Today, with the addition of approximately 10 new multiroom, hospital-based facilities in the past 10 years, throughput has increased to nearly 5000 patients per year. And this figure is expected to increase to nearly 15,000 per year over the next four to five years, when the nine facilities currently under construction become fully operational.1 This increase in patient capacity will undoubtedly benefit clinical research, due to the higher statistical power of co-operative clinical trials. Similarly, the growth will benefit the technology of proton therapy, as more scientists and more commercial vendors become involved.
The advantage of proton therapy is its ability to conform the deposited energy, or dose, to the intended target, as first described by Robert R. Wilson in 1946. Basically, protons lose energy more quickly as they slow down, so greater dose is deposited at depth (i.e., the target) than in the region between the surface and the target. Furthermore, there is no dose on the exit side of the target because the proton has no remaining energy. This scenario is in sharp contrast to the dose deposited by an X-ray beam, which is attenuated exponentially as it passes through matter (see figure 1).
Following Wilson's publication, treatments using proton beams began at Lawrence Berkeley Laboratory (Berkeley, CA) in 1954. By 1961, Harvard University (Cambridge, MA) and Uppsala University in Sweden were also treating patients at their research facilities. Much of the technology used today in proton radiotherapy was developed at these laboratories and, in many cases, advances in proton therapy were transferred to conventional X-ray therapy. Examples of such technology transfer include stereotactic localization, daily imaging of treatment position and three-dimensional treatment planning.2
Technology shared
Recent progress in imaging technologies has benefited all radiotherapy modalities. High-resolution CT, MRI and PET-CT allow better target definition, which has increased the demand for more conformal treatments. Conventional radiotherapy vendors responded by providing the tools needed for conformal treatment delivery: multileaf collimators, improved treatment-planning systems, computer-controlled treatments and intensity-modulated radiotherapy. The size of some treatment fields can be further reduced using fast multislice CT scanners and respiratory gating.
More precise treatment plans, in turn, require better targeting in the treatment room. Again, the conventional radiotherapy vendors responded with an array of solutions, including electronic portal imaging, cone-beam CT, implanted RF beacons, surface reconstruction using video cameras, plus an assortment of methods based on kilovoltage X-ray sources and detectors.
Some, although not all, of the advances in conventional radiotherapy were easily transferred to proton therapy. Others were difficult because, until recently, every proton facility was different. Thus a vendor would either have to develop specific technology or software for a single user (making it very expensive) or the users would have to do it themselves. Examples of technologies that have not been transferred well to proton therapy included: record-and-verify systems, multileaf collimators, cone-beam CT in the treatment room, and intensity-modulated treatment planning and delivery.
However, this pattern has already started to change. As the number of proton facilities reaches a critical mass, commercial manufacturers are exhibiting more interest in proton therapy. In addition, customers are demanding that proton-therapy equipment vendors provide the functionality to which they have become accustomed to in conventional radiotherapy rooms.
Our philosophy at the Roberts Proton Therapy Center at The University of Pennsylvania (Philadelphia, PA) is to have the proton-therapy vendor work with a conventional vendor to adapt their product to the proton environment. We want this for several reasons: the development time should be shorter; continuous technology improvement should be easier and should occur in parallel with developments in conventional radiotherapy; and it creates an integrated facility with similar tools and interfaces, making it much easier for staff to move between technologies.
Bright future
I believe that the most important proton therapy development in the next few years will be the expanded use of intensity-modulated proton therapy (IMPT) using scanned beams. Instead of spreading the beam laterally and longitudinally with scattering foils and modulator wheels, scanned-beam technology uses magnets to steer the beam into the desired position.
Currently this delivery method is only available at the Paul Scherrer Institute (PSI) in Switzerland3 (and, for carbon beams, at the Gesellschaft für Schwerionenforschung (GSI) in Germany). The technique not only produces better dose distributions but can be used for deeper targets. It can also create a larger field while generating fewer neutrons, which cause unwanted dose outside the treatment volume.
One area of research and development that's specific to proton therapy is the efficient use of the proton beam. Efficiency is an issue because proton facilities are expensive and some sites are designed with up to five treatment rooms sharing a single proton beam. As this proton beam can only be sent into one room at a time, the time taken to deliver the beam into each room and perform the treatment becomes increasingly important. At the Penn facility we expect a rapid beam switching time between rooms (10-15 s) and a treatment time of around one minute for a normal treatment dose (2 Gy). We are also developing a computer program that determines how to use the beam most effectively.
Another proton-therapy-specific development task is monitoring the delivered dose by examining the positron-emitting isotopes produced in the patient. One of the uncertainties in proton therapy is determining exactly where in the patient the sharp dose fall-off occurs. If the beam energy is too low, the target will not be treated completely. Conversely, if the energy is too high, normal tissue will be irradiated unnecessarily. For this reason, there has been great interest in verifying the beam path by measuring the positron-emitting isotopes with a PET detector and comparing the result to an expected distribution.
Much of the dose monitoring effort has involved imaging the patient in a standard PET or PET-CT scanner.4 Most of what is imaged is therefore 11C, which has a 20 minute half-life, because the 15O, with a two minute half-life, decays while the patient is transported to the scanner. At Penn (and elsewhere), efforts are underway to develop a means to image 15O in the treatment room, thus allowing faster and possibly more accurate imaging.
Now is a very exciting time to be involved in radiation therapy. Competing technologies are forcing vendors to develop new functionalities at a rapid pace. The expectation: at the least, that patient quality-of-life will improve by reducing exposure to normal tissues, and more optimistically, that long-term survival will improve, with better local control or a more effective combined-modality treatment.