Scott W. Hadley

A Phase I/II Trial of Intensity Modulated Radiation (IMRT) Dose Escalation With Concurrent Fixed-dose Rate Gemcitabine (FDR-G) in Patients With Unresectable Pancreatic Cancer

PURPOSE Local failure in unresectable pancreatic cancer may contribute to death. We hypothesized that intensification of local therapy would improve local control and survival. The objectives were to determine the maximum tolerated radiation dose delivered by intensity modulated radiation with fixed-dose rate gemcitabine (FDR-G), freedom from local progression (FFLP), and overall survival (OS). METHODS AND MATERIALS Eligibility included pathologic confirmation of adenocarcinoma, radiographically unresectable, performance status of 0-2, absolute neutrophil count of ≥ 1,500/mm(3), platelets ≥ 100,000/mm(3), creatinine <2 mg/dL, bilirubin <3 mg/dL, and alanine aminotransferase/aspartate aminotransferase ≤ 2.5 × upper limit of normal. FDR-G (1000 mg/m(2)/100 min intravenously) was given on days -22 and -15, 1, 8, 22, and 29. Intensity modulated radiation started on day 1. Dose levels were escalated from 50-60 Gy in 25 fractions. Dose-limiting toxicity was defined as gastrointestinal toxicity grade (G) ≥ 3, neutropenic fever, or deterioration in performance status to ≥ 3 between day 1 and 126. Dose level was assigned using TITE-CRM (Time-to-Event Continual Reassessment Method) with the target dose-limiting toxicity (DLT) rate set to 0.25. RESULTS Fifty patients were accrued. DLTs were observed in 11 patients: G3/4 anorexia, nausea, vomiting, and/or dehydration (7); duodenal bleed (3); duodenal perforation (1). The recommended dose is 55 Gy, producing a probability of DLT of 0.24. The 2-year FFLP is 59% (95% confidence interval [CI]: 32-79). Median and 2-year overall survival are 14.8 months (95% CI: 12.6-22.2) and 30% (95% CI 17-45). Twelve patients underwent resection (10 R0, 2 R1) and survived a median of 32 months. CONCLUSIONS High-dose radiation therapy with concurrent FDR-G can be delivered safely. The encouraging efficacy data suggest that outcome may be improved in unresectable patients through intensification of local therapy.

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.

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 patients 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. PACS number: 87.53.Dq

The Dosimetric Impact of Prostate Rotations During Electromagnetically Guided External-Beam Radiation Therapy

PURPOSE To study the impact of daily rotations and translations of the prostate on dosimetric coverage during radiation therapy (RT). METHODS AND MATERIALS Real-time tracking data for 26 patients were obtained during RT. Intensity modulated radiation therapy plans meeting RTOG 0126 dosimetric criteria were created with 0-, 2-, 3-, and 5-mm planning target volume (PTV) margins. Daily translations and rotations were used to reconstruct prostate delivered dose from the planned dose. D95 and V79 were computed from the delivered dose to evaluate target coverage and the adequacy of PTV margins. Prostate equivalent rotation is a new metric introduced in this study to quantify prostate rotations by accounting for prostate shape and length of rotational lever arm. RESULTS Large variations in prostate delivered dose were seen among patients. Adequate target coverage was met in 39%, 65%, and 84% of the patients for plans with 2-, 3-, and 5-mm PTV margins, respectively. Although no correlations between prostate delivered dose and daily rotations were seen, the data showed a clear correlation with prostate equivalent rotation. CONCLUSIONS Prostate rotations during RT could cause significant underdosing even if daily translations were managed. These rotations should be managed with rotational tolerances based on prostate equivalent rotations.

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 at the same time sending too many warnings; a loose tolerance will not catch all mistakes. We developed 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 xi. The ideal planned couch position xp is unknown before a patient starts treatment and must be estimated from the daily positions of xi. As such, xp is also a random variable. The tolerance, tol, is applied to the difference between the daily and planned position, di=xi−xp. 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 di such that couch positions that are more than two standard deviations away are considered out of tolerance. Using this framework, we investigated two methods of setting xp 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 di shrinks as more samples are used to determine xp and, as a result, 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 xp 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. PACS number: 87.55.Ne, 87.55.Qr, 87.55.tg, 87.55.tm

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. PACS number(s): 87.55.Ne, 87.55.Qr, 87.55.tg, 87.55.tmProper 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. PACS number(s): 87.55.Ne, 87.55.Qr, 87.55.tg, 87.55.tm.

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.

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 68.8Gy2 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. PACS number: 87.55.‐x

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 patients 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 Varians 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. PACS numbers: 87.55.T, 87.55.Qr

Development of a brachytherapy audit checklist tool

PURPOSE To develop a brachytherapy audit checklist that could be used to prepare for Nuclear Regulatory Commission or agreement state inspections, to aid in readiness for a practice accreditation visit, or to be used as an annual internal audit tool. METHODS AND MATERIALS Six board-certified medical physicists and one radiation oncologist conducted a thorough review of brachytherapy-related literature and practice guidelines published by professional organizations and federal regulations. The team members worked at two facilities that are part of a large, academic health care center. Checklist items were given a score based on their judged importance. Four clinical sites performed an audit of their program using the checklist. The sites were asked to score each item based on a defined severity scale for their noncompliance, and final audit scores were tallied by summing the products of importance score and severity score for each item. RESULTS The final audit checklist, which is available online, contains 83 items. The audit scores from the beta sites ranged from 17 to 71 (out of 690) and identified a total of 7-16 noncompliance items. The total time to conduct the audit ranged from 1.5 to 5 hours. CONCLUSIONS A comprehensive audit checklist was developed which can be implemented by any facility that wishes to perform a program audit in support of their own brachytherapy program. The checklist is designed to allow users to identify areas of noncompliance and to prioritize how these items are addressed to minimize deviations from nationally-recognized standards.