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Clinico-pathological nomogram for predicting BRAF mutational status of metastatic colorectal cancer
Authors:Fotios Loupakis  Roberto Moretto  Giuseppe Aprile  Marta Muntoni  Chiara Cremolini  Donatella Iacono  Mariaelena Casagrande  Laura Ferrari  Lisa Salvatore  Marta Schirripa  Daniele Rossini  Giovanna De Maglio  Gianpiero Fasola  Lorenzo Calvetti  Sara Pilotto  Luisa Carbognin  Gabriella Fontanini  Giampaolo Tortora  Alfredo Falcone  Isabella Sperduti  Emilio Bria
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.
Keywords:BRAF  nomogram  metastatic colorectal cancer
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