Which melanoma patient carries a BRAF-mutation? A comparison of predictive models.

// Thomas Eigentler 1 , Zeinab Assi 1 , Jessica C. Hassel 2 , Lucie Heinzerling 3 , Hans Starz 4 , Mark Berneburg 5 , Jurgen Bauer 1 , Claus Garbe 1 1 Department of Dermatology, Center for Dermato Oncology, University Medical Center Tubingen, Tubingen, Germany 2 Department of Dermatology and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany 3 Department of Dermatology, University Hospital Erlangen, Erlangen, Germany 4 Department of Dermatology and Allergology, Klinikum Augsburg, Augsburg, Germany 5 Department of Dermatology, University of Regensburg, Regensburg, Germany Correspondence to: Thomas Eigentler, email: thomas.eigentler@med.uni-tuebingen.de Keywords: advanced melanoma, BRAF, predictive models, binary logistic regression, classification and regression trees Received: November 27, 2015      Accepted: April 16, 2016      Published: May 02, 2016 ABSTRACT Background: In patients with advanced melanoma the detection of BRAF mutations is considered mandatory before the initiation of an expensive treatment with BRAF/MEK inhibitors. Sometimes it is difficult to perform such an analysis if archival tumor tissue is not available and fresh tissue has to be collected. Results: 514 of 1170 patients (44%) carried a BRAF mutation. All models revealed age and histological subtype of melanoma as the two major predictive variables. Accuracy ranged from 0.65–0.71, being best in the random forest model. Sensitivity ranged 0.76–0.84, again best in the random forest model. Specificity was low in all models ranging 0.51–0.55. Methods: We collected the clinical data and mutational status of 1170 patients with advanced melanoma and established three different predictive models (binary logistic regression, classification and regression trees, and random forest) to forecast the BRAF status. Conclusions: Up to date statistical models are not able to predict BRAF mutations in an acceptable accuracy. The analysis of the mutational status by sequencing or immunohistochemistry must still be considered as standard of care.