Radiotherapy Developments
Metrology Guided Radiation Therapy
North West Medical Physics
The North West Medical
Physics department (NWMP) provides a wide range of
services to The Christie NHS Foundation Trust and most other trusts
within the North-West, including radiotherapy and radiation
research.
The Developing Technologies Radiotherapy (DTRT) group, led by
Professor Christopher Moore, are a key collaborator on the Metrology Guided
Radiation Therapy (MEGURATH) project. Metrology Guided
Radiation Therapy allows measurement of the body, tumour and
tissues during radiotherapy beam delivery, and combines dynamic
deformable modeling for a meaningful comparison with the treatment
plan. The aim is to address patient positioning and allow better
targeting of radiotherapy to the tumour site and treatment delivery
for an individual patient.
Academic Department of Radiation Oncology
Academic department of radiation oncology (ADRO) is based at the
Christie and is directed by Professor Pat Price. It was established
in September 2000 by the Christie, in partnership with The
University of Manchester and Cancer Research UK.
ADRO was developed to meet our specific requirements as
contained in the 1996 Bill Duncan report, to provide clinical
oncology support for Professor Price's research base within ADRO
and the Wolfson Molecular Imaging Centre (WMIC), and to link with
other University, Trust and Paterson Institute for Cancer Research
(PICR) groups. The group receives support from the Christie, The
University of Manchester, Cancer Research UK, the Experimental
Cancer Medicine Centre (ECMC), the Paterson Institute for Cancer
Research (PICR) and Elekta Oncology Systems.
Currently ADRO comprises four main research
groups:
- Technical Radiotherapy
- Molecular Imaging Radiobiology
- Translational Radiogenomics
- Outcome Measures (see late effects)
Technical Radiotherapy Research Group
The major goal of our technical radiotherapy research group is
to improve radiation treatment outcome by developing and assessing
more accurate methods of delivering radiation dose to tumour
tissue. By investigating current inaccuracies and toxicity
associated with radiation delivery and evaluating the benefits of
innovative techniques and new imaging technologies, we aim to
improve and advance the field of technical radiotherapy
practice.
Approximately 50% of patients with cancer receive
radiotherapy at some point in their management. In many cases,
radiotherapy is the only prescribed curative treatment. The
curative potential of radiotherapy is high, but is limited by the
maximum radiation dose that can be delivered to tumours without
affecting surrounding normal tissue. Focusing the radiation dose on
the tumour and sparing the normal tissue are the most important
goals of radiation therapy techniques. This allows dose escalation,
and subsequently greater tumour control, with a lower rate of toxic
side effects.
Our three main aims are:
- To improve the definition of the volume of tissue we wish
to treat
- To improve the accuracy of radiation treatment
delivery
- Assess, minimise and account for inter/intra-fraction
organ motion and deformation
We aim to achieve this by developing novel image-guided
radiotherapy techniques, including online 3D x-ray volumetric
imaging, online fluoroscopic verification and infrared surface
sensing contouring.
Molecular Imaging/ Radiobiology Programme
The aim of our molecular imaging/radiobiology programme is
to investigate and develop positron emission tomography (PET) as a
tool for obtaining biological data in patients undergoing
radiotherapy. By evaluating biological data obtained using
non-invasive imaging, we will be able to increase our understanding
of the radiobiology of both tumour and normal tissue and develop
rational strategies for improving and optimising radiotherapy
delivery.
PET is a powerful nuclear medicine imaging tool which
quantitates the changing activity of radiotracers within anatomical
areas of interest defined by conventional cross-sectional imaging.
This is a non-invasive technique.
Blood flow, blood volume and hypoxia can all be imaged by
PET. They are closely interrelated, but these relationships are not
simple, and may depend on tumour size, tumour type, and method of
flow measurement. Flow may also be predictive for response of
cancer following treatment, and may allow modification of further
treatments accordingly. This is an evolving area of clinical
research, and has application to anti-cancer drug development and
radiotherapy.
Studies currently being run by the group
include:
Pancreatic cancer functional imaging translational (PACER-FIT)
study
This study will use a subset of patients from a larger
study (PACER) which aims to demonstrate the response rate (using
RECIST criteria) of cetuximab plus radiotherapy in locally advanced
pancreatic cancer patients.
The primary aims of PACER-FIT are to assess the value of FDG-PET
as a pharmacodynamic marker of tumour response, assess the value of
FDG-PET as a prognostic marker, and evaluate changes in tumour
perfusion with cetuximab/radiotherapy.
Head and neck cancer study
The aim of this project is to measure tumour blood flow
and volume using PET in 12 patients with cancers, to establish
optimum operating conditions for the new PET-CT scanner. We also
aim to calculate the lowest dose of radiation which we can
administer to patients. This information will also have application
for other centres wanting to optimise their PET
methodology.
Similar work has been done on older PET cameras and for brain
scanning, as opposed to scanning elsewhere in the body. The
improvement in count rate performance of the new generation of PET
cameras will mean that better quality data is possible, and to our
knowledge this has not been studied for radiolabelled water and
carbon monoxide.
Blood flow study
The aim of this project is to measure tumour blood flow and
volume using PET in 12 patients with cancers, to establish optimum
operating conditions for the new PET-CT scanner. We also aim to
calculate the lowest dose of radiation which we can administer to
patients. This information will also have application for other
centres wanting to optimise their PET methodology.
Similar work has been done on older PET cameras and for brain
scanning, as opposed to scanning elsewhere in the body. The
improvement in count rate performance of the new generation of PET
cameras will mean that better quality data is possible, and to our
knowledge this has not been studied for radiolabelled water and
carbon monoxide.
Figure 1: Dendogram of 59 head and neck cancers clustered using
a knowledge-based derived hypoxia transcriptome.
Translational Radiogenomics Group
This group is led by Dr Catharine West; it explores and develops
methods for the individualisation of radiation therapy. With the
advent of high-throughput techniques, it is interested in the
characterisation of molecular profiles that reflect relevant
biological phenotypes and predict tumour and normal tissue response
to radiation.
Hypoxia
Figure 2: HIF-1a expression was not observed in normal gastric
mucosa. Low and weak HIF-1a expression was observed in mucosa
infected with H. pylori and increased in percentage and intensity
with the sequence of H. pylori associated gastritis, intestinal
metaplasia, dysplasia and intestinal type adenocarcinoma (top to
bottom)
The knowledge that hypoxic cells are resistant to the
biological effects of sparsely ionising radiation has dominated
radiotherapy-associated radiobiology research for fifty years. Only
in recent years, however, has hypoxia been widely recognised as a
key factor driving malignant progression, metastasis formation and
cancer treatment resistance. The ability to measure the hypoxic
status of a tumour in a routine clinical setting would be a major
advance. Towards this goal we are conducting prospective studies
measuring tumour oxygenation in patients with head and neck, cervix
and gastric cancer.
Hypoxia transcriptome in head and neck cancer
A recent analysis of microarray data from patients with
head and neck cancer defined an in vivo hypoxia transcriptome
(Figure 1). The work identified several novel genes not previously
recognised as hypoxia regulated. The hypoxia transcriptome was an
independent prognostic factor for recurrence-free survival in an
unrelated dataset, outperforming the original intrinsic
classification.
Hypoxia in gastric cancer
There is a lack of published studies
looking at hypoxia or the expression of hypoxia inducible factor-1α
(HIF-1α) in gastric cancers. We are the first group to show that
HIF-1α expression increases in the progression of intestinal type
gastric carcinogenesis (Figure 2).
Intrinsic radiosensitivity
Another biological feature important in determining how a
patient responds to radiotherapy is their intrinsic sensitivity to
radiation. Some patients are inherently radiosensitive and likely
to develop severe long-term complications, which may not become
apparent for several months or even years following treatment. The
small numbers of patients who develop severe late-radiation
toxicity limit the total curative doses that can be safely
administered to all patients. The ability to predict patients
predisposed to developing toxicity early has potential for allowing
safe dose-escalation in others to increase their chance of a cure.
The translational radiogenomics group is interested in assessing
methods for measuring normal tissue radiosensitivity.
Radiogenomics: Assessment of Polymorphisms for Predicting the
Effects of Radiotherapy (RAPPER) is a national study funded by
Cancer Research UK and run by the group. The study aims to collect
blood from up to 3000 patients with breast, prostate or
gynaecological cancer who will undergo/underwent radiotherapy.
Polymorphisms in ADROund 50 candidate genes will be investigated in
relation to patient risk of radiotherapy morbidity.
Non-invasive imaging
The use of imaging (MRI, PET) to measure biologically
relevant phenotypes is also of interest. We are using dynamic
contrast-enhanced MRI to measure blood-flow-related parameters in
cancer patients and are able to correlate the data obtained with
measurements of hypoxia and angiogenesis. The increased
availability and use of PET in cancer diagnosis and management
provides a rationale for an expansion in its parallel development
as a tool for imaging tumour biology. PET is a powerful and
versatile tool for the sensitive and repeatable imaging and
quantifying of cellular and molecular processes in situ in humans.
In collaboration with the Wolfson Molecular Imaging Centre, we are
exploring the potential of PET for imaging mechanisms of
radiotherapy resistance such as hypoxia and blood flow
