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@ARTICLE{Haselmann:141330,
author = {V. Haselmann and C. Gebhardt$^*$ and I. Brechtel and A.
Duda and C. Czerwinski and A. Sucker$^*$ and T.
Holland-Letz$^*$ and J. Utikal$^*$ and D. Schadendorf$^*$
and M. Neumaier},
title = {{L}iquid {P}rofiling of {C}irculating {T}umor {DNA} in
{P}lasma of {M}elanoma {P}atients for {C}ompanion
{D}iagnostics and {M}onitoring of {BRAF} {I}nhibitor
{T}herapy.},
journal = {Clinical chemistry},
volume = {64},
number = {5},
issn = {1530-8561},
address = {Washington, DC},
publisher = {American Association for Clinical Chemistry},
reportid = {DKFZ-2018-01849},
pages = {830 - 842},
year = {2018},
note = {317},
abstract = {The current standard for determining eligibility of
patients with metastatic melanoma for BRAF-targeted therapy
is tissue-based testing of BRAF mutations. As patients are
rarely rebiopsied, detection in blood might be advantageous
by enabling a comprehensive assessment of tumor mutational
status in real time and thereby representing a noninvasive
biomarker for monitoring BRAF therapy.In all, 634 stage I to
IV melanoma patients were enrolled at 2 centers, and 1406
plasma samples were prospectively collected. Patients were
assigned to 3 separate study cohorts: study 1 for assessment
of circulating tumor DNA (ctDNA) as part of companion
diagnostics, study 2 for assessment of ctDNA for patients
with low tumor burden and for follow-up, and study 3 for
monitoring of resistance to BRAF inhibitor (BRAFi) or
mitogen-activated protein kinase inhibitor therapy.Overall,
a high degree of concordance between plasma and tissue
testing results was observed at $90.9\%$ (study 1) and
$90.1\%$ (study 2), respectively. Interestingly, discrepant
results were in some cases associated with nonresponse to
BRAFi (n = 3) or a secondary BRAF-mutant malignancy (n = 5).
Importantly, ctDNA results correlated with the clinical
course of disease in $95.7\%$ and with response to
treatment. Significantly, the detection of BRAF mutant ctDNA
preceded relapse assessed by Response Evaluation Criteria in
Solid Tumors, and was more specific than serum S100 and
lactate dehydrogenase.Blood-based testing compares favorably
with standard-of-care tissue-based BRAF mutation testing.
Importantly, blood-based BRAF testing correlates with the
clinical course, even for early-stage patients, and may be
used to predict response to treatment, recurrence, and
resistance before radioimaging under BRAFi therapy, thereby
enabling considerable improvements in patient treatment.},
cin = {G300 / C060 / L401},
ddc = {610},
cid = {I:(DE-He78)G300-20160331 / I:(DE-He78)C060-20160331 /
I:(DE-He78)L401-20160331},
pnm = {317 - Translational cancer research (POF3-317)},
pid = {G:(DE-HGF)POF3-317},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29483107},
doi = {10.1373/clinchem.2017.281543},
url = {https://inrepo02.dkfz.de/record/141330},
}