Dataset Information

Clinico-pathological nomogram for predicting BRAF mutational status of metastatic colorectal cancer.

ABSTRACT:

Background

In metastatic colorectal cancer (mCRC), BRAFV600E mutation has been variously associated to specific clinico-pathological features.

Methods

Two large retrospective series of mCRC patients from two Italian Institutions were used as training-set (TS) and validation-set (VS) for developing a nomogram predictive of BRAFV600E status. The model was internally and externally validated.

Results

In the TS, data from 596 mCRC patients were gathered (RAS wild-type (wt) 281 (47.1%); BRAFV600E mutated 54 (9.1%)); RAS and BRAFV600E mutations were mutually exclusive. In the RAS-wt population, right-sided primary (odds ratio (OR): 7.80, 95% confidence interval (CI) 3.05-19.92), female gender (OR: 2.90, 95% CI 1.14-7.37) and mucinous histology (OR: 4.95, 95% CI 1.90-12.90) were independent predictors of BRAFV600E mutation, with high replication at internal validation (100%, 93% and 98%, respectively). A predictive nomogram was calculated: patients with the highest score (right-sided primary, female and mucinous) had a 81% chance to bear a BRAFV600E-mutant tumour; accuracy measures: AUC=0.812, SE:0.034, sensitivity:81.2%; specificity:72.1%. In the VS (508 pts, RAS wt: 262 (51.6%), BRAFV600E mutated: 49 (9.6%)), right-sided primary, female gender and mucinous histology were confirmed as independent predictors of BRAFV600E mutation with high accuracy.

Conclusions

Three simple and easy-to-collect characteristics define a useful nomogram for predicting BRAF status in mCRC with high specificity and sensitivity.

SUBMITTER: Loupakis F

PROVIDER: S-EPMC4716533 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Publications

Clinico-pathological nomogram for predicting BRAF mutational status of metastatic colorectal cancer.

Loupakis Fotios F Moretto Roberto R Aprile Giuseppe G Muntoni Marta M Cremolini Chiara C Iacono Donatella D Casagrande Mariaelena M Ferrari Laura L Salvatore Lisa L Schirripa Marta M Rossini Daniele D De Maglio Giovanna G Fasola Gianpiero G Calvetti Lorenzo L Pilotto Sara S Carbognin Luisa L Fontanini Gabriella G Tortora Giampaolo G Falcone Alfredo A Sperduti Isabella I Bria Emilio E

British journal of cancer 20151117 1

<h4>Background</h4>In metastatic colorectal cancer (mCRC), BRAFV600E mutation has been variously associated to specific clinico-pathological features.<h4>Methods</h4>Two large retrospective series of mCRC patients from two Italian Institutions were used as training-set (TS) and validation-set (VS) for developing a nomogram predictive of BRAFV600E status. The model was internally and externally validated.<h4>Results</h4>In the TS, data from 596 mCRC patients were gathered (RAS wild-type (wt) 281 ...[more]

PMID: 26575603

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Project description:BackgroundWe previously reported that loss of KRAS mutations ("regressive" mutational trajectories) from primary tumors to metastases associated with the oligo-metastatic status in colorectal cancer (CRC). The present study was undertaken in order to analyze the mutational trajectories of KRAS in a well-characterized cohort of CRC patients who developed poly- or oligo-metastatic disease.Material and methodsPatients were treated and followed-up according to European Society of Medical Oncology guidelines. Primary CRC FFPE tissue and metastatic circulating-free DNA were extracted using the QIAamp DNA specific kits (Qiagen, Hilden, Germany). Samples were sequenced with the Oncomine Solid Tumour DNA kit (Thermo Fisher Scientific, Waltham, MA, USA). Plasma collection for liquid biopsy was done from 1 to 14 days before starting first-line chemotherapy. Analysis of the prognostic power of KRAS evolutionary trajectories was done with uni- and multivariate analyses.ResultsOne-hundred-fourteen patients were enrolled. Sixty-three patients presented with mutated KRAS (mutKRAS) and 51 with wild-type KRAS (wtKRAS). KRAS mutational concordance was high (70.1%).Two divergent subsets were identified: mutKRAS in primary tumors and wtKRAS in metastatic ones (regressive: mutKRAS → wtKRAS in 8.8% of patients), and vice versa (progressive: wtKRAS → mutKRAS in 21.1% of patients). An association between KRAS regressive trajectory and the oligo-metastatic status (P <0.0001) was found. At multivariate analysis, regressive and progressive mutational trajectories emerged as independent prognostic factors for survival, with Hazard Ratios of 0.22 (CI 95%: 0.08-0.61; median survival: not reached) and 2.70 (CI 95%: 1.11-6.56, median survival: 12.1 months), respectively.ConclusionsOur data provide evidence that the evolutionary trajectories of KRAS can have a strong clinical prognostic role and that they can be involved in discriminating between poly-metastatic aggressive vs oligo-metastatic indolent CRC.

Project description:ObjectivesThe present study aims to discover the risk factors of multiple metastases and develop a functional nomogram to forecast multiple metastases in metastatic colorectal cancer (mCRC) patients.MethodsmCRC cases were retrospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016. Survival times between multiple metastases and single metastasis were compared using Kaplan-Meier analysis and log-rank tests. Risk factors for multiple metastases were determined by univariate and multivariate logistic regression analyses, and a nomogram was developed to forecast the probability of multiple metastases in mCRC patients. We assessed the nomogram performance in terms of discrimination and calibration, including concordance index (C-index), area under the curve (AUC), and decision curve analysis (DCA). Bootstrap resampling was used as an internal verification method, and at the same time we select external data from Renmin Hospital of Wuhan University as independent validation sets.ResultsA total of 5,302 cases were included in this study as training group, while 120 cases were as validation group. The patients with single metastasis and multiple metastases were 3,531 and 1,771, respectively. The median overall survival (OS) and cancer-specific survival (CSS) for patients with multiple metastases or single metastasis were 19 vs. 31 months, and 20 vs. 33 months, respectively. Based on the univariate and multivariate analyses, clinicopathological characteristics were associated with number of metastasis and were used to establish nomograms to predict the risk of multiple metastases. The C-indexes and AUC for the forecast of multiple metastases were 0.715 (95% confidence interval (CI), 0.707-0.723), which showed the nomogram had good discrimination and calibration curves of the nomogram showed no significant bias from the reference line, indicating a good degree of calibration. In the validation group, the AUC was 0.734 (95% CI, 0.653-0.834), and calibration curve also showed no significant bias, indicating the favorable effects of our nomogram.ConclusionsWe developed a new nomogram to predict the risk of multiple metastases. The nomogram shows the good prediction effect and can provide assistance for clinical diagnosis and treatment.

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Dataset Information

Clinico-pathological nomogram for predicting BRAF mutational status of metastatic colorectal cancer.

Background

Methods

Results

Conclusions

Publications

Clinico-pathological nomogram for predicting BRAF mutational status of metastatic colorectal cancer.

Similar Datasets

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