scholarly journals Personalizing the Prediction of Colorectal Cancer Prognosis by Incorporating Comorbidities and Functional Status into Prognostic Nomograms

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1435 ◽  
Author(s):  
Daniel Boakye ◽  
Lina Jansen ◽  
Martin Schneider ◽  
Jenny Chang-Claude ◽  
Michael Hoffmeister ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Functional Status ◽  
Significant Risk ◽  
Disease Free Survival ◽  
Stage Iv ◽  
Tumor Location ◽  
Cancer Prognosis ◽  
Prognostic Models ◽  
Cox Models ◽  
Validation Set

Despite consistent evidence that comorbidities and functional status (FS) are strong prognostic factors for colorectal cancer (CRC) patients, these important characteristics are not considered in prognostic nomograms. We assessed to what extent incorporating these characteristics into prognostic models enhances prediction of CRC prognosis. CRC patients diagnosed in 2003–2014 who were recruited into a population-based study in Germany and followed over a median time of 4.7 years were randomized into training (n = 1608) and validation sets (n = 1071). In the training set, Cox models with predefined variables (age, sex, stage, tumor location, comorbidity scores, and FS) were used to construct nomograms for relevant survival outcomes. The performance of the nomograms, compared to models without comorbidity and FS, was evaluated in the validation set using concordance index (C-index). The C-indexes of the nomograms for overall and disease-free survival in the validation set were 0.768 and 0.737, which were substantially higher than those of models including tumor stage only (0.707 and 0.701) or models including stage, age, sex, and tumor location (0.749 and 0.718). The nomograms enabled significant risk stratification within all stages including stage IV. Our study suggests that incorporating comorbidities and FS into prognostic nomograms could substantially enhance prediction of CRC prognosis.

scholarly journals Prognostic Prediction Models for Colorectal Cancer Patients After Curative Resection

2016 ◽  
Vol 101 (9-10) ◽  
pp. 406-413 ◽  
Author(s):  
Norikatsu Miyoshi ◽  
Masayuki Ohue ◽  
Shingo Noura ◽  
Masayoshi Yasui ◽  
Keijiro Sugimura ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prediction Model ◽  
Prediction Models ◽  
Disease Free Survival ◽  
Tumor Location ◽  
Prognostic Models ◽  
Preoperative Treatment ◽  
Preoperative Serum ◽  
Serum Carcinoembryonic Antigen ◽  
Clinicopathologic Factors

To develop a prediction tool for recurrence and survival in colorectal cancer (CRC) patients following surgically curative resections. We developed a reliable prediction model for CRC patients after surgically curative resections. Using clinicopathologic factors, novel prediction models were constructed with the area under the curve (AUC) of 0.841 and 0.876 for DFS and CSS, respectively. Between January 2004 and December 2007, 376 CRC patients were investigated at the Osaka Medical Center for Cancer and Cardiovascular Diseases. Patients with at least 1 of the following criteria were excluded: preoperative treatment, synchronous distant metastasis, noncurative resection, and incomplete follow-up after operation. All patients were retrospectively analyzed. A Cox proportional hazards model was used to develop a prediction model for disease-free survival (DFS) and cancer-specific survival (CSS). In univariate and multivariate analyses of clinicopathologic factors, the following factors had significant correlation with DFS and CSS: tumor location, preoperative serum carcinoembryonic antigen (CEA), pathologically defined tumor invasion, and lymph node metastasis. Using these variables, novel prediction models were constructed by the logistic regression model with AUC of 0.840 and 0.876 for DFS and CSS, respectively. The prediction models were validated by external datasets in an independent patient group. This study showed novel and reliable personalized prognostic models, integrating not only TNM factors but also tumor location and preoperative serum CEA to predict patient prognosis. These individualized prediction models could help clinicians in the treatment of postoperative CRC patients.

scholarly journals Is microsatellite instability-high really a favorable prognostic factor for advanced colorectal cancer? A meta-analysis

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Bingyan Wang ◽  
Fei Li ◽  
Xin Zhou ◽  
Yanpeng Ma ◽  
Wei Fu
Keyword(s):  
Colorectal Cancer ◽  
Beneficial Effect ◽  
Microsatellite Instability ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Stage Iv ◽  
Stage Iii ◽  
Beneficial Result ◽  
Beneficial Effects

Abstract Background Stage II colorectal cancer with microsatellite instability-high (MSI-H) has been proven to have a better prognosis. However, in advanced stage, this trend remains controversial. This study aimed to explore the prognostic role of MSI-H in stage III and IV colorectal cancer (CRC) through meta-analysis. Methods A comprehensive search was performed in PubMed, Cochrane Central Library, and Embase databases. All randomized clinical trials and non-randomized studies were included based on inclusion and exclusion criteria and on survival after a radical operation with or without chemotherapy. The adjusted log hazard ratios (HRs) were used to estimate the prognostic value between MSI-H and microsatellite-stable CRCs. The random-effects model was used to estimate the pooled effect size. Results Thirty-six studies were included. Randomized controlled trials (RCT) and non-RCT were analyzed separately. For stage III CRCs, pooled HR for overall survival (OS) was 0.96 (95% confidence interval [CI] 0.75–.123) in the RCT subgroup and 0.89 (95% CI 0.62–1.28) in the non-RCT subgroup. For disease-free survival (DFS), the HR for the RCT group was 0.83 (95% CI 0.65–1.07), similar to the non-RCT subgroup (0.83, 95% CI 0.65–1.07). Disease-specific survival (DSS) was also calculated, which had an HR of 1.07 (95% CI 0.68–1.69) in the non-RCT subgroup. All these results showed that MSI-H has no beneficial effects in stage III CRC. For stage IV CRC, the HR for OS in the RCT subgroup was 1.23 (95% CI 0.92–1.64) but only two RCTs were included. For non-RCT study, the combined HR for OS and DFS was 1.10 (95% CI 0.77–1.51) and 0.72 (95% CI 0.53–0.98), respectively, suggesting the beneficial effect for DFS and non-beneficial effect for OS. Conclusion For stage III CRC, MSI-H had no prognostic effect for OS, DFS, and DSS. For stage IV CRC, DFS showed a beneficial result, whereas OS did not; however, the included studies were limited and needed further exploration.

Perioperative therapy in patients with metastatic colorectal cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18231-e18231
Author(s):  
Olatunji B. Alese ◽  
Katerina Mary Zakka ◽  
Xingyue Huo ◽  
Renjian Jiang ◽  
Walid Labib Shaib ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Multivariate Analyses ◽  
Stage Iv ◽  
Tumor Location ◽  
Primary Site ◽  
Perioperative Therapy ◽  
Younger Age ◽  
Male Preponderance ◽  
Metastatic Sites

e18231 Background: Knowledge about perioperative systemic therapy in metastatic colorectal cancer (mCRC) is limited. We aim to describe the nationwide pattern of use and survival outcomes of patients with mCRC treated with surgical resection. Methods: Data were obtained from all US hospitals that contributed to the National Cancer Database (NCDB) between 2004 and 2013. Univariate and multivariate analyses was done to identify factors associated with patient outcome. Results: A total of 61,940 patients with stage IV CRC older than 18 years were identified. Mean age was 63.4 years (SD±14), with a male preponderance (54.8%). About 80% were Caucasian and 69.9% had colon cancer. Compared to medical treatment only, resection of both primary and metastatic sites (13.5%; HR 0.40; 0.37-0.44; p < 0.001), or primary site resection alone (49.2%; HR 0.52; 0.48-0.56; p < 0.001) were associated with improved overall survival (OS). Other co-variates associated with improved survival included younger age group, year of diagnosis (2009-2013), colon tumor location, and < 3 metastatic sites (Table). Five-year OS for resection of primary and metastatic site (28.2%) was higher than for primary site resection alone (14.9%) or no surgical treatment (4.7%). Conclusions: Resection of metastatic sites or primary tumor was associated with improved survival in patients with stage IV CRC.[Table: see text]

Serum-based multiplex protein assay for early detection of colorectal cancer and precancerous lesions in a FIT positive population.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16145-e16145
Author(s):  
Herbert A. Fritsche ◽  
Jason Lee Liggett ◽  
Hong Zhang ◽  
Linnea Ferm ◽  
Ib Jarle Christensen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Stage Iv ◽  
Stage I ◽  
Stage Ii ◽  
Supervised Machine Learning ◽  
Stage Iii ◽  
Screening Programs ◽  
Medium Risk ◽  
Validation Set

e16145 Background: Colorectal cancer (CRC) is the second leading cancer worldwide in terms of incidence, 5-year prevalence and mortality for both women and men ages 45 years old and up. The current screening method for many countries with organized screening programs is the FIT test for fecal occult blood; however, this test can result in false positive rates as high as 65%. A FIT reflex test could reduce unnecessary colonoscopies while reducing wait times for those patients that need confirmatory colonoscopies the most. Methods: Danish FIT positive colonoscopy confirmed serum samples (n = 1,499) were divided into training and validation sets maintaining approximately equivalent percentages of clean colonoscopy (40%), low risk adenomas (16%), medium risk adenomas (19%), high risk adenomas (13%), stage I CRC (5%), stage II CRC (2%), stage III CRC (4%), and stage IV CRC (0.5%). Proteins were quantified by custom 16-plex immunoassays utilizing the Luminex xMAP platform. A support vector machine supervised machine learning algorithm was trained with the 16 biomarkers plus age and FIT concentration using 1,291 samples for the outcome medium risk adenoma, high risk adenoma, and CRC. Then this algorithm was tested on a blind 208 sample validation set. Results: The training set was 90% sensitive and 27% specific (AUC = 0.68) and the validation set was 93% sensitive and 21% specific (AUC = 0.63). The sensitivities of the validation by risk/stage was as follows: medium risk adenoma 91%, high risk adenomas 92%, stage I CRC 100%, stage II CRC 100%, stage III CRC 100%, stage IV CRC 93%. Conclusions: This study demonstrates feasibility of a novel blood-based multiplex protein immunoassay for use as a reflex to FIT positive results in population wide screening. It detected nearly all adenomas and carcinomas while reducing FIT false positives and thus unnecessary colonoscopies by more than 20%. A FIT reflex test could alleviate endoscopy burden experienced in countries with organized cancer screening programs, while providing better patient outcomes by detecting polyps and early-stage CRC with high sensitivity.

scholarly journals Clinicopathological Features Combined With Immune Infiltration Could Well Distinguish Outcomes in Stage II and Stage III Colorectal Cancer: A Retrospective Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Jiazi Ren ◽  
Linfeng Xu ◽  
Siyu Zhou ◽  
Jian Ouyang ◽  
Weiqiang You ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Good Accuracy ◽  
Disease Free Survival ◽  
Risk Groups ◽  
Clinicopathological Characteristics ◽  
Stage Ii ◽  
Prognostic Models ◽  
Risk Scores ◽  
Pn Stage ◽  
Multidimensional Models

BackgroundThe Immunoscore predicts prognosis in patients with colorectal cancer (CRC). However, a few studies have incorporated the Immunoscore into the construction of comprehensive prognostic models in CRC, especially stage II CRC. We aimed to construct and validate multidimensional models integrating clinicopathological characteristics and the Immunoscore to predict the prognosis of patients with stage II–III CRC.MethodsPatients (n = 254) diagnosed with stage II–III CRC from 2009 to 2016 were used to generate Cox models for predicting disease-free survival (DFS) and overall survival (OS). The variables included basic clinical indicators, blood inflammatory markers, preoperative tumor biomarkers, mismatch repair status, and the Immunoscore (CD3+ and CD8+ T-cell densities). Univariate and multivariate Cox proportional regressions were used to construct the prognostic models for DFS and OS. We validated the predictive accuracy and ability of the prognostic models in our cohort of 254 patients.ResultsWe constructed two predictive prognostic models with C-index values of 0.6941 for DFS and 0.7138 for OS in patients with stage II–III CRC. The Immunoscore was the most informative predictor of DFS (11.92%), followed by pN stage, carcinoembryonic antigen (CEA), and vascular infiltration. For OS, the Immunoscore was the most informative predictor (8.59%), followed by pN stage, age, CA125, and CEA. Based on the prognostic models, nomograms were developed to predict the 3- and 5-year DFS and OS rates. Patients were divided into three risk groups (low, intermediate, and high) according to the risk scores obtained from the nomogram, and significant differences were observed in the recurrence and survival of the different risk groups (p &lt; 0.0001). Calibration curve and time-dependent receiver operating characteristic (ROC) analysis showed good accuracy of our models. Furthermore, the decision curve analysis indicated that our nomograms had better net benefit than pathological TNM (pTNM) stage within a wide threshold probability. Especially, we developed a website based on our prognostic models to predict the risks of recurrence and death of patients with stage II–III CRC.ConclusionsMultidimensional models including the clinicopathological characteristics and the Immunoscore were constructed and validated, with good accuracy and convenience, to evaluate the risks of recurrence and death of stage II–III CRC patients.

scholarly journals Accumulation of Nicotinamide N-Methyltransferase (NNMT) in Cancer-associated Fibroblasts: A Potential Prognostic and Predictive Biomarker for Gastric Carcinoma

2020 ◽  
pp. 002215542097659
Author(s):  
Li Zhang ◽  
Mengmeng Song ◽  
Fan Zhang ◽  
Hao Yuan ◽  
Wenjun Chang ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Tumor Grade ◽  
Predictive Biomarker ◽  
Cancer Prognosis ◽  
Malignant Tissue ◽  
Cox Models ◽  
Free Survival ◽  
Disease Prognosis ◽  
Cox Analysis ◽  
Disease Free

Nicotinamide N-methyltransferase (NNMT), a major metabolic regulator, has been identified as a predictor of cancer prognosis in ovarian and colorectal cancers. The study aims to evaluate the significance of stromal NNMT in gastric cancer (GC). Expression of stromal NNMT in 612 GC and 92 non-malignant tissues specimens was investigated by immunohistochemistry (IHC). The association between NNMT expression and occurrence of cancer or patient outcome was further analyzed, and the factors contributing to disease prognosis were evaluated by multiple Cox models. Stromal NNMT expression was higher in the malignant tissue ( p<0.001). NNMT expression was significantly associated with GC stage ( p=0.006). Compared to stromal “NNMT-low” cases, “NNMT-high” cases has lower disease-specific survival (hazard ratio [HR], 2.356; 95% confidence interval [CI] = 1.591–3.488; p<0.001) and disease-free survival (HR = 2.265; 95% CI = 1.529–3.354; p<0.001), as observed by multivariate Cox analysis after adjusting for stromal NNMT expression with other factors such as tumor grade and size. Notably, patients with stage II NNMT-low GC might be negatively affected by adjuvant chemotherapy, but lower stromal NNMT expression predicted a more favorable prognosis for GC. Our study confirmed that stromal NNMT expression is significantly increased in GC, which predicts an unfavorable post-operative prognosis for GC:

-93G>A polymorphism of hMLH1 associated with prognosis for patients with colorectal cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4039-4039
Author(s):  
J. Kim ◽  
Y. Chae ◽  
S. Sohn ◽  
B. Kang ◽  
S. Lee ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Repair ◽  
Disease Free Survival ◽  
Stage Iv ◽  
Dna Repair Genes ◽  
Repair Capacity ◽  
Independent Prognostic Marker ◽  
Dna Repair Capacity ◽  
Pcr Rflp ◽  
Repair Genes

4039 Background: Polymorphisms in the DNA repair genes may contribute to variation in DNA repair capacity, thereby affecting the risk of carcinogenesis and prognosis of colorectal cancer. Accordingly, the present study analyzed polymorphisms of DNA repair genes and their impact on the prognosis for patients with colorectal cancer. Methods: Three hundred and ninety- seven consecutive patients with curatively resected colorectal adenocarcinoma were enrolled in the present study. The genomic DNA was extracted from fresh colorectal tissue and 14 polymorphisms of DNA repair genes (XRCC1, hMLH1, ERCC2, ERCC4, VARS2[rs2074511, rs2249459], XPA, XPC, POLR2A, POLR2B, RFC1, RFC4, XAB2, DNMT3B) determined using a PCR-RFLP assay. Results: The median age of the patients was 63 years (range, 21–85), and 218 (54.9%) patients had colon cancer and 179 (45.1%) patients rectal cancer. Pathologic stages after surgery were as follows: stage 0/I (n=86, 21.7%), stage II (n=146, 36.8%), stage III (n=145, 36.5%), and stage IV (n=20, 5.0%). Multivariate survival analysis including stage, differentiation, age, and CEA level showed that the survival for the patients with the -93AA genotype of hMLH1 was worse than for the patients with the combined -93GG and GA genotype (overall survival: hazard ratio [HR]=2.953, 95% Confidential Interval [CI], 1.273–6.850, P=0.012; disease-free survival: HR=2.299, 95% CI, 1.417–3.730, P=0.001), whereas the other polymorphisms were not associated with survival. Conclusions: The -93G>A polymorphism of hMLH1 was found to be an independent prognostic marker for patients with colorectal cancer. Accordingly, in addition to the pathologic stage, the analysis of -93G>A polymorphism of hMLH1 can help identify patient subgroups at high risk of a poor disease outcome. No significant financial relationships to disclose.

Disassociation of ARID1A with genomic ancestry and prognostic impact in an admixed cohort of Brazilian patients with gastric cancer (GC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15585-e15585
Author(s):  
Helano C. Freitas ◽  
Diana Noronha Nunes ◽  
Thais Fernanda Bartelli ◽  
Maria Galli de Amorim ◽  
Luiza Ferreira Araujo ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Stage Iv ◽  
Suppressor Gene ◽  
Tumor Location ◽  
Cancer Center ◽  
Prognostic Impact ◽  
Ancestry Informative Markers ◽  
Free Survival ◽  
Protein Inactivation ◽  
Worse Prognosis

e15585 Background: Loss of expression of ARID1A, a tumor suppressor gene involved in chromatin remodeling and transcription activation, has been associated with worse prognosis in Asian GC patients (Yang et al. 2016). Mutations in ARID1A have been found in 8-27% of GC, usually leading to gene/protein inactivation. Here we evaluated the possible involvement of ARID1A mutations and clinical characteristics, while considering genomic ancestry and survival, in a cohort of Brazilian GC patients. Methods: We included 112 pts diagnosed with GC and treated at AC Camargo Cancer Center before 2013. The study was approved by local IRB. Genomic DNA was used for capture-based enrichment of a customized gene panel including 99 genes. Libraries were sequenced in the NextSeq 500 platform (Illumina), using paired-end reads (2x75bp). For ancestry inference we used a set of ancestry informative markers, covered by target and off-target reads, described by Elhaik et al. (2014). Results: Median age was 64y (37-91), 63% were male, M:F ratio was 1.73. Most cases were classified as Diffuse (47.3%) followed by Intestinal (41.1%), Mixed (2.7%) and 8.9% were deemed unclassifiable by Lauren´s classification. 22.3% were stage I, 20.5% stage II, 42.9% stage III and 14.3% stage IV. 11.6% were in the GEJ and 80.4% were in corpus/antrum. Five patients were EBV positive (4.5%). Genomic ancestry was as follows: 55.4% European, 27.7% Asian, 8.9% African and 8% were highly admixed ( < 50% of any ancestry). ARID1A was mutated in 19% of cases and showed no association with age at diagnosis (p = 0.21), gender (p = 0.76), tumor location (p = 0.55), staging (p = 0.42), Lauren (p = 0.14) or EBV (p = 0.42). ARID1A had no impact on overall survival (OS) (HR 1.17; 95%CI 0.59-2.31; p = 0.6) or disease-free survival (DFS) (HR 1.24; 95%CI 0.66-2.32; p = 0.5), including the subgroup with Asian genomic background: OS-Asia (HR 1.08; 95%CI 0.31-3.81; p = 0.9), DFS-Asia (HR 1.15; 95%CI 0.32-4.12; p = 0.8). Conclusions: ARID1A is a common driver in GC among Brazilian patients. Unlike in Asians, ARID1A was not prognostic in this Brazilian cohort even in the subgroup with a predominant ( > 50%) Asian genomic ancestry.

scholarly journals KRAS Testing, Tumor Location, and Survival in Patients With Stage IV Colorectal Cancer: SEER 2010–2013

2017 ◽  
Vol 15 (12) ◽  
pp. 1484-1493 ◽  
Author(s):  
Mary E. Charlton ◽  
Amanda R. Kahl ◽  
Alissa A. Greenbaum ◽  
Jordan J. Karlitz ◽  
Chi Lin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stage Iv ◽  
Tumor Location ◽  
Stage Iv Colorectal Cancer

scholarly journals Colon cancer surgery in patients operated on an emergency basis

2017 ◽  
Vol 44 (5) ◽  
pp. 465-470
Author(s):  
Rodrigo Felippe Ramos ◽  
Lucas Carvalho Santos dos-Reis ◽  
Beatriz Esteves Borgeth Teixeira ◽  
Igor Maroso Andrade ◽  
Jaqueline Suelen Sulzbach ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Free Survival ◽  
Distant Metastases ◽  
Disease Recurrence ◽  
Tumor Location ◽  
Tnm Staging ◽  
Curative Intent ◽  
Initial Stage ◽  
Epidemiological Profile ◽  
Colorectal Cancer Patients

ABSTRACT Objective: to study the epidemiological profile of patients with colorectal cancer operated on an emergency basis at the Bonsucesso Federal Hospital. Methods: this is a retrospective study of patients operated between January 1999 and December 2012. We analyzed the following variables: age, gender, clinical data, TMN staging, tumor location, survival and types of surgery. Results: we evaluated 130 patients in the study period. The most frequent clinical picture was intestinal obstruction, in 78% of cases. Intestinal perforation was the surgical indication in 15%. The majority (39%) of the patients had advanced TNM staging, compared with 27% in the initial stage. There were 39 deaths (30%) documented in the period. The most common tumor site was the sigmoid colon (51%), followed by the ascending colon (16%). The curative intent was performed in most cases, with adjuvant treatment being performed in 40% of the patients. Distant metastases were found in 42% of the patients and 10% had documented disease recurrence. Disease-free survival at two and five years was 69% and 41%, respectively. Conclusion: there was a high mortality rate and a low survival rate in colorectal cancer patients operated on urgently.

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