bluuebunny/crossref_metadata_2025_split huggingface dataset:
Curative versus palliative therapy for patients with colorectal cancer presenting to the emergency department.
Authors: Barnett Andy Stuart , Chen Yiyi , Chen Zunqiu , Daya Mohamud , Thomas Charles R. , Herzig Daniel 
Published: February 2017

433 Background: Colorectal cancer (CRC) is the second leading cause of cancer death in the United States for men and women combined, and can present emergently with symptoms such as abdominal pain, bleeding, and obstruction. Emergency presentation as the first indication of colorectal cancer is generally thought to be associated with advanced disease and poor outcome. The specific aim of this analysis was to describe characteristics of patients (pts) presenting to the Emergency Department (ED) at their index diagnosis, and to determine whether emergency presentation precludes treatment with curative intent. Methods: We performed an IRB-approved retrospective cohort analysis. We queried the prospectively maintained institutional tumor registry to identify pts diagnosed with CRC from 2008-2010. EMRs were reviewed to identify which pts presented to the ED with acute symptoms of CRC as the initial sign of their illness. The primary outcome variable was treatment plan (curative vs. palliative). Secondary outcome variables included demographics, tumor type and location. Descriptive statistics were conducted for major variables. Χ2 and Fisher’s exact tests were used to detect the association between categorical variables. Two-sample t-test was used to identify the association between continuous and categorical variables. Results: Between Jan 1 2008 and Dec 31 2010, 376 pts were identified with CRC. 214(57%) were male and 162(43%) were female, with mean age 60.6; SD: 13.3. 33 (8.8%) pts initially presented to the ED, of which 5 (15.5%) received palliation. Of 339 pts who initially presented elsewhere, 69 (20.5%) received palliation. Acute ED presentation with CRC symptoms did not preclude treatment with curative intent (p = 0.47). Pts who presented emergently were more likely to be female (64% vs male 41%; p=0.01), and older (65 vs. 60; p=0.02). There was no statistically significant relationship between age, gender, tumor location or type and treatment approach. Conclusions: Pts with CRC may present to the ED with acute symptoms, which ultimately leads to the diagnosis. Emergent presentation of CRC does not preclude patients from receiving therapy with curative intent.
Correlation of postoperative CEA trends with survival and patterns of recurrence after hepatectomy for colorectal cancer metastases.
Authors: Shirley Lawrence Andrew , McNally Megan , Huntington Justin , Jones Natalie , Malhotra Lavina , Bloomston Mark , Schmidt Carl Richard 
Published: February 2017

436 Background: Pre-operative carcinoembryonic antigen (CEA) level is associated with outcome after hepatectomy for colorectal cancer metastases. In this study we sought to determine the relationship between post-operative CEA and outcome after hepatectomy. Methods: A single institution retrospective review of hospital records from 1993 to 2010 found 339 patients who underwent a liver resection for CRC metastases. Of these, 140 had CEA levels drawn pre-operatively, post-operatively, and at least once more in follow-up. A ΔCEA level was calculated by subtracting the initial post-operative CEA level from the highest CEA level drawn in follow-up. Outcomes were compared between patients with ΔCEA less than 5 and greater than 5. Results: Of 140 patients, 61 had ΔCEA less than 5 and 79 had ΔCEA greater than 5. Patients with low ΔCEA had improved median overall survival (OS) (70.2 months) compared to those with high ΔCEA (38.7 months, P=0.0001). However, there was no significant difference in progression-free survival (PFS) (13.0 months vs. 12.3 months, P=0.982). 100 patients had recurrence after hepatectomy, 69 with high ΔCEA and 31 with low ΔCEA. Patients with low ΔCEA were more likely to have a single site of recurrence (77.4% vs. 53.6%, P<0.0001). Conclusions: Although a rising CEA after hepatectomy for CRC metastases is associated with worse overall survival, there is no difference in progression-free survival between patients with rising CEA and those with stable-to-decreasing CEA. Patients with stable-to-decreasing CEA have patterns of recurrence more amenable to locoregional therapy. Post-operative CEA values are an important component of oncologic surveillance, and patterns of rise and fall may indicate patterns of recurrence.
Relationship of colorectal cancer incidence rate and age of diagnosis in eastern Kentucky.
Authors: Koura Adnan , Elsoueidi Raymond , Dignan Mark 
Published: February 2017

439 Background: Colorectal cancer is the third most commonly diagnosed cancer in US among men and women. Approximately 150,000 new cases of colorectal cancer are diagnosed each year and about 50,000 of them die. Nationally, it is documented that the highest percent of patients with colorectal cancer are diagnosed between the ages of 75-84. However, rates are higher in Eastern Kentucky and a larger proportion of cases appear to be diagnosed at a younger age. Methods: Data on newly diagnosed cases of colorectal cancer were collected from the Appalachian Regional Healthcare Cancer Registry, a registry serving seven county regions in Eastern Kentucky, and compared to data from Surveillance Epidemiology and End Results (SEER). Results: The age-adjusted incidence rate for SEER, 2004-2008, was 47.2 per 100,000 compared to 59.22 per 100,000 for Eastern Kentucky. The median age of diagnosis with colorectal cancer was 65 years in Eastern Kentucky, compared to age 70 in SEER and the proportion of patients diagnosed between age 35 and 64 was higher in Eastern Kentucky than in SEER: 6.96% vs. 3.90% for 35-44 and 25.35% vs. 19.60% for 45-64 (p < 0.05. For residents age 75-85+, the proportion in Eastern Kentucky was lower than SEER: 75 - 84 yrs 19.50% vs. 26.20% and 85+ yrs 5.85% vs. 12.20% (p < 0.05). Conclusions: The results of this study reflect an increase incidence of colorectal cancer among the younger population in Eastern Kentucky compared to US national data. Also there was a decrease incidence of newly diagnosed cases among the elderly population. This could be attributed to many domestic risk factors including genetic, diet, obesity, smoking or other factors. Further studies to stratify above possible factors are warranted.
Association of colorectal cancer susceptibility variants with tumor subtypes in three large prospective cohorts.
Authors: Garcia-Albeniz Xabier , Nan Hongmei , Fuchs Charles S. , Giovannucci Edward L. , Ma Jing , Ogino Shuji , Kraft Peter , Chan Andrew T. 
Published: February 2017

445 Background: Genome-wide association studies (GWAS) have identified 17 colorectal cancer (CRC) susceptibility variants. However, their association with specific tumor subtypes has not been fully defined. Methods: We genotyped (TaqMan OpenArray) 17 variants (rs6691170, rs6687758, rs10936599, rs11169552, rs7136702, rs6983267, rs16892766, rs10795668, rs3802842, rs4444235, rs4779584, rs9929218, rs4939827, rs10411210, rs961253 , rs7014346 and rs2151512 as proxy of rs4925386) in three independent prospective, CRC case-control studies nested within the Nurses’ Health Study, Health Professionals Follow-up Study, and Physicians Health Study cohorts (1227 cases, 2201 age- and race-matched controls). Genotyping success: 98.1%. All variants fitted HWE (P>0.05). We assessed the association of these variants with risk of CRC using logistic regression (LR) adjusted for age, race and study under an additive model. We used multinomial LR models to examine the association of variants to CRC according to T, N and M-stage, grade of differentiation, tumor site, and age at diagnosis. Heterogeneity in the associations were evaluated by a case-case only LR model. Results: We observed associations with CRC for rs6983267 (OR 0.86, 95% CI, 0.77-0.95; p=0.0028 -T allele-), rs3802842 (OR 1.18; 95% CI, 1.05-1.31; p=0.0036 -C allele-), rs7014346 (OR 1.15, 95% CI, 1.04-1.28, p=0.0082 -A allele-), rs11169552 (OR 0.88, 95% CI 0.78-0.99 -T allele-) and rs4939827 (OR 0.90, 95%CI 0.82-1.00, p=0.0508 – C allele-). The association between rs4939827 (MAF 48.34%) and risk of CRC was significantly different according to T stage (p for heterogeneity < 0.0001). rs4939827 was associated with a lower risk of CRC with tumor stage T1 or T2 (OR, 0.72; 95% CI, 0.63-0.84, p<.0001) but not of cancers with tumor stage T3 or T4 (OR, 1.04; 95% CI, 0.92-1.19). This result is consistent within each cohort. Conclusions: Among 17 CRC susceptibility variants, we observed that the minor allele of rs4939827 was associated with a lower risk of colorectal cancers with lower T stage but not higher T stage. These results suggest that rs4939827, which codes for an intronic region of SMAD7, may be mechanistically related to tumor invasiveness.
Impact of microRNA miR-345 in blood on survival and response in 144 patients with metastatic colorectal cancer treated with third-line cetuximab and irinotecan.
Authors: Schou Jakob Vasehus , Andersen Klaus Kaae , Jensen Benny Vittrup , Nielsen Dorte Lisbet , Høgdall Estrid V. , Johansen Julia S. 
Published: February 2017

451 Background: MicroRNAs (miR) are small non-coding RNAs regulating gene expression at a posttranscriptional level. A prognostic potential of miRs in cancer tissue, whole blood or serum/plasma has been proposed in a small subset of cancers. MiR-345 has been reported up-regulated in cancer tissue and involved in malignant transformation in cancer cells. The aim of the study was to describe the ability of miR-345 to predict OS and response in patients with metastatic colorectal cancer (mCRC) treated with 3. line cetuximab and irinotecan independent of their KRAS status. Methods: A total of 144 patients with mCRC were included in a prospective phase II study of 3. line treatment with cetuximab and irinotecan. All patients had progressed on 5-FU, oxaliplatin and irinotecan prior to the protocol. MiRs were isolated from whole blood collected in PAXgene Blood RNA tubes (Qiagen), and miRNA profiling was performed using TaqMan MicroRNA Array v2.0 (Applied Biosystems). Cox proportional hazard model was applied to study the correlation between baseline miR-345 expression and OS. Logistic regression analysis was applied to study response (PR (n=25) vs. PD (n=38)) and clinical benefit (PR+SD > 9 months (n=32)) vs. no clinical benefit (PD+SD < 4 months (n=87)). Hazard ratios (HR) and odds ratios are per inter quartile range. Results: High expression of miR-345 was associated with poor treatment response with an odds ratio of 1.43 (p= 0.002) for progressive disease as best overall response and 2.04 (p=0.01) for no clinical benefit. High expression of miR-345 was significantly associated with short OS (HR =5.01, 95% Confidence Interval (CI): 2.39-10.50) when adjusted for KRAS status and performance status. This finding was confirmed in the subgroup of patients with KRAS wild type (n=87) (HR=3.02, 95% CI: 1.00-9.07). Conclusions: High expression of miR-345 in whole blood is correlated to lack of response and short OS in mCRC patients treated with cetuximab and irinotecan. This suggests that miR-345 may be a new predictive and prognostic biomarker for treatment with cetuximab and irinotecan.
Use of KRAS codon 13 mutations to predict response to neoadjuvant chemoradiation therapy in patients with rectal adenocarcinoma.
Authors: Duldulao Marjun Philip , Lee Wendy , Chen Zhenbin , Li Wenyan , Nelson Rebecca A. , Kim Joseph , Garcia-Aguilar Julio 
Published: February 2017

453 Background: The predictive role of KRAS mutation in therapeutic management of metastatic colorectal cancer has been much investigated. However, the association between KRAS mutations and rectal cancer response to neoadjuvant chemoradiation therapy (CRT) remains unclear. Our objectives were to determine the incidence of KRAS mutations in patients with rectal cancer and identify potential correlations with response to CRT. Methods: Patients with Stage II-III rectal cancer (n=148) from a multicenter prospective clinical trial were assessed. DNA was extracted from pretreatment tumor biopsies; and genotyping of KRAS was completed by PCR and direct sequencing. All patients underwent pre-operative CRT followed by surgery; and treatment response was evaluated by a pathologist. Surgical specimens without evidence of residual disease were deemed to have a pathologic complete response (pCR). Results: Overall, 60 of 148 (40.5%) patients had KRAS mutation. Breakdown of the different KRAS mutations revealed that 40 (66.7%) mutations occurred in codon 12, 12 (20.0%) in codon 13, 5 (8.3%) in codon 61, and 3 (5.0%) in other locations. When examining the relationship between KRAS and CRT response, we observed that detection of any KRAS mutation was associated with a decreased rate of pCR compared to wild-type KRAS (13.3% vs. 33.0%, respectively; p=0.007). More specifically, patients with KRAS codon 13 mutations did not respond to CRT compared to non-codon 13 mutations (p=0.037). In contrast, the detection of codon 12 or codon 61 mutations was not associated with response to CRT ( Table ). Conclusions: Patients with KRAS mutation have lower response rates to CRT compared to patients with wild-type KRAS. However, our results indicate that this association does not apply to all KRAS mutations, rather to KRAS codon 13 mutation alone. Thus, these data are the first to show that patients with KRAS codon 13 mutations may not derive pCR from neoadjuvant CRT. [Table: see text]
Gene markers of progression of Barrett’s metaplasia to carcinoma.
Authors: Kemmner Wolfgang 
Published: February 2017

46 Background: The incidence of esophageal adenocarcinoma (EAC) has increased strongly during the past 30 years and 5-year survival remained poor at approximately 20%. Barrett’s esophagus (BE) metaplasia is considered to be the key precursor lesion of EAC. The aim of this study was to generate and validate biomarkers to stratify patients with BE in terms of their risk for developing cancer. Methods: We studied gene expression profiling of normal esophageal squamous epithelium (NE), BE, intraepithelial neoplasia (IEN) and esophageal adenocarcinoma (EAC). Laser capture microdissection (LMD) technique was applied to procure cells from defined regions. Microarray results were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in a second and independent cohort. Furthermore, immunohistochemistry was performed on a third independent cohort. Results: The expression profile of BE was compared to EAC and NE resulting in a short list of 16 genes which were differentially expressed among all 3 groups. Hierarchical clustering of all samples based on the expression of these 16 candidate marker genes allowed a clear discrimination of NE, BE and EAC. Validation of the microarray results in an independent patient cohort by qRT-PCR confirmed that the genes CTHRC1, INHBA, PROCR and ADH7 expression correlate with the histological progression to EAC. Accordingly, immunohistochemistry showed that the presence of CTHRC1 and INHBA was high only in EAC. Conclusions: Here, we focus on neoplastic progression and describe a set of genes representing potential biomarkers to predict oesophageal Barrett’s adenocarcinoma at its early stage. These biomarkers can be determined by quantitative expression analysis, which will complement conventional semi-quantitative immunohistochemical analysis in the future. This work was feasible only through intensive cross-discipline collaboration between clinical researchers, pathologists, and basic molecular researchers and is thought to be the starting point for a long-term multicenter study on the clinical validation of the putative markers described here.
Use of HER2 gene amplification to identify patients with metastatic colorectal cancer resistant to anti-EGFR monoclonal antibodies.
Authors: Barbara Cecilia , Martin Vittoria , Molinari Francesca , Landi Lorenza , Riva Alice , Saletti Piercarlo , de Dosso Sara , Geva Ravit , Tejpar Sabine , Fountzilas George , Kalogeras Konstantine T. , Frattini Milo , Cappuzzo Federico 
Published: February 2017

474 Background: KRAS mutation represents the only validated biomarker used in clinical practice for selection of metastatic colorectal cancer (mCRC) candidates for therapy with the anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibodies. Previous studies conducted in small cohorts of patients suggested that HER2, the major EGFR partner, could modify the sensitivity to anti-EGFR agents. Aim of the present study was to investigate the role of HER2 gene status in a cohort of mCRC patients treated with cetuximab or panitumumab. Methods: 266 chemorefractory mCRC patients treated with cetuximab or panitumumab alone or in combination with chemotherapy were collected in an international consortium effort. HER2 gene status was analyzed using the dual-color FISH assay LSI HER2/neu-CEP17 (PATHVYSION, Abbott) in one central lab, whereas KRAS/BRAF mutations were investigated locally. HER2 gene amplification was defined as the presence of a ratio between HER2 gene and chromosome 17 centromere > 2. Results: An objective response to anti-EGFR therapy (complete or partial response according to RECIST criteria) was observed in 79/266 (29%) of patients. Twelve cases (4.5%) showed the classical pattern of HER2 gene amplification (R>2) in the whole tissue (>80% of tumor cells). By matching HER2 gene status with clinical response we observed that HER2 gene amplification was significantly related to therapy resistance (p<0.0001). Moreover, analysis of follow-up data indicated that HER2 gene amplification was significantly associated with a worse progression free survival (PFS, p=0.0025) and with a trend for a worse overall survival (p=0.062). Similar associations were also observed in the KRAS/BRAF wild-type patients. Conclusions: Data from this large retrospective study suggest that HER2 gene status evaluated by FISH may represent an additional marker useful for the prediction of mCRC patients’ response to EGFR-targeted therapies, in line with very recent evidence. In particular, patients with HER2 gene amplification seem to be resistant and show a shorter PFS. Future studies are needed to deeply investigate the clinical and biological meaning of HER2 gene status deregulation in mCRC.
Circulating tumor cells as a surrogate marker for determining response to chemotherapy in Japanese patients with metastatic colorectal cancer.
Authors: Matsusaka Satoshi , Suenaga Mitsukuni , Mishima Yuji , Terui Yasuhito , Shinozaki Eiji , Mizunuma Nobuyuki , Hatake Kiyohiko 
Published: February 2017

486 Background: The purpose of this study was to investigate the potential of circulating tumor cells (CTCs) as a surrogate marker of clinical outcome in metastatic colorectal cancer (mCRC) patients in order to identify Japanese patients responsive to oxaliplatin-based chemotherapy. Methods: The treatment regimen was oxaliplatin-based chemotherapy. Collection of CTCs from whole blood was performed at baseline and at 2 and 8-12 weeks after initiation of chemotherapy. Isolation and enumeration of CTCs was performed using immunomagnetics. Results: Between January 2007 and April 2008, 64 patients with mCRC were enrolled in this prospective study.Patients with ≥3 CTCs at baseline and at 2 and 8-12 weeks had a shorter median progression-free survival (8.5, 7.3, and 1.9 months, respectively) than those with <3 CTCs (9.7, 10.4 and 9.1 months, respectively) (log-rank test: p=0.047, p<0.001, and p<0.001, respectively). Patients with ≥3 CTCs at 2 and 8-12 weeks had a shorter median overall survival (10.2 and 4.1 months, respectively) than those with <3 CTCs (29.1 and 29.1 months, respectively) (p<0.001 and p=0.001, respectively). A spurious early rise in CEA level was observed in 11 patients showing a partial response. On the other hand, no rise in early CTC level was observed among responders. Conclusions: The clinical utility of CTC enumeration in improving our ability to accurately assess treatment benefit and in expediting the identification of effective treatment regimens for individual Japanese patients.
Genetic polymorphisms by race/ethnicity among colon cancer patients in Los Angeles County.
Authors: Lee Wendy , Duldulao Marjun Philip , Nelson Rebecca A. , Shen Xiaoming , Li Wenyan , Lu Jianming , Garcia-Aguilar Julio , Kim Joseph 
Published: February 2017

492 Background: Though disparate outcomes in colon cancer may be multifactorial, racial/ethnic disparities persist despite adjusting for these factors. Genetic alterations, including single-nucleotide polymorphisms (SNPs), have been shown to predict treatment response in colorectal cancer. Here, we evaluate the variability of genetic alterations in colon cancer patients by examining SNPs in major racial/ethnic groups. Methods: We obtained 76 normal tissue specimens from colon cancer patients of different race/ethnicity at our institution. DNA was extracted and analyzed for 6 SNPs (MTHFR 677C>T, XRCC1 685C>T, XRCC1 1301G>A, XPD 2282A>C, TP53 215G>C, and CCND1 870G>A) by polymerase chain reaction and direct sequencing. Prevalence of each allelic combination was compared between groups by the chi-square test. Results: Archived colon cancer tissues were obtained from whites, blacks, Hispanics and Asians (n=19 per group). From genotyping, we identified statistically significant differences in prevalence of CCND1 870G>A between groups ( Table , p=0.0428). Specifically, whites and Asians had significantly higher prevalence of CCND1 870G>A than blacks and Hispanics (100% and 94%, vs. 68% and 79%, respectively). Furthermore, whites and Asians were more frequently heterozygous (G/A) for the SNP (89% in both), whereas Hispanics comprised the largest proportion (16%) of patients homozygous for CCND1 870G>A. Overall, the allelic frequency of CCND1 870G>A varied among the racial/ethnic groups. Other SNPs in treatment-related pathways were evaluated, but there was no difference in prevalence of the other 5 SNPs between groups. Conclusions: Our findings demonstrate that detection of specific genetic polymorphisms differs between the major racial/ethnic groups with colon cancer. Differences in the prevalence of CCND1 870G>A, which affects cell-cycle progression, suggests a potential mechanism for disparities in cancer susceptibility and progression. Therefore, identification of such genetic variability may support a genetic basis for racial disparities in cancer outcomes. [Table: see text]