bluuebunny/crossref_metadata_2025_split huggingface dataset:
5-year survival following radiotherapy in anal cancer audit in a single center.
Authors: Morgan Stacie Joanne , Best James , Giridharan Selvaraj 
Published: May 2019

e15070 Background: Anal cancer accounts for 1% of new cancer diagnoses. Incidence rates are increasing and predicted to rise. Randomised controlled trials have demonstrated superior outcomes with chemoradiation, the standard of care. The recommended dose for two phases is 50.4Gray in 28 fractions, with 5- fluorouracil (5-FU) and mitomycin C as per the UKCCCR ACT I trial. The addition of chemotherapy has been shown to improve outcomes, however is contraindicated in certain cases. Retrospective audit is important to ensure effectiveness of chemoradiation for anal cancer. Methods: Patients were identified retrospectively in a single centre, who had undergone radiotherapy for anal cancer between 2008 and 2013. The only histological subtype included was squamous cell carcinoma. Patients were included who received radiotherapy alone and concomitant chemotherapy. All TNM stages were included and patients treated with palliative intent at the outset were included. Available imaging was reviewed and staging updated in line with TNM 8th edition. 5 year survival was primarily evaluated. The proportion of patients who had a defunctioning stoma and subsequent reversal was investigated. Results: 55 patients were included in the analysis. The overall 5 year survival was 75% and 5 year relapse free survival 87%. 45 patients received chemoradiotherapy and 38 (84%) of this group received mitomycin C and 5-FU regimen. 7 (13%) patients relapsed, 3 (43%) of which were local. All of these patients proceeded to an abdomino-perineal resection. The commonest fractionation schedule used was 50.4 Gray in 28 fractions. The median stage at presentation of this cohort was T2 N0 M0. The mean age at diagnosis 61.4 years. 1 patient died whilst receiving treatment. 13 (24%) patients had a defunctioning stoma prior to radiation treatment. 3 (23%) had a subsequent reversal of the stoma. Conclusions: Chemoradiotherapy is an effective treatment for squamous cell carcinomas of the anal canal, with good relapse free survival. When a defunctioning stoma is performed prior to chemoradiation there is a low rate of reversal.
Long non-coding RNA Linc00525 as a prognostic factor to regulate proliferation and apoptosis in colorectal cancer.
Authors: Peng Peng , Zheng Qin 
Published: May 2019

e15085 Background: Colorectal cancer (CRC) is one of the most common digestive system tumors and poses a serious threat to human health. More and more studies have shown that long noncoding RNAs (lncRNAs) play an important role in the occurrence and development of various tumors. They regulate a variety of cancer biology, such as proliferation, apoptosis, invasion and metastasis. Abnormally expressed lncRNAs are closely related to colorectal cancer. The purpose of this study was to find lncRNAs associated with the development of colorectal cancer and to explore its function and mechanism. Methods: (1) By analyzing the expression profile of lncRNAs in colorectal cancer-normal tissues in GEO databases, the abnormal expression of lncRNA LINC00525 was screened. Colorectal cancer tissues, adjacent normal colon tissues and colorectal cancer cell lines (HCT116, DLD1, HT-29, SW480) were detected by qRT-PCR. We analyzed the relationship between expression of LINC00525 and clinical features. (2) The biological functions of LINC00525 in HCT116, DLD1 and SW480 were peformed in vitro by MTT, clone formation assay, EDU and flow cytometry. (3) The effect of LINC00525 on tumorigenesis in vivo was evaluated by nude mice model. (4) The expression of lncRNA LINC00525 was knocked down in colorectal cancer cell lines (HCT116, SW480), and the mRNA expression levels of P15, P21, P27 and KLF2 were detected by qRT-PCR. Results: (1) Microarray data and qRT-PCR verification showed that the expression of lncRNA LINC00525 in colorectal cancer tissues and colorectal cancer cell lines was significantly upregulated. The overexpression of LINC00525 was positively correlated with clinical stage and tumor size. (2) Knockdown of LINC00525 in colorectal cancer cell lines could inhibit cancer cell proliferation and induce apoptosis. In SW480 and HCT116 cell lines, cells were arrested in G0/G1 phase after knocking down LINC00525. (3) Subcutaneous xenograft experiments in nude mice further confirmed that knockdown of LINC00525 could inhibit the tumor growth. (4) After knocking down the expression of LINC00525 in HCT116 and SW480 cell lines, the expression of mRNAs of tumor suppressor genes P15, P21, P27 and KLF2 increased. Conclusions: Our studies suggested that LINC00525 was significantly upregulated in colorectal cancer tissues. Mechanism studies had shown that LINC00525 could regulate the expression of KLF2, P15, P21 and P27 in CRC cell lines, and then affect cell proliferation and apoptosis.
Histological growth pattern as a potential marker of oligometastatic disease in patients operated for colorectal liver metastases.
Authors: Bohlok Ali , Dezes Robin , Lucidi Valerio , Bouazza Fikri , Germanova Desislava , Van Laethem Jean Luc , Hendlisz Alain , Demetter Pieter , Larsimont Denis , Donckier Vincent , Vermeulen Peter B. 
Published: May 2019

e15093 Background: The identification of oligometastatic profile in patients with resectable colorectal liver metastases (CRLM) would represent a major progress to improve selection for surgery. Currently, in the absence of biomarkers, the most reliable method to identify oligometastatic (OLM) and non-oligometastatic (NOLM) tumors relies on the oncological outcome after metastases-targeted surgery. The histological growth pattern (HGP) of CRLM, defined as desmoplastic (dHGP) or replacement (rHGP), has recently been shown to have prognostic value. We analyzed HGP in a series of patients operated for CRLM, characterized as OLM in case of prolonged postoperative recurrence-free survival (RFS) or NOLM in case of rapid postoperative relapse. Methods: In 357 patients operated for CRLM, we identified OLM patients as those with RFS≥5 years (N = 64), and NOLM patients as those with RFS < 1 year (N = 77). Clinicopathologic and surgical parameters were analyzed. In each CRLM, HGP was assessed in archival H&E stained tissue sections, according to international consensus guidelines. Proportions of rHGP and dHGP were determined in each metastasis. In case of multiple metastases, the mean HGP was calculated in each patient. Patients were categorized as pure (> 95% rHGP or dHGP) or dominant phenotypes (> 50% rHGP or dHGP, of the entire tumor-liver interface). Results: Preoperative characteristics of primary tumor and CRLM, and surgical data were identical in OLM and NOLM groups. In a first set of analyses, HGP was determined in 39 OLM and 52 NOLM patients. Pure dHGP was observed in 54.3% of OLM and 17.3% of NOLM patients (p = 0.001). Pure rHGP was similarly distributed among OLM and NOLM groups. Sixty-nine% of the OLM patients displayed a dHGP-dominant phenotype, whereas 57.7% of the NOLM patients presented with a rHGP-dominant phenotype (p = 0.02). Conclusions: These results confirm the potential prognostic value of HGP in patients operated for CRLM. dHGP, associated with angiogenesis and inflammation, could represent a (surrogate) marker for oligometastatic progression, whereas rHGP appears strongly associated with rapid postoperative relapse.
Utility of effect size to define populations with durable clinical outcomes across trials of metastatic colorectal cancer.
Authors: Kratz Jeremy D. , Uboha Nataliya Volodymyrivna , LoConte Noelle K. , Lubner Sam Joseph , Mulkerin Daniel , Matkowskyj Kristina , Turk Anita Ahmed , Sprackling Carley M. , Eickhoff Jens C. , Deming Dustin A. 
Published: May 2019

e15104 Background: ASCO defined clinically meaningful trial endpoints in colorectal cancer (CRC) as absolute overall survival (OS) of 3-5 months and OS hazard ratio (HR) ≤0.67. Few tools predict clinically distinct subgroups from heterogeneous populations. Effect size (Glass’s delta) calculates the absolute difference in clinical outcomes relative to the standard deviation of control group. We hypothesized that effect sizes ≥1 would be useful in predicting subgroup populations of clinical significance for trials with an indeterminate HR. Methods: Prospective phase II-III trials in metastatic CRC were queried from clinicaltrials.gov and cataloged by clinical outcomes of PFS and OS. Effect size was back-calculated from trials reporting 95% confidence intervals and compared with absolute difference in clinical outcome and hazard ratio. Results: 46 prospective trials were evaluable including 49% with biomarker selection, 57% in the first-line setting, and more commonly studied with targeted therapy over chemotherapy (70 v. 30%; p < 0.001). EGFR inhibitors were studied in 34% and VEGF inhibitors in 23%. Both effect size and HR correlated similarly with PFS (correlation coefficients, R = 0.65 vs. 0.76) and OS (R = 0.83 vs. 0.84) across these studies. Of studies with an indeterminate HR (0.69-0.86; n = 24), 10 studies had a significant effect size (Glass’s delta > 1), indicating the potential for sub-populations with improved clinical benefit within the experimental treatment group. These included 4 trials with planned biomarker analyses. Remaining trials were enriched for studies investigating anti-angiogenic therapies (83% vs. 23%, p = 0.001), including bevacizumab, aflibercept, regorafenib, and ramucirumab. Conclusions: Effect size holds potential as a measure to indicate the presence of subpopulations of patients benefiting in clinical trials. Those trials with a significant effect size despite an indeterminate HR should be examined closely for such populations. In CRC, effect size indicates the potential of a subgroup of patients who benefit significantly from anti-angiogenic agents. Further investigations are needed to validate effect size as a tool to delineate improved clinical outcomes from heterogeneous populations.
Microsatellite instability status in metastatic colorectal cancer and effect of immune checkpoint inhibitors on survival in MSI-high metastatic colorectal cancer.
Authors: Okamoto Wataru , Nakamura Yoshiaki , Shiozawa Manabu , Komatsu Yoshito , Denda Tadamichi , Hara Hiroki , Kagawa Yoshinori , Narita Yukiya , Kawakami Hisato , Esaki Taito , Nishina Tomohiro , Izawa Naoki , Ando Koji , Moriwaki Toshikazu , Kato Takeshi , Nagashima Fumio , Satoh Taroh , Nomura Shogo , Yoshino Takayuki , Akagi Kiwamu 
Published: May 2019

e15106 Background: Tumor mismatch repair (MMR) predicts benefit of immune checkpoint inhibitors (ICIs) in metastatic colorectal cancer (mCRC). We conducted a large-scale prospective observational trial on microsatellite instability (MSI) status in mCRC: SCRUM-Japan GI-SCREEN CRC-MSI. Methods: mCRC patients (pts) appropriate for systemic chemotherapy were eligible. Paired tumor and normal DNA extracted from FFPE samples were analyzed by the MSI Analysis System, which includes 5 mononucleotide markers. Tumors exhibiting ≥2 unstable markers were defined as MSI-H, while those with ≤1 were labelled MSI-L/MSS. Results: From 2/2016 to 3/2018, 1,711 pts were enrolled, and 1,696 samples were submitted. MSI status was determined in 1,676 pts (98.8%); 51 pts (3.0%) were MSI-H. For MSI-H vs. MSI-L/MSS pts: Median age (years) 64/64; male gender (%) 51.0 vs. 43.8, p=0.31; right-sided primary (%) 70.6 vs. 25.0, p<0.001; and poorly differentiated histology (%) 33.3 vs. 8.9, p<0.001. Of the 864 pts who received parallel NGS testing, median tumor mutation burdens (TMB) in MSI-H and MSI-L/MSS were 32.8 and 12.6 mt/Mb, p<0.001. High TMB, defined as >20 mt/Mb, was observed in 27/29 (93.1%) MSI-H pts. The frequency of representative gene mutations (%) for MSI-H vs. MSI-L/MSS pts were: TP53 17.2 vs. 66.1, p<0.001; PIK3CA 48.3 vs. 13.2, p<0.001; BRAF 34.5 vs. 7.5, p<0.001; MSH2 17.2 vs. 0, p<0.001; CTNNB1 17.2 vs. 0.6, p<0.001; and ERBB2 10.3 vs. 1.4, p<0.001. ERBB2 amplification was detected only in MSI-L/MSS pts (2.3%). Two-year survival rates from first-line systemic therapy in 389 pts with MSI-L/MSS, 5 pts with MSI-H treated with ICI in any-line, and 5 pts with MSI-H not treated with ICI, were 77.7, 100, and 33.3%, respectively. Conclusions: MSI-H mCRC tumors were more frequent in right-sided colon primaries and with poorly differentiated histology. Median TMB was significantly greater in MSI-H pts, and a very high burden was frequently seen. Survival in MSI-H mCRC was poor before ICIs; these agents may improve outcomes for MSI-H pts. Clinical trial #UMIN000020437.
Molecular analysis of advanced colorectal cancer in a patient cohort of Hispanics, African Americans, and Caucasians within a diverse single institution.
Authors: Ashai Nadia , Mejia Saldarriaga Mateo , Rao Devika , Stuart Matthew , Zhang Wei , Goel Sanjay , Halmos Balazs , Rajdev Lakshmi 
Published: May 2019

e15121 Background: CRC survival and treatment response differences have been noted across racial and ethnic groups, particularly between Hispanics (HA), non-Hispanic AA (AA), and non-Hispanic Caucasian (CA). We examined if there are differences in molecular drivers between these groups that could explain such differences in our diverse medical center. Methods: We retrospectively examined 361 HA, AA, CA patients at Montefiore Medical Center diagnosed with metastatic CRC (mCRC) from 2007 to 2018. Mismatch repair proficiency (MMR-P), deficiency (MMR-D) was determined by immunohistochemistry. KRAS, NRAS, BRAF were determined by polymerase chain reaction or next generation sequencing. Mutations were then correlated with overall survival (OS). Results: Across subgroups, there was no differences in MMR, KRAS, NRAS, BRAF incidence (Table). Using a univariate analysis, the median survival for RAS mutated (M) patients was 33 months (ms), compared to 69 ms for RAS wild-type (WT, p = 0.01). The median OS for RAS mutated HA patients was 41 ms, compared to 41 ms and 33 ms for CA and AA respectively (p = 0.14). There was also no statistically significant difference between median OS for RAS WT HA patients (69 ms), compared to AA patients (51 ms) and CA (not reached, p = 0.75). Conclusions: In our single institution study, we found no difference in incidence of RAS (KRAS and NRAS), BRAF, MMR amongst HA, AA, and CA. Delivery of uniform care may account for similar OS outcomes in our patient population. RAS WT and M disease had improved OS compared to previously established rates in the literature. Additional studies are needed to evaluate known differences in treatment response and survival in minority populations.[Table: see text]
B7-H3 expression by immunohistochemistry as a negative prognostic biomarker in colorectal carcinoma (CRC) in a racially diverse population.
Authors: Kaumaya Meghan , Zhang Wei , Kuan Kevin , Gupta Sorab , Hu Shaomin , Rao Devika , Ohaegbulam Kim , Hwang Richard , Liu Qiang , Zang Xingxing , Goel Sanjay , Maitra Radhashree 
Published: May 2019

e15127 Background: In CRC, utility of immunotherapy (IT) remains limited to persons with microsatellite instability–high (MSI-H) status. Immunotyping of CRC patients is critical towards further establishing IT's potential. Both incidence and survival rates for CRC in the United States vary between races due to multiple factors including genetic heterogeneity. In this study, we have profiled tumor samples in a racially diverse population for the expression of four different members of the B7 family of immune check point regulators. Methods: Tissue microarray (TMA) was generated from 208 CRC patients. Formalin fixed paraffin embedded (FFPE) tissues were utilized for immunohistochemistry (IHC) post- antigen retrieval. Antibodies specific for IHC staining were used for B7-H3 (D9M2L), PD-L1(E1L3N), B7-H4/B7x(D1M81) and HHLA2(566.1). Each specimen was scored for percent staining of tumor tissue (4 quartile groups) and for intensity (1-4x), and then an overall score (1-16) was calculated. The clinical outcome of interest was overall survival (OS), measured as time from diagnosis of metastatic cancer to death. Analysis for differences in OS was by log rank test, while differences between mean staining was by t test. Race was designated as non-Hispanic white (NHW, n = 41), non-Hispanic black (NHB, n = 84), Hispanic (n = 75), and others (8). Results: B7-H3 protein expression showed strong cytoplasmic distribution. NHB patients had a mean lower expression than NHW patients (0.19 vs 0.41, p = 0.02). Correspondingly, NHB patients had a worse OS than NHW patients (606 vs 759 days). No discernible differences were found in Hispanic patients. PD-L1 showed membranous distribution with 17% expression without significant difference among patients of different racial origin. HHLA2 was more widely expressed with about 35% staining but without statistical significance. B7-H4/B7x failed to show any expression. Conclusions: Expression of B7H3 varies among patients with differential racial backgrounds. It has the potential to be a prognostic biomarker and may be a reason for worse outcome among NHB patients in our population. Other B7 immune checkpoint markers failed to show clinical relevance.
The mutational profile analysis of extramural vascular invasion in rectal cancer.
Authors: Wei Mingtian , Song Yane , Deng Xiangbing , Wu Lijia , Meng Wenjian , Yang Wanning , Mao Beibei , Yang Ying , Han Wenbo , Zhang Henghui , Wang Ziqiang 
Published: May 2019

e15128 Background: Extramural vascular invasion(EMVI) is a known independent predictor of poor prognosis in rectal cancer, as evidenced by a higher risk of developing metastases and a shorter DFS compared with negative tumours. However, the molecular mechanisms of EMVI genesis remains unclear. The objective of this study is to clarify the distinct molecular characterization of EMVI-positive tumours from that of EMVI-negative tumours. Methods: DNA was extracted from FFPE tumor specimens and matched normal tissue samples from rectal cancer patients who underwent surgical resection. Comprehensive genomic profiling analysis was performed using a 2.41M size panel covering exon regions of 1,622 genes based on next generation sequencing assay. Somatic Mutations were analyzed to determine the difference of molecular features between EMVI-positive and EMVI-negative patients. Results: In this retrospective study, a total of 48 rectal cancer patients without distant metastases were included: 17 patients in the EMVI-positive group and 31 patients in the EMVI-negative group. All the EMVI-postive patients had lymph node metastasis and 15 patients had lymph node metastasis in EMVI-negative group. Among all the tumours, the most frequently mutated genes were TP53, APC, KRAS, SMAD4, CHEK2, TCF7L2 and FBXW7. Mutations of TCF7L2 and CHEK2 were more frequently observed in EMVI-positive tumours than that in EMVI-negative tumours with p < 0.05. Survival analysis (Kaplan-Meier) indicated that patients with KRAS mutations(n = 9) had a shorter DFS than patients without KRAS mutations(n = 23) in patients with lymph node metastasis (p < 0.05). In addition, age was significantly associated with DFS according to the survival analysis (p < 0.05). Conclusions: Several possible candidate genes that may be helpful to characterize the distinct mutational profile of EMVI-positive tumours from EMVI-negative tumours were identified, which may be of great significance in disclosing the molecular mechanism underlying in EMVI initiation and progression. Expanded prospective cohorts are warranted to further elucidate these findings.
The results of 3000 Fit: A prospective study led at Saint Joseph University of Beirut.
Authors: Elkaddoum Ronaldo , Eid Roland , Haddad Fady , Germanos Myrna , Mehawej Cybel , Kourie Hampig Raphael , Kattan Joseph Gergi 
Published: May 2019

e15141 Background: In terms of frequency, colorectal cancer (CRC) is the 3rd cancer in Lebanon with 1093 incidences registered in 2015. To this date not a single screening campaign has been organized in the country. Fecal immunochemical test (FIT) is an advised screening technique. We found it useful to organize a screening campaign using FIT to determine the prevalence of CRC in a population of 3000 healthy Lebanese allowing the extraction of useful data. Methods: 3000 tubes were distributed to Lebanese adults (45-80 years old) at average risk of developing CRC, followed by explanations. FIT analysis was done at the medical genetics unit (UGM) of Saint-Joseph University and patients with positive FIT were asked to undergo further investigations. Results: Out of the 3000 distributed tests, 705 were returned (23.5%) with 459 fully analyzable. The age median was 56 (45-80). Sex ratio F/M 2.3. Out of the 459 patients, 278 (60.5%) showed 0ng/ml, 137 (29.8%) showed 1-79ng/ml, 3 (0.6%) showed 80-99ng/ml (intermediate risk values), 33 (7.1%) showed 100-800ng/ml considered as a positive value and finally 8 (1.7%) showed over range values. Among the 44 positive patients we contacted 41. Out of the 8 (18%) colonoscopies results received: 5 showed hemorrhoids leading to false positive, 1 ulcerative ileitis, 1 tubular adenomas and 1 carcinoma. Conclusions: While it was hard for us to quantify people for whom a free FIT was proposed, the low restitution rate among those who took the test shows the necessity of national screening and sensitization campaigns.
An evaluation of RAS testing and survival among mCRC patients in the United States.
Authors: Kiprilov Enko , Sangaré Laura , Lowe Kimberly , Christodoulopoulou Alexandra 
Published: May 2019

e15144 Background: The status of mutations in the rat sarcoma viral oncogene homolog ( RAS) family of genes, which includes Kirsten RAS ( KRAS) and Neuroblastoma RAS ( NRAS) predicts response to anti-EGFR therapies in metastatic colorectal cancer (mCRC) patients. Current treatment guidelines recommend all mCRC patients to receive RAS testing prior to initiating treatment with an anti-EGFR agent. This study sought to establish estimates of RAS testing among mCRC patients in the US prior to initiation of first and third lines of treatment, and to describe median survival by treatment groups. Methods: Data from the Oncology Services Comprehensive Electronic Records (OSCER) 2.0 dataset were utilized. Patients diagnosed with mCRC between January 1, 2011 and July 31, 2017 were eligible. Patients were followed for up to 1 year, or until death, following their mCRC diagnosis. Results: A total of 17,387 mCRC patients were included in the analysis, among which 69% were RAS tested and 31% were never tested. Among the RAS tested patients, 23% were tested prior to their mCRC diagnosis 60% received RAS testing following mCRC diagnosis but prior to first line of treatment, 3% were tested following first line treatment but prior to third line, and the remaining 14% were tested following third line. Demographic variables did not differ between tested and untested groups, overall and by line of treatment. The overall median survival of RAS WT patients was 31.1 months (95% CI: 30.0, 32.4). MCRC patients who were not RAS tested had a lower median survival of 20.7 months (95% CI: 19.1, 22.5). Conclusions: The timing of when patients are being tested varies greatly. While nearly 70% of patients had a RAS test, approximately 30% failed to be tested, identifying a large gap in testing practices. Universal RAS testing provides patients and their physicians with knowledge of their anti-EGFR treatment options and may result in improved survival.