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During the past half century, an ongoing technological revolution in cancer imaging and radiation treatment has taken us ever closer to the goal of treating localized tumors without harming normal tissues. In his visionary 1946 paper,1 Harvard physicist Robert Wilson suggested that energetic protons could provide a nearly ideal form of radiotherapy. What makes protons the preferred particle type for radiotherapy is their inverted dose profile, called the Bragg peak, in combination with the ability to place the Bragg peak at any depth in the patient, to spread out the peak to cover larger volumes, and to have zero dose behind the most distal peak position. In 1989, Dr Wilson visited the first clinical proton-treatment center at Loma Linda University Medical Center in California, which was about to begin its clinical operation (the first patient was treated in October 1990). The reasons more than 40 years elapsed between his original idea to its full technical and practical realization were manifold, but the lack of adequate image guidance, both in treatment planning and treatment itself, played a key role.
Computed tomography (CT) utilizing kilovolt (kV) X-rays was not developed until the early 1970s. For the first time this imaging modality provided three-dimensional (3-D) information about tumor location and at the same time about the electron density distribution required to perform 3-D dose calculations. Therefore, it was a natural choice to develop CT-based radiation treatment planning. Magnetic resonance imaging (MRI) entered the treatment planning scene about 10 years later and provided further details with respect to the geographical relationship between tumor and normal tissues, providing much higher spatial and contrast resolution than X-ray CT. It took another 15 years before positron emission tomography (PET), in particular its combination with X-ray CT, became available for radiation treatment planning and added another dimension to the ability to see tumors and to distinguish them from normal tissue, namely based on differential metabolism. For conformal radiation modalities, such as proton therapy, imaging technology is equally important in guiding the delivery of radiation therapy. Image-guided radiation therapy (IGRT), respiratory gating, and related technological advancements are about to enter the treatment room in many radiotherapy facilities. The idea behind this is that modern imaging can help not only to detect and outline tumors during treatment planning, but also to ensure that the dose delivered to the tumor in the treatment room is accurate and precise.
Current Role of Image Guidance in Proton Treatment Planning
Treatment Planning Volumes
Most patients coming to a proton-radiotherapy center for consultation have been diagnosed with localized, non-metastatic organ cancer, such as prostate or lung cancer, and seek proton therapy as their definitive therapy. In other instances, patients have received surgery as their first-line treatment and require post-operative radiation due to known residual tumor or suspected microscopic disease. Lastly, it is not uncommon to see previously irradiated patients who have failed their initial radiotherapy and reached tolerance dose in nearby organs or vital structures. In any of these cases, accurate imaging-based definition of treatment volumes is crucial. Standard radiation-planning volumes, previously defined for photon therapy by the International Commission on Radiation Units and Measurements (ICRU),2,3 are also suitable for proton therapy. The ICRU planning volumes are the gross tumor volume (GTV), including macroscopic tumors visible in imaging studies; the clinical target volume (CTV), containing suspected subclinical malignant disease; and the planning target volume (PTV), which expands GTV or CTV by a margin accounting for geometric uncertainties, including set-up errors and internal organ motion.