Fotios Loupakis et al., Clinico-pathological nomogram for predicting BRAF mutational status of metastatic colorectal cancer. British Journal of Cancer
Fotios Loupakis1,7, Roberto Moretto1,7, Giuseppe Aprile2, Marta Muntoni1, Chiara Cremolini1, Donatella Iacono2, Mariaelena Casagrande2, Laura Ferrari2, Lisa Salvatore1, Marta Schirripa1, Daniele Rossini1, Giovanna De Maglio3, Gianpiero Fasola2, Lorenzo Calvetti4, Sara Pilotto4, Luisa Carbognin4, Gabriella Fontanini5, Giampaolo Tortora4, Alfredo Falcone1, Isabella Sperduti6 and Emilio Bria4
1Oncologia Medica 2 Universitaria, Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy
2Dipartimento di Oncologia, Azienda Ospedaliero-Universitaria ‘Santa Maria della Misericordia’, Piazzale Santa Maria della Misericordia 15, 33100 Udine, Italy
3Dipartimento di Medicina di Laboratorio, Azienda Ospedaliero-Universitaria ‘Santa Maria della Misericordia’, Piazzale Santa Maria della Misericordia 15, 33100 Udine, Italy
4Dipartimento di Medicina, Oncologia Medica, University of Verona, Azienda Ospedaliera Universitaria Integrata, Piazzale Aristide Stefani 1, 37126 Verona, Italy
5Divisione di Patologia, Dipartimento di Chirurgia, University of Pisa, Via Roma 67, 56126 Pisa, Italy
6Direzione Scientifica, Biostatistics, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy
In metastatic colorectal cancer (mCRC), BRAFV600E mutation has been variously associated to specific clinico-pathological features.
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.
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.
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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