UICC World Cancer Congress 2006

Professor Janet E. Husband OBE, FMedSci, FRCP, FRCR

Introduction There is little in the history of medicine that can match the revolutionary advances which have taken place in cancer imaging over the last two to three decades. Thus today there is a wide spectrum of imaging modalities available for cancer patients which range from relatively simple techniques through to highly sophisticated modalities which require specialist knowledge and complex technical support to deliver the service. Such advances, set against a background of progress in the basic understanding and treatment of cancer, have placed imaging at the centre of patient management. However the persistent increase in incidence of cancer globally, together with improved survival rates for many cancers, has resulted in a relentless increase in demand for cancer imaging. As a result resources required for cancer imaging continue to escalate in both the developed and the developing world and in order to contain these escalating costs, it is important that appropriate strategies for cancer imaging are applied in the management of different tumour types.

The goal of cancer imaging is to improve patient outcome by providing uniform high quality service in which information regarding tumour morphology and tumour behaviour is timely, accurate and relevant to patient management. It is important to recognise that imaging for cancer is only effective if the chosen technology is appropriate for answering the question posed. Furthermore the results of imaging should have an impact on patient management and on clinical outcome, although the latter is extremely difficult to quantify. Recognition of the importance of appropriate assessment of imaging techniques and of their use in clinical practice is essential for cost effective and efficacious cancer imaging. Five levels of assessment to determine the efficacy of diagnostic imaging should be considered [1].

·Technical performance - ability to obtain high image quality. ·Diagnostic performance - ability to identify disease correctly. ·Diagnostic impact - a measure of sensitivity, specificity, positive predictive value, negative predictive value and accuracy. ·Therapeutic impact - influence of the result of imaging on clinical diagnostic confidence. Alteration in management based on results of imaging. ·Impact on health - influence of imaging on disease outcome.

The positive effect of one level is determined by the level above and in turn determines the possibility of a positive result at the level below.

Best practice dictates that the imaging technique which provides the best diagnostic performance will be used in all circumstances, but this is not always possible. In the many different indications for imaging in cancer the modality chosen will depend upon local factors such as the availability of equipment, expertise of medical and ancillary personnel and the demands made on imaging by the overall workload.

Imaging Strategies The appropriate use of imaging in cancer is a complex issue, but nevertheless, guidelines should be drawn up which address the choice of a particular imaging modality and protocols for the technique of imaging in different tumour types. It is important to recognise that as imaging techniques continue to evolve it may be appropriate to use a single more complex and expensive test early in the patient pathway rather than use several different less effective techniques to obtain the information required to direct patient management.

Close collaboration between the radiologist and clinician is essential. Clinical information regarding the suspected or known diagnosis, clinical stage, biochemical markers, previous treatment and coincidental disease should be available to the radiologist at the time of the examination and the imaging examination must be patient focussed.

Patient focus There are important questions at the forefront of every patient's mind whenever he or she undergoes an imaging test for cancer. These questions relate to the clinical impact of imaging in a given clinical situation:

Have I got cancer? Has my cancer spread? Has my treatment worked? Has my cancer come back?

Have I got cancer? The increasing use of population based screening programmes to detect cancer is having a major impact on radiology. In the western world national screening programmes using mammography in breast cancer are now well established and colorectal cancer screening programmes are currently under development. In prostate cancer screening is sporadic and variable and data on the use of spiral CT for screening lung cancer is still being collected in major trials internationally. In this presentation issues related to breast cancer screening with mammography and magnetic resonance imaging (MRI) as well as the need to introduce newer simpler technology to address the increasing incidence and mortality of breast cancer in the developing world will be highlighted [2].

Early detection of cancer is a key target for 21st century medicine. This places considerable challenges on imaging because early tumours are usually small and difficult to distinguish from benign lesions. Furthermore some tumours detected on imaging may have an indolent clinical course and therefore may not require active treatment during the patient's lifetime.

Prediction of tumour aggressiveness and prognosis is therefore an important area of clinical research which demands interrogation of tumour behaviour as well as tumour morphology to identify independent prognostic indicators. For example prostate cancer varies greatly in its potential to progress but conventional imaging with MRI cannot distinguish an aggressive lesion from one which will remain clinically dormant. Magnetic resonance spectroscopy (MRS) is a promising new tool to evaluate these tumours and if used widely may obviate the need for treatment in a large number of patients with non-aggressive prostate tumours [3]. Such research outcome data is not yet making an impact on routine clinical practice but the results of these studies will inform the most effective use of imaging in the years to come.

Has my cancer spread? Staging provides the clinician with information that is relevant to predicting prognosis and stratifying patients for the most appropriate treatment. The UICC TNM staging classification of tumours will be used in this presentation. A multidisciplinary approach to patient management is critical to achieve optimum results and the radiologist plays a central role within this team. Staging solid tumours is largely undertaken using cross-sectional imaging techniques. While computed tomography (CT) remains the workhorse of cancer imaging, endoscopic ultrasound and magnetic resonance imaging also have a well-defined place for staging some cancers, e.g. oesophageal cancer and cervical cancer. Positron emission tomography alone (PET) or combined with CT (PET-CT) are also being incorporated into the staging pathway of tumours such as lung and oesophageal cancer [4].

Rectal cancer provides an excellent example of the use of MRI as a single modality approach which combines staging the primary tumour (T) with nodal staging (N) and detection of metastases (M). By application of a strict imaging protocol and comparison with careful histological mapping, Brown and colleagues from our institution have demonstrated that MR staging of primary rectal cancers prior to total mesorectal excision (TME) can predict involvement of the circumferential tumour resection margin to within 1 mm of the mesorectal fascia with an accuracy of over 90% [5]. This has a direct impact on patient management because patients with a positive CRM have a significantly worse prognosis than those with a negative CRM and therefore may benefit from pre-operative chemo-radiation. This strategy of pre-operative MRI staging imaging has been expanded to a multicentre European study (MERCURY) [6]. The results have demonstrated a degree of concordance between centres in predicting CRM involvement at primary staging.

Nodal staging is a major challenge using ultrasound, CT and MR imaging due to the limitation of all these techniques in distinguishing benign from malignant enlarged nodes and in detecting nodal metastases in normal sized nodes. The use of PET-CT is currently under evaluation but is already proving to be of value in certain tumours, for example in lung cancer, oesophageal cancer and cervical cancer [4]. MR lymphography is a new technique which permits the detection of nodal deposits in normal sized nodes due to the deposition of ultra small iron oxide particles within normal nodes following intravenous infusion [7]. Results to date show a significant improvement in sensitivity of MR imaging in the detection of nodal metastases. However this technology is not yet available for routine clinical practice and is likely only to be used in selected centres and in selected groups of patients, dependent upon available resources.

In the detection of metastases (M), CT remains the most widely used technique, particularly for the assessment of the lungs, brain and liver. Today CT is increasingly widely available but inherent constraints of the technique render CT limited in its ability to detect and characterise lesions. Emerging evidence from PET-CT studies in lung cancer, the most common cancer in the world today, clearly shows that this new technology influences management in up to 30% of patients due to the detection of metastases thus obviating the need for surgery [8].

Has my treatment worked? Has my cancer come back? The majority of patients with cancer require follow-up imaging studies to assess response, identify residual disease, and to detect recurrence. As with staging, CT remains the most widely used technique for monitoring treatment response and is more accurate than ultrasound for measurement of tumour size regression and tumour re-growth. Thus in the follow-up of lymphoma CT is likely to remain the key imaging modality but MR imaging is valuable for imaging in the follow-up of tumours which are less well visualised on CT, such as spinal cord tumours and rectal cancer. While these technologies have stood the test of time and usually provide adequate data for management, a major area of research is in the field of functional imaging. The goal of non-invasive functional imaging is to predict individual patient response either before or early during therapy so that optimum treatment can be prescribed with the objective of improving patient outcomes and reducing unnecessary expenditure on ineffective treatment.

Both MR imaging and PET can be exploited to provide patho-physiological and metabolic tumour information about tumours. Where 18 FDG-PET is available in clinical practice it is now part of the routine imaging strategy in the management of lymphoma.

However the major focus of imaging research is in relation to functional imaging with MRI and PET, the aim of which is to identify surrogate markers of response which may be used to evaluate novel drugs targeted at specific biological targets. Such functional parameters include angiogenesis, glucose metabolism, hypoxia, apoptosis, cellular integrity, cellular proliferation, and tumour necrosis. New tracers in PET are currently being investigated for the evaluation of tumour response and include studies with 5 Misonidozole which provides information on tumour hypoxia [9].

Conclusions Cancer imaging is a rapidly growing integral part of cancer management. Technology for cancer imaging ranges from simple techniques through to highly complex and expensive modalities. While strategies for cancer imaging are continually evolving and the results of research become embedded in leading edge practice, it is equally important to focus on the use of imaging in those countries where resources are more limited and the newest technology is not widely available. It is therefore vital that research should be focussed on the cost-effectiveness and the impact on health of these extremely expensive technologies which remain limited in their availability. Many countries both in the developed and the developing world fall into this category. Globalisation of medicine and the dawn of the digital era offer news ways of sharing knowledge, education and healthcare, and as the 21st century unfolds it is hoped that appropriate imaging will become widely available to all patients with cancer.

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