SafetyNet: Streamlining and Automating QA in radiotherapy.

Proper quality assurance (QA) of the radiotherapy process can be time-consuming and expensive. Many QA efforts, such as data export and import, are inefficient when done by humans. Additionally, humans can be unreliable, lose attention, and fail to complete critical steps that are required for smooth operations. In our group we have sought to break down the QA tasks into separate steps and to automate those steps that are better done by software running autonomously or at the instigation of a human. A team of medical physicists and software engineers worked together to identify opportunities to streamline and automate QA. Development efforts follow a formal cycle of writing software requirements, developing software, testing and commissioning. The clinical release process is separated into clinical evaluation testing, training, and finally clinical release. We have improved six processes related to QA and safety. Steps that were previously performed by humans have been automated or streamlined to increase first-time quality, reduce time spent by humans doing low-level tasks, and expedite QA tests. Much of the gains were had by automating data transfer, implementing computer-based checking and automation of systems with an event-driven framework. These coordinated efforts by software engineers and clinical physicists have resulted in speed improvements in expediting patient-sensitive QA tests.

Primary peritoneal clear cell carcinoma treated with IMRT and interstitial HDR brachytherapy: a case report.

Primary peritoneal clear cell carcinoma (PP-CCC), which is a rare tumor with poor prognosis, is typically managed with surgery and/or chemotherapy. We present a unique treatment approach for a patient with a pelvic PP-CCC, consisting of postchemotherapy intensity-modulated radiation therapy (IMRT) followed by interstitial high-dose-rate (HDR) brachytherapy. A 54-year-old female with an inoperable pelvic-supravaginal 5.6 cm T3N0M0 PP-CCC tumor underwent treatment with 6 cycles of carboplatin and taxol chemotherapy. Postchemotherapy PET/CT scan revealed a residual 3.3 cm tumor. The patient underwent CT and MR planning simulation, and was treated with 50 Gy to the primary tumor and 45 Gy to the pelvis including the pelvic lymph nodes, using IMRT to spare bowel. Subsequently, the patient was treated with an interstitial HDR brachytherapy implant, planned using both CT and MR scans. A total dose of 15 Gy in 5 Gy fractions over two days was delivered with Ir-192 HDR brachytherapy. The total prescribed equivalent 2 Gy dose (EQD2) to the HDR planning target volume (PTV) from both the EBRT and HDR treatments ranged between 63 and 68.8 Gy2 due to differential dosing of the primary and pelvic targets. The patient tolerated radiotherapy well, except for mild diarrhea not requiring medication. There was no patient-reported acute toxicity one month following the radiotherapy course. At four months following adjuvant radiation therapy, the patient had near complete resolution of local tumor on PET/CT without any radiation-associated toxicity. However, the patient was noted to have metastatic disease outside of the radiation field, specifically lesions in the liver and bone. This case report illustrates the feasibility of the treatment of a pelvic PP-CCC with IMRT followed by interstitial HDR brachytherapy boost, which resulted in near complete local tumor response without significant morbidity.

Migration check tool: automatic plan verification following treatment management systems upgrade and database migration.

Software upgrades of the treatment management system (TMS) sometimes require that all data be migrated from one version of the database to another. It is necessary to verify that the data are correctly migrated to assure patient safety. It is impossible to verify by hand the thousands of parameters that go into each patient's radiation therapy treatment plan. Repeating pretreatment QA is costly, time-consuming, and may be inadequate in detecting errors that are introduced during the migration. In this work we investigate the use of an automatic Plan Comparison Tool to verify that plan data have been correctly migrated to a new version of a TMS database from an older version. We developed software to query and compare treatment plans between different versions of the TMS. The same plan in the two TMS systems are translated into an XML schema. A plan comparison module takes the two XML schemas as input and reports any differences in parameters between the two versions of the same plan by applying a schema mapping. A console application is used to query the database to obtain a list of active or in-preparation plans to be tested. It then runs in batch mode to compare all the plans, and a report of success or failure of the comparison is saved for review. This software tool was used as part of software upgrade and database migration from Varian's Aria 8.9 to Aria 11 TMS. Parameters were compared for 358 treatment plans in 89 minutes. This direct comparison of all plan parameters in the migrated TMS against the previous TMS surpasses current QA methods that relied on repeating pretreatment QA measurements or labor-intensive and fallible hand comparisons.

Predictors of Acute and Late Toxicity in Patients Receiving Chemoradiation for Unresectable Pancreatic Cancer.

Purpose: Patients with pancreatic cancer undergoing chemoradiation therapy may experience acute and chronic side effects. We conducted an exploratory analysis of patients with locally advanced pancreatic cancer (LAPC) undergoing definitive chemoradiation to identify factors influencing the occurrence of gastrointestinal (GI) bleeding, short-term radiation side effects, patterns of failure, and survival. Methods and Materials: Under an institutional review board-approved protocol, we retrospectively studied patients with LAPC treated with chemoradiation. Statistical models were used to test associations between clinical characteristics and outcomes, including upper GI bleeding, radiation treatment breaks, and weight loss during therapy. Results: Between 1999 and 2012, 211 patients were treated with radiation for pancreatic cancer. All patients received concurrent chemotherapy with either gemcitabine (174) or 5-fluorouracil (27), and 67 received intensity modulated radiation therapy (IMRT). Overall, 18 patients experienced an upper GI bleed related to treatment, with 70% of bleeds occurring in the stomach or duodenum, and among those patients, 11 (61%) patients had a pancreatic head tumor and 17 (94%) patients had a metallic biliary stent. IMRT was associated with decreased risk of postradiation nausea (odds ratio, 0.27 [0.11, 0.67], P = .006) compared with 3-dimensional conformal radiation. Regarding long-term toxicities, patients with a metallic biliary stent at the time of radiation therapy were at a significantly higher risk of developing upper GI bleeding (unadjusted hazard ratio [HR], 15.41 [2.02, 117.42], P = .008), even after controlling for radiation treatment modality and prescribed radiation dose (adjusted HR, 17.38 [2.26, 133.58], P = .006). Furthermore, biliary stent placement was associated with a higher risk of death (HR, 1.99 [1.41, 2.83], P < .001) after adjusting for demographic, treatment-related, and patient-related variables. Conclusions: Metallic biliary stents may be associated with an increased risk of upper GI bleeding and mortality. Furthermore, IMRT was associated with less nausea and short-term toxicity compared with 3-dimensional conformal therapy.

Potential use of ultrasound speckle tracking for motion management during radiotherapy: preliminary report.

We prospectively evaluated real-time ultrasound speckle tracking for monitoring soft tissue motion for image-guided radiotherapy. Two human volunteers and 1 patient with a proven hepatocellular carcinoma, who was being prepared for radiation therapy treatment, were scanned using a clinical ultrasound scanner modified to acquire and store radiofrequency signals. Scans were performed of the liver in the volunteers and the patient. In the patient, the speckle-tracking results were compared to those measured on a treatment-planning 4-dimensional computed tomogram with tumors contoured manually in each phase and with estimates made by hand on gray scale ultrasound images. The surface of the right lung and the prostate were scanned in a volunteer. The liver and lung surface were scanned during respiration. To simulate prostate motion, the ultrasound probe was rocked in an anterior-posterior direction. The correlation coefficients of all motion measurements were significantly correlated at all sites (P < .00001 for all sites) with 0 time delays. Ultrasound speckle-tracking motion estimates of tumor motion were within 2 mm of estimates made by hand tracking on gray scale ultrasound images and the 4-dimensional computed tomogram. The total tumor motion was greater than 20 mm. The angular displacement of the prostate was within 0.02 radians (1.1°) with displacements measured by hand. Speckle tracking could be used to monitor organ motion during radiotherapy.

A Safe and Practical Cycle for Team-Based Development and Implementation of In-House Clinical Software.

PURPOSE: Due to a gap in published guidance, we describe our robust cycle of in-house clinical software development and implementation, which has been used for years to facilitate the safe treatment of all patients in our clinics. METHODS AND MATERIALS: Our software development and implementation cycle requires clarity in communication, clearly defined roles, thorough commissioning, and regular feedback. Cycle phases include design requirements and use cases, development, physics evaluation testing, clinical evaluation testing, and full clinical release. Software requirements, release notes, test suites, and a commissioning report are created and independently reviewed before clinical use. Software deemed to be high-risk, such as those that are writable to a database, incorporate the use of a formal, team-based hazard analysis. Incident learning is used to both guide initial development and improvements as well as to monitor the safe use of the software. RESULTS: Our standard process builds in transparency and establishes high expectations in the development and use of custom software to support patient care. Since moving to a commercial planning system platform in 2013, we have applied our team-based software release process to 16 programs related to scripting in the treatment planning system for the clinic. CONCLUSIONS: The principles and methodology described here can be implemented in a range of practice settings regardless of whether or not dedicated resources are available for software development. In addition to teamwork with defined roles, documentation, and use of incident learning, we strongly recommend having a written policy on the process, using phased testing, and incorporating independent oversight and approval before use for patient care. This rigorous process ensures continuous monitoring for and mitigatation of any high risk hazards.

Analysis of couch position tolerance limits to detect mistakes in patient setup.

This work investigates the use of the tolerance limits on the treatment couch position to detect mistakes in patient positioning and warn users of possible treatment errors. Computer controlled radiotherapy systems use the position of the treatment couch as a surrogate for patient position and a tolerance limit is applied against a planned position. When the couch is out of tolerance a warning is sent to a user to indicate a possible mistake in setup. A tight tolerance may catch all positioning mistakes while as the same time sending too many warnings; while a loose tolerance will not catch all mistakes. We develop a statistical model of the absolute position for the three translational axes of the couch. The couch position for any fraction is considered a random variable x(i). The ideal planned couch position x(p) is unknown before a patient starts treatment and must be estimated from the daily positions x(i). As such x(p) is also a random variable. The tolerance, tol, is applied to the difference between the daily and planned position, d(i) = x(i) - x(p). The di is a linear combination of random variables and therefore the density of di is the convolution of distributions of xi and xp. Tolerance limits are based on the standard deviation of d(i) such that couch positions that are more than 2 standard deviation away are considered out of tolerance. Using this framework we investigate two methods of setting x(p) and tolerance limits. The first, called first day acquire (FDA), is to take couch position on the first day as the planned position. The second is to use the cumulative average (CumA) over previous fractions as the planned position. The standard deviation of d(i) shrinks as more samples are used to determine x(p) and so the tolerance limit shrinks as a function of fraction number when a CumA technique is used. The metrics of sensitivity and specificity were used to characterize the performance of the two methods to correctly identify a couch position as in or out of tolerance. These two methods were tested using simulated and real patient data. Five clinical sites with different indexed immobilization were tested. These were whole brain, head and neck, breast, thorax and prostate. Analysis of the head and neck data shows that it is reasonable to model the daily couch position as a random variable in this treatment site. Using an average couch position for x(p) increased the sensitivity of the couch interlock and reduced the chances of acquiring a couch position that was a statistical outlier. Analysis of variation in couch position for different sites allowed the tolerance limit to be set specifically for a site and immobilization device. The CumA technique was able to increase the sensitivity of detecting out of tolerance positions while shrinking tolerance limits for a treatment course. Making better use of the software interlock on the couch positions could have a positive impact on patient safety and reduce mistakes in treatment delivery.

Synchronized dynamic dose reconstruction.

Variations in target volume position between and during treatment fractions can lead to measurable differences in the dose distribution delivered to each patient. Current methods to estimate the ongoing cumulative delivered dose distribution make idealized assumptions about individual patient motion based on average motions observed in a population of patients. In the delivery of intensity modulated radiation therapy (IMRT) with a multi-leaf collimator (MLC), errors are introduced in both the implementation and delivery processes. In addition, target motion and MLC motion can lead to dosimetric errors from interplay effects. All of these effects may be of clinical importance. Here we present a method to compute delivered dose distributions for each treatment beam and fraction, which explicitly incorporates synchronized real-time patient motion data and real-time fluence and machine configuration data. This synchronized dynamic dose reconstruction method properly accounts for the two primary classes of errors that arise from delivering IMRT with an MLC: (a) Interplay errors between target volume motion and MLC motion, and (b) Implementation errors, such as dropped segments, dose over/under shoot, faulty leaf motors, tongue-and-groove effect, rounded leaf ends, and communications delays. These reconstructed dose fractions can then be combined to produce high-quality determinations of the dose distribution actually received to date, from which individualized adaptive treatment strategies can be determined.

A precision translation stage for reproducing measured target volume motions.

The development of 4D imaging, treatment planning and treatment delivery methods for radiation therapy require the use of a high-precision translation stage for testing and validation. These technologies may require spatial resolutions of 1 mm, and temporal resolutions of 2-30 Hz for CT imaging, electromagnetic tracking, and fluoroscopic imaging. A 1D programmable translation stage capable of reproducing idealized and measured anatomic motions common to the thorax has been design and built to meet these spatial and temporal resolution requirement with phantoms weighing up to 27 kg. The stage consists of a polycarbonate base and table, driven by an AC servo motor with encoder feedback by means of a belt-coupled precision screw. Complex motions are possible through a programmable motion controller that is capable of running multiple independent control and monitoring programs concurrently. Programmable input and output ports allow motion to be synchronized with beam delivery and other imaging and treatment delivery devices to within 2.0 ms. Average deviations from the programmed positions are typically 0.2 mm or less, while the average typical maximum positional errors are typically 0.5 mm for an indefinite number of idealized breathing motion cycles and while reproducing measured target volume motions for several minutes.

Influence of intrafraction motion on margins for prostate radiotherapy.

PURPOSE: To assess the impact of intrafraction intervention on margins for prostate radiotherapy. METHODS AND MATERIALS: Eleven supine prostate patients with three implanted transponders were studied. The relative transponder positions were monitored for 8 min and combined with previously measured data on prostate position relative to skin marks. Margins were determined for situations of (1) skin-based positioning, and (2) pretreatment transponder positioning. Intratreatment intervention was simulated assuming conditions of (1) continuous tracking, and (2) a 3-mm threshold for position correction. RESULTS: For skin-based setup without and with inclusion of intrafraction motion, prostate treatments would have required average margins of 8.0, 7.3, and 10.0 mm and 8.2, 10.2, and 12.5 mm, about the left-right, anterior-posterior, and cranial-caudal directions, respectively. Positioning by prostate markers at the start of the treatment fraction reduced these values to 1.8, 5.8, and 7.1 mm, respectively. Interbeam adjustment further reduced margins to an average of 1.4, 2.3, and 1.8 mm. Intrabeam adjustment yielded margins of 1.3, 1.5, and 1.5 mm, respectively. CONCLUSION: Significant reductions in margins might be achieved by repositioning the patient before each beam, either radiographically or electromagnetically. However, 2 of the 11 patients would have benefited from continuous target tracking and threshold-based intervention.

Target localization and real-time tracking using the Calypso 4D localization system in patients with localized prostate cancer.

PURPOSE: The Calypso 4D Localization System is being developed to provide accurate, precise, objective, and continuous target localization during radiotherapy. This study involves the first human use of the system, to evaluate the localization accuracy of this technique compared with radiographic localization and to assess its ability to obtain real-time prostate-motion information. METHODS AND MATERIALS: Three transponders were implanted in each of 20 patients. Eleven eligible patients of the 20 patients participated in a study arm that compared radiographic triangulated transponder locations to electromagnetically recorded transponder locations. Transponders were tracked for 8-min periods. RESULTS: The implantations were all successful, with no major complications. Intertransponder distances were largely stable. Comparison of the patient localization on the basis of transponder locations as per the Calypso system with the radiographic transponder localization showed an average (+/-SD) 3D difference of 1.5 +/- 0.9 mm. Upon tracking during 8 min, 2 of the 11 patients showed significant organ motion (>1 cm), with some motion lasting longer that 1 min. CONCLUSION: Calypso transponders can be used as magnetic intraprostatic fiducials. Clinical evaluation of this novel 4D nonionizing electromagnetic localization system with transponders indicates a comparable localization accuracy to isocenter, (within 2 mm) compared with X-ray localization.

Light field and crosshair quality assurance test using a simple lens system.

We describe here a simple lens system to test the positioning of the field light source and mylar crosshair for radiation therapy linear accelerators. Ideally the light source for the field light and the crosshair should be centered on the axis of rotation of the collimator. The traditional method for testing this coincidence uses the shadow of the crosshair caused by the field light source. The shadow of the crosshair is dependent on the position of both the field light source and mylar crosshair. Geometrically it is possible for the field light source and the mylar crosshair to be off the axis of rotation of the collimator and still cause the shadow of the crosshair to be on the axis of rotation at some distance. Using a lens system the motion of the field light source and crosshair can be observed in sharp focus independently of one another as the collimator is rotated.

Enhancing safety and quality through preplanning peer review for patients undergoing stereotactic body radiation therapy.

PURPOSE: Because of its high dose per fraction delivery, stereotactic body radiation therapy (SBRT) requires real-time process assurance to promote safe, high-quality treatments. In an effort to assure safety and first-time quality, we instituted a pilot, single-institution, SBRT peer review process before treatment planning. Here, we present a summary of the results of that process over a 26-month period. METHODS AND MATERIALS: Before planning, all patients were presented at an SBRT "rounds" that required, at a minimum, the treating attending or resident physician, an independent attending physician, a physicist, and a dosimetrist. Items reviewed included imaging, image registration, target contours, prescription, and planning goals. The results of peer review were prospectively recorded and logistic regression models were used to assess the relationship between various physician and case characteristics and the odds of a change being made. RESULTS: A total of 513 SBRT cases were peer reviewed before planning. In 22.6% of cases, at least 1 change was made because of this process. A lower change rate was observed in higher volume SBRT body sites (lung and liver). In all body sites, gross and planning target volume contours were changed 8.2% and 5.5% of the time, respectively. The prescription was changed 4.9% of the time, and organs at risk goals were changed 7.2% of the time. The odds of having a change were significantly lower when the treating oncologist had more SBRT experience. CONCLUSIONS: Preplanning peer review by an independent physician, physicist, and dosimetrist resulted in changes in nearly one-quarter of SBRT patients, potentially preventing suboptimal treatments. The odds of a change being required were decreased in higher volume body sites and when the treating oncologist was more experienced with SBRT, underscoring the potential importance of peer review in uncommon SBRT sites and at low-volume SBRT centers.

Effects of immobilization mask material on surface dose.

This work investigates the increase in surface dose caused by thermoplastic masks used for patient positioning and immobilization. A thermoplastic mask is custom fit by stretching a heated mask over the patient at the time of treatment simulation. This mask is then used at treatment to increase the reproducibility of the patient position. The skin sparing effect of mega-voltage X-ray beams can be reduced when the patient's skin surface is under the mask material. The sheet of thermoplastic mask has holes to reduce this effect and is available from one manufacturer with two different sizes of holes, one larger than the other. This work investigates the increase in surface dose caused by the mask material and quantifies the difference between the two samples of masks available. The change in the dose buildup was measured using an Attix parallel plate chamber by measuring tissue maximum ratios (TMRs) using solid water. Measurements were made with and without the mask material on the surface of the solid water for 6-MV and 15-MV X-ray beams. The effective thickness of equivalent water was estimated from the TMR curves, and the increase in surface dose was estimated. The buildup effect was measured to be equivalent to 2.2 mm to 0.6 mm for masks that have been stretched by different amounts. The surface dose was estimated to change from 16% and 12% for 6 MV and 15 MV, respectively, to 27% to 61% for 6 MV and 18% to 40% for 15 MV with the mask samples.

Prostate intrafraction translation margins for real-time monitoring and correction strategies.

The purpose of this work is to determine appropriate radiation therapy beam margins to account for intrafraction prostate translations for use with real-time electromagnetic position monitoring and correction strategies. Motion was measured continuously in 35 patients over 1157 fractions at 5 institutions. This data was studied using van Herk's formula of (αΣ + γσ') for situations ranging from no electromagnetic guidance to automated real-time corrections. Without electromagnetic guidance, margins of over 10 mm are necessary to ensure 95% dosimetric coverage while automated electromagnetic guidance allows the margins necessary for intrafraction translations to be reduced to submillimeter levels. Factors such as prostate deformation and rotation, which are not included in this analysis, will become the dominant concerns as margins are reduced. Continuous electromagnetic monitoring and automated correction have the potential to reduce prostate margins to 2-3 mm, while ensuring that a higher percentage of patients (99% versus 90%) receive a greater percentage (99% versus 95%) of the prescription dose.