bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of lymph node metastasis and prognosis in colorectal cancer patients using slug and vimentin expression.
Authors: Toiyama Yuji , Yasuda Hiromi , Saigusa Susumu , Okugawa Yoshinaga , Tanaka Koji , Inoue Yasuhiro , Uchida Keiichi , Mohri Yasuhiko , Tabata Tsutomu , Goel Ajay , Kusunoki Masato 
Published: March 2020

e14029 Background: Slug plays a critical role in regulating the epithelial-mesenchymal transition (EMT) by down-regulation of epithelial markers and up-regulation of mesenchymal markers. The purpose of the present study was to evaluate the clinical significance of Slug and Vimentin expression in colorectal cancer (CRC) and to perform in vitro characterization of Slug’s function. Methods: At first, the biological role of Slug in CRC was assessed by RNA interference in CRC cell lines to assess tumor progression, invasion and migration. We next analyzed Slug and Vimentin expression in surgical tissue specimens from 181 CRC patients by quantitative reverse transcriptase polymerase chain reaction and immunohistochemistry. Results: Knockdown of Slug in siRNA knockdown studies resulted in induction of EMT markers, inhibited cancer cell proliferation, invasion and migration abilities. Slug and Vimentin expression in cancer tissues was significantly higher in patients with high T stage, lymph node involvement, liver metastasis and advanced TNM stage. We also observed a significant correlation between Slug and Vimentin expression in CRC (rho = 0.467). Increased Slug and Vimentin expression were significantly associated with poor prognosis in Stage I-IV (p<0.0001, p=0.0005, log-rank test) and Stage II (p= 0.04, p=0.012, log-rank test) Furthermore, increased Slug expression was an independent predictive marker of lymph node metastasis (p=0.012) and prognostic factor (p= 0.025). Conclusions: Our data demonstrate that evaluation of Slug and Vimentin could be valuable in the identification of patients with lymph node metastasis or poor prognosis in CRC.
Treatment patterns and site of metastasis in patients with metastatic colorectal cancer (mCRC).
Authors: Iqbal Sheikh Usman , Thompson Stephen F , Naoshy Sarah , Ng Daniel B , Wooten Michael , Sherman Steven A , Malangone Elisabetta , Stern Lee , Gorritz-Kindu Magdaliz 
Published: March 2020

e14030 Background: The real-world impact of metastatic (met) site on Tx choice in mCRC is unknown. Therapeutic associations across metastases can identify gaps in care and inform clinical decision support systems. This study assessed Tx patterns in mCRC pts by met site. Methods: 4656 stage III/IV pts ≥18 yrs at mCRC diagnosis receiving anticancer agents were followed in a retrospective observational study using electronic medical records from the largest oncology database (SDI) from 1/1/04-7/31/11. 1st- (1L), 2nd- (2L), and 3rd-line (3L) therapies were identified for top 4 met sites. Logistic regression adjusting for met site overlap determined Tx use by met site and therapy line. Results: Pts were mostly male (54.1%) and on average 61.6 yrs. The top 4 met sites were liver (34.2%), lung (15.9%), lymph (15.8%), and bone (7.5%). Leading regimens are presented in the table below. Bevacizumab (B) use varied by met site and therapy line. Against other/unknown met sites, 1L B was more common in liver (OR=2.06 [1.75-2.42]) and bone (OR=1.46 [1.16-1.84]), less common in lymph (OR=0.60 [0.50-0.73]), and statistically equal in lung (OR=1.01 [0.85-1.20]). In 2L, B was more likely to be given for liver (OR=1.77 [1.48-2.11]) and lung (OR=1.45 [1.21-1.74]) vs no significant difference for bone (OR=1.17 [0.92-1.50]) and lymph (OR=0.87 [0.71-1.07]) sites. B use in 3L mirrored 2L. Conclusions: Besides 1L in pts with lymph metastases, top regimens across met sites for 1L, 2L, and 3L were FX + B, FR + B, and IRI + C, respectively; however, significant differences in B Tx patterns were evident. Further research should examine the impact of differential B use on outcomes. [Table: see text]
Association of genetic variants in plastin family genes with tumor recurrence in stage II/III colon cancer.
Authors: Ning Yan , Winder Thomas , Zhang Wu , Yang Dongyun , Loupakis Fotios , Wakatsuki Takeru , Bohanes Pierre Oliver , EI-Khoueiry Rita , Barzi Afsaneh , Iqbal Syma , EI-Khoueiry Anthony , Lenz Heinz-Josef 
Published: March 2020

e14031 Background: Plastins belong to a subclass of actin-binding proteins known as actin bundling proteins. Plastins family constitute of two isoforms in human as T-plastin (PLS3) and L-plastin (LCP1). Recent in vitro and in vivo studies found plastin genes are overexpressed in colon cancer cells and can lead to increased proliferation, invasion and metastasis. Here we tested the hypothesis whether potential functional tagging polymorphisms in PLS3 (rs6643869, rs5987947, rs2522188) and LCP1 (rs4941543, rs1409429, rs11342) may predict tumor recurrence in adjuvant colon cancer patients. Methods: Either blood or FFPE tissue specimens were obtained from 234 patients (107 females and 127 males; median age 59 years (range 22–78 years)) with stage II (105 patients) or III (129 patients) colon cancer at the University of Southern California/Norris Comprehensive Cancer Center. The median follow-up was 4.4 years. PLS3 and LCP1 SNPs were determined by PCR-RFLP or PCR-based direct sequence. The primary endpoint of the study was time to tumor recurrence (TTR). Results: In univariable analysis, PLS3 rs6643869 and LCP1 rs4941543 were significantly associated with time to tumor recurrence (TTR). Patients with PLS3 AA genotype had shortest median TTR 3.2 years (95% C.I: 1.5-10.7) compared to those with AG or GG genotype, which had median TTR 9.4 years (95% C.I: 5.7-12.2) (p=0.012, log-rank test). Patients with LCP1 CC genotype had longer median TTR 10.7 years (95% C.I: 5.7-16.8+) compared to those with CT and TT genotypes, which had shorter median TTR 4.9 years (95% C.I: 1.4-9.0+)(p=0.040, log-rank test). PLS3 rs6643869 remained significant in the multivariate Cox regression model adjusted by stage and type of adjuvant therapy and stratified by race (p=0.021). Conclusions: Our preliminary results demonstrated that polymorphisms in plastin family genes PLS3 and LCP1 might be potential molecular markers to predict TTR in adjuvant colon cancer. Further large and biomarker embedded trial needed to confirm our findings.
Standardization for lymphatic mapping in breast, melanoma, and GI cancers: An international survey.
Authors: Kanaan Mohammed Nawaf , Kitagawa Yuko , Zuber Markus , Manyam Madhavi , Gafford Philip , Wiese David , Beutler Thomas , Arora Madan L. , Takeuchi Hiroya , Saha Sukamal 
Published: March 2020

e14045 Background: The technique of SLNM varies between surgeons, hospitals, and countries in terms of type and amount of dye, pathologic examination of SLN, technical issues of dye injection. The purpose of this study is to evaluate the methods of lymphatic mapping in solid tumors around the world to create a form of international reference for all surgeons to use in patients with breast, melanoma, and GI cancers. Methods: A web-based survey form was created with 12 questions in regards to various aspects of SLNM, for melanoma, breast, esophagus, stomach, colon and rectal cancers. This questionnaire was distributed to 425 centers in the U.S, 60 in Europe, and 60 in Japan. Results: Of the 545 centers surveyed, 122 centers (22.4 %) responded. Of these, 47 were from U.S, 60 from Japan, and 15 from Europe. The order of frequency of the organ sites for lymphatic mapping were: Breast, melanoma, stomach, colon, esophagus, and rectum. There were 56 centers that perform SLNM in one organ site (most common breast), 39 on 2 organ sites, and 14 centers on 3 organ sites. Radiocolloid was the most common mapping agent used 80%. Most common blue dyes were Lymphazurin/Isosulfan in U.S, Patent Blue in Europe and Indocyanine Green in Japan. For breast , the most common site of injection was subareolar, while in upper GI submucosal, and in lower G.I it was subserosal. Overall the average volume of injection for mapping was 1-2 ml (range 0.4-5 ml). Pathological intraoperative interpretation varied from 74% in breast, 38% in melanoma, and 42% in upper G.I and 26% in lower G.I. Conclusions: Although a pattern of continuity emerged through this survey in regards to mapping techniques, there were significant variances between centers and organ sites.Thus, the need for standardization in lymphatic mapping for solid tumors to act as a reference point for future oncologists to follow. [Table: see text]
Tumor size as a prognostic factor for colon cancer patients undergoing sentinel lymph node mapping and conventional surgery.
Authors: Saha Sukamal , Kanaan Mohammed Nawaf , Mozayen Mohammad , Gafford Philip , Shaik Mohammed Saifullah , Johnston Gregory , Tesfaye Anteneh A. , Nagpal Sunil , Kaushal Sunil , Wiese David 
Published: March 2020

e14046 Background: Unlike other solid tumors, tumor size (TS) is not a part of the TNM staging system for colon cancer. Our goal is to correlate TS with TNM staging, nodal positivity (NP), and 5-year overall survival (OS) for patients (pts) with invasive colon cancer undergoing sentinel lymph node mapping (SLNM) vs. conventional surgery (CS). Methods: A retrospective review of 681 pts with invasive adenocarcinoma of the colon were reviewed and divided into two groups of pts (SLNM and CS). These groups were subdivided according to the size of the tumor in four groups (0-2, 2-4, 4-6 and more than 6 cm). 461 pts underwent SLNM between 1996-2010 compared to 220 pts who underwent CS between 1996-2006. The pathology reports reviewed for TS (the maximum diameter of the primary tumor), T staging, and NP. The OS was calculated from the social security database. Then all data was compared between both groups. Results: Pts with tumors <2cm were mainly T1+T2 (72%, 70%), whereas tumors >6 cm, majority of pts wereT3+T4 (94%, 85%). T1+T2 percentage consistently decreased as TS increased, and T3+T4 percentage was increasing consistently with increased TS (Table 1A). NP according to TS for SLNM pts were (16%, 53%, 56%, 48%) NP and for CS pts were (15%, 32%, 34%, 39%). In both groups, NP increased as TS increased compared to 0-2 cm group. The overall NP in both groups was 47% and 31% (Table 1B). OS for SLNM and CS pts were calculated in each group according to TS. Overall SLNM pts had better OS when compared to CS pts (65 %, 54%). Conclusions: Increasing TS was consistent with increasing T staging for both SLNM and CS pts. NP and OS were worse with increased TS for SLNM and CS pts. SLNM pts had higher NP and better outcome in OS when compared to CS pts, hence TS should be considered as a prognostic factor in pts with adenocarcinoma of the colon. [Table: see text] [Table: see text]
Patterns of peri-operative systemic therapy in liver-limited metastatic colorectal cancer (mCRC).
Authors: Kellock Trenton Tyler , Renouf Daniel John , Speers Caroline , Cheung Winson Y. 
Published: March 2020

e14048 Background: Treatment for liver-limited mCRC is increasingly multi-disciplinary, frequently involving systemic therapy and surgery. Our aims were to 1) explore the use and choice of systemic therapy pre- and post-liver resection and 2) examine if specific regimens were associated with improved outcomes. Methods: All patients diagnosed with liver-limited mCRC in British Columbia, Canada from 2006 to 2007 were reviewed. Summary statistics were used to describe surgical and systemic treatment patterns. Kaplan-Meier methodology was used to characterize the relationship between systemic regimen and survival. Results: Among 374 patients, 42% were aged >/=70 years, 60% were men, 24/39/37% were ECOG 0/1/2+, 80% had primary tumor surgery, and 68% received prior adjuvant chemotherapy. For liver metastases, 95 (26%) were offered hepatic resection. Compared to those who did not receive liver surgery, resected patients were younger (median 60 vs 69), had better function (ECOG 0/1 88 vs 55%), largest liver lesion was smaller (median 3 vs 4 cm), and had fewer total lesions (median 1 vs 4) (all p<0.05). Patients who underwent liver surgery also had improved median overall survival (12.0 vs 9.4 months, p<0.05) than those who did not. Among resected patients, 47% received pre-operative chemotherapy: FOLFOX (28%, median 7 cycles), FOLFIRI (18%, median 9 cycles), or capecitabine (1%, median 6 cycles) while 74% received post-operative treatment: FOLFOX (26%, median 3 cycles), FOLFIRI (37%, median 9 cycles), or capecitabine (11%, median 8 cycles). About 15% and 31% of patients also received bevacizumab as part of their pre- and post-operative regimens, respectively. Median overall survival did not differ significantly based on choice of chemotherapy backbone: FOLFOX (13.9 months), FOLFIRI (11.5 months), and capecitabine (10.9 months) (p=0.44) or receipt of bevacizumab: yes (14.5 months) vs no (11.1 months) (p=0.57) Conclusions: In this retrospective cohort of liver-limited mCRC patients, hepatic resection was associated with improved survival. Among those offered peri-operative therapy, FOLFOX, FOLFIRI, and capecitabine, either alone or in combination with bevacizumab, appear to be reasonable options.
Burden of illness in second-line colorectal cancer: A systematic literature review.
Authors: Priedane Eugenia , Xu Yingxin , Wilson David , Jasso Mosqueda Juan Guillermo , Iqbal Sheikh Usman , Naoshy Sarah 
Published: March 2020

e14061 Background: Colorectal cancer (CRC) is the third and second most common cancer in males and females, respectively, worldwide. Based on cases diagnosed in 2008, the age-adjusted incidence rate of CRC was 47.2/100,000/year in the US. Approximately 15-25% of all new cases are diagnosed with metastases and half of all cases result in metastases, representing an increased health and economic burden. The objective of this study was to gain a more in-depth understanding of the epidemiology, clinical and economic burden of second-line CRC in the US, Europe big 5, BRIC-M countries, and Japan. Methods: A Cochrane standard systematic literature review was performed using EMBASE, PubMed, NHSEED databases, and data from key congresses. Searches were conducted using specifically tailored search algorithms for years 2006-2011. Results: Of the 1,377 citations reviewed, 10 studies were identified (6 were epidemiology studies). No information on the number of patients treated for second-line mCRC was found. Estimates of median overall survival were short and varied from 7-18.7 months. New chemotherapy regimens, younger patients, and patients without KRAS mutations are associated with longer overall survival. Information on clinical burden of disease was also limited. The majority of patients presented with liver metastases (73%) and cardiovascular disease (63%). Three clinical trials evaluated quality of life (QoL) with significant heterogeneities in study design, population, treatment regimens and assessment instruments used. No statistically significant results favored targeted therapy. Only 1 study conducted in the US assessed economic burden in patients treated with either bevacizumab or cetuximab. At 6 months the total health care cost was $73,712 and $81,781 respectively, with main cost drivers being outpatient and targeted therapy costs. Conclusions: A substantial evidence gap regarding knowledge of burden of illness in second-line mCRC limits informed clinical and economic decision making. Further research is required to evaluate country-specific epidemiologic and survival data, QoL, resource utilization and cost variation associated with active treatment and end of life care. Research funded by Sanofi/Regeneron.
Down-regulation of KRAS-interacting miRNA-143 to predict prognosis and response to EGFR-targeted agents in colorectal cancer.
Authors: Eisner Florian , Stotz Michael , Samonigg Hellmut , Lax Sigurd , Hoefler Gerald , Pichler Martin 
Published: March 2020

e14066 Background: MicroRNA-143 is frequently down-regulated in colorectal cancer (CRC) and influence CRC cell proliferation, apoptosis and sensitivity to 5-fluorouracil. mRNA encoded by the KRAS oncogene has been identified as a target of microRNA-143. However, the prognostic significance of microRNA-143 expression and the ability to predict the patient response to EGFR-targeted agents have not been explored yet. Methods: In this study, we analyzed 77 CRC harboring wild-type KRAS and obtaining treatment with the EGFR-targeting monoclonal antibodies cetuximab or panitumumab. MicroRNA-143 expression was measured by RT-PCR in both CRC and corresponding non-neoplastic colon tissue and the expression levels were correlated with clinico-pathological characteristics. Cancer-specific survival was calculated by uni- and multivariate analyses. The progression-free survival and objective response rates on EGFR-targeted therapy were also evaluated. Results: Down-regulation of microRNA-143 was observed in 47/77 (61%) CRC. Multivariate Cox regression analysis identified low levels of microRNA-143 expression as an independent prognostic factor with respect to cancer-specific survival (HR=1.92, CI=1.1-3.4, p=0.024). A significant difference was observed with respect to progression-free survival on EGFR-targeted therapy (p=0.031, log-rank test), but there were no significant differences with regard to the objective response rate. Conclusions: Our data suggest that microRNA-143 expression levels serve as independent prognostic biomarker for KRAS wild-type CRC patients but not as predictor for EGFR-targeted therapy. In addition, we consider microRNA-143 as a potential drug target for future therapy of CRC.
Tumor microRNA-29a expression and the risk of recurrence in stage II colon cancer.
Authors: Purim Ofer , Weismann-Brenner Alina , Kushnir Michal , Lithwick-Yanai Gila , Aharonov Ranit T. , Gibori Hadas , Kundel Yulia , Morgenstern Sara , Halpern Marisa , Niv Yaron , Brenner Baruch 
Published: March 2020

e14067 Background: To compare the microRNA (miRNA) profiles in the primary tumor of patients with recurrent and non-recurrent colon cancer. Methods: The study population included 110 patients, 51 (46%) with stage I and 59 (54%) with stage II disease, who underwent curative colectomies between 1995-2005 without adjuvant therapy and for whom reliable miR expression data was available. RNA was extracted from formalin-fixed paraffin-embedded tumor samples. Initial profiling, using microarrays, was done in order to identify potential biomarkers of recurrence. The miRNA expression was later verified by quantitative real-time polymerase chain reaction (qRT-PCR). Findings were compared between patients who had a recurrence within 36 months of surgery (bad prognosis group, n=23, 21%) and those who did not (good prognosis group, n=87, 79%) in the entire group and within each stage. Results: In stage I, none of the 903 miRNAs tested showed differential expression between patients with good prognosis compared with those with bad prognosis. In stage II, one miRNA, miR-29a, showed a clear differential expression between the groups (p=0.028). High expression of miR-29a was associated with a longer disease-free survival (DFS), on both univariate and multivariate analyses. Using miR-29a, the positive predictive value for non-recurrence was 94% (2 recurrences among 31 patients). The differential expression of miR-29a was verified by qRT-PCR, showing a similar impact of this miR on DFS. Conclusions: This study demonstrated a significant impact of miR-29a on the risk of recurrence in patients with stage II but not in patients with stage I colon cancer.
Evaluation of relapse-free survival in T3N0 colon cancer: The role of chemotherapy—A multicentric retrospective analysis.
Authors: Grande Roberta , Cosimelli Maurizio , Gemma Donatello , Ciancola Fabrizio , Corsi Domenico C. , Rossi Lorena , Sperduti Isabella , Fabbri Maria Agnese , Mancini Raffaello , Ruggeri Enzo , Longo Flavia , Quadrini Silvia , Zampa Germano , Bianchetti Sara , Gamucci Teresa 
Published: March 2020

e14082 Background: Use of adjuvant chemotherapy (AC) in Stage II Colon Cancer (CC) is still under debate. Choice should be based on patients (pts) and disease characteristics. According to worldwide guidelines AC should be considered in high-risk (H) T3N0 pts. No data are available for better option in low-risk (L) pts. Aim of the study is to evaluate relapse-free survival (RFS) and disease-free survival (DFS) retrospectively in T3N0 CC pts related to treatment. Methods: RFS and DFS are evaluated with Kaplan Meier method. In order to find the optimal cut off for node number the receiver operating characteristics curve analysis and Maximally Selected Rank Statistics were performed. Multivariate Cox proportional hazard model was developed using stepwise regression, enter limit and remove limit were p = 0.10 and p = 0.15 respectively. Results: 1,000 pts with T3N0 CC were recruited. To date, data of 926 pts are available. Median age was 69 (29-93), M/F 513/413, Grading 1/2/3 46/668/158; 360 L (39%), 411 H (44%), 155 unknown (17%); 137 (15%) pts showed symptoms (S) at diagnosis: 51 pts had perforation (P) or bowel obstruction (BO). Median sampled lymph nodes (LN) were 15 (1-76); 383 (41%) pts were treated with AC. Median follow up (fu) was 5 years (yr) (range 3-24). Survival analysis was performed only for pts with a minimum fu of 3 yr and younger than 80 (80%). 5 yr RFS was 78% and 5 yr DFS was 76% At multivariate analysis S and AC were prognostic factors for RFS. AC is prognostic factor for all endpoints (data are shown in table). In L group 5 yr RFS was 88% in treated pts and 75% in non-treated pts (p 0.03); in H group was respectively 82% and 72% (p 0.006). Conclusions: Preliminary data confirmed the role of known prognostic factors and suggest the relevance of AC also in L stage II T3N0 CC pts. However, the highest risk in L subgroup should be identified to be submitted to AC. Data collection is ongoing, update results will be presented. [Table: see text]