BRAF mutation testing in melanoma: results from a German observational multicenter study
Quality control of BRAF mutation testing methods used in routine practice is crucial for optimal treatment selection. In this prospective study, we assessed the impact of patient/sample characteristics on BRAF mutation testing results in patients with melanoma, during clinical practice. Data were collected on routine testing practices and documented mutation status in patients with melanoma stages IIIB, IIIC, or IV across 28 diagnostic pathology centers in Germany. Patient/sample data collected included: patient age, location of primary melanoma and metastases, origin of sample, melanoma subtype, and quality of tissue. Statistical influence of patient/sample characteristics on BRAF mutation rate was assessed using multiple logistic regression analyses and statistical models developed to predict the probability of BRAF mutations for individual patient cohorts. Data/samples from 642 patients with melanoma were analyzed. BRAF mutations were documented in 241/642 patients (37.5%). The primary statistical model to predict BRAF mutation rates included: age (continuous), origin of sample, method of mutation analysis, and quality of tissue. Analyses of post hoc collected data identified major deviations between documented mutation rates included in this study vs. routinely recorded mutation rates for three centers. When samples from these centers were excluded, the influence of testing method was no longer statistically significant. The final model included patient age, origin of sample (including metastasis location), and quality of tissue. Once validated in an independent population, this type of model could allow pathology centers to compare the performance of their testing methods with what would be expected based on patient, tumor, and sample characteristics.
KeywordsBRAF mutation Melanoma Quality control Mutational analysis Multiple logistic regression
We would like to thank the patients, their families, the nurses, and the investigators who participated in this study (see Online Resource 1 for the list of investigators). Funding for this study was provided by Roche Pharma AG, Germany. Support for third-party writing assistance for this manuscript, furnished by Rachel Johnson, PhD, of Health Interactions, was funded by Roche Pharma AG, Germany.
Author contribution statement
A Hartmann contributed to study design and study protocol development; A Hartmann, P Schirmacher, W Sterlacci, and C Garbe contributed to data acquisition; P Schirmacher, W Sterlacci, W Koch, DB Liesenfeld, and B Schif were involved in data analysis and A Hartmann, P Schirmacher, W Sterlacci, W Koch, DB Liesenfeld, B Schif, and C Garbe in data interpretation; W Koch, DB Liesenfeld, and B Schif were responsible for figure development. All authors were involved in writing the paper and had final approval of the submitted and published versions.
This study was funded by Roche Pharma AG, Grenzach-Wyhlen, Germany.
Compliance with ethical standards
Conflict of interest
A Hartmann has received research funding from Sysmex, BioNTech, Nanostring, and Novartis, and has received honoraria from Roche, AstraZeneca, BMS, and MSD, and payment for consultancy or advisory roles from Medoc, Roche, AstraZeneca, BMS, and MSD. P Schirmacher has received research funding from Roche, AstraZeneca, Novartis, Chugai, Thermo Fisher, and Sanofi Aventis, honoraria from Novartis, AstraZeneca, and Roche, and payment for consultancy or advisory roles from Roche, AstraZeneca, Novartis, BMS, MSD, Merck, and Amgen. W Sterlacci has received payment for consultancy or advisory roles from Roche. W Koch is an employee of BDS Koch, which receives payment for statistical services from Roche. B Schif and DB Liesenfeld are employed by Roche. C Garbe has received research funding from BMS, Novartis, and Roche, honoraria from Amgen, BMS, MSD, Novartis, and Roche, travel, accommodation, and other expenses from Amgen, BMS, MSD, Novartis, and Roche, and payment for consultancy or advisory roles from Amgen, BMS, MSD, Novartis, and Roche.
Ethics approval was obtained at the University of Erlangen-Nürnberg (approval no. 14_13 B dated Feb 19th 2013).
Informed consent was not required as all data were collected as part of routine testing and were fully anonymized prior to analysis.
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