Evaluation of the quality of cancer treatment in a population of patients (pts) with metastatic colorectal cancer (mCRC) in routine clinical practice in different regions of Russia.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18022-e18022
Author(s):  
Mikhail Fedyanin ◽  
Shamai Aliyeva ◽  
Liubov Yu Vladimirova ◽  
Sanal Erdniev ◽  
Alexander Ivanov ◽  
...  

e18022 Background: In Russia, there are no federal screening programs for detecting early stage of colon cancer; therefore we can assess the impact of various factors that could potentially affect the mortality of pts with mCRC Methods: We conducted a survey with 13 question according treatment of pts with CRC in 17 regional comprehensive cancer centers in 14 regions of Russia, with a total population of 26.347 billion. Results of the survey were conducted by methods of descriptive statistics. Effects of factors on mortality rate in regions were analyzed by a regression model Results: Only 34% pts with stage II-III received adjuvant chemotherapy. Mutation status of KRAS gene has been evaluated only in 33% pts with mCRC. In 2013, metastasectomy was performed only 13% of pts. Only 80% of pts who needed systemic treatment received chemotherapy (CT): doublets of CT (XELOX/FOLFOX/FLOX or FOLFIRI/XELIRI/IFL) - 49%, monotherapy of fluoropyrimidines - 39% of pts, bevacizumab – in 14% and anti-EGFR antibodies - 5% pts. Only 14% of pts with mCRC was placed central vein devices. Second line CT was performed in 47% pts: doublets – in 54%, monotherapy of fluoropyrimidines - in 24% pts, bevacizumab - 13% and anti-EGFR antibody - 8%. Third-line treatment was performed in 25% of pts: anti-EGFR antibodies - in 7.5%. According to regression analysis adjuvant chemotherapy (р = 0.01), bevacizumab only in the 1st line (р = 0.01), and installation of central venous devises (р = 0.07) and anti-EGFR antibody in the 1st line (р = 0.1) in wtKRAS pts had independent positive effect on the mortality rate in regions. We revealed a significant reverse connection between a high mortality rate in the region and administration of fluoropyrimidine monotherapy as 1st line treatment of metastatic disease (p = 0.01) Conclusions: The mortality with colorectal cancer is depended of complex factors that reflect the health care organization in the region, both at the stage of treatment of pts with early-stage and metastatic disease. We revealed that targeted agents are the most effective only in the 1st line settings.

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2869
Author(s):  
Laura Masfarré ◽  
Joana Vidal ◽  
Concepción Fernández-Rodríguez ◽  
Clara Montagut

Currently, the standard treatment for patients with localized colorectal cancer (CRC) includes surgical resection followed by adjuvant chemotherapy based on clinicopathological features. Recurrence risk stratification in those patients is of utmost importance to guide clinicians to avoid both under- and overtreatment. Recently, the concept of minimal residual disease (MRD) has emerged as the detection of circulating tumor DNA (ctDNA) carrying tumor-specific genomic or epigenomic alterations in the bloodstream of patients after surgery. Emerging studies described how the detection of MRD is a powerful prognostic biomarker to identify patients at higher risk of recurrence and who will potentially benefit the most from a systemic adjuvant treatment. Based on that unprecedented finding, several clinical trials involving stage II and III CRC patients are ongoing evaluating the impact of ctDNA guided treatment by escalating or deescalating adjuvant chemotherapy based on ctDNA MRD detection. This review provides a critical overview of current perspectives of liquid biopsy in early-stage CRC including technical, biological, and clinical key points, as well as ongoing ctDNA-based clinical trials that ultimately aim to improve clinical outcomes of patients with CRC.


2019 ◽  
Vol 18 (1) ◽  
pp. 19-27 ◽  
Author(s):  
Manuela Vasconcelos Castro Sales ◽  
Claudia K. Suemoto ◽  
Daniel Apolinario ◽  
ValeriaT. Serrao ◽  
Celi S. Andrade ◽  
...  

2021 ◽  
Author(s):  
Sangeetha Muthamilselvan ◽  
Abirami Raghavendran ◽  
Ashok Palaniappan

Abstract Background: Aberrant DNA methylation acts epigenetically to skew the gene transcription rate up or down, with causative roles in the etiology of cancers. However research on the role of DNA methylation in driving the progression of cancers is limited. In this study, we have developed a comprehensive computational framework for the stage-differentiated modelling of DNA methylation landscapes in colorectal cancer (CRC), and unravelled significant stagewise signposts of CRC progression. Methods: The methylation β - matrix was derived from the public-domain TCGA data, converted into M-value matrix, annotated with AJCC stages, and analysed for stage-salient genes using multiple approaches involving stage-differentiated linear modelling of methylation patterns and/or expression patterns. Differentially methylated genes (DMGs) were identified using a contrast against controls (adjusted p-value <0.001 and |log fold-change of M-value| >2). These results were filtered using a series of all possible pairwise stage contrasts (p-value <0.05) to obtain stage-salient DMGs. These were then subjected to a consensus analysis, followed by Kaplan–Meier survival analysis to evaluate the impact of methylation patterns of consensus stage-salient biomarkers on disease prognosis.Results: We found significant genome-wide changes in methylation patterns in cancer cases relative to controls agnostic of stage. Our stage-differentiated analysis yielded the following stage-salient genes: one stage-I gene (FBN1), one stage-II gene (FOXG1), one stage-III gene (HCN1) and four stage-IV genes (NELL1, ZNF135, FAM123A, LAMA1). All the biomarkers were hypermethylated, indicating down-regulation and signifying a CpG island Methylator Phenotype (CIMP) manifestation. A significant prognostic signature consisting of FBN1 and FOXG1 survived all the steps of our analysis pipeline, and represents a novel early-stage biomarker. Conclusions: We have designed a workflow for stage-differentiated consensus analysis, and identified stage-salient diagnostic biomarkers and an early-stage prognostic biomarker panel. Our studies further yield a novel CIMP-like signature of potential clinical import underlying CRC progression.


3 Biotech ◽  
2020 ◽  
Vol 10 (11) ◽  
Author(s):  
Qi Zheng ◽  
Jane J. Yu ◽  
Chenggang Li ◽  
Jiali Li ◽  
Jiping Wang ◽  
...  

AbstractOur study aims to investigate the impact of miR-224 on cell migration and invasion in colorectal cancer (CRC) as well as its molecular mechanisms. The results showed that miR-224 was significantly upregulated in CRC compared to normal tissues via the TCGA database. Overexpression of miR-224 promoted CRC cell migration and invasion, while inhibition of miR-224 demonstrated the opposite result via transwell assays. In addition, we found that BTRC was a target gene of miR-224 through the miRecords database and dual-luciferase assay, while western blot together with RT-qPCR showed that inhibition of miR-224 led to elevated BTRC expression in protein level but not in mRNA level, and also decreased the expression of β-catenin. In reference to the Human Protein Atlas, BTRC protein expression was higher in normal tissues than in CRC tissues. In conclusion, miR-224 regulates its target BTRC protein expression and its related Wnt/β-catenin pathway. Its impact on cell migration and invasion in CRC cells suggested that miR-224 could be a prospective therapeutic target for early-stage non-metastatic CRC.


2016 ◽  
Vol 82 (8) ◽  
pp. 685-691 ◽  
Author(s):  
Michelle Julien ◽  
James Dove ◽  
Kevin Quindlen ◽  
Kristen Halm ◽  
Mohsen Shabahang ◽  
...  

The Clinical Outcomes of Surgical Therapy Group (COST) Trial established laparoscopic procedures offer short-term benefits while preserving the same oncologic outcomes in colorectal cancer (CRC) patients compared with open procedures. The aim of this study was to evaluate the trend of laparoscopic resection for CRC before and after the publication of the COST Trial. Retrospective study of surgically treated CRC patients was conducted from January 2000 to December 2009. Surveillance, Epidemiology, and End Results Program and Medicare. Between 2000 and 2009, 147,388 patients underwent resection for CRC, 9,901 resections were performed laparoscopically. In 2000, 1.0 per cent of colorectal resections were performed laparoscopically. There was a dramatic increase in laparoscopic resections in 2009 to 30.4 per cent. During this time period, rates of laparoscopic resections increased for all tumor stages. Right colectomies and early stage tumors had the most significant rise from 3.1 per cent (2004) to 38.7 per cent (2009) and 4.41 per cent (2004) to 39.17 per cent (2009), respectively; whereas, rectal and later stage tumors resection rates were more modest from 2.1 per cent (2004) to 13.2 per cent (2009) and 1.41 per cent (2004) to 17.10 per cent (2009), respectively. This study demonstrates the COST Trial had a significant impact on utilization of laparoscopic colorectal resection for CRC. Although laparoscopic colorectal resections have been accepted for all types of CRCs, more difficult procedures are being adopted at slower rates.


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