Clinical Oncology 28 (2016) 71e72
Contents lists available at ScienceDirect
Clinical Oncology
journal homepage: www.clinicaloncologyonline.net
Editorial
Colorectal Cancer
D.C. Gilbert *, S.J. Falk y
* Sussex Cancer Centre, Royal Sussex County Hospital, Brighton, UK
y
Bristol Haematology and Oncology Centre, Bristol, UK
Received 9 November 2015; accepted 9 November 2015
Until recently, colorectal cancer has been treated as a
single disease entity with treatment decisions predomi-
nately based on patient and clinician preference as opposed
to any real biological confidence in identifying which agents
or strategies will probably be most effective. Therapeutic
strategies have not kept up with our knowledge of the
biology of the disease. This special issue aims to address
developments in molecular targeting, imaging and thera-
peutic decision making in this disease.
It is now well recognised that although 85% of colorectal
cancer develops classically via chromosomal instability ac-
cording to the adenoma carcinoma sequence [1], 15e20%
occurs more rapidly through an inability to repair very short
mismatches of DNA. The only molecular stratification to
date in widespread practice has been the avoidance of
adjuvant chemotherapy in Microsatellite unstable (MSI
high) stage II cases [2] and of epidermal growth factor re-
ceptor targeted agents in RAS/RAF mutated tumours [3].
However, a deeper understanding of the differing routes of
tumourigenesis, as outlined by Biswas et al. [4], is beginning
to reveal insights that should have therapeutic implications
and represent a real hope of clinically meaningful im-
provements in standards of care. In parallel with these ad-
vances in understanding runs the ongoing FOCUS4 trial, a
multi-arm, multi-stage platform testing novel agents in
biomarker stratified arms as maintenance therapy after
initial chemotherapy in the metastatic setting. One impor-
tant feature of this platform is the ability to adapt to new
discoveries (such as the apparent sensitivity of microsatel-
lite unstable colorectal cancer to immune checkpoint inhi-
bition [5]).
As a molecular understanding begins to guide treatment
decisions, so too must advanced imaging techniques. This is
of particular relevance in the multimodality treatment of
rectal cancer [6]. The value of magnetic resonance imaging
Author for correspondence: D.C. Gilbert, Sussex Cancer Centre, Royal
Sussex County Hospital, Eastern Road, Brighton BN2 5BE, UK.
E-mail address: duncan.gilbert@bsuh.nhs.uk (D.C. Gilbert).
http://dx.doi.org/10.1016/j.clon.2015.11.005
0936-6555/Ó 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
in accurately staging rectal cancers preoperatively has led to
real improvements in outcome nationally, namely in
reducing rates of positive resection margins and subsequent
local recurrences, and is a cornerstone of multidisciplinary
team working. Prezzi and Goh [6] describe how dynamic
techniques may better predict response to treatment and
subsequent toxicities.
Longstanding practical debates are covered too. Intro-
duction of intensity-modulated radiotherapy protocols for
rectal cancer has lagged behind other areas [7] but in this
special issue, Teoh and Muirhead [8] review the relevant
data that currently exist and suggest pointers for the future.
Surgery, of course, retains primary importance in the mul-
timodality treatment of rectal cancer and Renehan [9]
provides a comprehensive overview of current techniques
and areas for further development.
Given the general improvements in locoregional out-
comes in the management of rectal cancer, overall survival
outcomes become the primary concern. The use of preop-
erative chemoradiotherapy poses two questions. First, can
we improve on concurrent treatment with a fluoroxypyr-
imidine. Greenhalgh et al. [10] review where we are with
current data and discuss future approaches in terms of
novel agents to combine with chemoradiotherapy. Second,
Boustani et al. [11] address the frequent clinical question
around whether to follow the operation with further adju-
vant chemotherapy, showing why this is not supported by
current evidence, but suggesting future studies.
Undaunted by the lack of efficacy seen in the adjuvant
setting, and in keeping with the shift to the neoadjuvant
approach favoured in all gastrointestinal cancers (MAGIC),
Gollins and Sebag-Montefiore [12] set out the case for pri-
oritising testing further neoadjuvant chemotherapy
schedules.
At the other end of the spectrum are the patients who
experience an apparent complete clinical response in their
rectal cancer after chemoradiotherapy. Naturally, organ
preservation is an attractive option (comparing the
72 D.C. Gilbert, S.J. Falk / Clinical Oncology 28 (2016) 71e72

situation in anal cancer where chemoradiotherapy has
replaced surgery for all but the most superficial lesions as
first-line standard of care). In the case of rectal cancer,
however, this remains a divisive and emotive subject, with
proponents seeking to ever improve rates of complete
response and treat ever earlier cancers. Yet the optimal
surveillance pathways and predictors of success in this
approach remain controversial. In this regard we include a
balanced review of the evidence thus far and where we
might go next as a clinical community [13].
We hope you find that this collection of articles ad-
dresses current questions that weekly vex our multidisci-
plinary teams and gives insights into future directions.
[10] Greenhalgh TA, Dearman C, Sharma RA. Combination of novel
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