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Technological advances have greatly enhanced the specialty of radiation oncology by allowing more healthy tissue to be spared for the same or better tumour coverage. Developments in medical imaging are integral to radiation oncology, both for design of treatment plans and to localise the target for precise administration of radiation. At planning, definition of the tumour and healthy tissue is based on CT, augmented frequently with MRI and PET. At treatment, three-dimensional soft-tissue imaging can also be used to localise the target and tumour motion can be tracked with fluoroscopic imaging of radio-opaque markers implanted in or near the tumour. These developments allow changes in tumour position, size, and shape that take place during radiotherapy to be measured and accounted for to boost geometric accuracy and precision of radiation delivery. Image-guided treatment also enhances uniformity in doses administered in a population of patients, thus improving our ability to measure the effect of dosimetric and non-dosimetric factors on tumour and healthy tissue outcomes in clinical trials. Increased precision and accuracy of radiotherapy are expected to augment tumour control, reduce incidence and severity of toxic effects after radiotherapy, and facilitate development of more efficient shorter schedules than currently available. [ABSTRACT FROM AUTHOR]

Current practice for treatment planning optimization can be both inefficient and time consuming. In this paper, we propose an automated planning methodology that aims to combine both explorative and prescriptive approaches for improving the efficiency and the quality of the treatment planning process. Given a treatment plan, our explorative approach explores trade-offs between different objectives and finds an acceptable region for objective function weights via inverse optimization. Intuitively, the shape and size of these regions describe how 'sensitive' a patient is to perturbations in objective function weights. We then develop an integer programming-based prescriptive approach that exploits the information encoded by these regions to find a set of five representative objective function weight vectors such that for each patient there exists at least one representative weight vector that can produce a high quality treatment plan. Using 315 patients from Princess Margaret Cancer Centre, we show that the produced treatment plans are comparable and, for [Formula: see text] of cases, improve upon the inversely optimized plans that are generated from the historical clinical treatment plans.

We developed and evaluated a novel inverse optimization (IO) model to estimate objective function weights from clinical dose-volume histograms (DVHs). These weights were used to solve a treatment planning problem to generate 'inverse plans' that had similar DVHs to the original clinical DVHs. Our methodology was applied to 217 clinical head and neck cancer treatment plans that were previously delivered at Princess Margaret Cancer Centre in Canada. Inverse plan DVHs were compared to the clinical DVHs using objective function values, dose-volume differences, and frequency of clinical planning criteria satisfaction. Median differences between the clinical and inverse DVHs were within 1.1 Gy. For most structures, the difference in clinical planning criteria satisfaction between the clinical and inverse plans was at most 1.4%. For structures where the two plans differed by more than 1.4% in planning criteria satisfaction, the difference in average criterion violation was less than 0.5 Gy. Overall, the inverse plans were very similar to the clinical plans. Compared with a previous inverse optimization method from the literature, our new inverse plans typically satisfied the same or more clinical criteria, and had consistently lower fluence heterogeneity. Overall, this paper demonstrates that DVHs, which are essentially summary statistics, provide sufficient information to estimate objective function weights that result in high quality treatment plans. However, as with any summary statistic that compresses three-dimensional dose information, care must be taken to avoid generating plans with undesirable features such as hotspots; our computational results suggest that such undesirable spatial features were uncommon. Our IO-based approach can be integrated into the current clinical planning paradigm to better initialize the planning process and improve planning efficiency. It could also be embedded in a knowledge-based planning or adaptive radiation therapy framework to automatically generate a new plan given a predicted or updated target DVH, respectively.

This paper offers best practice recommendations for the maintenance and retention of radiotherapy health records and technical information for cancer programmes. The recommendations are based on a review of the published and grey literature, feedback from key informants from seven countries and expert consensus. Ideally, complete health records should be retained for 5 years beyond the patient's lifetime, regardless of where they are created and maintained. Technical information constituting the radiotherapy plan should also be retained beyond the patient's lifetime for 5 years, including the primary images, contours of delineated targets and critical organs, dose distributions and other radiotherapy plan objects. There have been increased data storage and access requirements to support modern image-guided radiotherapy. Therefore, the proposed recommendations represent an ideal state of radiotherapy record retention to facilitate ongoing safe and effective care for patients as well as meaningful and informed retrospective research and policy development., (Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

OBJECTIVE Craniospinal irradiation damages the white matter in children treated for medulloblastoma, but the treatment-intensity effects are unclear. In a cross-sectional retrospective study, the effects of treatment with the least intensive radiation protocol versus protocols that delivered more radiation to the brain, in addition to the effects of continuous radiation dose, on white matter architecture were evaluated. METHODS Diffusion tensor imaging was used to assess fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity. First, regional white matter analyses and tract-based spatial statistics were conducted in 34 medulloblastoma patients and 38 healthy controls. Patients were stratified according to those treated with 1) the least intensive radiation protocol, specifically reduced-dose craniospinal irradiation plus a boost to the tumor bed only (n = 17), or 2) any other dose and boost combination that delivered more radiation to the brain, which was also termed the "all-other-treatments" group (n = 17), and comprised patients treated with standard-dose craniospinal irradiation plus a posterior fossa boost, standard-dose craniospinal irradiation plus a tumor bed boost, or reduced-dose craniospinal irradiation plus a posterior fossa boost. Second, voxel-wise dose-distribution analyses were conducted on a separate cohort of medulloblastoma patients (n = 15). RESULTS The all-other-treatments group, but not the reduced-dose craniospinal irradiation plus tumor bed group, had lower fractional anisotropy and higher radial diffusivity than controls in all brain regions (all p < 0.05). The reduced-dose craniospinal irradiation plus tumor bed boost group had higher fractional anisotropy (p = 0.05) and lower radial diffusivity (p = 0.04) in the temporal region, and higher fractional anisotropy in the frontal region (p = 0.04), than the all-other-treatments group. Linear mixed-effects modeling revealed that the dose and age at diagnosis together 1) better predicted fractional anisotropy in the temporal region than models with either alone (p < 0.005), but 2) did not better predict fractional anisotropy in comparison with dose alone in the occipital region (p > 0.05). CONCLUSIONS Together, the results show that white matter damage has a clear association with increasing radiation dose, and that treatment with reduced-dose craniospinal irradiation plus tumor bed boost appears to preserve white matter in some brain regions.

Purpose: To determine how training set size affects the accuracy of knowledge-based treatment planning (KBP) models., Methods: The authors selected four models from three classes of KBP approaches, corresponding to three distinct quantities that KBP models may predict: dose-volume histogram (DVH) points, DVH curves, and objective function weights. DVH point prediction is done using the best plan from a database of similar clinical plans; DVH curve prediction employs principal component analysis and multiple linear regression; and objective function weights uses either logistic regression or K-nearest neighbors. The authors trained each KBP model using training sets of sizes n = 10, 20, 30, 50, 75, 100, 150, and 200. The authors set aside 100 randomly selected patients from their cohort of 315 prostate cancer patients from Princess Margaret Cancer Center to serve as a validation set for all experiments. For each value of n, the authors randomly selected 100 different training sets with replacement from the remaining 215 patients. Each of the 100 training sets was used to train a model for each value of n and for each KBT approach. To evaluate the models, the authors predicted the KBP endpoints for each of the 100 patients in the validation set. To estimate the minimum required sample size, the authors used statistical testing to determine if the median error for each sample size from 10 to 150 is equal to the median error for the maximum sample size of 200., Results: The minimum required sample size was different for each model. The DVH point prediction method predicts two dose metrics for the bladder and two for the rectum. The authors found that more than 200 samples were required to achieve consistent model predictions for all four metrics. For DVH curve prediction, the authors found that at least 75 samples were needed to accurately predict the bladder DVH, while only 20 samples were needed to predict the rectum DVH. Finally, for objective function weight prediction, at least 10 samples were needed to train the logistic regression model, while at least 150 samples were required to train the K-nearest neighbor methodology., Conclusions: In conclusion, the minimum required sample size needed to accurately train KBP models for prostate cancer depends on the specific model and endpoint to be predicted. The authors' results may provide a lower bound for more complicated tumor sites.

Purpose: To develop and evaluate the clinical applicability of advanced machine learning models that simultaneously predict multiple optimization objective function weights from patient geometry for intensity-modulated radiation therapy of prostate cancer., Methods: A previously developed inverse optimization method was applied retrospectively to determine optimal objective function weights for 315 treated patients. The authors used an overlap volume ratio (OV) of bladder and rectum for different PTV expansions and overlap volume histogram slopes (OVSR and OVSB for the rectum and bladder, respectively) as explanatory variables that quantify patient geometry. Using the optimal weights as ground truth, the authors trained and applied three prediction models: logistic regression (LR), multinomial logistic regression (MLR), and weighted K-nearest neighbor (KNN). The population average of the optimal objective function weights was also calculated., Results: The OV at 0.4 cm and OVSR at 0.1 cm features were found to be the most predictive of the weights. The authors observed comparable performance (i.e., no statistically significant difference) between LR, MLR, and KNN methodologies, with LR appearing to perform the best. All three machine learning models outperformed the population average by a statistically significant amount over a range of clinical metrics including bladder/rectum V53Gy, bladder/rectum V70Gy, and dose to the bladder, rectum, CTV, and PTV. When comparing the weights directly, the LR model predicted bladder and rectum weights that had, on average, a 73% and 74% relative improvement over the population average weights, respectively. The treatment plans resulting from the LR weights had, on average, a rectum V70Gy that was 35% closer to the clinical plan and a bladder V70Gy that was 29% closer, compared to the population average weights. Similar results were observed for all other clinical metrics., Conclusions: The authors demonstrated that the KNN and MLR weight prediction methodologies perform comparably to the LR model and can produce clinical quality treatment plans by simultaneously predicting multiple weights that capture trade-offs associated with sparing multiple OARs.

Unlabelled: Abstract Purpose: Numerous studies have implicated elevated second cancer risks as a result of radiation therapy. Our aim in this paper was to contribute to an understanding of the effects of radiation quality on second cancer risks. In particular, we developed a biologically motivated model to study the effects of linear energy transfer (LET) of charged particles (including protons, alpha particles and heavy ions Carbon and Neon) on the risk of second cancer., Materials and Methods: A widely used approach to estimate the risk uses the so-called initiation-inactivation-repopulation model. Based on the available experimental data for the LET dependence of radiobiological parameters and mutation rate, we generalized this formulation to include the effects of radiation quality. We evaluated the secondary cancer risks for protons in the clinical range of LET, i.e., around 4-10 (KeV/μm), which lies in the plateau region of the Bragg peak., Results: For protons, at a fixed radiation dose, we showed that the increase in second cancer risks correlated directly with increasing values of LET to a certain point, and then decreased. Interestingly, we obtained a higher risk for proton LET of 10 KeV/μm compared to the lower LET of 4 KeV/μm in the low dose region. In the case of heavy ions, the risk was higher for Carbon ions than Neon ions (even though they have almost the same LET). We also compared protons and alpha particles with the same LET, and it was interesting to note that the second cancer risks were higher for protons compared to alpha particles in the low-dose region., Conclusion: Overall, this study demonstrated the importance of including LET dependence in the estimation of second cancer risk. Our theoretical risk predictions were noticeably high; however, the biological end points should be tested experimentally for multiple treatment fields and to improve theoretical predictions.

Purpose: To demonstrate the large-scale clinical implementation and performance of an automated treatment planning methodology for tangential breast intensity modulated radiation therapy (IMRT)., Methods and Materials: Automated planning was used to prospectively plan tangential breast IMRT treatment for 1661 patients between June 2009 and November 2012. The automated planning method emulates the manual steps performed by the user during treatment planning, including anatomical segmentation, beam placement, optimization, dose calculation, and plan documentation. The user specifies clinical requirements of the plan to be generated through a user interface embedded in the planning system. The automated method uses heuristic algorithms to define and simplify the technical aspects of the treatment planning process., Results: Automated planning was used in 1661 of 1708 patients receiving tangential breast IMRT during the time interval studied. Therefore, automated planning was applicable in greater than 97% of cases. The time for treatment planning using the automated process is routinely 5 to 6 minutes on standard commercially available planning hardware. We have shown a consistent reduction in plan rejections from plan reviews through the standard quality control process or weekly quality review multidisciplinary breast rounds as we have automated the planning process for tangential breast IMRT. Clinical plan acceptance increased from 97.3% using our previous semiautomated inverse method to 98.9% using the fully automated method., Conclusions: Automation has become the routine standard method for treatment planning of tangential breast IMRT at our institution and is clinically feasible on a large scale. The method has wide clinical applicability and can add tremendous efficiency, standardization, and quality to the current treatment planning process. The use of automated methods can allow centers to more rapidly adopt IMRT and enhance access to the documented improvements in care for breast cancer patients, using technologies that are widely available and already in clinical use., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: Intensity-modulated radiation therapy (IMRT) treatment planning typically combines multiple criteria into a single objective function by taking a weighted sum. The authors propose a statistical model that predicts objective function weights from patient anatomy for prostate IMRT treatment planning. This study provides a proof of concept for geometry-driven weight determination., Methods: A previously developed inverse optimization method (IOM) was used to generate optimal objective function weights for 24 patients using their historical treatment plans (i.e., dose distributions). These IOM weights were around 1% for each of the femoral heads, while bladder and rectum weights varied greatly between patients. A regression model was developed to predict a patient's rectum weight using the ratio of the overlap volume of the rectum and bladder with the planning target volume at a 1 cm expansion as the independent variable. The femoral head weights were fixed to 1% each and the bladder weight was calculated as one minus the rectum and femoral head weights. The model was validated using leave-one-out cross validation. Objective values and dose distributions generated through inverse planning using the predicted weights were compared to those generated using the original IOM weights, as well as an average of the IOM weights across all patients., Results: The IOM weight vectors were on average six times closer to the predicted weight vectors than to the average weight vector, using l2 distance. Likewise, the bladder and rectum objective values achieved by the predicted weights were more similar to the objective values achieved by the IOM weights. The difference in objective value performance between the predicted and average weights was statistically significant according to a one-sided sign test. For all patients, the difference in rectum V54.3 Gy, rectum V70.0 Gy, bladder V54.3 Gy, and bladder V70.0 Gy values between the dose distributions generated by the predicted weights and IOM weights was less than 5 percentage points. Similarly, the difference in femoral head V54.3 Gy values between the two dose distributions was less than 5 percentage points for all but one patient., Conclusions: This study demonstrates a proof of concept that patient anatomy can be used to predict appropriate objective function weights for treatment planning. In the long term, such geometry-driven weights may serve as a starting point for iterative treatment plan design or may provide information about the most clinically relevant region of the Pareto surface to explore.

Background: This study sought to determine if preoperative image-guided intensity-modulated radiotherapy (IG-IMRT) can reduce morbidity, including wound complications, by minimizing dose to uninvolved tissues in adults with lower extremity soft tissue sarcoma., Methods: The primary endpoint was the development of an acute wound complication (WC). IG-IMRT was used to conform volumes to avoid normal tissues (skin flaps for wound closure, bone, or other uninvolved soft tissues). From July 2005 to June 2009, 70 adults were enrolled; 59 were evaluable for the primary endpoint. Median tumor size was 9.5 cm; 55 tumors (93%) were high-grade and 58 (98%) were deep to fascia., Results: Eighteen (30.5%) patients developed WCs. This was not statistically significantly different from the result of the National Cancer Institute of Canada SR2 trial (P = .2); however, primary closure technique was possible more often (55 of 59 patients [93.2%] versus 50 of 70 patients [71.4%]; P = .002), and secondary operations for WCs were somewhat reduced (6 of 18 patients [33%] versus 13 of 30 patients [43%]; P = .55). Moderate edema, skin, subcutaneous, and joint toxicity was present in 6 (11.1%), 1 (1.9%), 5 (9.3%), and 3 (5.6%) patients, respectively, but there were no bone fractures. Four local recurrences (6.8%, none near the flaps) occurred with median follow-up of 49 months., Conclusions: The 30.5% incidence of WCs was numerically lower than the 43% risk derived from the National Cancer Institute of Canada SR2 trial, but did not reach statistical significance. Preoperative IG-IMRT significantly diminished the need for tissue transfer. RT chronic morbidities and the need for subsequent secondary operations for WCs were lowered, although not significantly, whereas good limb function was maintained., (Copyright © 2013 American Cancer Society.)

Purpose: Understanding the relationship between normal tissue dose and delayed radiation toxicity is an important component of developing more effective radiation therapy. Late outcome data are generally available only for patients who have undergone 2-dimensional (2D) treatment plans. The purpose of this study was to evaluate the accuracy of 3D normal tissue dosimetry derived from reconstructed 2D treatment plans in Hodgkin's lymphoma (HL) patients., Methods and Materials: Three-dimensional lung, heart, and breast volumes were reconstructed from 2D planning radiographs for HL patients who received mediastinal radiation therapy. For each organ, a reference 3D organ was modified with patient-specific structural information, using deformable image processing software. Radiation therapy plans were reconstructed by applying treatment parameters obtained from patient records to the reconstructed 3D volumes. For each reconstructed organ mean dose (Dmean) and volumes covered by at least 5 Gy (V5) and 20 Gy (V20) were calculated. This process was performed for 15 patients who had both 2D and 3D planning data available to compare the reconstructed normal tissue doses with those derived from the primary CT planning data and also for 10 historically treated patients with only 2D imaging available., Results: For patients with 3D planning data, the normal tissue doses could be reconstructed accurately using 2D planning data. Median differences in Dmean between reconstructed and actual plans were 0.18 Gy (lungs), -0.15 Gy (heart), and 0.30 Gy (breasts). Median difference in V5 and V20 were less than 2% for each organ. Reconstructed 3D dosimetry was substantially higher in historical mantle-field treatments than contemporary involved-field mediastinal treatments: average Dmean values were 15.2 Gy vs 10.6 Gy (lungs), 27.0 Gy vs 14.3 Gy (heart), and 8.0 Gy vs 3.2 Gy (breasts)., Conclusions: Three-dimensional reconstruction of absorbed dose to organs at risk can be estimated accurately many years after exposure by using limited 2D data. Compared to contemporary involved-field treatments, normal tissue doses were significantly higher in historical mantle-field treatments. These methods build capacity to quantify the relationship between 3D normal tissue dose and observed late effects., (Copyright © 2012 Elsevier Inc. All rights reserved.)

We have developed a method to register and display 3D parametric data, in particular radiation dose, on two-dimensional endoscopic images. This registration of radiation dose to endoscopic or optical imaging may be valuable in assessment of normal tissue response to radiation, and visualization of radiated tissues in patients receiving post-radiation surgery. Electromagnetic sensors embedded in a flexible endoscope were used to track the position and orientation of the endoscope allowing registration of 2D endoscopic images to CT volumetric images and radiation doses planned with respect to these images. A surface was rendered from the CT image based on the air/tissue threshold, creating a virtual endoscopic view analogous to the real endoscopic view. Radiation dose at the surface or at known depth below the surface was assigned to each segment of the virtual surface. Dose could be displayed as either a colorwash on this surface or surface isodose lines. By assigning transparency levels to each surface segment based on dose or isoline location, the virtual dose display was overlaid onto the real endoscope image. Spatial accuracy of the dose display was tested using a cylindrical phantom with a treatment plan created for the phantom that matched dose levels with grid lines on the phantom surface. The accuracy of the dose display in these phantoms was 0.8-0.99 mm. To demonstrate clinical feasibility of this approach, the dose display was also tested on clinical data of a patient with laryngeal cancer treated with radiation therapy, with estimated display accuracy of ∼2-3 mm. The utility of the dose display for registration of radiation dose information to the surgical field was further demonstrated in a mock sarcoma case using a leg phantom. With direct overlay of radiation dose on endoscopic imaging, tissue toxicities and tumor response in endoluminal organs can be directly correlated with the actual tissue dose, offering a more nuanced assessment of normal tissue toxicities following radiation therapy and accurate registration of radiation dose to the surgical field.

Purpose: To examine the geometric relationship between local recurrence (LR) and external beam radiotherapy (RT) volumes for soft-tissue sarcoma (STS) patients treated with function-preserving surgery and RT., Methods and Materials: Sixty of 768 (7.8%) STS patients treated with combined therapy within our institution from 1990 through 2006 developed an LR. Thirty-two received preoperative RT, 16 postoperative RT, and 12 preoperative RT plus a postoperative boost. Treatment records, RT simulation images, and diagnostic MRI/CT data sets of the original and LR disease were retrospectively compared. For LR location analysis, three RT target volumes were defined according to the International Commission on Radiation Units and Measurements 29 as follows: (1) the gross tumor or operative bed; (2) the treatment volume (TV) extending 5 cm longitudinally beyond the tumor or operative bed unless protected by intact barriers to spread and at least 1-2 cm axially (the TV was enclosed by the isodose curve representing the prescribed target absorbed dose [TAD] and accounted for target/patient setup uncertainty and beam characteristics), and (3) the irradiated volume (IRV) that received at least 50% of the TAD, including the TV. LRs were categorized as developing in field within the TV, marginal (on the edge of the IRV), and out of field (occurring outside of the IRV)., Results: Forty-nine tumors relapsed in field (6.4% overall). Nine were out of field (1.1% overall), and 2 were marginal (0.3% overall)., Conclusions: The majority of STS tumors recur in field, indicating that the incidence of LR may be affected more by differences in biologic and molecular characteristics rather than aberrations in RT dose or target volume coverage. In contrast, only two patients relapsed at the IRV boundary, suggesting that the risk of a marginal relapse is low when the TV is appropriately defined. These data support the accurate delivery of optimal RT volumes in the most precise way using advanced technology and image guidance., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Biologically-based models that utilize 3D radiation dosimetry data to estimate the risk of late cardiac effects could have significant utility for planning radiotherapy in young patients. A major challenge arises from having only 2D treatment planning data for patients with long-term follow-up. In this study, we evaluate the accuracy of an advanced deformable image registration (DIR) and navigator channels (NC) adaptation technique to reconstruct 3D heart volumes from 2D radiotherapy planning images for Hodgkin's Lymphoma (HL) patients., Methods: Planning CT images were obtained for 50 HL patients who underwent mediastinal radiotherapy. Twelve image sets (6 male, 6 female) were used to construct a male and a female population heart model, which was registered to 23 HL "Reference" patients' CT images using a DIR algorithm, MORFEUS. This generated a series of population-to-Reference patient specific 3D deformation maps. The technique was independently tested on 15 additional "Test" patients by reconstructing their 3D heart volumes using 2D digitally reconstructed radiographs (DRR). The technique involved: 1) identifying a matching Reference patient for each Test patient using thorax measurements, 2) placement of six NCs on matching Reference and Test patients' DRRs to capture differences in significant heart curvatures, 3) adapting the population-to-Reference patient-specific deformation maps to generate population-to-Test patient-specific deformation maps using linear and bilinear interpolation methods, 4) applying population-to-Test patient specific deformation to the population model to reconstruct Test-patient specific 3D heart models. The percentage volume overlap between the NC-adapted reconstruction and actual Test patient's true heart volume was calculated using the Dice coefficient., Results: The average Dice coefficient expressed as a percentage between the NC-adapted and actual Test model was 89.4 ± 2.8%. The modified NC adaptation technique made significant improvements to the population deformation heart models (p = 0.01). As standard evaluation, the residual Dice error after adaptation was comparable to the volumetric differences observed in free-breathing heart volumes (p = 0.62)., Conclusions: The reconstruction technique described generates accurate 3D heart models from limited 2D planning data. This development could potentially be used to retrospectively calculate delivered dose to the heart for historically treated patients and thereby provide a better understanding of late radiation-related cardiac effects.

The January 2010 articles in The New York Times generated intense focus on patient safety in radiation treatment, with physics staffing identified frequently as a critical factor for consistent quality assurance. The purpose of this work is to review our experience with medical physics staffing, and to propose a transparent and flexible staffing algorithm for general use. Guided by documented times required per routine procedure, we have developed a robust algorithm to estimate physics staffing needs according to center-specific workload for medical physicists and associated support staff, in a manner we believe is adaptable to an evolving radiotherapy practice. We calculate requirements for each staffing type based on caseload, equipment inventory, quality assurance, educational programs, and administration. Average per-case staffing ratios were also determined for larger-scale human resource planning and used to model staffing needs for Ontario, Canada over the next 10 years. The workload specific algorithm was tested through a survey of Canadian cancer centers. For center-specific human resource planning, we propose a grid of coefficients addressing specific workload factors for each staff group. For larger scale forecasting of human resource requirements, values of 260, 700, 300, 600, 1200, and 2000 treated cases per full-time equivalent (FTE) were determined for medical physicists, physics assistants, dosimetrists, electronics technologists, mechanical technologists, and information technology specialists, respectively.

Purpose: Target delineation within volumetric imaging is a critical step in the planning process of intensity modulated radiation therapy. In endoluminal cancers, endoscopy often reveals superficial areas of visible disease beyond what is seen on volumetric imaging. Quantitatively relating these findings to the volumetric imaging is prone to human error during the recall and contouring of the target. We have developed a method to improve target delineation in the radiation therapy planning process by quantitatively registering endoscopic findings contours traced on endoscopic images to volumetric imaging., Methods: Using electromagnetic sensors embedded in an endoscope, 2D endoscopic images were registered to computed tomography (CT) volumetric images by tracking the position and orientation of the endoscope relative to a CT image set. Regions-of-interest (ROI) in the 2D endoscopic view were delineated. A mesh created within the boundary of the ROI was projected onto the 3D image data, registering the ROI with the volumetric image. This 3D ROI was exported to clinical radiation treatment planning software. The precision and accuracy of the procedure was tested on two solid phantoms with superficial markings visible on both endoscopy and CT images. The first phantom was T-shaped tube with X-marks etched on the interior. The second phantom was an anatomically correct skull phantom with a phantom superficial lesion placed on the pharyngeal surface. Markings were contoured on the endoscope images and compared with contours delineated in the treatment planning system based on the CT images. Clinical feasibility was tested on three patients with early stage glottic cancer. Image-based rendering using manually identified landmarks was used to improve the registration., Results: Using the T-shaped phantom with X-markings, the 2D to 3D registration accuracy was 1.5-3.5 mm, depending on the endoscope position relative to the markings. Intraobserver standard variation was 0.5 mm. Rotational accuracy was within 2°. Using the skull phantom, registration accuracy was assessed by calculating the average surface minimum distance between the endoscopy and treatment planning contours. The average surface distance was 0.92 mm with 93% of all points in the 2D-endoscopy ROI within 1.5 mm of any point within the ROI contoured in the treatment planning software. This accuracy is limited by the CT imaging resolution and the electromagnetic (EM) sensor accuracy. The clinical testing demonstrated that endoscopic contouring is feasible. With registration based on em tracking only, accuracy was 5.6-8.4 mm. Image-based registration reduced this error to less than 3.5 mm and enabled endoscopic contouring in all cases., Conclusions: Registration of contours generated on 2D endoscopic images to 3D planning space is feasible, with accuracy smaller than typical set-up margins. Used in addition to standard 3D contouring methods in radiation planning, the technology may improve gross tumour volume (GTV) delineation for superficial tumors in luminal sites that are only visible in endoscopy.

Purpose: To present an automated technique for two-field tangential breast intensity-modulated radiotherapy (IMRT) treatment planning., Method and Materials: A total of 158 planned patients with Stage 0, I, and II breast cancer treated using whole-breast IMRT were retrospectively replanned using automated treatment planning tools. The tools developed are integrated into the existing clinical treatment planning system (Pinnacle(3)) and are designed to perform the manual volume delineation, beam placement, and IMRT treatment planning steps carried out by the treatment planning radiation therapist. The automated algorithm, using only the radio-opaque markers placed at CT simulation as inputs, optimizes the tangential beam parameters to geometrically minimize the amount of lung and heart treated while covering the whole-breast volume. The IMRT parameters are optimized according to the automatically delineated whole-breast volume., Results: The mean time to generate a complete treatment plan was 6 min, 50 s ± 1 min 12 s. For the automated plans, 157 of 158 plans (99%) were deemed clinically acceptable, and 138 of 158 plans (87%) were deemed clinically improved or equal to the corresponding clinical plan when reviewed in a randomized, double-blinded study by one experienced breast radiation oncologist. In addition, overall the automated plans were dosimetrically equivalent to the clinical plans when scored for target coverage and lung and heart doses., Conclusion: We have developed robust and efficient automated tools for fully inversed planned tangential breast IMRT planning that can be readily integrated into clinical practice. The tools produce clinically acceptable plans using only the common anatomic landmarks from the CT simulation process as an input. We anticipate the tools will improve patient access to high-quality IMRT treatment by simplifying the planning process and will reduce the effort and cost of incorporating more advanced planning into clinical practice., (Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.)

The beam orientation optimization (BOO) problem in intensity modulated radiation therapy (IMRT) treatment planning is a nonlinear problem, and existing methods to obtain solutions to the BOO problem are time consuming due to the complex nature of the objective function and size of the solution space. These issues become even more difficult in total marrow irradiation (TMI), where many more beams must be used to cover a vastly larger treatment area than typical site-specific treatments (e.g., head-and-neck, prostate, etc). These complications result in excessively long computation times to develop IMRT treatment plans for TMI, so we attempt to develop methods that drastically reduce treatment planning time. We transform the BOO problem into the classical set cover problem (SCP) and use existing methods to solve SCP to obtain beam solutions. Although SCP is NP-Hard, our methods obtain beam solutions that result in quality treatments in minutes. We compare our approach to an integer programming solver for the SCP to illustrate the speed advantage of our approach.

Purpose: To investigate the effect of breathing motion and dose accumulation on the planned radiotherapy dose to liver tumors and normal tissues using deformable image registration., Methods and Materials: Twenty-one free-breathing stereotactic liver cancer radiotherapy patients, planned on static exhale computed tomography (CT) for 27-60 Gy in six fractions, were included. A biomechanical model-based deformable image registration algorithm retrospectively deformed each exhale CT to inhale CT. This deformation map was combined with exhale and inhale dose grids from the treatment planning system to accumulate dose over the breathing cycle. Accumulation was also investigated using a simple rigid liver-to-liver registration. Changes to tumor and normal tissue dose were quantified., Results: Relative to static plans, mean dose change (range) after deformable dose accumulation (as % of prescription dose) was -1 (-14 to 8) to minimum tumor, -4 (-15 to 0) to maximum bowel, -4 (-25 to 1) to maximum duodenum, 2 (-1 to 9) to maximum esophagus, -2 (-13 to 4) to maximum stomach, 0 (-3 to 4) to mean liver, and -1 (-5 to 1) and -2 (-7 to 1) to mean left and right kidneys. Compared to deformable registration, rigid modeling had changes up to 8% to minimum tumor and 7% to maximum normal tissues., Conclusion: Deformable registration and dose accumulation revealed potentially significant dose changes to either a tumor or normal tissue in the majority of cases as a result of breathing motion. These changes may not be accurately accounted for with rigid motion., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To evaluate inter- and intrafractional motion and rotational error for lower extremity soft tissue sarcoma patients by using cone beam computed tomography (CBCT) and an optical localization system., Methods and Materials: Thirty-one immobilized patients received CBCT image-guided intensity-modulated radiation therapy. Setup deviations of >3 mm from the planned isocenter were corrected. A second CBCT acquired before treatment delivery was registered to the planning CT to estimate interfractional setup error retrospectively. Interfractional error and rotational error were calculated in the left-right (LR), superoinferior (SI), and anteroposterior (AP) dimensions. Intrafractional motion was assessed by calculating the maximum relative displacement of optical localization system reflective markers placed on the patient's surface, combined with pre- and postfraction CBCT performed for 17 of the 31 patients once per week. The overall systematic error (SE) and random error (RE) were calculated for the interfractional and intrafractional motion for planning target volume margin calculation., Results: The standard deviation (SD) of the interfractional RE was 1.9 mm LR, 2.1 mm SI, and 1.8 mm AP, and the SE SD was 0.6 mm, 1.2 mm, and 0.7 mm in each dimension, respectively. The overall rotation (inter- and intrafractional) had an RE SD of 0.8° LR, 1.7° SI, and 0.7° AP and an SE SD of 1.1° LR, 1.3° SI, and 0.3° AP. The SD of the overall intrafractional RE was 1.6 mm LR, 1.6 mm SI, and 1.4 mm AP, and the SE SD was 0.7 mm AP, 0.6 mm SI, and 0.6 mm AP., Conclusions: A uniform 5-mm planning target volume margin was quantified for lower extremity soft tissue sarcoma patients and has been implemented clinically for image-guided intensity-modulated radiation therapy., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: Intensity-modulated radiotherapy (IMRT) may allow improvement in plan quality for treatment of liver cancer, however increasing radiation modulation complexity can lead to increased uncertainties and requirements for quality assurance. This study assesses whether target coverage and normal tissue avoidance can be maintained in liver cancer intensity-modulated radiotherapy (IMRT) plans by systematically reducing the complexity of the delivered fluence., Methods: An optimal baseline six fraction individualized IMRT plan for 27 patients with 45 liver cancers was developed which provided a median minimum dose to 0.5 cc of the planning target volume (PTV) of 38.3 Gy (range, 25.9-59.5 Gy), in 6 fractions, while maintaining liver toxicity risk <5% and maximum luminal gastrointestinal structure doses of 30 Gy. The number of segments was systematically reduced until normal tissue constraints were exceeded while maintaining equivalent dose coverage to 95% of PTV (PTVD95). Radiotherapy doses were compared between the plans., Results: Reduction in the number of segments was achieved for all 27 plans from a median of 48 segments (range 34-52) to 19 segments (range 6-30), without exceeding normal tissue dose objectives and maintaining equivalent PTVD95 and similar PTV Equivalent Uniform Dose (EUD(-20)) IMRT plans with fewer segments had significantly less monitor units (mean, 1892 reduced to 1695, p = 0.012), but also reduced dose conformity (mean, RTOG Conformity Index 1.42 increased to 1.53 p = 0.001)., Conclusions: Tumour coverage and normal tissue objectives were maintained with simplified liver IMRT, at the expense of reduced conformity.

Purpose: The beam model in a three dimensional treatment planning system (TPS) defines virtually the mechanical and dosimetric characteristics of a treatment unit. The manual optimization of a beam model during commissioning can be a time consuming task due to its iterative nature. Furthermore, the quality of the beam model commissioning depends on the user's ability to manage multiple parameters and assess their impact on the agreement between measured and calculated dose. The objective of this work is to develop and validate the performance of an automated beam model optimization system (ABMOS) based on intensity modulated radiotherapy (IMRT) beam measurements to improve beam model accuracy while streamlining the commissioning process., Methods: The ABMOS was developed to adjust selected TPS beam model parameters iteratively to maximize the agreement between measured and calculated 2D dose maps obtained for an IMRT beam pattern. A 2D diode array with high spatial resolution detectors was used to sample the entire IMRT beam pattern in a single dose measurement. The use of an IMRT beam pattern with large number of monitor units was selected to highlight the difference between planned and delivered dose and improve the signal to noise ratio in the low dose regions. ABMOS was applied to the optimization of a beam model for an Elekta Synergy S treatment unit. The optimized beam model was validated for two anatomical sites (25 paraspinal and 25 prostate cases) using two independent patient-specific IMRT quality control (QC) methods based on ion chamber and 2D diode array measurements, respectively. The conventional approach of comparing calculated and measured beam profiles and percent-depth dose curves was also used to assess improvement in beam model after ABMOS optimization. Elements of statistical process control were applied to the process of patient-specific QC performed with the ion chamber and the 2D array to complement the model comparison., Results: After beam model optimization with ABMOS, improvement in planned to delivered dose agreement was demonstrated with both patient-specific IMRT QC methods and the calculated to measured profile comparison. In terms of ion chamber measurements, the largest improvement was observed for the paraspinal cases with the mean measured to calculated dose difference at the low dose points decreasing from - 13.8% to 2.0% with the optimized beam model. The 2D diode array patient-specific QC also demonstrated clearly the improvement in beam model for both paraspinal and prostate cases with, on average, more than 96% of the diodes satisfying tolerances of 3% of dose difference or 2 mm of distance to agreement after ABMOS optimization. The capability index (C(pk)) for both patient-specific QC methods also increased with the optimized beam model., Conclusions: In this work, ABMOS was developed to use 2D diode array measurements of an IMRT beam pattern for the automated multivariable optimization of a TPS beam model. Based on the observed improvements in patient-specific QC results for 25 paraspinal and 25 prostate plans, optimization of the remaining clinical beam models using ABMOS is now ongoing in the institution.

Purpose: Late complications (cardiac toxicities, secondary lung, and breast cancer) remain a significant concern in the radiation treatment of Hodgkin's lymphoma (HL). To address this issue, predictive dose-risk models could potentially be used to estimate radiotherapy-related late toxicities. This study investigates the use of deformable image registration (DIR) and navigator channels (NCs) to reconstruct 3D lung models from 2D radiographic planning images, in order to retrospectively calculate the treatment dose exposure to HL patients treated with 2D planning, which are now experiencing late effects., Methods: Three-dimensional planning CT images of 52 current HL patients were acquired. 12 image sets were used to construct a male and a female population lung model. 23 "Reference" images were used to generate lung deformation adaptation templates, constructed by deforming the population model into each patient-specific lung geometry using a biomechanical-based DIR algorithm, MORFEUS. 17 "Test" patients were used to test the accuracy of the reconstruction technique by adapting existing templates using 2D digitally reconstructed radiographs. The adaptation process included three steps. First, a Reference patient was matched to a Test patient by thorax measurements. Second, four NCs (small regions of interest) were placed on the lung boundary to calculate 1D differences in lung edges. Third, the Reference lung model was adapted to the Test patient's lung using the 1D edge differences. The Reference-adapted Test model was then compared to the 3D lung contours of the actual Test patient by computing their percentage volume overlap (POL) and Dice coefficient., Results: The average percentage overlapping volumes and Dice coefficient expressed as a percentage between the adapted and actual Test models were found to be 89.2 +/- 3.9% (Right lung = 88.8%; Left lung = 89.6%) and 89.3 +/- 2.7% (Right = 88.5%; Left = 90.2%), respectively. Paired T-tests demonstrated that the volumetric reconstruction method made a statistically significant improvement to the population lung model shape (p < 0.05). The error in the results were also comparable to the volume overlap difference observed between inhale and exhale lung volumes during free-breathing respiratory motion (POL: p = 0.43; Dice: p = 0.20), which implies that the accuracies of the reconstruction method are within breathing constraints and would not be the confining factor in estimating normal tissue dose exposure., Conclusions: The result findings show that the DIR-NC technique can achieve a high degree of reconstruction accuracy, and could be useful in approximating 3D dosimetric representations of historical 2D treatment. In turn, this could provide a better understanding of the biophysical relationship between dose-volume exposure and late term radiotherapy effects.

Purpose: To evaluate the utility of a new complexity metric, the modulation complexity score (MCS), in the treatment planning and quality assurance processes and to evaluate the relationship of the metric with deliverability., Methods: A multisite (breast, rectum, prostate, prostate bed, lung, and head and neck) and site-specific (lung) dosimetric evaluation has been completed. The MCS was calculated for each beam and the overall treatment plan. A 2D diode array (MapCHECK, Sun Nuclear, Melbourne, FL) was used to acquire measurements for each beam. The measured and planned dose (PINNACLE3, Phillips, Madison, WI) was evaluated using different percent differences and distance to agreement (DTA) criteria (3%/ 3 mm and 2%/ 1 mm) and the relationship between the dosimetric results and complexity (as measured by the MCS or simple beam parameters) assessed., Results: For the multisite analysis (243 plans total), the mean MCS scores for each treatment site were breast (0.92), rectum (0.858), prostate (0.837), prostate bed (0.652), lung (0.631), and head and neck (0.356). The MCS allowed for compilation of treatment site-specific statistics, which is useful for comparing different techniques, as well as for comparison of individual treatment plans with the typical complexity levels. For the six plans selected for dosimetry, the average diode percent pass rate was 98.7% (minimum of 96%) for 3%/3 mm evaluation criteria. The average difference in absolute dose measurement between the planned and measured dose was 1.7 cGy. The detailed lung analysis also showed excellent agreement between the measured and planned dose, as all beams had a diode percentage pass rate for 3%/3 mm criteria of greater than 95.9%, with an average pass rate of 99.0%. The average absolute maximum dose difference for the lung plans was 0.7 cGy. There was no direct correlation between the MCS and simple beam parameters which could be used as a surrogate for complexity level (i.e., number of segments or MU). An evaluation criterion of 2%/ 1 mm reliably allowed for the identification of beams that are dosimetrically robust. In this study we defined a robust beam or plan as one that maintained a diode percentage pass rate greater than 90% at 2%/ 1 mm, indicating delivery that was deemed accurate when compared to the planned dose, even under stricter evaluation criterion. MCS and MU threshold criteria were determined by defining a required specificity of 1.0. A MCS threshold of 0.8 allowed for identification of robust deliverability with a sensitivity of 0.36. In contrast, MU had a lower sensitivity of 0.23 for a threshold of 50 MU., Conclusions: The MCS allows for a quantitative assessment of plan complexity, on a fixed scale, that can be applied to all treatment sites and can provide more information related to dose delivery than simple beam parameters. This could prove useful throughout the entire treatment planning and QA process.

Purpose: To examine the relationship between tumor location, bone dose, and irradiated bone length on the development of radiation-induced fractures for lower extremity soft tissue sarcoma (LE-STS) patients treated with limb-sparing surgery and radiotherapy (RT)., Methods and Materials: Of 691 LE-STS patients treated from 1989 to 2005, 31 patients developed radiation-induced fractures. Analysis was limited to 21 fracture patients (24 fractures) who were matched based on tumor size and location, age, beam arrangement, and mean total cumulative RT dose to a random sample of 53 nonfracture patients and compared for fracture risk factors. Mean dose to bone, RT field size (FS), maximum dose to a 2-cc volume of bone, and volume of bone irradiated to >or=40 Gy (V40) were compared. Fracture site dose was determined by comparing radiographic images and surgical reports to fracture location on the dose distribution., Results: For fracture patients, mean dose to bone was 45 +/- 8 Gy (mean dose at fracture site 59 +/- 7 Gy), mean FS was 37 +/- 8 cm, maximum dose was 64 +/- 7 Gy, and V40 was 76 +/- 17%, compared with 37 +/- 11 Gy, 32 +/- 9 cm, 59 +/- 8 Gy, and 64 +/- 22% for nonfracture patients. Differences in mean, maximum dose, and V40 were statistically significant (p = 0.01, p = 0.02, p = 0.01). Leg fractures were more common above the knee joint., Conclusions: The risk of radiation-induced fracture appears to be reduced if V40 <64%. Fracture incidence was lower when the mean dose to bone was <37 Gy or maximum dose anywhere along the length of bone was <59 Gy. There was a trend toward lower mean FS for nonfracture patients.

The concept of in-air output ratio (Sc) was introduced to characterize how the incident photon fluence per monitor unit (or unit time for a Co-60 unit) varies with collimator settings. However, there has been much confusion regarding the measurement technique to be used that has prevented the accurate and consistent determination of Sc. The main thrust of the report is to devise a theoretical and measurement formalism that ensures interinstitutional consistency of Sc. The in-air output ratio, Sc, is defined as the ratio of primary collision water kerma in free-space, Kp, per monitor unit between an arbitrary collimator setting and the reference collimator setting at the same location. Miniphantoms with sufficient lateral and longitudinal thicknesses to eliminate electron contamination and maintain transient electron equilibrium are recommended for the measurement of Sc. The authors present a correction formalism to extrapolate the correct Sc from the measured values using high-Z miniphantom. Miniphantoms made of high-Z material are used to measure Sc for small fields (e.g., IMRT or stereotactic radiosurgery). This report presents a review of the components of Sc, including headscatter, source-obscuring, and monitor-backscattering effects. A review of calculation methods (Monte Carlo and empirical) used to calculate Sc for arbitrary shaped fields is presented. The authors discussed the use of Sc in photon dose calculation algorithms, in particular, monitor unit calculation. Finally, a summary of Sc data (from RPC and other institutions) is included for QA purposes.

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.

Purpose: To evaluate the role of cone-beam CT (CBCT) guidance for setup error reduction and soft tissue visualization in accelerated partial breast irradiation (APBI)., Methods and Materials: Twenty patients were recruited for the delivery of radiotherapy to the postoperative cavity (3850 cGy in 10 fractions over 5 days) using an APBI technique. Cone-beam CT data sets were acquired after an initial skin-mark setup and before treatment delivery. These were registered online using the ipsilateral lung and external contours. Corrections were executed for translations exceeding 3 mm. The random and systematic errors associated with setup using skin-marks and setup using CBCT guidance were calculated and compared., Results: A total of 315 CBCT data sets were analyzed. The systematic errors for the skin-mark setup were 2.7, 1.7, and 2.4 mm in the right-left, anterior-posterior, and superior-inferior directions, respectively. These were reduced to 0.8, 0.7, and 0.8 mm when CBCT guidance was used. The random errors were reduced from 2.4, 2.2, and 2.9 mm for skin-marks to 1.5, 1.5, and 1.6 mm for CBCT guidance in the right-left, anterior-posterior, and superior-inferior directions, respectively., Conclusion: A skin-mark setup for APBI patients is sufficient for current planning target volume margins for the population of patients studied here. Online CBCT guidance minimizes the occurrence of large random deviations, which may have a greater impact for the accelerated fractionation schedule used in APBI. It is also likely to permit a reduction in planning target volume margins and provide skin-line visualization and dosimetric evaluation of cardiac and lung volumes.

The objective of this work is to develop a dosimetric phantom quality assurance (QA) of linear accelerators capable of cone-beam CT (CBCT) image guided and intensity-modulated radiotherapy (IG-IMRT). This phantom is to be used in an integral test to quantify in real-time both the performance of the image guidance and the dose delivery systems in terms of dose localization. The prototype IG-IMRT QA phantom consisted of a cylindrical imaging phantom (CatPhan) combined with an array of 11 radiation diodes mounted on a 10 cm diameter disk, oriented perpendicular to the phantom axis. Basic diode response characterization was performed for 6 and 18 MV photons. The diode response was compared to planning system calculations in the open and penumbrae regions of simple and complex beam arrangements. The clinical use of the QA phantom was illustrated in an integral test of an IG-IMRT treatment designed for a clinical spinal radiosurgery case. The sensitivity of the phantom to multileaf collimator (MLC) calibration and setup errors in the clinical setting was assessed by introducing errors in the IMRT plan or by displacing the phantom. The diodes offered good response linearity and long-term reproducibility for both 6 and 18 MV. Axial dosimetry of coplanar beams (in a plane containing the beam axes) was made possible with the nearly isoplanatic response of the diodes over 360 degrees of gantry (usually within +/-1%). For single beam geometry, errors in phantom placement as small as 0.5 mm could be accurately detected (in gradient > or = 1% /mm). In clinical setting, MLC systematic errors of 1 mm on a single MLC bank introduced in the IMRT plan were easily detectable with the QA phantom. The QA phantom demonstrated also sufficient sensitivity for the detection of setup errors as small as 1 mm for the IMRT delivery. These results demonstrated that the prototype can accurately and efficiently verify the entire IG-IMRT process. This tool, in conjunction with image guidance capabilities has the potential to streamline this QA process and improve the level of performance of image guided and intensity modulated radiotherapy.

Purpose: Cone-beam computed tomography (CBCT) in-room imaging allows accurate inter- and intrafraction target localization in stereotactic body radiotherapy of lung tumors., Methods and Materials: Image-guided stereotactic body radiotherapy was performed in 28 patients (89 fractions) with medically inoperable Stage T1-T2 non-small-cell lung carcinoma. The targets from the CBCT and planning data set (helical or four-dimensional CT) were matched on-line to determine the couch shift required for target localization. Matching based on the bony anatomy was also performed retrospectively. Verification of target localization was done using either megavoltage portal imaging or CBCT imaging; repeat CBCT imaging was used to assess the intrafraction tumor position., Results: The mean three-dimensional tumor motion for patients with upper lesions (n = 21) and mid-lobe or lower lobe lesions (n = 7) was 4.2 and 6.7 mm, respectively. The mean difference between the target and bony anatomy matching using CBCT was 6.8 mm (SD, 4.9, maximum, 30.3); the difference exceeded 13.9 mm in 10% of the treatment fractions. The mean residual error after target localization using CBCT imaging was 1.9 mm (SD, 1.1, maximum, 4.4). The mean intrafraction tumor deviation was significantly greater (5.3 mm vs. 2.2 mm) when the interval between localization and repeat CBCT imaging (n = 8) exceeded 34 min., Conclusion: In-room volumetric imaging, such as CBCT, is essential for target localization accuracy in lung stereotactic body radiotherapy. Imaging that relies on bony anatomy as a surrogate of the target may provide erroneous results in both localization and verification.

Purpose: To assess the feasibility of an online strategy for palliative radiotherapy (RT) of spinal bone metastasis, which integrates imaging, planning, and treatment delivery in a single step at the treatment unit. The technical challenges of this approach include cone-beam CT (CBCT) image quality for target definition, online planning, and efficient process integration., Methods and Materials: An integrated imaging, planning, and delivery system was constructed and tested with phantoms. The magnitude of CBCT image artifacts following the use of an antiscatter grid and a nonlinear scatter correction was quantified using phantom data and images of patients receiving conventional palliative RT of the spine. The efficacy of online planning was then assessed using corrected CBCT images. Testing of the complete process was performed on phantoms with assessment of timing and dosimetric accuracy., Results: The use of image corrections reduced the cupping artifact from 30% to 4.5% on CBCT images of a body phantom and improved the accuracy of CBCT numbers (water: +/- 20 Hounsfield unit [HU], and lung and bone: to within +/- 130 HU). Bony anatomy was clearly visible and was deemed sufficient for target definition. The mean total time (n = 5) for application of the online approach was 23.1 min. Image-guided dose placement was assessed using radiochromic film measurements with good agreement (within 5% of dose difference and 2 mm of distance to agreement)., Conclusions: The technical feasibility of CBCT-guided online planning and delivery for palliative single treatment has been demonstrated. The process was performed in one session equivalent to an initial treatment slot (<30 min) with dosimetric accuracy satisfying accepted RT standards.

Purpose: Three types of preoperative radiotherapy (RT) plans for extremity soft tissue sarcoma were compared to determine the amount of dose reduction possible to the planned surgical skin flaps required for tumor resection and wound closure, without compromising target coverage., Methods and Materials: Twenty-four untreated patients with large, deep, lower extremity STS treated with preoperative RT and limb salvage surgery had their original conventional treatment plans re-created. The same clinical target volume was used for all three plans. The future surgical skin flaps were created virtually through contouring by the treating surgeon and regarded as an organ at risk. The original, conformal, and intensity-modulated RT (IMRT) plans were created to deliver 50 Gy in 25 fractions to the clinical target volume. Clinical target volume and organ-at-risk dose-volume histograms were calculated and the plans compared for conformality, target coverage, and dose sparing., Results: The mean dose to the planned skin flaps was 42.62 Gy (range, 30.24-48.65 Gy) for the original plans compared with 40.12 Gy (range, 24.24-47.26 Gy) for the conformal plans and 26.71 Gy (range, 22.31-31.91 Gy) for the IMRT plans (p = 0.0008). An average of 86.4% (range, 53.2-97.4%) of the planned skin flaps received >or=30 Gy in the original plans compared with 83.4% (range, 36.2-96.2%) in the conformal plans and only 34.0% (range, 22.5-53.3%) in the IMRT plans (p = 0.0001). IMRT improved target conformality compared with the original and conformal plans (1.27, 2.34, and 1.76, respectively, p = 0.0001)., Conclusion: In a retrospective review, preoperative IMRT substantially lowered the dose to the future surgical skin flaps, sparing a greater percentage of this structure's volume without compromising target (tumor) coverage.

Purpose: The aim of this work was to assess the accuracy of kilovoltage (kV) cone-beam computed tomography (CBCT)-based setup corrections as compared with orthogonal megavoltage (MV) portal image-based corrections for patients undergoing external-beam radiotherapy of the prostate., Methods and Materials: Daily cone-beam CT volumetric images were acquired after setup for patients with three intraprostatic fiducial markers. The estimated couch shifts were compared retrospectively to patient adjustments based on two orthogonal MV portal images (the current clinical standard of care in our institution). The CBCT soft-tissue based shifts were also estimated by digitally removing the gold markers in each projection to suppress the artifacts in the reconstructed volumes. A total of 256 volumetric images for 15 patients were analyzed., Results: The Pearson coefficient of correlation for the patient position shifts using fiducial markers in MV vs. kV was (R2 = 0.95, 0.84, 0.81) in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions, respectively. The correlation using soft-tissue matching was as follows: R2 = 0.90, 0.49, 0.51 in the LR, AP and SI directions. A Bland-Altman analysis showed no significant trends in the data. The percentage of shifts within a +/-3-mm tolerance (the clinical action level) was 99.7%, 95.5%, 91.3% for fiducial marker matching and 99.5%, 70.3%, 78.4% for soft-tissue matching., Conclusions: Cone-beam CT is an accurate and precise tool for image guidance. It provides an equivalent means of patient setup correction for prostate patients with implanted gold fiducial markers. Use of the additional information provided by the visualization of soft-tissue structures is an active area of research.

Highly conformal radiation therapy tailors treatment to match the target shape and position, minimizing normal tissue damage to a greater extent than previously possible. Technological advances such as intensity-modulated radiation therapy, introduced a decade ago, have yielded significant gains in tumor control and reduced toxicity. Continuing advances have focused on the characterization and control of patient movement, organ motion, and anatomical deformation, which all introduce geometric uncertainty. These sources of uncertainty limit the effectiveness of high-precision treatment. Target localization, performed using appropriate technologies and frequency, is a critical component of treatment quality assurance. Until recently, the target position with respect to the beams has been inferred from surface marks on the patient's skin or through an immobilization device, and verified using megavoltage radiographs of the treatment portal. Advances in imaging technologies have made it possible to image soft tissue volumes in the treatment setting. Real-time tracking is also possible using a variety of technologies, including fluoroscopic imaging and radiopaque markers implanted in or near the tumor. The capacity to acquire volumetric soft tissue images in the treatment setting can also be used to assess anatomical changes over a course of treatment. Enhancing localization practices reduces treatment errors, and gives the capacity to monitor anatomical changes and reduce uncertainties that could influence clinical outcomes. This review presents the technologies available for target localization, and discusses some of the considerations that should be addressed in the implementation of many new clinical processes in radiation oncology.

Kilovoltage cone-beam computerized tomography (kV-CBCT) systems integrated into the gantry of linear accelerators can be used to acquire high-resolution volumetric images of the patient in the treatment position. Using on-line software and hardware, patient position can be determined accurately with a high degree of precision and, subsequently, set-up parameters can be adjusted to deliver the intended treatment. While the patient dose due to a single volumetric imaging acquisition is small compared to the therapy dose, repeated and daily image guidance procedures can lead to substantial dose to normal tissue. The dosimetric properties of a clinical CBCT system have been studied on an Elekta linear accelerator (Synergy RP, XVI system) and additional measurements performed on a laboratory system with identical geometry. Dose measurements were performed with an ion chamber and MOSFET detectors at the center, periphery, and surface of 30 and 16-cm-diam cylindrical shaped water phantoms, as a function of x-ray energy and longitudinal field-of-view (FOV) settings of 5,10,15, and 26 cm. The measurements were performed for full 360 degrees CBCT acquisition as well as for half-rotation scans for 120 kVp beams using the 30-cm-diam phantom. The dose at the center and surface of the body phantom were determined to be 1.6 and 2.3 cGy for a typical imaging protocol, using full rotation scan, with a technique setting of 120 kVp and 660 mAs. The results of our measurements have been presented in terms of a dose conversion factor fCBCT, expressed in cGy/R. These factors depend on beam quality and phantom size as well as on scan geometry and can be utilized to estimate dose for any arbitrary mAs setting and reference exposure rate of the x-ray tube at standard distance. The results demonstrate the opportunity to manipulate the scanning parameters to reduce the dose to the patient by employing lower energy (kVp) beams, smaller FOV, or by using half-rotation scan.

Purpose: To investigate the feasibility of a biomechanical-based deformable image registration technique for the integration of multimodality imaging, image guided treatment, and response monitoring., Methods and Materials: A multiorgan deformable image registration technique based on finite element modeling (FEM) and surface projection alignment of selected regions of interest with biomechanical material and interface models has been developed. FEM also provides an inherent method for direct tracking specified regions through treatment and follow-up., Results: The technique was demonstrated on 5 liver cancer patients. Differences of up to 1 cm of motion were seen between the diaphragm and the tumor center of mass after deformable image registration of exhale and inhale CT scans. Spatial differences of 5 mm or more were observed for up to 86% of the surface of the defined tumor after deformable image registration of the computed tomography (CT) and magnetic resonance images. Up to 6.8 mm of motion was observed for the tumor after deformable image registration of the CT and cone-beam CT scan after rigid registration of the liver. Deformable registration of the CT to the follow-up CT allowed a more accurate assessment of tumor response., Conclusions: This biomechanical-based deformable image registration technique incorporates classification, targeting, and monitoring of tumor and normal tissue using one methodology.

An image-guidance process for using cone-beam computed tomography (CBCT) for stereotactic body radiation therapy (SBRT) of peripheral lung lesions is presented. Respiration correlated CBCT on the treatment unit and four dimensional computed tomography (4DCT) from planning are evaluated for assessing respiration-induced target motion during planning and treatment fractions. Image-guided SBRT was performed for 12 patients (13 lesions) with inoperable early stage non-small cell lung carcinoma. Kilovoltage (kV) projections were acquired over a 360 degree gantry rotation and sorted based on the pixel value of an image-based aperture located at the air-tissue interface of the diaphragm. The sorted projections were reconstructed to provide volumetric respiration correlated CBCT image datasets at different phases of the respiratory cycle. The 4D volumetric datasets were directly compared with 4DCT datasets acquired at the time of planning. For ten of 12 patients treated, the lung tumour motion, as measured by respiration correlated CBCT on the treatment unit, was consistent with the tumour motion measured by 4DCT at the time of planning. However, in two patients, maximum discrepancies observed were 6 and 10 mm in the anterior-posterior and superior-inferior directions, respectively. Respiration correlated CBCT acquired on the treatment unit allows target motion to be assessed for each treatment fraction, allows target localization based on different phases on the breathing cycle, and provides the facility for adaptive margin design in radiation therapy of lung malignancies. The current study has shown that the relative motion and position of the tumour at the time of treatment may not match that of the planning 4DCT scan. Therefore, application of breathing motion data acquired at simulation for tracking or gating radiation therapy may not be suitable for all patients - even those receiving short course treatment techniques such as SBRT.

The geometric accuracy and precision of an image-guided treatment system were assessed. Image guidance is performed using an x-ray volume imaging (XVI) system integrated with a linear accelerator and treatment planning system. Using an amorphous silicon detector and x-ray tube, volumetric computed tomography images are reconstructed from kilovoltage radiographs by filtered backprojection. Image fusion and assessment of geometric targeting are supported by the treatment planning system. To assess the limiting accuracy and precision of image-guided treatment delivery, a rigid spherical target embedded in an opaque phantom was subjected to 21 treatment sessions over a three-month period. For each session, a volumetric data set was acquired and loaded directly into an active treatment planning session. Image fusion was used to ascertain the couch correction required to position the target at the prescribed iso-center. Corrections were validated independently using megavoltage electronic portal imaging to record the target position with respect to symmetric treatment beam apertures. An initial calibration cycle followed by repeated image-guidance sessions demonstrated the XVI system could be used to relocate an unambiguous object to within less than 1 mm of the prescribed location. Treatment could then proceed within the mechanical accuracy and precision of the delivery system. The calibration procedure maintained excellent spatial resolution and delivery precision over the duration of this study, while the linear accelerator was in routine clinical use. Based on these results, the mechanical accuracy and precision of the system are ideal for supporting high-precision localization and treatment of soft-tissue targets.

The recent development of intensity modulated radiation therapy (IMRT) allows the dose distribution to be tailored to match the tumour's shape and position, avoiding damage to healthy tissue to a greater extent than previously possible. Traditional treatment plans assume that the target structure remains in a fixed location throughout treatment. However, many studies have shown that because of organ motion, inconsistencies in patient positioning over the weeks of treatment, etc, the tumour location is not stationary. We present a probabilistic model for the IMRT inverse problem and show that it is identical to using robust optimization techniques, under certain assumptions. For a sample prostate case, our computational results show that this method is computationally feasible and promising-compared to traditional methods, our model has the potential to find treatment plans that are more adept at sparing healthy tissue while maintaining the prescribed dose to the target.

Purpose: To quantify prostate motion during a radiation therapy treatment using cine-magnetic resonance imaging (cine-MRI) for time frames comparable to that expected in an image-guided radiation therapy treatment session (20-30 min)., Materials and Methods: Six patients undergoing radiation therapy for prostate cancer were imaged on 3 days, over the course of therapy (Weeks 1, 3, and 5). Four hundred images were acquired during the 1-h MRI session in 3 sagittal planes through the prostate at 6-s intervals. Eleven anatomic points of interest (POIs) have been used to characterize prostate/bony pelvis/abdominal wall displacement. Motion traces and standard deviation for each of the 11 POIs have been determined. The probability of displacement over time has also been calculated., Results: Patients were divided into 2 groups according to rectal filling status: full vs. empty rectum. The displacement of POIs (standard deviation) ranged from 0.98 to 1.72 mm for the full-rectum group and from 0.68 to 1.04 mm for the empty-rectum group. The low standard deviations in position (2 mm or less) would suggest that these excursions have a low frequency of occurrence. The most sensitive prostate POI to rectal wall motion was the mid-posterior with a standard deviation of 1.72 mm in the full-rectum group vs. 0.79 mm in the empty-rectum group (p = 0.0001). This POI has a 10% probability of moving more than 3 mm in a time frame of approximately 1 min if the rectum is full vs. approximately 20 min if the rectum is empty., Conclusion: Motion of the prostate and seminal vesicles during a time frame similar to a standard treatment session is reduced compared to that reported in interfraction studies. The most significant predictor for intrafraction prostate motion is the status of rectal filling. A prostate displacement of <3 mm (90%) can be expected for the 20 min after the moment of initial imaging for patients with an empty rectum. This is not the case for patients presenting with full rectum. The determination of appropriate intrafraction margins in radiation therapy to accommodate the time-dependent uncertainty in positional targeting is a topic of ongoing investigations for the on-line image guidance model.

As more pretreatment imaging becomes integrated into the treatment planning process and full three-dimensional image-guidance becomes part of the treatment delivery the need for a deformable image registration technique becomes more apparent. A novel finite element model-based multiorgan deformable image registration method, MORFEUS, has been developed. The basis of this method is twofold: first, individual organ deformation can be accurately modeled by deforming the surface of the organ at one instance into the surface of the organ at another instance and assigning the material properties that allow the internal structures to be accurately deformed into the secondary position and second, multi-organ deformable alignment can be achieved by explicitly defining the deformation of a subset of organs and assigning surface interfaces between organs. The feasibility and accuracy of the method was tested on MR thoracic and abdominal images of healthy volunteers at inhale and exhale. For the thoracic cases, the lungs and external surface were explicitly deformed and the breasts were implicitly deformed based on its relation to the lung and external surface. For the abdominal cases, the liver, spleen, and external surface were explicitly deformed and the stomach and kidneys were implicitly deformed. The average accuracy (average absolute error) of the lung and liver deformation, determined by tracking visible bifurcations, was 0.19 (s.d.: 0.09), 0.28 (s.d.: 0.12) and 0.17 (s.d.: 0.07) cm, in the LR, AP, and IS directions, respectively. The average accuracy of implicitly deformed organs was 0.11 (s.d.: 0.11), 0.13 (s.d.: 0.12), and 0.08 (s.d.: 0.09) cm, in the LR, AP, and IS directions, respectively. The average vector magnitude of the accuracy was 0.44 (s.d.: 0.20) cm for the lung and liver deformation and 0.24 (s.d.: 0.18) cm for the implicitly deformed organs. The two main processes, explicit deformation of the selected organs and finite element analysis calculations, require less than 120 and 495 s, respectively. This platform can facilitate the integration of deformable image registration into online image guidance procedures, dose calculations, and tissue response monitoring as well as performing multi-modality image registration for purposes of treatment planning.

Purpose: The active breathing control (ABC) apparatus was used to quantify the effect of breathing motion on whole breast radiotherapy (RT) with standard wedges and intensity-modulated RT (IMRT)., Methods and Materials: Ten patients with early-stage breast cancer underwent routine free-breathing (FB) CT simulations for whole breast RT. An ABC apparatus was used to obtain two additional CT scans with the breath held at the end of normal inhalation and normal exhalation. The FB scan was used to develop both a standard treatment plan using wedged coplanar tangents and an IMRT plan using multiple static multileaf collimator segments. To simulate breathing, each plan was copied and applied to the normal inhalation and normal exhalation CT scans., Results: The medial field border (defined by a radiopaque catheter) for the normal inhalation and normal exhalation scans moved an average of 0.6 cm anteriorly and 0.3 cm posteriorly compared with the FB position, respectively. The corresponding movement of the lateral field border was an average of 0.4 cm anteriorly and 0.2 cm posteriorly compared with the FB position. For both the wedged and the IMRT techniques, the dose delivered to breast tissue, biopsy cavity, and ipsilateral lung was similar for each of the three CT scan positions. However, the internal mammary node dose varied significantly with breathing., Conclusions: The dose delivered to breast using standard wedges or step-and-shoot IMRT is relatively insensitive to the effects of breast motion during normal breathing. However, an appreciable portion of the internal mammary nodes are irradiated during normal inhalation, contributing to the uncertainty in the analysis of the efficacy of internal mammary nodal RT in breast treatment.

Intensity-modulated radiation therapy (IMRT) represents one of the most significant technical advances in radiation therapy since the advent of the medical linear accelerator. It allows the clinical implementation of highly conformal nonconvex dose distributions. This complex but promising treatment modality is rapidly proliferating in both academic and community practice settings. However, these advances do not come without a risk. IMRT is not just an add-on to the current radiation therapy process; it represents a new paradigm that requires the knowledge of multimodality imaging, setup uncertainties and internal organ motion, tumor control probabilities, normal tissue complication probabilities, three-dimensional (3-D) dose calculation and optimization, and dynamic beam delivery of nonuniform beam intensities. Therefore, the purpose of this report is to guide and assist the clinical medical physicist in developing and implementing a viable and safe IMRT program. The scope of the IMRT program is quite broad, encompassing multileaf-collimator-based IMRT delivery systems, goal-based inverse treatment planning, and clinical implementation of IMRT with patient-specific quality assurance. This report, while not prescribing specific procedures, provides the framework and guidance to allow clinical radiation oncology physicists to make judicious decisions in implementing a safe and efficient IMRT program in their clinics.

Introduction: We present our initial clinical experience using moderate deep-inspiration breath hold (mDIBH) with an active breathing control (ABC) device to reduce heart dose in the treatment of patients with early-stage, left-sided breast cancer using external beam radiation therapy (EBRT) limited to the whole breast., Methods and Materials: Between February and August 2002, 5 patients with Stages I/II left-sided breast cancer received EBRT limited to the whole breast using an ABC device. After standard virtual simulation, patients with >2% of the heart receiving >30 Gy in free breathing were selected. All patients underwent a training session with the ABC apparatus to determine their ability to comfortably maintain mDIBH at 75% of the maximum inspiration capacity. Three patients received 45 Gy to the whole breast in 25 fractions, and 2 patients received 50.4 Gy in 28 fractions. For each of the medial and lateral tangential beams, radiation was delivered during 2 or 3 breath hold durations that ranged from 18 to 26 s. "Step-and-shoot" intensity modulation was employed to achieve uniform dose distribution. Open beam segments were purposely delivered over 2 breath hold sessions and captured on electronic portal images to allow intra- and interfraction setup error analysis. All electronic portal images of the tangential beams were analyzed off-line using an in-house treatment verification tool to assess the anteroposterior, craniocaudal, and rotational uncertainties. Corrections were applied if necessary., Results: A comparison of treatment plans performed on breath-hold and free-breathing CTs showed that ABC treatments achieved a mean absolute reduction of 3.6% in heart volume receiving 30 Gy (heart V(30)) and 1.5% in the heart normal tissue complication probability. A total of 134 ABC treatment sessions were performed in the 5 patients. The average number of breath holds required per beam direction was 2.5 (4-6 per treatment) with a median duration of 22 s per breath hold (range: 10-26 s). Patients tolerated mDIBH well. The median treatment time was 18.2 min (range: 13-32 min), which was progressively shortened with increasing experience. A total of 509 portal images were analyzed. Combining measurements for all patients, the interfraction setup errors (1 SD) in the lateral and craniocaudal directions and in rotation were 2.4 mm, 3.2 mm, and 1 degrees, respectively, for the medial beam and 2.3 mm, 3.1 mm, and 1 degrees, respectively, for the lateral beam. For all patients, the intrafraction setup errors were about 1 mm and always less than 2 mm (1 SD)., Conclusion: Reduction in heart V(30) can be achieved in patients with left-sided breast cancer using mDIBH assisted with an ABC device. With increasing experience, ABC treatments were streamlined and could be performed within a 15-min treatment slot. Our results suggest that mDIBH using an ABC device may provide one of the most promising methods of improving the efficacy of EBRT in patients with left-sided breast cancer, particularly when wide tangential beams are employed. Breast cancer; Breath hold; Radiation therapy; Intensity modulated radiation therapy