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Molecular biomarkers and precision medicine in colorectal cancer: A systematic review of health economic analyses

Abstract:
An increased understanding of the biology of colorectal cancer (CRC) has fuelled identification of biomarkers with potential to drive a stratified precision medicine care approach in this common malignancy. We conducted a systematic review of health economic assessments of molecular biomarkers (MBMs) and their employment in patient stratification in CRC. Our analysis revealed scenarios where health economic analyses have been applied to evaluate the cost effectiveness of MBM-guided clinical interventions: (i) evaluation of Dihydropyrimidine dehydrogenase gene (DPYD) status to identify patients susceptible to 5-Fluouracil toxicity; (ii) determination of Uridine 5'-diphospho- glucuronosyltransferase family 1 member A1 gene (UGT1A1) polymorphism status to help guide irinotecan treatment; (iii) assessment of RAS/RAF mutational status to stratify patients for chemotherapy or Epidermal Growth Factor Receptor (EGFR) therapy and (iv) multigene expression analysis (Oncotype Dx) to identify and spare non-responders the debilitating effects of particular chemotherapy interventions. Our findings indicate that Oncotype Dx is cost-effective in high income settings within specific price points, by limiting treatment toxicity in CRC patients. DPYD status testing may also be cost effective in certain settings to avoid specific 5-FU toxicities post treatment. In contrast, current research does not support UGT1A1 polymorphism status as a cost-effective guide to irinotecan dosing, while the health economic evidence to support testing of KRAS/NRAS mutational status and chemo/EGFR therapy choice was inconclusive, despite its widespread adoption in CRC treatment management. However, we also show that there is a paucity of high-quality cost-effectiveness studies to support clinical application of precision medicine approaches in CRC.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.18632/oncotarget.26909

Authors


More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Oncology
Sub department:
CRUK/MRC Ox Inst for Radiation Oncology
Role:
Author
More by this author
Institution:
University of Oxford
Division:
Continuing Education
Department:
Continuing Education - EQ Central
Sub department:
Botnar Research Centre
Role:
Author


Publisher:
Impact Journals
Journal:
Oncotarget More from this journal
Volume:
10
Issue:
36
Pages:
3408-3423
Publication date:
2019-05-21
Acceptance date:
2019-04-21
DOI:
EISSN:
1949-2553
Pmid:
31164962


Language:
English
Keywords:
Pubs id:
pubs:1007326
UUID:
uuid:2312b2ad-8e77-4a61-b5c1-969aea4a2acb
Local pid:
pubs:1007326
Source identifiers:
1007326
Deposit date:
2019-06-19

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