bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving the AJCC/TNM staging for adenocarcinomas of the appendix: The prognostic impact of histologic grade.
Authors: Overman Michael J. , Fournier Keith F. , Hu Chung-Yuan , Wolff Robert A. , Eng Cathy , Taggart Melissa W. , Royal Richard E. , Mansfield Paul F. , Chang George J. 
Published: February 2017

402 Background: Though histological grade is known to have a major prognostic impact in metastatic mucinous appendiceal adenocarcinomas; the prognostic impact of grade in localized disease, and the validity of the AJCC Cancer Staging Manual 7th edition decision to combine moderately and poorly differentiated mucinous adenocarcinomas into a single mucinous high-grade category, is not known. Methods: Patients with adenocarcinoma of the appendix diagnosed between 1988-2007 were identified from the SEER database. Cancer-specific survival (CSS) stratified by histological subtype, stage and grade were calculated; and Cox proportional hazards regression analyses were performed. Results: We analyzed a total of 2,469 appendiceal adenocarcinomas, of which 1,375 had mucinous histology, 860 had non-mucinous histology, and 234 had signet-ring cell histology. Though overall CSS was similar for mucinous and non-mucinous subtypes, differences in stage distribution and stage-stratified CSS were seen. Female gender (57% vs.45%, P<0.01), stage IV disease (48% vs. 25%, P<0.01), and well differentiated histology (31% vs. 14%, P<0.01) were more common in mucinous as compared to non-mucinous adenocarcinomas. While histological grade for stage I-III cases was not statistically significant, it had strong prognostic impact for stage IV disease. The adjusted hazard ratios for stage IV well, moderately and poorly differentiated histological grade were 1 (reference), 1.63 (95%CI: 1.14-2.34) and 4.94 (95%CI: 3.32-7.35) for mucinous, in comparison to 1 (reference), 1.44 (95%CI: 0.82-2.52) and 1.90 (95%CI: 0.95-3.80) for non-mucinous histological subtypes, respectively. Conclusions: The strong prognostic impact of histological grade for mucinous adenocarcinomas is primarily restricted to stage IV disease. Stage IV moderately and poorly differentiated mucinous adenocarcinomas have distinctly different CSS and this data does not support the combination of these two histological grades in the recent AJCC 7th edition.
Intensive radiographic and CEA screening and salvage resection in patients with stage II and III colorectal cancer.
Authors: Fora Ahmad Ali , Patta Annie M , Attwood Kristopher , Wilding Gregory E. , Fakih Marwan 
Published: February 2017

405 Background: The objective of this study was to determine the rate of salvage resection in patients with stage II and III colorectal cancer following intensive surveillance. Methods: Patients with stage II and III colorectal cancer with a minimum follow-up of 3 years were included. CEA was obtained every 3 months for 2 years and then every 6 months for years 3 to 5. CT of the chest, abdomen and pelvis was performed every 6 months for 2 years and then yearly for years 3 to 5. Colonoscopy was performed at year 1 and then every 3 years. Results: 177 patients were followed for a median of 59.5 months. 51% were male, and 65 % had colon cancer. Compliance with screening was excellent with 92 % of patients undergoing all scheduled studies within 2 months of the planned date. At the time of this report, the median follow-up of the overall population was 5 years. 44 patients were diagnosed with recurrent disease. 91% of the recurrences were in the first 3 years of follow-up. CT and CEA were the first signs of recurrence in 68% and 14% of patients, respectively. Among the 30 patients diagnosed radiographically, 20 had a normal CEA. 25 patients (57%) with recurrent disease underwent curative intent resection, 12 of whom are still cancer free, with a median follow-up of 6.7 years from salvage surgery. The DFS and OS in the operated recurrent population from the time of salvage resection was 18.8 months (95% CI: 15.5 – 29.4) and not-reached (95% CI: 37.4, NR), respectively. The corresponding OS (from the time of recurrence) of the recurrent population without resection was 20.7 months (95% CI: 21.9, 63.4). The difference in OS between the two groups was highly significant (p = 0.0003). Among the patients undergoing resection, a significant difference was detected in the DFS of resected lung or liver metastases vs. extra-hepatic/pulmonary disease (p = 0.03) and a trend towards improved survival was noted (p = 0.07). Conclusions: Our intensive surveillance strategy resulted in the highest reported salvage rate in stage II and III colorectal cancer and led to a high rate of sustained remissions following salvage surgery. Intensive, 6-monthly, radiographic surveillance and its duration should be investigated further in randomized studies.
Sensitivity of second-generation blood-based methylated Septin9 assay for early-stage colorectal cancer.
Authors: Weiss Gunter , Fassbender Anne , Koenig Thomas , Tetzner Reimo 
Published: February 2017

419 Background: Early detection of colorectal cancer (CRC) has been shown to decrease mortality, although compliance to CRC screening is low. Availability of a blood-based test is expected to improve CRC screening compliance. Specific detection of CRC using the Septin9 biomarker (mSEPT9) in a large prospective trial of an average-risk CRC screening population exhibited 67% sensitivity for CRC with 88% specificity. Laboratory-developed tests detecting mSEPT9 in plasma are now available in North America and a 2nd generation molecular diagnostic blood test for mSEPT9 is available as a CE-marked kit in Europe. The current research evaluated the clinical performance of the 2nd generation mSEPT9 assay. Methods: Bisulfite-converted DNA (bisDNA) was prepared from 3.5 mL human plasma using the 2ndgeneration plasma DNA preparation kit. Resulting bisDNA was analyzed in triplicate on the ABI7500 Fast Dx (Life Technologies, Inc.) using proprietary HeavyMethyl real-time PCR technology for mSEPT9 and the 2nd generation real-time PCR kit. In a case – control design, plasma from 98 CRC patients (n = 87 stages I - III) and 99 age-matched, colonoscopy-verified normal individuals were processed with the mSEPT9 assay. In addition, plasma from 150 prospectively enrolled average risk individuals scheduled for screening colonoscopy was tested. mSEPT9 was qualitatively analyzed such that any detection of mSEPT9 in a PCR was called “positive”. Results: The revised mSEPT9 assay exhibited 95% sensitivity (95% CI: 89-98%) for CRC. Sensitivity for stage I was 89% (95% CI: 72-96%, n = 27) and sensitivity for stage II was 93% (95% CI: 78-98%, n = 29). The control group was positive at a rate of 16% (95% CI: 10-25%). Specificity of the mSEPT9 assay in the screening cohort was 85% (95% CI: 78-89%). Conclusions: The 2nd generation mSEPT9 assay demonstrated improved sensitivity for CRC without significant impact on specificity. The enhanced design and robustness of the assay will further facilitate its standardized use in routine laboratory settings. Finally, the increased sensitivity of the revised mSEPT9 assay improves the detection of early stage disease and demonstrates the feasibility of a blood-based CRC screening technology.
Clinicopathologic characteristics of patients with appendiceal adenocarcinoma (AA) and intra-thoracic metastasis.
Authors: Hill Joshua S. , Rafeeq Safia , Rice David C. , Overman Michael J. , Royal Richard E. , Mansfield Paul F. , Fournier Keith F. 
Published: February 2017

427 Background: Appendiceal adenocarcinoma (AA) is a rare disease with a prognosis related to tumor histology. Distant metastases, including those to the lung or pleura, are considered rare. We investigated the clinical characteristics and survival in patients with AA and intra-thoracic metastases. Methods: All patients with a pathologic diagnosis of AA who were evaluated at a single institution between September 1993 and July 2009 were retrospectively reviewed to identify patients with intra-thoracic metastasis. Parameters evaluated included demographics, histologic subtype and location of thoracic metastasis (parenchyma vs. pleural). Survival was calculated using the Kaplan-Meier method. Results: We evaluated 626 AA patients. Forty-two (6.7%) had intra-thoracic metastases: 24% pleural, 52 % parenchymal and 24% had both. Of those with intra-thoracic metastasis, the mean age at diagnosis was 54 years. Sixty percent were male. Histologic grade was: 19 (45%) low, 13 (31%) moderate and 9 (21%) grade high. Mean follow-up was 6.6 years. Median overall survival from diagnosis of the entire cohort was 5.2 years. Median overall survival by tumor grade: high 1.87 years, moderate 4.1 years, and not reached in low grade tumors (p=0.0001). The median overall survival from time of diagnosis of intra-thoracic metastasis is 1.44 years with survival by grade as follows: high-0.2 years, moderate-1.2 years, and low grade not reached (p=0.0003). Survival was not dependent on intra-thoracic location. Conclusions: Intra-thoracic metastasis in patients with AA occurs at a higher rate than previously thought, even in low grade tumors. This suggests that thoracic imaging should be considered in patients with AA. Overall survival depends heavily on tumor histology.
EORTC QLQ CR-29 evaluation in 500 patients with colorectal cancer.
Authors: Silva José Pedro Carvalho Moreira da 
Published: February 2017

429 Background: Colorectal cancer represents the 4th most frequent cancer in the world and is the 2nd leading cause of death due to cancer. This disease has a negative impact in the Quality of Life (QoL), due to its associated symptoms and due to the used treatments (surgery, chemotherapy and radiotherapy). Therefore it is fundamental to evaluate and assure a good quality of life of this patients and define the best QoL instrument in Colorectal cancer. Methods: Type of study: Transversal study The main objective was: validate for Portuguese population CR29 instrument. The QLQ-CR29 was administered with the QLQ-C30, core questionnaire, to 500 portuguese patients. Questionnaire scaling and reliability were established and clinical and psychometric validity examined. Patient acceptability and understanding were assessed with a debriefing questionnaire. Results: 57.4% (287) are male with a median of age of 66,67 years (Min.: 34 e Máx.: 88), 55.2% had rectal cancer (35.7% were Stage III disease at diagnosis. 46.4% had adjuvant and 27.4% had neoadjuvant treatment. The mean value of the QLQ-C30 Global Health Status was 58,75. The CR29 Multi-trait scaling analyses and face validity refined the module to four scales assessing urinary frequency, faecal seepage, stool consistency and body image and single items assessing other common problems following treatment for colorectal cancer identifying different groups of patients. High scores of cognitive and social functioning scales (QLQ C30), Subscale Corporal Image and the functional item Female Sexual function (QLQ-CR29) were related with good QoL. Low scores of Emotional Functioning subscales (QLQ C30) and Anxiety (QLQ-CR29), were related with poor QoL. A multivariable analysis reveals that sex, scholarship, marital status, distance between home and hospital and disease recurrence affect significantly the global health score. Conclusions: QLQ-CR29 Scale did not correlate with QLQ-C30 scales, demonstrating construct validity and it is a good instruments to identify a poor QoL in patients with colorectal cancer.
Physician’s awareness and practices toward colorectal cancer screening guidelines.
Authors: Kanna Sowjanya , Ali Asif , Anna Kiran , Ganapathi Thimmaiah Theethira , Sappati Biyyani Raja Shekhar Reddy , Mullen Kevin D 
Published: February 2017

431 Background: Colorectal cancer (CRC) is the second most common cancer with an estimated incidence of 72,090 men and 70,480 women and a cause specific mortality of 51,370 in 2010. Despite promotion of CRC screening by various professional societies ACG /AGA and USPSTF, there seems to be an under utilization of screening colonoscopy for unclear reasons. We aimed to study the awareness of physicians towards CRC screening across various levels of training in different specialities. Methods: A survey questionnaire of 16 questions, assessing awareness of CRC screening guidelines was provided to 100 physicians in our academic medical center who are at various levels of training in Primary Care Group (PCG comprising residents, attending physicians in Internal Medicine and Family Medicine) and Specialty Group (SG comprising fellows, attending physicians in Gastroenterology). Results: Out of 100 questionnaires, we received 59 responses (50 PCG and 9 SG) which are included in the results. About 54% of the study group followed CRC guidelines (32% USPSTF CRC screening guidelines compared to 22 % ACG/AGA guidelines) and 46% did not. All the physicians who did not follow the guidelines belonged to the PCG. Most common screening modality chosen was colonoscopy alone (46% PCG and 100% SG), followed by colonoscopy with FOBT (36% PCG), FOBT (12% PCG) and 3% PCG answered barium enema along with FOBT/ sigmoidoscopy. A 100% response from both SG and PCG was obtained for commencing screening colonoscopy at 50 years of age but only 27% of the PCG compared to 80% SG were aware of the screening cessation guidelines. Interestingly a vast majority of the study group (88%) text messaging as a better way of reminder to improve compliance compared to phone calls and postal letters. About 72% of the respondents themselves would want colonoscopy as screening modality compared to 17% for FOBT and 7% for sigmoidoscopy. An overwhelming majority of the study group (80% of both PCG and SG) felt the need for continued education in regards to guidelines for screening in didactic sessions. Conclusions: Despite clear guidelines for screening colonoscopy, we found a significant lack of awareness amongst PCG compared to SG, and our study emphasizes the need for continued education.
Identification of imaging biomarkers using 18fluorodeoxyglucose-positron emission tomography (FDG-PET) for the prediction of pathologic response in patients receiving neoadjuvant chemoradiotherapy for locally advanced rectal cancer.
Authors: Parekh Arti , Matalon Shanna , Subramaniam Rathan , Kachnic Lisa A. 
Published: February 2017

435 Background: Pre- and post-treatment FDG-PET imaging parameters may be useful for predicting pR following neoadjuvant CRT for LARC Methods: Between 2006 and 2010, 18 patients (pts) receiving preoperative CRT (5FU or capecitabine with concurrent 50.4 Gy conformal radiation) for LARC underwent a pre- (0-14 days before) and post-CRT (4 to 6 weeks after) PET/CT. Total mesorectal excision was performed 6 weeks post CRT. pR was dichotomized into complete (pCRs) and partial responders as reference standard. Pts with pathologic microscopic disease were classified as pCRs for this analysis. Changes in FDG metabolic parameters between pre and post-CRT scans, including maximum Standardized Uptake Value (SUVmax), metabolic tumor volume (MTV) and total glycolytic activity (TGA), were investigated as predictive imaging biomarkers for pR. Fixed SUVmax percentage threshold (30%, 40% and 50%) and gradient-based segmentation (PET Edge) were used to calculate the MTV and TGA. Receiver Operator Curve analysis was performed Results: Median pt age was 57.5 years (31-87); 67% M; 61% AJCC 2010 stage II, 33% III and 6% IV. pCR achieved in 44%. The 30% SUVmax threshold MTV best correlated with PET Edge MTV (Pearson r 0.99). Using ROC analysis, % change in SUVmax and PET edge TGA between pre and post-CRT scans were comparable and the most accurate parameters for predicting pR. SUVmax % change yielded an area under the curve (AUC) of 0.7125 (95% CI 0.4318-0.9932), while the AUC for PET Edge TGA % change was 0.7000 (95% CI 0.4209-0.9791). Based on ROC analysis, a cutoff of 78.9% change of PET Edge TGA had a likelihood ratio of 2.4, with a sensitivity of 90% and a specificity of 62.5% for predicting pCR. A cutoff of 88.7% change of PET Edge MTV yielded a likelihood ratio of 2.00 with a sensitivity of 50% and a specificity of 75%. Conclusions: The % change pre- to post-CRT in SUVmax and PET Edge Total Glycolytic Activity appears to be the most suitable FDG metabolic parameters for predicting pR following neoadjuvant CRT for LARC. As such, these PET-FDG biomarkers of CRT response should be validated in future prospective trials.
Anti-miR-135b in colon cancer treatment: Results from a preclinical study.
Authors: Valeri Nicola , Braconi Chiara , Gasparini Pierluigi , Grivennikow Sergei , Hart Jonathan R , Paone Alessio , Lovat Francesca , Fabbri Muller , Gafa' Roberta , Nuovo Gerard , Lanza Giovanni , Frankel Wendy , Vogt Peter K , Groden Joanna , Karin Michael , Croce Carlo M. 
Published: February 2017

457 Background: MicroRNAs (miRs) are small non coding RNAs involved in cell homeostasis. miRs are deregulated in colorectal cancer (CRC). Our study aimed at identifying miRs with a driver role in carcinogenesis altered by similar mechanisms in both human and mouse CRC. Goal of the study was to use CRC mouse models for the pre-clinical development of anti-miRs as therapeutic drugs. Methods: Azoximetane (AOM)/Dextran-Sulfate (DSS) treated mice or CDX2-CRE/APC-/- mice were used to study inflammation-associated and sporadic APC-related CRC. Human Inflammatory Bowel Disease associated (n=30), and sporadic (n=90) CRC with their matched normal tissues were collected according to Good Clinical Practice recommendation and subjected to RNA extraction using Trizol. miR and gene expression profiling was assessed by nCounter technology (Nanostring Seattle). Anti-miR-135b and scrambled probes for in vivo studies were synthesized by Girindus. Results: miRs profiling from AOM/DSS and CDX2-CRE/APC-/- CRC. revealed that miR-135b is one of the most up-regulated miRs in both models. In humans miR-135b over-expression was found in both IBD and sporadic CRC and was associated with reduced Progression Free Survival and Overall Survival in CRC patients. Molecular studies in Mouse Embryo Fibroblast and human CRC cell lines highlighted the role of two major pathways in the upstream activation of miR-135b: APC-β-Catenin and SRC-PI3K. MiR-135b up-regulation resulted in reduced apoptosis and increased invasion and metastasis due to the down-regulation of TGFRB2, DAPK1, APC and HIF1AN. Silencing of miR-135b in vivo reduced tumor multiplicity and tumor load in the AOM/DSS CRC model. Mice treated with anti-miR-135b showed well differentiated tumors and microacinar pattern while tumors in the control groups showed low differentiation and adenomatous pattern. Conclusions: Our data suggest that miR-135b is a key molecule whose activation is downstream of oncogenes and oncosuppressor genes frequently altered in CRC. Our study defines specific pathways that converge on the activation of the same microrna. The “in vivo” silencing of miR-135 shows preclinical efficacy with low toxicity and represents the first in vivo study for the use of antimiRs in CRC treatment.
A phase I trial of a recombinant CEA yeast-based vaccine targeting CEA-expressing cancers.
Authors: Bilusic Marijo , Gulley James L. , Hodge James W. , Tsang Kwong , Arlen Philip M. , Heery Christopher Ryan , Rauckhorst Myrna , McMahon Sheri , Intrivici Chiara , Ferrara Theresa A. , Cohn Allen , Apelian David , Franzusoff Alex , Guo Zhimin , Schlom Jeffrey , Madan Ravi A. 
Published: February 2017

458 Background: Saccharomyces cerevisiae (yeast) has been genetically modified to express CEA protein and employed as a heat-killed immune-stimulating, vector-based vaccine. Preclinical studies have shown that yeast CEA vaccine can induce a strong CEA-specific T-cell immune response (IR) and anti-tumor activity. Methods: Patients (Pts) were enrolled in this phase I trial at 3 dose levels: 4, 16, and 40 yeast units (each unit =107 yeast particles). The vaccine was administered equally at 4 sites subcutaneously in bilateral inguinal and anterior chest wall regions. Vaccine was administered at 2 week intervals for 3 months, then monthly. Eligible pts were required to have a serum CEA > 5 ng/ml or > 20% CEA+ positive tumor block and no autoimmune history. An expansion cohort of 10 pts was enrolled to focus on IR. Pts had re-staging scans at 3 months, then bimonthly. Peripheral blood was collected for analysis of IR including the Effector/Regulatory T-cell ratio, ELISPOT assay, changes in the myeloid-derived suppressor cells (MDSC) and natural killer cells (NK). Results: 25 pts with progressive metastatic CEA-expressing carcinoma were enrolled; 22 had colorectal adenocarcinoma. Vaccine was well tolerated with no dose limiting toxicities. The most common adverse event was grade 1/2 injection site reaction. Overall, 7 patients had stabilization or declines in serum CEA after treatment. Of them, 5 pts (3 with colorectal cancer) had stable disease beyond 3 months and 1 is still on-going (14 +, 8, 8, 4.5 and 4 months). No anti-CEA antibodies were detected. Post vs. pre-vaccination: a) five out of 9 evaluable pts showed evidence by ELISPOT of CEA-specific T-cell IRs b) 8/16 pts had increased and 8/16 pts had decreased CD4 Effector/Treg ratio and c) 6/13 pts had increased and 2/13pts had decreased NK frequency. Conclusions: Saccharomyces cerevisiae-CEA demonstrated an acceptable safety profile. Although this is an advanced disease population of pts which is not ideal for immune-based therapy, CEA serum stabilizations and CEA-specific IRs were seen in some pts. Randomized studies are required to determine the clinical benefit of this vaccine in a more appropriate patient population for vaccine therapy.
Target-based therapeutic matching in early-phase clinical trials in patients with advanced colorectal cancer and PIK3CA mutations.
Authors: Janku Filip , Naing Aung , Falchook Gerald Steven , Tsimberidou Apostolia Maria , Stepanek Vanda M. T. , Fu Siqing , Piha-Paul Sarina Anne , Luthra Rajyalakshmi , Hong David S. , Kurzrock Razelle 
Published: February 2017

459 Background: Therapeutic matching based on underlying molecular abnormalities showed promising results in patients with diverse advanced cancers in early phase clinical trials. PIK3CA mutations may predict response to therapies with PI3K/AKT/mTOR inhibitors. Methods: Tumors from patients with colorectal cancer referred to the Clinical Center for Targeted Therapy (Phase I Program) were analyzed for PIK3CA mutations. Patients with PIK3CA mutations were treated, whenever feasible, with agents targeting the PI3K/AKT/mTOR pathway. Results: Of 194 patients analyzed, 31 (16%) had PIK3CA mutations. Of 194 patients 175 (90%) were assessed for the presence of KRAS mutation. Patients with PIK3CA mutations had higher prevalence of simultaneous KRAS mutations than patients with wild-type (wt) PIK3CA (21/30, 70% vs. 63/145, 43%; p=0.009). Of the 31 patients with PIK3CA mutations, 17 (55%) were treated in clinical trials containing a PI3K/AKT/mTOR pathway inhibitor (median age, 57; median number of prior therapies, 4). Of these 17 patients, none achieved a partial or complete response (PR/CR) and only 1 (6%, 95% CI 0.01-0.27) patient had stable disease for more than 6 months (SD>6), which was not significantly different from the SD>6/PR/CR rate of 16% (11/67; 95% CI 0.09-0.27) in colorectal cancer patients without PIK3CA mutations treated on the same protocols targeting the PI3K/AKT/mTOR pathway (p=0.44). The median progression-free survival was only 1.9 months (95% CI 1.5-2.3). Conclusions: Heavily pretreated patients with PIK3CA-mutant advanced colorectal cancer do not seem to benefit from protocols incorporating PI3K/AKT/mTOR inhibitors. PIK3CA mutations are associated with simultaneous KRAS mutations, which might account for therapeutic resistance.