Search Results (19)

Radiotherapy (RT) has undergone transformative advancements since its inception over a century ago. This review highlights the most promising and impactful innovations shaping the current and future landscape of RT. Key technological advances include adaptive radiotherapy (ART), which tailors treatment to daily anatomical changes using integrated imaging and artificial intelligence (AI), and advanced image guidance systems, such as MR-LINACs, PET-LINACs, and surface-guided radiotherapy (SGRT), which enhance targeting precision and minimize collateral damage. AI and data science further support RT through automation, improved segmentation, dose prediction, and treatment planning. Emerging biological and targeted therapies, including boron neutron capture therapy (BNCT), radioimmunotherapy, and theranostics, represent the convergence of molecular targeting and radiotherapy, offering personalized treatment strategies. Particle therapies, notably proton and heavy ion RT, exploit the Bragg peak for precise tumor targeting while reducing normal tissue exposure. FLASH RT, delivering ultra-high dose rates, demonstrates promise in sparing normal tissue while maintaining tumor control, though clinical validation is ongoing. Spatially fractionated RT (SFRT), stereotactic techniques and brachytherapy are evolving to treat challenging tumor types with enhanced conformality and efficacy. Innovations such as 3D printing, Auger therapy, and hyperthermia are also contributing to individualized and site-specific solutions. Across these modalities, the integration of imaging, AI, and novel physics and biology-driven approaches is redefining the possibilities of cancer treatment. This review underscores the multidisciplinary and translational nature of modern RT, where physics, engineering, biology, and informatics intersect to improve patient outcomes. While many approaches are in various stages of clinical adoption and investigation, their collective impact promises to redefine the therapeutic boundaries of radiation oncology in the coming decade. Full article

FLASH radiotherapy is a novel irradiation modality that employs ultra-high mean dose rates exceeding 40–150 Gy/s, far surpassing the typical ~0.03 Gy/s used in conventional radiotherapy. This advanced technology delivers high doses of radiation within milliseconds, effectively targeting tumors while minimizing damage to the surrounding healthy tissues. However, the precise mechanism that differentiates responses between tumor and normal tissues is not yet understood. This study primarily examines the ROD hypothesis, which posits that oxygen undergoes transient radiolytic depletion following a radiation pulse. We developed a computational model to investigate the effects of dose rate on radiolysis in an aqueous environment that mimics a confined cellular space subjected to instantaneous pulses of energetic protons. This study employed the multi-track chemistry Monte Carlo simulation code, IONLYS-IRT, which has been optimized to model this radiolysis in a homogeneous and aerated medium. This medium is composed primarily of water, alongside carbon-based biological molecules (RH), radiation-induced bio-radicals (R^●), glutathione (GSH), ascorbate (AH⁻), nitric oxide (^●NO), and α-tocopherol (TOH). Our model closely monitors the temporal variations in these components, specifically focusing on oxygen consumption, from the initial picoseconds to one second after exposure. Simulations reveal that cellular oxygen is transiently depleted primarily through its reaction with R^● radicals, consistent with prior research, but also with glutathione disulfide radical anions (GSSG^●−) in roughly equal proportions. Notably, we show that, contrary to some reports, the peroxyl radicals (ROO^●) formed are not neutralized by recombination reactions. Instead, these radicals are rapidly neutralized by antioxidants present in irradiated cells, with AH⁻ and ^●NO proving to be the most effective in preventing the propagation of harmful peroxidation chain reactions. Moreover, our model identifies a critical dose rate threshold below which the FLASH effect, as predicted by the ROD hypothesis, cannot fully manifest. By comparing our findings with existing experimental data, we determine that the ROD hypothesis alone cannot entirely explain the observed FLASH effect. Our findings indicate that antioxidants might significantly contribute to the FLASH effect by mitigating radiation-induced cellular damage and, in turn, enhancing cellular radioprotection. Additionally, our model lends support to the hypothesis that transient oxygen depletion may partially contribute to the FLASH effect observed in radiotherapy. However, our findings indicate that this mechanism alone is insufficient to fully explain the phenomenon, suggesting the involvement of additional mechanisms or factors and warranting further investigation. Full article

Radiation therapy (RT) is a cornerstone in the management of pediatric central nervous system (CNS) tumors. Recent advancements in RT delivery and techniques aim to enhance therapeutic effectiveness while minimizing both acute and long-term complications associated with pediatric brain RT. This paper highlights innovative developments in the field, including the clinical indications, benefits, and challenges of proton therapy and stereotactic radiotherapy. The ongoing refinement of risk-adapted RT volumes is highlighted, with examples of newly proposed germinoma RT volumes and hippocampal-sparing RT. Additionally, emerging experimental approaches, including FLASH therapy and theranostics, are also discussed as promising future directions. Further prospective, multi-institutional collaborative studies are essential to validate and expand upon the benefits outlined in this review. Full article

Ultrahigh-dose-rate therapy, also known as FLASH radiotherapy (RT), is an emerging technique that is garnering significant interest in cancer treatment due to its potential to revolutionize therapy. This method can achieve comparable tumor control to conventional-dose-rate RT while offering the enhanced protection of normal tissue through the FLASH-sparing effect. This innovative technique has demonstrated promising results in preclinical studies involving animals and cell lines. Particularly noteworthy is its potential application in treating head and neck (HN) cancers, especially in patients with challenging recurrent tumors and reirradiation cases, where the toxicity rates with conventional radiotherapy are high. Such applications aim to enhance tumor control while minimizing side effects and preserving patients’ quality of life. In comparison to electron or photon FLASH modalities, proton therapy has demonstrated superior dosimetric and delivery characteristics and is a safe and effective FLASH treatment for human malignancies. Compared to the transmission proton FLASH, single-energy Bragg peak FLASH is a novel delivery method that allows highly conformal doses to targets and minimal radiation doses to crucial OARs. Proton Bragg peak FLASH for HN cancer has still not been well studied. This review highlights the significance of proton FLASH in enhancing cancer therapy by examining the advantages and challenges of using it for HN cancer reirradiation. Full article

Optical fibres are gaining popularity for relative dosimetry in proton therapy due to their spatial resolution and ability for near real-time acquisition. For FLASH proton therapy, these fibres need to handle higher dose rates and larger doses than for conventional proton dose rates. We developed a multi-point fibre sensor embedded in a 3D-printed phantom which can measure the profile of a FLASH proton beam. Seven PMMA fibres of 1 mm diameter were embedded in a custom 3D-printed plastic phantom of the same density as the fibres. The phantom was placed in a proton beam with FLASH dose rates at the TRIUMF Proton Therapy Research Centre (PTRC). The sensor was exposed to different proton energies, 13.5 MeV, 19 MeV and 40.4 MeV, achieved by adding PMMA bolus in front of the phantom and three different beam currents, varying the dose rates from 7.5 to 101 Gy/s. The array was able to record beam profiles in both transverse and axial directions in relative agreement with measurements from EBT-XD radiochromic films (transverse) and Monte Carlo simulations (axial). A decrease in light output over time was observed, which might be caused by radiation damage in the matrix of the fibre and characterised by an exponential decay function. Full article

Charged particle beams driven to ultra-high dose rates (UHDRs) have been shown to offer potential benefits for future clinical applications, particularly in the reduction of normal-tissue toxicity. Studies of the so-called FLASH effect have shown promise, generating huge interest in high dose rate radiation studies. With laser-driven proton beams, where the duration of the proton burst delivered to a sample can be as short as hundreds of picoseconds, the instantaneous dose rates are several orders of magnitude higher than those used for conventional radiotherapy. The dosimetry of these beam modalities is not trivial, with conventional active detectors, such as ionisation chambers, experiencing saturation effects making them unusable at the extremely high dose rates. Calorimeters, measuring the radiation-induced temperature rise in an absorber, offer an ideal candidate for the dosimetry of UHDR beams. However, their application in the measurement of laser-driven UHDR beams has so far not been trialled, and their effective suitability to work with the quasi-instantaneous and inhomogeneous dose deposition patterns and the harsh environment of a laser-plasma experiment has not been tested. The measurement of the absorbed dose of laser-driven proton beams was conducted in a first-of-its-kind investigation, employing the VULCAN-PW laser system of the Central Laser Facility (CLF) at the Rutherford Appleton Laboratory (RAL), using a small-body portable graphite calorimeter (SPGC) developed at the National Physical Laboratory (NPL) and radiochromic films. A small number of shots were recorded, with the corresponding absorbed dose measurements resulting from the induced temperature rise. The effect of the electromagnetic pulse (EMP) generated during laser–target interaction was assessed on the system, showing no significant effects on the derived signal-to-noise ratio. These proof-of-principle tests highlight the ability of calorimetry techniques to measure the absorbed dose for laser-driven proton beams. Full article

(1) Background: Water radiolysis leads to the formation of hydronium ions H₃O⁺ in less than 50 fs, resulting in the formation of transient acidic pH spikes in the irradiated water. The purpose of this study is to examine the time evolution of these spikes of acidity under irradiation conditions combining both high absorbed dose rate and high-LET radiation. (2) Methods: The early space–time history of the distributions of the various reactive species was obtained using our Monte Carlo multitrack chemistry simulation code IONLYS-IRT. To simulate different LETs, we used incident protons of varying energies as radiation sources. The “instantaneous pulse” (or Dirac) model was used to investigate the effect of dose rate. (3) Results: One major finding is that the combination of high dose rates and high LETs is clearly additive, with a very significant impact on the pH of the solution. For example, at 1 ns and for a dose rate of ~10⁷ Gy/s, the pH drops from ~4.7 to 2.7 as the LET increases from ~0.3 to 60 keV/μm. (4) Conclusions: Confirming previous work, this purely radiation chemical study raises the question of the possible importance and role of these spikes of acidity in underpinning the physical chemistry and biology of the “FLASH effect”. Full article

Radiotherapy (RT) using ultra-high dose rate (UHDR) radiation, known as FLASH RT, has shown promising results in reducing normal tissue toxicity while maintaining tumor control. However, implementing FLASH RT in clinical settings presents technical challenges, including limited depth penetration and complex treatment planning. Monte Carlo (MC) simulation is a valuable tool for dose calculation in RT and has been investigated for optimizing FLASH RT. Various MC codes, such as EGSnrc, DOSXYZnrc, and Geant4, have been used to simulate dose distributions and optimize treatment plans. Accurate dosimetry is essential for FLASH RT, and radiation detectors play a crucial role in measuring dose delivery. Solid-state detectors, including diamond detectors such as microDiamond, have demonstrated linear responses and good agreement with reference detectors in UHDR and ultra-high dose per pulse (UHDPP) ranges. Ionization chambers are commonly used for dose measurement, and advancements have been made to address their response nonlinearities at UHDPP. Studies have proposed new calculation methods and empirical models for ion recombination in ionization chambers to improve their accuracy in FLASH RT. Additionally, strip-segmented ionization chamber arrays have shown potential for the experimental measurement of dose rate distribution in proton pencil beam scanning. Radiochromic films, such as Gafchromic^TM EBT3, have been used for absolute dose measurement and to validate MC simulation results in high-energy X-rays, triggering the FLASH effect. These films have been utilized to characterize ionization chambers and measure off-axis and depth dose distributions in FLASH RT. In conclusion, MC simulation provides accurate dose calculation and optimization for FLASH RT, while radiation detectors, including diamond detectors, ionization chambers, and radiochromic films, offer valuable tools for dosimetry in UHDR environments. Further research is needed to refine treatment planning techniques and improve detector performance to facilitate the widespread implementation of FLASH RT, potentially revolutionizing cancer treatment. Full article

Image guidance for radiation therapy can improve the accuracy of the delivery of radiation, leading to an improved therapeutic ratio. Proton radiation is able to deliver a highly conformal dose to a target due to its advantageous dosimetric properties, including the Bragg peak. Proton therapy established the standard for daily image guidance as a means of minimizing uncertainties associated with proton treatment. With the increasing adoption of the use of proton therapy over time, image guidance systems for this modality have been changing. The unique properties of proton radiation present a number of differences in image guidance from photon therapy. This paper describes CT and MRI-based simulation and methods of daily image guidance. Developments in dose-guided radiation, upright treatment, and FLASH RT are discussed as well. Full article

The general concept of radiation therapy used in conventional cancer treatment is to increase the therapeutic index by creating a physical dose differential between tumors and normal tissues through precision dose targeting, image guidance, and radiation beams that deliver a radiation dose with high conformality, e.g., protons and ions. However, the treatment and cure are still limited by normal tissue radiation toxicity, with the corresponding side effects. A fundamentally different paradigm for increasing the therapeutic index of radiation therapy has emerged recently, supported by preclinical research, and based on the FLASH radiation effect. FLASH radiation therapy (FLASH-RT) is an ultra-high-dose-rate delivery of a therapeutic radiation dose within a fraction of a second. Experimental studies have shown that normal tissues seem to be universally spared at these high dose rates, whereas tumors are not. While dose delivery conditions to achieve a FLASH effect are not yet fully characterized, it is currently estimated that doses delivered in less than 200 ms produce normal-tissue-sparing effects, yet effectively kill tumor cells. Despite a great opportunity, there are many technical challenges for the accelerator community to create the required dose rates with novel compact accelerators to ensure the safe delivery of FLASH radiation beams. Full article

This article reviews the results of various non-surgical curative treatments for operable breast cancer. Radiotherapy is considered the most important among such treatments, but conventional radiotherapy alone and concurrent chemoradiotherapy do not achieve high cure rates. As a radiosensitization strategy, intratumoral injection of hydrogen peroxide before radiation has been investigated, and high local control rates (75–97%) were reported. The authors treated 45 patients with whole-breast radiotherapy, followed by stereotactic or intensity-modulated radiotherapy boost, with or without a radiosensitization strategy employing either hydrogen peroxide injection or hyperthermia plus oral tegafur-gimeracil-oteracil potassium. Stages were 0–I in 23 patients, II in 19, and III in 3. Clinical and cosmetic outcomes were good, with 5-year overall, progression-free, and local recurrence-free survival rates of 97, 86, and 88%, respectively. Trials of carbon ion radiotherapy are ongoing, with promising interim results. Radiofrequency ablation, focused ultrasound, and other image-guided ablation treatments yielded complete ablation rates of 20–100% (mostly ≥70%), but long-term cure rates remain unclear. In these treatments, combination with radiotherapy seems necessary to treat the extensive intraductal components. Non-surgical treatment of breast cancer is evolving steadily, with radiotherapy playing a major role. In the future, proton therapy with the ultra-high-dose-rate FLASH mode is expected to further improve outcomes. Full article

Laser plasma acceleration has made remarkable progress in the last few decades, but it also faces many challenges. Although the high gradient is a great potential advantage, the beam quality of the laser accelerator has a certain gap, or it is different from that of traditional accelerators. Therefore, it is important to explore and utilize its own features. In this article, some recent research progress on laser proton acceleration and its irradiation application, which was carried out on the compact laser plasma accelerator (CLAPA) platform at Peking University, have been introduced. By combining a TW laser accelerator and a monoenergetic beamline, proton beams with energies of less than 10 MeV, an energy spread of less than 1%, and with several to tens of pC charge, have been stably produced and transported in CLAPA. The beamline is an object–image point analyzing system, which ensures the transmission efficiency and the energy selection accuracy for proton beams with large initial divergence angle and energy spread. A spread-out Bragg peak (SOBP) is produced with high precision beam control, which preliminarily proved the feasibility of the laser accelerator for radiotherapy. Some application experiments based on laser-accelerated proton beams have also been carried out, such as proton radiograph, preparation of graphene on SiC, ultra-high dose FLASH radiation of cancer cells, and ion-beam trace probes for plasma diagnosis. The above applications take advantage of the unique characteristics of laser-driven protons, such as a micron scale point source, an ultra-short pulse duration, a wide energy spectrum, etc. A new laser-driven proton therapy facility (CLAPA II) is being designed and is under construction at Peking University. The 100 MeV proton beams will be produced via laser–plasma interaction by using a 2-PW laser, which may promote the real-world applications of laser accelerators in malignant tumor treatment soon. Full article

The prerequisite of any radiation therapy modality (X-ray, electron, proton, and heavy ion) is meant to meet at least a minimum prescribed dose at any location in the tumor for the best tumor control. In addition, there is also an upper dose limit within the tumor according to the International Commission on Radiation Units (ICRU) recommendations in order to spare healthy tissue as well as possible. However, healthy tissue may profit from the lower side effects when waving this upper dose limit and allowing a larger heterogeneous dose deposition in the tumor, but maintaining the prescribed minimum dose level, particularly in proton minibeam therapy. Methods: Three different longitudinally heterogeneous proton irradiation modes and a standard spread-out Bragg peak (SOBP) irradiation mode are simulated for their depth-dose curves under the constraint of maintaining a minimum prescribed dose anywhere in the tumor region. Symmetric dose distributions of two opposing directions are overlaid in a 25 cm-thick water phantom containing a 5 cm-thick tumor region. Interlaced planar minibeam dose distributions are compared to those of a broadbeam using the same longitudinal dose profiles. Results and Conclusion: All longitudinally heterogeneous proton irradiation modes show a dose reduction in the healthy tissue compared to the common SOBP mode in the case of broad proton beams. The proton minibeam cases show eventually a much larger mean cell survival and thus a further reduced equivalent uniform dose (EUD) in the healthy tissue than any broadbeam case. In fact, the irradiation mode using only one proton energy from each side shows better sparing capabilities in the healthy tissue than the common spread-out Bragg peak irradiation mode with the option of a better dose fall-off at the tumor edges and an easier technical realization, particularly in view of proton minibeam irradiation at ultra-high dose rates larger than ~10 Gy/s (so-called FLASH irradiation modes). Full article

Radiotherapy (RT) is a relatively safe and established treatment for cancer, where the goal is to kill tumoral cells with the lowest toxicity to healthy tissues. Using it for disorders involving cell loss is counterintuitive. However, ionizing radiation has a hormetic nature: it can have deleterious or beneficial effects depending on how it is applied. Current evidence indicates that radiation could be a promising treatment for neurodegenerative disorders involving protein misfolding and amyloidogenesis, such as Alzheimer’s or Parkinson’s diseases. Low-dose RT can trigger antioxidant, anti-inflammatory and tissue regeneration responses. RT has been used to treat peripheral amyloidosis, which is very similar to other neurodegenerative disorders from a molecular perspective. Ionizing radiation prevents amyloid formation and other hallmarks in cell cultures, animal models and pilot clinical trials. Although some hypotheses have been formulated, the mechanism of action of RT on systemic amyloid deposits is still unclear, and uncertainty remains regarding its impact in the central nervous system. However, new RT modalities such as low-dose RT, FLASH, proton therapy or nanoparticle-enhanced RT could increase biological effects while reducing toxicity. Current evidence indicates that the potential of RT to treat neurodegeneration should be further explored. Full article

Radiotherapy remains an effective conventional method of treatment for patients with cancer. However, the clinical efficacy of radiotherapy is compromised by the development of radioresistance of the tumor cells during the treatment. Consequently, there is need for a comprehensive understanding of the regulatory mechanisms of tumor cells in response to radiation to improve radiotherapy efficacy. The current study aims to highlight new developments that illustrate various forms of cancer cell death after exposure to radiation. A summary of the cellular pathways and important target proteins that are responsible for tumor radioresistance and metastasis is also provided. Further, the study outlines several mechanistic descriptions of the interaction between ionizing radiation and the host immune system. Therefore, the current review provides a reference for future research studies on the biological effects of new radiotherapy technologies, such as ultra-high-dose-rate (FLASH) radiotherapy, proton therapy, and heavy-ion therapy. Full article