Full bladder, empty rectum? Revisiting a paradigm in the era of adaptive radiotherapy.

BACKGROUND AND PURPOSE: Many patients find it challenging to comply with instructions regarding rectum and bladder filling during pelvic radiotherapy. With the implementation of online adaptive radiotherapy, the reproducibility of organ volumes is no longer a prerequisite. This study aims to analyze the sparing of the bladder and the posterior rectum wall (PRW) in conditions of full versus empty bladder and rectum. METHODS: 280 fractions from 14 patients with prostate cancer who underwent adaptive radiotherapy using the Varian Ethos system were analyzed post-hoc. Various metrics for the bladder and PRW were correlated with respect to organ volume. RESULTS: Our analysis quantitatively confirms the advantage of a full bladder during radiotherapy, as metrics V48Gy and V40Gy significantly inversely correlate with bladder filling for each patient individually. While bladder volume did not show a gradual decrease over the course of radiotherapy, it was observed to be higher during planning CT scans compared to treatment sessions. A full rectum condition either significantly improved (in 2 out of 7 patients) or at least did not impair (in 5 out of 7 patients) PRW sparing, as represented by the V30Gy metric, when patients were compared individually. The average V30Gy across all patients demonstrated a significant improvement in PRW sparing for the full rectum condition, with a [Formula: see text]-value of 0.039. CONCLUSION: Despite the implementation of adaptive therapy, maintaining a high bladder filling remains important. However, the recommendation for rectum filling can be abandoned, as reproducibility is not critical for adaptive radiotherapy and no dosimetric advantage per se is associated with an empty rectum. Patients may even be encouraged not to void their bowels shortly before treatment, as long as this is tolerated over the treatment session.

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.

Fan beam CT-guided online adaptive external radiotherapy of uterine cervical cancer: a dosimetric evaluation.

PURPOSE: To discuss the dosimetric advantages and reliability of the accurate delivery of online adaptive radiotherapy(online ART) for uterine cervical cancer(UCC). METHODS AND MATERIALS: Six UCC patients were enrolled in this study. 95% of the planning target volume (PTV) reached 100% of the prescription dose (50.4 Gy/28fractions/6weeks) was required. The patients were scanned with uRT-Linac 506c KV-FBCT then the target volume (TV) and organs at risk (OARs) were delineated by doctors. The dosimeters designed and obtained a routine plan (Plan0). KV-FBCT was used for image guidance before subsequent fractional treatment. The online ART was processed after registration, which acquired a virtual nonadaptive radiotherapy plan (VPlan) and an adaptive plan (APlan). VPlan was the direct calculation of Plan0 on the fractional image, while APlan required adaptive optimization and calculation. In vivo dose monitoring and three-dimensional dose reconstruction were required during the implementation of APlan. RESULTS: The inter-fractional volumes of the bladder and rectum changed greatly among the treatments. These changes influenced the primary gross tumor volume (GTVp) and the position deviation of GTVp and PTV and positively affected the prescription dose coverage of TV. GTVp decreased gradually along with dose accumulation. The Dmax, D98, D95, D50, and D2 of APlan were superior to those of VPlan in target dose distribution. APlan had good conformal index, homogeneity index and target coverage. The rectum V40 and Dmax, bladder V40, the small bowel V40 and Dmax of APlan were better than that of VPlan. The APlan's fractional mean γ passing rate was significantly higher than the international standard and the mean γ passing rate of all cases after the three-dimensional reconstruction was higher than 97.0%. CONCLUSION: Online ART in external radiotherapy of UCC significantly improved the dose distribution and can become an ideal technology to achieve individualized precise radiotherapy.

Clinical experiences with online adaptive radiotherapy of vulvar carcinoma.

BACKGROUND AND PURPOSE: Radiotherapy for vulvar carcinoma is challenging due to relatively high risk of locoregional disease recurrence, a technically challenging target, and postoperative lymphocele, and a high risk radiation sequelae. We aim to explore, if it is possible to reduce dose to normal tissue, while maintaining CTV coverage for this patient group with online adaptive radiotherapy. MATERIALS AND METHODS: 20 patients with vulvar carcinoma (527 fractions) were treated with online adaptation on a Varian Ethos accelerator. Setup CBCTs were acquired daily for adaptive planning. Verification CBCTs were acquired immediately prior to dose delivery. CTV dose coverage and dose to bladder and rectum were extracted from the scheduled and adapted plans as well as from adapted plans recalculated based on verification CBCTs. In addition, analysis of the decision of the adaptive procedure was performed for 17 patients (465 fractions). RESULTS: Mean CTV D95% and standard deviation was 98% ± 5% for the scheduled plan compared to 100.0 ± 0.3% and 100.0 ± 0.8% for the adapted plan on the setup and verification CBCT respectively. Dose to OARs varied substantially and did not show any benefit from adaption itself, however a margin reduction was implemented after the first patients treated. The adapted plan was chosen for 63.5% of the fractions and dominant reasons for not adapting were 'no significant dosimetric gain' (75 fractions, 14%) and 'Medical doctor (MD) not available for treatment' (50 fractions, 9.5%). The median adaption time was 15 min and the 25th and 75th percentile was 12 and 17 min, respectively. CONCLUSION: CTVs and PTVs dose coverage were significantly improved with adaptation compared to image-guided RT. This gain was robust during the treatment time.

Evaluation of a workflow for cone-beam CT-guided online adaptive palliative radiotherapy planned using diagnostic CT scans.

PURPOSE: Single-visit radiotherapy (RT) is beneficial for patients requiring pain control and can limit interruptions to systemic treatments. However, the requirement for a dedicated planning CT (pCT)-scan can result in treatment delays. We developed a workflow involving preplanning on available diagnostic CT (dCT) imaging, followed by online plan adaption using a cone-beam CT (CBCT)-scan prior to RT-delivery, in order to account for any changes in anatomy and target position. METHODS: Patients previously treated with palliative RT for bone metastases were selected from our hospital database. Patient dCT-images were deformed to treatment CBCTs in the Ethos platform (Varian Medical Systems) and a synthetic CT (sCT) generated. Treatment quality was analyzed by comparing a coverage of the V95% of the planning/clinical target volume and different organ-at-risk (OAR) doses between adapted and initial clinical treatment plans. Doses were recalculated on the CBCT and sCT in a separate treatment planning system. Adapted plan doses were measured on-couch using an anthropomorphic phantom with a Gafchromic EBT3 dosimetric film and compared to dose calculations. RESULTS: All adapted treatment plans met the clinical goals for target and OARs and outperformed the original treatment plans calculated on the (daily) sCT. Differences in V95% of the target volume coverage between the initial and adapted treatments were <0.2%. Dose recalculations on CBCT and sCT were comparable, and the average gamma pass rate (3%/2 mm) of dosimetric measurements was 98.8%. CONCLUSIONS: Online daily adaptive RT using dCTs instead of a dedicated pCT is feasible using the Ethos platform. This workflow has now been implemented clinically.

Do we need patient-specific QA for adaptively generated plans? Retrospective evaluation of delivered online adaptive treatment plans on Varian Ethos.

BACKGROUND: The clinical introduction of dedicated treatment units for online adaptive radiation therapy (OART) has led to widespread adoption of daily adaptive radiotherapy. OART allows for rapid generation of treatment plans using daily patient anatomy, potentially leading to reduction of treatment margins and increased normal tissue sparing. However, the OART workflow does not allow for measurement of patient-specific quality assurance (PSQA) during treatment delivery sessions and instead relies on secondary dose calculations for verification of adapted plans. It remains unknown if independent dose verification is a sufficient surrogate for PSQA measurements. PURPOSE: To evaluate the plan quality of previously treated adaptive plans through multiple standard PSQA measurements. METHODS: This IRB-approved retrospective study included sixteen patients previously treated with OART at our institution. PSQA measurements were performed for each patient's scheduled and adaptive plans: five adaptive plans were randomly selected to perform ion chamber measurements and two adaptive plans were randomly selected for ArcCHECK measurements. The same ArcCHECK 3D dose distribution was also sent to Mobius3D to evaluate the second-check dosimetry system. RESULTS: All (n = 96) ion chamber measurements agreed with the planned dose within 3% with a mean of 1.4% (± 0.7%). All (n = 48) plans passed ArcCHECK measurements using a 95% gamma passing threshold and 3%/2 mm criteria with a mean of 99.1% (± 0.7%). All (n = 48) plans passed Mobius3D second-check performed with 95% gamma passing threshold and 5%/3 mm criteria with a mean of 99.0% (± 0.2%). CONCLUSION: Plan measurement for PSQA may not be necessary for every online-adaptive treatment verification. We recommend the establishment of a periodic PSQA check to better understand trends in passing rates for delivered adaptive treatments.

A head and neck treatment planning strategy for a CBCT-guided ring-gantry online adaptive radiotherapy system.

PURPOSE: A planning strategy was developed and the utility of online-adaptation with the Ethos CBCT-guided ring-gantry adaptive radiotherapy (ART) system was evaluated using retrospective data from Head-and-neck (H&N) patients that required clinical offline adaptation during treatment. METHODS: Clinical data were used to re-plan 20 H&N patients (10 sequential boost (SEQ) with separate base and boost plans plus 10 simultaneous integrated boost (SIB)). An optimal approach, robust to online adaptation, for Ethos-initial plans using clinical goal prioritization was developed. Anatomically-derived isodose-shaping helper structures, air-density override, goals for controlling hotspot location(s), and plan normalization were investigated. Online adaptation was simulated using clinical offline adaptive simulation-CTs to represent an on-treatment CBCT. Dosimetric comparisons were based on institutional guidelines for Clinical-initial versus Ethos-initial plans and Ethos-scheduled versus Ethos-adapted plans. Timing for five components of the online adaptive workflow was analyzed. RESULTS: The Ethos H&N planning approach generated Ethos-initial SEQ plans with clinically comparable PTV coverage (average PTVHigh V100%  = 98.3%, Dmin,0.03cc  = 97.9% and D0.03cc  = 105.5%) and OAR sparing. However, Ethos-initial SIB plans were clinically inferior (average PTVHigh V100%  = 96.4%, Dmin,0.03cc  = 93.7%, D0.03cc  = 110.6%). Fixed-field IMRT was superior to VMAT for 93.3% of plans. Online adaptation succeeded in achieving conformal coverage to the new anatomy in both SEQ and SIB plans that was even superior to that achieved in the initial plans (which was due to the changes in anatomy that simplified the optimization). The average adaptive workflow duration for SIB, SEQ base and SEQ boost was 30:14, 22.56, and 14:03 (min: sec), respectively. CONCLUSIONS: With an optimal planning approach, Ethos efficiently auto-generated dosimetrically comparable and clinically acceptable initial SEQ plans for H&N patients. Initial SIB plans were inferior and clinically unacceptable, but adapted SIB plans became clinically acceptable. Online adapted plans optimized dose to new anatomy and maintained target coverage/homogeneity with improved OAR sparing in a time-efficient manner.

Evaluation and correlation of patient movement during online adaptive radiotherapy with CBCT and a surface imaging system.

PURPOSE: With the clinical implementation of kV-CBCT-based daily online-adaptive radiotherapy, the ability to monitor, quantify, and correct patient movement during adaptive sessions is paramount. With sessions lasting between 20-45 min, the ability to detect and correct for small movements without restarting the entire session is critical to the adaptive workflow and dosimetric outcome. The purpose of this study was to quantify and evaluate the correlation of observed patient movement with machine logs and a surface imaging (SI) system during adaptive radiation therapy. METHODS: Treatment machine logs and SGRT registration data log files for 1972 individual sessions were exported and analyzed. For each session, the calculated shifts from a pre-delivery position verification CBCT were extracted from the machine logs and compared to the SGRT registration data log files captured during motion monitoring. The SGRT calculated shifts were compared to the reported shifts of the machine logs for comparison for all patients and eight disease site categories. RESULTS: The average (±STD) net displacement of the SGRT shifts were 2.6 ± 3.4 mm, 2.6 ± 3.5 mm, and 3.0 ± 3.2 in the lateral, longitudinal, and vertical directions, respectively. For the treatment machine logs, the average net displacements in the lateral, longitudinal, and vertical directions were 2.7 ± 3.7 mm, 2.6 ± 3.7 mm, and 3.2 ± 3.6 mm. The average difference (Machine-SGRT) was -0.1 ± 1.8 mm, 0.2 ± 2.1 mm, and -0.5 ± 2.5 mm for the lateral, longitudinal, and vertical directions. On average, a movement of 5.8 ± 5.6 mm and 5.3 ± 4.9 mm was calculated prior to delivery for the CBCT and SGRT systems, respectively. The Pearson correlation coefficient between CBCT and SGRT shifts was r = 0.88. The mean and median difference between the treatment machine logs and SGRT log files was less than 1 mm for all sites. CONCLUSION: Surface imaging should be used to monitor and quantify patient movement during adaptive radiotherapy.

Evaluation of MRI-only based online adaptive radiotherapy of abdominal region on MR-linac.

PURPOSE: A hybrid magnetic resonance linear accelerator (MRL) can perform magnetic resonance imaging (MRI) with high soft-tissue contrast to be used for online adaptive radiotherapy (oART). To obtain electron densities needed for the oART dose calculation, a computed tomography (CT) is often deformably registered to MRI. Our aim was to evaluate an MRI-only based synthetic CT (sCT) generation as an alternative to the deformed CT (dCT)-based oART in the abdominal region. METHODS: The study data consisted of 57 patients who were treated on a 0.35 T MRL system mainly for abdominal tumors. Simulation MRI-CT pairs of 43 patients were used for training and validation of a prototype convolutional neural network sCT-generation algorithm, based on HighRes3DNet, for the abdominal region. For remaining test patients, sCT images were produced from simulation MRIs and daily MRIs. The dCT-based plans were re-calculated on sCT with identical calculation parameters. The sCT and dCT were compared in terms of geometric agreement and calculated dose. RESULTS: The mean and one standard deviation of the geometric agreement metrics over dCT-sCT-pairs were: mean error of 8 ± 10 HU, mean absolute error of 49 ± 10 HU, and Dice similarity coefficient of 55 ± 12%, 60 ± 5%, and 82 ± 15% for bone, fat, and lung tissues, respectively. The dose differences between the sCT and dCT-based dose for planning target volumes were 0.5 ± 0.9%, 0.6 ± 0.8%, and 0.5 ± 0.8% at D2% , D50% , and D98% in physical dose and 0.8 ± 1.4%, 0.8 ± 1.2%, and 0.6 ± 1.1% in biologically effective dose (BED). For organs-at-risk, the dose differences of all evaluated dose-volume histogram points were within [-4.5%, 7.8%] and [-1.1 Gy, 3.5 Gy] in both physical dose and BED. CONCLUSIONS: The geometric agreement metrics were within typically reported values and most average relative dose differences were within 1%. Thus, an MRI-only sCT-based approach is a promising alternative to the current clinical practice of the abdominal oART on MRL.

MRI-GUIDED RADIOTHERAPY FOR PROSTATE CANCER: A NEW PARADIGM.

Radiotherapy is one of the key treatment modalities for primary prostate cancer. During the last decade, significant advances were made in radiotherapy technology leading to increasing both physical and biological precision. Being a loco-regional treatment approach, radiotherapy requires accurate target dose deposition while sparing surrounding healthy tissue. Conventional radiotherapy is based on computerized tomography (CT) images both for radiotherapy planning and image-guidance, however, shortcomings of CT as soft tissue imaging tool are well known. Nowadays, our ability to further escalate radiotherapy dose using hypofractionation is limited by uncertainties in CT-based image guidance and verification. Magnetic resonance imaging (MRI) is a well established imaging method for pelvic organs. In prostate cancer specifically, MRI accurately depicts prostate zonal anatomy, rectum, bladder, and pelvic floor structures with previously unseen precision owing to its sharp soft tissue contrast. The advantages of including MRI in the clinical workflow of prostate cancer radiotherapy are multifold. MRI allows for true adaptive radiotherapy to unfold based on daily MRI images taken before, during and after each radiotherapy fraction. It enables accurate dose escalation to the prostate and intraprostatic tumor lesions. Technically, MRI high-strength magnetic field and linear accelerator high energy electromagnetic beams are hardly compatible, and important efforts were made to overcome these technical challenges and integrate MRI and linear accelerator into one single treatment device, called MRI-linac. Different systems are produced by two leading vendors in the field and currently, there are around 100 MRI-linacs worldwide in clinical operations. In this narrative review paper, we discuss historical perspective of image guidance in radiotherapy, basic elements of MRI, current clinical developments in MRI-guided prostate cancer radiotherapy, and challenges associated with the use of MRI-linac in clinical practice.

Initial analysis of the dosimetric benefit and clinical resource cost of CBCT-based online adaptive radiotherapy for patients with cancers of the cervix or rectum.

PURPOSE: This provides a benchmark of dosimetric benefit and clinical cost of cone-beam CT-based online adaptive radiotherapy (ART) technology for cervical and rectal cancer patients. METHODS: An emulator of a CBCT-based online ART system was used to simulate more than 300 treatments for 13 cervical and 15 rectal cancer patients. CBCT images were used to generate adaptive replans. To measure clinical resource cost, the six phases of the workflow were timed. To evaluate the dosimetric benefit, changes in dosimetric values were assessed. These included minimum dose (Dmin) and volume receiving 95% of prescription (V95%) for the planning target volume (PTV) and the clinical target volume (CTV), and maximum 2 cc's (D2cc) of the bladder, bowel, rectum, and sigmoid colon. RESULTS: The average duration of the workflow was 24.4 and 9.2 min for cervical and rectal cancer patients, respectively. A large proportion of time was dedicated to editing target contours (13.1 and 2.7 min, respectively). For cervical cancer patients, the replan changed the Dmin to the PTVs and CTVs for each fraction 0.25 and 0.25 Gy, respectively. The replan changed the V95% by 9.2 and 7.9%. The D2cc to the bladder, bowel, rectum, and sigmoid colon for each fraction changed -0.02, -0.08, -0.07, and -0.04 Gy, respectively. For rectal cancer patients, the replan changed the Dmin to the PTVs and CTVs for each fraction of 0.20 and 0.24 Gy, respectively. The replan changed the V95% by 4.1 and 1.5%. The D2cc to the bladder and bowel for each fraction changed 0.02 and -0.02 Gy, respectively. CONCLUSIONS: Dosimetric benefits can be achieved with CBCT-based online ART that is amenable to conventional appointment slots. The clinical significance of these benefits remains to be determined. Managing contours was the primary factor affecting the total duration and is imperative for safe and effective adaptive radiotherapy.

On the accuracy of bulk synthetic CT for MR-guided online adaptive radiotherapy.

PURPOSE: MR-guided radiotherapy (MRgRT) relies on the daily assignment of a relative electron density (RED) map to allow the fraction specific dose calculation. One approach to assign the RED map consists of segmenting the daily magnetic resonance image into five different density levels and assigning a RED bulk value to each level to generate a synthetic CT (sCT). The aim of this study is to evaluate the dose calculation accuracy of this approach for applications in MRgRT. METHODS: A planning CT (pCT) was acquired for 26 patients with abdominal and pelvic lesions and segmented in five levels similar to an online approach: air, lung, fat, soft tissue and bone. For each patient, the median RED value was calculated for fat, soft tissue and bone. Two sCTs were generated assigning different bulk values to the segmented levels on pCT: The sCTICRU uses the RED values recommended by ICRU46, and the sCTtailor uses the median patient-specific RED values. The same treatment plan was calculated on two the sCTs and the pCT. The dose calculation accuracy was investigated in terms of gamma analysis and dose volume histogram parameters. RESULTS: Good agreement was found between dose calculated on sCTs and pCT (gamma passing rate 1%/1 mm equal to 91.2% ± 6.9% for sCTICRU and 93.7% ± 5.3% b or sCTtailor). The mean difference in estimating V95 (PTV) was equal to 0.2% using sCTtailor and 1.2% using sCTICRU, respect to pCT values CONCLUSIONS: The bulk sCT guarantees a high level of dose calculation accuracy also in presence of magnetic field, making this approach suitable to MRgRT. This accuracy can be improved by using patient-specific RED values.

Evaluation of a simplified optimizer for MR-guided adaptive RT in case of pancreatic cancer.

PURPOSE: Magnetic resonance-guided adaptive radiotherapy (MRgART) is considered a promising resource for pancreatic cancer, as it allows to online modify the dose distribution according to daily anatomy. This study aims to compare the dosimetric performance of a simplified optimizer implemented on a MR-Linac treatment planning system (TPS) with those obtained using an advanced optimizer implemented on a conventional Linac. METHODS: Twenty patients affected by locally advanced pancreatic cancer (LAPC) were considered. Gross tumor volume (GTV) and surrounding organ at risks (OARs) were contoured on the average 4DCT scan. Planning target volume was generated from GTV by adding an isotropic 3 mm margin and excluding overlap areas with OARs. Treatment plans were generated by using the simple optimizer for the MR-Linac in intensity-modulated radiation therapy (IMRT) and the advanced optimizer for conventional Linac in IMRT and volumetric modulated arc therapy (VMAT) technique. Prescription dose was 40 Gy in five fractions. The dosimetric comparison was performed on target coverage, dosimetric indicators, and low dose diffusion. RESULTS: The simplified optimizer of MR-Linac generated clinically acceptable plans in 80% and optimal plans in 55% of cases. The number of clinically acceptable plans obtained using the advanced optimizer of the conventional Linac with IMRT was the same of MR-Linac, but the percentage of optimal plans was higher (65%). Using the VMAT technique, it is possible to obtain clinically acceptable plan in 95% and optimal plans in 90% of cases. The advanced optimizer combined with VMAT technique ensures higher target dose homogeneity and minor diffusion of low doses, but its actual optimization time is not suitable for MRgART. CONCLUSION: Simplified optimization solutions implemented in the MR-Linac TPS allows to elaborate in most of cases treatment plans dosimetrically comparable with those obtained by using an advanced optimizer. A superior treatment plan quality is possible using the VMAT technique that could represent a breakthrough for the MRgART if the modern advancements will lead to shorter optimization times.

Experience with patient-specific quality assurance of dosimetrist-led online adaptive prostate SBRT.

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.

Daily AI-Based Treatment Adaptation under Weekly Offline MR Guidance in Chemoradiotherapy for Cervical Cancer 1: The AIM-C1 Trial.

(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.

Clinical Workflow of Cone Beam Computer Tomography-Based Daily Online Adaptive Radiotherapy with Offline Magnetic Resonance Guidance: The Modular Adaptive Radiotherapy System (MARS).

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.

Performance characterization of a novel hybrid dosimetry insert for simultaneous spatial, temporal, and motion-included dosimetry for MR-linac.

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.

Enhancing Precision in Radiation Therapy for Locally Advanced Lung Cancer: A Case Study of Cone-Beam Computed Tomography (CBCT)-Based Online Adaptive Techniques and the Promise of HyperSight™ Iterative CBCT.

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.

Multi-institutional questionnaire-based survey on online adaptive radiotherapy performed using commercial systems in Japan in 2023.

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.

CT-Guided Online Adaptive Stereotactic Body Radiotherapy (SBRT) for Retroperitoneal Sarcoma After Previous Radiotherapy: A Case Report.

CT-guided online adaptive radiotherapy (OART) is a novel and robust treatment technique in radiotherapy. Thanks to its excellent accommodation of inter-fraction variations, OART is characterized by superior accuracy compared to other contemporary treatment techniques in radiotherapy such as image-guided radiotherapy (IGRT). Planning target volume (PTV), which takes into account interfraction movements, could therefore be reduced while utilizing OART with a consequent dose reduction for adjacent healthy tissue. Herein we report our successful experience in treating a patient with retroperitoneal sarcoma after previous radiotherapy and surgery. The tumor was in close proximity to the spinal canal and abutted a large bowel segment and the last portions of the duodenum. Radiotherapy regimen consisted of 30 Gy in five fractions. Treatment implementation and delivery were feasible and the treatment was given without any interruptions. After a follow-up period of nine months so far, the patient reported no radiation-related adverse effects. Furthermore, her post-treatment magnetic resonance imaging (MRI) scans demonstrate good radiographic response.  Our case highlights the use of OART to treat a challenging case in radiotherapy as it was given in the setting of re-irradiation to a mesenchymal tumor, which is considered exquisitely radio-resistant.