BACKGROUND: Proton beam therapy using pencil beam scanning is an advanced radiotherapy technique that utilises proton beams to precisely target tumours. It is known for its enhanced ability in sparing healthy tissue and potentially reducing toxicity. Clinical experience with pencil beam scanning in the treatment of mediastinal Hodgkin lymphoma remains limited. PATIENTS AND METHODS: This study aimed to evaluate the toxicity and outcomes of a prospectively observed cohort. A total of 162 patients were irradiated between May 2013 and December 2020, with a median age of 32 years (range: 18.4-79.2) and followed up until April 2024. The median applied dose was 30 GyE (range: 20-40). Deep inspiration breath hold was used in 146 patients to enhance targeting precision. RESULTS: The disease-free survival, overall survival and local control rates were 95.1 %, 98.8 % and 98.8 %, respectively. The median follow-up was 59.1 months (range: 4-120.1). The most common acute toxicities observed were oesophageal and skin toxicity. Grade 1 oesophageal mucositis occurred in 76 patients (47 %), grade 2 in 16 patients (10 %). Dermatitis of grade 1 and 2 was observed in 65 (40 %) and 4 (3 %) patients respectively. Grade 1 pulmonary toxicity presented in 8 patients (4.9 %), and grade 2 in one patient (0.6 %). The most predominant late toxicity was grade 2 hypothyroidism in 37 patients (23 %). Three patients (1.8 %) underwent coronary interventions during follow-up, and one patient was diagnosed with hepatocellular carcinoma 3 months post-RT. No unexpected acute or late toxicities were observed. CONCLUSION: Proton beam therapy using pencil beam scanning is a safe and effective technique in terms of toxicity and local control, even when irradiating mediastinal targets.
- MeSH
- celková dávka radioterapie MeSH
- dospělí MeSH
- Hodgkinova nemoc * radioterapie mortalita MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádory mediastina * radioterapie mortalita MeSH
- prospektivní studie MeSH
- protonová terapie * škodlivé účinky metody MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: With the increasing use of proton therapy, there is a growing emphasis on including radiation quality, often quantified by linear energy transfer, as a treatment plan optimization factor. The Timepix detectors offer energy-sensitive particle tracking useful for the characterization of proton linear energy transfer. To improve the detector's performance in mixed radiation fields produced in proton therapy, we customized the detector settings and performed the per-pixel energy calibration. METHODS: The detection threshold and per-pixel signal shaping time (IKrum current) were customized, and energy calibration was performed for MiniPIX Timepix3. The detector calibration was verified using α source and clinical proton beams, as well as Monte Carlo simulations. The effects on the detector's performance, in terms of spectral saturation and pixel occupancy, were evaluated. RESULTS: Measurements with proton beams showed a good agreement with simulations. With the customized settings, the measurable energy range in the detector data-driven mode was extended, and the signal duration time was reduced by 80%, while the yield of pixel time occupancy reduction depends on the number of occupied pixels. For performed measurements with proton beams, the number of occupied pixels was further reduced up to 40% due to the increased threshold. CONCLUSIONS: Customized detector configuration of the Timepix3 detector allowed for reduced pixel occupancy and mitigation of signal saturation in a data-driven mode without significantly interfering with the energy deposition measurement. The presented approach enables the extension of the operational range, including higher intensities and mixed-radiation fields in particle radiotherapy environments.
Radiation therapy manages pancreatic cancer in various settings; however, the proximity of gastrointestinal (GI) luminal organs at risk (OARs) poses challenges to conventional radiation therapy. Proton beam therapy (PBT) may reduce toxicities compared to photon therapy. This consensus statement summarizes PBT's safe and optimal delivery for pancreatic tumors. Our group has specific expertise using PBT for GI indications and has developed expert recommendations for treating pancreatic tumors with PBT. Computed tomography (CT) simulation: Patients should be simulated supine (arms above head) with custom upper body immobilization. For stomach/duodenum filling consistency, patients should restrict oral intake within 3 hours before simulation/treatments. Fiducial markers may be implanted for image guidance; however, their design and composition require scrutiny. The reconstruction field-of-view should encompass all immobilization devices at the target level (CT slice thickness 2-3 mm). Four-dimensional CT should quantify respiratory motion and guide motion mitigation. Respiratory gating is recommended when motion affects OAR sparing or reduces target coverage. Treatment planning: Beam-angle selection factors include priority OAR-dose minimization, water-equivalent-thickness stability along the beam path, and enhanced relative biological effect consideration due to the increased linear energy transfer at the proton beam end-of-range. Posterior and right-lateral beam angles that avoid traversing GI luminal structures are preferred (minimizing dosimetric impacts of variable anatomies). Pencil beam scanning techniques should use robust optimization. Single-field optimization is preferable to increase robustness, but if OAR constraints cannot be met, multifield optimization may be used. Treatment delivery: Volumetric image guidance should be used daily. CT scans should be acquired ad hoc as necessary (at minimum every other week) to assess the dosimetric impacts of anatomy changes. Adaptive replanning should be performed as required. Our group has developed recommendations for delivering PBT to safely and effectively manage pancreatic tumors.
- MeSH
- celková dávka radioterapie MeSH
- čtyřrozměrná počítačová tomografie MeSH
- dýchání MeSH
- imobilizace metody MeSH
- konsensus MeSH
- kritické orgány * diagnostické zobrazování účinky záření MeSH
- lidé MeSH
- nádory slinivky břišní * radioterapie diagnostické zobrazování MeSH
- plánování radioterapie pomocí počítače metody MeSH
- pohyb vnitřních orgánů MeSH
- pohyb MeSH
- protonová terapie * metody škodlivé účinky normy MeSH
- radiační poranění prevence a kontrola MeSH
- radioterapie řízená obrazem metody MeSH
- žaludek diagnostické zobrazování MeSH
- zaměřovací značky pro radioterapii MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- konsensus - konference MeSH
- MeSH
- imunoterapie MeSH
- nádory hlavy a krku * diagnóza komplikace radioterapie MeSH
- protonová terapie MeSH
- Publikační typ
- rozhovory MeSH
Artificial intelligence (AI) has made a tremendous impact in the space of healthcare, and proton therapy is not an exception. Proton therapy has witnessed growing popularity in oncology over recent decades, and researchers are increasingly looking to develop AI and machine learning tools to aid in various steps of the treatment planning and delivery processes. This review delves into the emergent role of AI in proton therapy, evaluating its development, advantages, intended clinical contexts, and areas of application. Through the analysis of 76 studies, we aim to underscore the importance of AI applications in advancing proton therapy and to highlight their prospective influence on clinical practices.
- MeSH
- lidé MeSH
- nádory * radioterapie terapie MeSH
- plánování radioterapie pomocí počítače metody MeSH
- protonová terapie * metody MeSH
- strojové učení MeSH
- umělá inteligence * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
PURPOSE: Patients with p16 positive tonsillar cancer (p16 + TC) have an excellent prognosis and long-life expectancy. Deintensification of therapy is a prevalent topic of discussion. Proton radiotherapy is one way to reduce radiation exposure and thus reduce acute and late toxicity. The aim is to evaluate treatment outcomes and toxicity of postoperative treatment with intensity-modulated proton therapy (IMPT). METHODS: Between September 2013 and November 2021, 47 patients with p16 + TC were treated postoperatively with IMPT. Median age was 54.9 (38.2-74.9) years, 31 were males and 16 were females. All patients had squamous cell carcinoma and underwent surgery as a primary treatment. Median dose of radiotherapy was 66 GyE in 33 fractions. Bilateral neck irradiation was used in 39 patients and unilateral in 8. Concomitant chemotherapy was applied in 24 patients. RESULTS: Median follow-up time was 4.2 (0.15-9.64) years. Five-year overall survival, relapse free survival and local control were 95.7%, 97.8% and 100%. The most common acute toxicities were dermatitis and mucositis, with grade 2 + in 61.7% and 70.2% of patients. No acute percutaneous gastrostomy insertion was necessary and intravenous rehydration was used in 12.8% of patients. The most common late toxicity was grade 1 xerostomia in 70.2% of patients and grade 2 in 10.6% of patients. Subcutaneous fibrosis of grades 2 and 3 occurred in 17.0% and 2.1% of patients, respectively. One patient developed late severe dysphagia and became PEG-dependent. CONCLUSION: IMPT for the postoperative treatment of p16 + TC is feasible with excellent efficiency and acceptable acute and late toxicity.
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- protonová terapie * metody škodlivé účinky MeSH
- radioterapie s modulovanou intenzitou * metody škodlivé účinky MeSH
- retrospektivní studie MeSH
- senioři MeSH
- spinocelulární karcinom * radioterapie patologie terapie chirurgie MeSH
- tonzilární nádory * radioterapie patologie chirurgie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Boron has been suggested to enhance the biological effectiveness of proton beams in the Bragg peak region via the p + 11B → 3α nuclear capture reaction. However, a number of groups have observed no such enhancement in vitro or questioned its proposed mechanism recently. To help elucidate this phenomenon, we irradiated DU145 prostate cancer or U-87 MG glioblastoma cells by clinical 190 MeV proton beams in plateau or Bragg peak regions with or without 10B or 11B isotopes added as sodium mercaptododecaborate (BSH). The results demonstrate that 11B but not 10B or other components of the BSH molecule enhance cell killing by proton beams. The enhancement occurs selectively in the Bragg peak region, is present for boron concentrations as low as 40 ppm, and is not due to secondary neutrons. The enhancement is likely initiated by proton-boron capture reactions producing three alpha particles, which are rare events occurring in a few cells only, and their effects are amplified by intercellular communication to a population-level response. The observed up to 2-3-fold reductions in survival levels upon the presence of boron for the studied prostate cancer or glioblastoma cells suggest promising clinical applications for these tumour types.
- MeSH
- bor chemie MeSH
- glioblastom radioterapie farmakoterapie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory prostaty radioterapie farmakoterapie MeSH
- protonová terapie * metody MeSH
- protony MeSH
- terapie metodou neutronového záchytu (bor-10) * metody MeSH
- viabilita buněk účinky léků účinky záření MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Ultra high dose rate (UHDR) radiotherapy using ridge filter is a new treatment modality known as conformal FLASH that, when optimized for dose, dose rate (DR), and linear energy transfer (LET), has the potential to reduce damage to healthy tissue without sacrificing tumor killing efficacy via the FLASH effect. PURPOSE: Clinical implementation of conformal FLASH proton therapy has been limited by quality assurance (QA) challenges, which include direct measurement of UHDR and LET. Voxel DR distributions and LET spectra at planning target margins are paramount to the DR/LET-related sparing of organs at risk. We hereby present a methodology to achieve experimental validation of these parameters. METHODS: Dose, DR, and LET were measured for a conformal FLASH treatment plan involving a 250-MeV proton beam and a 3D-printed ridge filter designed to uniformly irradiate a spherical target. We measured dose and DR simultaneously using a 4D multi-layer strip ionization chamber (MLSIC) under UHDR conditions. Additionally, we developed an "under-sample and recover (USRe)" technique for a high-resolution pixelated semiconductor detector, Timepix3, to avoid event pile-up and to correct measured LET at high-proton-flux locations without undesirable beam modifications. Confirmation of these measurements was done using a MatriXX PT detector and by Monte Carlo (MC) simulations. RESULTS: MC conformal FLASH computed doses had gamma passing rates of >95% (3 mm/3% criteria) when compared to MatriXX PT and MLSIC data. At the lateral margin, DR showed average agreement values within 0.3% of simulation at 100 Gy/s and fluctuations ∼10% at 15 Gy/s. LET spectra in the proximal, lateral, and distal margins had Bhattacharyya distances of <1.3%. CONCLUSION: Our measurements with the MLSIC and Timepix3 detectors shown that the DR distributions for UHDR scenarios and LET spectra using USRe are in agreement with simulations. These results demonstrate that the methodology presented here can be used effectively for the experimental validation and QA of FLASH treatment plans.
PURPOSE: The time structures of proton spot delivery in proton pencil beam scanning (PBS) radiation therapy are essential in many clinical applications. This study aims to characterize the time structures of proton PBS delivered by both synchrotron and synchrocyclotron accelerators using a non-invasive technique based on scattered particle tracking. METHODS: A pixelated semiconductor detector, AdvaPIX-Timepix3, with a temporal resolution of 1.56 ns, was employed to measure time of arrival of secondary particles generated by a proton beam. The detector was placed laterally to the high-flux area of the beam in order to allow for single particle detection and not interfere with the treatment. The detector recorded counts of radiation events, their deposited energy and the timestamp associated with the single events. Individual recorded events and their temporal characteristics were used to analyze beam time structures, including energy layer switch time, magnet switch time, spot switch time, and the scanning speeds in the x and y directions. All the measurements were repeated 30 times on three dates, reducing statistical uncertainty. RESULTS: The uncertainty of the measured energy layer switch times, magnet switch time, and the spot switch time were all within 1% of average values. The scanning speeds uncertainties were within 1.5% and are more precise than previously reported results. The measurements also revealed continuous sub-milliseconds proton spills at a low dose rate for the synchrotron accelerator and radiofrequency pulses at 7 μs and 1 ms repetition time for the synchrocyclotron accelerator. CONCLUSION: The AdvaPIX-Timepix3 detector can be used to directly measure and monitor time structures on microseconds scale of the PBS proton beam delivery. This method yielded results with high precision and is completely independent of the machine log files.
- MeSH
- časové faktory MeSH
- částice - urychlovače * přístrojové vybavení MeSH
- celková dávka radioterapie * MeSH
- lidé MeSH
- nádory radioterapie MeSH
- plánování radioterapie pomocí počítače * metody MeSH
- polovodiče * MeSH
- protonová terapie * přístrojové vybavení MeSH
- protony MeSH
- synchrotrony přístrojové vybavení MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Objective.This study aims to assess the composition of scattered particles generated in proton therapy for tumors situated proximal to some titanium (Ti) dental implants. The investigation involves decomposing the mixed field and recording Linear Energy Transfer (LET) spectra to quantify the influence of metallic dental inserts located behind the tumor.Approach.A therapeutic conformal proton beam was used to deliver the treatment plan to an anthropomorphic head phantom with two types of implants inserted in the target volume (made of Ti and plastic, respectively). The scattered radiation resulted during the irradiation was detected by a hybrid semiconductor pixel detector MiniPIX Timepix3 that was placed distal to the Spread-out Bragg peak. Visualization and field decomposition of stray radiation were generated using algorithms trained in particle recognition based on artificial intelligence neural networks (AI NN). Spectral sensitive aspects of the scattered radiation were collected using two angular positions of the detector relative to the beam direction: 0° and 60°.Results.Using AI NN, 3 classes of particles were identified: protons, electrons & photons, and ions & fast neutrons. Placing a Ti implant in the beam's path resulted in predominantly electrons and photons, contributing 52.2% of the total number of detected particles, whereas for plastic implants, the contribution was 65.4%. Scattered protons comprised 45.5% and 31.9% with and without metal inserts, respectively. The LET spectra were derived for each group of particles identified, with values ranging from 0.01 to 7.5 keVμm-1for Ti implants/plastic implants. The low-LET component was primarily composed of electrons and photons, while the high-LET component corresponded to protons and ions.Significance.This method, complemented by directional maps, holds the potential for evaluating and validating treatment plans involving stray radiation near organs at risk, offering precise discrimination of the mixed field, and enhancing in this way the LET calculation.
- MeSH
- fantomy radiodiagnostické * MeSH
- lidé MeSH
- lineární přenos energie * MeSH
- neuronové sítě MeSH
- plánování radioterapie pomocí počítače metody MeSH
- protézy a implantáty MeSH
- protonová terapie * metody přístrojové vybavení MeSH
- radiační rozptyl MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
