bluuebunny/crossref_metadata_2025_split huggingface dataset:
3D in vitro system for measuring treatment responses to immunotherapy in CRC patients.
Authors: Block Andreas , Stamm Hauke , Temovski Tamara Sutus , Konczalla Leonie , Brauneck Franziska , Stange Inke , Koellmann Sandra , Li Jun , Perez Daniel R. , Thastrup Jacob , Wellbrock Jasmin , Fiedler Walter M. , Kupper Juergen , Sturmheit Tabea 
Published: May 2019

e15114 Background: Current clinical guidelines for the treatment of cancer patients mainly rely on intrinsic characteristics of a given tumor, such as its localization, its staging and in some instances also known genetic markers. The success of treatment administered according to this proceeding is, however, undermined by large inter-individual variability of tumors. Embedded in a unique meshwork of extracellular matrix, stromal cell and bioactive factors, malignant cells accumulate a distinctive pattern of genetic, epigenetic and metabolic alterations, resulting in unrestricted growth. Despite the potential availability of tailored drugs, matching cancer drug therapy to the unique characteristics of a patient’s tumor, is generally unfeasible in clinical practice. Methods: Addressing this need, 2cureX developed a functional test (IndiTreat) for measuring the responsiveness of micro-tumors (tumoroids) derived from colorectal cancer (CRC) and liver metastases to chemotherapeutic agents, targeted therapies and combinations thereof. To further broaden the applicability of the IndiTreat test, the present study aims to adapt the assay system to functional testing of immunotherapeutics. The success of immunotherapeutic treatment (I/O) regimens is currently limited to a small subset of CRC patients such as those with microsatellite instability (MSI) high tumors. However, new chemo-immunotherapies may prove beneficial for a greater percentage of patients. Results: To pre-therapeutically assess the potential efficacy of I/O interventions for individual patients, we co-culture tumoroids and autologous PBMCs and monitor immune-mediated killing of tumoroids in vitro. Subsequently, these culture systems will be tested regarding their susceptibility towards an array of single or combined I/O drugs. Tumoroids recapitulate the highly individual disease of cancer patients and, as demonstrated by our allogenic setting, constitute a valuable platform for testing different aspects of immune-mediated tumor cell recognition and killing. Conclusions: In light of an increasing number of cost-intensive I/O treatment options becoming available to CRC patients, pre-therapeutic testing of individual responses to immunotherapy will be of key relevance in assisting the oncologist to select the most potent treatment regime for every patient available.
Pattern of expression of CDX2 in colorectal cancer and its role in prognosis.
Authors: SINGH JAGDEEP 
Published: May 2019

e15115 Background: CDX2 (Caudal Type Homeobox 2), a nuclear protein, is essential for the proliferation and development of intestinal epithelial cells and is frequently down-regulated during tumourogenesis. We have evaluated the pattern of expression of CDX2 in all stages of CRC (colorectal cancer) and its association with prognosis. Methods: We performed CDX2 staining by Immunohistochemistry (IHC) on the available biopsy block of patients of CRC registered with Medical Oncology, JIPMER, from January 2014-January 2018. CDX2 scoring was done by semi-quantitative method. Results: 286 patients were registered during study period, of which only 110 biopsy blocks were available for staining. Of 110 patients, 77 (70%) constituted colon cancer and 33 (30%) were rectal cancer. The median age was 54.2 years, 62 (56.4%) being male and 48 (43.6%) female with male to female ratio 1.3:1. In the study cohort, 33 (30%) patients had stage II disease, 30 (27.3%) stage III and 47(42.7%) were stage IV. 73 (66.4%) were positive for CDX2 and 37 (33.4%) were negative. Lack of CDX2 expression was significantly associated with advanced stage, rectal site, poor grade of differentiation, and presence of lympho-vascular invasion (LVSI). With median follow-up of 16 months, PFS (progression free survival) at 2 years was 30% for CDX2 negative patients compared to 67% CDX2 positive (P=0.009), while OS (overall survival) at 2 years was 46% for CDX2 negative versus 77% for positive patients (p=0.01). Conclusions: Lack of CDX2 is associated with significantly worse PFS and OS, serves as a poor prognostic factor in CRC. Lack of CDX2 expression is associated with advanced stage, higher tumor grade and presence of LVSI.
Turning on the lights in gastrointestinal oncology: How digital medicines reveal clinical insights on medication adherence and patient behaviors.
Authors: Morales Paul , Beiswenger Daniel , Lee Won Chan , Travis Ellen , Greeno Edward 
Published: May 2019

e15118 Background: Oral therapies in colorectal cancer (CRC) introduce unique complexities in care. Understanding adherence in patients using capecitabine can be challenging. The Discover Program, a novel digital medicine program (DMP), was integrated into the treatment of CRC patients at Fairview Health Services and University of Minnesota Health, the first ever DMP in the field of oncology. The DMP consists of DigiMeds (medications with ingestible sensors), a small wearable patch, and a mobile app, which enable collection of objective adherence data, alongside biometrics (e.g., steps, rest, resting heart rate) giving patients, caregivers, and providers the ability to confirm treatment start dates, address missed doses and observe changes in physical function. Methods: From September 2018 to December 2018, patients with CRC were enrolled in the DMP. Clinical pharmacists (CPs) monitored adherence data and patient metrics through a secure web portal to enhance regular follow-up, address barriers to adherence, reveal unreported Adverse Events (AE), provide coaching and education, and target therapy adjustments when appropriate. Qualitative data regarding pharmacists’ experiences with the DMP and their evolving interactions with patients were collected. Results: Seven patients were enrolled in the DMP (mean age: 62.1 ± 8.45 years (mean ± SD); 85.7% female; patch wear: 92.4% ± 6.8%; average adherence: 89.7%± 7.8%; average days on DMP: 55.6± 39.2 days). CPs reported that objective medication adherence data eliminated the challenge of navigating patient recall about their medication taking and health overall. The DMP allowed prompt and tailored interventions for patients struggling with adherence to prescribed regimens and/or AEs. These interventions were more focused, personalized, and clinically meaningful with improved shared decision-making, increased patient engagement/adherence, and more efficient/effective AE management. Conclusions: DMP data yielded significant insights that are not available in the absence of this novel technology. Future pragmatic, large real-world studies are recommended to assess the impact of DMP on adherence, AE management, and clinical and economic outcomes.
RAS mutations in patients with metastatic colorectal cancer in Central America and the Caribbean.
Authors: Garcia-Aceituno Luis , Castro Noe , Alvarado Francisco , Castro Salguero Hugo Raul , Loo Yong Pain , Castro Jenny Lissette , Ramos Pier Angelo , Cabreja Angela Margarita , Rosales Finlander , Barillas Allan , Ramos-Esquivel Allan , Umanzor Jorge , Umanzor Funez Gerardo Antonio , Guardia Mario , Bacon Fonseca Ludwing Alexander 
Published: May 2019

e15126 Background: Metastatic colorectal cancer (MCRC) survival has been improved in the last decade due to the identification of predictive and prognostic factors such as RAS gene status and also by the addition of targeted therapies to chemotherapy schemes. RAS mutation, a prognostic factor but must importantly a predictive factor for tumor response to monoclonal antibodies against the epidermal growth factor receptor in MCRC, has been reported between 16.3% and 43.6%. The aim of this study is to determine the frequency of RAS mutations in patients with MCRC in Central America and the Caribbean. Methods: This is a retrospective-descriptive analysis of RAS mutations performed in patients with MCRC in Central America and the Caribbean. An informed consent was required for the mutational analysis. The information obtained has been kept in an anonymized database. Results: 2,138 tissue samples were analyzed by real time PCR. RAS mutations were documented in 46.7% of the cases, of these 94.8% correspond to mutations in kRAS and 5.2% to mutations in nRAS. 67.5% of RAS mutations were found in codon 12, 21.3% in codon 13, 5.8% in codon 146 and 4% in codon 61. 51.5% of the mutations were in males and 48.5% in females. RAS mutations in central american population were identified in a 45.8% and in a 42.5% in the caribbean. Conclusions: This is the first report of RAS mutations in patients with MCRC in Central America and the Caribbean. Our findings are similar to the data reported in other regions of the world. A clinical and epidemiological analysis and correlation of these findings is underway.
Prognostic value of circulating cytokines in colorectal cancer: A prospective study in sixty colorectal cancer patients in Tunisia.
Authors: Ayari Jihene Braham , Guesmi Rania , Balti Mehdi , Ben Azaiz Mouna , Zribi Aref , Fendri Sana , Ben Nasr Sonia , Ghazouani Ezzedine , Agili Faida , Kullab Sharif Ahmed , Haddaoui Abderrazek 
Published: May 2019

e15130 Background: Colorectal cancer is the third most common malignancy and fourth most common cause of cancer mortality worldwide. It is responsible for more than 600,000 deaths annually, and incidence rates are increasing in most of the developing countries. Pathophysiology implicates pro-inflammatory conditions that promote the tumor malignant progression, invasion, and metastasis. The aim of this study is to measure the level of circulating cytokines (IL1b, IL6, IL8, IL10, IL22, IL23 and TNFα) in sixty colorectal cancer patients in Tunisia and to evaluate their implication as prognostic factors. Methods: Serum samples were collected prospectively from a cohort of sixty colorectal cancer patients in Tunisia. Levels of circulating inflammatory cytokines, TNF-α, IL1b, IL6 and IL8 were measured using the technique of a solid-phase, two-site chemo-luminescent enzyme immune-metric assay (Immulite 1000, Simens, USA). Serum levels of IL10 were measured by enzyme-linked immunosorbent assays (ELISA) sandwich method. Results: The mean age of patients is 58 years (24–82 years), Thirty-sex among them were m and 24 women with sex ratio of 1.5. Twenty-five patients were at metastatic setting, and hepatic metastasis was found in 25% of cases. The mean level of cytokines Il6, IL10, TNFα, IL8 and IL1b were respectively 12.26 +/- 18.7 pg/ ml (min 2, max 117pg/ ml), 0.93 +/- 5.23 pg/ ml (min 0, max 39.35 pg/ml), 8.31 +/- 4.99 pg/ ml (min 4, max 27.20 pg/ ml), 61.9 +/- 159.71 pg/ml (min 5, max 1173 pg/ ml) and 1.13 +/- 3.34 pg/ ml (min 5, max 15.7pg/ml. We found a significant correlation between a high level of IL8 and metastatic disease (p=0.001), especially in mutant RAS cases (p=0.001). We found also a significant correlation between high level of IL1b and lymphovascular invasion (p=0.013) and young patients (p=0.01). On the other hand, there was significant correlation between IL8 and IL6 (r = 0.560, p = 0.00001); IL8 and TNFα (r = 0.404, p = 0.001); and IL10 with IL1b (r = 0.297, p = 0.021). Conclusions: Our results highlight the role of circulating IL8, TNFα, IL1b and IL10 as potential prognostic biomarkers in colorectal cancer patients. These cytokines could contribute to tumor growth and progression, namely for IL-8 level that was significantly correlated with poor prognosis and advanced stages. This correlation needs to be evaluated in large prospective trials and suggests a rational for the development and use of cytokine blockade in treatment of colorectal cancer patients.
Meat consumption and BRAF mutation status in colorectal cancer.
Authors: Frias Rosa L. , Lam Michael , Overman Michael J. , Morris Van K. , Fogelman David R. , Kee Bryan K. , Dasari Arvind , Raghav Kanwal Pratap Singh , Shureiqi Imad , Jiang Zhi-Qin , Jensen-Loewe Patricia A. , Wolff Robert A. , Eng Cathy , Menter David , Kopetz Scott , Davis Jennifer S. 
Published: May 2019

e15135 Background: Consumption of red and processed meat has been associated with increased risk of developing colorectal cancers, but less is known about the association of meat consumption with tumor molecular features. In this study, we tested the association of total meat consumption with molecular features of colorectal cancer and overall survival in a local cohort of patients. Methods: Data on meat consumption were collected using self-directed environmental surveys from patients with stage IV/locally advanced, treatment refractory colorectal cancer who were enrolled on the Assessment of Targeted Therapies Against Colorectal Cancer clinical protocol. Data on tumor molecular features were collected through medical record review. Patients were categorized into low, medium or high meat consumption groups based on servings per day tertile. Associations between tumor molecular features and meat intake were evaluated by Chi-square and logistic regression. Potential effects of meat consumption on overall survival were assessed using Cox Proportional Hazards models. Analyses were conducted with IBM SPSS v25. Results: Patients consumed an average of 0.74, 1.57 and 3.32 servings of meat per day in the low, medium and high categories, respectively. Out of 593 patients with evaluable data, 27 were found to have a BRAF V600E mutation. Total meat consumption differed significantly by BRAF V600E mutation status (p value 0.02) and by sex (p value < .01), but did not differ by tumor location, microsatellite instability, or RAS mutation status. Using logistic regression, we found that compared to patients with the highest level of meat consumption, those in the medium consumption group may be less likely to have a BRAF V600E mutation (OR 0.24; p value 0.08). Although meat consumption may be associated with BRAF mutation status, it was not predictive of overall survival in our analyses. Conclusions: Among patients in our study, meat consumption may be associated with tumor BRAF V600E mutation status but is not directly associated with survival. Additional work is needed to test this association in cohorts including more BRAF mutant cases. If confirmed, this finding may add further insight into the etiology and biology of these tumors.
KRAS mutation and microsatellite instability in colorectal cancer: Screening pattern and mutational landscape across the US.
Authors: Uhlig Johannes , Stein Stacey , Lacy Jill , Kim Hyun S. 
Published: May 2019

e15138 Background: To assess screening patterns for KRAS mutation and microsatellite instability (MSI), associated mutational prevalence in colorectal cancer (CRC), and whether mutational screening affects survival. Methods: Patients with adenocarcinoma of the colon, sigmoid, and rectum were included from the 2010-2015 National Cancer Database. Socioeconomic, geographic and cancer factors were correlated with screening patterns. Propensity score matching was used to account for confounding. Overall survival was assessed in the matched cohort via Cox proportional hazards models. Results: 371,669 patients were included, of which 113,197 (30.4%) were screened: n=63,967 for MSI, n=33,319 for KRAS, and n=15,911 for MSI + KRAS. Younger patients with private insurance, high income locally advanced and metastatic sigmoid CRC treated at academic centers in Middle Atlantic and New England states were more likely to be screened. MSI was more prevalent among older female Caucasians from East South Central and Middle Atlantic States. KRAS mutation showed no significant discrepancies according to patient age or US geography, but was more prevalent among female African Americans. KRAS mutation was associated with locally advanced and metastatic CRC. MSI was more common in localized, non-metastatic CRC. Distinct mutational patterns were evident among primary CRC sites, with highest mutation rates in cecum/appendix and ascending colon (table). In the propensity score matched cohort with balanced distribution of confounders (n=157,678), mutational screening was not associated with overall survival (HR=1.012, 95% CI: 0.99-1.03, p=0.15). MSI versus MSS did not significantly influence patients´ overall survival (matched cohort n=26,014, HR=1.00, 95% CI: 0.96-1.05, p=0.88). Kras mutation versus wildtype showed decreased overall survival after accounting for confounders (matched cohort n=28,084, HR=1.11, 95% CI: 1.07-1.15, p<0.001). Conclusions: Testing for MSI and Kras mutation in CRC shows distinct patterns across the US, but does not influence outcomes. Decreased overall survival is observed in those patients with Kras mutation versus wildtype. [Table: see text]
Colorectal cancer in young patients: An institutional experience.
Authors: Hanayneh Wissam , Wang Yu , George Thomas J. , Cameron Miles , Tan Sanda , Iqbal Atif , Read Thomas , Allegra Carmen Joseph , Parekh Hiral D. 
Published: May 2019

e15140 Background: The incidence of colorectal cancer (CRC) in young patients (<50 years) is increasing but little is known about disease characteristics and treatment outcomes in this patient population. Methods: CRC patients diagnosed at < 50 years of age (UF registry 2000-2017) constituted the IRB approved study cohort. Statistical methods included descriptive statistics, uni-variable cox proportional hazard regression model, Pearson chi-square exact and Wilcoxon rank-sum test. Results: Young CRC patients (n= 286) comprised 16% of total CRC patients (n= 1806) treated at our institution. (See Table for demographics and tumor characteristics). The median age at diagnosis was 45 years (range 17-50) with 74% diagnosed between age 40-50. One third (35.7%) of patients had rectal primary. DNA mismatch repair gene deficiencies (dMMR) and/or microsatellite instability (MSI) was tested in 60.1%; 10.5% had MSI-H or dMMR tumors and 11 of those had confirmed Lynch syndrome. Next generation sequencing (n= 71) or mutational analysis (n= 79) was performed. Most common mutation was exon 12 of K- ras (40.7%, n = 61) followed by TP53 (7.33%; n = 11) and PIK3CA (5.33%; n = 8). BRAF V600E was seen in 5 patients. Patients who underwent curative resections had better hemoglobin (p=0.005), albumin levels (p <0.001) and lower CEA level (p<0.001). Factors associated with poor survival were low albumin ≤34 g/l, advanced primary tumor (T3/T4), nodal disease (N1/N2) and presence of diffuse metastases. For stage 4 disease, the cancer-specific survival (CSS) at 1 year was 77.2%, 3-year CSS was 46.1% and 5-year CSS was 29%; survival was better (HR=0.4; 95% CI 0.2-0.6, p<0.001) among patients who underwent metastatectomy. Conclusions: Our results reveal that the most young CRC were 40-50 years age group with a female preponderance. Young CRC patients were more likely to be managed in an aggressive manner with a higher proportion of early stage patients receiving perioperative therapy. A suggestion of an improved CSS was seen in advanced stage disease even with similar prognostic factors. Review of larger data sets are warranted. [Table: see text]
Metastatic pattern and tumor sidedness in colorectal cancer.
Authors: Muzaffar Mahvish , Naqash Abdul Rafeh , Liles Darla K. , Kachru Sumyra 
Published: May 2019

e15147 Background: Tumor side has emerged as an important prognostic and predictive factor in metastatic colon cancer. We sought to study its impact on the metastatic pattern of colorectal cancer. Methods: The SEER database (version 8.3.5) was reviewed for patients with Stage IV colorectal cancer diagnosed between 2004-2015. We only included patients with labeled primary site, and excluded appendiceal, unlabeled and autopsy alone cases. Variables included in the analysis were: age, race, gender, grade, primary tumor side and sites of metastasis at diagnosis. Primary outcome analyzed was overall survival and disease specific survival.Cox proportional hazard regression model was employed to test the association between survival and side of cancer/ site of metastasis. Results: A total of 74,768 cases were identified who met the eligibility criteria. The mean age was 68.5 yrs. for right colon cancer (RCC),64.0 yrs. for left colon cancer (LCC). and 62.9 yrs. for rectal cancer. White race was predominant group for RCC, LCC and rectum. More females were vs men in RCC (52% vs 48%), LCC (44% vs 56%) and rectum (60% vs 40%). (The cox regression model suggested inferior outcome for black race HR 1.05(1.03-1.07) (<0.001), high grade HR 1.32(1.30-1.35) p<.0001, right side tumors HR 1.23(1.21-1.250, p <.0001 (table). Conclusions: Over last few years tumor sidedness has emerged as an important prognostic and predictive factor in colon cancer. Our study also highlights the impact of sidedness on survival irrespective of distant metastatic pattern. This analysis contributes to the ongoing discussion that right and left colon cancer are two distinct disease entities. Impact of primary tumor side and metastatic site on survival in colorectal cancer. [Table: see text]
IGF-1 and IL-6 as predictors of sarcopenia in non-metastatic colorectal cancer patients.
Authors: Khaddour Karam , Castellanos Karla , Fantuzzi Giamila , Mutlu Ece , Gomez-Perez Sandra L 
Published: May 2019

e15150 Background: Insulin growth factor-1 (IGF1) and inflammatory biomarkers such as interleukin-6 (IL6) play a role in early carcinogenesis, predict prognosis and response to some therapies in colorectal cancer (CRC), and are altered in patients with sarcopenia. This study examines the association of IGF-1 and IL-6 with sarcopenia in patients with CRC. Methods: Fasting blood samples were collected at diagnosis of non-metastatic CRC (N = 59) and analyzed for serum IGF-1 and IL-6 by ELISA. Skeletal Muscle Index (SMI) was calculated from cross-sectional image at L3 from computed tomography. Sarcopenia was defined based on published cut points for adults with cancer stratified by body mass index (BMI) as: SMI < 43 cm2/m2 for men and < 41 cm2/m2 for women for normal and underweight; and SMI < 53 cm2/m2 for men and < 41 cm2/m2 for women for overweight and obese. Median and interquartile range (IQR) were reported for patients with sarcopenia versus those without sarcopenia. Spearman and logistic regression were used to examine associations between sarcopenia and serum biomarkers. Results: Median (IQR) age was 62 (49-85). Overall prevalence of sarcopenia was 44% (26/59). The prevalence of sarcopenia was 3% for males (2/59) and 5% for females (3/59) with a BMI < 25 and 27% for males (16/59) and 8% for females (5/59) with a BMI≥25. Median and (IQR) for serum biomarkers in patients with CRC and sarcopenia versus those without sarcopenia were: IGF-1 43 (16) vs. 58.7(27.9) ng/mL (p = 0.007). Correlation between IGF-1 and sarcopenia was (r = -0.4, p = 0.004), but was not statistically significant for IL-6 (r = 0.02, p = 0.88). Both IGF-1 (OR = 0.82, 95% CI 0.69-0.98, p = 0.03) and IL-6 (OR = 0.83, 95% CI 0.70-0.98, p = 0.002) were significant predictors of sarcopenia after adjusting for race and BMI. Conclusions: In this sample of patients with CRC, IGF-1 and IL-6 levels were both lower in patients with sarcopenia compared to those without sarcopenia and levels of both markers predicted the presence sarcopenia.