James A. Tanyi

Volumetric image-guidance: Does routine usage prompt adaptive re-planning? An institutional review

Purpose. To investigate how the use of volumetric image-guidance using an on-board cone-beam computed tomography (CBCT) system impacts on the frequency of adaptive re-planning. Material and methods. Treatment courses of 146 patients who have undergone a course of external beam radiation therapy (EBRT) using volumetric CBCT image-guidance were analyzed. Target locations included the brain, head and neck, chest, abdomen, as well as prostate and non-prostate pelvis. The majority of patients (57.5%) were treated with hypo-fractionated treatment regimens (three to 15 fraction courses). The frequency of image-guidance ranged from daily (87.7%) to weekly or twice weekly. The underlying medical necessity for adaptive re-planning as well as frequency and consequences of plan adaptation to dose-volume parameters was assessed. Results. Radiation plans of 34 patients (23.3%) were adapted at least once (up to six time) during their course of EBRT as a result of image-guidance CBCT review. Most common causes for adaptive planning were: tumor change (mostly shrinkage: 10 patients; four patients more than one re-plan), change in abdominal girth (systematic change in hollow organ filling; n=7, two patients more than one re-plan), weight loss (n=5), and systematic target setup deviation from simulation (n=5). Adaptive re-plan was required mostly for conventionally fractionated courses; only 5 patient plans undergoing hypo-fractionated treatment were adjusted. In over 91% of adapted plans, the dose-volume parameters did deviate from the prescribed plan parameters by more than 5% for at least 10% of the target volume, or organs-at-risk in close proximity to the target volume. Discussion. Routine use of volumetric image-guidance has in our practice increased the demand for adaptive re-planning. Volumetric CBCT image-guidance provides sufficient imaging information to reliably predict the need for dose adjustment. In the vast majority of cases evaluated, the initial and adapted dose-volume parameters differed to a degree that was considered clinically significant.

Incorporating priors for medical image segmentation using a genetic algorithm

Medical image segmentation is typically performed manually by a physician to delineate gross tumor volumes for treatment planning and diagnosis. Manual segmentation is performed by medical experts using prior knowledge of organ shapes and locations but is prone to reader subjectivity and inconsistency. Automating the process is challenging due to poor tissue contrast and ill-defined organ/tissue boundaries in medical images. This paper presents a genetic algorithm for combining representations of learned information such as known shapes, regional properties and relative position of objects into a single framework to perform automated three-dimensional segmentation. The algorithm has been tested for prostate segmentation on pelvic computed tomography and magnetic resonance images.

Electromagnetic navigational bronchoscopy-guided fiducial markers for lung stereotactic body radiation therapy: analysis of safety, feasibility, and interfraction stability.

Background:Embolization coils as fiducial markers for pulmonary stereotactic body radiation therapy (SBRT) are perceived to be the optimal marker type, given their ability to conform and anchor within the small airways. The aim of our study was to assess retention, placement, migration, feasibility, and safety of electromagnetic navigational bronchoscopy (ENB)-guided embolization coil markers throughout courses of SBRT. Methods:Thirty-one patients with 34 nodules underwent ENB-guided fiducial placement of several 4 mm fibered platinum embolization coils before SBRT. Patient and nodule positioning was confirmed with daily pretreatment cone-beam computed tomography (CBCT). Fiducial positional characteristics were analyzed utilizing radiation treatment-planning software comparing the simulation CT with daily CBCTs. Results:Of 105 fiducials placed, 103 were identifiable on simulation CT (retention rate: 98.1%). Incidence of asymptomatic pneumothoraces was 6%. One patient experienced hemoptysis requiring hospitalization. Eighty-six percent of fiducials were placed within 1 cm of the nodule, with 52% of fiducials placed directly on the nodule surface. Throughout a 5-fraction SBRT course, fiducial displacement was <7, 5, and 2 mm in 98%, 96%, and 67% of pretreatment CBCTs. Conclusions:ENB placement of embolization coils as fiducials for lung SBRT image guidance is associated with a low rate of iatrogenic pneumothoraces, and resulted in reliable placement of the fiducials in close proximity to the lung nodule. Embolization coils retained their relative position to the nodule throughout the course of SBRT, and provide an excellent alternative to linear gold seeds.

Impact of the high-definition multileaf collimator on linear accelerator-based intracranial stereotactic radiosurgery

OBJECTIVES The impact of two multileaf collimator (MLC) systems for linear accelerator-based intracranial stereotactic radiosurgery (SRS) was assessed. METHODS 68 lesions formed the basis of this study. 2.5 mm leaf width plans served as reference. Comparative plans, with identical planning parameters, were based on a 5 mm leaf width MLC system. Two collimation strategies, with collimation fixed at 0° or 90° and optimised per arc or beam, were also assessed. Dose computation was based on the pencil beam algorithm with allowance for tissue heterogeneity. Plan normalisation was such that 100% of the prescription dose covered 95% of the planning target volume. Plan evaluation was based on target coverage and normal tissue avoidance criteria. RESULTS The median conformity index difference between the MLC systems ranged between 0.8% and 14.2%; the 2.5 mm MLC exhibited better dose conformation. The median reduction of normal tissue exposed to ≥100%, ≥50% and ≥25% of the prescription dose ranged from 13.4% to 29.7%, favouring the 2.5 mm MLC system. Dose fall-off was steeper for the 2.5 mm MLC system with an overall median absolute difference ranging from 0.4 to 1.2 mm. The use of collimation optimisation resulted in a decrease in differences between the MLC systems. The results demonstrated the dosimetric merit of the 2.5 mm leaf width MLC system over the 5 mm leaf width system, albeit small, for the investigated range of intracranial SRS targets. CONCLUSION The clinical significance of these results warrants further investigation to determine whether the observed dosimetric advantages translate into outcome improvements.

MOSFET sensitivity dependence on integrated dose from high‐energy photon beams

The ability of a commercially available dual bias, dual MOSFET dosimetry system to measure therapeutic doses reproducibly throughout its vendor-defined dose-based lifetime has been evaluated by characterizing its sensitivity variation to integrated/cumulative doses from,high-energy (6 and 15 MV) photon radiotherapy beams. The variation of sensitivity as a function of total integrated dose was studied for three different dose-per-fraction levels; namely, 50, 200, and 1200 cGy/fraction. In standard sensitivity mode (i.e., measurements involving dose-per-fraction levels > or =100 cGy), the response of the MOSFET system to identical irradiations increased with integrated dose for both energies investigated. Dose measurement reproducibility for the low (i.e., 50 cGy) dose fractions was within 2.1% (if the system was calibrated before each in-phantom measurement) and 3.1% [if the system was calibrated prior to first use, with no intermediate calibration(s)]. Similarly, dose measurement reproducibility was between 2.2% and 6.6% for the conventional (i.e., 200 cGy) dose fractions and between 1.8% and 7.9% for escalated (i.e., 1200 cGy) dose fractions. The results of this study suggest that, due to the progressively increasing sensitivity resulting from the dual-MOSFET design, frequent calibrations are required to achieve measurement accuracy of < or =3% (within one standard deviation).

Volumetric-modulated arc radiotherapy for pancreatic malignancies: dosimetric comparison with sliding-window intensity-modulated radiotherapy and 3-dimensional conformal radiotherapy.

Volumetric-modulated arc radiotherapy (VMAT) is an iteration of intensity-modulated radiotherapy (IMRT), both of which deliver highly conformal dose distributions. Studies have shown the superiority of VMAT and IMRT in comparison with 3-dimensional conformal radiotherapy (3D-CRT) in planning target volume (PTV) coverage and organs-at-risk (OARs) sparing. This is the first study examining the benefits of VMAT in pancreatic cancer for doses more than 55.8 Gy. A planning study comparing 3D-CRT, IMRT, and VMAT was performed in 20 patients with pancreatic cancer. Treatments were planned for a 25-fraction delivery of 45 Gy to a large field followed by a reduced-volume 8-fraction external beam boost to 59.4 Gy in total. OARs and PTV doses, conformality index (CI) deviations from 1.0, monitor units (MUs) delivered, and isodose volumes were compared. IMRT and VMAT CI deviations from 1.0 for the large-field and the boost plans were equivalent (large field: 0.032 and 0.046, respectively; boost: 0.042 and 0.037, respectively; p > 0.05 for all comparisons). Both IMRT and VMAT CI deviations from 1.0 were statistically superior to 3D-CRT (large field: 0.217, boost: 0.177; p < 0.05 for all comparisons). VMAT showed reduction of the mean dose to the boost PTV (VMAT: 61.4 Gy, IMRT: 62.4 Gy, and 3D-CRT: 62.3 Gy; p < 0.05). The mean number of MUs per fraction was significantly lower for VMAT for both the large-field and the boost plans. VMAT delivery time was less than 3 minutes compared with 8 minutes for IMRT. Although no statistically significant dose reduction to the OARs was identified when comparing VMAT with IMRT, VMAT showed a reduction in the volumes of the 100% isodose line for the large-field plans. Dose escalation to 59.4 Gy in pancreatic cancer is dosimetrically feasible with shorter treatment times, fewer MUs delivered, and comparable CIs for VMAT when compared with IMRT.

Dynamic conformal arc cranial stereotactic radiosurgery: implications of multileaf collimator margin on dose–volume metrics

OBJECTIVE The effect of multileaf collimator (MLC) margin on target and normal tissue dose-volume metrics for intracranial stereotactic radiosurgery (SRS) was assessed. METHODS 118 intracranial lesions of 83 SRS patients formed the basis of this study. For each planning target volume (PTV), five separate treatment plans were generated with MLC margins of -1, 0, 1, 2 and 3 mm, respectively. Identical treatment planning parameters were employed with a median of five dynamic conformal arcs using the Varian/BrainLab high-definition MLC for beam shaping. Prescription dose (PD) was such that 22 Gy covered at least 95% of the PTV. Dose-volume and dose-response comparative metrics included conformity index, heterogeneity index, dose gradient, tumour control probability (TCP) and normal tissue complication probability (NTCP). RESULTS Target dose heterogeneity decreased with increasing MLC margin (p<0.001); mean heterogeneity index decreased from 70.4 ± 12.7 to 10.4 ± 2.2%. TCP decreased with increasing MLC margin (p<0.001); mean TCP decreased from 81.0 ± 2.3 to 62.2 ± 1.8%. Normal tissue dose fall-off increased with MLC margin (p<0.001); mean gradient increased from 3.1 ± 0.9 mm to 5.3 ± 0.7 mm. NTCP was optimal at 1 mm MLC margin. No unambiguous correlation was observed between NTCP and PTV volume. Plan delivery efficiency generally improved with larger margins (p<0.001); mean monitor unit per centigray of the PD decreased from 3.60 ± 1.30 to 1.56 ± 0.13. Conclusion Use of 1 mm MLC margins for dynamic conformal arc-based cranial radiosurgery resulted in optimal tumour control and normal tissue sparing. Clinical significance of these comparative findings warrants further investigation.

Characterization of a gated fiber-optic-coupled detector for application in clinical electron beam dosimetry

PURPOSE Assessment of the fundamental dosimetric characteristics of a novel gated fiber-optic-coupled dosimetry system for clinical electron beam irradiation. METHODS The response of fiber-optic-coupled dosimetry system to clinical electron beam, with nominal energy range of 6-20 MeV, was evaluated for reproducibility, linearity, and output dependence on dose rate, dose per pulse, energy, and field size. The validity of the detector systems response was assessed in correspondence with a reference ionization chamber. RESULTS The fiber-optic-coupled dosimetry system showed little dependence to dose rate variations (coefficient of variation +/- 0.37%) and dose per pulse changes (with 0.54% of reference chamber measurements). The reproducibility of the system was +/- 0.55% for dose fractions of approximately 100 cGy. Energy dependence was within +/- 1.67% relative to the reference ionization chamber for the 6-20 MeV nominal electron beam energy range. The system exhibited excellent linear response (R2 = 1.000) compared to reference ionization chamber in the dose range of 1-1000 cGy. The output factors were within +/- 0.54% of the corresponding reference ionization chamber measurements. CONCLUSIONS The dosimetric properties of the gated fiber-optic-coupled dosimetry system compare favorably to the corresponding reference ionization chamber measurements and show considerable potential for applications in clinical electron beam radiotherapy.

A Novel Application of Principal Surfaces to Segmentation in 4D-CT for Radiation Treatment Planning

Radiation therapy is one of the most effective options used in the treatment of about half of all people with cancer. A critical goal in radiation therapy is to deliver optimal radiation doses to the observed tumor while sparing the surrounding healthy tissues. Radiation oncologists typically manually delineate normal and diseased structures on three-dimensional computed tomography~(3D-CT) scans. Manual delineation is a labor intensive, tedious and time-consuming task. In recent years, concerns about respiration induced motion have led to the popularity of four-dimensional computed tomography~(4D-CT) for the tracking of tumors and deformation of organs. However, as manually contouring in all phases would be prohibitively expensive, the development of fast, robust, and automatic segmentation tools has been an active area of research in 4D radiotherapy. In this paper, we describe a novel application of principal surfaces for the propagation of contours in 4D-CT studies. Regions of interest~(ROIs) are manually delineated slice-by-slice in the reference 3D-CT scans. Edges are detected on all of the slices of the target 3D-CT phase. A kernel density estimation~(KDE) based on the detected edges is then calculated. The principal surface algorithm is applied to find the ridges of the edge KDE to provide the object contours. Manually drawn contours from the reference phase are used as an initialization. Contours of ROIs are propagated recursively in all consecutive phases to complete a respiration cycle. Results are provided for a phantom data set of simulated tumor motion as well as on a de-identified data set of the lung of a patient. Evaluation of the efficacy of automatic segmentation in organs and tumors are based on the comparison between manually drawn contours and automatically delineated contours. The Dice coefficients are approximately 0.97 for the lung tumor on the phantom data sets and 0.95 for the patient data sets. The centroid distances between manually delineated lung volume and automatically segmented lung volume in each CT direction are

Temporal Assessment of Regional and Remote Non Tumor Microvascular Response to High Dose Radiation Therapy Using Contrast Enhanced Ultrasound

• • Proximal hindlimb muscle of C57BL/6J mice were irradiated in a single fraction. • Regions for analysis included: high-dose (HD) RT (15 Gy), an immediately adjacent area of lower-dose (LD) RT (12 Gy), and a region on the unirradiated contralateral limb (Figure 1). • Control mice not undergoing any RT were also studied. • CEU of the hindlimb muscle was performed during intravenous infusion of lipid-shelled decafluorobutane microbubble contrast at day 1 and 8 after RT. • CEU time-intensity data were analyzed to quantify microvascular blood flow, microvascular blood transit rate (β), and microvascular blood volume. • Molecular imaging of endothelial activation was performed using MB targeted to P-selectin by virtue of surface conjugation of mAb RB40.34 (Figure 2). Methods • High-dose radiation therapy (RT) produces multifactorial microvascular injury in both tumor targets and normal tissue. • Contrast-enhanced ultrasound (CEU) is a highresolution perfusion imaging technique that is able to quantify microvascular blood flow and volume by using microbubble (MB) contrast agents that are confined in the vascular space. • CEU molecular imaging is also possible by using MBs bearing targeting ligands • We hypothesized that CEU could characterize alterations in microvascular blood flow in normal tissues exposed to RT.