Principles of intensity-modulated proton therapy treatment planning

Range uncertainties

The most important dose-sparing ability of the proton beam is that the proton can stop at roughly the end of the proton’s range. However, because of approximation of tissues on computed tomography (CT) scans into Hounsfield units (HUs), there are systematic range uncertainties of about 3% in our understanding of where protons stop in patient tissues. Fig. 5.3 shows the dose distribution of an original plan and the dose distribution of a plan assuming a 3.5% range overshooting. The target dose is well covered by the prescription in the original plan, but the target is severely underdosed if the plan is 3.5% undershot. If a beam of a plan stops right before a critical organ, such as the spinal cord or brain stem on an original plan, the brain stem or spinal cord will actually receive much more dose than if the beam is overshot by 3.5%. Currently, one of the rules of thumb of selecting beams is still to not select beams stopping right before critical organs.

Setup uncertainties

All modalities of radiation therapy, regardless of whether they are proton or photon, suffer from setup uncertainties. Setup uncertainties are attributed to the misalignment of incident beams and the patient anatomy and the realignment of internal heterogeneities among themselves and with respect to the target volume. For photon therapy, setup uncertainties are mitigated by the use of expansion margins from the clinical target volume (CTV) to the PTV. The margin approach works well for photon therapy and is based on a nice property of the photon: the spatial nature of photon dose distributions is minimally perturbed by uncertainties. In other words, a photon dose distribution is relatively robust in the face of uncertainties. Unkelbach et al. have used the term static dose cloud to describe a photon dose distribution. However, the margin approach does not work well for proton therapy. Distal and proximal to the beam direction, the margins for proton therapy should be determined by the range uncertainties. In the lateral direction, the static dose cloud will be broken under the lateral setup uncertainties. As shown in Fig. 5.4 , the symmetry of the dose cloud, shown as the red isodose line that covers the target (blue shaded region), is broken if the patient moved up by 5 mm. The target is still covered in the up direction but is underdosed in the middle. The underdose shown in Fig. 5.4 cannot be mitigated by the margin.

Motion/interplay uncertainties

Protons are sensitive to variations in tissue density in the beam path. ^, This is particularly important when the tissue moves, as in the case of tumors in the lung. The sensitivity of protons to moving anatomy can be seen by calculating dose distributions on different phases of four-dimensional CT (4D CT). Fig. 5.5 shows uncertainties caused by breathing motion imitated with a phantom. In this extreme case, we can see that the dose in the T0 phase is drastically different than in the T50 phase if the plan is designed using only the T50 phase.

Both PSPT and IMPT techniques have uncertainties in dose distribution in the different phases of CT. However, for the IMPT plan, there is an extra uncertainty. For the IMPT technique, a magnetically deflected particle beam scans the tumor volume laterally by sequentially delivering a series of scanning spots and longitudinally, layer by layer, by altering proton energy. If the target moves at the same time as the scanning beam is delivered, the motion of the pencil beam might interfere with the delivery of the intended dose distribution, causing deviations from the planned dose distributions. This interference usually results in local regions of underdoses and overdoses, referred to as interplay effects. As shown in Fig. 5.6 , if the tumor motion and dynamic delivery are synchronized unfavorably, we might have a complete miss of the target in extreme cases.

Anatomical change uncertainties

Anatomical changes during radiation therapy are sometimes a consequence of radiation therapy. Because radiation is used to eradicate tumors, the tumors will shrink during the course of treatment. This can be seen in Fig. 5.7 ; the tumor/gross tumor volume (GTV) at simulation is different from the tumor/GTV shown on the day 50 CT scan. Also, patients often lose weight during the course of treatment, especially those with head and neck (HN) cancer. The anatomical change during the course of the treatment affects proton much more than photon therapy. Because of the larger perturbation of the IMPT plan attributed to anatomical change, we propose that plan adaption is mandatory for lung cancer IMPT plans to ensure target coverage. At our center, more 30% of lung IMPT plans need adaptation during the course of treatment to compensate for the uncertainties caused by anatomical change.