Original ResearchThe relevance of primary tumour location in patients with metastatic colorectal cancer: A meta-analysis of first-line clinical trials
Section snippets
Background
Tumours arising from different regions of the colon are clinically and molecularly distinct [1], [2], [3], [4], [5]. Beside differences in the luminal content (e.g. bacterial flora), this might reflect also the ontogenesis with left-sided colon tumours (LC) deriving from the embryonic hindgut and right-sided colon tumours (RC) deriving from the embryonic midgut [6], [7]. As the embryological demarcation line at the distal third of the colon transversum is difficult to determine in retrospective
Search strategy and selection criteria
A PubMed-based search including the following search terms was conducted in October 2016: colon cancer, colorectal cancer, metastatic colorectal cancer, mCRC as well as primary tumour location, left-sided tumour, right-sided tumour, sidedness. Relevant MeSH terms (Medical Subject Headings) were used where possible. No restrictions were placed on the searches. The titles and abstracts of all remaining citations were reviewed and irrelevant citations were discarded. Potentially relevant studies
Overview of the included trials
In a total of 13 first-line RCTs and one prospective pharmacogenetic study (PROVETTA), the role of PTL was investigated (Table 1). In these studies, the weighted overall HRs for PTL with regard to OS and PFS were evaluated (Fig. 1).
For a total of seven trials, the impact of PTL on OS and PFS within the different treatment arms was evaluable (Supplementary Fig. S1). Supplementary Table S1 shows the corresponding survival times.
Five trials reported detailed outcome of the differential treatment
Discussion
Previous reports have suggested that PTL has prognostic implications and impacts on response to targeted therapy in patients with mCRC. Nevertheless, these analyses are limited by sample size and heterogeneity of molecular subgroups and treatments. The presented meta-analysis summarises the available evidence from clinical studies and investigates the prognostic and predictive relevance of PTL.
The data clearly indicate that RC is associated with an inferior prognosis compared to LC. In the RE
Conflict of interest statement
Julian Walter Holch: None declared. Ingrid Ricard: None declared. Sebastian Stintzing has received honoraria from Merck, Roche, Amgen, Bayer, Sanofi-aventis and has served on advisory boards for Merck Serono, Roche Travel support: Roche, Merck Serono, Sanofi-aventis. Dominik Paul Modest has received honoraria from Merck, Roche, Amgen, Bayer and has received research grant from Amgen (inst), Merck (inst), Roche (inst) and has received travel support from Amgen, Merck, Sanofi, Bayer and has
Acknowledgements
The authors thank all patients and families for participation in the studies, as well as all involved study centres, colleagues and nurses.
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