Primary and Secondary Prevention of Colorectal Cancer

peer reviewedColorectal cancer is really a public health problem. The authors review the literature about the environmental factors leading to colorectal cancer. Chemoprevention of colorectal cancer is also discussed, particularly by aspirin and non steroidal anti-inflammatory drugs. Development of specific cyclooxygenase-2 inhibitors constitutes a promising research's field. Secondary prevention by coloscopy and polypectomy must lead to a lower rate of colorectal cancer disease and improvement of mortality

Effects of COVID-19 pandemic on colorectal cancer surgery

BACKGROUND: The coronavirus disease-19 (COVID-19) pandemic has changed the course of diseases that require emergency surgery. OBJECTIVE: To evaluate the effect of the COVID-19 pandemic on colorectal cancer disease stage. DESIGN AND SETTING: Retrospective analysis in the city of Rize, Turkey. METHODS: This was a comparative analysis on two groups of patients with various symptoms who underwent surgical colorectal cancer treatment. Group 1 comprised patients operated between March 11, 2019, and December 31, 2019; while group 2 comprised patients at the same time of the year during the COVID-19 pandemic. RESULTS: Groups 1 and 2 included 56 and 48 patients, respectively. The rate of presentation to the emergency service was higher in Group 2 (P < 0.02). The stage of the pathological lymph nodes and the rate of liver metastasis was higher in Group 2 (P < 0.004 and P < 0.041, respectively). The disease stage was found to be more advanced in Group 2 (P < 0.005). The rate of postoperative complications was higher in Group 2 (P < 0.014). CONCLUSION: The presentation of patients with suspicious findings to the hospital was delayed, due both to the fear of catching COVID-19 and to the pandemic precautions that were proposed and implemented by healthcare authorities worldwide. Among the patients who presented to the hospital with emergency complaints and in whom colorectal cancer was detected, their disease was at a more advanced stage and thus a higher number of emergency oncological surgical procedures were performed on those patients

Colorectal Cancer Disease in Appalachia: Symptom Interpretation and Cancer Worry Predictors

In the Appalachian region, many cultural, religious, and psychological factors have been identified to affect health. These factors are expected to play a role in health disparities, such as higher rates of colorectal cancer (CRC) incidence and mortality. Appalachia-specific factors such as geographic isolationism, poverty, and Appalachian stereotypes have been reported to negatively affect preventive health care including CRC screening. Although previous research has investigating the impact of some of these Appalachia-specific factors on seeking health care, impact of symptom interpretation and psychological states of the Appalachian population on health care seeking behavior needs to be clarified. The objective of this study was to identify Appalachians\u27 knowledge, health care seeking behavior, and emotions with regard to CRC. The focus in this study was on two main issues. First, the study investigated appraisal delay due to incorrect symptom interpretation (not inferring illness when experiencing symptoms) and thoughts and feelings about CRC. These points are discussed in manuscript # 1. Second, due to the heavy influence of psychological state on health behavior, manuscript # 2 examined of the impact of perceived health, fatalism, religiosity, access to health care, and other demographic, cultural, and psychological variables on CRC worry. A qualitative analysis [Manuscript #1] was conducted on a sample of Appalachian men to explore their thoughts and feelings about CRC, appraisal delay, and symptom interpretation. The investigation of men\u27s perspective in this manuscript was due to the greater likelihood for men to undergo CRC screening as compared to women (Seeff et al., 2004). The investigation of these points enabled determining the uniqueness of the Appalachians\u27 health seeking behavior. Using a cross-sectional pilot study design, fifteen men above the age of 50 were interviewed. Interviews included semi-structured audio-taped recordings. Interviews were transcribed and analyzed through utilizing constructionism as an epistemology. Further, due to the fact that women report CRC worry more frequently than men do (McQueen, Vernon, Meissner, & Rakowski, 2008), a sample of Appalachian women was surveyed in the second part of this study [Manuscript # 2] in order to collect demographic, cultural (e.g., fatalism and religiosity), and psychological (e.g., CRC worry and general mood) quantitative data. The purpose was to investigate factors that were associated with CRC worry. The sample for this manuscript included 137 women who were at least 18 years old at the time of the study. The study was based on a cross-sectional structured mail survey. The epistemology utilized in this manuscript was objectivism. Participants for both manuscripts had no personal history of CRC. The Self-regulation Model (Leventhal et al., 1997) was utilized in both manuscripts to guide analysis.;Findings from the qualitative analysis [Manuscript # 1] on Appalachian-specific barriers to seeking healthcare showed that powerlessness was a common thought among many participants. Most participants indicated that the presence of barriers to seeking health care - barriers that participants had no ability to control or fix - was the reason for not adhering to recommended screening guidelines. Symptoms interpretation, and consequently referring an illness, was variable among participants. However, the presence of (1) Severe symptoms that negatively impact the functionality of the body or (2) persistent symptoms that last for a long period of time were the most two important symptom-related cues to seeking health care. Results from the analysis on CRC worry [Manuscript # 2] suggested that the following factors were associated with CRC worry: Higher education, greater magnitude of perceived absolute risk, tension/anxiety, and uncertainty about the access to health care. In conclusion, manuscript # 1 indicated that unawareness about health insurance programs, mistrust about health care providers and medical procedures, not having access to health care, and health illiteracy were some of the factors that influenced people\u27s health care behavior. Some thoughts have not been reported in the literature. Example are letting symptoms take care of themselves and asking old folks instead of seeking care from health professionals, thinking about CRC as a stigma, and believing that it was socially inacceptable to talk about CRC-related issues. Manuscript # 2 confirmed what previous research has found about the effect of education and absolute perceived risk for developing CRC on CRC worry, and suggested two other factors (perceived easiness of access to gastroenterologists and increased scores on the tension-anxiety sub-scale of the Profile of Mood States instrument) that were associated with CRC worry among Appalachian residents. The use of mixed methods [qualitative and quantitative] in this study helped not only in identifying statistics regarding health beliefs, but also in clarifying the reasons for certain beliefs and behaviors among the Appalachian residents. The use of qualitative methodology helped in clarifying the uniqueness of the Appalachian population regarding health beliefs and health behavior. Results of this study will aid in designing more targeted interventions in the future, which will help Appalachian residents follow health care professionals\u27 recommendations, and then, have better health care outcomes

The importance of circulating tumor products as „liquid biopsies” in colorectal cancer

Liquid biopsies represent an array of plasma analysis tests that are studied to evaluate and identify circulating tumor products, especially circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). Examining such biomarkers in the plasma of colorectal cancer patients has attracted attention due to its clinical significance in the treatment of malignant diseases. Given that tissue samples are sometimes challenging to procure or unsatisfactory for genomic profiling from patients with colorectal cancer, trustworthy biomarkers are mandatory for guiding treatment, monitoring therapeutic response, and detecting recurrence. This review considers the relevance of flowing tumor products like circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating messenger RNA (mRNA), circulating micro RNA (miRNA), circulating exosomes, and tumor educated platelets (TEPs) for patients with colorectal cancer

Survival endpoints in colorectal cancer and the effect of second primary other cancer on disease free survival

<p>Abstract</p> <p>Background</p> <p>In cancer research the selection and definitions of survival endpoints are important and yet they are not used consistently. The aim of this study was to compare different survival endpoints in patients with primary colorectal cancer (CRC) and to understand the effect of second primary other cancer on disease-free survival (DFS) calculations.</p> <p>Methods</p> <p>A population-based cohort of 415 patients with CRC, 332 of whom were treated with curative intention between the years 2000-2003, was analysed. Events such as locoregional recurrence, distant metastases, second primary cancers, death, cause of death and loss to follow-up were recorded. Different survival endpoints, including DFS, overall survival, cancer-specific survival, relapse-free survival, time to treatment failure and time to recurrence were compared and DFS was calculated with and without inclusion of second primary other cancers.</p> <p>Results</p> <p>The events that occurred most often in patients treated with curative intention were non-cancer-related death (n = 74), distant metastases (n = 66) and death from CRC (n = 59). DFS was the survival endpoint with most events (n = 170) followed by overall survival (n = 144) and relapse-free survival (n = 139). Fewer events were seen for time to treatment failure (n = 80), time to recurrence (n = 68) and cancer-specific survival (n = 59). Second primary other cancer occurred in 26 patients and its inclusion as an event in DFS calculations had a detrimental effect on the survival. The DFS for patients with stage I-III disease was 62% after 5 years if second primary other cancer was not included as an event, compared with 58% if it was. However, the difference was larger for stage II (68 vs 60%) than for stage III (49 vs 47%).</p> <p>Conclusions</p> <p>The inclusion of second primary other cancer as an endpoint in DFS analyses significantly alters the DFS for patients with CRC. Researchers and journals must clearly define survival endpoints in all trial protocols and published manuscripts.</p

Association Between Results of a Gene Expression Signature Assay and Recurrence-Free Interval in Patients With Stage II Colon Cancer in Cancer and Leukemia Group B 9581 (Alliance)

PURPOSE: Conventional staging methods are inadequate to identify patients with stage II colon cancer (CC) who are at high risk of recurrence after surgery with curative intent. ColDx is a gene expression, microarray-based assay shown to be independently prognostic for recurrence-free interval (RFI) and overall survival in CC. The objective of this study was to further validate ColDx using formalin-fixed, paraffin-embedded specimens collected as part of the Alliance phase III trial, C9581. PATIENTS AND METHODS: C9581 evaluated edrecolomab versus observation in patients with stage II CC and reported no survival benefit. Under an initial case-cohort sampling design, a randomly selected subcohort (RS) comprised 514 patients from 901 eligible patients with available tissue. Forty-nine additional patients with recurrence events were included in the analysis. Final analysis comprised 393 patients: 360 RS (58 events) and 33 non-RS events. Risk status was determined for each patient by ColDx. The Self-Prentice method was used to test the association between the resulting ColDx risk score and RFI adjusting for standard prognostic variables. RESULTS: Fifty-five percent of patients (216 of 393) were classified as high risk. After adjustment for prognostic variables that included mismatch repair (MMR) deficiency, ColDx high-risk patients exhibited significantly worse RFI (multivariable hazard ratio, 2.13; 95% CI, 1.3 to 3.5; P < .01). Age and MMR status were marginally significant. RFI at 5 years for patients classified as high risk was 82% (95% CI, 79% to 85%), compared with 91% (95% CI, 89% to 93%) for patients classified as low risk. CONCLUSION: ColDx is associated with RFI in the C9581 subsample in the presence of other prognostic factors, including MMR deficiency. ColDx could be incorporated with the traditional clinical markers of risk to refine patient prognosis

The Colorectal cancer disease-specific transcriptome may facilitate the discovery of more biologically and clinically relevant information

<p>Abstract</p> <p>Background</p> <p>To date, there are no clinically reliable predictive markers of response to the current treatment regimens for advanced colorectal cancer. The aim of the current study was to compare and assess the power of transcriptional profiling using a generic microarray and a disease-specific transcriptome-based microarray. We also examined the biological and clinical relevance of the disease-specific transcriptome.</p> <p>Methods</p> <p>DNA microarray profiling was carried out on isogenic sensitive and 5-FU-resistant HCT116 colorectal cancer cell lines using the Affymetrix HG-U133 Plus2.0 array and the Almac Diagnostics Colorectal cancer disease specific Research tool. In addition, DNA microarray profiling was also carried out on pre-treatment metastatic colorectal cancer biopsies using the colorectal cancer disease specific Research tool. The two microarray platforms were compared based on detection of probesets and biological information.</p> <p>Results</p> <p>The results demonstrated that the disease-specific transcriptome-based microarray was able to out-perform the generic genomic-based microarray on a number of levels including detection of transcripts and pathway analysis. In addition, the disease-specific microarray contains a high percentage of antisense transcripts and further analysis demonstrated that a number of these exist in sense:antisense pairs. Comparison between cell line models and metastatic CRC patient biopsies further demonstrated that a number of the identified sense:antisense pairs were also detected in CRC patient biopsies, suggesting potential clinical relevance.</p> <p>Conclusions</p> <p>Analysis from our <it>in vitro </it>and clinical experiments has demonstrated that many transcripts exist in sense:antisense pairs including <it>IGF2BP2</it>, which may have a direct regulatory function in the context of colorectal cancer. While the functional relevance of the antisense transcripts has been established by many studies, their functional role is currently unclear; however, the numbers that have been detected by the disease-specific microarray would suggest that they may be important regulatory transcripts. This study has demonstrated the power of a disease-specific transcriptome-based approach and highlighted the potential novel biologically and clinically relevant information that is gained when using such a methodology.</p

Development and assessment of a clinical calculator for estimating the likelihood of recurrence and survival among patients with locally advanced rectal cancer treated with chemotherapy, radiotherapy, and surgery

Importance: Predicting outcomes in patients receiving neoadjuvant therapy for rectal cancer is challenging because of tumor downstaging. Validated clinical calculators that can estimate recurrence-free survival (RFS) and overall survival (OS) among patients with rectal cancer who have received multimodal therapy are needed. Objective: To develop and validate clinical calculators providing estimates of rectal cancer recurrence and survival that are better for individualized decision-making than the American Joint Committee on Cancer (AJCC) staging system or the neoadjuvant rectal (NAR) score. Design, Setting, and Participants: This prognostic study developed risk models, graphically represented as nomograms, for patients with incomplete pathological response using Cox proportional hazards and multivariable regression analyses with restricted cubic splines. Because patients with complete pathological response to neoadjuvant therapy had uniformly favorable outcomes, their predictions were obtained separately. The study included 1400 patients with stage II or III rectal cancer who received treatment with chemotherapy, radiotherapy, and surgery at 2 comprehensive cancer centers (Memorial Sloan Kettering [MSK] Cancer Center and Siteman Cancer Center [SCC]) between January 1, 1998, and December 31, 2017. Patients from the MSK cohort received chemoradiation, surgery, and adjuvant chemotherapy from January 1, 1998, to December 31, 2014; these patients were randomly assigned to either a model training group or an internal validation group. Models were externally validated using data from the SCC cohort, who received either chemoradiation, surgery, and adjuvant chemotherapy (chemoradiotherapy group) or short-course radiotherapy, consolidation chemotherapy, and surgery (total neoadjuvant therapy with short-course radiotherapy group) from January 1, 2009, to December 31, 2017. Data were analyzed from March 1, 2020, to January 10, 2021. Exposures: Chemotherapy, radiotherapy, chemoradiotherapy, and surgery. Main Outcomes and Measures: Recurrence-free survival and OS were the outcome measures, and the discriminatory performance of the clinical calculators was measured with concordance index and calibration plots. The ability of the clinical calculators to predict RFS and OS was compared with that of the AJCC staging system and the NAR score. The models for RFS and OS among patients with incomplete pathological response included postoperative pathological tumor category, number of positive lymph nodes, tumor distance from anal verge, and large- and small-vessel venous and perineural invasion; age was included in the risk model for OS. The final clinical calculators provided RFS and OS estimates derived from Kaplan-Meier curves for patients with complete pathological response and from risk models for patients with incomplete pathological response. Results: Among 1400 total patients with locally advanced rectal cancer, the median age was 57.8 years (range, 18.0-91.9 years), and 863 patients (61.6%) were male, with tumors at a median distance of 6.7 cm (range, 0-15.0 cm) from the anal verge. The MSK cohort comprised 1069 patients; of those, 710 were assigned to the model training group and 359 were assigned to the internal validation group. The SCC cohort comprised 331 patients; of those, 200 were assigned to the chemoradiotherapy group and 131 were assigned to the total neoadjuvant therapy with short-course radiotherapy group. The concordance indices in the MSK validation data set were 0.70 (95% CI, 0.65-0.76) for RFS and 0.73 (95% CI, 0.65-0.80) for OS. In the external SCC data set, the concordance indices in the chemoradiotherapy group were 0.71 (95% CI, 0.62-0.81) for RFS and 0.72 (95% CI, 0.59-0.85) for OS; the concordance indices in the total neoadjuvant therapy with short-course radiotherapy group were 0.62 (95% CI, 0.49-0.75) for RFS and 0.67 (95% CI, 0.46-0.84) for OS. Calibration plots confirmed good agreement between predicted and observed events. These results compared favorably with predictions based on the AJCC staging system (concordance indices for MSK validation: RFS = 0.69 [95% CI, 0.64-0.74]; OS = 0.67 [95% CI, 0.58-0.75]) and the NAR score (concordance indices for MSK validation: RFS = 0.56 [95% CI, 0.50-0.63]; OS = 0.56 [95% CI, 0.46-0.66]). Furthermore, the clinical calculators provided more individualized outcome estimates compared with the categorical schemas (eg, estimated RFS for patients with AJCC stage IIIB disease ranged from 7% to 68%). Conclusions and Relevance: In this prognostic study, clinical calculators were developed and validated; these calculators provided more individualized estimates of the likelihood of RFS and OS than the AJCC staging system or the NAR score among patients with rectal cancer who received multimodal treatment. The calculators were easy to use and applicable to both short- and long-course radiotherapy regimens, and they may be used to inform surveillance strategies and facilitate future clinical trials and statistical power calculations