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Muscle invasive bladder cancer (MIBC) is an aggressive disease with a high risk of metastasis. Bladder preservation with trimodality therapy (TMT) is an option for well-selected patients or poor cystectomy candidates. Cone beam computed tomography (CBCT)-guided online adaptive radiotherapy (oART) shows promise in improving the dose to treatment targets while better sparing organs at risk (OARs). The following series presents two cases in which the capabilities of a CBCT-guided oART platform were leveraged to meet clinical challenges. The first case describes a patient with synchronous MIBC and high-risk prostate cancer with challenging target-OAR interfaces. The second recounts the case of a patient with a history of low dose rate (LDR) brachytherapy to the prostate who was later diagnosed with MIBC and successfully treated with CBCT-guided oART with reduced high-dose volume bladder targeting. To date, both patients report minimal side effects and are without disease recurrence. These cases illustrate how CBCT-guided online adaptive systems may efficiently aid radiation oncologists in treating patients with more complex clinical scenarios who desire bladder-sparing therapy.

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This study explores the dosimetric benefits of cone-beam computed tomography (CBCT)-based online adaptive radiation therapy (oART) for a non-small-cell lung cancer (NSCLC) patient exhibiting significant tumor shrinkage during ChemoRT. The patient was prescribed 60 Gray (Gy) in 30 fractions and was initially treated with conventional RT. After the delivery of the first four treatment fractions, the patient's treatment course was converted to oART due to tumor shrinkage seen on CBCT. Current oART dose calculations use a synthetic CT (sCT) image derived from deformable image registration (DIR) of the planning CT to the daily CBCT, and, as the tumor regressed, the discrepancy between the CBCT and the sCT increased, leading to a re-simulation after the delivery of the ninth fraction. In this case report, we first investigated dosimetric differences leveraged by converting this patient from conventional RT to oART. With oART using sCT, the patient's target coverage remained consistent with the reference plan while simultaneously changing lung V20 by 7.8 ± 1.4% and heart mean by 3.4 ± 1.5 Gy. Then, using this new simulation CT and comparing it with iterative CBCT (iCBCT) images acquired with the new HyperSight™ (HS) (Varian Medical Systems, Inc., Palo Alto, CA, USA) imaging system on the Ethos, we investigated the impact of direct dose calculation on HS-iCBCT as compared to sCT. The HS-iCBCT generated a dose distribution similar to the CT reference, achieving a 96.01% gamma passing rate using Task Group-218 (TG-218) criteria. Results indicate that HS-iCBCT has the potential to better reflect daily anatomical changes, resulting in improved dosimetric accuracy. This study highlights the advantages of oART in the presence of tumor response to therapy and underscores HS-iCBCT's potential to provide CT-level dose calculation accuracy in oART for NSCLC patients.

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In this study, we aimed to conduct a survey on the current clinical practice of, staffing for, commissioning of, and staff training for online adaptive radiotherapy (oART) in the institutions that installed commercial oART systems in Japan, and to share the information with institutions that will implement oART systems in future. A web-based questionnaire, containing 107 questions, was distributed to nine institutions in Japan. Data were collected from November to December 2023. Three institutions each with the MRIdian (ViewRay, Oakwood Village, OH, USA), Unity (Elekta AB, Stockholm, Sweden), and Ethos (Varian Medical Systems, Palo Alto, CA, USA) systems completed the questionnaire. One institution (MRIdian) had not performed oART by the response deadline. Each institution had installed only one oART system. Hypofractionation, and moderate hypofractionation or conventional fractionation were employed in the MRIdian/Unity and Ethos systems, respectively. The elapsed time for the oART process was faster with the Ethos than with the other systems. All institutions added additional staff for oART. Commissioning periods differed among the oART systems owing to provision of beam data from the vendors. Chambers used during commissioning measurements differed among the institutions. Institutional training was provided by all nine institutions. To the best of our knowledge, this was the first survey about oART performed using commercial systems in Japan. We believe that this study will provide useful information to institutions that installed, are installing, or are planning to install oART systems.

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Objective.To experimentally validate two online adaptive proton therapy (APT) workflows using Gafchromic EBT3 films and optically stimulated luminescent dosimeters (OSLDs) in an anthropomorphic head-and-neck phantom.Approach.A three-field proton plan was optimized on the planning CT of the head-and-neck phantom with 2.0 Gy(RBE) per fraction prescribed to the clinical target volume. Four fractions were simulated by varying the internal anatomy of the phantom. Three distinct methods were delivered: daily APT researched by the Paul Scherrer Institute (DAPTPSI), online adaptation researched by the Massachusetts General Hospital (OAMGH), and a non-adaptive (NA) workflow. All methods were implemented and measured at PSI. DAPTPSIperformed full online replanning based on analytical dose calculation, optimizing to the same objectives as the initial treatment plan. OAMGHperformed Monte-Carlo-based online plan adaptation by only changing the fluences of a subset of proton beamlets, mimicking the planned dose distribution. NA delivered the initial plan with a couch-shift correction based on in-room imaging. For all 12 deliveries, two films and two sets of OSLDs were placed at different locations in the phantom.Main results.Both adaptive methods showed improved dosimetric results compared to NA. For film measurements in the presence of anatomical variations, the [min-max] gamma pass rates (3%/3 mm) between measured and clinically approved doses were [91.5%-96.1%], [94.0%-95.8%], and [67.2%-93.1%] for DAPTPSI, OAMGH, and NA, respectively. The OSLDs confirmed the dose calculations in terms of absolute dosimetry. Between the two adaptive workflows, OAMGHshowed improved target coverage, while DAPTPSIshowed improved normal tissue sparing, particularly relevant for the brainstem.Significance.This is the first multi-institutional study to experimentally validate two different concepts with respect to online APT workflows. It highlights their respective dosimetric advantages, particularly in managing interfractional variations in patient anatomy that cannot be addressed by non-adaptive methods, such as internal anatomy changes.

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INTRODUCTION: The aim of this study was to assess the results of the local pre-treatment verifications of online adaptive prostate SBRT plans performed by dosimetrists METHODS AND MATERIALS: Prostate SBRT treatments are planned in our department using an online adaptive method developed and validated by our group. The adaptive plans were computed on the daily CBCT scan using the Acuros XB v. 16.1 algorithm of the Varian Eclipse treatment planning system. Adaptive plans consisted of a single VMAT with 6 MV flattening-filter-free (FFF) energy performed on a Varian TrueBeam linac. Pre-treatment verification of the adaptive "plan-of-the-day" (POD) created in each treatment session was performed using the Mobius 3D v. 3.1 secondary dose calculation program (M3D). Commissioning of M3D included the tuning of the dosimetric leaf gap correction (DLGc) parameter. Generic and specific DLGc values were then derived using a set of plans for typical sites (prostate, head and neck, brain, lung and bone palliative) and another set were determined for specific online SBRT PODs (gDLGc and sDLGc, respectively). The first 50 prostate patients treated with the PACE-B schedule (5 × 7.25 Gy) were included, i.e., 250 adaptive SBRT PODs were collected in this study. For each online adaptive POD, a global 3D gamma comparison between the Eclipse 3D dose and the M3D dose in the patient CBCT was performed. Gamma passing rates (GPRs) for the whole external patient contour (Body) and the PTV were recorded, using the 5 % global /3 mm criteria. The target mean dose and target coverage differences between the Eclipse and M3D doses were also analyzed (ΔDmean and ΔD90 %, respectively). The accuracy of M3D was assessed against PRIMO Monte Carlo software. Twenty-five online prostate SBRT PODs were randomly selected from the set of 250 adaptive plans and simulated with PRIMO. RESULTS: Values of -1 mm and -0.14 mm were found as optimal gDLGc and sDLGc, respectively. Over the 250 online adaptive PODs, excellent GPR values ∼ 100 % were obtained for the Body and PTV structures, regardless the type of DLGc used. The use of the sDLGc instead of the gDLGc provided better results for ΔDmean (0.1 % ± 0.5% vs. -1.9 ± 0.7 %) and ΔD90 % (-1.0 % ± 0.5 %. vs. -3.5 % ± 0.8 %). This issue was also observed when M3D calculations were compared to PRIMO simulations. CONCLUSIONS: M3D can be effectively used for independent pre-treatment verifications of online adaptive prostate SBRT plans. The use of a specific DLGc value is advised for this SBRT online adaptive technique.

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Stereotactic body radiotherapy (SBRT) to the central and ultra-central thorax is associated with infrequent but potentially serious adverse events. Adaptive SBRT, which provides more precise treatment planning and inter-fraction motion management, may allow the delivery of ablative doses to ultra-central tumors with effective local control and improved toxicity profiles. Herein, we describe the first reported case of cone beam computed tomography (CBCT)-guided stereotactic adaptive radiotherapy (CT-STAR) in the treatment of ultra-central non-small cell lung cancer (NSCLC) in a prospective clinical trial (NCT05785845). An 80-year-old man with radiographically diagnosed early-stage NSCLC presented for definitive management of an enlarging ultra-central lung nodule. He was prescribed 55 Gy in five fractions with CT-STAR. A simulation was performed using four-dimensional CT, and patients were planned for treatment at end-exhale breath-hold. Treatment plans were generated using a strict isotoxicity approach, which prioritized organ at risk (OAR) constraints over target coverage. During treatment, daily CBCTs were acquired and used to generate adapted contours and treatment plans based on the patient's anatomy-of-the-day, all while the patient was on the treatment table. The initial and adapted plans were compared using dose-volume histograms, and the superior plan was selected for treatment. The adapted plan was deemed superior and used for treatment in three out of five fractions. The adapted plan provided improved target coverage in two fractions and resolved an OAR hard constraint violation in one fraction. We report the successful treatment of a patient with ultra-central NSCLC utilizing CT-STAR. This case report builds on previously published in silico data to support the viability and dosimetric advantages of CT-STAR in the ablative treatment of this challenging tumor location. Further data are needed to confirm the toxicity and efficacy of this technique.

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Current online adaptive radiotherapy (oART) workflows require dedicated equipment. Our aim was to develop and implement an oART workflow for a C-arm linac which can be performed using standard clinically available tools. A workflow was successfully developed and implemented. Three patients receiving palliative radiotherapy for bladder cancer were treated, with 33 of 35 total fractions being delivered with the cone-beam computed tomography (CBCT)-guided oART workflow. Average oART fraction duration was 24 min from start of CBCT acquisition to end of beam on. This work shows how oART could be performed without dedicated equipment, broadening oART availability for application at existing treatment machines.

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The aim of this study was to investigate planning target volume (PTV) margin in online adaptive radiation therapy (oART) for gastric mucosa-associated lymphoid tissue (MALT) lymphomas. Four consecutive patients with gastric MALT lymphoma who received oART (30 Gy in 15 fractions) on the oART system were included in this study. One hundred and twenty cone-beam computed tomography (CBCT) scans acquired pre- and post-treatment of 60 fractions for all patients were used to evaluate intra- and interfractional motions. Patients were instructed on breath-holding at exhalation during image acquisition. To assess the intrafraction gastric motion, different PTVs were created by isotropically extending the CTV contoured on a pre-CBCT image (CTVpre) at1 mm intervals. Intrafraction motion was defined as the amount of expansion covering the contoured CTV on post-CBCT images (CTVpost). Interfractional motion was defined as the amount of reference CTV expansion that could cover each CTVpre, as well as the evaluation of the intrafractional motion. PTV margins were estimated from the cumulative proportion of fraction covering the intra- and interfractional motions. The extent of expansion covering the CTVs in 90% of fractions was adopted as the PTV margin. The PTV margin for intrafractional gastric motion using the oART system with breath-holding was 14 mm. In contrast, the PTV margin for interfractional gastric organ motion without the oART system was 25 mm. These results indicated that the oART system can reduce the PTV margin by >10 mm. Our results could be valuable data for oART cases.

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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.

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Background and Objective: In the field of radiation therapy, image-guided radiotherapy (IGRT) technology has been gradually improving and highly accurate radiation treatment has been possible. Research on IGRT using 1.5 Tesla magnetic resonance imaging (MRI) began in 1999, and a radiation therapy device called 1.5 Tesla magnetic resonance linear accelerator (MR-Linac), which combines a linear accelerator with 1.5 Tesla MRI, was developed in Europe. The aim of this review is to present an overview of 1.5 Tesla MR-Linac with a review of the literature and our experience. Methods: Reports related to 1.5 Tesla MR-Linac were searched for in PubMed and are discussed in relation to our experience. Key Content and Findings: The 1.5 Tesla MR-Linac enables IGRT using 1.5 Tesla MRI, further enhancing the precision of radiation therapy. Position verification by cone-beam computed tomography (CBCT) is performed in many institutions, but soft tissue contrast is often unclear in CBCT images of the abdomen and mediastinal organs. Since the 1.5 Tesla MR-Linac allows position verification using MRI, position verification can be performed using clear MRI even in regions where CBCT is unclear. With the 1.5 Tesla MR-Linac, it is possible to perform online adaptive radiotherapy (ART) using 1.5 Tesla MRI. Online ART is a method in which images are acquired while the patient is on the treatment table. The method is based on the current condition of the organs in the body on that day and an optimal treatment field is recreated. Additionally, it allows monitoring of tumor motion using cine images obtained by 1.5 Tesla MRI during the delivery of X-ray radiation. A previous report showed that patients with prostate cancer who received radiotherapy by MR-Linac had fewer side effects than those in patients who received conventional CBCT radiation therapy. Conclusions: The 1.5 Tesla MR-Linac obtained CE-mark certification in Europe in August 2018 and it has been used for clinical treatment. In Japan, clinical treatment using this device started in 2021. By using 1.5 Tesla MR-Linac, patients can be provided with higher precision radiotherapy. In this review, we provide an overview of 1.5 Tesla MR-Linac.

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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.

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PURPOSE: The Ethos (Varian Medical Systems) radiotherapy device combines semi-automated anatomy detection and plan generation for cone beam computer tomography (CBCT)-based daily online adaptive radiotherapy (oART). However, CBCT offers less soft tissue contrast than magnetic resonance imaging (MRI). This work aims to present the clinical workflow of CBCT-based oART with shuttle-based offline MR guidance. METHODS: From February to November 2023, 31 patients underwent radiotherapy on the Ethos (Varian, Palo Alto, CA, USA) system with machine learning (ML)-supported daily oART. Moreover, patients received weekly MRI in treatment position, which was utilized for daily plan adaptation, via a shuttle-based system. Initial and adapted treatment plans were generated using the Ethos treatment planning system. Patient clinical data, fractional session times (MRI + shuttle transport + positioning, adaptation, QA, RT delivery) and plan selection were assessed for all fractions in all patients. RESULTS: In total, 737 oART fractions were applied and 118 MRIs for offline MR guidance were acquired. Primary sites of tumors were prostate (n = 16), lung (n = 7), cervix (n = 5), bladder (n = 1) and endometrium (n = 2). The treatment was completed in all patients. The median MRI acquisition time including shuttle transport and positioning to initiation of the Ethos adaptive session was 53.6 min (IQR 46.5-63.4). The median total treatment time without MRI was 30.7 min (IQR 24.7-39.2). Separately, median adaptation, plan QA and RT times were 24.3 min (IQR 18.6-32.2), 0.4 min (IQR 0.3-1,0) and 5.3 min (IQR 4.5-6.7), respectively. The adapted plan was chosen over the scheduled plan in 97.7% of cases. CONCLUSION: This study describes the first workflow to date of a CBCT-based oART combined with a shuttle-based offline approach for MR guidance. The oART duration times reported resemble the range shown by previous publications for first clinical experiences with the Ethos system.

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Objective. In head-and-neck cancer intensity modulated proton therapy, adaptive radiotherapy is currently restricted to offline re-planning, mitigating the effect of slow changes in patient anatomies. Daily online adaptations can potentially improve dosimetry. Here, a new, fully automated online re-optimization strategy is presented. In a retrospective study, this online re-optimization approach was compared to our trigger-based offline re-planning (offlineTBre-planning) schedule, including extensive robustness analyses.Approach. The online re-optimization method employs automated multi-criterial re-optimization, using robust optimization with 1 mm setup-robustness settings (in contrast to 3 mm for offlineTBre-planning). Hard planning constraints and spot addition are used to enforce adequate target coverage, avoid prohibitively large maximum doses and minimize organ-at-risk doses. For 67 repeat-CTs from 15 patients, fraction doses of the two strategies were compared for the CTVs and organs-at-risk. Per repeat-CT, 10.000 fractions with different setup and range robustness settings were simulated using polynomial chaos expansion for fast and accurate dose calculations.Main results. For 14/67 repeat-CTs, offlineTBre-planning resulted in <50% probability ofD98%≥ 95% of the prescribed dose (Dpres) in one or both CTVs, which never happened with online re-optimization. With offlineTBre-planning, eight repeat-CTs had zero probability of obtainingD98%≥ 95%Dpresfor CTV7000, while the minimum probability with online re-optimization was 81%. Risks of xerostomia and dysphagia grade ≥ II were reduced by 3.5 ± 1.7 and 3.9 ± 2.8 percentage point [mean ± SD] (p< 10-5for both). In online re-optimization, adjustment of spot configuration followed by spot-intensity re-optimization took 3.4 min on average.Significance. The fast online re-optimization strategy always prevented substantial losses of target coverage caused by day-to-day anatomical variations, as opposed to the clinical trigger-based offline re-planning schedule. On top of this, online re-optimization could be performed with smaller setup robustness settings, contributing to improved organs-at-risk sparing.

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(1) Background: External beam radiotherapy (EBRT) and concurrent chemotherapy, followed by brachytherapy (BT), offer a standard of care for patients with locally advanced cervical carcinoma. Conventionally, large safety margins are required to compensate for organ movement, potentially increasing toxicity. Lately, daily high-quality cone beam CT (CBCT)-guided adaptive radiotherapy, aided by artificial intelligence (AI), became clinically available. Thus, online treatment plans can be adapted to the current position of the tumor and the adjacent organs at risk (OAR), while the patient is lying on the treatment couch. We sought to evaluate the potential of this new technology, including a weekly shuttle-based 3T-MRI scan in various treatment positions for tumor evaluation and for decreasing treatment-related side effects. (2) Methods: This is a prospective one-armed phase-II trial consisting of 40 patients with cervical carcinoma (FIGO IB-IIIC1) with an age ≥ 18 years and a Karnofsky performance score ≥ 70%. EBRT (45-50.4 Gy in 25-28 fractions with 55.0-58.8 Gy simultaneous integrated boosts to lymph node metastases) will be accompanied by weekly shuttle-based MRIs. Concurrent platinum-based chemotherapy will be given, followed by 28 Gy of BT (four fractions). The primary endpoint will be the occurrence of overall early bowel and bladder toxicity CTCAE grade 2 or higher (CTCAE v5.0). Secondary outcomes include clinical feasibility, quality of life, and imaging-based response assessment.

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Introduction: Advancements in MRI-guided radiotherapy (MRgRT) enable clinical parallel workflows (CPW) for online adaptive planning (oART), allowing medical physicists (MPs), physicians (MDs), and radiation therapists (RTTs) to perform their tasks simultaneously. This study evaluates the impact of this upgrade on the total treatment time by analyzing each step of the current 0.35T-MRgRT workflow. Methods: The time process of the workflow steps for 254 treatment fractions in 0.35 MRgRT was examined. Patients have been grouped based on disease site, breathing modality (BM) (BHI or FB), and fractionation (stereotactic body RT [SBRT] or standard fractionated long course [LC]). The time spent for the following workflow steps in Adaptive Treatment (ADP) was analyzed: Patient Setup Time (PSt), MRI Acquisition and Matching (MRt), MR Re-contouring Time (RCt), Re-Planning Time (RPt), Treatment Delivery Time (TDt). Also analyzed was the timing of treatments that followed a Simple workflow (SMP), without the online re-planning (PSt + MRt + TDt.). Results: The time analysis revealed that the ADP workflow (median: 34 min) is significantly (p < 0.05) longer than the SMP workflow (19 min). The time required for ADP treatments is significantly influenced by TDt, constituting 40 % of the total time. The oART steps (RCt + RPt) took 11 min (median), representing 27 % of the entire procedure. Overall, 79.2 % of oART fractions were completed in less than 45 min, and 30.6 % were completed in less than 30 min. Conclusion: This preliminary analysis, along with the comparative assessment against existing literature, underscores the potential of CPW to diminish the overall treatment duration in MRgRT-oART. Additionally, it suggests the potential for CPW to promote a more integrated multidisciplinary approach in the execution of oART.

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BACKGROUND: To determine the optimal planning target volume (PTV) margins for adequate coverage by daily iterative cone-beam computed tomography (iCBCT)-guided online adaptive radiotherapy (oART) in postoperative treatment of endometrial and cervical cancer and the benefit of reducing PTV margins. METHODS: Fifteen postoperative endometrial and cervical cancer patients treated with daily iCBCT-guided oART were enrolled in this prospective phase 2 study. Pre- and posttreatment iCBCT images of 125 fractions from 5 patients were obtained as a training cohort, and clinical target volumes (CTV) were contoured separately. Uniform three-dimensional expansions were applied to the PTVpre to assess the minimum margin required to encompass the CTVpost. The dosimetric advantages of the proposed online adaptive margins were compared with conventional margin plans (7-15 mm) using an oART emulator in another cohort of 125 iCBCT scans. A CTV-to-PTV expansion was verified on a validation cohort of 253 fractions from 10 patients, and further margin reduction and acute toxicity were studied. RESULTS: The average time from pretreatment iCBCT to posttreatment iCBCT was 22 min. A uniform PTV margin of 5 mm could encompass nodal CTVpost in 100% of the fractions (175/175) and vaginal CTVpost in 98% of the fractions (172/175). The margin of 5 mm was verified in our validation cohort, and the nodal PTV margin could be further reduced to 4 mm if ≥ 95% CTV coverage was predicted to be achieved. The adapted plan with a 5 mm margin significantly improved pelvic organ-at-risk dosimetry compared with the conventional margin plan. Grade 3 toxicities were observed in only one patient with leukopenia, and no patients experienced acute urinary toxicity. CONCLUSION: In the postoperative treatment of endometrial and cervical cancer, oART could reduce PTV margins to 5 mm, which significantly decrease the dose to critical organs at risk and potentially lead to a lower incidence of acute toxicity.

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BACKGROUND: Training senior radiation therapists as "adapters" to manage influencers and target editing is critical in daily online adaptive radiotherapy (oART) for cervical cancer. The purpose of this study was to evaluate the accuracy and dosimetric outcomes of automatic contouring and identify the key areas for modification. METHODS: A total of 125 oART fractions from five postoperative cervical cancer patients and 140 oART fractions from five uterine cervical cancer patients treated with daily iCBCT-guided oART were enrolled in this prospective study. The same adaptive treatments were replanned using the Ethos automatic contours workflow without manual contouring edits. The clinical target volume (CTV) was subdivided into several separate regions, and the average surface distance dice (ASD), centroid deviation, dice similarity coefficient (DSC), and 95% Hausdorff distance (95% HD) were used to evaluate contouring for the above portions. Dosimetric results from automatic oART plans were compared to supervised oART plans to evaluate target volumes and organs at risk (OARs) dose changes. RESULTS: Overall, the paired CTV had high overlap rates, with an average DSC value greater than 0.75. The uterus had the largest consistency differences, with ASD, centroid deviation, and 95% HD being 2.67 ± 1.79 mm, 17.17 ± 12 mm, and 10.45 ± 5.68 mm, respectively. The consistency differences of the lower nodal CTVleft and nodal CTVright were relatively large, with ASD, centroid deviation, and 95% HD being 0.59 ± 0.53 mm, 3.6 ± 2.67 mm, and 5.41 ± 4.08 mm, and 0.59 ± 0.51 mm, 3.6 ± 2.54 mm, and 4.7 ± 1.57 mm, respectively. The automatic online-adapted plan met the clinical requirements of dosimetric coverage for the target volume and improved the OAR dosimetry. CONCLUSIONS: The accuracy of automatic contouring from the Ethos adaptive platform is considered clinically acceptable for cervical cancer, and the uterus, upper vaginal cuff, and lower nodal CTV are the areas that need to be focused on in training.

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The present study aimed to evaluate whether an adapted plan with Ethos™ could be used for pharyngeal cancer. Ten patients with pharyngeal cancer who underwent chemoradiotherapy with available daily cone-beam computed tomography (CBCT) data were included. Simulated treatments were generated on the Ethos™ treatment emulator using CBCTs every four to five fractions for two plans: adapted and scheduled. The simulated treatments were divided into three groups: early (first-second week), middle (third-fourth week), and late (fifth-seventh week) periods. Dose-volume histogram parameters were compared for each period between the adapted and scheduled plans in terms of the planning target volume (PTV) (D98%, D95%, D50% and D2%), spinal cord (Dmax and D1cc), brainstem (Dmax) and ipsilateral and contralateral parotid glands (Dmedian and Dmean). The PTV D98%, D95% and D2% of the adapted plan were significantly higher than those of the scheduled plans in all periods, except for D98% in the late period. The adapted plan significantly reduced the spinal cord Dmax and D1cc compared with the scheduled plan in all periods. Ipsilateral and contralateral parotid glands Dmean of the adapted plan were lower than those of scheduled plan in the late period. In conclusion, the present study revealed that the adapted plans could maintain PTV coverage while reducing the doses to organs at risk in each period compared with scheduled plans.

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BACKGROUND: Several (online) adaptive radiotherapy procedures are available to maximize healthy tissue sparing in the presence of inter/intrafractional motion during stereotactic body radiotherapy (SBRT) on an MR-linac. The increased treatment complexity and the motion-delivery interplay during these treatments require MR-compatible motion phantoms with time-resolved dosimeters to validate end-to-end workflows. This is not possible with currently available phantoms. PURPOSE: Here, we demonstrate a new commercial hybrid film-scintillator cassette, combining high spatial resolution radiochromic film with four time-resolved plastic scintillator dosimeters (PSDs) in an MRI-compatible motion phantom. METHODS: First, the PSD's performance for consistency, dose linearity, and pulse repetition frequency (PRF) dependence was evaluated using an RW3 solid water slab phantom. We then demonstrated the MRI4D scintillator cassette's suitability for time-resolved and motion-included quality assurance for adapt-to-shape (ATS), trailing, gating, and multileaf collimator (MLC) tracking adaptations on a 1.5 T MR-linac. To do this, the cassette was inserted into the Quasar MRI4D phantom, which we used statically or programmed with artificial and patient-derived motion. Simultaneously with dose measurements, the beam-gating latency was estimated from the time difference between the target entering/leaving the gating window and the beam-on/off times derived from the time-resolved dose measurements. RESULTS: Experiments revealed excellent detector consistency (standard deviation ≤ $\le$ 0.6%), dose linearity (R2 = 1), and only very low PRF dependence ( ≤ $\le$ 0.4%). The dosimetry cassette demonstrated a near-perfect agreement during an ATS workflow between the time-resolved PSD and treatment planning system (TPS) dose (0%-2%). The high spatial resolution film measurements confirmed this with a 1%/1-mm local gamma pass-rate of 90%. When trailing patient-derived prostate motion for a prostate SBRT delivery, the time-resolved cassette measurements demonstrated how trailing mitigated the motion-induced dose reductions from 1%-17% to 1%-2% compared to TPS dose. The cassette's simultaneously measured spatial dose distribution highlighted the dosimetric gain of trailing by improving the 3%/3-mm local gamma pass-rates from 80% to 97% compared to the static dose. Similarly, the cassette demonstrated the benefit of real-time adaptations when compensating patient-derived respiratory motion by showing how the TPS dose was restored from 2%-56% to 0%-12% (gating) and 1%-26% to 1%-7% (MLC tracking) differences. Larger differences are explainable by TPS-PSD coregistration uncertainty combined with a steep dose gradient outside the PTV. The cassette also demonstrated how the spatial dose distributions were drastically improved by the real-time adaptations with 1%/1-mm local gamma pass-rates that were increased from 8 to 79% (gating) and from 35 to 89% (MLC tracking). The cassette-determined beam-gating latency agreed within ≤ $\le$ 12 ms with the ground truth latency measurement. Film and PSD dose agreed well for most cases (differences relative to TPS dose < $<$ 4%), while film-PSD coregistration uncertainty caused relative differences of 5%-8%. CONCLUSIONS: This study demonstrates the excellent suitability of a new commercial hybrid film-scintillator cassette for simultaneous spatial, temporal, and motion-included dosimetry.

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Interfraction anatomic deformations decrease the precision of radiotherapy, which can be improved by online adaptive radiation therapy (oART). However, oART takes time, allowing intrafractional deformations. In this study on focal radiotherapy for bladder cancer, we analyzed the time effect of oART on the equivalent uniform dose in the CTV (EUDCTV) per fraction and for the accumulated dose distribution over a treatment series as measure of effectiveness. A time-dependent digital CTV model was built from deformable image registration (DIR) between pre- and post-adaptation imaging. The model was highly dose fraction-specific. Planning target volume (PTV) margins were varied by shrinking the clinical PTV to obtain the margin-specific CTV. The EUDCTV per fraction decreased by-4.4 ± 0.9% of prescribed dose per min in treatment series with a steeper than average time dependency of EUDCTV. The EUDCTV for DIR-based accumulated dose distributions over a treatment series was significantly dependent on adaptation time and PTV margin (p < 0.0001, Chi2 test for each variable). Increasing adaptation times larger than 10 min by five minutes requires a 1.9 ± 0.24 mm additional margin to maintain EUDCTV for a treatment series. Adaptation time is an important determinant of the precision of oART for one half of the bladder cancer patients, and it should be aimed at to be minimized.