Evaluation of lung anatomy versus volume reproducibility for scanned proton treatments under Active Breathing Control

Purpose/Objective
Proton therapy is a highly conformal way to treat cancer. For the treatment of moving targets, scanned proton therapy delivery is a challenge, as it is sensitive to motion. The use of breath hold mitigates motion effects. Due to the treatment delivery over several fractions with delivery times extending the feasible breath hold duration, high reproducibility of breath holds is required. Active Breathing Control (ABC) is used to perform breath holds with controlled volumes. We investigated whether the lung anatomy is as reproducible as lung volumes under ABC, to consider ABC for scanned proton treatments.

Material/Methods
For five representative volunteers (3 male, 2 female, age: 25-58, BMI: 19 – 29) MR imaging was performed during ABC at two separate fractions. The image voxel size was 0.7x0.7x3.0 mm3. Each fraction consisted of four subsequent breath holds, resulting in a total of eight MRIs per volunteer. The interval between fractions was 1-4 weeks, keeping the same positioning. The intra-fraction reproducibility of the lung anatomy during breath hold was investigated, by comparing the MRI of the first breath hold with the three other MRIs of the same session. The inter-fraction anatomical reproducibility was investigated by comparing the first breath hold MRI of the first session with the four MRIs during the second session. To avoid any influence of setup variation, first a global rigid image registration was performed. Then the lung volume was semi-automatically segmented to define a region of interest for the deformable image registration (DIR). DIR was performed using Mirada RTx v1.2 (Mirada Medical, Ltd.), with a DIR grid resolution of 3.5x2x3 mm3. The deformation vector fields were analyzed using MATLAB v2014b. Magnitudes of the deformation vectors were calculated and combined for all five volunteers. The lung volumes were divided into six segments, to analyze the anatomical displacements on a local level. A boxplot showing the intra- and inter-fraction displacements with a schematic view of the six segments can be seen in figure 1.

Results
The lung volumes for all breath holds varied by 2% within and 7% between fractions. Looking at all five volunteers, up to 2 mm median intra- and inter-fraction displacements were found for all lung segments. The anatomical reproducibility decreased towards the caudal regions. Inter-fraction displacements were larger than intra-fractional displacements. Maximum displacements (99.3% of the magnitude vectors) reached 6 mm intra-fractionally and did not exceed 7 mm inter-fractionally.

Conclusion
While the lung volume differences were insignificant, relevant anatomical displacements were found. Moreover, a trend of increased displacements over time could be seen. ABC mitigates motion to some extent. Nevertheless, the remaining reproducibility uncertainties need to be considered during scanned proton therapy treatments. As next step, we aim to include this knowledge in a model to estimate their dosimetric influence for scanning proton therapy.