|Michael Shearar, PhD
The practice of radiation oncology is changing more rapidly now than at any time since the introduction of linear accelerators for therapeutic purposes. Three major developments are coinciding to prompt radiation oncologists, physicists, and biologists to re-evaluate how radiation is used to treat cancer. These developments are intensity modulated radiation therapy (IMRT), clinical radiation biology and genetics, and functional imaging.
IMRT uses standard radiation therapy equipment to deliver radiation in a radically new way. Instead of delivering large area beams of radiation, IMRT allows the delivery of very small beamlets that can be varied in intensity across the radiation field delivered to the patient. Since the only upgrades to existing equipment required to make this change are a software installation that drives the multi-leaf collimator normally used to shape the radiation field and new treatment planning software, the use of IMRT has become widespread extremely rapidly. IMRT now makes it possible to deliver radiation doses that are exquisitely contoured to the target, allowing the sparing of normal tissue and an increase in dose to the target. The question becomes: Can we define the target to the specific dimensions in which we can now deliver radiation using IMRT?
The second key development is the rapidly expanding knowledge of genetic changes that can be correlated with tumor aggressiveness and with response of tumors and normal tissues to radiation therapy. These genetic changes are now being correlated with histological measures of tumor aggressiveness and known radiation response factors such as hypoxia, tumor proliferative capacity, and inherent cellular radiation sensitivity.
Functional imaging may provide the key information to better define the target for radiation therapy, provide an imaging link for biological and genetic factors, and therefore allow the effective implementation of IMRT. Oncologic applications of positron emission tomography (PET), functional magnetic resonance imaging, magnetic resonance spectroscopy imaging, perfusion CT, and apoptosis imaging with ultrasound are being developed to define target volumes for radiation therapy and to monitor changes in tumors and normal tissues in response to therapy. Moreover, as functional imaging is further developed to allow in vivo 3D mapping of gene expression and specific biochemical pathway activity, we are likely to be able to develop a very detailed picture of radiation-specific tumor and normal tissue factors in every patient.
The New Excitement
The potential of combining IMRT, clinical radiation biology and genetics, and functional imaging is the cause of the current excitement in radiation oncology. Functional imaging combined with clinical radiation biology and genetics will provide patient-specific target and normal tissue parameters. IMRT will then provide the very precise radiation therapy system to deliver what we have termed biologically adapted radiation therapy (BART). This model will bring several established radiation treatment principles into review, including the total dose prescription, the dose delivered per fraction, and the potential for changing treatment midcourse based on evidence provided by, for example, intratreatment functional imaging.
The integration of imaging into radiation therapy calls for a close collaboration between radiation oncologists and radiologists. Currently, the link between these professional groups is often restricted to pretreatment diagnosis and staging by the radiologist. No further involvement of the radiologist is usually required and patients are normally treated with a standard total dose and dose-per-fraction based on pretreatment anatomical images of the tumor site. In the new model, the interpretation of functional imaging data, treatment planning based on these images, and changes in the images during a treatment course requires the delivery of radiation to become a cross-disciplinary team effort. The new radiation medicine team will require the services of radiologists, medical physicists with imaging expertise, experienced imaging technologists, clinical radiation biologists, and clinical radiation geneticists. The imaging professionals will in turn require specific training in radiation oncology to be effective in this new team environment. In the future, one could imagine radiation oncology imaging becoming a subspecialty of radiology that is recognized and taught in medical schools. This would bring us full circle as most radiation oncology departments began as extensions of radiology. Similarly, residency programs that train clinical radiation oncology physicists must now include clinical imaging physics training.
Blueprint for Change
The logistics of imaging for diagnosis, staging, and radiation treatment planning must also be rethought. For operational efficiency and patient convenience, all relevant imaging studies should be performed in one facility. This means, for example, that when a tumor is suspected, the anatomic and functional imaging should be done with the patient in treatment position for that tumor site. The imaging should also be performed on a radiation treatment couch so that the original imaging studies can be used to plan the treatment. In large academic centers, this will best work if dedicated imaging equipment, including PET, MRI, CT, and ultrasound equipment, modified for radiation treatment simulation, is located in the radiation medicine facility. This practice is already common with CT simulators and is now expanding to include the development of MR simulators and combined PET/CT systems for PET-based treatment planning. In small radiation therapy facilities, very close collaborations with imaging groups will be formed to ensure that imaging studies are useful for radiation treatment planning.
The changing practice of radiation oncology and the prospect of image-guided BART will force us to rethink our professional training, our organization, and the collaboration between radiologists and radiation oncologists. The change will be rapid because it is largely based on standard diagnostic and treatment delivery equipment. Information migration to patients via the Internet will produce economic pressure to make these new technologies widely available. It is therefore very important that the changes are implemented with the highest standards of clinical testing. If the collaborations do not occur, the investment in BART may be wasted or, worse, outcomes become poorer because of IMRT that is tightly conformed to a target that is poorly interpreted from imaging studies. In contrast, if the new model of collaboration is well developed, the potential exists for significant improvement in tumor control and normal tissue avoidance using BART.
Michael Sherar, PhD, is head, radiation physics, Princess Margaret Hospital