Cell Counting Kit-8 the higher concordance for newer biomark
the higher concordance for newer biomarkers such as NRAS. Third, the patients varied in the systemic treatments they received, and the impact of this on the metastasis (tumour regression after chemo- or radiother-apy) may have affected the sequencing result through adequacy of the sample. Fourth, it is important to note that any change in concordance may represent the Cell Counting Kit-8 of the tumour as it metastasises and there-fore the time between the primary tumour and metastasis sampling is an important factor to consider which could not be accounted for. Fi-nally inter-tumour heterogeneity means that sufficient samples may not have been possible to obtain in many of the studies to determine biomarker status especially at the metastatic sites.
Despite the above limitations, we feel that this study has demon-strated high biomarker concordance rate between primary tumours and the metastases with challenges in getting adequate sample size from metastatic sites likely to account for most discordance. This has important practical implications as it suggests there is little evidence
for separate biopsy of the primary and metastatic sites. Whether the evolving use of liquid biopsy through circulating tumour DNA (ctDNA) analysis adds anything further to a patient's treatment options remains to be seen. We also feel that little information is currently available on peritoneal metastases and this is an area for further research.
mCRC demonstrates remarkably high concordance across a number of individual biomarkers, suggesting that molecular testing of either the primary or liver and lung metastasis is adequate for determining bio-marker status to personalize treatment. More research is required to de-termine concordance in colorectal cancer peritoneal metastases which may explain why these tumours have a significantly worse prognosis compared to other sites. Clonal selection and tumour evolution add
Fig. 5. Forest plot for proportion of discordance of studies considering the overall molecular profiles. The estimate proportion and 95% CI interval at the level of the total number of cases reflects the calculation under a fixed effect model. The estimate proportion and 95% CI interval at the level of the Pooled Discordance Proportion are the random effects pooled estimates to take into account heterogeneity.
further inherent complexities that may be addressed through new sam-pling strategies and novel technologies in development.
Supplementary data to MtDNA article can be found online at https://doi.
Dilraj S Bhullar - Literature search, figures, study design, data collec-tion, data analysis, data interpretation, writing.
Omer Aziz - Literature search, figures, study design, data collection, data analysis, data interpretation, writing.
Sarah T O'Dwyer - Study design, data analysis, data interpretation, writing.
Jorge Barriuso - Figures, study design, data analysis, data interpreta-tion, writing.
Saifee Mullamitha - Data interpretation, writing.
Mark P Saunders - Data interpretation, writing.
Conflict of interest
The authors have declared no conflicts of interest.
 Galandiuk S, Wieand HS, Moertel CG, Cha SS, Fitzgibbons RJJ, Pemberton JH, et al. Patterns of recurrence after curative resection of carcinoma of the colon and rec-tum. Surg Gynecol Obstet 1992 Jan;174(1):27–32.
 Segelman J, Granath F, Holm T, Machado M, Mahteme H, Martling A. Incidence, prevalence and risk factors for peritoneal carcinomatosis from colorectal cancer. Br J Surg 2012 May;99(5):699–705.
 Koppe MJ, Boerman OC, Oyen WJG, Bleichrodt RP. Peritoneal carcinomatosis of co-lorectal origin: incidence and current treatment strategies. Ann Surg 2006 Feb;243 (2):212–22.
 Hurwitz HI, Tebbutt NC, Kabbinavar F, Giantonio BJ, Guan Z-Z, Mitchell L, et al. Ef-ficacy and safety of bevacizumab in metastatic colorectal cancer: pooled analysis from seven randomized controlled trials. Oncologist 2013;18(9):1004–12.
 Zhou M, Yu P, Qu J, Chen Y, Zhou Y, Fu L, et al. Efficacy of bevacizumab in the first-line treatment of patients with RAS mutations metastatic colorectal cancer: a sys-tematic review and network meta-analysis. Cell Physiol Biochem 2016;40(1–2): 361–9.
 Sorich MJ, Wiese MD, Rowland A, Kichenadasse G, McKinnon RA, Karapetis CS. Ex-tended RAS mutations and anti-EGFR monoclonal antibody survival benefit in met-astatic colorectal cancer: a meta-analysis of randomized, controlled trials. Ann Oncol Off J Eur Soc Med Oncol 2014 Jan;26(1):13–21.  Peeters M, Oliner KS, Price TJ, Cervantes A, Sobrero AF, Ducreux M, et al. Analysis of KRAS/NRAS Mutations in a phase III study of panitumumab with FOLFIRI compared with FOLFIRI alone as second-line treatment for metastatic colorectal cancer. Clin Cancer Res 2015 Dec;21(24):5469–79.