Carbon-ion scanning lung treatment planning with respiratory-gated phase-controlled rescanning: simulation study using 4-dimensional CT data

Fourteen patients with lung tumors treated by CIRT in our hospital were randomly selected. None were candidates for surgical resection due to medical reasons or patient refusal. All patients had stage I non-small cell lung cancer (NSCLC) or oligometastatic lung tumors as a single lesion. Patient characteristics are summarized in Table 1.

After providing written informed consent, patients underwent 4DCT under free-breathing conditions. 4DCT data were acquired by using a 256 multi-slice CT, which can be obtained approximately 13 cm in a single rotation, therefore, a single respiratory cycle was obtained during 4DCT imaging [4]. All patients were fixed on the patient bed in the supine or prone position using an immobilization device. The respiratory phase was monitored using a respiratory sensing system consisting of a position-sensitive detector and an infrared-emitting light marker (Toyonaka Kenkyujo, Osaka, Japan). For the reconstruction conditions, the voxel size was 0.78 × 0.78 × 0.50 mm and the 4DCT data sets were subdivided into 10 phases (T00: peak inhalation; T50: peak exhalation).

Gross tumor volume (GTV) and organs-at-risk (OARs), including the normal bilateral lung (excluding the defined GTV), spinal cord, and heart were manually delineated on T50. These contours were transferred to the other phases using B-spline-based deformable image registration (DIR) [5]. Clinical target volumes (CTVs) were created by adding 10 mm margins to the GTVs in all directions, and then, they were manually modified considering the distance from the target to chest wall and ribs.

Since charged particle beams are highly sensitive to geometrical variations in water-equivalent path length (WEPL), intrafractional variations result in either overshooting or undershooting the target. To account for these WEPL changes in all motion phases, the field-specific target volume (FTV) was designed using 4DCT data sets [6]. To account for intrafractional WEPL variations at the distal and proximal sides along the same ray-line at respective phases, the FTV for each beam direction was constructed by selecting the maximum and minimum WEPL values. Two types of FTV were calculated, the first using CTVs around exhalation (T40-T60) (FTVgated) and the second using CTVs around a full respiratory cycle (T00-T90) (FTVungated).

4D treatment planning was performed using 4DCT data in respective respiratory phases. Using single uniform field optimization, the FTV was enclosed at minimum by the 95% isodose line for the patient's dose prescription. In accordance with our routine lung treatment protocol, 48Gy(RBE) in a single fraction was delivered via four beam angles from the ipsilateral side of the tumor [7].

A reference dose distribution (planning dose) was calculated based on a FTV created spot map from the 4DCT data set. The spots were equally distributed over all phases in order to avoid the interplay effect. In addition, dose distributions in each of the respective phases were calculated using 4DCT data sets for PCR at respective beam spot positions by considering dose rate, energy change time, and respiratory cycles. The accumulated dose distribution was then calculated (treatment dose) by using DIR, which transforms the respective phase doses to the reference phase (T50) [5]. Our DIR accuracy averaged over all patients was 0.9 ± 1.4 mm, which was derived from the 4DCT data using the manual point matching method. The beam weight maps for the respective FTVs were optimized to obtain the uniform relative biological effectiveness (RBE) weighted absorbed dose, which was calculated by considering the non-linearity of RBE based on an experimental study [8]. The number of rescannings was varied from 1 to 10 [2],[3]. The starting phase of irradiation was T00 in the ungated strategy and T40 in the gated strategy. All beam spots of a layer were designed to be irradiated n times repeatedly within a single gating window. After finishing one layer, the energy was changed to irradiate the next proximal layer during the next gating window. Scanning beam irradiation time was longer than that for treatment planning CT acquisition. Therefore, when the accumulated dose was calculated, we assumed that the respiratory data of respective patients were repeated during scanning beam irradiation.

In our institution, PBS-CIRT is delivered using a range shifter and 11 synchrotron energies resulting in what we term hybrid depth scanning [9]. Beam spot positions and beam weights were optimized for the FTV. Spot spacing was 2.0 mm laterally and 3.0 mm in the beam direction, and lateral scatter (80-20%) was approximately 5.0 mm. Control times for the range shifter and synchrotron energy changes were 420 ms and 150 ms, respectively. We set the scanning speeds in the superior-inferior and left-right directions to 100 mm/ms and 50 mm/ms, respectively, and the scan path was optimized to minimize the total path length.

The results were then compared for the ungated and gated strategies. We assumed that the respiratory pattern remained unchanged throughout the treatment course. Dose-volume histograms (DVH) for the CTV and OARs at peak exhalation were calculated for both plans. The minimum/maximum dose (Dmin/max) and the dose delivered to 95% of the volume (D95) of the CTV were calculated at the reference phase. To evaluate the dose homogeneity, a dose homogeneity index (HI) was defined as the standard deviation (SD) of the dose voxel values within the CTV at the reference phase to the prescribed dose. For all OARs, the mean, maximum, and minimum doses were evaluated. The derived dosimetric parameters were averaged over all patients and their SD was calculated. The Wilcoxon signed-rank test was used to examine the differences in dose assessment metrics. For multiple comparisons, the Steel-Dwass test was performed. A probability value of less than 0.05 was considered to be significant. All 4D dose distributions were analyzed using the Aqualyzer system [10].