Respiratory motion is a challenge in abdominal radiotherapy. Motion mitigation strategies include gating or tracking, abdominal compression and breath-holding. With non-invasive mechanical ventilation (NIMV) regular breathing patterns can be imposed at typically 30 or 60 breaths per minute (brpm). NIMV at these high frequencies and with smaller tidal volumes reduce respiratory motion. Adding positive end-expiratory pressure (PEEP) to this regularized breathing also adds the advantage of increasing lung volume. The aim of this study was to compare respiratory motion of abdominal organs between free breathing and regularized breathing in volunteers. In two sessions on different days ten healthy volunteers were imaged during free breathing (FB), NIMV-imposed regularized breathing at a frequency of 30 (NIMV30) and 60 brpm with PEEP (NIMV60P). Alternating single-slice coronal and sagittal MR images were acquired with a frequency of 2.7 Hz during a period of 350 s. On a single image at mid-ventilation the liver, spleen and kidneys were delineated, if visible. Other images were deformably registered to this reference image, resulting in a deformation vector field for each image. Vector fields were used to determine the motion in each voxel of the reference image after excluding 5

Background and purpose:Image-guided radiotherapy (IGRT) for esophageal cancer requires large planning target volume (PTV) margins to account for interfraction variations, increasing radiation-associated side-effects. Cone-beam computed tomography-based (CBCT) online adaptive radiotherapy (oART) enables daily contour and plan adaptation, addressing anatomical changes and allowing for reduced PTV margins while ensuring target coverage. This study compared the dose-volume parameters of daily oART to non-adaptive IGRT in patients with esophageal cancer. Material and methods:Ten patients with distal esophageal or gastroesophageal junction cancer who received neoadjuvant chemoradiotherapy (41.4 Gy/23 fractions) were included retrospectively. Daily IGRT CBCTs were used to emulate oART with artificial intelligence (AI)-assisted target and organs-of-interest contouring, manual edits when necessary, and adaptive re-optimization. PTV margins (Anterior-Posterior, Left-Right, Caudal-Cranial) were reduced from 5, 7, 10 mm (IGRT) to 3, 5, 5 mm (oART), respectively. Mean organs-of-interest and fraction-equivalent (FE) dose-volume metrics between delivered and adaptive plans were compared. Results:Compared with IGRT, oART plans significantly reduced the number of fractions with internal clinical target volume underdosing (V95% < 98%: n = 32 vs. n = 1 fraction; p = 0.002) and median hotspot dose ( D 0.1 c m 3 : 106.2% vs. 103.9%; p = 0.002). Mean heart dose decreased by 10% (p = 0.037), and heart FE-V30Gy by 42% (7.3% vs. 4.3%; p = 0.002). Mean lung dose was reduced by 11% (p = 0.002), lung FE-V20Gy by 39% (4.2% vs. 2.6%; p = 0.002), and lung FE-V10Gy by 22% (24.6% vs. 19.3%; p = 0.002). Conclusion:CBCT-based oART improved dose distribution in esophageal cancer by enabling PTV margin reduction, improved target coverage and superior organs-of-interest sparing. These findings encourage clinical implementation to reduce radiation-associated side-effects.

PURPOSE:Stereotactic arrhythmia radiation therapy (STAR) is an emerging noninvasive treatment for patients with therapy-refractory ventricular tachycardia. However, STAR's targeting accuracy is challenged by cardiorespiratory motion, which may necessitate compromises in dose delivery to protect nearby organs-at-risk, particularly the stomach. Noninvasive mechanical ventilation (NIMV) at 60 breaths/min with 15 cmH₂O positive end-expiratory pressure (NIMV60P) has been shown to reduce respiratory motion and to potentially increase anatomic separation between thoracic structures. This study aimed to quantify the effect of NIMV60P on cardiorespiratory motion of the left diaphragm and the minimal heart-stomach distance. METHODS AND MATERIALS:We retrospectively analyzed magnetic resonance imaging (MRI) data from 22 healthy volunteers who underwent 2 sessions while free-breathing, breath-holding, and undergoing NIMV60P. Diaphragm motion was quantified using coronal cine MRIs. The minimal heart-stomach distance was measured using 3-dimensional MRIs during breath-hold inhalation (BH-inhalation), exhalation (BH-exhalation), and NIMV60P. Encompassing volumes of the heart and stomach were generated from BH-inhalation and BH-exhalation scans to evaluate overlap or separation during free-breathing. Lastly, cine frames were deformably registered to assess temporal heart-stomach distance variation. RESULTS:NIMV60P significantly reduced median cranial-caudal diaphragm motion by half from 30 mm (IQR, 16 mm) during free-breathing to 15 mm (IQR, 7 mm; P < .001). The median of the minimal heart-stomach distances increased to 16.8 mm with NIMV60P, significantly larger than during BH-inhalation (10.3 mm; P = .04) and BH-exhalation (4.6 mm; P < .01), whereas analysis emulating free-breathing showed frequent heart and stomach internal-volume overlap (27 of 41 sessions) or minimal median distance of 3.4 mm (IQR, 7 mm) between the heart and stomach, which can result in significant stomach dose during STAR. Median temporal heart-stomach distance was 19.2 mm during NIMV60P versus 7.1 mm during free-breathing. CONCLUSIONS:NIMV60P significantly reduces diaphragm motion and increases the distance between heart and stomach in healthy volunteers, supporting its integration with STAR to potentially improve targeting and reduce stomach toxicity, especially for inferior wall ventricular tachycardia targets.

Purpose: Accurate radiation therapy (RT) for lung cancer is challenging because of the respiratory motion of the tumor and surrounding organs at risk. Recently, non-invasive mechanical ventilation (NIMV) has been investigated as a novel respiratory motion management strategy. Using NIMV, respiratory motion can be minimized, while a larger lung volume yields less overall lung dose. The purpose of this study was to determine the potential benefit of NIMV to improve lung cancer RT using magnetic resonance imaging (MRI) data of healthy volunteers. Methods and Materials: Twelve healthy volunteers practiced NIMV at 60 breaths per minute (NIMV60) with added positive end-expiratory pressure (PEEP) in 2 sessions and subsequently underwent NIMV60 in 2 MRI sessions. We acquired single-slice sagittal 2-dimensional MRI images at 2.6 Hz for 6 minutes during free breathing and NIMV60. We quantified the motion of all visible cross-sections of lung arteries, as a surrogate for lung tumors, in cranio-caudal and anterior-posterior directions using deformable image registration, distinguishing between 4 quadrants in the lungs (posterior-cranial, posterior-caudal, anterior-caudal, and anterior-cranial). Also, we analyzed average lung area, as a surrogate for lung volume, on the sagittal images using automatic segmentation. Results: All volunteers were successfully trained to be ventilated with NIMV60, and completed all sessions. The reduction of the median lung artery motion in each of the quadrants varied from 61% to 67% (from 10.7-29.9 to 3.8-11.7 mm) in cranio-caudal direction and from 51% to 68% (from 8.0-13.7 to 3.0-5.1 mm) in anterior-posterior direction using NIMV60. NIMV60 increased the sagittal lung area by 35% compared with free breathing. Conclusions: NIMV60 with added PEEP is a promising way to improve lung cancer RT because of reduced respiratory motion and increased lung area compared with free breathing.

Abstract Background During the day-night cycle, gravity and applied stress to the body mass and spine causes a decrease in body height, which is restored overnight. This diurnal spine length variation has not yet been quantified during radiotherapy. Therefore, we aimed to quantify diurnal spine length variation on cone beam CTs (CBCTs) of pediatric patients (< 18 years) who underwent radiotherapy. Methods For this retrospective study, we included 32 patients (mean age 10.0, range 2.7–16.1 years) who received image guided radiotherapy between 2012 and 2018 in two institutes. Patients were included when they had two fractions per day, or when fractions were scheduled on varying time slots over the course of treatment. Daily CBCTs were registered to the planning CTs using two automatic registrations relative to the bony anatomy; one to vertebra T11 and one to vertebra L4. For each CBCT, the differences between the cranial-caudal (CC) position of the T11 and L4 vertebrae were calculated. To determine the diurnal spine length variation, the difference in vertebrae position between the morning and afternoon CBCTs was calculated. Furthermore, we investigated the possible correlation of diurnal spine length variation with the time slot differences (time interval) between CBCTs (Spearman’s ρ). Results Overall, the median spine length variation was -1.0 (range -3.9–0.1) mm, and we found a significant reduction in spine length over the day (p < 0.001) with substantial variations between patients. Time intervals between CBCTs ranging from 4.0 to 9.5 h were not correlated with spine length reduction (ρ=-0.01; p = 0.95). Conclusions We found a small but significant reduction in spine length (vertebrae T11 to L4) over the course of day in pediatric patients undergoing radiotherapy, measured on CBCT imaging. Spine length reduction did not correlate with CBCT time intervals. However, our results indicate that diurnal spine length reduction could induce a setup error during treatment, and therefore should be considered in pediatric radiotherapy.

Background: Respiratory motion presents a challenge in radiotherapy of thoracic and upper abdominal tumors. Techniques to account for respiratory motion include tracking. Using magnetic resonance imaging (MRI) guided radiotherapy systems, tumors can be tracked continuously. Using conventional linear accelerators, tracking of lung tumors is possible by determining tumor motion on kilo voltage (kV) imaging. But tracking of abdominal tumors with kV imaging is hampered by limited contrast. Therefore, surrogates for the tumor are used. One of the possible surrogates is the diaphragm. However, there is no universal method for establishing the error when using a surrogate and there are particular challenges in establishing such errors during free breathing (FB). Prolonged breath-holding might address these challenges. Purpose: The aim of this study was to quantify the error when using the right hemidiaphragm top (RHT) as surrogate for abdominal organ motion during prolonged breath-holds (PBH) for possible application in radiation treatments. Methods: Fifteen healthy volunteers were trained to perform PBHs in two subsequent MRI sessions (PBH-MRI1 and PBH-MRI2). From each MRI acquisition, we selected seven images (dynamics) to determine organ displacement during PBH by using deformable image registration (DIR). On the first dynamic, the RHT, right and left hemidiaphragm, liver, spleen and right and left kidney were segmented. We used the deformation vector fields (DVF), generated by DIR, to determine the displacement of each organ between two dynamics in inferior-superior (IS), anterior-posterior (AP), left-right (LR) direction and we calculated the 3D vector magnitude (vertical bar d vertical bar). The displacements of the RHT, both hemidiaphragms and the abdominal organs were compared using a linear fit to determine the correlation (R-2 of the fit) and the displacement ratio (DR, slope of the fit) between displacements of the RHT and each organ. We quantified the median difference between the DRs of PBH-MRI1 and PBH-MRI2 for each organ. Additionally, we estimated organ displacement in the second PBH by applying the DR from the first PBH to the displacement of the RHT measured during the second PBH. We compared the estimated organ displacement to the measured organ displacement during the second PBH. The difference between the two values was defined as the estimation error of using the RHT as a surrogate and assuming a constant DR over MRI sessions. Results: The linear relationships were confirmed by the high R-2 values of the linear fit between the displacements of the RHT and the abdominal organs (R-2 > 0.96) in the IS and AP direction and vertical bar d vertical bar, and high to moderate correlations in the LR direction (0.93 > R-2 > 0.64). The median DR difference between PBH-MRI1 and PBH-MRI2 varied between 0.13 and 0.31 for all organs. The median estimation error of the RHT as a surrogate varied between 0.4 and 0.8 mm/min for all organs. Conclusion: The RHT could serve as an accurate surrogate for abdominal organ motion during radiation treatments, for example, in tracking, provided the error of the RHT as motion surrogate is taken into account in the margins.

AbstractBackgroundFor accurate thoracic and abdominal radiotherapy, inter- and intrafractional geometrical uncertainties need to be considered to enable accurate margin sizes. We aim to quantify interfractional diaphragm and abdominal organ position variations, and intrafractional diaphragm motion in a large multicenter cohort of pediatric cancer patients (< 18 years). We investigated the correlation of interfractional position variations and intrafractional motion with age, and with general anesthesia (GA).MethodsIn 189 children (mean age 8.1; range 0.4–17.9 years) from six institutes, interfractional position variation of both hemidiaphragms, spleen, liver, left and right kidneys was quantified using a two-step registration. CBCTs were registered to the reference CT relative to the bony anatomy, followed by organ registration. We calculated the group mean, systematic and random errors (standard deviations Σ and σ, respectively) in cranial-caudal (CC), left-right and anterior-posterior directions. Intrafractional right hemidiaphragm motion was quantified using CBCTs on which the breathing amplitude, defined as the difference between end-inspiration and end-expiration peaks, was assessed (N = 79). We investigated correlations with age (Spearman’s ρ), and differences in motion between patients treated with and without GA (N = 75; all < 5.5 years).ResultsInterfractional group means were largest in CC direction and varied widely between patients, with largest variations in the right hemidiaphragm (range -13.0–17.5 mm). Interfractional group mean of the left kidney showed a borderline significant correlation with age (p = 0.047; ρ = 0.17). Intrafractional right hemidiaphragm motion in patients ≥ 5.5 years (mean 10.3 mm) was significantly larger compared to patients < 5.5 years treated without GA (mean 8.3 mm) (p = 0.02), with smaller Σ and σ values. We found a significant correlation between breathing amplitude and age (p < 0.001; ρ = 0.43). Interfractional right hemidiaphragm position variations were significantly smaller in patients < 5.5 years treated with GA than without GA (p = 0.004), but intrafractional motion showed no significant difference.ConclusionIn this large multicenter cohort of children undergoing thoracic and abdominal radiotherapy, we found that interfractional position variation does not depend on age, but the use of GA in patients < 5.5 years showed smaller systematic and random errors. Furthermore, our results showed that breathing amplitude increases with age. Moreover, variations between patients advocate the need for a patient-specific margin approach.