Search Results (202)

FLASH radiotherapy requires real-time, non-invasive beam monitoring systems capable of operating under ultra-high dose rate (UHDR) conditions without perturbing the therapeutic beam. In this work, we characterized the extraction system of Supersonic Gas Curtain-based Ionization Profile Monitor (SGC-IPM) for its capabilities as a transverse beam profile and position monitor for FLASH protons. The monitor utilizes a tilted gas curtain intersected by the incident beam, leading to the generation of ions that are extracted through a tailored electrostatic field, and detected using a two stage microchannel plate (MCP) coupled to a phosphor screen and CMOS camera. CST Studio Suite was employed to conduct electrostatic and particle tracking simulations evaluating the ability of the extraction system to measure both beam profile and position. The ion interface, at the interaction region of proton beam and gas curtain, was modeled with realistic proton beam parameters and uniform gas curtain density distributions. The ion trajectory was tracked to evaluate the performance across multiple beam sizes. The simulations suggest that the extraction system can reconstruct transverse beam profiles for different proton beam sizes. Simulations also supported the system’s capability as a beam position monitor within the boundary defined by the beam size, the dimensions of the extraction system, and the height of the gas curtain. Some simulation results were benchmarked against experimental data of 28 MeV proton beam with 70 nA average beam current. This study will further help to optimize the design of the extraction system to facilitate the integration of SGC-IPM in medical accelerators. Full article

The implementation of FLASH Radiotherapy (FLASH-RT), characterized by ultra-high dose rates (UHDRs) frequently exceeding ${10}^6$ Gy/s in microsecond pulses, imposes stringent requirements on real-time dosimetry. Conventional ionization chambers suffer severe ion recombination and space-charge limitations under these conditions. This review summarizes the state of SSD technologies—including conventional standard silicon diodes, advanced SiC diodes, Low-Gain Avalanche Detectors (LGADs), and pixel detectors—and compares their performance, linearity, and dynamic range in UHDR environments. Particular attention is devoted to operational modes (integrating vs. counting), saturation mechanisms, and readout electronics, which frequently dominate detector behavior at FLASH conditions. We discuss the experimental results from recent UHDR beamlines and highlight emerging concepts that will shape future clinical translation. Full article

Carbon ion radiation therapy (CIRT) is a high-LET radiotherapy, which distinguishes itself from traditional low-LET radiation, such as photons and protons, through its unique physical aspects, biological attributes, and the dramatically increased damage it causes within cellular DNA. Given its distinctive characteristics, it is expected to improve the therapeutic ratio of radiation treatments and enhance treatment outcomes in traditionally radiation-resistant tumor histologies. Despite these unique properties, much remains to be understood regarding the clinical use of CIRT before its full potential can be realized. In this review, we summarize the distinct advantages of CIRT with regard to its physical and biological qualities and discuss the possibilities for novel applications of this technology through the exploitation of its immunomodulatory potential, abscopal impacts, and its ability to generate direct, oxygen-independent radiation damage within treated tumors. Full article

This article presents a comprehensive overview of the current and emerging roles of cryogenics and superconductivity in medical diagnostics, imaging, and therapy. Beginning with the historical foundations of both fields and their technological maturation, this review emphasizes how cryogenic engineering and superconducting materials have become indispensable to modern medical systems. Cryogenic technologies are highlighted in applications such as cryosurgery, cryotherapy, cryostimulation, and cryopreservation, all of which rely on controlled exposure to extremely low temperatures for therapeutic or biological preservation purposes. This article outlines the operating principles of cryomedical devices, the refrigerants and cooling methods used, and the technological barriers. This paper reviews the latest applications of superconductivity phenomena in medicine and identifies those that could be used in the future. These include cryogenic therapy, radiotherapy (cyclotrons, particle accelerators, synchrotron radiation generation, isotope production, and proton and ion beam delivery), magnetic resonance imaging (MRI), nuclear magnetic resonance spectroscopy (NMR), positron emission tomography (PET), and ultra-sensitive magnetic signal transducers based on SQUIDs for detecting ultra-low bio-signals emitted by human body organs. CT, MRI/NMR, and PET features are compared using the operation principle, specific applications, safety, contraindications for patients, examination time, and additional valued peculiarities. This article outlines the prospects for the development of superconducting and cryogenic materials and technologies in medical applications. Advances in diagnostic imaging are reviewed, with particular attention on the progression from conventional MRI scanners to ultra-high-field (UHF) systems exceeding 7–10.5 T, culminating in the 11.7 T Iseult whole-body MRI magnet. Another important application area described in this article includes biofunctionalized magnetic nanoparticles and superconducting quantum interference devices (SQUIDs), which enable the ultrasensitive detection of biomagnetic fields and targeted cancer diagnostics. Finally, this article identifies future directions of development in superconducting and cryogenic technologies for medicine. Full article

Background/Objectives: Triple-negative breast cancer (TNBC) is among the most aggressive subtypes, lacking estrogen, progesterone, and HER2 receptors, which limits the efficacy of targeted therapies. Standard treatments often fail due to rapid drug resistance and poor long-term outcomes. Repurposing approved drugs with anticancer potential offers a promising alternative. Disulfiram (DSF), an FDA-approved alcohol-aversion drug, forms a copper complex [Cu(DDC)₂] with potent anticancer activity, but its clinical translation is hindered by poor solubility, limited stability, and inefficient delivery. Methods: Here, we present an amphiphilic dendrimer-stabilized [Cu(DDC)₂] nanoparticle (NP) platform synthesized via the stabilized metal ion ligand complex (SMILE) method. Results: The optimized nanocarrier achieved high encapsulation efficiency, enhanced serum stability, and potent cytotoxicity against TNBC cells. It induced immunogenic cell death (ICD) characterized by calreticulin exposure and ATP release, while modulating the tumor microenvironment by downregulating MMP-3, MMP-9, VEGF, and vimentin, and restoring epithelial markers. In a 4T1 TNBC mouse model, systemic [Cu(DDC)₂] NP treatment significantly inhibited tumor growth without combinational chemo- or radiotherapy. Conclusions: This DSF-based metal–organic NP integrates drug repurposing, immune activation, and tumor microenvironment remodeling into a single platform, offering strong translational potential for treating aggressive breast cancers. Full article

Background/Objectives: Surgery remains the mainstay of treatment for retroperitoneal sarcoma (RPS); however, definitive therapeutic strategies for patients with insufficient surgical margins and unresectable disease owing to locally advanced RPS remain unclear. Carbon ion radiotherapy (CIRT) has been employed in patients with unresectable RPS. This study aimed to evaluate the effectiveness of CIRT in this patient population. Methods: A retrospective analysis was conducted in 76 patients with unresectable RPS treated with CIRT. Of these, 95% had a confirmed prognosis until 2022. In 74 patients, the prescribed relative biological effectiveness dose was 70.4 Gy, delivered in 16 fractions over 4 weeks. Respiratory gating was used, and spot scanning irradiation has been performed in all patients since 2016. Results: The 3- and 5-year overall survival rates for the entire cohort were 68.3% and 49.4%, respectively, with a median overall survival time of 58.1 months. The 3- and 5-year local control rates were 79.0% and 72.0%, respectively. Among 47 naïve patients with treatment-naïve tumors, the 3- and 5-year abdominal recurrence-free survival rates were 51.1% and 29.1%, respectively. Late adverse events of grade 3 or higher occurred in 4 (5.2%) patients. Conclusions: CIRT represents a definitive treatment option for patients with unresectable RPS. In the future, multicenter studies should be conducted to evaluate the effectiveness of CIRT for RPS in larger patient cohorts. Full article

Alanine dosimetry based on Electron Paramagnetic Resonance (EPR) spectroscopy has been a reliable reference and transfer dosimetry method in high-dose applications, valued for its high precision, accuracy and long-term stability. Additional characteristics, such as dose-rate independence up to 10¹⁰ Gy/s under electron beam (e-beam) irradiation, electron energy independence and tissue equivalence, position alanine EPR as a promising candidate to address dosimetric challenges arising in e-beam Flash Radiotherapy (RT), where radiation energy is delivered at Ultra-High Dose-Rates (UHDR) ≥ 40 Gy/s. At such dose-rates, reliable real-time monitoring dosimeters such as ionization chambers in conventional RT, suffer from ion recombination, compromising accuracy in dose determination. Several studies are currently focused on developing real-time beam monitoring systems dedicated specifically for e-beam Flash RT. This creates a need for standardized reference dosimetry methods to validate beam parameters determined by these systems under investigation. This review provides an overview of the potential and limitations of the alanine EPR dosimetry method for control, validation and verification of e-beam Flash RT beam parameters at doses less than 10 Gy, where the method has shown low sensitivity and increased uncertainty. It further discusses strategies to optimize alanine EPR measurements to enhance sensitivity and accuracy at these dose levels. Improved measurement procedures will ensure reliable and accurate e-beam Flash RT accelerator commissioning, performance checks, patient safety and treatment efficacy across all therapeutic dose ranges. Full article

Cancer remains a major global health burden, representing one of the leading causes of mortality among noncommunicable diseases worldwide. Although conventional treatment modalities, including surgical resection, chemotherapy, radiotherapy, targeted therapy, and immunotherapeutic interventions, have demonstrated clinical benefits, their therapeutic efficacy is often constrained by inherent limitations such as low specificity, systemic toxicity, or tumor heterogeneity. These challenges underscore the imperative for developing innovative treatment strategies. Emerging evidence has implicated ion channels as critical players in oncogenesis and cancer progression. These proteins modulate diverse oncogenic phenotypes, including uncontrolled proliferation, metastatic dissemination, and apoptotic resistance. Their frequent dysregulation in malignancies correlates with disease aggressiveness and clinical outcomes, positioning them as promising targets for precision oncology. Notably, pharmacological modulation of ion channels exerts multifaceted antitumor effects, with several channel-targeting agents advancing through clinical trials. This review explores recent advances in ion channel-targeted therapies, emphasizing their mechanisms, clinical applications, and challenges. Furthermore, we examine the pathophysiological contributions of ion channels to tumor biology and evaluate their emerging utility as predictive biomarkers, providing perspectives on addressing critical gaps in current oncologic management. Full article

Very-high-energy electron (VHEE) beams, ranging from 50 to 300 or 400 MeV, are the subject of intense research investigation, with considerable interest concerning applications in radiation therapy due to their accurate energy deposition into large and deep-seated tissues, sharp beam edges, high sparing properties, and minimal radiation effects on normal tissues. The very-high-energy electron beam, which ranges from 50 to 400 MeV, and Ultra-High-Energy Electron beams up to 1–2 GeV, are considered extremely effective for human tumor therapy while avoiding the spatial requirements and cost of proton and heavy ion facilities. Many research laboratories have developed advanced testing infrastructures with VHEE beams in Europe, the USA, Japan, and other countries. These facilities aim to accelerate the transition to clinical application, following extensive simulations for beam transport that support preclinical trials and imminent clinical deployment. However, the clinical implementation of VHEE for FLASH radiation therapy requires advances in several areas, including the development of compact, stable, and efficient accelerators; the definition of sophisticated treatment plans; and the establishment of clinically validated protocols. In addition, the perspective of VHEE for accessing ultra-high dose rate (UHDR) dosimetry presents a promising procedure for the practical integration of FLASH radiotherapy for deep tumors, enhancing normal tissue sparing while maintaining the inherent dosimetry advantages. However, it has been proven that a strong effort is necessary to improve the main operational accelerator conditions, ensuring a stable beam over time and across space, as well as compact infrastructure to support the clinical implementation of VHEE for FLASH cancer treatment. VHEE-accessing ultra-high dose rate (UHDR) perspective dosimetry is integrated with FLASH radiotherapy and well-prepared cancer treatment tools that provide an advantage in modern oncology regimes. This study explores technological progress and the evolution of electron accelerator beam energy technology, as simulated by the ASTRA code, for developing VHEE and UHEE beams aimed at medical applications. FLUKA code simulations of electron beam provide dose distribution plots and the range for various energies inside the phantom of PMMA. Full article

Iron oxide nanoparticles (IONPs) have emerged as key materials in magnetic hyperthermia (MH), a minimally invasive cancer therapy capable of selectively inducing apoptosis, ferroptosis, and other cell death pathways while sparing surrounding healthy tissue. This review synthesizes advances in the design, functionalization, and biomedical application of magnetic nanoparticles (MNPs) for MH, highlighting strategies to optimize heating efficiency, biocompatibility, and tumor targeting. Key developments include tailoring particle size, shape, and composition; doping with metallic ions; engineering multicore nanostructures; and employing diverse surface coatings to improve colloidal stability, immune evasion, and multifunctionality. We discuss preclinical and clinical evidence for MH, its integration with chemotherapy, radiotherapy, and immunotherapy, and emerging theranostic applications enabling simultaneous imaging and therapy. Special attention is given to the role of MNPs in immunogenic cell death induction and metastasis prevention, as well as novel concepts for circulating tumor cell capture. Despite promising results in vitro and in vivo, clinical translation remains limited by insufficient tumor accumulation after systemic delivery, safety concerns, and a lack of standardized treatment protocols. Future progress will require interdisciplinary innovations in nanomaterial engineering, active targeting technologies, and real-time treatment monitoring to fully integrate MH into multimodal cancer therapy and improve patient outcomes. Full article

Experimental measurement of dose distributions is a pivotal step in the quality assurance of radiotherapy treatments, especially for those relying on high delivery accuracy such as hadron therapy. This study investigated the response of a polymer gel dosimeter to determine its suitability in performing geometric beam characterizations for hadron therapy under high-quenching conditions. Different extraction energies of proton and carbon ion beams were considered. Gel dose–response linearity and long-term stability were confirmed through optical measurements. Gel phantoms were irradiated with pencil beams and analyzed via magnetic resonance imaging. A multi-echo T₂-weighted sequence was used to reconstruct depth–dose profiles and transversal distributions acquired by the gels, which were benchmarked against reference data. As expected, a response-quenching effect in the Bragg peak region was noted. Nonetheless, the studied gel formulation proved reliable in acquiring the geometric characteristics of the beams, even without correcting for the quenching effect. Indeed, depth–dose distributions acquired by the gels showed an excellent agreement with measured particle range with respect to reference values, with mean discrepancies of 0.5 ± 0.2 mm. Single-spot transverse FWHM values at increasing depths also presented an average agreement within 1 mm with values determined with radiochromic films, thus supporting the excellent spatial resolving capabilities of the dosimetric gel. Full article

Hypoxia-induced radioresistance in non-small cell lung cancer (NSCLC) hinders radiotherapy efficacy. Fractionated schedules exploit reoxygenation between fractions to reverse this resistance, but the effects of post-irradiation reoxygenation remain unclear and may depend on radiation quality. We investigated survival, cell cycle progression, cytokine secretion, and gene expression in hypoxic (1 % O₂) and reoxygenated A549 cells irradiated with X-rays or carbon ions. Colony-forming assays revealed an Oxygen Enhancement Ratio (OER) > 1 for both hypoxic and reoxygenated cells after X-rays, indicating persistent radioresistance; carbon ion OER ≈ 1 reflected oxygen-independent cytotoxicity. Hypoxia weakened radiation-induced G₂ arrest, and this was unaffected by reoxygenation. IL-6 secretion increased after X-rays and IL-8 after carbon ions exposure; both were enhanced under hypoxia and reoxygenation. RNA sequencing revealed that hypoxia induced a pro-survival, epithelial-to-mesenchymal transition (EMT)-promoting, and immune-evasive transcriptional program, which was largely reversed by reoxygenation but without increased clonogenic killing. These findings indicate that short-term reoxygenation after irradiation can normalize hypoxia-driven transcriptional changes yet does not restore radiosensitivity, supporting the advantage of high-linear energy transfer (LET) carbon ions for targeting resistant hypoxic NSCLC cells. Full article

Background/Objectives: Carbon-ion radiotherapy (CIRT) offers precise dose distribution and enhanced biological effectiveness in localized prostate cancer. However, the safety of CIRT in patients with a history of surgery for benign prostatic hyperplasia (BPH), such as transurethral resection of the prostate (TURP), remains unclear. This study aimed to evaluate the long-term safety and oncological outcomes of CIRT in this population. Methods: A retrospective analysis was conducted in 74 of 3848 patients with prostate cancer and a history of surgery for BPH who underwent CIRT combined with risk-adapted androgen deprivation therapy between 2007 and 2023. Adverse events were assessed using CTCAE v5.0. Biochemical recurrence-free survival was estimated using the Kaplan–Meier method and risk factors for hematuria with multivariate logistic regression and receiver operation characteristic (ROC) analysis. Results: CIRT was generally well-tolerated. Early Grade 2 genitourinary (GU) adverse events occurred in 5.4% of patients, and late-Grade 2 or higher GU events occurred in 8.1%. The cumulative incidence of Grade 2 ≥ GU events remained 10% at 36 months. Compared to holmium laser enucleation of the prostate, a shorter interval between BPH surgery and CIRT initiation and a history of TURP were independently associated with an increased risk of hematuria. Notably, 5-year bRFS was 100% in low- and intermediate-risk groups and 88.6% in the high-risk group. Conclusions: CIRT demonstrates acceptable oncological outcomes and urinary complication rates in patients with prostate cancer and a history of BPH surgery. These findings suggest that CIRT can be a feasible treatment option in this surgically altered population, but careful patient selection, individualized treatment planning, and long-term follow-up are essential. Given the absence of a non-BPH control group, oncological efficacy should be interpreted with caution. Full article

Intra-fractional respiratory management represents one of the greatest challenges of modern cancer radiotherapy (RT), as significant breathing-induced lesion motion might affect target coverage and organs at risk (OARs) sparing, jeopardizing oncological and toxicity outcomes. The detrimental effects on dosage of uncompensated organ motion are exacerbated in RT with charged particles (e.g., protons and carbon ions), due to their higher ballistic selectivity. The simplest strategies to counteract this phenomenon are the use of larger treatment margins and reductions in or control of respiration (e.g., by means of compression belts, breath hold). Gating and tracking, which synchronize beam delivery with the respiratory signal, also represent widely adopted solutions. When tracking the tumor itself or surrogates, invasive procedures (e.g., marker implantation), an unnecessary imaging dose (e.g., in X-ray-based fluoroscopy), or expensive equipment (e.g., magnetic resonance imaging, MRI) is usually required. When chest and abdomen excursions are measured to infer internal tumor displacement, the additional devices needed to perform this task, such as pressure sensors or surface cameras, present inherent limitations that can impair the procedure itself. In this context, radars have intrigued the radiation oncology community, being inexpensive, non-invasive, contactless, and insensitive to obstacles. Even if real-world clinical implementation is still lagging behind, there is a growing body of research unraveling the potential of these devices in this field. The purpose of this narrative review is to provide an overview of the studies that have delved into the potential of radar-based technologies for motion-adaptive photon and particle RT applications. Full article

Background: Biochemical recurrence after radiotherapy for prostate cancer is commonly defined by the Phoenix criteria (prostate-specific antigen [PSA] nadir + 2 ng/mL). However, some patients experience PSA elevation without clinical recurrence, which is known as PSA bounce. This study aimed to evaluate PSA kinetics after scanning-method carbon ion radiotherapy (CIRT) in patients with high-risk prostate cancer (HR-PCa) and to assess the clinical validity of the Phoenix criteria. Methods: We retrospectively analyzed 171 patients with HR-PCa who underwent CIRT and 2 years of androgen deprivation therapy. Patients were classified into three groups based on post-treatment PSA kinetics: non-recurrence, pseudo-recurrence (PR; PSA > 2 ng/mL followed by spontaneous decline without salvage therapy), and recurrence (R; PSA > 2 ng/mL with salvage therapy). PSA bounce was defined as a transient PSA increase > 0.4 ng/mL followed by spontaneous decline. Kaplan–Meier and receiver operating characteristic (ROC) analyses were used to evaluate biochemical relapse-free survival and determine the optimal PSA cutoff. Results: Among 171 patients, 18 (10.5%) met the Phoenix criteria (R+PR), of whom 6 (33.3%) experienced spontaneous PSA decline. The 5-year biochemical relapse-free survival rate was 90.0%. PSA bounce occurred in 33.9%. ROC analysis identified an optimal PSA cutoff of 1.91 ng/mL (area under the curve: 0.985), whereas the positive predictive value at the 2 ng/mL cutoff was as low as 61.1% due to the influence of PSA bounce. Conclusions: After CIRT, a PSA rise of >2 ng/mL does not always indicate HR-PCa recurrence and should be interpreted with caution to avoid overtreatment. Full article