Optimization of treatment workflow for 0.35T MR-Linac system.

PURPOSE: This study presents a novel and comprehensive framework for evaluating magnetic resonance guided radiotherapy (MRgRT) workflow by integrating the Failure Modes and Effects Analysis (FMEA) approach with Time-Driven Activity-Based Costing (TDABC). We assess the workflow for safety, quality, and economic implications, providing a holistic understanding of the MRgRT implementation. The aim is to offer valuable insights to healthcare practitioners and administrators, facilitating informed decision-making regarding the 0.35T MRIdian MR-Linac system's clinical workflow. METHODS: For FMEA, a multidisciplinary team followed the TG-100 methodology to assess the MRgRT workflow's potential failure modes. Following the mitigation of primary failure modes and workflow optimization, a treatment process was established for TDABC analysis. The TDABC was applied to both MRgRT and computed tomography guided RT (CTgRT) for typical five-fraction stereotactic body RT (SBRT) treatments, assessing total workflow and costs associated between the two treatment workflows. RESULTS: A total of 279 failure modes were identified, with 31 categorized as high-risk, 55 as medium-risk, and the rest as low-risk. The top 20% risk priority numbers (RPN) were determined for each radiation oncology care team member. Total MRgRT and CTgRT costs were assessed. Implementing technological advancements, such as real-time multi leaf collimator (MLC) tracking with volumetric modulated arc therapy (VMAT), auto-segmentation, and increasing the Linac dose rate, led to significant cost savings for MRgRT. CONCLUSION: In this study, we integrated FMEA with TDABC to comprehensively evaluate the workflow and the associated costs of MRgRT compared to conventional CTgRT for five-fraction SBRT treatments. FMEA analysis identified critical failure modes, offering insights to enhance patient safety. TDABC analysis revealed that while MRgRT provides unique advantages, it may involve higher costs. Our findings underscore the importance of exploring cost-effective strategies and key technological advancements to ensure the widespread adoption and financial sustainability of MRgRT in clinical practice.

Electron streaming dose measurements and calculations on a 1.5 T MR-Linac.

PURPOSE: To evaluate the accuracy of different dosimeters and the treatment planning system (TPS) for assessing the skin dose due to the electron streaming effect (ESE) on a 1.5 T magnetic resonance (MR)-linac. METHOD: Skin dose due to the ESE on an MR-linac (Unity, Elekta) was investigated using a solid water phantom rotated 45° in the x-y plane (IEC61217) and centered at the isocenter. The phantom was irradiated with 1 × 1, 3 × 3, 5 × 5, 10 × 10, and 22 × 22 cm2 fields, gantry at 90°. Out-of-field doses (OFDs) deposited by electron streams generated at the entry and exit surface of the angled phantom were measured on the surface of solid water slabs placed ±20.0 cm from the isocenter along the x-direction. A high-resolution MOSkin™ detector served as a benchmark due to its shallower depth of measurement that matches the International Commission on Radiological Protection (ICRP) recommended depth for skin dose assessment (0.07 mm). MOSkin™ doses were compared to EBT3 film, OSLDs, a diamond detector, and the TPS where the experimental setup was modeled using two separate calculation parameters settings: a 0.1 cm dose grid with 0.2% statistical uncertainty (0.1 cm, 0.2%) and a 0.2 cm dose grid with 3.0% statistical uncertainty (0.2 cm, 3.0%). RESULTS: OSLD, film, the 0.1 cm, 0.2%, and 0.2 cm, 3.0% TPS ESE doses, underestimated skin doses measured by the MOSkin™ by as much as -75.3%, -7.0%, -24.7%, and -41.9%, respectively. Film results were most similar to MOSkin™ skin dose measurements. CONCLUSIONS: These results show that electron streams can deposit significant doses outside the primary field and that dosimeter choice and TPS calculation settings greatly influence the reported readings. Due to the steep dose gradient of the ESE, EBT3 film remains the choice for accurate skin dose assessment in this challenging environment.

Randomized phase II trial of MRI-guided salvage radiotherapy for prostate cancer in 4 weeks versus 2 weeks (SHORTER).

BACKGROUND: Ultra-hypofractionated image-guided stereotactic body radiotherapy (SBRT) is increasingly used for definitive treatment of localized prostate cancer. Magnetic resonance imaging-guided radiotherapy (MRgRT) facilitates improved visualization, real-time tracking of targets and/or organs-at-risk (OAR), and capacity for adaptive planning which may translate to improved targeting and reduced toxicity to surrounding tissues. Given promising results from NRG-GU003 comparing conventional and moderate hypofractionation in the post-operative setting, there is growing interest in exploring ultra-hypofractionated post-operative regimens. It remains unclear whether this can be done safely and whether MRgRT may help mitigate potential toxicity. SHORTER (NCT04422132) is a phase II randomized trial prospectively evaluating whether salvage MRgRT delivered in 5 fractions versus 20 fractions is non-inferior with respect to gastrointestinal (GI) and genitourinary (GU) toxicities at 2-years post-treatment. METHODS: A total of 136 patients will be randomized in a 1:1 ratio to salvage MRgRT in 5 fractions or 20 fractions using permuted block randomization. Patients will be stratified according to baseline Expanded Prostate Cancer Index Composite (EPIC) bowel and urinary domain scores as well as nodal treatment and androgen deprivation therapy (ADT). Patients undergoing 5 fractions will receive a total of 32.5 Gy over 2 weeks and patients undergoing 20 fractions will receive a total of 55 Gy over 4 weeks, with or without nodal coverage (25.5 Gy over 2 weeks and 42 Gy over 4 weeks) and ADT as per the investigator's discretion. The co-primary endpoints are change scores in the bowel and the urinary domains of the EPIC. The change scores will reflect the 2-year score minus the pre-treatment (baseline) score. The secondary endpoints include safety endpoints, including change in GI and GU symptoms at 3, 6, 12 and 60 months from completion of treatment, and efficacy endpoints, including time to progression, prostate cancer specific survival and overall survival. DISCUSSION: The SHORTER trial is the first randomized phase II trial comparing toxicity of ultra-hypofractionated and hypofractionated MRgRT in the salvage setting. The primary hypothesis is that salvage MRgRT delivered in 5 fractions will not significantly increase GI and GU toxicities when compared to salvage MRgRT delivered in 20 fractions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04422132. Date of registration: June 9, 2020.

A randomized phase II trial of MR-guided prostate stereotactic body radiotherapy administered in 5 or 2 fractions for localized prostate cancer (FORT).

BACKGROUND: Ultra-hypofractionated regimens for definitive prostate cancer (PCa) radiotherapy are increasingly utilized due in part to promising safety and efficacy data complemented by greater patient convenience from a treatment course requiring fewer sessions. As such, stereotactic body radiation therapy (SBRT) is rapidly emerging as a standard definitive treatment option for patients with localized PCa. The commercially available magnetic resonance linear accelerator (MR-LINAC) integrates MR imaging with radiation delivery, providing several theoretical advantages compared to computed tomography (CT)-guided radiotherapy. MR-LINAC technology facilitates improved visualization of the prostate, real-time intrafraction tracking of prostate and organs-at-risk (OAR), and online adaptive planning to account for target movement and anatomical changes. These features enable reduced treatment volume margins and improved sparing of surrounding OAR. The theoretical advantages of MR-guided radiotherapy (MRgRT) have recently been shown to significantly reduce rates of acute grade ≥ 2 GU toxicities as reported in the prospective randomized phase III MIRAGE trial, which compared MR-LINAC vs CT-based 5 fraction SBRT in patients with localized PCa (Kishan et al. JAMA Oncol 9:365-373, 2023). Thus, MR-LINAC SBRT-utilizing potentially fewer treatments-is warranted and clinically relevant for men with low or intermediate risk PCa electing for radiotherapy as definitive treatment. METHODS/DESIGN: A total of 136 men with treatment naïve low or intermediate risk PCa will be randomized in a 1:1 ratio to 5 or 2 fractions of MR-guided SBRT using permuted block randomization. Randomization is stratified by baseline Expanded PCa Index Composite (EPIC) bowel and urinary domain scores. Patients undergoing 5 fractions will receive 37.5 Gy to the prostate over 10-14 days and patients undergoing 2 fractions will receive 25 Gy to the prostate over 7-10 days. The co-primary endpoints are GI and GU toxicities as measured by change scores in the bowel and urinary EPIC domains, respectively. The change scores will be calculated as pre-treatment (baseline) score subtracted from the 2-year score. DISCUSSION: FORT is an international, multi-institutional prospective randomized phase II trial evaluating whether MR-guided SBRT delivered in 2 fractions versus 5 fractions is non-inferior from a gastrointestinal (GI) and genitourinary (GU) toxicity standpoint at 2 years post-treatment in men with low or intermediate risk PCa. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04984343 . Date of registration: July 30, 2021. PROTOCOL VERSION: 4.0, Nov 8, 2022.

Evaluating motion of pancreatic tumors and anatomical surrogates using cine MRI in 0.35T MRgRT under free breathing conditions.

Treatment tolerability is a significant limitation to pancreatic cancer treatment with radiotherapy due to proximity to highly radiosensitive organs and respiratory motion necessitating expanded target margins. Further, pancreatic tumors are difficult to visualize on conventional radiotherapy systems. Surrogates are often used to locate the tumor but are often inconsistent and do not provide strong positional relations throughout the respiratory cycle. This work utilizes a retrospective dataset of 45 pancreatic cancer patients treated on an MR-Linac system with cine MRI acquired for real-time target tracking. We investigated intra-fraction motion of tumors and two abdominal surrogates, leading to prediction models between the tumor and surrogate. Patient specific motion evaluation and prediction models were generated from 225 cine MRI series acquired during treatment. Tumor contours were used to evaluate the pancreatic tumor motion. Linear regression and principal component analysis (PCA) based models were used to predict tumor position from the anterior-posterior (AP) motion of the abdominal surface, the superior-inferior (SI) motion of the diaphragm, or a combination. Models were evaluated using mean squared error (MSE) and mean absolute error (MAE). Contour analysis showed the average pancreatic tumor motion range was 7.4 ± 2.7 mm and 14.9 ± 5.8 mm in the AP and SI directions, respectively. The PCA model had MSE of 1.4 mm2 and 0.6 mm2 , for the SI and AP directions, respectively, with both surrogates as inputs for the models. When only the abdomen surrogate was used, MSE was 1.3 mm2 and 0.4 mm2 in the SI and AP directions, while it was 0.4 mm2 and 1.3 mm2 when only the diaphragm surrogate was used. We evaluated intra-fraction pancreatic tumor motion and demonstrated prediction models between the tumor and surrogate. The models calculated the pancreatic tumor position from diaphragm, abdominal, or both contours within standard pancreatic cancer target margin, and the process could be applied to other disease sites in the abdominothoracic cavity.

Commissioning, clinical implementation, and initial experience with a new brain tumor treatment package on a low-field MR-linac.

To evaluate the image quality, dosimetric properties, setup reproducibility, and planar cine motion detection of a high-resolution brain coil and integrated stereotactic brain immobilization system that constitute a new brain treatment package (BTP) on a low-field magnetic resonance imaging (MRI) linear accelerator (MR-linac). Image quality of the high-resolution brain coil was evaluated with the 17 cm diameter spherical phantom and the American College of Radiology (ACR) Large MRI Phantom. Patient imaging studies approved by the institutional review board (IRB) assisted in selecting image acquisition parameters. Radiographic and dosimetric evaluation of the high-resolution brain coil and the associated immobilization devices was performed using dose calculations and ion chamber measurements. End-to-end testing was performed simulating a cranial lesion in a phantom. Inter-fraction setup variability and motion detection tests were evaluated on four healthy volunteers. Inter-fraction variability was assessed based on three repeat setups for each volunteer. Motion detection was evaluated using three-plane (axial, coronal, and sagittal) MR-cine imaging sessions, where volunteers were asked to perform a set of specific motions. The images were post-processed and evaluated using an in-house program. Contrast resolution of the high-resolution brain coil is superior to the head/neck and torso coils. The BTP receiver coils have an average HU value of 525 HU. The most significant radiation attenuation (3.14%) of the BTP, occurs through the lateral portion of the overlay board where the high-precision lateral-profile mask clips attach to the overlay. The greatest inter-fraction setup variability occurred in the pitch (average 1.08 degree) and translationally in the superior/inferior direction (average 4.88 mm). Three plane cine imaging with the BTP was able to detect large and small motions. Small voluntary motions, sub-millimeter in magnitude (maximum 0.9 mm), from motion of external limbs were detected. Imaging tests, inter-fraction setup variability, attenuation, and end-to-end measurements were quantified and performed for the BTP. Results demonstrate better contrast resolution and low contrast detectability that allows for better visualization of soft tissue anatomical changes relative to head/neck and torso coil systems.

Characterization of mechanical and radiation isocenter on an MR-guided radiotherapy (MRgRT) Linac.

BACKGROUND AND PURPOSE: In the emerging paradigm of stereotactic radiosurgery being proposed for MR-guided radiotherapy (MRgRT), assessment of mechanical geometric accuracy is critical for the implementation of stereotactic delivery. We benchmarked the mechanical accuracy of an MR Linac system that lacks an onboard detector/array. Our mechanical tests utilize a half beam block (HBB) geometry that takes advantage of the sensitivity of a partially occluded detector. MATERIALS AND METHODS: Mechanical tests benchmarked the couch, MLC, and gantry geometric accuracy for an MR-Linac system. An HBB technique was used to irradiate an ionization chamber profiler (ICP) array with partial occlusion of individual detectors for characterization of MLC skew, beam divergence displacement, and RT isocenter localization. The sensitivity of the partially occluded detector's ICP-X (detector width) and ICP-Y (detector length) was characterized by displacing the detector relative to radiation isocenter by 0.2 mm increments, introduced through couch motion. The accuracy of the HBB ICP technique was verified with a starshot using radiochromic film, and the reproducibility was verified on a conventional C-arm Linac and compared to Winston-Lutz. RESULTS: The sensitivity of the HBB technique as quantified through the dose difference normalized to open field as a function of displacement from RT isocenter was 6.4%/mm and 13.0%/mm for the ICP-X and ICP-Y orientation, respectively, due to the oblong detector orientation. Couch positional accuracy and sag was within ±0.1 mm. Maximum MLC positional displacement was 0.7 mm with mean MLC skew at 0.07°. The maximum beam divergence displacement was 0.03 mm. The gantry angle was within 0.1°. Independent verification of the RT isocenter localization procedure produced repeatable results. CONCLUSION: This work serves for characterizing the mechanical and geometric radiation accuracy for the foundation of an MR-guided stereotactic radiosurgery program, as demonstrated with high sensitivity and independent validation.

Quantifying uncertainties associated with reference dosimetry in an MR-Linac.

BACKGROUND: Magnetic resonance (MR)-guided radiation therapy provides capabilities to utilize high-resolution and real-time MR imaging before and during treatment, which is critical for adaptive radiotherapy. This emerging modality has been promptly adopted in the clinic settings in advance of adaptations to reference dosimetry formalism that are needed to account for the presence of strong magnetic fields. In particular, the influence of magnetic field on the uncertainty of parameters in the reference dosimetry equation needs to be determined in order to fully characterize the uncertainty budget for reference dosimetry in MR-guided radiation therapy systems. PURPOSE: To identify and quantify key sources of uncertainty in the reference dosimetry of external high energy radiotherapy beams in the presence of a strong magnetic field. METHODS: In the absence of a formalized Task Group report for reference dosimetry in MR-integrated linacs, the currently suggested formalism follows the TG-51 protocol with the addition of a quality conversion factor kBQ accounting for the effects of the magnetic field on ionization chamber response. In this work, we quantify various sources of uncertainty that impact each of the parameters in the formalism, and evaluate their overall contribution to the final dose. Measurements are done in a 1.5 T MR-Linac (Unity, Elekta AB, Stockholm, Sweden) which integrates a 1.5 T Philips MR scanner and a 7 MVFFF linac. The responses of several reference-class small volume ionization chambers (Exradin:A1SL, IBA:CC13, PTW:Semiflex-3D) and Farmer type ionization chambers (Exradin:A19, IBA:FC65-G) were evaluated throughout this process. Long-term reproducibility and stability of beam quality, TPR 10 20 ${\mathrm{TPR}}_{10}^{20}$ , was also measured with an in-house built phantom. RESULTS: Relative to the conventional external high energy linacs, the uncertainty on overall reference dose in MR-linac is more significantly affected by the chamber setup: A translational displacement along y-axis of ± 3 mm results in dose variation of < |0.20| ± 0.02% (k = 1), while rotation of ± 5° in horizontal and vertical parallel planes relative to relative to the direction of magnetic field, did not exceed variation of < |0.44| ± 0.02% for all 5 ionization chambers. We measured a larger dose variation for xy-plane (horizontal) rotations (< |0.44| ± 0.02% (k = 1)) than for yz-plane (vertical) rotations (< ||0.28| ± 0.02% (k = 1)), which we associate with the gradient of kB,Q as a function of chamber orientation with respect to direction of the B0 -field. Uncertainty in Pion (for two depths), Ppol (with various sub-studies including effects of cable length, cable looping in the MRgRT bore, connector type in magnetic environment), and Prp were determined. Combined conversion factor kQ × kB,Q was provided for two reference depths at four cardinal angle orientations. Over a two-year period, beam quality was quite stable with TPR 10 20 ${\mathrm{TPR}}_{10}^{20}$ being 0.669 ± 0.01%. The actual magnitude of TPR 10 20 ${\mathrm{TPR}}_{10}^{20}$ was measured using identical equipment and compared between two different Elekta Unity MR-Linacs with results agreeing to within 0.21%. CONCLUSION: In this work, the uncertainty of a number of parameters influencing reference dosimetry was quantified. The results of this work can be used to identify best practice guidelines for reference dosimetry in the presence of magnetic fields, and to evaluate an uncertainty budget for future reference dosimetry protocols for MR-linac.

An independent Monte Carlo-based IMRT QA tool for a 0.35 T MRI-guided linear accelerator.

PURPOSE: To develop an independent log file-based intensity-modulated radiation therapy (IMRT) quality assurance (QA) tool for the 0.35 T magnetic resonance-linac (MR-linac) and investigate the ability of various IMRT plan complexity metrics to predict the QA results. Complexity metrics related to tissue heterogeneity were also introduced. METHODS: The tool for particle simulation (TOPAS) Monte Carlo code was utilized with a previously validated linac head model. A cohort of 29 treatment plans was selected for IMRT QA using the developed QA tool and the vendor-supplied adaptive QA (AQA) tool. For 27 independent patient cases, various IMRT plan complexity metrics were calculated to assess the deliverability of these plans. A correlation between the gamma pass rates (GPRs) from the AQA results and calculated IMRT complexity metrics was determined using the Pearson correlation coefficients. Tissue heterogeneity complexity metrics were calculated based on the gradient of the Hounsfield units. RESULTS: The median and interquartile range for the TOPAS GPRs (3%/3 mm criteria) were 97.24% and 3.75%, respectively, and were 99.54% and 0.36% for the AQA tool, respectively. The computational time for TOPAS ranged from 4 to 8 h to achieve a statistical uncertainty of <1.5%, whereas the AQA tool had an average calculation time of a few minutes. Of the 23 calculated IMRT plan complexity metrics, the AQA GPRs had correlations with 7 out of 23 of the calculated metrics. Strong correlations (|r| > 0.7) were found between the GPRs and the heterogeneity complexity metrics introduced in this work. CONCLUSIONS: An independent MC and log file-based IMRT QA tool was successfully developed and can be clinically deployed for offline QA. The complexity metrics will supplement QA reports and provide information regarding plan complexity.

Linac-based versus MR-guided SBRT for localized prostate cancer: a comparative evaluation of acute tolerability.

AIM: This study aims to compare acute toxicity of prostate cancer (PCa) stereotactic body radiotherapy (SBRT) delivered by MR-guided radiotherapy (MRgRT) with 1.5-T MR-linac or by volumetric modulated arc (VMAT) with conventional linac. METHODS: Patients with low-to-favorable intermediate risk class PCa were treated with exclusive SBRT (35 Gy in five fractions). Patients treated with MRgRT were enrolled in an Ethical Committee (EC) approved trial (Prot. n° 23,748), while patients treated with conventional linac were enrolled in an EC approved phase II trial (n° SBRT PROG112CESC). The primary end-point was the acute toxicity. Patients were included in the analysis if they had at least 6 months of follow-up for the primary end-point evaluation. Toxicity assessment was performed according to CTCAE v5.0 scale. International Prostatic Symptoms Score (IPSS) was also performed. RESULTS: A total of 135 patients were included in the analysis. Seventy-two (53.3%) were treated with MR-linac and 63 (46.7%) with conventional linac. The median initial PSA before RT was 6.1 ng/ml (range 0.49-19). Globally, acute G1, G2, and G3 toxicity occurred in 39 (28.8%), 20 (14.5%), and 5 (3.7%) patients. At the univariate analysis, acute G1 toxicity did not differ between MR-linac and conventional linac (26.4% versus 31.8%), as well as G2 toxicity (12.5% versus 17.5%; p = 0.52). Acute G2 gastrointestinal (GI) toxicity occurred in 7% and 12.5% of cases in MR-linac and conventional linac group, respectively (p = 0.06), while acute G2 genitourinary toxicity occurred in 11% and 12.8% in MR-linac and conventional linac, respectively (p = 0.82). The median IPSS before and after SBRT was 3 (1-16) and 5 (1-18). Acute G3 toxicity occurred in two cases in the MR-linac and three cases in the conventional linac group (p = n.s.). CONCLUSION: Prostate SBRT with 1.5-T MR-linac is feasible and safe. Compared to conventional linac, MRgRT might to potentially reduce the overall G1 acute toxicity at 6 months, and seems to show a trend toward a lower incidence of grade 2 GI toxicity. A longer follow-up is necessary to assess the late efficacy and toxicity.

Stereotactic ablative radiotherapy or best supportive care in patients with localized pancreatic cancer not receiving chemotherapy and surgery (PANCOSAR): a nationwide multicenter randomized controlled trial according to a TwiCs design.

BACKGROUND: Significant comorbidities, advanced age, and a poor performance status prevent surgery and systemic treatment for many patients with localized (non-metastatic) pancreatic ductal adenocarcinoma (PDAC). These patients are currently treated with 'best supportive care'. Therefore, it is desirable to find a treatment option which could improve both disease control and quality of life in these patients. A brief course of high-dose high-precision radiotherapy i.e. stereotactic ablative body radiotherapy (SABR) may be feasible. METHODS: A nationwide multicenter trial performed within a previously established large prospective cohort (the Dutch Pancreatic cancer project; PACAP) according to the 'Trial within cohorts' (TwiCs) design. Patients enrolled in the PACAP cohort routinely provide informed consent to answer quality of life questionnaires and to be randomized according to the TwiCs design when eligible for a study. Patients with localized PDAC who are unfit for chemotherapy and surgery or those who refrain from these treatments are eligible. Patients will be randomized between SABR (5 fractions of 8 Gy) with 'best supportive care' and 'best supportive care' only. The primary endpoint is overall survival from randomization. Secondary endpoints include preservation of quality of life (EORTC-QLQ-C30 and -PAN26), NRS pain score response and WHO performance scores at baseline, and, 3, 6 and 12 months. Acute and late toxicity will be scored using CTCAE criteria version 5.0: assessed at baseline, day of last fraction, at 3 and 6 weeks, and 3, 6 and 12 months following SABR. DISCUSSION: The PANCOSAR trial studies the added value of SBRT as compared to 'best supportive care' in patients with localized PDAC who are medically unfit to receive chemotherapy and surgery, or refrain from these treatments. This study will assess whether SABR, in comparison to best supportive care, can relieve or delay tumor-related symptoms, enhance quality of life, and extend survival in these patients. TRIAL REGISTRATION: Clinical trials, NCT05265663 , Registered March 3 2022, Retrospectively registered.

Neurovascular-Sparing MR-Guided Adaptive Radiotherapy in Prostate Cancer; Defining the Potential Population for Erectile Function-Sparing Treatment.

BACKGROUND: Magnetic resonance-guided adaptive radiotherapy (MRgRT) enables neurovascular-sparing treatment for localized prostate cancer (PCa). The aim of this treatment is preservation of erectile function by sparing the neurovascular bundles, the internal pudendal arteries, the corpora cavernosa, and the penile bulb. Internal pudendal arteries, corpora cavernosa, and penile bulb sparing can generally be achieved in all patients, but NVB sparing can be challenging due to its proximity to the prostate and is therefore dependent on tumor location. PCa patients that have sufficient erectile function at baseline and favorable tumor characteristics might benefit from this treatment. Currently, it is unclear what proportion of patients are eligible for neurovascular-sparing treatment and to what extent this is technically feasible. AIM: To define the eligibility and technical feasibility for neurovascular-sparing MRgRT in intermediate-risk localized PCa patients. METHODS: A consecutive series of men that received 5 × 7.25 gray (Gy) MRgRT for localized PCa were included. Baseline erectile function was assessed using the International Index of Erectile Function (IIEF)-5 questionnaire. Additionally, the ability of sparing the neurovascular bundles was assessed in all patients. Per neurovascular-sparing protocol, the dominant intraprostatic lesion with a 4 mm isotropic margin should receive 34.44 Gy in ≥ 99% of the volume (i.e., high-dose area). When the high-dose area directly borders or overlaps the NVB because of a dorsolateral position of the dominant intraprostatic lesion, sparing of the NVB was considered not feasible on that side. OUTCOMES: Patient-reported IIEF-5 baseline questionnaires and the technical feasibility of NVB sparing were assessed. RESULTS: Of the 102 men that completed the IIEF-5 questionnaire at baseline, 49.0% of patients reported to have an IIEF-5 score of ≥ 17. In those patients, the NVB could technically have been spared bilaterally in 20.0% and unilaterally in 68.0%. CLINICAL IMPLICATIONS: Our findings define the potential population for neurovascular-sparing MRgRT for localized PCa and indicate the proportion in which the NVB can technically be spared. STRENGTH & LIMITATIONS: The major strength of this study is the prospective collection of data. The limitations include that the neurovascular-sparing feasibility definition is based on pre-clinical planning data. CONCLUSION: A substantial group of 49.0% of patients in our study had mild or no erectile dysfunction at baseline. Of these patients, the NVB could technically have been spared bilaterally in 20.0% and unilaterally in 68.0% during MRgRT. Trials need to assess the effect of neurovascular-sparing MRgRT on erectile function. Teunissen FR, van der Voort van Zyp JRN, Verkooijen HM, et al., Neurovascular-Sparing MR-Guided Adaptive Radiotherapy in Prostate Cancer; Defining the Potential Population for Erectile Function-Sparing Treatment. J Sex Med 2022;19:1196-1200.

Commissioning a secondary dose calculation software for a 0.35 T MR-linac.

Secondary external dose calculations for a 0.35 T magnetic resonance image-guided radiation therapy (MRgRT) are needed within the radiation oncology community to follow safety standards set forth within the field. We evaluate the commercially available software, RadCalc, in its ability to accurately perform monitor unit dose calculations within a magnetic field. We also evaluate the potential effects of a 0.35 T magnetic field upon point dose calculations. Monitor unit calculations were evaluated with (wMag) and without (noMag) a magnetic field considerations in RadCalc for the ViewRay MRIdian. The magnetic field is indirectly accounted for by using asymmetric profiles for calculation. The introduction of double-stacked multi-leaf collimator leaves was also included in the monitor unit calculations and a single transmission value was determined. A suite of simple and complex geometries with a variety field arrangements were calculated for each method to demonstrate the effect of the 0.35 T magnetic field on monitor unit calculations. Finally, 25 patient-specific treatment plans were calculated using each method for comparison. All simple geometries calculated in RadCalc were within 2% of treatment planning system (TPS) values for both methods, except for a single noMag off-axis comparison. All complex muilt-leaf collimator (MLC) pattern calculations were within 5%. All complex phantom geometry calculations were within 5% except for a single field within a lung phantom at a distal point. For the patient calculations, the noMag method average percentage difference was 0.09 ± 2.5% and the wMag average percentage difference was 0.08 ± 2.5%. All results were within 5% for the wMag method. We performed monitor unit calculations for a 0.35 T MRgRT system using a commercially available secondary monitor unit dose calculation software and demonstrated minimal impact of the 0.35 T magnetic field on monitor unit dose calculations. This is the first investigation demonstrating successful calculations of dose using RadCalc in the low-field 0.35 T ViewRay MRIdian system.

Evaluation of diffusion-weighted MRI and geometric distortion on a 0.35T MR-LINAC at multiple gantry angles.

Diffusion-weighted imaging (DWI) provides a valuable diagnostic tool for tumor evaluation. Yet, it is difficult to acquire daily MRI data sets in the traditional radiotherapy clinical setting due to patient burden and limited resources. However, integrated MRI radiotherapy treatment systems facilitate daily functional MRI acquisitions like DWI during treatment exams. Before ADC values from MR-RT systems can be used clinically their reproducibility and accuracy must be quantified. This study used a NIST traceable DWI phantom to verify ADC values acquired on a 0.35 T MR-LINAC system at multiple gantry angles. A diffusion-weighted echo planar imaging sequence was used for all image acquisitions, with b-values of 0, 500, 900, 2000 s/mm2 for the 1.5 T and 3.0 T systems and 0, 200, 500, 800 s/mm2 for the 0.35 T system. Images were acquired at multiple gantry angles on the MR-LINAC system from 0° to 330° in 30° increments to assess the impact of gantry angle on geometric distortion and ADC values. CT images, and three fiducial markers were used as ground truth for geometric distortion measurements. The distance between fiducial markers increased by as much as 7.2 mm on the MR-LINAC at gantry angle 60°. ADC values of deionized water vials from the 1.5 T and 3.0 T systems were 8.30 × 10-6  mm2 /s and -0.85 × 10-6  mm2 /s off, respectively, from the expected value of 1127 × 10-6  mm2 /s. The MR-LINAC system provided an ADC value of the pure water vials that was -116.63 × 10-6  mm2 /s off from the expected value of 1127 × 10-6  mm2 /s. The MR-LINAC also showed a variation in ADC across all gantry angles of 33.72 × 10-6  mm2 /s and 20.41 × 10-6  mm2 /s for the vials with expected values of 1127 × 10-6  mm2 /s and 248 × 10-6  mm2 /s, respectively. This study showed that variation of the ADC values and geometric information on the 0.35 T MR-LINAC system was dependent on the gantry angle at acquisition.

First clinical experience of correcting phantom-based image distortion related to gantry position on a 0.35T MR-Linac.

MR-guided radiotherapy requires strong imaging spatial integrity to deliver high quality plans and provide accurate dose calculation. The MRI system, however, can be compromised by the integrated linear accelerator (Linac), resulting in inaccurate imaging isocenter position and geometric distortion. Dependence on gantry position further complicates the correction of distortions. This work presents a new clinical application of a commercial phantom and software system that quantifies isocenter alignment and geometric distortion, as well as providing a deformation vector field (DVF). A large distortion phantom and a smaller grid phantom were imaged at multiple gantry angles from 0 to 330° on a 0.35 T integrated MR-Linac. The software package was used to assess geometric distortion and generate DVFs to correct distortions within the phantom volume. The DVFs were applied to the grid phantom with resampling software then evaluated using structural similarity index measure (SSIM). Scans were also performed with a ferromagnetic clip near the phantom to investigate the correction of more severe artifacts. The mean magnitude isocenter shift was 0.67 mm, ranging from 0.25 to 1.04 mm across all angles. The DVF had a mean component value of 0.27 ± 0.02, 0.24 ± 0.01, and 0.19 ± 0.01 mm in the right-left (RL), anterior-posterior (AP), and superior-inferior (SI) directions. The ferromagnetic clip increased isocenter position error from 1.98 mm to 2.20 mm and increased mean DVF component values in the RL and AP directions. The resampled grid phantom had an increased SSIM for all gantry angles compared to original images, increasing from 0.26 ± 0.001 to 0.70 ± 0.004. Through this clinical assessment, we were able to correct geometric distortion and isocenter shift related to gantry position on a 0.35 T MR-Linac using the distortion phantom and software package. This provides encouragement that it could be used for quality assurance and clinically to correct systematic distortion caused by imaging at different gantry angles.

Clinical assessment of geometric distortion for a 0.35T MR-guided radiotherapy system.

PURPOSE: To estimate the overall spatial distortion on clinical patient images for a 0.35 T MR-guided radiotherapy system. METHODS: Ten patients with head-and-neck cancer underwent CT and MR simulations with identical immobilization. The MR images underwent the standard systematic distortion correction post-processing. The images were rigidly registered and landmark-based analysis was performed by an anatomical expert. Distortion was quantified using Euclidean distance between each landmark pair and tagged by tissue interface: bone-tissue, soft tissue, or air-tissue. For baseline comparisons, an anthropomorphic phantom was imaged and analyzed. RESULTS: The average spatial discrepancy between CT and MR landmarks was 1.15 ± 1.14 mm for the phantom and 1.46 ± 1.78 mm for patients. The error histogram peaked at 0-1 mm. 66% of the discrepancies were <2 mm and 51% <1 mm. In the patient data, statistically significant differences (p-values < 0.0001) were found between the different tissue interfaces with averages of 0.88 ± 1.24 mm, 2.01 ± 2.20 mm, and 1.41 ± 1.56 mm for the air/tissue, bone/tissue, and soft tissue, respectively. The distortion generally correlated with the in-plane radial distance from the image center along the longitudinal axis of the MR. CONCLUSION: Spatial distortion remains in the MR images after systematic distortion corrections. Although the average errors were relatively small, large distortions observed at bone/tissue interfaces emphasize the need for quantitative methods for assessing and correcting patient-specific spatial distortions.

An investigation of using log-file analysis for automated patient-specific quality assurance in MRgRT.

OBJECTIVE: Adaptive radiation therapy (ART) is an integral part of MR-guided RT (MRgRT), requiring a new RT plan for each treatment fraction and resulting in a significant increase in patient-specific quality assurance (PSQA). This study investigates the possibility of using treatment log-file for automated PSQA. METHOD: All treatment plans were delivered in 1.5T Unity MR-Linac (Elekta). A Unity compatible version of LinacView (Standard Imaging) was commissioned to automatically monitor and analyze the log-files. A total of 220 fields were delivered and measured by ArcCheck® -MR (Sun Nuclear) and LinacView. Thirty incorrectly matched fields were also delivered to check for error detection sensitivity. The gamma analysis, γ, with 3%, 3 mm criteria was used in both ArcCheck® -MR and LinacView. Additionally, the gantry angle, jaws, and multileaf collimators (MLC) positions reported in the log-file were compared with plan positions using TG-142 criteria. RESULT: The γ (3%, 3 mm) for the 190 plans were found to be between the range of 72.5%-100.0% and 95.4%-100.0% for ArcCheck® -MR and LinacVeiw, respectively. All the delivered gantry angle and jaws were found to be within 0.2° and 2 mm. MLCs that were outside the guard leaves or under the diaphragms were found to have more than 1.0 mm discrepancy. This was attributed to the linac internal override for these MLCs and had no dosimetric impact. Excluding these discrepancies, all MLC positions were found to be within 1.0 mm. The γ (3%, 3 mm) for the 30 incorrectly matched fields were found to be 3.9%-84.8% and 0.1%-64.4% for ArcCheck® -MR and LinacVeiw, respectively. CONCLUSION: Significant ranked correlation demonstrates the automated log-file analysis can be used for PSQA and expedite the ART workflow. Ongoing PSQA will be compared with log-file analysis to investigate the longer term reproducibility and correlation.

Direct tumor visual feedback during free breathing in 0.35T MRgRT.

To present a tumor motion control system during free breathing using direct tumor visual feedback to patients in 0.35 T magnetic resonance-guided radiotherapy (MRgRT). We present direct tumor visualization to patients by projecting real-time cine MR images on an MR-compatible display system inside a 0.35 T MRgRT bore. The direct tumor visualization included anatomical images with a target contour and an auto-segmented gating contour. In addition, a beam-status sign was added for patient guidance. The feasibility was investigated with a six-patient clinical evaluation of the system in terms of tumor motion range and beam-on time. Seven patients without visual guidance were used for comparison. Positions of the tumor and the auto-segmented gating contour from the cine MR images were used in probability analysis to evaluate tumor motion control. In addition, beam-on time was recorded to assess the efficacy of the visual feedback system. The direct tumor visualization system was developed and implemented in our clinic. The target contour extended 3 mm outside of the gating contour for 33.6 ± 24.9% of the time without visual guidance, and 37.2 ± 26.4% of the time with visual guidance. The average maximum motion outside of the gating contour was 14.4 ± 11.1 mm without and 13.0 ± 7.9 mm with visual guidance. Beam-on time as a percentage was 43.9 ± 15.3% without visual guidance, and 48.0 ± 21.2% with visual guidance, but was not significantly different (P = 0.34). We demonstrated the clinical feasibility and potential benefits of presenting direct tumor visual feedback to patients in MRgRT. The visual feedback allows patients to visualize and attempt to minimize tumor motion in free breathing. The proposed system and associated clinical workflow can be easily adapted for any type of MRgRT.

Characterization of radiotherapy component impact on MR imaging quality for an MRgRT system.

Radiotherapy components of an magnetic resonnace-guided radiotherapy (MRgRT) system can alter the magnetic fields, causing spatial distortion and image deformation, altering imaging and radiation isocenter coincidence and the accuracy of dose calculations. This work presents a characterization of radiotherapy component impact on MR imaging quality in terms of imaging isocenter variation and spatial integrity changes on a 0.35T MRgRT system, pre- and postupgrade of the system. The impact of gantry position, MLC field size, and treatment table power state on imaging isocenter and spatial integrity were investigated. A spatial integrity phantom was used for all tests. Images were acquired for gantry angles 0-330° at 30° increments to assess the impact of gantry position. For MLC and table power state tests all images were acquired at the home gantry position (330°). MLC field sizes ranged from 1.66 to 27.4 cm edge length square fields. Imaging isocenter shift caused by gantry position was reduced from 1.7 mm at gantry 150° preupgrade to 0.9 mm at gantry 120° postupgrade. Maximum spatial integrity errors were 0.5 mm or less pre- and postupgrade for all gantry angles, MLC field sizes, and treatment table power states. However, when the treatment table was powered on, there was significant reduction in SNR. This study showed that gantry position can impact imaging isocenter, but spatial integrity errors were not dependent on gantry position, MLC field size, or treatment table power state. Significant isocenter variation, while reduced postupgrade, is cause for further investigation.

MOSFET dosimeter characterization in MR-guided radiation therapy (MRgRT) Linac.

PURPOSE: With the increasing use of MR-guided radiation therapy (MRgRT), it becomes important to understand and explore accuracy of medical dosimeters in the presence of magnetic field. The purpose of this work is to characterize metal-oxide-semiconductor field-effect transistors (MOSFETs) in MRgRT systems at 0.345 T magnetic field strength. METHODS: A MOSFET dosimetry system, developed by Best Medical Canada for in-vivo patient dosimetry, was used to study various commissioning tests performed on a MRgRT system, MRIdian® Linac. We characterized the MOSFET dosimeter with different cable lengths by determining its calibration factor, monitor unit linearity, angular dependence, field size dependence, percentage depth dose (PDD) variation, output factor change, and intensity modulated radiation therapy quality assurance (IMRT QA) verification for several plans. MOSFET results were analyzed and compared with commissioning data and Monte Carlo calculations. RESULTS: MOSFET measurements were not found to be affected by the presence of 0.345 T magnetic field. Calibration factors were similar for different cable length dosimeters either placed at the parallel or perpendicular direction to the magnetic field, with variations of less than 2%. The detector showed good linearity (R2  = 0.999) for 100-600 MUs range. Output factor measurements were consistent with ionization chamber data within 2.2%. MOSFET PDD measurements were found to be within 1% for 1-15 cm depth range in comparison to ionization chamber. MOSFET normalized angular response matched thermoluminescent detector (TLD) response within 5.5%. The IMRT QA verification data for the MRgRT linac showed that the percentage difference between ionization chamber and MOSFET was 0.91%, 2.05%, and 2.63%, respectively for liver, spine, and mediastinum. CONCLUSION: MOSFET dosimeters are not affected by the 0.345 T magnetic field in MRgRT system. They showed physics parameters and performance comparable to TLD and ionization chamber; thus, they constitute an alternative to TLD for real-time in-vivo dosimetry in MRgRT procedures.