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. 2016 Jan 12;114(1):30-6.
doi: 10.1038/bjc.2015.399. Epub 2015 Nov 17.

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

Fotios Loupakis  1 , Roberto Moretto  1 , Giuseppe Aprile  2 , Marta Muntoni  1 , Chiara Cremolini  1 , Donatella Iacono  2 , Mariaelena Casagrande  2 , Laura Ferrari  2 , Lisa Salvatore  1 , Marta Schirripa  1 , Daniele Rossini  1 , Giovanna De Maglio  3 , Gianpiero Fasola  2 , Lorenzo Calvetti  4 , Sara Pilotto  4 , Luisa Carbognin  4 , Gabriella Fontanini  5 , Giampaolo Tortora  4 , Alfredo Falcone  1 , Isabella Sperduti  6 , Emilio Bria  4
Affiliations

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

Fotios Loupakis et al. Br J 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.

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Figures

Figure 1
Figure 1
Clinico-pathological nomogram for predicting BRAF mutational status. A predictive score is assigned to each variable and the sum of scores is converted to the probability of BRAF mutation occurrence.
Figure 2
Figure 2
ROC curves in TS (panel A) and in VS (panel B) populations. Abbreviations: AUC=area under the curve; SE=standard error.
Figure 3
Figure 3
Kaplan–Meier curves of the probability of OS in RAS and BRAF wt (blue), RAS-mutant (red) and BRAF-mutant (black) patients. A full colour version of this figure is available at the British Journal of Cancer journal online.
See this image and copyright information in PMC

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