Impact of organ motion on volumetric and dosimetric parameters in stomach lymphomas treated with intensity-modulated radiotherapy.

PURPOSE: Interplay effects may influence dose distributions to a moving target when using dynamic delivery techniques such as intensity-modulated radiotherapy (IMRT). The aim of this study was to evaluate the impact of organ motion on volumetric and dosimetric parameters in stomach lymphomas treated with IMRT. METHODS: Ten patients who had been treated with IMRT for stomach lymphomas were enrolled. The clinical target volume (CTV) was contoured as the whole stomach. Considering interfractional uncertainty, the internal target volume (ITV) margin was uniformly 1.5 cm to the CTV and then modified based on the 4DCT images in case of the large respiratory motion. The planning target volume (PTV) was created by adding 5 mm to the ITV. The impact of organ motion on the volumetric and dosimetric parameters was evaluated retrospectively (4D simulation). The organ motion was reproduced by shifting the isocenter on the radiation treatment planning system. Several simulation plans were created to test the influence of the beam-on timing in the respiration cycle on the dose distribution. The homogeneity index (HI), volume percentage of stomach covered by the prescribed dose (Vp ), and D99 of the CTV were evaluated. RESULTS: The organ motion was the largest in the superior-inferior direction (10.1 ± 4.5 mm [average ± SD]). Stomach volume in each respiratory phase compared to the mean volume varied approximately within a ± 5% range in most of the patients. The PTV margin was sufficiently large to cover the CTV during the IMRT. There was a significant reduction in Vp and D99 but not in HI in the 4D simulation in free-breathing and multiple fractions compared to the clinically-used plan (P < 0.05) suggesting that interplay effects deteriorate the dose distribution. The absolute difference of D99 was less than 1% of the prescribed dose. CONCLUSIONS: There were significant interplay effects affecting the dose distribution in stomach IMRT. The magnitude of the dose reduction was small when patients were treated on free-breathing and multiple fractions.

An effective method to reduce the interplay effects between respiratory motion and a uniform scanning proton beam irradiation for liver tumors: A case study.

PURPOSE: For scanning particle beam therapy, interference between scanning patterns and interfield organ motion may result in suboptimal dose within target volume. In this study, we developed a simple offline correction technique for uniform scanning proton beam (USPB) delivery to compensate for the interplay between scanning patterns and respiratory motion and demonstrate the effectiveness of our technique in treating liver cancer. METHODS: The computed tomography (CT) and respiration data of two patients who had received stereotactic body radiotherapy for hepatocellular carcinoma were used. In the simulation, the relative beam weight delivered to each respiratory phase is calculated for each beam layer after treatment of each fraction. Respiratory phases with beam weights higher than 50% of the largest weight are considered "skipped phases" for the next fraction. For the following fraction, the beam trigger is regulated to prevent beam layers from starting irradiation in skipped phases by extending the interval between each layer. To calculate dose-volume histogram (DVH), the dose of the target volume at end-exhale (50% phase) was calculated as the sum of each energy layer, with consideration of displacement due to respiratory motion and relative beam weight delivered per respiratory phase. RESULTS: For a single fraction, D1% , D99% , and V100% were 114%, 88%, and 32%, respectively, when 8 Gy/min of dose rate was simulated. Although these parameters were improved with multiple fractions, dosimetric inhomogeneity without motion management remained even at 30 fractions, with V100% 86.9% at 30 fractions. In contrast, the V100% values with adaptation were 96% and 98% at 20 and 30 fractions, respectively. We developed an offline correction technique for USPB therapy to compensate for the interplay effects between respiratory organ motion and USPB beam delivery. CONCLUSIONS: For liver tumor, this adaptive therapy technique showed significant improvement in dose uniformity even with fewer treatment fractions than normal USPB therapy.

Dosimetric comparison of distal esophageal carcinoma plans for patients treated with small-spot intensity-modulated proton versus volumetric-modulated arc therapies.

BACKGROUND: Esophageal carcinoma is the eighth most common cancer in the world. Volumetric-modulated arc therapy (VMAT) is widely used to treat distal esophageal carcinoma due to high conformality to the target and good sparing of organs at risk (OAR). It is not clear if small-spot intensity-modulated proton therapy (IMPT) demonstrates a dosimetric advantage over VMAT. In this study, we compared dosimetric performance of VMAT and small-spot IMPT for distal esophageal carcinoma in terms of plan quality, plan robustness, and interplay effects. METHODS: 35 distal esophageal carcinoma patients were retrospectively reviewed; 19 patients received small-spot IMPT and the remaining 16 of them received VMAT. Both plans were generated by delivering prescription doses to clinical target volumes (CTVs) on phase-averaged 4D-CT's. The dose-volume-histogram (DVH) band method was used to quantify plan robustness. Software was developed to evaluate interplay effects with randomized starting phases for each field per fraction. DVH indices were compared using Wilcoxon rank-sum test. For fair comparison, all the treatment plans were normalized to have the same CTVhigh D95% in the nominal scenario relative to the prescription dose. RESULTS: In the nominal scenario, small-spot IMPT delivered statistically significantly lower liver Dmean and V30Gy[RBE] , lung Dmean , heart Dmean compared with VMAT. CTVhigh dose homogeneity and protection of other OARs were comparable between the two treatments. In terms of plan robustness, the IMPT and VMAT plans were comparable for kidney V18Gy[RBE] , liver V30Gy[RBE] , stomach V45Gy[RBE] , lung Dmean , V5Gy[RBE] , and V20Gy[RBE] , cord Dmax and D 0.03 c m 3 , liver Dmean , heart V20Gy[RBE] , and V30Gy[RBE] , but IMPT was significantly worse for CTVhigh D95% , D 2 c m 3 , and D5% -D95% , CTVlow D95% , heart Dmean , and V40Gy[RBE] , requiring careful and experienced adjustments during the planning process and robustness considerations. The small-spot IMPT plans still met the standard clinical requirements after interplay effects were considered. CONCLUSIONS: Small-spot IMPT decreases doses to heart, liver, and total lung compared to VMAT as well as achieves clinically acceptable plan robustness. Our study supports the use of small-spot IMPT for the treatment of distal esophageal carcinoma.

Small-spot intensity-modulated proton therapy and volumetric-modulated arc therapies for patients with locally advanced non-small-cell lung cancer: A dosimetric comparative study.

PURPOSE: To compare dosimetric performance of volumetric-modulated arc therapy (VMAT) and small-spot intensity-modulated proton therapy for stage III non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: A total of 24 NSCLC patients were retrospectively reviewed; 12 patients received intensity-modulated proton therapy (IMPT) and the remaining 12 received VMAT. Both plans were generated by delivering prescription doses to clinical target volumes (CTV) on averaged 4D-CTs. The dose-volume-histograms (DVH) band method was used to quantify plan robustness. Software was developed to evaluate interplay effects with randomized starting phases of each field per fraction. DVH indices were compared using Wilcoxon rank sum test. RESULTS: Compared with VMAT, IMPT delivered significantly lower cord Dmax , heart Dmean , and lung V5 Gy[ RBE ] with comparable CTV dose homogeneity, and protection of other OARs. In terms of plan robustness, the IMPT plans were statistically better than VMAT plans in heart Dmean , but were statistically worse in CTV dose coverage, cord Dmax , lung Dmean , and V5 Gy[ RBE ] . Other DVH indices were comparable. The IMPT plans still met the standard clinical requirements with interplay effects considered. CONCLUSIONS: Small-spot IMPT improves cord, heart, and lung sparing compared to VMAT and achieves clinically acceptable plan robustness at least for the patients included in this study with motion amplitude less than 11 mm. Our study supports the usage of IMPT to treat some lung cancer patients.

Impact of Dosimetric Parameters on Interplay Effects in 6 MV Flattening Filter-Free Photon Beams to Treat Lung Cancer.

Context: Interplay effects have become the significant problem in lung cancer radiotherapy. Since these effects yield dose variation within the target and surrounding tissues. Aim: The aim of this study is to investigate the effect of the dosimetric parameters of interplay effects in 6 MV flattening filter-free (FFF) photon beams for lung cancer. Settings and Design: This study performed planning, measurement, and data analysis sections for examining different breathing amplitudes and phases, doses, dose rates, field sizes, and fractionations. Subjects and Methods: Standard and clinical plans were created on the eclipse treatment planning system. The static and dynamic measurements were performed using a robotic platform and two-dimensional (2D) diode array. The gamma passing rates were defined as the percent of dose variation caused by the interplay effects. Statistical Analysis Used: Unpaired t-test. Results: The outcomes showed three trends between gamma passing rates (γ) and dosimetric parameters. First, a decreasing trend was breathing amplitudes. The lowest γ of maximum amplitudes (2 cm) in both one dimensional and 2D were <25%. Second, an increasing trend was field sizes. The lowest γ of minimum field size (4 cm × 4 cm2) was <55%. Third, constant outcomes were breathing phases, doses, dose rates, and a number of fractions. The γ values of these factors were 53.1%, 55.1%, 34.7%, and 36.7%, respectively. Conclusions: Lung tumor motion-induced interplay effects in 6 MV FFF photon beams are more pronounced for higher breathing amplitudes and smaller field sizes.

Statistical breathing curve sampling to quantify interplay effects of moving lung tumors in a 4D Monte Carlo dose calculation framework.

PURPOSE: The interplay between respiratory tumor motion and dose application by intensity modulated radiotherapy (IMRT) techniques can potentially lead to undesirable and non-intuitive deviations from the planned dose distribution. We developed a 4D Monte Carlo (MC) dose recalculation framework featuring statistical breathing curve sampling, to precisely simulate the dose distribution for moving target volumes aiming at a comprehensive assessment of interplay effects. METHODS: We implemented a dose accumulation tool that enables dose recalculations of arbitrary breathing curves including the actual breathing curve of the patient. This MC dose recalculation framework is based on linac log-files, facilitating a high temporal resolution up to 0.1 s. By statistical analysis of 128 different breathing curves, interplay susceptibility of different treatment parameters was evaluated for an exemplary patient case. To facilitate prospective clinical application in the treatment planning stage, in which patient breathing curves or linac log-files are not available, we derived a log-file free version with breathing curves generated by a random walk approach. Interplay was quantified by standard deviations σ in D5%, D50% and D95%. RESULTS: Interplay induced dose deviations for single fractions were observed and evaluated for IMRT and volumetric arc therapy (σD95% up to 1.3 %) showing a decrease with higher fraction doses and an increase with higher MU rates. Interplay effects for conformal treatment techniques were negligible (σ<0.1%). The log-file free version and the random walk generated breathing curves yielded similar results (deviations in σ< 0.1 %) and can be used as substitutes for interplay assessment. CONCLUSION: It is feasible to combine statistically sampled breathing curves with MC dose calculations. The universality of the presented framework allows comprehensive assessment of interplay effects in retrospective and prospective clinically relevant scenarios.

How should we model and evaluate breathing interplay effects in IMPT?

Breathing interplay effects in Intensity Modulated Proton Therapy (IMPT) arise from the interaction between target motion and the scanning beam. Assessing the detrimental effect of interplay and the clinical robustness of several mitigation techniques requires statistical evaluation procedures that take into account the variability of breathing during dose delivery. In this study, we present such a statistical method to model intra-fraction respiratory motion based on breathing signals and assess clinical relevant aspects related to the practical evaluation of interplay in IMPT such as how to model irregular breathing, how small breathing changes affect the final dose distribution, and what is the statistical power (number of different scenarios) required for trustworthy quantification of interplay effects. First, two data-driven methodologies to generate artificial patient-specific breathing signals are compared: a simple sinusoidal model, and a precise probabilistic deep learning model generating very realistic samples of patient breathing. Second, we investigate the highly fluctuating relationship between interplay doses and breathing parameters, showing that small changes in breathing period result in large local variations in the dose. Our results indicate that using a limited number of samples to calculate interplay statistics introduces a bigger error than using simple sinusoidal models based on patient parameters or disregarding breathing hysteresis during the evaluation. We illustrate the power of the presented statistical method by analyzing interplay robustness of 4DCT and Internal Target Volume (ITV) treatment plans for a 8 lung cancer patients, showing that, unlike 4DCT plans, even 33 fraction ITV plans systematically fail to fulfill robustness requirements.

Mitigation of the Interplay Effects of Combining 4D Robust With Layer Repainting Techniques in Proton-Based SBRT for Patients With Early-Stage Non-small Cell Lung Cancer.

OBJECTIVE: The objective of this study was to evaluate the interplay effects in proton-based stereotactic body radiotherapy (SBRT) using 4D robust optimization combined with iso-energy layer repainting techniques for non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Twelve patients with early-stage NSCLC who underwent 4DCT were retrospectively selected. A robust CTV-based 4D plan was generated for each based on commercial Treatment planning system (TPS), considering patient setup errors, range uncertainties, and organ motion. The 4D static dose (4DSD) and 4D dynamic dose (4DDD) were calculated using a hybrid deformable algorithm and simulated proton delivery system. An index Δ I M R ( % ) was developed to quantitatively evaluate the interplay effects. The interplay effects of the 4D robust plan and multiple iso-energy layers (3, 4, 5, 6, and 7) of the robust repainting 4D plan were calculated based on Δ I M R ( % ) to select the optimal times for layer repainting. RESULTS: Due to the interplay effects, the mean target values D2 and D5 increased to 1.28 and 1.01%, and the target values D98 and D95 decreased to 2.01 and 1.77%, respectively, for the 4D Robust SBRT plan. After multiple iso-energy repainting times, the interplay effects of the target values D98 and D95 tended to migrate, from 2.01 to 0.92% in target value D98 and from 1.77 to 0.89% in target value D95, respectively. Moreover, a positive linear correlation was observed between the optimal interplay effect mitigation and target range of motion. CONCLUSION: In proton-based 4D Robust SBRT, the interplay effects degraded the target dose distribution but were mitigated using iso-energy layer repainting techniques. However, there was no significant correlation between the number of repainting layers and improvements in the dose distributions. The optimal layer repainting times based on the interplay effect index were ascertained according to the patient characteristics.

Free Breathing versus Breath-Hold Scanning Beam Proton Therapy and Cardiac Sparing in Breast Cancer.

PURPOSE: To assess dose errors caused by the interplay effects of free-breathing (FB) motion and to assess the value of breath-hold (BH) in terms of cardiac dose reduction for scanning beam proton therapy (SBPT). MATERIALS AND METHODS: Three patients with left-sided breast cancer previously treated with photon therapy were included in this dosimetric study: 2 following breast-conserving surgery with 2 hypothetical target volumes (whole breast alone and whole breast plus regional nodes, including supraclavicular, axillary, and internal mammary lymph nodes); and 1 postmastectomy, with the target volume including the chest wall plus regional nodes. SBPT plans were generated with various beam angles that ranged between 2 tangential directions. For treatment with FB, nominal dose and dose with interplay effects considered were calculated based on FB 4-dimensional computed tomography scans. SBPT plans on the BH computed tomography were also calculated for one of the patients, who was selected to be treated with photon therapy with BH. RESULTS: Dosimetric differences between nominal and interplay dose were small (average target mean dose, -0.06 Gy; range, -0.23 to 0.06 Gy; average heart mean dose, 0.001 Gy; range, -0.12 to 0.05 Gy). The largest dose deviations occurred in plans calculated with tangential beam arrangements; the smallest was noted with the en face beam. The average value of the mean heart dose with FB was <1 Gy. For the selected patient, the mean heart doses were 0.5 and 0.2 Gy for FB and BH, respectively. CONCLUSION: Dose deviations caused by the interplay effects of respiratory motion during FB do not have a significant impact in SBPT with en face beam arrangement. BH does not significantly reduce cardiac dose. SBPT delivery is feasible with FB and can provide optimal target coverage and maximal sparing of the cardiopulmonary system, which can translate into improved clinical outcomes and a decrease in treatment-related morbidity in left-sided breast cancer patients or those who require internal mammary node coverage.