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Latest & greatest articles for colorectal cancer
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Role of chemotherapy in resectable liver metastases from colorectalcancer: food for thought from pooled evidence 29942665 2019 01 30 2059-7029 3 4 2018 ESMO open ESMO Open Role of chemotherapy in resectable liver metastases from colorectalcancer: food for thought from pooled evidence. e000367 10.1136/esmoopen-2018-000367 Mauri Davide D Department of Medical Oncology, University Medical School of Ioannina, Ioannina, Greece. Filis Panagiotis P Department of Medical Oncology, University Medical (...) 2018 05 01 2018 6 27 6 0 2018 6 27 6 0 2018 6 27 6 1 epublish 29942665 10.1136/esmoopen-2018-000367 esmoopen-2018-000367 PMC6012563 Lancet Oncol. 2013 Nov;14(12):1208-15 24120480 J Clin Oncol. 2007 Oct 10;25(29):4575-80 17925551 Neoplasia. 2017 Feb;19(2):93-99 28088688 J Clin Oncol. 2006 Nov 1;24(31):4976-82 17075115 Surg Clin North Am. 2002 Oct;82(5):1075-90, x-xi 12507210 BMC Cancer. 2015 Mar 26;15:180 25884448 Lancet Oncol. 2014 May;15(6):601-11 24717919
Phase Ib/II trial evaluating the safety, tolerability and immunological activity of durvalumab (MEDI4736) (anti-PD-L1) plus tremelimumab (anti-CTLA-4) combined with FOLFOX in patients with metastatic colorectalcancer 5-Fluorouracil plus irinotecan or oxaliplatin alone or in association with target therapy are standard first-line therapy for metastatic colorectalcancer (mCRC). Checkpoint inhibitors targeting PD-1/PD-L1 demonstrated efficacy on mCRC with microsatellite instability but remain (...) ineffective alone in microsatellite stable tumour. 5-Fluorouracil and oxaliplatin were known to present immunogenic properties. Durvalumab (D) is a human monoclonal antibody (mAb) that inhibits binding of programmed cell death ligand 1 (PD-L1) to its receptor. Tremelimumab (T) is a mAb directed against the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). This study is designed to evaluate whether the addition of PD-L1 and CTLA-4 inhibition to oxaliplatin, fluorouracil and leucovorin (FOLFOX
Validation of the Survival Benefits of Metformin in Middle Eastern Patients With Type II Diabetes Mellitus and ColorectalCancer Purpose Epidemiologic data from several populations suggest that metformin may decrease cancer risk and mortality in patients with colorectalcancer (CRC) and type II diabetes mellitus (DM). Although type II DM and CRC are major health problems in the Middle East, no investigations have been performed to test the effect metformin has on the outcome of patients (...) with type II DM and CRC who are also treated with metformin. Materials and Methods We retrospectively reviewed the medical records of 1,902 patients diagnosed with CRC at King Hussein Cancer Center between January 2004 and December 2012, and identified 349 patients (18%) with type II DM; we censored the data of 28 patients because their antidiabetic medications were unknown. We then categorized these 321 patients into two groups: 192 patients treated with metformin (group A) and 129 patients treated
Clonal evolution of colorectalcancer in a patient with serially resected metastases and liquid biopsies: a case report and discussion of the literature Metastatic colorectalcancer represents a striking example of clonal heterogeneity and tumour evolution, which generates acquired resistance to therapy. Once hard to perform, the study of clonal heterogeneity is now significantly aided by the use of liquid biopsies.We herein report a case of a patient with colorectalcancer and serial (...) development of multiple metastases which were all resected and genotyped. A rare point mutation was identified in the primary tumour (but not in any of the organ metastatic sites), as well as in the first and the last out of three consecutive liquid biopsies. The review of the literature offered some insight in the evolution of the patient's tumour and general directions on how to interpret liquid biopsy results.This patient case emphasises the need for large prospective studies designed to bridge liquid
Assessing Clinical Outcomes in ColorectalCancer with Assays for Invasive Circulating Tumor Cells Colorectalcarcinoma (CRC) is the second leading cause of cancer-related mortality. The goals of this study are to evaluate the association between levels of invasive circulating tumor cells (iCTCs) with CRC outcomes and to explore the molecular characteristics of iCTCs. Peripheral blood from 93 patients with Stage I⁻IV CRC was obtained and assessed for the detection and characterization of iCTCs (...) using a functional collagen-based adhesion matrix (CAM) invasion assay. Patients were followed and assessed for overall survival. Tumor cells isolated by CAM were characterized using cell culture and microarray analyses. Of 93 patients, 88 (95%) had detectable iCTCs, ranging over 0⁻470 iCTCs/mL. Patients with Stage I⁻IV disease exhibited median counts of 0.0 iCTCs/mL (n = 6), 13.0 iCTCs/mL (n = 12), 41.0 iCTCs/mL (n = 12), and 133.0 iCTCs/mL (n = 58), respectively (p < 0.001). Kaplan⁻Meier curve
A data-driven, knowledge-based approach to biomarker discovery: application to circulating microRNA markers of colorectalcancer prognosis Recent advances in high-throughput technologies have provided an unprecedented opportunity to identify molecular markers of disease processes. This plethora of complex-omics data has simultaneously complicated the problem of extracting meaningful molecular signatures and opened up new opportunities for more sophisticated integrative and holistic approaches (...) comprising 11 circulating microRNAs. The identified signature predicts the patients' survival outcome and targets pathways underlying colorectalcancer progression. The altered expression of the identified microRNAs was confirmed in an independent public data set of plasma samples of patients in early stage vs advanced colorectalcancer. Furthermore, the generality of the proposed method was demonstrated across three publicly available miRNA data sets associated with biomarker studies in other diseases.
Modified XELIRI (capecitabine plus irinotecan) versus FOLFIRI (leucovorin, fluorouracil, and irinotecan), both either with or without bevacizumab, as second-line therapy for metastatic colorectalcancer (AXEPT): a multicentre, open-label, randomised, non- Studies of a modified XELIRI (mXELIRI; capecitabine plus irinotecan) regimen suggest promising efficacy and tolerability profiles in the first-line and second-line settings. Therefore, we aimed to compare the efficacy and safety of the mXELIRI (...) regimen with that of standard FOLFIRI (leucovorin, fluorouracil, and irinotecan), with or without bevacizumab in both regimens, as a second-line therapy for metastatic colorectal cancer.We did a multicentre, open-label, randomised, non-inferiority, phase 3 trial. We enrolled patients from 98 hospitals in Japan, China, and South Korea who were aged 20 years or older with histologically confirmed and unresectable colorectaladenocarcinoma, and who had withdrawn from first-line chemotherapy
done at 244 centres. Patients aged 18 years or older with high-risk stage II and stage III colorectalcancer underwent central randomisation with minimisation for centre, choice of regimen, sex, disease site, N stage, T stage, and the starting dose of capecitabine. Patients were assigned (1:1) to receive 3 months or 6 months of adjuvant oxaliplatin-containing chemotherapy. The chemotherapy regimens could consist of CAPOX (capecitabine and oxaliplatin) or FOLFOX (bolus and infused fluorouracil (...) 3 versus 6 months of adjuvant oxaliplatin-fluoropyrimidine combination therapy for colorectalcancer (SCOT): an international, randomised, phase 3, non-inferiority trial 6 months of oxaliplatin-containing chemotherapy is usually given as adjuvant treatment for stage 3 colorectalcancer. We investigated whether 3 months of oxaliplatin-containing chemotherapy would be non-inferior to the usual 6 months of treatment.The SCOT study was an international, randomised, phase 3, non-inferiority trial
and abdomen and serum carcinoembryonic antigen at 6, 12, 18, 24, and 36 months after surgery (high-frequency group; n = 1253 patients) or at 12 and 36 months after surgery (low-frequency group; n = 1256 patients).The primary outcomes were 5-year overall mortality and colorectalcancer-specific mortality rates. The secondary outcome was the colorectalcancer-specific recurrence rate. Both intention-to-treat and per-protocol analyses were performed.Among 2555 patients who were randomized, 2509 were included (...) Effect of More vs Less Frequent Follow-up Testing on Overall and ColorectalCancer-Specific Mortality in Patients With Stage II or III ColorectalCancer: The COLOFOL Randomized Clinical Trial. Intensive follow-up of patients after curative surgery for colorectalcancer is common in clinical practice, but evidence of a survival benefit is limited.To examine overall mortality, colorectalcancer-specific mortality, and colorectalcancer-specific recurrence rates among patients with stage II or III
Association Between Intensity of Posttreatment Surveillance Testing and Detection of Recurrence in Patients With ColorectalCancer. Surveillance testing is performed after primary treatment for colorectalcancer (CRC), but it is unclear if the intensity of testing decreases time to detection of recurrence or affects patient survival.To determine if intensity of posttreatment surveillance is associated with time to detection of CRC recurrence, rate of recurrence, resection for recurrence (...) , or overall survival.A retrospective cohort study of patient data abstracted from the medical record as part of a Commission on Cancer Special Study merged with records from the National Cancer Database. A random sample of patients (n=8529) diagnosed with stage I, II, or III CRC treated at a Commission on Cancer-accredited facilities (2006-2007) with follow-up through December 31, 2014.Intensity of imaging and carcinoembryonic antigen (CEA) surveillance testing derived empirically at the facility level
Initial experience with the bispecific anti-CEA anti-CD3 antibody and its expected impact on future treatment for patients with colorectalcancer 29862052 2018 06 04 2059-7029 3 4 2018 ESMO open ESMO Open Initial experience with the bispecific anti-CEA anti-CD3 antibody and its expected impact on future treatment for patients with colorectalcancer. e000377 10.1136/esmoopen-2018-000377 Argiles Guillem G GastrointestinalMalignancies Program, Vall d'Hebron University Hospital, Barcelona, Spain (...) . eng Journal Article 2018 05 20 England ESMO Open 101690685 2059-7029 colorectalcancer Competing interests: None declared. 2018 6 5 6 0 2018 6 5 6 0 2018 6 5 6 1 epublish 29862052 10.1136/esmoopen-2018-000377 esmoopen-2018-000377 PMC5976108
Lysyl oxidase: A colorectalcancer biomarker of lung and hepatic metastasis Colorectalcancer (CRC) is a common and lethal disease in which distant metastasis remains the primary cause of death. Paradoxical roles of LOX have been reported in CRC, and the intracellular function of LOX has also recently been determined. Correlations of LOX expression and its intracellular localization with clinicopathological features in CRC patients remain largely unknown. The aim of the present study (...) nuclear localization was found to correlate with lung/hepatic metastasis, elevated serum carcinoembryonic antigen concentration, and mucinous tumor type (P < 0.05). Nuclear LOX expression was found to be associated with poor overall and disease-free survival (P < 0.05), and postoperative lung/hepatic metastasis (P < 0.05). Knockdown of YAP or TEAD4 induced downregulation of LOX expression.LOX nuclear localization was significantly associated with poor survival in patients with CRC. Nuclear LOX
Interaction between Host MicroRNAs and the Gut Microbiota in ColorectalCancer Although variation in gut microbiome composition has been linked with colorectalcancer (CRC), the factors that mediate the interactions between CRC tumors and the microbiome are poorly understood. MicroRNAs (miRNAs) are known to regulate CRC progression and are associated with patient survival outcomes. In addition, recent studies suggested that host miRNAs can also regulate bacterial growth and influence (...) studies have found an association between colorectalcancer (CRC) and the gut microbiota. One potential mechanism by which the microbiota can influence host physiology is through affecting gene expression in host cells. MicroRNAs (miRNAs) are small noncoding RNA molecules that can regulate gene expression and have important roles in cancer development. Here, we investigated the link between the gut microbiota and the expression of miRNA in CRC. We found that dozens of miRNAs are differentially
Association of Colonoscopy Adenoma Findings With Long-term ColorectalCancer Incidence. Individuals with adenomatous polyps are advised to undergo repeated colonoscopy surveillance to prevent subsequent colorectalcancer (CRC), but the relationship between adenomas at colonoscopy and long-term CRC incidence is unclear.To compare long-term CRC incidence by colonoscopy adenoma findings.Multicenter, prospective cohort study of participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO (...) -2.7], P = .68).Over a median of 13 years of follow-up, participants with an advanced adenoma at diagnostic colonoscopy prompted by a positive flexible sigmoidoscopy result were at significantly increased risk of developing colorectalcancer compared with those with no adenoma. Identification of nonadvanced adenoma may not be associated with increased colorectalcancer risk.clinicaltrials.gov Identifier: NCT00002540.
Differential diagnosis of gastrointestinal stromal tumor by histopathology and immunohistochemistry Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal (GI) tract. GISTs account for approximately 80% of the clinically relevant GI mesenchymal tumors. Although most GISTs show spindle cell morphology, 10-15% of GISTs show pure epithelioid configuration. Therefore, not only spindle cell tumors but also epithelioid cell ones developing in the GI (...) cell morphology, consist of approximately 10% of the clinically relevant GI mesenchymal tumors and are almost positive for desmin and negative for KIT and S100 protein. Schwannomas which nearly always show the spindle cell pattern, comprise up to 5% of the GI mesenchymal tumors, and almost all of them are positive for S100 protein and negative for KIT and desmin. Thus, most GI mesenchymal tumors are differentially diagnosed by immunohistochemistry (IHC) of KIT, desmin and S100 protein. However
International validation of the consensus Immunoscore for the classification of coloncancer: a prognostic and accuracy study. The estimation of risk of recurrence for patients with coloncarcinoma must be improved. A robust immune score quantification is needed to introduce immune parameters into cancer classification. The aim of the study was to assess the prognostic value of total tumour-infiltrating T-cell counts and cytotoxic tumour-infiltrating T-cells counts with the consensus (...) Immunoscore assay in patients with stage I-III colon cancer.An international consortium of 14 centres in 13 countries, led by the Society for Immunotherapy of Cancer, assessed the Immunoscore assay in patients with TNM stage I-III coloncancer. Patients were randomly assigned to a training set, an internal validation set, or an external validation set. Paraffin sections of the colontumour and invasive margin from each patient were processed by immunohistochemistry, and the densities of CD3+ and cytotoxic
Should rectal cancer located 10-15â€‰cm from the anal verge be defined as coloncancer. 27836884 2018 05 08 2018 05 08 1569-8041 28 3 2017 03 01 Annals of oncology : official journal of the European Society for Medical Oncology Ann. Oncol. Should rectal cancer located 10-15 cm from the anal verge be defined as coloncancer. 664-665 10.1093/annonc/mdw620 Swets M M Departments of Surgery; 2Medical Oncology, Leiden University Medical Centre, Leiden, The Netherlands. Breugom A J AJ Departments (...) ColonicNeoplasms classification diagnosis pathology therapy Humans Neoadjuvant Therapy Neoplasm Staging Rectal Neoplasms classification diagnosis pathology therapy 2016 11 12 6 0 2018 5 9 6 0 2016 11 13 6 0 ppublish 27836884 mdw620 10.1093/annonc/mdw620
Optimising the use of cetuximab in the continuum of care for patients with metastatic colorectalcancer The anti-epidermal growth factor receptor (EGFR) monoclonal antibody cetuximab in combination with chemotherapy is a standard of care in the first-line treatment of RAS wild-type (wt) metastatic colorectalcancer (mCRC) and has demonstrated efficacy in later lines. Progressive disease (PD) occurs when tumours develop resistance to a therapy, although controversy remains about whether PD (...) because they have probably developed resistance to the chemotherapeutic agents rather than the biologic component of the regimen. Conversely, patients whose disease progresses on cetuximab-based therapy due to drug-selected clonal expansion of RAS-mutant tumour cells may regain sensitivity to cetuximab following a defined break from anti-EGFR therapy. Looking to the future, we propose that RAS status determination at disease progression by liquid, needle or excisional biopsy may identify patients
to 31 March 2015 included in the National BowelCancer Audit.Public reporting of surgeon specific 90 day mortality in elective colorectalcancer surgery in England introduced in June 2013.Proportion of patients with colorectalcancer who had an elective major resection, predicted 90 day mortality based on characteristics of patients and tumours, and observed 90 day mortality adjusted for differences in characteristics of patients and tumours, comparing patients who had surgery between April 2011 (...) Effect of public reporting of surgeons' outcomes on patient selection, "gaming," and mortality in colorectalcancer surgery in England: population based cohort study. To determine the effect of surgeon specific outcome reporting in colorectalcancer surgery on risk averse clinical practice, "gaming" of clinical data, and 90 day postoperative mortality.National cohort study.English National Health Service hospital trusts.111 431 patients diagnosed as having colorectalcancer from 1 April 2011