You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output.
Click here to find out more.
X Demographics
Mendeley readers
Attention Score in Context
| Title |
Tumour pharmacodynamics and circulating cell free DNA in patients with refractory colorectal carcinoma treated with regorafenib
|
|---|---|
| Published in |
Journal of Translational Medicine, February 2015
|
| DOI | 10.1186/s12967-015-0405-4 |
| Pubmed ID | |
| Authors |
Andrea Li Ann Wong, Joline Si Jing Lim, Arvind Sinha, Anil Gopinathan, Robert Lim, Chee-Seng Tan, Thomas Soh, Sudhakar Venkatesh, Christina Titin, Nur Sabrina Sapari, Soo-Chin Lee, Wei-Peng Yong, David Shao Ping 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. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 104 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 | 102 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 19 | 18% |
| Student > Ph. D. Student | 15 | 14% |
| Other | 11 | 11% |
| Student > Doctoral Student | 9 | 9% |
| Student > Bachelor | 8 | 8% |
| Other | 20 | 19% |
| Unknown | 22 | 21% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 35 | 34% |
| Biochemistry, Genetics and Molecular Biology | 17 | 16% |
| Agricultural and Biological Sciences | 9 | 9% |
| Pharmacology, Toxicology and Pharmaceutical Science | 5 | 5% |
| Nursing and Health Professions | 2 | 2% |
| Other | 6 | 6% |
| Unknown | 30 | 29% |
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
#14,801,174
of 22,789,076 outputs
Outputs from Journal of Translational Medicine
#1,972
of 3,988 outputs
Outputs of similar age
#202,096
of 357,818 outputs
Outputs of similar age from Journal of Translational Medicine
#58
of 115 outputs
Altmetric has tracked 22,789,076 research outputs across all sources so far. This one is in the 32nd percentile – i.e., 32% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,988 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.5. 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 357,818 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 40th percentile – i.e., 40% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 115 others from the same source and published within six weeks on either side of this one. This one is in the 41st percentile – i.e., 41% of its contemporaries scored the same or lower than it.