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Image-guided radiation therapy

James Balter
University of Michigan Medical Center
Ann Arbor, MI

Radiation oncology has undergone a renaissance in the past decade in which advanced technology has affected nearly every aspect of patient treatment. Developments are based on the premise that improvements in the precision of radiation planning and delivery can reduce co-morbidity and permit safe radiation dose increases, thereby increasing local controls – and potentially the long-term survival of the patient.

On the treatment-planning side, advances in computer tools such as intensity-modulated radiation therapy (IMRT) has allowed us to improve our understanding of how to deliver radiation in three dimensions and to vary its pattern spatially.

The challenge has been how to relate this complex and very precise radiation pattern back to a patient who would be treated anywhere between one and 40-plus times. Patients need to be positioned so that their tumour lines up appropriately to the linear accelerator delivering the radiation.  As treatments become more complex, it is also important to ensure that some of the critical normal organs such as the spinal cord are also in the same relative position to the tumour for each treatment so that the precisely planned radiation pattern can continue to avoid causing damage. Complicating this process are factors such as the flexibility of the human body (it is hard to reproduce the same shape repeatedly), rotational positioning of the patient, and movement of internal anatomy due to voluntary motions as well as physiologic processes such as breathing, heartbeat, peristalsis and bladder filling.

To address the need to achieve repeatedly precise shaping, orienting and positioning of patients, a large number of scientific and technical endeavours have been undertaken which focus on two core principles: immobilisation and localisation. Immobilisation involves ways of keeping the patient and tumour still while radiation is delivered. These systems can be static (eg, custom-shaped cradles to conform to the patient’s body shape) or dynamic (eg, breath hold or respiratory gating systems that only permit radiation to be delivered when the patient is at a known breathing state).

Localisation consumes the vast majority of technology and effort that has driven advances in precision radiation treatment. Image-guided radiation therapy (IGRT) refers to developments that integrate imaging with the precise positioning of patients.  Although positioning is the major focus of IGRT, further advances in imaging also permit us to understand early on the geometry for treatment and to assess potential outcomes (both for tumours and normal organs) during or following treatment.

Types of image guidance systems
The most common form of image guidance uses electronic portal imagers (EPIDs). These take relatively poor-quality X-ray images as they use the high-energy treatment beam instead of diagnostic X-ray energies. These systems are one of the earlier forms of image guidance and are present in practically every clinic. They certainly have value, but they tend to require identification of skeletal anatomy that is assumed to move with the tumour in order to determine patient position.

Significant advances over EPIDs have come from the addition of diagnostic X-ray systems to the treatment room. Commercial systems (BrainLab, Accuray) place X-ray tubes in the floor or at the ceiling of the room. Before treatment begins, pairs of X-rays are compared with a previously acquired CT (computed tomography) scan of the patient to determine the best possible position correction. These systems typically continue to monitor position and breathing movement by combining continuous data on the external surface of the patient (through reflective markers on the skin) with periodic internal data (from repeated X-ray images).

More recently, these X-ray imaging systems have been attached to linear accelerator gantries. This modification permits a dual role for X-ray imaging. In addition to making higher-quality radiographic images than EPIDs, these systems can now, via gantry rotation, acquire volumetric (cone-beam) CT scans of the patient in treatment position. These images are beginning to alter dramatically how positioning and treatment monitoring is practised. Small intrathoracic tumours, previously invisible and at best inferred by local skeletal features on EPIDs, are now easily visualised for precise positioning. These improvements have powered IMRT as well as stereotactic body radiotherapy (SBRT) in which ablative doses are given to small focal tumours in one-to-five fractions.

Other integrations include the installation of CT scanners in proximity to a linear accelerator and integrating megavoltage (MV) CT into the actual treatment delivery system. Although MVCT was described nearly two decades ago, there is now a widely propagated commercial implementation (tomotherapy).

Many other related advances in IGRT have focused on changes in the patient. These may be short term (eg, due to breathing) or long term (eg, due to tumour response). An emerging concept of adaptive radiotherapy, currently at an early stage, attempts to take into account the changes a patient undergoes during the course of treatment. It gives feedback from routine imaging to modify treatment plans in order to maintain safe delivery of high doses to the changing patient anatomy.

The subject of breathing-related motion, however, has received extensive attention. Breathing impacts the quality of imaging as well as the ability to maintain tumour position precisely. Here, radiation oncology has become a nurturing ground for a whole class of tracking and imaging technology aimed at breathing management. A major development, four-dimensional (4D) CT, involves over-sampling CT data in the body and sorting them by estimated breathing state. The results are a series of CT scans of the patient, each representative of a given state between inhale and exhale. Such CT “movies” are beginning to change our attitude to breathing motion and its management. Imaging and treatment gated to operate at specific breathing states has both improved the clarity of images used for patient positioning and also reduced the chances of large motions occurring during delivery of precision high-dose radiation treatment.

Summary and future indications
The impact of new imaging technology and procedures has been rapid and dramatic, improving both precision and confidence in treatment. But there is more to come. A major new focus involves the integration of functional imaging into practice. Functional imaging includes nuclear medicine images (eg, FDG [fluorodeoxyglucose] PET [positron imaging tomography], SPECT [single-photon emission computed tomography] perfusion and ventilation), as well as physiological mapping from dynamic CT and MRI (magnetic resonance imaging). These tools are being applied to refine further target definition for increased precision as well as staging patients for overall treatment choices. They are beginning to be applied to help study long-term effects of radiation treatment, with a goal of finding precursors to tumour response and normal tissue toxicity that will permit us to customise individual patient treatments. The drive for advanced imaging in the treatment room continues as well, with multiple efforts currently aimed at integrating MRI with radiation treatment equipment.