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Clinical Oncology 28 (2016) 71 e 72 Contents lists available at ScienceDirect Clinical Oncology journal homepage:

Contents lists available at ScienceDirect

Clinical Oncology

journal homepage:

Oncology journal homepage: Editorial Colorectal Cancer D.C. Gilbert * , S.J. Falk y


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 con dence 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] , 15 e 20% occurs more rapidly through an inability to repair very short mismatches of DNA. The only molecular stratication 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 stratied 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: (D.C. Gilbert).

address: (D.C. Gilbert). in accurately staging rectal cancers preoperatively has led
address: (D.C. Gilbert). in accurately staging rectal cancers preoperatively has led

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 uoroxypyr- 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 ef cacy seen in the adjuvant setting, and in keeping with the shift to the neoadjuvant approach favoured in all gastrointestinal cancers (MAGIC), Gollins and Sebag-Monte ore [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

0936-6555/ 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.


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 super cial lesions as rst-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 nd that this collection of articles ad- dresses current questions that weekly vex our multidisci- plinary teams and gives insights into future directions.