[en] Intensity-modulated proton therapy (IMPT) offers excellent dose conformity and healthy tissue sparing, but it can be substantially compromised in the presence of anatomical changes. A major dosimetric effect is caused by density changes, which alter the planned proton range in the patient. Three different methods, which automatically restore an IMPT plan dose on a daily CT image were implemented and compared: (1) simple dose restoration (DR) using optimization objectives of the initial plan, (2) voxel-wise dose restoration (vDR), and (3) isodose volume dose restoration (iDR). Dose restorations were calculated for three different clinical cases, selected to test different capabilities of the restoration methods: large range adaptation, complex dose distributions and robust re-optimization. All dose restorations were obtained in less than 5 min, without manual adjustments of the optimization settings. The evaluation of initial plans on repeated CTs showed large dose distortions, which were substantially reduced after restoration. In general, all dose restoration methods improved DVH-based scores in propagated target volumes and OARs. Analysis of local dose differences showed that, although all dose restorations performed similarly in high dose regions, iDR restored the initial dose with higher precision and accuracy in the whole patient anatomy. Median dose errors decreased from 13.55 Gy in distorted plan to 9.75 Gy (vDR), 6.2 Gy (DR) and 4.3 Gy (iDR). High quality dose restoration is essential to minimize or eventually by-pass the physician approval of the restored plan, as long as dose stability can be assumed. Motion (as well as setup and range uncertainties) can be taken into account by including robust optimization in the dose restoration. Restoring clinically-approved dose distribution on repeated CTs does not require new ROI segmentation and is compatible with an online adaptive workflow. (paper)

[en] Highlights: • Fast (4-6 us) and stress-confined, delivery enables thermoacoustic range verification. • Submillimeter range accuracy was achieved for beamlets that delivered ~0.5 Gy to soft tissue. • Estimates are accurate relative to ultrasound images soundspeed inhomogeneity • Synchrocyclotrons deliver stress-confined proton pulses. • Acoustic ringing indicated beam traversed bone; metallic implants will also cause ringing. The purpose of this phantom study is to demonstrate that thermoacoustic range verification could be performed clinically. Thermoacoustic emissions generated in an anatomical multimodality imaging phantom during delivery of a clinical plan are compared to simulated emissions to estimate range shifts compared to the treatment plan.

[en] Purpose: To evaluate the impact of intra-fraction motion induced by regular breathing on treatment quality for helical tomotherapy treatments. Material and methods: Four patients treated by simultaneous-integrated boost (SIB) and three by hypo-fractionated stereotactic treatments (hypo-fractionated, 18 Gy/fraction) were included. All patients were coached to ensure regular breathing. For the SIB group, the tumor volume was delineated using CT information only (CTV_CT) and the boost region was based on PET information (GTV_PET, no CTV extension). In the hypo-fractionated group, a GTV based on CT information was contoured. In both groups, ITVs were defined according to 4D data. The PTV included the ITV plus a setup error margin. The treatment was planned using the tomotherapy TPS on 3D CT images. In order to verify the impact of intra-fraction motion and interplay effects, dose calculations were performed using a previously validated Monte Carlo model of tomotherapy (TomoPen): first on the planning 3D CT (“planned dose”) and second, on the 10 phases of the 4D scan. For the latter, two dose distributions, termed “interplay simulated” or “no interplay” were computed with and without beamlet-phase correlation over the 10 phases and combined using deformable dose registration. Results: In all cases, DVHs of “interplay simulated” dose distributions complied within 1% of the original clinical objectives used for planning, defined according to ICRU (report 83) and RTOG (trials 0236 and 0618) recommendations, for SIB and hypo-fractionated groups, respectively. For one patient in the hypo-fractionated group, D_mean to the CTV_CT was 2.6% and 2.5% higher than “planned” for “interplay simulated” and “no interplay”, respectively. Conclusion: For the patients included in this study, assuming regular breathing, the results showed that interplay of breathing and tomotherapy delivery motions did not affect significantly plan delivery accuracy. Hence, accounting for intra-fraction motion through the definition of an ITV volume was sufficient to ensure tumor coverage.

[en] Four-dimensional cone-beam computed tomography (4D-CBCT) of the free-breathing thorax is a valuable tool in image-guided radiation therapy of the thorax and the upper abdomen. It allows the determination of the position of a tumor throughout the breathing cycle, while only its mean position can be extracted from three-dimensional CBCT. The classical approaches are not fully satisfactory: respiration-correlated methods allow one to accurately locate high-contrast structures in any frame, but contain strong streak artifacts unless the acquisition is significantly slowed down. Motion-compensated methods can yield streak-free, but static, reconstructions. This work proposes a 4D-CBCT method that can be seen as a trade-off between respiration-correlated and motion-compensated reconstruction. It builds upon the existing reconstruction using spatial and temporal regularization (ROOSTER) and is called motion-aware ROOSTER (MA-ROOSTER). It performs temporal regularization along curved trajectories, following the motion estimated on a prior 4D CT scan. MA-ROOSTER does not involve motion-compensated forward and back projections: the input motion is used only during temporal regularization. MA-ROOSTER is compared to ROOSTER, motion-compensated Feldkamp–Davis–Kress (MC-FDK), and two respiration-correlated methods, on CBCT acquisitions of one physical phantom and two patients. It yields streak-free reconstructions, visually similar to MC-FDK, and robust information on tumor location throughout the breathing cycle. MA-ROOSTER also allows a variation of the lung tissue density during the breathing cycle, similar to that of planning CT, which is required for quantitative post-processing. (paper)

[en] The treatment of moving targets with pencil beam scanned proton therapy (PBS-PT) may rely on rescanning strategies to smooth out motion induced dosimetric disturbances. PBS-PT machines, such as Proteus®Plus (PPlus) and Proteus®One (POne), deliver a continuous or a pulsed beam, respectively. In PPlus, scaled (or no) rescanning can be applied, while POne implies intrinsic ‘rescanning’ due to its pulsed delivery. We investigated the efficacy of these PBS-PT delivery types for the treatment of lung tumours. In general, clinically acceptable plans were achieved, and PPlus and POne showed similar effectiveness. (note)

[en] In proton therapy, quantification of the proton range uncertainty is important to achieve dose distribution compliance. The promising accuracy of prompt gamma imaging (PGI) suggests the development of a mathematical framework using the range measurements to convert population based estimates of uncertainties into patient specific estimates with the purpose of plan adaptation. We present here such framework using Bayesian inference. The sources of uncertainty were modeled by three parameters: setup bias m , random setup precision r and water equivalent path length bias u. The evolution of the expectation values E (m), E (r) and E (u) during the treatment was simulated. The expectation values converged towards the true simulation parameters after 5 and 10 fractions, for E (m) and E (u), respectively. E (r) settle on a constant value slightly lower than the true value after 10 fractions. In conclusion, the simulation showed that there is enough information in the frequency distribution of the range errors measured by PGI to estimate the expectation values and the confidence interval of the model parameters by Bayesian inference. The updated model parameters were used to compute patient specific lateral and local distal margins for adaptive re-planning. (paper)

[en] Prompt gamma (PG) imaging is widely investigated as one of the most promising methods for proton range verification in proton therapy. The performance of this technique is affected by several factors like tissue heterogeneity, number of protons in the considered pencil beam and the detection device. Our previous work proposed a new treatment planning concept which boosts the number of protons of a few PG monitoring-friendly pencil beams (PBs), selected on the basis of two proposed indicators quantifying the conformity between the dose and PG at the emission level, above the desired detectability threshold. To further explore this method at the detection level, in this work we investigated the response of a knife-edge slit PG camera which was deployed in the first clinical application of PG to proton therapy monitoring. The REGistration Graphical User Interface (REGGUI) is employed to simulate the PG emission, PG detection as well as the corresponding dose distribution. As the PG signal detected by this kind of PG camera is sensitive to the relative position of the camera and PG signal falloff, we optimized our PB selection method for this camera by introducing a new camera position indicator identifying whether the expected falloff of the PG signal is centered in the field of view of the camera or not. Our camera-adapted PB selection method is investigated using computed tomography (CT) scans at two different treatment time points of a head and neck, and a prostate cancer patient under scenarios considering different statistics level. The results show that a precision of 0.8 mm for PG falloff identification can be achieved when a PB has more than 2 × 10⁸ primary protons. Except for one case due to unpredictable and comparably large anatomical changes, the PG signals of most of the PBs recommended by all our indicators are observed to be reliable for proton range verification with deviations between the inter-fractional shift of proton range (as deduced from the PB dose distribution) and the detected PG signal within 2.0 mm. In contrast, a shift difference up to 9.6 mm has been observed for the rejected PBs. The magnitude of the proton range shift due to the inter-fractional anatomical changes is observed to be up to 23 mm. The proposed indicators are shown to be valuable for identifying and recommending reliable PBs to create new PG monitoring-friendly TPs. Comparison between our PB boosting method and the alternative PB aggregation, which combines the signal of nearby PBs to reach the desired counting statistics, is also discussed. (paper)

[en] Ventilation-induced tumour motion remains a challenge for the accuracy of proton therapy treatments in lung patients. We investigated the feasibility of using a 4D virtual CT (4D-vCT) approach based on deformable image registration (DIR) and motion-aware 4D CBCT reconstruction (MA-ROOSTER) to enable accurate daily proton dose calculation using a gantry-mounted CBCT scanner tailored to proton therapy. Ventilation correlated data of 10 breathing phases were acquired from a porcine ex-vivo functional lung phantom using CT and CBCT. 4D-vCTs were generated by (1) DIR of the mid-position 4D-CT to the mid-position 4D-CBCT (reconstructed with the MA-ROOSTER) using a diffeomorphic Morphons algorithm and (2) subsequent propagation of the obtained mid-position vCT to the individual 4D-CBCT phases. Proton therapy treatment planning was performed to evaluate dose calculation accuracy of the 4D-vCTs. A robust treatment plan delivering a nominal dose of 60 Gy was generated on the average intensity image of the 4D-CT for an approximated internal target volume (ITV). Dose distributions were then recalculated on individual phases of the 4D-CT and the 4D-vCT based on the optimized plan. Dose accumulation was performed for 4D-vCT and 4D-CT using DIR of each phase to the mid position, which was chosen as reference. Dose based on the 4D-vCT was then evaluated against the dose calculated on 4D-CT both, phase-by-phase as well as accumulated, by comparing dose volume histogram (DVH) values (D${}_{mean}$, D${}_{2\mathrm{\%<!--\; \%\; -->}}$, D${}_{98\mathrm{\%<!--\; \%\; -->}}$, D${}_{95\mathrm{\%<!--\; \%\; -->}}$) for the ITV, and by a 3D-gamma index analysis (global, 3%/3 mm, 5 Gy, 20 Gy and 30 Gy dose thresholds). Good agreement was found between the 4D-CT and 4D-vCT-based ITV-DVH curves. The relative differences ((CT-vCT)/CT) between accumulated values of ITV D${}_{mean}$, D${}_{2\mathrm{\%<!--\; \%\; -->}}$, D${}_{95\mathrm{\%<!--\; \%\; -->}}$ and D${}_{98\mathrm{\%<!--\; \%\; -->}}$ for the 4D-CT and 4D-vCT-based dose distributions were -0.2%, 0.0%, -0.1% and -0.1%, respectively. Phase specific values varied between -0.5% and 0.2%, -0.2% and 0.5%, -3.5% and 1.5%, and -5.7% and 2.3%. The relative difference of accumulated D${}_{mean}$ over the lungs was 2.3% and D${}_{mean}$ for the phases varied between -5.4% and 5.8%. The gamma pass-rates with 5 Gy, 20 Gy and 30 Gy thresholds for the accumulated doses were 96.7%, 99.6% and 99.9%, respectively. Phase-by-phase comparison yielded pass-rates between 86% and 97%, 88% and 98%, and 94% and 100%. Feasibility of the suggested 4D-vCT workflow using proton therapy specific imaging equipment was shown. Results indicate the potential of the method to be applied for daily 4D proton dose estimation.

[en] Purpose: To measure the acoustic signal generated by a pulsed proton spill from a hospital-based clinical cyclotron. Methods: An electronic function generator modulated the IBA C230 isochronous cyclotron to create a pulsed proton beam. The acoustic emissions generated by the proton beam were measured in water using a hydrophone. The acoustic measurements were repeated with increasing proton current and increasing distance between detector and beam. Results: The cyclotron generated proton spills with rise times of 18 μs and a maximum measured instantaneous proton current of 790 nA. Acoustic emissions generated by the proton energy deposition were measured to be on the order of mPa. The origin of the acoustic wave was identified as the proton beam based on the correlation between acoustic emission arrival time and distance between the hydrophone and proton beam. The acoustic frequency spectrum peaked at 10 kHz, and the acoustic pressure amplitude increased monotonically with increasing proton current. Conclusions: The authors report the first observation of acoustic emissions generated by a proton beam from a hospital-based clinical cyclotron. When modulated by an electronic function generator, the cyclotron is capable of creating proton spills with fast rise times (18 μs) and high instantaneous currents (790 nA). Measurements of the proton-generated acoustic emissions in a clinical setting may provide a method for in vivo proton range verification and patient monitoring

[en] Background and purpose: Adaptive strategies in radiotherapy (RT) require the knowledge of the total dose given to every organ of the body. Because of anatomical changes and setup errors non-rigid registration is necessary to map the different dose fractions to a common reference. This study evaluates practically if the accumulation of all of these registered dose fractions must take radiobiology into account in a classical clinical setting. Materials and methods: Ten patients with head and neck tumors treated by chemo-RT were used. Contrast-enhanced CT scans were acquired prior and during RT following delivery of mean doses of 14.2, 24.5, 35.0 and 44.9 Gy and the planned pre-treatment helical tomotherapy sinograms were applied on the per-treatment CTs to create a series of per-treatment dose distributions corresponding to each per-treatment CT image. In order to calculate the cumulative dose distribution, the per-treatment dose maps were non-rigidly deformed by using the deformation map computed by a non-rigid registration. The deformed dose maps were then summed in two ways: one while taking radiobiology into account and one without. These two strategies were compared using clinical surrogates in the target volumes (TV) and in surrounding organs at risk (OAR). Results: The differences between the strategies, while statistically significant (p < 0.05), are clinically irrelevant. In the OARs, the mean differences stay in the 0.01-0.07 Gy range for the total dose. In the targets, all mean differences stay in the 0.001-0.012 Gy range. However, some local high difference spots appear leading to punctual errors as high as 2.5 Gy. Conclusion: If using current radiotherapy practices and clinical recommendations based on dose surrogates computed globally on OARs and TVs, one does not need to take radiobiological effects into account while accumulating total dose as these lead to very small differences compared to a simple accumulation technique consisting of a linear sum of the dose fractions. However, care must be taken if other adaptive strategies, based on local rather than global information, are used.