Asymptomatic Colorectal Cancer Research Articles

The Impact of Primary Tumor Resection on Survival in Asymptomatic Colorectal Cancer Patients With Unresectable Metastases.

PurposeThis study was conducted to evaluate the effectiveness of primary tumor resection (PTR) in asymptomatic colorectal cancer (CRC) patients with unresectable metastases using the inverse probability of treatment weighting (IPTW) method to minimize selection bias.MethodsWe selected 146 patients diagnosed with stage IV CRC with unresectable metastasis between 2001 and 2018 from our institutional database. In a multivariate logistic regression model using the patients’ baseline covariates associated with PTR, we applied the IPTW method based on a propensity score and performed a weighted Cox proportional regression analysis to estimate survival according to PTR.ResultsUpfront PTR was performed in 98 patients, and no significant differences in baseline factors were detected. The upweighted median survival of the PTR group was 18 months and that of the non-PTR group was 15 months (P = 0.15). After applying the IPTW, the PTR was still insignificant in the univariate Cox regression (hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.5–1.21). However, in the multivariate weighted Cox regression with adjustment for other covariates, the PTR showed a significantly decreased risk of cancer-related death (HR, 0.61; 95% CI, 0.40–0.94).ConclusionIn this study, we showed that asymptomatic CRC patients with unresectable metastases could gain a survival benefit from upfront PTR by analysis with the IPTW method. However, randomized controlled trials are mandatory.

Primary Tumor Resection in Asymptomatic Colorectal Cancer Patients With Unresectable Metastases: Can It Improve Survival?

Primary Tumor Resection in Asymptomatic Colorectal Cancer Patients With Unresectable Metastases: Can It Improve Survival?

Machine Learning–based Differentiation of Benign and Premalignant Colorectal Polyps Detected with CT Colonography in an Asymptomatic Screening Population: A Proof-of-Concept Study

Background CT colonography does not enable definite differentiation between benign and premalignant colorectal polyps. Purpose To perform machine learning-based differentiation of benign and premalignant colorectal polyps detected with CT colonography in an average-risk asymptomatic colorectal cancer screening sample with external validation using radiomics. Materials and Methods In this secondary analysis of a prospective trial, colorectal polyps of all size categories and morphologies were manually segmented on CT colonographic images and were classified as benign (hyperplastic polyp or regular mucosa) or premalignant (adenoma) according to the histopathologic reference standard. Quantitative image features characterizing shape (n = 14), gray level histogram statistics (n = 18), and image texture (n = 68) were extracted from segmentations after applying 22 image filters, resulting in 1906 feature-filter combinations. Based on these features, a random forest classification algorithm was trained to predict the individual polyp character. Diagnostic performance was validated in an external test set. Results The random forest model was fitted using a training set consisting of 107 colorectal polyps in 63 patients (mean age, 63 years ± 8 [standard deviation]; 40 men) comprising 169 segmentations on CT colonographic images. The external test set included 77 polyps in 59 patients comprising 118 segmentations. Random forest analysis yielded an area under the receiver operating characteristic curve of 0.91 (95% CI: 0.85, 0.96), a sensitivity of 82% (65 of 79) (95% CI: 74%, 91%), and a specificity of 85% (33 of 39) (95% CI: 72%, 95%) in the external test set. In two subgroup analyses of the external test set, the area under the receiver operating characteristic curve was 0.87 in the size category of 6-9 mm and 0.90 in the size category of 10 mm or larger. The most important image feature for decision making (relative importance of 3.7%) was quantifying first-order gray level histogram statistics. Conclusion In this proof-of-concept study, machine learning-based image analysis enabled noninvasive differentiation of benign and premalignant colorectal polyps with CT colonography. © RSNA, 2021 Online supplemental material is available for this article.

Classifying interval cancers as false negatives or newly occurring in fecal immunochemical testing.

To classify interval colorectal cancers as false negatives or newly occurring cases in a biennial Fecal immunochemical test (FIT) screening program and by various interscreening intervals. Data from the Taiwanese biennial colorectal cancer screening program involving FIT from 2004 to 2014 were used to estimate the incidence rate of asymptomatic colorectal cancer and the rate of its subsequent progression to clinical mode. The sensitivity of detecting asymptomatic colorectal cancers excluding newly developed colorectal cancers was compared to the conventional estimate of sensitivity, the complementary FIT interval cancer rate as a percentage of the expected incidence rate ((1-I/E)%). The relative contribution of newly developed or false-negative cases to FIT interval colorectal cancers was estimated by age and interscreening intervals. The Taiwanese biennial fecal immunochemical test screening program had a conventional sensitivity estimate of 70.2%. After newly developed colorectal cancers were separated from FIT interval cancers, the ability to detect asymptomatic colorectal cancers increased to 75.5%. FIT interval colorectal cancers from the biennial program mainly resulted from newly developed colorectal cancers (68.8%). The corresponding figures decreased to 61.1% for the annual program but increased to 74.7% for the triennial program. The preponderance of newly developed colorectal cancers among FIT interval cancers was more prominent in screenees aged 50-59 than in those aged 60-69. Newly developed colorectal cancers showed a predominance among the FIT interval colorectal cancers in particular in the younger population screened. It is desirable to identify high-risk individuals to offer them a short interscreening interval or advanced detection methods to reduce their odds of developing interval cancer.

Superiority of fecal carcinoembryonic antigen as diagnosis marker for adenomatous polyposis coli and asymptomatic colorectal cancer.

Background:Non-invasive diagnostic tools of adenomatous polyposis coli (APC) and asymptomatic colorectal cancer (CRC) are urgently needed. Although fecal carcinoembryonic antigen (FCEA) has been documented in some studies, the diagnostic potential for the detection of APC and asymptomatic CRC has not been described yet.Methods:This is a retrospective study. The pre-diagnostic serum carcinoembryonic antigen (SCEA) and fecal occult blood test (FOBT) levels were retrospectively analyzed in 212 patients with intestinal diseases group (IDG) and 224 controls. The levels of FCEA across all the studied groups were measured using electronic chemiluminescence immunoassay (ECLIA), and their sensitivity and specificity were used to evaluate their diagnostic potential. The individual diagnostic accuracy of the three indices, as well as their combined diagnostic potential, was compared using the receiver operating characteristic (ROC) curve and chi-square test.Results:The FCEA had low sensitivity (50%) and high specificity (93.91%) for the diagnosis of IDG, with the area under the curve (AUC) value of 0.781. The AUC of FCEA was higher than that of SCEA for the diagnosis of APC and CRC in the APC, asymptomatic CRC, and APC + CRC-stage I patients. The AUCs of FCEA were 0.708 and 0.691 for the ‘double-negative patients’ and ‘triple-negative patients’, respectively. In addition, FCEA could diagnose 45.5% of the ‘double-negative’ patients, 43.3% of the asymptomatic patients, and 42.9% of the ‘triple-negative’ patients. The combination of FCEA and FOBT improved the diagnostic value (AUC = 0.916).Conclusion:FCEA has been demonstrated to be a favorable diagnostic marker in intestinal diseases, especially in the APC, asymptomatic CRC, and ‘double-negative’ or ‘triple-negative’ CRC patients.

S0305 Analysis of Utilization of Fecal Immuno Chemical Testing (FIT) as a Colorectal Cancer Screening Modality in African American Patients From a Large Urban Safety Net Hospital

INTRODUCTION: Colorectal cancer (CRC) is the third most common cancer diagnosed in both men and women in the United States (U.S). Over the past 10 years, the incidence and mortality rates of CRC in the U.S has steadily declined however, reductions have been significantly slower amongst African Americans (AA) who continue to have the highest rate of mortality amongst other racial groups. Several meta-analysis studies evaluated FIT to other modalities for detection of asymptomatic CRC. Pooled analysis revealed FIT sensitivity 79% and specificity 94%. In a study by Quintero et. al authors in 2012 NEJM compared one-time colonoscopy (26503) with FIT (26599) every 2 years. More compliance was noted with FIT group compared to colonoscopy group. Given AA are disproportionately affected by CRC and data on the utilization of FIT testing amongst AA population is scanty and poorly studied, we aim to study the utilization of FIT testing amongst AA. METHODS: We retrieved electronic medical records from a large safety net hospital between January 2010 and January 2019. We identified average risk patients who received screening for CRC using FIT, colonoscopy or sigmoidoscopy or either. Data regarding screening modalities for CRC were obtained. We utilized ICD-9 and ICD-10 procedure codes for FIT, colonoscopy and sigmoidoscopy. MS excel and STAT software were used for data management and analyses. Two-sided P-value <0.05 was considered statistically significant. RESULTS: Our study revealed that over all utilization of FIT was less compared to colonoscopy with 21.5 % vs 70.23% respectively at our institution. Similarly, the percentage of AA patients who received only FIT as a screening from total AA population for CRC was about 20.7% only and colonoscopy was about 70.9%. Table 1.0 summarizes total demographics and percentages of each screening modality. Table 3.0 summarizes trends of CRC screening trends in AA pts. CONCLUSION: Multiple screening tests such as colonoscopy, FIT, sigmoidoscopy, Fecal Occult Blood Test (FOBT) and FIT DNA are available to detect CRC. But FIT is most specific (96.4%) compared to other screening modalities. Our study reveals that only 20.7 % of AA patients received FIT as a screening tool for CRC compared to 70.9% who received traditional colonoscopy. More multi center studies are needed to analyze the barriers in utilization of FIT especially amongst AA patients. One potential barrier could be the awareness of FIT as a screening modality for CRC amongst primary care physicians.Table 1.: Summarizes demographics and utilization of CRC screening modality in total patientsTable 2.: Summarizes radical trends of utilization of CRC screening methodsTable 3.: Summarizes radical trends of utilization of CRC screening in African American population

Inflammatory bowel disease in a colorectal cancer screening population: Diagnosis and follow-up

BackgroundInflammatory bowel disease (IBD) is usually diagnosed in subjects with gastrointestinal symptoms, but may also be asymptomatic and diagnosed incidentally. Aimsto determine the prevalence of IBD in asymptomatic adults. Methodswe identified subjects who underwent colonoscopy between 1 September 2013 and 31 August 2019 in a regional colorectal cancer screening program with endoscopic findings suggestive of IBD, and retrieved their clinical, histological and therapeutic information. Results5116 subjects underwent colonoscopy, and 4640 persons were considered assessable. Of these, 54 (1.16%) had endoscopic findings suggestive of IBD, including 40 of Crohn's disease (CD) and 14 of ulcerative colitis (UC). A definite diagnosis of IBD was made in 19 patients, for an overall IBD prevalence of 0.41%, with 13 cases of CD (0.28%) and 6 of UC (0.13%). The mean follow-up was 26.8 months after the first colonoscopy. Therapy was started in 5 of 13 CD patients and all UC patients. ConclusionEndoscopic findings suggestive of IBD are not infrequent in an asymptomatic colorectal cancer screening population. Visualization of the terminal ileum is recommended in this setting. A definite diagnosis of IBD was made in about 1 out of 3 subjects with endoscopic lesions. Most IBD patients had a mild form of disease, but some needed biologic therapy.

The Role of Primary Tumor Resection in Colorectal Cancer Patients with Asymptomatic, Synchronous, Unresectable Metastasis: A Multicenter Randomized Controlled Trial.

We aimed to assess the survival benefits of primary tumor resection (PTR) followed by chemotherapy in patients with asymptomatic stage IV colorectal cancer with asymptomatic, synchronous, unresectable metastases compared to those of upfront chemotherapy alone. This was an open-label, prospective, randomized controlled trial (ClnicalTrials.gov Identifier: NCT01978249). From May 2013 to April 2016, 48 patients (PTR, n = 26; upfront chemotherapy, n = 22) diagnosed with asymptomatic colorectal cancer with unresectable metastases in 12 tertiary hospitals were randomized (1:1). The primary endpoint was two-year overall survival. The secondary endpoints were primary tumor-related complications, PTR-related complications, and rate of conversion to resectable status. The two-year cancer-specific survival was significantly higher in the PTR group than in the upfront chemotherapy group (72.3% vs. 47.1%; p = 0.049). However, the two-year overall survival rate was not significantly different between the PTR and upfront chemotherapy groups (69.5% vs. 44.8%, p = 0.058). The primary tumor-related complication rate was 22.7%. The PTR-related complication rate was 19.2%, with a major complication rate of 3.8%. The rates of conversion to resectable status were 15.3% and 18.2% in the PTR and upfront chemotherapy groups. While PTR followed by chemotherapy resulted in better two-year cancer-specific survival than upfront chemotherapy, the improvement in the two-year overall survival was not significant.

Treatment strategies and overall survival for incurable metastatic colorectal cancer – A EURECCA international comparison including 21,196 patients from the Netherlands and Norway

BackgroundThe potential benefit of surgery of the primary tumour in patients with asymptomatic metastatic colorectal cancer is debated. This EURECCA international comparison analyses treatment strategies and overall survival in the Netherlands and Norway in patients with incurable metastatic colorectal cancer. MethodsNational cohorts (2007–2013) from the Netherlands and Norway including all patients with synchronous metastatic colorectal cancer were compared on treatment strategy and overall survival. Using country as an instrumental variable, we assessed the effect of different treatment strategies on mortality in the first year. ResultsOf 21,196 patients (16,144 Dutch and 5052 Norwegian), 38.6% Dutch and 51.5% (p < 0.001) Norwegian patients underwent resection of the primary tumour. In the Netherlands, 58.2% received chemotherapy compared with 21.4% in Norway. Radiotherapy was given in 9.5% of Dutch patients and 7.2% of Norwegian patients. Using the Netherlands as reference, the adjusted HR for overall survival was 0.96 (95% CI 0.93–0.99; p = 0.024). Instrumental variable analysis showed an adjusted OR of 1.00 (95% CI 0.99–1.02; p = 0.741). ConclusionsTreatment strategies varied significantly between the Netherlands and Norway, with more surgery and less radiotherapy in Norway. Adjusted overall survival was better in Norway for all patients and patients <75 years, but not for patients ≥75 years. Instrumental variable analysis showed no benefit in one-year mortality for a treatment strategy with a higher proportion of surgery and a lower proportion of radiotherapy. Our findings emphasise the need for further research to select patients with incurable metastatic colorectal cancer for different treatment options.

Asymptomatic Inflammatory Bowel Disease and Colorectal Cancer Screening Programs: How Common Is It and What Should be Done About It?

The growing international popularity of screening programs for the early detection of pre-cancerous changes or early cancer in the colon has brought to the fore the issue of people with asymptomatic inflammatory bowel disease. What are the legal and clinical responsibilities for endoscopists and managers of screening programs towards such patients? This review assesses the magnitude of the problem and discusses the legal responsibilities, including human rights issues. In addition, it discusses whether such patients who do not have symptoms should be given active treatment.

Survival differences with immediate versus delayed chemotherapy for asymptomatic incurable metastatic colorectal cancer.

For patients with asymptomatic, incurable, metastatic colorectal cancer, palliative, systemic treatment can be started immediately, or can be delayed until disease-related symptoms occur. How the potential survival benefit of starting palliative, systemic treatment immediately after diagnosis weighs up against the potential side effects is currently under debate, and was investigated in this review. To assess the effects of immediate versus delayed chemotherapy, with or without targeted therapy, on overall survival, toxicity, quality of life, progression-free survival, and compliance with chemotherapy for individuals with asymptomatic, metastatic, incurable colorectal cancer. We searched CENTRAL; 2018, Issue 8, MEDLINE Ovid, Embase Ovid, PsycINFO, the World Health Organization International Clinical Trials Registry Platform, and Clinicaltrials.gov, from inception to 23 August 2018. We did not apply limitations based on language or date of publication. We searched the reference lists of all included studies to identify trials that may not have been identified from the electronic searches. Randomised controlled trials evaluating immediate versus delayed chemotherapy in persons with asymptomatic, metastatic, incurable colorectal cancer. We applied standard methodological procedures, according to the recommendations of Cochrane and Cochrane Colorectal Cancer. Two review authors independently reviewed the studies identified by literature searches, selected relevant trials, extracted data, and assessed risk of bias of the included studies. We used the Cochrane tool to assess risk of bias, Review Manager 5 software for meta-analysis, GRADE methods to evaluate the quality of the evidence, and GRADEpro GDT software to develop a 'Summary of findings' table. We included three randomised controlled trials (351 participants) investigating immediate versus delayed chemotherapy in people diagnosed with asymptomatic, metastatic, incurable colorectal cancer. Giving immediate versus delayed chemotherapy may make little or no difference to overall survival (hazard ratio (HR) 1.17, 95% confidence interval (CI) 0.93 to 1.46; 3 studies, 351 persons; low-quality evidence). For toxicity, giving immediate versus delayed chemotherapy may make little or no difference to the risk of grade 3 or 4 nausea and vomiting (risk ratio (RR) 0.84, 95% CI 0.31 to 2.25; 2 studies, 140 persons; very low-quality evidence), stomatitis (RR 1.10, 95% CI 0.47 to 2.55; 2 studies, 140 persons; very low-quality evidence), or diarrhoea (RR 0.69, 95% CI 0.34 to 1.40; 2 studies, 140 persons, very low-quality evidence). We are uncertain whether delayed chemotherapy made a difference to quality of life (very low-quality evidence), progression-free survival (low-quality evidence), or compliance with chemotherapy (low-quality evidence), as we had insufficient data to pool for these outcomes. Based on a limited number of trials, very sparse data, and uncertainty of the evidence, this review was unable to establish whether there was a difference in overall survival or other clinically relevant outcomes, between immediate or delayed chemotherapy in persons with metastatic, incurable, colorectal cancer. The results should be interpreted with caution.

To resect or not to resect: The hamletic dilemma of primary tumor resection in patients with asymptomatic stage IV colorectal cancer.

Primary tumor resection (PTR) in advanced asymptomatic colorectal cancer (CRC) has been a matter of intense debate for long time. With the advances in systemic treatments, this practice has decreased over the years, although it remains still pervasive. Although the removal of primary tumor has been extensively interrogated both in retrospective and prospective studies, it still remains a clinical conundrum. There are many arguments for and against PTR in CRC both from the preclinical and the clinical point of view. Two scoring models have been published aiming at identifying patients who are suitable candidate for PTR, but they deserve further investigations in larger datasets. While awaiting the results of ongoing randomized clinical trials (RCTs) on this controversial topic, both upfront systemic treatment and PTR followed by chemotherapy should be considered valid options in patients with asymptomatic mCRC. Clinical selection and a shared-decision making approach are the keys to success.

Abstract 5604: Novel DNA methylation biomarkers show high sensitivity and specificity for blood-based detection of colorectal cancer - A clinical biomarker discovery and validation study

Abstract Background: Screening for colorectal cancer (CRC) using fecal occult blood tests (FOBT) reduces CRC mortality, and many CRC screening programs therefore use FOBT. However, FOBT is not the best approach; first, because population acceptance is low due to unpleasantness of fecal sampling; second, because bowel tumors bleed only intermittently, which limits FOBT sensitivity. Development of a novel blood-based screening approach may alleviate these problems. Objective: This study aims to develop and validate novel blood-based biomarker assays to achieve high patient compliance, sensitivity and specificity. Methods and materials: CRC-specific DNA methylation biomarker candidates were identified using a genome-wide discovery strategy based on &amp;gt;4,000 Illumina 450K DNA methylation arrays. We designed digital droplet PCR assays to detect top biomarker candidates in circulating cell-free DNA (cfDNA) isolated from plasma. Initially, sensitivity and specificity of biomarkers were evaluated in validation cohort 1 consisting of plasma collected from 114 symptomatic CRC patients and 86 colonoscopy-confirmed healthy controls. To ensure comparable technical sensitivities for all assays in all samples, we used a fixed cfDNA input of 4,500 copies per ddPCR reaction. Next, we tested markers in validation cohort 2, a selected cohort of 8 mL plasma collected from participants in the Danish national screening program. This cohort comprised 131 asymptomatic CRCs and 869 controls enriched for comorbidities like adenomas, other cancers, diabetes, arthritis, hypertension, inflammatory bowel disease and arteriosclerosis. Results: Our discovery identified 12 DNA methylation biomarkers. Their performance was evaluated in validation cohort 1, and the three best performing markers showed a sensitivity of 89% at a specificity of 99%, which is superior to FOBT. Sensitivity increased with stage, reaching 65%, 85%, 78% and 83% for stage I-IV, respectively. When evaluated in validation cohort 2, the sensitivity was 51% for CRC samples with an input of at least 4,500 copies of cfDNA, and sensitivity was reduced equally for all disease stages compared with results from validation cohort 1. Sensitivity correlated positively with cfDNA input, and it is therefore critical to collect sufficient plasma volumes to achieve high sensitivities in clinical practice. Finally, specificity was 92.4 % even though we enriched for comorbidities in this cohort, and specificity was 95.7% in controls with a clean colon and no comorbidities. Conclusion: Our systematic biomarker discovery and validation study identified a three-gene DNA methylation panel with superior performance in plasma compared to FOBT. Citation Format: Sarah Østrup Jensen, Mai-Britt Worm Ørntoft, Nadia Øgaard, Helle Kristensen, Mads Heilskov Rasmussen, Jesper Bertram Bramsen, Peter Mouritzen, Mogens Rørbæk, Anne-Sofie Kannerup, Søren Laurberg, Hans Jørgen Nielsen, Claus Lindbjerg Andersen. Novel DNA methylation biomarkers show high sensitivity and specificity for blood-based detection of colorectal cancer - A clinical biomarker discovery and validation study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5604.

Prognostic value of primary tumour resection in synchronous metastatic colorectal cancer: Individual patient data analysis of first-line randomised trials from the ARCAD database

Indication for primary tumour resection (PTR) in asymptomatic metastatic colorectal cancer (mCRC) patients is unclear. Previous retrospective analyses suggest a survival benefit for patients who underwent PTR. The aim was to evaluate the prognostic value of PTR in patients with synchronous mCRC by analysis of recent large RCTs including systemic therapy with modern targeted agents.Individual patient data (IPD) of 3423 patients enrolled into 8 randomised controlled trials (RCTs) with first-line systemic therapy in the ARCAD (Aide et Recherche en Cancérologie Digestive) database were analysed.The number of patients with unresected synchronous mCRC, resected synchronous mCRC and metachronous mCRC was 710 (21%), 1705 (50%) and 1008 (29%), respectively. Adjusting for age, gender, performance status (PS) and prior chemotherapy, the unresected group had a significantly worse median overall survival (16.4 m) compared with the synchronous resected (22.2 m; hazard ratio [HR] 1.60, 95% CI 1.43–1.78) and metachronous (22.4 m; HR 1.81, 95% CI 1.58–2.07) groups. Similarly, median progression-free survival was significantly worse for the unresected group compared with the synchronous resected (HR 1.31, 95% CI 1.19–1.44) and metachronous (HR 1.47, 95% CI 1.30–1.66) groups. In a multivariate analysis, the observed associations remained significant.This largest IPD analysis of mCRC trials to date demonstrates an improved survival in synchronous mCRC patients after PTR. These results may be subject to bias since reasons for (non)resection were not available. Until results of ongoing RCTs are available, both upfront PTR followed by systemic treatment and upfront systemic treatment are considered appropriate treatment strategies.

An Analysis of Relationship Between RAS Mutations and Prognosis of Primary Tumour Resection for Metastatic Colorectal Cancer Patients

Background/Aims: Non-radical primary tumour resection (PTR) of asymptomatic metastatic colorectal cancer (mCRC) can prolong survival time of some patients. Patients with mutated RAS gene have worse survival outcome. This study aimed to investigate the impact of RAS gene mutations on the prognosis of asymptomatic unresectable mCRC patients who underwent PTR. Methods: A retrospective observational cohort study was deduced among mCRC patients who experienced PTR or had intact primary tumour (IPT). All of them had the primary tumour tissue genotyping tested for RAS (KRAS and NRAS) gene mutations. The tumour-related overall survival (OS) time and progression-free survival (PFS) time was estimated. From January 2011 to June 2014, 421 mCRC patients with asymptomatic, unresectable, metastatic disease were enrolled in this study. Among them, 282 patients underwent PTR and 139 patients had IPT. Results: The mutation rate of RAS was 53.8% (221/411). With a median followed-up time of 46.5 months, the overall survival time of mCRC patients harboring wtRAS or mtRAS was 28.0 versus 22.0 months (p = 0.043) in PTR group and was 21.6 versus 17.8 months (p=0.071) in IPT groups. A Multivariate regression analysis suggested that RAS gene (p=0.039, HR=1.288,95%CI [1.072∼2.911]), metastatic organ number (p=0.033, HR=3.091,95%CI [1.090∼5.755]) and systemic therapy response (p=0.019, HR=0.622,95%CI [0.525∼0.811]) were independent prognostic factors in PTR population. Conclusion: We found that wild-type RAS gene was a favorable factor for the asymptomatic unresectable mCRC patients experiencing PTR.

Interpretation of faecal haemoglobin concentration data in colorectal cancer screening and in assessment of symptomatic patients

Faecal immunochemical tests for haemoglobin (FIT) are used in asymptomatic colorectal cancer screening and in assessment of patients presenting in primary care with lower gastrointestinal symptoms. Many qualitative and quantitative FIT are available. Qualitative FIT give dichotomous results and the most important characteristic for interpretation of test results is the C 50 , often described as the cut-off. Qualitative FIT have different C 50 and thus give different clinical outcomes in screening. These are often stated to be simple, but both their performance and interpretation of results are fraught with difficulties. Quantitative FIT have many advantages. In screening, the faecal haemoglobin concentration (f-Hb) used as cut-off can be decided for each endeavour. As the f-Hb cut-off is increased, positivity rate, neoplasia detection rate and sensitivity decrease, while positive predictive value, specificity and interval cancer proportion increase. Different FIT give different outcomes and comparisons are best done using a consistent positivity rate. Many factors affect f-Hb and, although controversial, it has been suggested that sex and age stratified f-Hb cut-offs would have advantages. In consequence, current attention is becoming more focused on risk-scoring approaches incorporating f-Hb and on application of precision medicine strategies. FIT must have a low f-Hb in assessment of the symptomatic. The detection capability of FIT requires harmonisation with regard to terminology, determination and application in both academic research and routine clinical practice. The limit of quantitation is the lowest f-Hb that can be determined when some predefined analytical performance specifications (APS) for the characteristics of bias and imprecision (or total error) are satisfied. Proposals for interim APS are documented. The reporting of numerical data on f-Hb requires further consideration and creation and promulgation of consensus guidelines by international professional bodies.

Primary tumor location as a predictor of the benefit of palliative resection for colorectal cancer with unresectable metastasis

BackgroundIt is still under debate that whether stage IV colorectal cancer patients with unresectable metastasis can benefit from primary tumor resection, especially for asymptomatic colorectal cancer patients. Retrospective studies have shown controversial results concerning the benefit from surgery. This retrospective study aims to evaluate whether the site of primary tumor is a predictor of palliative resection in asymptomatic stage IV colorectal cancer patients.MethodsOne hundred ninety-four patients with unresectable metastatic colorectal cancer were selected from Sun Yat-sen University Cancer Center Database in the period between January 2007 and December 2013. All information was carefully reviewed and collected, including the treatment, age, sex, carcinoembryonic antigen, site of tumor, histology, cancer antigen 199, number of liver metastases, and largest diameter of liver metastasis. The univariate and multivariate analyses were used to detect the relationship between primary tumor resection and overall survival of unresectable stage IV colorectal cancer patients.ResultsOne hundred twenty-five received palliative resection, and 69 received only chemotherapy. Multivariate analysis indicated that primary tumor site was one of the independent factors (RR 0.569, P = 0.007) that influenced overall survival. For left-side colon cancer patients, primary tumor resection prolonged the median overall survival time for 8 months (palliative resection vs. no palliative resection: 22 vs. 14 months, P = 0.009); however, for right-side colon cancer patients, palliative resection showed no benefit (12 vs. 10 months, P = 0.910).ConclusionsThis study showed that left-side colon cancer patients might benefit from the primary tumor resection in terms of overall survival. This result should be further explored in a prospective study.

Abstract IA16: Current and emerging molecular diagnostic assays for colorectal cancer

Abstract IA16: Current and emerging molecular diagnostic assays for colorectal cancer

Genetic Biomarker Prevalence Is Similar in Fecal Immunochemical Test Positive and Negative Colorectal Cancer Tissue

Fecal immunochemical test (FIT) screening detects most asymptomatic colorectal cancers. Combining FIT screening with stool-based genetic biomarkers increases sensitivity for cancer, but whether DNA biomarkers (biomarkers) differ for cancers detected versus missed by FIT screening has not been evaluated in a community-based population. To evaluate tissue biomarkers among Kaiser Permanente Northern California patients diagnosed with colorectal cancer within 2years after FIT screening. FIT-negative and FIT-positive colorectal cancer patients 50-77years of age were matched on age, sex, and cancer stage. Adequate DNA was isolated from paraffin-embedded specimens in 210 FIT-negative and 211 FIT-positive patients. Quantitative allele-specific real-time target and signal amplification assays were performed for 7 K-ras mutations and 10 aberrantly methylated DNA biomarkers (NDRG4, BMP3, SFMBT2_895, SFMBT2_896, SFMBT2_897, CHST2_7890, PDGFD, VAV3, DTX1, CHST2_7889). One or more biomarkers were found in 414 of 421 CRCs (98.3%). Biomarker expression was not associated with FIT status, with the exception of higher SFMBT2_897 expression in FIT-negative (194 of 210; 92.4%) than in FIT-positive cancers (180 of 211; 85.3%; p=0.02). There were no consistent differences in biomarker expression by FIT status within age, sex, stage, and cancer location subgroups. The biomarkers of a currently in-use multi-target stool DNA test (K-ras, NDRG4, and BMP3) and eight newly characterized methylated biomarkers were commonly expressed in tumor tissue specimens, independent of FIT result. Additional study using stool-based testing with these new biomarkers will allow assessment of sensitivity, specificity, and clinical utility.

Asymptomatic primary tumour in incurable metastatic colorectal cancer: is there a role for surgical resection prior to systematic therapy or not?

IntroductionThe role of the resection of asymptomatic primary colorectal cancer in patients with incurable disease is questionable.AimTo evaluate the impact of the resection of asymptomatic primary tumour on overall survival in patients with unresectable distant metastases.Material and methodsPatients treated in the National Cancer Institute, Lithuania, in the period 2008–2012, were selected retrospectively. The main inclusion criteria were: metastatic colorectal cancer (mCRC), endoscopically and histologically confirmed adenocarcinoma, without any symptoms for urgent operation, and at least one cycle of palliative chemotherapy administered. Information on patients’ age, gender, tumour histology, localization of the tumour, regional lymph node involvement, number of metastatic sites, surgery and systemic treatment was collected prospectively. Eligible patients for the study were divided into two groups according to the initial treatment – surgery (patients who underwent primary tumour resection) and chemotherapy (patients who received chemotherapy without surgery). The impact of initial treatment strategy, tumour size and site, regional lymph nodes, grade of differentiation of adenocarcinoma and application of biotherapy on overall cumulative survival was estimated using the Kaplan-Meier method. To compare survival between groups the log-rank test was used. Cox regression analysis was employed to assess the effects of variables on patient survival.ResultsThe study group consisted of 183 patients: 103 men and 80 women. The median age was 66 years (range: 37–91). There were no notable imbalances with regard to age, gender, number of metastatic sites, metastases (such as pulmonary, peritoneal, liver, metastases into non-regional lymph nodes and other metastases), the number of received cycles of chemotherapy, first line chemotherapy type or biological therapy. Only 27 (14.8%) patients received biological therapy and the majority of them (n = 25, 92.6%) were treated with bevacizumab. For surgically treated patients 1-year survival was 71.2% (95% CI: 62.1–78.5) and 5-year survival was 4.0% (95% CI: 1.0–10.5). In the chemotherapy group, survival rates were lower – 43.9% (95% CI: 31.4–55.7) and 1.7% (95% CI: 0.1–8.1), respectively. Better survival rates were in the palliative surgery group. Multivariate analysis using the Cox proportional hazards model revealed that the initial palliative surgery and the application of biological therapy were statistically significant independent prognostic factors for survival.ConclusionsOur findings suggest that palliative resectional surgery for the primary tumour in patients with incurable mCRC improves survival. Of course, one can argue that patients in the surgery group were “less problematic”. Prospective randomized trials are needed to delineate precisely the role of palliative surgery of the primary tumour in these patients.