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Pryanichnikov, A. A., P. B. Zhogolev, A. E. Shemyakov, M. A. Belikhin, A. P. Chernyaev, and V. Rykalin. "Low Intensity Beam Extraction Mode on the Protom Synchrotron for Proton Radiography Implementation." Journal of Physics: Conference Series 2058, no. 1 (October 1, 2021): 012041. http://dx.doi.org/10.1088/1742-6596/2058/1/012041.
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Abstract Proton radiography is one of the most important and actual areas of research that can significantly improve the quality and accuracy of proton therapy. Currently, the calculation of the proton range in patients receiving proton therapy is based on the conversion of Hounsfield CT units of the patient's tissues into the relative stopping power of protons. Proton radiography is able to reduce these uncertainties by directly measuring proton stopping power. The study demonstrates the possibility of Protom synchrotron-based proton therapy facilities to operate in a special mode which makes it possible to implement proton radiography. This work presents the status of the new low beam intensity extraction mode. The paper describes algorithms of low flux beam control, calibration procedures and experimental measurements. Measurements and calibration procedures were performed with certified Protom Faraday Cup, PTW Bragg Peak Chamber and specially designed experimental external.
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Bussière, Marc R., and Judith A. Adams. "Treatment Planning for Conformal Proton Radiation Therapy." Technology in Cancer Research & Treatment 2, no. 5 (October 2003): 389–99. http://dx.doi.org/10.1177/153303460300200504.
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Clinical results from various trials have demonstrated the viability of protons in radiation therapy and radiosurgery. This has motivated a few large medical centers to design and build expensive hospital based proton facilities based proton facilities (current cost estimates for a proton facility is around $100 million). Until this development proton therapy was done using retrofitted equipment originally designed for nuclear experiments. There are presently only three active proton therapy centers in the United States, 22 worldwide. However, more centers are under construction and being proposed in the US and abroad. The important difference between proton and x-ray therapy is in the dose distribution. X-rays deposit most of their dose at shallow depths of a few centimeters with a gradual decay with depth in the patient. Protons deliver most of their dose in the Bragg peak, which can be delivered at most clinically required depths followed by a sharp fall-off. This sharp falloff makes protons sensitive to variations in treatment depths within patients. Treatment planning incorporates all the knowledge of protons into a process, which allows patients to be treated accurately and reliably. This process includes patient immobilization, imaging, targeting, and modeling of planned dose distributions. Although the principles are similar to x-ray therapy some significant differences exist in the planning process, which described in this paper. Target dose conformality has recently taken on much momentum with the advent of intensity modulated radiation therapy (IMRT) with photon beams. Proton treatments provide a viable alternative to IMRT because they are inherently conformal avoiding normal tissue while irradiating the intended targets. Proton therapy will soon bring conformality to a new high with the development of intensity modulated proton therapy (IMPT). Future challenges include keeping the cost down, increasing access to conventional proton therapy as well as the clinical implementation of IMPT. Computing advances are making Monte Carlo techniques more accessible to treatment planning for all modalities including proton therapy. This technique will allow complex delivery configurations to be properly modeled in a clinical setting.
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Raldow, Ann, James Lamb, and Theodore Hong. "Proton beam therapy for tumors of the upper abdomen." British Journal of Radiology 93, no. 1107 (March 2020): 20190226. http://dx.doi.org/10.1259/bjr.20190226.
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Proton radiotherapy has clear dosimetric advantages over photon radiotherapy. In contrast to photons, which are absorbed exponentially, protons have a finite range dependent on the initial proton energy. Protons therefore do not deposit dose beyond the tumor, resulting in great conformality, and offers the promise of dose escalation to increase tumor control while minimizing toxicity. In this review, we discuss the rationale for using proton radiotherapy in the treatment of upper abdominal tumors—hepatocellular carcinomas, cholangiocarcinomas and pancreatic cancers. We also review the clinical outcomes and technical challenges of using proton radiotherapy for the treatment of these malignancies. Finally, we discuss the ongoing clinical trials implementing proton radiotherapy for the treatment of primary liver and pancreatic tumors.
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Foocharoen, C., P. Kingkaew, Y. Teerawattananon, A. Mahakkanukrauh, S. Suwannaroj, W. Manasirisuk, J. Chaiyarit, and A. Sangchan. "AB0923 COST-EFFECTIVENESS OF ALGINIC ACID IN COMBINATION WITH PROTON PUMP INHIBITOR FOR THE TREATMENT OF GASTROESOPHAGEAL REFLUX DISEASE IN SYSTEMIC SCLEROSIS PATIENTS." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 1678.1–1678. http://dx.doi.org/10.1136/annrheumdis-2023-eular.495.
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BackgroundSystemic sclerosis (SSc) patients often become refractory to proton pump inhibitor (PPI)—a standard treatment for gastroesophageal reflux disease (GERD)—and intolerant to PPI in combination with domperidone. PPI with alginic acid is an alternative treatment option, but alginic acid is costly.ObjectivesWe compared the costs and effectiveness of alginic acid plus proton pump inhibitor (PPI) versus standard treatments (PPI with/without antacids as needed and lifestyle modifications) for gastroesophageal reflux disease (GERD) in systemic sclerosis (SSc) patients unsuitable for, or intolerant to, domperidone.MethodsAn economic evaluation using the Markov model was conducted among SSc patients between 40 and 65 with GERD, having a partial or non-response to 4 weeks of standard-dose omeprazole (40 mg/d) and being unsuitable for or intolerance to domperidone. Using a societal perspective, we computed the incremental cost-effectiveness ratios (ICERs) in terms of Thai baht (THB) per quality-adjusted life-years (QALY) between a combination of alginic acid plus PPI and standard treatment for GERD. The lifetime time horizon was used.ResultsThe ICER for alginic acid plus PPI versus standard treatments was 377,101THB/QALY. According to the one-way sensitivity analysis, the cost of alginic acid was the most impactful parameter. If the market prices of alginic acid plus PPI were reduced by 61%, this treatment option would become cost-effective at the willingness-to-pay threshold of 160,000THB/QALY (34.71 THB/USD data on 3 December 2022). Furthermore, if alginic acid were included in the public health insurance program, the national budget would be increased by 66,313THB per patient resulting in an overall budget increase of 5,106,101 to 8,885,942THB compared to the standard treatment.ConclusionAlginic acid plus PPI does not represent good value for money compared to the standard treatment among such SSc patients in Thailand unless its price is reduced significantly.References[1]Foocharoen C, Peansukwech U, Mahakkanukrauh A, Suwannaroj S, Pongkulkiat P, Khamphiw P, et al. Clinical characteristics and outcomes of 566 Thais with systemic sclerosis: A cohort study. Int J Rheum Dis 2020;23:945–57.[2]Chunlertrith K, Noiprasit A, Foocharoen C, Mairiang P, Sukeepaisarnjaroen W, Sangchan A, et al. GERD questionnaire for diagnosis of gastroesophageal reflux disease in systemic sclerosis. Clin. Exp. Rheumatol. 2014;32:S-98-102.[3]Foocharoen C, Chunlertrith K, Mairiang P, Mahakkanukrauh A, Suwannaroj S, Namvijit S, et al. Prevalence and predictors of proton pump inhibitor partial response in gastroesophageal reflux disease in systemic sclerosis: a prospective study. Sci Rep 2020;10:769.[4] Foocharoen C, Chunlertrith K, Mairiang P, Mahakkanukrauh A, Suwannaroj S, Namvijit S, et al. Effectiveness of add-on therapy with domperidone vs alginic acid in proton pump inhibitor partial response gastro-oesophageal reflux disease in systemic sclerosis: randomized placebo-controlled trial. Rheumatology (Oxford) 2017;56:214–22.[5] Lei WY, Chang WC, Wen SH, Yi CH, Liu TT, Hung JS, et al. Predicting factors of recurrence in patients with gastroesophageal reflux disease: a prospective follow-up analysis. Therap Adv Gastroenterol 2019;12:1756284819864549.[6] Teerawattananon Y, Chaikledkaew U. Thai health technology assessment guideline development. J Med Assoc Thai 2008;91 Suppl 2:S11-15.[7] BOI: The Board of Investment of Thailand [Internet]. [cited 2022 Apr 19];Available from:https://www.boi.go.th/index.php?page=demographic.[8] Nimdet K, Ngorsuraches S. Willingness to pay per quality-adjusted life year for life-saving treatments in Thailand. BMJ Open 2015;5:e008123.Acknowledgements:NIL.Disclosure of InterestsChingching Foocharoen Speakers bureau: Boehringer Ingelheim, Norvatis, Janssen, Pritaporn Kingkaew: None declared, Yot Teerawattananon: None declared, Ajanee Mahakkanukrauh: None declared, Siraphop Suwannaroj: None declared, Witsarut Manasirisuk: None declared, Jitjira Chaiyarit: None declared, Apichat Sangchan: None declared.
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Patyal, Baldev. "Dosimetry Aspects of Proton Therapy." Technology in Cancer Research & Treatment 6, no. 4_suppl (August 2007): 17–23. http://dx.doi.org/10.1177/15330346070060s403.
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High-energy photons and high-energy protons are very different in the ways they interact with matter. These differences lead to distinct advantages of protons over photons for treatment of cancer. Some aspects of proton interactions with tissue that make this modality superior for treating cancer are: (i) Initially, the protons lose energy very slowly as they enter the body; this results in a low entrance dose and low doses to the normal tissues proximal to the tumor. (ii) Near the end of range, protons lose energy very rapidly and deposit all their energy over a very small volume before they come to rest. This is the Bragg peak, a property that results in delivery of the maximum dose to the tumor. (iii) Beyond the Bragg peak, the energy deposited by the protons is zero; no dose is received by normal tissues distal to the tumor. Therefore, protons deliver their maximum dose to the tumor, a low dose to normal structures proximal to the tumor, and no dose to the normal structures beyond the tumor, ideal properties of a radiation modality to treat cancer. One distinct advantage of protons over photons is the ease with which the tumor target can be irradiated conformably to a high dose, and at the same time the normal structures in the vicinity of the tumor can be protected conformably from that high dose. Given the same dose to the tumor via photons and protons, protons inherently deliver less integral dose and, thus, lead to fewer normal-tissue complications. In addition, proton interactions also offer distinct radiobiological advantages over photons. Superior physical and radiobiological proton interactions lead naturally to the concepts of dose escalation and hypofractionation. The superiority of treatment delivery with protons as contrasted with photons is demonstrated by treatment plans.
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Giovannini, Daniela, Cinzia De Angelis, Maria Denise Astorino, Emiliano Fratini, Evaristo Cisbani, Giulia Bazzano, Alessandro Ampollini, et al. "In Vivo Radiobiological Investigations with the TOP-IMPLART Proton Beam on a Medulloblastoma Mouse Model." International Journal of Molecular Sciences 24, no. 9 (May 5, 2023): 8281. http://dx.doi.org/10.3390/ijms24098281.
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Protons are now increasingly used to treat pediatric medulloblastoma (MB) patients. We designed and characterized a setup to deliver proton beams for in vivo radiobiology experiments at a TOP-IMPLART facility, a prototype of a proton-therapy linear accelerator developed at the ENEA Frascati Research Center, with the goal of assessing the feasibility of TOP-IMPLART for small animal proton therapy research. Mice bearing Sonic-Hedgehog (Shh)-dependent MB in the flank were irradiated with protons to test whether irradiation could be restricted to a specific depth in the tumor tissue and to compare apoptosis induced by the same dose of protons or photons. In addition, the brains of neonatal mice at postnatal day 5 (P5), representing a very small target, were irradiated with 6 Gy of protons with two different collimated Spread-Out Bragg Peaks (SOBPs). Apoptosis was visualized by immunohistochemistry for the apoptotic marker caspase-3-activated, and quantified by Western blot. Our findings proved that protons could be delivered to the upper part while sparing the deepest part of MB. In addition, a comparison of the effectiveness of protons and photons revealed a very similar increase in the expression of cleaved caspase-3. Finally, by using a very small target, the brain of P5-neonatal mice, we demonstrated that the proton irradiation field reached the desired depth in brain tissue. Using the TOP-IMPLART accelerator we established setup and procedures for proton irradiation, suitable for translational preclinical studies. This is the first example of in vivo experiments performed with a “full-linac” proton-therapy accelerator.
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Katsoulakis, Evangelia, Natalya Chernichenko, and David Schreiber. "Proton Therapy in the Treatment of Head and Neck Cancer." International Journal of Head and Neck Surgery 8, no. 2 (2017): 45–48. http://dx.doi.org/10.5005/jp-journals-10001-1305.
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ABSTRACT Aim To examine the value of proton therapy in relation to other treatment modalities in head and neck cancer. Review Proton therapy has evolved into more sophisticated and costly intensity-modulated proton therapy and has resulted in even greater dose reduction to normal critical structures at risk as compared with photon therapy. Early clinical studies in head and neck cancers, especially for tumors of the skull base and paranasal sinuses, suggest that proton therapy is excellent in terms of local control and is comparable to intensity-modulated radiation therapy photons but with lower rates of morbidity. Results There are many potential advantages to radiation therapy with protons. While there are many single institution studies examining the added value of protons to photon therapy, the value of proton therapy must be examined in prospective randomized clinical studies and across many subsites of head and neck cancer. Additional evidence is necessary to guide efficient clinical practice, patient selection, and tumors that are most likely to benefit from this treatment modality and justify proton therapy use given its significant cost. How to cite this article Katsoulakis E, Chernichenko N, Schreiber D. Proton Therapy in the Treatment of Head and Neck Cancer. Int J Head Neck Surg 2017;8(2):45-48.
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Pullia, Marco G. "Synchrotrons for Hadrontherapy." Reviews of Accelerator Science and Technology 02, no. 01 (January 2009): 157–78. http://dx.doi.org/10.1142/s1793626809000284.
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Since 1990, when the world's first hospital-based proton therapy center opened in Loma Linda, California, interest in dedicated proton and carbon ion therapy facilities has been growing steadily. Today, many proton therapy centers are in operation, but the number of centers offering carbon ion therapy is still very low. This difference reflects the fact that protons are well accepted by the medical community, whereas radiotherapy with carbon ions is still experimental. Furthermore, accelerators for carbon ions are larger, more complicated and more expensive than those for protons only. This article describes the accelerator performance required for hadrontherapy and how this is realized, with particular emphasis on carbon ion synchrotrons.
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Rohollahpour, Elham, and Hadi Taleshi Ahangari. "Feasibility of Proton Range Estimation with Prompt Gamma Imaging in Proton Therapy of Lung Cancer: Monte Carlo Study." Journal of Medical Physics 49, no. 4 (October 2024): 531–38. https://doi.org/10.4103/jmp.jmp_74_24.
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Context: Using prompt gamma (PG) ray is proposed as a promising solution for in vivo monitoring in proton therapy. Despite significant and diverse approaches explored over the past two decades, challenges still persist for more effective utilization. Aims: The feasibility of estimating proton range with PG imaging (PGI) as an online imaging guide in an anthropomorphic phantom with lung cancer was investigated through GATE/GEANT4 Monte Carlo simulation. Setting and Design: Once the GATE code was validated for use as a simulation tool, the gamma energy spectra of NURBS-based cardiac-torso (NCAT) and polymethyl methacrylate phantoms, representing heterogeneous and homogeneous phantoms respectively, were compared with the gamma emission lines known in nuclear interactions with tissue elements. A 5-mm radius spherical tumor in the lung region of an NCAT phantom, without any physiological or morphological changes, was simulated. Subjects and Methods: The proton pencil beam source was defined as a function of the tumor size to encompass the tumor volume. The longitudinal spatial correlation between the proton dose deposition and the distribution of detected PG rays by the multi-slit camera was assessed for proton range estimation. The simulations were conducted for both 108 and 109 protons. Results: The deviation between the proton range and the range estimated by PGI following proton beam irradiation to the center of the lung tumor was determined by evaluating the longitudinal profiles at the 80% fall-off point, measuring 1.9 mm for 109 protons and 4.5 mm for 108 protons. Conclusions: The accuracy of proton range estimation through PGI is greatly influenced by the number of incident protons and tissue characteristics. With 109 protons, it is feasible to utilize PGI as a real-time monitoring technique during proton therapy for lung cancer.
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Ma, Jie, Hao Shen, and Zhaohong Mi. "Enhancing Proton Therapy Efficacy Through Nanoparticle-Mediated Radiosensitization." Cells 13, no. 22 (November 7, 2024): 1841. http://dx.doi.org/10.3390/cells13221841.
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Proton therapy, characterized by its unique Bragg peak, offers the potential to optimize the destruction of cancer cells while sparing healthy tissues, positioning it as one of the most advanced cancer treatment modalities currently available. However, in comparison to heavy ions, protons exhibit a relatively lower relative biological effectiveness (RBE), which limits the efficacy of proton therapy. The incorporation of nanoparticles for radiosensitization presents a novel approach to enhance the RBE of protons. This review provides a comprehensive discussion of the recent advancements in augmenting the biological effects of proton therapy through the use of nanoparticles. It examines the various types of nanoparticles that have been the focus of extensive research, elucidates their mechanisms of radiation sensitization, and evaluates the factors influencing the efficiency of this sensitization process. Furthermore, this review discusses the latest synergistic therapeutic strategies that integrate nanoparticle-mediated radiosensitization and outlines prospective directions for the future application of nanoparticles in conjunction with proton therapy.
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Cammarata, F. P., F. Torrisi, A. M. Pavone, S. Denaro, S. D'Aprile, D. Rotili, L. Botta, et al. "A novel boron-conjugated SRC inhibitor for Proton Boron Capture Therapy in glioblastoma treatment." Journal of Instrumentation 19, no. 04 (April 1, 2024): C04051. http://dx.doi.org/10.1088/1748-0221/19/04/c04051.
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Abstract The ability of protons to deliver the maximum dose at the tumor region can work synergistically with boron atoms to emit alpha particles, enhancing therapy effects with less damage to healthy tissue. Protons and boron nuclear fusion reaction is the principle for the so-called Proton Boron Capture Therapy, that can contribute to high therapy efficiency by using smaller flux than conventional proton therapy, especially for radioresistant brain tumors such as glioblastoma. Glioblastoma is the most infiltrating and aggressive tumor of the brain with a very low life expectancy, ranging from 6 to 24 months. In this study we evaluated the protons combined effectwithanovelboron-conjugated compound, which is a pyrazolo[3,4-d]pyrimidine derivative, acting as SRC tyrosine kinase inhibitor. Indeed, this drug includes a boron cluster, that can be directed in tumor cells using the ATP-competitive mechanism of the pyrazolo[3,4 d]pyrimidine ring in activated SRC form of glioblastoma cells, achieving tumor uptake of boron for Proton Boron Capture Therapy reaction. This preliminary study showed interesting results that could offer important contributions for further experiments.
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Deurvorst, F. R., G. Collado Lara, A. Matalliotakis, H. J. Vos, N. de Jong, V. Daeichin, and M. D. Verweij. "A spatial and temporal characterisation of single proton acoustic waves in proton beam cancer therapy." Journal of the Acoustical Society of America 151, no. 2 (February 2022): 1200–1210. http://dx.doi.org/10.1121/10.0009567.
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An in vivo range verification technology for proton beam cancer therapy, preferably in real-time and with submillimeter resolution, is desired to reduce the present uncertainty in dose localization. Acoustical imaging technologies exploiting possible local interactions between protons and microbubbles or nanodroplets might be an interesting option. Unfortunately, a theoretical model capable of characterising the acoustical field generated by an individual proton on nanometer and micrometer scales is still missing. In this work, such a model is presented. The proton acoustic field is generated by the adiabatic expansion of a region that is locally heated by a passing proton. To model the proton heat deposition, secondary electron production due to protons has been quantified using a semi-empirical model based on Rutherford's scattering theory, which reproduces experimentally obtained electronic stopping power values for protons in water within 10% over the full energy range. The electrons transfer energy into heat via electron-phonon coupling to atoms along the proton track. The resulting temperature increase is calculated using an inelastic thermal spike model. Heat deposition can be regarded as instantaneous, thus, stress confinement is ensured and acoustical initial conditions are set. The resulting thermoacoustic field in the nanometer and micrometer range from the single proton track is computed by solving the thermoacoustic wave equation using k-space Green's functions, yielding the characteristic amplitudes and frequencies present in the acoustic signal generated by a single proton in an aqueous medium. Wavefield expansion and asymptotic approximations are used to extend the spatial and temporal ranges of the proton acoustic field.
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Freeman, Tami. "Painting with protons: treatment beams recreate classic works of art." Physics World 36, no. 11 (November 1, 2023): 6ii. http://dx.doi.org/10.1088/2058-7058/36/11/07.
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Rich, Tyvin, Dongfeng Pan, Mahendra Chordia, Cynthia Keppel, David Beylin, Pavel Stepanov, Mira Jung, Dalong Pang, Scott Grindrod, and Anatoly Dritschilo. "18Oxygen Substituted Nucleosides Combined with Proton Beam Therapy: Therapeutic Transmutation In Vitro." International Journal of Particle Therapy 7, no. 4 (March 1, 2021): 11–18. http://dx.doi.org/10.14338/ijpt-d-20-00036.1.
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Abstract Purpose Proton therapy precisely delivers radiation to cancers to cause damaging strand breaks to cellular DNA, kill malignant cells, and stop tumor growth. Therapeutic protons also generate short-lived activated nuclei of carbon, oxygen, and nitrogen atoms in patients as a result of atomic transmutations that are imaged by positron emission tomography (PET). We hypothesized that the transition of 18O to 18F in an 18O-substituted nucleoside irradiated with therapeutic protons may result in the potential for combined diagnosis and treatment for cancer with proton therapy. Materials and Methods Reported here is a feasibility study with a therapeutic proton beam used to irradiate H218O to a dose of 10 Gy produced by an 85 MeV pristine Bragg peak. PET imaging initiated >45 minutes later showed an 18F decay signal with T1/2 of ∼111 minutes. Results The 18O to 18F transmutation effect on cell survival was tested by exposing SQ20B squamous carcinoma cells to physiologic 18O-thymidine concentrations of 5 μM for 48 hours followed by 1- to 9-Gy graded doses of proton radiation given 24 hours later. Survival analyses show radiation sensitization with a dose modification factor (DMF) of 1.2. Conclusions These data support the idea of therapeutic transmutation in vitro as a biochemical consequence of proton activation of 18O to 18F in substituted thymidine enabling proton radiation enhancement in a cancer cell. 18O-substituted molecules that incorporate into cancer targets may hold promise for improving the therapeutic window of protons and can be evaluated further for postproton therapy PET imaging.
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Hong, Zifei, Zhuocheng Liu, and Yutong Tu. "Analysis of the Proton Therapy Controlling System and Application." Highlights in Science, Engineering and Technology 72 (December 15, 2023): 381–88. http://dx.doi.org/10.54097/e1rz5n66.
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In recent years, the cancel therapy remains a key issue that needs to be addressed for human beings. As a matter of fact, the proton beam therapy (PBT) is a new kind of way to treat tumor by emitting proton beam. Different from conventional radiation therapy, the main principal is to cut the DNA of the tumor cells and prevent further development. In this case, this study will discuss the proton therapy controlling system as well as demonstrate the applications. Comparing to the X-rays, protons can align tumors more precisely and decrease the effect of other normal tissues, which also decrease the side effects. Nevertheless, the proton therapy is still be developed further. Many proton centers are being built and will begin operating in the future. This article popularizes the basic knowledge of proton therapy, from the basic principle, the applications to the limitations. These results shed light on guiding further exploration of proton therapy.
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Jumaniyazova, Enar, Daniil Smyk, Polina Vishnyakova, Timur Fatkhudinov, and Konstantin Gordon. "Photon- and Proton-Mediated Biological Effects: What Has Been Learned?" Life 13, no. 1 (December 22, 2022): 30. http://dx.doi.org/10.3390/life13010030.
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The current understanding of the effects of radiation is gradually becoming broader. However, it still remains unclear why some patients respond to radiation with a pronounced positive response, while in some cases the disease progresses. This is the motivation for studying the effects of radiation therapy not only on tumor cells, but also on the tumor microenvironment, as well as studying the systemic effects of radiation. In this framework, we review the biological effects of two types of radiotherapy: photon and proton irradiations. Photon therapy is a commonly used type of radiation therapy due to its wide availability and long-term history, with understandable and predictable outcomes. Proton therapy is an emerging technology, already regarded as the method of choice for many cancers in adults and children, both dosimetrically and biologically. This review, written after the analysis of more than 100 relevant literary sources, describes the local effects of photon and proton therapy and shows the mechanisms of tumor cell damage, interaction with tumor microenvironment cells and effects on angiogenesis. After systematic analysis of the literature, we can conclude that proton therapy has potentially favorable toxicological profiles compared to photon irradiation, explained mainly by physical but also biological properties of protons. Despite the fact that radiobiological effects of protons and photons are generally similar, protons inflict reduced damage to healthy tissues surrounding the tumor and hence promote fewer adverse events, not only local, but also systemic.
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Zhong, Yubin, and Jiamin Li. "Technical advancement and clinical prospective of proton radiotherapy." Journal of X-Ray Science and Technology: Clinical Applications of Diagnosis and Therapeutics 15, no. 1 (January 2007): 49–56. http://dx.doi.org/10.3233/xst-2007-00169.
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Proton therapy is a new and advanced external beam radiotherapy technique where the energetic ionizing particles, protons, are directed to the target turmors. This report reviews the basic principle and the advantages of proton therapy in terms superior dose distribution as compared to photon therapy. The suitable clinical application of this new technique is also described based on the experiences at Wanjie Hospital in China. It is reasonable to expect that, with the rapid advancements in equipment and planning methods, proton therapy will become an important clinical choice in cancer treatments in near future.
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Stick, Line Bjerregaard, Maria Fuglsang Jensen, Søren M. Bentzen, Claus Kamby, Anni Young Lundgaard, Maja Vestmø Maraldo, Birgitte Vrou Offersen, Jen Yu, and Ivan Richter Vogelius. "Radiation-Induced Toxicity Risks in Photon Versus Proton Therapy for Synchronous Bilateral Breast Cancer." International Journal of Particle Therapy 8, no. 4 (November 11, 2021): 1–13. http://dx.doi.org/10.14338/ijpt-21-00023.1.
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Abstract Purpose This study compares photon and proton therapy plans for patients with synchronous bilateral early breast cancer and estimates risks of early and late radiation-induced toxicities. Materials and Methods Twenty-four patients with synchronous bilateral early breast cancer receiving adjuvant radiation therapy using photons, 3-dimensional conformal radiation therapy or volumetric modulated arc therapy, were included and competing pencil beam scanning proton therapy plans were created. Risks of dermatitis, pneumonitis, acute esophageal toxicity, lung and breast fibrosis, hypothyroidism, secondary lung and esophageal cancer and coronary artery events were estimated using published dose-response relationships and normal tissue complication probability (NTCP) models. Results The primary clinical target volume V95% and/or nodal clinical target volume V90% were less than 95% in 17 photon therapy plans and none of the proton plans. Median NTCP of radiation dermatitis ≥ grade 2 was 18.3% (range, 5.4-41.7) with photon therapy and 58.4% (range, 31.4-69.7) with proton therapy. Median excess absolute risk (EAR) of secondary lung cancer at age 80 for current and former smokers was 4.8% (range, 0.0-17.0) using photons and 2.7% (range, 0.0-13.6) using protons. Median EAR of coronary event at age 80, assuming all patients have preexisting cardiac risk factors, was 1.0% (range, 0.0-5.6) with photons and 0.2% (range, 0.0-1.3) with protons. Conclusion Proton therapy plans improved target coverage and reduced risk of coronary artery event and secondary lung cancer while increasing the risk of radiation dermatitis.
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Graber, Jerome, Reed Ritterbusch, and Lia Halasz. "NIMG-64. DISTINCT IMAGING PATTERNS OF PSEUDOPROGRESSION IN GLIOMA PATIENTS FOLLOWING PROTON VERSUS PHOTON RADIATION THERAPY." Neuro-Oncology 22, Supplement_2 (November 2020): ii162. http://dx.doi.org/10.1093/neuonc/noaa215.677.
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Abstract PURPOSE Radiologic Assessment in Neuro-Oncology (RANO) criteria define pseudoprogression (Ps) after photon radiation for gliomas, as occurring less than twelve weeks from radiation, within the high dose radiation field. However, some patients receiving proton manifest lesions that appear subjectively different from photon Ps based on timing and location (more than six months from radiation and deeper to the prior tumor), which would be called tumor progression by RANO. We retrospectively reviewed MRI changes after proton or photon radiation for gliomas. We propose criteria to characterize proton pseudoprogression (ProPs) distinct from photon pseudoprogression or tumor progression. METHODS Post-treatment MRIs of patients with gliomas were reviewed, along with clinical and pathological data. 77 proton patients were reviewed for the presence of ProPs, and 64 photon patients were reviewed for imaging changes. Data collected included the location, timing, and morphology of the lesions, tumor type, chemotherapy, and clinical symptoms. RESULTS 16 (21%) of the patients who received protons had imaging changes unique to protons, at a mean of 14.6 months after radiation. We established the following criteria to characterize ProPs: not immediately in or adjacent to the resection cavity; ~ 2cm opposite from target beam entry; can resolve without treatment; subjectively multifocal, patchy, small (< 1cm). None of the photon patients had lesions that met our criteria for ProPs (p< 0.001). CONCLUSION Patients who receive protons can have a unique subtype of pseudoprogression (Ps), which we refer to as proton pseudoprogression (or ProPs). These lesions could be mistaken for tumor progression, but typically resolve spontaneously. ProPs can possibly be explained by the increased relative biological effectiveness of protons and beam angle selection which may deposit at ~2cm deep to the target. Recognizing these lesions can prevent unnecessary treatment for mistaken tumor progression, especially in the context of clinical trials that include proton.
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Bonaccorsi, Santa Gabriella, Thomas Tessonnier, Line Hoeltgen, Eva Meixner, Semi Harrabi, Juliane Hörner-Rieber, Thomas Haberer, Amir Abdollahi, Jürgen Debus, and Andrea Mairani. "Exploring Helium Ions’ Potential for Post-Mastectomy Left-Sided Breast Cancer Radiotherapy." Cancers 16, no. 2 (January 18, 2024): 410. http://dx.doi.org/10.3390/cancers16020410.
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Proton therapy presents a promising modality for treating left-sided breast cancer due to its unique dose distribution. Helium ions provide increased conformality thanks to a reduced lateral scattering. Consequently, the potential clinical benefit of both techniques was explored. An explorative treatment planning study involving ten patients, previously treated with VMAT (Volumetric Modulated Arc Therapy) for 50 Gy in 25 fractions for locally advanced, node-positive breast cancer, was carried out using proton pencil beam therapy with a fixed relative biological effectiveness (RBE) of 1.1 and helium therapy with a variable RBE described by the mMKM (modified microdosimetric kinetic model). Results indicated that target coverage was improved with particle therapy for both the clinical target volume and especially the internal mammary lymph nodes compared to VMAT. Median dose value analysis revealed that proton and helium plans provided lower dose on the left anterior descending artery (LAD), heart, lungs and right breast than VMAT. Notably, helium therapy exhibited improved ipsilateral lung sparing over protons. Employing NTCP models as available in the literature, helium therapy showed a lower probability of grade ≤ 2 radiation pneumonitis (22% for photons, 5% for protons and 2% for helium ions), while both proton and helium ions reduce the probability of major coronary events with respect to VMAT.
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Akulinichev, S. V., D. A. Kokontcev, G. V. Merzlikin, and I. A. Yakovlev. "Formation and Dosimetry of Proton Beams for Flash Therapy Study." Meditsinskaya Fizika, no. 4 (December 30, 2024): 4–12. https://doi.org/10.52775/1810-200x-2024-104-4-4-12.
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Purpose: To develop methods for tuning and dosimetry of proton beams in the widest possible range of proton current, including flash therapy modes with extremely high dose rates. Studies of flash therapy patterns, which have become much more active in recent years, have increased interest in the methods of forming therapeutic proton beams, including the method of passive proton scattering used in this work. Material and methods: The characteristics of the highcurrent linear proton accelerator of the INR RAS make it a unique facility and allow work with proton beams of record intensity. The therapeutic beam formation system is developed based on the principle of double passive proton scattering, which allows instantaneous irradiation of biological objects of significant size with a uniform dose regardless of the beam intensity. The primary adjustment of the formation system is performed using a standard MP-3 water phantom (PTW, Germany) at low proton currents, i.e. in the conventional irradiation mode. The proposed method of setting up the beam formation system allows combining the secondary shaped scatterer with the beam center and finding the optimal angle of the energy modulator, thereby optimizing the depth dose distribution. The used methods of dosimetry and beam control with film detectors and a Cherenkov monitor are also applicable at high proton currents, which allows setting up the beam formation system and irradiating biological objects in flash therapy modes. Results and conclusion: The work developed methods for the formation and dosimetry of proton beams applicable in the widest possible range of proton beam intensities, up to proton current values of about 10 mA. The main practical result of the work is the implemented irradiation of biological targets weighing up to 100 g with protons in a single pulse with a record average dose rate for protons per fraction of about 106Gy/s. For this purpose, original methods for setting up the beam formation system elements and Cherenkov beam monitors were used.
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Carbone, Giorgio Giuseppe, Stefania Mariano, Alessandra Gabriele, Sabrina Cennamo, Vitantonio Primiceri, Muhammad Rizwan Aziz, Elisa Panzarini, and Lucio Calcagnile. "Exploring the Potential of Gold Nanoparticles in Proton Therapy: Mechanisms, Advances, and Clinical Horizons." Pharmaceutics 17, no. 2 (January 30, 2025): 176. https://doi.org/10.3390/pharmaceutics17020176.
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Proton therapy represents a groundbreaking advancement in cancer radiotherapy, leveraging the unique spatial energy distribution of protons to deliver precise, high-dose radiation to tumors while sparing surrounding healthy tissues. Despite its clinical success, proton therapy faces challenges in optimizing its therapeutic precision and efficacy. Recent research has highlighted the potential of gold nanoparticles to enhance proton therapy outcomes. Due to their high atomic number and favorable biological properties, gold nanoparticles act as radiosensitizers by amplifying the generation of secondary electrons and reactive oxygen species upon proton irradiation. This enhances DNA damage in tumor cells while preserving healthy tissues. Additionally, functionalization of gold nanoparticles with tumor-targeting ligands offers improved precision, making proton therapy more effective against a broader range of cancers. This review synthesizes current knowledge on the mechanisms of gold nanoparticle radiosensitization, preclinical evidence, and the technological hurdles that must be addressed to integrate this promising approach into clinical practice, aiming to advance the efficacy and accessibility of proton therapy in cancer therapy.
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Penner, Crystal, Samuel Usherovich, Jana Niedermeier, Camille Belanger-Champagne, Michael Trinczek, Elisabeth Paulssen, and Cornelia Hoehr. "Organic Scintillator-Fibre Sensors for Proton Therapy Dosimetry: SCSF-3HF and EJ-260." Electronics 12, no. 1 (December 20, 2022): 11. http://dx.doi.org/10.3390/electronics12010011.
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In proton therapy, the dose from secondary neutrons to the patient can contribute to side effects and the creation of secondary cancer. A simple and fast detection system to distinguish between dose from protons and neutrons both in pretreatment verification as well as potentially in vivo monitoring is needed to minimize dose from secondary neutrons. Two 3 mm long, 1 mm diameter organic scintillators were tested for candidacy to be used in a proton–neutron discrimination detector. The SCSF-3HF (1500) scintillating fibre (Kuraray) and EJ-260 plastic scintillator (Eljen Technology) were irradiated at the TRIUMF Neutron Facility and the Proton Therapy Research Centre. In the proton beam, we compared the raw Bragg peak and spread-out Bragg peak response to the industry standard Markus chamber detector. Both scintillator sensors exhibited quenching at high LET in the Bragg peak, presenting a peak-to-entrance ratio of 2.59 for the EJ-260 and 2.63 for the SCSF-3HF fibre, compared to 3.70 for the Markus chamber. The SCSF-3HF sensor demonstrated 1.3 times the sensitivity to protons and 3 times the sensitivity to neutrons as compared to the EJ-260 sensor. Combined with our equations relating neutron and proton contributions to dose during proton irradiations, and the application of Birks’ quenching correction, these fibres provide valid candidates for inexpensive and replicable proton-neutron discrimination detectors.
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Schilling, Isabelle, Claus Maximilian Bäcker, Christian Bäumer, Carina Behrends, Marius Hötting, Jana Hohmann, Kevin Kröninger, Beate Timmermann, and Jens Weingarten. "Measuring the Beam Energy in Proton Therapy Facilities Using ATLAS IBL Pixel Detectors." Instruments 6, no. 4 (November 29, 2022): 80. http://dx.doi.org/10.3390/instruments6040080.
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The accurate measurement of the beam range in the frame of quality assurance (QA) is a requirement for clinical use of a proton therapy machine. Conventionally used detectors mostly estimate the range by measuring the depth dose distribution of the protons. In this paper, we use pixel detectors designed for individual particle tracking in the high-radiation environment of the ATLAS experiment at LHC. The detector measures the deposited energy in the sensor for individual protons. Due to the limited dynamic energy range of the readout chip, several ways to measure the proton energy or range are examined. A staircase phantom is placed on the detector to perform an energy calibration relative to the NIST PSTAR stopping power database. In addition, track length measurements are performed using the detector aligned parallel with the beam axis to investigate the Linear Energy Transfer (LET) per pixel along the trajectory of individual protons. In this proof-of-principle study, we show that this radiation hardness detector can successfully be used to determine the initial proton energy for protons impinging on the sensor with an energy below 44 MeV after the range shifters. It becomes clear that an improvement of the energy resolution of the readout chip is required for clinical use.
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Iwata, Hiromitsu, Tsuyoshi Shuto, Shunsuke Kamei, Kohei Omachi, Masataka Moriuchi, Chihiro Omachi, Toshiyuki Toshito, et al. "Combined effects of cisplatin and photon or proton irradiation in cultured cells: radiosensitization, patterns of cell death and cell cycle distribution." Journal of Radiation Research 61, no. 6 (September 3, 2020): 832–41. http://dx.doi.org/10.1093/jrr/rraa065.
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Abstract The purpose of the current study was to investigate the biological effects of protons and photons in combination with cisplatin in cultured cells and elucidate the mechanisms responsible for their combined effects. To evaluate the sensitizing effects of cisplatin against X-rays and proton beams in HSG, EMT6 and V79 cells, the combination index, a simple measure for quantifying synergism, was estimated from cell survival curves using software capable of performing the Monte Carlo calculation. Cell death and apoptosis were assessed using live cell fluorescence imaging. HeLa and HSG cells expressing the fluorescent ubiquitination-based cell cycle indicator system (Fucci) were irradiated with X-rays and protons with cisplatin. Red and green fluorescence in the G1 and S/G2/M phases, respectively, were evaluated and changes in the cell cycle were assessed. The sensitizing effects of ≥1.5 μM cisplatin were observed for both X-ray and proton irradiation (P < 0.05). In the three cell lines, the average combination index was 0.82–1.00 for X-rays and 0.73–0.89 for protons, indicating stronger effects for protons. In time-lapse imaging, apoptosis markedly increased in the groups receiving ≥1.5 μM cisplatin + protons. The percentage of green S/G2/M phase cells at that time was higher when cisplatin was combined with proton beams than with X-rays (P < 0.05), suggesting more significant G2 arrest. Proton therapy plus ≥1.5 μM cisplatin is considered to be very effective. When combined with cisplatin, proton therapy appeared to induce greater apoptotic cell death and G2 arrest, which may partly account for the difference observed in the combined effects.
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Slater, Jerry D. "Development and Operation of the Loma Linda University Medical Center Proton Facility." Technology in Cancer Research & Treatment 6, no. 4_suppl (August 2007): 67–72. http://dx.doi.org/10.1177/15330346070060s411.
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The Proton Treatment Center at Loma Linda University Medical Center, the world's first hospital-based proton facility, opened in 1990 after two decades of development. Its early years were marked by a deliberately cautious approach in clinical utilization of protons, with intent to establish hospital-based proton therapy on a scientific basis. The facility was designed to be upgradeable, and development since 1990 has proceeded in three distinct phases of upgrades, both in technology and clinical applications. Upgrades continue, all of them based on an underlying program of basic and clinical research; future new applications of proton radiation therapy are expected to follow.
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Kobeissi, Jana M., Lara Hilal, Charles B. Simone, Haibo Lin, Christopher H. Crane, and Carla Hajj. "Proton Therapy in the Management of Hepatocellular Carcinoma." Cancers 14, no. 12 (June 12, 2022): 2900. http://dx.doi.org/10.3390/cancers14122900.
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Proton radiation therapy plays a central role in the treatment of hepatocellular carcinoma (HCC). Because of the near-zero exit dose and improved sparing of normal liver parenchyma, protons are being used even in challenging scenarios, including larger or multifocal liver tumors, and those associated with vascular tumor thrombus. There is a mounting level of evidence that suggests that protons are superior to photons in terms of survival and toxicity outcomes, specifically the progression to liver failure. A randomized controlled trial comparing protons to photons is currently underway to verify this hypothesis.
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Szymonowicz, Klaudia, Adam Krysztofiak, Jansje van der Linden, Ajvar Kern, Simon Deycmar, Sebastian Oeck, Anthony Squire, et al. "Proton Irradiation Increases the Necessity for Homologous Recombination Repair Along with the Indispensability of Non-Homologous End Joining." Cells 9, no. 4 (April 5, 2020): 889. http://dx.doi.org/10.3390/cells9040889.
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Technical improvements in clinical radiotherapy for maximizing cytotoxicity to the tumor while limiting negative impact on co-irradiated healthy tissues include the increasing use of particle therapy (e.g., proton therapy) worldwide. Yet potential differences in the biology of DNA damage induction and repair between irradiation with X-ray photons and protons remain elusive. We compared the differences in DNA double strand break (DSB) repair and survival of cells compromised in non-homologous end joining (NHEJ), homologous recombination repair (HRR) or both, after irradiation with an equal dose of X-ray photons, entrance plateau (EP) protons, and mid spread-out Bragg peak (SOBP) protons. We used super-resolution microscopy to investigate potential differences in spatial distribution of DNA damage foci upon irradiation. While DNA damage foci were equally distributed throughout the nucleus after X-ray photon irradiation, we observed more clustered DNA damage foci upon proton irradiation. Furthermore, deficiency in essential NHEJ proteins delayed DNA repair kinetics and sensitized cells to both, X-ray photon and proton irradiation, whereas deficiency in HRR proteins sensitized cells only to proton irradiation. We assume that NHEJ is indispensable for processing DNA DSB independent of the irradiation source, whereas the importance of HRR rises with increasing energy of applied irradiation.
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Thomas, Heike, and Beate Timmermann. "Paediatric proton therapy." British Journal of Radiology 93, no. 1107 (March 2020): 20190601. http://dx.doi.org/10.1259/bjr.20190601.
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Proton beam therapy is a highly conformal form of radiation therapy, which currently represents an important therapeutic component in multidisciplinary management in paediatric oncology. The precise adjustability of protons results in a reduction of radiation-related long-term side-effects and secondary malignancy induction, which is of particular importance for the quality of life. Proton irradiation has been shown to offer significant advantages over conventional photon-based radiotherapy, although the biological effectiveness of both irradiation modalities is comparable. This review evaluates current data from clinical and dosimetric studies on the treatment of tumours of the central nervous system, soft tissue and bone sarcomas of the head and neck region, paraspinal or pelvic region, and retinoblastoma. To date, the clinical results of irradiating childhood tumours with high-precision proton therapy are promising both with regard to tumour cure and the reduction of adverse events. Modern proton therapy techniques such as pencil beam scanning and intensity modulation are increasingly established modern facilities. However, further investigations with larger patient cohorts and longer follow-up periods are required, in order to be able to have clear evidence on clinical benefits.
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Marc, Louise, Silvia Fabiano, Niklas Wahl, Claudia Linsenmeier, Antony J. Lomax, and Jan Unkelbach. "Combined proton–photon treatment for breast cancer." Physics in Medicine & Biology 66, no. 23 (November 22, 2021): 235002. http://dx.doi.org/10.1088/1361-6560/ac36a3.
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Abstract Objective. Proton therapy remains a limited resource due to gantry size and its cost. Recently, a new design without a gantry has been suggested. It may enable combined proton–photon therapy (CPPT) in conventional bunkers and allow the widespread use of protons. In this work, we explore this concept for breast cancer. Methods. The treatment room consists of a LINAC for intensity modulated radiation therapy (IMRT), a fixed proton beamline (FBL) with beam scanning and a motorized couch for treatments in lying positions with accurate patient setup. Thereby, proton and photon beams are delivered in the same fraction. Treatment planning is performed by simultaneously optimizing IMRT and IMPT plans based on the cumulative dose. The concept is investigated for three breast cancers where the goal is to minimize mean dose to the heart and lung while delivering 40.05 Gy in 15 fractions to the PTV with a SIB of 48 Gy to the tumor bed. The probabilistic approach is applied to mitigate the sensitivity to range uncertainties. Results. CPPT is particularly advantageous for irradiating concave target volumes that wrap around a curved chest wall. There, protons may deliver dose to the peripheral and medial parts of the target volume including lymph nodes. Thereby, the mean dose in normal tissues is reduced compared to single-modality IMRT. However, tangential photon beams may treat parts of the target volume near the interface to the lung. To ensure target coverage for range undershoot in an IMPT plan, proton beams have to deliberately overshoot into the lung tissue—a problem that can be mitigated via the photon component which ensures plan conformity and robustness. Conclusion. CPPT using an FBL may represent a realistic approach to make protons available to more patients. In addition, CPPT may generally improve treatment quality compared to both single-modality proton and photon treatments.
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V, Suhag, Sunita BS, and Vats P. "Proton Beam Therapy for Prostate Cancer: An Overview." International Journal of Trend in Scientific Research and Development Volume-3, Issue-2 (February 28, 2019): 586–88. http://dx.doi.org/10.31142/ijtsrd21439.
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DeLaney, Thomas F. "Clinical Proton Radiation Therapy Research at the Francis H. Burr Proton Therapy Center." Technology in Cancer Research & Treatment 6, no. 4_suppl (August 2007): 61–66. http://dx.doi.org/10.1177/15330346070060s410.
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The Francis H. Burr Proton Therapy Center has a 230 MeV cyclotron from which proton beams are directed to two isocentric gantries, a stereotactic intracranial beam line, and an eye line. Because of improved physical dose distribution, proton radiotherapy allows dose escalation to improve local tumor control in anatomic sites and histologies where local control is suboptimal with photons. The improved dose localization also reduces normal-tissue doses with an anticipated reduction in acute and late toxicity. Clinical treatment protocols, developed to exploit the dosimetric advantages of protons over photons, have been grouped into two broad categories. In the first, dose is escalated for anatomic sites where local control with conventional radiation doses has been suboptimal. In the second, normal-tissue sparing with protons is designed to minimize acute and late toxicity. Treatment of patients on clinical research protocols has been encouraged. Patient treatments began on the first gantry in November 2001; on the eye line in April 2002; on the second gantry in May 2002; and on the stereotactic intracranial line in August 2006. The facility currently treats 60 patients per day, including up to six children daily under anesthesia. Dose-escalation studies have been completed for early stage prostate cancer (in conjunction with Loma Linda University) and sarcomas of the cervical spine/base of skull and thoracolumbosacral spine. Protocols are in progress or development for carcinoma of the nasopharynx, paranasal sinus carcinoma, non-small-cell lung carcinoma, locally advanced carcinoma of the prostate, hepatocellular carcinoma, and pancreatic cancer. Studies evaluating the use of protons for morbidity reduction include protocols for craniospinal irradiation in conjunction with systemic chemotherapy for medulloblastoma, retinoblastoma, pediatric rhabdomyosarcoma, other pediatric sarcomas, and accelerated, hypofractionated partial breast irradiation for T1N0 breast carcinomas. For pediatric patients, protons have also been accepted as an alternative to photons for children enrolled in Children's Oncology Group (COG) protocols. Treatment of patients on these studies has often required the development of new treatment techniques ( i.e., matching abutting fields for craniospinal irradiation), respiratory gating, and development of appropriate clinical infrastructure support ( i.e., increase in availability of pediatric anesthesia) to allow appropriate treatment. In addition, a clinical research infrastructure for protocol development and data management is required. Results to date indicate that proton radiation therapy offers several potential treatment advantages to patients that can be studied in the setting of clinical trials. Patients' willingness to enter these clinical trials seems to be quite high; accrual to selected studies has been favorable.
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Beketov, Yevgeniy, Yelena Isaeva, Aleksey Solovev, Olga Golovanova, Liliya Ulyanenko, Yegor Malakhov, Anastas Kisel, et al. "BIOLOGICAL DOSE UNIFORMITY IN SPREAD-OUT BRAGG PEAK OF PROTON SCANNING BEAM THERAPEUTIC FACILITY." Problems in oncology 65, no. 4 (April 1, 2019): 532–36. http://dx.doi.org/10.37469/0507-3758-2019-65-4-532-536.
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Introduction. Biological dose uniformity in SOBP of the modem proton therapy facilities is an important issue. The results of a number of studies reveal an increased biological efficiency at the distal area of SOBP. The aim of the study was to verify this effect for Prometeus facility, which provides proton therapy with a scanning pencil beam. Material and methods. The study was conducted at A. Tsyb MRRC. Melanoma B16F10 cells were used for the experiments. The biological efficacy of protons was evaluated by clonogenic assay (cell survival) and comet assay (DNA damage). Proton dose range within the experiments was 4-8 Gy. Cells were irradiated both in monolayer and suspension conditions. Proton biological efficacy along SOBP was evaluated in the proximal, middle and distal positions. All irradiations were carried out with one field. Results of in vitro experiments indicate that Prometeus facility treatment planning system in case of single-field irradiation provides the uniformity of the biological dose in SOBP. According to cell survival, there is a tendency for a slightly greater efficiency of protons in the proximal part of SOBP. Data on DNA damage confirm this conclusion. Conclusion. Therefore, unlike a number of modern installations for proton therapy in the case of the facility used in the study, there is no increase of biological dose in the distal area of SOBP.
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Dzhuzha, Dmitry. "Charged particles therapy in radiation oncology." Radiation Diagnostics, Radiation Therapy, no. 1 (2020): 39–49. http://dx.doi.org/10.37336/2707-0700-2020-1-4.
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The physical and biological features of using protons and heavy ions in the treatment of malignant tumours were reviewed. It is showed that proton therapy is an effective method for treatment of malignant tumours, which has certain benefits comparing photon therapy. This modality may be recommended to 10-15 % of oncological patients. Carbon ion radiation therapy is especially perspective as it has local relative biological effectiveness till 2,0-3,5. The clinical efficacy of charged particles therapy at most expansive tumours was revealed. The cost efficacy of this type of radiation therapy was given. Key words: proton therapy, ion therapy, charged particles therapy, clinical efficacy of charged particles therapy.
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Dini, Valentina, Mauro Belli, and Maria Antonella Tabocchini. "Targeting cancer stem cells: protons versus photons." British Journal of Radiology 93, no. 1107 (March 2020): 20190225. http://dx.doi.org/10.1259/bjr.20190225.
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Recent studies on cancer stem cells revealed they are tumorigenic and able to recapitulate the characteristics of the tumour from which they derive, so that it was suggested that elimination of this population is essential to prevent recurrences after any treatment. However, there is evidence that cancer stem cells are inherently resistant to conventional (photon) radiotherapy. Since the use of proton beam therapy in cancer treatment is growing rapidly worldwide, mainly because of their excellent dosimetric properties, the possibility could be considered that they also have biological advantages through preferential elimination of cancer stem cells. Indeed, a review of preclinical data suggest that protons and photons differ in their biological effects on cancer stem cells, with protons offering potential advantages, although the heterogeneity of cancer stem cells and the different proton irradiation modalities make the comparison of the results not so easy. Further research to understand the mechanisms underlying such effects is important for their possible exploitation in clinics and to perform proton beam therapy optimization.
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Schreuder, Andries N., and Jacob Shamblin. "Proton therapy delivery: what is needed in the next ten years?" British Journal of Radiology 93, no. 1107 (March 2020): 20190359. http://dx.doi.org/10.1259/bjr.20190359.
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Proton radiation therapy has been used clinically since 1952, and major advancements in the last 10 years have helped establish protons as a major clinical modality in the cancer-fighting arsenal. Technologies will always evolve, but enough major breakthroughs have been accomplished over the past 10 years to allow for a major revolution in proton therapy. This paper summarizes the major technology advancements with respect to beam delivery that are now ready for mass implementation in the proton therapy space and encourages vendors to bring these to market to benefit the cancer population worldwide. We state why these technologies are essential and ready for implementation, and we discuss how future systems should be designed to accommodate their required features.
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Ricciardi, Valerio, Pavel Bláha, Raffaele Buompane, Giuseppina Crescente, Giacomo Cuttone, Lucio Gialanella, Katarina Michaličková, Severina Pacifico, Giuseppe Porzio, and Lorenzo Manti. "A New Low-Energy Proton Irradiation Facility to Unveil the Mechanistic Basis of the Proton-Boron Capture Therapy Approach." Applied Sciences 11, no. 24 (December 16, 2021): 11986. http://dx.doi.org/10.3390/app112411986.
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Protontherapy (PT) is a fast-growing cancer therapy modality thanks to much-improved normal tissue sparing granted by the charged particles’ inverted dose-depth profile. Protons, however, exhibit a low biological effectiveness at clinically relevant energies. To enhance PT efficacy and counteract cancer radioresistance, Proton–Boron Capture Therapy (PBCT) was recently proposed. PBCT exploits the highly DNA-damaging α-particles generated by the p + 11B→3α (pB) nuclear reaction, whose cross-section peaks for proton energies of 675 keV. Although a significant enhancement of proton biological effectiveness by PBCT has been demonstrated for high-energy proton beams, validation of the PBCT rationale using monochromatic proton beams having energy close to the reaction cross-section maximum is still lacking. To this end, we implemented a novel setup for radiobiology experiments at a 3-MV tandem accelerator; using a scattering chamber equipped with an Au foil scatterer for beam diffusion on the biological sample, uniformity in energy and fluence with uncertainties of 2% and 5%, respectively, was achieved. Human cancer cells were irradiated at this beamline for the first time with 685-keV protons. The measured enhancement in cancer cell killing due to the 11B carrier BSH was the highest among those thus far observed, thereby corroborating the mechanistic bases of PBCT.
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Asuroglu, Tunc. "Enhancing precision in proton therapy: Utilizing machine learning for predicting Bragg curve peak location in cancer treatment." Communications Faculty of Sciences University of Ankara Series A2-A3 Physical Sciences and Engineering 66, no. 2 (March 5, 2024): 140–61. http://dx.doi.org/10.33769/aupse.1417403.
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In proton beam therapy, the Bragg peak is the point where protons lose energy the fastest. This point is crucial for dose control, preserving healthy tissues, minimizing lateral scattering, and the success of treatment planning. However, accurately predicting the location of the Bragg peak is challenging due to the complex interactions of protons with tissues. This study proposes a machine learning (ML) approach to predict the exact location of the Bragg peak from phantom tissue proton beam therapy experiments. A dataset comprising the eight most commonly used biomaterials, which mimic human tissue in proton therapy procedures, has been curated for this study. Various ML models are benchmarked to find the most successful approach. ML model parameters are further optimized using a metaheuristic approach to achieve the highest prediction capability. In addition, feature contributions of each feature in the dataset are analyzed using an explainable artificial intelligence (XAI) technique. According to experimental results, Random Forest (RF) model that is optimized with Genetic Algorithm (GA) achieved 0.742 Correlation Coefficient (CC) value, 0.069 Mean Absolute Error (MAE) and 0.145 Root Mean Square Error (RMSE) outperforming other ML models. The proposed approach can track and predict the movement of the proton beam in real-time during treatment, enhancing treatment safety and contributing to the more effective management of the treatment process. This study is the first to predict exact Bragg curve peak locations from proton beam therapy experiments using ML approaches. The optimized ML model can provide higher precision in identifying the needed beam dosage for targeted tumor and improving treatment outcomes.
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Choi, Park, Cho, and Choi. "Cyclin D1 is Associated with Radiosensitivity of Triple-Negative Breast Cancer Cells to Proton Beam Irradiation." International Journal of Molecular Sciences 20, no. 19 (October 7, 2019): 4943. http://dx.doi.org/10.3390/ijms20194943.
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Proton therapy offers a distinct physical advantage over conventional X-ray therapy, but its biological advantages remain understudied. In this study, we aimed to identify genetic factors that contribute to proton sensitivity in breast cancer (BC). Therefore, we screened relative biological effectiveness (RBE) of 230 MeV protons, compared to 6 MV X-rays, in ten human BC cell lines, including five triple-negative breast cancer (TNBC) cell lines. Clonogenic survival assays revealed a wide range of proton RBE across the BC cell lines, with one out of ten BC cell lines having an RBE significantly different from the traditional generic RBE of 1.1. An abundance of cyclin D1 was associated with proton RBE. Downregulation of RB1 by siRNA or a CDK4/6 inhibitor increased proton sensitivity but not proton RBE. Instead, the depletion of cyclin D1 increased proton RBE in two TNBC cell lines, including MDA-MB-231 and Hs578T cells. Conversely, overexpression of cyclin D1 decreased the proton RBE in cyclin D1-deficient BT-549 cells. The depletion of cyclin D1 impaired proton-induced RAD51 foci formation in MDA-MB-231 cells. Taken together, this study provides important clues about the cyclin D1-CDK4-RB1 pathway as a potential target for proton beam therapy in TNBC.
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Choi, Changhoon, Ga Haeng Lee, Arang Son, Gyu Sang Yoo, Jeong Il Yu, and Hee Chul Park. "Downregulation of Mcl-1 by Panobinostat Potentiates Proton Beam Therapy in Hepatocellular Carcinoma Cells." Cells 10, no. 3 (March 4, 2021): 554. http://dx.doi.org/10.3390/cells10030554.
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Epigenetic modulation by histone deacetylase (HDAC) inhibitors is an attractive anti-cancer strategy for diverse hematological and solid cancers. Herein, we explored the relative effectiveness of the pan-HDAC inhibitor panobinostat in combination with proton over X-ray irradiation in HCC cells. Clonogenic survival assays revealed that radiosensitization of Huh7 and Hep3B cells by panobinostat was more evident when combined with protons than X-rays. Panobinostat increased G2/M arrest and production of intracellular reactive oxygen species, which was further enhanced by proton irradiation. Immunofluorescence staining of γH2AX showed that panobinostat enhanced proton-induced DNA damage. Panobinostat dose-dependently decreased expression of an anti-apoptotic protein, Mcl-1, concomitant with increasing acetylation of histone H4. The combination of panobinostat with proton irradiation enhanced apoptotic cell death to a greater extent than that with X-ray irradiation. Depletion of Mcl-1 by RNA interference enhanced proton-induced apoptosis and proton radiosensitization, suggesting a potential role of Mcl-1 in determining proton sensitivity. Together, our findings suggest that panobinostat may be a promising combination agent for proton beam therapy in HCC treatment.
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Azarkin, Maxim, Martin Kirakosyan, and Vladimir Ryabov. "Study of Nuclear Reactions in Therapy of Tumors with Proton Beams." International Journal of Molecular Sciences 24, no. 17 (August 29, 2023): 13400. http://dx.doi.org/10.3390/ijms241713400.
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This paper presents an assessment of nuclear reaction yields of protons, α-particles, and neutrons in human tissue-equivalentmaterial in proton therapy using a simulation with Geant 4. In this study, we also check an enhancement of nuclear reactions due to the presence of Bi, Au, 11B, and 10B radiosensitizer nanoparticles. We demonstrate that a proton beam induces a noticeable amount of nuclear reactions in the tissue. Nevertheless, the enhancement of nuclear reaction products due to radiosensitizer nanoparticles is found to be negligible.
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Williams, Vonetta, Lia Halasz, Jason Rockhill, and James Fink. "RTHP-14. PSEUDOPROGRESSION IN HIGH GRADE GLIOMA PATIENTS AFTER PROTON OR PHOTON THERAPY." Neuro-Oncology 21, Supplement_6 (November 2019): vi213. http://dx.doi.org/10.1093/neuonc/noz175.887.
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Abstract Pseudoprogression is defined as the appearance of false progression on MR imaging following radiation therapy. Proton therapy is thought to have increased relative biological effectiveness-the ratio of the doses required by two types of radiation to cause the same level of effect-near the edges of the high dose volume. This could lead to different rates of pseudoprogression for protons compared to photons. In our IRB approved study, a board-certified neuroradiologist reviewed serial imaging of 74 patients (photons: n=37, protons: n=37) treated from 2013–2018 with either proton or photon radiotherapy to 59.4–60 Gy in 30–33 fractions and temozolomide for high grade glioma. MR imaging was performed 1 month after completion of treatment and then every 3 months. True progression was scored based on updated RANO criteria. Pseudoprogression was determined if imaging improved without change in therapy. Cumulative incidences of these outcomes and survival were calculated utilizing Kaplan-Meier analyses. Patient and treatment factors were analyzed for their association with incidence of pseudoprogression. Median follow-up for alive patients in the proton and photon groups were 15 and 29 months, respectively. Median age was 49 years in the proton group and 54 years in the photon group (p=0.17). Among proton patients, 14 had grade III glioma and 23 had grade IV glioblastoma. Among photon patients, 1 had grade III glioma. Median survival was 23 and 35 months for the proton and photon groups, respectively (p=0.57). The cumulative incidence of pseudoprogression was 14.4% and 10.4% at 12 months for the proton and photon groups, respectively (p=0.53). Grade, extent of resection, age, and IDH status, were not significantly associated with development of pseudoprogression. MGMT methylated tumors showed a trend toward association with pseudoprogression compared to unmethylated tumors (p=0.058). We concluded that the incidence of pseudoprogression is similar regardless of whether proton or photon therapy was utilized.
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Lesmana, Hadi, Wahyu Setia Budi, Rasito Rasito, and Pandji Triadyaksa. "MONTE CARLO NEUTRON DOSE MEASUREMENT IN PROTON THERAPY FOR HEALTHCARE WORKER RADIATION SAFETY." Jurnal Kedokteran Diponegoro (Diponegoro Medical Journal) 12, no. 3 (May 22, 2023): 157–66. http://dx.doi.org/10.14710/dmj.v12i3.38660.
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Background: Proton therapy is an innovative and highly advanced external radiation therapy modality for cancer treatment that uses positively charged atomic particles. The usage of proton therapy facilities in Asia has been increasing and will be followed by Indonesia in the short-coming years. In line with its significant benefits, the application of proton therapy also requires radiation protection awareness due to its higher energy used by protons produces scattered photon and neutron radiation in proton interactions. Therefore, optimal verification is needed in the commissioning process for designing proton therapy shielding bunkers. Objective: This research aims to examine the effect of concrete density on proton shielding by calculating the equivalent dose H*(10) of neutrons in the treatment control room (TCR) and the door of the compact proton therapy facility (CPTC) using Particle and Heavy Ion Transport code System (PHITS) simulation software. Method: The proton facility modeled for this simulation uses a compact proton therapy type planned to be built at one of the radiotherapy facilities in Indonesia. The proton therapy bunker model consists of a synchrocyclotron accelerator room and an examination room with standard configurations, wall thicknesses, and modeling areas under compact proton therapy standards. The analysis is focused on assessing the suitability of concrete materials and wall thicknesses and determining the neutron exposure dose values in the TCR and CPTC doors. The geometry, radiation source, and type of concrete in the wall are simulated from a conservative assumption to a more realistic model. Result: At the designated points in the TCR and CPTC door, measurements are taken from the simulation, which indicates that the equivalent dose H*(10) value is below one mSv/year. Conclusion: This value indicates that the dose rate passing through the wall does not exceed the dose limit value already set at one mSv/year for the general public.
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Farr, Jonathan B., Allan F. Thornton, Avril O’Ryan-Blair, Chris E. Allgower, Arnold L. Schroeter, and Andries N. Schreuder. "Granulomatous slack skin disease: a new combined proton and photon therapy approach with a reported case response." Journal of Radiotherapy in Practice 14, no. 1 (July 30, 2014): 4–9. http://dx.doi.org/10.1017/s1460396914000296.
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AbstractPurposeHere, we report the feasibility and long-term efficacy of a granulomatous slack skin disease (GSSD) treatment with combined high-energy photon and proton beams.Patient and methodsA GSSD patient with abdominal disease volume 25×15×2–4 cm deep was recommended for treatment at this institution. In addition to photons and electrons, high-energy protons delivered with advanced planning techniques and patient positioning were used. The patient was irradiated to a total dose of 40 Gy by using 20 Gy matched photon and electrons followed by 20 Gy equivalent protons delivered by using innovative range compensation and patient positioning.ResultsThe test patient tolerated the treatment well and is now a 10-year survivor of the disease.ConclusionsTreatment of GSSD with protons is feasible. The range and narrow penumbra properties of the proton beam provided an ideal capability to match fields accurately to cover large volumes while also sparing underlying normal tissues.
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López, J. A., S. S. Romero González, O. Hernández Rodríguez, J. Holmes, and R. Alarcon. "GEANT4 Study of Proton–Body Interactions." Journal of Nuclear Physics, Material Sciences, Radiation and Applications 8, no. 2 (February 10, 2021): 121–27. http://dx.doi.org/10.15415/jnp.2021.82015.
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Proton therapy uses a beam of protons to destroy cancer cells. A problem of the method is the determination of what part of the body the protons are hitting during the irradiation. In a previous study we determine that by capturing the gamma rays produced during the irradiation one can determine the location of the proton-body interaction, in this work we investigate if by examining the gamma rays produced it is possible to determine the body part that produced the gamma rays by the proton collision. This study uses GEANT4 computer simulations of interactions of proton-tissue, protonbrain, proton-bone, etc., which produce gamma rays, to determine the characteristics of the gamma rays produced. We then analyze the characteristics of the gamma rays to find signatures that could be used to determine the source of the rays. In particular, we study the distribution of gamma ray energies, their full-width half-maximum, energy resolution, maximum height, and total number of counts. This study concludes that it is possible to use the gamma ray spectra to determine what body part produced it.
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McNamara, Aimee, Henning Willers, and Harald Paganetti. "Modelling variable proton relative biological effectiveness for treatment planning." British Journal of Radiology 93, no. 1107 (March 2020): 20190334. http://dx.doi.org/10.1259/bjr.20190334.
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Dose in proton radiotherapy is generally prescribed by scaling the physical proton dose by a constant value of 1.1. Relative biological effectiveness (RBE) is defined as the ratio of doses required by two radiation modalities to cause the same level of biological effect. The adoption of an RBE of 1.1. assumes that the biological efficacy of protons is similar to photons, allowing decades of clinical dose prescriptions from photon treatments and protocols to be utilized in proton therapy. There is, however, emerging experimental evidence that indicates that proton RBE varies based on technical, tissue and patient factors. The notion that a single scaling factor may be used to equate the effects of photons and protons across all biological endpoints and doses is too simplistic and raises concern for treatment planning decisions. Here, we review the models that have been developed to better predict RBE variations in tissue based on experimental data as well as using a mechanistic approach.
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Regentova, O. S., O. I. Shcherbenko, E. V. Kumirova, F. F. Antonenko, and V. A. Solodkiy. "Proton therapy in pediatric neuro-oncology. Potential advantages and the relationship between cost and results." Siberian journal of oncology 23, no. 2 (May 12, 2024): 92–100. http://dx.doi.org/10.21294/1814-4861-2024-23-2-92-100.
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The aim of study: to analyze the accumulated experience and try to identify those clinical situations in which the use of protons will be economically and clinically more effective than photon radiation therapy. Material and methods. The articles devoted to the study of the evaluation and comparison of the effectiveness of proton and photon radiation beams in the treatment of tumors of the central nervous system and published over the past 25 years were searched in the Medline, Embase and the Cochrane Library databases. Results. the analysis of available publications has shown that accelerated protons do not improve survival rates and disease-free rates in all forms of brain tumors compared with photon therapy. However, protons can significantly increase the level of dose distribution conformity and reduce the dose to critical structures (pituitary gland, cochlea, eye lenses, hypothalamus), thus reducing the risk of hearing and visual impairment as well as hormonal and cognitive disorders. All this is critically important for potentially curable malignant tumors, such as medulloblastoma and germinoma, for low malignant potential tumors (grade 1–2 glioma) or tumors with decreased metastatic potential, since proton therapy compared to photon therapy reduces the risk of late side effects that worsen the quality of life of cured children. Conclusion. central nervous system tumors are one of the most common solid malignant neoplasms in children. Radiation therapy (RT) is recognized as an important therapeutic component of treatment and is often used in strategies for multimodal therapy of tumors of the central nervous system in children. Proton radiation therapy is one of the attractive methods of radiotherapy with minimal dose distribution to normal tissues and a decrease in the absorbed dose. The precision of protons reduces the risk of long-term side effects associated with this type of treatment and the induction of secondary malignancies, which is of particular importance for the quality of life.
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Giri, K., and R. Khanal. "Energy Loss of Proton Beam on Ovary Tumor." Journal of Nepal Physical Society 5, no. 1 (December 26, 2019): 24–29. http://dx.doi.org/10.3126/jnphyssoc.v5i1.26879.
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Proton beam therapy is more effective method than most common radiation (x-rays or photons) therapy and is a new type of irradiation that destroys the tumor or cancer cells in the human body. In the proton therapy, the beam consists of charged nuclei of hydrogen atoms i.e. hydrogen ions or protons. The beam of proton loses the most of its energy to the targeted tissue like ovary tumor cells, with less impact of healthy tissues and organs. This property of a proton beam makes it ideal for clinical applications. When organ safe keeping is our priority then proton beam therapy is the most effective tool to damage nearby affected tissues. For efficient treatment planning in ovary tumor, the maximal energy loss of proton beam in its tissues must be exactly calculated. The method of computer simulation, SRIM is employed for the calculation of energy loss by energized proton beam irradiation on ovary tumor at a depth of 43.3 mm. The stopping power and range data agrees with standard reference data. 65 Mev energy loss is caused by ionization and the energy loss in various layers viz. skin, adipose tissue, soft muscle and ovary are approximately 2.6 MeV, 15 MeV, 7 MeVand 40 MeV respectively, ensuring less injury to healthy cells.
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Kubes, Jiří. "Clinical application of proton beam radiation therapy in the tumor's treatment." Russian Journal of Oncology 19, no. 5 (October 15, 2014): 4–10. http://dx.doi.org/10.17816/onco40069.
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Despite the rapid technological development, standard photon radiotherapy still brings a number of issues. Main problems are: 1. lack of effectiveness for a number of indications; partly due to the inability to safely deliver the effective dose to the tumors; 2. late and very late side effects of treatment caused by the unwanted dose delivered to the surrounding healthy tissue. The aim of the new methods in radiotherapy is to maximally reduce the dose to healthy tissue and to deliver the dose to the tumors as accurately as possible. Proton therapy comes closest to this goal from the all available methods. The principle ofproton radiotherapy is use of accelerated hydrogen particles - protons, which are directed to the tumors. Due to the interaction of protons with the tissue, majority of the energy is deposed at a certain depth in tissue, in the so-called Bragg peak of absorption. The dose of radiation is very precisely delineated and there is no extra dose behind the tumors it. High-precise proton therapy requires a high-end technology within the whole radiotherapy chain. Tumor has to be examined and defined using combination of CT, MRI and PET. Reproducibility of the patient position requires special fixation devices. Each individual fraction of radiation must be done with image - guidance (IGRT) technology. The benefit of protons is minimizing the dose delivery to the healthy tissue. This applies for organs near the tumors and also for integral dose of organism. Therefore; proton therapy is most appropriate in situations where we expect a significant chance of curability in patient with expected long-term survival and high risk of side effects. Typical cases for proton radiotherapy are children with a malignant disease or brain tumors (meningioma, low-grade glioma) in young cancer patients. The second group of indications is cancers that are not curable with photon radiotherapy due to their location or low sensitivity to radiation. This group includes for example cancer of the pancreas or retroperitoneal sarcoma. Treatment results for various diagnoses will be presented. Proton radiotherapy is a new option in treatment of malignant tumors that pushes the limits of radiation oncology forward, onto a higher level.
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Slater, Jerry D. "Clinical Applications of Proton Radiation Treatment at Loma Linda University: Review of a Fifteen-year Experience." Technology in Cancer Research & Treatment 5, no. 2 (April 2006): 81–89. http://dx.doi.org/10.1177/153303460600500202.
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Proton radiation therapy has been used at Loma Linda University Medical Center for 15 years, sometimes in combination with photon irradiation, surgery, and chemotherapy, but often as the sole modality. Our initial experience was based on established studies showing the utility of protons for certain management problems, but since then we have engaged in a planned program to exploit the capabilities of proton radiation and expand its applications in accordance with progressively accumulating clinical data. Our cumulative experience has confirmed that protons are a superb tool for delivering conformal radiation treatments, enabling delivery of effective doses of radiation and sparing normal tissues from radiation exposure.