Empirical planning target volume modeling for high precision MRI guided intracranial radiotherapy.

Purpose: Magnetic resonance image-guided radiotherapy for intracranial indications is a promising advance; however, uncertainties remain for both target localization after translation-only MR setup and intrafraction motion. This investigation quantified these uncertainties and developed a population-based planning target volume (PTV) model to explore target and organ-at-risk (OAR) volumetric coverage tradeoffs. Methods: Sixty-six patients, 49 with a primary brain tumor and 17 with a post-surgical resection cavity, treated on a 1.5T-based MR-linac across 1329 fractions were included. At each fraction, patients were setup by translation-only fusion of the online T1 MRI to the planning image. Each fusion was independently repeated offline accounting for rotations. The six degree-of-freedom difference between fusions was applied to transform the planning CTV at each fraction (CTVfx). A PTV model parameterized by volumetric CTVfx coverage, proportion of fractions, and proportion of patients was developed. Intrafraction motion was quantified in a 412 fraction subset as the fusion difference between post- and pre-irradiation T1 MRIs. Results: For the left-right/anterior-posterior/superior-inferior axes, mean ± SD of the rotational fusion differences were 0.1 ± 0.8/0.1 ± 0.8/-0.2 ± 0.9°. Covering 98 % of the CTVfx in 95 % of fractions in 95 % of patients required a 3 mm PTV margin. Margin reduction decreased PTV-OAR overlap; for example, the proportion of optic chiasm overlapped by the PTV was reduced up to 23.5 % by margin reduction from 4 mm to 3 mm. Conclusions: An evidence-based PTV model was developed for brain cancer patients treated on the MR-linac. Informed by this model, we have clinically adopted a 3 mm PTV margin for conventionally fractionated intracranial patients.

Control charts for evaluation of quality of low-dose-rate brachytherapy for prostate cancer.

Purpose: Variations in dosimetric outcomes among patients treated with low-dose-rate brachytherapy for prostate cancer exist, even when implants are within dose constraints. Here, we used control charts to investigate reasons for intra-patient dosimetric variability. Material and methods: Univariate and multivariate control charts for prostate V100 (percentage of prostate volume that received 100% of prescribed radiation dose), D90 (radiation dose to 90% of prostate volume), and RV100 (rectal wall volume that received 100% of prescribed radiation dose) were generated for 212 consecutive prostate cancer patients implanted with iodine-125 (125I) radioactive seeds at the Princess Margaret Cancer Centre. Control limits were calculated based on the first fifty implants. Data points that were out of control were identified, and their pre-treatment and post-treatment dosimetric and clinical parameters were compared to data points that were in-control, using Student's t-test. Results: All implants were clinically acceptable. Twelve data points exceeded multivariate control limits. Ten of those points fell below the lower control limit of V100 control chart. Average prostate edema in the 10 out-of-control patients on both multivariate and V100 charts was 8.3%, as compared to 0.4% for in-control patients (p < 0.04). Two patients were observed to be out-of-control on multivariate control chart, but not on V100 control chart, and were found to have a reduction in prostate volume of 19.1% and 20.1% at one month after seed implant, compared to prostate volumes of pre-implantation evaluations. Conclusions: Control charts helped in identifying cases with out-of-control variability in post-plan prostate dosimetry. Post-treatment prostatic edema and contraction are important factors predicting variability in patients treated with 125I permanent seed brachytherapy.

Auto-segmentation of normal and target structures in head and neck CT images: a feature-driven model-based approach.

PURPOSE: Intensity modulated radiation therapy (IMRT) allows greater control over dose distribution, which leads to a decrease in radiation related toxicity. IMRT, however, requires precise and accurate delineation of the organs at risk and target volumes. Manual delineation is tedious and suffers from both interobserver and intraobserver variability. State of the art auto-segmentation methods are either atlas-based, model-based or hybrid however, robust fully automated segmentation is often difficult due to the insufficient discriminative information provided by standard medical imaging modalities for certain tissue types. In this paper, the authors present a fully automated hybrid approach which combines deformable registration with the model-based approach to accurately segment normal and target tissues from head and neck CT images. METHODS: The segmentation process starts by using an average atlas to reliably identify salient landmarks in the patient image. The relationship between these landmarks and the reference dataset serves to guide a deformable registration algorithm, which allows for a close initialization of a set of organ-specific deformable models in the patient image, ensuring their robust adaptation to the boundaries of the structures. Finally, the models are automatically fine adjusted by our boundary refinement approach which attempts to model the uncertainty in model adaptation using a probabilistic mask. This uncertainty is subsequently resolved by voxel classification based on local low-level organ-specific features. RESULTS: To quantitatively evaluate the method, they auto-segment several organs at risk and target tissues from 10 head and neck CT images. They compare the segmentations to the manual delineations outlined by the expert. The evaluation is carried out by estimating two common quantitative measures on 10 datasets: volume overlap fraction or the Dice similarity coefficient (DSC), and a geometrical metric, the median symmetric Hausdorff distance (HD), which is evaluated slice-wise. They achieve an average overlap of 93% for the mandible, 91% for the brainstem, 83% for the parotids, 83% for the submandibular glands, and 74% for the lymph node levels. CONCLUSIONS: Our automated segmentation framework is able to segment anatomy in the head and neck region with high accuracy within a clinically-acceptable segmentation time.

4D-CT Attenuation Correction in Respiratory-Gated PET for Hypoxia Imaging: Is It Really Beneficial?

Previous literature has shown that 4D respiratory-gated positron emission tomography (PET) is beneficial for quantitative analysis and defining targets for boosting therapy. However the case for addition of a phase-matched 4D-computed tomography (CT) for attenuation correction (AC) is less clear. We seek to validate the use of 4D-CT for AC and investigate the impact of motion correction for low signal-to-background PET imaging of hypoxia using radiotracers such as FAZA and FMISO. A new insert for the Modus Medicals' QUASAR™ Programmable Respiratory Motion Phantom was developed in which a 3D-printed sphere was placed within the "lung" compartment while an additional compartment is added to simulate muscle/blood compartment required for hypoxia quantification. Experiments are performed at 4:1 or 2:1 signal-to-background ratio consistent with clinical FAZA and FMISO imaging. Motion blur was significant in terms of SUVmax, mean, and peak for motion ≥1 cm and could be significantly reduced (from 20% to 8% at 2-cm motion) for all 4D-PET-gated reconstructions. The effect of attenuation method on precision was significant (σ2 hCT-AC = 5.5%/4.7%/2.7% vs σ2 4D-CT-AC = 0.5%/0.6%/0.7% [max%/peak%/mean% variance]). The simulated hypoxic fraction also significantly decreased under conditions of 2-cm amplitude motion from 55% to 20% and was almost fully recovered (HF = 0.52 for phase-matched 4D-CT) using gated PET. 4D-gated PET is valuable under conditions of low radiotracer uptake found in hypoxia imaging. This work demonstrates the importance of using 4D-CT for AC when performing gated PET based on its significantly improved precision over helical CT.

[18F]DCFPyL PET-MRI/CT for unveiling a molecularly defined oligorecurrent prostate cancer state amenable for curative-intent ablative therapy: study protocol for a phase II trial.

INTRODUCTION: The oligometastatic (OM) disease hypothesis of an intermediate metastatic state with limited distant disease deposits amenable for curative therapies remains debatable. Over a third of prostate cancer (PCa) patients treated with radical prostatectomy and postoperative radiotherapy experience disease recurrence; these patients are considered incurable by current standards. Often the recurrence cannot be localised by conventional imaging (CT and bone scan). Combined anatomical imaging with CT and/or MR with positron emission tomography (PET) using a novel second-generation prostate-specific membrane antigen (PSMA) probe, [18F]DCFPyL, is a promising imaging modality to unveil disease deposits in these patients. A new and earlier molecularly defined oligorecurrent (OR) state may be amenable to focal-targeted ablative curative-intent therapies, such as stereotactic ablative radiotherapy (SABR) or surgery, thereby significantly delaying or completely avoiding the need for palliative therapies in men with recurrent PCa after maximal local treatments. METHODS AND ANALYSIS: This ongoing single-institution phase II study will enrol up to 75 patients total, to include up to 37 patients with response-evaluable disease, who have rising prostate-specific antigen (range 0.4-3.0 ng/mL) following maximal local therapies with no evidence of disease on conventional imaging. These patients will undergo [18F]DCFPyL PET-MR/CT imaging to detect disease deposits, which will then be treated with SABR or surgery. The primary endpoints are performance of [18F]DCFPyL PET-MR/CT, and treatment response rates following SABR or surgery. Demographics and disease characteristics will be summarised and analysed descriptively. Response rates will be described with waterfall plots and proportions. ETHICS AND DISSEMINATION: Ethics approval was obtained from the institutional Research Ethics Board. All patients will provide written informed consent. [18F]DCFPyL has approval from Health Canada. The results of the study will be disseminated by the principal investigator. Patients will not be identifiable as individuals in any publication or presentation of this study. TRIAL REGISTRATION NUMBERS: NCT03160794.

A method to analyze the cord geometrical uncertainties during head and neck radiation therapy using cone beam CT.

We developed a method to analyze quantitatively the residual cord geometrical uncertainties after image registration during head and neck radiation therapy by using sequential cone beam CT (CBCT). The geometrical centroid line of cervical spinal canal was computed to serve as a cord surrogate. We found that the cord motions were non-uniform from C1 to C6, and that the patterns of motion were variable across patients. This method has potential applications in monitoring cord setup accuracy and in designing treatment margins.

The importance of obtaining conjugate views on renographic evaluation of large hydronephrotic kidneys: an in vitro and ex vivo analysis.

PURPOSE: It is postulated that significant obstruction leads to decreased ipsilateral renal function. However, maintained or even increased differential renal function is often seen in patients with large hydronephrotic kidneys. The reason for such a phenomenon is unclear. We designed an in vitro and ex vivo experimental model that permits the controlled orientation of thinned renal parenchyma and background activity during gamma camera detection. MATERIALS AND METHODS: A 5-step experimental study was designed with balloons or reservoirs containing known amounts of radioisotope. A balloon was incrementally compressed between 2 Plexiglas sheets (step 1). Simultaneous measurement of radio emission was done of 5 glass beakers of varying diameters filled with the same amount of water and (99m)Tc (step 2). A single beaker containing diluted (99m)Tc was interfaced with air (step 3) or water (step 4) at different distances from the gamma camera. Pig kidneys previously injected with dimercapto-succinic acid were removed and scanned (step 5). One of the kidneys was then progressively sliced, thinning its parenchyma, and sliced and nonsliced kidneys were simultaneously scanned again. RESULTS: Progressively increased counts were detected as the projected surface area of the radioactive balloons (step 1) and beakers (step 2) increased. Counts detected were inversely proportional to the amount of water interfaced between the container and the gamma camera. Significantly more radiation was detectable in sliced kidneys containing dimercapto-succinic acid than in intact control kidneys. CONCLUSIONS: These findings suggest that the artifactual supranormal differential renal function that is observed during renographic evaluation of large hydronephrotic kidneys actually exists. Parenchymal proximity and distribution in relation to the pelvis are critical determinants. These findings suggest that the conjugate view technique may be more suitable for renographic evaluation of large hydronephrotic kidneys.

Dosimetric comparison of IMRT vs. 3D conformal radiotherapy in the treatment of cancer of the cervical esophagus.

BACKGROUND AND PURPOSE: Radiotherapy planning for cervical esophageal cancer is challenging. We compared IMRT and 3D conformal radiotherapy (CRT) with respect to conformality of target coverage and normal tissue sparing. MATERIALS AND METHODS: We selected five patients with cervical esophagus cancer, who represented the heterogeneity of clinical cases, treated to radical dose and planned with Pinnacle v6.2. Target doses for CRT plans were 50, 60, and 70Gy (single-phase IMRT 56, 63, and 70). We compared PTV coverage by the 95% isodose (PTV(95)), conformality ratio (CR), conformation number (CN), and maximum or mean doses (D(max), D(mean)) to normal structures. RESULTS: Median PTV(95) for IMRT plans for PTV70, PTV63, and PTV56 were 97%, 99%, and 98% (CRT 91%, 98%, and 85%). IMRT plans demonstrated lower D(max) to the spinal cord and brainstem (42 and 36Gy) compared to CRT (46 and 39Gy). Median left parotid D(mean) was 35Gy (IMRT) vs. 53Gy (CRT). Median right parotid D(mean) was 35Gy (IMRT) vs. 36Gy (CRT). The median CR50/56Gy was 1.4 (CRT) vs. 1.2 (IMRT), CR70Gy 1.7 (CRT) vs. 1.1 (IMRT). CN50/56 and CN70 values were 0.80 and 0.85 (IMRT) vs. 0.56 and 0.5 (CRT). CONCLUSIONS: IMRT provides superior target volume coverage and conformality, with decreased dose to normal structures.

Statistical process control for IMRT dosimetric verification.

Patient-specific measurements are typically used to validate the dosimetry of intensity-modulated radiotherapy (IMRT). To evaluate the dosimetric performance over time of our IMRT process, we have used statistical process control (SPC) concepts to analyze the measurements from 330 head and neck (H&N) treatment plans. The objectives of the present work are to: (i) Review the dosimetric measurements of a large series of consecutive head and neck treatment plans to better understand appropriate dosimetric tolerances; (ii) analyze the results with SPC to develop action levels for measured discrepancies; (iii) develop estimates for the number of measurements that are required to describe IMRT dosimetry in the clinical setting; and (iv) evaluate with SPC a new beam model in our planning system. H&N IMRT cases were planned with the PINNACLE treatment planning system versions 6.2b or 7.6c (Philips Medical Systems, Madison, WI) and treated on Varian (Palo Alto, CA) or Elekta (Crawley, UK) linacs. As part of regular quality assurance, plans were recalculated on a 20-cm-diam cylindrical phantom, and ion chamber measurements were made in high-dose volumes (the PTV with highest dose) and in low-dose volumes (spinal cord organ-at-risk, OR). Differences between the planned and measured doses were recorded as a percentage of the planned dose. Differences were stable over time. Measurements with PINNACLE3 6.2b and Varian linacs showed a mean difference of 0.6% for PTVs (n=149, range, -4.3% to 6.6%), while OR measurements showed a larger systematic discrepancy (mean 4.5%, range -4.5% to 16.3%) that was due to well-known limitations of the MLC model in the earlier version of the planning system. Measurements with PINNACLE3 7.6c and Varian linacs demonstrated a mean difference of 0.2% for PTVs (n=160, range, -3.0%, to 5.0%) and -1.0% for ORs (range -5.8% to 4.4%). The capability index (ratio of specification range to range of the data) was 1.3 for the PTV data, indicating that almost all measurements were within +/-5%. We have used SPC tools to evaluate a new beam model in our planning system to produce a systematic difference of -0.6% for PTVs and 0.4% for ORs, although the number of measurements is smaller (n=25). Analysis of this large series of H&N IMRT measurements demonstrated that our IMRT dosimetry was stable over time and within accepted tolerances. These data provide useful information for assessing alterations to beam models in the planning system. IMRT is enhanced by the addition of statistical process control to traditional quality control procedures.

Image registration assessment in radiotherapy image guidance based on control chart monitoring.

Image guidance with cone beam computed tomography in radiotherapy can guarantee the precision and accuracy of patient positioning prior to treatment delivery. During the image guidance process, operators need to take great effort to evaluate the image guidance quality before correcting a patient's position. This work proposes an image registration assessment method based on control chart monitoring to reduce the effort taken by the operator. According to the control chart plotted by daily registration scores of each patient, the proposed method can quickly detect both alignment errors and image quality inconsistency. Therefore, the proposed method can provide a clear guideline for the operators to identify unacceptable image quality and unacceptable image registration with minimal effort. Experimental results demonstrate that by using control charts from a clinical database of 10 patients undergoing prostate radiotherapy, the proposed method can quickly identify out-of-control signals and find special cause of out-of-control registration events.

Brachytherapy patient safety events in an academic radiation medicine program.

PURPOSE: To describe the incidence and type of brachytherapy patient safety events over 10 years in an academic brachytherapy program. METHODS AND MATERIALS: Brachytherapy patient safety events reported between January 2007 and August 2016 were retrieved from the incident reporting system and reclassified using the recently developed National System for Incident Reporting in Radiation Treatment taxonomy. A multi-incident analysis was conducted to identify common themes and key learning points. RESULTS: During the study period, 3095 patients received 4967 brachytherapy fractions. An additional 179 patients had MR-guided prostate biopsies without treatment as part of an interventional research program. A total of 94 brachytherapy- or biopsy-related safety events (incidents, near misses, or programmatic hazards) were identified, corresponding to a rate of 2.8% of brachytherapy patients, 1.7% of brachytherapy fractions, and 3.4% of patients undergoing MR-guided prostate biopsy. Fifty-one (54%) events were classified as actual incidents, 29 (31%) as near misses, and 14 (15%) as programmatic hazards. Two events were associated with moderate acute medical harm or dosimetric severity, and two were associated with high dosimetric severity. Multi-incident analysis identified five high-risk activities or clinical scenarios as follows: (1) uncommon, low-volume or newly implemented brachytherapy procedures, (2) real-time MR-guided brachytherapy or biopsy procedures, (3) use of in-house devices or software, (4) manual data entry, and (5) patient scheduling and handoffs. CONCLUSIONS: Brachytherapy is a safe treatment and associated with a low rate of patient safety events. Effective incident management is a key element of continuous quality improvement and patient safety in brachytherapy.

Intraobserver and interobserver variability in GTV delineation on FDG-PET-CT images of head and neck cancers.

PURPOSE: To determine if the addition of fluorodeoxyglucose positron emission tomography (FDG-PET) data changes primary site gross tumor volumes (GTVs) in head and neck cancers. METHODS AND MATERIALS: Computed tomography (CT), contrast-enhanced CT, and FDG-PET-CT scans were obtained in 10 patients with head and neck cancers. Eight experienced observers (6 head and neck oncologists and 2 neuro-radiologists) with access to clinical and radiologic reports outlined primary site GTVs on each modality. Three cases were recontoured twice to assess intraobserver variability. The magnitudes of the GTVs were compared. Intra- and interobserver variability was assessed by a two-way repeated measures analysis of variance. Inter- and intraobserver reliability were calculated. RESULTS: There were no significant differences in the GTVs across the image modalities when compared as ensemble averages; the Wilcoxon matched-pairs signed-rank test showed that CT volumes were larger than PET-CT. Observers demonstrated the greatest consistency and were most interchangeable on contrast-enhanced CT; they performed less reliably on PET-CT. CONCLUSIONS: The addition of PET-CT to primary site GTV delineation of head and neck cancers does not change the volume of the GTV defined by this group of expert observers in this patient sample. An FDG-PET may demonstrate differences in neck node delineation and in other disease sites.

Quantitative PET comparing gated with nongated acquisitions using a NEMA phantom with respiratory-simulated motion.

UNLABELLED: This study evaluated the use of gated versus nongated PET acquisitions for absolute quantification of radioisotope concentration (RC) in a respiratory motion-simulated moving phantom filled with radioactive spheres and background for both 2-dimensional (2D) and 3-dimensional (3D) acquisitions. METHODS: An image-quality phantom with all 6 spheres filled with the same (18)F RC (range, 19-62 kBq/mL) was scanned with PET/CT at rest and in motion with and without gating. The background was filled with (18)F solution to yield sphere-to-background ratios of approximately 5, 10, 15, and 20 to 1. Both 2D and 3D acquisitions were used for all combinations. Respiratory motion was simulated by using a motor-driven plastic platform to move the phantom periodically with a displacement of 2 cm and a cycle time of 5.8 s. For gated acquisitions, the phantom was tracked using a real-time position management system. Images were reconstructed, and regions of interest with the same sizes as the actual spheres were manually placed on axial slices to determine maximum and mean pixel RC. A threshold method (70% and 94% for 2D and 3D modes) was also used to determine a mean voxel RC. All values were compared with the expected RC; percentage differences were calculated for each sphere. To reduce partial-volume effects, only data for the 4 largest spheres were analyzed. RESULTS: The mean pixel method was the only method with linear responses for all 3 scan types, enabling direct comparisons. The ranges of RC percentage differences were underestimated for all scan types (using the mean pixel method). The overall mean percentage differences were 37, 49, and 41 in 2D mode and 40, 51, and 41 in 3D mode for static, nongated, and gated acquisitions, respectively. Gated acquisitions improved quantification (by reducing underestimation) over nongated acquisitions by 8% and 10% for 2D and 3D modes. CONCLUSION: In the presence of motion, the use of gated PET acquisitions appears to improve quantification accuracy over nongated acquisitions, almost restoring the results to those observed when the phantom is static.

Effect of Standard Radiotherapy With Cisplatin vs Accelerated Radiotherapy With Panitumumab in Locoregionally Advanced Squamous Cell Head and Neck Carcinoma: A Randomized Clinical Trial.

IMPORTANCE: The Canadian Cancer Trials Group study HN.6 is the largest randomized clinical trial to date comparing the concurrent administration of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies with radiotherapy (RT) to standard chemoradiotherapy in locoregionally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). OBJECTIVE: To compare progression-free survival (PFS) in patients with LA-SCCHN treated with standard-fractionation RT plus high-dose cisplatin vs accelerated-fractionation RT plus the anti-EGFR antibody panitumumab. DESIGN, SETTING, AND PARTICIPANTS: A randomized phase 3 clinical trial in 17 Canadian centers. A total of 320 patients were randomized between December 2008 and November 2011. INTERVENTIONS: Patients with TanyN+M0 or T3-4N0M0 LA-SCCHN were randomized 1:1 to receive standard-fractionation RT (70 Gy/35 over 7 weeks) plus cisplatin at 100 mg/m2 intravenous for 3 doses (arm A) vs accelerated-fractionation RT (70 Gy/35 over 6 weeks) plus panitumumab at 9 mg/kg intravenous for 3 doses (arm B). MAIN OUTCOMES AND MEASURES: Primary end point was PFS. Due to an observed declining event rate, the protocol was amended to a time-based analysis. Secondary end points included overall survival, local and regional PFS, distant metastasis-free survival, quality of life, adverse events, and safety. RESULTS: Of 320 patients randomized (268 [84%] male; median age, 56 years), 156 received arm A and 159 arm B. A total of 93 PFS events occurred. By intention-to-treat, 2-year PFS was 73% (95% CI, 65%-79%) in arm A and 76% (95% CI, 68%-82%) in arm B (hazard ratio [HR], 0.95; 95% CI, 0.60-1.50; P = .83). The upper bound of the HR 95% CI exceeded the prespecified noninferiority margin. Two-year overall survival was 85% (95% CI, 78%-90%) in arm A and 88% (95% CI, 82%-92%) in arm B (HR, 0.89; 95% CI, 0.54-1.48; P = .66). Incidence of any grade 3 to 5 nonhematologic adverse event was 88% in arm A and 92% in arm B (P = .25). CONCLUSIONS AND RELEVANCE: With a median follow-up of 46 months, the PFS of panitumumab plus accelerated-fractionation RT was not superior to cisplatin plus standard-fractionation RT in LA-SCCHN and noninferiority was not proven. Despite having negative results, HN.6 has contributed important data regarding disease control and toxic effects of these treatment strategies. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00820248.

Spinal cord planning risk volumes for intensity-modulated radiation therapy of head-and-neck cancer.

PURPOSE: To assess planning organ at risk volume (PRV) margins of the spinal cord in intensity-modulated radiotherapy (IMRT) of oropharyngeal cancers, by modeling the effect of geometric uncertainties to estimate the probability of the spinal cord receiving a particular dose. METHODS AND MATERIALS: Five patients with oropharyngeal cancer were treated by IMRT with simultaneous doses of 66 Gy (gross disease) and 54 Gy (subclinical disease) in 30 fractions. Spinal cord doses were limited to 45 Gy. The probability, due to random and systematic patient positioning uncertainties (3-mm standard deviation), of the cord receiving a particular dose was determined. The effect of an on-line setup correction protocol was also modeled. RESULTS: The mean probability of a maximum spinal cord dose of 45 Gy was 1%, with a 6-mm PRV margin. The mean probability of a maximum dose exceeding 40 Gy was 37% (range, 13-77%); this probability is reduced with a setup correction protocol. CONCLUSION: A spinal cord PRV generated with a 6-mm margin leads to a 99% probability of maintaining the maximum spinal cord dose below 45 Gy. The application of an on-line setup correction protocol reduces the cord dose by approximately 5 Gy.

A facility for magnetic resonance-guided radiation therapy.

Magnetic resonance (MR) imaging is routinely employed in the design of radiotherapy (RT) treatment plans for many disease sites. It is evident that tighter integration of MR imaging into the RT process would increase confidence in dose placement and facilitate the integration of new MR imaging information (including anatomical and functional imaging) into the therapy process. To this end, a dedicated MR-guided RT (MRgRT) facility has been created that integrates a state-of-the-art linear accelerator delivery system, high-dose rate brachytherapy afterloader, and superconducting MR scanner to allow MR-based online treatment guidance, adaptive replanning, and response monitoring while maintaining the clinical functionality of the existing delivery systems. This system is housed within a dedicated MRgRT suite and operates in a coordinated fashion to assure safe and efficient MRgRT treatments.

Technical challenges of sparing infrahyoid swallowing organs at risk in oropharynx squamous cell cancer treated with IMRT.

This study reports clinical performance in the sparing of infrahyoid swallowing organs at risk (SWOARs) in oropharynx cancer intensity-modulated radiation therapy (IMRT) plans. Rates of meeting dose-volume planning goals are reported and compared with geometry-based estimates of what is achievable. This study also develops 3 measures of target-SWOAR geometry and tests their usefulness in providing geometry-based dose-volume planning goals. A total of 50 oropharynx cancer IMRT plans were reviewed. Success rates in meeting institutional dose-volume goals were determined for the glottic larynx (G), postcricoid pharynx (P), and esophagus (E). The following 3 measures of target-SWOAR geometry were investigated as methods of identifying geometry-based planning goals: presence of gross disease in neck levels 3 to 4, target-SWOAR overlap, and a 3-dimensional (3D) measure of target-SWOAR geometry. Locally advanced disease was predominant in this patient population with target volumes overlapping SWOARs in 68% to 98% of cases. Clinical rates of success in meeting dose-volume goals varied by SWOAR (16% to 82%) but compared well with estimated potentially achievable rates in most cases (14% average difference between clinical and potential). Cases grouped by the presence of levels 3 to 4 neck nodes or target-SWOAR overlap did not have significantly different SWOAR doses. Cases grouped using a 3D measure of target-SWOAR geometry differed significantly, providing useful geometry-based planning goals (e.g., mean Glottis dose <45Gy was achieved 19%, 44%, or 81% of the time in each of 3 groups). This study describes the technical challenge of sparing SWOARs and investigates several potential methods for grouping cases to assist with treatment plan evaluation. Quantifying the 3-D relationship between the targets and SWOARs is a promising way of approaching this complex problem. Data presented in this paper may be useful to evaluate treatment plans using objective geometry-based goals.

A Practice-based Taxonomy for Radiation Treatment Errors.

PURPOSE: An absence of a common language for incident classification limits knowledge sharing within and between organizations in the radiotherapy community. This challenge provided the motivation to develop a clinically relevant taxonomy for radiotherapy errors. MATERIALS AND METHODS: This was a multicenter, prospective study that consisted of three phases: (1) an initial version of the taxonomy was developed based on the World Health Organization Conceptual Framework for the International Classification for Patient Safety and taxonomy models from radiotherapy and other industries; (2) the taxonomy was evaluated using actual incident data from a single practitioner and revised; and (3) face validity testing of the taxonomy was performed by two additional practitioners from different radiotherapy centers using simulated incident cases. RESULTS: The taxonomy consisted of seven classes: incident nature, impact, incident type, stage of origin, stage of discovery, contributing factors, and preventative strategies. Each class was divided into subcategories containing increasingly detailed information. A total of 191 consecutive incidents were classified in phase 2 to ensure no further revision to the taxonomy was required. In phase 3, low interobserver agreement (<60%) was obtained for most classes of the taxonomy in the first face validity test. After revisions were made to the taxonomy based on practitioners' feedback, a second face validity test yielded a high degree of agreement (70%-93%) for all classes. CONCLUSIONS: Our multiphase, iterative approach has yielded a workable and multidimensional set of incident classifiers that can be scaled to accommodate local, regional and discipline-specific requirements. Opportunities exist to implement this taxonomy in institutional and national incident databases to facilitate incident learning within and between institutions.

Implementation of remote 3-dimensional image guided radiation therapy quality assurance for radiation therapy oncology group clinical trials.

PURPOSE: To report the process and initial experience of remote credentialing of three-dimensional (3D) image guided radiation therapy (IGRT) as part of the quality assurance (QA) of submitted data for Radiation Therapy Oncology Group (RTOG) clinical trials; and to identify major issues resulting from this process and analyze the review results on patient positioning shifts. METHODS AND MATERIALS: Image guided radiation therapy datasets including in-room positioning CT scans and daily shifts applied were submitted through the Image Guided Therapy QA Center from institutions for the IGRT credentialing process, as required by various RTOG trials. A centralized virtual environment is established at the RTOG Core Laboratory, containing analysis tools and database infrastructure for remote review by the Physics Principal Investigators of each protocol. The appropriateness of IGRT technique and volumetric image registration accuracy were evaluated. Registration accuracy was verified by repeat registration with a third-party registration software system. With the accumulated review results, registration differences between those obtained by the Physics Principal Investigators and from the institutions were analyzed for different imaging sites, shift directions, and imaging modalities. RESULTS: The remote review process was successfully carried out for 87 3D cases (out of 137 total cases, including 2-dimensional and 3D) during 2010. Frequent errors in submitted IGRT data and challenges in the review of image registration for some special cases were identified. Workarounds for these issues were developed. The average differences of registration results between reviewers and institutions ranged between 2 mm and 3 mm. Large discrepancies in the superior-inferior direction were found for megavoltage CT cases, owing to low spatial resolution in this direction for most megavoltage CT cases. CONCLUSION: This first experience indicated that remote review for 3D IGRT as part of QA for RTOG clinical trials is feasible and effective. The magnitude of registration discrepancy between institution and reviewer was presented, and the major issues were investigated to further improve this remote evaluation process.

The Effect of Registration Volume Extent on Residual Errors Assessed Using Cone-Beam Computed Tomography in Radiation Treatment of Head and Neck Cancer.

PURPOSE: The objective of this study was to investigate the effect of the varying extent of cone-beam computed tomography (CBCT) registration volumes (RVs) on setup errors for head and neck (H&N) radiotherapy. METHODS AND MATERIALS: Daily CBCT images for 31 patients receiving H&N intensity-modulated radiotherapy (IMRT) were reviewed. Registrations using anatomically defined RVs with a fixed superior border at base of sella and varying inferior extent were used retrospectively to evaluate patient setup. The inferior extent was defined as the number of cervical bodies included, from none (C0) to six (C6). The frequency of residual displacements at four landmarks (clivus, vertebral bodies C5-C6, manubrium-sterni, and anterior body of mandible) was assessed. RESULTS: Expansion of the RVs inferiorly reduced the occurrence of residual displacements for the C5-C6 vertebral bodies (from 57% to 93% of fractions with residual displacements ≤ 3 mm) and increased the rate of simultaneous positioning of C5-C6 and clivus (from 41% to 76%). Maximum residual displacements for mandible (48%-64% ≤ 3 mm) and manubrium (73%-81% ≤ 3 mm) varied somewhat by the inferior extent of the RV. Residual displacements for clivus were small (88%-96% ≤ 3 mm) in all cases. Random and systematic errors were clinically acceptable for a 5-mm planning margin around the clinical targets. CONCLUSIONS: In conclusion, expansion of the RV inferiorly to include C6 will improve the positioning of structures in the C5-C6 region (adjacent nodal zones 3 and 4) without compromising clival positioning. Insufficient inferior extent of the RV reduces reliability of low neck positioning. Substantial variability can occur for structures not included in the RV. Based on these data, we use the C6 RV except in cases with planning concerns outside this volume.