Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Boakye D

PROVIDER: S-EPMC6826360 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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

Boakye Daniel D Jansen Lina L Schneider Martin M Chang-Claude Jenny J Hoffmeister Michael M Brenner Hermann H

Cancers 20190926 10

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 i ...[more]

PMID: 31561507

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Project description:BackgroundColorectal cancer is one of the most frequent neoplasms worldwide, and the majority of patients are diagnosed in advanced stages. Metastatic colorectal cancer (mCRC) harbors several mutations with different prognostic and predictive values; KRAS, NRAS, and BRAF mutations are the best known. Indeed, RAS and BRAF molecular status are associated with a different response to monoclonal antibodies (Anti-epidermal growth factor receptor and anti-vascular endothelial growth factor receptor agents), which are usually added to chemotherapy in first-line, and thus allow to select the optimal therapy for patients with mCRC. Furthermore, sidedness is an important predictive and prognostic factor in mCRC, which is explained by the different molecular profile of left and right-sided tumors. Recently, microsatellite instability-high has emerged as a predictive factor of response and survival from immune checkpoint inhibitors in mCRC. Finally, several other alterations have been described in lower frequencies, such as human epidermal growth factor receptor-2 overexpression/amplification, PIK3CA pathway alterations, phosphatase and tension homolog loss, and hepatocyte growth factor/mesenchymal-epithelial transition factor pathway dysregulation, with several targeted therapies already demonstrating activity or being tested in currently ongoing clinical trials.AimTo review the importance of studying the predictive and prognostic roles of the molecular profile of mCRC, the changes occurred in recent years and how they would potentially change in the near future, to guide physicians in treatment decisions.Relevance for patientsToday, several different therapeutic options can be offered to patients in the first-line setting of mCRC. Therapies at present approved or under investigation in clinical trials will be thoroughly reviewed, with special emphasis on the molecular rationale behind them. Understanding the molecular status, resistance mechanisms and potential new druggable targets may allow physicians to choose the best therapeutic option in the first-line mCRC.

Project description:Cancer treatments for older patients must account for heterogeneity in health and functional status. Guidelines advocate the use of geriatric assessments (GAs), but comprehensive assessments are laborious and the utility of specific GA domains remains unclear. The identification of specific domains as prognostic factors may support survival predictions and treatment decisions. We aimed to evaluate the associations between several GA domains and overall survival in older cancer patients. We linked cancer registry data and administrative claims data from cancer patients residing in Osaka Prefecture, Japan. The subjects were patients aged ≥70 years who received a diagnosis of gastric, colorectal, or lung cancer between 2010 and 2014 at 36 designated cancer care hospitals. The following three GA domains were assessed at cancer diagnosis: functional status through activities of daily living (ADL), comorbidities, and nutritional status through body mass index. Cox proportional hazards models were constructed for the three cancer types to estimate each domain's prognostic effect while adjusting for gender, age, and cancer stage. Adjusted hazard ratios (HRs) for all-cause mortality were calculated. We identified 5,559, 4,746, and 4,837 patients with gastric, colorectal, and lung cancer respectively. ADL impairment (HRs: 1.39-3.34, 1.64-2.86, and 1.24-3.21 for gastric, colorectal, and lung cancer, respectively), comorbidities (1.32-1.58, 1.33-1.97, and 1.19-1.29 for gastric, colorectal, and lung cancer, respectively), and underweight (1.36, 1.51, and 1.54 for gastric, colorectal, and lung cancer, respectively) were significantly associated with poorer overall survival. In contrast, overweight was significantly associated with improved overall survival (HRs: 0.82 and 0.89 for gastric and lung cancer respectively). The addition of the three domains increased the models' C-statistics (0.816 to 0.836, 0.764 to 0.787, and 0.759 to 0.783 for gastric, colorectal, and lung cancer respectively). Incorporating these factors into initial patient evaluations during diagnosis may aid prognostic predictions and treatment strategies in geriatric oncology.

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Project description:BackgroundAs the most common gastrointestinal malignancy worldwide, liver metastases occur in half colorectal cancer (CRC) patients. Early detection can help treat them early and reduce mortality in patients with colorectal cancer liver metastases (CRLM). Finding useful biomarkers for CRLM is thus essential.MethodsThe TCGA and GEO databases were used to download the expression profiles and clinical data of the patients. Differential analysis screened for genes associated with CRLM, and univariate Cox regression analysis identified genes associated with prognosis. The least absolute shrinkage and selection operator (LASSO) method further preferred genes to construct a prognostic signature. Kaplan-Meier survival curves were used to show patients' overall survival (OS). Receiver operating characteristic (ROC) curves showed the accuracy of the model. Risk scores and clinical characteristics of patients were included in multivariate Cox regression analysis to identify independent risk factors, and a nomogram was constructed. The proportion of immune cells and infiltration were assessed using the 'CIBERSORT' package and the 'ESTIMATE' package.ResultsWe constructed a signature consisting of seven CRLM-associated genes, and signature-based risk scores have great potential in estimating the prognosis of CRC patients. Moreover, the poor response to immunotherapy in high-risk patients might contribute to the poor prognosis of individuals. Furthermore, we found that overexpression of Hepcidin antimicrobial peptide (HAMP), the only gene highly expressed in CRC and liver metastatic tissues, promoted CRC development and that it was associated with tumor mutation burden (TMB), DNA mismatch repair (MMR) genes, and microsatellite instability (MSI) in various tumors. Finally, we found that in CRC patients, low expression of HAMP also represented a better immunotherapeutic outcome, reflecting the critical role of HAMP in guiding immunotherapy.ConclusionWe identified a prognostic signature containing 7 CRLM-associated genes, and the signature was specified as an independent predictor and a nomogram containing the risk score was built accordingly. In addition, the derived gene HAMP could help guide the exploration of profitable immunotherapeutic strategies.

Dataset Information

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

Publications

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

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