PhD Studentships in New bio-imaging techniques
for staging high-risk rectal cancer
Imperial Cancer Research UK Centre
Biosurgery and Surgical Technology, Division of Surgery,
Department of Surgery and Cancer
Imperial College London, St Mary’s Hospital Campus, Chelsea and
Westminster Campus and Royal Marsden Hospital
Applications are invited from motivated individuals for a PhD studentship in Bio-Imaging,
focusing on techniques for staging high-risk rectal cancer. The post will be based in Division
of Surgery, Chelsea and Westminster Campus. The primary supervisors are Professor Ara
Darzi and Mr Paris Tekkis, and collaboration with Professor Yang and Dr Gina Brown. Full
details of the programme and application forms can be found below.
Imperial College has recently been awarded Cancer Research UK Centre status and the
position is funded from the Centre Training Grant. The studentship will form part of the
Surgery and Robotics, Radiation and Laser Therapy theme within the centre. As the UK’s
first Academic Health Science Centre (AHSC) and largest NHS Trust, Imperial College
Healthcare stands at the forefront of the cancer research and patient care. Our aspiration is
to create a Cancer Research UK Centre that is globally competitive in the development of
treatments tailored to individual cancer patients. Imperial hosts an impressive portfolio of
cancer services and research and is committed to develop interdisciplinary research
programmes that translate basic, laboratory research into clinical practice and point of care
treatment.
Background
In the UK, approximately 14,000 new patients are diagnosed with rectal cancer per year. 3040% of these patients are classed as high risk for local recurrence and may be offered neoadjuvant chemoradiotherapy in order to reduce the risk of local recurrence. Previous work from
our group suggested that “high-risk” patients are often selected based on the following preoperative imaging and histopathologic criteria: (1) threatened resection margins, (2) presence
of extra-mural vascular invasion, (3) locally advanced and recurrent rectal cancer, (4) tumour in
the lower third of the rectum and (5) presence of nodal disease in the mesorectum and pelvic
side wall, (6) mucin producing tumours, (7) poor differentiated and (8) signet cell cancers.1-2
The response to neo-adjuvant therapy is variable and at present we have no means of
predicting who may or may not respond to treatment. There are no validated criteria or
guidelines for judging curative resectability of “high risk” rectal cancer. Selection of patients for
radical surgery and operative planning is usually made following discussion at the MDT
meeting, based on the combination of the patient’s history, clinical examination and evaluation
of the functional and anatomical pre-operative images. Incorrect pre-operative staging and
planning can result in patients undergoing unnecessary surgery (up to 10%) or refused a
potentially curative operation in 17% of cases.
Pre-operative staging using diffusion-weighted MRI and PET-CT are evolving imaging
modalities that offer both anatomical and functional information for patients with rectal cancer.
Although these imaging modalities are often used for staging extra-pelvic (stage IV) disease,
their role for preoperative planning, and characterization of the ‘high risk” patient who may not
respond to conventional treatment remains to be established.
Aims of project
1. To improve surgical understanding and operative planning by evaluation of anatomical,
morphological, functional and physiological tumour parameters assessable preoperatively
using combined high resolution MRI, diffusion weighted MRI, PET-CT and MRI-PET fusion.
2. To develop and validate bioimaging prognostic markers for efficacy of treatment in high
risk rectal cancer
3. To improve preoperative predictive markers for response to neoadjuvant treatment and
the possibility of obtaining a curative resection.
4. Develop tumour tissue biobank of advanced cancers with carefully validated imaging
and pathology staging, prognostic and outcome data: develop integrated imaging and
pathology datasets for future collaborations.
Methodology
Consecutive patients, diagnosed with high-risk locally advanced primary or recurrent rectal
cancer undergoing surgery at Imperial College or at the Royal Marsden Hospital will be
included in the study. All patients will be assessed pre-operatively by high resolution MRI,
diffusion weighted-MRI and PET-CT. Fusion of PET and MRI images will be undertaken on a
Hermes workstation 3 using pre-defined anatomical landmarks for image overlay. Two
radiologists specialised in pelvic imaging, will be reviewing each study separately using
dedicated proformas and blinded to the other modalities and clinical findings. Their findings will
be compared against intra-operative findings and histopathology (gold Standard).
High resolution MRI will be used to scan the surgically resected specimens and a 3D model
developed portraying the complex relationship between blood vessels, nerves, target organs
and anatomical planes of resection. Two expert radiologists and surgeons will independently
assess the 3D MRI scans and equivalent histopathology specimen of the pelvis marking the
resection margins and the threatened circumferential resection margins. The structural 3D
anatomy will be mapped out, correlated and validated with histopathology using equivalent
megablocks corresponding to the radiological sections.
Data collection will be prospective on imaging reporting, intra-operative findings, peri-operative
outcomes, histopathological tumour clearance and characteristics of local recurrence and
disease free survival. Dedicated proformas will be used for routine histopathology reporting as
well as data on markers of proliferation and apoptosis, cytokeratin profile, lymphogenesis and
perineural involvement. Hard copy data will be collated and stored in a secure research office
for a period of 5 years after the study completion.
Successful applicants will undertake a PhD, commencing in 2010. To be eligible, applicants
should hold or expect to obtain a first or upper-second class honours degree or equivalent in
a relevant biological science. In addition, for admission to a PhD research programme
Imperial College would normally expect you to hold or achieve a Master's degree.
The stipend for year 1 will be £ 17,500pa. Interested applicants should submit a curriculum
vitae, a personal statement and names of two referees to Dr Karen Kerr
(k.kerr@imperial.ac.uk). UK/EU citizens can apply: only UK/EU student fees are available.
For further information please contact Mr Paris Tekkis: p.tekkis@imperial.ac.uk.
Closing date:
31st August 2010.