**3. Treatment techniques**

#### **3.1. Treatment simulation**

variations, such as tumor shrinkage and other anatomical changes, plan adaptation is often

The chapter aims at illustrating the rationale and process in adaptive proton treatment of lung cancers, as well as the strategies and practical considerations in plan adaptation, with a focus

Depending on how proton beams are spread out laterally and in depth, there are mainly three proton delivery systems in clinical use: passive scattering proton therapy (PSPT), uniform scanning proton therapy (USPT), and pencil beam scanning (PBS). In PSPT, the proton beam is spread out laterally by a static scatterer (or double scatterers) located in the beam axis, and the beam modulation in depth is typically achieved by using a rotating range modulation wheel, which is composed of multiple steps of various thicknesses. Both USPT and PBS proton therapy use scanning magnets to sweep proton beams laterally and deliver the dose to a target volume layer by layer at various depths using proton beams of various energies. The main dif‐ ference between USPT and PBS is that proton beams are scanned continuously with a uniform intensity in a zigzag pattern at a fixed frequency for each energy layer in USPT, while deliv‐ ered with various beam intensities from one spot to another or continuously for each layer in PBS. PBS can be further divided into single field uniform dose (SFUD) delivery, which deliv‐ ers a uniform dose to the target for each field, and multiple field uniform dose (MFUD), which delivers a heterogeneous dose to the target for each field but achieves a homogeneous com‐ bined dose from all fields. MFUD is also called intensity modulated proton therapy (IMPT).

Since our main focus for this chapter is USPT, a detailed description of a USPT system at our center is described below. The proton therapy center is equipped with an IBA Cyclotron (IBA, Louvain‐la‐Neuve, Belgium), which accelerates proton beams to approximately 230 MeV before they are extracted to treatment rooms through a beam transportation system. The proton beam passes through an energy degrader, which can lower the energy when necessary, and an energy selection system (ESS) is then transported to a nozzle in the treatment room. After entering the nozzle, the proton beam will first pass through a first scatterer, which broadens the beam laterally to achieve the desired spot size at isocenter. The beam then passes through a range modulator wheel, which does not rotate continuously for uniform scanning beam delivery and mainly serves as an energy degrader. Together with the first scatterer, the modulator wheel lowers the proton energy to deliver a peak dose layer by layer in depth. The beam is scanned laterally with a constant frequency by two scanning magnets in a zigzag pattern to deliver a uniform dose for a near rectangular scanning area. It then passes through the main and backup ionization chambers that monitor the proton dose. At the end of the nozzle is a snout that holds an aperture and a compensator and can translate along the beam axis to achieve variable snout to isocenter positions. An aperture is used to collimate the beam to the treatment target later‐ ally, and a range compensator is used to conform the proton penetration to the distal boundary of the treatment target. More details on this system were described by Zheng *et al.* [5]. **Figure 1** shows a schematic diagram of the uniform scanning nozzle at our proton therapy center.

needed in proton therapy of lung cancer.

**2. Proton therapy system**

46 Radiotherapy

on the use of uniform scanning proton beams.

Patient immobilization and simulation for lung cancer patients under proton therapy are similar to those under photon therapy. However, since proton beams are very sensitive to setup uncertainty and patient motion, the reproducibility of immobilization and proper motion management are critical in proton therapy. At our center, patients typically lie supine, are immobilized with a vacuum bag, which is on top of an index fixed framing device (wing board), and with their arms up and hands holding the pegs on the wing board, as shown in **Figure 2**. The patient is scanned at 2.5 mm slice thickness. If contrast is used, one computerized tomography (CT) scan should be taken before the contrast is injected in addition to one after the injection. The CT data with intravenous contrast will be used primarily for target delineation, and the CT data set without contrast will be used for dose calculation.

Four dimensional (4D) computerized tomography (CT) scanning is typically used for lung cancer patients in proton therapy to evaluate patient motion. The motion can be monitored by a belt system or a Varian RPM system during the 4D CT scan. The magnitude of tumor motion is typically evaluated for each 4D CT scan and used to determine the strategies in motion management. Depending on facility and beam delivery system, a limit of motion magnitude is set, beyond which the patient will need additional motion management or be excluded from proton treatment. For example, at our center, we generally treat patients using USPT with a maximum motion of 10–15 mm, while at the MD Anderson Proton Therapy Center, 5 mm maximum motion was used for patients under PBS proton treatment [6]. While respira‐ tory gating or breath holding could reduce the tumor motion, currently, it is only used clini‐ cally in a very few proton centers due to challenges such as relatively low proton dose rate that leads to long treatment time for gated treatment, lack of connection between the respira‐ tory device and the proton beam delivery machine, and difficulty of holding breath for lung cancer patients.

**Figure 2.** Typical CT simulation and immobilization technique for lung cancer treatment using uniform scanning proton therapy.

#### **3.2. Treatment planning**

Treatment planning can be performed on the average CT based on the 4D CT scan, or at a cer‐ tain respiratory phase when gating or breast holding is used. At our center, we use the average CT and an Internal target volume (ITV) approach to account for motion effect during treatment, which is similar to what used at MD Anderson Cancer Center for lung treatment using pas‐ sive scattering proton beams [7]. The internal gross target volume (IGTV) is contoured on the maximum intensity pixel (MIP) images and expanded 7–10 mm to generate the clinical target volume (CTV), which is expanded further by 5 mm to obtain the planning target volume (PTV). The average CT will be used for treatment planning and dose calculation. The magnitude of motion will be evaluated by a physicist, and the treatment of lung patient with uniform scan‐ ning proton beams is often limited to those who have a motion magnitude of 10 mm or less. To be conservative, a smearing of 10 mm is used in compensator calculation for all lung cancer treatment planning. To ensure adequate coverage of the target at the presence of tumor motion, the stopping power ratio of IGTV is overridden with the average stopping power ratio of the tumor tissue, which is about 1.01 based on sampling of over 10 lung patients treated at our cen‐ ter. Each patient is treated with uniform scanning proton beams typically using 2–4 fields. The prescription is typically 74 Cobalt Gray‐equivalent (CGE) at 2 CGE per fraction for 37 fractions.

#### **3.3. Dosimetric advantages**

Proton beams provide a superior dose distribution for lung cancer treatment compared to photon beams. Chang *et al.* reported that PSPT significantly reduced dose to normal tissues and the integral dose to patients with non‐small cell lung cancer (NSCLC) compared to three‐ dimensional conformal radiation therapy (3D‐CRT) and intensity modulated radiation ther‐ apy (IMRT) [2]. Kadoya *et al.* reported that using proton beam significantly reduced Lung dose compared to stereotactic body radiation therapy (SBRT) for Stage I non‐small‐cell lung cancer [8]. The mean dose, V5, V10, V15, and V20 were 4.6 Gy, 13.2%, 11.4%, 10.1%, and 9.1% for pro‐ ton therapy compared to 7.8 Gy, 32%, 21.8%, 15.3%, and 11.4%, respectively, for SBRT with a prescribed dose for 66 Gy. In a similar study, Hoppe *et al.* reported that in addition to better dose sparing to the lung, PSPT delivered less dose (D0.1cm 3 and D5cm 3 ) to the heart, esophagus and bronchus compared to SBRT [9]. For locally advanced Stage III NSCLC patients, Wu *et al.* found that proton beam therapy was feasible and superior to three‐dimensional conformal radiotherapy for several dosimetric parameters such as the mean dose for lung, heart, and spinal cord [3]. Using IMPT, doses to normal tissues, such as the lung, spinal cord, heart, and esophagus, can be further reduced compared to passive scattering proton therapy and IMRT for extensive Stage IIIB NSCLC, as reported by Zhang *et al.* [10]. The dosimetric advantage of IMPT would allow further dose escalation from 74 to 84.4 Gy while keeping normal tissue sparing at a lower or similar lever. IMPT proved also advantageous in terms of lung sparing compared to both Tomotherapy and IMRT in a study by Stuschke *et al.* [11]. A brief summary of literature on plan comparison between proton and photon therapy discussed here is listed in **Table 1**.

When uniform scanning proton therapy is used, similar normal tissue sparing to passive scat‐ tering proton therapy can be achieved. **Figure 3** shows the dose comparison of USPT versus IMRT for a lung case. The patient was a 72‐year‐old female with severe chronic obstructive pulmonary disease (COPD) and Stage IIIA (cT1aN2MpG2) squamous cell carcinoma of the right upper lung.


Abbreviations: MDACC: M. D. Anderson Cancer Center; STPTC: Southern Tohoku Proton Therapy Center; UFTPI: University of Florida Proton Therapy Institute; NCCHE: National Cancer Center Hospital East; UHE: University Hospital Essen. Others see above.

Note: Reports from the literature.

**3.2. Treatment planning**

therapy.

48 Radiotherapy

**3.3. Dosimetric advantages**

Treatment planning can be performed on the average CT based on the 4D CT scan, or at a cer‐ tain respiratory phase when gating or breast holding is used. At our center, we use the average CT and an Internal target volume (ITV) approach to account for motion effect during treatment, which is similar to what used at MD Anderson Cancer Center for lung treatment using pas‐ sive scattering proton beams [7]. The internal gross target volume (IGTV) is contoured on the maximum intensity pixel (MIP) images and expanded 7–10 mm to generate the clinical target volume (CTV), which is expanded further by 5 mm to obtain the planning target volume (PTV). The average CT will be used for treatment planning and dose calculation. The magnitude of motion will be evaluated by a physicist, and the treatment of lung patient with uniform scan‐ ning proton beams is often limited to those who have a motion magnitude of 10 mm or less. To be conservative, a smearing of 10 mm is used in compensator calculation for all lung cancer treatment planning. To ensure adequate coverage of the target at the presence of tumor motion, the stopping power ratio of IGTV is overridden with the average stopping power ratio of the tumor tissue, which is about 1.01 based on sampling of over 10 lung patients treated at our cen‐ ter. Each patient is treated with uniform scanning proton beams typically using 2–4 fields. The prescription is typically 74 Cobalt Gray‐equivalent (CGE) at 2 CGE per fraction for 37 fractions.

**Figure 2.** Typical CT simulation and immobilization technique for lung cancer treatment using uniform scanning proton

Proton beams provide a superior dose distribution for lung cancer treatment compared to photon beams. Chang *et al.* reported that PSPT significantly reduced dose to normal tissues

**Table 1.** Comparison studies between proton and photon therapy for NSCLC patients.

**Figure 3.** Dose comparison of Uniform Scanning proton plan and IMRT plan. (a) Proton plan, (b) IMRT plan, and (c) DVH comparison (solid line—proton, dashed line—IMRT). The prescribed dose was 74 cobalt gray equivalent (CGE) at 2 CGE per fraction for 37 fractions.
