scholarly journals Predicting Microsatellite Instability Status in Colorectal Cancer Based on Triphasic Enhanced Computed Tomography Radiomics Signatures: A Multicenter Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Yuntai Cao ◽  
Guojin Zhang ◽  
Jing Zhang ◽  
Yingjie Yang ◽  
Jialiang Ren ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Computed Tomography ◽  
Validation Cohort ◽  
Excellent Performance ◽  
Training Cohort ◽  
Enhanced Ct ◽  
Venous Phase ◽  
Phase Models ◽  
Colorectal Cancer Patients ◽  
Radiomics Signature

BackgroundThis study aimed to develop and validate a computed tomography (CT)-based radiomics model to predict microsatellite instability (MSI) status in colorectal cancer patients and to identify the radiomics signature with the most robust and high performance from one of the three phases of triphasic enhanced CT.MethodsIn total, 502 colorectal cancer patients with preoperative contrast-enhanced CT images and available MSI status (441 in the training cohort and 61 in the external validation cohort) were enrolled from two centers in our retrospective study. Radiomics features of the entire primary tumor were extracted from arterial-, delayed-, and venous-phase CT images. The least absolute shrinkage and selection operator method was used to retain the features closely associated with MSI status. Radiomics, clinical, and combined Clinical Radiomics models were built to predict MSI status. Model performance was evaluated by receiver operating characteristic curve analysis.ResultsThirty-two radiomics features showed significant correlation with MSI status. Delayed-phase models showed superior predictive performance compared to arterial- or venous-phase models. Additionally, age, location, and carcinoembryonic antigen were considered useful predictors of MSI status. The Clinical Radiomics nomogram that incorporated both clinical risk factors and radiomics parameters showed excellent performance, with an AUC, accuracy, and sensitivity of 0.898, 0.837, and 0.821 in the training cohort and 0.964, 0.918, and 1.000 in the validation cohort, respectively.ConclusionsThe proposed CT-based radiomics signature has excellent performance in predicting MSI status and could potentially guide individualized therapy.

Pathway analysis of hypoxia-related factors in early colorectal cancer patients with poor prognosis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3613-3613
Author(s):  
Yingxin Tan ◽  
Yuming Rong ◽  
Zhaoliang Yu ◽  
Feng Gao ◽  
Yufeng Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Validation Cohort ◽  
Early Stage ◽  
Microarray Dataset ◽  
Gene Signature ◽  
Stage I ◽  
Training Cohort ◽  
Cell Cycle Pathway ◽  
Colorectal Cancer Patients

3613 Background: Colorectal cancer is one of the most common malignancies with a high mortality rate. Patients with stage I and stage II colorectal cancer have limited options for treatment. Hypoxia affects the activation and regulation of colorectal cancer cells and participates in its invasion and migration. However, there is lack of an accurate and non-invasive method for assessing tumor hypoxia. The aim of this study was developing and validating a hypoxia gene signature for predicting the outcome in stage I/II colorectal cancer patients. At the same time , we hypothesized that analysis of database of CIT microarray dataset could identify important biomarkers for stage I/II colorectal cancer patients. Methods: A total of 309 colorectal cancer patients of early stage with complete clinical information were enrolled for construction generation of hypoxia-related gene signature (HRGS) based on the CIT microarray dataset. 1877 colorectal cancer patients with complete prognostic information in 5 independent datasets were divided into a training cohort and two validation cohort (TCGA and meta-validation). Prognostic analysis was assessed in these cohort to evaluate the predictive value of HRGS. Results: A model of prognostic HRGS containing 14 hypoxia-related genes was developed. In training cohort and two validation cohorts, patients in hypoxia high-risk group satisfied by our HRGS had significant poor disease free survival compared with those in the in the low risk group (HR=4.35, 95% CI=2.30-8.23, P<0.001 in training cohort, HR=2.14, 95% CI=1.09-4.21, P=0.024 in TCGA cohort, HR=1.91, 95% CI=1.08-3.39, P=0.024 in meta-validation cohort). When compared with Oncotype DX, HRGS achieved an improved survival correlation in the training cohort (mean C-index, 0.80 vs 0.65, P<0.05) and the validation cohort (mean C-index, 0.70 vs 0.61 in the TCGA cohort, mean C-index, 0.68 vs 0.73 in the meta-validation cohort). Analysis of the data found that patients with low survival rates have significant relationships with genes regulated by the cell cycle pathway, such as mTROC1, E2F, G2-M, mitotic, oxidative phosphorylation, MYC, PI3K-AKT-mTOR (P<0.005). Conclusions: HRGS was a satisfactory prognostic prediction model for early stage colorectal patients. Hypoxia-related genes that regulate the cell cycle pathway were associated with prognosis in patients with stage I and stage II colorectal cancer. Further researches are needed to assess the clinical effectiveness of the system and the treatment options for biological targets.

scholarly journals Polymorphisms within Immune Regulatory Pathways Predict Cetuximab Efficacy and Survival in Metastatic Colorectal Cancer Patients

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2947
Author(s):  
Nico B. Volz ◽  
Diana L. Hanna ◽  
Sebastian Stintzing ◽  
Wu Zhang ◽  
Dongyun Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Validation Cohort ◽  
Direct Sequencing ◽  
Nucleotide Polymorphisms ◽  
Training Cohort ◽  
Regulatory Pathways ◽  
Dependent Cell ◽  
Colorectal Cancer Patients ◽  
In Fire

Cetuximab, an IgG1 EGFR-directed antibody, promotes antibody-dependent cell-mediated cytotoxicity. We hypothesized that single-nucleotide polymorphisms (SNPs) in immune regulatory pathways may predict outcomes in patients with metastatic colorectal cancer treated with cetuximab-based regimens. A total of 924 patients were included: 105 received cetuximab in IMCL-0144 and cetuximab/irinotecan in GONO-ASL608LIOM01 (training cohort), 225 FOLFIRI/cetuximab in FIRE-3 (validation cohort 1), 74 oxaliplatin/cetuximab regimens in JACCRO CC-05/06 (validation cohort 2), and 520 FOLFIRI/bevacizumab in FIRE-3 and TRIBE (control cohorts). Twelve SNPs in five genes (IDO1; PD-L1; PD-1; CTLA-4; CD24) were evaluated by PCR-based direct sequencing. We analyzed associations between genotype and clinical outcomes. In the training cohort; patients with the CD24 rs52812045 A/A genotype had a significantly shorter median PFS and OS than those with the G/G genotype (PFS 1.3 vs. 3.6 months; OS 2.3 vs. 7.8 months) in univariate (PFS HR 3.62; p = 0.001; OS HR 3.27; p = 0.0004) and multivariate (PFS HR 3.18; p = 0.009; OS HR 4.93; p = 0.001) analyses. Similarly; any A allele carriers in the JACCRO validation cohort had a significantly shorter PFS than G/G carriers (9.2 vs. 11.8 months; univariate HR 1.90; p = 0.011; multivariate HR 2.12; p = 0.018). These associations were not demonstrated in the control cohorts. CD24 genetic variants may help select patients with metastatic colorectal cancer most likely to benefit from cetuximab-based therapy.

scholarly journals The Prognostic Value of Preoperative Serum Lactate Dehydrogenase (LDH) Levels in Patients Underwent Curative-intent Hepatectomy For Colorectal Liver Metastases: A Two-Center Cohort Study

2021 ◽  
Author(s):  
Long Bai ◽  
Ze-Yu Lin ◽  
Yun-Xin Lu ◽  
Qin Chen ◽  
Han Zhou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lactate Dehydrogenase ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Colorectal Liver Metastases ◽  
Validation Cohort ◽  
Curative Intent ◽  
Training Cohort ◽  
Preoperative Serum ◽  
Colorectal Cancer Patients

Abstract Background: The prognostic value of lactate dehydrogenase (LDH) in colorectal cancer patients has remained inconsistent between non-metastatic and metastatic settings. So far very few studies have included LDH in prognostic analysis for patients with colorectal liver metastases (CRLM) who underwent curative-intent hepatectomy. Patients and Methods: Consecutive metastatic colorectal cancer patients who underwent curative-intent resection for CRLM from two Chinese medical centers treated in 2000-2019 were enrolled in the training cohort (434 patients) and the validation cohort (146 patients). Overall survival (OS) was the primary endpoint. Cox regression model was performed to identify the prognostic values of LDH and other clinicopathology variables. A modification of the established Fong scoring system comprising LDH was developed within this Chinese population.Results: In the training cohort, preoperative LDH > upper limit of normal (ULN) was the strongest independent prognostic factor both for RFS (HR 2.11, 95% confidence intervals [CIs], 1.54-2.89; P < .001) and OS (HR 2.41, 95% CI, 1.72-3.39; P < .001) in multivariate analysis. 5-year survival rates were 23.7% and 52.9% in the LDH > ULN group and LDH < ULN group, respectively. These data were also confirmed in the validation cohort and then in pooled cohort. Replacing carcinoembryonic antigen (CEA) with LDH in the Fong score contributed to an improvement in the predictive value.Conclusions: Preoperative serum LDH is a reliable and independent predictor for curative-intent CRLM resection. Composite of LDH and Fong score is a potential stratification tool for CRLM resection.

scholarly journals Computed Tomography-Based Radiomics Nomogram: Potential to Predict Local Recurrence of Gastric Cancer After Radical Resection

2021 ◽  
Vol 11 ◽  
Author(s):  
Liebin Huang ◽  
Bao Feng ◽  
Yueyue Li ◽  
Yu Liu ◽  
Yehang Chen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Gastric Cancer ◽  
Computed Tomography ◽  
Validation Cohort ◽  
Radical Resection ◽  
Curve Analysis ◽  
Internal Validation ◽  
Training Cohort ◽  
Clinical Model ◽  
Radiomics Signature

ObjectiveAccurate prediction of postoperative recurrence risk of gastric cancer (GC) is critical for individualized precision therapy. We aimed to investigate whether a computed tomography (CT)-based radiomics nomogram can be used as a tool for predicting the local recurrence (LR) of GC after radical resection.Materials and Methods342 patients (194 in the training cohort, 78 in the internal validation cohort, and 70 in the external validation cohort) with pathologically proven GC from two centers were included. Radiomics features were extracted from the preoperative CT imaging. The clinical model, radiomics signature, and radiomics nomogram, which incorporated the radiomics signature and independent clinical risk factors, were developed and verified. Furthermore, the performance of these three models was assessed by using the area under the curve (AUC) of receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA).ResultsThe radiomics signature, which was comprised of two selected radiomics features, namely, contrast_GLCM and dissimilarity_GLCM, showed better performance than the clinical model in predicting the LR of GC, with AUC values of 0.83 in the training cohort, 0.84 in the internal validation cohort, and 0.73 in the external cohort, respectively. By integrating the independent clinical risk factors (N stage, bile acid duodenogastric reflux and nodular or irregular outer layer of the gastric wall) into the radiomics signature, the radiomics nomogram achieved the highest accuracy in predicting LR, with AUC values of 0.89, 0.89 and 0.80 in the three cohorts, respectively. DCA in the validation cohort showed that radiomics nomogram added more net benefit than the clinical model within the range of 0.01-0.98.ConclusionThe CT-based radiomics nomogram has the potential to predict the LR of GC after radical resection.

Identifying an immune-related gene-pair for prognosis prediction of metastatic colorectal cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15565-e15565
Author(s):  
Qiqi Zhu ◽  
Du Cai ◽  
Wei Wang ◽  
Min-Er Zhong ◽  
Dejun Fan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Prognostic Value ◽  
Validation Cohort ◽  
Risk Group ◽  
High Risk Group ◽  
Related Gene ◽  
Training Cohort ◽  
Gene Pairs ◽  
Immune Related Gene

e15565 Background: Few robust predictive biomarkers have been applied in clinical practice due to the heterogeneity of metastatic colorectal cancer (mCRC) . Using the gene pair method, the absolute expression value of genes can be converted into the relative order of genes, which can minimize the influence of the sequencing platform difference and batch effects, and improve the robustness of the model. The main objective of this study was to establish an immune-related gene pairs signature (IRGPs) and evaluate the impact of the IRGPs in predicting the prognosis in mCRC. Methods: A total of 205 mCRC patients containing overall survival (OS) information from the training cohort ( n = 119) and validation cohort ( n = 86) were enrolled in this study. LASSO algorithm was used to select prognosis related gene pairs. Univariate and multivariate analyses were used to validate the prognostic value of the IRGPs. Gene sets enrichment analysis (GSEA) and immune infiltration analysis were used to explore the underlying biological mechanism. Results: An IRGPs signature containing 22 gene pairs was constructed, which could significantly separate patients of the training cohort ( n = 119) and validation cohort ( n = 86) into the low-risk and high-risk group with different outcomes. Multivariate analysis with clinical factors confirmed the independent prognostic value of IRGPs that higher IRGPs was associated with worse prognosis (training cohort: hazard ratio (HR) = 10.54[4.99-22.32], P < 0.001; validation cohort: HR = 3.53[1.24-10.08], P = 0.012). GSEA showed that several metastasis and immune-related pathway including angiogenesis, TGF-β-signaling, epithelial-mesenchymal transition and inflammatory response were enriched in the high-risk group. Through further analysis of the immune factors, we found that the proportions of CD4+ memory T cell, regulatory T cell, and Myeloid dendritic cell were significantly higher in the low-risk group, while the infiltrations of the Macrophage (M0) and Neutrophil were significantly higher in the high-risk group. Conclusions: The IRGPs signature could predict the prognosis of mCRC patients. Further prospective validations are needed to confirm the clinical utility of IRGPs in the treatment decision.

scholarly journals Monitoring treatment response in metastasic colorectal cancer: Economic evaluation of PrediCTC versus computed tomography scan

2019 ◽  
Vol 2019 ◽  
pp. 228424031985833
Author(s):  
Cristina Antón Rodríguez ◽  
Miguel Abal Posada ◽  
Lorena Alonso Alconada ◽  
Sonia Candamio Folgar ◽  
Rafael López López ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Computed Tomography ◽  
Side Effects ◽  
Adverse Events ◽  
Treatment Response ◽  
Cancer Patients ◽  
Societal Perspective ◽  
Cost Utility ◽  
Life Years ◽  
Colorectal Cancer Patients

Background: Late state colorectal cancer treatments have important side effects that should be avoided in patients where drug effectiveness is not adequate. PrediCTC is a new biomarkers blood test developed to determinate the chemotherapy response in unresectable metastatic colorectal cancer patients that could allow to obviate unnecessary treatments. Aim: To assess from the Spanish Societal Perspective the cost-utility of the test PrediCTC compared to the computed tomography in aim to evaluate chemotherapy treatment response in late stage colorectal cancer patients. Methods: Based on the results of Barbazán et al., a Markov model has been developed, in which the different lines and cycles that the colorectal patient can receive and how they can move between them according to the computed tomography or PrediCTC have been represented. The effectiveness has been expressed in quality adjusted life years (QALYs), avoiding adverse events. Results: Base case analysis shows savings in different types of costs for PrediCTC (per patient): €14.30 in those arise from adverse events, €22,345.73 in chemotherapy costs, €4849.61 in other direct costs, and €306.21 in indirect costs. Although computed tomography 12-week assessed patients gain 0.17 QALYs compared with PrediCTC. Conclusions: From the Spanish Societal Perspective, PrediCTC is not a cost-utility option but allows to identify earlier patients who are not benefiting from first-line chemotherapy avoiding unnecessary side effects and costs.

scholarly journals Assessment of the Clinical Usefulness of Preoperative Computed Tomography in Colorectal Cancer Patients Who Received Unplanned Reoperation

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Rui Wang ◽  
Yi Gao ◽  
Jia-Yi Li ◽  
Zhong-Hui Wang ◽  
Qin-qing Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Computed Tomography ◽  
Postoperative Complications ◽  
Cancer Patients ◽  
Ct Imaging ◽  
Preoperative Imaging ◽  
Imaging Evaluation ◽  
Preoperative Ct ◽  
Colorectal Cancer Patients ◽  
Statistical Indicators

Background. In the unplanned reoperation of colorectal cancer patients, computed tomography (CT) is increasingly utilized to locate postoperative complications and previously unlocalized lesions. The purpose of this study is to explore the application of CT in the mortality and complications of the reoperation of colorectal cancer. Patients and Methods. We performed a retrospective review of collected data from the colorectal surgeries of 90 identified colorectal cancer patients who received an unplanned reoperation from 2010 to 2018. Patients were stratified according to those with preoperative CT imaging (CT group, n=36) and those without preoperative CT imaging (NCT group, n=54). Twenty-four statistical indicators of each patient were studied, including their preoperative risk, surgical characteristics, and postoperative outcomes, and satisfaction was evaluated. All data were statistically analysed for predicting postoperative complications by univariate and multivariate logistic regression analyses. Results. Ninety patients received an unplanned reoperation in the study, and 40% (36/90) of these patients underwent preoperative CT examination. Patients’ risk factors were similar between CT and NCT groups. Preoperative imaging was more commonly performed for reoperative new anastomosis + ileostomy but less common for reoperative Dixon’s procedure. The operative duration of the NCT group was longer (139 vs. 104 min, respectively, P=0.01). Preoperative NCT examination (OR 1.24; 95% CI=1.09‐1.42; P=0.01) was an independent predictor of postoperative complications. Importantly, three patients died after an unplanned reoperation for colorectal cancer, which occurred only in the NCT group (5.6% vs. 0.0%, P=0.01). Conclusion. The use of conventional preoperative CT optimizes the choice of the surgical site and the strategy of laparotomy, so as to reduce the length of operation. Preoperative imaging evaluation should be performed for patients undergoing repeat abdominal surgery.

scholarly journals The Prognostic Significance of Tumor Deposit Count for Colorectal Cancer Patients after Radical Surgery

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Kuo Zheng ◽  
Nanxin Zheng ◽  
Cheng Xin ◽  
Leqi Zhou ◽  
Ge Sun ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Value ◽  
Validation Cohort ◽  
Cutoff Point ◽  
Disease Specific Survival ◽  
Optimal Cutoff ◽  
Training Cohort ◽  
Tumor Deposit ◽  
Optimal Cutoff Point ◽  
Disease Specific

Background. The prognostic value of tumor deposit (TD) count in colorectal cancer (CRC) patients has been rarely evaluated. This study is aimed at exploring the prognostic value of TD count and finding out the optimal cutoff point of TD count to differentiate the prognoses of TD-positive CRC patients. Method. Patients diagnosed with CRC from Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2010, to December 31, 2012, were analyzed. X-tile program was used to identify the optimal cutoff point of TD count in training cohort, and a validation cohort was used to test this cutoff point after propensity score matching (PSM). Univariate and multivariate Cox proportional hazard models were used to assess the risk factors of survival. Results. X-tile plots identified 3 (P<0.001) as the optimal cutoff point of TD count to divide the patients of training cohort into high and low risk subsets in terms of disease-specific survival (DSS). This cutoff point was validated in validation cohort before and after PSM (P<0.001, P=0.002). More TD count, which was defined as more than 3, was validated as an independent risk prognostic factor in univariate and multivariate analysis (P<0.001). Conclusion. More TD count (TD count≥4) was significantly associated with poor disease-specific survival in CRC patients.

Chest Computed Tomography Screening in Colorectal Cancer Patients

2009 ◽  
Vol 33 (6) ◽  
pp. 1325-1326 ◽  
Author(s):  
Carl Chartrand-Lefebvre ◽  
Réal Lapointe ◽  
Louise Samson ◽  
Marie-Pierre Cordeau ◽  
Julie Prenovault
Keyword(s):  
Colorectal Cancer ◽  
Computed Tomography ◽  
Cancer Patients ◽  
Chest Computed Tomography ◽  
Colorectal Cancer Patients
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