What is still needed to make focal therapy an accepted segment of standard therapy?

PURPOSE OF REVIEW: Focal therapy is gaining interest and this organ-preserving treatment is heading towards becoming an alternative for the conventional surgery and radiation. The purpose of this review is to determine what evidence is required to make focal therapy a viable option for treatment of localized prostate cancer. RECENT FINDINGS: There is still a lack of high-level evidence for the different focal treatment modalities. The early-stage focal therapy trials are conducted including a various selection of patients and different pretreatment assessment and follow-up, resulting in incomparable data. Recent literature shows it is paramount to extend the amount of biopsies and to alter the way of taking the biopsies with the template-assisted or image-guided approach. To date, multiparametric MRI is the most effective imaging technique in selecting patients for focal therapy. SUMMARY: Focal therapy trials are at the early stage of clinical development, with the majority still being phase I studies. To make focal therapy an accepted segment of standard therapy, it needs to proceed toward phase II and III trials. These trials should be conducted with an effective trial design, which will lead to more comparable oncological, functional and quality of life outcomes. Furthermore, it is essential to improve the localization of tumor foci in order to increase the accuracy of spatial targeting of cancer.

An EPID based method for performing high accuracy calibration between an optical external marker tracking device and the LINAC reference frame.

PURPOSE: With the increasing use of external 3D optical tracking cameras to guide modern radiation therapy procedures, it has become vitally important to have an accurate camera to linear accelerator (LINAC) reference frame calibration. To eliminate errors present in current calibration procedures based on the manual hand alignment of a device using the light field crosshairs and in room guidance lasers, a semiautomated quantitative calibration approach requiring only use of an electronic portal imaging device (EPID) was developed. METHODS: A phantom comprised of seven highly IR reflective plastic BBs was placed on the LINAC treatment couch and imaged with both a 3D stereoscopic IR imager and the on board megavoltage (MV) EPID imager. Having knowledge of the optically determined 3D positions and projected EPID images of the BBs, simulated annealing was used to optimize the location of the BBs in the LINAC frame using four different optimization functions. Singular value decomposition was then used to calculate the transformation matrix between the camera and LINAC reference frames. Results were then compared to a traditional camera calibration method for overall accuracy. RESULTS: Using modeled data, the simulated annealing process was able to determine the actual locations of the BBs with a RMSE of 0.23 mm. Using projection images acquired with an MV imager, the process was able to determine locations of BBs within .26 mm. The results depend on the choice of optimization function. CONCLUSIONS: Results show that the method can be used to provide highly accurate spatial registration between an external 3D imaging reference frame and the LINAC frame. The experimental MV imager results, while not as precise as the simulated results, exceed 1 mm accuracy and the current accepted AAPM TG-142 standard of ≤2 mm positioning accuracy.

kV cone-beam CT-based IGRT: a clinical review.

AIMS AND METHODS: Delivery of high radiation doses while simultaneously sparing organs at risk requires advanced imaging for target volume definition, highly conformal dose distributions of intensity modulated radiotherapy (IMRT), and narrow planning target volume (PTV) margins. Three-dimensional image-guided radiotherapy (IGRT) with cone-beam computer tomography (CBCT), which results in more precise target localization, is quickly replacing two-dimensional (2D) IGRT. An overview on the clinical applications of kilovoltage gantry-mounted CBCT systems with emphasis on the most frequently targeted body sites (prostate, lung, head and neck) is provided based on a review of the relevant literature. Alternative imaging methods and their advantages/disadvantages are discussed. RESULTS: IGRT with soft tissue detection improves set-up accuracy and is currently replacing 2D verification and frame-based stereotactic treatments; safety margins are significantly reduced by this IGRT technology. In addition, systematic changes of tumor volume and shape and of the normal tissue can be monitored allowing for adaptation of radiotherapy. IGRT in combination with conformal treatment planning allows for hypofractionated dose escalation, which results in improved rates of local tumor control with low rates of toxicity. CONCLUSION: CBCT allows for daily pretreatment position verification and online correction of set-up errors which improves the precision of patient repositioning with the possibility of shrinking safety margins, sparing organs at risk, and escalating radiation doses. A trend for better clinical outcome can be observed.

3-D fiducial motion tracking using limited MV projections in arc therapy.

PURPOSE: In-treatment fiducial tracking has recently received attention as a method for improving treatment accuracy, dose conformity, and sparing of healthy tissue. 3-D fiducial localization in arc-radiotherapy remains challenging due to the motion of targets and the complexity of arc deliveries. We propose a novel statistical method for estimating 3-D fiducial motion using limited 2-D megavoltage (MV) projections. METHODS: 3-D fiducial motion was estimated by a maximum a posteriori (MAP) approach to integrating information of fiducial projections with prior knowledge of target motion. To obtain the imaging geometries, short sequences of MV projections were selected in which fiducials were continuously visible. The MAP algorithm estimated the 3-D motion by maximizing the probability of displacement of fiducials in the sequences. Prior knowledge of target motion from a large statistical sample was built into the model to enhance the accuracy of estimation. In the case that a motion prior was unavailable, the algorithm can be simplified to the maximum likelihood (ML) approach. To compare tracking performance, a multiprojection geometric method was also presented by extending the typical two-project ion geometric estimation approach. The algorithms were evaluated using clinical prostate motion traces, and the performance was measured in quality indices and statistical evaluation. RESULTS: The results showed that the MAP method significantly outperforms the geometric method in all measures. In our simulations, the MAP method achieved an accuracy of less than 1 mm RMS error using only five continuous projections, whereas the geometric method required 15 projections to achieve a similar result. CONCLUSIONS: The approach presented can accurately estimate tumor motion using a limited number of continuous projections. The MAP motion estimation is superior to both the ML and geometric estimation methods.

Independent quality assurance of a helical tomotherapy machine using the dose magnifying glass.

PURPOSE: Helical tomotherapy is a complex delivery technique, integrating CT image guidance and intensity modulated radiotherapy in a single system. The integration of the CT detector ring on the gantry not only allows patient position verification but is also often used to perform various QA procedures. This convenience lacks the rigor of a machine-independent QA process. METHODS: In this article, a Si strip detector, known as the Dose Magnifying Glass (DMG), was used to perform machine-independent QA measurements of the multileaf collimator alignment, leaf open time threshold, and leaf fluence output factor (LFOF). RESULTS: The DMG measurements showed good agreements with EDR2 film for the MLC alignment test while the CT detector agrees well with DMG measurements for leaf open time threshold and LFOF measurements. The leaf open time threshold was found to be approximately 20 ms. The LFOF measured with the DMG agreed within error with the CT detector measured LFOF. CONCLUSIONS: The DMG with its 0.2 mm spatial resolution coupled to TERA ASIC allowed real-time high temporal resolution measurements of the tomotherapy leaf movement. In conclusion, DMG was shown to be a suitable tool for machine-independent QA of a tomotherapy unit.

Development of an optical-based image guidance system: technique detecting external markers behind a full facemask.

PURPOSE: Optical image-guided systems (e.g., AlignRT, frameless SonArray, ExacTrac) have been used with advantages of avoiding excessive radiation exposure and real-time patient monitoring. Although these systems showed proven accuracy, they need to modify a full facemask for patients with H&N cancer and brain tumor. We developed an optical-based guidance system to manage interfractional and intrafractional setup errors by tracking external markers behind a full facemask. METHODS: Infra-red (IR) reflecting markers were attached on the face of a head phantom and then the phantom was immobilized by a full face thermoplastic mask. A stereo camera system consisting of two CCD cameras was mounted on the inferior wall of treatment room. The stereo camera system was calibrated to reconstruct 3D coordinates of multiple markers with respect to the isocenter using the direct linear transform (DLT) algorithm. The real-time position of the phantom was acquired, through the stereo camera system, by detecting the IR markers behind the full facemask. The detection errors with respect to the reference positions of planning CT images were calculated in six degrees of freedom (6-DOF) by a rigid-body registration technique. RESULTS: The calibration accuracy of the system was in submillimeter (0.33 mm +/- 0.27 mm), which was comparable to others. The mean distance between each of marker positions of optical images and planning CT images was 0.50 mm +/- 0.67 mm. The maximum deviations of 6-DOF registration were less than 1 mm and 1 degrees for the couch translation and rotation, respectively. CONCLUSIONS: The developed system showed the accuracy and consistency comparable to the commercial optical guided systems, while allowing us to simultaneously immobilize patients with a full face thermoplastic mask.

Volume assessment accuracy in computed tomography: a phantom study.

There is a broad push in the cancer imaging community to eventually replace linear tumor measurements with three-dimensional evaluation of tumor volume. To evaluate the potential accuracy of volume measurement in tumors by CT, a gelatin phantom consisting of 55 polymethylmethacrylate (PMMA) spheres spanning diameters from 1.6 mm to 25.4 mm was fabricated and scanned using thin slice (0.625 mm) CT (GE LightSpeed 16). Nine different reconstruction combinations of field of view dimension (FOV = 20, 30, 40 cm) and CT kernel (standard, lung, bone) were analyzed. Contiguous thin-slice images were averaged to produce CT images with greater thicknesses (1.25, 2.50, 5.0 mm). Simple grayscale thresholding techniques were used to segment the PMMA spheres from the gelatin background, where a total of 1800 spherical volumes were evaluated across the permutations studied. The geometric simplicity of the phantom established upper limits on measurement accuracy. In general, smaller slice thickness and larger sphere diameters produced more accurate volume assessment than larger slice thickness and smaller sphere diameter. The measured volumes were smaller than the actual volumes by a common factor depending on slice thickness; overall, 0.625 mm slices produced on average 18%, 1.25 mm slices produced 22%, 2.5 mm CT slices produced 29%, and 5.0 mm slices produced 39% underestimates of volume (mm3). Field of view did not have a significant effect on volume accuracy. Reconstruction algorithm significantly affected volume accuracy (p < 0.0001), with the lung kernel having the smallest error, followed by the bone and standard kernels. The results of this investigation provide guidance for CT protocol development and may guide the development of more advanced techniques to promote quantitatively accurate CT volumetric analysis of tumors.

Evaluation of target volume margins for radiotherapy of prostate implanted with fiducial markers.

The planning target volume (PTV) depends on the method of radiotherapy guidance. This study aimed to measure the systemic and random errors using an online marker matching and offline bone structure matching to estimate PTVmarker, PTVbone, or PTVlaser for treatment verification and radiotherapy guidance, especially in centers lacking radiotherapy fiducial markers (FMs). Thirty patients with localized prostate cancer who were treated with FM-based dose escalation protocol were included. The initial set-up was done with laser marks and daily megavoltage images were acquired. The systematic and random errors were calculated. PTVmarker, defined as the sum of maximum marker migration, and PTV calculated to compensate for the difference between online marker matching and offline analysis of marker matching. PTVmarker was added to estimated PTV from online marker matching to obtain PTVlaser. PTVskin marks migration, was calculated and deducted from PTVlaser to acquire PTVbone. The mean maximum marker migration was 2 ± 1.2 mm. The resultant values of PTVmarker were 2.7 ± 0.6 mm, 3.3 ± 1.1 mm, and 4.4 ± 2.2 mm, in the lateral (lat.), longitudinal (long) & vertical (vert.) directions, respectively, whereas values of PTVlaser were 13 ± 0.6 mm, 17.7 ± 1.1 mm, and 15.8 ± 2.2 mm, and PTVbone were 5.9 ± 0.6 mm, 8.6 ± 1.1 mm, 7.2 ± 2.2 mm, respectively, in the lat., long., and vert. directions. Our results show that PTV needed with FM-based image guidance ranged between 3 and 4 mm in the three cardinal directions, was 10 mm smaller than that required with laser skin marks guidance, and narrower by 5 mm compared to that obtained by offline bone structure image matching.

Image-guided small animal radiation research platform: calibration of treatment beam alignment.

Small animal research allows detailed study of biological processes, disease progression and response to therapy with the potential to provide a natural bridge to the clinical environment. The small animal radiation research platform (SARRP) is a portable system for precision irradiation with beam sizes down to approximately 0.5 mm and optimally planned radiation with on-board cone-beam CT (CBCT) guidance. This paper focuses on the geometric calibration of the system for high-precision irradiation. A novel technique for the calibration of the treatment beam is presented, which employs an x-ray camera whose precise positioning need not be known. Using the camera system we acquired a digitally reconstructed 3D 'star shot' for gantry calibration and then developed a technique to align each beam to a common isocenter with the robotic animal positioning stages. The calibration incorporates localization by cone-beam CT guidance. Uncorrected offsets of the beams with respect to the calibration origin ranged from 0.4 mm to 5.2 mm. With corrections, these alignment errors can be reduced to the sub-millimeter range. The calibration technique was used to deliver a stereotactic-like arc treatment to a phantom constructed with EBT Gafchromic films. All beams were shown to intersect at a common isocenter with a measured beam (FWHM) of approximately 1.07 mm using the 0.5 mm collimated beam. The desired positioning accuracy of the SARRP is 0.25 mm and the results indicate an accuracy of 0.2 mm. To fully realize the radiation localization capabilities of the SARRP, precise geometric calibration is required, as with any such system. The x-ray camera-based technique presented here provides a straightforward and semi-automatic method for system calibration.

Developing quality assurance processes for image-guided adaptive radiation therapy.

Quality assurance has long been implemented in radiation treatment as systematic actions necessary to provide adequate confidence that the radiation oncology service will satisfy the given requirements for quality care. The existing reports from the American Association of Physicists in Medicine Task Groups 40 and 53 have provided highly detailed QA guidelines for conventional radiotherapy and treatment planning. However, advanced treatment processes recently developed with emerging high technology have introduced new QA requirements that have not been addressed previously in the conventional QA program. Therefore, it is necessary to expand the existing QA guidelines to also include new considerations. Image-guided adaptive radiation therapy (IGART) is a closed-loop treatment process that is designed to include the individual treatment information, such as patient-specific anatomic variation and delivered dose assessed during the therapy course in treatment evaluation and planning optimization. Clinical implementation of IGART requires high levels of automation in image acquisition, registration, segmentation, treatment dose construction, and adaptive planning optimization, which brings new challenges to the conventional QA program. In this article, clinical QA procedures for IGART are outlined. The discussion focuses on the dynamic or four-dimensional aspects of the IGART process, avoiding overlap with conventional QA guidelines.

Quality assurance of serial 3D image registration, fusion, and segmentation.

Radiotherapy relies on images to plan, guide, and assess treatment. Image registration, fusion, and segmentation are integral to these processes; specifically for aiding anatomic delineation, assessing organ motion, and aligning targets with treatment beams in image-guided radiation therapy (IGRT). Future developments in image registration will also improve estimations of the actual dose delivered and quantitative assessment in patient follow-up exams. This article summarizes common and emerging technologies and reviews the role of image registration, fusion, and segmentation in radiotherapy processes. The current quality assurance practices are summarized, and implications for clinical procedures are discussed.

Quality assurance for the geometric accuracy of cone-beam CT guidance in radiation therapy.

The introduction of volumetric X-ray image-guided radiotherapy systems allows improved management of geometric variations in patient setup and internal organ motion. As these systems become a routine clinical modality, we propose a daily quality assurance (QA) program for cone-beam computed tomography (CBCT) integrated with a linear accelerator. The image-guided system used in this work combines a linear accelerator with conventional X-ray tube and an amorphous silicon flat-panel detector mounted orthogonally from the accelerator central beam axis. This article focuses on daily QA protocols germane to geometric accuracy of the CBCT systems and proposes tolerance levels on the basis of more than 3 years of experience with seven CBCT systems used in our clinic. Monthly geometric calibration tests demonstrate the long-term stability of the flex movements, which are reproducible within +/-0.5 mm (95% confidence interval). The daily QA procedure demonstrates that, for rigid phantoms, the accuracy of the image-guided process can be within 1 mm on average, with a 99% confidence interval of +/-2 mm.

Quality assurance issues in conducting multi-institutional advanced technology clinical trials.

The National Cancer Institute-sponsored Advanced Technology Quality Assurance (QA) Consortium, which consisted of the Image-Guided Therapy QA Center, Radiation Therapy Oncology Group, Radiological Physics Center, Quality Assurance Review Center, and Resource Center for Emerging Technologies, has pioneered the development of an infrastructure and QA method for advanced technology clinical trials that requires volumetric digital data submission of a protocol patient's treatment plan and verification data. In particular, the Image-Guided Therapy QA Center has nearly 15 years experience in facilitating QA review for Radiation Therapy Oncology Group advanced technology clinical trials. This QA process includes (1) a data integrity review for completeness of protocol required elements, the format of data, and possible data corruption, and recalculation of dose-volume histograms; (2) a review of compliance with target volume and organ-at-risk contours by study chairs; and (3) a review of dose prescription and dose heterogeneity compliance by the Radiation Therapy Oncology Group Headquarters Dosimetry Group or the Radiological Physics Center dosimetrists (for brachytherapy protocols). This report reviews the lessons learned and the QA challenges presented by the use of advanced treatment modalities in clinical trials requiring volumetric digital data submission.

Quality assurance for kilo- and megavoltage in-room imaging and localization for off- and online setup error correction.

In-room radiography is not a new concept for image-guided radiation therapy. Rapid advances in technology, however, have made this positioning method convenient, and thus radiograph-based positioning has propagated widely. The paradigms for quality assurance of radiograph-based positioning include imager performance, systems integration, infrastructure, procedure documentation and testing, and support for positioning strategy implementation.

QA issues for computer-controlled treatment delivery: this is not your old R/V system any more!

State-of-the-art radiotherapy treatment delivery has changed dramatically during the past decade, moving from manual individual field setup and treatment to automated computer-controlled delivery of complex treatments, including intensity-modulated radiotherapy and other similarly complex delivery strategies. However, the quality assurance methods typically used to ensure treatment is performed precisely and correctly have not evolved in a similarly dramatic way. This paper reviews the old manual treatment process and use of record-and-verify systems, and describes differences with modern computer-controlled treatment delivery. The process and technology used for computer-controlled treatment delivery are analyzed in terms of potential (and actual) problems, as well as relevant published guidance on quality assurance. The potential for improved quality assurance for computer-controlled delivery is discussed.

Quality assurance challenges for motion-adaptive radiation therapy: gating, breath holding, and four-dimensional computed tomography.

Compared with conventional three-dimensional (3D) conformal radiation therapy and intensity-modulated radiation therapy treatments, quality assurance (QA) for motion-adaptive radiation therapy involves various challenges because of the added temporal dimension. Here we discuss those challenges for three specific techniques related to motion-adaptive therapy: namely respiratory gating, breath holding, and four-dimensional computed tomography. Similar to the introduction of any other new technologies in clinical practice, typical QA measures should be taken for these techniques also, including initial testing of equipment and clinical procedures, as well as frequent QA examinations during the early stage of implementation. Here, rather than covering every QA aspect in depth, we focus on some major QA challenges. The biggest QA challenge for gating and breath holding is how to ensure treatment accuracy when internal target position is predicted using external surrogates. Recommended QA measures for each component of treatment, including simulation, planning, patient positioning, and treatment delivery and verification, are discussed. For four-dimensional computed tomography, some major QA challenges have also been discussed.

Cyberknife image-guided delivery and quality assurance.

The CyberKnife is a complex, emerging technology that is a significant departure from current stereotactic radiosurgery and external beam radiotherapy technologies. In its clinical application and quality assurance (QA) approach, the CyberKnife is currently situated somewhere in between stereotactic radiosurgery and radiotherapy. The clinical QA for this image-guided treatment delivery system typically follows the vendor's guidance, mainly because of the current lack of vendor-independent QA recommendations. The problem has been exacerbated because very little published data are available for QA for the CyberKnife system, especially for QA of the interaction between individual system components. The tools and techniques for QA of the CyberKnife are under development and will continue to improve with longer clinical experience of the users. The technology itself continues to evolve, forcing continuous changes and adaptation of QA. To aid in the process of developing comprehensive guidance on CyberKnife QA, a database of errors based on users reporting incidents and corrective actions would be desirable. The goal of this work was to discuss the status of QA guidelines in the clinical implementation of the CyberKnife system. This investigation was done from the perspective of an active clinical and research site using the CyberKnife.

Current external beam radiation therapy quality assurance guidance: does it meet the challenges of emerging image-guided technologies?

The traditional prescriptive quality assurance (QA) programs that attempt to ensure the safety and reliability of traditional external beam radiation therapy are limited in their applicability to such advanced radiation therapy techniques as three-dimensional conformal radiation therapy, intensity-modulated radiation therapy, inverse treatment planning, stereotactic radiosurgery/radiotherapy, and image-guided radiation therapy. The conventional QA paradigm, illustrated by the American Association of Physicists in Medicine Radiation Therapy Committee Task Group 40 (TG-40) report, consists of developing a consensus menu of tests and device performance specifications from a generic process model that is assumed to apply to all clinical applications of the device. The complexity, variation in practice patterns, and level of automation of high-technology radiotherapy renders this "one-size-fits-all" prescriptive QA paradigm ineffective or cost prohibitive if the high-probability error pathways of all possible clinical applications of the device are to be covered. The current approaches to developing comprehensive prescriptive QA protocols can be prohibitively time consuming and cost ineffective and may sometimes fail to adequately safeguard patients. It therefore is important to evaluate more formal error mitigation and process analysis methods of industrial engineering to more optimally focus available QA resources on process components that have a significant likelihood of compromising patient safety or treatment outcomes.

Quality assurance of immobilization and target localization systems for frameless stereotactic cranial and extracranial hypofractionated radiotherapy.

The success of stereotactic radiosurgery has stimulated significant interest in the application of such an approach for the treatment of extracranial tumors. The potential benefits of reduced healthcare costs and improved patient outcomes that could be realized in a high-precision, hypofractionated treatment paradigm are numerous. Image-guidance technologies are eliminating the historic requirement for rigid head fixation and will also accelerate the clinical implementation of the approach in extracranial sites. An essential prerequisite of "frameless" stereotactic systems is that they provide localization accuracy consistent with the safe delivery of a therapeutic radiation dose given in one or few fractions. In this report, we reviewed the technologies for frameless localization of cranial and extracranial targets with emphasis on the quality assurance aspects.

Quality assurance of positron emission tomography/computed tomography for radiation therapy.

Recent advances in radiation delivery techniques, such as intensity-modulated radiation therapy, provide unprecedented ability to exquisitely control three-dimensional dose distribution. Development of on-board imaging and other image-guidance methods significantly improved our ability to better target a radiation beam to the tumor volume. However, in reality, accurate definition of the location and boundary of the tumor target is still problematic. Biologic and physiologic imaging promises to solve the problem in a fundamental way and has a more and more important role in patient staging, treatment planning, and therapeutic assessment in radiation therapy clinics. The last decade witnessed a dramatic increase in the use of positron emission tomography and computed tomography in radiotherapy practice. To ensure safe and effective use of nuclide imaging, a rigorous quality assurance (QA) protocol of the imaging tools and integration of the imaging data must be in place. The application of nuclide imaging in radiation oncology occurs at different levels of sophistication. Quantitative use of the imaging data in treatment planning through image registration and standardized uptake value calculation is often involved. Thus, QA should not be limited to the performance of the scanner, but should also include the process of implementing image data in treatment planning, such as data transfer, image registration, and quantitation of data for delineation of tumors and sensitive structures. This presentation discusses various aspects of nuclide imaging as applied to radiotherapy and describes the QA procedures necessary for the success of biologic image-guided radiation therapy.