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21 pages, 7112 KB  
Article
A Two-Plane Proton Radiography System Using ATLAS IBL Pixel-Detector Modules
by Hendrik Speiser, Claus Maximillian Bäcker, Johannes Esser, Alina Hild, Marco Iampieri, Ann-Kristin Lüvelsmeyer, Annsofie Tappe, Helen Thews, Kevin Kröninger and Jens Weingarten
Instruments 2025, 9(4), 23; https://doi.org/10.3390/instruments9040023 - 14 Oct 2025
Abstract
Accurate knowledge of a patient’s anatomy during every treatment fraction in proton therapy is an important prerequisite to ensure a correct dose deposition in the target volume. Adaptive proton therapy aims to detect those changes and adjust the treatment plan accordingly. One way [...] Read more.
Accurate knowledge of a patient’s anatomy during every treatment fraction in proton therapy is an important prerequisite to ensure a correct dose deposition in the target volume. Adaptive proton therapy aims to detect those changes and adjust the treatment plan accordingly. One way to trigger a daily re-planning of the treatment is to take a proton radiograph from the beam’s-eye view before the treatment to check for possible changes in the water equivalent thickness (WET) along the path due to daily changes in the patient’s anatomy. In this paper, the Two-Plane Imaging System (TPIS) is presented, comprising two ATLAS IBL silicon pixel-detector modules developed for the tracking detector of the ATLAS experiment at CERN. The prototype of the TPIS is described in detail, and proof-of-principle WET images are presented, of two-step phantoms and more complex phantoms with bone-like inlays (WET 10 to 40mm). This study shows the capability of the TPIS to measure WET images with high precision. In addition, the potential of the TPIS to accurately determine WET changes over time down to 1mm between subsequently taken WET images of a changing phantom is shown. This demonstrates the possible application of the TPIS and ATLAS IBL pixel-detector module in adaptive proton therapy. Full article
(This article belongs to the Special Issue Medical Applications of Particle Physics, 2nd Edition)
19 pages, 4096 KB  
Review
Review of VHEE Beam Energy Evolution for FLASH Radiation Therapy Under Ultra-High Dose Rate (UHDR) Dosimetry
by Nikolaos Gazis and Evangelos Gazis
Quantum Beam Sci. 2025, 9(4), 29; https://doi.org/10.3390/qubs9040029 - 9 Oct 2025
Viewed by 194
Abstract
Very-high-energy electron (VHEE) beams, ranging from 50 to 300 or 400 MeV, are the subject of intense research investigation, with considerable interest concerning applications in radiation therapy due to their accurate energy deposition into large and deep-seated tissues, sharp beam edges, high sparing [...] Read more.
Very-high-energy electron (VHEE) beams, ranging from 50 to 300 or 400 MeV, are the subject of intense research investigation, with considerable interest concerning applications in radiation therapy due to their accurate energy deposition into large and deep-seated tissues, sharp beam edges, high sparing properties, and minimal radiation effects on normal tissues. The very-high-energy electron beam, which ranges from 50 to 400 MeV, and Ultra-High-Energy Electron beams up to 1–2 GeV, are considered extremely effective for human tumor therapy while avoiding the spatial requirements and cost of proton and heavy ion facilities. Many research laboratories have developed advanced testing infrastructures with VHEE beams in Europe, the USA, Japan, and other countries. These facilities aim to accelerate the transition to clinical application, following extensive simulations for beam transport that support preclinical trials and imminent clinical deployment. However, the clinical implementation of VHEE for FLASH radiation therapy requires advances in several areas, including the development of compact, stable, and efficient accelerators; the definition of sophisticated treatment plans; and the establishment of clinically validated protocols. In addition, the perspective of VHEE for accessing ultra-high dose rate (UHDR) dosimetry presents a promising procedure for the practical integration of FLASH radiotherapy for deep tumors, enhancing normal tissue sparing while maintaining the inherent dosimetry advantages. However, it has been proven that a strong effort is necessary to improve the main operational accelerator conditions, ensuring a stable beam over time and across space, as well as compact infrastructure to support the clinical implementation of VHEE for FLASH cancer treatment. VHEE-accessing ultra-high dose rate (UHDR) perspective dosimetry is integrated with FLASH radiotherapy and well-prepared cancer treatment tools that provide an advantage in modern oncology regimes. This study explores technological progress and the evolution of electron accelerator beam energy technology, as simulated by the ASTRA code, for developing VHEE and UHEE beams aimed at medical applications. FLUKA code simulations of electron beam provide dose distribution plots and the range for various energies inside the phantom of PMMA. Full article
(This article belongs to the Section Instrumentation and Facilities)
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13 pages, 2731 KB  
Article
Suitability of Polyacrylamide-Based Dosimetric Gel for Proton and Carbon Ion Beam Geometric Characterization
by Riccardo Brambilla, Luca Trombetta, Gabriele Magugliani, Stefania Russo, Alessia Bazani, Eleonora Rossi, Eros Mossini, Elena Macerata, Francesco Galluccio, Mario Mariani and Mario Ciocca
Gels 2025, 11(10), 794; https://doi.org/10.3390/gels11100794 - 2 Oct 2025
Viewed by 213
Abstract
Experimental measurement of dose distributions is a pivotal step in the quality assurance of radiotherapy treatments, especially for those relying on high delivery accuracy such as hadron therapy. This study investigated the response of a polymer gel dosimeter to determine its suitability in [...] Read more.
Experimental measurement of dose distributions is a pivotal step in the quality assurance of radiotherapy treatments, especially for those relying on high delivery accuracy such as hadron therapy. This study investigated the response of a polymer gel dosimeter to determine its suitability in performing geometric beam characterizations for hadron therapy under high-quenching conditions. Different extraction energies of proton and carbon ion beams were considered. Gel dose–response linearity and long-term stability were confirmed through optical measurements. Gel phantoms were irradiated with pencil beams and analyzed via magnetic resonance imaging. A multi-echo T2-weighted sequence was used to reconstruct depth–dose profiles and transversal distributions acquired by the gels, which were benchmarked against reference data. As expected, a response-quenching effect in the Bragg peak region was noted. Nonetheless, the studied gel formulation proved reliable in acquiring the geometric characteristics of the beams, even without correcting for the quenching effect. Indeed, depth–dose distributions acquired by the gels showed an excellent agreement with measured particle range with respect to reference values, with mean discrepancies of 0.5 ± 0.2 mm. Single-spot transverse FWHM values at increasing depths also presented an average agreement within 1 mm with values determined with radiochromic films, thus supporting the excellent spatial resolving capabilities of the dosimetric gel. Full article
(This article belongs to the Special Issue Application of Gel Dosimetry)
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37 pages, 437 KB  
Review
Role of Radiation Therapy for Biliary Tract Cancers
by Molly A. Chakraborty, Ritesh Kumar, Brett L. Ecker, Haejin In, Russell C. Langan, Mariam Eskander and Salma K. Jabbour
Curr. Oncol. 2025, 32(10), 545; https://doi.org/10.3390/curroncol32100545 - 28 Sep 2025
Viewed by 259
Abstract
Biliary tract cancers include cholangiocarcinoma, gallbladder cancer, and ampullary cancer. Although overall rare, the incidence is increasing globally, particularly the subset of intrahepatic cholangiocarcinoma. Surgery is currently considered to be the only curative treatment approach; however, survival outcomes after surgery remain poor. Moreover, [...] Read more.
Biliary tract cancers include cholangiocarcinoma, gallbladder cancer, and ampullary cancer. Although overall rare, the incidence is increasing globally, particularly the subset of intrahepatic cholangiocarcinoma. Surgery is currently considered to be the only curative treatment approach; however, survival outcomes after surgery remain poor. Moreover, many patients already have advanced-stage, unresectable disease at the time of diagnosis. Herein, we will review the role of adjuvant radiotherapy to improve local control after surgery, the role of neoadjuvant radiotherapy to increase the proportion of patients able to undergo surgery, and the use of definitive/palliative radiotherapy to provide local control/symptom relief for patients who have inoperable disease. Most studies observed a survival benefit associated with radiotherapy, with the strongest evidence for those with high-risk disease features (e.g., positive surgical margins, lymph node involvement). However, due to the low incidence of biliary tract cancers, most existing studies are retrospective; there is very limited randomized data and prospective studies tend to have small sample sizes, underscoring the need for more high-quality research on radiotherapy for biliary tract cancers. As some studies show evidence of a dose-dependent response, further investigation into the delivery of dose-escalated radiotherapy with modern techniques such as proton therapy is warranted. Full article
(This article belongs to the Special Issue Biliary Tract Cancer Updates: Advancements and Insights)
28 pages, 3057 KB  
Article
Proton Interactions with Biological Targets: Inelastic Cross Sections, Stopping Power, and Range Calculations
by Camila Strubbia Mangiarelli, Verónica B. Tessaro, Michaël Beuve and Mariel E. Galassi
Atoms 2025, 13(10), 83; https://doi.org/10.3390/atoms13100083 - 24 Sep 2025
Viewed by 325
Abstract
Proton therapy enables precise dose delivery to tumors while sparing healthy tissues, offering significant advantages over conventional radiotherapy. Accurate prediction of biological doses requires detailed knowledge of radiation interactions with biological targets, especially DNA, a key site of radiation-induced damage. While most biophysical [...] Read more.
Proton therapy enables precise dose delivery to tumors while sparing healthy tissues, offering significant advantages over conventional radiotherapy. Accurate prediction of biological doses requires detailed knowledge of radiation interactions with biological targets, especially DNA, a key site of radiation-induced damage. While most biophysical models (LEM, mMKM, NanOx) rely on water as a surrogate, this simplification neglects the complexity of real biomolecules. In this work, we calculate the stopping power and range of protons in liquid water, dry DNA, and hydrated DNA using semi-empirical cross sections for ionization, electronic excitation, electron capture, and electron loss by protons and neutral hydrogen in the 10 keV–100 MeV energy range. Additionally, ionization cross sections for uracil are computed to explore potential differences between DNA and RNA damage. Our results show excellent agreement with experimental and ab initio data, highlighting significant deviations in stopping power and range between water and DNA. Notably, the stopping power of DNA exceeds that of water at most energies, reducing proton ranges in dry and hydrated DNA by up to 20% and 26%, respectively. These findings provide improved input for Monte Carlo simulations and biophysical models, enhancing RBE predictions and dose accuracy in hadrontherapy. Full article
(This article belongs to the Section Atomic, Molecular and Nuclear Spectroscopy and Collisions)
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18 pages, 1346 KB  
Review
Understanding and Exacerbating the Biological Response of Uveal Melanoma to Proton Beam Therapy
by Laura Hawkins, Helen Kalirai, Karen Aughton, Rumana N. Hussain, Sarah E. Coupland and Jason L. Parsons
Cancers 2025, 17(19), 3104; https://doi.org/10.3390/cancers17193104 - 24 Sep 2025
Viewed by 354
Abstract
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, associated with a high tendency for metastasis to the liver. Proton beam therapy (PBT) is the preferred external radiotherapy treatment for primary UM of certain sizes and locations in the eye, [...] Read more.
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, associated with a high tendency for metastasis to the liver. Proton beam therapy (PBT) is the preferred external radiotherapy treatment for primary UM of certain sizes and locations in the eye, due to its efficacy and good local tumour control, as well as its precision to spare surrounding ocular structures. PBT is an effective alternative to surgical enucleation and other non-precision-targeted radiotherapies. Despite this, the radiobiology of UM in response to PBT is still not fully understood. This enhanced knowledge would help to further optimise UM treatment and improve patient outcomes through reducing radiation dosage to ocular structures, treating larger tumours that would otherwise require enucleation, or even offering a treatment strategy for the otherwise fatal liver metastases. In this review, we explore current knowledge of the treatment of UM with PBT, evaluating the biological responses to the therapy. Molecular factors, such as tumour size, oxygen tension levels, DNA damage proficiency, and autophagy, are known to influence the cellular response to radiotherapy, and these will be discussed. Furthermore, we examine innovative strategies to enhance radiotherapy outcomes, such as combination therapies with DNA damage repair and autophagy modulators, as well as advancements in PBT planning and delivery. By integrating current research and emerging technologies, we aim to provide opportunities to improve the therapeutic effectiveness of PBT in UM management. Full article
(This article belongs to the Special Issue Advances in Uveal Melanoma)
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30 pages, 387 KB  
Review
Radiotherapeutic Modalities and Advancements in the Treatment of Cutaneous Malignancies
by Noor Malik, Irini Yacoub, Kristin Hsieh, J. Isabelle Choi, Arpit Chhabra and Charles B. Simone
J. Clin. Med. 2025, 14(18), 6547; https://doi.org/10.3390/jcm14186547 - 17 Sep 2025
Viewed by 569
Abstract
Cutaneous malignancies represent the most common cancers worldwide and pose a growing public health burden. While surgical excision remains the primary curative modality, radiotherapy offers an effective adjuvant therapy for high-risk histopathologic features and an established, organ-preserving alternative for patients with inoperable disease [...] Read more.
Cutaneous malignancies represent the most common cancers worldwide and pose a growing public health burden. While surgical excision remains the primary curative modality, radiotherapy offers an effective adjuvant therapy for high-risk histopathologic features and an established, organ-preserving alternative for patients with inoperable disease or lesions in cosmetically or functionally sensitive sites. Advances in radiotherapeutic techniques, including brachytherapy and proton therapy, have expanded the therapeutic armamentarium, allowing tailored treatment based on tumor depth, extent, and anatomical location. Contemporary evidence highlights favorable local control and toxicity outcomes with modern radiation therapy approaches, yet data remain fragmented, with most studies limited by small cohorts, heterogeneous methodologies, and limited follow-up durations. Furthermore, the role of radiotherapy in complex scenarios, such as perineural invasion, recurrent disease, and previously irradiated fields, continues to evolve. This review synthesizes the current literature on radiotherapeutic management of skin cancer, critically evaluates dosimetric and clinical outcomes across modalities, and identifies key gaps in evidence. Emphasis is placed on the need for prospective, multicenter investigations to better define comparative effectiveness, optimize dose-fractionation regimens, and integrate emerging technologies into clinical practice. Radiotherapy remains an indispensable modality in dermatological oncology, offering curative potential with preservation of cosmesis and function, yet its optimal utilization demands further high-quality research to refine patient selection and therapeutic strategies. Full article
(This article belongs to the Special Issue Skin Cancer: Prevention, Diagnosis and Treatment)
10 pages, 249 KB  
Review
When a Sellar Mass Is Not a Pituitary Adenoma: A Literature Review and Lessons from a Case of Pituicytoma
by Maria Petersson and Charlotte Höybye
Endocrines 2025, 6(3), 45; https://doi.org/10.3390/endocrines6030045 - 10 Sep 2025
Viewed by 785
Abstract
Background: Pituicytomas are rare, low-grade gliomas arising from pituicytes in the posterior pituitary or infundibulum. Due to its rarity and nonspecific clinical and radiological characteristics, it is frequently misdiagnosed as pituitary adenomas or other sellar tumors. Aims: To present an overview of pituicytoma, [...] Read more.
Background: Pituicytomas are rare, low-grade gliomas arising from pituicytes in the posterior pituitary or infundibulum. Due to its rarity and nonspecific clinical and radiological characteristics, it is frequently misdiagnosed as pituitary adenomas or other sellar tumors. Aims: To present an overview of pituicytoma, including clinical presentation, radiological and histopathological characteristics, differential diagnosis and treatment strategies, illustrated by a case report. Methods: A literature review was conducted to contextualize our patient with a sellar tumor, and to highlight key diagnostic and therapeutic considerations. Results/Case report: A 12-year-old boy presented with visual disturbances. MRI revealed a well-defined contrast-enhancing sellar mass, and the patient underwent transsphenoidal surgery. The diagnosis was assumed to be a nonfunctioning pituitary adenoma (NFPA). Two years later a residual tumor was treated with proton irradiation. Six years after the radiotherapy, the patient had epistaxis. Imaging showed a tumor in the sphenoidale sinus, which was surgically resected. The tumor had histopathological features of pituicytoma and immunoreactivity for TTF-1 and S100. The tissue from the first operation was reviewed, showing more characteristics with pituicytoma than NFPA, leading to re-definition of the initial diagnosis. Follow-up has been without any signs of residual tumor. Conclusion: Our case and literature review emphasize the importance of considering pituicytoma in the differential diagnosis among sellar lesions. The diagnosis relies on a combination of preoperative imaging, intraoperative findings and histopathology. Pituitary surgery is the first-line treatment, and the outcome is generally good. Increased awareness of pituicytomas is necessary to improve preoperative diagnostic accuracy and guide appropriate management. Full article
(This article belongs to the Section Neuroendocrinology and Pituitary Disorders)
15 pages, 3262 KB  
Article
Comparison of a Multi-Scenario Robustness Evaluation Method with Measurements for Proton Teletherapy
by Qiangxing Yang, Michael F. Moyers and Zhuangming Shen
Cancers 2025, 17(17), 2927; https://doi.org/10.3390/cancers17172927 - 6 Sep 2025
Viewed by 1600
Abstract
Background/Objectives: Multi-scenario calculational methods have been used to evaluate proton teletherapy plan robustness but few studies have been performed to determine the accuracy of these calculational methods. This study evaluates a multi-scenario method by comparing calculations to measurements made in phantoms that [...] Read more.
Background/Objectives: Multi-scenario calculational methods have been used to evaluate proton teletherapy plan robustness but few studies have been performed to determine the accuracy of these calculational methods. This study evaluates a multi-scenario method by comparing calculations to measurements made in phantoms that simulate the effects of possible uncertainties. Methods: Plans were made using four phantoms in which the delivered dose was highly sensitive to positional and penetration uncertainties. The effects of alignment and penetration uncertainties on the dose distributions of each of those phantoms were simulated by performing calculations using nine different uncertainty scenarios and comparing the calculations to measurements with induced physical alignment displacements. Measured dose distributions were obtained by exposing films placed inside the phantoms and extracting multiple linear profiles. The maximum and minimum doses obtained for each of the calculational scenarios were compared with the measured dose profiles. In addition, comparisons of DVHs for nominal and uncertainty scenarios were performed. Results: The results showed that, under the influence of uncertainties, the minimum dose for the four phantoms decreased by more than 20 Gy, the V95% coverage fluctuated by more than 10%, but the maximum dose parameter changed by less than 5 Gy. This was expected, as no margins for uncertainties were applied around the targets. The envelope bounded by the maximum and minimum possible calculated doses contained most of the measurements, although the shapes of the dose profiles displayed some mismatches for wedge and head phantoms. There were a few points where the measured maximum dose for bone and lung slab phantom cases was slightly higher than the maximum dose calculated from the nine scenarios. Conclusions: This study demonstrates that a nine-scenario method can adequately evaluate the robustness of simple mono-directional plans containing heterogeneities. Full article
(This article belongs to the Special Issue The Advance of Pencil Beam Scanning Proton Beam Therapy in Cancers)
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20 pages, 634 KB  
Review
Radar Technologies in Motion-Adaptive Cancer Radiotherapy
by Matteo Pepa, Giulia Sellaro, Ganesh Marchesi, Anita Caracciolo, Arianna Serra, Ester Orlandi, Guido Baroni and Andrea Pella
Appl. Sci. 2025, 15(17), 9670; https://doi.org/10.3390/app15179670 - 2 Sep 2025
Viewed by 565
Abstract
Intra-fractional respiratory management represents one of the greatest challenges of modern cancer radiotherapy (RT), as significant breathing-induced lesion motion might affect target coverage and organs at risk (OARs) sparing, jeopardizing oncological and toxicity outcomes. The detrimental effects on dosage of uncompensated organ motion [...] Read more.
Intra-fractional respiratory management represents one of the greatest challenges of modern cancer radiotherapy (RT), as significant breathing-induced lesion motion might affect target coverage and organs at risk (OARs) sparing, jeopardizing oncological and toxicity outcomes. The detrimental effects on dosage of uncompensated organ motion are exacerbated in RT with charged particles (e.g., protons and carbon ions), due to their higher ballistic selectivity. The simplest strategies to counteract this phenomenon are the use of larger treatment margins and reductions in or control of respiration (e.g., by means of compression belts, breath hold). Gating and tracking, which synchronize beam delivery with the respiratory signal, also represent widely adopted solutions. When tracking the tumor itself or surrogates, invasive procedures (e.g., marker implantation), an unnecessary imaging dose (e.g., in X-ray-based fluoroscopy), or expensive equipment (e.g., magnetic resonance imaging, MRI) is usually required. When chest and abdomen excursions are measured to infer internal tumor displacement, the additional devices needed to perform this task, such as pressure sensors or surface cameras, present inherent limitations that can impair the procedure itself. In this context, radars have intrigued the radiation oncology community, being inexpensive, non-invasive, contactless, and insensitive to obstacles. Even if real-world clinical implementation is still lagging behind, there is a growing body of research unraveling the potential of these devices in this field. The purpose of this narrative review is to provide an overview of the studies that have delved into the potential of radar-based technologies for motion-adaptive photon and particle RT applications. Full article
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27 pages, 415 KB  
Review
Radiotherapy in Glioblastoma Multiforme: Evolution, Limitations, and Molecularly Guided Future
by Castalia Fernández, Raquel Ciérvide, Ana Díaz, Isabel Garrido and Felipe Couñago
Biomedicines 2025, 13(9), 2136; https://doi.org/10.3390/biomedicines13092136 - 1 Sep 2025
Viewed by 1817
Abstract
Glioblastoma multiforme (GBM), the most aggressive primary brain tumor in adults, has a poor prognosis due to rapid recurrence and treatment resistance. This review examines the evolution of radiotherapy (RT) for GBM management, from whole-brain RT to modern techniques like intensity-modulated RT (IMRT) [...] Read more.
Glioblastoma multiforme (GBM), the most aggressive primary brain tumor in adults, has a poor prognosis due to rapid recurrence and treatment resistance. This review examines the evolution of radiotherapy (RT) for GBM management, from whole-brain RT to modern techniques like intensity-modulated RT (IMRT) and volumetric modulated arc therapy (VMAT), guided by 2023 European Society for Radiotherapy and Oncology (ESTRO)-European Association of Neuro-Oncology (EANO) and 2025 American Society for Radiation Oncology (ASTRO) recommendations. The standard Stupp protocol (60 Gy/30 fractions with temozolomide [TMZ]) improves overall survival (OS) to 14.6 months, with greater benefits in O6-methylguanine-DNA methyltransferase (MGMT)-methylated tumors (21.7 months). Tumor Treating Fields (TTFields) extend median overall survival (mOS) to 31.6 months in MGMT-methylated patients and 20.9 months overall in supratentorial GBM (EF-14 trial). However, 80–90% of recurrences occur within 2 cm of the irradiated field due to tumor infiltration and radioresistance driven by epidermal growth factor receptor (EGFR) amplification, phosphatase and tensin homolog (PTEN) mutations, cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletions, tumor hypoxia, and tumor stem cells. Pseudoprogression, distinguished using Response Assessment in Neuro-Oncology (RANO) criteria and positron emission tomography (PET), complicates response evaluation. Targeted therapies (e.g., bevacizumab; PARP inhibitors) and immunotherapies (e.g., pembrolizumab; oncolytic viruses), alongside advanced imaging (multiparametric magnetic resonance imaging [MRI], amino acid PET), support personalized RT. Ongoing trials evaluating reirradiation, hypofractionation, stereotactic radiosurgery, neoadjuvant therapies, proton therapy (PT), boron neutron capture therapy (BNCT), and AI-driven planning aim to enhance efficacy for GBM IDH-wildtype, but phase III trials are needed to improve survival and quality of life. Full article
(This article belongs to the Special Issue Glioblastoma: From Pathophysiology to Novel Therapeutic Approaches)
19 pages, 554 KB  
Review
Carbon-Ion Radiotherapy for Hepatocellular Carcinoma: Current Status and Future Prospects: A Narrative Review
by Reina Sasaki-Tanaka, Hiroyuki Abe, Tomoaki Yoshida, Yusuke Watanabe, Naruhiro Kimura, Takeshi Yokoo, Akira Sakamaki, Hiroteru Kamimura, Kenya Kamimura, Tatsuo Kanda and Shuji Terai
J. Clin. Med. 2025, 14(17), 6107; https://doi.org/10.3390/jcm14176107 - 29 Aug 2025
Viewed by 1471
Abstract
Because hepatocellular carcinoma (HCC) is a radiosensitive cancer, radiation therapy has been used for the treatment of HCC; however, external beam therapies are currently not described in most of the guidelines for the treatment of HCC. External beam therapies include photon beam therapies [...] Read more.
Because hepatocellular carcinoma (HCC) is a radiosensitive cancer, radiation therapy has been used for the treatment of HCC; however, external beam therapies are currently not described in most of the guidelines for the treatment of HCC. External beam therapies include photon beam therapies and particle beam therapies, which are composed of X-rays or gamma rays and beams of carbon ions or protons, respectively. The focus of this narrative review is carbon-ion radiotherapy (C-ion RT). C-ion RT is well tolerated by elderly patients with HCC and/or sarcopenic patients. In general, a single HCC greater than 30 mm is a good indication for C-ion RT in patients with Child Grade A/B or ALBI Grade 1/2. The local control rates and overall survival rates at 5 years after C-ion RT for HCCs larger than 30 mm are excellent, with fewer adverse events, such as radiation-induced liver damage. Advanced HCC with portal vein tumor thrombus is also an indication for C-ion RT in certain selected patients. C-ion RT is a promising therapeutic option for patients with HCC. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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14 pages, 1010 KB  
Review
The Use of Particle Radiotherapy and Radiation Sensitizers for Treatment of Chordomas: A Narrative Review
by Aarti Kishore Jain, Sahdev S. Baweja, Beatrice Campilan, Madison J. Michles, Aviva Berkowitz and Patricia L. Zadnik Sullivan
Targets 2025, 3(3), 28; https://doi.org/10.3390/targets3030028 - 15 Aug 2025
Viewed by 619
Abstract
Chordomas are primary tumors of the skull base and vertebral column typically derived from the notochord. Treatment options consist of surgical resection, radiotherapy, and chemotherapy. This study reviews clinical trials focused on radiotherapy techniques, such as photon therapy and carbon ion radiotherapy, as [...] Read more.
Chordomas are primary tumors of the skull base and vertebral column typically derived from the notochord. Treatment options consist of surgical resection, radiotherapy, and chemotherapy. This study reviews clinical trials focused on radiotherapy techniques, such as photon therapy and carbon ion radiotherapy, as well as the concomitant use of radia-tion sensitizers. We completed a literature review on all published clinical trials on the usage of photon, proton, and carbon ion radiotherapy (CIRT) for chordoma in adults and all published literature on radiation sensitizers used for treatment in chordoma from 2000 to 2025. We reviewed all nine current clinical trials on radiotherapy for chordoma in adults. All clinical trials were able to achieve an overall survival rate above 50% at 3-year follow-up. Seven publications were found on the use of radiation sensitizers for chordomas, both in vitro and in vivo. The completed clinical trials evaluate the effectiveness of proton, photon, and CIRT for treatment of the skull base, spine, and sacral chordoma. Current trials continue these efforts and compare the different radiotherapies and determine appropriate doses. Research on radiation sensitizers for chordomas shows various therapies, ranging from hyperthermia to pharmaceutical options, that require further study. Full article
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25 pages, 5913 KB  
Article
Retrieving Proton Beam Information Using Stitching-Based Detector Technique and Intelligent Reconstruction Algorithms
by Chi-Wen Hsieh, Hong-Liang Chang, Yi-Hsiang Huang, Ming-Che Lee and Yu-Jen Wang
Sensors 2025, 25(16), 4985; https://doi.org/10.3390/s25164985 - 12 Aug 2025
Viewed by 465
Abstract
In view of the great need for quality assurance in radiotherapy, this paper proposes a stitching-based detector (SBD) technique and a set of intelligent algorithms that can reconstruct the information of projected particle beams. The reconstructed information includes the intensity, sigma value, and [...] Read more.
In view of the great need for quality assurance in radiotherapy, this paper proposes a stitching-based detector (SBD) technique and a set of intelligent algorithms that can reconstruct the information of projected particle beams. The reconstructed information includes the intensity, sigma value, and location of the maximum intensity of the beam under test. To verify the effectiveness of the proposed technique and algorithms, this research study adopts the pencil beam scanning (PBS) form of proton beam therapy (PBT) as an example. Through the SBD technique, it is possible to utilize 128 × 128 ionization chambers, which constitute an ionization plate of 25.6 cm2, with an acceptable number of 4096 analog-to-digital converters (ADCs) and a resolution of 0.25 mm. Through simulation, the proposed SBD technique and intelligent algorithms are proven to exhibit satisfactory and practical performance. By using two kinds of maximum intensity definitions, sigma values ranging from 10 to 120, and two definitions in an erroneous case, the maximum error rate is found to be 3.95%, which is satisfactorily low. Through analysis, this research study discovers that most errors occur near the symmetrical and peripheral boundaries. Furthermore, lower sigma values tend to aggravate the error rate because the beam becomes more like an ideal particle, which leads to greater imprecision caused by symmetrical sensor structures as its sigma is reduced. However, because proton beams are normally not projected onto the border region of the sensed area, the error rate in practice can be expected to be even lower. Although this research study adopts PBS PBT as an example, the proposed SBD technique and intelligent algorithms are applicable to any type of particle beam reconstruction in the field of radiotherapy, as long as the particles under analysis follow a Gaussian distribution. Full article
(This article belongs to the Section Biomedical Sensors)
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14 pages, 2557 KB  
Article
An In Silico Feasibility Study of Dose-Escalated Hypofractionated Proton Therapy for Rectal Cancer
by Erik Almhagen, Ali Alkhiat, Bruno Sorcini, Freja Alpsten, Camilla J. S. Kronborg, Heidi S. Rønde, Marianne G. Guren, Sara Pilskog and Alexander Valdman
Cancers 2025, 17(16), 2627; https://doi.org/10.3390/cancers17162627 - 11 Aug 2025
Viewed by 772
Abstract
Background/Objectives: The current standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy, or total neoadjuvant therapy (TNT), followed by total mesorectal excision (TME). If the neoadjuvant treatment results in a clinical complete response (cCR), non-operative management of LARC might be [...] Read more.
Background/Objectives: The current standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy, or total neoadjuvant therapy (TNT), followed by total mesorectal excision (TME). If the neoadjuvant treatment results in a clinical complete response (cCR), non-operative management of LARC might be possible. It is hypothesized that cCR rates will increase with increasing radiotherapy doses. By using proton therapy, doses to organs at risk (OAR) may be decreased. In preparation for a clinical trial on dose-escalated proton therapy for LARC, the purpose of this study is to establish the feasibility of proton therapy for dose-escalated hypofractionated radiotherapy of LARC. Methods: Ten patients, having previously received short course radiotherapy (SCRT) for LARC, were included in this planning study. Two photon plans and two proton plans were created for each patient: one with a standard 5 × 5 Gy fractionation and one dose-escalated up to 5 × 7 Gy. Proton plans were robustly optimized. For all plans the integral dose (ID) was computed, and for the proton plans relative biological effectiveness (RBE) distributions were calculated. Feasibility was assessed in terms of target coverage and OAR doses. Results: All treatment plans satisfied target coverage criteria. Three of the photon and two of the proton dose-escalated plans exceeded recommended OAR objectives. Proton IDs were on average lower by a factor of 1.97 compared to photon IDs. Mean doses to OAR were, in general, lower for protons. All proton RBE values in the escalated target volumes were between 1.09 and 1.16. Conclusions: The proposed dose escalation was found to be feasible. Protons can reduce the integral dose and mean doses to OARs compared to photons in both the dose-escalated and non-escalated cases. Differences in RBE between escalated and standard fractionation were small. Full article
(This article belongs to the Special Issue The Advance of Pencil Beam Scanning Proton Beam Therapy in Cancers)
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