• Adaptive radiotherapy
• Offline adaptive radiotherapy
• Online adaptive radiotherapy
• Pattern of practice
• RTT roles

• Adaptive Therapy
• External beam Radiotherapy
• Uncertainty analysis

• Uncertainty
• Humans
• Radiotherapy Planning, Computer-Assisted/methods
• Organs at Risk/radiation effects
• Abdomen/radiation effects
• Abdomen/diagnostic imaging
• Radiotherapy, Image-Guided/methods
• Tomography, X-Ray Computed
• Radiotherapy Dosage
• Cone-Beam Computed Tomography

• P30 CA006927 NCI NIH HHS

• Humans
• Pancreatic Neoplasms/radiotherapy
• Male
• Female
• Aged
• Middle Aged
• Retrospective Studies
• Radiotherapy, Image-Guided/methods
• Radiotherapy, Image-Guided/adverse effects
• Adenocarcinoma/radiotherapy
• Adenocarcinoma/pathology
• Radiotherapy Dosage
• Organs at Risk/radiation effects
• Radiosurgery/methods
• Radiosurgery/adverse effects
• Radiation Injuries/etiology
• Aged, 80 and over
• Adult
• Magnetic Resonance Imaging/methods
• Radiotherapy Planning, Computer-Assisted/methods

• MR-guided SBRT
• Oligometastases
• Pancreatic metastases
• Renal cell carcinoma

• F30 CA278357 NCI NIH HHS
• R37 CA262510 NCI NIH HHS

• Locally advanced rectal cancer (LARC)
• MR-guided adaptive radiotherapy (MRgART)
• Positive lymph node
• Primary lesion
• Randomized controlled trial
• Simultaneous integrated boost (SIB)
• Surgical difficulty
• pCR

• Humans
• Rectal Neoplasms/pathology
• Rectal Neoplasms/therapy
• Rectal Neoplasms/radiotherapy
• Neoadjuvant Therapy/methods
• Female
• Adult
• Male
• Middle Aged
• Aged
• Radiotherapy, Image-Guided/methods
• Chemoradiotherapy
• Magnetic Resonance Imaging
• Radiotherapy, Intensity-Modulated/methods
• Radiotherapy, Intensity-Modulated/adverse effects
• Lymph Nodes/pathology
• Lymphatic Metastasis/radiotherapy
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Young Adult

• 82272753 National Natural Science Foundation of China
• ZR2021LZL002 Natural Science Foundation of Shandong Province
• flzh202103 Bethune Cancer Radiotherapy Translational Medicine Research Fund

• Humans
• Proton Therapy/methods
• Retrospective Studies
• Radiotherapy Planning, Computer-Assisted/methods
• Lung Neoplasms/radiotherapy
• Radiotherapy Dosage
• Radiation Injuries
• Male
• Organs at Risk/radiation effects
• Female
• Time Factors

• Humans
• Radiosurgery/methods
• Reproducibility of Results
• Magnetic Resonance Imaging/methods
• Particle Accelerators
• Phantoms, Imaging
• Radiotherapy Planning, Computer-Assisted/methods
• Radiotherapy Dosage
• Magnetic Resonance Spectroscopy

• Head and neck cancer
• online adaptive radiotherapy
• treatment planning

• Humans
• Radiotherapy Dosage
• Radiotherapy Planning, Computer-Assisted
• Retrospective Studies
• Spiral Cone-Beam Computed Tomography
• Organs at Risk
• Radiotherapy, Intensity-Modulated

• Varian Medical Systems, Palo Alto, CA

• Dose variation
• Interfraction
• Pancreas

• MR-guided radiotherapy
• Online adaptive radiotherapy
• Pancreatic radiotherapy
• SBRT

• Adaptive radiotherapy (ART)
• Cone-beam computed tomography (CBCT)
• Ethos™

• Humans
• Artificial Intelligence
• Radiation Oncology
• Cone-Beam Computed Tomography
• Machine Learning
• Motion
• Radiation Injuries

• CT image
• MLP-Mixer
• abdomen organ segmentation
• efficient segmentation network

• Humans
• Tomography, X-Ray Computed
• Neural Networks, Computer
• Abdomen/diagnostic imaging
• Algorithms
• Lung
• Image Processing, Computer-Assisted/methods

• R01 EB032680 NIBIB NIH HHS
• R01 CA215718 NCI NIH HHS
• R01 EB028324 NIBIB NIH HHS
• R56 EB033332 NIBIB NIH HHS

• MR-guided radiation therapy
• biliary stent
• image guidance
• pancreatic SBRT

• cognitive function
• dose reduction
• glioblastoma
• hippocampi
• radiotherapy
• resection cavity

• R37 CA262510 NCI NIH HHS

• Deformable registration
• Dose accumulation
• Liver SBRT
• Sorafenib

• Humans
• Adenocarcinoma/radiotherapy
• Adenocarcinoma/drug therapy
• Albumins
• Antineoplastic Combined Chemotherapy Protocols/adverse effects
• Gemcitabine
• Paclitaxel
• Pancreatic Neoplasms/radiotherapy
• Pancreatic Neoplasms/drug therapy

• P30 CA091842 NCI NIH HHS
• P50 CA272213 NCI NIH HHS

• online adaptive radiotherapy
• patient-specific quality assurance
• second check dosimetry

• Humans
• Magnetic Resonance Imaging/methods
• Neoplasms/diagnostic imaging
• Neoplasms/radiotherapy
• Quality of Life
• Radiotherapy Planning, Computer-Assisted/methods
• Radiotherapy, Image-Guided/methods

• 28284 Cancer Research UK
• C7224/A28724 Cancer Research UK
• Department of Health
• C33589/A28284 Cancer Research UK

Hybrid magnetic resonance (MR)-Linac systems have recently been introduced into clinical practice. The systems allow online adaption of the treatment plan with the aim of compensating for interfractional anatomical changes. The aim of this study was to evaluate the dose volume histogram (DVH)-based dosimetric benefits of online adaptive MR-guided radiotherapy (oMRgRT) across different tumor entities and to investigate which subgroup of plans improved the most from adaption.

Fifty patients treated with oMRgRT for five different tumor entities (liver, lung, multiple abdominal lymph nodes, pancreas, and prostate) were included in this retrospective analysis. Various target volume (gross tumor volume GTV, clinical target volume CTV, and planning target volume PTV) and organs at risk (OAR) related DVH parameters were compared between the dose distributions before and after plan adaption.

All subgroups clearly benefited from online plan adaption in terms of improved PTV coverage. For the liver, lung and abdominal lymph nodes cases, a consistent improvement in GTV coverage was found, while many fractions of the prostate subgroup showed acceptable CTV coverage even before plan adaption. The largest median improvements in GTV near-minimum dose (D_98%) were found for the liver (6.3%, p < 0.001), lung (3.9%, p < 0.001), and abdominal lymph nodes (6.8%, p < 0.001) subgroups. Regarding OAR sparing, the largest median OAR dose reduction during plan adaption was found for the pancreas subgroup (-87.0%). However, in the pancreas subgroup an optimal GTV coverage was not always achieved because sparing of OARs was prioritized.

With online plan adaptation, it was possible to achieve significant improvements in target volume coverage and OAR sparing for various tumor entities and account for interfractional anatomical changes.

With the implementation of MR-LINACs, real-time adaptive radiotherapy has become a possibility within the clinic. However, the process of adapting a patient’s plan is time consuming and often requires input from the entire clinical team, which translates to decreased throughput and limited patient access. In this study, the authors propose and simulate a workflow to address these inefficiencies in staffing and patient throughput. Two physicians, three radiation therapists (RTT), and a research fellow each adapted bladder and bowel contours for 20 fractions from 10 representative patient plans. Contouring ability was compared via calculation of a Dice Similarity Index (DSI). The DSI for bladder and bowel based on each potential physician–therapist pair, as well as an inter-physician comparison, exhibited good overlap amongst all comparisons (p = 0.868). Plan quality was compared through calculation of the conformity index (CI), as well as an evaluation of the plan’s dose to a ‘gold standard’ set of structures. Overall, non-physician plans passed 91.2% of the time. Of the eight non-physician plans that failed their clinical evaluation, six also failed their evaluation against the ‘gold standard’. Another two plans that passed their clinical evaluation subsequently failed in their evaluation against the ‘gold standard’. Thus, the PF-ROAR process has a success rate of 97.5%, with 78/80 plans correctly adapted to the gold standard or halted at treatment. These findings suggest that a physician-free workflow can be well tolerated provided RTTs continue to develop knowledge of MR anatomy and careful attention is given to understanding the complexity of the plan prior to treatment.

• MR-guided radiation therapy
• adaptive radiotherapy
• contour comparison

Pancreatic cancer is a malignancy with one of the poorest prognoses amongst all cancers. Patients with unresectable tumours either receive palliative care or undergo various chemoradiotherapy regimens. Conventional techniques are often associated with acute gastrointestinal toxicities, as adjacent critical structures such as the duodenum ultimately limits delivered doses. Stereotactic body radiotherapy (SBRT) is an advanced radiation technique that delivers highly ablative radiation split into several fractions, with a steep dose fall-off outside target volumes.

To discuss the latest data on SBRT and whether there is a role for magnetic resonance-guided techniques in multimodal management of locally advanced, unresectable pancreatic cancer.

We conducted a search on multiple large databases to collate the latest records on radiotherapy techniques used to treat pancreatic cancer. Out of 1229 total records retrieved from our search, 36 studies were included in this review.

Studies indicate that SBRT is associated with improved clinical efficacy and toxicity profiles compared to conventional radiotherapy techniques. Further dose escalation to the tumour with SBRT is limited by the poor soft-tissue visualisation of computed tomography imaging during radiation planning and treatment delivery. Magnetic resonance-guided techniques have been introduced to improve imaging quality, enabling treatment plan adaptation and re-optimisation before delivering each fraction.

Therefore, SBRT may lead to improved survival outcomes and safer toxicity profiles compared to conventional techniques, and the addition of magnetic resonance-guided techniques potentially allows dose escalation and conversion of unresectable tumours to operable cases.

• Magnetic resonance imaging
• Pancreatic cancer
• Radiotherapy
• Stereotactic
• Adaptive techniques

• Humans
• Magnetic Resonance Imaging/methods
• Magnetic Resonance Spectroscopy
• Pancreatic Neoplasms/diagnostic imaging
• Pancreatic Neoplasms/pathology
• Pancreatic Neoplasms/radiotherapy
• Radiosurgery/adverse effects
• Radiosurgery/methods
• Treatment Outcome

• Animals
• Autophagy/genetics
• Autophagy/radiation effects
• Humans
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/mortality
• Pancreatic Neoplasms/pathology
• Pancreatic Neoplasms/radiotherapy
• Radiation-Sensitizing Agents/pharmacology
• Radiation-Sensitizing Agents/therapeutic use
• Survival Analysis
• Pancreatic Neoplasms

The implementation of the radiation oncology alternative payment model (RO-APM) has raised concerns regarding the development of MRI-guided adaptive radiotherapy (MRgART). We sought to compare technical fee reimbursement under Fee-For-Service (FFS) to the proposed RO-APM for a typical MRI-Linac (MRL) patient load and distribution of 200 patients. In an exploratory aim, a modifier was added to the RO-APM (mRO-APM) to account for the resources necessary to provide this care. Traditional Medicare FFS reimbursement rates were compared to the diagnosis-based reimbursement in the RO-APM. Reimbursement for all selected diagnoses were lower in the RO-APM compared to FFS, with the largest differences in the adaptive treatments for lung cancer (−89%) and pancreatic cancer (−83%). The total annual reimbursement discrepancy amounted to −78%. Without implementation of adaptive replanning there was no difference in reimbursement in breast, colorectal and prostate cancer between RO-APM and mRO-APM. Accommodating online adaptive treatments in the mRO-APM would result in a reimbursement difference from the FFS model of −47% for lung cancer and −46% for pancreatic cancer, mitigating the overall annual reimbursement difference to −54%. Even with adjustment, the implementation of MRgART as a new treatment strategy is susceptible under the RO-APM.

• MRI-Linac
• MRgART
• RO-APM
• adaptive radiotherapy
• medicare
• radiation oncology
• reimbursement

• Abdominal Neoplasms/radiotherapy
• Brain Neoplasms/radiotherapy
• Head and Neck Neoplasms/radiotherapy
• Humans
• Magnetic Resonance Imaging/methods
• Neoplasms/radiotherapy
• Particle Accelerators
• Patient Positioning
• Radiotherapy, Image-Guided/methods
• Thoracic Neoplasms/radiotherapy

Stereotactic body radiotherapy (SBRT) is a noninvasive treatment option for lymph node metastases (LNM). Magnetic resonance (MR)-guidance offers superior tissue contrast and enables treatment of targets in close vicinity to radiosensitive organs at risk (OAR). However, literature on MR-guided SBRT of LNM is scarce with no report on outcome parameters.

We report a subgroup analysis of a prospective observational study comprising patients with LNM. Patients received MR-guided SBRT at our MRIdian Linac (ViewRay Inc., Mountain View, CA, USA) between January 2019 and February 2020. Local control (LC), progression-free survival (PFS) and overall survival (OS) analysis were performed using the Kaplan–Meier method with log rank test to test for significance (p < 0.05). Our patient-reported outcome questionnaire was utilized to evaluate patients’ perspective. The CTCAE (Common Terminology Criteria for Adverse Events) v. 5.0 was used to describe toxicity.

Twenty-nine patients (72.4% with prostate cancer; 51.7% with no distant metastases) received MR-guided SBRT for in total 39 LNM. Median dose was 27 Gy in three fractions, prescribed to the 80% isodose. At 1‑year, estimated LC, PFS and OS were 92.6, 67.4 and 100.0%. Compared to baseline, six patients (20.7%) developed new grade I toxicities (mainly fatigue). One grade II toxicity occurred (fatigue), with no adverse event grade ≥III. Overall treatment experience was rated particularly positive, while the technically required low room temperature still represents the greatest obstacle in the pursuit of the ideal patient acceptance.

MR-guided SBRT of LNM was demonstrated to be a well-accepted treatment modality with excellent preliminary results. Future studies should evaluate the clinical superiority to conventional SBRT.

The online version of this article contains one video. The article and the video are available online (10.1007/s00066-021-01834-w). The video can be found in the article back matter as “Supplementary Information”.

• Abdomen
• Organs at risk
• Patient acceptance
• Pelvis
• Visability

Stereotactic body radiotherapy (SBRT) delivers ablative doses with excellent local control. However, implementing SBRT for abdominal and pelvic tumors has been limited by the risk for treatment‐related gastrointestinal toxicity. MRI‐guided radiotherapy may ameliorate these risks and increase the therapeutic ratio. We report the clinical outcomes of stereotactic MRI‐guided adaptive radiotherapy (SMART) for primary and metastatic tumors in the abdomen and pelvis.

From November 2014 to August 2017, the first 106 consecutive patients with 121 tumors in the abdomen and pelvis were treated with SMART at a single institution. Of the cohort, 41.5%, 15.1%, and 43.4% had primary, locally recurrent, and oligometastatic tumors, respectively. SMART was delivered using a tri‐cobalt‐60 gantry with on‐board 0.35 Tesla MRI with respiratory breath‐hold and daily adaptive re‐planning when anatomically necessary. A median of 40Gy in five fractions was prescribed. The Common Terminology Criteria for Adverse Events v.4.03 was used to score treatment‐related toxicities. Local control (LC), progression‐free survival (PFS), and overall survival (OS) were estimated using Kaplan–Meier method.

Of the 510 treatments, seventy‐one (13.9%) were adapted. Fatigue, nausea, and pain were the most common acute toxicities. 0.9 and 0% of patients experienced acute grade three and four toxicities, respectively. 5.2 and 2.1% of patients experienced late grade three and four toxicities, respectively. After a median follow‐up of 20.4 months, the 2‐year LC rate was 74% on a per‐lesion basis. Two‐year LC was 96% for lesions that were treated with BED₁₀≥100 versus 69% for BED₁₀<100 (p = 0.02). PFS was significantly different between patients with and without locally controlled tumors (2‐year PFS 21 vs. 8%, p = 0.03). Two‐year OS was 57% for the entire cohort.

Favorable LC and PFS outcomes were observed with minimal morbidity for tumors in the abdomen and pelvis treated with SMART. Future prospective clinical trials to validate these findings are warranted.

• MR-guided radiation therapy
• abdominal pelvic tumors
• cancer management
• stereotactic ablative radiotherapy
• stereotactic body radiation therapy

• acute toxicity
• late toxicity
• pancreas
• radiation

We aimed to present our initial clinical experience on the implementation of a stereotactic MR-guided online adaptive radiation therapy (SMART) for the treatment of liver metastases in oligometastatic disease.

Twenty-one patients (24 lesions) with liver metastasis treated with SMART were included in this retrospective study. Step-and-shoot intensity-modulated radiotherapy technique was used with daily plan adaptation. During delivery, real-time imaging was used by acquiring planar magnetic resonance images in sagittal plane for monitoring and gating. Acute and late toxicities were recorded both during treatment and follow-up visits.

The median follow-up time was 11.6 months (range, 2.2 to 24.6 months). The median delivered total dose was 50 Gy (range, 40 to 60 Gy); with a median fraction number of 5 (range, 3 to 8 fractions) and the median fraction dose was 10 Gy (range, 7.5 to 18 Gy). Ninety-three fractions (83.7%) among 111 fractions were re-optimized. No patients were lost to follow-up and all patients were alive except one at the time of analysis. All of the patients had either complete (80.9%) or partial (19.1%) response at irradiated sites. Estimated 1-year overall survival was 93.3%. Intrahepatic and extrahepatic progression-free survival was 89.7% and 73.5% at 1 year, respectively. There was no grade 3 or higher acute or late toxicities experienced during the treatment and follow-up course.

SMART represents a new, noninvasive and effective alternative to current ablative radiotherapy methods for treatment of liver metastases in oligometastatic disease with the advantages of better visualization of soft tissue, real-time tumor tracking and potentially reduced toxicity to organs at risk.

• Image guidance
• Liver
• MRI
• Metastases
• Oligometastatic disease
• Stereotactic radiation therapy

Variation in target positioning represents a challenge to set-up reproducibility and reliability of dose delivery with stereotactic body radiation therapy (SBRT) for pancreatic adenocarcinoma (PDAC). While on-board imaging for fiducial matching allows for daily shifts to optimize target positioning, the magnitude of the shift as a result of inter- and intra-fraction variation may directly impact target coverage and dose to organs-at-risk. Herein, we characterize the variation patterns for PDAC patients treated at a high-volume institution with SBRT.

We reviewed 30 consecutive patients who received SBRT using active breathing coordination (ABC). Patients were aligned to bone and then subsequently shifted to fiducials. Inter-fraction and intra-fraction scans were reviewed to quantify the mean and maximum shift along each axis, and the shift magnitude. A linear regression model was conducted to investigate the relationship between the inter- and intra-fraction shifts.

The mean inter-fraction shift in the LR, AP, and SI axes was 3.1 ± 1.8 mm, 2.9 ± 1.7 mm, and 3.5 ± 2.2 mm, respectively, and the mean vector shift was 6.4 ± 2.3 mm. The mean intra-fraction shift in the LR, AP, and SI directions were 2.0 ± 0.9 mm, 2.0 ± 1.3 mm, and 2.3 ± 1.4 mm, respectively, and the mean vector shift was 4.3 ± 1.8 mm. A linear regression model showed a significant relationship between the inter- and intra-fraction shift in the AP and SI axis and the shift magnitude.

Clinically significant inter- and intra-fraction variation occurs during treatment of PDAC with SBRT even with a comprehensive motion management strategy that utilizes ABC. Future studies to investigate how these variations could lead to variation in the dose to the target and OAR should be investigated. Strategies to mitigate the dosimetric impact, including real time imaging and adaptive therapy, in select cases should be considered.

The online version contains supplementary material available at 10.1186/s13014-021-01782-w.

• Active breathing coordination
• Motion management
• PTV design
• Pancreatic adenocarcinoma
• SBRT

MRI is the standard modality to assess anatomy and response to treatment in brain and spine tumors given its superb anatomic soft tissue contrast (e.g., T1 and T2) and numerous additional intrinsic contrast mechanisms that can be used to investigate physiology (e.g., diffusion, perfusion, spectroscopy). As such, hybrid MRI and radiotherapy (RT) devices hold unique promise for Magnetic Resonance guided Radiation Therapy (MRgRT). In the brain, MRgRT provides daily visualizations of evolving tumors that are not seen with cone beam CT guidance and cannot be fully characterized with occasional standalone MRI scans. Significant evolving anatomic changes during radiotherapy can be observed in patients with glioblastoma during the 6-week fractionated MRIgRT course. In this review, a case of rapidly changing symptomatic tumor is demonstrated for possible therapy adaptation. For stereotactic body RT of the spine, MRgRT acquires clear isotropic images of tumor in relation to spinal cord, cerebral spinal fluid, and nearby moving organs at risk such as bowel. This visualization allows for setup reassurance and the possibility of adaptive radiotherapy based on anatomy in difficult cases. A review of the literature for MR relaxometry, diffusion, perfusion, and spectroscopy during RT is also presented. These techniques are known to correlate with physiologic changes in the tumor such as cellularity, necrosis, and metabolism, and serve as early biomarkers of chemotherapy and RT response correlating with patient survival. While physiologic tumor investigations during RT have been limited by the feasibility and cost of obtaining frequent standalone MRIs, MRIgRT systems have enabled daily and widespread physiologic measurements. We demonstrate an example case of a poorly responding tumor on the 0.35 T MRIgRT system with relaxometry and diffusion measured several times per week. Future studies must elucidate which changes in MR-based physiologic metrics and at which timepoints best predict patient outcomes. This will lead to early treatment intensification for tumors identified to have the worst physiologic responses during RT in efforts to improve glioblastoma survival.

• MRI
• MRgRT
• brain and spine tumors
• glioblastoma
• pseudoprogression
• radiotherapy

Abdominal compression can minimize breathing motion in stereotactic radiotherapy, though it may impact the positioning of dose‐limiting normal tissues. This study quantified the reproducibility of abdominal normal tissues and respiratory motion with the use of an abdominal compression device using MR imaging.

Twenty healthy volunteers had repeat MR over 3 days under an abdominal compression plate device. Normal tissues were delineated on daily axial T2‐weighted MR and compared on days 2 and 3 relative to day 1, after adjusting for baseline shifts relative to bony anatomy. Inter‐fraction organ deformation was computed using deformable registration of axial T2 images. Deformation > 5 mm was assumed to be clinically relevant. Inter‐fraction respiratory amplitude changes and intra‐fraction baseline drifts during imaging were quantified on daily orthogonal cine‐MR (70 s each), and changes > 3 mm were assumed to be relevant.

On axial MR, the mean inter‐fraction normal tissue deformation was > 5 mm for all organs (range 5.1–13.4 mm). Inter‐fraction compression device misplacements > 5 mm and changes in stomach volume > 50% occurred at a rate of 93% and 38%, respectively, in one or more directions and were associated with larger adjacent organ deformation, in particular for the duodenum. On cine‐MR, inter‐fraction amplitude changes > 3 mm on day 2 and 3 relative to day 1 occurred at a rate of < 12.5% (mean superior–inferior change was 1.6 mm). Intra‐fraction baseline drifts > 3 mm during any cine‐MR acquisition occurred at a rate of 23% (mean superior–inferior changes was 2.4 mm).

Respiratory motion under abdominal compression is reproducible in most subjects within 3 mm. However, inter‐fraction deformations greater than 5 mm in normal tissues were common and larger than inter‐ and intra‐fraction respiratory changes. Deformations were driven mostly by variable stomach contents and device positioning. The magnitude of this motion may impact normal tissue dosimetry during stereotactic radiotherapy.

• abdominal compression
• breathing motion
• organ deformation

• MR-guided radiotherapy
• magnetic resonance
• pancreatic cancer
• radiomics