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Tumour pharmacodynamics and circulating cell free DNA in patients with refractory colorectal carcinoma treated with regorafenib

Overview of attention for article published in Journal of Translational Medicine, January 2015
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Mentioned by

twitter
2 tweeters

Citations

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39 Dimensions

Readers on

mendeley
67 Mendeley
citeulike
1 CiteULike
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Title
Tumour pharmacodynamics and circulating cell free DNA in patients with refractory colorectal carcinoma treated with regorafenib
Published in
Journal of Translational Medicine, January 2015
DOI 10.1186/s12967-015-0405-4
Pubmed ID
Authors

Andrea Wong, Joline Lim, Arvind Sinha, Anil Gopinathan, Robert Lim, Chee-Seng Tan, Thomas Soh, Sudhakar Venkatesh, Christina Titin, Nur Sapari, Soo-Chin Lee, Wei-Peng Yong, David Tan, Brendan Pang, Ting-Ting Wang, Ying-Kiat Zee, Richie Soong, Zuzana Trnkova, Chetan Lathia, Jean-Paul Thiery, Scott Wilhelm, Michael Jeffers, Boon-Cher Goh

Abstract

Regorafenib, a multi-kinase inhibitor, is used in the treatment of patients with metastatic colorectal cancer refractory to standard therapy. However, this benefit was limited to 1.4 months improvement in overall survival, with more than half of patients experiencing grade 3 to 4 adverse events. We aim to elucidate the pharmacodynamic effects of regorafenib in metastatic colorectal cancer and discover potential biomarkers that may predict clinical benefit. Patients with metastatic colorectal adenocarcinoma refractory to standard therapy with tumours amenable to biopsy were eligible for the study. Regorafenib was administered orally at 160 mg daily for 3 out of 4 weeks with tumour assessment every 2 cycles. Metabolic response was assessed by FDG PET-CT scans (pre-treatment and day 15); paired tumour biopsies (pre-treatment and day 21 post-treatment) were sampled for immunohistochemistry and proteomic profiling analyses. Plasma circulating cell free DNA was quantified serially before and after treatment. There were 2(6%) partial responses out of 35 patients, and 8(23%) patients had stable disease for more than 7 months. Adverse event profile was similar to reported data. Recurrent somatic mutations in K-RAS, PIK3CA and BRAF were detected in plasma circulating cell free DNA in 14 patients; some mutations were not found in archival tumour. Total plasma circulating cell free DNA inversely correlated with progression free survival (PFS), and presence of KRAS mutations associated with shorter PFS. Immunohistochemistry of pre- and post- treatment biopsies showed majority of patients had downregulation of phosphorylated-VEGFR2, podoplanin, phosphorylated-AKT, Ki-67 and upregulation of the MEK-ERK axis, phosphorylated-C-MET, phosphorylated-SRC, phosphorylated-STAT3 and phosphorylated-JUN. Proteomic analysis of fine needle tumour aspirates showed down-regulation of PI3K was associated with longer PFS. Plasma circulating cell free DNA may yield potential predictive biomarkers of regorafenib treatment. Downregulation of the PI3K-AKT axis may be an important predictor of clinical benefit.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 67 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Ireland 1 1%
Austria 1 1%
Unknown 65 97%

Demographic breakdown

Readers by professional status Count As %
Researcher 21 31%
Student > Ph. D. Student 11 16%
Other 8 12%
Student > Bachelor 6 9%
Student > Master 5 7%
Other 12 18%
Unknown 4 6%
Readers by discipline Count As %
Medicine and Dentistry 25 37%
Biochemistry, Genetics and Molecular Biology 13 19%
Agricultural and Biological Sciences 8 12%
Pharmacology, Toxicology and Pharmaceutical Science 4 6%
Psychology 3 4%
Other 4 6%
Unknown 10 15%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 14 January 2016.
All research outputs
#3,236,230
of 6,975,036 outputs
Outputs from Journal of Translational Medicine
#770
of 1,651 outputs
Outputs of similar age
#106,362
of 234,533 outputs
Outputs of similar age from Journal of Translational Medicine
#46
of 107 outputs
Altmetric has tracked 6,975,036 research outputs across all sources so far. This one has received more attention than most of these and is in the 50th percentile.
So far Altmetric has tracked 1,651 research outputs from this source. They receive a mean Attention Score of 4.8. This one is in the 44th percentile – i.e., 44% 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 234,533 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 50% of its contemporaries.
We're also able to compare this research output to 107 others from the same source and published within six weeks on either side of this one. This one is in the 45th percentile – i.e., 45% of its contemporaries scored the same or lower than it.