Fig. 18.1
Dose distribution of various radiations in the body. The neutron, X-ray, and gamma ray beams release their maximum radiation dose to tissues immediately after entering the body, whereas the proton and carbon ion beams penetrate the body and release low doses of radiation while traveling before releasing the maximum dose at the target site. The dose falls off steeply (Cited by Radiological Sciences 2007; 50: p51)
18.3.1 Carbon Ion Radiotherapy at NIRS
Carbon ion beams are generated from accelerators. The HIMAC at NIRS in Japan is the world’s first heavy ion accelerator complex dedicated to medical use in a hospital setting. The accelerator system is composed of the injector at the ion source, linear accelerators, and a synchrotron. Carbon ion beams are accelerated to approximately 70–80 % of the speed of light and extracted for treatment. The accelerated energy of the beam available for treatment ranges from 290 to 430 MeV. The range of the 290 MeV carbon ion beam is approximately 15 cm in water, that of the 350 MeV beam is 20 cm, and that of the 400 MeV carbon ion beam is 25 cm. The beam lines are in fixed horizontal and vertical lines. A rotating gantry does not apply.
Two different systems of beam delivery are employed at NIRS. One is the passive beam delivery that has been used for 20 years, since the treatment started. To modulate the Bragg peak to conform to a target shape, the beam lines are equipped with a pair of wobbler magnets, beam scatters, ridge filters, multileaf collimators, and a compensation bolus. An appropriately sized ridge filter, which determines the size of the spread-out Bragg peak (SOBP), is selected in each port to adjust the irradiated field. Twelve different sizes of ridge filters cover the field size from 2 to 15 cm. The compensation bolus is fabricated for each patient to make the distal configuration of the SOBP similar to any irregular shape of the target volume. The collimator defines the margins of the target volume.
Another system is active beam delivery, which is a scanning system launched in 2010 at NIRS. The fixed horizontal and vertical beams are used in this system, as in the passive beam delivery. The delivery system does not use beam scatters, collimators, or a compensation bolus. Instead of using wobbler magnets, it employs scanning magnets to produce sophisticated beam control. It is more flexible and can make an irradiated field fitting the complex shape of a tumor [15]. Compared to passive delivery, active delivery generates fewer neutrons because the materials like bolus and collimators are not inserted in the beam line [16]. To ensure precise irradiation, tailor-made, body-fixed devices are prepared, and patients are positioned in customized cradles and immobilized with thermoplastic plates (Fig. 18.2). A set of 1-2.5-mm-thick CT images is taken with the immobilization devices for treatment planning. Respiratory gating of both the CT acquisition and the treatment is performed when indicated. A margin of 5 mm is usually added to the clinical target volume (CTV) to create the planning target volume (PTV) using a three-dimensional treatment planning system. When the tumor is located close to critical organs such as the spinal cord or bowel, the margin is reduced accordingly. The CTV is covered by at least 90 % of the prescribed dose [17]. Dose was expressed in gray equivalent (GyE = carbon physical dose [Gy] × relative biologic effectiveness [RBE]). Carbon ion radiotherapy is given once daily, 4 days a week (Tuesday to Friday). Patients with axial sarcomas are treated with more than three irregularly shaped ports. One port is treated in each session. At every treatment session, the patient’s position is verified with a computer-aided, on-line positioning system. The patient is positioned on the treatment couch with the immobilization devices, and digital orthogonal x-ray television images are taken in that position and transferred to the positioning computer. They are compared with the reference image on the computer screen and the differences are measured. The treatment couch is then moved to the matching position until the largest deviation from the field edge, and the iso-center position is <2 mm [17].
Fig. 18.2
A patient in the prone position in the treatment room. Patients are fixed using an immobilization device to the couch. It takes 30 min to examine the position on the images obtained in the room. Patients receive radiation for a few minutes. This photo shows irradiation in the vertical beam line
18.3.2 Special Techniques in Carbon Ion Radiotherapy
18.3.2.1 Patch Combination Technique
Treatment of spinal and paraspinal tumors makes the best use of the characteristics of the charged particle beam, if the tumors are unresectable due to the high risk of sacrifice to the spinal cord. The radiation tolerance limit using photon beams to the spinal cord is generally 40–46 Gy in 20–25 fractions.
The “patch combination technique” is used when the tumors are both close to and surrounding the spinal cord. The target volume is divided into two segments, and each segment is treated by a separate radiation field using an anterior–posterior or posterior–anterior field and a right–left or left–right field. By using the sharp dose drop-off after the Bragg peak, the distal edge of one field is matched with the lateral edge of the second field. The combination of the two fields provides at least two varied patterns because the matching lines of the two fields where the lateral edge of one portal abuts the distal end of the stopping beam are utilized on alternating days to reduce potential dose inhomogeneity [18–20]. In the case of spinal sarcoma, by means of the patch technique, the dose distribution is doughnut shaped to avoid irradiation of the spinal cord (Fig. 18.3).
Fig. 18.3
Dose distribution in spinal sarcoma. This figure shows a tumor encompassing the spinal cord. The dose distribution was doughnut shaped to avoid irradiation of the spinal cord. This irradiation field uses the patch technique. The red line is 96 % of the total irradiation dose, pink is 70 %, light green is 50 %, and deep green is 30 %
Irradiation of the spinal cord should be minimized. The dose constraint of the carbon ion beams directed in cross-sections involving the spinal cord is thought to be almost 30 GyE administered in 16 fractions, based on clinical experience at NIRS. As the incidence of radiation-induced myelopathy is quite rare, accumulation of more spinal sarcoma cases and further analysis of the relation between irradiated dose and adverse events are needed.
18.3.2.2 Inserting Spacers
In cases where the tumors are located close to or abutting the digestive tract, there is a high risk of adverse events related to irradiation of the digestive tract. To avoid excessive irradiation doses over the tolerance dose of the digestive tract, a spacer is sometimes inserted. The surgical procedure involves placement of a spacer to separate the target tumor from the digestive tract before carbon ion radiotherapy [21]. The spacer is usually a sheet made from expanded polytetrafluoroethylene, which is affinitive to body tissues, and there is usually no need to remove it after irradiation (Fig. 18.4). Creating space between the tumor and digestive tract enables a sufficient dose of radiation to be applied to the tumor while avoiding adverse bowel events such as bloody discharge, perforation, and stenosis.
Fig. 18.4
Inserting a spacer between the bowels and a tumor. Creation of a space between the tumor and the bowels enables delivery of sufficient radiation to the tumor while avoiding adverse events in the bowels. The sheet is made from expanded polytetrafluoroethylene, which is an affinitive material to body tissues, and there is usually no need to remove it after irradiation. The inserted sheet was calcified
However, this surgical intervention has some risks. One is a risk of tumor progression. It usually takes >1 month to complete the surgery and move the patient to a hospital for carbon ion radiotherapy. During that period, the patients receive no antitumor therapy. After surgery to place the spacer, if the size of the tumor exceeds that which carbon ion radiotherapy can treat or if the tumor shows systemic spread, it will be impossible to undergo carbon ion radiotherapy. The risk is especially high in cases where the tumor either has a poor reaction to chemotherapy or grows rapidly, such as a high-grade sarcoma. Another risk is that of infection in the spacer. If infection occurs and spreads to the tumor, it can be difficult to control and the infection in the tumor is not suitable for carbon ion radiotherapy. Thus, a patient’s risk of inserting a spacer should be examined well before the surgery.
18.3.3 Patient Eligibility
General eligibility criteria for carbon ion radiotherapy are shown in Table 18.1. Tumors directly invading critical organs such as the skin, digestive tract organs, and bronchus are excluded. Patients with metal instrumentation in the treatment area are also excluded because the metal implants cause artifacts on CT images for treatment planning, complicating determination of accurate dose distribution. It has also been reported that metal implantation was one of the causes of local failure after charged particle therapy [22]. If a patient with spinal sarcoma had previously undergone decompression surgery and metal instrumentation, the metal objects should be removed before initiating carbon ion radiotherapy.
Table 18.1
Major eligibility for carbon ion radiotherapy for bone and soft tissue sarcomas
