bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of early postoperative PET-CT in patients with pathological stage III colon cancer: Results from a large single institution study.
Authors: Moore Assaf , Ben-Aharon Irit , Purim Ofer , Perl Gali , Ulitsky Olga , Amit Limor , Kundel Yulia , Lewin Ron , Wasserberg Nir , Asman Yael , Kashtan Hanoch , Brenner Baruch 
Published: March 2017

562 Background: Current staging of patients (pts) with pathological stage III colon cancer is suboptimal; many pts still recur despite unremarkable preoperative staging work-up. We previously reported that early postoperative PET-CT can alter the stage and management of pts with high risk stage III colon cancer in up to 19% of patients. The aim of the current study was to expand the previous one to a larger cohort and to determine the role of early postoperative PET-CT in the general population of stage III colon cancer pts, regardless of their individual risk. Methods: A retrospective chart review of all consecutive pts with stage III colon cancer who underwent early postoperative PET-CT between 2007 and 2016. Demographic and clinicopathological data were collected. Results: 247 pts, 124 (50%) males, with a median age of 66 years (range, 30-92), were included. Pathological stage was IIIA, IIIB and IIIC in 18 (7.3%), 161 (65.1%) and 72 (29.1%) pts, respectively. The median number of lymph nodes retrieved was 15 (range, 6-64) and that of positive lymph nodes was 2 (range, 0-21). High FDG-uptake was observed in 52 (21.0%) pts, including 6 (2.4%) who had clear postoperative changes, 10 (4.0%) who had a false positive abnormal uptake of whom 6 underwent invasive diagnostic procedures. The PET-CT results modified the management of 36 pts (14.5%) who were found to have true positive findings: 30 (12.1%) were proven to have overt metastatic disease and in 6 (2.4%) a second primary was discovered. With the median follow-up of 39.0 months (range 7.2-98.4 months), of the 30 pts found to be metastatic, 10 (33.3%) underwent curative treatments and are currently with no evidence of disease (NED). Updated data, on more patients and a longer follow-up, will be presented at the meeting. Conclusions: Early postoperative PET-CT changed the staging and treatment of 14.5% of resected stage III pts, and has the potential for early detection of curable metastatic disease. We currently evaluate this strategy and its actual impact in a prospective trial.
Investigations of a novel diagnostic technology for colorectal cancer.
Authors: Tao Hongmei , Du Xuedong , Ding Shijin , Tang Xing , Lou Da , Lin Yue , Yu Chris Chang 
Published: March 2017

564 Background: Currently endoscopy examination takes an important role in the diagnosis of colorectal cancer, and there are no other clinically viable non-invasive diagnostic methods. In this investigation, a newly developed, novel IVD cancer diagnostic technology named Cancer Differentiation Analysis (CDA) Technology was investigated for colorectal cancer diagnosis. CDA is a new technology using multi-level and multi-parameter information which measures information relating to both protein fragments and cellular signals in blood samples in one single test. Methods: Peripheral blood was drawn in EDTA tubes for CDA tests. Intravenous blood samples from individuals with colorectal cancer (n = 193), as well as control samples (n = 705) were collected. Cancer group has been clinically diagnosed, and individuals in control group have been confirmed by physical examinations free of cancer. All blood samples were tested using a CDA device, and collected data were analyzed in the SPSS Packages. Results: Data analysis (using T test) showed a significant statistical difference with P value < 0.05 between colorectal cancer group and control group. Details of CDA test results were given in Table 1. Based on initial data, the area under curve (AUC), sensitivity and specificity of CDA technology for colorectal cancer were determined to be 0.861, 76.7% and 76.7% (cut-off value was set at a level at which sensitivity and specificity are comparable), respectively. Conclusions: CDA technology is able to statistically distinguish control group from colorectal cancer group with reasonably high sensitivity and specificity (both above 75%). As a non-invasive and potentially cost effective method capable of large population screening, CDA technology could be a very promising approach for the screening and diagnosis of colorectal cancer. [Table: see text]
Inequality trends in proximal and distal colon cancers.
Authors: Bodek Daniel David , Patel Pavan 
Published: March 2017

565 Background: Recently, the USPHTF released new colon cancer screening guidelines. No priority was given to any screening method. Given studies showing that Blacks had a greater proportion of proximal cancers, we sought to better highlight the inequalities in outcomes in order to consider the appropriateness of sigmoidoscopies versus colonoscopies. Methods: The SEER database was utilized to pull incidence and 5 year relative survival data (1992-2013). Patients aged 50-84 were divided by race and percentage of a county’s population below the poverty line ( < or > 15%). Adenocarcinomas were divided between distal cancer in the sigmoid, rectum, and anus versus cancer in the remainder of the colon. This data was analyzed using HDCalc, modelling rate difference, rate ratio, and the Index of Disparity. The Joinpoint regression program was then used to model Average Annual Percent Change (AAPC). Results: The AAPC in distal cancer incidence among Whites (-3.2%, [95% CI = -3.5%, -2.8%], p < 0.05) was greater than in Hispanics (-1.6%, [95% Cl = -2.1%, -1.1%], p < 0.05), or Blacks (-2.3%, [95% CI = -2.9%, -1.8%], p < 0.05). This resulted in a decline in the Index of Disparity (AAPC: -6.6, [95% Cl: -9.1, -4.0], p < 0.05) largely due to Whites' greater gains relative to Hispanics (Rate Ratio AAPC: -1.6%, [95% Cl: -1.9%, -1.3%], p < 0.05). Less impressive were AAPC trends in proximal cancers, which were significant in Whites (-1.8%, [95% CI: -2.2%, -1.5%], p < 0.05) and Blacks (-1.3%, [95% Cl: -1.8%, -0.8%], p < 0.05). Additionally, the AAPC for proximal cancer’s Index of Disparity was also lower (-3.1%, [95% Cl: -3.8%, -2.4%], p < 0.05). In terms of survival, only distal cancer’s AAPC for its Index of Disparity was significant (-3%, (95% Cl: -5%, -1.1%), p < 0.05). Poorer counties performed worse in incidence reduction across races but similarly in survival improvements. Conclusions: While it is encouraging to see improvements in distal colon cancer outcomes, it is troubling to see that measures in proximal cancers are lagging behind. The slower improvements among the Black population and higher baseline mortality and incidence of such cancers would seem to indicate a need to further study the comparative value of more aggressive screening, particularly in this group.
Validation of diagnosis codes to identify side of colon in an electronic health record registry.
Authors: Luhn Patricia , Kuk Deborah , Carrigan Gillis , Nussbaum Nathan , Sorg Rachael , Rohrer Rebecca , Tucker Melisa , Arnieri Brandon , Taylor Michael , Abernethy Amy Pickar 
Published: March 2017

568 Background: The anatomical side of the colon from which a tumor arises is prognostic. Real-world evidence (RWE) studies in colon cancer should include this information. Can International Classification of Diseases (ICD) codes be reliably used to determine side of tumor, and, if so, when? Should electronic health records (EHR) be reviewed to supplement? Methods: Flatiron Health maintains an EHR-derived registry for metastatic colon cancer patients (current N = 9403). A random sample of 100 patients was included in this study. Data about tumor site was compared using ICD codes versus data abstracted from unstructured documents in the EHR (e.g., surgical notes). Concordance was determined via observed agreement and Cohen’s kappa coefficient (𝜿). Accuracy of ICD codes was determined by calculating the sensitivity, specificity, and positive predictive values, and corresponding 95% confidence intervals (CI), using abstracted data as the gold standard. Results: Sampled patients had similar side of colon distribution compared with the full registry: left colon (32% vs. 30%, respectively), right (17% vs. 25%), transverse (7% vs. 5%), unspecified side (39% vs. 37%), and rectum (5% vs. 2%). ICD codes can be general, or specific to the side of tumor. The observed agreement between the ICD codes and abstracted data for tumor site for all sampled patients was 0.57 (𝜿 = 0.42). When restricting to the 56% of patients with a side-specific ICD code, the observed agreement was 0.91 (𝜿 = 0.85). See table for all accuracy estimates. Conclusions: RWE offers growing opportunities for oncology research. Before meaningful RWE analyses can take place, data must be carefully characterized. Here, we describe tumor side EHR data in colon cancer and find that ICD codes specifying tumor side are available over half of the time. When these ICD codes are available, the accuracy of tumor side information in ICD codes is high. When not available, the dataset can be supplemented by chart abstraction. [Table: see text]
Clinicopathological associations and prognostic implications of KRAS mutation in metastatic colorectal cancer (CRC) population over 9 years at a single institute.
Authors: Melinamani Shruthi , Buckingham Lela , Hill Marisa E. , Leslie William T. 
Published: March 2017

573 Background: Mutations in Kirstin RAS (KRAS) oncogene play a significant role in the constitutive activation of RAS/RAF/MEK/ERK pathway in CRC. Our objective was to evaluate the association of KRAS mutation status with the clinicopathological characteristics of the tumor and analyze prognostic implications of KRAS mutation in CRC patients. Methods: A total of 154 CRC patients diagnosed between 2007 and 2016 were included in this study. Formalin-fixed paraffin-embedded tissue from CRC patients who had metastatic disease were analyzed for KRAS mutations by allele-specific PCR. Baseline clinicopathological features and survival times were retrieved from electronic medical records. χ2, Fisher’s exact tests and Pearson’s correlation were used for association and binomial logistic regression to calculate the odds ratio. Kaplan Meier analysis and log rank test were used to compare survival outcomes. Results: KRAS mutations were identified in 61(39.6%) patients, 29(47.5%) were Caucasians, 22(36.1%) African Americans, 5(8.2%) Asians & 5(8.2%) other ethnic groups. The median age was 65 years with 31(44.9%) male and 30(35.3%) female patients. The majority of KRAS mutations were G12D (27 cases, 44.26%) and G12V (17 cases, 27.86%). KRAS mutations were most frequent in CRC adenocarcinomas (50 cases, 86.2%; P = 0.011) with poorly differentiated histology (p < 0.001) and current/former smokers (60.7% vs. 41.4%; P  = 0.03). Advancing age (OR = 1.150; 95% CI = 1.049 to 1.261; P = 0.003), increasing body weight (OR = 1.799; 95% CI = 1.118 to 1.954; P = 0.034) and increasing BMI (OR = 1.131; 95% CI = 1.05 to 1.204; P = 0.002) were associated with increasing likelihood of KRAS mutation. Patients with KRAS mutation had a tendency to shorter median overall survival than those with wild-type KRAS (30.9 vs. 33.1 months; P = 0.951). Subgroup analysis demonstrated that the patients with KRAS mutations showed worse survival in the group with poorly differentiated histology (median, 5.7 vs. 21.6 months; P = 0.04). Conclusions: CRC patients harboring KRAS mutation constitute a heterogeneous group with distinct tumor characteristics and clinicopathological associations.
Long-standing Crohn’s disease and its implication on anal squamous cell cancer management.
Authors: Moncrief Sara , Mathis Kellie L. , Lightner Amy 
Published: March 2017

576 Background: Anal squamous cell carcinoma (ASCC) is rare, accounting for 1% of gastrointestinal malignancies, but the incidence is rising. Risk factors for the development of ASCC in patients with Crohn’s disease (CD) include immunotherapy, increased duration of disease, and chronic fistulizing perianal disease. We sought to understand management strategies for ASCC in the setting of CD. Methods: A retrospective review from 2001-2016 was conducted for ICD-9/10 codes pertaining to Crohn’s disease (CD) (555.9/ K50) and ASCC (154.3/C44.520). Adult patients with a diagnosis of CD at the time of ASCC diagnosis were included. Results: A total of 7 patients (5 female) were included with a median age of 50 years. The majority presented with perianal pain (4) and bleeding (3). The mean duration of CD was 20 years, and all patients had perianal disease for > 10 years. Five patients had perianal fistulizing disease at the time of ASCC presentation. Clinical stage at diagnosis of ASCC was stage 0 (n = 1), I (n = 1), II (n = 1), III (n = 2), IV (n = 1), and unknown (n = 1). All patients were treated with Nigro protocol which included radiation (50-55Gy), 5-fluorouracil, and mitomycin; 1 patient received cisplatin due to concurrent Non-Hodgkin’s Lymphoma. Three patients required fecal diversion during radiation due to significant perianal disease. Two patients experienced complications related to radiation including anal and vaginal stenosis and an anovaginal fistula. One additional patient required an APR with rectus abdominis myocutaneous flap for uncontrolled CD after treatment. During follow-up, 3 of the 7 patients undergoing definitive chemoradiation developed residual or recurrent disease and required salvage APR. All patients were alive at last follow-up, 2 with metastatic disease. 5-year disease free survival was 56%. Conclusions: Patients with ASCC in the setting of CD may be managed with the standard Nigro protocol, but complications from radiation are common in this setting. Three of seven patients required salvage surgery for residual or recurrent disease, and an additional patient required APR for palliation of CD symptoms. Given the aggressive nature of ASCC in this population, surveillance guidelines are necessary.
Multivariate analysis of determinant factors in adjuvant chemotherapy (AC) utilization in patients with stage II colon cancer (CC): Analysis of the National Cancer Database (NCDB).
Authors: Huynh Donny V. , Mukkamalla Shiva Kumar Reddy , Somasundar Ponnandai Sadasivan , Rathore Ritesh 
Published: March 2017

577 Background: Evidence from randomized controlled trials does not support routine use of AC for patients with stage II CC. Clinical guidelines recommend discussion of AC in patients with high-risk disease. In our study, we analyzed NCDB data to determine factors favoring the use of AC in this setting. Methods: NCDB data was extracted on a total of 45,098 patients from 2004 to 2009 with stage II CC. Descriptive characteristics were analyzed using Chi-square test and odds ratios were calculated using multiple logistic regression. Results: Frequency of AC was significantly different among patients belonging to different age groups, tumor laterality, grade, pathologic tumor status (pT), and clinical nodal status (cN) (Chi-square test; p < 0.0001). Age distribution analysis revealed higher frequency of AC administration among patients of 18-64 years compared to those of 65-74 years and older, irrespective of single-agent or multi-agent regimens (p < 0.0001). Multivariate analysis was performed using multiple logistic regression technique. The odds of AC administration increased with increasing pT status, worsening tumor grade, and inadequate lymph node dissection ( < 12 lymph nodes evaluated) (p < 0.0001). AC administration was also more likely with left sided primary tumors (p < 0.0001). Conclusions: Using NCDB data, our analysis reveals conventional factors which are associated with AC administration in patients with resected stage II CC. Use of single-agent vs. multi-agent regimens did not differ, though elderly patients and those without left sided tumors were less likely to receive AC. Oncologists should be able to utilize these findings in discussions with stage II CC patients regarding the use of AC. [Table: see text]
The relationship between the degree of aberrant methylation in colorectal cancer tissue and appearance of tumor-derived DNA in blood.
Authors: Symonds Erin L , Pedersen Susanne Kartin , Baker Rohan , Mansfield Scott , Bastin Dawn , Young Graeme P 
Published: March 2017

579 Background: We have developed a blood test for colorectal cancer (CRC) detecting circulating tumor DNA (ctDNA) by measuring the presence of methylated BCAT1 and IKZF1. This study aimed to compare the levels of methylated BCAT1/IKZF1 in tissue from patients with colorectal cancer to those in blood before and after tumor resection. Methods: 80 people with invasive CRC had blood collected prior to resection. Tumor and adjacent non-tumor colorectal tissue was collected at surgery. Five patients had tissue collected from secondary cancers in the liver. Additional blood samples were collected within a year of surgery from 45 of these patients. DNA was extracted from all samples and assayed for methylated BCAT1 and IKZF1 DNA. Results: The median % BCAT1 and IKZF1 methylation in colorectal tissues were 45.7% and 59.9% (tumor), and 4.8% and 0% (non-tumor), p < 0.001. Median methylation levels in secondary tumors of the liver were 4.9% for BCAT1 and 29.5% for IKZF1, compared to 0% for both biomarkers in non-tumor liver tissue (p < 0.01). The methylation levels did not differ across CRC stages (p > 0.05), whereas the detection of ctDNA in the blood was significantly associated with tumor staging (p < 0.01). Of the 21 ctDNA positive CRC patients, 18 (86%) tested negative post resection. Of the 3 that remained blood positive post resection, further cancers were confirmed in two (one with recurrence in the lung, one with thyroid cancer). Conclusions: Aberrant BCAT1 and IKZF1 methylation is an early event in CRC development and is localised to the tumor tissue. Methylated BCAT1 and IKZF1 in blood are dependent on tumor stage and measuring minimal residual disease by detecting ctDNA based on methylated BCAT1 and IKZF1 may inform completeness of tumor resection.
Evaluation of meaningful change in bowel move frequency for patients with carcinoid syndrome.
Authors: Hudgens Stacie , Gable Jonathon , Kulke Matthew H. , Bergsland Emily , Anthony Lowell Brian , Caplin Martyn E. , Oberg Kjell E. , Pavel Marianne E. , Banks Phillip , Yang Qi Melissa , Lapuerta Pablo 
Published: March 2017

583 Background: Telotristat ethyl is a tryptophan hydroxylase inhibitor in development for the treatment of carcinoid syndrome (CS) in patients who receive somatostatin analog (SSA) therapy. In TELESTAR, a pivotal Phase 3 study, telotristat ethyl significantly reduced bowel movement (BM) frequency compared to placebo. Objective: The objective of this study was to psychometrically assess meaningful change in BM frequency using data collected within the TELESTAR study. Methods: An anchor-based approach consisted of mapping change from baseline in BM frequency to other patient reported assessments of change. These included the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core Questionnaire (EORTC QLQ-C30) Diarrhea Symptom responders, the EORTC GI.NET21 GI Symptom responders, and patient reported adequate relief at Week 12 (responders had a ≥ 10-point decrease in scores from Day 1 to Week 12). Parameters included within group mean change from baseline to Week 12, t-tests of the change (Wilcoxon Rank Sum for adequate relief), effect size (ES: calculated as the difference between mean on-treatment and baseline BM frequency, divided by the standard deviation of the baseline), and related confidence intervals. Results: There were 135 patients with CS, with a mean age of 63.6 years and mean baseline BM frequency of 5.7 BM/day. Anchor-based analyses indicated significant differences in BM frequency between adequate relief groups at Week 12 (ES: -1.58 vs. -0.79; p = 0.014), responders and non-responders on the EORTC QLQ-C30 Diarrhea Symptoms domain (ES: -1.24 vs. -0.59; p < 0.0001), and responders and non-responders on the EORTC GI.NET21 GI Symptoms Domain (ES: -1.49 vs. -0.75; p = 0.0053). These corresponded to BM frequency reductions of 1.7-1.9 BM/day, or ≥ 30%. Conclusions: Results of this study indicated that patients with CS experienced clinically meaningful reductions in BM frequency of ≥ 30% over the course of 12 weeks.
SMAD4 loss in colorectal cancer: Correlation with recurrence, chemoresistance, and immune infiltrate.
Authors: Wasserman Isaac , Lee Lik Hang , Shia Jinru , Wu Chao , Chen Xi , Guillem Jose G. , Paty Philip , Weiser Martin R. , Nash Garrett Michael , Temple Larissa K. F. , Saltz Leonard , Yaeger Rona D. , Barlas Afsar , Manova-Todorova Katia O , Vakiani Efsevia , Elghouayel Arthur E , Kemeny Nancy E. , Garcia-Aguilar Julio , Sawyers Charles L. , Smith Jesse Joshua 
Published: March 2017

587 Background: Few markers reliably identify colorectal cancer (CRC) patients at risk of recurrence and death. SMAD4 loss occurs in 10-20% of cases and has shown promise in identifying high-risk stage II/III patients. We examined SMAD4 status and association with clinical/pathologic features in 446 stage I-IV CRC patients at Memorial Sloan Kettering (MSK). Methods: Patients undergoing curative resection were included (1981-2010). Familial polyposis syndrome patients and those with inadequate tissue were excluded. Tissue microarrays were constructed (n=364). Immunohistochemistry for SMAD4 and mismatch repair (MMR) proteins was completed. SMAD4 nuclear stain intensity was scored (scale=0-3; 0=loss). On whole sections, MMR proteins (present or absent), tumor-infiltrating lymphocytes (TILs) and peritumoral lymphocyte aggregates (PLAs) were scored (scale=0-3). Associations between clinical/pathologic features and SMAD4 loss vs. retention were analyzed. Kaplan-Meier estimates and log-rank test were used for recurrence-free and overall survival analyses (RFS and OS). Results: SMAD4 loss was noted in 13%. Median age at diagnosis was 53 years, and 51% were male. The cohort consisted of 61% hindgut tumors and 62% stage II/III patients. With up to 33 years of follow-up, the mean was 6 years. SMAD4 loss correlated with higher tumor and nodal stage, adjuvant therapy use, and lower TIL and PLA scores (p<0.04 for all). Unlike prior studies, no significant differences in OS based on SMAD4 status across the entire cohort were noted; however, older patients (>median) were noted to have worse OS with SMAD4 loss (p<0.01). SMAD4 loss did correlate with worse RFS (p=0.02), persisting even when excluding MMR-deficient patients. Additionally, SMAD4 loss was associated with worse RFS in both the adjuvant chemotherapy group (median RFS=3.8 vs. 13 years; p=0.06) and the resection-only group (median RFS=4.2 years vs. not yet reached; p< 0.01). Conclusions: SMAD4 loss correlates with worse RFS and resistance to adjuvant therapy. SMAD4 loss also correlates with lower TIL and PLA scores. Future work will address chemoresistance mechanisms, relevance to adjuvant therapy use, and loss of immune infiltrate in SMAD4-null tumors.