Is it beneficial to use apertures in proton radiosurgery with a scanning beam? A dosimetric comparison in neurinoma and meningioma patients.

PURPOSE: To assess the dosimetric advantages of apertures in intracranial single fraction proton radiosurgery. MATERIALS AND METHODS: Six neuroma and 10 meningioma patients were investigated. For each patient, six plans were computed, with two spot spacing and three aperture settings (no apertures, 5 and 8 mm margin between aperture and clinical target volume [CTV]). All plans were optimized on the CTV with the same beam arrangement and the same single-field robust optimization (2 mm setup errors, 3.5% range uncertainties). Robustness analysis was performed with 0.5 and 1.0 mm systematic setup errors and 3.5% range uncertainties. CTV coverage in the perturbed scenarios and healthy brain tissue sparing in the surrounding of the CTV were compared. RESULTS: Meningiomas were larger and at a shallow depth than neuromas. In neuromas, spot spacing did not affect OAR doses or the robustness of CTV coverage and the apertures reduced brain dose without any significant impact on CTV robustness. In meningiomas, smaller spot spacing produced a reduction in brain V5Gy and improved robustness of CTV coverage; in addition, an 8 mm margin aperture reduced low and medium brain tissue doses without affecting robustness in the 0.5 mm perturbed scenario. A 5 mm margin aperture caused a reduction of plan robustness. CONCLUSION: The optimal use of apertures is a trade-off between sparing of low and medium dose to the healthy brain and robustness of target coverage, also depending on size and depth of the lesion.

Dosimetric comparison of five different techniques for craniospinal irradiation across 15 European centers: analysis on behalf of the SIOP-E-BTG (radiotherapy working group).

PURPOSE: Conventional techniques (3D-CRT) for craniospinal irradiation (CSI) are still widely used. Modern techniques (IMRT, VMAT, TomoTherapy®, proton pencil beam scanning [PBS]) are applied in a limited number of centers. For a 14-year-old patient, we aimed to compare dose distributions of five CSI techniques applied across Europe and generated according to the participating institute protocols, therefore representing daily practice. MATERIAL AND METHODS: A multicenter (n = 15) dosimetric analysis of five different techniques for CSI (3D-CRT, IMRT, VMAT, TomoTherapy®, PBS; 3 centers per technique) was performed using the same patient data, set of delineations and dose prescription (36.0/1.8 Gy). Different treatment plans were optimized based on the same planning target volume margin. All participating institutes returned their best treatment plan applicable in clinic. RESULTS: The modern radiotherapy techniques investigated resulted in superior conformity/homogeneity-indices (CI/HI), particularly in the spinal part of the target (CI: 3D-CRT:0.3 vs. modern:0.6; HI: 3D-CRT:0.2 vs. modern:0.1), and demonstrated a decreased dose to the thyroid, heart, esophagus and pancreas. Dose reductions of >10.0 Gy were observed with PBS compared to modern photon techniques for parotid glands, thyroid and pancreas. Following this technique, a wide range in dosimetry among centers using the same technique was observed (e.g., thyroid mean dose: VMAT: 5.6-24.6 Gy; PBS: 0.3-10.1 Gy). CONCLUSIONS: The investigated modern radiotherapy techniques demonstrate superior dosimetric results compared to 3D-CRT. The lowest mean dose for organs at risk is obtained with proton therapy. However, for a large number of organs ranges in mean doses were wide and overlapping between techniques making it difficult to recommend one radiotherapy technique over another.

Proton CT on biological phantoms for x-ray CT calibration in proton treatment planning.

Objective.To present and characterize a novel method for x-ray computed tomography (xCT) calibration in proton treatment planning, based on proton CT (pCT) measurements on biological phantoms.Approach.A pCT apparatus was used to perform direct measurements of 3D stopping power relative to water (SPR) maps on stabilized, biological phantoms. Two single-energy xCT calibration curves-i.e. tissue substitutes and stoichiometric-were compared to pCT data. Moreover, a new calibration method based on these data was proposed, and verified against intra- and inter-species variability, dependence on stabilization, beam-hardening conditions, and analysis procedures.Main results.Biological phantoms were verified to be stable in time, with a dependence on temperature conditions, especially in the fat region: (-2.5 0.5) HU °C-1. The pCT measurements were compared with standard xCT calibrations, revealing an average SPR discrepancy within ±1.60% for both fat and muscle regions. In the bone region the xCT calibrations overestimated the pCT-measured SPR of the phantom, with a maximum discrepancy of about +3%. As a result, a new cross-calibration curve was directly extracted from the pCT data. Overall, the SPR uncertainty margin associated with this curve was below 3%; fluctuations in the uncertainty values were observed across the HU range. Cross-calibration curves obtained with phantoms made of different animal species and anatomical parts were reproducible with SPR discrepancies within 3%. Moreover, the stabilization procedure did not affect the resulting curve within a 2.2% SPR deviation. Finally, the cross-calibration curve was affected by the beam-hardening conditions on xCTs, especially in the bone region, while dependencies below 2% resulted from the image registration procedure.Significance.Our results showed that pCT measurements on biological phantoms may provide an accurate method for the verification of current xCT calibrations and may represent a tool for the implementation of a new calibration method for proton treatment planning.

Patterns of practice of image guided particle therapy for cranio-spinal irradiation: A site specific multi-institutional survey of European Particle Therapy Network.

PURPOSE: To investigate the current practice patterns in image-guided particle therapy (IGPT) for cranio-spinal irradiation (CSI). METHODS: A multi-institutional survey was distributed to European particle therapy centres to analyse all aspects of IGPT. Based on the survey results, a Delphi consensus analysis was developed to define minimum requirements and optimal workflow for clinical practice. The centres participating in the institutional survey were invited to join the Delphi process. RESULTS: Eleven centres participated in the survey. Imaging for treatment planning was rather similar among the centres with Computed Tomography (CT) being the main modality. For positioning verification, 2D IGPT was more commonly used than 3D IGPT. Two centres performed routinely imaging for plan adaptation, by the rest ad hoc. Eight centres participated in the Delphi consensus analysis. The full consensus was reached on the use of CT imaging without contrast for treatment planning and the role of magnetic resonance imaging (MRI) in target and organs-at-risk delineation. There was an agreement on the necessity to perform patient position verification and correction before each isocentre. The most important outcome was the clear need for standardization and harmonization of the workflow. CONCLUSION: There were differences in CSI IGPT clinical practice among the European particle therapy centres. Moreover, the optimal workflow as identified by experts was not yet reached. There is a strong need for consensus guidelines. The state-of-the-art imaging technology and protocols need to be implemented into clinical practice to improve the quality of IGPT for CSI.

Clinical practice in European centres treating paediatric posterior fossa tumours with pencil beam scanning proton therapy.

BACKGROUND AND PURPOSE: As no guidelines for pencil beam scanning (PBS) proton therapy (PT) of paediatric posterior fossa (PF) tumours exist to date, this study investigated planning techniques across European PT centres, with special considerations for brainstem and spinal cord sparing. MATERIALS AND METHODS: A survey and a treatment planning comparison were initiated across nineteen European PBS-PT centres treating paediatric patients. The survey assessed all aspects of the treatment chain, including but not limited to delineations, dose constraints and treatment planning. Each centre planned two PF tumour cases for focal irradiation, according to their own clinical practice but based on common delineations. The prescription dose was 54 Gy(RBE) for Case 1 and 59.4 Gy(RBE) for Case 2. For both cases, planning strategies and relevant dose metrics were compared. RESULTS: Seventeen (89 %) centres answered the survey, and sixteen (80 %) participated in the treatment planning comparison. In the survey, thirteen (68 %) centres reported using the European Particle Therapy Network definition for brainstem delineation. In the treatment planning study, while most centres used three beam directions, their configurations varied widely across centres. Large variations were also seen in brainstem doses, with a brainstem near maximum dose (D2%) ranging from 52.7 Gy(RBE) to 55.7 Gy(RBE) (Case 1), and from 56.8 Gy(RBE) to 60.9 Gy(RBE) (Case 2). CONCLUSION: This study assessed the European PBS-PT planning of paediatric PF tumours. Agreement was achieved in e.g. delineation-practice, while wider variations were observed in planning approach and consequently dose to organs at risk. Collaboration between centres is still ongoing, striving towards common guidelines.

Does variable RBE affect toxicity risks for mediastinal lymphoma patients? NTCP-based evaluation after proton therapy treatment.

INTRODUCTION: Mediastinal lymphoma (ML) is a solid malignancy affecting young patients. Modern combined treatments allow obtaining good survival probability, together with a long life expectancy, and therefore with the need to minimize treatment-related toxicities. We quantified the expected toxicity risk for different organs and endpoints in ML patients treated with intensity-modulated proton therapy (IMPT) at our centre, accounting also for uncertainties related to variable RBE. METHODS: Treatment plans for ten ML patients were recalculated with a TOPAS-based Monte Carlo code, thus retrieving information on LET and allowing the estimation of variable RBE. Published NTCP models were adopted to calculate the toxicity risk for hypothyroidism, heart valve defects, coronary heart disease and lung fibrosis. NTCP was calculated assuming both constant (i.e. 1.1) and variable RBE. The uncertainty associated with individual radiosensitivity was estimated by random sampling α/ß values before RBE evaluation. RESULTS: Variable RBE had a minor impact on hypothyroidism risk for 7 patients, while it led to significant increase for the remaining three (+24% risk maximum increase). Lung fibrosis was slightly affected by variable RBE, with a maximum increase of â‰… 1%. This was similar for heart valve dysfunction, with the exception of one patient showing an about 10% risk increase, which could be explained by means of large heart volume and D1 increase. DISCUSSION: The use of NTCP models allows for identifying those patients associated with a higher toxicity risk. For those patients, it might be worth including variable RBE in plan evaluation.

The INFN proton computed tomography system for relative stopping power measurements: calibration and verification.

Objective. This paper describes the procedure to calibrate the three-dimensional (3D) proton stopping power relative to water (SPR) maps measured by the proton computed tomography (pCT) apparatus of the Istituto Nazionale di Fisica Nucleare (INFN, Italy). Measurements performed on water phantoms are used to validate the method. The calibration allowed for achieving measurement accuracy and reproducibility to levels below 1%.Approach. The INFN pCT system is made of a silicon tracker for proton trajectory determination followed by a YAG:Ce calorimeter for energy measurement. To perform the calibration, the apparatus has been exposed to protons of energies ranging from 83 to 210 MeV. Using the tracker, a position-dependent calibration has been implemented to keep the energy response uniform across the calorimeter. Moreover, correction algorithms have been developed to reconstruct the proton energy when this is shared in more than one crystal and to consider the energy loss in the non-uniform apparatus material. To verify the calibration and its reproducibility, water phantoms have been imaged with the pCT system during two data-taking sessions.Main results. The energy resolution of the pCT calorimeter resulted to beσEE≅0.9%at 196.5 MeV. The average values of the water SPR in fiducial volumes of the control phantoms have been calculated to be 0.995±0.002. The image non-uniformities were below 1%. No appreciable variation of the SPR and uniformity values between the two data-taking sessions could be identified.Significance. This work demonstrates the accuracy and reproducibility of the calibration of the INFN pCT system at a level below 1%. Moreover, the uniformity of the energy response keeps the image artifacts at a low level even in the presence of calorimeter segmentation and tracker material non-uniformities. The implemented calibration technique allows the INFN-pCT system to face applications where the precision of the SPR 3D maps is of paramount importance.

Automation of pencil beam scanning proton treatment planning for intracranial tumours.

PURPOSE: To evaluate the feasibility of comprehensive automation of an intra-cranial proton treatment planning. MATERIALS AND METHODS: Class solution (CS) beam configuration selection allows the user to identify predefined beam configuration based on target localization; automatic CS (aCS) will then explore all the possible CS beam geometries. Ten patients, already used for the evaluation of the automatic selection of the beam configuration, have been also employed to training an algorithm based on the computation of a benchmark dose exploit automatic general planning solution (GPS) optimization with a wish list approach for the planning optimization. An independent cohort of ten patients has been then used for the evaluation step between the clinical and the GPS plan in terms of dosimetric quality of plans and the time needed to generate a plan. RESULTS: The definition of a beam configuration requires on average 22 min (range 9-29 min). The average time for GPS plan generation is 18 min (range 7-26 min). Median dose differences (GPS-Manual) for each OAR constraints are: brainstem -1.60 Gy, left cochlea -1.22 Gy, right cochlea -1.42 Gy, left eye 0.55 Gy, right eye -2.33 Gy, optic chiasm -1.87 Gy, left optic nerve -4.45 Gy, right optic nerve -2.48 Gy and optic tract -0.31 Gy. Dosimetric CS and aCS plan evaluation shows a slightly worsening of the OARs values except for the optic tract and optic chiasm for both CS and aCS, where better results have been observed. CONCLUSION: This study has shown the feasibility and implementation of the automatic planning system for intracranial tumors. The method developed in this work is ready to be implemented in a clinical workflow.

Characterization of the INFN proton CT scanner for cross-calibration of x-ray CT.

Objective. The goal of this study was to assess the imaging performances of the pCT system developed in the framework of INFN-funded (Italian National Institute of Nuclear Physics) research projects. The spatial resolution, noise power spectrum (NPS) and RSP accuracy has been investigated, as a preliminary step to implement a new cross-calibration method for x-ray CT (xCT).Approach. The INFN pCT apparatus, made of four planes of silicon micro-strip detectors and a YAG:Ce scintillating calorimeter, reconstructs 3D RSP maps by a filtered-back projection algorithm. The imaging performances (i.e. spatial resolution, NPS and RSP accuracy) of the pCT system were assessed on a custom-made phantom, made of plastic materials with different densities ((0.66, 2.18) g cm-3). For comparison, the same phantom was acquired with a clinical xCT system.Main results. The spatial resolution analysis revealed the nonlinearity of the imaging system, showing different imaging responses in air or water phantom background. Applying the Hann filter in the pCT reconstruction, it was possible to investigate the imaging potential of the system. Matching the spatial resolution value of the xCT (0.54 lp mm-1) and acquiring both with the same dose level (11.6 mGy), the pCT appeared to be less noisy than xCT, with an RSP standard deviation of 0.0063. Concerning the RSP accuracy, the measured mean absolute percentage errors were (0.23+-0.09)% in air and (0.21+-0.07)% in water.Significance. The obtained performances confirm that the INFN pCT system provides a very accurate RSP estimation, appearing to be a feasible clinical tool for verification and correction of xCT calibration in proton treatment planning.

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.

Toxicity and Clinical Results after Proton Therapy for Pediatric Medulloblastoma: A Multi-Centric Retrospective Study.

Medulloblastoma is the most common malignant brain tumor in children. Even if current treatment dramatically improves the prognosis, survivors often develop long-term treatment-related sequelae. The current radiotherapy standard for medulloblastoma is craniospinal irradiation with a boost to the primary tumor site and to any metastatic sites. Proton therapy (PT) has similar efficacy compared to traditional photon-based radiotherapy but might achieve lower toxicity rates. We report on our multi-centric experience with 43 children with medulloblastoma (median age at diagnosis 8.7 years, IQR 6.6, M/F 23/20; 26 high-risk, 14 standard-risk, 3 ex-infant), who received active scanning PT between 2015 and 2021, with a focus on PT-related acute-subacute toxicity, as well as some preliminary data on late toxicity. Most acute toxicities were mild and manageable with supportive therapy. Hematological toxicity was limited, even among HR patients who underwent hematopoietic stem-cell transplantation before PT. Preliminary data on late sequelae were also encouraging, although a longer follow-up is needed.

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 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.

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.

Direct tumor in vivo dosimetry in highly-conformal radiotherapy: a feasibility study of implantable MOSFETs for hypofractionated extracranial treatments using the Cyberknife system.

PURPOSE: In highly-conformal radiotherapy, due to the complexity of both beam configurations and dose distributions, traditional in vivo dosimetry is unpractical or even impossible. The ideal dosimeter would be implanted inside the planning treatment volume so that it can directly measure the total delivered dose during each fraction with no additional uncertainty due to calculation models. The aim of this work is to verify if implantable metal oxide semiconductors field effect transistors (MOSFETs) can achieve a sufficient degree of dosimetric accuracy when used inside extracranial targets undergoing radiotherapy treatments using the Cyberknife system. METHODS: Based on the preliminary findings of this study, new prototypes for high dose fractionations were developed to reduce the time dependence for long treatment delivery times. These dosimeters were recently cleared and are marketed as DVS-HFT. Multiple measurements were performed using both Virtual Water and water phantoms to characterize implantable MOSFETs under the Cyberknife beams, and included the reference-dosimetry consistency, the dependence of the response on the collimator size, on the daily delivered dose, and the time irradiation modality. Finally a Cyberknife prostate treatment simulation using a body phantom was conducted, and both MOSFET and ionization readings were compared to Monte Carlo calculations. The feasibility analysis was conducted based on the ratios of the absorbed dose divided by the dose reading, named as "further calibration factor" (FCF). RESULTS: The average FCFs resulted to be 0.98 for the collimator dependence test, and about 1.00 for the reference-dosimetry test, the dose-dependence test, and the time-dependence test. The average FCF of the prostate treatment simulation test was 0.99. CONCLUSIONS: The obtained results are well within DVS specifications, that is, the factory calibration is still valid for such kind of treatments using the Cyberknife system, with no need of further calibration factors to be applied. The final accuracy of implantable MOSFETs when used for such kind of treatments was estimated to be within +/- 4%. Additional investigations using dose/fraction higher than 12 Gy, different beam configurations, and tracking systems could extend the present findings to other kind of treatments. MOSFET technology was proven to have high versatility in fast adaptation of existing detectors to new applications. It is plausible to expect a general feasibility of implantable MOSFET technology for in vivo dosimetry of the extracranial-targets treatments using the Cyberknife, provided each particular application will be validated by suitable both physical and clinical studies.

The Role of Plan Robustness Evaluation in Comparing Protons and Photons Plans - An Application on IMPT and IMRT Plans in Skull Base Chordomas.

PURPOSE: To analyze robustness of treatment plans optimized using different approaches in intensity modulated proton therapy (IMPT) and investigate the necessity of robust optimization and evaluation in intensity modulated radiotherapy (IMRT) plans for skull base chordomas. MATERIALS AND METHODS: Two photon plans, standard IMRT and robustly optimized IMRT (RB-IMRT), and two IMPT plans, robustly optimized multi field optimization (MFO) and hybrid-MFO (HB-MFO), were created in RayStation TPS for five patients previously treated using single field uniform optimization (SFO). Both set-up and range uncertainties were incorporated during robust optimization of IMPT plans whereas only set-up uncertainty was used in RB-IMRT. The dosimetric outcomes from the five planning techniques were compared for every patient using standard dose volume indices and integral dose (ID) estimated for target and organs at risk (OARs). Robustness of each treatment plan was assessed by introducing set-up uncertainties of ±3 mm along the three translational axes and, only in protons, an additional range uncertainty of ±3.5%. RESULTS: All the five nominal plans provided comparable and clinically acceptable target coverage. In comparison to nominal plans, worst case decrease in D95% of clinical target volume-high risk (CTV-HR) were 11.1%, 13.5%, and 13.6% for SFO, MFO, and HB-MFO plans respectively. The corresponding values were 13.7% for standard IMRT which improved to 11.5% for RB-IMRT. The worst case increased in high dose (D1%) to CTV-HR was highest in IMRT (2.1%) and lowest in SFO (0.7%) plans. Moreover, IMRT showed worst case increases in D1% for all neurological OARs and were lowest for SFO plans. The worst case D1% for brainstem, chiasm, spinal cord, optic nerves, and temporal lobes were increased by 29%, 41%, 30%, 41% and 14% for IMRT and 18%, 21%, 21%, 24%, and 7% for SFO plans, respectively. In comparison to IMRT, RB-IMRT improved D1% of all neurological OARs ranging from 5% to 14% in worst case scenarios. CONCLUSION: Based on the five cases presented in the current study, all proton planning techniques (SFO, MFO and HB-MFO) were robust both for target coverage and OARs sparing. Standard IMRT plans were less robust than proton plans in regards to high doses to neurological OARs. However, robust optimization applied to IMRT resulted in improved robustness in both target coverage and high doses to OARs. Robustness evaluation may be considered as a part of plan evaluation procedure even in IMRT.

An avoidance method to minimize dose perturbation effects in proton pencil beam scanning treatment of patients with small high-Z implants.

To implement a multi-field-optimization (MFO) technique for treating patients with high-Z implants in pencil beam scanning proton-therapy and generate treatment plans that avoids small implants. Two main issues were addressed: (i) the assessment of the optimal CT acquisition and segmentation technique to define the dimension of the implant and (ii) the distance of pencil beams from the implant (avoidance margin) to assure that it does not affect dose distribution. Different CT reconstruction protocols (by O-MAR or standard reconstruction and by 12 bit or 16 bit dynamic range) followed by thresholding segmentation were tested on a phantom with lead spheres of different sizes. The proper avoidance margin was assessed on a dedicated phantoms of different materials (copper/tantalum and lead), shape (square slabs and spheres) and detectors (two-dimensional array chamber and radio-chromic films). The method was then demonstrated on a head-and-neck carcinoma patient, who underwent carotid artery embolization with a platinum coil close to the target. Regardless the application of O-MAR reconstruction, the CT protocol with a full 16 bit dynamic range allowed better estimation of the sphere volumes, with maximal error around -5% in the greater sphere only. Except the configuration with a shallow target (which required a pre-absorber), particularly with a retracted snout, an avoidance margin of around 0.9-1.3 cm allowed to keep the difference between planned and measured dose below 5-10%. The patient plan analysis showed adequate plan quality and confirmed effective implant avoidance. Potential target under-dosage can be produced by patient misalignment, which could be minimized by daily alignment on the implant, identifiable on orthogonal kilovolt images. By implant avoidance MFO it was possible to minimize potential dose perturbation effects produced by small high-Z implants. An advantage of such approach lies in its potential applicability for any type of implant, regardless the precise knowledge of its composition.

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.