Cosmetic Outcomes of a Phase 1 Dose Escalation Study of 5-Fraction Stereotactic Partial Breast Irradiation for Early Stage Breast Cancer.

PURPOSE: Our purpose was to evaluate cosmetic changes after 5-fraction adjuvant stereotactic partial breast irradiation (S-PBI). METHODS AND MATERIALS: Seventy-five women with in situ or invasive breast cancer stage 0, I, or II, with tumor size ≤3 cm, were enrolled after lumpectomy in a phase 1 dose escalation trial of S-PBI into cohorts receiving 30, 32.5, 35, 37.5, or 40 Gy in 5 fractions. Before S-PBI, 3 to 4 gold fiducial markers were placed in the lumpectomy cavity for tracking with the Synchrony respiratory tracking system. S-PBI was delivered with a CyberKnife robotic radiosurgery system. Patients and physicians evaluated global cosmesis using the Harvard Breast Cosmesis Scale. Eight independent panelists evaluated digital photography for global cosmesis and 10 subdomains at baseline and follow-up. McNemar tests were used to evaluate change in cosmesis, graded as excellent/good or fair/poor, from baseline to year 3. Wilcoxon signed rank tests were used to evaluate change in subdomains. Cohen's kappa (κ) statistic was used to estimate interobserver agreement (IOA) between raters, and Fleiss' κ was used to estimate IOA between panelists. RESULTS: Median cosmetic follow-up was 5, 5, 5, 4, and 3 years for the 30, 32.5, 35, 37.5, and 40 Gy cohorts. Most patients reported excellent/good cosmesis at both baseline (86.3%) and year 3 (89.8%). No dose cohort had significantly worsened cosmesis by year 3 on McNemar analysis. No cosmetic subdomain had significant worsening by year 3. IOA was fair for patient-physician (κ = 0.300, P < .001), patient-panel (κ = 0.295, P < .001), physician-panel (κ = 0.256, P < .001), and individual panelists (Fleiss κ = 0.327, P < .001). CONCLUSIONS: Dose escalation of S-PBI from 30 to 40 Gy in 5 fractions for early stage breast cancer was not associated with a detectable change in cosmesis by year 3. S-PBI is a promising modality for treatment of early stage breast cancer.

Risk Factors for Fat Necrosis After Stereotactic Partial Breast Irradiation for Early-Stage Breast Cancer in a Phase 1 Clinical Trial.

PURPOSE: This study reports predictive dosimetric and physiologic factors for fat necrosis after stereotactic-partial breast irradiation (S-PBI). METHODS AND MATERIALS: Seventy-five patients with ductal carcinoma-in situ or invasive nonlobular epithelial histologies stage 0, I, or II, with tumor size <3 cm were enrolled in a dose-escalation, phase I S-PBI trial between January 2011 and July 2015. Fat necrosis was evaluated clinically at each follow-up. Treatment data were extracted from the Multiplan Treatment Planning System (Cyberknife, Accuray). Univariate and stepwise logistic regression analyses were conducted to identify factors associated with palpable fat necrosis. RESULTS: With a median follow-up of 61 months (range: 4.3-99.5 months), 11 patients experienced palpable fat necrosis, 5 cases of which were painful. The median time to development of fat necrosis was 12.7 months (range, 3-42 months). On univariate analyses, higher V32.5-47.5 Gy (P < .05) and larger breast volume (P < .01) were predictive of any fat necrosis; higher V35-50 Gy (P < .05), receiving 2 treatments on consecutive days (P = .02), and higher Dmax (P = .01) were predictive of painful fat necrosis. On multivariate analyses, breast volume larger than 1063 cm3 remained a predictive factor for any fat necrosis; receiving 2 treatments on consecutive days and higher V45 Gy were predictive of painful fat necrosis. Breast laterality, planning target volume (PTV), race, body mass index, diabetic status, and tobacco or drug use were not significantly associated with fat necrosis on univariate analysis. CONCLUSIONS: Early-stage breast cancer patients treated with breast conserving surgery and S-PBI in our study had a fat necrosis rate comparable to other accelerated partial breast irradiation modalities, but S-PBI is less invasive. To reduce risk of painful fat necrosis, we recommend not delivering fractions on consecutive days; limiting V42.5 < 50 cm3, V45 < 20 cm3, V47.5 < 1 cm3, Dmax ≤ 48 Gy and PTV < 100 cm3 when feasible; and counseling patients about the increased risk for fat necrosis when constraints are not met and for those with breast volume >1000 cm3.

Margin-Free Fractionated Stereotactic Radiation Therapy for Pediatric Brain Tumors.

PURPOSE: Conventional radiation therapy (RT) to pediatric brain tumors exposes a large volume of normal brain to unwarranted radiation causing late toxicity. We hypothesized that in well demarcated pediatric tumors lacking microscopic extensions, fractionated stereotactic RT (SRT), without target volume expansions, can reduce high dose normal tissue irradiation without affecting local control. METHODS AND MATERIALS: Between 2008 and 2017, 52 pediatric patients with brain tumors were treated using the CyberKnife (CK) with SRT in 180 to 200 cGy per fraction. Thirty representative cases were retrospectively planned for intensity modulated RT (IMRT) with 4-mm PTV expansion. We calculated the volume of normal tissue within the high or intermediate dose region adjacent to the target. Plan quality and radiation dose-volume dosimetry parameters were compared between CK and IMRT plans. We also reported overall survival, progression-free survival (PFS), and local control. RESULTS: Tumors included low-grade gliomas (n = 28), craniopharyngiomas (n = 16), and ependymomas (n = 8). The volumes of normal tissue receiving high (≥80% of prescription dose or ≥40 Gy) or intermediate (80% > dose ≥50% of the prescription dose or 40 Gy > dose ≥25 Gy) dose were significantly smaller with CK versus IMRT plans (P < .0001 for all comparisons). With a median follow-up of 3.7 years (range, 0.1-9.0), 3-year local control was 92% for all patients. Eight failures occurred: 1 craniopharyngioma (marginal), 2 ependymomas (both in-field), and 5 low-grade gliomas (2 in-field, 1 marginal, and 2 distant). CONCLUSIONS: Fractionated SRT using CK without target volume expansion appears to reduce the volume of irradiated tissue without majorly compromising local control in pediatric demarcated brain tumors. These results are hypothesis generating and should be tested and validated in prospective studies.

Phase 1 Fractional Dose-Escalation Study of Equipotent Stereotactic Radiation Therapy Regimens for Early-Stage Glottic Larynx Cancer.

PURPOSE: Early-stage glottic larynx squamous cell carcinoma (GLC) is a relatively common disease with excellent oncologic control, but treatment is associated with acute dysphagia and long-term voice quality changes. This phase 1 study of hypofractionated radiation therapy for early-stage GLC increased the fraction size while reducing the number of fractions until 5-fraction stereotactic ablative radiation therapy (SABR) was delivered. METHODS AND MATERIALS: Eligible patients had received a diagnosis of stage Tis to T2 GLC. Patients who had undergone prior curative-intent surgery were excluded. The equipotent dose levels were as follows: (1) level 0, 50 Gy in 15 fractions (n = 4); (2) level 1, 45 Gy in 10 fractions (n = 13); and (3) level 2, 42.5 Gy in 5 fractions (SABR level, n = 12). Grade 3 or 4 laryngeal edema, voice, dyspnea, stridor, or cough were the predefined dose-limiting toxicities. RESULTS: Twenty-nine patients were enrolled from November 2013 to March 2017. The median and minimum follow-up times were 39.2 and 13 months, respectively. Two actively smoking patients, 1 treated in level 1 (grade 4 laryngeal edema, grade 3 dysphagia) and 1 treated in level 2 (grade 3 laryngeal necrosis, dysphagia), developed dose-limiting toxicities. The former patient soon developed a local recurrence, and the latter patient recovered. There were a total of 5 local recurrences: 2 in level 0 and 3 in level 1. The Voice Handicap Index results showed robust long-term voice quality with median values of 7 and 0 at 6 and 12 months, respectively. CONCLUSIONS: Given the tolerability, excellent voice outcomes, and preliminary efficacy data of 5-fraction glottic larynx SABR, this regimen warrants further study.

A Phase 2 Clinical Trial of SABR Followed by Immediate Vertebroplasty for Spine Metastases.

PURPOSE: To determine the pain response and prevention of vertebral compression fractures (VCFs) after single-fraction stereotactic ablative radiation therapy (SABR) in conjunction with immediate vertebroplasty for spine metastases. METHODS AND MATERIALS: Patients with localized spine metastases free from VCF associated with loss of vertebral height with a pain score ≥4 using the visual analog scale were enrolled. Spine SABR was performed with 20 Gy delivered to the gross disease and 14 Gy to the contiguous bone marrow in a single fraction. Immediate, prophylactic vertebroplasty was performed within 1 month after spine SABR. The primary endpoint was pain response at 3 months compared to the historical control with external beam radiation therapy from Radiation Therapy Oncology Group study 9714. Secondary endpoints included pain response at 1 month, duration of pain response, vertebroplasty rate, VCF rate, local control, and overall survival. RESULTS: Thirty-five patients were enrolled, of whom 29 were deemed eligible and underwent single-fraction spine SABR. Twenty-three of these patients subsequently underwent prophylactic vertebroplasty. The 3-month pain response was significantly improved compared to Radiation Therapy Oncology Group study 9714: 95% versus 51% (P < .0001). The local control with a median follow-up of 9.6 months was 92%. The freedom from VCF was 90% at 1 year. Spine SABR was well tolerated with no grade 2 or higher toxicities. A single patient with disease extending from the vertebral body into the spinal canal developed vertebroplasty-related myelopathy, which was corrected with surgery. CONCLUSIONS: Single-fraction SABR immediately followed by prophylactic vertebroplasty improves pain response compared with conventional radiation therapy while providing long-term pain control and structural stability of the treated spine. Vertebroplasty is well tolerated as a prophylactic measure in patients without loss of vertebral height after spine SABR. Pain response and VCF rates are similar to patients undergoing SABR alone. Thus, patients who would benefit most from the addition of vertebroplasty need to be further identified.

Cyberknife stereotactic radiosurgery and radiation therapy treatment planning system.

CyberKnife is an image-guided stereotactical dose delivery system designed for both focal irradiation and radiation therapy (SRT). Focal irradiation refers the use of many small beams to deliver highly focus dose to a small target region in a few fractions. The system consists of a 6-MV linac mounted to a robotic arm, coupled with a digital x-ray imaging system. The radiation dose is delivered using many beams oriented at a number of defined or nodal positions around the patients. The CyberKnife can be used for both intracranial and extracranial treaments unlike the Gamma Knife which is limited to intracranial cases. Multiplan (Accuray Inc., Sunnyvale, CA) is the treatment planning system developed to cooperate with this accurate and versatile SRS and SRT system, and exploit the full function of Cyberknife in high-precision radiosurgery and therapy. Optimized inverse treatment plan can be achieved by fine-tuning contours and planning parameters. Precision is the newest version of Cyberknife treatment planning system (TPS) and an upgrade to Multiplan. It offers several new features such as Monte Carlo for multileaf collimator (MLC) and retreatment for other modalities that added more support for the Cyberknife system. The Cybeknife TPS is an easy-to-use and versatile inverse planning platform, suitable for stereotactic radiosurgery and radiation therapy. The knowledge and experience of the planner in this TPS is essential to improve the quality of patient care.

Multistage stereotactic radiosurgery for large cerebral arteriovenous malformations using the Gamma Knife platform.

PURPOSE: Radiosurgery is an established technique to treat cerebral arteriovenous malformations (AVMs). Obliteration of larger AVMs (> 10-15 cm3 or diameter > 3 cm) in a single session is challenging with current radiosurgery platforms due to toxicity. We present a novel technique of multistage stereotactic radiosurgery (SRS) for large intracranial arteriovenous malformations (AVM) using the Gamma Knife system. MATERIALS/METHODS: Eighteen patients with large (> 10-15 cm3 or diameter > 3 cm) AVMs, which were previously treated using a staged SRS technique on the Cyberknife platform, were retrospectively selected for this study. The AVMs were contoured and divided into 3-8 subtargets to be treated sequentially in a staged approach at half to 4 week intervals. The prescription dose ranged from 15 Gy to 20 Gy, depending on the subtarget number, volume, and location. Gamma Knife plans using multiple collimator settings were generated and optimized. The coordinates of each shot from the initial plan covering the total AVM target were extracted based on their relative positions within the frame system. The shots were regrouped based on their location with respect to the subtarget contours to generate subplans for each stage. The delivery time of each shot for a subtarget was decay corrected with 60 Co for staging the treatment course to generate the same dose distribution as that planned for the total AVM target. Conformality indices and dose-volume analysis were performed to evaluate treatment plans. RESULTS: With the shot redistribution technique, the composite dose for the multistaged treatment of multiple subtargets is equivalent to the initial plan for total AVM target. Gamma Knife plans resulted in an average PTV coverage of 96.3 ± 0.9% and a PITV of 1.23 ± 0.1. The resulting Conformality indices, V12Gy and R50 dose spillage values were 0.76 ± 0.05, 3.4 ± 1.8, and 3.1 ± 0.5 respectively. CONCLUSION: The Gamma Knife system can deliver a multistaged conformal dose to treat large AVMs when correcting for translational setup errors of each shot at each staged treatment.

Preliminary Results of a Phase 1 Dose-Escalation Trial for Early-Stage Breast Cancer Using 5-Fraction Stereotactic Body Radiation Therapy for Partial-Breast Irradiation.

PURPOSE: To evaluate the tolerability of a dose-escalated 5-fraction stereotactic body radiation therapy for partial-breast irradiation (S-PBI) in treating early-stage breast cancer after partial mastectomy; the primary objective was to escalate dose utilizing a robotic stereotactic radiation system treating the lumpectomy cavity without exceeding the maximum tolerated dose. METHODS AND MATERIALS: Eligible patients included those with ductal carcinoma in situ or invasive nonlobular epithelial histologies and stage 0, I, or II, with tumor size <3 cm. Patients and physicians completed baseline and subsequent cosmesis outcome questionnaires. Starting dose was 30 Gy in 5 fractions and was escalated by 2.5 Gy total for each cohort to 40 Gy. RESULTS: In all, 75 patients were enrolled, with a median age of 62 years. Median follow-up for 5 cohorts was 49.9, 42.5, 25.7, 20.3, and 13.5 months, respectively. Only 3 grade 3 toxicities were experienced. There was 1 dose-limiting toxicity in the overall cohort. Ten patients experienced palpable fat necrosis (4 of which were symptomatic). Physicians scored cosmesis as excellent or good in 95.9%, 100%, 96.7%, and 100% at baseline and 6, 12, and 24 months after S-PBI, whereas patients scored the same periods as 86.5%, 97.1%, 95.1%, and 95.3%, respectively. The disagreement rates between MDs and patients during those periods were 9.4%, 2.9%, 1.6%, and 4.7%, respectively. There have been no recurrences or distant metastases. CONCLUSION: Dose was escalated to the target dose of 40 Gy in 5 fractions, with the occurrence of only 1 dose-limiting toxicity. Patients felt cosmetic results improved within the first year after surgery and stereotactic body radiation therapy. Our results show minimal toxicity with excellent cosmesis; however, further follow-up is warranted in future studies. This study is the first to show the safety, tolerability, feasibility, and cosmesis results of a 5-fraction dose-escalated S-PBI treatment for early-stage breast cancer in the adjuvant setting.

Phantom-to-clinic development of hypofractionated stereotactic body radiotherapy for early-stage glottic laryngeal cancer.

The purpose of this study was to commission and clinically test a robotic stereotactic delivery system (CyberKnife, Sunnyvale, CA) to treat early-stage glottic laryngeal cancer. We enrolled 15 patients with cTis-T2N0M0 carcinoma of the glottic larynx onto an institutional review board (IRB)-approved clinical trial. Stereotactic body radiotherapy (SBRT) plans prescribed 45 Gy/10 fractions to the involved hemilarynx. SBRT dosimetry was compared with (1) standard carotid-sparing laryngeal intensity-modulated radiation therapy (IMRT) and (2) selective hemilaryngeal IMRT. Our results demonstrate that SBRT plans improved sparing of the contralateral arytenoid (mean 20.0 Gy reduction, p <0.001), ipsilateral carotid Dmax (mean 20.6 Gy reduction, p <0.001), contralateral carotid Dmax (mean 28.1 Gy reduction, p <0.001), and thyroid Dmean (mean 15.0 Gy reduction, p <0.001) relative to carotid-sparing IMRT. SBRT also modestly improved dose sparing to the contralateral arytenoid (mean 4.8 Gy reduction, p = 0.13) and spinal cord Dmax (mean 4.9 Gy reduction, p = 0.015) relative to selective hemilaryngeal IMRT plans. This "phantom-to-clinic" feasibility study confirmed that hypofractionated SBRT treatment for early-stage laryngeal cancer can potentially spare dose to adjacent normal tissues relative to current IMRT standards. Clinical efficacy and toxicity correlates continue to be collected through an ongoing prospective trial.

Commissioning and initial stereotactic ablative radiotherapy experience with Vero.

The purpose of this study is to describe the comprehensive commissioning process and initial clinical performance of the Vero linear accelerator, a new radiotherapy device recently installed at UT Southwestern Medical Center specifically developed for delivery of image-guided stereotactic ablative radiotherapy (SABR). The Vero system utilizes a ring gantry to integrate a beam delivery platform with image guidance systems. The ring is capable of rotating ± 60° about the vertical axis to facilitate noncoplanar beam arrangements ideal for SABR delivery. The beam delivery platform consists of a 6 MV C-band linac with a 60 leaf MLC projecting a maximum field size of 15 × 15 cm² at isocenter. The Vero planning and delivery systems support a range of treatment techniques, including fixed beam conformal, dynamic conformal arcs, fixed gantry IMRT in either SMLC (step-and-shoot) or DMLC (dynamic) delivery, and hybrid arcs, which combines dynamic conformal arcs and fixed beam IMRT delivery. The accelerator and treatment head are mounted on a gimbal mechanism that allows the linac and MLC to pivot in two dimensions for tumor tracking. Two orthogonal kV imaging subsystems built into the ring facilitate both stereoscopic and volumetric (CBCT) image guidance. The system is also equipped with an always-active electronic portal imaging device (EPID). We present our commissioning process and initial clinical experience focusing on SABR applications with the Vero, including: (1) beam data acquisition; (2) dosimetric commissioning of the treatment planning system, including evaluation of a Monte Carlo algorithm in a specially-designed anthropomorphic thorax phantom; (3) validation using the Radiological Physics Center thorax, head and neck (IMRT), and spine credentialing phantoms; (4) end-to-end evaluation of IGRT localization accuracy; (5) ongoing system performance, including isocenter stability; and (6) clinical SABR applications.

Multi-staged robotic stereotactic radiosurgery for large cerebral arteriovenous malformations.

PURPOSE: To investigate a multi-staged robotic stereotactic radiosurgery (SRS) delivery technique for the treatment of large cerebral arteriovenous malformations (AVMs). The treatment planning process and strategies to optimize both individual and composite dosimetry are discussed. METHODS: Eleven patients with large (30.7 ± 19.2 cm(3)) AVMs were selected for this study. A fiducial system was designed for fusion of targets between planar angiograms and simulation CT scans. AVMs were contoured based on single contrast CT, MRI and orthogonal angiogram images. AVMs were divided into 3-8 sub-target volumes (3-7 cm(3)) for sequential treatment at 1-4 week intervals to a prescription dose of 16-20 Gy. Forward and inversely developed treatment plans were optimized for 95% coverage of the total AVM volume by dose summation from each sub-volume, while minimizing dose to surrounding tissues. Dose-volume analysis was used to evaluate the PTV coverage, dose conformality (CI), and R50 and V12 Gy parameters. RESULTS: The treatment workflow was commissioned and able to localize within 1mm. Inverse optimization outperformed forward planning for most patients for each index considered. Dose conformality was shown comparable to staged Gamma Knife treatments. CONCLUSION: The CyberKnife system is shown to be a practical delivery platform for multi-staged treatments of large AVMs using forward or inverse planning techniques.

Optimization of normalized prescription isodose selection for stereotactic body radiation therapy: conventional vs robotic linac.

PURPOSE: Although modern technology has allowed for target dose escalation by minimizing normal tissue dose, the dose delivered to a tumor and surrounding tissues still depends largely on the inherent characteristics of the radiation delivery platform. This work aims to determine the optimal prescription isodose line that minimizes normal tissue irradiation for stereotactic body radiation therapy (SBRT) for a conventional linear accelerator and a robotic delivery platform. METHODS: Spherical targets with diameters of 10, 20, and 30 mm were constructed in the lungs and liver of a computer based digital torso phantom which simulates respiratory and cardiac motion. Normal tissue contours included normal lung, normal liver, and a concentric 10 mm shell of normal tissue extending from the spherical target surface. For linac planning, noncoplanar, nonopposing three dimensional (3D) conformal beams were designed, and variable prescription isodose lines were achieved by varying the MLC block margin. For CyberKnife planning, variable prescription isodose lines were achieved by inverse planning. True 4D dose calculations were used for the moving target and surrounding tissue based on each of ten phases of a 4D CT dataset. Doses of 60 Gy in three fractions were prescribed to cover 95% of the target tumor. Commonly used conformality, dosimetric, and radiobiological indices for lung and liver SBRT were used to compare different plans and determine the optimally prescribed isodose line for each treatment platform. RESULTS: For linac plans, the average optimal prescription isodose line based on all indices evaluated occurred between 59% and 69% for lung tumors and between 67% and 77% for liver tumors depending on the tumor size. CyberKnife plans had average optimal prescription isodose lines occurring between 40% and 48% for lung tumors and between 41% and 42% depending on the tumor size. However, prescription isodose lines under 50% are not advised to prevent large heterogeneous dose distributions within the target. CONCLUSIONS: The choice of prescription isodose line was shown to have a significant impact on parameters commonly used as constraints for lung and liver SBRT treatment planning for both linac-based and CyberKnife delivery platforms. By methodically choosing the prescription isodose line, normal tissue toxicities from SBRT may be reduced.

Dosimetric and motion analysis of margin-intensive therapy by stereotactic ablative radiotherapy for resectable pancreatic cancer.

BACKGROUND: The retroperitoneal margin is a common site of positive surgical margins in patients with resectable pancreatic cancer. Preoperative margin-intensive therapy (MIT) involves delivery of a single high dose of ablative radiotherapy (30 Gy) focused on this surgically inaccessible margin, utilizing stereotactic techniques in an effort to reduce local failure following surgery. In this study, we investigated the motion of regional organs at risk (OAR) utilizing 4DCT, evaluated the dosimetric effects of abdominal compression (AC) to reduce regional motion, and compared various planning techniques to optimize MIT. METHODS: 10 patients were evaluated with 4DCT scans. All 10 patients had scans using AC and seven of the 10 patients had scans both with and without AC. The peak respiratory abdominal organ and major vessel centroid excursion was measured. A "sub-GTV" region was defined by a radiation oncologist and surgical oncologist encompassing the retroperitoneal margin typically lateral and posterior to the superior mesenteric artery (SMA), and a 3-5 mm margin was added to constitute the PTV. Identical 3D non-coplanar SABR (3DSABR) plans were designed for the average compression and non-compression scans. Compression scans were planned with 3DSABR, coplanar IMRT (IMRT), and Cyberknife (CK) planning techniques. Dose volume analysis was undertaken for various endpoints, comparing OAR doses with and without AC and for different planning methods. RESULTS: The mean PTV size was 20.2 cm3. Regional vessel motion of the SMA, celiac trunk, and renal vessels was small (< 5 mm) and not significantly impacted by AC. Mean pancreatic motion was > 5 mm, so AC has been used in all patients enrolled thus far. AC did not significantly increase OAR dose including the stomach and traverse colon. There were several statistically significant differences in the doses to OARs as a function of the type of planning modality used. CONCLUSIONS: AC does not significantly reduce the limited motion of structures in close proximity to the MIT target and does not significantly increase the dose to OARs that can be displaced by the compression plate. The treatment planning techniques evaluated in this study have different advantages with no clearly superior method in our analysis. Dose to adjacent vessels may be reduced with 3DSABR or IMRT techniques, while conformality is increased with IMRT or CK.

A dosimetric comparison of stereotactic body radiation therapy techniques for lung cancer: robotic versus conventional linac-based systems.

The aim of this study is to compare the dosimetric characteristics of robotic and conventional linac-based SBRT techniques for lung cancer, and to provide planning guidance for each modality. Eight patients who received linac-based SBRT were retrospectively included in this study. A dose of 60 Gy given in three fractions was prescribed to each target. The Synchrony Respiratory Tracking System and a 4D dose calculation methodology were used for CyberKnife and linac-based SBRT, respectively, to minimize respiratory impact on dose calculation. Identical image and contour sets were used for both modalities. While both modalities can provide satisfactory target dose coverage, the dose to GTV was more heterogeneous for CyberKnife than for linac planning/delivery in all cases. The dose to 1000 cc lung was well below institutional constraints for both modalities. In the high dose region, the lung dose depended on tumor size, and was similar between both modalities. In the low dose region, however, the quality of CyberKnife plans was dependent on tumor location. With anteriorly-located tumors, the CyberKnife may deliver less dose to normal lung than linac techniques. Conversely, for posteriorly-located tumors, CyberKnife delivery may result in higher doses to normal lung. In all cases studied, more monitor units were required for CyberKnife delivery for given prescription. Both conventional linacs and CyberKnife provide acceptable target dose coverage while sparing normal tissues. The results of this study provide a general guideline for patient and treatment modality selection based on dosimetric, tumor and normal tissue sparing considerations.

A study on the dosimetric accuracy of treatment planning for stereotactic body radiation therapy of lung cancer using average and maximum intensity projection images.

PURPOSE: To assess the accuracy of current stereotactic body radiation therapy (SBRT) lung treatment planning methodologies on irregular breathing patterns, we have performed a systematic dosimetric evaluation in phantoms by utilizing maximum intensity projection (MIP) and average (AVG) images generated from four dimensional computed tomography (4DCT). METHODS: A custom built programmable lung phantom was used to simulate tumor motions due to various breathing patterns of patients. 4DCT scans were obtained in helical mode, and reconstructed AVG and MIP datasets were imported into the Pinnacle 8.0 h treatment planning system. SBRT plans were generated and executed, and delivered doses were measured by radiochromic film for analysis. RESULTS: For targets moving regularly or irregularly within a small range (7.0+/-1.8 mm, n=6), we observed good agreement between the measured and computed dose distributions. However, for targets moving irregularly with a larger range (20.8+/-2.6 mm, n=4), the measured isodose lines were found to be shifted relative to the planned distribution, resulting in an under-dosing (over 10%) in a portion of the PTV. We further observed that the discrepancy between planned and measured dose distribution is due to the inaccurate representation of irregular target motion in the MIP images generated from 4DCT. CONCLUSIONS: Caution should be used when planning from 4DCT images in the presence of large and irregular target motion. The inaccuracy inherent in 4DCT MIP and AVG images can be mitigated through the application of methodologies to reduce respiratory motion, such as abdominal compression, and through the use of volumetric image guidance (e.g., cone beam CT-CBCT) to assure precise targeting with minimal shifts.

The effect of respiratory cycle and radiation beam-on timing on the dose distribution of free-breathing breast treatment using dynamic IMRT.

In breast cancer treatment, intensity-modulated radiation therapy (IMRT) can be utilized to deliver more homogeneous dose to target tissues to minimize the cosmetic impact. We have investigated the effect of the respiratory cycle and radiation beam-on timing on the dose distribution in free-breathing dynamic breast IMRT treatment. Six patients with early stage cancer of the left breast were included in this study. A helical computed tomography (CT) scan was acquired for treatment planning. A four-dimensional computed tomography (4D CT) scan was obtained right after the helical CT scan with little or no setup uncertainty to simulate patient respiratory motion. After optimizing based on the helical CT scan, the sliding-window dynamic multileaf collimator (DMLC) leaf sequence was segmented into multiple sections that corresponded to various respiratory phases per respiratory cycle and radiation beam-on timing. The segmented DMLC leaf sections were grouped according to respiratory phases and superimposed over the radiation fields of corresponding 4D CT image set. Dose calculation was then performed for each phase of the 4D CT scan. The total dose distribution was computed by accumulating the contribution of dose from each phase to every voxel in the region of interest. This was tracked by a deformable registration program throughout all of the respiratory phases of the 4D CT scan. A dose heterogeneity index, defined as the ratio between (D20-D80) and the prescription dose, was introduced to numerically illustrate the impact of respiratory motion on the dose distribution of treatment volume. A respiratory cycle range of 4-8 s and randomly distributed beam-on timing were assigned to simulate the patient respiratory motion during the free-breathing treatment. The results showed that the respiratory cycle period and radiation beam-on timing presented limited impact on the target dose coverage and slightly increased the target dose heterogeneity. This motion impact tended to increase the variation of target dose coverage and heterogeneity between treatment fractions with different radiation beam-on timing. The target dose coverage and heterogeneity were more susceptible to the radiation beam-on timing for patients with long respiratory cycle (longer than 6 s) and large breast motion amplitudes (larger than 0.7 cm). The same results could be found for respiratory cycle up to 8 s and respiratory motion amplitude up to 1 cm. The heart dose distribution did not change significantly regardless of respiratory cycle and radiation beam-on timing.

Performance characteristics and quality assurance aspects of kilovoltage cone-beam CT on medical linear accelerator.

A medical linear accelerator equipped with optical position tracking, ultrasound imaging, portal imaging, and radiographic imaging systems was installed at University of Pittsburgh Cancer Institute for the purpose of performing image-guided radiation therapy (IGRT) and image-guided radiosurgery (IGRS) in October 2005. We report the performance characteristics and quality assurance aspects of the kilovoltage cone-beam computed tomography (kV-CBCT) technique. This radiographic imaging system consists of a kilovoltage source and a large-area flat panel amorphous silicon detector mounted on the gantry of the medical linear accelerator via controlled arms. The performance characteristics and quality assurance aspects of this kV-CBCT technique involves alignment of the kilovoltage imaging system to the isocenter of the medical linear accelerator and assessment of (a) image contrast, (b) spatial accuracy of the images, (c) image uniformity, and (d) computed tomography (CT)-to-electron density conversion relationship were investigated. Using the image-guided tools, the alignment of the radiographic imaging system was assessed to be within a millimeter. The low-contrast resolution was found to be a 6-mm diameter hole at 1% contrast level and high-contrast resolution at 9 line pairs per centimeter. The spatial accuracy (50 mm +/- 1%), slice thickness (2.5 mm and 5.0 mm +/- 5%), and image uniformity (+/- 20 HU) were found to be within the manufacturer's specifications. The CT-to-electron density relationship was also determined. By using well-designed procedures and phantom, the number of parameter checks for quality assurance of the IGRT system can be carried out in a relatively short time.

Myocardial contrast echocardiography of radiofrequency ablation lesions.

INTRODUCTION: The study tested the feasibility of differentiating radiofrequency ablation lesions from normal myocardium and quantifying their dimensions by myocardial contrast echocardiography (MCE). METHODS AND RESULTS: In 11 normal dogs, we created 14 focal and 4 linear lesions at different left ventricular sites.MCE was performed both before and after ablation by using an intracardiac echocardiography catheter (9 MHz)and infusing contrast microbubbles through the left coronary artery. An independent observer examined the lesion pathology. We found that intracardiac echocardiography alone could not delineate lesion dimensions. However, after ablation, MCE localized the lesions as well-defined, low-contrast areas within the normally opacified myocardium. Lesion dimensions byMCE immediately after ablation and 30 minutes later were similar. In 12 focal lesions, the average maximum depth (5.55 +/- 1.38 mm) and average maximum diameter(10.38 +/- 2.09 mm) by MCE were in excellent agreement with the pathologic depth (5.20 +/- 1.45 mm) and diameter(10.61 +/- 1.67 mm). Two focal lesions could not be detected by MCE and later were found to be superficial. Three-dimensional MCE correctly reconstructed the extent and shape of linear lesions compared to pathology (length: 18.7+/- 5.7 vs 18.5 +/- 5.6 mm; maximum longitudinal cross-sectional area: 81.2 +/- 9.6 vs 76.0 +/-10.3 mm(2)). CONCLUSION: MCE accurately localized and quantified radiofrequency ablation lesions in the normal leftv entricle. This new application of MCE may advance'ablation for managing ventricular arrhythmias that involve intramural or epicardial regions by providing instantaneous anatomic feedback on the effects of ablation during catheterization.

Dynamic three-dimensional visualization of the left ventricle by intracardiac echocardiography.

Cardiac function and hemodynamics are routinely evaluated during catheterization in patients with heart disease. Although intracardiac echocardiography (ICE) has been employed in guiding electrophysiology procedures, it has not been effectively used in assessing hemodynamics. We tested the utility of ICE in measuring left ventricular (LV) volume throughout the cardiac cycle. In four normal dogs (weight = 26 to 37 kg), a 10-F sheath was inserted through the femoral artery and placed inside the LV along its major axis. An ICE catheter (9 F, 9 MHz) was then inserted through the sheath into the LV. The ICE catheter was pulled back inside the sheath in 1-mm intervals starting from the apex, and 2-D tomographic images were continuously acquired while gating to respiration. Subsequently, the ICE catheter was replaced by a conductance catheter to measure single-beat volume signals. Stroke volume was determined by thermodilution for validation. All measurements were made in each dog while pacing the atrium at two different cycle lengths (range = 300 to 500 ms). The endocardial boundary was digitized from the ICE images throughout the cardiac cycle and LV volume was computed by integrating multiple segments along the major axis (range = 55 to 70 mm). We found that ICE accurately reconstructed LV 3-D anatomy. Stroke volume by ICE was in excellent agreement with thermodilution (error = 3.8 +/- 3.0%, r = 0.99, n = 8) and was highly reproducible. Morphology of LV volume signals correlated well with corresponding instantaneous volume signals derived by conductance (r = 0.93, n = 8). In conclusion, ICE accurately reconstructs LV anatomy and volume throughout the cardiac cycle in the normal heart. This approach could facilitate interventional diagnostic and therapeutic procedures.