A Pareto-based beam orientation optimization method for spot scanning intensity-modulated proton therapy.

PURPOSE: To provide a proof of principle of a Pareto-based method to automatically generate optimal intensity-modulated proton therapy (IMPT) plans for various noncoplanar beam orientations. METHODS: A novel multicriteria beam orientation optimization (MCBOO) method was developed to generate Pareto database of optimal plans. The MCBOO method automatically explores the beam orientations and the scalarization parameters of the IMPT plans simultaneously. The MCBOO method is based on multicriteria bilevel optimization (i.e., hierarchical optimization with two nested levels, named the upper and lower level optimization). In MCBOO, the upper level optimization explores the noncoplanar beam orientation space, while the lower level explores the scalarization parameters for a given beam orientation. Differential evolution method was used in both levels, and the Pareto optimal plans were aggregated from the bilevel optimizations to construct the Pareto database. The MCBOO method was implemented on a multinode multi-GPU cluster, and it was tested on three brain tumor patient cases. The Pareto database of the three patients was generated for a set of DVH-based objectives. A statistical analysis was performed between a selected set of MCBOO plans and the manual plan (plan with manually selected beam orientation based on the clinical experience and optimized with the same single plan iterative optimizer used in the MCBOO). The selected set of MCBOO plans consisted of plans that matched the performance of the manual plan [i.e., MCBOO plans that have the same target coverage (within 2%) as the manual plan or better and achieved the same dose (within 2%) or lower to all of the organs at risks (OARs) but one OAR]. Additionally, a dosimetric comparison between of one of the selected MCBOO plans vs the manual plan was conducted. RESULTS: The multicriteria beam orientation optimization algorithm automatically generated Pareto plans for the three noncoplanar brain tumor cases. The MCBOO plans provided an alternative objective trade-offs to the manual plan. The selected MCBOO plans showed a reduction in dose to multiple organs at risk vs the manual plan with a maximum value which ranged between 10.8 and 12.9 Gy for the three patients. The trade-off of the OAR dose reduction resulted in higher dose to no more than one OAR for each of the selected MCBOO plans vs the manual plan. The maximum dose increase in the MCBOO plans over the manual plan ranged from 7.8 to 11.8 Gy. CONCLUSIONS: A novel multicriteria beam orientation optimization method was developed and tested on three IMPT patient cases. The method automatically generates Pareto plans database by exploring the noncoplanar beam orientations. The method was able to identify beam orientations with Pareto optimal plans that are comparable to the manually created plans with varying objective trade-offs.

Highly efficient and sensitive patient-specific quality assurance for spot-scanned proton therapy.

The purpose of this work was to develop an end-to-end patient-specific quality assurance (QA) technique for spot-scanned proton therapy that is more sensitive and efficient than traditional approaches. The patient-specific methodology relies on independently verifying the accuracy of the delivered proton fluence and the dose calculation in the heterogeneous patient volume. A Monte Carlo dose calculation engine, which was developed in-house, recalculates a planned dose distribution on the patient CT data set to verify the dose distribution represented by the treatment planning system. The plan is then delivered in a pre-treatment setting and logs of spot position and dose monitors, which are integrated into the treatment nozzle, are recorded. A computational routine compares the delivery log to the DICOM spot map used by the Monte Carlo calculation to ensure that the delivered parameters at the machine match the calculated plan. Measurements of dose planes using independent detector arrays, which historically are the standard approach to patient-specific QA, are not performed for every patient. The nozzle-integrated detectors are rigorously validated using independent detectors in regular QA intervals. The measured data are compared to the expected delivery patterns. The dose monitor reading deviations are reported in a histogram, while the spot position discrepancies are plotted vs. spot number to facilitate independent analysis of both random and systematic deviations. Action thresholds are linked to accuracy of the commissioned delivery system. Even when plan delivery is acceptable, the Monte Carlo second check system has identified dose calculation issues which would not have been illuminated using traditional, phantom-based measurement techniques. The efficiency and sensitivity of our patient-specific QA program has been improved by implementing a procedure which independently verifies patient dose calculation accuracy and plan delivery fidelity. Such an approach to QA requires holistic integration and maintenance of patient-specific and patient-independent QA.

Adaptive method for multicriteria optimization of intensity-modulated proton therapy.

PURPOSE: Provide an adaptive multicriteria optimization (MCO) method for intensity-modulated proton therapy (IMPT) utilizing GPU technology. Previously described limitations of MCO such as Pareto approximation and limitation on the number of objectives were addressed. METHODS: The treatment planning process for IMPT must account for multiple objectives, which requires extensive treatment planning resources. Often a large number of objectives (>10) are required. Hence the need for an MCO algorithm that can handle large number of objectives. The novelty of the MCO method presented here lies on the introduction of the adaptive weighting scheme that can generate a well-distributed and dense representation of the Pareto surface for a large number of objectives in an efficient manner. In our approach the generated Pareto surface is constructed for a set of DVH objectives. The MCO algorithm is based on the augmented weighted Chebychev metric (AWCM) method with an adaptive weighting scheme. This scheme uses the differential evolution (DE) method to generate a set of well-distributed Pareto points. The quality of the Pareto points' distribution in the objective space was assessed quantitatively using the Pareto sampling metric. The MCO algorithm was developed to perform multiple parallel searches to achieve a rapid mapping of the Pareto surface, produce clinically deliverable plans, and was implemented on a GPU cluster. The MCO algorithm was tested on two clinical cases with 10 and 18 objectives. For each case one of the MCO-generated plans was selected for comparison with the clinically generated plan. The MCO plan was randomly selected out of the set of MCO plans that had target coverage similar to the clinically generated plan and the same or better sparing of the organs at risk (OAR). Additionally, a validation study of the AWCM method vs the weighted sum method was performed. RESULTS: The adaptive MCO algorithm generated Pareto points on the Pareto hypersurface in a fast (2-3 hr) and efficient manner for 2 cases with 10 and 18 objectives. The MCO algorithm generated a dense and well-distributed set of Pareto points on the objective space, and was able to achieve minimization of the Pareto sampling metric. The selected MCO plan showed an improvement of the DVH objectives in comparison to the clinically optimized plan in both cases. For case one, the MCO plan showed a 48% reduction of the 50% dose to OARs and a 16% reduction of the 1% dose to OARs. For case 2, the MCO plan showed a 72% reduction of the 50% dose to OARs and a 42% reduction of the 1% dose to OARs. The comparison of AWCM to WS showed that the AWCM method has a dosimetric advantage over WS for both patient cases. CONCLUSION: We introduced an adaptive MCO algorithm for IMPT accelerated using GPUs. The algorithm is based on an adaptive method for generating Pareto plans in the objective space. We have shown that the algorithm can provide rapid and efficient mapping of the multicriteria Pareto surface with clinically deliverable plans.

Modeling of Acute Rectal Toxicity to Compare Two Patient Positioning Methods for Prostate Cancer Radiotherapy: Can Toxicity Modeling be Used for Quality Assurance?

PURPOSE: Intensity Modulated Radiation Therapy (IMRT) allows for significant dose reductions to organs at risk in prostate cancer patients. However, the accurate delivery of IMRT plans can be compromised by patient positioning errors. The purpose of this study was to determine if the modeling of grade ≥ 2 acute rectal toxicity could be used to monitor the quality of IMRT protocols. MATERIALS AND METHODS: 79 patients treated with Image and Fiducial Markers Guided IMRT (FMIGRT) and 302 patients treated with trans-abdominal ultrasound guided IMRT (USGRT) was selected for this study. Treatment plans were available for the FMIGRT group, and hand recorded dosimetric indices were available for both groups. We modeled toxicity in the FMIGRT group using the Lyman Kutcher Burman (LKB) and Univariate Logistic Regression (ULR) models, and we modeled toxicity in USGRT group using the ULR model. We performed Receiver Operating Characteristics (ROC) analysis on all of the models and compared the Area under the ROC curve (AUC) for the FMIGRT and the USGRT groups. RESULTS: The observed Incidence of grade ≥ 2 rectal toxicity was 20% in FMIGRT patients and 54% in USGRT patients. LKB model parameters in the FMIGRT group were TD50=56.8 Gy, slope m=0.093, and exponent n=0.131. The most predictive indices in the ULR model for the FMIGRT group were D25% and V50 Gy. AUC for both models in the FMIGRT group was similar (AUC=0.67). The FMIGRT URL model predicted less than a 37% incidence of grade ≥ 2 acute rectal toxicity in the USGRT group. A fit of the ULR model to USGRT data did not yield a predictive model (AUC=0.5). CONCLUSION: Modeling of acute rectal toxicity provided a quantitative measure of the correlation between planning dosimetry and this clinical endpoint. Our study suggests that an unusually weak correlation may indicate a persistent patient positioning error.

Spatial working memory deficits in obsessive compulsive disorder are associated with excessive engagement of the medial frontal cortex.

Recent studies have shown that obsessive compulsive disorder (OCD) is associated with a specific deficit in spatial working memory, especially when task difficulty (i.e., working memory load) is high. It is not clear whether this deficit is associated with dysfunction of the brain system that subserves spatial working memory, or whether it is associated with a more generalized effect on executive functions. In contrast to studies in healthy volunteers and schizophrenia, spatial working memory in OCD has not been investigated before using functional neuroimaging techniques. We conducted a functional MRI study in 11 treatment-free female patients with OCD and 11 for sex-, age-, education-, and handedness pairwise-matched healthy controls in order to assess performance on a parametric spatial n-back task as well as the underlying neuronal substrate and its dynamics. Patients with OCD performed poorly at the highest level of task difficulty and engaged the same set of brain regions as the matched healthy controls. In this set, the effect of difficulty on magnitude of brain activity was the same in patients and in controls except for a region covering the anterior cingulate cortex. In this region activity was significantly elevated in patients with OCD at all levels of the parametric task. These findings do not provide evidence for a deficit of the spatial working memory system proper, but suggest that the abnormal performance pattern may be secondary to another aspect of executive dysfunctioning in OCD.

Utilizing an electronic portal imaging device to monitor light and radiation field congruence.

A method to investigate light and radiation field congruence utilizing a commercially available amorphous silicon electronic portal imaging device (EPID) was developed. This method employed an EPID, the associated EPI software, and a diamond-shaped template. The template was constructed from a block tray in which Sn/Pb wires, 1 mm in diameter, were embedded into a diamond shaped groove milled into the tray. The collimator jaws of the linac were aligned such that the light field fell directly on the corners of the diamond. A radiation detection algorithm within the EPI software determined the extent of the radiation field. The light and radiation field congruence was evaluated by comparing the vertexes of the diamond reference structure to the detected radiation field. In addition, the digital jaw settings were recorded and later compared to the light field detected on the films and EPIs. Three linear accelerators were tracked for a period ranging from 2-8 months. Light radiation field congruence tests with films and EPIs were comparable, yielding a difference of less than 0.6 mm, well within the allowed 2-mm tolerance. A disparity was observed in the magnitude of the detected light field. The X and Y dimensions of the light field measured with film differed by less than or equal to 1.4 mm from the digital collimator settings, whereas the values extracted from the EPIs differed by up to 2.5 mm. Based on these findings, EPIs were found to be a quick and reliable alternative to film for qualitative and relative analyses.

Clinical use of electronic portal imaging: report of AAPM Radiation Therapy Committee Task Group 58.

AAPM Task Group 58 was created to provide materials to help the medical physicist and colleagues succeed in the clinical implementation of electronic portal imaging devices (EPIDs) in radiation oncology. This complex technology has matured over the past decade and is capable of being integrated into routine practice. However, the difficulties encountered during the specification, installation, and implementation process can be overwhelming. TG58 was charged with providing sufficient information to allow the users to overcome these difficulties and put EPIDs into routine clinical practice. In answering the charge, this report provides; comprehensive information about the physics and technology of currently available EPID systems; a detailed discussion of the steps required for successful clinical implementation, based on accumulated experience; a review of software tools available and clinical use protocols to enhance EPID utilization; and specific quality assurance requirements for initial and continuing clinical use of the systems. Specific recommendations are summarized to assist the reader with successful implementation and continuing use of an EPID.

Treatment of extraprostatic cancer in clinically organ-confined prostate cancer by permanent interstitial brachytherapy: is extraprostatic seed placement necessary?

PURPOSE: Successful treatment with ultrasound-guided transperineal interstitial permanent prostate brachytherapy (TIPPB) relies on effective radiation coverage of intraprostatic and clinically occult extraprostatic cancer. This study examines prostatectomy findings as they relate to treatment of extraprostatic extension (EPE) of cancer and TIPPB techniques and dosimetry. MATERIALS AND METHODS: A total of 313 prostatectomy specimens from patients with clinical tumor classification T1-T2b adenocarcinomas, serum prostate-specific antigen <20 ng/mL, and Gleason score <8 were whole mounted and evaluated for intraprostatic cancer volume and extraprostatic radial distance, area of perforation, and cancer density. From these data, extraprostatic cancer volume is calculated and used to estimate extraprostatic tumor control probabilities using the linear quadratic radiobiological model and Poisson statistics. TIPPB dose-gradient characteristics at the prostate periphery are examined. RESULTS: Intraprostatic cancer volume ranges from 0 to 38 cc, whereas extraprostatic cancer volume ranges from 0 to 4.6 cc (mean 0.06 cc). The radial distance of EPE ranges from 0 to 4.4 mm (mean 0.18 mm). The ratio of extraprostatic to intraprostatic cancer volume ranges from 0% to 18% (mean 0.4%). CONCLUSIONS: Only small amounts of clinically occult extraprostatic cancer were identified in the majority of specimens with EPE. Tumor control probability calculations suggest that this volume of cancer may be treated effectively with TIPPB. Treatment of this cancer possibly is achieved with an intraprostatic implant, but treatment of all cancers identified in this study suggests that some extraprostatic seed placement is desirable.

Guide to clinical use of electronic portal imaging.

The Electronic Portal Imaging Device (EPID) provides localization quality images and computer-aided analysis, which should in principal, replace portal film imaging. Modern EPIDs deliver superior image quality and an array of analysis tools that improve clinical decision making. It has been demonstrated that the EPID can be a powerful tool in the reduction of treatment setup errors and the quality assurance and verification of complex treatments. However, in many radiation therapy clinics EPID technology is not in routine clinical use. This low utilization suggests that the capability and potential of the technology alone do not guarantee its full adoption. This paper addresses basic considerations required to facilitate clinical implementation of the EPID technology and gives specific examples of successful implementations.

Acute radiation dermatitis following radiofrequency catheter ablation of atrioventricular nodal reentrant tachycardia.

Radiation exposure during fluoroscopic imaging poses potential risks to patients and physicians, especially during protracted cardiovascular or radiological interventional procedures. We describe a woman with refractory paroxysmal supraventricular tachycardia who underwent radiofrequency catheter ablation of the slow pathway involved in atrioventricular nodal reentrant tachycardia. The patient subsequently returned 4 weeks later with acute radiation dermatitis that was retrospectively attributed to a malfunction in the fluoroscopy unit that lacked a maximum current output cut-off switch. Using dose reconstruction studies and her estimated biological response, we determined that she received between 15 and 20 Gy (1 Gy = 100 rads) to the skin on her back during the procedure. The exposure will result in an increase in her lifelong risk of skin and lung cancer. This article underscores the potential for radiation-induced injury during lengthy therapeutic procedures using x-ray equipment.

Hodgkin and non-Hodgkin lymphoma: local-regional radiation therapy after bone marrow transplantation.

PURPOSE: To assess the acute toxicity and therapeutic effect of local-regional radiation therapy after bone marrow transplantation performed for lymphoma in resistant relapse. MATERIALS AND METHODS: Twenty-one patients with Hodgkin (n = 12) or non-Hodgkin lymphoma (n = 9) underwent local-regional radiation therapy after bone marrow transplantation. Posttransplantation radiation was delivered to the dominant site of pretransplantation disease. Three patients with Hodgkin lymphoma and four with non-Hodgkin lymphoma underwent radiation therapy for posttransplantation recurrence. Total body irradiation was used in 10 patients. Mean radiation dose was lower in patients who underwent total body irradiation than in those who did not (P = .05). RESULTS: Nineteen of 21 patients completed local-regional therapy. Nonhematologic toxicity was mild in 20 patients. Hematologic toxicity was severe in five patients, four of whom began radiation therapy with low platelet counts. In-field disease progression occurred in six of 15 patients with relapse, including four with disease progression at the start of radiation therapy. Median progression-free survival was 12 months in patients with Hodgkin lymphoma and 1 month in patients with non-Hodgkin lymphoma. CONCLUSION: Posttransplantation local-regional radiation therapy can be safely administered in patients with lymphoma. Severe hematologic toxicity is a concern, however, in patients with low platelet counts.

Clinical use of on-line portal imaging for daily patient treatment verification.

PURPOSE: To determine the ease of use by clinical staff and reliability of an electronic portal imaging system and evaluate the potential to utilize on-line imaging to assess accuracy of daily patient treatment positioning in radiation therapy. METHODS AND MATERIALS: A computer controlled fluorescent screen-mirror imaging system was used to acquire on-line portal images. A physician panel assessed on-line image quality relative to standard portal film. Clinical use of the imager was implemented through a protocol where images were obtained during the first six monitor units of external beam. The images were visually compared to a reference portal and patient setup was adjusted for errors exceeding 5 mm. Subsequent off-line analysis was utilized to give insight into the magnitude of clinical setup error in the visually accepted images. RESULTS: Physician evaluation of on-line image quality with an initial 211 images found that 70% were comparable or superior to standard film portal images. Eighty percent of treatment fields fit completely within the on-line imaging area. Eight percent of on-line images were rejected due to poor image quality. Twelve percent of the daily treatment setups imaged required adjustment overall, but specific field types predictably required more frequent adjustment (pelvic and mantle fields). Off-line analysis of accepted images demonstrates that 18% of the final images had setup errors exceeding 5 mm. CONCLUSION: On-line imaging facilitated daily portal alignment and verification. Ease of use, almost instantaneous viewing and consistent ability to identify and locate anatomical landmarks imply the potential for on-line imaging to replace film based approaches. Retrospective analysis of daily images reveals that visual assessment of setup is not sufficient for eliminating localization errors. Further improvement is required with respect to detecting localization error and fully encompassing larger field sizes.

The Oncology Clinical Information System.

This presentation provides an overview of the functions of the Oncology Clinical Information System (OCIS) focusing on three new applications. The first part of the presentation will describe the structure of OCIS and show the basic clinical decision-support aspects of the system on-line. The second part of the presentation will provide on-line demonstrations of three new applications: a sophisticated blood products ordering systems, a chemotherapy and treatment scheduling system, and a radiation therapy scheduling system.

On-line portal imaging: computer-assisted error measurement.

A microcomputer-based system was implemented in an on-line portal imaging system to determine portal misalignment in radiation therapy. Reference markers derived from a patient simulation film are superposed on the daily on-line portal images for visual evaluation of placement accuracy. The ability to check the alignment after administration of 3-6 cGy of radiation and the minimal operator interaction required make this system useful in radiation therapy delivery.