To derive and validate a statistical model of motion and deformation for the clinical target volume (CTV) of early-stage rectal cancer patients.
For 16 patients, 4 to 5 magnetic resonance images ...(MRI) were acquired before each fraction was administered. The CTV was delineated on each MRI. Using a leave-one-out methodology, we constructed a population-based principal component analysis (PCA) model of the CTV motion and deformation of 15 patients, and we tested the model on the left-out patient. The modeling error was calculated as the amount of the CTV motion-deformation of the left-out-patient that could not be explained by the PCA model. Next, the PCA model was used to construct a PCA target volume (PCA-TV) by accumulating motion-deformations simulated by the model. A PCA planning target volume (PTV) was generated by expanding the PCA-TV by uniform margins. The PCA-PTV was compared with uniform and nonuniform CTV-to-PTV margins. To allow comparison, geometric margins were determined to ensure adequate coverage, and the volume difference between the PTV and the daily CTV (CTV-to-PTV volume) was calculated.
The modeling error ranged from 0.9 ± 0.5 to 2.9 ± 2.1 mm, corresponding to a reduction of the CTV motion-deformation between 6% and 60% (average, 23% ± 11%). The reduction correlated with the magnitude of the CTV motion-deformation (P<.001, R=0.66). The PCA-TV and the CTV required 2-mm and 7-mm uniform margins, respectively. The nonuniform CTV-to-PTV margins were 4 mm in the left, right, inferior, superior, and posterior directions and 8 mm in the anterior direction. Compared to uniform and nonuniform CTV-to-PTV margins, the PCA-based PTV significantly decreased (P<.001) the average CTV-to-PTV volume by 128 ± 20 mL (49% ± 4%) and by 35 ± 6 mL (20% ± 3.5%), respectively.
The CTV motion-deformation of a new patient can be explained by a population-based PCA model. A PCA model-generated PTV significantly improved sparing of organs at risk compared to uniform and nonuniform CTV-to-PTV margins.
Purpose
To develop and implement an acceptance procedure for the new Elekta Unity 1.5 T MRI‐linac.
Methods
Tests were adopted and, where necessary adapted, from AAPM TG106 and TG142, IEC 60976 and ...NCS 9 and NCS 22 guidelines. Adaptations were necessary because of the atypical maximum field size (57.4 × 22 cm), FFF beam, the non‐rotating collimator, the absence of a light field, the presence of the 1.5 T magnetic field, restricted access to equipment within the bore, fixed vertical and lateral table position, and the need for MR image to MV treatment alignment. The performance specifications were set for stereotactic body radiotherapy (SBRT).
Results
The new procedure was performed similarly to that of a conventional kilovoltage x‐ray (kV) image guided radiation therapy (IGRT) linac. Results were acquired for the first Unity system.
Conclusions
A comprehensive set of tests was developed, described and implemented for the MRI‐linac. The MRI‐linac met safety requirements for patients and operators. The system delivered radiation very accurately with, for example a gantry rotation locus of isocenter of radius 0.38 mm and an average MLC absolute positional error of 0.29 mm, consistent with use for SBRT. Specifications for clinical introduction were met.
•The Elekta Unity MR-linac adaptive radiotherapy concept is explained.•The adapt to shape and adapt to position workflows are compared.•Different methods for dose re-calculation and optimization are ...discussed.•Full online re-planning is the most robust adaptive planning method for the Unity.•Faster methods are available, but should be dosimetrically explored per use case.
The promise of the MR-linac is that one can visualize all anatomical changes during the course of radiotherapy and hence adapt the treatment plan in order to always have the optimal treatment. Yet, there is a trade-off to be made between the time spent for adapting the treatment plan against the dosimetric gain. In this work, the various daily plan adaptation methods will be presented and applied on a variety of tumour sites. The aim is to provide an insight in the behavior of the state-of-the-art 1.5 T MRI guided on-line adaptive radiotherapy methods.
To explore the different available plan adaptation workflows and methods, we have simulated online plan adaptation for five cases with varying levels of inter-fraction motion, regions of interest and target sizes: prostate, rectum, esophagus and lymph node oligometastases (single and multiple target). The plans were evaluated based on the clinical dose constraints and the optimization time was measured.
The time needed for plan adaptation ranged between 17 and 485 s. More advanced plan adaptation methods generally resulted in more plans that met the clinical dose criteria. Violations were often caused by insufficient PTV coverage or, for the multiple lymph node case, a too high dose to OAR in the vicinity of the PTV. With full online replanning it was possible to create plans that met all clinical dose constraints for all cases.
Daily full online replanning is the most robust adaptive planning method for Unity. It is feasible for specific sites in clinically acceptable times. Faster methods are available, but before applying these, the specific use cases should be explored dosimetrically.
To assess the pathologic and radiologic response in patients with low-risk breast cancer treated with magnetic resonance (MR) guided neoadjuvant partial breast irradiation (NA-PBI) and to evaluate ...toxicity and patient-reported outcomes (PROs).
For this single-arm prospective trial, women with unifocal, non-lobular tumors with a maximum diameter of 20 mm (age, 50-70 years) or 30 mm (age, ≥70 years) and tumor-negative sentinel node(s) were eligible. Patients were treated with a single ablative dose of NA-PBI followed by breast-conserving surgery after an interval of 6 to 8 months. Target volumes were defined on radiation therapy planning computed tomography scan and additional magnetic resonance imaging. Prescribed doses to gross tumor volume and clinical target volume (gross tumor volume plus 20 mm margin) were 20 Gy and 15 Gy, respectively. Primary outcome was pathologic complete response (pCR). Secondary outcomes were radiologic response (on magnetic resonance imaging), toxicity (Common Terminology Criteria for Adverse Events), PROs (European Organisation for Research and Treatment of Cancer QLQ-BR23, Hospital Anxiety and Depression Scale), and cosmesis (assessed by patient, radiation oncologist, and BCCT.core software).
Thirty-six patients were treated with NA-PBI, and pCR was reported in 15 patients (42%; 95% confidence interval, 26%-59%). Radiologic complete response was observed in 15 patients, 10 of whom had pCR (positive predictive value, 67%; 95% confidence interval, 39%-87%). After a median follow-up of 21 months (range, 12-41), all patients experienced grade 1 fibrosis in the treated breast volume. Transient grade 2 and 3 toxicity was observed in 31% and 3% of patients, respectively. Local recurrences were absent. No deterioration in PROs or cosmetic results was observed.
NA-PBI has the potential to induce pCR in a substantial proportion of patients, with acceptable toxicity. This treatment seems a feasible alternative to standard postoperative irradiation and could even result in postponement or omission of surgery if pCR can be accurately predicted in selected low-risk patients.
The aim of this study was to determine the changes in the excision cavity volume due to the resolution of the surgical effects during the whole breast treatment.
Seventy-seven patients with ...early-stage (T1-2 N0) breast cancer treated with breast-conserving therapy were included for this study. All patients underwent a standard planning computed tomography (CT) scan before irradiation treatment. A second CT scan was performed in the week before the start of the boost. Excision cavity volumes were delineated based on the surgical clips and the (surrounding) seroma or hematoma or other surgical changes on both scans by an experienced physician. This resulted in the gross tumor volumes GTV1 and GTV2.
The delineated volumes of the GTVs were on average 78.7 cm(3) (range, 1.1-236.0 cm(3)) and 29.7 cm(3) (range, 1.3-123.6 cm(3)) for, respectively, GTV1 and GTV2. The time between the CT scans was on average 37 days (range, 29-74 days). This resulted in a reduction of on average 62%. The absolute reduction per day of the GTV1 was -1.3 cm(3)/day (range, 0.3 to -5.4 cm(3)/day). A linear correlation (correlation coefficient r(2) = 0.81) was observed between the absolute volume of GTV1 and the absolute reduction per day.
A significant reduction in excision cavity volume during whole breast irradiation was shown. The observed correlation might be helpful in the decision to perform a second CT scan to adapt the treatment plan.
The UMC Utrecht MRI/linac (MRL) design provides image guidance with high soft-tissue contrast, directly during radiotherapy (RT). Breast cancer patients are a potential group to benefit from better ...guidance in the MRL. However, due to the electron return effect, the skin dose can be increased in presence of a magnetic field. Since large skin areas are generally involved in breast RT, the purpose of this study is to investigate the effects on the skin dose, for whole-breast irradiation (WBI) and accelerated partial-breast irradiation (APBI). In ten patients with early-stage breast cancer, targets and organs at risk (OARs) were delineated on postoperative CT scans co-registered with MRI. The OARs included the skin, comprising the first 5 mm of ipsilateral-breast tissue, plus extensions. Three intensity-modulated RT techniques were considered (2× WBI, 1× APBI). Individual beam geometries were used for all patients. Specially developed MRL treatment-planning software was used. Acceptable plans were generated for 0 T, 0.35 T and 1.5 T, using a class solution. The skin dose was augmented in WBI in the presence of a magnetic field, which is a potential drawback, whereas in APBI the induced effects were negligible. This opens possibilities for developing MR-guided partial-breast treatments in the MRL.
The output of MRI-integrated photon therapy (MRgXT) devices is measured in terms of absorbed dose to water, Dw. Traditionally this is done with reference type ion chambers calibrated in a beam ...quality Q0 without magnetic field. To correct the ion chamber response for the application in the magnetic field, a factor needs to be applied that corrects for both beam quality Q and the presence of the magnetic field B, kQ,B. This can be expressed as the product of kQ, without magnetic field, and ion chamber magnetic field correction, kB. kB depends on the magnetic field strength and its direction, the direction of the beam and the orientation and type of the ion chamber. In this study, for the first time, both kQ and kB were measured directly for six waterproof ion chambers (3 × PTW 30013 and 3 × IBA FC65-G) in a pre-clinical 7 MV MRI-linac at 0 T and at 1.5 T. Measurements were done with the only available primary standard built for this purpose, a water calorimeter. Resulting kQ factors for PTW and IBA chambers were 0.985(5) and 0.990(4), respectively. kB factors were measured with the chambers in antiparallel direction to the magnetic field (|| 180°), and perpendicular direction ( −90°). kB|| and kB for the PTW chambers were 0.985(6) and 0.963(4), respectively and for IBA chambers 0.995(4) and 0.956(4). Agreement with the available literature values was shown, partly caused by the relatively large standard deviation (SD) in those values. The values in this study are currently the only available measured values for kQ and kB in an MRI-linac that are directly linked to the international traceability framework for the quantity absorbed dose to water, Dw.
For commissioning and quality assurance for adaptive workflows on the MR‐linac, a dosimeter which can measure time‐resolved dose during MR image acquisition is desired. The Blue Physics model 10 ...scintillation dosimeter is potentially an ideal detector for such measurements. However, some detectors can be influenced by the magnetic field of the MR‐linac. To assess the calibration methods and magnetic field dependency of the Blue Physics scintillator in the 1.5 T MR‐linac. Several calibration methods were assessed for robustness. Detector characteristics and the influence of the calibration methods were assessed based on dose reproducibility, dose linearity, dose rate dependency, relative output factor (ROF), percentage depth dose profile, axial rotation and the radial detector orientation with respect to the magnetic field. The potential application of time‐resolved dynamic dose measurements during MRI acquisition was assessed. A variation of calibration factors was observed for different calibration methods. Dose reproducibility, dose linearity and dose rate stability were all found to be within tolerance and were not significantly affected by different calibration methods. Measurements with the detector showed good correspondence with reference chambers. The ROF and radial orientation dependence measurements were influenced by the calibration method used. Axial detector dependence was assessed and relative readout differences of up to 2.5% were observed. A maximum readout difference of 10.8% was obtained when rotating the detector with respect to the magnetic field. Importantly, measurements with and without MR image acquisition were consistent for both static and dynamic situations. The Blue Physics scintillation detector is suitable for relative dosimetry in the 1.5 T MR‐linac when measurements are within or close to calibration conditions.
•Magnetic resonance guided intrafraction drift correction was researched.•Target coverage benefits of intrafraction adaptation methods were shown.•Two adaptation methods both showed a median target ...coverage of 100.0% for 55 fractions.•The experimental results verified the new method with a gamma passing rate of 99.1%.
MRI-guided online adaptive treatments can account for interfractional variations, however intrafraction motion reduces treatment accuracy. Intrafraction plan adaptation methods, such as the Intrafraction Drift Correction (IDC) or sub-fractionation, are needed. IDC uses real-time automatic monitoring of the tumor position to initiate plan adaptations by repositioning segments. IDC is a fast adaptation method that occurs only when necessary and this method could enable margin reduction. This research provides a treatment planning evaluation and experimental validation of the IDC.
An in silico treatment planning evaluation was performed for 13 prostate patients mid-treatment without and with intrafraction plan adaptation (IDC and sub-fractionation). The adaptation methods were evaluated using dose volume histogram (DVH) metrics. To experimentally verify IDC a treatment was mimicked whereby a motion phantom containing an EBT3 film moved mid-treatment, followed by repositioning of segments. In addition, the delivered treatment was irradiated on a diode array phantom for plan quality assurance purposes.
The planning study showed benefits for using intrafraction adaptation methods relative to no adaptation, where the IDC and sub-fractionation showed consistently improved target coverage with median target coverages of 100.0%. The experimental results verified the IDC with high minimum gamma passing rates of 99.1% and small mean dose deviations of maximum 0.3%.
The straightforward and fast IDC technique showed DVH metrics consistent with the sub-fractionation method using segment weight re-optimization for prostate patients. The dosimetric and geometric accuracy was shown for a full IDC workflow using film and diode array dosimetry.
Background and purposeRadiotherapy plan verification is generally performed on the reference plan based on the pre-treatment anatomy. However, the introduction of online adaptive treatments demands a ...new approach, as plans are created daily on different anatomies. The aim of this study was to experimentally validate the accuracy of total doses of multi-fraction plan adaptations in magnetic resonance imaging guided radiotherapy in a phantom study, isolated from the uncertainty of deformable image registration.Materials and methodsWe experimentally verified the total dose, measured on external beam therapy 3 (EBT3) film, using a treatment with five online adapted fractions. Three series of experiments were performed, each focusing on a category of inter-fractional variation; translations, rotations and body modifications. Variations were introduced during each fraction and adapted plans were generated and irradiated. Single fraction doses and total doses over five online adapted fractions were investigated.ResultsThe online adapted measurements and calculations showed a good agreement for single fractions and multi-fraction treatments for the dose profiles, gamma passing rates, dose deviations and distances to agreement. The gamma passing rate using a 2%/2 mm criterion ranged from 99.2% to 99.5% for a threshold dose of 10% of the maximum dose (Dmax) and from 96.2% to 100% for a threshold dose of 90% of Dmax, for the total translations, rotations and body modifications.ConclusionsThe total doses of multi-fraction treatments showed similar accuracies compared to single fraction treatments, indicating an accurate dosimetric outcome of a multi-fraction treatment in adaptive magnetic resonance imaging guided radiotherapy.
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