bluuebunny/crossref_metadata_2025_split huggingface dataset:
Morbidity of staged proctectomy after hepatectomy for colorectal cancer: A matched case-control analysis.
Authors: Tzeng Ching-Wei David , Chang George J. , Curley Steven A. , Vauthey Jean-Nicolas , Ellis Lee M. , Skibber John Michael , Feig Barry W. , Abdalla Eddie K. , Aloia Thomas A. , You Y. Nancy , Rodriguez-Bigas Miguel A. 
Published: February 2017

629 Background: Proctectomy after hepatectomy, or the “reverse approach,” is an alternative to traditional sequencing for advanced liver metastases with asymptomatic colorectal primaries. However, perioperative morbidity from staged proctectomy remains uncharacterized. We sought to identify risk factors for morbidity in these patients. Methods: A single-institution colorectal database was queried for patients treated with proctectomy after previous hepatectomy from 2003-2011. Reverse approach patients (31) were matched 1:2 with a cohort of standard proctectomy patients (62), using operation, age, sex, and surgeon. Perioperative factors were analyzed by univariate/multivariate models for associations with complications graded by Dindo-Clavien criteria. Results: 31 patients with adenocarcinoma ≤20 cm from the anal verge underwent proctectomy after hepatectomy. Median time from hepatectomy to proctectomy was 5.1 mo. Median tumor distance was 8.5 cm from the anal verge. No patients with primary tumors in situ recurred in the liver while awaiting proctectomy after hepatectomy. Prior to proctectomy, there were 28 (90%) major hepatectomies and 7 (22%) portal vein embolizations. Grade ≥2 complications developed in 42% of reverse approach and 27% of standard proctectomies (p=0.17). Grade 3 complications developed in 10% and 8%, respectively (p=1.00). There were no perioperative deaths. Reverse approach patients did not differ from the control cohort in operation, demographics, body mass index (BMI), comorbidities, tumor distance, operative time, estimated blood loss (EBL), length of stay, or complication rates (p>0.05). Independent predictors of Grade ≥2 complications were BMI ≥30 (p=0.007), operative time ≥300 min (p=0.012), intraoperative transfusion (p=0.044), concurrent procedures (p=0.024), and age ≥50 (p=0.030). Independent factors for Grade 3 complications were operative time ≥300 min (p=0.015), intraoperative transfusion (p=0.011), and EBL ≥300 ml (p=0.047). Conclusions: Risk factors for morbidity of staged proctectomy are similar to those for standard proctectomy. When applied to selected patients, the reverse approach is safe with acceptable morbidity.
Long-term survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy compared with hepatic resection for metastatic colorectal cancer.
Authors: Blackham Aaron Udell , Russell Greg B. , Stewart John H. , Votanopoulos Konstantinos Ioannis , Levine Edward Allen , Shen Perry 
Published: February 2017

630 Background: Surgical resection of peritoneal metastases (PM) from colorectal cancer has been reported to yield outcomes similar to liver resection for hepatic metastases (HM). However recent data suggests PM may have a worse prognosis than other metastatic sites. Methods: A review of metastatic colorectal cancer patients obtained from prospective databases (1992-2010) comparing liver resection for HM to cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for PM. Results: 181 patients underwent hepatic resection and 182 patients underwent CS/HIPEC with a median follow-up of 55 and 106 months respectively. A margin-negative resection was obtained in 168 (93%) hepatic resections, while 89 patients (49%) with PM had complete cytorection of all gross disease (R0/R1). A comparison of these two groups demonstrated significant differences in age, pre-operative chemotherapy and performance status. Disease-free median survival was 15.2 months after hepatic resection and 9.9 months after CS/ HIPEC (p=0.02). The 5-year overall survival (OS) for HM patients was 33% with a median OS of 45.0 months; while 5-year OS was 23% and median OS was 32.3 months for PM patients (p=0.02). In a proportional hazards regression model, performance status and pre-operative chemotherapy had no significant effect on survival, while increased age (p=0.02) and PM (p=0.03) were associated with decreased OS. Postoperative morbidity was 38% versus 51% (p=0.04) and mortality was 3.0% versus 2.3% (p=0.73) in the HM and PM groups, respectively. Conclusions: Disease-free survival and OS are worse for patients who received complete cytoreduction and CS/HIPEC for PM compared to margin-negative liver resection for HM suggesting a more aggressive tumor biology in PM.
The influence of seminal events on the transition from adjuvant to neoadjuvant chemoradiation in the treatment of locally advanced rectal adenocarcinoma (LARC).
Authors: Warner Jeremy , Miksad Rebecca A. , Nagle Deborah , Najarian Robert , Goldstein Michael 
Published: February 2017

631 Background: Factors leading to uptake of new oncology treatment innovations are poorly understood. In particular, the degree to which seminal events, such as report of pivotal phase III trials, influence practice is unclear. For example, preoperative (pre-op) 5-fluorouracil + radiation (5-FU + RT) is the current standard of care for definitive treatment of LARC. However, postoperative (post-op) 5-FU + RT was standard before the seminal German Rectal Cancer Study Group (GRCSG) results were published. We investigated the impact of seminal events on the change in practice pattern from pre- to post-op 5-FU + RT at our institution. Methods: Patients with LARC (T2N+; any T3; any T4) treated at our institution between 1994-2010 were identified from the cancer registry. The date of diagnosis was compared to the dates of three seminal events: A) JAMA meta-analysis publication; B) publication of GRCSG results; C) founding of a multidisciplinary clinic at our institution. Pearson Chi square was used for univariate analysis. Results: 334 patients were evaluable. RT +/- 5-FU was delivered pre-op for 207 patients, post-op for 127 patients. The unadjusted odds ratio (OR) for receiving pre-op treatment after vs. before each seminal event was similar: (A) 4.16; (B) 4.08; (C) 3.91. When patients diagnosed prior to (A) or after (C) were excluded, (B) appeared to have a smaller effect, OR 2.07 (p = .053) (Table). Conclusions: All seminal events had similar associated OR, indicating that the process of uptake of the innovation of pre-op 5-FU + RT was gradual. The seminal GRCSG publication, when temporally isolated, had only modest effect. This suggests that report of seminal results is necessary but not sufficient for uptake of a new therapy innovation in LARC at our institution. Whether this pattern of uptake is generalizable is worthy of further investigation. [Table: see text]
Panitumumab (Pmab) versus cetuximab (Cmab)/irinotecan (Iri) therapy among patients with KRAS wild-type (wt) metastatic colorectal cancer (MCRC).
Authors: Kennecke Hagen F. , Chen Leo , Blanke C. D. , Cheung Winson Y. , Schaff Kimberly , Speers Caroline 
Published: February 2017

640 Background: In British Columbia, use of anti-EGFR therapy for KRAS wt MCRC is limited to patients (pts) previously treated with both irinotecan and oxaliplatin. Physicians may choose either Pmab monotherapy or Cmab/Iri combination therapy. We sought to compare the characteristics and outcomes of all pts treated with Pmab/Cmab referred to 5 provincial cancer centers since July, 2009. Methods: Eligible patients received at least one dose of either Pmab (6mg/kg q2w) or Cetuximab (500mg/m2 q2w) plus Iri (180mg/m2 q2w). Baseline characteristics and systemic therapy were prospectively collected, while ECOG and metastatectomy status were retrospectively collected. Kaplan-Meier survival analysis was conducted from the first day of Pmab/Cmab. Results: Among 178 eligible pts, Pmab was chosen 3 times more often than Cmab/Iri (see table). Pts treated with Cmab/Iri were significantly younger and had better performance status than those treated with Pmab. There were no statistically significant differences in other prognostic variables, and a similar proportion received chemotherapy after Pmab vs. Cmab/Iri. Overall survival was slightly longer among patients receiving Cmab/Iri (8.3 mo), vs. Pmab (7.7 mo) (p=.03). Conclusions: Pmab was chosen more often than Cmab/Iri for similarly eligible patients. Cmab/Iri pts were younger, were more likely to have ECOG performance status 0/1 and achieved a modestly longer overall survival. Either regimen appears to be suitable for previously treated pts with KRAS wt MCRC. [Table: see text]
Modified FOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizumab beyond first progression in advanced colorectal cancer: CCOG-0801 study.
Authors: Ishigure Kiyoshi , Nakayama Goro , Uehara Keisuke , Yokoyama Hiroyuki , Ishiyama Akiharu , Eguchi Takehiko , Tsuboi Kenji , Ando Yuichi , Kodera Yasuhiro 
Published: February 2017

641 Background: Bevacizumab provides survival benefit as the first-line and second-line therapies in metastatic colorectal cancer (mCRC). A large observational study suggested use of bevacizumab beyond first progression (BBP) improved survival. This prompted us to conduct a multicenter phase II study of mFOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizimab in mCRC to further explore the strategy of BBP in Japanese patients. Methods: Previously untreated patients with assessable disease were treated with mFOLFOX6 plus bevacizumab until tumor progression, followed by FOLFIRI plus bevacizumab. The primary endpoint of the study was the second progression-free survival (2nd PFS), defined as duration from enrollment until progression after the second-line therapy. If the patient failed to receive the second-line treatment due to medical reasons or refusal, the PFS during the first-line therapy was used for analysis. Secondary endpoints were PFS, overall survival (OS), response rate (RR), disease control rate (DCR) and safety. Results: In the first-line therapy, 47 patients treated with mFOLFOX6 plus bevacizumab achieved RR of 61.7%, DCR of 89.4% and median PFS of 11.7 months. Thirty patients went on to receive the second-line therapy with FOLFIRI plus bevacizumab and achieved RR of 27.6%, DCR of 62.1%, and median PFS of 6.0 months. Median 2nd PFS was 16.2 months. Median survival time did not reach the median follow-up time of 27.4 months. Severe adverse events associated with bevacizumab during the first-line therapy were a venous thromboembolic event in one case (2%), a grade 2 bleeding event in one case (2%) and GI perforation in one case (2%). However, no critical events associated with bevacizumab were reported during the second-line therapy. Conclusions: The planned continuation of bevacizumab during the second line treatment is feasible in Japanese mCRC patients. A prospective randomized control study to confirm the efficacy has to be conducted in the future.
A phase I/II study of biweekly XELIRI plus bevacizumab for patients with metastatic colorectal cancer as second-line chemotherapy (BIXER study): Reports of phase I part and interim analysis of phase II part.
Authors: Suenaga Mitsukuni , Matsusaka Satoshi , Shinozaki Eiji , Mizunuma Nobuyuki , Hatake Kiyohiko , Yamaguchi Toshiharu 
Published: February 2017

643 Background: Capecitabine is an oral fluoropyrimidine prodrug, which is converted to fluorouracil (5-FU) predominantly in the tumor cells. In Japan, capecitabine is mainly used in combination with oxaliplatin (XELOX) in treatment for metastatic colorectal cancer (mCRC) since its approval in 2009. The results of capecitabine plus Irinotecan (CPT) (XELIRI) with or without bevacizumab (BV) in EU or US patients were previously reported, but not in Japanese. Thus, we conducted this study to assess the safety and efficacy of XELIRI plus BV in Japanese patients with mCRC. Methods: Patients with prior chemotherapy including oxaliplatin and BV for mCRC, wild or hetero type of UGT1A1 *6*28 were eligible for this study. This was a phase I study composed of two steps, and dose limiting toxicity (DLT) was assessed during the first treatment cycle. Treatment comprised capecitabine 1,000 mg/m2 twice daily from the evening of day 1 to the morning of day 8, intravenous CPT 180 mg/m2 on day 1, and BV 5mg/kg on day 1 every two weeks. To evaluate the initial safety, 3-6 patients received XELIRI+BV (CPT 150mg/m2) in step 1, and 6 patients received XELIRI+BV (CPT 180mg/m2) in step 2. If DLT occurred in 1 patient in step1, 3 patients would be newly added to step 1, and if in none of 3 or 1-2 of 6 patients, the step 2 would be started. If DLT occurred in less than or equal to 2 of 6 patients in step 2, phase II study would be proceeded, and if In more than 2 of 6 patients, phase II would be conducted at the recommended dose of step 1. Results: In step 1 and 2 of phase I, initial safety of 9 patients was confirmed without occurrence of DLT. Adverse events observed in step 1 and 2 were: neutropenia in 2 and 1; anorexia in 1 and 1; diarrhea in 1 and 1; stomatitis in 1 and 1; alanine or aspartate aminotransferase increased in 1 and 3, respectively. There was no grade 3 or greater adverse events. Conclusions: In mCRC patients with wild or hetero of UGT1A1*6*28 genotype, safety of biweekly XELIRI+BV was confirmed and recommended dose of CPT-11 was determined as 180mg/m2. Interim analysis of safety of phase II part will be reported at the meeting.
Effectiveness of gemcitabine and capecitabine in advanced colorectal cancer patients: A retrospective analysis.
Authors: Salgado Mercedes , Reboredo Margarita , Medina Ana , Quintero Guillermo , Pellon Maria Luz , Romero Reinoso Carlos , Jorge Mónica , Fernandez-Montes Ana ,   Asociacion Grupo Gallego de Investigacion en Tumores Digestivos (GITuD)
Published: February 2017

649 Background: In ASCO2004, Y. Fernandez et al. showed their experience in gemcitabine/capecitabine use in patients with metastatic advanced colorectal cancer (ACRC), with previous progression or contraindicated standar treatment, with encouraging results. This study was design to evaluate the efficacy and safety of this combination in these patients, in our area. Methods: This is an observational, multicentric and retrospective study performed in metastatic colorectal cancer patients refractory to treatment. The study treatment was to evaluate the gemcitabine/capecitabine (gemcitabine 1000 mg/m2, day 1+ capecitabine 1250 mg/m2/12hours, days 1-7, every 15 days) until progression or unacceptable toxicity. The principal endpoint was the best overall response rate achieved during the study period. Secondary endpoints were Progresión Free Survival (PFS), Overall Survival (OS) and safety profile. Results: Of 45 patients recruited a total of 39 patients were evaluated. Median age was 66(37-78) and 69.2 were male. 86.8% of the patients were ECOG PS 1. Mean time from diagnostic was 2.7±2.4 years. Primary tumor was: colon 73.7%, rectum 23.7% and both 2.6%. Adjuvant therapy was received in 34.3% of the patients. Metastatic locations were: liver 82.1%, lung 64.1% and lymph nodes 25.6%. Previous treatment lines received: two 48.7%, three 23.1%, four 17.9%, five 7.7% and six 2.6%. The mean of cycles were 6.4±6 and mean time of treatment was 3.3±2.8 months. Best response during treatment period was partial response 2.9%, stable disease 17.6% and progression 79.4%. OS was 7.32 months and median PFS was 3.02 months. Most frequent toxicities grade 3 experienced: Palmar plantar erythrodysesthesia 5.1%, neutropenia 5.1%, asthenia 2.6%, dyspnea 2.6% and hiperbilirrubinemia 2.6%. No grade 4 toxicities were reported. Conclusions: Despite of the adequate safety profile of the gemcitabine/capecitabine combination, our study does not confirm the efficacy figures reported by others authors. New agents or combinations should be investigated in the treatment of this patient subgroup.
Prescribing patterns for bevacizumab in first-line metastatic colorectal cancer: Exploring the introduction of a new drug into routine clinical practice.
Authors: Field Kathryn Maree , Desai Jayesh , Tie Jeanne , Kosmider Suzanne , Bae Susie , McKendrick Joseph James , Harold Michael , Gibbs Peter 
Published: February 2017

665 Background: Clinical trials support the addition of bevacizumab (Bev) to first line chemotherapy for metastatic colorectal cancer (mCRC). However, given that there are alternate biological agents that can be used with chemotherapy; and rare but potentially serious toxicities with Bev, there has been variable use of the drug in routine care. The purpose of this study was to prospectively explore 1st line use of Bev in routine clinical care. Methods: A multi-site data collection was initiated in July 2009 when Bev became publicly available in Australia. A particular focus was capturing information regarding clinician decision-making that is not routinely recorded or is often poorly documented. Comprehensive comorbidity data was collected, along with specific factors, both patient (pt) and disease-related, that may impact on treatment decisions. Major adverse events that may be related to Bev were also recorded. Results: For the 2-year period from July 2009-June 2011, a database search identified 278 pts diagnosed with mCRC at five participating hospitals. 240 pts (86%) had received 1st line chemotherapy. 102 (43%) also received Bev, the majority in combination with oxaliplatin based chemotherapy (n = 81, 79%). Bev use increased significantly from 40.4% (34/84) of all pts receiving chemotherapy in July-December 2009, to 65.8% (25/38) in January-June 2011 (p=0.0114). Overall the most frequent reasons for clinicians advising against the use of Bev were a bleeding or asymptomatic primary in situ (n=28, 23%), known hypertension (n=14, 11%), clinical trial participation (n=14, 11%), poor performance status (n=9, 7%), and perceived risk of arterial ischemic event (n=8, 6.5%). There have been four episodes of gastro-intestinal perforation, 3 in pts receiving Bev (2.9% of Bev treated patients). Conclusions: Bev use in first line mCRC has significantly increased over time, presumably as further positive safety data emerges regarding safety in older and frailer pts, and clinician prescribing experience increases. The major grounds for not using Bev in the 1st line mCRC setting were specific clinical contexts where the risk of adverse events may be increased.
Development of a comprehensive set of colorectal cancer care quality metrics.
Authors: McCahill Laurence E. , Kokko Jamie , Werkemma Chris , Ebrom Pierson , Khandavalli Sarat 
Published: February 2017

670 Background: Institute of Medicine report calls for improved quality of cancer care. Numerous entities have sought measures of health care quality, but there is limited consensus regarding metrics for quality of colorectal cancer (CRC) care. Current measures are very limited; there exist no comprehensive metrics for quality of CRC care across the continuum of care. We sought to identify robust quality metrics, including measures related to pathology, coordination of cancer care, surgery, radiation, chemotherapy and surveillance, in order to identify gaps in quality of CRC care. Methods: National guidelines (NCCN and ASCO), National Quality Forum, and select peer reviewed publications were reviewed to develop evidence based metrics to assess quality of CRC care from diagnosis to post treatment surveillance and survivorship. A core group of health care providers, including a surgical oncologist, a pathologist and a Cancer nurse practitioner developed the metrics based on literature review. Measures were reviewed by key physician stakeholders including Radiation Oncology, Medical Oncology, General surgery, and Gastroenterology to obtain support for the quality initiative at our institution. Results: Twenty-three quality metrics were developed including 6 metrics related to access and process, 6 related to pathology, 7 related to multidisciplinary care and 4 measures related to surveillance and survivorship. Novel metrics included documentation of a three generational cancer family history, documentation of preoperative CT imaging of chest/abdomen/pelvis, MSI and KRAS testing in specific populations, appropriate pre-operative radiation oncologist evaluation for rectal cancer, multidisciplinary team planning prior to treatment initiation for rectal cancer and patients with newly identified liver metastases, appropriate referral for genetic counseling and surveillance annual CT scans for 3 years post treatment. Conclusions: These novel and comprehensive metrics allow for detailed review of the quality of CRC care received by patients at our institution. Individual patient data are currently being abstracted to assess the utility and logistics of implementing these quality metrics at a community cancer center.
Retrospective analysis of pathologic response in colorectal cancer liver-only metastases following treatment with bevacizumab.
Authors: Vera Ruth , Figueras Joan , Gomez Dorronsoro Maria Luisa , Lopez-Ben S. , Viúdez Antonio , Queralt Bernardo , Hernandez Irene , Scalzone R. , Zazpe Cruz , Ortiz R. 
Published: February 2017

674 Background: Recent reports have shown that pathological response predicts for better outcome (overall survival) following preoperative chemotherapy and surgical resection of colorectal cancer (CRC) liver-only metastases. The aim of this retrospective analysis was to evaluate the effect of adding bevacizumab to standard chemotherapy on pathological response in patients with CRC liver only metastases. Methods: Patients with stage IV CRC with liver metastases who received neoadjuvant chemotherapy (oxaliplatin-or irinotecan-based) at two Spanish centres were analysed retrospectively. Pathological response was evaluated as follows: complete pathological response (cPR), PR1 (25% of residual tumour), PR2 (25–50% of residual tumour), PR3 (>50% of residual tumour). cPR or PR1 was considered to be a good response, and PR2 or PR3 a poor response. Results: A total of 81 patients were evaluated. Of these, 43 received chemotherapy alone and 38 received chemotherapy plus bevacizumab. Baseline characteristics were as follows: median age 61.0 years (range 43.0–80.0 years); male/female (67%/33%); tumour location – colon (69%) / rectum (31%); hepatic metastases – synchronous (74%) / metachronous (26%); In terms of pathological response, 58% of patients receiving bevacizumab had a good response (cPR + PR1) compared with 28% of those receiving chemotherapy alone. At the end of the analysis, 68% of patients were still alive. Conclusions: Adding bevacizumab to oxaliplatin-based chemotherapy in the neoadjuvant setting improves the pathological response of liver metastases in patients with stage IV CRC. These findings indicate that pathological response might be a good indicator of outcome for patients receiving bevacizumab in the neoadjuvant setting.