bluuebunny/crossref_metadata_2025_split huggingface dataset:
The clinical impact of MicroRNA-21 in low rectal cancers treated with curative radiotherapy in the organ preserving setting.
Authors: Hansen Torben , Thomsen Caroline Brenner , Andersen Rikke Fredslund , Jensen Lars Henrik , Jakobsen Anders Kristian Moeller 
Published: May 2020

e16120 Background: Neoadjuvant chemoradiotherapy (CRT) in curatively intended doses may result in clinical complete response (cCR) in selected patients, allowing for non-surgical management (NSM) of patients with low rectal cancers. MicroRNA-21-5p (miR-21), ubiquitous upregulated in cancer, has been associated with treatment response in rectal cancers treated with standard preoperative CRT. The aim of the present study was to investigate this association in low rectal cancers treated in the NSM setting. Methods: Forty eight patients from our single-arm phase II trial (NCT00952926) were available for analyses. All patients had resectable, T2 or T3, N0–N1, low adenocarcinomas and received 65Gy (intensity-modulated radiotherapy plus brachytherapy boost) and oral tegafur-uracil. Patients with cCR 6 weeks after treatment (clinical examination, magnetic-resonance imaging and biopsy) were referred to observation and followed closely. The miR expression, in the diagnostic biopsies, was measured by qPCR in 20 µl reactions using TaqMan MicroRNA Assays. The protocol using custom RT and preamplification pools was followed. The miR-193a-5p, -27a and –let7g were used for normalization based on previous recommendations from our group. The relationship between miR-21 expression and cCR was assessed using the Wilcoxon rank-sum tests. Results: Thirty-eight patients achieved cCR after treatment and were followed in observation while 10 patients proceeded to surgery due to a non-cCR. MicroRNA-21 was successfully analyzed in all samples. The median tumor expression of miR-21 in patients proceeding to surgery was significantly higher compared to patients achieving cCR, 24.3 (95% confidence interval (CI) 17.1-36.8) and 16.6 (95% CI 13.9-21.1), p = 0.02, respectively. Conclusions: The present results support a clinical impact of miR-21 in rectal cancer treated with CRT, comparable with results seen in patients treated in the standard preoperative setting, and may assist in the selection of patients for an organ preserving approach.
Phase II trial of induction chemotherapy plus chemoradiotherapy with aspirin or placebo in high-risk rectal cancer (ICAR).
Authors: Souza Juliana , Araujo Rodrigo Otavio , Valadão Marcus , Santos Victor Marcondes Lopes , Gonzaga Jamille , Padoan Monica Luciana Agostinho , Barbosa Monique Alvares , Torres Claudia , Guimarães Raquel , Carvalho Juliana , Gil Roberto de Almeida , Small Isabele , Ferreira Maria Aparecida , Correa João Pedro Araujo Simões , Oliveira Ivanir Martins , Mello Eduardo Linhares Rielo , Melo Andreia Cristina De , Araujo Luiz H. 
Published: May 2020

e16131 Background: Induction chemotherapy (IC) followed by chemoradiation (CRT) is an attractive approach in locally-advanced, high-risk rectal cancer. Additionally, aspirin has shown potential to lower recurrence rate in colorectal cancer, and improve outcomes alongside CRT in rectal cancer, with higher rate of tumor downstaging. Methods: Randomized, double-blind phase 2 trial to evaluate induction treatment with XELOX, followed by capecitabine-based chemoradiotherapy with aspirin or placebo in a high risk population selected by MRI. The aim of this study was to evaluate MRI response after total neoadjuvant treatment with aspirin or placebo. Results: Of the 25 pts who started treatment between January 2018 and March 2019, 4 pts did not complete (1 pt grade 5 diarrhea; 1pt treatment adherence). Median age was 55yo (32.9 - 73.6), 8 pts (32%) were women, and 80% had 3 or more high-risk criteria. 20 pts (80%) showed symptom improvement in the first cycle of IC. Of the 21 patients who finished treatment until interim analysis, 11 pts received aspirin (2 pts had MRI complete response (CR), 3 pts had minor/no response, and 3 pts had progression disease (PD)). 10 pts received placebo (4 MRI CR, 3 pts had minor/no response, and no PD). Conclusions: Aspirin added to chemoradiotherapy was safe but did not improve response to total neoadjuvant treatment. The study was closed due absence of benefit. Clinical trial information: NCT03170115 .
Circulating mitochondrial DNA (mtDNA) variants to predict metastatic progression of rectal cancer.
Authors: Ree Anne Hansen , Bousquet Paula A , Bjørnetrø Tonje , Fuglestad Anniken Jørlo , Lüders Torben , Esbensen Ying , Johansen Christin , Juul Hedvig V , Inderberg Else Marit , Kersten Christian , Redalen Kathrine Røe , Meltzer Sebastian 
Published: May 2020

e16132 Background: High rates of systemic failure after curative-intent therapy in locally advanced rectal cancer (LARC) call for new diagnostic tools to improve risk-based treatment stratification. We hypothesized that blood mtDNA polymorphisms, generated by the high mtDNA mutation rate when the mitochondrial biogenesis is mobilized during clonal immune cell activation, correlate with systemic immune control of LARC dissemination and thus can be used as diagnostic marker. Methods: 41 LARC patients given neoadjuvant (chemo)radiotherapy had DNA extracted from whole blood (WB) sampled at the time of diagnosis, for high-throughput full-length mtDNA sequencing followed by annotation of mtDNA variants using the curated reference genome (mitomap.org). The composition of peripheral blood mononuclear cell (PBMC) subpopulations was analyzed by high-dimensional single-cell mass cytometry. Metastatic events were recorded over 24-60 months of follow-up after completion of the multimodal treatment. Results: The total number of WB-mtDNA variants was strikingly different across the study cases but without correlation to patient’s age, body mass index, or metformin use, which may affect mitochondrial function, or to the disease extension at presentation or the local tumor response to the neoadjuvant therapy. All patients had microsatellite-stable tumor. The higher the number of variants in MT-RNR2, encoding one of the two ribosomal subunits of mitochondria, the better distant metastasis-free survival (DMFS). For each patient, two MT-RNR2 sites were homoplasmic for either the normal or a deletion (3105AC > A, 3106CN > C) variant, categorizing the patients into two groups that comprised the same cases for both mtDNA sites. Nine of a total of 10 DMFS events occurred during the 18 first months of follow-up in one of the patient groups ( n = 23). The single event in the other group ( n = 18) appeared in a patient who had declined primary tumor surgery. In the former group, a low number of variants in the ribosomal subunit MT-RNR1 identified all patients who had metastatic progression. These patients had reduced PBMC frequency of CD8+ (cytolytic) T cells that were positive for CXCR4 ( p = 0.001), a chemokine receptor that promotes their homing to tumor sites. Conclusions: The WB-ribosomal mtDNA polymorphisms reflected systemic immune cells endowed with cytolytic and tumor-homing properties. The actual mtDNA variants were single-base alterations and might thus be analyzed by PCR and developed as a feasible assay for metastatic risk assessment in rectal cancer. Clinical trial information: 01816607 .
A prospective pilot study of pharmacogenetic-based dosing of 5-fluouracil (5-FU) and irinotecan (IRI) in patients (pts) with gastrointestinal (GI) malignancies.
Authors: Chi Jeffrey , Hakim Nausheen , Rehman Hasan , Moriarty Linda , Maloney Antonia , Smith Melissa H , Jose Jyothi , Saif Wasif M. 
Published: May 2020

e16138 Background: 5-FU and IRI are core components of chemotherapies for GI malignancies. Previous studies have shown that mutations in DPYP and TYMS predispose the pts to 5-FU toxicities. Mutations in UGT1A1 predispose pts to increased IRI toxicities. Retrospective data suggest that these mutations may have implications in selecting dosage and/or schedule of 5-FU and IRI. We present here a prospective study of upfront pharmacogenetic testing with tailored dose of respective drugs in pts with these mutations. Methods: Pts with GI malignancies were tested for DPYD, TYMS and UGT1A1 mutations before initiating 5-FU and/or IRI. Mutation analyses were performed at Quest Diagnostics Nichols Institute. Pts were dosed at 50% if DPYD was abnormal and 25% dose reduction if indicated by TYMS or UGT1A1 * 28 (homozygous) abnormality. Adverse events (AEs) were graded according to CTCAE v.5.0. We compared AEs to our previously collected data in DPYD, TYMS deficient pts who underwent genetic testing due to toxicity to 5-FU. Results: Of 226 pts screened, 5 pts had DPYP mutations with genotypes (3: c.1905+1G/A; 1: c.2846A/T; 1: c.557A/G). TYMS mutations were identified in 24 pts. For 3'-UTR, distributions were: intermediate expression genotype 4: INS/DEL, low expression genotype 5: DEL/DEL. For 5'TSER, distributions were: low expression genotypes (6:2R/2R; 3:2R/3RC; 4: 3RC/3RC) and high expression genotypes (2: 2R/3RG, 2: 3RG/3RC, 1: 3RG/3RG). UGT1A1*28 mutation was identified in 53 pts – 19 homozygous and 34 heterozygous. No grade ≥3 neutropenia was observed with reduced dose of IRI in UGT1A 1 variant pts compared to 33% reported in pts not tested. For TYMS and DPYD variants, no grade ≥3 AEs were seen. Comparison of AEs in pts with post treatment genetic testing is listed in Table. Conclusions: Pharmacogenetic based dosing of 5-FU and IRI led to less frequent, less severe toxicities and no death related to AEs was observed in our pts. This can improve pts’ quality of life and lessen economic burden of managing severe AEs. Currently, there are no formal guidelines regarding testing for DPYD, TYMS and UGT1A1. Although non-randomized, this study advocates for systemic screening of pharmacogenetic testing in pts with GI malignancies. [Table: see text]
Prospective evaluation of current RAS mutation testing practices in newly diagnosed metastatic colorectal cancer: Middle East and North Africa Registry (MORE-RAS) Study.
Authors: Oukkal Mohammed , Kamel Bouzid , Bounedjar Adda , Alnajjar Abdelsalam , Abu-Taleb Fouad , Alsharm Abdullah , Mahfouf Hassen , Blaha Larbaoui , Elsaid Amr A. , Ouamer Assia , Basir Linah 
Published: May 2020

e16141 Background: RAS testing is essential for treatment selection in metastatic colorectal cancer (mCRC), as anti-EGFR treatment is indicated only in patients with wild-type (WT) RAS. MORE-RAS was a multicenter, multicountry, observational, ambispective (retrospective + prospective) study designed to evaluate RAS mutation status among patients with mCRC in the Middle East and North Africa (MENA) region. Results of the retrospective study over a prior 2-year period have been previously presented. Here, we report on the prospective evaluation of testing practices in newly diagnosed patients from the same centers. Methods: Five countries (Algeria, Egypt, KSA, Kuwait, Lebanon) enrolled patients between Dec 2014 and Feb 2019. Patients with a new diagnosis of histologically proven mCRC, at least 1 measurable lesion per RECIST criteria, and tissue availability for biomarker analysis were included; those with co-existing malignancies or life expectancy < 6 months were excluded. The primary endpoint was evaluation of the rate of RAS mutation in newly diagnosed patients. Follow-up was for 2 years. Results: 500 patients (mean age 54.6 years; 58% female) were included; 96.4% had Stage 4 disease. Primary tumor sites were sigmoidal colon: 33.4%; rectum: 29.6%; ascending colon: 18.4%; descending colon: 11.4%; transverse colon: 5.2%; and unknown: 1.4%. Most frequent sites of metastasis were liver: 43.4%, lung: 16.0%, and peritoneum: 10.1%. Overall, 407 pts (81.4%; 95% CI, 78%–85%) received prescription for RAS testing. RAS WT was found in 58.4% and mutant in 41.6%; the test was inconclusive in 1 pt. Non-prescription was attributed to test unavailability and medical or financial reasons. The distribution of mutations was KRAS: 85%, NRAS: 4.9%, and not available: 10.1%. Predictors of RAS testing prescription were older age, primary tumor localization in ascending colon, and high tumor grade. Knowledge of RAS status resulted in the addition of bevacizumab or anti-EGFR therapy in 20.4% and 21.2% of pts, respectively at Visit 1 (baseline). Conclusions: RAS testing is now routinely prescribed for newly diagnosed mCRC in the MENA region and can change therapy patterns. The RAS mutation rate in this region differs from that in Western countries.
Serum-based multiplex protein assay for early detection of colorectal cancer and precancerous lesions in a FIT positive population.
Authors: Fritsche Herbert A. , Liggett Jason Lee , Zhang Hong , Ferm Linnea , Christensen Ib Jarle , Nielsen Hans J. 
Published: May 2020

e16145 Background: Colorectal cancer (CRC) is the second leading cancer worldwide in terms of incidence, 5-year prevalence and mortality for both women and men ages 45 years old and up. The current screening method for many countries with organized screening programs is the FIT test for fecal occult blood; however, this test can result in false positive rates as high as 65%. A FIT reflex test could reduce unnecessary colonoscopies while reducing wait times for those patients that need confirmatory colonoscopies the most. Methods: Danish FIT positive colonoscopy confirmed serum samples (n = 1,499) were divided into training and validation sets maintaining approximately equivalent percentages of clean colonoscopy (40%), low risk adenomas (16%), medium risk adenomas (19%), high risk adenomas (13%), stage I CRC (5%), stage II CRC (2%), stage III CRC (4%), and stage IV CRC (0.5%). Proteins were quantified by custom 16-plex immunoassays utilizing the Luminex xMAP platform. A support vector machine supervised machine learning algorithm was trained with the 16 biomarkers plus age and FIT concentration using 1,291 samples for the outcome medium risk adenoma, high risk adenoma, and CRC. Then this algorithm was tested on a blind 208 sample validation set. Results: The training set was 90% sensitive and 27% specific (AUC = 0.68) and the validation set was 93% sensitive and 21% specific (AUC = 0.63). The sensitivities of the validation by risk/stage was as follows: medium risk adenoma 91%, high risk adenomas 92%, stage I CRC 100%, stage II CRC 100%, stage III CRC 100%, stage IV CRC 93%. Conclusions: This study demonstrates feasibility of a novel blood-based multiplex protein immunoassay for use as a reflex to FIT positive results in population wide screening. It detected nearly all adenomas and carcinomas while reducing FIT false positives and thus unnecessary colonoscopies by more than 20%. A FIT reflex test could alleviate endoscopy burden experienced in countries with organized cancer screening programs, while providing better patient outcomes by detecting polyps and early-stage CRC with high sensitivity.
Genetic landscape of 43 patients with dMMR gastric cancer and its clinical implications.
Authors: Wang Dongliang , Hu Nana , Xu Quan , Meng Erhong , Li Zhongwu , Shen Lin 
Published: May 2020

e16501 Background: The FDA has approved immune checkpoint inhibitors for dMMR/MSI-H patients with solid tumors, but the efficacy varies greatly, so that more molecular biomarkers are needed to guide the clinical practice. Methods: In this study, the gene status of tumor tissues of 43 patients with dMMR gastric cancer previously identified by immunohistochemistry (IHC) was measured using TSO500, and the gene profile was preliminarily determined. Results: The genetic landscape is different between these 43 dMMR gastric cancer and TCGA as well as 200 cases of ordinary gastric cancer in China. The top five mutational genes in patients with dMMR gastric cancer were LRP1B (65.12%), RNF43 (62.79%), TP53 (58.14%), ARID1A (58.14%), BRCA2 (44.19%). In TCGA, the top five mutational genes were TP53 (48.1%), MUC16 (41.8%), SYNE1(32.1%), ARIDIA (31.4%) and LRP1B (30.7%). In 200 cases of patients with ordinary gastric cancer in China, the top five mutational genes were MUC6 (86.6%), MUC16 (84.6%), MACF1 (68.7%), DST (66.2%) and ZFHX4 (65.7%). The frequently abnormal signaling pathways in patients with dMMR gastric cancer were RTK/RAS (84%), P53 (77%), PI3K (74%), Notch (74%), Wnt (70%), Myc (47%),TGF-β(40%) signaling pathway. In addition, it was found that 40% of patients with dMMR gastric cancer were microsatellite-stable (MSS). Among the four dMMR biomarkers, 91.11% MLH1 negative or 86.67% MSH6 negative patients with dMMR gastric cancer were microsatellite-instable(MSI)–H, while only 11.11% MSH2 negative or 6.67% MSH6 negative patients with dMMR were MSI-H. Conclusions: This study provided important novel insight into the biology of dMMR gastric cancer and identified clinically genetic features for the future improvement management of patients with dMMR gastric cancer. It also suggested that in clinical practice, IHC is only suitable for preliminary screening. [Table: see text]
Hepatic arterial infusion oxaliplatin plus oral S-1 chemotherapy to improve prognosis for gastric cancer with multiple liver metastases.
Authors: Wang Kangxin , Yang Yang 
Published: May 2020

e16508 Background: Gastric cancer with multiple liver metastases (GCLM) is associated with a high disease burden with synchronous or metachronous tumour invasions of other organs. In order to improve patient outcome, this study combined hepatic artery infusion (HAI) oxaliplatin with oral S-1 chemotherapy as a first-line palliative therapy. The aim is to assess efficacy and safety of this combination mode. Methods: We reviewed the records of ten patients with GCLM who received HAI oxaliplatin (70-80 mg/m2 2h d1,15) administered via a port-catheter system and S-1 with oral (35-40 mg/m2 twice daily for d1-14, 28 days for one cycle). Follow-up examination and efficacy evaluation were executed periodically. Results: Until the 4th cycle response evaluation, the local effective rate and control rate was 60% and 90% respectively, only one patient developed progression. HAI oxaliplatin plus oral S-1 chemotherapy had a better local control against hepatic metastases (median progression-free survival: hepatic, 9.0 months vs. extrahepatic, 6.5 months), which showed potential benefit of the combination regimen in gaining local tumour control, maintaining function and improving life quality. Conclusions: HAI oxaliplatin plus oral S-1 chemotherapy can be regarded as an optimized treatment strategy for GCLM, which is also a crucial way for controlling of extrahepatic lesions without much systemic toxicity.
Esophageal cancer, five years of experience in a regional oncologic reference center in Mexico.
Authors: Alcorta-Garza Adelina , Cessa-Zanatta José Carlos , Alcorta-Nuñez Fernando , Muñoz-Ayala Juan Manuel , Hernández-Barajas David , Gonzalez Guerrero Juan Francisco , Vidal-Gutiérrez Oscar 
Published: May 2020

e16515 Background: Esophageal cancer is a highly lethal entity. Within this group of tumors, squamous cell carcinoma (SCC) and esophageal adenocarcinoma (ACE) represent 95% of the total. For most of the twentieth century, the SCC predominated throughout the world, however, this trend has changed dramatically in Western countries, including ours. Mexican patients with esophageal cancer are diagnosed at later stages of the disease and have worse therapeutic outcomes than reported in the world literature. Methods: Retrospective, observational and descriptive study. The research subjects were obtained from the population of patients who attended the service of the Centro Universitario Contra el Cancer of the University Hospital "Dr. José Eleuterio González” between 2012 and 2017 (sample size calculated n = 120).The clinical and demographic characteristics of patients with esophageal cancer in our population were described. The results from international guides (AIMS65, New International Score, Glasgow-Blatchford scale and Rockall pre-endoscopic) were used to compare cut-off points with our population and their correlation with mortality. Results: A total of 179 research subjects were included in the study. The average age was 55 years, 62% male and 38% female. Various demographic characteristics such as in-hospital mortality (n = 42, 23.5%), 30-day mortality (n = 36, 20.1%), re-bleeding (n = 49, 27.4%) and transfusions (n = 99, 55.3%) were studied as incidence of positive cases to the event. We also studied the mean days of hospital stay (4.6 days), systolic blood pressure (108 mmHg) and diastolic blood pressure (66mmHg), hemoglobin (8.9 g / dL), among others. The type of bleeding was variceal in 122 subjects, and non-variceal in 57. In total, 117 subjects were treated with endoscopic treatment and 53, without endoscopic treatment. The Glasgow Blatchford scale obtained a higher discriminative score (AUROC 0.73) to predict in-hospital mortality in our subjects, compared to ASA (0.72 p < 0.001), New International score (0.76 p < 0.001) and AIMS65 (0.66 p < 0.001). Conclusions: The used scales had no positive predictive value for bleeding risk. The Glasgow Blatchford scale was the only score that showed an AUROC of 0.65 p < 0.001 to predict the efficiency of transfusion in patients compared to the other scores that showed no significant value. ASA was the predictive discriminative score (AUROC 0.73) for a 30-day in-hospital mortality (p < 0.001), followed by the Glasgow Blatchford scale (0.61 p < 0.04).
Identification and expression distribution of esophageal carcinoma autoantigens.
Authors: Si Fuchun 
Published: May 2020

e16520 Background: To identify the autoantigen protein molecules with autoserum in the tissues from the esophageal carcinoma (EC) patients, analyze autoantigen expression distribution in EC tissues, so as to provide basis for the molecular pathogenesis and clinical medication of EC. Methods: 69 cases of EC patients tissues and serum and 81 cases of healthy people serum were collected, serological proteome analysis (SERPA) was modified with sequential extraction of subcellular protein fractions to identify esophageal oncopathgensis stages autoantigen with autoserum in the tissues from the EC patients. Another 93 cases of EC patients tissue were collected, immunohistochemical and western blot method were used to detect expression distribution of EC autoantigens in esophageal carcinoma tissue, para-carcinoma tissue and normal tissue. Results: Autoantigens CK13, CK16, CaD, ACTG2, tumor rejection antigen (gp96) 1 variant, heat shock protein gp96 precursor were identified, among wihich, CK16, CaD, ACTG2, tumor rejection antigen (gp96)1 variant, heat shock protein gp96 precursor were firstly reported as EC autoantigens. Expression of autoantigens CK16, CaD, ACTG2 were increased in EC carcinoma tissue than para-carcinoma tissue and normal tissue, while CK13 were decreased. Positive expression level of CK16 in normal tissue, para-carcinoma tissue and cancer tissue of EC patients was 0.0076±0.0033, 0.0158±0.0065, 0.0356±0.0165 respectively, CaD was 0.0085±0.0048, 0.0107±0.0056, 0.0177±0.0103 respectively, ACTG2 was 0.0091±0.0039, 0.0136±0.0043, 0.0214±0.0110 respectively, and CK13 was 0.2053±0.0311, 0.1633±0.0280, 0.0412±0.0239 respectively. Conclusions: 6 EC autoantigens were identified, and 5 were first reported. Autoantigens CK13, CK16, CaD and ACTG2 were expressed in EC patients carcinoma tissue, which can be the potential biomarkers of esophageal carcinoma. This study provides new basis for the EC molecular mechanism and development of molecular drugs.