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Vemurafenib plus cobimetinib in unresectable stage IIIc or stage IV melanoma: response monitoring and resistance prediction with positron emission tomography and tumor characteristics (REPOSIT)…

Overview of attention for article published in BMC Cancer, September 2017
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Title
Vemurafenib plus cobimetinib in unresectable stage IIIc or stage IV melanoma: response monitoring and resistance prediction with positron emission tomography and tumor characteristics (REPOSIT): study protocol of a phase II, open-label, multicenter study
Published in
BMC Cancer, September 2017
DOI 10.1186/s12885-017-3626-5
Pubmed ID
Authors

Bernies van der Hiel, John B.A.G. Haanen, Marcel P.M. Stokkel, Daniel S. Peeper, Connie R. Jimenez, Jos H. Beijnen, Bart A. van de Wiel, Ronald Boellaard, Alfons J.M. van den Eertwegh, REPOSIT study group

Abstract

In patients with BRAFV600 mutated unresectable stage IIIc or metastatic melanoma, molecular targeted therapy with combined BRAF/MEK-inhibitor vemurafenib plus cobimetinib has shown a significantly improved progression-free survival and overall survival compared to treatment with vemurafenib alone. Nevertheless, the majority of BRAFV600 mutation-positive melanoma patients will eventually develop resistance to treatment. Molecular imaging with (18)F-Fluorodeoxyglucose ((18)F-FDG) PET has been used to monitor response to vemurafenib in some BRAFV600 mutated metastatic melanoma patients, showing a rapid decline of (18)F-FDG uptake within 2 weeks following treatment. Furthermore, preliminary results suggest that metabolic alterations might predict the development of resistance to treatment. (18)F-Fluoro-3'-deoxy-3'L-fluorothymidine ((18)F-FLT), a PET-tracer visualizing proliferation, might be more suitable to predict response or resistance to therapy than (18)F-FDG. This phase II, open-label, multicenter study evaluates whether metabolic response to treatment with vemurafenib plus cobimetinib in the first 7 weeks as assessed by 18F-FDG/18F-FLT PET can predict progression-free survival and whether early changes in 18F-FDG/18F-FLT can be used for early detection of treatment response compared to standard response assessment with RECISTv1.1 ceCT at 7 weeks. Ninety patients with BRAFV600E/K mutated unresectable stage IIIc/IV melanoma will be included. Prior to and during treatment all patients will undergo (18)F-FDG PET/CT and in 25 patients additional (18)F-FLT PET/CT is performed. Histopathological tumor characterization is assessed in a subset of 40 patients to unravel mechanisms of resistance. Furthermore, in all patients, blood samples are taken for pharmacokinetic analysis of vemurafenib/cobimetinib. Outcomes are correlated with PET/CT-imaging and therapy response. The results of this study will help in linking PET measured metabolic alterations induced by targeted therapy of BRAFV600 mutated melanoma to molecular changes within the tumor. We will be able to correlate both (18)F-FDG and (18)F-FLT PET to outcome and decide on the best modality to predict long-term remissions to combined BRAF/MEK-inhibitors. Results coming from this study may help in identifying responders from non-responders early after the initiation of therapy and reveal early development of resistance to vemurafenib/cobimetinib. Furthermore, we believe that the results can be fundamental for further optimizing individual patient treatment. Clinicaltrials.gov identifier: NCT02414750. Registered 10 April 2015, retrospectively registered.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 35 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 35 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 6 17%
Other 5 14%
Student > Master 5 14%
Student > Bachelor 4 11%
Student > Ph. D. Student 3 9%
Other 5 14%
Unknown 7 20%
Readers by discipline Count As %
Medicine and Dentistry 13 37%
Unspecified 3 9%
Nursing and Health Professions 3 9%
Business, Management and Accounting 1 3%
Biochemistry, Genetics and Molecular Biology 1 3%
Other 5 14%
Unknown 9 26%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 September 2017.
All research outputs
#18,572,844
of 23,003,906 outputs
Outputs from BMC Cancer
#5,460
of 8,357 outputs
Outputs of similar age
#242,686
of 316,191 outputs
Outputs of similar age from BMC Cancer
#84
of 120 outputs
Altmetric has tracked 23,003,906 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 8,357 research outputs from this source. They receive a mean Attention Score of 4.3. This one is in the 21st percentile – i.e., 21% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 316,191 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 12th percentile – i.e., 12% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 120 others from the same source and published within six weeks on either side of this one. This one is in the 15th percentile – i.e., 15% of its contemporaries scored the same or lower than it.