Loupakis, Fotio, Moretto, Roberto, Aprile, Giuseppe, Muntoni, Marta, Cremolini, Chiara, Iacono, Donatella, Casagrande, Mariaelena, Ferrari, Laura, Salvatore, Lisa, Schirripa, Marta, Rossini, Daniele, De Maglio, Giovanna, Fasola, Gianpiero, Calvetti, Lorenzo, Pilotto, Sara, Carbognin, Luisa, Fontanini, Gabriella, Tortora, Giampaolo, Falcone, Alfredo, Sperduti, Isabella, Bria, Emilio, Bria, Emilio (ORCID:0000-0002-2333-704X), Loupakis, Fotio, Moretto, Roberto, Aprile, Giuseppe, Muntoni, Marta, Cremolini, Chiara, Iacono, Donatella, Casagrande, Mariaelena, Ferrari, Laura, Salvatore, Lisa, Schirripa, Marta, Rossini, Daniele, De Maglio, Giovanna, Fasola, Gianpiero, Calvetti, Lorenzo, Pilotto, Sara, Carbognin, Luisa, Fontanini, Gabriella, Tortora, Giampaolo, Falcone, Alfredo, Sperduti, Isabella, Bria, Emilio, and Bria, Emilio (ORCID:0000-0002-2333-704X)
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.