Jose Garcia-Ramirez

PERFORMANCE EVALUATION OF AN 85-cm-BORE X-RAY COMPUTED TOMOGRAPHY SCANNER DESIGNED FOR RADIATION ONCOLOGY AND COMPARISON WITH CURRENT DIAGNOSTIC CT SCANNERS

INTRODUCTION The demand for computed tomography (CT) virtual simulation is constantly increasing with the wider adoption of three-dimensional conformal and intensity-modulated radiation therapy. Virtual simulation CT studies are typically acquired on conventional diagnostic scanners equipped with an external patient positioning laser system and specialized planning and visualization software. Virtual simulation technology has matured to a point where conventional simulators may be replaced with CT scanners. However, diagnostic CT scanner gantry bores (typically 65-70 cm) can present an obstacle to the CT simulation process by limiting patient positions, compared to those that can be attained in a conventional simulator. For example, breast cancer patients cannot always be scanned in the treatment position without compromising reproducibility and appropriateness of setup. Extremely large patients or patients requiring special immobilization or large setup devices are often unable to enter the limited-bore gantry. A dedicated 85-cm-bore radiation oncology CT scanner has the potential to eliminate these problems. The scanner should provide diagnostic-quality images at diagnostic-comparable dose levels. The purpose of this study was to independently evaluate the performance of a novel 85-cm-bore CT X-ray scanner designed specifically for radiation oncology and compare it against diagnostic-type, 70-cm-bore scanners that may be used in the same setting. MATERIALS AND METHODS We performed image quality and dosimetric measurements on an 85-cm-bore CT scanner (AcQSim CT, Marconi Medical Systems, Inc., Cleveland, OH) and a 70-cm-bore, diagnostic-type scanner (UltraZ CT, Marconi Medical Systems, Inc.). Image quality measurements were performed using a manufacturer-supplied phantom (Performance Phantom, Marconi Medical Systems, Inc.), following the manufacturers suggested testing procedures, and an independent image quality phantom (CATPHAN 500, The Phantom Laboratory, New York, NY). The standard image quality parameters evaluated for the purpose of comparison were as follows: slice thickness accuracy, high-contrast resolution (limiting spatial resolution), low-contrast resolution, uniformity and noise, and CT number accuracy and linearity. Standard head and body protocols were employed throughout most of our measurements and were kept equal between the two scanners. The computed tomography dose index was measured for standard head and body imaging protocols using accepted methods and procedures. For comparison purposes, data for a diagnostic-type, 70-cm-bore scanner (GE HighSpeed CT/i) were extracted from the literature. The results obtained for the 85-cm-bore scanner are compared with the following: (1) manufacturer-provided autoperformance phantom test results (validating its use for routine quality assurance), (2) a similar set of measurements performed on a conventional 70-cm-bore, diagnostic-type CT scanner (UltraZ CT, Marconi Medical Systems, Inc.), and (3) current available data on other diagnostic-type CT scanners (GE HighSpeed CT/i). RESULTS Head and body doses seem on average to be slightly (1-2 cGy) higher for the 85-cm-bore unit than for conventional 70-cm units. Measured slice thickness was within acceptable criteria, +/-0.5 mm. There does not seem to be any significant difference in high-contrast resolution. Both units render a limiting value of approximately 7-8 lp/cm for slice thickness 8-10 mm. Both units exhibit comparable CT number uniformity, accuracy, and linearity. Noise levels seem to be slightly increased (by approximately 0.05-0.2%) for the large-bore geometry. Low-contrast resolution for both units was comparable (4.5-5.5 mm @ 0.35%). All image quality parameters are well within diagnostic acceptable levels. CONCLUSION The overall imaging performance and mechanical integrity of the 85-cm-bore scanner are comparable to those of conventional diagnostic scanners that may be employed in a radiation oncology setting.

Salvage Radioembolization of Liver-dominant Metastases with a Resin-based Microsphere: Initial Outcomes

PURPOSE The use of radioembolization of hepatic metastases with yttrium-90 ((90)Y) microspheres is increasing. The present report describes the outcomes in a cohort of patients with metastatic liver tumors treated with a resin-based microsphere agent. MATERIALS AND METHODS Thirty patients with colon (n = 13), breast (n = 7), and other primary cancers (n = 10) were treated after the failure of first- and second-line therapy. Overall survival (OS), time to progression (TTP), and time to treatment failure (TTTF) were calculated from the first treatment. Response was measured according to Response Evaluation Criteria In Solid Tumors at interval follow-up imaging. RESULTS Thirty patients underwent 56 infusions of (90)Y, and 18 remained alive at the end of the study. Fourteen patients (47%) had a partial response or stable disease. OS (604 vs 251 days), TTP (223 vs 87 days), and TTTF (363 vs 87 days) were all significantly longer for patients who had a partial response or stable disease (P < .05). Median OS, TTP, and TTTF for patients with colorectal carcinoma were 357, 112, and 107 days, respectively, versus 638, 118, and 363 days in patients with other metastatic sources. Median survival was not reached for patients with breast carcinoma, and the TTP and TTTF were each 282 days. One patient (3%) experienced grade 3 toxicity (gastrointestinal ulceration). CONCLUSIONS (90)Y microsphere therapy produced promising survival rates compared with systemic salvage options, with minimal toxicity.

Tilting of radioactive plaques after initial accurate placement for treatment of uveal melanoma.

OBJECTIVE To evaluate plaque movement as a potential factor in local failure using intraoperative ultrasonography at plaque insertion and removal. METHODS Prospective study of 162 patients with uveal melanoma undergoing intraoperative B-scan ultrasonography at insertion and removal of iodine 125 plaques. RESULTS Tilting of the posterior plaque edge more than 1.0 mm away from the sclera was detected in 15 patients (9%) at plaque insertion and in 85 patients (53%) at plaque removal (P < .001). Factors associated with tilt at plaque removal included male sex (P = .009), decreased tumor distance to the fovea and optic disc (P < .001 for both), notched plaque (P = .001), and episcleral hematoma (P = .009). Plaque tilt caused a reduction greater than 10% in actual radiation dose to the tumor apex in 37 patients (23%). Local failure occurred in only 3 patients (2%), all of whom had tilt of 1.95 mm or greater at plaque removal. CONCLUSIONS Plaque tilt after initial accurate placement occurs frequently during brachytherapy for uveal melanomas and may represent an important cause of local treatment failure. Recognizing and counteracting the effects of plaque tilt may reduce the risk of local failure. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00459849.

Clinical evaluations of an amplitude-based binning algorithm for 4DCT reconstruction in radiation therapy

PURPOSE Phase-binning algorithms are commonly utilized in 4DCT image reconstruction for characterization of tumor or organ shape and respiration motion, but breathing irregularities occurring during 4DCT acquisition can cause considerable image distortions. Recently, amplitude-binning algorithms have been evaluated as a potential improvement to phase-binning algorithms for 4DCT image reconstruction. The purpose of this study was to evaluate the performance of the first commercially available on-line retrospective amplitude-binning algorithm for comparison to the traditional phase-binning algorithm. METHODS Both phantom and clinical data were used for evaluation. A phantom of known geometry was mounted on a 4D motion platform programmed with seven respiratory waves (two computer generated and five patient trajectories) and scanned with a Philips Brilliance Big bore 16-slice CT simulator. 4DCT images were reconstructed using commercial amplitude- and phase-binning algorithms. Image quality of the amplitude- and phase-binned image sets was compared by evaluation of shape and volume distortions in reconstructed images. Clinical evaluations were performed on 64 4DCT patient image sets in a blinded review process. The amplitude- and phase-binned 4DCT maximum intensity projection (MIP) images were further evaluated for 28 stereotactic body radiation therapy (SBRT) cases of total 64 cases. A preliminary investigation of the effects of respiratory amplitude and pattern irregularities on motion artifact severity was conducted. RESULTS The phantom experiments illustrated that, as expected, maximum inhalation occurred at the 0% amplitude and maximum exhalation occurred at the 50% amplitude of the amplitude-binned 4DCT image sets. The phantom shape distortions were more severe in the images reconstructed from the phase-binning algorithm. In the clinical study, compared to the phase-binning algorithm, the amplitude-binning algorithm yielded fewer or less severe motion artifacts in 37.5% of the cases (24∕64), comparable artifacts in 54.7% of the cases (35∕64), and slightly greater artifacts in 7.8% of the cases (5∕64). Evaluation of SBRT cases demonstrated that the reconstructed tumor sizes and locations were comparable in 96% (1∕28) of the MIP image pairs generated from both amplitude- and phase-binning algorithms. In this case the amplitude-binned image set rendered a smaller tumor size, which was likely due to very shallow respiratory amplitudes occurring over several breathing cycles. CONCLUSIONS Overall, the amplitude-binning algorithm for 4DCT reconstruction reduced the severity of tumor distortion and image artifacts compared to the phase-binning algorithm. However, the full range of motion may not be characterized using amplitude-binning algorithms. Despite superior performance, amplitude binning can still be susceptible to motion artifacts caused by large variations in amplitude of respiratory waves.

Cervical Gross Tumor Volume Dose Predicts Local Control Using Magnetic Resonance Imaging/Diffusion-Weighted Imaging—Guided High-Dose-Rate and Positron Emission Tomography/Computed Tomography—Guided Intensity Modulated Radiation Therapy

PURPOSE Magnetic resonance imaging/diffusion weighted-imaging (MRI/DWI)-guided high-dose-rate (HDR) brachytherapy and (18)F-fluorodeoxyglucose (FDG) - positron emission tomography/computed tomography (PET/CT)-guided intensity modulated radiation therapy (IMRT) for the definitive treatment of cervical cancer is a novel treatment technique. The purpose of this study was to report our analysis of dose-volume parameters predicting gross tumor volume (GTV) control. METHODS AND MATERIALS We analyzed the records of 134 patients with International Federation of Gynecology and Obstetrics stages IB1-IVB cervical cancer treated with combined MRI-guided HDR and IMRT from July 2009 to July 2011. IMRT was targeted to the metabolic tumor volume and lymph nodes by use of FDG-PET/CT simulation. The GTV for each HDR fraction was delineated by use of T2-weighted or apparent diffusion coefficient maps from diffusion-weighted sequences. The D100, D90, and Dmean delivered to the GTV from HDR and IMRT were summed to EQD2. RESULTS One hundred twenty-five patients received all irradiation treatment as planned, and 9 did not complete treatment. All 134 patients are included in this analysis. Treatment failure in the cervix occurred in 24 patients (18.0%). Patients with cervix failures had a lower D100, D90, and Dmean than those who did not experience failure in the cervix. The respective doses to the GTV were 41, 58, and 136 Gy for failures compared with 67, 99, and 236 Gy for those who did not experience failure (P<.001). Probit analysis estimated the minimum D100, D90, and Dmean doses required for ≥90% local control to be 69, 98, and 260 Gy (P<.001). CONCLUSIONS Total dose delivered to the GTV from combined MRI-guided HDR and PET/CT-guided IMRT is highly correlated with local tumor control. The findings can be directly applied in the clinic for dose adaptation to maximize local control.

Outcomes of iodine-125 plaque brachytherapy for uveal melanoma with intraoperative ultrasonography and supplemental transpupillary thermotherapy

PURPOSE To assess the impact on local tumor control of intraoperative ultrasonographic plaque visualization and selective application of transpupillary thermotherapy (TTT) in the treatment of posterior uveal melanoma with iodine-125 (I-125) episcleral plaque brachytherapy (EPB). METHODS AND MATERIALS Retrospective analysis of 526 patients treated with I-125 EPB for posterior uveal melanoma. Clinical features, dosimetric parameters, TTT treatments, and local tumor control outcomes were recorded. Statistical analysis was performed using Cox proportional hazards and Kaplan-Meier life table method. RESULTS The study included 270 men (51%) and 256 women (49%), with a median age of 63 years (mean, 62 years; range, 16-91 years). Median dose to the tumor apex was 94.4 Gy (mean, 97.8; range, 43.9-183.9) and to the tumor base was 257.9 Gy (mean, 275.6; range, 124.2-729.8). Plaque tilt >1 mm away from the sclera at plaque removal was detected in 142 cases (27%). Supplemental TTT was performed in 72 patients (13.7%). One or 2 TTT sessions were required in 71 TTT cases (98.6%). After a median follow-up of 45.9 months (mean, 53.4 months; range, 6-175 months), local tumor recurrence was detected in 19 patients (3.6%). Local tumor recurrence was associated with lower dose to the tumor base (P=.02). CONCLUSIONS Ultrasound-guided plaque localization of I-125 EPB is associated with excellent local tumor control. Detection of plaque tilt by ultrasonography at plaque removal allows supplemental TTT to be used in patients at potentially higher risk for local recurrence while sparing the majority of patients who are at low risk. Most patients require only 1 or 2 TTT sessions.

Outpatient-based high-dose-rate interstitial brachytherapy for gynecologic malignancies

PURPOSE To evaluate outpatient-based high-dose-rate (HDR) interstitial brachytherapy (ISBT) in the treatment of gynecologic malignancies. METHODS AND MATERIALS Between December 2006 and July 2012, 50 patients were treated with twice-daily outpatient-based HDR iridium-192 ISBT at our institution. Thirty-two patients had vaginal cancers, 13 vulvar, 3 urethral, and 2 cervical cancers. The most common histologies were squamous cell carcinoma (58%) and endometrioid adenocarcinoma (26%). Twenty-six patients were treated with definitive radiation therapy with or without platinum-based chemotherapy, 16 were treated for recurrent disease, 5 were treated in the postoperative setting, and 3 were treated palliatively. Forty patients received external beam radiation therapy before ISBT. RESULTS Median followup was 13.7 months. Median interstitial dose was 18 Gy in 2.25 Gy twice-daily fractions prescribed to the implant volume. Median external beam dose was 50.4 Gy in 1.8 Gy daily fractions prescribed to the primary disease site. Eight patients (16%) were seen in the emergency room or were admitted to the hospital during treatment. Six patients (17%) experienced significant complications after treatment (3 ulcerations at the primary site, 1 vaginal necrosis, 1 vaginal abscess, and 1 patient with urinary obstruction). Larger volume encompassing 100% of the prescribed dose was correlated with significant complications on multivariate analysis (p = 0.039). Actuarial local control at 1 year was 72%, with univariate analysis demonstrating worse local control for nonendometrioid adenocarcinoma compared with squamous cell carcinoma (20% vs. 84%, p = 0.044). CONCLUSIONS Outpatient-based HDR ISBT is feasible and safe, with toxicity and local control rates consistent with historical outcomes.

Enhanced efficiency in helical tomotherapy quality assurance using a custom-designed water-equivalent phantom

Tomotherapy is an image-guided, intensity-modulated radiation therapy system that delivers highly conformal dose distributions in a helical fashion. This system is also capable of acquiring megavoltage computed-tomography images and registering them to the planning kVCT images for accurate target localization. Quality assurance (QA) of this device is time intensive, but can be expedited by improved QA tools and procedures. A custom-designed phantom was fabricated to improve the efficiency of daily QA of our Tomotherapy machine. The phantom incorporates ionization chamber measurement points, plugs of different densities and slide-out film cartridges. The QA procedure was designed to verify in less than 30 min the vital components of the tomotherapy system: static beam quality and output, image quality, correctness of image registration and energy of the helical dose delivery. Machine output, percent depth dose and off-axis factors are simultaneously evaluated using a static 5 x 40 cm(2) open field. A single phantom scan is used to evaluate image quality and registration accuracy. The phantom can also be used for patient plan-specific QA. The QA results over a period of 6 months are reported in this paper. The QA process was found to be simple, efficient and capable of simultaneously verifying several important parameters.

Clinical implementation of multisequence MRI-based adaptive intracavitary brachytherapy for cervix cancer.

The purpose of this study was to describe the clinical implementation of a magnetic resonance image (MRI)‐based approach for adaptive intracavitary brachytherapy (ICBT) of cervix cancer patients. Patients were implanted with titanium tandem and colpostats. MR imaging was performed on a 1.5‐T Philips scanner using T2‐weighted (T2W), proton‐density weighted (PDW), and diffusion‐weighted (DW) imaging sequences. Apparent diffusion coefficient (ADC) maps were generated from the DW images. All images were fused. T2W images were used for the definition of organs at risk (OARs) and dose points. ADC maps in conjunction with T2W images were used for target delineation. PDW images were used for applicator definition. Forward treatment planning was performed using standard source distribution rules normalized to Point A. Point doses and dose‐volume parameters for the tumor and OARs were exported to an automated dose‐tracking application. Brachytherapy doses were adapted for tumor shrinkage and OAR variations during the course of therapy. The MRI‐based ICBT approach described here has been clinically implemented and is carried out for each brachytherapy fraction. Total procedure time from patient preparation to delivery of treatment is typically 2 hrs. Implementation of our technique for structure delineation, applicator definition, dose tracking, and adaptation is demonstrated using treated patient examples. Based on published recommendations and our clinical experience in the radiation treatment of cervix cancer patients, we have refined our standard approach to ICBT by 1) incorporating a multisequence MRI technique for improved visualization of the target, OARs, and applicator, and by 2) implementing dose adaptation by use of automated dose tracking tools. PACS numbers: 87.61.‐c, 87.53.Jw, 87.19.xjThe purpose of this study was to describe the clinical implementation of a magnetic resonance image (MRI)-based approach for adaptive intracavitary brachytherapy (ICBT) of cervix cancer patients. Patients were implanted with titanium tandem and colpostats. MR imaging was performed on a 1.5-T Philips scanner using T2-weighted (T2W), proton-density weighted (PDW), and diffusion-weighted (DW) imaging sequences. Apparent diffusion coefficient (ADC) maps were generated from the DW images. All images were fused. T2W images were used for the definition of organs at risk (OARs) and dose points. ADC maps in conjunction with T2W images were used for target delineation. PDW images were used for applicator definition. Forward treatment planning was performed using standard source distribution rules normalized to Point A. Point doses and dose-volume parameters for the tumor and OARs were exported to an automated dose-tracking application. Brachytherapy doses were adapted for tumor shrinkage and OAR variations during the course of therapy. The MRI-based ICBT approach described here has been clinically implemented and is carried out for each brachytherapy fraction. Total procedure time from patient preparation to delivery of treatment is typically 2 hrs. Implementation of our technique for structure delineation, applicator definition, dose tracking, and adaptation is demonstrated using treated patient examples. Based on published recommendations and our clinical experience in the radiation treatment of cervix cancer patients, we have refined our standard approach to ICBT by 1) incorporating a multisequence MRI technique for improved visualization of the target, OARs, and applicator, and by 2) implementing dose adaptation by use of automated dose tracking tools. PACS numbers: 87.61.-c, 87.53.Jw, 87.19.xj.

Three-dimensional dose accumulation in pseudo-split-field IMRT and brachytherapy for locally advanced cervical cancer

PURPOSE Dose accumulation of split-field external beam radiotherapy (EBRT) and brachytherapy (BT) is challenging because of significant EBRT and BT dose gradients in the central pelvic region. We developed a method to determine biologically effective dose parameters for combined split-field intensity-modulated radiation therapy (IMRT) and image-guided BT in locally advanced cervical cancer. METHODS AND MATERIALS Thirty-three patients treated with split-field-IMRT to 45.0-51.2 Gy in 1.6-1.8 Gy per fraction to the elective pelvic lymph nodes and to 20 Gy to the central pelvis region were included in this study. Patients received six weekly fractions of high-dose rate BT to 6.5-7.3 Gy per fraction. A dose tracker software was developed to compute the equivalent dose in 2-Gy fractions (EQD2) to gross tumor volume (GTV), organs-at-risk and point A. Total dose-volume histogram parameters were computed on the 3D combined EQD2 dose based on rigid image registration. The dose accumulation uncertainty introduced by organ deformations between IMRT and BT was evaluated. RESULTS According to International Commission on Radiation Unit and Measurement and GEC European Society for Therapeutic Radiology and Oncology recommendations, D98, D90, D50, and D2cm3 EQD2 dose-volume histogram parameters were computed. GTV D98 was 84.0 ± 26.5 Gy and D2cc was 99.6 ± 13.9 Gy, 67.4 ± 12.2 Gy, 75.0 ± 10.1 Gy, for bladder, rectum, and sigmoid, respectively. The uncertainties induced by organ deformation were estimated to be -1 ± 4 Gy, -3 ± 5 Gy, 2 ± 3 Gy, and -3 ± 5 Gy for bladder, rectum, sigmoid, and GTV, respectively. CONCLUSIONS It is feasible to perform 3D EQD2 dose accumulation to assess high and intermediate dose regions for combined split-field IMRT and BT.