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.

Early outcomes of MR-guided SBRT for patients with recurrent pancreatic adenocarcinoma.

BACKGROUND: Local treatment options for locally recurrent pancreatic adenocarcinoma (LR-PAC) are limited, with median survival time (MST) of 9-13 months (mos) following recurrence. MRI-guided stereotactic body radiation therapy (MRgSBRT) provides the ability to dose escalate while sparing normal tissue. Here we report on the early outcomes of MRgSBRT for LR-PAC. METHODS: Patients with prior resection of pancreatic adenocarcinoma with local recurrence treated with MRgSBRT at a single tertiary referral center from 5-2021 to 2-2023 were identified from our prospective database. MRgSBRT was delivered to 40-50 Gy in 4-5 fractions with target and OAR delineation per institutional standards. Endpoints included local control per RECIST v1.1, distant failure, overall survival (OS), and acute and chronic toxicities per Common Terminology Criteria for Adverse Events, v5. RESULTS: Fifteen patients with LR-PAC were identified with median follow-up of 10.6 mos (2.8-26.5 mos) from MRgSBRT. There were 8 females and 7 males, with a median age of 69 years (50-83). One patient underwent neoadjuvant radiation for 50.4 Gy in 28 fractions followed by resection, and one underwent adjuvant radiation for 45 Gy in 25 fractions prior to recurrence. MRgSBRT was delivered a median of 18.8 mos (3.5-52.8 mos) following resection. OS following recurrence at 6 and 12 mos were 87% and 51%, respectively, with a median survival time of 14.1 mos (3.2-27.4 mos). Three patients experienced local failure at 5.9, 7.8, and 16.6 months from MgSBRT with local control of 92.3% and 83.9% at 6 and 12 months. 10 patients experienced distant failure at a median of 2.9 mos (0.3-6.7 mos). Grade 1-2 acute GI toxicity was noted in 47% of patients, and chronic GI toxicity in 31% of patients. No grade > 3 toxicities were noted. CONCLUSIONS: This is the first report on toxicity and outcomes of MRgSBRT for LR-PAC in the literature. MRgSBRT is a safe, feasible treatment modality with the potential for improved local control in this vulnerable population. Future research is necessary to better identify which patients yield the most benefit from MRgSBRT, which should continue to be used with systemic therapy as tolerated. TRIAL REGISTRATION: Jefferson IRB#20976, approved 2/17/21.

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.

Dataset of weekly intra-treatment diffusion weighted imaging in head and neck cancer patients treated with MR-Linac.

Radiation therapy (RT) is a crucial treatment for head and neck squamous cell carcinoma (HNSCC); however, it can have adverse effects on patients' long-term function and quality of life. Biomarkers that can predict tumor response to RT are being explored to personalize treatment and improve outcomes. While tissue and blood biomarkers have limitations, imaging biomarkers derived from magnetic resonance imaging (MRI) offer detailed information. The integration of MRI and a linear accelerator in the MR-Linac system allows for MR-guided radiation therapy (MRgRT), offering precise visualization and treatment delivery. This data descriptor offers a valuable repository for weekly intra-treatment diffusion-weighted imaging (DWI) data obtained from head and neck cancer patients. By analyzing the sequential DWI changes and their correlation with treatment response, as well as oncological and survival outcomes, the study provides valuable insights into the clinical implications of DWI in HNSCC.

Managing Inconsistent Bladder Volumes in the Prostate Cancer Patient Using Daily Online Adaptive RT: A Case Report.

PURPOSE: We report the use of online adaptive radiotherapy (OART) aiming to improve dosimetric parameters in the prostate cancer patient who had lower urinary tract symptoms that caused him not to adhere to the standard bladder filling protocol. METHODS AND MATERIALS: The reference treatment plan for adaptive radiotherapy plan was generated for the pelvis and the solitary bony lesion using the Ethos treatment planning system. For each treatment session, high-quality iterative reconstructed cone beam CT (CBCT) images were acquired, and the system automatically generated an optimal adaptive plan after verification of contours. Image-guided RT (IGRT) plans were also created using the reference plan recalculated on the CBCT scan and were compared with adaptive plans. RESULTS: The reference bladder volume in the planning CT scan was 173 cc, and the mean bladder volume difference over the course was 25.4% ± 16.6%. The ART offered superior target coverage for PTV 70 Gy over online IGRT (V95: 90.5 ± 3.2 % Vs 97.3 ± 0.4%; p=0.000) and the bladder was also better spared from the high dose (V65 Gy: 17.9 ± 9.1% vs 14.8 ± 3.6%; p=0.03). However, the mean rectum V65 doses were very similar in both plans. CONCLUSION: Managing the inconsistent bladder volume was feasible in the prostate cancer patient using the CBCT-guided OART and our analysis confirmed that adaptive plans offered better target coverage while sparing the bladder from high radiation doses in comparison to online IGRT plans. KEY WORDS: radiotherapy, CBCT, online adaptive radiotherapy, image-guided RT.

Effective timing of hyaluronate gel injection in image-guided adaptive brachytherapy for uterine cervical cancer: a proposal of the 'adjusted dose score'.

Hyaluronate gel injection (HGI) in the rectovaginal septum and vesicovaginal septum is effective in the setting of high-dose-rate image-guided adaptive brachytherapy (IGABT) for cervical cancer. We aimed to retrospectively investigate optimal conditions for HGI to achieve optimal dose distribution with a minimum number of HGI. We classified 50 IGABT plans of 13 patients with cervical cancer who received IGABT both with and without HGI in the rectovaginal septum and vesicovaginal septum into the following two groups: plan with (number of plans = 32) and plan without (number of plans = 18) HGI. The irradiation dose parameters of high-risk clinical target volume (CTVHR) and organs at risk per fraction were compared between these groups. We also developed the adjusted dose score (ADS), reflecting the overall irradiation dose status for four organs at risk and CTVHR in one IGABT plan and investigated its utility in determining the application of HGI. HGI reduced the maximum dose to the most exposed 2.0 cm3 (D2.0 cm3) of the bladder while increasing the minimum dose covering 90% of CTVHR and the percentage of CTVHR receiving 100% of the prescription dose in one IGABT plan without causing any associated complications. An ADS of ≥2.60 was the optimum cut-off value to decide whether to perform HGI. In conclusion, HGI is a useful procedure for improving target dose distribution while reducing D2.0 cm3 in the bladder in a single IGABT plan. The ADS can serve as a useful indicator for the implementation of HGI.

Online Adaptive MR-Guided Ultrahypofractionated Radiotherapy of Prostate Cancer on a 1.5 T MR-Linac: Clinical Experience and Prospective Evaluation.

The use of hypofractionated radiotherapy in prostate cancer has been increasingly evaluated, whereas accumulated evidence demonstrates comparable oncologic outcomes and toxicity rates compared to normofractionated radiotherapy. In this prospective study, we evaluate all patients with intermediate-risk prostate cancer treated with ultrahypofractionated (UHF) MRI-guided radiotherapy on a 1.5 T MR-Linac within our department and report on workflow and feasibility, as well as physician-recorded and patient-reported longitudinal toxicity. A total of 23 patients with intermediate-risk prostate cancer treated on the 1.5 T MR-Linac with a dose of 42.7 Gy in seven fractions (seven MV step-and-shoot IMRT) were evaluated within the MRL-01 study (NCT04172753). The duration of each treatment step, choice of workflow (adapt to shape-ATS or adapt to position-ATP) and technical and/or patient-sided treatment failure were recorded for each fraction and patient. Acute and late toxicity were scored according to RTOG and CTC V4.0, as well as the use of patient-reported questionnaires. The median follow-up was 12.4 months. All patients completed the planned treatment. The mean duration of a treatment session was 38.2 min. In total, 165 radiotherapy fractions were delivered. ATS was performed in 150 fractions, 5 fractions were delivered using ATP, and 10 fractions were delivered using both ATS and ATP workflows. Severe acute bother (G3+) regarding IPS-score was reported in five patients (23%) at the end of radiotherapy. However, this tended to normalize and no G3+ IPS-score was observed later at any point during follow-up. Furthermore, no other severe genitourinary (GU) or gastrointestinal (GI) acute or late toxicity was observed. One-year biochemical-free recurrence survival was 100%. We report the excellent feasibility of UHF MR-guided radiotherapy for intermediate-risk prostate cancer patients and acceptable toxicity rates in our preliminary study. Randomized controlled studies with long-term follow-up are warranted to detect possible advantages over current state-of-the-art RT techniques.

Prostate intra-fraction motion recorded by transperineal ultrasound.

Infra-fraction motion of the prostate was recorded during 3.423 fractions of image guided radiotherapy (IGRT) in 191 patients, 14 of which were treated by intensity modulated radiation therapy (IMRT), and 177 of which were treated by volumetric arc therapy (VMAT). The prostate was imaged by three-dimensional and time-resolved transperineal ultrasound (4D-US) of type Clarity by Elekta AB, Stockholm, Sweden. The prostate volume was registered and the prostate position (center of volume) was recorded at a frequency of 2.0 samples per second. This raw data set contains a total of 1.985.392 prostate and patient couch positions over a time span of 272 hours, 52 minutes and 34 seconds of life radiotherapy as exported by the instrument software. This data set has been used for the validation of models of prostate intra-fraction motion and for the estimation of the dosimetric impact of actual intra-fraction motion on treatment quality and side effects. We hope that this data set may be reused by other groups for similar purposes.

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.

Commissioning of a novel PET-Linac for biology-guided radiotherapy (BgRT).

BACKGROUND: Biology-guided radiotherapy (BgRT) is a novel radiotherapy delivery technique that utilizes the tumor itself to guide dynamic delivery of treatment dose to the tumor. The RefleXion X1 system is the first radiotherapy system developed to deliver SCINTIX® BgRT. The X1 is characterized by its split arc design, employing two 90-degree positron emission tomography (PET) arcs to guide therapeutic radiation beams in real time, currently cleared by FDA to treat bone and lung tumors. PURPOSE: This study aims to comprehensively evaluate the capabilities of the SCINTIX radiotherapy delivery system by evaluating its sensitivity to changes in PET contrast, its adaptability in the context of patient motion, and its performance across a spectrum of prescription doses. METHODS: A series of experimental scenarios, both static and dynamic, were designed to assess the SCINTIX BgRT system's performance, including an end-to-end test. These experiments involved a range of factors, including changes in PET contrast, motion, and prescription doses. Measurements were performed using a custom-made ArcCHECK insert which included a 2.2 cm spherical target and a c-shape structure that can be filled with a PET tracer with varying concentrations. Sinusoidal and cosine4 motion patterns, simulating patient breathing, was used to test the SCINTIX system's ability to deliver BgRT during motion-induced challenges. Each experiment was evaluated against specific metrics, including Activity Concentration (AC), Normalized Target Signal (NTS), and Biology Tracking Zone (BTZ) bounded dose-volume histogram (bDVH) pass rates. The accuracy of the delivered BgRT doses on ArcCHECK and EBT-XD film were evaluated using gamma 3%/2 mm and 3%/3 mm analysis. RESULTS: In static scenarios, the X1 system consistently demonstrated precision and robustness in SCINTIX dose delivery. The end-to-end delivery to the spherical target yielded good results, with AC and NTS values surpassing the critical thresholds of 5 kBq/mL and 2, respectively. Furthermore, bDVH analysis consistently confirmed 100% pass rates. These results were reaffirmed in scenarios involving changes in PET contrast, emphasizing the system's ability to adapt to varying PET avidities. Gamma analysis with 3%/2 mm (10% dose threshold) criteria consistently achieved pass rates > 91.5% for the static tests. In dynamic SCINTIX delivery scenarios, the X1 system exhibited adaptability under conditions of motion. Sinusoidal and cosine4 motion patterns resulted in 3%/3 mm gamma pass rates > 87%. Moreover, the comparison with gated stereotactic body radiotherapy (SBRT) delivery on a conventional c-arm Linac resulted in 93.9% gamma pass rates and used as comparison to evaluate the interplay effect. The 1 cm step shift tests showed low overall gamma pass rates of 60.3% in ArcCHECK measurements, while the doses in the PTV agreed with the plan with 99.9% for 3%/3 mm measured with film. CONCLUSIONS: The comprehensive evaluation of the X1 radiotherapy delivery system for SCINTIX BgRT demonstrated good agreement for the static tests. The system consistently achieved critical metrics and delivered the BgRT doses per plan. The motion tests demonstrated its ability to co-localize the dose where the PET signal is and deliver acceptable BgRT dose distributions.

Dosimetric Effect of Target Position Accuracy on Single-Isocenter Multiple Liver Metastases SBRT.

Purpose: To evaluate the dosimetric effects of intrafraction baseline shifts combined with rotational errors on Four-dimensional computed tomography-guided stereotactic body radiotherapy for multiple liver metastases (MLMs). Methods: A total of 10 patients with MLM (2 or 3 lesions) were selected for this retrospective study. Baseline shift errors of 0.5, 1.0, and 2.0 mm; and rotational errors of 0.5°, 1°, and 1.5°, were simulated about all axes. All of the baseline shifts and rotation errors were simulated around the planned isocenter using a matrix transformation of 6° of freedom. The coverage degradation of baseline shifts and rotational errors were analyzed according to the dose to 95% of the planning target volume (D95) and the volume covered by 95% of the prescribed dose (V95), and related changes in gross tumor volume were also analyzed. Results: At the rotation error of 0.5° and the baseline offset of less than 0.5 mm, the D95 and V95 values of all targets were >95%. For rotational errors of 1.0° (combined with all baseline shift errors), 36.3% of targets had D95 and V95 values of <95%. Coverage worsened substantially when the baseline shift errors were increased to 1.0 mm. D95 and V95 values were >95% for about 77.3% of the targets. Only 11.4% of the D95 and V95 values were >95% when the baseline shift errors were increased to 2.0 mm. When the rotational error was increased to 1.5° and baseline shift errors increased to 1.0 mm, the D95 and V95 values were >95% in only 3 cases. Conclusions: The multivariate regression model analysis in this study showed that the coverage of the target decreased further with reduced target volume, increasing the baseline drift, the rotation error, and the distance to the target.

Reactive Oxygen Species Amplifier for Apoptosis-Ferroptosis Mediated High-Efficiency Radiosensitization of Tumors.

Insufficient reactive oxygen species (ROS) production and radioresistance have consistently contributed to the failure of radiotherapy (RT). The development of a biomaterial capable of activating ROS-induced apoptosis and ferroptosis is a potential strategy to enhance RT sensitivity. To achieve precision and high-efficiency RT, the theranostic nanoplatform Au/Cu nanodots (Au/CuNDs) were designed for dual-mode imaging, amplifying ROS generation, and inducing apoptosis-ferroptosis to sensitize RT. A large amount of ROS is derived from three aspects: (1) When exposed to ionizing radiation, Au/CuNDs effectively absorb photons and emit various electrons, which can interact with water to produce ROS. (2) Au/CuNDs act as a catalase-like to produce abundant ROS through Fenton reaction with hydrogen peroxide overexpressed of tumor cells. (3) Au/CuNDs deplete overexpressed glutathione, which causes the accumulation of ROS. Large amounts of ROS and ionizing radiation further lead to apoptosis by increasing DNA damage, and ferroptosis by enhancing lipid peroxidation, significantly improving the therapeutic efficiency of RT. Furthermore, Au/CuNDs serve as an excellent nanoprobe for high-resolution near-infrared fluorescence imaging and computed tomography of tumors. The promising dual-mode imaging performance shows their potential application in clinical cancer detection and imaging-guided precision RT, minimizing damage to adjacent normal tissues during RT. In summary, our developed theranostic nanoplatform integrates dual-mode imaging and sensitizes RT via ROS-activated apoptosis-ferroptosis, offering a promising prospect for clinical cancer diagnosis and treatment.

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.

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.

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.

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.

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.

Utility of a skin marker-less setup procedure using surface-guided imaging: a comparison with the traditional laser-based setup in extremity irradiation.

This study aimed to assess the feasibility of a skin marker-less patient setup using a surface-guided radiotherapy (SGRT) system for extremity radiotherapy. Twenty-five patients who underwent radiotherapy to the extremities were included in this retrospective study. The first group consisted of 10 patients and underwent a traditional setup procedure using skin marks and lasers. The second group comprised 15 patients and had a skin marker-less setup procedure that used an SGRT system only. To compare the two setup procedures for setup accuracy, the mean 3D vector shift magnitude was 0.9 mm for the traditional setup procedure and 0.5 mm for the skin marker-less setup procedure (p < 0.01). In addition, SGRT systems have been suggested to improve the accuracy and reproducibility of patient setups and consistently reduce interfractional setup errors. These results indicate that a skin marker-less patient setup procedure using an SGRT system is useful for extremity irradiation.

Assessment of the deep learning-based gamma passing rate prediction system for 1.5 T magnetic resonance-guided linear accelerator.

Measurement-based verification is impossible for the patient-specific quality assurance (QA) of online adaptive magnetic resonance imaging-guided radiotherapy (oMRgRT) because the patient remains on the couch throughout the session. We assessed a deep learning (DL) system for oMRgRT to predict the gamma passing rate (GPR). This study collected 125 verification plans [reference plan (RP), 100; adapted plan (AP), 25] from patients with prostate cancer treated using Elekta Unity. Based on our previous study, we employed a convolutional neural network that predicted the GPRs of nine pairs of gamma criteria from 1%/1 mm to 3%/3 mm. First, we trained and tested the DL model using RPs (n = 75 and n = 25 for training and testing, respectively) for its optimization. Second, we tested the GPR prediction accuracy using APs to determine whether the DL model could be applied to APs. The mean absolute error (MAE) and correlation coefficient (r) of the RPs were 1.22 ± 0.27% and 0.29 ± 0.10 in 3%/2 mm, 1.35 ± 0.16% and 0.37 ± 0.15 in 2%/2 mm, and 3.62 ± 0.55% and 0.32 ± 0.14 in 1%/1 mm, respectively. The MAE and r of the APs were 1.13 ± 0.33% and 0.35 ± 0.22 in 3%/2 mm, 1.68 ± 0.47% and 0.30 ± 0.11 in 2%/2 mm, and 5.08 ± 0.29% and 0.15 ± 0.10 in 1%/1 mm, respectively. The time cost was within 3 s for the prediction. The results suggest the DL-based model has the potential for rapid GPR prediction in Elekta Unity.