Intensity‐modulated proton therapy (IMPT) interplay effect evaluation of asymmetric breathing with simultaneous uncertainty considerations in patients with non‐small cell lung cancer

Abstract

Purpose Intensity‐modulated proton therapy (IMPT) is sensitive to uncertainties from patient setup and proton beam range, as well as interplay effect. In addition, respiratory motion may vary from cycle to cycle, and also from day to day. These uncertainties can severely degrade the original plan quality and potentially affect patient’s outcome. In this work, we developed a new tool to comprehensively consider the impact of all these uncertainties and provide plan robustness evaluation under them. Methods We developed a comprehensive plan robustness evaluation tool that considered both uncertainties from patient setup and proton beam range, as well as respiratory motion simultaneously. To mimic patients' respiratory motion, the time spent in each phase was randomly sampled based on patient‐specific breathing pattern parameters as acquired during the four‐dimensional (4D)‐computed tomography (CT) simulation. Spots were then assigned to one specific phase according to the temporal relationship between spot delivery sequence and patients’ respiratory motion. Dose in each phase was calculated by summing contributions from all the spots delivered in that phase. The final 4D dynamic dose was obtained by deforming all doses in each phase to the maximum exhalation phase. Three hundred (300) scenarios (10 different breathing patterns with 30 different setup and range uncertainty scenario combinations) were calculated for each plan. The dose‐volume histograms (DVHs) band method was used to assess plan robustness. Benchmarking the tool as an application’s example, we compared plan robustness under both three‐dimensional (3D) and 4D robustly optimized IMPT plans for 10 nonrandomly selected patients with non‐small cell lung cancer. Results The developed comprehensive plan robustness tool had been successfully applied to compare the plan robustness between 3D and 4D robustly optimized IMPT plans for 10 lung cancer patients. In the presence of interplay effect with uncertainties considered simultaneously, 4D robustly optimized plans provided significantly better CTV coverage (D95%, P = 0.002), CTV homogeneity (D5%‐D95%, P = 0.002) with less target hot spots (D5%, P = 0.002), and target coverage robustness (CTV D95% bandwidth, P = 0.004) compared to 3D robustly optimized plans. Superior dose sparing of normal lung (lung Dmean, P = 0.020) favoring 4D plans and comparable normal tissue sparing including esophagus, heart, and spinal cord for both 3D and 4D plans were observed. The calculation time for all patients included in this study was 11.4 ± 2.6 min. Conclusion A comprehensive plan robustness evaluation tool was successfully developed and benchmarked for plan robustness evaluation in the presence of interplay effect, setup and range uncertainties. The very high efficiency of this tool marks its clinical adaptation, highly practical and versatile nature, including possible real‐time intra‐fractional interplay effect evaluation as a potential application for future use.

Technical Note: 4D robust optimization in small spot intensity‐modulated proton therapy (IMPT) for distal esophageal carcinoma

“…However, the flexibility of IMPT creates vulnerabilities of plans with increased sensitivity to proton beam range and patient setup uncertainties 10–12 . Additionally, the interplay effect, caused by the interference between the respiration‐related intra‐faction tumor motion and the dynamic delivery of each beamlet, can also result in the deterioration of the IMPT dose distribution 9,13–29 Although robust optimization 9,23–28,30–46 has been proven effective in mitigating the impact of the aforementioned uncertainties, techniques to mitigate the interplay effect are less developed.…”

“…Tumor tracking 51,52 is still hampered by hardware limitations and is not ready for clinical use. Recently, four‐dimensional (4D) optimization 22,28,53–56 has been proposed to address the interplay effect directly in treatment planning. Graeff et al 57 .…”

Treatment planning and 4D robust evaluation strategy for proton therapy of lung tumors with large motion amplitude

“…Several authors have suggested a dose evaluation strategy similar to the one presented by Ribeiro et al, 17 where beam delivery characteristics are considered by splitting the spots into the appropriate phase of the 4DCT, though mainly without the inclusion of repeat CTs. 5 , 7 , 25 , 26 , 27 , 28 Most studies simply simulate the beam delivery pattern based on assumed standard settings for the energy layer switching times and in‐plane sweeping times, whereas some use the machine log files to extract the actual spot delivery times. Moreover, the breathing pattern of the patient was either seen as constant by using a fixed breathing period for all patients (e.g., 4 s 5 or 5 s 17 ) or by applying the patient‐specific breathing period extracted from the breathing signal recorded during 4DCT acquisition 28 or even during the daily treatments.…”

“…5 , 7 , 25 , 26 , 27 , 28 Most studies simply simulate the beam delivery pattern based on assumed standard settings for the energy layer switching times and in‐plane sweeping times, whereas some use the machine log files to extract the actual spot delivery times. Moreover, the breathing pattern of the patient was either seen as constant by using a fixed breathing period for all patients (e.g., 4 s 5 or 5 s 17 ) or by applying the patient‐specific breathing period extracted from the breathing signal recorded during 4DCT acquisition 28 or even during the daily treatments. 29 However, Ribeiro et al 17 and Shan et al 28 also take robustness into account in combination with interplay evaluation performed by the spot splitting into subplans.…”

Dosimetry, Efficacy, Safety, and Cost-Effectiveness of Proton Therapy for Non-Small Cell Lung Cancer

“…IMPT is also sensitive to uncertainties or target motion. Four-dimensional (4D)computed tomography (CT) ventilation imaging-guided proton therapy, based on breathing patterns, may be helpful for reducing uncertainties and dosing to the normal tissues [31][32][33]. IMPT via a deep-inspiration breath-hold, deformable image registration with daily adaptive proton therapy, and liver-ultrasound-based motion modeling may also provide additional benefits [34][35][36][37].…”