Dataset Information

Personalizing Survival Predictions in Advanced Colorectal Cancer: The ARCAD Nomogram Project.

ABSTRACT: Background:Estimating prognosis on the basis of clinicopathologic factors can inform clinical practice and improve risk stratification for clinical trials. We constructed prognostic nomograms for one-year overall survival and six-month progression-free survival in metastatic colorectal carcinoma by using the ARCAD database. Methods:Data from 22 674 patients in 26 randomized phase III clinical trials since 1997 were used to construct and validate Cox models, stratified by treatment arm within each study. Candidate variables included baseline age, sex, body mass index, performance status, colon vs rectal cancer, prior chemotherapy, number and location of metastatic sites, tumor mutation status (BRAF, KRAS), bilirubin, albumin, white blood cell count, hemoglobin, platelets, absolute neutrophil count, and derived neutrophil-to-lymphocyte ratio. Missing data (<11%) were imputed, continuous variables modeled with splines, and clinically relevant pairwise interactions tested if P values were less than .001. Final models were internally validated via bootstrapping to obtain optimism-corrected calibration and discrimination C-indices, and externally validated on a 10% holdout sample from each trial (n = 2257). Results:In final models, all included variables were associated with overall survival except for lung metastases, and all but total white cell count associated with progression-free survival. No clinically relevant pairwise interactions were identified. Final nomogram calibration was good (C = 0.68 for overall and C = 0.62 for progression-free survival), as was external validity (concordance between predicted >50% vs < 50% probability) and actual (yes/no) survival (72.8% and 68.2% concordance, respectively, for one-year overall and six-month progression-free survival, between predicted [>50% vs < 50% probability] and actual [yes/no] overall and progression-free survival). Median survival predictions fell within the actual 95% Kaplan-Meier confidence intervals. Conclusions:The nomograms are well calibrated and internally and externally valid. They have the potential to aid prognostication and patient-physician communication and balance risk in colorectal cancer trials.

SUBMITTER: Sjoquist KM

PROVIDER: S-EPMC6005015 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Personalizing Survival Predictions in Advanced Colorectal Cancer: The ARCAD Nomogram Project.

Sjoquist Katrin M KM Renfro Lindsay A LA Simes R John RJ Tebbutt Niall C NC Clarke Stephen S Seymour Matthew T MT Adams Richard R Maughan Timothy S TS Saltz Leonard L Goldberg Richard M RM Schmoll Hans-Joachim HJ Van Cutsem Eric E Douillard Jean-Yves JY Hoff Paulo M PM Hecht Joel Randolph JR Tournigand Christophe C Punt Cornelis J A CJA Koopman Miriam M Hurwitz Herbert H Heinemann Volker V Falcone Alfredo A Porschen Rainer R Fuchs Charles C Diaz-Rubio Eduardo E Aranda Enrique E Bokemeyer Carsten C Souglakos Ioannis I Kabbinavar Fairooz F FF Chibaudel Benoist B Meyers Jeffrey P JP Sargent Daniel J DJ de Gramont Aimery A Zalcberg John R JR

Journal of the National Cancer Institute 20180601 6

<h4>Background</h4>Estimating prognosis on the basis of clinicopathologic factors can inform clinical practice and improve risk stratification for clinical trials. We constructed prognostic nomograms for one-year overall survival and six-month progression-free survival in metastatic colorectal carcinoma by using the ARCAD database.<h4>Methods</h4>Data from 22 674 patients in 26 randomized phase III clinical trials since 1997 were used to construct and validate Cox models, stratified by treatment ...[more]

PMID: 29267900

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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:Background and purpose: The aim of this study is to develop a prognostic nomogram, quantify survival benefit, and guide risk-dependent adjuvant therapy for locally advanced esophageal squamous cell carcinoma (LA-ESCC) after esophagectomy. Materials and methods: This was a single-center, retrospective study of consecutive LA-ESCCs treated by curative-intent esophagectomy with internal validation and independent external validation in a randomized controlled trial. After factor selection by the least absolute shrinkage and selection operator regression, a nomogram was developed to estimate 5-year overall survival (OS) based on the Cox proportional hazards model. The area under the curve (AUC) and calibration plot were used to determine its discriminative and predictive capacities, respectively. Survival improvement from adjuvant therapy was quantified and plotted corresponding to nomogram score. Results: A total of 1077, 718, and 118 patients were included for model development, internal validation, and external validation, respectively. The nomogram identified eight significant prognostic factors: gender, pathological T and N stages, differentiation, surgical margin, lymphovascular invasion, number of lymph node resection, and adjuvant therapy. The nomogram showed superior discriminative capacity than TNM stage (AUC: 0.76 vs. 0.72, p < 0.01), with significant survival differences among different risk stratifications. The calibration plot illustrated a good agreement between nomogram-predicated and actual 5-year OS. Consistent results were concluded after external validation. At least 10% 5-year OS improvement from adjuvant chemoradiotherapy and chemotherapy was expected in almost all patients (nomogram score 110 to 260) and patients mainly with high-intermediate risk (nomogram score 159 to 207), respectively. Conclusions: The clinicopathological nomogram predicting 5-year OS for LA-ESCC after esophagectomy was developed with high accuracy. The proposed nomogram showed better performance than TNM stage and provided risk-dependent and individualized adjuvant treatment recommendations.

Project description:BackgroundMost colorectal cancer (CRC) patients are at an advanced stage when they are first diagnosed. Risk factors for predicting overall survival (OS) in advanced stage CRC patients are crucial, and constructing a prognostic nomogram model is a scientific method for survival analysis.MethodsA total of 2956 advanced stage CRC patients were randomised into training and validation groups at a 7:3 ratio. Univariate and multivariate Cox proportional hazards regression analyses were used to screen risk factors for OS and subsequently construct a prognostic nomogram model for predicting 1-, 3-, 5-, 8- and 10-year OS of advanced stage CRC patients. The performance of the model was demonstrated by the area under the curve (AUC) values, calibration curves and decision curve analysis (DCA). Kaplan-Meier curves were used to plot the survival probabilities for different strata of each risk factor.ResultsThere was no statistically significant difference (p > 0.05) in the 32 clinical variables between patients in the training and validation groups. Univariate and multivariate Cox proportional hazards regression analyses demonstrated that age, location, TNM, chemotherapy, liver metastasis, lung metastasis, MSH6, CEA, CA199, CA125 and CA724 were risk factors for OS. We estimated the AUC values for the nomogram model to predict 1-, 3-, 5-, 8- and 10-year OS, which in the training group were 0.826 (95% CI: 0.807-0.845), 0.836 (0.819-0.853), 0.839 (0.820-0.859), 0.835 (0.809-0.862) and 0.825 (0.779-0.870) respectively; in the validation group, the corresponding AUC values were 0.819 (0.786-0.852), 0.831 (0.804-0.858), 0.830 (0.799-0.861), 0.815 (0.774-0.857) and 0.802 (0.723-0.882) respectively. Finally, the 1-, 3-, 5-, 8- and 10-year OS rates for advanced stage CRC patients were 73.4 (71.8-75.0), 49.5 (47.8-51.4), 43.3 (41.5-45.2), 40.1 (38.1-41.9) and 38.6 (36.6-40.8) respectively.ConclusionWe constructed and validated an original nomogram for predicting the postoperative OS of advanced stage CRC patients, which can help facilitates physicians to accurately assess the individual survival of postoperative patients and identify high-risk patients.

Project description:Metastatic colorectal cancer (mCRC) is a heterogeneous disease that can evoke discordant responses to therapy among different lesions in individual patients. The Response Evaluation Criteria in Solid Tumors (RECIST) criteria do not take into consideration response heterogeneity. We explored and developed lesion-based measurement response criteria to evaluate their prognostic effect on overall survival (OS).Patients and methodsPatients enrolled in 17 first-line clinical trials, who had mCRC with ≥ 2 lesions at baseline, and a restaging scan by 12 weeks were included. For each patient, lesions were categorized as a progressing lesion (PL: > 20% increase in the longest diameter (LD)), responding lesion (RL: > 30% decrease in LD), or stable lesion (SL: neither PL nor RL) based on the 12-week scan. Lesion-based response criteria were defined for each patient as follows: PL only, SL only, RL only, and varied responses (mixture of RL, SL, and PL). Lesion-based response criteria and OS were correlated using stratified multivariable Cox models. The concordance between OS and classifications was measured using the C statistic.ResultsAmong 10,551 patients with mCRC from 17 first-line studies, varied responses were noted in 51.6% of patients, among whom, 3.3% had RL/PL at 12 weeks. Among patients with RL/SL, 52% had stable disease (SD) by RECIST 1.1, and they had a longer OS (median OS (mOS) = 19.9 months) than those with SL only (mOS = 16.8 months, HR (95% CI) = 0.81 (0.76, 0.85), p < 0.001), although a shorter OS than those with RL only (mOS = 25.8 months, HR (95% CI) = 1.42 (1.32, 1.53), p < 0.001). Among patients with SL/PL, 74% had SD by RECIST 1.1, and they had a longer OS (mOS = 9.0 months) than those with PL only (mOS = 8.0 months, HR (95% CI) = 0.75 (0.57, 0.98), p = 0.040), yet a shorter OS than those with SL only (mOS = 16.8 months, HR (95% CI) = 1.98 (1.80, 2.18), p < 0.001). These associations were consistent across treatment regimen subgroups. The lesion-based response criteria showed slightly higher concordance than RECIST 1.1, although it was not statistically significant.ConclusionVaried responses at first restaging are common among patients receiving first-line therapy for mCRC. Our lesion-based measurement criteria allowed for better mortality discrimination, which could potentially be informative for treatment decision-making and influence patient outcomes.

Dataset Information

Personalizing Survival Predictions in Advanced Colorectal Cancer: The ARCAD Nomogram Project.

Publications

Personalizing Survival Predictions in Advanced Colorectal Cancer: The ARCAD Nomogram Project.

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