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Objective:To develop and validate a radiomics biomarker for the preoperative estimation of the tumor-stroma ratio (TSR) in rectal cancer.Methods:From January 2016 to March 2019, totally 149 patients with rectal cancer were enrolled retrospectively at Fudan University Shanghai Cancer Center. The patients were divided into two cohorts using a random number table, 119 in the training and 30 in validation cohorts. The patients were classified into the TSR-high group (TSR>50%) and TSR-low group (TSR≤50%) according to the content of tumor stroma in pathology. All patients underwent T 2WI, enhanced T 1WI and DWI. The lesions on the T 2WI, enhanced T 1WI, DWI and ADC images were delineated and radiomics features were extracted. A radiomics signature (rad-score) was generated by using the least absolute shrinkage and selection operator (LASSO) algorithm. The Spearman correlation coefficients were used to determine the association between rad-score and TSR. The area under the ROC curve (AUC) was used to assess the diagnostic performance of the rad-score. The reliability of the rad-score was quantified by calculating the sensitivity, specificity and accuracy of TSR. Results:With LASSO, a rad-score with 13 radiomics parameters was successfully constructed and was positively correlated with TSR score in the training ( r=0.72, P<0.001) and validation cohorts ( r=0.46, P=0.011). In the training cohort, the AUC of the rad-score was 0.940, with the sensitivity, specificity, accuracy of 100%, 87.3%, 92.4%. In the validation cohort, the AUC was 0.796, with the sensitivity, specificity, accuracy of 83.3%, 67.7%, 73.3%. Conclusions:The rad-score is of promising value for TSR estimation in rectal cancer. It is a promising supplement for patient stratification and may inform decision-making.
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Colorectal cancer is one of the most common malignant tumors in the world, threatening human health. The treatment strategy of stage II and stage III colorectal cancer has changed from surgery alone to multidisciplinary mode emphasizing perioperative treatment. The indication of adjuvant chemotherapy for stage II colon cancer is still defined by high-risk factors, but only microsatellite status and BRAF gene mutation can help predict efficacy of chemotherapy. Combined chemotherapy is the main adjuvant therapy for stage III colon cancer. The recommended course of adjuvant chemotherapy is 6 months. Based on the results of the IDEA study, the three-month CapeOX regimen (oxaliplatin and capecitabine) is recommended for the treatment of patients with T1-3 and N1 tumors. Neoadjuvant chemotherapy for locally advanced colon cancer is still in the exploratory stage of clinical trials. The difference between the treatment of rectal cancer and colon cancer lies in the application of radiotherapy. Chemoradiotherapy combined with TME (total mesorectal excision) surgery and adjuvant chemotherapy has become the standard treatment for locally advanced rectal cancer. Nowadays, the research hotspots in neoadjuvant therapy of rectal cancer include neoadjuvant chemotherapy and total neoadjuvant therapy (TNT). This article will review the progress of perioperative treatment for colorectal cancer.
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<p><b>OBJECTIVE</b>To explore the trend change of the morbidity and mortality of colorectal cancer in China in order to provide reference to the prevention and control of colorectal cancer.</p><p><b>METHODS</b>According to the 1-3 volumes of "Pathogenesis and death of malignancies in pilot program city and county of China", "Pathogenesis and death of cancer in China"(2003-2007) and "Registration annual report of tumor in China" published in 2011 and 2012, data of pathogenesis and death of colorectal cancer from 10 tumor registration spots, including Beijing urban, Shanghai urban, Wuhan urban, Harbin urban (defined as city urban), and Hebei Ci County, Jiangsu Qidong District, Zhejiang Jiashan District, Guangxi Fusui County, Fujian Changle District, Henan Lin County (defined as rural district), between 1988 and 2009 were collected. The morbidity and mortality were elucidated with world population standardized rate. Ratio of pathogenesis to death was calculated with crude rate of morbidity and mortality. Data of 22 years were enrolled into the linear regression analysis to calculate the annual change rate of morbidity and mortality statistically.</p><p><b>RESULTS</b>(1) Colon cancer: morbidity presented increasing trend; male morbidity in city urban increased faster; mortality presented increasing trend as well; no significant difference of increasing velocity was observed between city urban and rural district; morbidity and mortality in city urban were higher compared to rural district; morbidity and mortality of males were higher compared to females; except stable Fujian Changle District, ratio of pathogenesis to death presented decreased trend in Shanghai urban and Hebei Ci County, and increased trend in other 7 spots (all P<0.05). (2) Rectal cancer: morbidity presented increasing trend, and its increasing velocity of city urban was faster compared to rural district; mortality presented decreased trend, especially in females, and this trend in rural district was worse compared to city urban; morbidity and mortality of males were higher compared to females, while no significant difference was observed between city urban and rural district; morbidity and mortality of males and females in Zhejiang Jiashan District were all decreased (all P<0.05); except stable Harbin city, ratio of pathogenesis to death presented increased trend in other 9 spots (all P<0.05). (3) Ratio analysis of morbidity and mortality showed that percentage of colon cancer increased gradually in all 10 spots between 1988-2009.</p><p><b>CONCLUSIONS</b>In the past 2 decades, the overall morbidity and mortality of colorectal cancer are higher in city urban and in male as compared with rural district and female. Colon cancer has higher morbidity than rectal cancer and its morbidity and mortality present increased trend, while morbidity of rectal cancer presents increased trend but its mortality presents decreased trend.</p>
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Colorectal cancer is the third high-incidence of malignant tumors in the world, and also a kind of tumor with good biological behavior and good efficacy. Colorectal cancer heterogeneity is a very important trait of its biological behavior, which can be reflected in many different aspects, including tumor type, pathogenesis, molecular phenotyping and time-space heterogeneity. Different pathogenesis produces different tumor phenotypes, which are generated in the process of natural evolution and intervention. Various phenotypes show the difference among different individuals of colorectal cancer, in terms of clinical characteristics, treatment response and prognosis. Understanding the heterogeneity of colorectal cancer has important clinical value for individualized treatment.
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Familial adenomatous polyposis (FAP) is one of the most common hereditary colorectal cancers. Its intestinal and extra-intestinal manifestations are correlated with mutation sties of the APC gene. Potential gene modulation sites in patients who have typical clinical manifestations but with unidentified APC mutations are also discussed, which included MUTYH gene, AXIN gene and certain epigenetic changes. With the generalization of Precision Medicine, to offer individualized treatment and surveillance strategy based on the genotype-phenotype correlation will be of great value for FAP patients. This review focuses on the research advance in genotype - phenotype correlation studies of FAP patients.
Subject(s)
Humans , Adenomatous Polyposis Coli , Genetics , Axin Protein , Genetics , DNA Glycosylases , Genetics , Genes, APC , Genetic Association Studies , Genetic Predisposition to Disease , Mutation , beta Catenin , GeneticsABSTRACT
Background and purpose:Microsatellite instability (MSI) status is commonly applied to predict the prognosis and chemosensitivity in stage Ⅱ and stage Ⅲ colorectal cancer patients. However, researches of its function on metastasis colorectal cancer are limited. This study investigated its value on prognosis and chemosensitivity in metastatic colorectal cancer (CRC) patients.Methods:We retrospectively investigated tumor tissues from metastasis CRC patients who were treated with oxaliplatin and 5-FU-based therapy regimens (FOLFOX and XELOX). Immunostaining of proteins of the mismatch repair genehMLH1,hMSH2,hMSH6 andhPMS2 was performed. Prognostic value and chemosensitivity in patients with MSI status were also determined.Results:Clinical features from 113 patients were analyzed. No cor-relation of overall survival (OS) and chemosensitivity with MSI status was found. We further investigated 79 patients with synchronous metastasis and palliatively tumor resection. Median progression free survival (PFS) from 22 MSI patients was significant longer than that in 57 MSS patients (19.9 monthsvs 7 months,P=0.005). No significant difference was seen in OS comparison (P=0.07). MSI status was also an independent prognostic factors of PFS by Cox multivariate analysis (MSS/MSI,HR=2.079,P=0.043). Moreover, in this group, MSI patients had improved disease control rate (59.1%vs 31.6%, P=0.025) in chemosensitivity analysis than MSS patients.Conclusion:A better PFS in MSI patients with synchronous metastasis and palliative tumor resection was found after treated with oxaliplatin and 5-FU-based therapy and a better chemosensitivity in MSI patients was also found.
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<p><b>OBJECTIVE</b>To investigate the differences of clinical characteristics and molecular features among colorectal cancer subsides and provide evidence for colorectal cancer protection, diagnosis and treatment.</p><p><b>METHODS</b>All of 4 316 colorectal patients from Shanghai cancer center were selected for clinical character analysis, among which, 2 224 subjects for molecular feature analysis. Clinic pathological characteristics like age, gender, tumor types, histological types, differentiation and T-stage, as well as molecular features like hMLH1, hMSH2, CD44, p21, p53, COX2,E-cadherin, Her2 and Ki-67, were involved into this research.</p><p><b>RESULTS</b>It showed that compared with left-sided colon and rectal cancers, right-sided cancers occurred more in women (46.0% (541/1 176); 39.2% (424/1 083); 41.2% (848/2 057), respectively, χ² = 11.85, P < 0.01), had more mucinous or signet-ring carcinoma (12.0% (128/1 064), 5.8% (56/960), 4.0% (75/1 859), respectively, χ² = 31.27, P < 0.01), poor differentiated carcinoma (32.1% (343/1 069), 19.5% (201/1 033), 19.3% (380/1 967), respectively, χ² = 72.66, P < 0.01) , and advanced T stage (87.9% (992/1 129), 83.2% (869/1 045), 72.2% (1 486/2 057), respectively, χ² = 121.44, P < 0.01). Meanwhile, the rates of hMLH1 were higher in right-sided colon cancers when compared with rectal cancers (13.4% (59/439) vs 8.5% (88/1 035), OR (95%CI): 1.67 (1.18-2.37)), as well as the rates of hMSH2 negative expression (4.9% (22/452) vs 2.4% (26/1 083), OR (95% CI): 2.08(1.17-3.71)). The rates of p53 positive expression were higher in right-sided colon cancers when compared with rectal cancers (76.2% (321/421) vs 68.4%, (776/1 134), OR (95% CI): 0.68 (0.52-0.87)). Compared with right-sided colon cancers, the rates of Her2 positive expression were higher in rectal cancers (19.3% (176/913) vs 13.2% (45/340), OR (95% CI): 1.57 (1.10-2.23)) , as well as the rates of Ki-67 expression which was positive in more than 50% cells (73.6% (840/1 141) vs 65.6% (299/456), OR (95% CI): 0.68 (0.54-0.86)).</p><p><b>CONCLUSION</b>There are specific characteristics in right-sided colon cancers. The difference of molecular features between right-sided colon and rectal cancers are more significant.</p>