Use of radiobiological modeling in treatment plan evaluation and optimization of prostate cancer radiotherapy

There are many tools available that are used to evaluate a radiotherapy treatment plan, such as isodose distribution charts, dose volume histograms (DVH), maximum, minimum and mean doses of the dose distributions as well as DVH point dose constraints. All the already mentioned evaluation tools are dosimetric only without taking into account the radiobiological characteristics of tumors or OARs. It has been demonstrated that although competing treatment plans might have similar mean, maximum or minimum doses they may have significantly different clinical outcomes (Mavroidis et al. 2001). For performing a more complete treatment plan evaluation and comparison the complication-free tumor control probability (P+) and the biologically effective uniform dose (D ) have been proposed (Källman et al. 1992a, Mavroidis et al. 2000). The D concept denotes that any two dose distributions within a target or OAR are equivalent if they produce the same probability for tumor control or normal tissue complication, respectively (Mavroidis et al. 2001)..

Segmentation, separation and pose estimation of prostate brachytherapy seeds in CT images.

International audienceIn this paper, we address the development of an automatic approach for the computation of pose information (position + orientation) of prostate brachytherapy loose seeds from 3D CT images. From an initial detection of a set of seed candidates in CT images using a threshold and connected component method, the orientation of each individual seed is estimated by using the principal components analysis (PCA) method. The main originality of this approach is the ability to classify the detected objects based on a priori intensity and volume information and to separate groups of closely spaced seeds using three competing clustering methods: the standard and a modified k-means method and a Gaussian mixture model with an Expectation-Maximization algorithm. Experiments were carried out on a series of CT images of two phantoms and patients. The fourteen patients correspond to a total of 1063 implanted seeds. Detections are compared to manual segmentation and to related work in terms of detection performance and calculation time. This automatic method has proved to be accurate and fast including the ability to separate groups of seeds in a reliable way and to determine the orientation of each seed. Such a method is mandatory to be able to compute precisely the real dose delivered to the patient post-operatively instead of assuming the alignment of seeds along the theoretical insertion direction of the brachytherapy needles

Prostate volume delineation and seed localization using a 3-T magnetic resonance spectrometer

With approximately one in six men affected by prostate cancer at some point in their lives, effective treatment of the disease remains a focus of oncology research. Effective treatment using radiation requires the delivery of a significant dose to the prostate volume while sparing surrounding sensitive structures. Treatment success can then be determined by localization of the seeds following implantation and the calculation of a dose distribution across the target volume. Magnetic Resonance Imaging (MRI) yields images with soft tissue contrast that is superior to CT or ultrasound, but has been under-appreciated as a dosimetric tool due to the difficulty in localizing the implanted seeds; To optimize scan parameters for seed localization, a phantom was constructed of tissue-equivalent gelatin. Seeds were implanted during construction so various scan protocols could be tested for seed visualization and volume calculation prior to patient studies. Five healthy volunteers and five patients with permanently implanted seeds were then imaged to validate the phantom studies. Images were evaluated based on anatomical clarity and seed visualization rates; Optimization of the scan protocols for use with this equipment yields images with clearly defined anatomical boundaries as well as clearly defined seeds. Phantom volume measurements deviated from known values by less than 2.5% T2-weighted images provide superior anatomical delineation, but suffer from broad susceptibility artifacts that make determination of seed locations difficult. Proton density-weighted images clearly show seed locations and tissue margins. The selection of a 1 mm slice thickness and a 4 mm interstice gap allowed maximum seed visualization rates of 93.3%; Keywords: prostate, brachytherapy, dosimetry, magnetic resonance imaging

Encapsulated Contrast Agent Markers for MRI-based Post-implant Dosimetry

Low-dose-rate prostate brachytherapy involves the implantation of tiny radioactive seeds into the prostate to treat prostate cancer. The current standard post-implant imaging modality is computed tomography (CT). On CT images, the radioactive seeds can be distinctively localized but delineation of the prostate and surrounding soft tissue is poor. Magnetic resonance imaging (MRI) provides better prostate and soft tissue delineation, but seed localization is difficult. To aid with seed localization, MRI markers with encapsulated contrast agent that provide positive-contrast on MRI images (Sirius MRI markers; C4 Imaging, Houston, TX) have been proposed to be placed adjacent to the negative-contrast seeds. This dissertation describes the development of the Sirius MRI markers for prostate post-implant dosimetry. First, I compared the dose-volume histogram and other dosimetry parameters generated by MIM Symphony (a brachytherapy treatment planning system that allow the use of MRI images for treatment planning; MIM Software Inc., Cleveland, OH) and VariSeed (a widely used brachytherapy treatment planning system; Varian Medical Systems, Inc., Palo Alto, CA), and found the dosimetry between both brachytherapy treatment planning systems to be comparable. To gain more insight into the MRI contrast characteristics of the Sirius MRI markers, I measured the Sirius MRI marker contrast agent\u27s spin-lattice and spin-spin relaxivities, and studied the relaxation characteristics\u27 dependence on MRI field strength, temperature, and orientation. From the Sirius MRI marker\u27s contrast agent relaxation characteristics, I systematically studied the effect of varying MRI scan parameters such as flip angle, number of excitations, bandwidth, field of view, slice thickness, and encoding steps, on the Sirius MRI markers\u27 signal and contrast, as well as image noise, artifact and scan time. On patients implanted with Sirius MRI markers, I evaluated the visibility of the Sirius MRI markers and image artifacts. Lastly, I semi-automated the localization of markers and seeds to more enable the efficient incorporation of Sirius MRI markers as part of the clinical post-implant workflow. Ultimately, the Sirius MRI markers may change the paradigm from CT-based to MRI-based post-implant dosimetry, for a more accurate understanding of dose-response relationships in patients undergoing low dose rate prostate brachytherapy

Deformable registration of X-ray and MRI for post-implant dosimetry in low-dose-rate prostate brachytherapy

Purpose Dosimetric assessment following permanent prostate brachytherapy (PPB) commonly involves seed localization using CT and prostate delineation using coregistered MRI. However, pelvic CT leads to additional imaging dose and requires significant resources to acquire and process both CT and MRI. In this study, we propose an automatic postimplant dosimetry approach that retains MRI for soft‐tissue contouring, but eliminates the need for CT and reduces imaging dose while overcoming the inconsistent appearance of seeds on MRI with three projection x rays acquired using a mobile C‐arm. Methods Implanted seeds are reconstructed using x rays by solving a combinatorial optimization problem and deformably registered to MRI. Candidate seeds are located in MR images using local hypointensity identification. X ray‐based seeds are registered to these candidate seeds in three steps: (a) rigid registration using a stochastic evolutionary optimizer, (b) affine registration using an iterative closest point optimizer, and (c) deformable registration using a local feature point search and nonrigid coherent point drift. The algorithm was evaluated using 20 PPB patients with x rays acquired immediately postimplant and T2‐weighted MR images acquired the next day at 1.5 T with mean 0.8 × 0.8 × 3.0 mmurn:x-wiley:00942405:media:mp13667:mp13667-math-0001 voxel dimensions. Target registration error (TRE) was computed based on the distance from algorithm results to manually identified seed locations using coregistered CT acquired the same day as the MRI. Dosimetric accuracy was determined by comparing prostate D90 determined using the algorithm and the ground truth CT‐based seed locations. Results The mean ± standard deviation TREs across 20 patients including 1774 seeds were 2.23 ± 0.52 mm (rigid), 1.99 ± 0.49 mm (rigid + affine), and 1.76 ± 0.43 mm (rigid + affine + deformable). The corresponding mean ± standard deviation D90 errors were 5.8 ± 4.8%, 3.4 ± 3.4%, and 2.3 ± 1.9%, respectively. The mean computation time of the registration algorithm was 6.1 s. Conclusion The registration algorithm accuracy and computation time are sufficient for clinical PPB postimplant dosimetry

Salvage brachytherapy in combination with interstitial hyperthermia for locally recurrent prostate carcinoma following external beam radiation therapy: a prospective phase II study.

Optimal treatment for patients with only local prostate cancer recurrence after external beam radiation therapy (EBRT) failure remains unclear. Possible curative treatments are radical prostatectomy, cryosurgery, and brachytherapy. Several single institution series proved that high-dose-rate brachytherapy (HDRBT) and pulsed-dose-rate brachytherapy (PDRBT) are reasonable options for this group of patients with acceptable levels of genitourinary and gastrointestinal toxicity. A standard dose prescription and scheme have not been established yet, and the literature presents a wide range of fractionation protocols. Furthermore, hyperthermia has shown the potential to enhance the efficacy of re-irradiation. Consequently, a prospective trial is urgently needed to attain clear structured prospective data regarding the efficacy of salvage brachytherapy with adjuvant hyperthermia for locally recurrent prostate cancer. The purpose of this report is to introduce a new prospective phase II trial that would meet this need. The primary aim of this prospective phase II study combining Iridium-192 brachytherapy with interstitial hyperthermia (IHT) is to analyze toxicity of the combined treatment; a secondary aim is to define the efficacy (bNED, DFS, OS) of salvage brachytherapy. The dose prescribed to PTV will be 30 Gy in 3 fractions for HDRBT, and 60 Gy in 2 fractions for PDRBT. During IHT, the prostate will be heated to the range of 40-47°C for 60 minutes prior to brachytherapy dose delivery. The protocol plans for treatment of 77 patients

A 3D US Guidance System for Permanent Breast Seed Implantation: Development and Validation

Permanent breast seed implantation (PBSI) is a promising breast radiotherapy technique that suffers from operator dependence. We propose and have developed an intraoperative 3D ultrasound (US) guidance system for PBSI. A tracking arm mounted to a 3D US scanner registers a needle template to the image. Images were validated for linear and volumetric accuracy, and image quality in a volunteer. The tracking arm was calibrated, and the 3D image registered to the scanner. Tracked and imaged needle positions were compared to assess accuracy and a patient-specific phantom procedure guided with the system. Median/mean linear and volumetric error was ±1.1% and ±4.1%, respectively, with clinically suitable volunteer scans. Mean tracking arm error was 0.43mm and 3D US target registration error ≤0.87mm. Mean needle tip/trajectory error was 2.46mm/1.55°. Modelled mean phantom procedure seed displacement was 2.50mm. To our knowledge, this is the first reported PBSI phantom procedure with intraoperative 3D image guidance

Prostate deformation from inflatable rectal probe cover and dosimetric effects in prostate seed implant brachytherapy: Deformation on prostate permanent brachytherapy dosimetry

Prostate brachytherapy is an important treatment technique for patients with localized prostate cancer. An inflatable rectal ultrasound probe cover is frequently utilized during the procedure to adjust for unfavorable prostate position relative to the implant grid. However, the inflated cover causes prostate deformation, which is not accounted for during dosimetric planning. Most of the therapeutic dose is delivered after the procedure when the prostate and surrounding organs-at-risk are less deformed. The aim of this study is to quantify the potential dosimetry changes between the initial plan (prostate deformed) and the more realistic dosimetry when the prostate is less deformed without the cover