Identify Colorectal Cancer Patients Research Articles

Colorectal cancer prognosis based on dietary pattern using synthetic minority oversampling technique with K-nearest neighbors approach

Generally, a person’s life span depends on their food consumption because it may cause deadly diseases like colorectal cancer (CRC). In 2020, colorectal cancer accounted for one million fatalities globally, representing 10% of all cancer casualties. 76,679 males and 78,213 females over the age of 59 from ten states in the United States participated in this analysis. During follow-up, 1378 men and 981 women were diagnosed with colon cancer. This prospective cohort study used 231 food items and their variants as input features to identify CRC patients. Before labelling any foods as colorectal cancer-causing foods, it is ethical to analyse facts like how many grams of food should be consumed daily and how many times a week. This research examines five classification algorithms on real-time datasets: K-Nearest Neighbour (KNN), Decision Tree (DT), Random Forest (RF), Logistic Regression with Classifier Chain (LRCC), and Logistic Regression with Label Powerset (LRLC). Then, the SMOTE algorithm is applied to deal with and identify imbalances in the data. Our study shows that eating more than 10 g/d of low-fat butter in bread (RR 1.99, CI 0.91–4.39) and more than twice a week (RR 1.49, CI 0.93–2.38) increases CRC risk. Concerning beef, eating in excess of 74 g of beef steak daily (RR 0.88, CI 0.50–1.55) and having it more than once a week (RR 0.88, CI 0.62–1.23) decreases the risk of CRC, respectively. While eating beef and dairy products in a daily diet should be cautious about quantity. Consuming those items in moderation on a regular basis will protect us against CRC risk. Meanwhile, a high intake of poultry (RR 0.2, CI 0.05–0.81), fish (RR 0.82, CI 0.31–2.16), and pork (RR 0.67, CI 0.17–2.65) consumption negatively correlates to CRC hazards.

A Four-Gene Panel in Rectal Swab Samples as a Biomarker for Colorectal Cancer Screening.

The dysregulation of gene expression is one of the key molecular features of colorectal cancer (CRC) development. This study aimed to investigate whether such dysregulation is reflected in rectal swab specimens of CRC patients and to evaluate its potential as a non-invasive approach for screening. We compared the expression level of 14 CRC-associated genes in tumor and adjacent non-tumor tissue of CRC patients and examined the correlation of their levels in tissue with paired rectal swab specimens. The level of these 14 genes in rectal swab specimens was compared among patients with CRC or polyp and control subjects, and the diagnostic potential of each dysregulated gene and the gene panel were evaluated. The expression of CXCR2, SAA, COX1, PPARδ, PPARγ, Groγ, IL8, p21, c-myc, CD44 and CSF1 was significantly higher in CRC, and there was a significant correlation in the levels of most of them between the CRC and rectal swab specimens. In the training study, we showed that CD44, IL8, CXCR2 and c-myc levels were significantly higher in the rectal swab specimens of the CRC patients. Such result was confirmed in the validation study. A panel of these four genes was developed, and ROC analysis showed that this four-gene panel could identify CRC patients with an AUC value of 0.83 and identify overall polyp and precancerous adenoma patients with AUC values of 0.6522 and 0.7322, respectively. Finally, the predictive study showed that the four-gene panel demonstrated sensitivities of 63.6%, 76.9% and 88.9% in identifying overall polyp, precancerous adenoma and CRC patients, respectively, whereas the specificity for normal subjects was 72.2%. The expression of CRC-associated genes in rectal swab specimens reflects the dysregulation status in colorectal tissue, and the four-gene panel is a potential non-invasive biomarker for early precancerous adenoma and CRC screening.

Colorectal Cancer Diagnosis through Breath Test Using a Portable Breath Analyzer-Preliminary Data.

Screening methods available for colorectal cancer (CRC) to date are burdened by poor reliability and low patient adherence and compliance. An altered pattern of volatile organic compounds (VOCs) in exhaled breath has been proposed as a non-invasive potential diagnostic tool for distinguishing CRC patients from healthy controls (HC). The aim of this study was to evaluate the reliability of an innovative portable device containing a micro-gas chromatograph in enabling rapid, on-site CRC diagnosis through analysis of patients' exhaled breath. In this prospective trial, breath samples were collected in a tertiary referral center of colorectal surgery, and analysis of the chromatograms was performed by the Biomedical Engineering Department. The breath of patients with CRC and HC was collected into Tedlar bags through a Nafion filter and mouthpiece with a one-way valve. The breath samples were analyzed by an automated portable gas chromatography device. Relevant volatile biomarkers and discriminant chromatographic peaks were identified through machine learning, linear discriminant analysis and principal component analysis. A total of 68 subjects, 36 patients affected by histologically proven CRC with no evidence of metastases and 32 HC with negative colonoscopies, were enrolled. After testing a training set (18 CRC and 18 HC) and a testing set (18 CRC and 14 HC), an overall specificity of 87.5%, sensitivity of 94.4% and accuracy of 91.2% in identifying CRC patients was found based on three VOCs. Breath biopsy may represent a promising non-invasive method of discriminating CRC patients from HC.

Understanding causes of racial/ethnic survival disparity in 47,178 patients with colorectal cancer: A quantitative evaluation of molecular, socioeconomic, and clinical covariates.

20 Background: A disparity in overall survival (OS) of colorectal cancer (CRC) patients based on self-reported race has been observed. Separately, differing frequencies of driver gene mutations among racial groups have been observed. The contribution of these molecular differences to disparity in outcomes is not well understood. We conducted a systematic investigation of molecular, socioeconomic (SES) and clinical covariates to quantitate the degree to which each influences the OS disparity. Methods: The Foundry software platform was used to query electronic health records to identify CRC patients and extract clinical and molecular data. The relative contribution of each variable to OS disparity was determined using mediation analysis consisting of sequential multivariate Cox regression models. Results: 47,178 patients with CRC diagnosed between 1973 and 2023 with self-reported race were identified. Relative to Non-Hispanic white (NHW), African American (AA) had worse OS (HR=1.16, P= 1.5E-6), while Asians and Hispanics had better OS (HR=0.66, P=4.2E-13 and HR=0.86, P=3.4E-6, respectively). The magnitude of disparity between AA and NHW was greater in metastatic disease (HR 1.2, P=1.7E-4). Among 7,628 patients with clinical molecular testing, five genes differed significantly in mutation frequencies; APC (54% NHW, 62% AA, 57% Hispanics, 46% Asian, FDR= 0.01), KRAS (45%, 58%, 50%, 44%, FDR=8.4E-9), PIK3CA (17%, 23%, 17%, 12%, FDR=0.006) were higher in AA, while BRAF (8%, 3%, 4%, 7%, FDR=2.4E-8), KIT (4%, 1%, 2%, 3%, FDR=0.013) were higher in NHW. In multivariate analysis mutations of BRAF (HR= 1.9, P=1.2E-8), KRAS (HR= 1.39, P=1.7E-7), and APC (HR= 0.81, P= 5E-4) were significantly associated with OS as was national area deprivation index (HR= 1.07, P=0.004), marital status (HR= 1.16, P=0.03), performance status (HR= 1.42, P= 5.3E-29), disease stage (HR= 1.502, P=4.4E-26), right sided tumors (HR= 1.23, P=0.003), tumor differentiation (HR= 1.22, P=0.004) and MSI-high (HR= 0.37, P=1.8E-7). Mediation analysis identified neighborhood SES as the greatest contributor to disparity (38%), followed by primary tumor side (10%), and molecular characteristics (MSI-status, KRAS and BRAF mutations, 10%). After including all covariates, 39% of disparity remained unaccounted. Conclusions: Systematic evaluation of a large cohort from a single institution confirmed substantial racial disparity in survival and frequencies of driver mutations. SES factors have the largest contribution but account only for forty percent of the disparity, with tumor molecular features also contributing. Molecular characteristics should be incorporated in multicentric studies of racial survival disparity. Future clinical studies should ideally account for genetic ancestry and molecular features when evaluating chemotherapy outcomes.

Abstract C078: Comprehensive evaluation for contribution of molecular, socioeconomic and disease covariates to colorectal cancer racial survival disparity of 47,178 patients

Abstract Background: Racial disparities in survival of Colorectal cancer (CRC), as well as differing frequency of driver gene mutation, have been observed before. Here we observe that self-reported race is associated with overall survival (OS) in a single institutional cohort of 47,178 patients with CRC. we conducted a systematic investigation of molecular, Socioeconomic (SES) and Disease covariates to quantitate the degree to which each influences OS. Methods: Under an approved IRB protocol, the Palantir-Foundry software system was used to query the MD Anderson (MDA) patient database to identify CRC patients and extract outcomes data and covariates. Genetic mutations that showed significant difference were included with other SES and Disease covariates in Cox-proportional hazard regression model for OS. Preliminary mediation analysis was done to quantify the contribution of each covariate to the OS disparity. Results: 47,178 patients with CRC adenocarcinoma diagnosed between 1973 and 2023 were identified and race (self-reported) was extracted (Asian 1433, 3.0%; African American (AA) 4126, 8.7%; Hispanic 4166, 8.8%; non-Hispanic White (NHW) 37453, 79.4%). Relative to NHW, AA had worse OS (HR=1.22, P= 8.03E-8), while Asians and Hispanics had better OS (HR=0.68, P= 1.06E-8 and HR=0.88, P= 7E-4). Restricting to stage 4 patients, these disparities persisted; AA HR 1.2 (p=1.7E-4) Asian HR 0.67 (p= 1.64E-5), Hispanic HR 0.88 (p= 1.4E-2) relative to NHW. Among 7,628 patients with clinical mutational testing, five genes had significant differences in mutation frequency; APC (45% Asian, 62% AA, 44% NHW, 57% Hispanics, P= 5.83E-3), KRAS (43%, 57%, 44%, 50%, P=3.43E-9), PIK3CA (13%, 23%, 17%, 17%, P=3.37E-3), BRAF (8%, 3%, 8%, 4%, P=1.15E-8), KIT (3%, 2%, 5%, 2%, p=0.046). In multivariate analysis the survival difference between Asians, Hispanics or AA compared to NHW was no longer significant (HR= 0.91, P=0.59, HR= 0.87, P=0.21 and HR=1.14, P= 0.18). In contrast KRAS (HR= 1.5, P=9.22E-9), BRAF (HR= 1.64, P=1E-4) APC mutation (HR= 0.77, P=1E-4) were independently associated with OS, as was higher ECOG (HR= 1.39, P=7.14E-23), higher stage (HR= 1.5, P=3.57E-20), higher national area deprivation index (ADI) quantile (HR=1.08, P= 2.7E-3), being married (HR=1.2, P= 1.52E-2), right side colon tumor (HR=1.22, P= 1.03E-2), poorly differentiated tumors (HR= 1.2, P=1.47E-2), undergoing surgical intervention (HR= 0.47, P=1.54E-29) and MSI-high (HR= 0.41, P=2.16E-6). In our single institution study preliminary mediation analysis showed that ADI, marital status, right sided affection, KRAS mutation, BRAF mutation were the main drivers of the survival disparities in contrast to stage, grade, performance status, surgical intervention and MSI-status. Conclusions: Racial survival disparity is complex and multifactorial. Our single center systematic evaluation showed that SES, driver gene mutations and site of colon affected by the tumor made an important contribution to the racial survival disparity. Further investigation of germline variation, and treatment response is warranted. Citation Format: Mahmoud Yousef, Abdelrahman Yousef, Mohammad Zeineddine, Saikat Chowdhury, Mohammad Fanaeian, Naoko Little-Jackson, Mark Knafl, Kristin Alfaro-Munoz, Abinheet Uppal, Scott Kopetz, Wenyi Wang, Jason Willis, John Paul Shen. Comprehensive evaluation for contribution of molecular, socioeconomic and disease covariates to colorectal cancer racial survival disparity of 47,178 patients [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C078.

A nomogram based on collagen signature for predicting the immunoscore in colorectal cancer.

The Immunoscore can categorize patients into high- and low-risk groups for prognostication in colorectal cancer (CRC). Collagen plays an important role in immunomodulatory functions in the tumor microenvironment (TME). However, the correlation between collagen and the Immunoscore in the TME is unclear. This study aimed to construct a collagen signature to illuminate the relationship between collagen structure and Immunoscore. A total of 327 consecutive patients with stage I-III stage CRC were included in a training cohort. The fully quantitative collagen features were extracted at the tumor center and invasive margin of the specimens using multiphoton imaging. LASSO regression was applied to construct the collagen signature. The association of the collagen signature with Immunoscore was assessed. A collagen nomogram was developed by incorporating the collagen signature and clinicopathological predictors after multivariable logistic regression. The performance of the collagen nomogram was evaluated via calibration, discrimination, and clinical usefulness and then tested in an independent validation cohort. The prognostic values of the collagen nomogram were assessed using Cox regression and the Kaplan-Meier method. The collagen signature was constructed based on 16 collagen features, which included 6 collagen features from the tumor center and 10 collagen features from the invasive margin. Patients with a high collagen signature were more likely to show a low Immunoscore (Lo IS) in both cohorts (P<0.001). A collagen nomogram integrating the collagen signature and clinicopathological predictors was developed. The collagen nomogram yielded satisfactory discrimination and calibration, with an AUC of 0.925 (95% CI: 0.895-0.956) in the training cohort and 0.911 (95% CI: 0.872-0.949) in the validation cohort. Decision curve analysis confirmed that the collagen nomogram was clinically useful. Furthermore, the collagen nomogram-predicted subgroup was significantly associated with prognosis. Moreover, patients with a low-probability Lo IS, rather than a high-probability Lo IS, could benefit from chemotherapy in high-risk stage II and stage III CRC patients. The collagen signature is significantly associated with the Immunoscore in the TME, and the collagen nomogram has the potential to individualize the prediction of the Immunoscore and identify CRC patients who could benefit from adjuvant chemotherapy.

A senescence-based prognostic gene signature for colorectal cancer and identification of the role of SPP1-positive macrophages in tumor senescence.

Senescence is significantly associated with cancer prognosis. This study aimed to construct a senescence-related prognostic model for colorectal cancer (CRC) and to investigate the influence of senescence on the tumor microenvironment. Transcriptome and clinical data of CRC cases were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Senescence-related prognostic genes detected by univariate Cox regression were included in Least Absolute Shrinkage and Selection Operator (LASSO) analysis to construct a model. The efficacy of the model was validated using the receiver operating characteristic (ROC) curve and survival analysis. Differentially expressed genes (DEGs) were identified and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed. CIBERSORT and Immuno-Oncology Biological Research (IOBR) were used to investigate the features of the tumor microenvironment. Single-cell RNA-seq data were used to investigate the expression levels of model genes in various cell types. Immunofluorescence staining for p21, SPP1, and CD68 was performed with human colon tissues. A seven-gene (PTGER2, FGF2, IGFBP3, ANGPTL4, DKK1, WNT16 and SPP1) model was finally constructed. Patients were classified as high- or low-risk using the median score as the threshold. The area under the ROC curve (AUC) for the 1-, 2-, and 3-year disease-specific survival (DSS) were 0.731, 0.651, and 0.643, respectively. Survival analysis showed a better 5-year DSS in low-risk patients in the construction and validation cohorts. GO and KEGG analyses revealed that DEGs were enriched in extracellular matrix (ECM)-receptor interactions, focal adhesion, and protein digestion and absorption. CIBERSORT and IOBR analyses revealed an abundance of macrophages and an immunosuppressive environment in the high-risk subgroup. Low-risk patients had higher response rates to immunotherapy than high-risk patients. ScRNA-seq data revealed high expression of SPP1 in a subset of macrophages with strong senescence-associated secretory phenotype (SASP) features. Using CRC tumor tissues, we discovered that SPP1+ macrophages were surrounded by a large number of senescent tumor cells in high-grade tumors. Our study presents a novel model based on senescence-related genes that can identify CRC patients with a poor prognosis and an immunosuppressive tumor microenvironment. SPP1+ macrophages may correlate with cell senescence leading to poor prognosis.

Agreement between individual and neighborhood income measures in patients with colorectal cancer in Canada.

With increasing interest in income-related differences in cancer outcomes, accurate measurement of income is imperative. Misclassification of income can result in wrong conclusions as to the presence of income inequalities. We determined misclassification between individual- and neighborhood-level income and their association with overall survival among colorectal cancer (CRC) patients. The Canadian Census Health and Environment Cohorts were used to identify CRC patients diagnosed from 1992 to 2017. We used neighborhood income quintiles from Statistics Canada and created individual income quintiles from the same data sources to be as similar as possible. Agreement between individual and neighborhood income quintiles was measured using cross-tabulations and weighted kappa statistics. Cox proportional hazards and Lin semiparametric hazards models were used to determine the effects of individual and neighborhood income independently and jointly on survival. Analyses were also stratified by rural residence. A total of 103 530 CRC patients were included in the cohort. There was poor agreement between individual and neighborhood income with only 17% of respondents assigned to the same quintile (weighted kappa = 0.18). Individual income had a greater effect on relative and additive survival than neighborhood income when modeled separately. The interaction between individual and neighborhood income demonstrated that the most at risk for poor survival were those in the lowest individual and neighborhood income quintiles. Misclassification was more likely to occur for patients residing in rural areas. Cancer researchers should avoid using neighborhood income as a proxy for individual income, especially among patients with cancers with demonstrated inequalities by income.

Expansion of Colorectal Cancer Biomarkers Based on Gut Bacteria and Viruses.

Simple SummaryThe current study identified microbial (including bacterial and viral) diagnostic models that could discriminate colorectal tumor patients from healthy controls, expanding the potential biomarkers for colorectal tumors. A combination of five colorectal cancer-associated gut bacteria was identified in this study for the discrimination of colorectal cancer patients from healthy controls, with verifiable performance in multiple cohorts. The gene pathways regulated by aberrant gut bacteria were also identified, providing possible directions for studying bacterial carcinogenesis mechanisms. Furthermore, this study revealed the potential interactions of gut bacteria with viruses and within bacteria in adenoma-carcinoma sequences, which may extend our understanding of dysbiosis in colorectal carcinogenesis.The alterations in gut bacteria are closely related to colorectal cancer. However, studies on adenoma are still scarce. Besides, the associations of gut viruses with colorectal tumor, and the interactions of bacteria with viruses in colorectal tumors are still under exploration. Therefore, a metagenomic sequencing of stool samples from patients with colorectal adenoma (CRA), colorectal cancer (CRC), and healthy controls was performed to identify changes in gut microbiome in patients with colorectal tumors. Five CRC-enriched bacteria (Peptostreptococcus stomatis, Clostridium symbiosum, Hungatella hathewayi, Parvimonas micra, and Gemella morbillorum) were identified as a diagnostic model to identify CRC patients, and the efficacy of the diagnostic model was verifiable in 1523 metagenomic samples from ten cohorts of eight different countries. We identified the positive association of Bacteroides fragilis with PD-L1 expression and PD-1 checkpoint pathway, providing a possible direction for studying bacterial carcinogenesis mechanisms. Furthermore, the increased interactions within the microbiome in patients may play roles in the development of CRC. In conclusion, this study identified novel microbiota combinations with discrimination for colorectal tumor, and revealed the potential interactions of gut bacteria with viruses in the adenoma-carcinoma sequence, which implies that the microbiome, but not only bacteria, should be paid more attention in further studies.

PPsNet: An improved deep learning model for microsatellite instability high prediction in colorectal cancer from whole slide images

Background and ObjectiveRecent studies have shown that colorectal cancer (CRC) patients with microsatellite instability high (MSI-H) are more likely to benefit from immunotherapy. However, current MSI testing methods are not available for all patients due to the lack of available equipment and trained personnel, as well as the high cost of the assay. Here, we developed an improved deep learning model to predict MSI-H in CRC from whole slide images (WSIs). MethodsWe established the MSI-H prediction model based on two stages: tumor detection and MSI classification. Previous works applied fine-tuning strategy directly for tumor detection, but ignoring the challenge of vanishing gradient due to the large number of convolutional layers. We added auxiliary classifiers to intermediate layers of pre-trained models to help propagate gradients back through in an effective manner. To predict MSI status, we constructed a pair-wise learning model with a synergic network, named parameter partial sharing network (PPsNet), where partial parameters are shared among two deep convolutional neural networks (DCNNs). The proposed PPsNet contained fewer parameters and reduced the problem of intra-class variation and inter-class similarity. We validated the proposed model on a holdout test set and two external test sets. Results144 H&E-stained WSIs from 144 CRC patients (81 cases with MSI-H and 63 cases with MSI-L/MSS) were collected retrospectively from three hospitals. The experimental results indicate that deep supervision based fine-tuning almost outperforms training from scratch and utilizing fine-tuning directly. The proposed PPsNet always achieves better accuracy and area under the receiver operating characteristic curve (AUC) than other solutions with four different neural network architectures on validation. The proposed method finally achieves obvious improvements than other state-of-the-art methods on the validation dataset with an accuracy of 87.28% and AUC of 94.29%. ConclusionsThe proposed method can obviously increase model performance and our model yields better performance than other methods. Additionally, this work also demonstrates the feasibility of MSI-H prediction using digital pathology images based on deep learning in the Asian population. It is hoped that this model could serve as an auxiliary tool to identify CRC patients with MSI-H more time-saving and efficiently.

Development of novel models for predicting mismatch repair protein deficiency and relevant disease-free survival in colorectal cancer patients.

DNA mismatch repair (MMR) protein deficiency has attached more attention for its potential to be a biomarker of immunotherapy for colorectal cancer (CRC) patients. However, clinical models involving the expression status of MMR protein are rare. Herein, we sought to develop two clinical models (a diagnostic model for the prediction of MMR status and a prognostic model for the prediction of disease-free survival) for CRC patients. A total of 582 CRC patients were finally included. There were 53 patients with deficient expression of MMR protein. The differences between the deficient MMR (dMMR) group and the proficient MMR (pMMR) group were analyzed. Compared to pMMR patients, those with dMMR status were younger and had better pathological features (depth of invasion, lymph node metastasis, distant metastasis, pathological stage, perineuronal invasion, and PLT level) and disease-free survival (DFS). The tumor location of the left colon, adenocarcinoma, and abnormal PLT level were identified as the independent predictors for pMMR. Based on these data, we developed the diagnostic model using Logistic regression analysis. It showed a satisfactory accuracy (AUC = 82.3% in the derivate set; AUC = 73.6% in the validation set). Furthermore, pMMR, poorer differentiation, perineuronal invasion, distant metastasis, lower hemoglobin level, and abnormal CEA level were established as the independent prognostic factors of poorer DFS. Based on them, a prognostic model with valuable performance (1-year AUC = 75.5%/3-year AUC = 76.9% in the derivate set; 1-year AUC = 72.3%/3-year AUC = 73.8% in the validation set) was developed. Our diagnostic and prognostic models could identify CRC patients at risk for pMMR protein expression and disease recurrence. It may contribute to improving the diagnosis and treatment of CRC patients at an individual level.

Temporal trends in self-reported general and mental health status among colorectal cancer patients: racial/ethnic disparities in a population-based analysis.

Patient-reported outcomes are essential to patient-centered cancer care. We sought to determine the relationships between colorectal cancer (CRC) diagnosis and trends in self-reported general health status (GHS) and mental health status (MHS) among racial/ethnic groups. We used population-based Surveillance, Epidemiology, and End Results (SEER)-Consumer Assessment of Healthcare Providers and Systems (CAHPS) data to identify CRC patients diagnosed from 1996 to 2011 who reported GHS and/or MHS on a CAHPS survey within 6years before or after diagnosis and were 65 or older at survey completion. Multivariable logistic regression assessed relationships of patient race/ethnicity and CRC diagnosis with the odds of reporting fair or poor GHS or MHS. Five thousand five hundred forty-five patients reported GHS and/or MHS within 6years before CRC diagnosis and 4,604 reported GHS and/or MHS within 6years after diagnosis. 80.9% were non-Hispanic white (NHW), 7.1% were non-Hispanic black (NHB), 6.7% were Hispanic, and 5.3% were non-Hispanic Asian. Being diagnosed with CRC was associated with increased odds of reporting fair or poor GHS (OR = 1.55, 95% CI = 1.40-1.72) and MHS (OR = 1.33, 95% CI = 1.13-1.58). For GHS, this trend held for all race/ethnicities except NHBs, and for MHS, this trend held for NHWs and Hispanics only. CRC diagnosis is an important driver of increased likelihood of fair and poor GHS and MHS, but the relationship is complicated by effect modification by race/ethnicity. Efforts to further understand the race/ethnicity-specific relationships between CRC diagnosis and declines in GHS and MHS are necessary to promote equitable care for all patients.

Patient navigation for hereditary colorectal cancer: Design of a randomized controlled trial to determine the effectiveness of pathways to genetic counseling

BackgroundDiagnosis of Lynch and other hereditary colorectal cancer (CRC) syndromes through germline genetic testing has important implications for treatment and risk-management, yet guideline-recommended genetic counseling referral and attendance is suboptimal. MethodsOur team developed an adapted patient navigation program—Pathways to Genetic Counseling—to address multilevel barriers to genetic counseling referral and receipt. This paper describes the methods of a randomized controlled trial (RCT) testing Pathways to Genetic Counseling's effectiveness at increasing genetic counseling attendance in the University of Washington Medicine health system. We will identify CRC patients eligible for genetic counseling (diagnosed before age 50 or at any age with evidence of inherited mismatch repair deficiency) through a combination of structured electronic health record queries and manual chart review. Patients will be randomized 1:1 prior to consent and receive either care as usual (no contact) or be invited to participate in patient navigation. We will use chart review to compare rates of genetic counseling referral and attendance within six months of randomization, regardless of patients' engagement with navigation. We plan to identify and randomize 161 eligible CRC patients over a nine-month period beginning in late 2021. DiscussionOur pragmatic RCT design will provide real-world data on the potential for patient navigation to address longstanding care gaps in preventive genomic medicine. If effective, we hope to pilot Pathways to Genetic Counseling in additional settings with a long-term goal of improving appropriate diagnosis of hereditary CRC syndromes and subsequent cascade screening of eligible family members.

Clinicopathological and molecular characteristics of early-onset vs late-onset colorectal cancer according to tumor location.

The incidence of early-onset colorectal cancer (EOCRC) is rapidly increasing worldwide in decade when screening of colorectal cancer (CRC) is more prevalent. The clinicopathological and molecular characteristics of EOCRC have not yet been clarified. This study aims to evaluate clinicopathological and molecular features among EOCRC and late-onset colorectal cancer (LOCRC) patients according to different tumor locations. We identified CRC patients from a prospectively maintained CRC database between January 2015 and December 2018. The clinicopathological and molecular characteristics including dMMR, mutation of PIK3CA, BRAF and KRAS were compared between EOCRC and LOCRC. The relationships according to different tumor locations were assessed. Totally 4468 patients were analyzed in this study. Compared to LOCRC patients, EOCRC patients were more likely to have status of dMMR (OR, 2.52; P < 0.001), regardless of tumor location. EOCRC patients were more likely to be detected with mutation of PIK3CA (OR, 1.24; P = 0.041), which only tended to exist in the left-side colon (OR, 1.51; P = 0.06), but not in the right-side colon or rectum. No significant difference was found for BRAF or KRAS mutation, but mutation of KRAS was more frequently found in left-side colon (OR, 1.34; P = 0.04) among EOCRC patients. Status of dMMR, mutation of PIK3CA, BRAF and KRAS was different between EOCRC and LOCRC patients according to different tumor locations, which implied that EOCRC might be a unique subgroup of CRC patients. Further investigations of molecular and genetic differences should be performed to help define new diagnosing and therapeutical strategies for EOCRC patients.

Clinical features of intracerebral hemorrhage in patients with colorectal cancer and its underlying pathogenesis.

BACKGROUNDThe diagnosis of both cancer and intracerebral hemorrhage (ICH) in the same patient is not uncommon, but the clinical features and pathogenesis of patients with colorectal cancer (CRC) and ICH are still not well known.AIMTo investigate the clinical features and underlying pathogenesis of ICH in patients with CRC. METHODSA retrospective review of CRC patients complicated with ICH from three centers between January 2014 and December 2020 was performed. Clinical data such as laboratory examinations, imaging features, prognosis, and underlying pathogenesis were analyzed.RESULTSOf 16673 identified CRC patients, 20 (0.12%) suffered from ICH. There were 13 males and 7 females, with an average age (mean ± SD) of 68.45 ± 10.66 years. Fourteen patients (70%) had distant metastases and most patients (85%) showed an elevation of one or more cancer biomarkers. The hemorrhagic lesions in 13 patients (65%) were in the intracerebral lobe. Four patients were completely dependent and 4 died within 30 days after hemorrhage. Intratumoral hemorrhage (50%) and coagulopathy (50%) accounted for the majority of hemorrhages.CONCLUSIONPatients with ICH and CRC often have clinical features with lobar hemorrhage, distant metastases and poor prognosis. Intratumoral hemorrhage and coagulopathy are the main causes of ICH in patients with CRC.

Cigarette smoking associated with colorectal cancer survival: a nationwide, population-based cohort study

BACKGROUND AND AIM: The association between cigarette smoking and survival in patients with colorectal cancer (CRC) is inconsistent. Thus, we aim to investigate whether cigarette smoking is associated with the overall survival rates of CRC patients using a nationwide population-based cohort study in Taiwan. METHODS: Taiwan Cancer Registry and Taiwan’s national health insurance research database were used to identify CRC patients from 2011 to 2017. All patients were censored to date of death or the end of 2017. Tobacco use was evaluated by smoking status, duration, and amount of cigarette smoking before cancer diagnosis. Survival was estimated using Kaplan-Meier analysis and Cox regression was used to investigate the effect of smoking on overall survival (OS). RESULTS:A total of 49,837 CRC patients were included for analysis. The Kaplan–Meier survival analysis illustrated smoking to be significant association with OS in CRC patients (log-rank p=0.0123). The multivariable Cox model showed that CRC patients with ever smoking habit had 1.11-fold mortality risk (HR=1.11, 95% CI=1.05-1.16; p.0001) compared with CRC patients whom never smoking. This increased risk was also present in CRC patients who smoking cigarettes 20 per day (HR=1.13; 95% CI=1.02-1.25; p=0.0149) or smoking year of 11-30 years (HR=1.15; 95% CI=1.06-1.24; p=0.0004). Furthermore, stratified analysis of sex and tumour location showed the impact of smoking was higher in male CRC patients or cancer developed in rectum. CONCLUSIONS:Our results indicate that cigarette smoking significantly associates with worse survival in CRC patients. An integrated smoking cessation campaign is warranted to prevent the CRC mortality. KEYWORDS: Colorectal cancer, Cigarette smoking, Survival

A Pilot Study Investigating the Expression Levels of Pluripotency-Associated Genes in Rectal Swab Samples for Colorectal Polyp and Cancer Diagnosis and Prognosis

Change in gene expression is inevitable in cancer development. With more studies demonstrating the contributions of cancer stem cells (CSCs) in colorectal cancer (CRC) development, this study is aimed at investigating whether rectal swab specimen serves as a tool for detection of dysregulation of CSC or stem cell (SC) markers and at evaluating its potential as a new promising screening method for high-risk patients. Expression levels of 15 pluripotency-associated genes were assessed by quantitative PCR in 53 rectal swab specimens referred for endoscopic screening. Dysregulated genes and joint panels based on such genes were examined for their diagnostic potentials for both polyp and CRC. Out of 15 genes, Oct4, CD26, c-MYC, and CXCR4 showed significantly differential expression among normal, polyp, and CRC patients. A panel of Oct4 and CD26 showed an AUC value of 0.80 (p = 0.003) in identifying CRC patients from polyp/normal subjects, with sensitivity and specificity of 84.6% and 69.2%. A panel of c-MYC and CXCR4 achieved CRC/polyp identification with an AUC value of 0.79 (p = 0.002), with a sensitivity of 82.8% and specificity of 80.0%. The sensitivity for polyp and CRC was 80.0% and 85.7%, respectively. Further analysis showed that higher c-MYC and CXCR4 level was detected in normal subjects who developed polyps after 5-6 years, in comparison with subjects with no lesion developed, and the AUC of the c-MYC and CXCR4 panel increased to 0.88 (p < 0.001), with sensitivity and specificity of 84.4% and 92.3%, respectively, when these patients were included in the polyp group. This study suggests that the Oct4 and CD26 panel is a promising biomarker for distinguishing CRC from normal and polyp patients, whereas the c-MYC and CXCR4 panel may identify polyp and CRC from normal individuals.

Cannabis use is associated with patient and clinical factors in a population-based sample of colorectal cancer survivors.

This study aimed to characterize patient and clinical factors associated with cannabis (marijuana) use among patients diagnosed with colorectal cancer (CRC). We identified CRC patients, diagnosed from 2016 to 2018, using the Seattle-Puget Sound Surveillance, Epidemiology, and End Results (SEER) cancer registry. CRC patients were recruited via mail and telephone, and participants completed a questionnaire eliciting information on medical history, demographics, and lifestyle factors, including cannabis use. Cancer stage was obtained from SEER registry data. Of 1,433 survey respondents, 339 (24%) were current cannabis users. Current cannabis use was associated with younger age at diagnosis, lower BMI, and a higher prevalence of cigarette smoking and alcohol consumption (p-value < 0.05). Cannabis use was also associated with lower quality of life scores (FACT-C) and advanced-stage cancer (p-value < 0.05). Cannabis use among CRC patients was common. Patients with more advanced disease were more likely to report cannabis use. Use also varied by some personal factors, consistent with patterns in the general population. Given the high prevalence of cannabis use among CRC patients, research is needed to determine the benefits and harms of cannabis use for symptom management in cancer patients.

Can Lymphovascular and Perineural Invasion be Additional Staging Criteria in Colorectal Cancer?

To identify additional staging information, venous, lymphatic, and neural invasionas potential prognostic factors in colorectal cancer (CRC). A descriptive study. Place and Duration of the Study: University of Health Sciences, Tepecik Training and Research Hospital, Izmir, Turkey; from May 2007 to June 2019. Retrospective analyses were performed on 855 CRC patients, who were treated with surgery. Patient and treatment characteristics, lymphovascular (LVI), and perineural (PNI) invasion were documented. The impact of LVI and PNI was determined using Cox proportional hazards model. The cohort examined had 346 (40.5%) LVI and 150 (17.5%) PNI positive patients. After surgery, mortality was 18.4% for LVI and 8% for PNI patients. Although increased ASA score (for ASA 2 hazard ratio [HR]=0.555, p=0.001 and ASA 3-4 HR=0.723, p=0.014), adjuvant chemotherapy (HR=2.5, p<0.001), LVI (HR=1.961, p<0.001) and PNI (HR=1.625, p<0.001) involvement increased the risk of death based on univariate analysis, multivariate Cox analysis showed a risk of death increase with increased ASA score (for ASA 2 HR=0.53, p<0.001 and ASA 3-4 HR=0.703, p=0.008), adjuvant chemotherapy (HR=2.114, p<0.001) and LVI involvement (HR=1.640, p<0.001). LVI and PNI may be useful in identifying CRC patients who might benefit the most from adjuvant systemic therapy. On the other hand, the presence of LVI and PNI reflects a shorter patient survival. Key Words: Lymphovascular invasion, Perineural invasion, Colorectal cancer, Cancer staging.

Radiomics Features of 18F-Fluorodeoxyglucose Positron-Emission Tomography as a Novel Prognostic Signature in Colorectal Cancer.

Simple SummaryCurrently, the optimal treatment for colorectal cancer (CRC) is planned on the basis of the results of preoperative imaging studies. Previous studies investigating the impact of radiomics signatures derived from positron-emission tomography (PET) images mainly focused on patients with rectal cancer, who underwent preoperative chemoradiotherapy, and included a relatively small number of patients, without a validation set. The impact of PET-based radiomics signature analysis in patients undergoing curative-intent radical surgery, with or without chemotherapy, has not been extensively investigated. Thus, we aimed to identify the prognostic value of radiomics signature from18F-fluorodeoxyglucose (18F-FDG) PET images by assessing the imaging features to predict the progression-free survival in patients with CRC. This study demonstrated that radiomics features derived from PET-CT images can help stratify patient prognosis and additionally increase diagnostic accuracy with respect to conventional clinicopathological data-driven prediction model in patients with CRC.The aim of this study was to investigate the prognostic value of radiomics signatures derived from 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography (PET) in patients with colorectal cancer (CRC). From April 2008 to Jan 2014, we identified CRC patients who underwent 18F-FDG-PET before starting any neoadjuvant treatments and surgery. Radiomics features were extracted from the primary lesions identified on 18F-FDG-PET. Patients were divided into a training and validation set by random sampling. A least absolute shrinkage and selection operator Cox regression model was applied for prognostic signature building with progression-free survival (PFS) using the training set. Using the calculated radiomics score, a nomogram was developed, and its clinical utility was assessed in the validation set. A total of 381 patients with surgically resected CRC patients (training set: 228 vs. validation set: 153) were included. In the training set, a radiomics signature labeled as a rad_score was generated using two PET-derived features, such as gray-level run length matrix long-run emphasis (GLRLM_LRE) and gray-level zone length matrix short-zone low-gray-level emphasis (GLZLM_SZLGE). Patients with a high rad_score in the training and validation set had a shorter PFS. Multivariable analysis revealed that the rad_score was an independent prognostic factor in both training and validation sets. A radiomics nomogram, developed using rad_score, nodal stage, and lymphovascular invasion, showed good performance in the calibration curve and comparable predictive power with the staging system in the validation set. Textural features derived from 18F-FDG-PET images may enable detailed stratification of prognosis in patients with CRC.