PRESS RELEASE

ViewRay, Inc. (Nasdaq: VRAY) announced today the launch of a multi-center prospective clinical trial for locally advanced unresectable pancreatic cancer using MRIdian, the world’s first and only FDA-cleared MRI-guided radiation therapy system. This study is the first initiative of ViewRay’s Clinical Cooperative Think Tank (C2T2), a group of MRIdian clinical users focused on evidence gathering to support MR-guided radiation therapy.

Purpose

To report a single-institutional experience using magnetic resonance imaging (MRI) guided radiation therapy for the reirradiation of recurrent and second cancers of the head and neck.

Methods and materials

Between October 2014 and August 2016, 13 consecutive patients with recurrent or new primary cancers of the head and neck that occurred in a previously irradiated field were prospectively enrolled in an institutional registry trial to investigate the feasibility and efficacy of MRI guided radiation therapy using a 0.35-T MRI scanner with a cobalt-60 radiation therapy source called the ViewRay system (ViewRay Inc., Cleveland, OH). Eligibility criteria included biopsy-proven evidence of recurrent or new primary squamous cell carcinoma of the head and neck, measurable disease, and previous radiation to >60 Gy. MRI guided reirradiation was delivered either using intensity modulated radiation therapy with conventional fractionation to a median dose of 66 Gy or stereotactic body radiation therapy (SBRT) using 7 to 8 Gy fractions on nonconsecutive days to a median dose of 40 Gy. Two patients (17%) received concurrent chemotherapy.

Results

The 1- and 2-year estimates of in-field control were 72% and 72%, respectively. A total of 227 daily MRI scans were obtained to guide reirradiation. The 2-year estimates of overall survival and progression-free survival were 53% and 59%, respectively. There were no treatment-related fatalities or hospitalizations. Complications included skin desquamation, odynophagia, otitis externa, keratitis and/or conjunctivitis, and 1 case of aspiration pneumonia.

Conclusions

Our preliminary findings show that reirradiation with MRI guided radiation therapy results in effective disease control with relatively low morbidity for patients with recurrent and second primary cancers of the head and neck. The superior soft tissue resolution of the MRI scans that were used for planning and delivery has the potential to improve the therapeutic ratio.

PURPOSE

Magnetic resonance image (MRI) guided radiotherapy enables gating directly on the target position. We present an evaluation of an MRI-guided radiotherapy system's gating performance using an MRI-compatible respiratory motion phantom and radiochromic film. Our evaluation is geared toward validation of our institution's clinical gating protocol which involves planning to a target volume formed by expanding 5 mm about the gross tumor volume (GTV) and gating based on a 3 mm window about the GTV.

METHODS

The motion phantom consisted of a target rod containing high-contrast target inserts which moved in the superior-inferior direction inside a body structure containing background contrast material. The target rod was equipped with a radiochromic film insert. Treatment plans were generated for a 3 cm diameter spherical planning target volume, and delivered to the phantom at rest and in motion with and without gating. Both sinusoidal trajectories and tumor trajectories measured during MRI-guided treatments were used. Similarity of the gated dose distribution to the planned, motion-frozen, distribution was quantified using the gamma technique.

RESULTS

Without gating, gamma pass rates using 4%/3 mm criteria were 22-59% depending on motion trajectory. Using our clinical standard of repeated breath holds and a gating window of 3 mm with 10% target allowed outside the gating boundary, the gamma pass rate was 97.8% with 3%/3 mm gamma criteria. Using a 3 mm window and 10% allowed excursion, all of the patient tumor motion trajectories at actual speed resulting in at least 95% gamma pass rate at 4%/3 mm.

CONCLUSIONS

Our results suggest that the device can be used to compensate respiratory motion using a 3 mm gating margin and 10% allowed excursion results in conjunction with repeated breath holds. Full clinical validation requires a comprehensive evaluation of tracking performance in actual patient images, outside the scope of this study.

OBJECTIVE

To evaluate the feasibility of on-board diffusion-weighted imaging (DWI) with an integrated low-field MRI radiotherapy system to assess responses to neoadjuvant chemoradiation (NAC) in rectal cancer.

METHODS

A spin echo-based planar imaging diffusion sequence on a 0.35-T MRI radiotherapy system was acquired over the course of NAC. The apparent diffusion coefficients (ADCs) from the tumour regions of interest (ROIs) were calculated. A functional diffusion map (fDM) was created showing a pixelwise ADC analysis of the ROI over the course of treatment. Surgical pathology was correlated with ADC data.

RESULTS

Consecutive patients treated on a 0.35-T MRI radiotherapy system were evaluated. Patient A had the worst pathological response to NAC with a tumour regression score of 1 and was the only patient with a negative slope in the change of ADC values over the entire course of NAC, and during both the first and second half of NAC. The fDM from the first half of NAC for Patient A showed discrete dark areas in the tumour ROI, reflecting subregions with decreasing ADC values during NAC. Patient C had the most favourable pathological response to NAC with a Grade 3 response and was the only patient who had an increase in the slope in the change of ADC values from the first to the second half of NAC.

CONCLUSION

DWI using a low-field MRI radiotherapy system for evaluating the responses to NAC is feasible. Advances in knowledge: ADC values obtained using a 0.35-T MRI radiotherapy system over the course of NAC for rectal cancer correlate with pathological responses.

PURPOSE

Magnetic resonance imaging-guided radiation therapy has entered clinical practice at several major treatment centers. Treatment of early-stage non-small cell lung cancer with stereotactic body radiation therapy is one potential application of this modality, as some form of respiratory motion management is important to address. We hypothesize that magnetic resonance imaging-guided tri-cobalt-60 radiation therapy can be used to generate clinically acceptable stereotactic body radiation therapy treatment plans. Here, we report on a dosimetric comparison between magnetic resonance imaging-guided radiation therapy plans and internal target volume-based plans utilizing volumetric-modulated arc therapy.

MATERIALS AND METHODS

Ten patients with early-stage non-small cell lung cancer who underwent radiation therapy planning and treatment were studied. Following 4-dimensional computed tomography, patient images were used to generate clinically deliverable plans. For volumetric-modulated arc therapy plans, the planning tumor volume was defined as an internal target volume + 0.5 cm. For magnetic resonance imaging-guided plans, a single mid-inspiratory cycle was used to define a gross tumor volume, then expanded 0.3 cm to the planning tumor volume. Treatment plan parameters were compared.

RESULTS

Planning tumor volumes trended larger for volumetric-modulated arc therapy-based plans, with a mean planning tumor volume of 47.4 mL versus 24.8 mL for magnetic resonance imaging-guided plans ( P = .08). Clinically acceptable plans were achievable via both methods, with bilateral lung V20, 3.9% versus 4.8% ( P = .62). The volume of chest wall receiving greater than 30 Gy was also similar, 22.1 versus 19.8 mL ( P = .78), as were all other parameters commonly used for lung stereotactic body radiation therapy. The ratio of the 50% isodose volume to planning tumor volume was lower in volumetric-modulated arc therapy plans, 4.19 versus 10.0 ( P < .001). Heterogeneity index was comparable between plans, 1.25 versus 1.25 ( P = .98).

CONCLUSION

Magnetic resonance imaging-guided tri-cobalt-60 radiation therapy is capable of delivering lung high-quality stereotactic body radiation therapy plans that are clinically acceptable as compared to volumetric-modulated arc therapy-based plans. Real-time magnetic resonance imaging provides the unique capacity to directly observe tumor motion during treatment for purposes of motion management.

PURPOSE

The purpose of this study was to investigate the dosimetric feasibility of liver stereotactic body radiation therapy (SBRT) using a teletherapy system equipped with 3 rotating (60)Co sources (tri-(60)Co system) and a built-in magnetic resonance imager (MRI). We hypothesized tumor size and location would be predictive of favorable dosimetry with tri-(60)Co SBRT.

METHODS AND MATERIALS

The primary study population consisted of 11 patients treated with SBRT for malignant hepatic lesions whose linear accelerator (LINAC)-based SBRT plans met all mandatory Radiation Therapy Oncology Group (RTOG) 1112 organ-at-risk (OAR) constraints. The secondary study population included 5 additional patients whose plans did not meet the mandatory constraints. Patients received 36 to 60 Gy in 3 to 5 fractions. Tri-(60)Co system SBRT plans were planned with ViewRay system software.

RESULTS

All patients in the primary study population had tri-(60)Co SBRT plans that passed all RTOG constraints, with similar planning target volume coverage and OAR doses to LINAC plans. Mean liver doses and V10Gy to the liver, although easily meeting RTOG 1112 guidelines, were significantly higher with tri-(60)Co plans. When the 5 additional patients were included in a univariate analysis, the tri-(60)Co SBRT plans were still equally able to pass RTOG constraints, although they did have inferior ability to pass more stringent liver and kidney constraints (P < .05). A multivariate analysis found the ability of a tri-(60)Co SBRT plan to meet these constraints depended on lesion location and size. Patients with smaller or more peripheral lesions (as defined by distance from the aorta, chest wall, liver dome, and relative lesion volume) were significantly more likely to have tri-(60)Co plans that spared the liver and kidney as well as LINAC plans did (P < .05).

CONCLUSIONS

It is dosimetrically feasible to perform liver SBRT with a tri-(60)Co system with a built-in MRI. Patients with smaller or more peripheral lesions are more likely to have optimal liver and kidney sparing, with the added benefit of MRI guidance, when receiving tri-(60)Co-based SBRT. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Purpose

To demonstrate the feasibility of online adaptive magnetic resonance (MR) image guided radiation therapy (MR-IGRT) through reporting of our initial clinical experience and workflow considerations.

Methods and Materials

The first clinically deployed online adaptive MR-IGRT sys- tem consisted of a split 0.35T MR scanner straddling a ring gantry with 3 multileaf collimator-equipped 60Co heads. The unit is supported by a Monte Carlo based treatment planning system that allows real-time adaptive planning with the patient on the table. All patients undergo computed tomography and MR imaging (MRI) simulation for initial treatment planning. A volumetric MRI scan is acquired for each patient at the daily treatment setup. Deformable registration is performed using the planning computed tomography data set, which allows for the transfer of the initial contours and the electron density map to the daily MRI scan. The deformed electron density map is then used to recalculate the original plan on the daily MRI scan for physician evaluation. Recontouring and plan reoptimization are performed when required, and patient-specific quality assurance (QA) is performed using an independent in-house software system.

Results

The first online adaptive MR-IGRT treatments consisted of 5 patients with abdominopelvic malignancies. The clinical setting included neoadjuvant colorectal (n=3), unresectable gastric (n=1), and unresectable pheochromocytoma (n=1). Re- contouring and reoptimization were deemed necessary for 3 of 5 patients, and the initial plan was deemed sufficient for 2 of the 5 patients. The reasons for plan adaptation included tumor progression or regression and a change in small bowel anatomy. In a subsequently expanded cohort of 170 fractions (20 patients), 52 fractions (30.6%) were reoptimized online, and 92 fractions (54.1%) were treated with an online-adapted or previously adapted plan. The median time for recontouring, reoptimization, and QA was 26 minutes.

Conclusion

Online adaptive MR-IGRT has been successfully implemented with planning and QA workflow suitable for routine clinical application. Clinical trials are in development to formally evaluate adaptive treatments for a variety of disease sites.

Purpose

To use magnetic resonance image guided radiation therapy (MR-IGRT) for accelerated partial-breast irradiation (APBI) to (1) determine intrafractional motion of the breast surgical cavity; and (2) assess delivered dose versus planned dose.

Methods and Materials

Thirty women with breast cancer (stages 0-I) who underwent breast-conserving surgery were enrolled in a prospective registry evaluating APBI using a 0.35-T MR-IGRT system. Clinical target volume was defined as the surgical cavity plus a 1-cm margin (excluding chest wall, pectoral muscles, and 5 mm from skin). No additional margin was added for the planning target volume (PTV). A volumetric MR image was acquired before each fraction, and patients were set up to the surgical cavity as visualized on MR imaging. To determine the delivered dose for each fraction, the electron density map and contours from the computed tomography simulation were transferred to the pretreatment MR image via rigid registration. Intrafractional motion of the surgical cavity was determined by applying a tracking algorithm to the cavity contour as visualized on cine MR.

Results

Median PTV volume was reduced by 52% when using no PTV margin compared with a 1-cm PTV margin used conventionally. The mean (± standard deviation) difference between planned and delivered dose to the PTV (V95) was 0.6% ± 0.1%. The mean cavity displacement in the anterior–posterior and superior–inferior directions was 0.6 ± 0.4 mm and 0.6 ± 0.3 mm, respectively. The mean margin required for at least 90% of the cavity to be contained by the margin for 90% of the time was 0.7 mm (5th-95th percentile: 0-2.7 mm).

Conclusion

Minimal intrafractional motion was observed, and the mean difference between planned and delivered dose was less than 1%. Assessment of efficacy and cosmesis of this MR-guided APBI approach is under way.

Purpose

Magnetic resonance imaging (MRI) guidance in radiation therapy brings real-time imaging and adaptive planning into the treatment vault where it can account for interfraction and intrafraction movement of soft tissue. The only commercially available MRI-guided radiation therapy device is a three-head 60Co and MRI system with an integrated treatment planning system (TPS). Couch attenuation of the beam of up to 20% is well modeled in the TPS. Variations in the patient's day-to-day position introduce discrepancies in the actual couch attenuation as modeled in the treatment plan. For this reason, the authors’ institution avoids plans with beams that pass through or near the couch edges. This study investigates the effects of differential beam attenuation by the couch due to couch shifts in order to determine whether couch edge avoidance restrictions can be lifted. Couch shifts were simulated using a Monte Carlo treatment planning system and ion chamber measurements performed for validation.

Methods

A total of 27 plans from 23 patients were investigated. Couch shifts of 1 and 2 cm were introduced in combinations of lateral and vertical directions to simulate patient position variations giving 16 shifted plans per reference plan. The 1 and 2 cm shifts were based on shifts recorded in 320 treatment fractions.

Results

Following TG176 recommendations for measurement methods, couch attenuation measurements agreed with TPS modeled attenuation to within 2.1%. Planning target volume D95 changed less than 1% for 1 and 2 cm couch shifts in only the x-direction and less than 3% for all directions.

Conclusions

Dosimetry of all plans tested was robust to couch shifts up to ±2 cm. In general, couch shifts resulted in clinically insignificant dosimetric deviations. It is conceivable that in certain cases with large systematic couch shifts and plans that are particularly sensitive to shifts, dosimetric changes might rise to a clinically significant level.

Abstract

On-board magnetic resonance (MR) image guidance during radiation therapy offers the potential for more accurate treatment delivery. To utilize the real-time image information, a crucial prerequisite is the ability to successfully segment and track regions of interest (ROI). The purpose of this work is to evaluate the performance of different segmentation algorithms using motion images (4 frames per second) acquired using a MR image-guided radiotherapy (MR-IGRT) system. Manual con­tours of the kidney, bladder, duodenum, and a liver tumor by an experienced radia­tion oncologist were used as the ground truth for performance evaluation. Besides the manual segmentation, images were automatically segmented using thresholding, fuzzy k-means (FKM), k-harmonic means (KHM), and reaction-diffusion level set evolution (RD-LSE) algorithms, as well as the tissue tracking algorithm provided by the ViewRay treatment planning and delivery system (VR-TPDS). The performance of the five algorithms was evaluated quantitatively by comparing with the manual segmentation using the Dice coefficient and target registration error (TRE) measured as the distance between the centroid of the manual ROI and the centroid of the automatically segmented ROI. All methods were able to successfully segment the bladder and the kidney, but only FKM, KHM, and VR-TPDS were able to segment the liver tumor and the duodenum. The performance of the thresholding, FKM, KHM, and RD-LSE algorithms degraded as the local image contrast decreased, whereas the performance of the VP-TPDS method was nearly independent of local image contrast due to the reference registration algorithm. For segmenting high-contrast images (i.e., kidney), the thresholding method provided the best speed (< 1 ms) with a satisfying accuracy (Dice = 0.95). When the image contrast was low, the VR-TPDS method had the best automatic contour. Results suggest an image quality determination procedure before segmentation and a combination of different methods for optimal segmentation with the on-board MR-IGRT system.