections: attitudes towards CT participation, reasons to participate, and reasons to decline participation. Pts were given three CT scenarios and were asked if they would participate: these included a cancer prevention/screening CT; a CT comparing standard to new treatment and a trial of a new drug where no standard exists. Summary statistics were used to describe the respondents. Differences between the groups were investigated using the Fishers exact test. Results: From March 2014, 69 pts were accrued, 31 <65 yrs (32-64) and 38 ≥65 yrs (65–85). Five (16%) younger and 3 (8%) older pts had been or were actively enrolled on a CT (p=0.45). An additional 4 (17%) younger and 5 (13%) older pts were invited to participate in a CT, all of whom declined. No patient in either group had actively enquired about CT availability. For the CT scenarios, 22 (71%) younger vs. 22 (58%) older pts would participate in a prevention/screening CT (p=0.32); 14 (45%) vs. 19 (50%) for standard vs. new drug CT (p=0.81), and 23 (74%) vs. 31 (82%) for a CT where no standard exists (p=0.56). The most common reasons to participate in a CT included the potential to feel better, reported in 100% of younger and older pts, the potential to live longer (100% vs. 92%) and the potential to help others (97% vs 89%). Age was deemed an important consideration in 20 (65%) younger and 25 (66%) older pts. Conclusions: The attitudes of older and younger pts to cancer CTs are similar. Physician barriers and availability of appropriate studies impact accrual of both older and younger cancer pts into trials. No patient in this study actively sought out a CT, suggesting a need for better patient awareness and education. This study is ongoing and updated results will be presented.