Safety and Tolerability of Online Adaptive High-Field Magnetic Resonance-Guided Radiotherapy.

Importance: In 2018, the first online adaptive magnetic resonance (MR)-guided radiotherapy (MRgRT) system using a 1.5-T MR-equipped linear accelerator (1.5-T MR-Linac) was clinically introduced. This system enables online adaptive radiotherapy, in which the radiation plan is adapted to size and shape changes of targets at each treatment session based on daily MR-visualized anatomy. Objective: To evaluate safety, tolerability, and technical feasibility of treatment with a 1.5-T MR-Linac, specifically focusing on the subset of patients treated with an online adaptive strategy (ie, the adapt-to-shape [ATS] approach). Design, Setting, and Participants: This cohort study included adults with solid tumors treated with a 1.5-T MR-Linac enrolled in Multi Outcome Evaluation for Radiation Therapy Using the MR-Linac (MOMENTUM), a large prospective international study of MRgRT between February 2019 and October 2021. Included were adults with solid tumors treated with a 1.5-T MR-Linac. Data were collected in Canada, Denmark, The Netherlands, United Kingdom, and the US. Data were analyzed in August 2023. Exposure: All patients underwent MRgRT using a 1.5-T MR-Linac. Radiation prescriptions were consistent with institutional standards of care. Main Outcomes and Measures: Patterns of care, tolerability, and technical feasibility (ie, treatment completed as planned). Acute high-grade radiotherapy-related toxic effects (ie, grade 3 or higher toxic effects according to Common Terminology Criteria for Adverse Events version 5.0) occurring within the first 3 months after treatment delivery. Results: In total, 1793 treatment courses (1772 patients) were included (median patient age, 69 years [range, 22-91 years]; 1384 male [77.2%]). Among 41 different treatment sites, common sites were prostate (745 [41.6%]), metastatic lymph nodes (233 [13.0%]), and brain (189 [10.5%]). ATS was used in 1050 courses (58.6%). MRgRT was completed as planned in 1720 treatment courses (95.9%). Patient withdrawal caused 5 patients (0.3%) to discontinue treatment. The incidence of radiotherapy-related grade 3 toxic effects was 1.4% (95% CI, 0.9%-2.0%) in the entire cohort and 0.4% (95% CI, 0.1%-1.0%) in the subset of patients treated with ATS. There were no radiotherapy-related grade 4 or 5 toxic effects. Conclusions and Relevance: In this cohort study of patients treated on a 1.5-T MR-Linac, radiotherapy was safe and well tolerated. Online adaptation of the radiation plan at each treatment session to account for anatomic variations was associated with a low risk of acute grade 3 toxic effects.

Functional imaging guided stereotactic ablative body radiotherapy (SABR) with focal dose escalation and bladder trigone sparing for intermediate and high-risk prostate cancer: study protocol for phase II safo trial.

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is an emerging treatment alternative for patients with localized low and intermediate risk prostate cancer patients. As already explored by some authors in the context of conventional moderate hypofractionated radiotherapy, focal boost of the index lesion defined by magnetic resonance imaging (MRI) is associated with an improved biochemical outcome. The objective of this phase II trial is to determine the effectiveness (in terms of biochemical, morphological and functional control), the safety and impact on quality of life, of prostate SABR with MRI guided focal dose intensification in males with intermediate and high-risk localized prostate cancer. METHODS: Patients with intermediate and high-risk prostate cancer according to NCCN definition will be treated with SABR 36.25 Gy in 5 fractions to the whole prostate gland with MRI guided simultaneous integrated focal boost (SIB) to the index lesion (IL) up to 50 Gy in 5 fractions, using a protocol of bladder trigone and urethra sparing. Intra-fractional motion will be monitored with daily cone beam computed tomography (CBCT) and intra-fractional tracking with intraprostatic gold fiducials. Androgen deprivation therapy (ADT) will be allowed. The primary endpoint will be efficacy in terms of biochemical and local control assessed by Phoenix criteria and post-treatment MRI respectively. The secondary endpoints will encompass acute and late toxicity, quality of life (QoL) and progression-free survival. Finally, the subgroup of high-risk patients will be involved in a prospective study focused on immuno-phenotyping. DISCUSSION: To the best of our knowledge, this is the first trial to evaluate the impact of post-treatment MRI on local control among patients with intermediate and high-risk prostate cancer undergoing SABR and MRI guided focal intensification. The results of this trial will enhance our understanding of treatment focal intensification through the employment of the SABR technique within this specific patient subgroup, particularly among those with high-risk disease, and will help to clarify the significance of MRI in monitoring local responses. Hopefully will also help to design more personalized biomarker-based phase III trials in this specific context. Additionally, this trial is expected to be incorporated into a prospective radiomics study focused on localized prostate cancer treated with radiotherapy. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT05919524; Registered 17 July 2023. TRIAL SPONSOR: IRAD/SEOR (Instituto de Investigación de Oncología Radioterápica / Sociedad Española de Oncología Radioterápica). STUDY SETTING: Clinicaltrials.gov identifier: NCT05919524; Registered 17 July 2023. TRIAL STATUS: Protocol version number and date: v. 5/ 17 May-2023. Date of recruitment start: August 8, 2023. Date of recruitment completion: July 1, 2024.

Advancements and future directions in positron emission tomography-guided radiotherapy: a narrative review.

BACKGROUND AND OBJECTIVE: Positron emission tomography (PET) imaging has been useful in delineating tumor volumes and allowing for improved radiation treatment. The field of PET-guided radiotherapy is rapidly growing and will have significant impact on radiotherapy delivery in the future. This narrative review provides an overview of the current state of PET-guided radiotherapy as well as the future directions of the field. METHODS: For this narrative review, PubMed was searched for articles from 2010-2023. A total of 18 keywords or phrases were searched to provide an overview of PET-guided radiotherapy, radiotracers, the role of PET-guided radiotherapy in oligometastatic disease, and biology-guided radiotherapy (BgRT). The first 300 results for each keyword were searched and relevant articles were extracted. The references of these articles were also reviewed for relevant articles. KEY CONTENT AND FINDINGS: In radiotherapy, 18F-2-fluoro-2-deoxy-D-glucose (F-FDG or FDG) is the major radiotracer for PET and when combined with computed tomography (CT) scan allows for anatomic visualization of metabolically active malignancy. Novel radiotracers are being explored to delineate certain cell types and numerous tumor metrics including metabolism, hypoxia, vascularity, and cellular proliferation. This molecular and functional imaging will provide improved tumor characterization. Through these radiotracers, radiation plans can employ dose painting by creating different dose levels based upon specific risk factors of the target volume. Additionally, biologic imaging during radiotherapy can allow for adaptation of the radiation plan based on response to treatment. Dose painting and adaptive radiotherapy should improve the therapeutic ratio through more selective dose delivery. The novel PET-linear accelerator hopes to combine these techniques and more by using radiotracers to deliver BgRT. The areas of radiotracer uptake will serve as fiducials to guide radiotherapy to themselves. This technique may prove promising in the growing area of oligometastatic radiation treatment. CONCLUSIONS: Significant challenges exist for the future of PET-guided radiotherapy. However, with the advancements being made, PET imaging is set to change the delivery of radiotherapy.

Pelvic target volume inter-fractional motion during radiotherapy for cervical cancer with daily iterative cone beam computed tomography.

BACKGROUND: Tumor regression and organ movements indicate that a large margin is used to ensure target volume coverage during radiotherapy. This study aimed to quantify inter-fractional movements of the uterus and cervix in patients with cervical cancer undergoing radiotherapy and to evaluate the clinical target volume (CTV) coverage. METHODS: This study analyzed 303 iterative cone beam computed tomography (iCBCT) scans from 15 cervical cancer patients undergoing external beam radiotherapy. CTVs of the uterus (CTV-U) and cervix (CTV-C) contours were delineated based on each iCBCT image. CTV-U encompassed the uterus, while CTV-C included the cervix, vagina, and adjacent parametrial regions. Compared with the planning CTV, the movement of CTV-U and CTV-C in the anterior-posterior, superior-inferior, and lateral directions between iCBCT scans was measured. Uniform expansions were applied to the planning CTV to assess target coverage. RESULTS: The motion (mean ± standard deviation) in the CTV-U position was 8.3 ± 4.1 mm in the left, 9.8 ± 4.4 mm in the right, 12.6 ± 4.0 mm in the anterior, 8.8 ± 5.1 mm in the posterior, 5.7 ± 5.4 mm in the superior, and 3.0 ± 3.2 mm in the inferior direction. The mean CTV-C displacement was 7.3 ± 3.2 mm in the left, 8.6 ± 3.8 mm in the right, 9.0 ± 6.1 mm in the anterior, 8.4 ± 3.6 mm in the posterior, 5.0 ± 5.0 mm in the superior, and 3.0 ± 2.5 mm in the inferior direction. Compared with the other tumor (T) stages, CTV-U and CTV-C motion in stage T1 was larger. A uniform CTV planning treatment volume margin of 15 mm failed to encompass the CTV-U and CTV-C in 11.1% and 2.2% of all fractions, respectively. The mean volume change of CTV-U and CTV-C were 150% and 51%, respectively, compared with the planning CTV. CONCLUSIONS: Movements of the uterine corpus are larger than those of the cervix. The likelihood of missing the CTV is significantly increased due to inter-fractional motion when utilizing traditional planning margins. Early T stage may require larger margins. Personal radiotherapy margining is needed to improve treatment accuracy.

Markerless liver online adaptive stereotactic radiotherapy: feasibility analysisCervantes.

Objective. Radio-opaque markers are recommended for image-guided radiotherapy in liver stereotactic ablative radiotherapy (SABR), but their implantation is invasive. We evaluate in thisin-silicostudy the feasibility of cone-beam computed tomography-guided stereotactic online-adaptive radiotherapy (CBCT-STAR) to propagate the target volumes without implanting radio-opaque markers and assess its consequence on the margin that should be used in that context.Approach. An emulator of a CBCT-STAR-dedicated treatment planning system was used to generate plans for 32 liver SABR patients. Three target volume propagation strategies were compared, analysing the volume difference between the GTVPropagatedand the GTVConventional, the vector lengths between their centres of mass (lCoM), and the 95th percentile of the Hausdorff distance between these two volumes (HD95). These propagation strategies were: (1) structure-guided deformable registration with deformable GTV propagation; (2) rigid registration with rigid GTV propagation; and (3) image-guided deformable registration with rigid GTV propagation. Adaptive margin calculation integrated propagation errors, while interfraction position errors were removed. Scheduled plans (PlanNon-adaptive) and daily-adapted plans (PlanAdaptive) were compared for each treatment fraction.Main results.The image-guided deformable registration with rigid GTV propagation was the best propagation strategy regarding tolCoM(mean: 4.3 +/- 2.1 mm), HD95 (mean 4.8 +/- 3.2 mm) and volume preservation between GTVPropagatedand GTVConventional. This resulted in a planning target volume (PTV) margin increase (+69.1% in volume on average). Online adaptation (PlanAdaptive) reduced the violation rate of the most important dose constraints ('priority 1 constraints', 4.2 versus 0.9%, respectively;p< 0.001) and even improved target volume coverage compared to non-adaptive plans (PlanNon-adaptive).Significance. Markerless CBCT-STAR for liver tumours is feasible using Image-guided deformable registration with rigid GTV propagation. Despite the cost in terms of PTV volumes, daily adaptation reduces constraints violation and restores target volumes coverage.

Salvage Radiotherapy PSMA PET/CT-guided in Men With PSA Recurrence.

BACKGROUND/AIM: To evaluate the clinical outcome in men with recurrent prostate cancer (PCa) treated by salvage radiotherapy (sRT) prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT)-guided. PATIENTS AND METHODS: From January 2021 to January 2023, 33 patients who previously underwent definitive/systemic therapy were submitted to sRT PSMA PET/CT-guided for PCa recurrence: 16 (48.5%) on the prostate bed (PB), 12 (36.4%) on the lymph node (LN) and five (15.1%) on the bone. The median PSA value was 3.3 ng/ml (range=0.3-15.5 ng/ml): 0.2-0.5 ng/ml (18.2% cases), 0.51-1 ng/ml (39.4% cases) and >1 ng/ml (42.4% cases). Median 18F PSMA PET/CT standardized uptake value (SUVmax) was evaluated on PB, vs. LN vs. bones PCa recurrences and was equal to 12.5 vs. 19.0 vs. 30.1, respectively. RESULTS: Overall, at a median follow up of 12 months, 23/33 patients (69.7%) had local control without distant progression (PSA and SUVmax evaluation): 14/16 (87.5%) vs. 7/12 (58.3%) vs. 2/5 (40%) underwent sRT on the PB vs. LN vs. bone metastases, respectively. CONCLUSION: PSMA PET/CT allows to perform sRT early in men with PCa recurrence and low PSA values obtaining a complete clinical response in approximately 70% of the cases one year from treatment.

REPeated mAgnetic resonance Image-guided stereotactic body Radiotherapy (MRIg-reSBRT) for oligometastatic patients: REPAIR, a mono-institutional retrospective study.

BACKGROUND: Oligo-progression or further recurrence is an open issue in the multi-integrated management of oligometastatic disease (OMD). Re-irradiation with stereotactic body radiotherapy (re-SBRT) technique could represent a valuable treatment option to improve OMD clinical outcomes. MRI-guided allows real-time visualization of the target volumes and online adaptive radiotherapy (oART). The aim of this retrospective study is to evaluate the efficacy and toxicity profile of MRI-guided repeated SBRT (MRIg-reSBRT) in the OMD setting and propose a re-SBRT classification. METHODS: We retrospectively analyzed patients (pts) with recurrent liver metastases or abdominal metastatic lesions between 1 and 5 centimeters from liver candidate to MRIg-reSBRT showing geometric overlap between the different SBRT courses and assessing whether they were in field (type 1) or not (type 2). RESULTS: Eighteen pts completed MRIg-reSBRT course for 25 metastatic hepatic/perihepatic lesions from July 2019 to January 2020. A total of 20 SBRT courses: 15 Type 1 re-SBRT (75%) and 5 Type 2 re-SBRT (25%) was delivered. Mean interval between the first SBRT and MRIg-reSBRT was 8,6 months. Mean prescribed dose for the first treatment was 43 Gy (range 24-50 Gy, mean BEDα/ß10=93), while 41 Gy (range 16-50 Gy, mean BEDα/ß10=92) for MRIg-reSBRT. Average liver dose was 3,9 Gy (range 1-10 Gy) and 3,7 Gy (range 1,6-8 Gy) for the first SBRT and MRIg-reSBRT, respectively. No acute or late toxicities were reported at a median follow-up of 10,7 months. The 1-year OS and PFS was 73,08% and 50%, respectively. Overall Clinical Benefit was 54%. CONCLUSIONS: MRIg-reSBRT could be considered an effective and safe option in the multi-integrated treatment of OMD.

Adaptive radiotherapy for head and neck cancer: Pitfalls and possibilities from the radiation oncologist's point of view.

BACKGROUND: Patients with head and neck cancer (HNC) may experience substantial anatomical changes during the course of radiotherapy treatment. The implementation of adaptive radiotherapy (ART) proves effective in managing the consequent impact on the planned dose distribution. METHODS: This narrative literature review comprehensively discusses the diverse strategies of ART in HNC and the documented dosimetric and clinical advantages associated with these approaches, while also addressing the current challenges for integration of ART into clinical practice. RESULTS AND CONCLUSION: Although based on mainly non-randomized and retrospective trials, there is accumulating evidence that ART has the potential to reduce toxicity and improve quality of life and tumor control in HNC patients treated with RT. However, several questions remain regarding accurate patient selection, the ideal frequency and timing of replanning, and the appropriate way for image registration and dose calculation. Well-designed randomized prospective trials, with a predetermined protocol for both image registration and dose summation, are urgently needed to further investigate the dosimetric and clinical benefits of ART.

Evaluation of safety margins for cone beam CT-based adaptive prostate radiotherapy.

Adaptive radiotherapy is characterized by the use of a daily imaging system, such as CBCT (Cone-Beam Computed Tomography) images to re-optimize the treatment based on the daily anatomy and position of the patient. By systematically re-delineating the Clinical Target Volume (CTV) at each fraction, target delineation uncertainty features a random component instead of a pure systematic. The goal of this work is to identify the random and systematic contributions of the delineation error and compute a new relevant Planning Target Volume (PTV) safety margin. 169 radiotherapy sessions from 10 prostate cancer patients treated on the Varian ETHOS treatment system have been analyzed. Intra-patient and inter-patient delineation variabilities were computed in six directions, by considering the prostate as a rigid, non-rotating volume. By doing so, we were able to directly compare the delineations done by the physicians on daily CBCT images with the initial delineation done on the CT-sim and MRI, and sort them by direction using the polar coordinates of the points. The computed variabilities were then used to compute a PTV margin based on Van Herk margin recipe. The total margin computed with random and systematic delineation uncertainties was of 2.7, 2.4, 5.6, 4.8, 4.9 and 3.6 mm in the left, right, anterior, posterior, cranial and caudal directions, respectively. According to our results, the gain offered by the separation of the delineation uncertainty into systematic and random contributions due to the adaptive delineation process justifies a reduction of the PTV margin down to 3 to 5 mm in every direction.

Image quality characterization of an ultra-high-speed kilovoltage cone-beam computed tomography imaging system on an O-ring linear accelerator.

PURPOSE: The quality of on-board imaging systems, including cone-beam computed tomography (CBCT), plays a vital role in image-guided radiation therapy (IGRT) and adaptive radiotherapy. Recently, there has been an upgrade of the CBCT systems fused in the O-ring linear accelerators called HyperSight, featuring a high imaging performance. As the characterization of a new imaging system is essential, we evaluated the image quality of the HyperSight system by comparing it with Halcyon 3.0 CBCT and providing benchmark data for routine imaging quality assurance. METHODS: The HyperSight features ultra-fast scan time, a larger kilovoltage (kV) detector, a more substantial kV tube, and an advanced reconstruction algorithm. Imaging protocols in the two modes of operation, treatment mode with IGRT and the CBCT for planning (CBCTp) mode were evaluated and compared with Halcyon 3.0 CBCT. Image quality metrics, including spatial resolution, contrast resolution, uniformity, noise, computed tomography (CT) number linearity, and calibration error, were assessed using a Catphan and an electron density phantom and analyzed with TotalQA software. RESULTS: HyperSight demonstrated substantial improvements in contrast-to-noise ratio and noise in both IGRT and CBCTp modes compared to Halcyon 3.0 CBCT. CT number calibration error of HyperSight CBCTp mode (1.06%) closely matches that of a full CT scanner (0.72%), making it suitable for adaptive planning. In addition, the advanced hardware of HyperSight, such as ultra-fast scan time (5.9 s) or 2.5 times larger heat unit capacity, enhanced the clinical efficiency in our experience. CONCLUSIONS: HyperSight represented a significant advancement in CBCT imaging. With its image quality, CT number accuracy, and ultra-fast scans, HyperSight has a potential to transform patient care and treatment outcomes. The enhanced scan speed and image quality of HyperSight are expected to significantly improve the quality and efficiency of treatment, particularly benefiting patients.

Radiotherapy protocols for mouse cancer model.

Radiotherapy is a crucial treatment modality for cancer patients, with approximately 60% of individuals undergoing ionizing radiation as part of their disease management. In recent years, there has been a growing trend toward minimizing irradiation fields through the use of image-guided dosimetry and innovative technologies. These advancements allow for selective irradiation, delivering higher local doses while reducing the number of treatment sessions. Consequently, computer-assisted methods have significantly enhanced the effectiveness of radiotherapy in the curative and palliative treatment of various cancers. Although radiation therapy alone can effectively achieve local control in some cancer types, it may not be sufficient for others. As a result, further preclinical research is necessary to explore novel approaches including new schedules of radiotherapy treatments. Unfortunately, there is a concerning lack of correlation between clinical outcomes and experiments conducted on mouse models. We hypothesize that this disparity arises from the differences in irradiation strategies employed in preclinical studies compared to those used in clinical practice, which ultimately affects the translatability of findings to patients. In this study, we present two comprehensive radiotherapy protocols for the treatment of orthotopic melanoma and glioblastoma tumors. These protocols utilize a small animal radiation research platform, which is an ideal radiation device for delivering localized and precise X-ray doses to the tumor mass. By employing these platforms, we aim to limit the side effects associated with irradiating healthy surrounding tissues. Our detailed protocols offer a valuable framework for conducting preclinical studies that closely mimic clinical radiotherapy techniques, bridging the gap between experimental results and patient outcomes.

ROAR-A: re-optimization based Online Adaptive Radiotherapy of anal cancer, a prospective phase II trial protocol.

BACKGROUND: Chemo-radiotherapy with curative intent for anal cancer has high complete remission rates, but acute treatment-related gastrointestinal (GI) toxicity is significant. Toxicity occurs due to irradiation of surrounding normal tissue. Current radiotherapy requires the addition of large planning margins to the radiation field to ensure target coverage regardless of the considerable organ motion in the pelvic region. This increases the irradiated volume and radiation dose to the surrounding normal tissue and thereby toxicity. Online adaptive radiotherapy uses artificial intelligence to adjust the treatment to the anatomy of the day. This allows for the reduction of planning margins, minimizing the irradiated volume and thereby radiation to the surrounding normal tissue.This study examines if cone beam computed tomography (CBCT)-guided oART with daily automated treatment re-planning can reduce acute gastrointestinal toxicity in patients with anal cancer. METHODS/DESIGN: The study is a prospective, single-arm, phase II trial conducted at Copenhagen University Hospital, Herlev and Gentofte, Denmark. 205 patients with local only or locally advanced anal cancer, referred for radiotherapy with or without chemotherapy with curative intent, are planned for inclusion. Toxicity and quality of life are reported with Common Terminology Criteria of Adverse Events and patient-reported outcome questionnaires, before, during, and after treatment. The primary endpoint is a reduction in the incidence of acute treatment-related grade ≥ 2 diarrhea from 36 to 25% after daily online adaptive radiotherapy compared to standard radiotherapy. Secondary endpoints include all acute and late toxicity, overall survival, and reduction in treatment interruptions. RESULTS: Accrual began in January 2022 and is expected to finish in January 2026. Primary endpoint results are expected to be available in April 2026. DISCUSSION: This is the first study utilizing online adaptive radiotherapy to treat anal cancer. We hope to determine whether there is a clinical benefit for the patients, with significant reductions in acute GI toxicity without compromising treatment efficacy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05438836. Danish Ethical Committee: H-21028093.

Characterization of the IDENTIFYTM surface scanning system for radiation therapy setup on a closed-bore linac.

PURPOSE: In radiation therapy, surface guidance can be used for patient setup and intra-fraction motion monitoring. The surface guided radiation therapy (SGRT) system from Varian Medical systems, IDENTIFYTM, consists of three pods, including cameras and a random pattern projector, mounted on the ceiling. The information captured by the cameras is used to make a reconstruction of the surface. The aim of the study was to assess the technical performance of this SGRT system on a closed-bore linac. METHODS: Phantom measurements were performed to assess the accuracy, precision, reproducibility and temporal stability of the system, both in align and in load position. Translations of the phantoms in lateral, longitudinal, and vertical direction, and rotations around three axes (pitch, roll and yaw) were performed with an accurate, in-house built, positioning stage. Different phantom geometries and different surface colors were used, and various ambient light intensities were tested. RESULTS: The accuracy of the IDENTIFYTM system at the closed-bore linac was 0.07 mm and 0.07 degrees at load position, and 0.06 mm and 0.01 degrees at align position for the white head phantom. The precision was 0.02 mm and 0.02 degrees in load position, and 0.01 mm and 0.02 degrees in align position. The accuracy for the Penta-Guide phantom was comparable to the white head phantom, with 0.06 mm and 0.01 degrees in align position. The system was slightly less accurate for translations of the CIRS lung phantom in align position (0.20 mm, 0.05 degrees). Reproducibility measurements showed a variation of 0.02 mm in load position. Regarding the temporal stability, the maximum drift over 30 min was 0.33 mm and 0.02 degrees in load position. No effect of ambient light level on the accuracy of the IDENTIFYTM system was observed. Regarding different surface colors, the accuracy of the system for a black phantom was slightly worse compared to a white surface, but not clinical relevant. CONCLUSION: The IDENTIFYTM system can adequately be used for motion monitoring on a closed-bore linac with submillimeter accuracy. The results of the performed measurements meet the clinical requirements described in the guidelines of the AAPM and the ESTRO.

SAPPHIRE -establishment of small animal proton and photon image-guided radiation experiments.

Thein vivoevolution of radiotherapy necessitates innovative platforms for preclinical investigation, bridging the gap between bench research and clinical applications. Understanding the nuances of radiation response, specifically tailored to proton and photon therapies, is critical for optimizing treatment outcomes. Within this context, preclinicalin vivoexperimental setups incorporating image guidance for both photon and proton therapies are pivotal, enabling the translation of findings from small animal models to clinical settings. TheSAPPHIREproject represents a milestone in this pursuit, presenting the installation of the small animal radiation therapy integrated beamline (SmART+ IB, Precision X-Ray Inc., Madison, Connecticut, USA) designed for preclinical image-guided proton and photon therapy experiments at University Proton Therapy Dresden. Through Monte Carlo simulations, low-dose on-site cone beam computed tomography imaging and quality assurance alignment protocols, the project ensures the safe and precise application of radiation, crucial for replicating clinical scenarios in small animal models. The creation of Hounsfield lookup tables and comprehensive proton and photon beam characterizations within this system enable accurate dose calculations, allowing for targeted and controlled comparison experiments. By integrating these capabilities,SAPPHIREbridges preclinical investigations and potential clinical applications, offering a platform for translational radiobiology research and cancer therapy advancements.

PET/SPECT/Spectral-CT/CBCT imaging in a small-animal radiation therapy platform: A Monte Carlo study-Part II: Biologically guided radiotherapy.

BACKGROUND: This study addresses the technical gap between clinical radiation therapy (RT) and preclinical small-animal RT, hindering the comprehensive validation of innovative clinical RT approaches in small-animal models of cancer and the translation of preclinical RT studies into clinical practices. PURPOSE: The main aim was to explore the feasibility of biologically guided RT implemented within a small-animal radiation therapy (SART) platform, with integrated quad-modal on-board positron emission tomography (PET), single-photon emission computed tomography, photon-counting spectral CT, and cone-beam CT (CBCT) imaging, in a Monte Carlo model as a proof-of-concept. METHODS: We developed a SART workflow employing quad-modal imaging guidance, integrating multimodal image-guided RT and emission-guided RT (EGRT). The EGRT algorithm was outlined using positron signals from a PET radiotracer, enabling near real-time adjustments to radiation treatment beams for precise targeting in the presence of a 2-mm setup error. Molecular image-guided RT, incorporating a dose escalation/de-escalation scheme, was demonstrated using a simulated phantom with a dose painting plan. The plan involved delivering a low dose to the CBCT-delineated planning target volume (PTV) and a high dose boosted to the highly active biological target volume (hBTV) identified by the 18F-PET image. Additionally, the Bayesian eigentissue decomposition method illustrated the quantitative decomposition of radiotherapy-related parameters, specifically iodine uptake fraction and virtual noncontrast (VNC) electron density, using a simulated phantom with Kidney1 and Liver2 inserts mixed with an iodine contrast agent at electron fractions of 0.01-0.02. RESULTS: EGRT simulations generated over 4,000 beamlet responses in dose slice deliveries and illustrated superior dose coverage and distribution with significantly lower doses delivered to normal tissues, even with a 2-mm setup error introduced, demonstrating the robustness of the novel EGRT scheme compared to conventional image-guided RT. In the dose-painting plan, doubling the dose to the hBTV while maintaining a low dose for the PTV resulted in an organ-at-risk (OAR) dose comparable to the low-dose treatment for the PTV alone. Furthermore, the decomposition of radiotherapy-related parameters in Kidney1 and Liver2 inserts, including iodine uptake fractions and VNC electron densities, exhibited average relative errors of less than 1.0% and 2.5%, respectively. CONCLUSIONS: The results demonstrated the successful implementation of biologically guided RT within the proposed quad-model image-guided SART platform, with potential applications in preclinical RT and adaptive RT studies.

Surface guided radiotherapy practice in paediatric oncology: a survey on behalf of the SIOPE Radiation Oncology Working Group.

INTRODUCTION: Surface guided radiotherapy (SGRT) is increasingly being implemented to track patient's surface movement and position during radiation therapy. However, limited information is available on the SGRT use in paediatrics. The aim of this double survey was to map SIOPE (European Society for Paediatric Oncology)-affiliated centres using SGRT and to gain information on potential indications, observed, or expected benefits. METHODS: A double online survey was distributed to 246 SIOPE-affiliated radiotherapy (RT) centres. Multiple choices, yes/no, and open answers were included. The first survey (41 questions) was active from February to March 2021. A shortened version (13 questions) was repeated in March 2023 to detect trends in SGRT use within the same community. RESULTS: Respectively, 76/142 (54%) and 28/142 (20%) responding centres used and planned to use SGRT clinically, including 4/34 (12%) new centres since 2021. Among the SGRT users, 33/76 (43%) already applied this technology to paediatric treatments. The main benefits of improved patient comfort, better monitoring of intrafraction motion, and more accurate initial patient set-up expected by future users did not differ from current SGRT-users (P = .893). Among non-SGRT users, the main hurdles to implement SGRT were costs and time for installation. In paediatrics, SGRT is applied to all anatomical sites. CONCLUSION: This work provides information on the practice of SGRT in paediatrics across SIOPE-affiliated RT centres which can serve as a basis for departments when considering the purchase of SGRT systems. ADVANCES IN KNOWLEDGE: Since little information is available in the literature on the use of SGRT in paediatrics, the results of this double survey can serve as a basis for departments treating children when considering the purchase of an SGRT system.

Targeting the CXCL12/CXCR4 pathway to reduce radiation treatment side effects.

High precision, image-guided radiotherapy (RT) has increased the therapeutic ratio, enabling higher tumor and lower normal tissue doses, leading to improved patient outcomes. Nevertheless, some patients remain at risk of developing serious side effects.In many clinical situations, the radiation tolerance of normal tissues close to the target volume limits the dose that can safely be delivered and thus the potential for tumor control and cure. This is particularly so in patients being re-treated for tumor progression or a second primary tumor within a previous irradiated volume, scenarios that are becoming more frequent in clinical practice.Various normal tissue 'radioprotective' drugs with the potential to reduce side effects have been studied previously. Unfortunately, most have failed to impact clinical practice because of lack of therapeutic efficacy, concern about concurrent tumor protection or excessive drug-related toxicity. This review highlights the evidence indicating that targeting the CXCL12/CXCR4 pathway can mitigate acute and late RT-induced injury and reduce treatment side effects in a manner that overcomes these previous translational challenges. Pre-clinical studies involving a broad range of normal tissues commonly affected in clinical practice, including skin, lung, the gastrointestinal tract and brain, have shown that CXCL12 signalling is upregulated by RT and attracts CXCR4-expressing inflammatory cells that exacerbate acute tissue injury and late fibrosis. These studies also provide convincing evidence that inhibition of CXCL12/CXCR4 signalling during or after RT can reduce or prevent RT side effects, warranting further evaluation in clinical studies. Greater dialogue with the pharmaceutical industry is needed to prioritize the development and availability of CXCL12/CXCR4 inhibitors for future RT studies.

Paediatric radiation therapy without anaesthesia - Are the children moving?

PURPOSE: Children who require radiation therapy (RT) should ideally be treated awake, without anaesthesia, if possible. Audiovisual distraction is a known method to facilitate awake treatment, but its effectiveness at keeping children from moving during treatment is not known. The aim of this study was to evaluate intrafraction movement of children receiving RT while awake. METHODS: In this prospective study, we measured the intrafraction movement of children undergoing treatment with fractionated RT, using pre- and post-RT cone beam CT (CBCT) with image matching on bony anatomy. Study CBCTs were acquired at first fraction, weekly during RT, and at last fraction. The primary endpoint was the magnitude of vector change between the pre- and post-RT scans. Our hypothesis was that 90 % of CBCT acquisitions would have minimal movement, defined as <3 mm for head-and-neck (HN) treatments and <5 mm for non-HN treatments. RESULTS: A total of 65 children were enrolled and had evaluable data across 302 treatments with CBCT acquisitions. Median age was 11 years (range, 2-18; 1st and 3rd quartiles 7 and 14 years, respectively). Minimal movement was observed in 99.4 % of HN treatments and 97.2 % of non-HN treatments. The study hypothesis of >90 % of evaluations having minimal movement was met. Children who were age >11 years moved less at initial evaluation but tended to move more as a course of radiation progressed, as compared to children who were younger. CONCLUSION: Children receiving RT with audiovisual distraction while awake had small magnitudes of observed intrafraction movement, with minimal movement in >97 % of observed RT fractions. This study validates methods of anaesthesia avoidance using audiovisual distraction for selected children.

Image-guided moderately hypofractionated radiotherapy for localized prostate cancer: a multicentric retrospective study (IPOPROMISE).

BACKGROUND: Moderate hypofractionated radiotherapy is a treatment option for the cure of localized prostate cancer (PCa) patients based on the results of randomized prospective trials, but there is a clinical concern about the relatively short length of follow-up, and real-world results on outcome and toxicity based on cutting-edge techniques are lacking. The objective of this study is to present the long-term results of a large multicentric series. MATERIALS AND METHODS: We retrospectively evaluated 1325 PCa patients treated with daily volumetric image-guided hypofractionated radiotherapy between 2007 and 2020 in 16 Centers. For survival endpoints, we used Kaplan-Meier survival curves and fitted univariate and multivariable Cox's proportional hazards regression models to study the association between the clinical variables and each survival type. RESULTS: At the end of the follow-up, 11 patients died from PCa. The 15-year values of cancer-specific survival (CSS) and biochemical relapse-free survival (b-RFS) were 98.5% (95%CI 97.3-99.6%) and 85.5% (95%CI 81.9-89.4%), respectively. The multivariate analysis showed that baseline PSA, Gleason score, and the use of androgen deprivation therapy were significant variables for all the outcomes. Acute gastrointestinal (GI) and genitourinary (GU) toxicities of grade ≥ 2 were 7.0% and 16.98%, respectively. The 15-year late grade ≥ 2 GI and GU toxicities were 5% (95%CI 4-6%) and 6% (95%CI 4-8%), respectively. CONCLUSION: Real-world long-term results of this multicentric study on cutting-edge techniques for the cure of localized PCa demonstrated an excellent biochemical-free survival rate of 85.5% at 15 years, and very low rates of ≥ G3 late GU and GI toxicity (1.6% and 0.9% respectively), strengthening the results of the available published trials.