Proton Beam Research Articles

A Case of Cervical Chordoma

A 48 year old male presented with neck pain and left arm pain that worsened with movement alongside left arm weakness, numbness, and tingling. The differential diagnosis for a patient with symptoms of a neck mass includes benign tumors like neurofibromas, malignant tumors like chordomas, and non-neoplastic conditions like cervical spondylitis. A magnetic resonance imaging (MRI) study of the cervical spine with and without contrast identified a T1 hypointense, T2 hyperintense, heterogeneously enhancing prevertebral mass with parapharyngeal extension. A direct laryngoscopy with biopsy was performed and revealed a paraspinal tumor. The patient’s diagnosis of cervical chordoma was confirmed upon detection of Brachyury, a gene that encodes a transcription factor which promotes epithelial mesenchymal transition (EMT) in chordoma pathogenesis. Chordomas are slow-growing tumors located within the body’s midline and they are associated with poorer outcomes because of neurovascular encasement at time of presentation. Chordomas are rare, with an incidence of 1 in 1,000,000. Approximately 6% of chordomas are located in the cervical spine. They are typically treated with surgery followed by radiation therapy. The patient underwent anterior resection for the prevertebral mass in the C2-C6 section of the cervical spinal cord. Surgery achieved subtotal resection and involved removal of the spinous processes of C3-C5 and reconstruction of the cervical spine with implants. The patient will be starting proton beam radiotherapy for his adjuvant treatment. Although rare, it is important to keep chordomas in the differential diagnosis when evaluating a patient with a neck mass.

A review and bibliometric analysis of global research on proton radiotherapy.

Proton beam therapy (PBT) has great advantages as tumor radiotherapy and is progressively becoming a more prevalent choice for individuals undergoing radiation therapy. The objective of this review is to pinpoint collaborative efforts among countries and institutions, while also exploring the hot topics and future outlook in the field of PBT. Data from publications were downloaded from the Web of Science Core Collection. CiteSpace and Excel 2016 were used to conduct the bibliometric and knowledge map analysis. A total of 6516 publications were identified, with the total number of articles steadily increasing and the United States being the most productive country. Harvard University took the lead in contributing the highest number of publications. Paganetti Harald published the most articles and had the most cocitations. PHYS MED BIOL published the greatest number of PBT-related articles, while INT J RADIAT ONCOL received the most citations. Paganetti Harald, 2012, PHYS MED BIOL can be classified as classic literature due to its high citation rate. We believe that research on technology development, dose calculation and relative biological effectiveness were the knowledge bases in this field. Future research hotspots may include clinical trials, flash radiotherapy, and immunotherapy.

Experimental comparison of cylindrical and plane parallel ionization chambers for reference dosimetry in continuous and pulsed scanned proton beams

Objective. In this experimental work we compared the determination of absorbed dose to water using four ionization chambers (ICs), a PTW-34045 Advanced Markus, a PTW-34001 Roos, an IBA-PPC05 and a PTW-30012 Farmer, irradiated under the same conditions in one continuous- and in two pulsed-scanned proton beams. Approach. The ICs were positioned at 2 cm depth in a water phantom in four square-field single-energy scanned-proton beams with nominal energies between 80 and 220 MeV and in the middle of 10 × 10 × 10 cm3 dose cubes centered at 10 cm or 12.5 cm depth in water. The water-equivalent thickness (WET) of the entrance window and the effective point of measurement was considered when positioning the plane parallel (PP) ICs and the cylindrical ICs, respectively. To reduce uncertainties, all ICs were calibrated at the same primary standards laboratory. We used the beam quality (k Q ) correction factors for the ICs under investigation from IAEA TRS-398, the newly calculated Monte Carlo (MC) values and the anticipated IAEA TRS-398 updated recommendations. Main results. Dose differences among the four ICs ranged between 1.5% and 3.7% using both the TRS-398 and the newly recommended k Q values. The spread among the chambers is reduced with the newly k Q values. The largest differences were observed between the rest of the ICs and the IBA-PPC05 IC, obtaining lower dose with the IBA-PPC05. Significance. We provide experimental data comparing different types of chambers in different proton beam qualities. The observed dose differences between the ICs appear to be related to inconsistencies in the determination of the k Q values. For PP ICs, MC studies account for the physical thickness of the entrance window rather than the WET. The additional energy loss that the wall material invokes is not negligible for the IBA-PPC05 and might partially explain the low k Q values determined for this IC. To resolve this inconsistency and to benchmark MC values, k Q values measured using calorimetry are needed.

Reduced interface effect of proton beam irradiation on the electrical properties of WSe2/hBN field effect transistors

Two-dimensional transition metal dichalcogenide (TMDC) semiconductors are emerging as strong contenders for electronic devices that can be used in highly radioactive environments such as outer space where conventional silicon-based devices exhibit nonideal characteristics for such applications. To address the radiation-induced interface effects of TMDC-based electronic devices, we studied high-energy proton beam irradiation effects on the electrical properties of field-effect transistors (FETs) made with tungsten diselenide (WSe2) channels and hexagonal boron-nitride (hBN)/SiO2 gate dielectrics. The electrical characteristics of WSe2 FETs were measured before and after the irradiation at various proton beam doses of 1013, 1014, and 1015 cm−2. In particular, we demonstrated the dependence of proton irradiation-induced effects on hBN layer thickness in WSe2 FETs. We observed that the hBN layer reduces the WSe2/dielectric interface effect which would shift the transfer curve of the FET toward the positive direction of the gate voltage. Also, this interface effect was significantly suppressed when a thicker hBN layer was used. This phenomenon can be explained by the fact that the physical separation of the WSe2 channel and SiO2 dielectric by the hBN interlayer prevents the interface effects originating from the irradiation-induced positive trapped charges in SiO2 reaching the interface. This work will help improve our understanding of the interface effect of high-energy irradiation on TMDC-based nanoelectronic devices.

Proton beam radiotherapy for treatment of functional pituitary adenomas

Proton beam radiotherapy for treatment of functional pituitary adenomas

A study on the effects of long-term radiation exposure on superconducting magnets in MRI-Guided proton therapy

In this publication, we offer the first assessment of the long-term radiation impact on superconducting magnets utilized in MRI-guided proton therapy. We explore both uniform and non-uniform magnetic fields and create three improved therapy plans for shallow (brain), medium (liver), and deep (prostate) targets. The evaluation of radiation damage in superconducting magnets using therapy plans is carried out through the implementation of the Monte Carlo method, molecular dynamics method, and modified NRT model. The results of the three plans show that a large amount of particles do enter the superconducting magnet during the treatment, with a preponderance of photons and neutrons. For superconducting magnets in MRI systems, the closer the coil is to the target area, the greater the radiation damage, and the extent of radiation damage increases with the energy of the incident proton beam. The PKA with high energy can induce temperature fluctuations locally in the superconducting coils, but does not pose a threat to its mechanical properties. Following 20 years of continuous operation, the DPA of the internal coils is about 2.3097E-17, and the maximum dose to insulating layer is about 1.25 Gy. The results of this paper show that MRI-guided proton therapy poses no threat to the long-term operation of superconducting magnets.

Optimal collimation of proton beams accelerated by a Laguerre–Gaussian laser with a proper pulse duration

In this study, three-dimensional particle-in-cell (PIC) simulations were conducted to evaluate a collimated proton beam accelerated by an intense Laguerre–Gaussian (LG) laser with different pulse durations. The flux and energy of the collimated proton beam could be simultaneously enhanced by selecting an optimal pulse duration. This phenomenon can be primarily attributed to the correlation between the LG laser driven self-generated magnetic field and pulse duration, and this correlation enables the collimation of protons during their interaction and transport. The results obtained in this study elucidate the formation mechanism of different collimated proton patterns, driven by femtosecond and picosecond LG lasers, observed in previous experiments. In addition, based on these results, an optimum pulse duration for high-quality proton beams is proposed for various future applications.

Radiophotoluminescence response of LiF:Mg,Ti pellets irradiated with clinical proton beams in the 70–200 MeV energy range

Lithium fluoride doped with Mg and Ti (LiF:Mg,Ti) has been used for several decades as thermoluminescent dosimeter material, but recently also its radiophotoluminescence has been investigated for applications in dosimetry. In this work, LiF:Mg,Ti pellets (TLD-100) were irradiated in a water phantom at CNAO (Pavia, Italy) with therapeutic proton beams at five energies from 70 to 200 MeV in the dose range from 2 to 20 Gy. After irradiation, their visible radiophotoluminescence spectra were measured in controlled conditions and the spectrally-integrated red emission response of radiation-induced color centers has been investigated. The radiophotoluminescence signal, excited by a 445 nm continuous wave laser, was integrated within a 50 nm-wide band around the emission peak of the F2 color centers, located around 670 nm in LiF. The spectrally-integrated signal of the samples irradiated at the energy of 147.7 MeV exhibited a linear dependence with dose. Moreover, this radiophotoluminescence response appears independent from Linear Energy Transfer in the range from 0.8 to 1.6 keV/μm in all the samples irradiated at the dose of 5 Gy. Such independence was found up to 10.3 keV/μm in samples irradiated within two spread out Bragg peaks made of 36 energy components in the entire investigated proton energy range. The radiophotoluminescence response of the TLD-100 pellets was compared to that of nominally-pure LiF crystals irradiated in the same conditions, which show a similar behavior. The results are encouraging for the exploitation of TLD-100 pellets as passive solid-state radiophotoluminescent dosimeters for proton therapy.

Design and optimization of a dedicated Faraday cup for UHDR proton dosimetry: Implementation in a UHDR irradiation station

We describe in detail an Ultra High Dose Rate (UHDR) setup on a 2 MV tandem accelerator for investigating the FLASH effect in radiotherapy. Addressing UHDR dosimetry challenges, we have developed a specialized Faraday Cup (FC) as a dose rate-independent solution. Utilizing Monte Carlo simulations, the geometry and materials used for the FC's design has been optimized for a 4 MeV proton beam. According to the simulations, the virtual error on the charge collection is negligible. This three-part UHDR setup also integrates a beam profiler to ensure the beam homogeneity and an electrostatic chopper to irradiate for precise short times (down to 10 μs), replicating the macro beam structure of typical clinical proton accelerator structures such as the S2C2 and C230 (IBA, Louvain-la-Neuve). The integrated setup ensures dose deposition with an error ≤ 5% for dose rate from 140 to 1000 Gy/s.

High transmission efficiency collection system for laser-accelerated proton beams based on permanent magnet quadrupoles prefocusing

High transmission efficiency collection system for laser-accelerated proton beams based on permanent magnet quadrupoles prefocusing

Abstract PO4-22-03: Intensity Modulated Proton Therapy (IMPT) for the Definitive Adjuvant Management of Women with Breast Cancer: A Single Institutional Experience of 5-Year Oncologic Outcomes

Abstract Purpose: There is limited data reporting the oncologic outcomes of breast cancer patients treated definitively with adjuvant proton beam therapy. Here we report a single institutional experience of oncologic outcomes, treating a predominantly vulnerable breast cancer patient population and compare these to historical standards primarily utilizing photon therapy. Materials and Methods: Unver IRB approval, we retrospectively reviewed 453 definitively treated breast cancer patients from 2016 – 2023 using adjuvant IMPT as part of their cancer care. Patients with recurrent disease, receiving re-irradiation, and those with less than 1-year of follow up were excluded from this analysis. Patients were treated with surgery and systemic therapies as per standards of care. Radiation therapy was administered using pencil beam scanning IMPT with daily image guidance. χ2 and Mann-Whitney U tests were performed to determine differences between select variables. Kaplan-Meier analysis and Cox proportional hazard models were used to analyze overall survival (OS). Results: With a median follow up of 22 months for the entire cohort, 453 patients were treated at XXXX as part of definitive adjuvant management for their breast cancer. Nearly 30% of patients self-identified as black (n=135), average patient age was 54 and 56% (n=255) self-identified as being married with approximately 25% (n=109) of patients having Medicare/Medicaid insurance. 198 patients (43.8%) had an intact breast and the remainder mastectomy of which 37.4% had reconstruction at the time of their radiation. 229 patients (50.7%) received neoadjuvant chemotherapy while 55 patients (12%) received concurrent chemotherapy which was either her2+ directed or Xeloda. The number of patients (%) corresponding to the AJCC 8th edition anatomical staging is as follows: Stage 0: 12 (2.7%); Stage I: 91 (20.1%); Stage 2: 197 (43.6%); Stage 3: 152 (33.6%). Median RT dose delivered for patients receiving comprehensive treatment was 50.4 Gy with 81% of patients receiving a boost to either scar, lumpectomy cavity and/or LN regions. Median RT dose delivered for patients receiving whole breast radiation was 42.56 Gy with a 10 Gy lumpectomy cavity boost. 5-yr OS by stage was 0: 100%; stage I: 98.8%; stage 2: 93.5%; stage 3: 90.8%. Five-year OS for black, white and other race patients were 85.3%, 95.8% and 96%, respectively (White as Ref: HR 3.176, 95% CI: 1.313-7.681, p=0.010 for black patients). For the entire cohort, patients with triple negative disease had a 5-yr OS of 80.4% (HR: 4.33, 95% CI 1.87-10.04, p< 0.001) and there was no difference in OS when insurance status was considered (p=0.378). Conclusions: To the best of our knowledge this represents the largest series of definitively treated breast cancer patients utilizing adjuvant proton therapy and the 5-year OS rates in our analysis coincide with published standards1. Results from the on-going randomized RADCOMP study will provide further guidance as to which patients benefit the most from proton therapy and will further support equivalent oncological outcomes when compared to photon therapy. 1. Weiss A, Chavez-MacGregor M, Lichtensztajn DY, et al. Validation study of the American Joint Committee on Cancer eighth edition prognostic stage compared with the anatomic stage in breast cancer. JAMA Oncol. 4(2):203-209, 2018. Citation Format: Elizabeth Nichols, Gurbani Singh, Desiree Lejano, Sarah McAvoy, Mark Mishra, Melissa Vyfhuis. Intensity Modulated Proton Therapy (IMPT) for the Definitive Adjuvant Management of Women with Breast Cancer: A Single Institutional Experience of 5-Year Oncologic Outcomes [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-22-03.

The burden of skull base chordomas: insights from a meta-analysis of observational studies.

The aim of this study was to provide a quantitative synthesis of the survival outcomes for patients with skull base chordomas, focusing on the role of 1) the extent of resection (gross-total [GTR] vs non-GTR), 2) the type of surgery (primary vs revision), 3) tumor histology, and 4) the different use of adjuvant therapies (proton beam radiotherapy [PBRT], photon radiotherapy [RT], or none). A systematic review with a meta-analysis was conducted following the 2020 PRISMA guidelines. Observational studies describing adult and pediatric patient cohorts harboring skull base chordomas were included. The primary outcome measures were represented by the 5-year overall survival (OS) and progression-free survival (PFS) rates. The main intervention effects were represented by the extent of resection (GTR vs non-GTR), type of surgical excision (primary vs revision surgeries), tumor histology, and the different use of adjuvant therapies (PBRT, RT, or none). The pooled estimates were calculated using random forest models. The risk of bias was evaluated using the Joanna Briggs Institute checklist for case series. Six hundred forty-four studies were identified through a database and register search. After study selection, 51 studies and 3871 patients were included in the meta-analysis. The overall 5-year OS rate was 73%, which increased to 84% among patients undergoing GTR. The overall 5-year PFS rate was 52%, increasing to 74% for patients receiving GTR. The 5-year OS and PFS rates for patients undergoing PBRT were 86% and 71%, compared with 71% and 54% for patients receiving RT, and 55% and 25% when no adjuvant treatments were used. Patients undergoing their first surgery had 2.13-fold greater chances of being disease-free and 1.4-fold greater chances of being alive at 5 years follow-up compared with patients who received a revision surgery. Patients harboring chondroid chordomas had 1.13- and 1.9-fold greater chances of being alive at 5 years compared with patients with conventional and de-differentiated chordomas, respectively. The overall risk of bias was low in the included studies. The results of this comprehensive meta-analysis highlight the tremendous impact of GTR and adjuvant PBRT on improving OS and PFS of patients harboring skull base chordomas, with better survival rates demonstrated for patients with chondroid tumors. Even in experienced hands, the rate of surgical morbidity remains high. Proper management in high-volume centers is mandatory to reach the expected resection goal at the first surgical attempt and to reduce surgical morbidity. The introduction of the endoscopic endonasal approach was related to improved surgical and functional outcomes.

Field tuning study and RF electromagnetic design of a continuous-wave RFQ with ramped inter-vane voltage for AB-BNCT

A compact radio frequency quadrupole (RFQ) linac for accelerator-based boron neutron capture therapy is being developed at Xi'an Jiaotong University. By adopting a ramped inter-vane voltage in the beam dynamics design, the RFQ could accelerate a continuous wave proton beam to 2.6 MeV over a length of 4 m, effectively decreasing costs and saving space. To meet the beam-dynamics requirements, both the vane width and undercut were optimized during the electromagnetic design. In addition, π-mode stabilization loops were included to increase the mode separation, and fixed tuners with varying diameters were installed to obtain close frequency-tuning sensitivity. It was established that the field unflatness can be controlled within ±1.5% when all tuners remain at their nominal insertion depth. Optimized cooling-channel design was completed, and multi-physics analysis was conducted. The water tuning coefficients of the vane and wall channels were analyzed to establish the ability to fine tune the RFQ during operation.

Optimizing radiotherapy strategies for skull base chordoma: a comprehensive meta-analysis and systematic review of treatment modalities and outcomes.

In the treatment of skull base chordoma (SBC) surgery is considered the mainstay approach, and gross-total resection has an established relationship with progression-free survival (PFS) and overall survival (OS). However, the tumor's location often interferes with attempts at complete resection. In this case, surgery for maximal resection followed by high-dose radiotherapy has been demonstrated to be the standard treatment. In this context, various modalities are available, yet no consensus exists on the most effective. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of different radiotherapy modalities for SBC. Following PRISMA guidelines, the authors systematically searched for the treatment of SBC with radiation modalities in the PubMed, Cochrane, Web of Science, and EMBASE databases. Outcomes assessed for each modality were as follows: OS, PFS, local control (LC), and complications. The random-effects model was adopted. A single-proportion analysis with 95% CI was used to measure the effects in single-arm analysis. For the comparative analysis, the OR with 95% CI was used to compare outcome treatment effects. Heterogeneity was assessed using I2 statistics, and statistical significance was defined as p < 0.05. A total of 32 studies comprising 3663 patients, with 2322 patients who were treated with radiotherapeutic modalities, were included. Regarding 5-year OS findings in each modality study, the findings were as follows: in photon fractionated radiotherapy, an estimated rate of 77% (69%-84%, 568 patients); in conventional fractionated radiotherapy, 76% (65%-87%, 517 cases); in proton-based + carbon ion-based radiotherapy, 85% (82%-88%, 622 cases); and in a comparative analysis of proton-based and carbon ion-based therapy, there was an OR of 1.2 (95% CI 0.59-2.43, 306 cases). Regarding the 5-year PFS estimate, the rates were as follows: 35% (26%-45%, 95 cases) for photon fractionated therapy; 35% (25%-45%, 85 cases) for stereotactic radiotherapy; 77% (50%-100%, 180 cases) for proton-based and carbon ion-based radiotherapy; and 74% (45%-100%, 102 cases) for proton-based radiotherapy. Regarding LC in periods of 3 and 5 years after proton- and carbon ion-based therapy, the overall estimated rates were 84% (78%-90%, 326 cases) and 75% (65%-85%, 448 cases), respectively. For proton-based radiotherapy and carbon ion-based therapy, the 5-year LC rates were 76% (67%-86%, 259 cases) and 75% (59%-91%, 189 cases), respectively. The analysis highlights the finding that particle-based modalities like proton beam radiotherapy and carbon ion radiotherapy are the most effective radiation therapies available for the treatment of SBC. Furthermore, it reinforces the idea that surgery followed by radiotherapy constitutes the standard treatment.

Design and beam dynamics simulation of an 8 MeV compact accelerator-driven neutron source

A compact accelerator-driven neutron source is proposed at Sino-French Institute of Nuclear Engineering and Technology, Sun Yat-Sen University, called Sun Yat-Sen University Proton Accelerator Facility (SYSU-PAFA). The proton accelerator is composed of a proton electron cyclotron resonance source, a four-vane radio frequency quadrupole (RFQ), and an alternative phase focusing drift tube linac (APF-DTL). It can accelerate 10 mA proton beam to 8 MeV. Due to the high current, beam matching is particularly important. In order to achieve beam matching between various components, beam transport sections are needed. The beam transport line is divided into three segments. The Low Energy Beam Transport (LEBT) ensures that the beam parameters are matched before entering the RFQ. The Medium Energy Beam Transport (MEBT) segment efficiently transfers the beam between the RFQ and DTL. The High Energy Beam Transport (HEBT) focuses on transporting the beam to the targets. The design goal of beam transport line is as short as possible while ensuring high efficiency of beam transportation. SYSU-PAFA has an overall transmission efficiency of 99%, with optimal transverse matching conditions between beam transport and RFQ or DTL accelerators. The efficient use of solenoids and magnets allows for a compact transmission section, resulting in a total length of 13.6 meters, shorter than most accelerators at the same beam energy. This paper will provide the detailed beam dynamics of the compact accelerator.

Thermal and Structural Analysis on Simulated Model of a Beam Dump

This paper deals with the design, thermal and structural analysis for stopping the proton beam. A conical beam dump is being designed to handle the thermal and structural stresses resulting due to high heat load and hydraulic pressure of coolant, while handling 600 KW proton beam power in CW operation at 20 MeV energy. Pressure drop and heat transfer calculations are done considering spiral channel cooling system. The heat flux has been calculated by using Bi-Gaussian distribution density function of particles in beam. Nickel is selected as the beam dump material because of its favorable properties. In order to understand the thermal performance of beam dump a finite element model has been developed to predict the steady state temperature and stress distributions within the beam stop material. Key Word: Beam dump design, FEM, Thermal and Structural stress.

Cyclotron and linear accelerator generated scanning proton beams for lung cancer SBRT: Interplay effects and mitigations.

Pencil beam scanning (PBS) proton therapy for moving targets is known to be impacted by interplay effects between the scanning beam and organ motion. While respiratory motion in the thoracic region is the major cause for organ motion, interplay effects depend on the delivery characteristics of proton accelerators. To evaluate the impact of different types of PBS proton accelerators and spot sizes on interplay effects, mitigations, and plan quality for Stereotactic Body Radiation Therapy (SBRT) treatment of non-small cell lung cancer (NSCLC). Twenty NSCLC patients treated with photon SBRT were selected to represent varying tumor volumes and respiratory motion amplitudes (median: 0.6cm with abdominal compression) for this retrospective study. For each patient, plans were created using: (1) cyclotron-generated proton beams (CPB) with spot sizes of σ=2.7-7.0mm; (2) linear accelerator proton beams (LPB) (σ=2.9-5.5mm); and (3) linear accelerator proton minibeams (LPMB) (σ=0.9-3.9mm). The energy switching time is one second for CPB, and 0.005 s for LPMB and LPB. Plans were robustly optimized on the gross tumor volume (GTV) using each individual phase of four-dimensional computed tomography (4DCT) scans. Initially, single-field optimization (SFO) plans were evaluated; if the plan quality did not meet the dosimetric requirement, multi-field optimization (MFO) was used. MFO plans were created for all patients for comparisons. For each patient, all plans were normalized to have the same dose received by 99% of the GTV. Interplay effects were evaluated by computing the dose on 10 breathing phases, based on the spot distribution. Volumetric repainting (VR) was performed 2-6 times for each plan. We compared volume receiving 100% of the prescribed dose (V100%RX) of the GTV, and normal lung V20Gy. Twelve of 20 plans can be optimized sufficiently with SFO. SFO plans were less sensitive to the interplay effect compared to MFO plans in terms of target coverage for both LPB and LPMB. The following comparisons showed results utilizing the MFO technique. In the interplay evaluation without repainting, the mean V100%RX of the GTV were 99.42±0.6%, 97.52±3.9%, and 94.49±7.3% for CPB, LPB, and LPMB plans, respectively. Following VR (2 × for CPB; 3 × for LPB; 5 × for LPMB), V100%RX of the GTV were improved (on average) by 0.13%, 1.84%, and 4.63%, respectively, achieving the acceptance criteria of V100%RX>95%. Because of fast energy switch in linear accelerator proton machines, the delivery time for VR plans was the lowest for LPB plans, while delivery time for LPMB was on average 1 min longer than CPB plans. The advantage of small spot machines was better sparing in normal lung V20Gy, even when VR was applied. In the absence of repainting, proton machines with large spot sizes generated more robust plans against interplay effects. The number of VR increased with decreasing spot sizes to achieve the acceptance criteria. VR improved the plan robustness against interplay effects for modalities with small spot sizes and fast energy changes, preserving the low dose sparing aspect of the LPMB, even when motion is included.

Proton Beam Radiotherapy as a Curative Alternative to Radiofrequency Ablation for Newly Diagnosed Hepatocellular Carcinoma.

This study aimed to compare the oncological outcomes of proton beam radiotherapy (PBT) with those of radiofrequency ablation (RFA) for newly diagnosed hepatocellular carcinoma (HCC). This study included 323 patients who underwent PBT (n=40) or RFA (n=283) as a curative treatment for previously untreated HCC between October 2016 and June 2021. The primary endpoints were local progression and toxicity. The median follow-up was 3.4 years (range=1.1-5.7 years). In terms of portal vein tumor thrombosis, tumor size, alpha-fetoprotein, and prothrombin-induced by vitamin K absence-II, the PBT group had significantly more severe tumor burdens than those of the RFA group (p<0.0001, p<0.0001, p=0.0004, and p<0.0001, respectively). No significant difference was observed in cumulative local progression rate (10.4% in PBT vs. 7.8% in RFA at 3-years, p=0.895). Grade 3 or higher toxicity was reported in only one patient (0.4%) after RFA. Multivariable analysis demonstrated that treatment modality was not a significant prognostic factor for local progression (hazard ratio=1.05; 95% confidence interval=0.32-3.48; p=0.934). PBT demonstrated comparable local control with acceptable toxicity to RFA in newly diagnosed HCC. Therefore, PBT may be a valid alternative.

Proton Therapy in Non-Rhabdomyosarcoma Soft Tissue Sarcomas of Children and Adolescents.

This paper provides insights into the use of Proton Beam Therapy (PBT) in pediatric patients with non-rhabdomyosarcoma soft tissue sarcomas (NRSTS). NRSTS are a heterogeneous group of rare and aggressive mesenchymal extraskeletal tumors, presenting complex and challenging clinical management scenarios. The overall survival rate for patients with NRSTS is around 70%, but the outcome is strictly related to the presence of various variables, such as the histological subtype, grade of malignancy and tumor stage at diagnosis. Multimodal therapy is typically considered the preferred treatment for high-grade NRSTS. Radiotherapy plays a key role in the treatment of children and adolescents with NRSTS. However, the potential for radiation-induced side effects partially limits its use. Therefore, PBT represents a very suitable therapeutic option for these patients. The unique depth-dose characteristics of protons can be leveraged to minimize doses to healthy tissue significantly, potentially allowing for increased tumor doses and enhanced preservation of surrounding tissues. These benefits suggest that PBT may improve local control while reducing toxicity and improving quality of life. While clear evidence of therapeutic superiority of PBT over other modern photon techniques in NRSTS is still lacking-partly due to the limited data available-PBT can be an excellent treatment option for young patients with these tumors. A dedicated international comprehensive collaborative approach is essential to better define its role within the multidisciplinary management of NRSTS. Shared guidelines for PBT indications-based on the patient's age, estimated outcome, and tumor location-and centralization in high-level referral centers are needed to optimize the use of resources, since access to PBT remains a challenge due to the limited number of available proton therapy facilities.

Prompt gamma timing for proton range verification with TlBr and TlCl as pure Cherenkov emitters.

Objective.Prompt gamma timing (PGT) uses the detection time of prompt gammas emitted along the proton track in proton radiotherapy to verify Bragg peak positioning. Cherenkov detectors offer the possibility of enhanced signal-to-noise ratio (SNR) due to Cherenkov physics which enhances detection of high energy prompt gamma rays relative to other induced uncorrelated signals. In this work, the PGT technique was applied to 3 semiconductor materials that emit only Cherenkov light: a 3x3x20 mm3TlBr, a 12x12x12 mm3TlBr, and a 5x5x5 mm3 TlCl.Approach.A polymethyl methacrylate (PMMA) target was exposed to a 67.5 MeV, 0.5-nA proton beam and shifted in 3-mm increments at the Crocker Nuclear Laboratory (CNL) in Davis, CA, USA. A fast plastic scintillator coupled to a PMT provided the start reference for the proton time of flight (TOF). TOF distributions were generated using this reference and the gamma ray timestamp in the Cherenkov detector.Main results.The SNR of the proton correlated peaks relative to the background was 20, 29, and 30 for each of the three samples, respectively. The upper limit of the position resolutions with the TlCl sample were 2 mm, 3 mm, and 5 mm for 30k, 10k, and 5k detected events, respectively. The time distribution of events with respect to the reference reproduced with clarity the periodicity of the beam, implying a very high SNR of the Cherenkov crystals to detect prompt-gammas. Background presence from the neutron-induced continuum, prompt-gammas from deuterium, or positron activation were not observed. Material choice and crystal dimensions did not seem to affect significantly the outcome of the results.Significance.These results show the high SNR of the pure Cherenkov emitters TlBr and TlCl for the detection of prompt-gammas in a proton beam with current of clinical significance and their potential for verifying the proton range.