Proton Therapy Treatment Research Articles

3D in vivo dose verification in prostate proton therapy with deep learning-based proton-acoustic imaging

Dose delivery uncertainty is a major concern in proton therapy, adversely affecting the treatment precision and outcome. Recently, a promising technique, proton-acoustic (PA) imaging, has been developed to provide real-time in vivo 3D dose verification. However, its dosimetry accuracy is limited due to the limited-angle view of the ultrasound transducer. In this study, we developed a deep learning-based method to address the limited-view issue in the PA reconstruction. A deep cascaded convolutional neural network (DC-CNN) was proposed to reconstruct 3D high-quality radiation-induced pressures using PA signals detected by a matrix array, and then derive precise 3D dosimetry from pressures for dose verification in proton therapy. To validate its performance, we collected 81 prostate cancer patients’ proton therapy treatment plans. Dose was calculated using the commercial software RayStation and was normalized to the maximum dose. The PA simulation was performed using the open-source k-wave package. A matrix ultrasound array with 64 × 64 sensors and 500 kHz central frequency was simulated near the perineum to acquire radiofrequency (RF) signals during dose delivery. For realistic acoustic simulations, tissue heterogeneity and attenuation were considered, and Gaussian white noise was added to the acquired RF signals. The proposed DC-CNN was trained on 204 samples from 69 patients and tested on 26 samples from 12 other patients. Predicted 3D pressures and dose maps were compared against the ground truth qualitatively and quantitatively using root-mean-squared-error (RMSE), gamma-index (GI), and dice coefficient of isodose lines. Results demonstrated that the proposed method considerably improved the limited-view PA image quality, reconstructing pressures with clear and accurate structures and deriving doses with a high agreement with the ground truth. Quantitatively, the pressure accuracy achieved an RMSE of 0.061, and the dose accuracy achieved an RMSE of 0.044, GI (3%/3 mm) of 93.71%, and 90%-isodose line dice of 0.922. The proposed method demonstrates the feasibility of achieving high-quality quantitative 3D dosimetry in PA imaging using a matrix array, which potentially enables the online 3D dose verification for prostate proton therapy.

Robustness Evaluation for Proton Therapy with a Spirometry Based Deep Inhalation Breath Hold System

<h3>Purpose/Objective(s)</h3> Deep inhalation breath hold (DIBH) treatment allows for greater sparing of healthy tissue by minimizing target motion due to respiration. However, the breath hold level achieved during simulation and throughout treatment is not perfectly reproducible. DIBH techniques such as spirometry define an allowed variation in the nominal breath hold level to facilitate treatment. This variation represents an uncertainty which must be incorporated into the robust evaluation which is essential in proton therapy treatment planning. The aim of this study is to evaluate the dosimetric impact of this uncertainty for DIBH patients treated with proton therapy using a spirometry system with visual feedback and to determine the ideal clinical workflow to ensure robustness. <h3>Materials/Methods</h3> A dedicated workflow involving simulation, treatment planning and quality assurance was developed and implemented in our clinic to assess the potential dosimetric impact of this uncertainty. The workflow involved a multi-scan simulation procedure in which patients were simulated under their nominal breath hold level and two additional breath hold levels at ± 100 mL tidal lung volume with respect to the nominal. This variation was chosen as it represents twice the allowed variation during treatment in order to be conservative. The additional scans were used to assess motion near the target and to determine the best techniques to be used during plan optimization to ensure robustness. In particular a 5 mm motion threshold was used by physics to recommend the use of simultaneous optimization across all three image sets. The final treatment plan was forward calculated on the additional image sets to guarantee robustness. Patient data, including on-treatment imaging and verification CT scans (QA-CT), were analyzed to assess plan robustness for 30 patients treated under this workflow over two years. <h3>Results</h3> Out of 30 DIBH patients treated under this workflow the simultaneous optimization tool was recommended in three cases but ultimately not utilized in planning at MD/dosimetry discretion balancing dose to OARs and robustness. All thirty patients passed the robust evaluation procedure and there were no cases for which QA-CT indicated a need to revise a treatment plan due to a variation in the breath hold level. <h3>Conclusion</h3> Our initial experience indicates that in proton therapy utilizing spirometry based DIBH with visual feedback the uncertainty associated with the variation in breath hold level does not have a significant dosimetric impact on plan robustness. Given these results, the decision was made to reduce the workload and simplify the workflow by eliminating the additional scans and utilizing a single breath hold level during simulation.

The impact of organ motion and the appliance of mitigation strategies on the effectiveness of hypoxia-guided proton therapy for non-small cell lung cancer

Background and PurposeTo investigate the impact of organ motion on hypoxia-guided proton therapy treatments for non-small cell lung cancer (NSCLC) patients. Materials and MethodsHypoxia PET and 4D imaging data of six NSCLC patients were used to simulate hypoxia-guided proton therapy with different motion mitigation strategies including rescanning, breath-hold, respiratory gating and tumour tracking. Motion-induced dose degradation was estimated for treatment plans with dose painting of hypoxic tumour sub-volumes at escalated dose levels. Tumour control probability (TCP) and dosimetry indices were assessed to weigh the clinical benefit of dose escalation and motion mitigation. In addition, the difference in normal tissue complication probability (NTCP) between escalated proton and photon VMAT treatments has been assessed. ResultsMotion-induced dose degradation was found for target coverage (CTV V95% up to −4%) and quality of the dose-escalation-by-contour (QRMS up to 6%) as a function of motion amplitude and amount of dose escalation. The TCP benefit coming from dose escalation (+4–13%) outweighs the motion-induced losses (<2%). Significant average NTCP reductions of dose-escalated proton plans were found for lungs (−14%), oesophagus (−10%) and heart (−16%) compared to conventional VMAT plans. The best plan dosimetry was obtained with breath hold and respiratory gating with rescanning. ConclusionNSCLC affected by hypoxia appears to be a prime target for proton therapy which, by dose-escalation, allows to mitigate hypoxia-induced radio-resistance despite the sensitivity to organ motion. Furthermore, substantial reduction in normal tissue toxicity can be expected compared to conventional VMAT. Accessibility and standardization of hypoxia imaging and clinical trials are necessary to confirm these findings in a clinical setting.

Multi-arrays of 3D cylindrical microdetectors for beam characterization and microdosimetry in proton therapy

The present work shows the performance of two new large microdosimetry multi-array systems having two different configurations, namely, pixel and strip configurations. They cover radiation sensitive areas of 1.9 cm × 0.1 cm and 5.1 cm × 0.1 cm, respectively. The microdosimetry systems are based on arrays of 3D cylindrical silicon microdetectors. The 3D electrodes are etched inside the silicon and have a 25 μm diameter and a 20 μm depth. Each of these unit cells is completely isolated from the others and has a well defined 3D micrometric radiation sensitive volume. The pixel-type device consists of 25 × 5 independent silicon-based detectors (500 in total), each one connected to a readout channel, collecting information in 2D in the transverse planes to the particle beam direction. The distance between the individual detectors (pitch) is 200 μm in the horizontal axis and 250 μm in the vertical one. In the case of the strip-type system, we have 512 “columns” (or strips) of 10 detectors per column. Each strip is connected to a readout channel, giving us information in one dimension, but with better statistics than a single pixel. In this system, both the horizontal and vertical pitches are 100 μm.Both systems have been tested under proton beam irradiations at different energies between 6 and 24 MeV to obtain the corresponding microdosimetry quantities along the Bragg peak and distal edge. The measurements were performed at the Accélérateur Linéaire et Tandem à Orsay (ALTO, France). The microdosimetry quantities were successfully obtained with spatial resolutions of 100–250 μm. Experimental results were compared to Monte Carlo simulations and an overall good agreement was found. Both microdetector systems showed a good microdosimetry performance under clinical-equivalent fluence rates along distances of several centimeters. This work demonstrates that the two new systems having different configurations can be clinically used as microdosimeters for measuring the lineal energy distributions in the context of proton therapy treatments. Additionally, they could be also used for beam monitoring.

In-vivo range verification analysis with in-beam PET data for patients treated with proton therapy at CNAO.

Morphological changes that may arise through a treatment course are probably one of the most significant sources of range uncertainty in proton therapy. Non-invasive in-vivo treatment monitoring is useful to increase treatment quality. The INSIDE in-beam Positron Emission Tomography (PET) scanner performs in-vivo range monitoring in proton and carbon therapy treatments at the National Center of Oncological Hadrontherapy (CNAO). It is currently in a clinical trial (ID: NCT03662373) and has acquired in-beam PET data during the treatment of various patients. In this work we analyze the in-beam PET (IB-PET) data of eight patients treated with proton therapy at CNAO. The goal of the analysis is twofold. First, we assess the level of experimental fluctuations in inter-fractional range differences (sensitivity) of the INSIDE PET system by studying patients without morphological changes. Second, we use the obtained results to see whether we can observe anomalously large range variations in patients where morphological changes have occurred. The sensitivity of the INSIDE IB-PET scanner was quantified as the standard deviation of the range difference distributions observed for six patients that did not show morphological changes. Inter-fractional range variations with respect to a reference distribution were estimated using the Most-Likely-Shift (MLS) method. To establish the efficacy of this method, we made a comparison with the Beam’s Eye View (BEV) method. For patients showing no morphological changes in the control CT the average range variation standard deviation was found to be 2.5 mm with the MLS method and 2.3 mm with the BEV method. On the other hand, for patients where some small anatomical changes occurred, we found larger standard deviation values. In these patients we evaluated where anomalous range differences were found and compared them with the CT. We found that the identified regions were mostly in agreement with the morphological changes seen in the CT scan.

Analysis of the Results of Proton Radiation Therapy of Patients with Squamous Cell Carcinoma of the Head and Neck

Purpose: To evaluate the severity of early radiation reactions and the first results of proton therapy treatment of patients with squamous cell carcinoma of the head and neck. Material and methods: From January 2019 to March 2022, more than 1 400 patients received proton therapy on the proton-cyclotron complex ProteusPlus235. The search for patients was carried out in the database of patients who received proton radiation therapy for oncological diseases in the FMBA system of Russia. The study included 62 patients with confirmed squamous cell carcinoma and the unifying model was: proton therapy in the mode of five-day fractionation of SFD 2 Gr, TFD 50 Gy for locoregional lymphatic collector zones and TFD 60–70 Gy for the area of the primary tumor focus and high-risk zones. The age group is from 18 to 78 years. According to the classification of ICD10 — 35 patients were diagnosed with C00–C14 “Malignant neoplasms of the lip, oral cavity and pharynx” (56,4 %), 27 patients with C30–C32 “Malignant neoplasms of the upper respiratory organs” (43,5 %). Results: The assessment of long-term treatment results and the severity of radiation complications requires a systematic and uniform approach and is the subject of further research, along with the development of optimal patient models for treatment by proton pencil-beam scanning therapy. Conclusions: Proton beam and proton chemoradiotherapy have demonstrated decreasing trends or comparable frequency and severity of radiation reactions compared to photon therapy. In this regard, the decision to choose a treatment method should be based on an assessment of clinical efficacy, relapse-free and event-free survival, which is the subject of further scientific research.

P03.06.B Proton irradiation (PT) for benign meningiomas, Grade I clinical experience of the first 100 patients from REGI-MA-002015

Abstract Background Meningiomas are the most common CNS tumors and the majority is regarded as benign. However, a subset of patients presents with complex tumors involving several anatomic compartments of the skull base - eluding any concepts of gross total resection. Proton therapy (PT) is applied as definitive treatment for primary or recurrent disease or postoperatively following subtotal resection. We report on the first 100 adult patients treated with PT at MedAustron. Material and Methods All patients were enrolled in a prospective registry trial (ClinicalTrials.gov Identifier: NCT03049072). Target volume definition was based on CT, MR and DOTA-PET/CT. PT treatment plans were generated by applying a Simultaneous Integrated Boost (SIB) concept with the Single Field-optimisation method and utilizing 2-4 beams per plan with a beam spacing of &amp;gt;30°. Prescribed doses to PTV1 were 50.49Gy_RBE at 1.87Gy_RBE/fr and 54.0Gy_RBE at 2.0Gy_RBE/fr to PTV2 in overall 27 fractions. Follow up status was assessed by MRI at 6, 12 months and annually thereafter, side effects were assessed using CTCAE v4.0. and quality of life (QoL) using EORTC-CTC30 and BN20 questionnaires. The scores entered by the patients were added and normalized to 0-100 scale according to previously described protocols. Results Between 08/2017 and 04/2021, 100 patients were treated, 22% (n=22) male and 78% (n=78) female patients. Median age at therapy was 54a (25a-82a). In 57% (n=57) PT was the definitive treatment (no resection or surgery &amp;gt;12 mo prior to PT). 43% (n=43) underwent postoperative PT with at least one surgery (range 1-3), and median time from last resection to start of PT of 6mo (3mo-11mo). 89% (n=89) meningiomas were located in the skull base with involvement of multiple anatomic compartments. The median GTV size was 24cc (1cc-226cc) and the median CTV 41cc (2cc-352cc), respectively. At median follow-up of 31.1 months (range 6.6-51.6), 2 local in-field failures were observed (both patients treated postoperatively) resulting in disease-specific survival of 100% and local control of 98% at 3 years, respectively. No &amp;gt; Grade 2 acute toxicity was observed. During follow-up two Grade 3 toxicities occurred: One patient developed symptomatic radiation induced brain lesion (RIBL) which resolved within 12 month; one patient was hospitalized for new onset of epilepsy without corresponding radiographic findings. 9% (n=9) developed G1/G2 RIBL, which resolved spontaneously. The general QoL including the global health status and all functioning domains remained stable and did not decrease significantly following PT. Conclusion First clinical data demonstrate that PT based on a SIB concept is a safe and efficient treatment of anatomically complex, low grade meningiomas. Acute and late toxicity incidences in our series were low with excellent, prospectively assessed preservation of QoL.

Neutron Radiation Dose Measurements in a Scanning Proton Therapy Room: Can Parents Remain Near Their Children During Treatment?

PurposeThis study aims to characterize the neutron radiation field inside a scanning proton therapy treatment room including the impact of different pediatric patient sizes.Materials and MethodsWorking Group 9 of the European Radiation Dosimetry Group (EURADOS) has performed a comprehensive measurement campaign to measure neutron ambient dose equivalent, H*(10), at eight different positions around 1-, 5-, and 10-year-old pediatric anthropomorphic phantoms irradiated with a simulated brain tumor treatment. Several active detector systems were used.ResultsThe neutron dose mapping within the gantry room showed that H*(10) values significantly decreased with distance and angular deviation with respect to the beam axis. A maximum value of about 19.5 µSv/Gy was measured along the beam axis at 1 m from the isocenter for a 10-year-old pediatric phantom at 270° gantry angle. A minimum value of 0.1 µSv/Gy was measured at a distance of 2.25 m perpendicular to the beam axis for a 1-year-old pediatric phantom at 140° gantry angle.The H*(10) dependence on the size of the pediatric patient was observed. At 270° gantry position, the measured neutron H*(10) values for the 10-year-old pediatric phantom were up to 20% higher than those measured for the 5-year-old and up to 410% higher than for the 1-year-old phantom, respectively.ConclusionsUsing active neutron detectors, secondary neutron mapping was performed to characterize the neutron field generated during proton therapy of pediatric patients. It is shown that the neutron ambient dose equivalent H*(10) significantly decreases with distance and angle with respect to the beam axis. It is reported that the total neutron exposure of a person staying at a position perpendicular to the beam axis at a distance greater than 2 m from the isocenter remains well below the dose limit of 1 mSv per year for the general public (recommended by the International Commission on Radiological Protection) during the entire treatment course with a target dose of up to 60 Gy. This comprehensive analysis is key for general neutron shielding issues, for example, the safe operation of anesthetic equipment. However, it also enables the evaluation of whether it is safe for parents to remain near their children during treatment to bring them comfort. Currently, radiation protection protocols prohibit the occupancy of the treatment room during beam delivery.

An ion-independent phenomenological relative biological effectiveness (RBE) model for proton therapy

BackgroundA relative biological effectiveness (RBE) of 1.1 is used for proton therapy though clinical evidence of varying RBE was raised. Clinical studies on RBE variability have been conducted for decades for carbon radiation, which could advance the understanding of the clinical proton RBE given an ion-independent RBE model. In this work, such a model, linear and simple, using the beam quantity Q = Z2/E (Z = ion charge, E = kinetic energy per nucleon) was tested and compared to the commonly used, proton-specific and linear energy transfer (LET) based Wedenberg RBE model. Material and methodsThe Wedenberg and Q models, both predicting RBEmax and RBEmin (i.e., RBE at vanishing and very high dose, respectively), are compared in terms of ion-dependence and prediction power. An experimental in-vitro data ensemble covering 115 publications for various ions was used as dataset. ResultsThe model parameter of the Q model was observed to be similar for different ions (in contrast to LET). The Q model was trained without any prior knowledge of proton data. For proton RBE, the differences between experimental data and corresponding predictions of the Wedenberg or the Q model were highly comparable. ConclusionsA simple linear RBE model using Q instead of LET was proposed and tested to be able to predict proton RBE using model parameter trained based on only RBE data of other particles in a clinical proton energy range for a large in-vitro dataset. Adding (pre)clinical knowledge from carbon ion therapy may, therefore, reduce the dominating biological uncertainty in proton RBE modelling. This would translate in reduced RBE related uncertainty in proton therapy treatment planning.

OC-0628 Proton therapy treatment verification with prompt gamma rays and fast neutrons – a feasibility study

OC-0628 Proton therapy treatment verification with prompt gamma rays and fast neutrons – a feasibility study

PO-1685 Creating clinically competitive FLASH proton therapy treatment plans

PO-1685 Creating clinically competitive FLASH proton therapy treatment plans

Consolidative active scanning proton therapy for mediastinal lymphoma: selection criteria, treatment implementation and clinical feasibility.

Proton therapy (PT) represents an advanced form of radiotherapy with unique physical properties which could be of great advantage in reducing long-term radiation morbidity for cancer survivors. Here, we aim to describe the whole process leading to the clinical implementation of consolidative active scanning proton therapy treatment (PT) for mediastinal lymphoma. The process included administrative, technical and clinical issues. Authorization of PT is required in all cases as mediastinal lymphoma is currently not on the list of diseases reimbursable by the Italian National Health Service. Technically, active scanning PT treatment for mediastinal lymphoma is complex, due to the interaction between actively scanned protons and the usually irregular and large volumes to be irradiated, the nearby healthy tissues and the target motion caused by breathing. Aroad map to implement the technical procedures was prepared. The clinical selection of patients was of utmost importance and took into account both patient and tumor characteristics. The first mediastinal lymphoma was treated at our PT center in 2018, four years after the start of the clinical activities. The treatment technique implementation included mechanical deep inspiration breath-hold simulation computed tomography (CT), clinical target volume (CTV)-based multifield optimization planning and plan robustness analysis. The ultimate authorization rate was 93%. In 4cases aproton-photon plan comparison was required. Between May 2018 and February, 2021, 14patients were treated with consolidative PT. The main clinical reasons for choosing PT over photons was abulky disease in 8patients (57%), patient's age in 11patients (78%) and the proximity of the lymphoma to cardiac structures in 10patients (71%). With amedian follow-up of 15months (range, 1-33months) all patients but one(out-of-field relapse) are without evidence of disease, all are alive and no late toxicities were observed during the follow-up period. The clinical implementation of consolidative active scanning PT for mediastinal lymphoma required specific technical procedures and aprolonged experience with PT treatments. An accurate selection of patients for which PT could be of advantage in comparison with photons is mandatory.

A dead-time-free data acquisition system for prompt gamma-ray measurements during proton therapy treatments

In cancer patients undergoing proton therapy, a very intense secondary radiation is produced during the treatment, which lasts around one minute. About one billion prompt gamma-rays are emitted per second, and their detection with fast scintillation detectors is useful for monitoring a correct beam delivery. To cope with the expected count rate and pile-up, as well as the scarce statistics due to the short treatment duration, we developed an eidetic data acquisition system capable of continuously digitizing the detector signal with a high sampling rate and without any dead time. By streaming the fully unprocessed waveforms to the computer, complex pile-up decomposition algorithms can be applied and optimized offline. We describe the data acquisition architecture and the multiple experimental tests designed to verify the sustained data throughput speed and the absence of dead time. While the system is tailored for the proton therapy environment, the methodology can be deployed in any other field requiring the recording of raw waveforms at high sampling rates with zero dead time.

Evaluating Proton Dose and Associated Range Uncertainty Using Daily Cone-Beam CT.

PurposeThis study aimed to quantitatively evaluate the range uncertainties that arise from daily cone-beam CT (CBCT) images for proton dose calculation compared to CT using a measurement-based technique.MethodsFor head and thorax phantoms, wedge-shaped intensity-modulated proton therapy (IMPT) treatment plans were created such that the gradient of the wedge intersected and was measured with a 2D ion chamber array. The measured 2D dose distributions were compared with 2D dose planes extracted from the dose distributions using the IMPT plan calculated on CT and CBCT. Treatment plans of a thymoma cancer patient treated with breath-hold (BH) IMPT were recalculated on 28 CBCTs and 9 CTs, and the resulting dose distributions were compared.ResultsThe range uncertainties for the head phantom were determined to be 1.2% with CBCT, compared to 0.5% for CT, whereas the range uncertainties for the thorax phantom were 2.1% with CBCT, compared to 0.8% for CT. The doses calculated on CBCT and CT were similar with similar anatomy changes. For the thymoma patient, the primary source of anatomy change was the BH uncertainty, which could be up to 8 mm in the superior–inferior (SI) direction.ConclusionWe developed a measurement-based range uncertainty evaluation method with high sensitivity and used it to validate the accuracy of CBCT-based range and dose calculation. Our study demonstrated that the CBCT-based dose calculation could be used for daily dose validation in selected proton patients.

The Microstrip Silicon Detector (MSD) data acquisition system architecture for the FOOT experiment

The FOOT (FragmentatiOn Of Target) multi-detector experiment aims at improving the accuracy of oncological hadrontherapy for tumor treatment. It studies the nuclear fragmentation due to the interactions of charged particle beams with patient tissues employing the inverse kinematic approach to boost the fragments in the laboratory reference system. Hence it is necessary a tracking system in a magnetic field to measure the momentum of the charged fragments. The Microstrip Silicon Detector (MSD) is part of the charged-ions-tracking magnetic spectrometer for the evaluation of the Linear Energy Transfer LET (dE/dx) and the nuclear fragments momentum. Here we describe the MSD architecture and its data acquisition system whose task is to collect and digitize the detectors output, generating a data packet to be sent to the experiment’s central acquisition. This data acquisition system is designed and tested to withstand the trigger rate and detector’s throughput; it has a small size and is easily portable, a necessary feature for an experiment that will move among the available ion beam accelerators and proton therapy treatment rooms.

Proceedings to the 7th Annual Conference of the Particle Therapy Cooperative Group North America (PTCOG-NA)

Proceedings to the 7th Annual Conference of the Particle Therapy Cooperative Group North America (PTCOG-NA)

Towards machine learning aided real-time range imaging in proton therapy

Compton imaging represents a promising technique for range verification in proton therapy treatments. In this work, we report on the advantageous aspects of the i-TED detector for proton-range monitoring, based on the results of the first Monte Carlo study of its applicability to this field. i-TED is an array of Compton cameras, that have been specifically designed for neutron-capture nuclear physics experiments, which are characterized by gamma -ray energies spanning up to 5–6 MeV, rather low gamma -ray emission yields and very intense neutron induced gamma -ray backgrounds. Our developments to cope with these three aspects are concomitant with those required in the field of hadron therapy, especially in terms of high efficiency for real-time monitoring, low sensitivity to neutron backgrounds and reliable performance at the high gamma -ray energies. We find that signal-to-background ratios can be appreciably improved with i-TED thanks to its light-weight design and the low neutron-capture cross sections of its LaCl_{3} crystals, when compared to other similar systems based on LYSO, CdZnTe or LaBr_{3}. Its high time-resolution (CRT sim 500 ps) represents an additional advantage for background suppression when operated in pulsed HT mode. Each i-TED Compton module features two detection planes of very large LaCl_{3} monolithic crystals, thereby achieving a high efficiency in coincidence of 0.2% for a point-like 1 MeV gamma -ray source at 5 cm distance. This leads to sufficient statistics for reliable image reconstruction with an array of four i-TED detectors assuming clinical intensities of 10^{8} protons per treatment point. The use of a two-plane design instead of three-planes has been preferred owing to the higher attainable efficiency for double time-coincidences than for threefold events. The loss of full-energy events for high energy gamma -rays is compensated by means of machine-learning based algorithms, which allow one to enhance the signal-to-total ratio up to a factor of 2.

Proton Therapy for Prostate Cancer: Challenges and Opportunities.

Simple SummaryReported clinical outcomes of proton therapy (PT) for localized prostate cancer are similar to photon-based external beam radiotherapy. Apparently, the dosimetric advantages of PT have yet to be translated to clinical benefits. The suboptimal clinical outcomes of PT might be attributable to inadequate dose prescription, as indicated by the ASCENDE-RT trial. Moreover, uncertainties involved in the treatment planning and delivery processes, as well as technological limitations in PT treatment systems, may lead to discrepancies between planned doses and actual doses delivered to patients. In this article, we reviewed the current status of PT for prostate cancer and discussed different clinical implementations that could potentially improve the clinical outcome of PT for prostate cancer. Various technological advancements under which uncertainties in dose calculations can be minimized, including MRI-guided PT, dual-energy photon-counting CT and high-resolution Monte Carlo-based treatment planning systems, are highlighted.The dosimetric advantages of proton therapy (PT) treatment plans are demonstrably superior to photon-based external beam radiotherapy (EBRT) for localized prostate cancer, but the reported clinical outcomes are similar. This may be due to inadequate dose prescription, especially in high-risk disease, as indicated by the ASCENDE-RT trial. Alternatively, the lack of clinical benefits with PT may be attributable to improper dose delivery, mainly due to geometric and dosimetric uncertainties during treatment planning, as well as delivery procedures that compromise the dose conformity of treatments. Advanced high-precision PT technologies, and treatment planning and beam delivery techniques are being developed to address these uncertainties. For instance, external magnetic resonance imaging (MRI)-guided patient setup rooms are being developed to improve the accuracy of patient positioning for treatment. In-room MRI-guided patient positioning systems are also being investigated to improve the geometric accuracy of PT. Soon, high-dose rate beam delivery systems will shorten beam delivery time to within one breath hold, minimizing the effects of organ motion and patient movements. Dual-energy photon-counting computed tomography and high-resolution Monte Carlo-based treatment planning systems are available to minimize uncertainties in dose planning calculations. Advanced in-room treatment verification tools such as prompt gamma detector systems will be used to verify the depth of PT. Clinical implementation of these new technologies is expected to improve the accuracy and dose conformity of PT in the treatment of localized prostate cancers, and lead to better clinical outcomes. Improvement in dose conformity may also facilitate dose escalation, improving local control and implementation of hypofractionation treatment schemes to improve patient throughput and make PT more cost effective.

Spatiotemporal optimisation of prostate intensity modulated proton therapy (IMPT) treatments

Objective. In intensity modulated particle therapy (IMPT), the adoption of spatially and temporally heterogeneous dose distributions allows to decouple the fractionation scheme from the patient anatomy, so that an hypofractionated schedule can be selectively created inside the tumour, while simultaneously exploiting the fractionation effect in the healthy tissues. In this paper, the authors show the reproducibility of the method on a set of prostate patients, quantifying the dependencies of the achievable benefit with respect to conventional and hypofractionated schemes and the sensitivity of the method to setup errors and range uncertainty. Approach. On a cohort of 9 patients, non-uniform IMPT plans were optimised and compared to conventional and hypofractionated schedules. For each patient, the comparison of the three strategies has been based on the output of the cost function used to optimise the treatments. The analysis has been repeated considering different α/β ratios for the tumour, namely 1.5, 3 and 4.5 Gy. For a single patient, setup errors and beam range uncertainty have been analysed: the plans, for each optimisation strategy, have been iteratively forward planned 500 times with randomly varying the patient position in each fraction, and 200 times for systematic range shift. Main results. An average 10% benefit has been shown for the lowest α/β ratio considered for the tumour, where the non-uniform schedule generally converges to hypofractionation; the benefit decreases to 5%–7% for higher α/β ratios, for which the non-uniform schedule always showed better outcomes with respect to the other fractionation schedules. An increased sensitivity to uncertainty, especially for setup errors, has been shown, which can be associated to the spatial non-uniformity of the dose distributions peculiar of the spatiotemporal plans. Significance. This work represents the first investigation of spatiotemporal fractionation for prostate cancer and the beginning of further investigations before clinical implementation can be considered.

A patient-specific hybrid phantom for calculating radiation dose and equivalent dose to the whole body

Objective. As cancer survivorship increases, there is growing interest in minimizing the late effects of radiation therapy such as radiogenic second cancer, which may occur anywhere in the body. Assessing the risk of late effects requires knowledge of the dose distribution throughout the whole body, including regions far from the treatment field, beyond the typical anatomical extent of clinical computed tomography (CT) scans. Approach. A hybrid phantom was developed which consists of in-field patient CT images extracted from ground truth whole-body CT scans, out-of-field mesh phantoms scaled to basic patient measurements, and a blended transition region. Four of these hybrid phantoms were created, representing male and female patients receiving proton therapy treatment in pelvic and cranial sites. To assess the performance of the hybrid approach, we simulated treatments using the hybrid phantoms, the scaled and unscaled mesh phantoms, and the ground truth whole-body CTs. We calculated absorbed dose and equivalent dose in and outside of the treatment field, with a focus on neutrons induced in the patient by proton therapy. Proton and neutron dose was calculated using a general purpose Monte Carlo code. Main results. The hybrid phantom provided equal or superior accuracy in calculated organ dose and equivalent dose values relative to those obtained using the mesh phantoms in 78% in all selected organs and calculated dose quantities. Comparatively the default mesh and scaled mesh were equal or superior to the other phantoms in 21% and 28% of cases respectively. Significance. The proposed methodology for hybrid synthesis provides a tool for whole-body organ dose estimation for individual patients without requiring CT scans of their entire body. Such a capability would be useful for personalized assessment of late effects and risk-optimization of treatment plans.