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Purpose: The purpose of this article was to highlight current and future trends in radiobiology in an effort to move hadron therapy forward through the application of new knowledge in DNA damage and subsequent response to heavy ion radiotherapy, immune oncology and the interconnection between. Methods: The subject matter begins with a description of the role of radiation in eliciting either an immunogenic or tolerogenic response to radiation exposure. The role of fragmented DNA in an immunogenic response is described, followed by the definitive role that DNA damage and subsequent repair, or not, of complex DNA damage after hadron exposure plays in the survival response of hadron irradiated cells. Results: The process by which ionizing radiation elicits an immunogenic rather than tolerogenic response is becoming clearer. The timing of fractionated radiotherapy when combined with an immune checkpoint inhibitor is not clear and may be tumor site specific. Furthermore, whether hadron therapy is more effective at generating a durable immunogenic response is unknown. Conclusions: Cytosolic DNA plays a significant role in eliciting an innate immune response with the likelihood that hadron therapy would generate complex DNA damage that because it is less likely to be repaired, is more likely to become cytosolic DNA, and more likely to activate an immunogenic response. Lastly, DNA repair pathway choice appears to be a credible bio-indicator for hadron therapy selection as well identify druggable targets to enhance hadron therapy. [ABSTRACT FROM AUTHOR]

Introduction: Hadron therapy is today an established modality in cancer radiation therapy that, world-wide, is available in about hundred centres. About 90% of them are devoted to proton therapy and the rest also to carbon ion therapy. Based on the superior ballistic and radiobiological properties of fast ions, this discipline experienced a remarkable growth in the last 30 years. Purpose: This paper reviews the history of hadron therapy starting from the initial work done at Berkeley in the 30's. Methods: Fast neutron therapy is not forgotten but the main accent is on the parallel development of proton and carbon ion therapy. For space reasons pion therapy, to which a lot of efforts have been devoted without success, is not discussed. Results: The activities of the main protagonists in USA, Japan and Europe are shortly presented so that the reader can appreciate the relevance of the contribution given by each of them to the advancement of the field. Conclusions: The review ends in 2005, when the carbon ion centres HIT in Heidelberg and CNAO in Pavia were under construction, with the aim of putting at the disposal of European citizens advanced treatments of radioresistant tumours, which cannot be effectively treated neither with X rays nor with protons. [ABSTRACT FROM AUTHOR]

Purpose: Hadron therapy, utilizing carbon Ions and protons, is a promising medical treatment for cancer. However, the effectiveness of carbon ions is constrained by infrastructure limitations, particularly in accelerator halls with standard resistive magnet synchrotrons and gantries. The advent of superconducting (SC) magnets presents a transformative solution. The purpose of this study is to give an overview of the superconducting magnets projects led by INFN focused on the hadron therapy. Methods: In the introduction the study analyzes the current infrastructure limitations of hadron Therapy. Furthermore, ongoing European projects such as HITRIplus, I.FAST, and SIG, driven by the INFN, are examined to highlight the momentum toward SC magnets in hadron therapy. Initiatives like ESABLIM and IRIS, emphasizing energy-saving technologies, are also discussed in the context of operational infrastructure plans. Results: The implementation of superconducting magnets in hadron therapy gantries yields significant advantages. These include a substantial reduction in weight, a decrease in the number of required magnets, a smaller footprint, and lower costs. Moreover, compact accelerators and gantries minimize the need for extensive civil construction. The reduction in power consumption further underscores the superiority of SC magnets over their normal conducting counterparts. Conclusion: The integration of superconducting magnets in heavy ions facilities for medical applications offers more compact and economically sustainable structures. Collaborative projects like HITRIplus, SIG, I.FAST, ESABLIM, and IRIS are advancing superconducting magnet technology for medical accelerators and gantry magnets. This mutual interest between superconducting magnet technology and hadron therapy signifies promising advancements in healthcare innovation. [ABSTRACT FROM AUTHOR]

Purpose: MedAustron mission is to cure cancer by providing advanced patient care, clinical trials, applied and basic research, and know-how transfer. The facility is constantly striving to improve the therapy method of ion beam therapy, to increase its effectiveness and to make the treatment accessible to more people. Methods: The MedAustron particle therapy accelerator facility is located in Austria and delivers protons in the energy range 60–250 MeV and carbon ions 120–400 MeV/n for tumor treatment to four irradiation rooms. Clinical treatment includes two rooms with fixed beam lines horizontal and horizontal/vertical and a third room with a rotating beam line, the proton gantry. A fourth irradiation room is dedicated to research delivering carbon and helium beams and where proton beams up to 800 MeV are also provided. Results: The facility has been built, the commissioning has been completed and MedAustron is now successfully operating at its full functionality. Since the first patient treatment in December 2016, more than 2,000 patients have been treated at MedAustron. Conclusions: In this paper, we provide an overview of the facility including the world-wide first so-called rotator system used, synchronously with the gantry, to improve the quality of the beam delivered at the patient. Furthermore, we discuss about the ongoing projects for improvement of the facility, the areas of research and potential topics for collaboration. [ABSTRACT FROM AUTHOR]

Purpose: This study provides a comprehensive overview of the progress in hadron therapy within Europe, particularly highlighting the critical roles of the Proton Ion Medical Machine Study (PIMMS) and the European Network for Light Ion Hadron Therapy (ENLIGHT). Methods: Our approach includes a retrospective analysis of the advances in hadron therapy facilities, facilitated by a synthesis of interdisciplinary collaboration data gathered from ENLIGHT's annual meetings since 2002, and an assessment of European-funded projects and networks' contributions to the field. Results: The results showcase significant advancements in cancer treatment due to collective efforts in hadron therapy, underscored by ENLIGHT's pivotal role in fostering interdisciplinary cooperation and the harmonization of treatment protocols across Europe. Conclusion: The evolution of hadron therapy, from its inception to its current impact on patient care, demonstrates the successful realization of complex medical technologies through sustained collaboration and standardized practices across European institutions and projects. [ABSTRACT FROM AUTHOR]

Initially, the growth of particle detectors was focused on the identification of particles, but new detector designs have made it possible to build new diagnostic techniques. Clinical settings and medical research facilities utilize cutting-edge methods developed from particle accelerators, detectors, and physics computers, including imaging technologies, accelerators specifically designed for cancer therapy, simulations, data analysis, and nuclear medicine. It is still obvious that research in nuclear and basic particle physics is what motivates and propels the development of particle detectors for medical applications. The applications of the particle physics detector in medical science will be the main topic of this paper. [ABSTRACT FROM AUTHOR]

Background & Aims: Inoperable hepatocellular carcinoma (HCC) can be treated by stereotactic body radiotherapy. However, carbon ion radiotherapy (CIRT) is more effective for sparing non-tumorous liver. High linear energy transfer could promote therapy efficacy. Japanese and Chinese studies on hypofractionated CIRT have yielded excellent results. Because of different radiobiological models and the different etiological spectrum of HCC, applicability of these results to European cohorts and centers remains questionable. The aim of this prospective study was to assess safety and efficacy and to determine the optimal dose of CIRT with active raster scanning based on the local effect model (LEM) I. Methods: CIRT was performed every other day in four fractions with relative biological effectiveness (RBE)-weighted fraction doses of 8.1–10.5 Gy (total doses 32.4–42.0 Gy [RBE]). Dose escalation was performed in five dose levels with at least three patients each. The primary endpoint was acute toxicity after 4 weeks. Results: Twenty patients received CIRT (median age 74.7 years, n = 16 with liver cirrhosis, Child-Pugh scores [CP] A5 [n = 10], A6 [n = 4], B8 [n = 1], and B9 [n = 1]). Median follow up was 23 months. No dose-limiting toxicities and no toxicities exceeding grade II occurred, except one grade III gamma-glutamyltransferase elevation 12 months after CIRT, synchronous to out-of-field hepatic progression. During 12 months after CIRT, no CP elevation occurred. The highest dose level could be applied safely. No local recurrence developed during follow up. The objective response rate was 80%. Median overall survival was 30.8 months (1/2/3 years: 75%/64%/22%). Median progression-free survival was 20.9 months (1/2/3 years: 59%/43%/43%). Intrahepatic progression outside of the CIRT target volume was the most frequent pattern of progression. Conclusions: CIRT of HCC yields excellent local control without dose-limiting toxicity. Impact and implications: To date, safety and efficacy of carbon ion radiotherapy for hepatocellular carcinoma have only been evaluated prospectively in Japanese and Chinese studies. The optimal dose and fractionation when using the local effect model for radiotherapy planning are unknown. The results are of particular interest for European and American particle therapy centers, but also of relevance for all specialists involved in the treatment and care of patients with hepatocellular carcinoma, as we present the first prospective data on carbon ion radiotherapy in hepatocellular carcinoma outside of Asia. The excellent local control should encourage further use of carbon ion radiotherapy for hepatocellular carcinoma and design of randomized controlled trials. Clinical Trials Registration: The study is registered at ClinicalTrials.gov (NCT01167374).

Introduction: Charged Particle Therapy plays a key role in the treatment of deep-seated tumours, because of the advantageous energy deposition culminating in the Bragg peak. However, knowledge of the dose delivered in the entrance channel is limited by the lack of data on the beam and fragmentation of the target. Methods: The FOOT experiment has been designed to measure the cross sections of the nuclear fragmentation of projectile and target with two different detectors: an electronic setup for the identification of Z > 3 fragments and a nuclear emulsion spectrometer for Z < 3 fragments. In this paper, we analyze the data taken by exposing four nuclear emulsion spectrometers, with C and C2H4 targets, to 200 MeV/n and 400 MeV/n oxygen beams at GSI Helmholtzzentrum für Schwerionenforschung (Darmstadt, Germany), and we report the charge identification of produced fragments based on the controlled fading induced on nuclear emulsion films. Results: The goal of identifying fragments as heavy as lithium has been achieved. Discussion: The results will contribute to a better understanding of the nuclear fragmentation process in charged particle therapy and have implications for refining treatment planning in the presence of deep-seated tumors. [ABSTRACT FROM AUTHOR]

Hadron therapy (HT) is a technique that uses accelerated ions, notably protons, and carbon ions, to destroy tumors. It has demonstrated high success rates in the treatment of certain cancers resistant to irradiation. In HT, the majority of the dose is delivered to the tumor volume by electromagnetic interactions with atomic electrons. However, it is important to note that the primary particles used in HT can induce nuclear reactions, generating undesirable secondary radiation, certainly neutrons. As a result, a significant portion of the patients' body may be exposed to the secondary background radiation field. Thus, these unwanted secondary neutrons should be evaluated. The purpose of this research in first is to characterize the secondary neutron production (SNP) during the administration of Hadrons with energies 140 MeV proton, and 264 MeV/u carbon ions ( C) in a soft tissue phantom. Second, comparing the neutron spectrum for different angles for protons and carbon ions for carbon targets to experimental data. Our results show that the neutron spectra (thick target neutron yields TTNYs) at energies less than 20 MeV, using the INCL4.6/GEM models and JQMD/GEM across a wide range would be suitable for the Monte Carlo transport simulation. [ABSTRACT FROM AUTHOR]

Carbon-12 ion beams in the energy range of 100-450 MeV/u have excellent conditions for radiation-resistant and deep-seated tumors. At energies above 400 MeV/u, radiation is significantly affected by nuclear fragmentation processes of increasing depth. In this project, using the Geant4 toolkit, three physical models of Binary Intranuclear Cascade (BIC), Lige Intranuclear Cascade (INCL), and Quantum Molecular Dynamics (QMD) for heavy particles are defined in this toolkit. By examining the QMD model available in the Geant4 toolkit, the effects of heavy particles because of fragmentation of the nucleus by calculating the abundance of nuclei produced with an atomic number in the range 5>Z>1 (H, He, Li, Be and B particles) at different depths of the water phantom before and after the Bragg peak and the angular distribution of these particles have been investigated by this model. The particle abundance graph shows that particle production decreases with an increasing atomic number. H and He particles are the most abundant and their range is much broader than the range of primary carbon ions. Also, according to the angular distribution diagram, H and He particles have shown a much wider distribution. This is because they have the highest dose of deposition in the area outside the treatment field. Also, with increasing atomic numbers, the angular distribution decreases.

The inevitable progress from betatron to high energy circular induction accelerators is described. On the basis of an example of induction synchrotrons that has been put to practical use, characteristics and figures of benefit of circular induction accelerators are explained in detail. Details of the slow cycling induction synchrotron and the fast-cycling induction synchrotron which have been proven at KEK since 2004 are described. The existing RF acceleration systems in the KEK 12 GeV proton synchrotron and the 500 MeV Booster ring have been fully replaced by induction acceleration systems. A series of studies performed after the demonstration of induction synchrotron strongly indicated that existing circular RF accelerators such as cyclotron, microtron, and FFAG can be replaced by circular induction accelerators with increased flexibility and performance. Attractive applications such as the next generation of hadron therapy, the high energy cluster ion generator, or heavy ion inertial fusion are introduced.

Objective. Determine the extent of sublethal radiation damage (SRD) in a cell population that received a given dose of radiation and the impact of this damage on cell survival. Approach. We developed a novel formalism to account for accumulation of SRD with increasing dose. It is based on a very general formula for cell survival that correctly predicts the basic properties of cell survival curves, such as the transition from the linear-quadratic to a linear dependence at high doses. Using this formalism we analyzed extensive experimental data for photons, protons and heavy ions to evaluate model parameters, quantify the extent of SRD and its impact on cell survival. Main results. Significant accumulation of SRD begins at doses below 1 Gy. As dose increases, so does the number of damaged cells and the amount of SRD in individual cells. SRD buildup in a cell increases the likelihood of complex irrepairable damage. For this reason, during a dose fraction delivery, each dose increment makes cells more radiosensitive. This gradual radosensitization is evidenced by the increasing slope of survival curves observed experimentally. It continues until the fraction is delivered, unless radiosensitivity reaches its maximum first. The maximum radiosensitivity is achieved when SRD accumulated in most cells is the maximum damage they can repair. After this maximum is reached, the slope of a survival curve, logarithm of survival versus dose, becomes constant, dose independent. The survival curve becomes a straight line, as experimental data at high doses show. These processes are random. They cause large cell-to-cell variability in the extent of damage and radiosensitivity of individual cells. Significance. SRD is in effect a radiosensitizer and its accumulation is a significant factor affecting cell survival, especially at high doses. We developed a novel formalism to study this phenomena and reported pertinent data for several particle types. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy has increasingly assumed a central role in the multidisciplinary treatment of skull base lesions. Unfortunately, it is often burdened by relevant radio-induced damage to the pituitary function and the surrounding structures and systems. Patients who were treated with radiotherapy around the sellar region especially have a high risk of developing radio-induced hypopituitarism. Particle therapy has the potential advantage of delivering a higher radiation dose to the target while potentially sparing the sellar region and pituitary function. The aim of this study is to evaluate the pituitary function in adult patients who have undergone hadron therapy for anterior skull base lesions involving or surrounding the pituitary gland. Methods: This is a retrospective, observational, and noncontrolled study. We evaluated pituitary and peripheral hormone levels in all patients referring to National Center for Oncological Hadrontherapy, Pavia, Italy for anterior skull base tumors. Furthermore, we performed a magnetic resonance imaging for every follow-up to evaluate potential tumoral growth. Results: We evaluated 32 patients with different tumoral lesions with a mean follow-up of 27.9 months. The mean hadron therapy (HT) dose was 60 ± 14 Gray, with a mean dose per fraction of 2.3 ± 2.1 Gray. Six patients were treated with carbon ions and 26 with protons. Pituitary hormone alteration of some kind was reported for six patients. No patient experienced unexpected severe adverse events related to particle therapy. Conclusion: Particle radiotherapy performed on anterior skull base lesions has proved to cause limited damage to pituitary function in the adult population. [ABSTRACT FROM AUTHOR]

Real time radioluminescence fibre-based detectors were investigated for application in proton, helium, and carbon therapy dosimetry. The Al2O3:C probes are made of one single crystal (1 mm) and two droplets of micro powder in two sizes (38 μm and 4 μm) mixed with a water-equivalent binder. The fibres were irradiated behind different thicknesses of solid slabs, and the Bragg curves presented a quenching effect attributed to the nonlinear response of the radioluminescence (RL) signal as a function of linear energy transfer (LET). Experimental data and Monte Carlo simulations were utilised to acquire a quenching correction method, adapted from Birks' formulation, to restore the linear dose–response for particle therapy beams. The method for quenching correction was applied and yielded the best results for the '4 μm' optical fibre probe, with an agreement at the Bragg peak of 1.4% (160 MeV), and 1.5% (230 MeV) for proton-charged particles; 2.4% (150 MeV/u) for helium-charged particles and of 4.8% (290 MeV/u) and 2.9% (400 MeV/u) for the carbon-charged particles. The most substantial deviations for the '4 μm' optical fibre probe were found at the falloff regions, with ~3% (protons), ~5% (helium) and 6% (carbon). [ABSTRACT FROM AUTHOR]

Particle therapy is a developing area of radiotherapy, mostly involving the use of protons, neutrons and carbon ions for cancer treatment. The reduction of side effects on healthy tissues in the peritumoral area is an important advantage of particle therapy. In this review, we analyze state-of-the-art particle therapy, as compared to conventional photon therapy, to identify clinical benefits and specify the mechanisms of action on tumor cells. Systematization of published data on particle therapy confirms its successful application in a wide range of cancers and reveals a variety of biological effects which manifest at the molecular level and produce the particle therapy-specific molecular signatures. Given the rapid progress in the field, the use of particle therapy holds great promise for the near future. [ABSTRACT FROM AUTHOR]

Real-time radioluminescence two-dimensional coatings have potential as dosemeters in proton and carbon therapeutic beams. We investigated coatings made of nano and micro-(C 44 H 38 P 2)MnCl 4 and (C 38 H 36 P 2)MnBr 4 crystals mixed with a water-equivalent substrate. The response of the radioluminescence signal of the coatings along the Bragg curves presented an ionization quenching effect, but less prominent than what has been observed in our previous works using Al 2 O 3 :X (X = C and C,Mg) coatings. We hypothesize that this results from their lower crystal sizes and effective atomic number (Z eff). Combined experimental results and Monte Carlo simulations resulted in correction factors to address the linear energy transfer dependence and restore the constant response for particle therapy beams. The quenching correction method was applied to the studied proton and carbon ion beams and yielded the best results for the nano-(C 44 H 38 P 2)MnCl 4, coating, followed by the micro-(C 44 H 38 P 2)MnCl 4 , nano-(C 38 H 36 P 2)MnBr 4 , and micro-(C 38 H 36 P 2)MnBr 4. • Real-time RL coatings developed for proton and carbon ion dosimetry, using nano and micro crystals. • Quenching effects in RL coatings less prominent than Al 2 O 3 :C and Al 2 O 3 :C,Mg due to lower crystal sizes and Zeff. • Quenching correction best in nano-(C44H38P2)MnCl4 coating, followed by other tested coatings. [ABSTRACT FROM AUTHOR]

Experimental data concerning projectile and target fragmentation is limited, increasing the uncertainty on the dose in the entrance channel in particle therapy treatments. The FOOT experiment measures nuclear fragmentation cross sections with two complementary detectors. The performance of the FOOT nuclear emulsion detectors in identifying the charge of nuclear fragments has recently been studied using 16 O beams at 200 and 400 MeV/n , directed at carbon and polyethylene targets. This work extends the previous analysis, comparing experimental data and FLUKA Monte Carlo predictions, focusing on the angular distribution and relative abundances of fragments with Z ≤ 5 originating from the interactions of a 400 MeV/n oxygen beam with a carbon target. [ABSTRACT FROM AUTHOR]

Protons and carbon ions (hadrons) have useful properties for the treatments of patients affected by oncological pathologies. They are more precise than conventional X-rays and possess radiobiological characteristics suited for treating radio-resistant or inoperable tumours. This paper gives an overview of the status of hadron therapy around the world. It focusses on the Italian National Centre for Oncological Hadron therapy (CNAO), introducing operation procedures, system performance, expansion projects, methodologies and modelling to build individualized treatments. There is growing evidence that supports safety and effectiveness of hadron therapy for a variety of clinical situations. However, there is still a lack of high-level evidence directly comparing hadron therapy with modern conventional radiotherapy techniques. The results give an overview of pre-clinical and clinical research studies and of the treatments of 3700 patients performed at CNAO. The success and development of hadron therapy is strongly associated with the creation of networks among hadron therapy facilities, clinics, universities and research institutions. These networks guarantee the growth of cultural knowledge on hadron therapy, favour the efficient recruitment of patients and present available competences for R&D (Research and Development) programmes.

The use of hadron beams, especially proton beams, in cancer radiotherapy has expanded rapidly in the past two decades. To fully realize the advantages of hadron therapy over traditional x-ray and gamma-ray therapy requires accurate positioning of the Bragg peak throughout the tumor being treated. A half century ago, suggestions had already been made to use protons themselves to develop images of tumors and surrounding tissue, to be used for treatment planning. The recent global expansion of hadron therapy, coupled with modern advances in computation and particle detection, has led several collaborations around the world to develop prototype detector systems and associated reconstruction codes for proton computed tomography (pCT), as well as more simple proton radiography, with the ultimate intent to use such systems in clinical treatment planning and verification. Recent imaging results of phantoms in hospital proton beams are encouraging, but many technical and programmatic challenges remain to be overcome before pCT scanners will be introduced into clinics. This review introduces hadron therapy and the perceived advantages of pCT and proton radiography for treatment planning, reviews its historical development, and discusses the physics related to proton imaging, the associated experimental and computation issues, the technologies used to attack the problem, contemporary efforts in detector and computational development, and the current status and outlook.

The FRagment Separator FRS at GSI is a versatile spectrometer and separator for experiments with relativistic in-flight separated short-lived exotic beams. One branch of the FRS is connected to the target hall where the bio-medical cave (Cave M) is located. Recently a joint activity between the experimental groups of the FRS and the biophysics at the GSI and Department of physics at LMU was started to perform biomedical experiments relevant for hadron therapy with positron emitting carbon and oxygen beams. This paper presents the new ion-optical mode and commissioning results of the FRS-Cave M branch where positron emitting 15O-ions were provided to the medical cave for the first time. An overall conversion efficiency of 2. 9 ± 0. 2 × 1 0 − 4 15O fragments per primary 16O ion accelerated in the synchrotron SIS18 was reached. [ABSTRACT FROM AUTHOR]

Objective. Although in heavy-ion therapy, the quantum molecular dynamics (QMD) model is one of the most fundamental physics models providing an accurate daughter-ion production yield in the final state, there are still non-negligible differences with the experimental results. The aim of this study is to improve fragment production in water phantoms by developing a more accurate QMD model in Geant4. Approach. A QMD model was developed by implementing modern Skyrme interaction parameter sets, as well as by incorporating with an ad hoc α -cluster model in the initial nuclear state. Two adjusting parameters were selected that can significantly affect the fragment productions in the QMD model: the radius to discriminate a cluster to which nucleons belong after the nucleusâ€"nucleus reaction, denoted by R, and the squared standard deviation of the Gaussian packet, denoted by L. Squared Mahalanobis’s distance of fragment yields and angular distributions with 1, 2, and the higher atomic number for the produced fragments were employed as objective functions, and multi-objective optimization (MOO), which make it possible to compare quantitatively the simulated production yields with the reference experimental data, was performed. Main results. The MOO analysis showed that the QMD model with modern Skyrme parameters coupled with the proposed α -cluster model, denoted as SkM* α, can drastically improve light fragments yields in water. In addition, the proposed model reproduced the kinetic energy distribution of the fragments accurately. The optimized L in SkM* α was confirmed to be realistic by the charge radii analysis in the ground state formation. Significance. The proposed framework using MOO was demonstrated to be very useful in judging the superiority of the proposed nuclear model. The optimized QMD model is expected to improve the accuracy of heavy-ion therapy dosimetry. [ABSTRACT FROM AUTHOR]

The interest in hadron therapy is growing fast thanks to the latest technological advances in accelerators and delivery technologies, to the development of more and more efficient and comprehensive treatment planning tools, and due to its increasing clinical adoption proving its efficacy. A precise and reliable beam quality assessment and an accurate and effective inclusion of the biological effectiveness of different radiation qualities are fundamental to exploit at best its advantages with respect to conventional radiotherapy. Currently, in clinical practice, the quality assurance (QA) is carried out by means of conventional dosimetry, while the biological effectiveness of the radiation is taken into account considering the Relative Biological Effectiveness (RBE). The RBE is considered a constant value for protons and it is estimated as a function of the absorbed dose in case of carbon ions. In this framework, microdosimetry could bring a significant improvement to both QA and RBE estimation. By measuring the energy deposited by the radiation into cellular or sub-cellular volumes, microdosimetry could provide a unique characterisation of the beam quality on one hand, and a direct link to radiobiology on the other. Different detectors have been developed for microdosimetry, from the more conventional tissue equivalent proportional counter (TEPC), silicon-based and diamond-based solid-state detectors, to ΔE-E telescope detectors, gas electrons multiplier (GEM), hybrid microdosimeters and a micro-bolometer based on Superconducting QUantum Interference Device (SQUID) technology. However, because of their different advantages and drawbacks, a standard device and an accredited experimental methodology have not been unequivocally identified yet. The establishment of accepted microdosimetry standard protocols and code of practice is needed before the technique could be employed in clinical practice. Hoping to help creating a solid ground on which future research, development and collaborations could be planned and inspired, a comprehensive state of the art of the detector technologies developed for microdosimetry is presented in this review, discussing their use in clinical hadron therapy conditions and considering their advantages and drawbacks.

Objectives. Microdosimetry is proving to be a reliable and powerful tool to be applied in different fields such as radiobiology, radiation protection and hadron therapy. However, accepted standard protocols and codes of practice are still missing. With this regard, a systematic and methodical uncertainty analysis is fundamental to build an accredited uncertainty budget of practical use. This work studied the contribution of counting statistics (i.e. number of events collected) to the final frequency-mean and dose-mean lineal energy uncertainties, aiming at providing guidelines for good experimental and simulation practice. The practical limitation of current technologies and the non-negligible probability of nuclear reactions require careful considerations and nonlinear approaches. Approach. Microdosimetric data were obtained by means of the particle tracking Monte Carlo code Geant4. The uncertainty analysis was carried out relying on a Monte Carlo based numerical analysis, as suggested by the BIPM's ‘Guide to the expression of uncertainty in measurement’. Final uncertainties were systematically investigated for proton, helium and carbon ions at an increasing number of detected events, for a range of different clinical-relevant beam energies. Main results. Rare events generated by nuclear interactions in the detector sensitive volume were found to massively degrade microdosimetric uncertainties unless a very high statistics is collected. The study showed an increasing impact of such events for increasing beam energy and lighter ions. For instance, in the entrance region of a 250 MeV proton beam, about 5 ∗ 107 events need to be collected to obtain a dose-mean lineal energy uncertainty below 10%. Significance. The results of this study help define the necessary conditions to achieve appropriate statistics in computational microdosimetry, pointing out the importance of properly taking into account nuclear interaction events. Their impact on microdosimetric quantities and on their uncertainty is significant and cannot be overlooked, particularly when characterising clinical beams and radiobiological response. This work prepared the ground for deeper investigations involving dedicated experiments and for the development of a method to properly evaluate the counting statistics uncertainty contribution in the uncertainty budget, whose accuracy is fundamental for the clinical transition of microdosimetry. [ABSTRACT FROM AUTHOR]

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Protons and carbon ions (hadrons) have useful properties for the treatments of patients affected by oncological pathologies. They are more precise than conventional X-rays and possess radiobiological characteristics suited for treating radio-resistant or inoperable tumours. This paper gives an overview of the status of hadron therapy around the world. It focusses on the Italian National Centre for Oncological Hadron therapy (CNAO), introducing operation procedures, system performance, expansion projects, methodologies and modelling to build individualized treatments. There is growing evidence that supports safety and effectiveness of hadron therapy for a variety of clinical situations. However, there is still a lack of high-level evidence directly comparing hadron therapy with modern conventional radiotherapy techniques. The results give an overview of pre-clinical and clinical research studies and of the treatments of 3700 patients performed at CNAO. The success and development of hadron therapy is strongly associated with the creation of networks among hadron therapy facilities, clinics, universities and research institutions. These networks guarantee the growth of cultural knowledge on hadron therapy, favour the efficient recruitment of patients and present available competences for R&D (Research and Development) programmes. [ABSTRACT FROM AUTHOR]

Radiation therapy with protons and heavier ions is an attractive form of cancer treatment that could enhance local control and survival of cancers that are currently difficult to cure and lead to less side effects due to sparing of normal tissues. However, particle therapy faces a significant technical challenge because one cannot accurately predict the particle range in the patient using data provided by existing imaging technologies. Proton computed tomography (pCT) is an emerging imaging modality capable of improving the accuracy of range prediction. In this paper, we describe the successive pCT scanners designed and built by our group with the goal to support particle therapy treatment planning and image guidance by reconstructing an accurate 3D map of the stopping power relative to water in patient tissues. The pCT scanners we have built to date consist of silicon telescopes, which track the proton before and after the object to be reconstructed, and an energy or range detector, which measures the residual energy and/or range of the protons used to evaluate the water equivalent path length (WEPL) of each proton in the object. An overview of a decade-long evolution of the conceptual design of pCT scanners and their calibration is given. Results of scanner performance tests are presented, which demonstrate that the latest pCT scanner approaches readiness for clinical applications in hadron therapy.

In this study on radiotherapy by charged particles, it was a question of using the Monte Carlo FLUKA method to study and compare the deep dose deposit of carbon and helium ions in order to evaluate the potential benefits that these particles can contribute to radiotherapy. The dosimetry aspect studied in this study was the deep dose deposition. The results of this study showed the shape of the dose deposition curve in depth of the two particles was practically identical but certain differences such as the difference in dose deposition in depth at identical energy and the presence of a fragmentation of the ions. Carbon was observable. [ABSTRACT FROM AUTHOR]

Fourier transform infrared microspectroscopy using a synchrotron radiation source (SR-μFTIR) has great potential in the study of the ionizing radiation effects of human cells by analyzing the biochemical changes occurring in cell components. SR-μFTIR spectroscopy has been usefully employed in recent years in some seminal work devoted to shedding light on processes occurring in cells treated by hadron therapy, that is, radiotherapy with charged heavy particles (mainly protons and carbon ions), which is gaining popularity as a cancer treatment modality. These studies are particularly useful for increasing the effectiveness of radiotherapy cancer treatments with charged particles that can offer significant progress in the treatment of deep-seated and/or radioresistant tumors. In this paper, we present a concise revision of these studies together with the basic principles of μFTIR spectroscopy and a brief presentation of the main characteristics of infrared SR sources. From the analysis of the literature regarding the SR-μFTIR spectroscopy investigation on human cells exposed to proton beams, it is clearly shown that changes in DNA, protein, and lipid cell components are evident. In addition, this review points out that the potential offered by SR-μFTIR in investigating the effects induced by charged particle irradiation have not been completely explored. This is a crucial point for the continued improvement of hadron therapy strategies. [ABSTRACT FROM AUTHOR]

To improve the irradiation accuracy in hadron therapy, a lot of studies are in the evaluation uncluding how to integrate MRI and PET at the treatment of cancer patients. These two future techniques will offer simultaneously the monitoring of the beam during the irradiation. In this study and for the first time, we calculated the dose distribution in a head volume for several carbon ion energies and at different values of the magnetic field B using fluka MC code. Afterwards, either longitudinal or radial dose deflection was simulated with and without B. Basically, the Z axis is entered by the beam and the radial deflections mean the ones corresponded to the X axis which has the same direction of B. The maximum longitudinal deviation of bragg pick depth was 0.672 mm at 200 MeV and the maximum radial deflection was almost 4.23 cm at 100 MeV. Both of them are in the presence of B = 1.5 T. Our results are in a good agreement with previous experimental results (a maximum relative error founded of 2.08%). The results of this study will offer the monitoring of the dose deposition with good accuracy in the presence of a magnetic field in carbon ion therapy. [ABSTRACT FROM AUTHOR]

Particle therapy is a developing area of radiotherapy, mostly involving the use of protons, neutrons and carbon ions for cancer treatment. The reduction of side effects on healthy tissues in the peritumoral area is an important advantage of particle therapy. In this review, we analyze state-of-the-art particle therapy, as compared to conventional photon therapy, to identify clinical benefits and specify the mechanisms of action on tumor cells. Systematization of published data on particle therapy confirms its successful application in a wide range of cancers and reveals a variety of biological effects which manifest at the molecular level and produce the particle therapy-specific molecular signatures. Given the rapid progress in the field, the use of particle therapy holds great promise for the near future.

Real time radioluminescence fibre-based detectors were investigated for application in proton, helium, and carbon therapy dosimetry. The Al2O3:C probes are made of one single crystal (1 mm) and two droplets of micro powder in two sizes (38 μm and 4 μm) mixed with a water-equivalent binder. The fibres were irradiated behind different thicknesses of solid slabs, and the Bragg curves presented a quenching effect attributed to the nonlinear response of the radioluminescence (RL) signal as a function of linear energy transfer (LET). Experimental data and Monte Carlo simulations were utilised to acquire a quenching correction method, adapted from Birks’ formulation, to restore the linear dose–response for particle therapy beams. The method for quenching correction was applied and yielded the best results for the ‘4 μm’ optical fibre probe, with an agreement at the Bragg peak of 1.4% (160 MeV), and 1.5% (230 MeV) for proton-charged particles; 2.4% (150 MeV/u) for helium-charged particles and of 4.8% (290 MeV/u) and 2.9% (400 MeV/u) for the carbon-charged particles. The most substantial deviations for the ‘4 μm’ optical fibre probe were found at the falloff regions, with ~3% (protons), ~5% (helium) and 6% (carbon).

Experimental microdosimetry measures the energy deposited in a microscopic sensitive volume (SV) by single ionizing particles traversing the SV or passing by. The fundamental advantage of experimental microdosimetry over the computational approach is that the first allows to determine distributions of energy deposition when information on the energy and nature of the charged particles at the point of interest is incomplete or fragmentary. This is almost always the case in radiation protection applications, but discrepancies between the modelled and the actual scenarios should be considered also in radiation therapy. Models for physical reality are always imperfect and rely both on basic input data and on assumptions and simplifications that are necessarily implemented. Furthermore, unintended events due to human errors or machine/system failures can be minimized but cannot be completely avoided.Though in proton radiation therapy (PRT) a constant relative biological effectiveness (RBE) of 1.1 is assumed, there is evidence of an increasing RBE towards the end of the proton penetration depth. Treatment Planning Systems (TPS) that take into account a variable linear energy transfer (LET) or RBE are already available and could be implemented in PRT in the near future. However, while the calculated dose distributions produced by the TPS are routinely verified with ionization chambers as part of the quality assurance program of every radiotherapy center, there is no commercial detector currently available to perform routine verification of the radiation quality, calculated by the TPS through LET or RBE distributions. Verification of calculated LET is required to make sure that a complex robustly optimized plan will be delivered as planned. The scientific community is coming to conclusion that a new domain of Quality Assurance additionally to the physical dose verification is required, and microdosimetry can be the right approach to address that. A first important prerequisite is the repeatability and reproducibility of microdosimetric measurements. This work aims at studying experimentally the repeatability and reproducibility of microdosimetric measurements performed with a miniaturized Tissue Equivalent Proportional Counter (mini-TEPC) in a 62 MeV proton beam. Experiments were carried out within 1 year and without propane gas recharging and by different operators. RBE was also calculated by applying the Loncol’s weighting function r(y) to microdosimetric distributions. Demonstration of reproducibility of measured microdosimetric quantities y¯F, y¯D and RBE10 in 62 MeV proton beam makes this TEPC a possible metrological tool for LET verification in proton therapy. Future characterization will be performed in higher energy proton beams.

Featured Application: An optical readout GEM-based detector based on a matrix of organic photodiodes with an active area of 60 × 80 mm2, called the LaGEMPix, was assembled and characterized, using low energy X-rays as a preliminary step toward the development of a 200 × 200 mm2 detector for use in Quality Assurance in hadron therapy. Quality Assurance (QA) in hadron therapy is crucial to ensure safe and accurate dose delivery to patients. This can be achieved with fast, reliable and high-resolution detectors. In this paper, we present a novel solution that combines a triple Gas Electron Multiplier (GEM) and a highly pixelated readout based on a matrix of organic photodiodes fabricated on top of an oxide-based thin-film transistor backplane. The first LaGEMPix prototype with an active area of 60 × 80 mm2 was developed and characterized using low energy X-rays. The detector comprises a drift gap of 3.5 mm, a triple-GEM stack for electron amplification, and a readout featuring 480 × 640 pixels at a 126 µm pitch. Here, we describe the measurements and results in terms of spatial resolution for various experimental configurations. A comparison with GAFCHROMIC® films and the GEMPix detector used in the charge readout mode was performed to better understand the contribution to the spatial resolution from both the electron diffusion and the isotropic emission of photons. The measurements were compared to Monte Carlo simulations, using the FLUKA code. The simulation predictions are in good agreement with the GEMPix results. Future plans with respect to applications in hadron therapy are discussed. [ABSTRACT FROM AUTHOR]

New silicon 3-D-microdetectors have been developed to perform microdosimetry measurements for applications in hadron therapy. In this work, the charge collection efficiency (CCE) of an improved second generation of microdetectors having two different thicknesses (10 and 20 $\mu \text{m}$) and a diameter of 25 $\mu \text{m}$ has been studied by means of the ion beam induced charge (IBIC) technique. New methods to study the active volume and the CCE of microdosimeters are proposed and verified here. The results show that, for this new generation of microdetectors, the CCE is 100% for radial distances up to 10.2 $\mu \text{m}$ from the center of the device, and it rapidly decays between 10.2 $\mu \text{m}$ and the detector edge. The characterization of the CCE conducted here will allow us to completely explain the energy spectra obtained during the microdosimetry studies performed in clinical centers. [ABSTRACT FROM AUTHOR]

In a cancer radiation treatment, Hadron therapy plays an important role as a technique with a high accuracy providing treatment results better than conventional radiation therapy methods such as chemotherapy. The laser-based Hadron therapy techniques are attractive due to their compactness in producing miniaturized particle accelerators and supporting a more intense electric field compared to other methods. A good-quality laser beam focusing and guiding in a cold plasma channel leads to an accurate and precise laser spot after focus, which is an important necessity in medical aims and occurs in μm -wavelength (ultra-short pulse) laser types. A method used to level up this treatment approach has been emerged by using high-power lasers along with plasma channels as a source for high energy to more effectively perform the Hadron therapy. Additionally, cancer treatment by using ions as the particle transferor is preferred over other methods for Hadron therapy due to some physical properties such as maximum energy deposition to the cancerous targets providing a better dose delivery to the tumor. In this paper, multiple simulations around the dose delivery procedures were presented for efficient dosimetric evaluations. Moreover, the effects of the electric field on the particle energy enhancement were evaluated in the presence of the plasma channel. Finally, it was demonstrated that the use of Oxygen ion in the presence of plasma channel is the appropriate approach due to its minor energy dissipation through matter on the way to the tumor for a better dose delivery which was impressed with radially polarized laser accelerator simultaneously. The proposed research demonstrated that the Hadrons can reach the maximum accelerated energy and convey the maximum path through the body to the cancerous target and finally deliver the sufficient dose to the tumor by using Oxygen ion beam in a cold plasma channel, which is low in density, with appropriate laser power. Consequently, Hadron therapy by using Oxygen ionization in the laser-plasma based accelerator is an impressive and efficient method for precise cancer treatment. Lastly, Laser-Plasma accelerators have three important limitation factors of “Energy Spread”, “Dephasing Length”, and “Pump Depletion”, which can limit the energy increasing. In this paper, facing up to these limitations was a critical challenge in Hadron therapy for better Hadron acceleration and dose delivery.

Introdution: A careful study of the physical and biological properties of helium ion radiation on the various cell lines is essential for the treatment planning. In this study, the biological response of several different cell lines has been investigated in 4He ions. Methods: Physical dose profiles and Linear Energy Transfer (LET) calculations were performed using the Monte Carlo Geant4 code. By studying the mixed radiation field, the biological effect of 4He primary ions, 3He and 6He secondary ions, as well as secondary proton, deuteron and triton are considered in calculations. Results: Biological doses and cell survival levels have been compared for these cell lines. The variation of relative biological effectiveness (RBE) for each cell line is calculated as a function of the phantom depth. The results have shown that the cell lines with the highest (α/β)ph levels have a higher sensitivity to damage cells against 4He radiation. Conclusion: Among the studied cell lines, the most appropriate treatment for 4He ion, the Colon adenocarcinoma cancer cell line has been selected. In addition, due to the large variation in RBE relative to the depth in the phantom, it is necessary to consider a variable RBE instead of a constant RBE.

The size and weight of ion-beam cancer therapy gantries are frequently determined by a large aperture, curved, ninety degree, dipole magnet. The higher fields achievable with superconducting technology promise to greatly reduce the size and weight of this magnet and therefore also the gantry as a whole. This paper reports advances in the design of winding mandrels for curved, canted cosine-theta (CCT) magnets in the context of a preliminary magnet design for a proton gantry. The winding mandrel is integral to the CCT design and significantly affects the construction cost, stress management, winding feasibility, eddy current power losses, and field quality of the magnet. A laminated mandrel design using a minimum symmetry in the winding path is introduced and its feasibility demonstrated by a rapid prototype model. Piecewise construction of the mandrel using this laminated approach allows for increased manufacturing techniques and material choices. Sectioning the mandrel also reduces eddy currents produced during field changes accommodating the scan of beam energies during treatment. This symmetry concept can also greatly reduce the computational resources needed for 3D finite element calculations. It is shown that the small region of symmetry forming the laminations combined with periodic boundary conditions can model the entire magnet geometry disregarding the ends. © 2013 Elsevier B.V.

• Submillimeter resolution 2-D dose imaging detector for hadron therapy. • Removing Cherenkov light contamination improved dosimetry response. • Well-type Glass GEM structure significantly improved LET dependance. • A Bragg peak of a carbon beam peak-to-plateau ratio of more than 4 was measured. The use of carbon ion beams in cancer therapy (also known as hadron therapy) is steadily growing worldwide; therefore, the demand for more efficient dosimetry systems is also increasing because daily quality assurance (QA) measurements of hadron radiotherapy is one of the most complex and time consuming tasks. The aim of this study is to develop a two-dimensional dosimetry system that offers high spatial resolution, a large field of view, quick data response, and a linear dose–response relationship. We demonstrate the dose imaging performance of a novel digital dose imager using carbon ion beams for hadron therapy. The dose imager is based on a newly-developed gaseous detector, a well-type glass gas electron multiplier. The imager is successfully operated in a hadron therapy facility with clinical intensity beams for radiotherapy. It features a high spatial resolution of less than 1 mm and an almost linear dose–response relationship with no saturation and very low linear-energy-transfer dependence. Experimental results show that the dose imager has the potential to improve dosimetry accuracy for daily QA. [ABSTRACT FROM AUTHOR]

The GEMPix is a small gaseous detector with a highly pixelated readout, consisting of a drift region, three Gas Electron Multipliers (GEMs) for signal amplification, and four Timepix ASICs with 55 µm pixel pitch and a total of 262,144 pixels. A continuous flow of a gas mixture such as Ar:CO2:CF4, Ar:CO2 or propane-based tissue equivalent gas is supplied externally at a rate of 5 L/h. This article reviews the medical applications of the GEMPix. These include relative dose measurements in conventional photon radiation therapy and in carbon ion beams, by which on-line 2D dose images provided a similar or better performance compared to gafchromic films. Depth scans in a water phantom with 12C ions allowed measuring the 3D energy deposition and reconstructing the Bragg curve of a pencil beam. Microdosimetric measurements performed in neutron and photon fields allowed comparing dose spectra with those from Tissue Equivalent Proportional Counters and, additionally, to obtain particle track images. Some preliminary measurements performed to check the capabilities as the detector in proton tomography are also illustrated. The most important on-going developments are: (1) a new, larger area readout to cover the typical maximum field size in radiation therapy of 20 × 20 cm2; (2) a sealed and low-pressure version to facilitate measurements and to increase the equivalent spatial resolution for microdosimetry; (3) 3D particle track reconstruction when operating the GEMPix as a Time Projection Chamber. [ABSTRACT FROM AUTHOR]

Hypoxia contributes significantly to resistance in radiotherapy. Our research rigorously examines the influence of microvascular morphology on radiotherapy outcome, specifically focusing on how microvasculature shapes hypoxia within the microenvironment and affects resistance to a standard treatment regimen (30×2Gy RBE ). Our computational modeling extends to the effects of different radiation sources. For photons and protons, our analysis establishes a clear correlation between hypoxic volume distribution and treatment effectiveness, with vascular density and regularity playing a crucial role in treatment success. On the contrary, carbon ions exhibit distinct effectiveness, even in areas of intense hypoxia and poor vascularization. This finding points to the potential of carbon-based hadron therapy in overcoming hypoxia-induced resistance to RT. Considering that the spatial scale analyzed in this study is closely aligned with that of imaging data voxels, we also address the implications of these findings in a clinical context envisioning the possibility of detecting subvoxel hypoxia., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background & Aims: Inoperable hepatocellular carcinoma (HCC) can be treated by stereotactic body radiotherapy. However, carbon ion radiotherapy (CIRT) is more effective for sparing non-tumorous liver. High linear energy transfer could promote therapy efficacy. Japanese and Chinese studies on hypofractionated CIRT have yielded excellent results. Because of different radiobiological models and the different etiological spectrum of HCC, applicability of these results to European cohorts and centers remains questionable. The aim of this prospective study was to assess safety and efficacy and to determine the optimal dose of CIRT with active raster scanning based on the local effect model (LEM) I., Methods: CIRT was performed every other day in four fractions with relative biological effectiveness (RBE)-weighted fraction doses of 8.1-10.5 Gy (total doses 32.4-42.0 Gy [RBE]). Dose escalation was performed in five dose levels with at least three patients each. The primary endpoint was acute toxicity after 4 weeks., Results: Twenty patients received CIRT (median age 74.7 years, n = 16 with liver cirrhosis, Child-Pugh scores [CP] A5 [n = 10], A6 [n = 4], B8 [n = 1], and B9 [n = 1]). Median follow up was 23 months. No dose-limiting toxicities and no toxicities exceeding grade II occurred, except one grade III gamma-glutamyltransferase elevation 12 months after CIRT, synchronous to out-of-field hepatic progression. During 12 months after CIRT, no CP elevation occurred. The highest dose level could be applied safely. No local recurrence developed during follow up. The objective response rate was 80%. Median overall survival was 30.8 months (1/2/3 years: 75%/64%/22%). Median progression-free survival was 20.9 months (1/2/3 years: 59%/43%/43%). Intrahepatic progression outside of the CIRT target volume was the most frequent pattern of progression., Conclusions: CIRT of HCC yields excellent local control without dose-limiting toxicity., Impact and Implications: To date, safety and efficacy of carbon ion radiotherapy for hepatocellular carcinoma have only been evaluated prospectively in Japanese and Chinese studies. The optimal dose and fractionation when using the local effect model for radiotherapy planning are unknown. The results are of particular interest for European and American particle therapy centers, but also of relevance for all specialists involved in the treatment and care of patients with hepatocellular carcinoma, as we present the first prospective data on carbon ion radiotherapy in hepatocellular carcinoma outside of Asia. The excellent local control should encourage further use of carbon ion radiotherapy for hepatocellular carcinoma and design of randomized controlled trials., Clinical Trials Registration: The study is registered at ClinicalTrials.gov (NCT01167374)., Competing Interests: PH and JL are funded by the Physician-Scientist Program of Heidelberg University, Faculty of Medicine. PH received fees for an advisory board from NovoCure GmbH. FW received speaker fees from AstraZeneca and Merck Sharp & Dohme. JD received grants from Accuray International Sàrl, Merck Serono GmbH, CRI – The Clinical Research Institute GmbH, View Ray Inc., Accuray Incorporated, RaySearch Laboratories AB, Vision RT limited, Astellas Pharma GmbH, Astra Zeneca GmbH, Solution Akademie GmbH, Ergomed PLC Surrey Research Park, Siemens Healthcare GmbH, Quintiles GmbH, NovoCure, Pharmaceutical Research Associates GmbH, Boehringer Ingelheim Pharma GmbH Co, PTW-Freiburg Dr Pychlau GmbH, Nanobiotix A.A. and IntraOP Medical outside the submitted work. JHR received speaker fees and travel reimbursement from ViewRay Inc., travel reimbursement from IntraOP Medical and Elekta Instrument AB, and a grant from IntraOP Medical outside the submitted work. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2024 The Authors.)

The early delayed effects of accelerated carbon ions and protons on the cognitive functions of mice using tests of the total activity, spatial learning, and long-term and short-term hippocampal-dependent memory were studied. The obtained results showed that irradiated animals do not develop an altered behavioral pattern: the level of anxiety is not increased, the exploratory model of behavior is clearly pronounced, and there is no deficiency of hippocampal-dependent memory. However, the long-term memory test revealed fewer errors in finding an escape box in a group of animals irradiated with protons compared to the control animals and mice irradiated with carbon ions. The results may indicate a better preservation of memory traces under these conditions. [ABSTRACT FROM AUTHOR]

Fourier transform infrared microspectroscopy using a synchrotron radiation source (SR-μFTIR) has great potential in the study of the ionizing radiation effects of human cells by analyzing the biochemical changes occurring in cell components. SR-μFTIR spectroscopy has been usefully employed in recent years in some seminal work devoted to shedding light on processes occurring in cells treated by hadron therapy, that is, radiotherapy with charged heavy particles (mainly protons and carbon ions), which is gaining popularity as a cancer treatment modality. These studies are particularly useful for increasing the effectiveness of radiotherapy cancer treatments with charged particles that can offer significant progress in the treatment of deep-seated and/or radioresistant tumors. In this paper, we present a concise revision of these studies together with the basic principles of μFTIR spectroscopy and a brief presentation of the main characteristics of infrared SR sources. From the analysis of the literature regarding the SR-μFTIR spectroscopy investigation on human cells exposed to proton beams, it is clearly shown that changes in DNA, protein, and lipid cell components are evident. In addition, this review points out that the potential offered by SR-μFTIR in investigating the effects induced by charged particle irradiation have not been completely explored. This is a crucial point for the continued improvement of hadron therapy strategies.