scholarly journals Superpixel Image Segmentation of the Tumoral Microenvironment in Colorectal Cancer: Frontiers Beyond the Microscope

2021 ◽  
Author(s):  
Sean Hacking ◽  
Dongling Wu ◽  
Claudine Alexis ◽  
Mansoor Nasim
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trials ◽  
Quality Assurance ◽  
Image Segmentation ◽  
Digital Image Analysis ◽  
Tumor Stage ◽  
Gi Tract ◽  
Myxoid Stroma ◽  
Common Malignancy ◽  
Whole Slide Images

Abstract Colorectal cancer (CRC) is the most common malignancy of the gastrointestinal (GI) tract and accounts for 9% of all cancers. The stroma and the tumoral microenvironment represent brave new frontiers for patients with colorectal cancer. Here we demonstrate novel superpixel image segmentation (SIS) techniques for whole slide images (WSI) to unravel this biology. Findings of significance include the association of low proportionated stromal area (PSA), high immature stromal percentage (ISP) and high myxoid stroma ratio (MSR) with worse prognostic outcomes in our CRC patients. Overall, stromal markers outperformed all others at predicting clinical outcomes. In particular, MSR may be able to prognosticate patients independent of tumor stage and may be the most optimal way to effectively prognosticate CRC patients which circumvents the need for more extensive deep learning (DL) based computational profiling. Approaches demonstrated here can be performed by a trained pathologist and very easily recorded during synoptic cancer reporting with appropriate quality assurance. Future well-designed, robust clinical trials will have the ultimate say in determining whether digital image analysis and superpixel image segmentation can better tailor the need for adjuvant therapy in patients with colorectal cancer.

scholarly journals Superpixel Image Segmentation of the Tumoral Microenvironment in Colorectal Cancer: Frontiers Beyond the Microscope

2021 ◽  
Author(s):  
Sean Hacking ◽  
Dongling Wu ◽  
Claudine Alexis ◽  
Mansoor Nasim
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trials ◽  
Image Analysis ◽  
Quality Assurance ◽  
Image Segmentation ◽  
Digital Image Analysis ◽  
Tumor Stage ◽  
Gi Tract ◽  
Common Malignancy ◽  
Whole Slide Images

Abstract Colorectal cancer (CRC) is the most common malignancy of the gastrointestinal (GI) tract and accounts for 9% of all cancers. The stroma and the tumoral microenvironment represent brave new frontiers for patients with colorectal cancer. Here we demonstrate novel superpixel image segmentation (SIS) techniques for whole slide images (WSI) to unravel this biology. Findings of significance include the association of low proportionated stromal area (PSA), high immature stromal percentage (ISP) and high myxoid stromal ratio (MSR) with worse prognostic outcomes in our CRC patients. Overall, stromal markers outperformed all others at predicting clinical outcomes. In particular, MSR may be able to prognosticate patients independent of tumor stage and may be the most optimal way to effectively prognosticate CRC patients which circumvents the need for more extensive deep learning (DL) based computational profiling. Approaches demonstrated here can be performed by a trained pathologist and very easily recorded during synoptic cancer reporting with appropriate quality assurance. Future well-designed, robust clinical trials will have the ultimate say in determining whether digital image analysis and superpixel image segmentation can better tailor the need for adjuvant therapy in patients with colorectal cancer.

scholarly journals Superpixel Image Segmentation of VISTA Expression in Colorectal Cancer: Implications for Immunotherapy

2020 ◽  
Author(s):  
Dongling Wu ◽  
Sean Hacking ◽  
Taisia Vitkovski ◽  
Mansoor Nasim
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trials ◽  
Image Segmentation ◽  
T Cell Activation ◽  
Cell Activation ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Tumor Stage ◽  
Infiltrating Lymphocytes ◽  
Patient Enrollment

Abstract Colorectal cancer is an overall bad player and accounts for 9% of all cancers. Today, advancements in immune checkpoint inhibition has provided therapeutics for many, but not all cancer patients. This issue is in part due to the tumoral microenvironment; which plays a significant role in determining response to immune check point therapeutics. This study serves as the first to evaluate a potent inhibitory checkpoint: V-domain immunoglobulin suppressor of T cell activation (VISTA) and its role in CRC. This was evaluated with both conventional light microscope and superpixel image segmentation. Here we found VISTA expression to be associated with low tumor budding, lower tumor stage, high tumor infiltrating lymphocytes, mature stromal differentiation, BRAF mutation status and better disease-free survival in colorectal cancer. When comparing methodologies; superpixel image segmentation better stratified patients into prognostic groups. Anti-VISTA clinical trials are now open and recruiting for patient enrollment for patients with certain advanced solid tumors. Considering raised VISTA expression is associated with improved survival for patients with colorectal cancer: careful, well-designed and robust clinical trials should be pursued in this cancer subtype.

scholarly journals Superpixel image segmentation of VISTA expression in colorectal cancer and its relationship to the tumoral microenvironment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dongling Wu ◽  
Sean Hacking ◽  
Taisia Vitkovski ◽  
Mansoor Nasim
Keyword(s):  
Colorectal Cancer ◽  
Image Segmentation ◽  
T Cell Activation ◽  
Cell Activation ◽  
Disease Free Survival ◽  
Tumor Stage ◽  
The United States ◽  
Mutational Status ◽  
Microsatellite Stability

AbstractColorectal cancer (CRC) is the third most common cause of cancer related death in the United States (Jasperson et al. in Gastroenterology 138:2044–2058, 10.1053/j.gastro.2010.01.054, 2010). Many studies have explored prognostic factors in CRC. Today, much focus has been placed on the tumor microenvironment, including different immune cells and the extracellular matrix (ECM). The present study aims to evaluate the role of V-domain immunoglobulin suppressor of T cell activation (VISTA). We utilized QuPath for whole slides image analysis, performing superpixel image segmentation (SIS) on a 226 patient-cohort. High VISTA expression correlated with better disease-free survival (DFS), high tumor infiltrative lymphocyte, microsatellite instability, BRAF mutational status as well as lower tumor stage. High VISTA expression was also associated with mature stromal differentiation (SD). When cohorts were separated based on SD and MMR, only patients with immature SD and microsatellite stability were found to correlate VISTA expression with DFS. Considering raised VISTA expression is associated with improved survival, TILs, mature SD, and MMR in CRC; careful, well-designed clinical trials should be pursued which incorporate the underlying tumoral microenvironment.

Signaling inhibition with radiation in colorectal cancer: Clinical trials

2003 ◽  
Vol 30 (3 Suppl 6) ◽  
pp. 56-67 ◽  
Author(s):  
W. Gillies McKenna ◽  
Ruth J. Muschel ◽  
Anjali Gupta ◽  
Stephen Hahn ◽  
Eric J. Bernhard
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trials ◽  
Cancer Clinical Trials

Cancer Stem Cell Niche in Colorectal Cancer and Targeted Therapies

2020 ◽  
Vol 26 (17) ◽  
pp. 1979-1993 ◽  
Author(s):  
Hao Wang ◽  
Guihua Cui ◽  
Bo Yu ◽  
Meiyan Sun ◽  
Hong Yang
Keyword(s):  
Colorectal Cancer ◽  
Stem Cell Niche ◽  
Tumor Initiating Cells ◽  
Ideal Model ◽  
Cytotoxic Effects ◽  
Therapeutic Value ◽  
Cancer Initiation ◽  
Cell Niche ◽  
New Strategies ◽  
Common Malignancy

Cancer stem cells (CSCs), also known as tumor-initiating cells, are a sub-population of tumor cells found in many human cancers that are endowed with self-renewal and pluripotency. CSCs may be more resistant to conventional anticancer therapies than average cancer cells, as they can easily escape the cytotoxic effects of standard chemotherapy, thereby resulting in tumor relapse. Despite significant progress in related research, effective elimination of CSCs remains an unmet clinical need. CSCs are localized in a specialized microenvironment termed the niche, which plays a pivotal role in cancer multidrug resistance. The niche components of CSCs, such as the extracellular matrix, also physically shelter CSCs from therapeutic agents. Colorectal cancer is the most common malignancy worldwide and presents a relatively transparent process of cancer initiation and development, making it an ideal model for CSC niche research. Here, we review recent advances in the field of CSCs using colorectal cancer as an example to illustrate the potential therapeutic value of targeting the CSC niche. These findings not only provide a novel theoretical basis for in-depth discussions on tumor occurrence, development, and prognosis evaluation, but also offer new strategies for the targeted treatment of cancer.

A Critical Review of Second-generation anti-EGFR Monoclonal Antibodies in Metastatic Colorectal Cancer

2020 ◽  
Vol 21 ◽  
Author(s):  
Daniel Sur ◽  
Andrei Havasi ◽  
Alecsandra Gorzo ◽  
Claudia Burz
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Metastatic Colorectal Cancer ◽  
Second Generation ◽  
Current Data ◽  
Braf Mutations ◽  
Durable Response ◽  
Ongoing Research

Background: Anti-EGFR monoclonal antibodies (mAbs) have become a relevant solution for the treatment of patients with metastatic colorectal cancer. Current anti-EGFR monoclonal antibodies face a series of problems, including resistance and non-durable response, and RAS and BRAF mutations serve as exclusion criteria for treatment with anti-EGFR mAbs. Advances in molecular tumor profiling and information on subsequent pathways responsible for disease progression and drug resistance helped develop a new generation of anti-EGFR mAbs. These second-generation mAbs have been developed to overcome existing resistance mechanisms and to limit common side effects. For the moment, existing literature suggests that these novel anti-EGFR mAbs are far from finding their way to clinical practice soon. Objective: In this review, we summarize and evaluate current data regarding ongoing research and completed clinical trials for different second-generation anti-EGFR monoclonal antibodies. Conclusion: Anti-EGFR mAbs exhibit efficacy in advanced colorectal cancer, but second-generation mAbs failed to prove their benefit in the treatment of metastatic colorectal cancer. Understanding the biological basis of primary and acquired drug resistance could allow scientists to design better clinical trials and develop improved second-generation mAbs.

scholarly journals National Colorectal Cancer Screening Program in Lithuania: Description of the 5-Year Performance on Population Level

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1129
Author(s):  
Audrius Dulskas ◽  
Tomas Poskus ◽  
Inga Kildusiene ◽  
Ausvydas Patasius ◽  
Rokas Stulpinas ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Quality Assurance ◽  
Cancer Screening ◽  
Colorectal Cancer Screening ◽  
Screening Program ◽  
Histopathological Examination ◽  
Insurance Fund ◽  
Crc Screening ◽  
Cancer Screening Program ◽  
The Impact

We aimed to report the results of the implementation of the National Colorectal Cancer (CRC) Screening Program covering all the country. The National Health Insurance Fund (NHIF) reimburses the institutions for performing each service; each procedure within the program has its own administrative code. Information about services provided within the program was retrieved from the database of NHIF starting from the 1 January 2014 to the 31 December 2018. Exact date and type of all provided services, test results, date and results of biopsy and histopathological examination were extracted together with the vital status at the end of follow-up, date of death and date of emigration when applicable for all men and women born between 1935 and 1968. Results were compared with the guidelines of the European Union for quality assurance in CRC screening and diagnosis. The screening uptake was 49.5% (754,061 patients) during study period. Participation rate varied from 16% to 18.1% per year and was higher among women than among men. Proportion of test-positive and test-negative results was similar during all the study period—8.7% and 91.3% annually. Between 9.2% and 13.5% of test-positive patients received a biopsy of which 52.3–61.8% were positive for colorectal adenoma and 4.6–7.3% for colorectal carcinoma. CRC detection rate among test-positive individuals varied between 0.93% and 1.28%. The colorectal cancer screening program in Lithuania coverage must be improved. A screening database is needed to systematically evaluate the impact and performance of the national CRC screening program and quality assurance within the program.

scholarly journals First-Line Maintenance Treatment in Metastatic Colorectal Cancer (mCRC): Quality and Clinical Benefit Overview

2021 ◽  
Vol 10 (3) ◽  
pp. 470
Author(s):  
Marta Martín-Richard ◽  
Maria Tobeña
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trials ◽  
Clinical Benefit ◽  
Maintenance Treatment ◽  
Randomized Clinical Trials ◽  
Line Treatment ◽  
First Line ◽  
Design Quality ◽  
Primary Endpoints ◽  
First Line Treatment

Different strategies of maintenance therapy (sequential CT, intermittent CT, intermittent CT and MAbs, or de-escalation MAbs monotherapy) after first-line treatment are undertaken. Many randomized clinical trials (RCT), which evaluated these approaches, suffer from incorrect design, heterogenous primary endpoints, inadequate size, and other methodology flaws. Drawing any conclusions becomes challenging and recommendations are mainly vague. We evaluated those studies from another perspective, focusing on the design quality and the clinical benefit measure with a more objective and accurate methodology. These data allowed a clearer and more exact overview of the statement in maintenance treatment.

scholarly journals Non-Steroidal Anti-Inflammatory Drugs in Colorectal Cancer Chemoprevention

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 594
Author(s):  
Jadwiga Maniewska ◽  
Dagmara Jeżewska
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Clinical Trials ◽  
Cancer Chemoprevention ◽  
Tumor Cell Proliferation ◽  
Double Blind ◽  
New Approach ◽  
Randomized Controlled ◽  
Inflammatory Drugs ◽  
Chemopreventive Effect

Since colorectal cancer is one of the world’s most common cancers, studies on its prevention and early diagnosis are an emerging area of clinical oncology these days. For this study, a review of randomized controlled, double-blind clinical trials of selected NSAIDs (aspirin, sulindac and celecoxib) in chemoprevention of colorectal cancer was conducted. The main molecular anticancer activity of NSAIDs is thought to be a suppression of prostaglandin E2 synthesis via cyclooxygenase-2 inhibition, which causes a decrease in tumor cell proliferation, angiogenesis, and increases apoptosis. The lower incidence of colorectal cancer in the NSAID patients suggests the long-lasting chemopreventive effect of drugs studied. This new approach to therapy of colorectal cancer may transform the disease from a terminal to a chronic one that can be taken under control.

scholarly journals Are there sex differences among colorectal cancer patients in treatment and survival? A Swiss cohort study

2021 ◽  
Vol 147 (5) ◽  
pp. 1407-1419
Author(s):  
Manuela Limam ◽  
Katarina Luise Matthes ◽  
Giulia Pestoni ◽  
Eleftheria Michalopoulou ◽  
Leonhard Held ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Regression Models ◽  
Proportional Hazards ◽  
Treatment Decision ◽  
Tumor Stage ◽  
Primary Treatment ◽  
Cox Proportional Hazards ◽  
Men And Women ◽  
Logistic Regression Models ◽  
Comorbidity Index

Abstract Background Colorectal cancer (CRC) is among the three most common incident cancers and causes of cancer death in Switzerland for both men and women. To promote aspects of gender medicine, we examined differences in treatment decision and survival by sex in CRC patients diagnosed 2000 and 2001 in the canton of Zurich, Switzerland. Methods Characteristics assessed of 1076 CRC patients were sex, tumor subsite, age at diagnosis, tumor stage, primary treatment option and comorbidity rated by the Charlson Comorbidity Index (CCI). Missing data for stage and comorbidities were completed using multivariate imputation by chained equations. We estimated the probability of receiving surgery versus another primary treatment using multivariable binomial logistic regression models. Univariable and multivariable Cox proportional hazards regression models were used for survival analysis. Results Females were older at diagnosis and had less comorbidities than men. There was no difference with respect to treatment decisions between men and women. The probability of receiving a primary treatment other than surgery was nearly twice as high in patients with the highest comorbidity index, CCI 2+, compared with patients without comorbidities. This effect was significantly stronger in women than in men (p-interaction = 0.010). Survival decreased with higher CCI, tumor stage and age in all CRC patients. Sex had no impact on survival. Conclusion The probability of receiving any primary treatment and survival were independent of sex. However, female CRC patients with the highest CCI appeared more likely to receive other therapy than surgery compared to their male counterparts.

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