Vascular Findings in the Choriocapillaris in a Case of Radiation Retinopathy Secondary to Choroidal Melanoma.

The effects of radiation retinopathy on the retinal vasculature have been well established; however, the literature describing the pathologic changes in the choriocapillaris is relatively lacking. In this report, we describe the histologic findings of a donor eye with a choroidal melanoma with special attention to the choriocapillaris. Clinical and histological findings, including immunohistochemistry and transmission electron microscopy, are described for the retina and choroid of a donor eye affected by radiation retinopathy secondary to treatment of choroidal melanoma. Cells within the tumor exhibited an epithelioid structure and balloon melanosomes. Notable infiltration of macrophages with elongated morphology was also observed. Atrophy of photoreceptors, retinal pigmented epithelium, and choriocapillaris was observed on the inferior edge of the lesion and extending past the tumor. The choriocapillaris endothelium showed more severe dropout at the periphery of the lesion where loss of fenestration, thickened cytosol, and degenerated pericytes were observed. Morphologic analysis revealed choriocapillaris loss with pronounced degeneration of choroidal pericytes. Understanding the differences in sensitivity to radiation injury between different cell types and different patients will provide better insight into radiation retinopathy.

Stereotactic radiotherapy of appropriately selected meningiomas and metastatic brain tumor beds with gamma knife icon versus volumetric modulated arc therapy.

PURPOSE: To determine if the gamma knife icon (GKI) can provide superior stereotactic radiotherapy (SRT) dose distributions for appropriately selected meningioma and post-resection brain tumor bed treatments to volumetric modulated arc therapy (VMAT). MATERIALS AND METHODS: Appropriately selected targets were not proximal to great vessels, did not have sensitive soft tissue including organs-at-risk (OARs) within the planning target volume (PTV), and did not have concave tumors containing excessive normal brain tissue. Four of fourteen candidate meningioma patients and six of six candidate patients with brain tumor cavities were considered for this treatment planning comparison study. PTVs were generated for GKI and VMAT by adding 1 mm and 3 mm margins, respectively, to the GTVs. Identical PTV V100% -values were obtained for the GKI and VMAT plans for each patient. Meningioma and tumor bed prescription doses were 52.7-54.0 in 1.7-1.8 Gy fractions and 25 Gy in 5 Gy fractions, respectively. GKI dose rate was 3.735 Gy/min for 16 mm collimators. RESULTS: PTV radical dose homogeneity index was 3.03 ± 0.35 for GKI and 1.27 ± 0.19 for VMAT. Normal brain D1% , D5% , and D10% were lower for GKI than VMAT by 45.8 ± 10.9%, 38.9 ± 11.5%, and 35.4 ± 16.5% respectively. All OARs considered received lower maximum doses for GKI than VMAT. GKI and VMAT treatment times for meningioma plans were 12.1 ± 4.13 min and 6.2 ± 0.32 min, respectively, and, for tumor cavities, were 18.1 ± 5.1 min and 11.0 ± 0.56 min, respectively. CONCLUSIONS: Appropriately selected meningioma and brain tumor bed patients may benefit from GKI-based SRT due to the decreased normal brain and OAR doses relative to VMAT enabled by smaller margins. Care must be taken in meningioma patient selection for SRT with the GKI, even if they are clinically appropriate for VMAT.

Commissioning of a 3D image-based treatment planning system for high-dose-rate brachytherapy of cervical cancer.

The objective of this work is to present commissioning procedures to clinically implement a three-dimensional (3D), image-based, treatment-planning system (TPS) for high-dose-rate (HDR) brachytherapy (BT) for gynecological (GYN) cancer. The physical dimensions of the GYN applicators and their values in the virtual applicator library were varied by 0.4 mm of their nominal values. Reconstruction uncertainties of the titanium tandem and ovoids (T&O) were less than 0.4 mm on CT phantom studies and on average between 0.8-1.0 mm on MRI when compared with X-rays. In-house software, HDRCalculator, was developed to check HDR plan parameters such as independently verifying active tandem or cylinder probe length and ovoid or cylinder size, source calibration and treatment date, and differences between average Point A dose and prescription dose. Dose-volume histograms were validated using another independent TPS. Comprehensive procedures to commission volume optimization algorithms and process in 3D image-based planning were presented. For the difference between line and volume optimizations, the average absolute differences as a percentage were 1.4% for total reference air KERMA (TRAK) and 1.1% for Point A dose. Volume optimization consistency tests between versions resulted in average absolute differences in 0.2% for TRAK and 0.9 s (0.2%) for total treatment time. The data revealed that the optimizer should run for at least 1 min in order to avoid more than 0.6% dwell time changes. For clinical GYN T&O cases, three different volume optimization techniques (graphical optimization, pure inverse planning, and hybrid inverse optimization) were investigated by comparing them against a conventional Point A technique. End-to-end testing was performed using a T&O phantom to ensure no errors or inconsistencies occurred from imaging through to planning and delivery. The proposed commissioning procedures provide a clinically safe implementation technique for 3D image-based TPS for HDR BT for GYN cancer.

Dosimetric characterization and application of an imaging beam line with a carbon electron target for megavoltage cone beam computed tomography.

Imaging dose from megavoltage cone beam computed tomography (MVCBCT) can be significantly reduced without loss of image quality by using an imaging beam line (IBL), with no flattening filter and a carbon, rather than tungsten, electron target. The IBL produces a greater keV-range x-ray fluence than the treatment beam line (TBL), which results in a more optimal detector response. The IBL imaging dose is not necessarily negligible, however. In this work an IBL was dosimetrically modeled with the Philips Pinnacle3 treatment planning system (TPS), verified experimentally, and applied to clinical cases. The IBL acquisition dose for a 200 degrees gantry rotation was verified in a customized acrylic cylindrical phantom at multiple imaging field sizes with 196 ion chamber measurements. Agreement between the measured and calculated IBL dose was quantified with the 3D gamma index. Representative IBL and TBL imaging dose distributions were calculated for head and neck and prostate patients and included in treatment plans using the imaging dose incorporation (IDI) method. Surface dose was measured for the TBL and IBL for four head and neck cancer patients with MOSFETs. The IBL model, when compared to the percentage depth dose and profile measurements, had 97% passing gamma indices for dosimetric and distance acceptance criteria of 3%, 3 mm, and 100% passed for 5.2%, 5.2 mm. For the ion chamber measurements of phantom image acquisition dose, the IBL model had 93% passing gamma indices for acceptance criteria of 3%, 3 mm, and 100% passed for 4%, 4 mm. Differences between the IBL- and TBL-based IMRT treatment plans created with the IDI method were dosimetrically insignificant for both the prostate and head and neck cases. For IBL and TBL beams with monitor unit values that would result in the delivery of the same dose to the depth of maximum dose under standard calibration conditions, the IBL imaging surface dose was higher than the TBL imaging surface dose by an average of 18%, with a standard deviation of 8% (p = 2 x 10(-6)). The IBL can be modeled with acceptable accuracy using a standard TPS, and accounting for IBL dose in treatment plans with the IDI method is straightforward. The resulting composite dose distributions, assuming similar imaging doses, are negligibly different from those of the TBL. The increased IBL surface dose relative to the TBL is likely clinically insignificant.

Radiation therapy plan checks in a paperless clinic.

Traditional quality assurance checks of a patient's radiation therapy plan involve printing out treatment parameters from the treatment planning system and the "record and verify" (R&V) system and visually checking the information for one-to-one correspondence. In a paperless environment, one can automate this process through independent software that can read the treatment planning data directly and compare it against the parameters in the R&V system's database. In addition to verifying the data integrity, it is necessary to check the logical consistency of the data and the accuracy of various calculations. The results are then imported into the patient's electronic medical record. Appropriate workflows must be developed to ensure that no steps of the QA process are missed. This paper describes our electronic QA system (EQS), consisting of in-house software and workflows. The EQS covers 3D conformal and intensity modulated radiation therapy, electrons, stereotactic radiosurgery, total body irradiation, and clinical set ups with and without virtual simulation. The planning systems handled by our EQS are ADAC Pinnacle and Varian FASTPLAN, while the R&V systems are LANTIS and VARIS. The improvement in our plan check process over the paperless system is described in terms of the types of detected errors. The potential problems with the implementation and use of the EQS, as well as workarounds for data that are not easily accessible through electronic means, are described.

Image-guided stereotactic radiosurgery using a specially designed high-dose-rate linac.

Stereotactic radiosurgery and image-guided radiotherapy (IGRT) place enhanced demands on treatment delivery machines. In this study, we describe a high-dose-rate output accelerator as a part of our stereotactic IGRT delivery system. The linac is a Siemens Oncor without a flattening filter, and enables dose rates to reach 1000 monitor units (MUs) per minute. Even at this high-dose-rate, the linac dosimetry system remains robust; constancy, linearity, and beam energy remain within 1% for 3 to 1000 MU. Dose profiles for larger field sizes are not flat, but they are radially symmetric and, as such, able to be modeled by a treatment planning system. Target localization is performed via optical guidance utilizing a 3-dimensional (3D) ultrasound probe coupled to an array of 4 infrared light-emitting diodes. These diodes are identified by a fixed infrared camera system that determines diode position and, by extension, all objects imaged in the room coordinate system. This system provides sub-millimeter localization accuracy for cranial applications and better than 1.5 mm for extracranial applications. Because stereotactic IGRT can require significantly longer times for treatment delivery, the advantages of the high-dose-rate design and its direct impact on IGRT are discussed.

Initial clinical experience with frameless radiosurgery for patients with intracranial metastases.

PURPOSE: To review the initial clinical experience with frameless stereotactic radiosurgery (SRS) for treating intracranial metastatic disease. METHODS AND MATERIALS: Sixty-four patients received frameless SRS for intracranial metastatic disease. Minimum follow-up was 6 months with none lost to follow-up. Patients had a median of 2 metastases and a maximum of 4. The median number of isocenters was 2 with median arcs of 10 and median dose of 17.5 Gy. Thirteen patients were treated for progressive/recurrent disease after surgical resection or whole brain radiotherapy (WBRT). Fifty-one patients were treated with frameless SRS as an an adjunct to initial treatment. Of the total treated, 17 were treated with SRS alone, 20 were treated with WBRT plus SRS, 16 were treated with surgical resection plus SRS, and the remaining 11 were treated with surgical resection plus WBRT plus SRS. RESULTS: With a median actuarial follow-up period of 8.2 months, ultimate local control was 88%. The median time to progression was 8.1 months. The median overall survival was 8.7 months. Of the 17 patients treated with SRS alone, 86% had ultimate local control with mean overall survival of 7.1 months. Of the 13 patients who received surgical resection plus SRS without WBRT as primary treatment, there was 85% ultimate local control with an overall survival of 10.3 months. Three patients treated with initial surgery alone had recurrence treated with SRS 2-3 months after resection. All these patients obtained local control and median survival was >10 months. Of the 13 patients who received WBRT followed by SRS as boost treatment, 92% had local control and mean overall survival was 7.3 months. Of 7 patients who received SRS after recurrence after WBRT, 100% had local control with median survival of 8.2 months. For 8 patients who received surgery followed by WBRT and SRS, local control was 50%; however, ultimate intracranial control was achieved in 7 of 8 patients with repeat SRS and surgical resection. The overall survival in this group of patients was 14.7 months. No patient had a serious (Grade 3 or higher) complication requiring intervention. CONCLUSIONS: Frameless optically guided radiosurgery is less invasive, can be performed as a standard radiotherapy-based simulation procedure, and maintains submillimetric accuracy. Our initial results with frameless SRS for metastatic disease suggest survival times and local control (88%) eqiuvalent to frame-based methodologies. Practical noninvasive delivery makes treatment and potential retreatment to avoid WBRT more feasible.

Effects of vessel geometry and catheter position on dose delivery in intracoronary brachytherapy.

In-stent restenosis is commonly observed in coronary arteries after intervention. Intravascular brachytherapy has been found effective in reducing the recurrence of restenosis after stent placement. Conventional dosing models for brachytherapy with beta (beta) radiation neglect vessel geometry as well as the position of the delivery catheter. This paper demonstrates in computer simulations on phantoms and on in vivo patient data that the estimated dose distribution varies substantially in curved vessels. In simulated phantoms of 50-mm length with a shape corresponding to a 60 degrees - 180 degrees segment of a respectively sized torus, the average dose in 2-mm depth was decreased by 2.70%-7.48% at the outer curvature and increased by 2.95%-9.70% at the inner curvature as compared with a straight phantom. In vivo data were represented in a geometrically correct three-dimensional model that was derived by fusion of intravascular ultrasound (IVUS) and biplane angiography. These data were compared with a simplified tubular model reflecting common assumptions of conventional dosing schemes. The simplified model yielded significantly lower estimates of the delivered radiation and the dose variability as compared with a geometrically correct model (p < 0.001). The estimated dose in ten vessel segments of eight patients was on average 8.76% lower at the lumen/plaque and 6.52% lower at the media/adventitia interfaces (simplified tubular model relative to geometrically correct model). The differences in dose estimates between the two models were significantly higher in the right coronary artery as compared with the left coronary artery (p < 0.001).

Ultrasound-guided extracranial radiosurgery: technique and application.

PURPOSE: Stereotactic radiosurgery is an effective treatment modality for many intracranial lesions, but target mobility limits its utility for extracranial applications. We have developed a new technique for extracranial radiosurgery based on optically guided three-dimensional ultrasound (3DUS). The 3DUS system provides the ability to image the target volume and critical structures in real time and determine any misregistration of the target volume with the linear accelerator. In this paper, we describe the system and its initial clinical application in the treatment of localized metastatic disease. METHODS AND MATERIALS: The extracranial stereotactic system consists of an ultrasound unit that is optically tracked and registered with the linear accelerator coordinate system. After an initial patient positioning based on computed tomographic (CT) simulation, stereotactic ultrasound images are acquired and correlated with the CT-based treatment plan to determine any soft-tissue shifts between the time of the planning CT and the actual treatment. Optical tracking is used to correct any patient offsets that are revealed by the real-time imaging. RESULTS: Preclinical testing revealed that the ultrasound-based stereotactic navigation system is accurate to within 1.5 mm in comparison with an absolute coordinate phantom. Between March 2001 and March 2002, the system was used to deliver extracranial radiosurgery to 17 metastatic lesions in 16 patients. Treatments were delivered in 1 or 2 fractions, with an average fractional dose of 16 Gy (range 12.5-24 Gy) delivered to the 80% isodose surface. Before each fraction, the target misalignment from isocenter was determined using the 3DUS system and the misalignments averaged over all patients were anteroposterior = 4.8 mm, lateral = 3.6 mm, axial = 2.1 mm, and average total 3D displacement = 7.4 mm (range = 0-21.0 mm). After correcting patient misalignment, each plan was delivered as planned using 6-11 noncoplanar fields. No acute complications were reported. CONCLUSIONS: A system for high-precision radiosurgical treatment of metastatic tumors has been developed, tested, and applied clinically. Optical tracking of the ultrasound probe provides real-time tracking of the patient anatomy and allows computation of the target displacement before treatment delivery. The patient treatments reported here suggest the feasibility and safety of the technique.

In vivo determination of extra-target doses received from serial tomotherapy.

BACKGROUND AND PURPOSE: The purpose of this study was to perform in-vivo measurements of extracranial doses received by patients undergoing serial tomotherapy of the head and neck. MATERIAL AND METHODS: Intensity modulated radiotherapy treatment (IMRT) plans were designed for nine patients using the CORVUS treatment planning system (NOMOS Corp.). These plans were delivered using a tertiary collimator dedicated for serial tomotherapy attached to a 10-MV linear accelerator. For each patient, one optically stimulated luminescence dosimeter (OSLD) was placed on the sternum and one on the lower abdomen. The OSLDs were then processed, thereby estimating the in vivo absorbed doses to the sternum and gonads as a function of distance from the treatment site. RESULTS: The OSLDs were shown to measure known doses to within 5%, thereby validating their accuracy for this dose and energy range. In the patient studies, the dose received by the OSLDs varied in direct proportion to the number of monitor units delivered and inversely with the distance from the target volume; the patient dose at a distance of 15 cm from the target is approximately 0.4% of the total monitor units delivered, and drops to below 0.1% of the total MUs at approximately 40 cm from the center of the target. The average sternal dose was 1353 mSv and the average abdominal dose was 327 mSv for an average prescribed dose of 60.1 Gy. This can be attributed, at least partially, to the inefficient treatment delivery that on average required 9.9 MU/0.01 Gy. CONCLUSIONS: While IMRT reduces the normal tissue volume in the high-dose region, it also increases the overall monitor units delivered, and hence the whole-body dose, when compared with conventional treatment delivery. As has been noted in existing literature, these increases in whole-body dose from radiotherapy delivery may increase the likelihood of a radiation-induced secondary malignancy. Therefore, it is important to assess the risk of secondary malignancies from IMRT delivery, and compare this relative risk against the potential benefits of decreased normal tissue complication probabilities.