Consensus guide on CT-based prediction of stopping-power ratio using a Hounsfield look-up table for proton therapy.

BACKGROUND AND PURPOSE: Studies have shown large variations in stopping-power ratio (SPR) prediction from computed tomography (CT) across European proton centres. To standardise this process, a step-by-step guide on specifying a Hounsfield look-up table (HLUT) is presented here. MATERIALS AND METHODS: The HLUT specification process is divided into six steps: Phantom setup, CT acquisition, CT number extraction, SPR determination, HLUT specification, and HLUT validation. Appropriate CT phantoms have a head- and body-sized part, with tissue-equivalent inserts in regard to X-ray and proton interactions. CT numbers are extracted from a region-of-interest covering the inner 70% of each insert in-plane and several axial CT slices in scan direction. For optimal HLUT specification, the SPR of phantom inserts is measured in a proton beam and the SPR of tabulated human tissues is computed stoichiometrically at 100 MeV. Including both phantom inserts and tabulated human tissues increases HLUT stability. Piecewise linear regressions are performed between CT numbers and SPRs for four tissue groups (lung, adipose, soft tissue, and bone) and then connected with straight lines. Finally, a thorough but simple validation is performed. RESULTS: The best practices and individual challenges are explained comprehensively for each step. A well-defined strategy for specifying the connection points between the individual line segments of the HLUT is presented. The guide was tested exemplarily on three CT scanners from different vendors, proving its feasibility. CONCLUSION: The presented step-by-step guide for CT-based HLUT specification with recommendations and examples can contribute to reduce inter-centre variations in SPR prediction.

Proton therapy in the treatment of hepatocellular carcinoma.

Liver cancer represents one of the most common causes of death from cancer worldwide. Hepatocellular carcinoma (HCC) accounts for 90% of all primary liver cancers. Among local therapies, evidence regarding the use of radiation therapy is growing. Proton therapy currently represents the most advanced radiation therapy technique with unique physical properties which fit well with liver irradiation. Here, in this review, we aim to 1) illustrate the rationale for the use of proton therapy (PT) in the treatment of HCC, 2) discuss the technical challenges of advanced PT in this disease, 3) review the major clinical studies regarding the use of PT for HCC, and 4) analyze the potential developments and future directions of PT in this setting.

Clinical necessity of multi-image based (4DMIB) optimization for targets affected by respiratory motion and treated with scanned particle therapy - A comprehensive review.

4D multi-image-based (4DMIB) optimization is a form of robust optimization where different uncertainty scenarios, due to anatomy variations, are considered via multiple image sets (e.g., 4DCT). In this review, we focused on providing an overview of different 4DMIB optimization implementations, introduced various frameworks to evaluate the robustness of scanned particle therapy affected by breathing motion and summarized the existing evidence on the necessity of using 4DMIB optimization clinically. Expected potential benefits of 4DMIB optimization include more robust and/or interplay-effect-resistant doses for the target volume and organs-at-risk for indications affected by anatomical variations (e.g., breathing, peristalsis, etc.). Although considerable literature is available on the research and technical aspects of 4DMIB, clinical studies are rare and often contain methodological limitations, such as, limited patient number, motion amplitude, motion and delivery time structure considerations, number of repeat CTs, etc. Therefore, the data are not conclusive. In addition, multiple studies have found that robust 3D optimized plans result in dose distributions within the set clinical tolerances and, therefore, are suitable for a treatment of moving targets with scanned particle therapy. We, therefore, consider the clinical necessity of 4DMIB optimization, when treating moving targets with scanned particle therapy, as still to be demonstrated.

Technical challenges in the treatment of mediastinal lymphomas by proton pencil beam scanning and deep inspiration breath-hold.

PURPOSE: To comprehensively describe the treatment of mediastinal lymphoma by pencil beam scanning (PBS) proton therapy. METHODS: Fourteen patients underwent PBS proton treatment in a supine position in deep inspiration breath-hold (DIBH). Three DIBH computed tomography (CT) scans were acquired for each patient to delineate the Internal Target Volume (ITV). Intensity-modulated proton therapy (IMPT) was planned by min-max robust optimization on the ITV, with a 6 mm setup and 3.5% range uncertainties. Robustness analysis was performed and dose coverage was visually inspected on the corresponding voxel-wise minimum map. Layer repainting was set equal to 5 to compensate for cardiac motion. Intra-fraction reproducibility during treatment was assessed by repeated daily DIBH X-ray imaging. Finally, an additional CT was acquired at half treatment to estimate the impact of inter-fraction dosimetric reproducibility. RESULTS: IMPT guaranteed robust mediastinal target coverage and organs-at-risk sparing. However, visual voxel-wise robustness evaluation showed that in five patients a second optimization with focused objectives in the cost-function was necessary to achieve a robust coverage of the target regions at the interface between lungs and soft tissue. In six patients, repainting was not used due to excessive treatment time length and poor patient compliance. Intra-fraction average reproducibility was within 1 mm/1degree. On repeated CT scans, inter-fraction setup errors and/or anatomical changes showed minimal dosimetric differences in CTV coverage. CONCLUSION: IMPT in DIBH is effective and reproducible to treat mediastinal lymphomas. Caution is recommended to guarantee robust dose delivery to high-risk regions at the interface between lungs and soft tissue.

Clinical validation of a GPU-based Monte Carlo dose engine of a commercial treatment planning system for pencil beam scanning proton therapy.

PURPOSE: To perform the validation of the GPU-based (Graphical Processing Unit based) proton Monte Carlo (MC) dose engine implemented in a commercial TPS (RayStation 10B) and to report final dose calculation times for clinical cases. MATERIALS AND METHODS: 440 patients treated at the Proton Therapy Center of Trento, Italy, between 2018 and 2019 were selected for this study. 636 approved plans with 3361 beams computed with the clinically implemented CPU-MC dose engine (version 4.2 and 4.5), were used for the validation of the new algorithm. For each beam, the dose was recalculated using the new GPU-MC dose engine with the initial CPU computation settings and compared to the original CPU-MC dose. Beam dose difference distributions were studied to ensure that the two dose distributions were equal within the expected fluctuations of the MC statistical uncertainty (s) of each computation. Plan dose distributions were compared with respect to the dosimetric indices D98, D50 and D1 of all ROIs defined as targets. A complete assessment of the computation time as a function of s and dose grid voxel size was done. RESULTS: The median over all mean beam dose differences between CPU- and GPU-MC was -0.01% and the median of the corresponding standard deviations was close to (√2s) both for simulations with an s of 0.5% and 1.0% per beam. This shows that the two dose distributions can be considered equal. All the DVH indices showed an average difference below 0.04%. About half of the plans were computed with 1.0% statistical uncertainty on a 2 mm dose calculation grid, for which the median computation time was 5.2 s. The median computational speed for all plans in the study was 8.4 million protons/second. CONCLUSION: A validation of a clinical MC algorithm running on GPU was performed on a large pool of patients treated with pencil beam scanning proton therapy. We demonstrated that the differences with the previous CPU-based MC were only due to the intrinsic statistical fluctuations of the MC method, which translated to insignificant differences on plan dose level. The significant increase in dose calculation speed is expected to facilitate new clinical workflows.

Experimental assessment of inter-centre variation in stopping-power and range prediction in particle therapy.

PURPOSE: Experimental assessment of inter-centre variation and absolute accuracy of stopping-power-ratio (SPR) prediction within 17 particle therapy centres of the European Particle Therapy Network. MATERIAL AND METHODS: A head and body phantom with seventeen tissue-equivalent materials were scanned consecutively at the participating centres using their individual clinical CT scan protocol and translated into SPR with their in-house CT-number-to-SPR conversion. Inter-centre variation and absolute accuracy in SPR prediction were quantified for three tissue groups: lung, soft tissues and bones. The integral effect on range prediction for typical clinical beams traversing different tissues was determined for representative beam paths for the treatment of primary brain tumours as well as lung and prostate cancer. RESULTS: An inter-centre variation in SPR prediction (2σ) of 8.7%, 6.3% and 1.5% relative to water was determined for bone, lung and soft-tissue surrogates in the head setup, respectively. Slightly smaller variations were observed in the body phantom (6.2%, 3.1%, 1.3%). This translated into inter-centre variation of integral range prediction (2σ) of 2.9%, 2.6% and 1.3% for typical beam paths of prostate-, lung- and primary brain-tumour treatments, respectively. The absolute error in range exceeded 2% in every fourth participating centre. The consideration of beam hardening and the execution of an independent HLUT validation had a positive effect, on average. CONCLUSION: The large inter-centre variations in SPR and range prediction justify the currently clinically used margins accounting for range uncertainty, which are of the same magnitude as the inter-centre variation. This study underlines the necessity of higher standardisation in CT-number-to-SPR conversion.

Technical Note: CT calibration for proton treatment planning by cross-calibration with proton CT data.

PURPOSE: This study explores the possibility of a new method for x-ray computed tomography (CT) calibration by means of cross-calibration with proton CT (pCT) data. The proposed method aims at a more accurate conversion of CT Hounsfield Units (HU) into proton stopping power ratio (SPR) relative to water to be used in proton-therapy treatment planning. METHODS: X-ray CT scan was acquired on a synthetic anthropomorphic phantom, composed of different tissue equivalent materials (TEMs). A pCT apparatus was instead adopted to obtain a reference three-dimensional distribution of the phantom's SPR values. After rigid registration, the x-ray CT was artificially blurred to the same resolution of pCT. Then a scatter plot showing voxel-by-voxel SPR values as a function of HU was employed to link the two measurements and thus obtaining a cross-calibrated x-ray CT calibration curve. The cross-calibration was tested at treatment planning system and then compared with a conventional calibration based on exactly the same TEMs constituting the anthropomorphic phantom. RESULTS: Cross-calibration provided an accurate SPR mapping, better than by conventional TEMs calibration. The dose distribution of single beams optimized on the reference SPR map was recomputed on cross-calibrated CT, showing, with respect to conventional calibration, minor deviation at the dose fall-off (lower than 1%). CONCLUSIONS: The presented data demonstrated that, by means of reference pCT data, a heterogeneous phantom can be used for CT calibration, paving the way to the use of biological samples, with their accurate description of patients' tissues. This overcomes the limitations of conventional CT calibration requiring homogenous samples, only available by synthetic TEMs, which fail in accurately mimicking the properties of biological tissues. Once a heterogeneous biological sample is provided with its corresponding reference SPR maps, a cross-calibration procedure could be adopted by other PT centers, even when not equipped with a pCT system.

Clinical implementation of pencil beam scanning proton therapy for liver cancer with forced deep expiration breath hold.

PURPOSE: To present our technique for liver cancer treatments with proton therapy in pencil beam scanning mode and to evaluate the impact of uncertainties on plan quality. MATERIALS AND METHODS: Seventeen patients affected by liver cancer were included in this study. Patients were imaged and treated in forced breath-hold using the Active Breathing Coordinator system and monitored with an optical tracking system. Three simulation CTs were acquired to estimate the anatomical variability between breath-holds and generate an internal target volume (ITV). The treatment plans were optimized with a Single Field Optimization technique aimed at minimizing the use of range shifter. Plan robustness was tested simulating systematic range and setup uncertainties, as well as the interplay effect between breath-holds. The appropriateness of margin was further verified based on the actual positioning data acquired during treatment. RESULTS: The dose distributions of the nominal plans achieved a satisfactory target coverage in 11 out of 17 patients, while in the remaining 6 D95 to the PTV was affected by the constraint on mean liver dose. The constraints for all other organs at risk were always within tolerances. The interplay effect had a limited impact on the dose distributions: the worst case scenario showed a D95 reduction in the ITV < 3.9 GyRBE and no OAR with D1 > 105% of the prescription dose. The robustness analysis showed that for 13 out of 17 patients the ITV coverage in terms of D95 was better than D95 of the PTV in the nominal plan. For the remaining 4 patients, the maximum difference between ITV D95 and PTV D95 was ≤0.7% even for the largest simulated setup error and it was deemed clinically acceptable. Hot spots in the OARs were always lower than 105% of the prescription dose. Positioning images confirmed that the breath hold technique and the PTV margin were adequate to compensate for inter- and intra-breath-hold variations in liver position. CONCLUSION: We designed and clinically applied a technique for the treatment of liver cancer with proton pencil beam scanning in forced deep expiration breath-hold. The initial data on plan robustness and patient positioning suggest that the choices in terms of planning technique and treatment margins are able to reach the desired balance between target coverage and organ at risk sparing.

Clinical results of active scanning proton therapy for primary liver tumors.

BACKGROUND: Evidence for the efficacy of radiation therapy for primary liver cancer is growing. In this context, proton therapy (PT) can potentially improve the therapeutic ratio, as demonstrated by recent clinical studies. Here we report the first European clinical experience on the use of PT for primary liver cancer. METHODS: All patients treated for primary liver cancer in our center entered the analysis. Patients were simulated during deep expiration breath-hold. A 15-fraction treatment schedule was adopted using active scanning PT. Clinical outcome and toxicity were retrospectively analyzed. RESULTS: Between January 2018 and December 2019, 18 patients were treated. Fourteen patients had hepatocellular carcinoma (HCC), three patients had intrahepatic cholangiocarcinoma (ICC), and one patient had synchronous ICC-HCC. The Child-Pugh score was A5 in the majority of patients with HCC (71.4%). Median prescription dose was 58.05 Gy (range, 50.31-67.5). Median follow-up was 10 months (range, 1-19). The majority of deaths occurred from liver tumor progression. One-year overall survival (OS) was 63%. A significant correlation between worse OS and patient performance status, vascular invasion, and tumor stage was recorded. One-year local control was 90%. Toxicity was low, with a decrease in Child-Pugh score ⩾2 points detected in one patient. No cases of classic radiation-induced liver disease occurred. CONCLUSIONS: Our initial results of active scanning PT for primary liver cancer demonstrated the feasibility, safety, and effectiveness of this advanced technique in this setting. The potential of the combination of PT with other locoregional therapies is under evaluation.

Proton pencil beam scanning reduces secondary cancer risk in breast cancer patients with internal mammary chain involvement compared to photon radiotherapy.

PURPOSE: Proton pencil beam scanning (PBS) represents an interesting option for the treatment of breast cancer (BC) patients with nodal involvement. Here we compare tangential 3D-CRT and VMAT to PBS proton therapy (PT) in terms of secondary cancer risk (SCR) for the lungs and for contralateral breast. METHODS: Five BC patients including supraclavicular (SVC) nodes in the target (Group 1) and five including SVC plus internal-mammary-nodes (IMNs, Group 2) were considered. The Group 1 patients were planned by PT versus tangential 3D-CRT in free-breathing (FB). The Group 2 patients were planned by PT versus VMAT considering both FB and deep-inspiration breath hold (DIBH) irradiation. The prescription dose to the target volume was 50 Gy (2 Gy/fraction). A constant RBE = 1.1 was assumed for PT. The SCR was evaluated with the excess absolute risk (EAR) formalism, considering also the age dependence. A cumulative EAR was finally computed. RESULTS: According to the linear, linear-exponential and linear-plateau dose response model, the cumulative EAR for Group 1 patients after PT was equal to 45 ± 10, 17 ± 3 and 15 ± 3, respectively. The corresponding relative increase for tangential 3D-CRT was equal to a factor 2.1 ± 0.5, 2.1 ± 0.4 and 2.3 ± 0.4. Group 2 patients showed a cumulative EAR after PT in FB equal to 65 ± 3, 21 ± 1 and 20 ± 1, according to the different models; the relative risk obtained with VMAT increased by a factor 3.5 ± 0.2, 5.2 ± 0.3 and 5.1 ± 0.3. Similar values emerge from DIBH plans. Contrary to photon radiotherapy, PT appears to be not sensitive to the age dependence due to the very low delivered dose. CONCLUSIONS: PBS PT is associated to significant SCR reduction in BC patients compared to photon radiotherapy. The benefits are maximized for young patients with both SVC and IMNs involvement. When combined with the improved sparing of the heart, this might contribute to the establishment of effective patient-selection criteria for proton BC treatments.

Proton or photon radiosurgery for cardiac ablation of ventricular tachycardia? Breath and ECG gated robust optimization.

PURPOSE: Ventricular tachycardia (VT) is a life-threatening heart disorder. The aim of this preliminary study is to assess the feasibility of stereotactic body radiation therapy (SBRT) photon and proton therapy (PT) plans for the treatment of VT, adopting robust optimization technique for both irradiation techniques. METHODS: ECG gated CT images (in breath hold) were acquired for one patient. Conventional planning target volume (PTV) and robust optimized plans (25GyE in single fraction) were simulated for both photon (IMRT, 5 and 9 beams) and proton (SFO, 2 beams) plans. Robust optimized plans were obtained both for protons and photons considering in the optimization setup errors (5 mm in the three orthogonal directions), range (±3.5%) and the clinical target volume (CTV) motion due to heartbeat and breath-hold variability. RESULTS: The photon robust optimization method, compared to PTV-based plans, showed a reduction in the average dose to the heart by about 25%; robust optimization allowed also reducing the mean dose to the left lung from 3.4. to 2.8 Gy for 9-beams configuration and from 4.1 to 2.9 Gy for 5-beams configuration. Robust optimization with protons, allowed further reducing the OAR doses: average dose to the heart and to the left lung decreased from 7.3 Gy to 5.2 GyE and from 2.9 Gy to 2.2 GyE, respectively. CONCLUSIONS: Our study demonstrates the importance of the optimization technique adopted in the treatment planning system for VT treatment. It has been shown that robust optimization can significantly reduce the dose to healthy cardiac tissues and that PT further increases this gain.

Accurate proton treatment planning for pencil beam crossing titanium fixation implants.

PURPOSE: To present a planning strategy for proton pencil-beam scanning when titanium implants need to be crossed by the beam. METHODS: We addressed three issues: the implementation of a CT calibration curve to assign to titanium the correct stopping power; the effect of artefacts on CT images and their reduction by a dedicated algorithm; the differences in dose computation depending on the dose engine, pencil-beam vs Monte-Carlo algorithms. We performed measurement tests on a simple cylinder phantom and on a real implant. These phantoms were irradiated with three geometries (single spots, uniform mono-energetic layer and uniform box), measuring the exit dose either by radio-chromic film or multi-layer ionization chamber. The procedure was then applied on two patients treated for chordoma. RESULTS: We had to set in the calibration curve a mass density equal to 4.37 g/cm3 to saturated Hounsfield Units, in order to have the correct stopping power assigned to titanium in TPS. CT artefact reduction algorithm allowed a better reconstruction of the shape and size of the implant. Monte-Carlo resulted accurate in computing the dose distribution whereas the pencil-beam algorithm failed due to sharp density interfaces between titanium and the surrounding material. Finally, the treatment plans obtained on two patients showed the impact of the dose engine algorithm, with 10-20% differences between pencil-beam and Monte-Carlo in small regions distally to the titanium screws. CONCLUSION: The described combination of CT calibration, artefacts reduction and Monte-Carlo computation provides a reliable methodology to compute dose in patients with titanium implants.

Clinical implementation in proton therapy of multi-field optimization by a hybrid method combining conventional PTV with robust optimization.

To implement a robust multi-field optimization (MFO) technique compatible with the application of a Monte Carlo (MC) algorithm and to evaluate its robustness. Nine patients (three brain, five head-and-neck, one spine) underwent proton treatment generated by a novel robust MFO technique. A hybrid (hMFO) approach was implemented, planning dose coverage on isotropic PTV compensating for setup errors, whereas range calibration uncertainties are incorporated into PTV robust optimization process. hMFO was compared with single-field optimization (SFO) and full robust multi-field optimization (fMFO), both on the nominal plan and the worst-case scenarios assessed by robustness analysis. The SFO and the fMFO plans were normalized to hMFO on CTV to obtain iso-D95 coverage, and then the organs at risk (OARs) doses were compared. On the same OARs, in the normalized nominal plans the potential impact of variable relative biological effectiveness (RBE) was investigated. hMFO reduces the number of scenarios computed for robust optimization (from twenty-one in fMFO to three), making it practicable with the application of a MC algorithm. After normalizing on D95 CTV coverage, nominal hMFO plans were superior compared to SFO in terms of OARs sparing (p  < 0.01), without significant differences compared to fMFO. The improvement in OAR sparing with hMFO with respect to SFO was preserved in worst-case scenarios (p  < 0.01), confirming that hMFO is as robust as SFO to physical uncertainties, with no significant differences when compared to the worst case scenarios obtained by fMFO. The dose increase on OARs due to variable RBE was comparable to the increase due to physical uncertainties (i.e. 4-5 Gy(RBE)), but without significant differences between these techniques. hMFO allows improving plan quality with respect to SFO, with no significant differences with fMFO and without affecting robustness to setup, range and RBE uncertainties, making clinically feasible the application of MC-based robust optimization.

An advanced junction concept in pediatric craniospinal irradiation by proton pencil beam scanning.

PURPOSE: To present an advanced junction concept in craniospinal irradiation (CSI) by proton pencil beam scanning (PBS). MATERIALS AND METHODS: In PBS CSI, whole brain irradiation (WBI) is commonly delivered by opposed lateral-beams, whereas spine irradiation is delivered by posterior entrances. Since lateral-beams would cross a large portion of the patient at the shoulder level, the junction between WBI and spine irradiation cannot extend below that level, thus the size of the lateral-beams needs to be limited and the number of required isocenters can increase. To overcome such limitation, a pseudo-junction was introduced below the posterior fossa, to turn in this region the WBI beam arrangement to a single posterior beam pointed at the same isocenter, that was matched to the posterior spinal beam more caudally, below shoulder level, in the true-junction. After assessing robustness of the technique to range and setup uncertainties, twenty-three treated patients were reviewed to estimate the percentage that might benefit of being treated by two instead of three isocenters. RESULTS: Target coverage at the junction levels resulted robust, with D95% > 95% on pseudo-junction and D95% > 90% on the true-junction. By the advanced junction concept, 91% of patients might by treated with only two isocenters, whereas, by the conventional method, 83% of patients required three isocenters. CONCLUSION: With the presented junction concept the number of isocenters can be reduced, with a consequent relevant reduction of treatment time, which is particularly valuable in the management of pediatric patients under anesthesia.

A pre-absorber optimization technique for pencil beam scanning proton therapy treatments.

PURPOSE: To implement a new proton therapy planning method for the treatment of shallow lesions with PBS and to compare it to the standard method. METHODS AND MATERIALS: In order to treat shallow lesions, a pre-absorber, usually called range-shifter (RS), is needed: it is used to degrade the beam energy and treat tumors shallower than the minimum range available. Its use is associated to dose calculation uncertainties and plan quality degradation which should be minimized. We studied five tumor localizations requiring RS and created three plans for each case: a) standard method with the RS close to the patient surface, b) with the RS used only for the shallow part of the tumor (when strictly needed) and completely retracted and c) as the b) approach but with the RS close to the patient. We called these two approaches 'Range Shifter Optimization' (RSO) techniques. We compared those plans in terms of dose distribution quality, delivery time and patient-specific-QA results. RESULTS: In most cases a good dose reduction to OARs with no significant loss in terms of target coverage was obtained when the RSO techniques were used. Patient-specific-QA gave very good results in terms of γ-Passing-Rate (PR) (3%, 3 mm) for both RSO techniques (mean 98.09%), while the standard had some very low PR (minimum 81.09%). The delivery time increased (5.0 min on average per treatment) but was still acceptable in terms of patient compliance. CONCLUSION: We developed a new planning technique for shallow lesions and we demonstrated its superiority in terms of both plan quality and patient-specific-QA results with respect to the standard method. This technique is routinely used to treat patients in our center.

FLUKA particle therapy tool for Monte Carlo independent calculation of scanned proton and carbon ion beam therapy.

While Monte Carlo (MC) codes are considered as the gold standard for dosimetric calculations, the availability of user friendly MC codes suited for particle therapy is limited. Based on the FLUKA MC code and its graphical user interface (GUI) Flair, we developed an easy-to-use tool which enables simple and reliable simulations for particle therapy. In this paper we provide an overview of functionalities of the tool and with the presented clinical, proton and carbon ion therapy examples we demonstrate its reliability and the usability in the clinical environment and show its flexibility for research purposes. The first, easy-to-use FLUKA MC platform for particle therapy with GUI functionalities allows a user with a minimal effort and reduced knowledge about MC details to apply MC at their facility and is expected to enhance the popularity of the MC for both research and clinical quality assurance and commissioning purposes.

Implementation of proton therapy treatments with pencil beam scanning of targets with limited intrafraction motion.

PURPOSE: To report on the implementation, validation and results of the first two proton therapy PBS treatments of limited amplitudes moving targets performed at our center. METHODS AND MATERIALS: A real time optical tracking system was used to monitor the patient surface during the CT scan and treatment. This system is also able to trigger the beam during the treatment. A 4DCT (10 phases) and a Free-Breathing CT (FBCT) were used for the planning. The physician used the 4DCT for ITV delineation, while planning was performed on the FBCT. The approved plan was evaluated in two ways:The largest breathing amplitude recorded during 4DCT scan was used as gating safety threshold during treatment delivery. This planning and treatment workflow was then applied for two patients affected by thoracic thymoma. RESULTS: The dosimetric evaluation of the plan showed no interplay effect. The second patient showed an overdosage to the coronary and Left Anterior Descending area in the worst case scenario but it was below the constraints. Duty Cycle together with number of beam interruptions gave information about the patient compliance to the treatment: the first patient breath is stable and within thresholds, whilst the second patient had more variations, causing multiple beam interruptions. CONCLUSION: We defined and used for two patients a protocol for the treatment of small amplitude moving targets. The planning and delivery of the treatments gave very good results in terms of coverage, OARs sparing, 4D dose evaluation of the plan and interplay effect assessment.

Improvements in pencil beam scanning proton therapy dose calculation accuracy in brain tumor cases with a commercial Monte Carlo algorithm.

A commercial Monte Carlo (MC) algorithm (RayStation version 6.0.024) for the treatment of brain tumors with pencil beam scanning (PBS) proton therapy is validated and compared via measurements and analytical calculations in clinically realistic scenarios. For the measurements a 2D ion chamber array detector (MatriXX PT) was placed underneath the following targets: (1) an anthropomorphic head phantom (with two different thicknesses) and (2) a biological sample (i.e. half a lamb's head). In addition, we compared the MC dose engine versus the RayStation pencil beam (PB) algorithm clinically implemented so far, in critical conditions such as superficial targets (i.e. in need of a range shifter (RS)), different air gaps, and gantry angles to simulate both orthogonal and tangential beam arrangements. For every plan the PB and MC dose calculations were compared to measurements using a gamma analysis metrics (3%, 3 mm). For the head phantom the gamma passing rate (GPR) was always >96% and on average >99% for the MC algorithm; the PB algorithm had a GPR of ⩽90% for all the delivery configurations with a single slab (apart 95% GPR from the gantry of 0° and small air gap) and in the case of two slabs of the head phantom the GPR was >95% only in the case of small air gaps for all three (0°, 45°, and 70°) simulated beam gantry angles. Overall the PB algorithm tends to overestimate the dose to the target (up to 25%) and underestimate the dose to the organ at risk (up to 30%). We found similar results (but a bit worse for the PB algorithm) for the two targets of the lamb's head where only two beam gantry angles were simulated. Our results suggest that in PBS proton therapy a range shifter (RS) needs to be used with caution when planning a treatment with an analytical algorithm due to potentially great discrepancies between the planned dose and the dose delivered to the patient, including in the case of brain tumors where this issue could be underestimated. Our results also suggest that a MC evaluation of the dose has to be performed every time the RS is used and, mostly, when it is used with large air gaps and beam directions tangential to the patient surface.

A fast and reliable method for daily quality assurance in spot scanning proton therapy with a compact and inexpensive phantom.

In a radiotherapy center, daily quality assurance (QA) measurements are performed to ensure that the equipment can be safely used for patient treatment on that day. In a pencil beam scanning (PBS) proton therapy center, spot positioning, spot size, range, and dose output are usually verified every day before treatments. We designed, built, and tested a new, reliable, sensitive, and inexpensive phantom, coupled with an array of ionization chambers, for daily QA that reduces the execution times while preserving the reliability of the test. The phantom is provided with 2 pairs of wedges to sample the Bragg peak at different depths to have a transposition on the transverse plane of the depth dose. Three "boxes" are used to check spot positioning and delivered dose. The box thickness helps spread the single spot and to fit a Gaussian profile on a low resolution detector. We tested whether our new QA solution could detect errors larger than our action levels: 1 mm in spot positioning, 2 mm in range, and 10% in spot size. Execution time was also investigated. Our method is able to correctly detect 98% of spots that are actually in tolerance for spot positioning and 99% of spots out of 1 mm tolerance. All range variations greater than the threshold (2 mm) were correctly detected. The analysis performed over 1 month showed a very good repeatability of spot characteristics. The time taken to perform the daily quality assurance is 20 minutes, a half of the execution time of the former multidevice procedure. This "in-house build" phantom substitutes 2 very expensive detectors (a multilayer ionization chamber [MLIC] and a strip chamber, reducing by 5 times the cost of the equipment. We designed, built, and validated a phantom that allows for accurate, sensitive, fast, and inexpensive daily QA procedures in proton therapy with PBS.