scholarly journals A deep learning quantified stroma-immune score to predict survival of patients with stage II–III colorectal cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zeyan Xu ◽  
Yong Li ◽  
Yingyi Wang ◽  
Shenyan Zhang ◽  
Yanqi Huang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Deep Learning ◽  
External Validation ◽  
Survival Rates ◽  
Tnm Stage ◽  
Stage Ii ◽  
Disease Stage ◽  
Immune Score ◽  
Development Group

Abstract Background Profound heterogeneity in prognosis has been observed in colorectal cancer (CRC) patients with intermediate levels of disease (stage II–III), advocating the identification of valuable biomarkers that could improve the prognostic stratification. This study aims to develop a deep learning-based pipeline for fully automatic quantification of immune infiltration within the stroma region on immunohistochemical (IHC) whole-slide images (WSIs) and further analyze its prognostic value in CRC. Methods Patients from two independent cohorts were divided into three groups: the development group (N = 200), the internal (N = 134), and the external validation group (N = 90). We trained a convolutional neural network for tissue classification of CD3 and CD8 stained WSIs. A scoring system, named stroma-immune score, was established by quantifying the density of CD3+ and CD8+ T-cells infiltration in the stroma region. Results Patients with higher stroma-immune scores had much longer survival. In the development group, 5-year survival rates of the low and high scores were 55.7% and 80.8% (hazard ratio [HR] for high vs. low 0.39, 95% confidence interval [CI] 0.24–0.63, P < 0.001). These results were confirmed in the internal and external validation groups with 5-year survival rates of low and high scores were 57.1% and 78.8%, 63.9% and 88.9%, respectively (internal: HR for high vs. low 0.49, 95% CI 0.28–0.88, P = 0.017; external: HR for high vs. low 0.35, 95% CI 0.15–0.83, P = 0.018). The combination of stroma-immune score and tumor-node-metastasis (TNM) stage showed better discrimination ability for survival prediction than using the TNM stage alone. Conclusions We proposed a stroma-immune score via a deep learning-based pipeline to quantify CD3+ and CD8+ T-cells densities within the stroma region on WSIs of CRC and further predict survival.

scholarly journals Expression Patterns of Microenvironmental Factors and Tenascin-C at the Invasive Front of Stage II And III Colorectal Cancer: Novel Tumor Prognostic Markers

2021 ◽  
Author(s):  
Mai Hashimoto ◽  
Noriyuki Uesugi ◽  
Mitsumasa Osaka ◽  
Naoki Yanagawa ◽  
Koki Otsuka ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Prognostic Markers ◽  
Multivariate Analyses ◽  
Expression Patterns ◽  
Stage Ii ◽  
High Expression ◽  
Disease Stage ◽  
Neoplastic Progression ◽  
Tenascin C

Abstract Background. Biological markers expressed in cancer cells and the surrounding cancer-associated fibroblasts (CAF) can be used for prediction of patient prognosis in colorectal cancer (CRC). Here, we used immunohistochemical techniques to evaluate cancer cells’ expression of specific biomarkers that are closely associated with neoplastic progression. Patients and Methods. Immunohistochemical markers included Ki-67, p53, β-catenin, MMP7, E-cadherin and HIF1-α. We also characterized microenvironmental markers expressed by CAF, including expression of α-smooth muscle actin, CD10, podoplanin, fibroblast specific protein 1, platelet derived growth factor β, fibroblast association protein, tenascin-C (TNC), ZEB1 and TWIST1. The study population consisted of 286 CRC patients with stage II and III disease. Stage II and III CRC were divided into a first and a second cohort (for validation). The CRCs were stratified using cluster analysis. To identify the utility of prognostic markers in stage II and III CRC, univariate and multivariate analyses were performed in both cohorts. Results. Stage II and III CRCs were stratified into 3 subgroups. Specific subgroups were significantly correlated to disease-free survival using univariate and multivariate analyses in the first cohort. High expression of TNC was identified as a single prognostic marker in both cohorts by univariate and multivariate analyses. Conclusions. We suggest that the presence of a specific subgroup defined by multiple markers can be used for prediction of CRC outcome in stages II and III. In addition, we showed that high expression of TNC was correlated with a poorer prognosis in stages II and III of CRC.

Is more aggressive lymph node assessment associated with improved survival in stage II-III colorectal cancer? Evidence from the Surveillance, Epidemiology and End Results (SEER) cancer registry

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4048-4048
Author(s):  
Y. Yeh ◽  
Q. Cai ◽  
J. Chao ◽  
M. Russell
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
Proportional Hazards ◽  
Survival Rates ◽  
Cox Proportional Hazards ◽  
Stage Ii ◽  
Rank Test ◽  
Stage Iiia ◽  
Nccn Guidelines ◽  
Cox Proportional Hazards Models

4048 Background: NCCN guidelines recommend assessment of =12 lymph nodes (LN) to improve accuracy in colorectal cancer (CRC) staging. Previous studies have used various cut-points to assess the relationship between the number of LN sampled and survival. The association between NCCN guideline-compliant nodal sampling and survival is assessed, while controlling for other risk factors. Methods: We selected 145,485 adult patients newly diagnosed with stage II or III from SEER during 1990–2003. Kaplan-Meier curves were compared using the log-rank test. Cox proportional hazards models were constructed to determine the effect of sampling ≥ 12 LN on survival. Results: Median patient follow-up was 5.7 years. The table shows overall survival rates in CRC patients with < 12 versus =12 LN assessed: After adjusting for age, sex, tumor size and grade, sampling ≥ 12 LN was independently associated with improved survival. For patients with =12 versus <12 LN assessed, survival increased by 13% for stage IIa [HR=0.75; 95%CI 0.72–0.78; p< .001], 16% for stage IIb [HR=0.69; 95%CI 0.67- 0.71; p< .001], 12% for stage IIIb [HR=0.75; 95%CI 0.72–0.77], and 10% for stage IIIc [HR=0.85, 95%CI 0.81–0.89]. The association was not statistically significant for stage IIIa patients. Conclusion: Consistent with previous reports, this analysis found that optimal nodal sampling increased survival across stage II and III, specifically when ≥ 12 LN are sampled and when controlling for other risk factors. Furthermore, the results underscore the need for adhering to the NCCN guidelines. The lack of a statistically significant association in stage IIIa patients may be due to small cohort size. [Table: see text] [Table: see text]

The effect of chemotherapy on overall survival of stage II colon cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 625-625
Author(s):  
M. Omaira ◽  
M. Mozayen ◽  
K. Katato
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Survival Rate ◽  
Survival Rates ◽  
Stage Ii ◽  
Disease Stage ◽  
Overall Survival Rate ◽  
Significant Difference ◽  
Stage Ii Colon Cancer

625 Background: Surgical resection of local colon cancer is the only curative treatment, at the same time adjuvant chemotherapy is clearly shown to be beneficial as the standard of care for node positive disease (stage III) colon cancer. However the role of chemotherapy for stage II colon cancer treatment is still conflicting. We aim to compare the overall survival rate of stage II colon cancer patient's with and without chemotherapy. Methods: A retrospective observational study was conducted from 1990-2006. Patients with stage II colon cancer were included. Patient's characteristics including age, gender, common site of involvement, histology patterns, overall survival rate and treatment with chemotherapy were recorded. Results: A total of 138 consecutive patients were identified from 1990-2006. The median age was 68 (21-91) year, males (44%), African Americans (47.6%). The most common sites of the primary tumor were sigmoid and cecum (22.4%) each. Adenocarcinoma being the most common pathology. Majority of the patients (86.2%) were found to have T 3 tumors. Of the patients that received chemotherapy (29/44) 66% had an overall survival rate of three years or more, whereas (53/94) 57% of the patients who did not receive chemotherapy had a survival rate of three years or more. The difference of survival rates between the two groups of patients was not statistically significant. Conclusions: The role of chemotherapy in stage II colon ancer is still controversial. There was no significant difference in overall survival between the two groups who did and did not receive chemotherapy; thus more studies are warranted to explore the factors that predict the survival of stage II colon cancer. No significant financial relationships to disclose.

scholarly journals Identification of Two Novel Circular RNAs Deriving from BCL2L12 and Investigation of Their Potential Value as a Molecular Signature in Colorectal Cancer

2020 ◽  
Vol 21 (22) ◽  
pp. 8867
Author(s):  
Paraskevi Karousi ◽  
Pinelopi I. Artemaki ◽  
Christina D. Sotiropoulou ◽  
Spyridon Christodoulou ◽  
Andreas Scorilas ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Tnm Stage ◽  
Stage Ii ◽  
Molecular Signature ◽  
Circular Rnas ◽  
Tissue Samples ◽  
Related Family

The utility of circular RNAs (circRNAs) as molecular biomarkers has recently emerged. However, only a handful of them have already been studied in colorectal cancer (CRC). The purpose of this study was to identify new circRNAs deriving from BCL2L12, a member of the BCL2 apoptosis-related family, and investigate their potential as biomarkers in CRC. Total RNA extracts from CRC cell lines and tissue samples were reversely transcribed. By combining PCR with divergent primers and nested PCR followed by Sanger sequencing, we were able to discover two BCL2L12 circRNAs. Subsequently, bioinformatical tools were used to predict the interactions of these circRNAs with microRNAs (miRNAs) and RNA-binding proteins (RBPs). Following a PCR-based pre-amplification, real-time qPCR was carried out for the quantification of each circRNA in CRC samples and cell lines. Biostatistical analysis was used to assess their potential prognostic value in CRC. Both novel BCL2L12 circRNAs likely interact with particular miRNAs and RBPs. Interestingly, circ-BCL2L12-2 expression is inversely associated with TNM stage, while circ-BCL2L12-1 overexpression is associated with shorter overall survival in CRC, particularly among TNM stage II patients. Overall, we identified two novel BCL2L12 circRNAs, one of which can further stratify TNM stage II patients into two subgroups with substantially distinct prognosis.

Racial disparities in survival after young-onset colorectal cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 524-524
Author(s):  
Elena Martinez Stoffel ◽  
Julie Ruterbusch ◽  
Laura S. Rozek ◽  
Michele L. Cote
Keyword(s):  
Colorectal Cancer ◽  
Racial Disparities ◽  
Early Stage ◽  
Tumor Biology ◽  
Cox Proportional Hazards ◽  
Stage Ii ◽  
Disease Stage ◽  
Early Stage Disease ◽  
Young Onset ◽  
Black And White

524 Background: Despite overall reductions in morbidity and mortality from colorectal cancer (CRC), racial disparities persist. In addition, incidence among individuals age <50 is rising. Our aim was to compare survival of young onset CRC cases diagnosed in black and white individuals. Methods: Using data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program we identified individuals with CRC between the ages of 20 to 49, diagnosed in 2000-2008. Kaplan-Meier and Cox proportional hazards models were used to compare stage-specific 5 year survival between black and white individuals with young onset CRC. Results: A total of 26,236 incident young onset CRC cases (22,121 white, 4,115 black) were identified during the 9 year study period. Overall survival at 5 years following CRC diagnosis was 54.8% among blacks and 67.4% among whites (p<0.001), with blacks having a significantly higher hazard of death after adjusting for age, sex, stage, tumor site, and treatment history (HR 1.34, 95% CI 1.26-1.43). Stratifying by stage at CRC diagnosis, blacks had worse survival at every disease stage compared with whites, with the greatest racial disparities observed among stage II cancers of colon (HR 1.68 95% CI 1.38-2.04) and stage II and III cancers of the rectum (HR 1.78, 95% CI 1.51-2.09, and HR 1.86, 95% CI 1.54-2.24, respectively). Conclusions: Survival after diagnosis of CRC at young age is significantly worse among blacks compared to whites, even among individuals with early stage disease. These findings suggest that differences in tumor biology may play a role in racial disparities in CRC outcomes, which may have implications for adjuvant treatment.

Selecting patients with stage II/III colorectal cancer for 5-fluorouracil-based adjuvant chemotherapy using proteomic analysis.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 708-708
Author(s):  
Dongyao Yan ◽  
Ji Hyung Hong ◽  
Hee Yeon Lee ◽  
Jae Ho Byun ◽  
Fabiola Cecchi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mass Spectrometry ◽  
Cohort Analysis ◽  
Tumor Stage ◽  
Stage Ii ◽  
Disease Stage ◽  
Rank Test ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Student’S T

708 Background: 5-fluorouracil (5-FU) is a common adjuvant treatment for stage III and high-risk stage II colorectal cancer (CRC). However, about 20% of patients relapse within 48 months of treatment with 5-FU, even when combined with oxaliplatin. To improve patient selection, tumor biomarkers that predict sensitivity to 5-FU have been proposed. These include proteins involved in 5-FU activation or metabolism such as uridine-cytidine kinase 2 (UCK2) and thymidylate synthase (TYMS). We used multiplexed mass spectrometry to evaluate the utility these biomarkers in the archived tumor samples of patients with stage II/III CRC. Methods: Tumor samples were from 143 patients with stage II/III CRC who received adjuvant 5-FU, folinic acid, and oxaliplatin during 2000-2014; 83% of patients received 12 cycles and the others received ≤ 11 cycles. Tumor cells were microdissected and solubilized, and 67 candidate biomarkers were quantitated using mass spectrometry. Overall survival (OS) and relapse-free survival (RFS) were assessed using the Kaplan-Meier method and log-rank test. Protein expression by tumor stage, lymph node (LN) status, tumor sidedness was compared using the Student’s t-test. Results: Of 143 patients, 45 had recurrence and 98 patients did not. UCK2 was detected in all samples, ranging from 187 to 1606 attomoles per microgram of total protein (amol/µg). Patients with UCK2 expression above 335 amol/μg (n = 109) had significantly longer OS than patients with lower expression (n = 34; HR: 0.42; p= 0.009). There was no significant difference in RFS (HR: 0.6; p= 0.088). UCK2 expression did not differ by disease stage, LN metastasis status, or tumor sidedness. TYMS expression was not associated with survival in this cohort. Analysis of other biomarkers associated with response to 5-FU and platinum is in progress. Conclusions: In stage II/III CRC, UCK2 expression above 335 amol/μg identifies a subgroup of 5-FU-treated CRC patients with longer survival, suggesting that quantitated UCK2 has potential for use in selecting patients for treatment. These findings warrant validation in larger cohorts.

Impact of primary tumor size/horizontal extent on survival in colorectal cancer.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 125-125
Author(s):  
Olatunji B. Alese ◽  
Wei Zhou ◽  
Renjian Jiang ◽  
Katerina Mary Zakka ◽  
Walid Labib Shaib ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Tumor Size ◽  
Primary Tumor ◽  
Survival Rates ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Primary Tumor Size ◽  
The Impact

125 Background: Pathologic staging in colorectal cancer (CRC) is crucial in patient management. Data regarding the impact of size/horizontal tumor extent is limited, contradictory and currently excluded from the American Joint Committee on Cancer (AJCC) staging model. However, a previously published SEER analysis showed that AJCC stages I and IIIA have similar 2- and 5- year survival rates, and worse rates for stage II. Using the largest cohort to date, we report the impact of primary tumor size on CRC survival. Methods: Data were obtained from all US hospitals that contributed to the National Cancer Database (NCDB) between 2010 and 2015. Univariate and multivariate analyses were performed to identify factors associated with patient outcome. Kaplan-Meier analysis and Cox proportional hazards models were used to assess the association between tumor/patient characteristics and overall survival (OS). Results: A total of 61,145 patients were identified with a similar gender distribution (M/F:50.9%/49.1%). The mean age was 62.7years (SD+/-14.1) and 82% were non-Hispanic Whites. Majority had colon primary (82.7%) and 82.4% had microsatellite stable (MSS) disease. Distribution across stages I-IV was 20.1%, 32.1%, 34.7% and 13.2% respectively. Among the total study population, AJCC stage correlated closely with OS on multivariate analysis (HR 1.49, 2.29, 8.38 for stages II to IV compared to stage I), while the distinguishing power for tumor size was relatively mild (HR 1.19 and 1.33 for 5-10 cm and >5cm compared to <5cm). Among patients with stage II disease, tumors >10cm were associated with worse survival compared to those <5cm (HR 1.2; 1.03-1.39; p=0.22). Stage III disease also had differential survival rates; patients with tumors 5-10cm (HR 1.21; 1.14-1.28; p<0.001) and >10cm (HR 1.57; 1.37-1.80; p<0.001) had worse survival than those <5cm. Patients with stage II who did not receive adjuvant chemotherapy (CTX) had worse survival outcomes (HR 1.29; 1.08-1.55; p=0.005) compared to stage III disease who did. Accounting for tumor size, there was no statistically significant survival differences between stage I patients and stages II and III patients who received adjuvant chemotherapy. Conclusions: Tumors larger than 10cm have inferior outcomes among patients in the same AJCC stages. Stage II patients without adjuvant CTX did worse than stage III with CTX. Further studies are needed to clarify the role of tumor size in staging models. [Table: see text]

SP1.1.5Association between prior screening involvement and presentation and outcomes in patients with colorectal cancer

2021 ◽  
Vol 108 (Supplement_7) ◽  
Author(s):  
Afnan Mshihadani ◽  
Allan M Golder ◽  
David Mansouri ◽  
Donald C McMillan ◽  
Paul G Horgan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Screening Programme ◽  
Adverse Outcomes ◽  
Tnm Stage ◽  
Screening Tests ◽  
Disease Stage ◽  
Emergency Presentation ◽  
Screening Participation ◽  
Co Morbidity ◽  
Bowel Cancer Screening

Abstract Aims Population bowel cancer screening (BCS) is well established, however many patients still present acutely or with advanced disease. Within a cohort of patients with colorectal cancer (CRC), this study aimed to analyse the relationship between prior engagement with the screening programme and mode of presentation, disease stage and survival. Methods All patients diagnosed with CRC from 2011-2014 in West of Scotland were identified from a regional database and linked into the Bowel Screening dataset for screening participation within two years preceding diagnosis. Results 6551 patients were diagnosed with CRC, 19% (n = 1217) through screening. 39% of patients were not invited for screening and 29% of patients did not respond to invite. Non-response to invite was associated with male sex, increasing age, socioeconomic deprivation, co-morbidity and smoking (all p &lt; 0.001). 13% had previously returned negative screening tests. Negative screening was associated with female sex, anaemia, right sided, poorly differentiated and EMVI positive tumours, and screening with gFOBT versus FIT (all p ≤ 0.001).  2% did not undergo further investigation of a positive test, and &lt;1% had a negative colonoscopy. Participation in screening was associated with reduced emergency presentations (8%vs22%), lower TNM Stage, and improved 3-year CSS (88%vs74%) and OS (85%vs69%) (all p &lt; 0.001). Conclusion Most new cases of CRC are diagnosed outwith the screening programme, predominantly due to non-invite/failure to respond to invite. This has a significant association with adverse outcomes including emergency presentation, advanced TNM stage and poorer survival. Further work is required to increase screening uptake and widen access to BCS.

Abstract 2096: A deep learning system to predict disease-specific survival in stage II and stage III colorectal cancer

2020 ◽  
Author(s):  
Ellery Wulczyn ◽  
David F. Steiner ◽  
Melissa Moran ◽  
Markus Plass ◽  
Robert Reihs ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Deep Learning ◽  
Learning System ◽  
Stage Ii ◽  
Stage Iii ◽  
Disease Specific Survival ◽  
Disease Specific
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