bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association of human epidermal growth factor receptor-2 (HER-2) expression with clinicopathologic findings in patients with colorectal cancer receiving adjuvant therapy.
Authors: Karaca Halit , Berk Veli , Inanc Mevlude , Deniz Kemal , Ozkan Metin 
Published: March 2020

e14089 Background: Colorectal cancers (CRC) are the third frequent cancer worldwide. Like in other cancers; factors which might be associated with prognosis and treatment of the disease are investigated in molecular basis. In this study, it was aimed to determine the levels of HER-2 expression and it’s association with clinicopathological findings in patients with CRC receiving adjuvant therapy. Methods: A total of 80 patients (48 female, 32 male) whom were diagnosed with CRC and received adjuvant FOLFOX-4 from March 2006 to September 2010 were included in the study. The parameters; age, gender, histopathological diagnosis, tumor localization, presence of obsruction-perforation-bleeding history, grades, presence of perineural-lymphovascular invasion, pathological TNM staging at time of diagnosis, findings of relapse-metastasis, history of surgery and radiotherapy, the chemotherapy regimens received in adjuvant and metastatic stages, follow up intervals and survival data were analyzed. HER-2 receptors were stained immunohistochemically. FISH was performed for samples which were stained (++) or (+++). Statistical analysis was performed for the data. Results: Median follow up was found 24 months (min-max: 1-67) and median age was 59 (min-max: 33-84). Thirteen patients (16%) died and 17 patients relapsed (21%) during follow-up. The median disease-free survival was found 55 months (95% CI: 42.84-55.95). Themedian overall survival was not reached yet.In immunohistochemical stainings; (+++) staining was found in 2 patients (2.5%) while (++) was in 13 (16%) patients. All of 15 patients were performed FISH for HER-2; samples which were (+++) showed positivity but the ones with (++) were negative for FISH. No significant correlation was found between HER-2 expression and clinicopathological findings (p>0.05). Also, no statistical significance was found between HER-2 expression and survival (p>0.05). Conclusions: To current data; prognostic and predictive value of HER-2 overexpression for CRC seems to be poor. Larger, prospective and long-lasting studies are required to clarify this controversial topic.
KRAS mutation profile in Puerto Rican patients with colorectal cancer: Trends in expression of KRAS mutation in PR between April 2009 to January 2011.
Authors: Ruiz Yelitza , Miranda Christine , Hunter Robert F. 
Published: March 2020

e14102 Background: The prevalence of a mutated KRAS gene in colorectal cancer shows ethnic variation with a range between 30-48% among the Caucasian, Asian, and European populations. The purpose of this study was to define the profile of KRAS mutation in colorectal cancer patients in Puerto Rico. Methods: Between April 2009 and January 2011, we collected the expression of KRAS gene among colorectal cancer patients in Puerto Rico. The assay was performed by a central laboratory which began to offer the test in the island in April 2009 (GENOPTIX). Data for the presence and type of mutation, age, sex, cancer histology, site of tumor, and cancer stage were collected. The site of the mutation in codon 12 and 13 were identified by the real time polymerase chain reaction (PCR). The study was approved by IRB. A total of 501 cases were available for study. SPPS version 14 was used for statistical analysis. Results: A mutated KRAS was present in 39% (n=195) of the cohort, more commonly in the 51-69 age group (55.4%; p=0.004), in females (55.4%; p=0.095), in the proximal area of colon (43.8%; p=0.017), in the codon 12 (91.2%), and 8.8% in the codon 13. The majority of mutated genes were in codon 12 (91.2%) with 12 ASP (39.5%) and 12 VAL (25.4%) most often seen. Mucinous histology was associated with 46.7% mutated KRAS, poorly differentiated tumor with 40.0% of KRAS mutation. The mutant expression of KRAS in cases with rectum carcinoma was 39.5%, where the most common mutation was 12 VAL. Conclusions: The prevalence of KRAS mutation in Puerto Rican population is similar to other reported studies. A higher prevalence of 12 VAL mutation in rectal carcinoma and a trend towards a higher mutation rate in females are different in this cohort as compared with published studies. This study was supported by NIH grant numbers G12RR-03035 & 8U54MD007587-03.
Midcourse neoadjuvant chemoradiation for locally advanced rectal cancer.
Authors: Ko Sanghwa , Oh Nahmgun 
Published: March 2020

e14121 Background: Neoadjuvant chemoradiotherapy is considered a standard approach for locally advanced rectal cancer. Many studies have showed that short-course radiation (25Gy in 5 fractions) and long-course chemoradiotherapy (50.4-55Gy/25 fractions over 5 weeks with oral capecitabine 825 mg/m2 twice daily on radiotherapy days) have similar long-term survival, local recurrence, and late morbidity. The aim of this study is to show the efficacy and safety of a newly modulated mid-course chemoradiotherapy with capecitabine in locally advanced rectal cancer. Methods: 252 patients with low lying (within 7cm from anal verge) locally advanced rectal cancer were recruited. All patients received a total irradiation dose of 30 Gy with conventional fractions for 3 weeks (2 Gy on weekdays). Capecitabine was administered 1000mg/m2 twice a day on 21 days during radiotherapy, followed total mesorectal excision surgery in a week without resting period. Results: The mean patients age was 60.2 years, and 57.9% (146/252) were men. The mean location of cancer was at 4.7cm from anal verge (1-7cm). There were 8 patients (3.2%) with pathologic complete response. 32 patients (12.7%) underwent abdominoperineal resection or Hartmann's operation. Among other 220 patients, 163 patients (74.1%) concomittent diverting ileostomy. Anastomotic leakage was confirmed in 32 patients (14.5%) in the patients with sphincter-saving surgery. There was one case of septicemia, which was recovered. The postoperative mortality was none. Eight patients (3.2%) experienced locoregional recurrence of pelvic cavity. 3-year overall survival rate was 84.1%. Conclusions: Preoperative mid-course chemoradiotherapy using oral capecitabine 2,000 mg/m2/day on 21 days during 2 Gy radiation of each 15 weekdays is seemed to be a tolerable and effective modality, in patients with low lying, locally advanced rectal cancer.
Correlation of VEGFR activation within the tumor-associated stroma with an aggressive colon cancer phenotype.
Authors: Huijbers Anouck , Pin Elisa , Pierobon Mariaelena , Pelt Gabi W. van , Belluco Claudio , Silvestri Alessandra , Liotta Lance A. , Tollenaar Rob A , Petricoin Emanuel , Mesker Wilma E 
Published: March 2020

e14151 Background: The tumour microenvironment, and especially the stroma surrounding the tumor cells, is an important target for cancer therapy. Previous results published by our group showed that colon cancer (CC) patients with a high (>50%) intra-tumor stroma ratio had poor prognosis compared to patients with low intra-tumor stroma ratios. In order to evaluate the contribution of the underpinning signalling and molecular architecture of the tumor associated stroma (TAS) to this aggressive phenotype, we utilized laser capture microdissection (LCM) coupled to broad-scale protein pathway activation mapping using reverse phase protein microarrays (RPMA). Such analysis could identify new stromal-based targeted treatment options through the identification of activated pathways within the TAS of patients with aggressive CC. Methods: CC stage II and III tissue specimens were scored for the amount of stroma and a stroma-high and a stroma-low group were defined. Correspondent frozen tumor specimens were selected for a pilot study (n=30; 15 high and 15 low TAS) and subjected to LCM to enrich for TAS cells. RPMA was performed on the resultant lysates whereby an initial set of 30 total and phospho-proteins, known to be involved in stroma proliferation and activation, were analyzed. Results: Unsupervised hierarchical clustering analysis showed partial grouping of stroma high and stroma low samples with phosphorylation of VEGFR-2 being significantly higher in the stroma high group compared to the stroma low (p=0.030). Conclusions: These preliminary results reveal the potential presence of biochemical derangements in the TAS of tumors from patients with aggressive CC with increased activation of VEGFR-2. Considering the central role this protein plays in angiogenesis and cell migration, these results suggest that anti-VEGFR targeted therapy could be considered for a pre-stratified group of patients with aggressive tumors with high recurrence rates. Ongoing expanded pathway analysis with additional signalling proteins including downstream signalling components of VEGFR are being conducted in order to validate this pilot finding and identify new TAS related signalling derangements.
A phase II-III clinical study with the immunomodulator MGN1703 in patients with advanced colorectal carcinoma: The IMPACT study.
Authors: Tschaika Marina , Schmoll Hans-Joachim , Riera-Knorrenschild Jorge , Kröning Hendrik , Mayer Frank , Weith Ekaterina , Schroff Matthias , Krikov Maxim , Schmidt Manuel , Wittig Burghardt 
Published: March 2020

e14152 Background: Based on promising data from a phase 1 study of MGN1703 in patients with metastatic solid tumors including those with CRC, a phase 2-3 study was initiated in patients with advanced CRC having disease control after first-line therapy. MGN1703 is a synthetic DNA-based immunomodulator which acts as an agonist of toll-like receptor 9. The objective of the study is to assess efficacy and safety of treatment with MGN1703 in comparison to placebo. Methods: The IMPACT study is designed as an international, multicentric, randomized double-blind placebo-controlled phase 2-3 study. It is conducted in patients with advanced CRC showing disease control after 1st-line therapy with standard chemotherapy regimen. The study treatment is administered s.c. twice weekly (60 mg MGN1703 or placebo; ratio 2:1). 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 is continued until tumor progression, intolerable toxicity, exclusion criteria or withdrawal of consent. Results: Up to now, the patients received a maximum of 132 (mean: 32.1) treatment administrations, which equals 66 weeks. Drug-related adverse events (as assessed by the investigator) include mild fever, injection site itching, muscle aching, arthralgia, fatigue, paresthesia, rash, and moderate subfebril temperature and increased ANA in single patients. These represent only 16% of all adverse events reported in the study so far. Nine serious adverse events have been reported and only one was assessed as probably drug-related (“atypical pneumonia”). Local reactions reported in single patients include such symptoms as mild redness and swelling at injection site. Currently no laboratory or clinical signs of dose-limiting toxicities have been reported. Conclusions: The preliminary results of the ongoing clinical study in patients with advanced CRC show a good safety profile of the treatment with MGN1703 at the dosage of 60 mg. Most adverse events which were assessed as possibly drug-related belong to expected study drug reactions known for immune modulating drugs.
Hepatic resection for colorectal cancer metastasis: A retrospective review of the Ottawa Hospital Cancer Centre over 7 years.
Authors: Boame Nana , Gresham Gillian , Martel Guillaume , Rekman Janelle , Jonker Derek J. , Alnajjar Abdulsalam , Mohammad Waleed , Balaa Fady , Asmis Timothy R. 
Published: March 2020

e14154 Background: The timing of chemotherapy (adjuvant vs neoadjuvant) for patients undergoing potentially curative hepatic resection of metastasis from colorectal cancer origin is controversial. Methods: We performed a retrospective review of all patients at TOHCC who underwent successful surgical resection of hepatic metastasis from CRC between 2002-2009. Patients receiving intra-operative radiofrequency ablation (RFA) as part of their management were included. Factors associated with overall survival were evaluated. Results: 168 patients had median age 62 years (31-84), 57/43% male/female. Median pre-op CEA was 5.5 ng/ml (0.3 - 529.2). Primary tumor location included 40% left, 35% rectum, 20% right, 5% transverse. 61.5% patients were node positive. Following hepatectomy 10.2% had positive resection margins. Intra-operative RFA was used in 26 (15.4%) patients. Chemotherapy was administered in a neo-adjuvant (47.6%), adjuvant (58.4%) or “perioperative” (both neoadjuvant and adjuvant; 36.1% ) setting. Use of intraoperative RFA vs. no RFA was not associated with overall survival (HR: 0.94 [95%CI: 0.49-1.80],p=0.85). In both univariate and multivariate analysis, the only adverse factor found associated with survival was R1 status (HR 2.38 [95% CI 1.49-5.0], p=0.0198). Other baseline variables (age, gender, node status, histologic grade, primary tumour site, timing of metastatic diagnosis [metachronous vs. synchronous]) did not reach statistical significance. Conclusions: While statistical significance was not achieved, ability to demonstrate benefit of chemotherapy may have been limited by sample size. Hazard ratios suggest trend to greatest benefit with use of post-operative adjuvant chemotherapy. 3y and 5y survival data is encouraging. Use of RFA where required as an adjunct to hepatic resection appeared as effective as resection of all disease in this series. Recurrence and morbidity data will be presented. [Table: see text]
ERCC1, KRAS mutation, redox status, and oxaliplatin sensitivity in colorectal cancer: “Radical” change in an old model.
Authors: Orlandi Armando , Di Salvatore Mariantonietta , Basso Michele , Bagalà Cinzia , Strippoli Antonia , Plastino Francesca , Dadduzio Enzo , Di Lascio Simona , Cursio Elisabetta , Amoruso Alessia , Rodriquenz Mariagrazia , Cassano Alessandra , Astone Antonio , Barone Carlo 
Published: March 2020

e14156 Background: Oxaliplatin (Oxa) is widely used in metastatic colorectal cancer, but currently there are not valid predictors of response to this drug. In our recent retrospective clinical study we have shown a greater efficacy of Oxa in patients with metastatic colorectal cancer with mutated (mt) K-RAS. We hypothesized that the mutational status of K-RAS could influence the expression of ERCC1 and cellular Redox status. Methods: We used four cell lines of colorectal cancer: two K-RAS wild type (wt) (HCT-8, HT-29) and two K-RAS mt (SW620, SW480). We evaluated the sensitivity of these cell lines to Oxa by MTT-test and the ERCC1 levels before and after 24h exposure to Oxa by RT-PCR. We silenced K-RAS in a K-RAS mt cell lines to evaluate the impact on Oxa sensitivity and ERCC1 levels. We also silenced ERCC1 in order to confirm the importance of this protein as a Oxa resistance factor. Cellular oxidative stress was determined by DCFDA. Results: The K-RAS mt cell lines were more sensitive to Oxa (p<0.001). The basal levels of ERCC1 did not show significant differences between K-RAS mt and wt cell line, however, after 24h exposure to Oxa, only the K-RAS wt lines showed the ability to induce ERCC1, with a statistically significant difference (p<0.005). The silencing of K-RAS in K-RAS mt cell lines (SW620s) demonstrated to reduce sensitivity to Oxa associated with the acquisition of the ability to induce ERCC1. The silencing of ERCC1 in K-RAS wt cell lines enhance the sensibility to Oxa. The levels of reactive oxygen species were higher in K-RAS mt cell lines. The Pearson correlation test showed a statistically significant relationship between basal levels of ROS and sensitivity to Oxa ("r" -0,988, p<0.01). The baseline levels of ROS were higher SW620 than the line SW620s. The administration of Oxa in these cell lines resulted in a statistically higher fluorescence index in SW620 versus SW620s (p<0.003). Conclusions: The K-RAS mutated cell lines were more sensitive to Oxa. This feature seems to be secondary to the inability of these cells to induce ERCC1 after exposure to Oxa and to the synergism between K-RAS mutation and Oxa in increasing oxidative stress. K-RAS can thus be a predictor of response to Oxa in colorectal cancer.
Should patients with peritoneal carcinomatosis of colorectal origin with synchronous liver metastases be treated with curative intent? A case-control study.
Authors: Diane Goere , Maggiori Leon , Viana Benjamin , Dumont Frédéric , Honoré Charles , Malka David , Elias Dominique 
Published: March 2020

e14158 Background: This aim of this case-control study was to assess the prognostic impact of the presence of liver metastases (LM) in patients operated on colorectal peritoneal carcinomatosis (PC) who underwent complete cytoreductive surgery (CRS) and LM resection followed by intraperitoneal chemotherapy. Methods: From a prospectively maintained database, all patients with colorectal PC and synchronous LM who underwent CRS followed by intraperitoneal chemotherapy, were manually matched to all identical patients with isolated PC, operated on over the same period, on the following matching criteria: age, peritoneal cancer index (PCI), site of the primary colorectal cancer (colon or rectum), lymph node involvement on the primary colorectal cancer specimen (pN), and postoperative chemotherapy. Results: From 1993 to 2009, 37 patients with PC and LM were matched to 61 patients with isolated PC. After a mean follow-up of 36 months, 3-year overall (OS) and disease free survival rates were significantly lower in patients with PC and LM, respectively 40% and 66% (p=0.04) and 6% and 27% (p=0.001). In Cox regression analysis, a PCI ≥ 12 (Odds-ratio (OR): 4.6), a pN+ status (OR: 3.3), no adjuvant chemotherapy (OR: 3.0) and presence of LM (OR: 2.0) were identified as independent factors of poor OS. Thus, 3 groups could be identified: 1) patients with a low PCI (<12) and no LM, with an associated a median OS of 76 months; 2) patients with a low PCI (<12) and 1 or 2 LM, with an associated OS of 40 months; and 3) patients with a high PCI (≥12) or patients with ≥ 3 LM, with an associated OS of 27 months. Conclusions: This first case-control study confirms that prolonged survival can be achieved in highly selected patients operated on limited carcinomatosis and liver metastases less than 3. When the peritoneal and the liver involvement are greater, the complete surgical treatment followed by intraperitoneal chemotherapy should be discussed according to criteria of aggressiveness of the tumor disease.
Prognostic factors for metastatic colorectal cancer with and without bevacizumab therapy.
Authors: Osuorji Ikenna , Dyson Greg , Yerasuri Durga , Philip Philip Agop , Shields Anthony Frank , Choi Minsig 
Published: March 2020

e14163 Background: Metastatic colorectal disease is generally incurable and treatment is palliative with the intent to balance toxicity with quality of life. Coin 3 trial showed that pre-chemotherapy platelet counts > 400,000 per μL were associated with poor survival when intermittent chemotherapy was used, whereas patients with lower platelet counts did not have any significant difference between the intermittent and continuous chemotherapy arms. Methods: We reviewed retrospectively 775 stage IV colorectal cancer patients at Karmanos Cancer Center over a 10 year period to see if high platelet count was associated with a poor outcome irrespective of treatment. Our analysis included 480 patients with adenocarcinoma who had not received chemotherapy prior to referral, and where information on the baseline platelet count, race, and age was available. We also analyzed the impact of race, age and bevacizumab use. We used Cox regression model for analysis. Results: Among the patients 48.3% were African American (AA) and 51.7% were Caucasians (C). 34.4 % had had PLT > 400,000 per μL. For those with lower platelet counts the median survival was 26.2 months in the C and 14.1 months in the AA groups respectively. Patients with platelet above 400,000 had a median survival of 15.2 months for C and 12.6 months for AA. Cox regression analysis, showed hazard ratios for outcome of death were; 1.16(1.07-1.26) p<0.001 for age (per 10 yrs), 1.60(1.31-1.94) [AA versus C(ref)] p< 0.001 for race and 1.35(1.10-1.65)[>400 versus <] p<0.004 for platelet count. In subset analysis, 296(61.7%) patients who received chemotherapy had data regarding use of bevacizumab (B). Among the 31.7% who received B, the median survival was 25.6 months compared to14.1 months in the no B arm. A Cox regression model using B as a stratification variable showed that the impact of race {hazard ratio = 1.32 (1.02-1.69) p =0.03} and platelet count {hazard ratio = 1.27(0.97-1.65) p =0.08} were much less. Conclusions: Pre-chemotherapy Platelet count< 400,000, C race and younger age are associated with improved survival. Use of bevacizumab may mitigate the impact of these factors.
Optimizing the sequence of biological agents in advanced colorectal cancer: A decision analysis.
Authors: Riesco Martinez Maria C. , Berry Scott R. , Ko Yoo-Joung , Chan Kelvin 
Published: March 2020

e14171 Background: Patients (pts) with wild-type (WT) K-ras metastatic colorectal cancer(mCRC) may benefit from the following five drugs/classes: fluoropyrimidines (FP), oxaliplatin (O), irinotecan (I), bevacizumab (B) and EGFR inhibitors (EGFRI). However, pending the results of ongoing randomized trials, the optimal sequencing of these agents is unclear. Methods: A Markov model was constructed for a hypothetical cohort of pts with WT K-ras unresectable mCRC to examine the outcomes of 3 different treatment strategies over a time horizon of 5 years. Strategy A: 1st line B+FP+O/I, 2nd line FP+I/O, 3rd line EGFRI monotherapy. Strategy B: 1st line B+FP+O/I, 2nd line FP+I/O, 3rd line EGFRI + I. Strategy C: 1st line EGFRI+FP+O/I, 2nd line B+ FP+I/O, 3rd line best supportive care. Efficacy and probability data were obtained from published clinical trials identified through a systematic review using MEDLINE, EMBASE and the Cochrane Central registry of clinical trials. The primary endpoint was mean overall survival (OS). Results: The results are shown in the table below. One-way sensitivity analyses revealed that strategy C may be preferred to B when less than 30% of pts were eligible to receive 3rd line treatment (base case was 34%), or when the relative benefit of 3rd line EGFRI+I to EGFRI alone had a hazard ratio (HR) of more than 0.57 (base case HR = 0.54). First order micro-simulation (n=100,000) suggested that 77% and 82% of the simulations revealed the differences between strategies B and C to be less than 1 month and 3 months respectively. Only 6% of the simulations suggested strategy B was superior to others by more than 3 months, while only 12% suggested strategy C was superior to others by more than 3 months. Conclusions: All 3 strategies appeared to result in similar OS for pts with unresectable mCRC. Objective evidence regarding the proportion of patients eligible for 3rd line EGFRI treatment in clinical practice would be useful given the implications for a preferred strategy to maximize OS. [Table: see text]