MR-guided prostate biopsy for planning of focal salvage after radiation therapy.

PURPOSE: To determine if the integration of diagnostic magnetic resonance (MR) imaging and MR-guided biopsy would improve target delineation for focal salvage therapy in men with prostate cancer. MATERIALS AND METHODS: Between September 2008 and March 2011, 30 men with biochemical failure after radiation therapy for prostate cancer provided written informed consent and were enrolled in a prospective clinical trial approved by the institutional research ethics board. An integrated diagnostic MR imaging and interventional biopsy procedure was performed with a 1.5-T MR imager by using a prototype table and stereotactic transperineal template. Multiparametric MR imaging (T2-weighted, dynamic contrast material-enhanced, and diffusion-weighted sequences) was followed by targeted biopsy of suspicious regions and systematic sextant sampling. Biopsy needle locations were imaged and registered to diagnostic images. Two observers blinded to clinical data and the results of prior imaging studies delineated tumor boundaries. Area under the receiver operating characteristic curve (Az) was calculated based on generalized linear models by using biopsy as the reference standard to distinguish benign from malignant lesions. RESULTS: Twenty-eight patients were analyzed. Most patients (n = 22) had local recurrence, with 82% (18 of 22) having unifocal disease. When multiparametric volumes from two observers were combined, it increased the apparent overall tumor volume by 30%; however, volumes remained small (mean, 2.9 mL; range, 0.5-8.3 mL). Tumor target boundaries differed between T2-weighted, dynamic contrast-enhanced, and diffusion-weighted sequences (mean Dice coefficient, 0.13-0.35). Diagnostic accuracy in the identification of tumors improved with a multiparametric approach versus a strictly T2-weighted or dynamic contrast-enhanced approach through an improvement in sensitivity (observer 1, 0.65 vs 0.35 and 0.44, respectively; observer 2, 0.82 vs 0.64 and 0.53, respectively; P < .05) and improved further with a 5-mm expansion margin (Az = 0.85 vs 0.91 for observer 2). After excluding three patients with fewer than six informative biopsy cores and six patients with inadequately stained margins, MR-guided biopsy enabled more accurate delineation of the tumor target volume be means of exclusion of false-positive results in 26% (five of 19 patients), false-negative results in 11% (two of 19 patients) and by guiding extension of tumor boundaries in 16% (three of 19 patients). CONCLUSION: The integration of guided biopsy with diagnostic MR imaging is feasible and alters delineation of the tumor target boundary in a substantial proportion of patients considering focal salvage.

4D-CT Attenuation Correction in Respiratory-Gated PET for Hypoxia Imaging: Is It Really Beneficial?

Previous literature has shown that 4D respiratory-gated positron emission tomography (PET) is beneficial for quantitative analysis and defining targets for boosting therapy. However the case for addition of a phase-matched 4D-computed tomography (CT) for attenuation correction (AC) is less clear. We seek to validate the use of 4D-CT for AC and investigate the impact of motion correction for low signal-to-background PET imaging of hypoxia using radiotracers such as FAZA and FMISO. A new insert for the Modus Medicals' QUASAR™ Programmable Respiratory Motion Phantom was developed in which a 3D-printed sphere was placed within the "lung" compartment while an additional compartment is added to simulate muscle/blood compartment required for hypoxia quantification. Experiments are performed at 4:1 or 2:1 signal-to-background ratio consistent with clinical FAZA and FMISO imaging. Motion blur was significant in terms of SUVmax, mean, and peak for motion ≥1 cm and could be significantly reduced (from 20% to 8% at 2-cm motion) for all 4D-PET-gated reconstructions. The effect of attenuation method on precision was significant (σ2 hCT-AC = 5.5%/4.7%/2.7% vs σ2 4D-CT-AC = 0.5%/0.6%/0.7% [max%/peak%/mean% variance]). The simulated hypoxic fraction also significantly decreased under conditions of 2-cm amplitude motion from 55% to 20% and was almost fully recovered (HF = 0.52 for phase-matched 4D-CT) using gated PET. 4D-gated PET is valuable under conditions of low radiotracer uptake found in hypoxia imaging. This work demonstrates the importance of using 4D-CT for AC when performing gated PET based on its significantly improved precision over helical CT.

Novel dosimetric phantom for quality assurance of volumetric modulated arc therapy.

The objective of this work is to assess the suitability and performance of a new dosimeter system with a novel geometry for the quality assurance (QA) of volumetric modulated arc therapy (VMAT). The new dosimeter system consists of a hollow cylinder (15 and 25 cm inner and outer diameters) with 124 diodes embedded in the phantom's cylindrical wall forming four rings of detectors. For coplanar beams, the cylindrical geometry and the ring diode pattern offer the advantage of invariant perpendicular incidence on the beam central axis for any gantry angle and also have the benefit of increasing the detector density as both walls of the cylinder sample the beam. Other advantages include real-time readout and reduced weight with the hollow phantom shape. A calibration method taking into account the variation in radiation sensitivity of the diodes as a function of gantry angle was developed and implemented. In this work, the new dosimeter system was used in integrating mode to perform composite dose measurements along the cylindrical surface supporting the diodes. The reproducibility of the dosimeter response and the angular dependence of the diodes were assessed using simple 6 MV photon static beams. The performance of the new dosimeter system for VMAT QA was then evaluated using VMAT plans designed for a head and neck, an abdominal sarcoma, and a prostate patient. These plans were optimized with 90 control points (CPs) and additional versions of each plan were generated by increasing the number of CPs to 180 and 360 using linear interpolation. The relative dose measured with the dosimeter system for the VMAT plans was compared to the corresponding TPS dose map in terms of relative dose difference (% deltaD) and distance to agreement (DTA). The dosimeter system's sensitivity to gantry rotation offset and scaling errors as well as setup errors was also evaluated. For static beams, the dosimeter system offered good reproducibility and demonstrated small residual diode angular dependence after calibration. For VMAT deliveries, the agreement between measured and calculated doses was good with > or = 86.4% of the diodes satisfying 3% of % deltaD or 2 mm DTA for the 180 CP plans. The phantom offered sufficient sensitivity for the detection of small gantry rotation offset (3 degrees) and scaling errors (1 degree) as well as phantom setup errors of 1 mm, although the results were plan dependent. With its novel geometry, the dosimeter system was also able to experimentally demonstrate the discretization effect of the number of CPs used in the TPS to simulate a continuous arc. These results demonstrate the suitability of the new dosimeter system for the patient-specific QA of VMAT plans and suggest that the dosimeter system can be an effective tool in the routine QA and commissioning of treatment machines capable of VMAT delivery and cone-beam CT image guidance.

Intraobserver and interobserver variability in GTV delineation on FDG-PET-CT images of head and neck cancers.

PURPOSE: To determine if the addition of fluorodeoxyglucose positron emission tomography (FDG-PET) data changes primary site gross tumor volumes (GTVs) in head and neck cancers. METHODS AND MATERIALS: Computed tomography (CT), contrast-enhanced CT, and FDG-PET-CT scans were obtained in 10 patients with head and neck cancers. Eight experienced observers (6 head and neck oncologists and 2 neuro-radiologists) with access to clinical and radiologic reports outlined primary site GTVs on each modality. Three cases were recontoured twice to assess intraobserver variability. The magnitudes of the GTVs were compared. Intra- and interobserver variability was assessed by a two-way repeated measures analysis of variance. Inter- and intraobserver reliability were calculated. RESULTS: There were no significant differences in the GTVs across the image modalities when compared as ensemble averages; the Wilcoxon matched-pairs signed-rank test showed that CT volumes were larger than PET-CT. Observers demonstrated the greatest consistency and were most interchangeable on contrast-enhanced CT; they performed less reliably on PET-CT. CONCLUSIONS: The addition of PET-CT to primary site GTV delineation of head and neck cancers does not change the volume of the GTV defined by this group of expert observers in this patient sample. An FDG-PET may demonstrate differences in neck node delineation and in other disease sites.

Quantitative Imaging in Radiation Oncology: An Emerging Science and Clinical Service.

Radiation oncology has long required quantitative imaging approaches for the safe and effective delivery of radiation therapy. The past 10 years has seen a remarkable expansion in the variety of novel imaging signals and analyses that are starting to contribute to the prescription and design of the radiation treatment plan. These include a rapid increase in the use of magnetic resonance imaging, development of contrast-enhanced imaging techniques, integration of fluorinated deoxyglucose-positron emission tomography, evaluation of hypoxia imaging techniques, and numerous others. These are reviewed with an effort to highlight challenges related to quantification and reproducibility. In addition, several of the emerging applications of these imaging approaches are also highlighted. Finally, the growing community of support for establishing quantitative imaging approaches as we move toward clinical evaluation is summarized and the need for a clinical service in support of the clinical science and delivery of care is proposed.

A new and simple calibration-independent method for measuring the beam energy of a cyclotron.

This work recommends a new and simple-to-perform method for measuring the beam energy of an accelerator. The proposed method requires the irradiation of two monitor foils interspaced by an energy degrader. The primary advantage of the proposed method, which makes this method unique from previous energy evaluation strategies that employ the use of monitor foils, is that this method is independent of the detector efficiency calibration. This method was evaluated by performing proton activation of (nat)Cu foils using both a cyclotron and a tandem Van de Graaff accelerator. The monitor foil activities were read using a dose calibrator set to an arbitrary calibration setting. Excellent agreement was noted between the nominal and measured proton energies.