bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiofrequency ablation for unresectable colorectal hepatic metastases: Prognostic factors and the effect of postoperative chemotherapy on survival.
Authors: Ross Louis , Berber Eren , Mitchell Jamie , Siperstein Allan 
Published: February 2017

581 Background: Radiofrequency ablation (RFA) is a recognized treatment modality in the management of patients with colorectal cancer liver metastasis (CRCLM). Our goal was to assess factors affecting long-term survival of patients undergoing RFA of CRCLM. Methods: We prospectively evaluated patients with unresectable CRCLM that underwent laparoscopic RFA. Patients were assessed pre- and postoperatively using triphasic computed tomography (CT) and intraoperatively using laparoscopic ultrasound. All information was entered into an IRB approved database. Pre-operative predictors were identified using Cox modeling. Postoperative chemotherapy was analyzed for its affect on survival. Results: 312 patients underwent 397 RFA sessions from 1999 to 2010. Patients averaged 2.7 lesions, with a dominant diameter of 3.4 cm and a preoperative CEA of 76. 28% had preoperative extrahepatic disease. Median survival on Kaplan-Meier analysis was 32 months, with 3 and 5 years survivals of 44% and 22%, respectively. The following were statistically significant on univariate and multivariable analysis: number of tumors (hazard ratio (HR) of 1.13 per tumor p=0.0002), dominate tumor diameter (HR 1.14 per cm p=0.03), pre-operative CEA (HR of 1.002 per one point rise p<.0001), and pre-operative extrahepatic disease (HR 1.4 p=0.05). Post-operative chemotherapy was shown to improve survival after controlling for the presence of new disease in follow-up. Conclusions: To our knowledge, this is both the largest and longest follow-up of RFA for unresectable CRCLM. The number and size of tumors, and preoperative CEA value are strong predictors of survival whereas pre-operative extrahepatic disease had mild impact on survival. Post-operative chemotherapy was shown to improve survival after controlling for other factors.
Clinical research in surgical oncology: An analysis of clinicaltrials.gov.
Authors: Menezes Amber S , Barnes Alison , Scheer Adena S , Moloo Husein , Boushey Robin P , Auer Rebecca Ann C 
Published: February 2017

591 Background: The conduction of randomized clinical trials has expanded in medical specialties, but to a far lesser degree in surgery. This is due to design challenges with standardization of treatment, blinding and lack of surgeon equipoise. The objective of this study was to assess the current landscape of clinical trials in surgical oncology registered at clinicaltrials.gov. Methods: Data was extracted from clinicaltrials.gov using the following search engine criteria: ‘Cancer’ as Condition, ‘Surgery OR Operation OR Resection’ as Intervention, and Non-Industry sponsored. The search was limited to Canada and the United States and included trials registered from January 1, 2001 to January 1, 2011. The search was performed on March 23, 2011 by three investigators in parallel. The total number of oncology trials was also obtained. Results: Of 9990 oncology trials, 1049 (10.5%) included any type of surgical intervention. Of these trials, 125 (11.9%; 1.3% of all oncology trials) manipulated a surgical variable, 773 (73.7%) assessed adjuvant/neoadjuvant therapies, and 151 (14.4%) were observational studies. Trials assessing adjuvant therapies focused on systemic treatment (362 trials, 46.8%) and multimodal therapy (129 trials, 16.7%). Of the 125 trials where surgery was the manipulated variable, 59 trials (47.2%) focused on surgical techniques (including minimally invasive) or devices, 45 trials (36.0%) studied invasive diagnostic methods, and 21 trials (16.8%) evaluated surgery vs. no surgery. The majority of the 125 trials were non- randomized (72, 57.6%), and Phase III trials accounted for less than one-quarter (29, 23.2%). Conclusions: The number of registered surgical oncology trials is small in comparison to oncology trials as a whole. Clinical trials specifically designed to assess surgical interventions are vastly outnumbered by trials focusing on adjuvant therapies, and are frequently non-randomized. Randomized surgical oncology trials account for <1% of all registered cancer trials. Barriers to the design and implementation of randomized trials in surgical oncology need to be clarified to facilitate higher-level evidence in surgical decision making.
Characterization of colon cancer–associated antigens that would be key therapeutic targets in the prevention of disease relapse or progression.
Authors: Broussard Elizabeth Kyungsun , Coveler Andrew L. , Whiting Samuel H. , Kim Rachel , Rastetter Lauren , Gad Ekram , Higgins Doreen , Slota Meredith , Gyurkey Grace , Childs Jennifer , Disis Mary Lenora 
Published: February 2017

594 Background: Colon cancer (CRC) is an immunogenic tumor and adaptive immunity may play a role in inhibiting disease relapse. A vaccine to boost cellular immunity in CRC patients could prevent disease recurrence, but there have been few defined immunogenic proteins identified as vaccine candidates. TVG has shown that overexpressed tumor associated proteins, abundant in the cancer state but expressed at basal levels in normal cells, can be immunogenic. We hypothesized that ideal candidate antigens would be ones already validated as prognostic markers in multivariate analysis. Methods: From a directed literature review we selected antigens based on (1) incidence of expression, (2) independent predictor of poor prognosis or early disease recurrence, and (3) known biologic function in CRC pathogenesis. We identified peptides that were predicted to be high affinity binders across multiple HLA DR alleles. We evaluated immunogenicity of peptides with IFN-g ELISPOT assays in CRC and control patients. We then evaluated the efficacy of vaccination in reducing tumors in the AOM mouse model. We evaluated immunogenicity of peptides with IFN-g ELISPOT assays using vaccinated mice splenocytes. We quantified antigen protein expression in AOM tumors. Results: The eight proteins are: CDC25B, COX-2, EBAG9, EGFR, Fascin-1, IGF-1R, PRL-3 and VCP. For all candidate antigens there was a greater IFN-g response in CRC patients than in controls. Four antigens (COX-2 p<.0001, CDC25B p<.0002, and EGFR p=.01, Fascin-1 p=.05) demonstrated a statistically significant reduction in the development of colon tumors compared to vaccination with adjuvant alone. Conclusions: We conclude that: 1. biologically relevant CRC associated proteins can be identified that are associated with prognosis, 2. epitopes predicted to bind multiple DR alleles, derived from candidate antigens, elicit T cell responses greater in CRC patients than in normal controls, 3. vaccination with peptides derived from four antigens resulted in a statistically significant reduction in the development of colon tumors in a mouse model, and 4. these antigens may represent novel immunologic targets for CRC.
Outcome of trimodality-eligible esophagogastric cancer (EC) patients who declined surgery after preoperative chemoradiation.
Authors: Taketa Takashi , Correa Arlene M , Suzuki Akihiro , Blum Mariela Anabel , Lee Jeffrey Edwin , Welsh James , Lin Steven H. , Maru Dipen , Erasmus Jeremy J. , Bhutani Manoop S. , Weston Brian , Rice David C. , Swisher Stephen , Hofstetter Wayne Lewis , Ajani Jaffer A. 
Published: February 2017

6 Background: Patients with localized EC eligible for resection at presentation should receive trimodality therapy (chemoradiation and surgery). However, surgical resection is not always performed in these patients because of poor performance status or reluctance in eligible patients to proceed with surgical resection after preoperative chemoradiation. Reports on the outcome of such patients are rare. Methods: Between 2002 and 2010, we identified 599 trimodality-eligible EC patients in our prospective database. All patients had extensive baseline staging, preoperative chemoradiation, and preoperative staging that included endoscopic biopsy and PET-CT. Of 599 patients, 32 patients declined surgery. Results: The median age was 70 years (range, 55-81), 29 patients (90.6%) were men and 30 (93.8%) were Caucasian. Majority had baseline stage II (44%) or III (38%) cancer. All 32 patients had an adenocarcinoma (moderate: 53.1%, poorly: 46.9%) and reached a clinical complete response (negative biopsy and PET in the physiologic range) post-chemoradiation. Four patients had salvage surgery and 3 are alive. Overall, 22 patients remain alive at a median follow up of 33.1 months (95% CI, 28.1-38.1). 3-year overall survival (OS) and relapse-free survival (RFS) were 65.1±10.4% and 37.5±10.3%. Median OS and RFS were 54.2 months (95% CI, 25.7-82.7), 30.4 months (95% CI, 16.3-44.5). Conclusions: Although the outcome of patients with EC who decline surgical resection after chemoradiation is reasonable, the lack of a validated approach to esophageal preservation dictates that trimodality therapy remains the standard of care in patients with potentially resectable EC.
Phase I study of biweekly liposome irinotecan (PEP02, MM-398) in metastatic colorectal cancer failed on first-line oxaliplatin-based chemotherapy.
Authors: Chen Li-Tzong , Shiah Her-Shyong , Lin Peng-Chan , Lee Jenq-Chang , Su Wu-Chou , Wang Yi-Wen , Yeh Grace , Chang Jang-Yang 
Published: February 2017

613 Background: PEP02 (MM-398) is a nanoliposomal formulation of irinotecan (CPT-11) that has improved pharmacokinetics (PK) and tumor distribution of CPT-11 and its active metabolite, SN-38. PEP02 single agent q3w has shown preliminary efficacy and safety in Phase II pancreatic and gastric cancer studies. Since irinotecan is approved for metastatic colorectal cancer (mCRC) and biweekly regimens are widely used, the aims of this study are to determine the maximum tolerated dose (MTD), characterize the PK and pharmacogenetics (PGx), and explore the efficacy of PEP02 q2w in mCRC. Methods: Patients (pts) with disease progression after 1st-line oxaliplatin-based chemotherapy, ECOG PS 0-1, and without prior exposure to irinotecan were eligible. PEP02 was given on day 1 and 15 of each 28 day treatment cycle. The starting dose was 80 mg/m2 and escalated by 10 mg/m2 to the target dose of 100 mg/m2. PK was evaluated during the 1st cycle and the tumor response was assessed by RECIST. Results: A total of 18 pts (M/F 9/9; median age 57.5) were enrolled, with 6 at each dose level. Dose-limiting toxicity manifested as G3 diarrhea was observed in one pt per dose level. The target dose of 100 mg/m2 was determined to be the MTD. Nine pts had dose delayed (4, 3, 2 at 80, 90, 100 mg/m2), mostly because of neutropenia. The PK and PGx are being analysed. As of August 2011, there are 3 pts still on study treatment and 17 pts evaluable for tumor response. Four pts (2 at 80 mg/m2, 1 each at 90 and 100 mg/m2) showed partial response (3 after 2 cycles and 1 after 8 cycles) and 8 pts (3 each at 80 and 90 mg/m2, 2 at 100 mg/m2) maintained stable disease for at least 2 cycles, which resulted in a response rate (RR) of 23.5% and a disease control rate (DCR) of 70.6%. Current median progression-free survival (PFS) is 4 months and 8 pts (47%) had PFS ≥ 6 months. Conclusions: The MTD of biweekly PEP02 is 100 mg/m2. As a 2nd-line monotherapy after oxaliplatin-based chemotherapy, the efficacy results indicate the potential benefit of PEP02 for mCRC (FOLFIRI-1 achieved only 4% RR, 34% DCR, and 2.5 months PFS in FOLFOX pretreated pts). A randomized Phase II study evaluating PEP02 plus 5-FU/LV (FUPEP regimen) vs. FOLFIRI is currently ongoing in France.
Tumor shrinkage and overall survival (OS) from multicenter phase II study of modified FOLFOX7 (combination chemotherapy of infusional 5-FU/l-leucovorin and intermittent oxaliplatin) with bevacizumab in the first-line therapy of colorectal cancer: CRAFT trial.
Authors: Koda Keiji , Ishida Hideyuki , Katoh Ryoji , Maeda Kotaro , Tezuka Toru , Mishima Hideyuki , Tomita Naohiro , Saito Norio , Hamada Chikuma , Sakamoto Junichi 
Published: February 2017

616 Background: Additional bevacizumab (BV) to FOLFOX has been established as a standard 1st-line therapy for mCRC. The intermittent administration of L-OHP can reduce the peripheral sensory neurotoxicity as reported in OPTIMOX and CONcePT study. CRAFT trial was conducted to confirm the effectiveness of stop and go strategy of mFOLFOX7+BV. We previously reported the feasibility and good progression free survival (PSF) in that study (K. Ishibashi et al. ECCO2011). This time, the overall survival (OS) and possibilities for conversion surgery were reported. Methods: We administered 8cycles of mFOLFOX7/BV followedby 8 cycles of FULV/BV as a maintenance, and reintroduction of 8 cycles of mFOLFOX7/BV until disease progression. Patients who had progressive disease during maintenance phase are allowed to receive oxaliplatin ahead of schedule. The primary endpoint is the duration from the study enrollment to disease progression (PFS I). The secondary endpoints are survival time from the study enrollment to disease progression or death plus from 1st PD in the maintenance phase to 2nd PD (PFS II), tme to treatment failure (TTF) ,OS, and safety. Results: Between March 2009 and June 2010, 52pts were enrolled. Median PFS I was 13.2 (95%CI,10.3-15.0) months. PFS II was 13.5(95%CI,12.5-15.1) months. Median, TTF was 10.3 (95%CI, 5.6-12.1) months, OS was 27.4 (95%CI, 21.0-32.8) months. There was no uncontrollable toxicity. The range of tumor shrinkage wasup to - 91.0% and 3 patients received conversion surgery. Conclusions: This study met its primary endpoint PFS I (K.Ishibashi et al. ECCO 2011.). The current data indicated that stop and go strategy is effective to prolong the duration of 1st line treatment and to improve survival in mCRC. Tumor shrinkage data also suggested mFOLFOX7+BV has possibilities to make a conversion surgery. Water fall plot for all patients will be presented at the meeting.
Molecular predictors of treatment response in colon and gastric cancer.
Authors: Fanta Paul Timothy , Roeland Eric , Shen John P. , Shimabukuro Kelly Anne , Hwang Michael , Ramamoorthy Sonia , Lowy Andrew M. 
Published: February 2017

619 Background: With the noted exception of KRAS mutational status, currently there exists limited data regarding the incorporation of tumor-derived biomarkers in the clinical management of gastrointestinal malignancies. High ERCC1 levels have been associated with inferior results in platinum-treated patients with non-small cell lung cancer, esophageal cancers, and head and neck cancer. Lenz et al. concluded ERCC-1 gene expression levels may allow the selection of patients who may benefit from FOLFOX chemotherapy in metastatic colon cancer. Low intra-tumoral ERCC1 mRNA expression predicted improved PFS and OS in patients with esophageal adenocarcinoma who were treated with tri-modality therapy in the SWOG 0356 correlative study. Methods: To determine the prevalence and patterns of expression of select tumor biomarkers including ERCC1, TS, HER-2, KRAS, BRAF, and EGFR gene expression was measured in metastatic gastric and colorectal cancers using formalin fixed paraffin embedded tumor samples from 120 metastatic colorectal and 20 metastatic gastric cancer were dissected using laser-captured micro-dissection and analyzed for ERCC-1, TS, EGFR, RRM1, and VEGFR2a mRNA expression using a quantitative RT-PCR methodology. Gene expression values (relative mRNA levels) were recorded as ratios between the target gene and internal reference gene (beta-actin). A retrospective review of the patient’s response to therapy was planned. Results: In colorectal patients, the incidence of KRAS mutations was 50%, specifically Gly12Ser 4%, Gly12Val 11%, Gly12Asp 20%, Gly12 Cys 7% Gly12Ala 2% and Gly13Asp 8%. BRAF expression analysis displayed 91% wild type with 9% V600E mutations. Median expression values for ERCC1, TS, EGFR, RRM1, and VEGFR2A expression levels using RT-PCR were 1.23, 2.28, 1.90, 1.05, and 1.61 respectively in the colorectal subset. In gastric cancer, ERCC1, TS, and Her-2 median expression levels using RT-PCR were 1.54, 3.56, and 0.08 respectively. Correlation with clinical outcome is pending and will be reported later.
Treatment of colorectal liver metastasis: Comparison of radiofrequency ablation and hepatic resection.
Authors: Yoon Min Yong , Kim Hyung Ook 
Published: February 2017

637 Background: Hepatic resection is the mainstay of management for colorectal liver metastases. But, the treatment for colorectal liver metastases requires a multidisciplinary therapeutic strategy. The aim of this study was to compare recurrence and survival rates for patients treated with hepatic resection or radiofrequency ablation (RFA) for colorectal liver metastases. Methods: Between July 2002 and September 2010, 52 patients underwent hepatic resection and 58 underwent RFA for synchronous or metachronous colorectal liver metastases. A retrospective analysis was performed. Patients with extrahepatic metastases were excluded. Results: The two groups had similar mean age, comorbid medical conditions, primary disease stage, and number of tumors. Preoperative median serum carcinoembryonic antigen (CEA) level was significantly higher in the resection group (13.8 ng/mL vs. 3.1 ng/mL; p = 0.001). Median diameter of main tumors was significantly greater in resection group (4.1 cm vs. 2.0 cm; p = 0.002). Recurrence rate after treatment was 46.2% (24/52) in the resection group and 70.7% (41/58) in the RFA group. Marginal recurrence after resection or RFA was observed in 7.6% (4/52) and 46.6% (27/58), respectively (p = 0.003). Median recurrence free survival (28.0 vs. 12.0 months; p = 0.007) and median overall survival (43.0 vs. 26.0 months; p = 0.023) were significantly longer in the resection group. Conclusions: Hepatic resection is the treatment of choice for colorectal liver metastases. RFA for colorectal liver metastases was associated with higher marginal recurrence rate and shorter recurrence free and overall survival.
Prevalence of bowel dysfunction in colorectal cancer survivors.
Authors: Sall Karanvir , Cheung Winson Y. 
Published: February 2017

638 Background: There is limited research on the long-term bowel health outcomes of colorectal cancer (CRC) survivors even though colorectal surgery, radiation, and chemotherapy can pose significant morbidity for patients. Our aims were to characterize the prevalence of specific bowel complications in CRC survivors and to compare their outcomes with those of non-CRC survivors and non-cancer controls. Methods: Using population-based data from the 2009 U.S. National Health and Nutrition Examination Survey, we identified 3 different groups of adult patients: CRC survivors, non-CRC survivors, and non-cancer controls. Weighted multivariate logistic regression models were constructed to determine the relationship between survivor status and bowel health outcomes, while controlling for patient and disease characteristics. Main outcomes included leakage of gas, mucus, liquid stool, and solid stool. Stratified analyses were subsequently conducted to assess for effect modification based on gender (men vs. women), age (≤ 60 vs. >60), and ethnicity (white vs. non-white). Results: In total, 10,894 subjects were included: 75 CRC survivors, 910 non-CRC survivors, and 9909 non-cancer controls. Baseline characteristics were similar among all 3 patient groups. In univariate analyses, more CRC survivors reported bowel dysfunction, including leakage of: gas (15 vs. 12 vs. 10%, p=0.01), liquid stool (8 vs. 7 vs. 4%, p<0.001), and solid stool (2 vs. 0 vs. 0%, p<0.001) than non-CRC survivors and non-cancer controls. In multivariate analyses, CRC survivors continued to have significantly higher odds of solid stool incontinence (OR 2.09, 95% CI 1.24-3.53, p<0.05) when compared to the other groups. The association between surviving CRC and presence of bowel dysfunction was not modified by ethnicity, but specific outcomes, such as solid stool leakage, were more prominent in women (p=0.003) and those who were aged >60 years (p=0.002). Conclusions: Bowel problems are significantly more frequent among CRC survivors than non-CRC survivors and non-cancer patients, especially for women and the elderly. Studies to develop interventions that minimize these bowel complications are needed in order to improve the long-term health and quality of life for CRC survivors.
Colorectal treatment effectiveness in a population-based registry: A 1991-1994 and 2001-2005 comparison.
Authors: Lin Ge 
Published: February 2017

647 Background: Providing state and regional cancer treatment prognoses, and comparing them over time are important for both local patients and physicians. The present study is the first in Nebraska, US to compare the change in prognostic factors for five-year survival of CC patients to those of RC patients from two time periods, 1991-1994 to 2001-2005. Methods: CC and RC Patients aged 19 years and older were selected from the Nebraska Cancer Registry the two time periods. The outcome variable was five-year survival (survived or not) from the date of diagnosis up to five years or more. Treatment was divided into five groups: surgery alone, surgery with chemotherapy and radiation therapy (S+CT+RT), surgery with chemotherapy (S+CT), other treatments, and no treatment. Multivariate logistic regression analysis was used to examine the effect of prognostic factors on five-year survival. Results: There was a 7% five-year survival improvement in RC patients from time 1 to time 2 but no survival improvement in CC patients. Younger age, female, being married, and early stage at diagnosis were associated with CC survival advantage in time 1 and time 2. In contrast, for RC patients, female had no survival advantage in time 2 while those in the 65-74 age group showed improved survival with time. With regard to treatment, surgery alone was the most consistent prognostic factor through time, while S+ CT+RT became the most important prognostic factor for survival in RC in time 2, and S+CT became the most important prognostic factor for survival in CC in time 2. Conclusions: There was marked change in treatment modalities for both CC and RC patients between the 1991-1995 and 2001-2005 periods, with a general trend toward better five-year survival prognosis. The most effective treatments for CC and RC patients in the most recent period are Surg+CT and S+CT+RT, respectively.