Optimizing Planning and Delivery of High-Precision Robotic Radiotherapy and Intensity-Modulated Proton Therapy

__Abstract__ High-precision robotic radiotherapy and intensity-modulated proton therapy (IMPT) are two relatively new radiotherapy techniques that particularly aim at a highly localized delivery of a curative dose to the tumor, while achieving excellent sparing of the surrounding healthy tissues and critical organs. However, the use of hundreds (in high-precision robotic radiotherapy) or thousands (in IMPT) of small radiation beams to achieve a highly localized dose delivery is also associated with a number of issues regarding the efficiency and accuracy of treatment planning and delivery. These issues currently obstruct a more widespread use of high-precision robotic radiotherapy and IMPT. In this thesis, we have aimed at improving treatment planning and treatment delivery for both treatment modalities in order to overcome these obstacles. We have developed and evaluated several methods to reduce the treatment delivery time and the treatment planning time. This resulted in average delivery time reductions of 16%–38% and optimization times to be shortened by a factor of 2.8–5.6 on average. Next to that, we have investigated for both treatment modalities the sensitivity to treatment uncertainties and the effectiveness of techniques to reduce treatment errors or their impact on the delivered dose. This allowed us to establish favorable treatment strategies to achieve adequate dose delivery in the presence of intrafraction tumor motion and uncertainties in patient position, patient anatomy and proton range (for IMPT). These efforts will contribute to a more efficient, effective and safe delivery of a highly localized dose to the tumor using the CyberKnife and IMPT

Shortening delivery times of intensity modulated proton therapy by reducing proton energy layers during treatment plan optimization

Purpose To shorten delivery times of intensity modulated proton therapy by reducing the number of energy layers in the treatment plan. Methods and Materials We have developed an energy layer reduction method, which was implemented into our in-house-developed multicriteria treatment planning system "Erasmus-iCycle." The method consisted of 2 components: (1) minimizing the logarithm of the total spot weight per energy layer; and (2) iteratively excluding low-weighted energy layers. The method was benchmarked by comparing a robust "time-efficient plan" (with energy layer reduction) with a robust "standard clinical plan" (without energy layer reduction) for 5 oropharyngeal cases and 5 prostate cases. Both plans of each patient had equal robust plan quality, because the worst-case dose parameters of the standard clinical plan were used as dose constraints for the time-efficient plan. Worst-case robust optimization was performed, accounting for setup errors of 3 mm and range errors of 3% + 1 mm. We evaluated the number of energy layers and the expected delivery time per fraction, assuming 30 seconds per beam direction, 10 ms per spot, and 400 Giga-protons per minute. The energy switching time was varied from 0.1 to 5 seconds. Results The number of energy layers was on average reduced by 45% (range, 30%-56%) for the oropharyngeal cases and by 28% (range, 25%-32%) for the prostate cases. When assuming 1, 2, or 5 seconds energy switching time, the average delivery time was shortened from 3.9 to 3.0 minutes (25%), 6.0 to 4.2 minutes (32%), or 12.3 to 7.7 minutes (38%) for the oropharyngeal cases, and from 3.4 to 2.9 minutes (16%), 5.2 to 4.2 minutes (20%), or 10.6 to 8.0 minutes (24%) for the prostate cases. Conclusions Delivery times of intensity modulated proton therapy can be reduced substantially without compromising robust plan quality. Shorter delivery times are likely to reduce treatment uncertainties and costs

Impact of spot reduction on the effectiveness of rescanning in pencil beam scanned proton therapy for mobile tumours.

Objective. In pencil beam scanning proton therapy, individually calculated and positioned proton pencil beams, also referred to as 'spots', are used to achieve a highly conformal dose distributions to the target. Recent work has shown that this number of spots can be substantially reduced, resulting in shorter delivery times without compromising dosimetric plan quality. However, the sensitivity of spot-reduced plans to tumour motion is unclear. Although previous work has shown that spot-reduced plans are slightly more sensitive to small positioning inaccuracies of the individual pencil beams, the resulting shorter delivery times may allow for more rescanning. The aim of this study was to assess the impact of tumour motion and the effectiveness of 3D volumetric rescanning for spot-reduced treatment plans.Approach.Three liver and two lung cancer patients with non-negligible motion amplitudes were analysed. Conventional and probabilistic internal target volume definitions were used for planning considering single or multiple breathing cycles respectively. For each patient, one clinical and two spot-reduced treatment plans were created using identical field geometries. 4D dynamic dose calculations were then performed and resulting target coverage (V95%), dose homogeneity (D5%-D95%) and hot spots (D2%) evaluated for 1-25 rescans.Main results. Over all patients investigated, spot reduction reduced the number of spots by 91% in comparison to the clinical plan, reducing field delivery times by approximately 50%. This reduction, together with the substantially increased dose per spot resulting from the spot reduction process, allowed for more rescans in the same amount of time as for clinical plans and typically improved dosimetric parameters, in some cases to values better than the reference static (3D calculated) plans. However, spot-reduced plans had an increased possibility of interference with the breathing cycle, especially for simulations of perfectly repeatable breathing.Significance.For the patients analysed in this study, spot-reduced plans were found to be a valuable option to increase the efficiency of 3D volumetric rescanning for motion mitigation, if attention is paid to possible interference patterns

Ultra-fast pencil beam scanning proton therapy for locally advanced non-small-cell lung cancers: field delivery within a single breath-hold.

PURPOSE The use of motion mitigation techniques such as breath-hold can reduce the dosimetric uncertainty of lung cancer proton therapy. We studied the feasibility of pencil beam scanning (PBS) proton therapy field delivery within a single breath-hold at PSI's Gantry 2. METHODS In PBS proton therapy, the delivery time for a field is determined by the beam-on time and the dead time between proton spots (the time required to change the energy and/or lateral position). We studied ways to reduce beam-on and lateral scanning time, without sacrificing dosimetric plan quality, aiming at a single field delivery time of 15 seconds at maximum. We tested this approach on 10 lung cases with varying target volumes. To reduce the beam-on time, we increased the beam current at the isocenter by developing new beam optics for PSI's PROSCAN beamline and Gantry 2. To reduce the dead time between the spots, we used spot-reduced plan optimization. RESULTS We found that it is possible to achieve conventional fractionated (2 Gy(RBE)/fraction) and hypofractionated (6 Gy(RBE)/fraction) field delivery times within a single breath-hold (<15 sec) for a variety non-small-cell lung cancer cases. CONCLUSION In summary, the combination of spot reduction and improved beam line transmission is a promising approach for the treatment of mobile tumours within clinically achievable breath-hold durations