Treatment planning for MR-guided SBRT of pancreatic tumors on a 1.5 T MR-Linac: A global consensus protocol.

Background and purpose: Treatment planning for MR-guided stereotactic body radiotherapy (SBRT) for pancreatic tumors can be challenging, leading to a wide variation of protocols and practices. This study aimed to harmonize treatment planning by developing a consensus planning protocol for MR-guided pancreas SBRT on a 1.5 T MR-Linac. Materials and methods: A consortium was founded of thirteen centers that treat pancreatic tumors on a 1.5 T MR-Linac. A phased planning exercise was conducted in which centers iteratively created treatment plans for two cases of pancreatic cancer. Each phase was followed by a meeting where the instructions for the next phase were determined. After three phases, a consensus protocol was reached. Results: In the benchmarking phase (phase I), substantial variation between the SBRT protocols became apparent (for example, the gross tumor volume (GTV) D99% ranged between 36.8 - 53.7 Gy for case 1, 22.6 - 35.5 Gy for case 2). The next phase involved planning according to the same basic dosimetric objectives, constraints, and planning margins (phase II), which led to a large degree of harmonization (GTV D99% range: 47.9-53.6 Gy for case 1, 33.9-36.6 Gy for case 2). In phase III, the final consensus protocol was formulated in a treatment planning system template and again used for treatment planning. This not only resulted in further dosimetric harmonization (GTV D99% range: 48.2-50.9 Gy for case 1, 33.5-36.0 Gy for case 2) but also in less variation of estimated treatment delivery times. Conclusion: A global consensus protocol has been developed for treatment planning for MR-guided pancreatic SBRT on a 1.5 T MR-Linac. Aside from harmonizing the large variation in the current clinical practice, this protocol can provide a starting point for centers that are planning to treat pancreatic tumors on MR-Linac systems.

Online Adaptive MRI-Guided Stereotactic Body Radiotherapy for Pancreatic and Other Intra-Abdominal Cancers.

A 1.5T MRI combined with a linear accelerator (Unity®, Elekta; Stockholm, Sweden) is a device that shows promise in MRI-guided stereotactic body radiation treatment (SBRT). Previous studies utilized the manufacturer's pre-set MRI sequences (i.e., T2 Weighted (T2W)), which limited the visualization of pancreatic and intra-abdominal tumors and organs at risk (OAR). Here, a T1 Weighted (T1W) sequence was utilized to improve the visualization of tumors and OAR for online adapted-to-position (ATP) and adapted-to-shape (ATS) during MRI-guided SBRT. Twenty-six patients, 19 with pancreatic and 7 with intra-abdominal cancers, underwent CT and MRI simulations for SBRT planning before being treated with multi-fractionated MRI-guided SBRT. The boundary of tumors and OAR was more clearly seen on T1W image sets, resulting in fast and accurate contouring during online ATP/ATS planning. Plan quality in 26 patients was dependent on OAR proximity to the target tumor and achieved 96 ± 5% and 92 ± 9% in gross tumor volume D90% and planning target volume D90%. We utilized T1W imaging (about 120 s) to shorten imaging time by 67% compared to T2W imaging (about 360 s) and improve tumor visualization, minimizing target/OAR delineation uncertainty and the treatment margin for sparing OAR. The average time-consumption of MRI-guided SBRT for the first 21 patients was 55 ± 15 min for ATP and 79 ± 20 min for ATS.

A target definition based on electroanatomic maps for stereotactic arrhythmia radioablation.

PURPOSE: Identifying the target region is critical for successfully treating ventricular tachycardia (VT) with single fraction stereotactic arrhythmia radioablation (STAR). We report the feasibility of target definition based on direct co-registration of electroanatomic maps (EAM) and radioablation planning images. MATERIALS AND METHODS: The EAM consists of 3D cardiac anatomy representation with electrical activity at endocardium and is acquired by a cardiac electrophysiologist (CEP) during electrophysiology study. The CEP generates an EAM using a 3D cardiac mapping system anticipating radioablation planning. Our in-house software read these non-DICOM EAMs, registered them to a planning image set, and converted them to DICOM structure files. The EAM based target volume was finalized based on a consensus of CEPs, radiation oncologists and medical physicists, then expanded to ITV and PTV. The simulation, planning, and treatment is performed with a standard STAR technique: a single fraction of 25 Gy using volumetric-modulated arc therapy or dynamic conformal arc therapy depending on the target shape. RESULTS: Seven patients with refractory VT were treated by defining the target based on registering EAMs on the planning images. Dice similarity indices between reference map and reference contours after registration were 0.814 ± 0.053 and 0.575 ± 0.199 for LV and LA/RV, respectively. CONCLUSIONS: The quality of the transferred EAMs on the MR/CT images was sufficient to localize the treatment region. Five of 7 patients demonstrated a dramatic reduction in VT events after 6 weeks. Longer follow-up is required to determine the true safety and efficacy of this therapy using EAM-based direct registration method.

A volume-independent conformity index for stereotactic radiosurgery.

PURPOSE: To develop a volume-independent conformity metric called the Gaussian Weighted Conformity Index (GWCI) to evaluate stereotactic radiosurgery/radiotherapy (SRS/SRT) plans for small brain tumors. METHODS: A signed bi-directional local distance (BLD) between the prescription isodose line and the target contour is determined for each point along the tumor contour (positive distance represents under-coverage). A similarity score function (SF) is derived from Gaussian function, penalizing under- and over-coverage at each point by assigning standard deviations of the Gaussian function. Each point along the dose line contour is scored with this SF. The average of the similarity scores determines the GWCI. A total of 40 targets from 18 patients who received Gamma-Knife SRS/SRT treatments were analyzed to determine appropriate penalty criteria. The resulting GWCIs for test cases already deemed clinically acceptable are presented and compared to the same cases scored with the New Conformity Index to determine the influence of tumor volumes on the two conformity indices (CIs). RESULTS: A total of four penalty combinations were tested based on the signed BLDs from the 40 targets. A GWCI of 0.9 is proposed as a cutoff for plan acceptability. The GWCI exhibits no target volume dependency as designed. CONCLUSION: A limitation of current CIs, volume dependency, becomes apparent when applied to SRS/SRT plans. The GWCI appears to be a more robust index, which penalizes over- and under-coverage of tumors and is not skewed by the tumor volume.

Dosimetric benefits of dynamic conformal arc therapy-combined with active breath-hold in lung stereotactic body radiotherapy.

To test the hypothesis that dynamic conformal arc therapy (DCAT) in Monaco, compared with volumetric modulated arc therapy (VMAT), maintains plan quality with higher delivery efficiency for lung stereotactic body radiotherapy (SBRT) and to investigate dosimetric benefits of DCAT with active breath-hold (DCAT+ABH), compared with free-breathing (DCAT+FB) for varying tumor sizes and motions. Fifty DCAT plans were used for lung SBRT. Randomly selected 17 DCAT plans were evaluated with respect to the retrospectively generated volumetric modulated arc therapy (VMAT) plans. The maximum dose at 2 cm from planning target volume (PTV) in any direction (D2cm/Rx), the ratio of 50% prescription isodose volume to the PTV (R50%), conformity index (CI), the lung volume receiving ≥20 Gy (V20), and monitor unit (MU) were evaluated. A t-test was used to evaluate the difference of plan quality between DCAT and VMAT. Internal target volume (ITV)/integrated-gross target volume (GTV) attributed by intra-fraction motion and lung V20 were stratified for DCAT+ABH and DCAT+FB across varying GTVs. DCAT maintained plan quality (p = 0.154 for D2cm/Rx, p = 0.089 for R50%, p = 0.064 for CI, and p = 0.780 for lung V20) while reducing MUs up to 30% (p <0.001) from 2748 MU (VMAT) to 1868 MU (DCAT). DCAT+ABH, compared to DCAT+FB, reduced tumor motion, resulting in 19% volume reduction of PTV and 60% reduction in lung V20, on average. The difference in lung V20 between DCAT+ABH and DCAT+FB increased as the target size increased. The DCAT is a favorable approach compared with VMAT. These results support the utility of DCAT as a routine planning platform for lung SBRT, especially when utilized with respiratory motion management using the ABH.

Dynamic Modulated Brachytherapy (DMBT) Balloon Applicator for Accelerated Partial Breast Irradiation.

PURPOSE: To propose a novel high-dose-rate brachytherapy applicator for balloon-based dynamic modulated brachytherapy (DMBT) for accelerated partial breast irradiation (APBI) and to demonstrate its dosimetric advantage compared to the widely used Contura applicator. METHODS AND MATERIALS: The DMBT balloon device consists of a fixed central channel enabling real-time, in vivo dosimetry and an outer motion-dynamic, adjustable-radius channel capable of moving to any angular position within the balloon. This design allows placement of dwell positions anywhere within the balloon volume, guaranteeing optimal placement and generation of the applicator and treatment plan, respectively. Thirteen clinical treatment plans for patients with early-stage breast cancer receiving APBI after lumpectomy using Contura were retrospectively obtained under institutional review board approval. New treatment plans were created by replacing the Contura with the DMBT device. DMBT plans were limited to 4 angular positions and an outer channel radius of 1.5 cm. The new plans were optimized to limit dose to ribs and skin while maintaining target coverage similar to that of the clinical plan. RESULTS: Similar target coverage was obtained for the DMBT plans compared with clinical Contura plans. Across all patients the mean (standard deviation) reductions in D0.1 cc to the ribs and skin were 6.70% (6.28%) and 5.13% (6.54%), respectively. A threshold separation distance between the balloon surface and the organ at risk (OAR), below which dosimetric changes of greater than 5% were obtained, was observed to be 12 mm for ribs and skin. When both OARs were far from the balloon, DMBT plans were of similar quality to Contura plans, as expected. CONCLUSIONS: This study demonstrates the superior ability of the APBI DMBT applicator to spare OARs while achieving target coverage comparable to current treatment plans, especially when in close proximity. The DMBT balloon may enable new modes of dynamic high-dose-rate treatment delivery and allow for ultrahypofractionated dose regimens to be safely used.

Technical Note: The design, construction, and evaluation of a liquid-based single phantom solution for TG128 brachytherapy ultrasound QA.

PURPOSE: Since the publication of the AAPM TG128 report for the quality assurance (QA) of prostate brachytherapy ultrasound systems, no commercially available phantoms have been developed which satisfy all of the task group recommendations. Current solid phantoms require a separate user-implemented setup using a container with liquid medium to evaluate the alignment between the needle template and the electronic grid, a test of geometric accuracy with critical implications in dosimetric quality. Utilizing a 3D printer, we constructed a cost-effective, liquid-based phantom that provides a complete TG128 solution which improves the efficiency of brachytherapy ultrasound QA. METHODS: The TG128 report was used to guide the design process of the liquid-based phantom. The needle template and electronic grid alignment setup served as the foundation with specific components developed to integrate all remaining tests. Water was chosen as the liquid medium, with speed of sound adjusted to 1,540 m/s via salinity per the task group recommendations. The proof of concept was evaluated by comparing the time stamps labeled on QA images between the liquid-based phantom and a commercially available one for both a new and experienced user. RESULTS: A TG128 QA trial run demonstrated that all recommended tests can be completed with the single phantom setup. Evaluation of the time data revealed a total QA duration of 45 min (average of two trials) with the liquid-based phantom, compared to 70 and 90 min with the commercial phantom for a new and experienced user. CONCLUSIONS: The liquid-based phantom is specifically designed to satisfy the recommendations of the TG128 report. The incorporation of 3D printing allows simple design modifications to adapt the phantom on-the-fly if needed. The resulting product improves the efficiency of brachytherapy ultrasound QA by eliminating the need for multiple phantom setups.

Deformable image registration in radiation therapy.

The number of imaging data sets has significantly increased during radiation treatment after introducing a diverse range of advanced techniques into the field of radiation oncology. As a consequence, there have been many studies proposing meaningful applications of imaging data set use. These applications commonly require a method to align the data sets at a reference. Deformable image registration (DIR) is a process which satisfies this requirement by locally registering image data sets into a reference image set. DIR identifies the spatial correspondence in order to minimize the differences between two or among multiple sets of images. This article describes clinical applications, validation, and algorithms of DIR techniques. Applications of DIR in radiation treatment include dose accumulation, mathematical modeling, automatic segmentation, and functional imaging. Validation methods discussed are based on anatomical landmarks, physical phantoms, digital phantoms, and per application purpose. DIR algorithms are also briefly reviewed with respect to two algorithmic components: similarity index and deformation models.

A novel method to quantify and compare anatomical shape: application in cervix cancer radiotherapy.

Adaptive radiation therapy (ART) had been proposed to restore dosimetric deficiencies during treatment delivery. In this paper, we developed a technique of Geometric reLocation for analyzing anatomical OBjects' Evolution (GLOBE) for a numerical model of tumor evolution under radiation therapy and characterized geometric changes of the target using GLOBE. A total of 174 clinical target volumes (CTVs) obtained from 32 cervical cancer patients were analyzed. GLOBE consists of three main steps; step (1) deforming a 3D surface object to a sphere by parametric active contour (PAC), step (2) sampling a deformed PAC on 642 nodes of icosahedron geodesic dome for reference frame, and step (3) unfolding 3D data to 2D plane for convenient visualization and analysis. The performance was evaluated with respect to (1) convergence of deformation (iteration number and computation time) and (2) accuracy of deformation (residual deformation). Based on deformation vectors from planning CTV to weekly CTVs, target specific (TS) margins were calculated on each sampled node of GLOBE and the systematic (Σ) and random (σ) variations of the vectors were calculated. Population based anisotropic (PBA) margins were generated using van Herk's margin recipe. GLOBE successfully modeled 152 CTVs from 28 patients. Fast convergence was observed for most cases (137/152) with the iteration number of 65 ± 74 (average ± STD) and the computation time of 13.7 ± 18.6 min. Residual deformation of PAC was 0.9 ± 0.7 mm and more than 97% was less than 3 mm. Margin analysis showed random nature of TS-margin. As a consequence, PBA-margins perform similarly to ISO-margins. For example, PBA-margins for 90% patients' coverage with 95% dose level is close to 13 mm ISO-margins in the aspect of target coverage and OAR sparing. GLOBE demonstrates a systematic analysis of tumor motion and deformation of patients with cervix cancer during radiation therapy and numerical modeling of PBA-margin on 642 locations of CTV surface.

Hybrid adaptive radiotherapy with on-line MRI in cervix cancer IMRT.

PURPOSE: Substantial organ motion and tumor shrinkage occur during radiotherapy for cervix cancer. IMRT planning studies have shown that the quality of radiation delivery is influenced by these anatomical changes, therefore the adaptation of treatment plans may be warranted. Image guidance with off-line replanning, i.e. hybrid-adaptation, is recognized as one of the most practical adaptation strategies. In this study, we investigated the effects of soft tissue image guidance using on-line MR while varying the frequency of off-line replanning on the adaptation of cervix IMRT. MATERIALS AND METHOD: 33 cervical cancer patients underwent planning and weekly pelvic MRI scans during radiotherapy. 5 patients of 33 were identified in a previous retrospective adaptive planning study, in which the coverage of gross tumor volume/clinical target volume (GTV/CTV) was not acceptable given single off-line IMRT replan using a 3mm PTV margin with bone matching. These 5 patients and a randomly selected 10 patients from the remaining 28 patients, a total of 15 patients of 33, were considered in this study. Two matching methods for image guidance (bone to bone and soft tissue to dose matrix) and three frequencies of off-line replanning (none, single, and weekly) were simulated and compared with respect to target coverage (cervix, GTV, lower uterus, parametrium, upper vagina, tumor related CTV and elective lymph node CTV) and OAR sparing (bladder, bowel, rectum, and sigmoid). Cost (total process time) and benefit (target coverage) were analyzed for comparison. RESULTS: Hybrid adaptation (image guidance with off-line replanning) significantly enhanced target coverage for both 5 difficult and 10 standard cases. Concerning image guidance, bone matching was short of delivering enough doses for 5 difficult cases even with a weekly off-line replan. Soft tissue image guidance proved successful for all cases except one when single or more frequent replans were utilized in the difficult cases. Cost and benefit analysis preferred (soft tissue) image guidance over (frequent) off-line replanning. CONCLUSIONS: On-line MRI based image guidance (with combination of dose distribution) is a crucial element for a successful hybrid adaptive radiotherapy. Frequent off-line replanning adjuvantly enhances adaptation quality.

Tumor and normal tissue dosimetry changes during MR-guided pulsed-dose-rate (PDR) brachytherapy for cervical cancer.

BACKGROUND AND PURPOSE: To analyze systematic changes in tumor and normal tissue anatomy and dosimetry using serial MR imaging during pulsed dose rate brachytherapy (PDR BT) for cervical cancer. MATERIAL AND METHODS: Forty-three patients with cervical cancer underwent MR-guided PDR BT using an intrauterine applicator alone after external beam radiotherapy. MR imaging was repeated on days 2 and 3 of treatment and the day 1 plan was applied to the re-contoured volumes. RESULTS: The mean uterine volume and mean HR CTV increased during treatment. This resulted in a decrease in the mean HR CTV D90 relative to the day 1 planned dose. There was no change in the mean bladder volume during treatment but the mean rectal volume increased. This correlated with an increase in the mean rectal dose. There were four local recurrences. There was no apparent relationship between either the planned or the delivered HR CTV D90 and local recurrence. There was only one case of late bladder toxicity but nine patients developed late rectal toxicity. The cumulative rectal dose during treatment was a better predictor of late rectal toxicity than the planned dose. CONCLUSIONS: Significant changes in tumor and normal tissue anatomy and dosimetry can occur during PDR BT and should be tracked and corrected using serial imaging and plan adaptation, especially when the day 1 tumor or normal tissue doses are close to the planning constraints.

Measurements of dose discrepancies due to inhomogeneities and radiographic contrast in balloon catheter brachytherapy.

Recently, a device called MammoSite, consisting of a balloon and a catheter, was developed to perform partial-breast irradiation using a high-dose-rate (HDR) brachytherapy unit with ease and reproducibility. However, the actual dose to the skin does not agree well with the calculated dose by the treatment planning system because of the difference between the calculation condition and the real treatment condition (i.e., homogeneous water and full scatter condition vs contrast solution and lack of full scatter condition). In this study, the authors experimentally estimated dose discrepancies due to contrast and lack of full scatter in breast HDR brachytherapy with MammoSite. Using metal-oxide-semiconductor field-effect transistor detectors and a breast phantom, the dose discrepancies between the calculation and the treatment conditions were measured according to contrast concentration (10% and 20% volume ratios), balloon size (35 and 60 cm3), and source to detector distance ranging from 25 to 50 mm. The source was an Ir-192 isotope from Nucletron HDR unit. The dose discrepancies from the calculation condition due to both contrast and lack of full scatter combined ranged from about -1.4 +/- 2.5% to -18.2 +/- 2.0% in the studied cases (error bound is in two sided confidence interval of 80% based on Student's t distribution). In all cases, the effect of lack of full scatter was dominant to that of contrast and significant dose discrepancies existed between the calculation and the real treatment conditions, indicating that the actual skin dose is less than that which is currently calculated.

How image quality affects determination of target displacement when using kilovoltage cone-beam computed tomography.

The advent of kilovoltage cone-beam computed tomography (CBCT) integrated with a linear accelerator allows for more accurate image-guided radiotherapy (IGRT). The IGRT technique corrects target displacement based on internal body information obtained by acquiring the CBCT image set and registering it with the simulation CT image set just before the beam is delivered. In the present paper, we compare registration results by CBCT reconstruction quality (either high or medium). We analyzed data from a total of 56 CBCT projections from 6 patients. The translational vector differences were within 1 mm in all but 3 cases. The rotational displacement differences considered components of all three axes, and in 3 of 168 cases (56 projections by 3 axes), showed more than 1 degree of difference.

Development of a rapid planning technique based on heuristic target shaping for stereotactic radiosurgery.

Stereotactic radiosurgery (SRS) is a technique to delivering a high dose to a target region and a low dose to a critical organ by using only one or a few irradiations. Traditionally, SRS is performed using a Gamma knife with using 201 cobalt 60 sources or a linear accelerator with equally spaced noncoplanar arcs. Finding a specific condition that includes the target in the prescription dose while sparing the critical organ is tedious, because there are many combinations of positions and collimator sizes for each isocenter. Many methods of identifying suitable planning condition automatically have been proposed. However, there are some limitations using these methods. These include a long calculation time to obtain the final plan, and difficulties finding a unique solution due to different tumor shapes. This study uses three steps to solve these problems. (1) The dose distribution of one isocenter is modeled as a sphere. This makes it possible to reduce the time needed to obtain the result due to the absence of a dose calculation. (2) The target was constructed by piling up cylinders along a virtual axis, which was the longest line in a given target. (3) Spheres were then packed in each cylinder according to the position and diameter of each cylinder in order to cover each target divided by the height of the cylinder. The results of applying three imaginary targets were found to be satisfactory in terms of: target coverage-more than 50%, the reproducibility of the result and the calculation time-several tens of seconds. The PITV ratio was less than 2.0. However, the dose applied to normal tissue around the target must be reduced slightly. Planner or conventional optimization algorithms might easily solve this limitation.