Objective: To summarize our institutional prostate stereotactic body radiation therapy (SBRT) experience using auto beam hold (ABH) technique for intrafractional prostate motion and assess ABH tolerance of 10-millimeter (mm) diameter.Approach: Thirty-two patients (160 fractions) treated using ABH technique between 01/2018 and 03/2021 were analyzed. During treatment, kV images were acquired every 20-degree gantry rotation to visualize 3-4 gold fiducials within prostate to track target motion. If the fiducial center fell outside the tolerance circle (diameter = 10 mm), beam was automatically turned off for reimaging and repositioning. Number of beam holds and couch translational movement magnitudes were recorded. Dosimetric differences from intrafractional motion were calculated by shifting planned isocenter.Main Results: Couch movement magnitude (mean ± SD) in vertical, longitudinal and lateral directions were -0.7 ± 2.5, 1.4 ± 2.9 and -0.1 ± 0.9 mm, respectively. For most fractions (77.5%), no correction was necessary. Number of fractions requiring one, two, or three corrections were 15.6%, 5.6% and 1.3%, respectively. Of the 49 corrections, couch shifts greater than 3 mm were seen primarily in the vertical (31%) and longitudinal (39%) directions; corresponding couch shifts greater than 5 mm occurred in 2% and 6% of cases. Dosimetrically, 100% coverage decreased less than 2% for clinical target volume (CTV) (-1 ± 2%) and less than 10% for PTV (-10 ± 6%). Dose to bladder, bowel and urethra tended to increase (Bladder: ΔD10%:184 ± 466 cGy, ΔD40%:139 ± 241 cGy, Bowel: ΔD1 cm3:54 ± 129 cGy; ΔD5 cm3:44 ± 116 cGy, Urethra: ΔD0.03 cm3:1 ± 1%). Doses to the rectum tended to decrease (Rectum: ΔD1 cm3:-206 ± 564 cGy, ΔD10%:-97 ± 426 cGy; ΔD20%:-50 ± 251 cGy).Significance: With the transition from conventionally fractionated intensity modulated radiation therapy to SBRT for localized prostate cancer treatment, it is imperative to ensure that dose delivery is spatially accurate for appropriate coverage to target volumes and limiting dose to surrounding organs. Intrafractional motion monitoring can be achieved using triggered imaging to image fiducial markers and ABH to allow for reimaging and repositioning for excessive motion.

The purpose of this study is to compare three commonly used radiotherapy fractionation schedules for bone metastasis in terms of clinical and radiological effectiveness. A total of 93 patients with osteolytic bone metastasis were randomized to receive 8 Gyin a single fraction (group A), 20 Gy in 5 fractions (group B) and 30 Gy in 10 fractions (group C). Changes in bone density were measured using the Relative Electron Density (RED) type corrected by Thomas (pe = HU/1.950 + 1.0), where HU is Hounsfield Units. Pain response was assessed according to the Brief Pain Inventory tool. Quality of life was estimated using the EORTC QLQ-C30 and the MD Anderson Symptom (MDAS) tools.After RT, RED, together with the parameters of EORTC QLQ-C30, MDAS and SAT, significantly increased in all groups (p < 0.001).Specifically, the increase of RED was higher in group C compared to group Athree months post-RT (p = 0.014). Group C was also superior to group A in terms of QoL and BPI three months post-treatment. Multifractionated radiotherapy for osteolytic bone metastasis is superior to single fraction radiotherapy in terms of improvement in quality of life and bone remineralization three months post-RT.

BACKGROUND: Magnetic resonance guided radiotherapy (MRgRT) allows daily adaptation of treatment plans to compensate for positional changes of target volumes and organs at risk (OARs). However, current adaptation times are relatively long and organ movement occurring during the adaptation process might offset the benefit gained by adaptation. The aim of this study was to evaluate the dosimetric impact of these intrafractional changes. Additionally, a method to predict the extent of organ movement before the first treatment was evaluated in order to have the possibility to compensate for them, for example by adding additional margins to OARs.
METHODS: Twenty patients receiving adaptive MRgRT for treatment of abdominal lesions were retrospectively analyzed. Magnetic resonance (MR) images acquired at the start of adaptation and immediately before irradiation were used to calculate adapted and pre-irradiation dose in OARs directly next to the planning target volume. The extent of organ movement was determined on MR images acquired during simulation sessions and adaptive treatments, and their agreement was evaluated. Correlation between the magnitude of organ movement during simulation and the duration of simulation session was analyzed in order to assess whether organ movement might be relevant even if the adaptation process could be accelerated in the future.
RESULTS: A significant increase in dose constraint violations was observed from adapted (6.9%) to pre-irradiation (30.2%) dose distributions. Overall, OAR dose increased significantly by 4.3% due to intrafractional organ movement. Median changes in organ position of 7.5 mm (range 1.5-10.5 mm) were detected within a median time of 17.1 min (range 1.6-28.7 min). Good agreement was found between the range of organ movement during simulation and adaptation (66.8%), especially if simulation sessions were longer and multiple MR images were acquired. No correlation was determined between duration of simulation sessions and magnitude of organ movement.
CONCLUSIONS: Intrafractional organ movement can impact dose distributions and lead to violations of OAR tolerance doses, which impairs the benefit of daily on-table plan adaptation. By application of simulation images, the extent of intrafractional organ movement can be predicted, which possibly allows to compensate for them.

Orbital radiotherapy for Graves\' ophthalmopathy is an example of non-oncological radiotherapy. First introduced in the 1930s, this treatment has become widely used since the 1980s with several studies showing proof of both effectiveness and safety: a decrease of soft tissue involvement in 70 to 80% of patients and an improvement of ocular mobility in 30 to 80% of patients. Nowadays, it\'s one of the second line treatment options recognized by the European Group on Graves\' orbitopathy in the management of a moderate to severe and active disease after failure of glucocorticoids. In that setting, orbital radiotherapy should be combined with glucocorticoids. To our knowledge, there are no practical recommendations on how orbital radiotherapy should be planned and conducted for Graves\' ophthalmopathy. Optimal dose is not defined however the most frequent regimen consists of 20Gy in ten fractions of 2Gy, though other options may yield better results. Lastly, the use of modern technique of radiotherapy such as intensity-modulated radiation therapy may allow a better sparing of organs at risk compared to three-dimensional radiotherapy using lateral opposing fields.

High doses of ionizing radiation are the risk factor of cognitive dysfunction and anxiety disorders developing in humans and experimental animals. However, the data on the effect of low doses, especially in case of chronic or fractionated exposure, is limited and contradictory. Here we studied the effect of fractionated γ-radiation at cumulative doses of 0.1, 1, and 5 Gy on the parameters of the anxiety-like behavior in neonatal C57BL/6 mice. The anxiety was evaluated using the marble burying test and elevated plus maze. Fractionated irradiation resulted in dose-dependent changes in mouse behavior: the low dose caused an increase in anxiety, wherein the dose raise led to the decrease in anxiety-like behavior indicators compared to non-irradiated animals.

FLASH radiotherapy (RT) is emerging as a potentially revolutionary advancement in cancer treatment, offering the potential to deliver RT at ultra-high dose rates (>40 Gy/s) while significantly reducing damage to healthy tissues. Democratizing FLASH RT by making this cutting-edge approach more accessible and affordable for healthcare systems worldwide would have a substantial impact in global health. Here, we review recent developments in FLASH RT and present perspective on further developments that could facilitate the democratizing of FLASH RT. These include upgrading and validating current technologies that can deliver and measure the FLASH radiation dose with high accuracy and precision, establishing a deeper mechanistic understanding of the FLASH effect, and optimizing dose delivery conditions and parameters for different types of tumors and normal tissues, such as the dose rate, dose fractionation, and beam quality for high efficacy. Furthermore, we examine the potential for democratizing FLASH radioimmunotherapy leveraging evidence that FLASH RT can make the tumor microenvironment more immunogenic, and parallel developments in nanomedicine or use of smart radiotherapy biomaterials for combining RT and immunotherapy. We conclude that the democratization of FLASH radiotherapy represents a major opportunity for concerted cross-disciplinary research collaborations with potential for tremendous impact in reducing radiotherapy disparities and extending the cancer moonshot globally.

Radiation treatment has been the cornerstone in cancer management. However, long term treatment-related morbidity always accompanies tumor control which has significant impact on quality of life of the patient who has survived the cancer. Spatially fractionated radiation has the potential to achieve both cure and to avoid dreaded long term sequelae. The first ever randomized study of mini-beam radiation treatment (MBRT) of canine brain tumor has clearly shown the ability to achieve this goal. Dogs have gyrencephalic brains functionally akin to human brain. We here report long term follow-up and final outcome of the dogs, revealing both tumor control and side effects on normal brain. The results augur potential for conducting human studies with MBRT.

A large proportion of cancer patients present with unresectable bulky disease at baseline or following treatment failure. The data available in the literature suggest that the vast majority of these patients do not benefit from available standard therapies. Therefore the clinical outcomes are poor; patients are desperate and usually relegated to palliative or best supportive care as the only options. Large tumor masses are usually hypoxic, resistant to radiation and systemic therapy, with extensive regional infiltration of the surrounding critical organs, the presence of which makes it impossible to deliver a radical dose of radiation. Promising data in terms of improved therapeutic ratio where such complex tumors are concerned can be seen with the use of new emerging unconventional radiotherapy techniques known as spatially fractionated radiotherapies (SFRT). One of them is PATHY, or PArtial Tumor irradiation targeting HYpoxic segment, which is characterized by a very short treatment course offering a large spectrum of therapeutic benefits in terms of the symptom relief, quality of life, local tumor control, neoadjuvant and immunomodulatory effects.

Treating radioresistant and bulky tumors is challenging due to their inherent resistance to standard therapies and their large size. GRID and lattice spatially fractionated radiation therapy (simply referred to GRID RT and LRT) offer promising techniques to tackle these issues. Both approaches deliver radiation in a grid-like or lattice pattern, creating high-dose peaks surrounded by low-dose valleys. This pattern enables the destruction of significant portions of the tumor while sparing healthy tissue. GRID RT uses a 2-dimensional pattern of high-dose peaks (15-20 Gy), while LRT delivers a three-dimensional array of high-dose vertices (10-20 Gy) spaced 2-5 cm apart. These techniques are beneficial for treating a variety of cancers, including soft tissue sarcomas, osteosarcomas, renal cell carcinoma, melanoma, gastrointestinal stromal tumors (GISTs), pancreatic cancer, glioblastoma, and hepatocellular carcinoma. The specific grid and lattice patterns must be carefully tailored for each cancer type to maximize the peak-to-valley dose ratio while protecting critical organs and minimizing collateral damage. For gynecologic cancers, the treatment plan should align with the international consensus guidelines, incorporating concurrent chemotherapy for optimal outcomes. Despite the challenges of precise dosimetry and patient selection, GRID RT and LRT can be cost-effective using existing radiation equipment, including particle therapy systems, to deliver targeted high-dose radiation peaks. This phased approach of partial high-dose induction radiation therapy with standard fractionated radiation therapy maximizes immune modulation and tumor control while reducing toxicity. Comprehensive treatment plans using these advanced techniques offer a valuable framework for radiation oncologists, ensuring safe and effective delivery of therapy for radioresistant and bulky tumors. Further clinical trials data and standardized guidelines will refine these strategies, helping expand access to innovative cancer treatments.

Spatially fractionated radiation therapy (SFRT), also known as the GRID and LATTICE radiotherapy (GRT, LRT), the concept of treating tumors by delivering a spatially modulated dose with highly non-uniform dose distributions, is a treatment modality of growing interest in radiation oncology, physics, and radiation biology. Clinical experience in SFRT has suggested that GRID and LATTICE therapy can achieve a high response and low toxicity in the treatment of refractory and bulky tumors. Limited initially to GRID therapy using block collimators, advanced, and versatile multi-leaf collimators, volumetric modulated arc technologies and particle therapy have since increased the capabilities and individualization of SFRT and expanded the clinical investigation of SFRT to various dosing regimens, multiple malignancies, tumor types and sites. As a 3D modulation approach outgrown from traditional 2D GRID, LATTICE therapy aims to reconfigure the traditional SFRT as spatial modulation of the radiation is confined solely to the tumor volume. The distinctively different beam geometries used in LATTICE therapy have led to appreciable variations in dose-volume distributions, compared to GRID therapy. The clinical relevance of the variations in dose-volume distribution between LATTICE and traditional GRID therapies is a crucial factor in determining their adoption in clinical practice. In this Point-Counterpoint contribution, the authors debate the pros and cons of GRID and LATTICE therapy. Both modalities have been used in clinics and their applicability and optimal use have been discussed in this article.