Abstract
Brain metastases are common in patients with advanced melanoma and constitute a major cause of morbidity and mortality. Between 40% and 60% of melanomas harbor BRAF mutations. Selective BRAF inhibitor therapy has yielded improvement in clinical outcome; however, genetic discordance between the primary lesion and the metastatic tumor has been shown to occur. Currently, the only way to characterize the genetic landscape of a brain metastasis is by tissue sampling, which carries risks and potential complications. The aim of this study was to investigate the use of radiomics analysis for non-invasive identification of BRAF mutation in patients with melanoma brain metastases, based on conventional magnetic resonance imaging (MRI) data. We applied a machine-learning method, based on MRI radiomics features for noninvasive characterization of the BRAF status of brain metastases from melanoma (BMM) and applied it to BMM patients from two tertiary neuro-oncological centers. All patients underwent surgical resection for BMM, and their BRAF mutation status was determined as part of their oncological work-up. Their routine preoperative MRI study was used for radiomics-based analysis in which 195 features were extracted and classified according to their BRAF status via a support vector machine. The BRAF status of 53 study patients, with 54 brain metastases (25 positive, 29 negative for BRAF mutation) was predicted with mean accuracy = 0.79 ± 0.13, mean precision = 0.77 ± 0.14, mean sensitivity = 0.72 ± 0.20, mean specificity = 0.83 ± 0.11 and with a 0.78 area under the receiver operating characteristic curve for positive BRAF mutation prediction. Radiomics-based noninvasive genetic characterization is feasible and should be further verified using large prospective cohorts.
Highlights
Brain metastases are common in patients with advanced melanoma and constitute a major cause of morbidity and mortality
The BRAF mutation status of a metastasis cannot be determined without invasively obtaining tissue samples during surgery, which is associated with morbidity, hospitalizations, and is prone to sampling errors
We conducted a retrospective analysis of data obtained from 53 melanoma patients with central nervous system (CNS) involvement who underwent resection of their brain metastases from melanoma (BMM) tumors and for whom the BRAF mutation status was available
Summary
Brain metastases are common in patients with advanced melanoma and constitute a major cause of morbidity and mortality. The aim of this study was to investigate the use of radiomics analysis for non-invasive identification of BRAF mutation in patients with melanoma brain metastases, based on conventional magnetic resonance imaging (MRI) data. BRAF mutations drive oncogenic behavior of melanoma cells, leading to unrestricted cell growth, increased cell survival, and local invasion through activation of the mitogen-activated protein kinase (MAPK) pathway[11] Following identification of this mutation, combination therapy with BRAF and MEK inhibitors have improved patient outcomes dramatically, with the median overall survival (OS) of patients with metastatic melanoma increasing from approximately 9 months before the introduction of these treatments to over 2 years in 201912,13. Discrepancies of BRAF mutation status between the primary tumor and the distant metastases reportedly range from 18% to 26%, and patients with a BRAF negative primary melanoma may still manifest BRAF positive BMM and vice versa[15] This information is crucial for appropriate management when considering non-surgical treatment for a brain metastasis.
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