bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor marker CA 11-19 as a new serum blood test for monitoring colorectal cancer.
Authors: Costanzi John J. , Jordan Tommye Ann , Jensen-long Lisa 
Published: February 2017

536 Background: Colorectal cancer remains the third most frequent cause of cancer deaths globally. The FOBT (fecal occult blood test) and FIT (fecal immunochemical test) as well as CEA are increasingly being used to screen or monitor patients at increased risk for colorectal cancer (CRC), however none has optimal performance in terms of both sensitivity and specificity. Data was recently published* on the new serum blood test colorectal tumor marker CA11-19. This data showed a sensitivity of 98% (95% CI, 93.1%-99.5%) and specificity of 84% (95% CI, 80.0%-87.9%) at a cut-off value of 6.5 U/mL with a high sensitivity for detection of early stage CRC as opposed to CEA whose values are reported ~40% and ~30–80%** respectively for sensitivity and specificity. This study will look at case studies that show an array of long-term monitoring outcomes which suggest possible use of CA 11-19 instead of CEA. Methods: Using a sandwich ELISA assay, a new colon cancer antigen, CA 11-19, (100 kDa glycoprotein) was measured in samples of 7 patients with a variety of conditions in normal, benign GI diseases, polyps and colon cancer. This long-term follow up is recorded from 8 to 20 years. Results: Serum samples previously frozen were used to measure the CA11-19 antigen. An average follow up time of 15 years (range 8 to 20 years) was recorded. Elevated levels of CA11-19 were detected in patients with polyps and CRC prior to treatment and decreased levels were measured after the removal of the polyps or cancer. Importantly, rising rates of CA11-19 were seen in patients with cancer recurrences of colorectal cancers. Conclusions: CA 11-19 is a serologic tumor marker for colorectal cancer with a published sensitivity of 97.7% and a specificity of 84.4%*. Preliminary reports from 7 cases show long-term data which could be more helpful in monitoring and or follow-up of high risk patients for CRC than the current CEA testing method. Additional studies are needed to further validate the use of CA 11-19 in these patient groups.
Tumor genomic profiling (TGP) in metastatic colorectal cancer (CRC): Bridging the community and the tertiary cancer center through genomic consultation (GC).
Authors: Kaczmar John M. , Gustafson Karen S. , Wong Yu Ning , Minniti Carl J. , Sandilya Vijay Krishna , Sprandio John David , Chertock Yana , Hart Caitlin , Hall Michael J. 
Published: February 2017

538 Background: TGP of cancers is increasingly accessible to oncologists (MDs) and patients (pts). Despite efforts to provide clinical interpretation and decision support within TGP reports, results are complex and their interpretation remains fraught with uncertainty. In an ongoing pilot, we provide community MDs access to a 50-gene next generation sequencing (NGS)-based TGP assay and expert guidance through remote access to genomic tumor board (GTB) resources via telephone-based GC. Our goal is to explore how access to GTB expertise impacts community patterns of care. In parallel, we examine MDs and pts perceptions of TGP with a focus on awareness and expectations. Methods: MDs from 4 community practices participated. Participating MDs and their pts with metastatic unresectable CRC receiving 2nd line or beyond chemotherapy provide informed consent and complete baseline and follow-up surveys. Adequate tumor samples are tested with the Fox Chase 50-gene NGS-based TGP assay. All results are presented at a bi-monthly GTB or are reviewed with the GTB chair. MDs have a ~10 min GC by telephone with the PI to summarize findings and convey GTB recommendations. Results: 9 MDs have enrolled 22 pts and TGP has been completed on 15 samples (4 additional in process and 3 insufficient for TGP). Pts report diverse ancestry (24% Hispanic or non-White) and SES (33% income < $25K). To date, all completed TGPs have reported > 1 mutation. Of 11 pts who have received TGP results, 1 has sought consultation at a tertiary center for a clinical trial. Pts with higher education were more aware of TGP (p = 0.05). Most (80%) pts felt TGP would improve their MD’s ability to treat their cancer. Male sex and higher education were associated with stronger belief that TGP will improve life expectancy. Conclusions: A partnership with community MDs to provide TGP and GTB expertise through GC is feasible. Pts exhibit high expectations of TGP, despite limited data to support improved outcomes from TGP-guided treatment. Further research into optimizing partnership between community MDs and tertiary centers is valuable to guide treatment and clinical trial participation based on TGP results.
Post-treatment surveillance in locally advanced squamous cell carcinoma (SCCA) of the anal canal: A global subspecialist survey.
Authors: Eng Cathy , Adams Richard A. , Kachnic Lisa A. , Das Prajnan , Ernst Randy Devereux , Rodriguez-Bigas Miguel A. , Dupont Elisabeth , Benson Al Bowen ,   on behalf of the International Rare Cancer Initiative (IRCI) Working Group
Published: February 2017

573 Background: Squamous cell carcinoma of the anal canal will be diagnosed in 28,000 individuals globally. Considered a rare cancer, the incidence of anal carcinoma continues to rise annually. Majority of patients present with locally advanced disease in which concurrent chemoradiation (CRT) will be provided with curative intent. The Anal Cancer IRCI Working Group was created to pursue novel approaches to the diagnosis, treatment, and surveillance of patients. Yet, surveillance following completion of CRT is not well established and varies as per NCCN (v2.2015) and ESMO guidelines. Methods: A 22-question survey provided to anonymous international GI subspecialists in various fields. Questions pertained to timing and type of diagnostic imaging, surveillance interval, approach to detection of complete response (CR), and prevention of sexual dysfunction. Results: Survey distribution was initiated in March 2015 and still ongoing. Thus far, 96 physicians responded. Conclusions: Carcinoma of the anal canal continues to rise in incidence annually. Surveillance following completion of CRT is warranted; however, global variability in practice patterns for surveillance exists. As such, the IRCI Anal Cancer Working Group intends to provide an international consensus surveillance statement. [Table: see text]
Emerging transcriptional landscape and putative therapeutic targets in young patients with metastatic colorectal cancer (CRC).
Authors: Lieu Christopher Hanyoung , Pitts Todd M. , Kim Jihye , Tan Aik-Choon , Messersmith Wells A. , You Y. Nancy , Eng Cathy , Eckhardt S. Gail 
Published: February 2017

605 Background: Patients younger than 50 yrs of age comprise roughly 10% of the total incidence of CRC, but the incidence in the younger population is increasing. Recent data suggest that younger patients are at higher risk of progression of disease and death from CRC. The purpose of this pilot study was to investigate genomic differences between younger and older CRC tumors to generate hypotheses regarding potential differences in tumor biology that may explain worse outcome in young patients. Methods: To determine genomic differences in tumors from younger and older patients with CRC, a cohort of metastatic microsatellite stable CRC tumors was selected using tumors from 9 younger patients (< 35 yrs) and 7 older patients (> 70 yrs). Total RNA was extracted from tumor tissues and sequenced with Illumina HiSeq 2000. On average, 45 million reads were obtained from individual tumor samples. Sequencing reads were mapped to the reference genome using Bowtie; exon junctions were mapped using TopHat and transcript assembly was performed using Cufflinks. Results: The median ages for the younger and older cohorts were 31 and 73, respectively. From the RNA-seq analysis, gene expression profiles from younger patients were enriched for pathways involved in cell proliferation. Specifically ERBB2, NOTCH3, CAV1 were upregulated in multiple pathways in young patients (p < 0.00001). The expression pattern was noted to be different in older patients with enrichment for CDX2, HMGB3, and EPHB2 within pathways involved in regulation of cell differentiation (p = 0.07). In total 77 genes were noted to be enriched in younger patients compared with older patients and 23 genes were enriched in older patients compared with young patients (FDR < 0.05). These data, although preliminary, may provide support to explore ERBB2, NOTCH, and downstream signaling pathways as therapeutic targets for younger patients. Conclusions: In this pilot study, patients < 35 yrs with metastatic CRC exhibited gene sets enriched for several cellular proliferation pathways, including significant upregulation of ERRB2, NOTCH3, and CAV1. These results are hypothesis generating and are being investigated further in a larger validation cohort.
Micro-RNAs as positive biomarkers of pathological complete response after neoadjuvant chemoradiotherapy in locally advanced rectal carcinoma.
Authors: Ruiz Garcia Erika B. , Lopez-Rosas Gilberto , Lopez-Camarillo Cesar , Namendys-Silva Silvio , Lino-Silva Leonardo , Lopez-Yañez Alicia , Ortega Alette , Caderillo-Ruiz German , Diaz Dr. Consuelo , Herrera MaryTere , Marchat Laurence , Moreno Jesus Zamora , Sarmiento Itzel Vela , Meneses-Garcia Abelardo , Astudillo Horacio 
Published: February 2017

624 Background: Neoadjuvant chemoradiotherapy (nCRT) follow by surgery, as treatment for locally advanced rectal carcinoma (LARC), has improve local disease control, increase of complete pathological response (cPR) and preserve anal sphincter. cPR is associated with better prognosis. CRT act mainly through induction of DNA damage. MicroRNAs (miRNAs) are small non-coding RNAs able to regulate gene expression at post-transcriptional level. miRNAs are involved in the regulation of DNA damage/repair mechanism. Our goal was to measure expression of miRNAs involved in DNA damage/repair genes and correlated with cPR. Methods: Retrospectively, we analyzed the initial paraffin embedded tissue block of 20 Mexican patients with LARC treated with nCRT at National Cancer Institute of Mexico between 2010-2013. Treatment response was evaluated with Ryan Classification. Ten patients had cPR (Ryan Grade 0) meanwhile other 10 poor response (Ryan Grade 3). RNA extraction was done with RNeasy FFPE (Qiagen) Kit. RNA concentration and purity was assessed using NanoDrop 2000 Spectrophotometer. miRNAs expression were evaluated by real-time polymerase chain reaction (PCR) analysis with TaqMan Probes from Applied Biosystems. Statistical analysis was carried out with IBM SPSS Statistics 22.0. Differential expression between the two groups was performed with Chi square test. Results: There wasn’tsignificant difference betweenclinical/demographic features between the 2 groups. All patients received CRT at a total dose of 4500 cGy of pelvic irradiation, concomitantly with fluoropyrimidine. Surgical treatment was performed 14 weeks after completion of nCRT. The 2 miRNAs (188-5p and 590-5p) was overexpressed in the cPR group vs poor response group (p = 0.011 and p = 0.057, respectively). Conclusions: We evaluated the expression of miR590-5p and miR188-5p because they are related to DNA repair genes such as: MSH2, ERCC3, BRCC3 and XRCC5. We found overexpression in both miRNAs. Even though miR590 5p didn't reach statistical significance this maybe because of simple size.Our results now are been analyzed with a biological and functional genes network platform: Ingenuity Pathway Analysis.
Suppressive signals in colorectal cancer: RasGRP1 a new marker for anti-EGFR therapy?
Authors: Roose Jeroen , Depeille Philippe , Warren Robert S. 
Published: February 2017

625 Background: Treatment of metastatic colorectal cancer (mCRC) is largely palliative, making potentially curative therapy via molecular inhibition of specific cellular targets in CRC is a highly sought-after goal. One target of considerable focus in both basic and clinical investigation in CRC is the Epidermal Growth Factor Receptor (EGFR). Despite widespread EGFR expression in CRC, clinical trials have shown modest benefit from the use of anti-EGFR blocking antibodies and tumors with activating mutations in KRAS (KRASMUT) do not benefit from EGFR blockade. Given the ubiquitous expression of EGFR in CRC, why does such a large subset of patients fail to benefit from anti-EGFR antibodies? Methods: We combine the analysis of genetic mouse models, CRC cell line, and CRC patient database information and tumor samples. Results: We recently reported that two structurally distinct types of RasGEFs, SOS1 and RasGRP1, are co-expressed in both normal intestinal epithelial cells and in CRC cells. We observed that EGFR signals in CRC cells with KRASMUT result in even more RAS activation, arguing that RasGEFs load more RAS molecules with GTP following EGF stimulation. Indeed, we found that both SOS1 and RasGRP1 are activated downstream of the EGFR. Quite surprisingly, SOS1 and RasGRP1 have opposing functions here. Biochemically, RasGRP1 limits the amount of EGFR-SOS1-RAS signals. Biologically, knockdown of RasGRP1 expression in KRASMUT CRC cells leads to increased tumor growth in a xenograft mouse model. Conclusions: We hypothesize that anti-EGFR therapy may lead to unwanted inhibition of the inhibitory EGFR signals when CRC tumor express significant levels of RasGRP1 protein. We will discuss our current research that focuses on RasGRP1 as a prognostic marker of CRC outcome but also as a diagnostic indicator for EGFR therapy.
Sorafenib and irinotecan combination for pre-treated RAS-mutated metastatic colorectal cancer patients: A multicentre randomized phase II trial (NEXIRI 2).
Authors: Samalin Emmanuelle , De La Fouchardiere Christelle , Thezenas Simon , Boige Valérie , Senellart Hélène , Guimbaud Rosine , Taïeb Julien , Francois Eric , Galais Marie-Pierre , Adenis Antoine , Lievre Astrid , Seitz Jean-François , Metges Jean-Philippe , Bouche Olivier , Fonck Marianne , Di Fiore Frédéric , Artru Pascal , Aparicio Thomas , Mazard Thibault , Ychou Marc 
Published: February 2017

635 Background: Sorafenib and irinotecan (NEXIRI regimen) showed promising activity with a disease control rate (DCR) of 65% in heavily pretreated mutated (mt) KRAS metastatic colorectal cancer (mCRC) patients in a phase I/II trial (Samalin et al. 2014).This multicentre randomized phase II trial aimed to determine the 2-month progression-free survival rate (2-PFS) of NEXIRI versus irinotecan or sorafenib monotherapy in mtRAS mCRC patients after failure of all approved active drugs at the time of the study. Methods: Patients PS ≤ 1 with progressive measurable and non-resectable mtKRAS (then RAS) mCRC pre-treated with irinotecan, oxaliplatin, fluoropyrimidines and bevacizumab (none regorafenib), were randomized in 3 arms: NEXIRI (irinotecan IV 120 (C1), 150 (C2) and 180mg/m² (C3) if diarrhea grade < 1 in a biweekly regimen combined with a fixed dose of sorafenib, 400mg twice daily) versus irinotecan alone (180mg/m²) versus sorafenib alone until progression or toxicity, with cross over to NEXIRI at progression for the monotherapy arms. The primary endpoint was the 2-PFS (RECIST v1.1). Pharmacokinetic, pharmacogenetics and pathologic translational studies were undertaken. Results: We included 173 patients (median age 62 [31-82]; PS 0/1: 38/61%) between 2012/09 and 2014/07 in 17 French centres. Main results are shown below (median follow-up 17.5 months). Conclusions: We confirmed the NEXIRI regimen efficacy in a randomized study for refractory mtRAS mCRC patients. These results justify comparing this combination to regorafenib or TAS 102 monotherapies in this population. Ancillary studies are ongoing to identify biomarkers. Clinical trial information: NCT01715441. [Table: see text]
SIRFLOX: Differences in site of first progression between mFOLFOX6 ± bevacizumab (bev) versus mFOLFOX6 ± bev + selective internal radiation therapy (SIRT) in first-line patients (pts) with metastatic colorectal cancer (mCRC).
Authors: Gibbs Peter , Heinemann Volker , Sharma Navesh K. , Findlay Michael P. N. , Ricke Jens , Peeters Marc , Perez David , Robinson Bridget Anne , Strickland Andrew , Ferguson Tom , Rodriguez Javier , Kroening Hendrik , Wolf Ido , Ganju Vinod , Walpole Euan Thomas , Boucher Eveline , Tichler Thomas E. , Gebski Val , Van Buskirk Mark , Van Hazel Guy A. 
Published: February 2017

637 Background: SIRFLOX, an international multi-centre open-label RCT in first-line pts with non-resectable, liver-only or liver-dominant mCRC, showed that compared to FOLFOX (± bev) chemotherapy alone [arm A] FOLFOX (± bev) plus SIRT using Y-90 resin microspheres [arm B] did not improve overall PFS (median 10.2 v 10.7 months arm A v B, HR: 0.93; 95% CI 0.77–1.12; p = 0.429). However, liver PFS by competing risk analysis was improved with the addition of SIRT (median 12.6 v 20.5 months in arm A v B, HR: 0.69; 95% CI 0.55–0.90; p = 0.002). The current analysis examines patterns of disease progression and potential impact on the primary study endpoint. Methods: Site and pattern (intra/extra-hepatic) of first progression, and whether progression was due to growth of existing lesions or the appearance of new lesions, was judged by an independent reader blinded to study arm. Results: From Oct 2006 to Apr 2013, 530 pts were randomised (arm A, n = 263; arm B, n = 267); 212 (40%) had extra-hepatic metastases at study entry; 292 (55%) were stratified to receive bev. As of 31 Jan 2015, the total number of patients with disease progression in arm A v B were 178 and 166, respectively. The site of first progression was more frequently in the liver (± other sites) in arm A v B (92.1% v 72.3%; p < 0.001). Conversely, site of first progression was less frequent in the lung (± other sites) in arm A v B (19.1% v 42.8%; p < 0.001). A higher proportion of first progression occurred in the liver alone in arm A v B (77.0% v 52.4%; p < 0.001). Conversely, a lower proportion of first progression occurred only in non-liver sites, primarily lung, in arm A v B (7.9% v 47.7%; p < 0.001). Of patients with first progression in the liver, a higher proportion occurred in existing liver lesions (± extrahepatic sites) in arm A v B (72.5% v48.2%; p < 0.001). Conclusions: The addition of SIRT to FOLFOX chemotherapy alone (± bev) reduced the frequency at which first disease progression occurred in the liver. Where first progression did occur in the liver, the addition of SIRT led to this more frequently being due to the appearance of lesions not evident on baseline imaging. Clinical trial information: NCT00724503.
TAS-102 versus placebo (PBO) in patients (pts) ≥65 years (y) with metastatic colorectal cancer (mCRC): An age-based analysis of the recourse trial.
Authors: Van Cutsem Eric , Benedetti Fabio M. , Mizuguchi Hirokazu , Mayer Robert J. , Falcone Alfredo , Garcia-Carbonero Rocio , Tabernero Josep , Sobrero Alberto F. , Peeters Marc , Zaniboni Alberto , Yoshino Takayuki , Shimada Yasuhiro , Yamazaki Kentaro , Komatsu Yoshito , Hochster Howard S. , Lenz Heinz-Josef , Tran Ben , Ohtsu Atsushi ,   on behalf of the RECOURSE Study Group
Published: February 2017

638 Background: TAS-102 is comprised of an antineoplastic thymidine-based nucleoside analog, trifluridine, and the thymidine phosphorylase inhibitor, tipiracil hydrochloride, at a molar ratio of 1:0.5 (weight ratio, 1:0.471). Efficacy and safety of TAS-102 in pts with mCRC refractory to standard therapies were evaluated in the RECOURSE trial; enrollment criteria included ≥2 prior lines of standard chemotherapy. Primary results of RECOURSE demonstrated a significant improvement in overall survival (OS) (TAS-102 7.1 mo vs PBO 5.3 mo; HR=0.68; P<0.0001) and progression-free survival (PFS) (HR=0.48; P<0.0001). Methods: This prespecified analysis compared the efficacy and safety of TAS-102 vs PBO in pts ≥65 y and <65 y with mCRC. A retrospective analysis of pts ≥75 y was also performed. Results: Of 800 randomized pts, 352 (44.0%) were ≥65 y and 60 (7.5%) were ≥75 y. Median OS in pts ≥65 y was 7.0 mo with TAS-102 vs 4.6 mo with PBO (HR=0.62, 95% CI: 0.48-0.80, P=0.0002). PFS HR was 0.41 (95% CI: 0.32-0.52, P<0.0001) for pts ≥65 y, also favoring TAS-102. In pts ≥65 y, disease control rate (complete or partial response or stable disease) was 48.7% with TAS-102 vs 15.5% with PBO. An age-related difference in overall incidence of adverse events (AEs) was not observed in either treatment arm. Treatment-related AEs, ≥ Grade 3 AEs, and severe AEs were generally more common in pts ≥65 y than in pts <65 y (Table). Mean drug exposure was similar among pts ≥65 y and ≥75 y, as was overall safety profile. Conclusions: Significant improvements in OS and PFS were observed in pts ≥65 y who received TAS-102 vs PBO, with a mild increase in toxicity. Pts ≥65 y and <65 y showed a generally favorable safety profile. A significant increase in toxicity in pts ≥75 y was not apparent vs the overall ≥65 y population. Clinical trial information: NCT01607957. [Table: see text]
An open label, randomized phase III trial evaluating the treatment (tx) effects of panitumumab (pmab) + best supportive care (BSC) versus BSC in chemorefractory wild-type (WT) KRAS exon 2 metastatic colorectal cancer (mCRC) and in WT RAS mCRC.
Authors: Kim Tae Won , Elme Anneli , Kusic Zvonko , Park Joon Oh , Udrea Anghel Adrian , Kim Sun Young , Ahn Joong Bae , Villalobos Valencia Ricardo , Srinivasan Krishnan , Bilic Ante , Manojlovic Nebojsa , Dong Jun , Guan Xuesong , Lofton-Day Catherine , Jung A. Scott , Vrdoljak Eduard 
Published: February 2017

642 Background: An overall survival (OS) benefit in WT KRAS exon 2 mCRC was not seen with pmab monotherapy in study 20020408 possibly due to crossover of patients (pts) in the BSC arm. Retrospective analyses have indicated that other KRAS and NRAS mutations beyond KRAS exon 2 are predictive of anti-EGFR tx effects. Study 20100007 assesses the OS benefit of pmab in chemorefractory WT KRAS exon 2 mCRC and is the first phase 3 trial to prospectively evaluate pmab tx effects in WT RAS (exons 2, 3, and 4 of KRAS and NRAS) mCRC. Methods: Anti-EGFR naive pts were randomized 1:1 to receive pmab (6 mg/kg Q2W) + BSC or BSC. KRAS exon 2 and RAS mutation status of tumors were determined centrally. The primary endpoint was OS in WT KRAS exon 2 mCRC. Secondary endpoints were OS in WT RAS mCRC and progression-free survival (PFS), objective response rate (ORR), and safety in both WT KRAS exon 2 and WT RAS groups. Crossover was not permitted. Results: 377 pts with WT KRAS exon 2 mCRC were enrolled. RAS ascertainment rate was 86%. OS was significantly improved with pmab + BSC vs BSC in both WT KRAS exon 2 (HR=0.73, 95% CI=0.57-0.93, P=0.0096) and WT RAS (HR=0.70, 95% CI=0.53-0.93, P=0.0135) mCRC (results in table). Pts with mutant RAS mCRC did not benefit from pmab tx (OS HR=0.99, 95% CI=0.49-2.00). No new safety signals were seen. Conclusions: Pmabsignificantly improved OS in chemorefractory WT KRAS exon 2 mCRC. The tx effects in OS and PFS were more pronounced in those with WT RAS mCRC, further substantiating the importance of RAS testing at diagnosis to best inform the use of pmab to treat mCRC. Clinical trial information: NCT01412957. [Table: see text]