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Purpose: To report early clinical outcomes of helical tomotherapy (HT)-based image-guided intensity-modulated radiation therapy (IMRT) in brain tumors of varying shape, size, and location. Materials and Methods: Patients with residual, recurrent, and/or progressive low-grade intracranial and skull-base tumors were treated on a prospective protocol of HT-based IMRT and followed clinicoradiologically. Standardized metrics were used for plan evaluation and outcome analysis. Results: Twenty-seven patients with 30 lesions were treated to a median radiotherapy dose of 54 Gy in 30 fractions. All HT plans resulted in excellent target volume coverage with steep dose-gradients. The mean (standard deviation) dose homogeneity index and conformity index was 0.07 (0.05) and 0.71 (0.08) respectively. At first response assessment, 20 of 30 lesions were stable, whereas 9 showed partial regression. One patient with a recurrent clival chordoma though neurologically stable showed imaging-defined progression, whereas another patient with stable disease on serial imaging had sustained neurologic worsening. With a median follow-up of 19 months (interquartile range, 11–26 months), the 2-year clinicoradiological progression-free survival and overall survival was 93.3% and 100% respectively. Conclusions: Careful selection of radiotherapy technique is warranted for benign/low-grade brain tumors to achieve durable local control with minimum long-term morbidity. Large or complex-shaped tumors benefit most from IMRT. Our early clinical experience of HT-based IMRT for brain tumors has been encouraging. [ABSTRACT FROM AUTHOR]

Purpose: To report a single-institutional experience using intensity-modulated radiotherapy with daily image-guided radiotherapy for the reirradiation of recurrent and second cancers of the head and neck. Methods and Materials: Twenty-one consecutive patients were prospectively treated with intensity-modulated radiotherapy from February 2006 to March 2009 to a median dose of 66 Gy (range, 60–70 Gy). None of these patients received concurrent chemotherapy. Daily helical megavoltage CT scans were obtained before each fraction as part of an image-guided radiotherapy registration protocol for patient alignment. Results: The 1- and 2-year estimates of in-field control were 72% and 65%, respectively. A total of 651 daily megavoltage CT scans were obtained. The mean systematic shift to account for interfraction motion was 1.38 ± 1.25 mm, 1.79 ± 1.45 mm, and 1.98 ± 1.75 mm for the medial–lateral, superior–inferior, and anterior–posterior directions, respectively. Pretreatment shifts of >3 mm occurred in 19% of setups in the medial–lateral, 27% in the superior–inferior, and 33% in the anterior–posterior directions, respectively. There were no treatment-related fatalities or hospitalizations. Complications included skin desquamation, odynophagia, otitis externa, keratitis, naso-lacrimal duct stenosis, and brachial plexopathy. Conclusions: Intensity-modulated radiotherapy with daily image guidance results in effective disease control with relatively low morbidity and should be considered for selected patients with recurrent and second primary cancers of the head and neck. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether the volume of a patient''s breast is correlated with reliable daily setup in treatment of breast cancer with a helical tomotherapy treatment unit. Methods and Materials: Thirty-six consecutive patients with breast cancer were treated on a helical tomotherapy unit. During simulation, kilovoltage CT images were obtained for treatment planning. These were fused with daily megavoltage CT scans, and after setup based on skin marks and laser alignment the necessary shifts were carried out. The magnitude of daily shifts (in millimeters) was retrospectively obtained from the daily image fusions, and the breast volume was obtained from the treatment plan. A total of 873 fusion scans were reviewed. Random error for absolute and directional daily shifts was evaluated for correlation to volume. Variation over time was also evaluated. Results: Mean (SD) random shift for all patients in the lateral, longitudinal, and vertical directions was 2.7 (2.0), 3.1 (1.5), and 3.2 (2.6) mm, respectively. Mean (SD) absolute distance shifted was 6.0 (3.5) mm. There was no significant correlation between mean absolute or mean directional daily shift and breast volume (0.08, 0.08, 0.22, and 0.07, respectively). There was no correlation between setup variation and time. Conclusions: In this cohort, there was no correlation between breast volume and degree of daily shift. There was no correlation between time course and setup variation. Therefore, setup variation does not improve or degrade with repeated treatment setups. [Copyright &y& Elsevier]

Purpose: To integrate three-dimensional (3D) digital rotation angiography (DRA) and two-dimensional (2D) digital subtraction angiography (DSA) imaging into a targeting methodology enabling comprehensive image-guided robotic radiosurgery of arteriovenous malformations (AVMs). Methods and Materials: DRA geometric integrity was evaluated by imaging a phantom with embedded markers. Dedicated DSA acquisition modes with preset C-arm positions were configured. The geometric reproducibility of the presets was determined, and its impact on localization accuracy was evaluated. An imaging protocol composed of anterior-posterior and lateral DSA series in combination with a DRA run without couch displacement between acquisitions was introduced. Software was developed for registration of DSA and DRA (2D-3D) images to correct for: (a) small misalignments of the C-arm with respect to the estimated geometry of the set positions and (b) potential patient motion between image series. Within the software, correlated navigation of registered DRA and DSA images was incorporated to localize AVMs within a 3D image coordinate space. Subsequent treatment planning and delivery followed a standard image-guided robotic radiosurgery process. Results: DRA spatial distortions were typically smaller than 0.3 mm throughout a 145-mm × 145-mm × 145-mm volume. With 2D-3D image registration, localization uncertainties resulting from the achievable reproducibility of the C-arm set positions could be reduced to about 0.2 mm. Overall system-related localization uncertainty within the DRA coordinate space was 0.4 mm. Image-guided frameless robotic radiosurgical treatments with this technique were initiated. Conclusions: The integration of DRA and DSA into the process of nidus localization increases the confidence with which radiosurgical ablation of AVMs can be performed when using only an image-guided technique. Such an approach can increase patient comfort, decrease time pressure on clinical and technical staff, and possibly reduce the number of cerebral angiograms needed for a particular patient. [Copyright &y& Elsevier]

Purpose: Breath-hold (BH) treatment minimizes internal target volumes (ITV) when treating sites prone to motion. Digital tomosynthesis (DTS) imaging has advantages over cone-beam CT (CBCT) for BH imaging: BH-DTS scan can be completed during a single breath-hold, whereas BH-CBCT is usually acquired by parsing the gantry rotation into multiple BH segments. This study evaluates the localization accuracy of DTS for BH treatment of liver tumors. Methods: Both planning CT and on-board DTS/CBCT images were acquired under BH, using the planning CT BH window as reference. Onboard imaging data sets included two independent DTS orientations (coronal and sagittal), and CBCT images. Soft tissue target positioning was measured by each imaging modality and translated into couch shifts. Performance of the two DTS orientations was evaluated by comparing target positioning with the CBCT benchmark, determined by two observers. Results: Image data sets were collected from thirty-eight treatment fractions (14 patients). Mean differences between the two DTS methods and the CBCT method were <1 mm in all directions (except the lateral direction with sagittal-DTS: 1.2 mm); the standard deviation was in the range of 2.1–3.5 mm for all techniques. The Pearson correlation showed good interobserver agreement for the coronal-DTS (0.72–0.78). The interobserver agreement for the sagittal-DTS was good for the in-plane directions (0.70–0.82), but poor in the out-of-plane direction (lateral, 0.26). Conclusions: BH-DTS may be a simpler alternative to BH-CBCT for onboard soft tissue localization of the liver, although the precision of DTS localization appears to be somewhat lower because of the presence of subtle out-of-plane blur. [ABSTRACT FROM AUTHOR]

Purpose: To determine planning target volume margins for prostate intensity-modulated radiotherapy based on inter- and intrafraction motion using four daily localization techniques: three-point skin mark alignment, volumetric imaging with bony landmark registration, volumetric imaging with implanted fiducial marker registration, and implanted electromagnetic transponders (beacons) detection. Methods and Materials: Fourteen patients who underwent definitive intensity-modulated radiotherapy for prostate cancer formed the basis of this study. Each patient was implanted with three electromagnetic transponders and underwent a course of 39 treatment fractions. Daily localization was based on three-point skin mark alignment followed by transponder detection and patient repositioning. Transponder positioning was verified by volumetric imaging with cone-beam computed tomography of the pelvis. Relative motion between the prostate gland and bony anatomy was quantified by offline analyses of daily cone-beam computed tomography. Intratreatment organ motion was monitored continuously by the Calypso® System for quantification of intrafraction setup error. Results: As expected, setup error (that is, inter- plus intrafraction motion, unless otherwise stated) was largest with skin mark alignment, requiring margins of 7.5 mm, 11.4 mm, and 16.3 mm, in the lateral (LR), longitudinal (SI), and vertical (AP) directions, respectively. Margin requirements accounting for intrafraction motion were smallest for transponder detection localization techniques, requiring margins of 1.4 mm (LR), 2.6 mm (SI), and 2.3 mm (AP). Bony anatomy alignment required 2.1 mm (LR), 9.4 mm (SI), and 10.5 mm (AP), whereas image-guided marker alignment required 2.8 mm (LR), 3.7 mm (SI), and 3.2 mm (AP). No marker migration was observed in the cohort. Conclusion: Clinically feasible, rapid, and reliable tools such as the electromagnetic transponder detection system for pretreatment target localization and, subsequently, intratreatment target location monitoring allow clinicians to reduce irradiated volumes and facilitate safe dose escalation, where appropriate. [Copyright &y& Elsevier]

Purpose: Hypofractionated high-dose radiotherapy for small lung tumors has typically been based on stereotaxy. Cone-beam computed tomography and breath-hold techniques have provided a noninvasive basis for precise cranial and extracranial patient positioning. The cone-beam computed tomography acquisition time of 60 s, however, is beyond the breath-hold capacity of patients, resulting in respiratory motion artifacts. By combining megavoltage (MV) and kilovoltage (kV) photon sources (mounted perpendicularly on the linear accelerator) and accelerating the gantry rotation to the allowed limit, the data acquisition time could be reduced to 15 s. Methods and Materials: An Elekta Synergy 6-MV linear accelerator, with iViewGT as the MV- and XVI as the kV-imaging device, was used with a Catphan phantom and an anthropomorphic thorax phantom. Both image sources performed continuous image acquisition, passing an angle interval of 90° within 15 s. For reconstruction, filtered back projection on a graphics processor unit was used. It reconstructed 100 projections acquired to a 512 × 512 × 512 volume within 6 s. Results: The resolution in the Catphan phantom (CTP528 high-resolution module) was 3 lines/cm. The spatial accuracy was within 2–3 mm. The diameters of different tumor shapes in the thorax phantom were determined within an accuracy of 1.6 mm. The signal-to-noise ratio was 68% less than that with a 180°-kV scan. The dose generated to acquire the MV frames accumulated to 82.5 mGy, and the kV contribution was <6 mGy. Conclusion: The present results have shown that fast breath-hold, on-line volume imaging with a linear accelerator using simultaneous kV–MV cone-beam computed tomography is promising and can potentially be used for image-guided radiotherapy for lung cancer patients in the near future. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies have shown that lumpectomy cavity volumes can change significantly in the weeks following surgery. The effect of this volume change on the surrounding tissue that constitutes the clinical target volume (CTV) for accelerated partial breast irradiation and boost treatment after whole breast irradiation has not been previously studied. In the present study, we used deformable registration to estimate the effect of lumpectomy cavity volume changes on the CTV for accelerated partial breast irradiation and discuss the implications for target construction. Methods and Materials: The data from 13 accelerated partial breast irradiation patients were retrospectively analyzed. Deformable registration was used to propagate contours from the initial planning computed tomography scan to a later computed tomography scan acquired at the start of treatment. The changes in cavity volume and CTV, distance between cavity and CTV contours (i.e., CTV margin), and CTV localization error after cavity registration were determined. Results: The mean ± standard deviation change in cavity volume and CTV between the two computed tomography scans was −35% ± 23% and −14% ± 12%, respectively. An increase in the cavity-to-CTV margin of 2 ± 2 mm was required to encompass the CTV, and this increase correlated with the cavity volume change. Because changes in the cavity and CTV were not identical, a localization error of 2–3 mm in the CTV center of mass occurred when the cavity was used as the reference for image guidance. Conclusion: Deformable registration suggested that CTV margins do not remain constant as the cavity volume changes. This finding has implications for planning target volume and CTV construction. [ABSTRACT FROM AUTHOR]

Purpose: To report on the physical aspects of a system in which radiotherapy functionality was added to a micro-computed tomography (microCT) scanner, to evaluate the accuracy of this instrument, and to and demonstrate the application of this technology for irradiating tumors growing within the lungs of mice. Methods and Materials: A GE eXplore RS120 microCT scanner was modified by the addition of a two-dimensional subject translation stage and a variable aperture collimator. Quality assurance protocols for these devices, including measurement of translation stage positioning accuracy, collimator aperture accuracy, and collimator alignment with the X-ray beam, were devised. Use of this system for image-guided radiotherapy was assessed by irradiation of a solid water phantom as well as of two mice bearing spontaneous MYC-induced lung tumors. Radiation damage was assessed ex vivo by immunohistochemical detection of γH2AX foci. Results: The positioning error of the translation stage was found to be <0.05 mm, whereas after alignment of the collimator with the X-ray axis through adjustment of its displacement and rotation, the collimator aperture error was <0.1 mm measured at isocenter. Computed tomography image-guided treatment of a solid water phantom demonstrated target localization accuracy to within 0.1 mm. Gamma-H2AX foci were detected within irradiated lung tumors in mice, with contralateral lung tissue displaying background staining. Conclusions: Addition of radiotherapy functionality to a microCT scanner is an effective means of introducing image-guided radiation treatments into the preclinical setting. This approach has been shown to facilitate small-animal conformal radiotherapy while leveraging existing technology. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the toxicity and clinical outcomes for cervical cancer patients treated definitively with intensity-modulated radiation therapy (IMRT) compared with non-IMRT treatment. Methods and Materials: This prospective cohort study included 452 patients with newly diagnosed cervical cancer treated with curative intent (135 IMRT and 317 non-IMRT). Treatment involved external irradiation and brachytherapy, and 85% of patients received concurrent chemotherapy. All IMRT patients underwent an F-18 fluorodeoxyglucose positron emission tomography (FDG-PET/CT) simulation. A 3-month post-therapy PET was obtained to evaluate treatment response. Toxicity was scored by the Common Terminology Criteria for Adverse Events Version 3.0. Results: The IMRT and non-IMRT groups had similar stage distribution and histology. For all patients, the post-therapy FDG-PET response correlated with overall recurrence risk (p < 0.0001) and cause-specific survival (p < 0.0001). Post-treatment FDG-PET findings were not significantly different between the IMRT and non-IMRT patients (p = 0.9774). The mean follow-up for all patients alive at the time of last follow-up was 52 months (72 months non-IMRT, 22 months IMRT). At last follow-up, 178 patients (39 IMRT, 139 non-IMRT) had developed a recurrence. The difference in recurrence-free survival between the two groups did not reach statistical significance (p = 0.0738), although the IMRT group showed better overall and cause-specific survivals (p < 0.0001). Of the patients, 62 patients (8 IMRT and 54 non-IMRT) developed Grade 3 or greater bowel or bladder complications, and by cumulative hazard function analysis the risk was significantly less for patients treated with IMRT (p = 0.0351). Conclusion: Cervical cancer patients treated with FDG-PET/CT-guided IMRT have improved survival and less treatment-related toxicity compared with patients treated with non-IMRT radiotherapy. [Copyright &y& Elsevier]

Purpose: To prospectively compare setup error in standard thermoplastic masks and skin-sparing masks (SSMs) modified with low neck cutouts for head-and-neck intensity-modulated radiation therapy (IMRT) patients. Methods and Materials: Twenty head-and-neck IMRT patients were randomized to be treated in a standard mask (SM) or SSM. Cone-beam computed tomography (CBCT) scans, acquired daily after both initial setup and any repositioning, were used for initial and residual interfraction evaluation, respectively. Weekly, post-IMRT CBCT scans were acquired for intrafraction setup evaluation. The population random (σ) and systematic (Σ) errors were compared for SMs and SSMs. Skin toxicity was recorded weekly by use of Radiation Therapy Oncology Group criteria. Results: We evaluated 762 CBCT scans in 11 patients randomized to the SM and 9 to the SSM. Initial interfraction σ was 1.6 mm or less or 1.1° or less for SM and 2.0 mm or less and 0.8° for SSM. Initial interfraction Σ was 1.0 mm or less or 1.4° or less for SM and 1.1 mm or less or 0.9° or less for SSM. These errors were reduced before IMRT with CBCT image guidance with no significant differences in residual interfraction or intrafraction uncertainties between SMs and SSMs. Intrafraction σ and Σ were less than 1 mm and less than 1° for both masks. Less severe skin reactions were observed in the cutout regions of the SSM compared with non-cutout regions. Conclusions: Interfraction and intrafraction setup error is not significantly different for SSMs and conventional masks in head-and-neck radiation therapy. Mask cutouts should be considered for these patients in an effort to reduce skin toxicity. [Copyright &y& Elsevier]

Purpose: To characterize nonrandom intrafraction target motions for spine stereotactic body radiotherapy and to develop a method of correction via image guidance. The dependence of target motions, as well as the effectiveness of the correction strategy for lesions of different locations within the spine, was analyzed. Methods and Materials: Intrafraction target motions for 64 targets in 64 patients treated with a total of 233 fractions were analyzed. Based on the target location, the cases were divided into three groups, i.e., cervical (n = 20 patients), thoracic (n = 20 patients), or lumbar-sacrum (n = 24 patients) lesions. For each case, time-lag autocorrelation analysis was performed for each degree of freedom of motion that included both translations (x, y, and z shifts) and rotations (roll, yaw, and pitch). A general correction strategy based on periodic interventions was derived to determine the time interval required between two adjacent interventions, to overcome the patient-specific target motions. Results: Nonrandom target motions were detected for 100% of cases regardless of target locations. Cervical spine targets were found to possess the highest incidence of nonrandom target motion compared with thoracic and lumbar-sacral lesions (p < 0.001). The average time needed to maintain the target motion to within 1 mm of translation or 1° of rotational deviation was 5.5 min, 5.9 min, and 7.1 min for cervical, thoracic, and lumbar-sacrum locations, respectively (at 95% confidence level). Conclusions: A high incidence of nonrandom intrafraction target motions was found for spine stereotactic body radiotherapy treatments. Periodic interventions at approximately every 5 minutes or less were needed to overcome such motions. [Copyright &y& Elsevier]

Purpose: To compare the dose distribution between customized planning (CP) and adopting a single plan (SP) in multifractionated high-dose-rate brachytherapy and to establish predictors for the necessity of CP in a given patient. Methods and Materials: A total of 50 computed tomography-based plans for 10 patients were evaluated. Each patient had received 6 Gy for five fractions. The clinical target volume and organs at risk (i.e., rectum, bladder, sigmoid, and small bowel) were delineated on each computed tomography scan. For the SP approach, the same dwell position and time was used for all fractions. For the CP approach, the dwell position and time were reoptimized for each fraction. Applicator position variation was determined by measuring the distance between the posterior bladder wall and the tandem at the level of the vaginal fornices. Results: The organs at risk D2cc (dose to 2 cc volume) was increased with the SP approach. The dose variation was statistically similar between the tandem and ring and tandem and ovoid groups. The bladder D2cc dose was 81.95–105.42 Gy2 for CP and 82.11–122.49 Gy2 for SP. In 5 of the 10 patients, the bladder would have been significantly overdosed with the SP approach. The variation of the posterior bladder wall distance from that in the first fraction was correlated with the increase in the bladder D2cc (SP/CP), with a correlation coefficient of −0.59. Conclusion: Our results support the use of CP instead of the SP approach to help avoid a significant overdose to the bladder. This is especially true for a decrease in the posterior wall distance of ≥0.5 cm compared with that in the first fraction. [Copyright &y& Elsevier]

Purpose: To design and evaluate a magnetic resonance imaging (MRI) protocol to be incorporated in the simulation process for external beam accelerated partial breast irradiation. Methods and Materials: An imaging protocol was developed based on an existing breast MRI technique with the patient in the prone position on a dedicated coil. Pulse sequences were customized to exploit T1 and T2 contrast mechanisms characteristic of lumpectomy cavities. A three-dimensional image warping algorithm was included to correct for geometric distortions related to nonlinearity of spatially encoding gradients. Respiratory motion, image distortions, and susceptibility artifacts of 3.5-mm titanium surgical clips were examined. Magnetic resonance images of volunteers were acquired repeatedly to analyze residual setup deviations resulting from breast tissue deformation. Results: The customized sequences generated high-resolution magnetic resonance images emphasizing lumpectomy cavity morphology. Respiratory motion was negligible with the subject in the prone position. The gradient-induced nonlinearity was reduced to less than 1 mm in a region 15 cm away from the isocenter of the magnet. Signal-void regions of surgical clips were 4 mm and 8 mm for spin echo and gradient echo images, respectively. Typical residual repositioning errors resulting from breast deformation were estimated to be 3 mm or less. Conclusions: MRI guidance for accelerated partial breast irradiation with the patient in the prone position with adequate contrast, spatial fidelity, and resolution is possible. [Copyright &y& Elsevier]

Purpose: To determine the feasibility and benefits of optimized magnetic resonance imaging (MRI)-guided brachytherapy (BT) for cancer of the cervix. Methods and Materials: A total of 20 patients with International Federation of Gynecology and Obstetrics Stage IB-IV cervical cancer had an MRI-compatible intrauterine BT applicator inserted after external beam radiotherapy. MRI scans were acquired, and the gross tumor volume at diagnosis and at BT, the high-risk (HR) and intermediate-risk clinical target volume (CTV), and rectal, sigmoid, and bladder walls were delineated. Pulsed-dose-rate BT was planned and delivered in a conventional manner. Optimized MRI-based plans were developed and compared with the conventional plans. Results: The HR CTV and intermediate-risk CTV were adequately treated (the percentage of volume treated to ≥100% of the intended dose was >95%) in 70% and 85% of the patients with the conventional plans, respectively, and in 75% and 95% of the patients with the optimized plans, respectively. The minimal dose to the contiguous 2 cm3 of the rectal, sigmoid, and bladder wall volume was 16 ± 6.2, 25 ± 8.7, and 31 ± 9.2 Gy, respectively. With MRI-guided BT optimization, it was possible to maintain coverage of the HR-CTV and reduce the dose to the normal tissues, especially in patients with small tumors at BT. In these patients, the HR percentage of volume treated to ≥100% of the intended dose approached 100% in all cases, and the minimal dose to the contiguous 2-cm3 of the rectum, sigmoid, and bladder was 12–32% less than with conventional BT planning. Conclusion: MRI-based BT for cervical cancer has the potential to optimize primary tumor dosimetry and reduce the dose to critical normal tissues, particularly in patients with small tumors. [Copyright &y& Elsevier]

Purpose: Image-guided intensity-modulated radiotherapy can improve protection of organs at risk when large abdominal target volumes are irradiated. We estimated the daily positioning accuracy of ultrasound-based image guidance for abdominal target volumes by a direct comparison of daily imaging obtained with cone beam computed tomography (CBCT). Methods and Materials: Daily positioning (n = 83 positionings) of 15 patients was completed by using ultrasound guidance after an initial CBCT was obtained. Residual error after ultrasound was estimated by comparison with a second CBCT. Ultrasound image quality was visually rated using a scale of 1 to 4. Results: Of 15 patients, 7 patients had good sonographic imaging quality, 5 patients had satisfactory sonographic quality, and 3 patients were excluded because of unsatisfactory sonographic quality. When image quality was good, residual errors after ultrasound were −0.1 ± 3.11 mm in the x direction (left-right; group systematic error M = −0.09 mm; standard deviation [SD] of systematic error, Σ = 1.37 mm; SD of the random error, σ = 2.99 mm), 0.93 ± 4.31 mm in the y direction (superior-inferior, M = 1.12 mm; Σ = 2.96 mm; σ = 3.39 mm), and 0.71 ± 3.15 mm in the z direction (anteroposterior; M = 1.01 mm; Σ = 2.46 mm; σ = 2.24 mm). For patients with satisfactory image quality, residual error after ultrasound was −0.6 ± 5.26 mm in the x (M = 0.07 mm; Σ = 5.67 mm; σ = 4.86 mm), 1.76 ± 4.92 mm in the y (M = 3.54 mm; Σ = 4.1 mm; σ = 5.29 mm), and 1.19 ± 4.75 mm in the z (M = 0.82 mm; Σ = 2.86 mm; σ = 3.05 mm) directions. Conclusions: In patients from whom good sonographic image quality could be obtained, ultrasound improved daily positioning accuracy. In the case of satisfactory image quality, ultrasound guidance improved accuracy compared to that of skin marks only minimally. If sonographic image quality was unsatisfactory, daily CBCT scanning improved treatment accuracy distinctly over that of ultrasound. Use of daily ultrasound or CBCT imaging can help to reduce PTV margins and protect organs at risk compared to the use of skin mark-based positioning. [Copyright &y& Elsevier]

Purpose: To evaluate the accuracy of direct reconstruction of mid-ventilation and peak-phase four-dimensional (4D) computed tomography (CT) frames based on the external breathing signal. Methods and Materials: For 11 patients with 15 pulmonary targets, a respiration-correlated CT study (4D CT) was acquired for treatment planning. After retrospective time-based sorting of raw projection data and reconstruction of eight CT frames equally distributed over the breathing cycle, mean tumor position (Pmean), mid-ventilation frame, and breathing motion were evaluated based on the internal tumor trajectory. Analysis of the external breathing signal (pressure sensor around abdomen) with amplitude-based sorting of projections was performed for direct reconstruction of the mid-ventilation frame and frames at peak phases of the breathing cycle. Results: On the basis of the eight 4D CT frames equally spaced in time, tumor motion was largest in the craniocaudal direction, with 12 ± 7 mm on average. Tumor motion between the two frames reconstructed at peak phases was not different in the craniocaudal and anterior–posterior directions but was systematically smaller in the left–right direction by 1 mm on average. The 3-dimensional distance between Pmean and the tumor position in the mid-ventilation frame based on the internal tumor trajectory was 1.2 ± 1 mm. Reconstruction of the mid-ventilation frame at the mean amplitude position of the external breathing signal resulted in tumor positions 2.0 ± 1.1 mm distant from Pmean. Breathing-induced motion artifacts in mid-ventilation frames caused negligible changes in tumor volume and shape. Conclusions: Direct reconstruction of the mid-ventilation frame and frames at peak phases based on the external breathing signal was reliable. This makes the reconstruction of only three 4D CT frames sufficient for application of the mid-ventilation technique in clinical practice. [Copyright &y& Elsevier]

There is increasing interest in how to incorporate functional and molecular information obtained by noninvasive, three-dimensional tumor imaging into radiotherapy. The key issues are to identify radioresistant regions that can be targeted for dose escalation, and to develop radiation dose prescription and delivery strategies providing optimal treatment for the individual patient. In the present work, we review the proposed strategies for biologic image-guided dose escalation with intensity-modulated radiation therapy. Biologic imaging modalities and the derived images are discussed, as are methods for target volume delineation. Different dose escalation strategies and techniques for treatment delivery and treatment plan evaluation are also addressed. Furthermore, we consider the need for response monitoring during treatment. We conclude with a summary of the current status of biologic image-based dose escalation and of areas where further work is needed for this strategy to become incorporated into clinical practice. [Copyright &y& Elsevier]

Purpose: This prospective study investigates gynecologic malignancy online treatment setup error corrections using planar kilovoltage/megavoltage (KV/MV) imaging and helical MV computed tomography (MVCT) imaging. Methods and Materials: Twenty patients were divided into two groups. The first group (10 patients) was imaged and treated using a conventional linear accelerator (LINAC) with image-guidance capabilities, whereas the second group (10 patients) was treated using tomotherapy with MVCT capabilities. Patients treated on the LINAC underwent planar KV and portal MV imaging and a two-dimensional image registration algorithm was used to match these images to digitally reconstructed radiographs (DRRs). Patients that were treated using tomotherapy underwent MVCT imaging, and a three-dimensional image registration algorithm was used to match planning CT to MVCT images. Subsequent repositioning shifts were applied before each treatment and recorded for further analysis. To assess intrafraction motion, 5 of the 10 patients treated on the LINAC underwent posttreatment planar imaging and DRR matching. Based on these data, patient position uncertainties along with estimated margins based on well-known recipes were determined. Results: The errors associated with patient positioning ranged from 0.13 cm to 0.38 cm, for patients imaged on LINAC and 0.13 cm to 0.48 cm for patients imaged on tomotherapy. Our institutional clinical target volume-PTV margin value of 0.7 cm lies inside the confidence interval of the margins established using both planar and MVCT imaging. Conclusion: Use of high-quality daily planar imaging, volumetric MVCT imaging, and setup corrections yields excellent setup accuracy and can help reduce margins for the external beam treatment of gynecologic malignancies. [Copyright &y& Elsevier]

Purpose: To determine the target coverage for proton therapy with and without image guidance and daily prebeam reorientation. Methods and Materials: A total of 207 prostate positions were analyzed for 9 prostate cancer patients treated using our low-risk prostate proton therapy protocol (University of Florida Proton Therapy Institute 001). The planning target volume was defined as the prostate plus a 5-mm axial and 8-mm superoinferior extension. The prostate was repositioned using 5- and 10-mm shifts (anteriorly, inferiorly, posteriorly, and superiorly) and for Points A–D using a combination of 10-mm multidimensional movements (anteriorly or inferiorly; posteriorly or superiorly; and left or right). The beams were then realigned using the new prostate position. The prescription dose was 78 Gray equivalent (GE) to 95% of the planning target volume. Results: For small movements in the anterior, inferior, and posterior directions within the planning target volume (≤5 mm), treatment realignment demonstrated small, but significant, improvements in the clinical target volume (CTV) coverage to the prescribed dose (78 GE). The anterior and posterior shifts also significantly increased the minimal CTV dose (Δ +1.59 GE). For prostate 10-mm movements in the inferior, posterior, and superior directions, the beam realignment produced larger and significant improvements for both the CTV V78 (Δ +6.4%) and the CTV minimal dose (Δ +8.22 GE). For the compounded 10-mm multidimensional shifts, realignment significantly improved the CTV V78 (Δ +11.8%) and CTV minimal dose (Δ +23.6 GE). After realignment, the CTV minimal dose was >76.6 GE (>98%) for all points (A–D). Conclusion: Proton beam realignment after target shift will enhance CTV coverage for different prostate positions. [Copyright &y& Elsevier]

Purpose: To quantify the dosimetric and radiobiological changes seen when using intensity-modulated radiation therapy (IMRT) or planning target volume (PTV) margin reduction with consistent planning parameters in a representative sample of localized prostate cancer patients. Methods and Materials: Twenty patients were randomly selected from a cohort that received 79.8 Gy using six-field conformal radiotherapy. Using the clinical contours, PTV margin, planning system, and dose constraints, five-field IMRT plans were generated for 79.8, 83.8, and 88.0 Gy. The 88.0-Gy IMRT plan was then reoptimized with a PTV margin reduced to 3 mm. These plans were then compared using various dosimetric and radiobiological endpoints calculated for various α/β. Results: Intensity-modulated RT resulted in greater conformity to the PTV (p < 0.001). No improvement in mean normal tissue complication probabilities in the rectal wall (NTCPrw) was seen, and the modified therapeutic ratio (TRmod) was largely unchanged between six-field conformal and IMRT for the majority of the patients. When IMRT was used to escalate dose, NTCPrw increased by 9% at each 5% prescription increase (p < 0.001). Reducing the posterior PTV margin from 7 mm to 3 mm for an IMRT plan reduced the mean NTCPrw by 12% (p < 0.001) and resulted in a trend toward increased TRmod(p = 0.005). Changes in TRmod between conformal and IMRT planning or PTV reduction showed large interpatient variability. Conclusions: Changing from conformal to IMRT, or from PTV10–7 to PTV3, did not produce a uniform interpatient increase in TRmodwhen the CTV contained the prostate alone. Radiobiological benefits of these two methods seem to be dependent on the particular anatomy of individual patients, supporting the use of patient-specific margin, planning, and dose prescription strategies. [Copyright &y& Elsevier]

Purpose: Newly emerged four-dimensional (4D) imaging techniques such as 4D-computed tomography (CT), 4D-cone beam CT, 4D-magnetic resonance imaging, and 4D-positron emission tomography are effective tools to reveal the spatiotemporal details of patients'' anatomy. To use the 4D data acquired under different conditions or using different modalities, an algorithm for registering 4D images must be in place. We developed an automated 4D-4D registration method to take advantage of 4D information. Methods and Materials: We used 4D-4D matching to find the appropriate three-dimensional anatomy in the fixed image for each phase of the moving image and spatially register them. A search algorithm was implemented to simultaneously find the best phase and spatial match of two 4D inputs. An interpolation scheme capable of deriving an image set based on temporally adjacent three-dimensional data sets was developed to deal with the situation in which the discrete temporal points of the two inputs do not coincide or correspond. Results: In a phantom study, our technique was able to reproduce the known “ground truth” with high spatial fidelity. The technique regenerated all deliberately introduced “missing” three-dimensional images at different phases of the input using temporal interpolation. In the registration of gated-magnetic resonance imaging and 4D-CT, the algorithm was able to select the appropriate CT phase. The technique was also able to register 4D-CT with 4D-cone beam CT and two 4D-CT scans acquired at different times. A spatial accuracy of <3 mm was achieved in 98% of voxels in all cases. Conclusion: Automated 4D-4D registration can find the best possible spatiotemporal match between two 4D data sets and is useful for image-guided radiotherapy applications. [Copyright &y& Elsevier]

Purpose: To assess the accuracy of ultrasound-based repositioning (BAT) before prostate radiation with fiducial-based three-dimensional matching with cone-beam computed tomography (CBCT). Patients and Methods: Fifty-four positionings in 8 patients with 125I seeds/intraprostatic calcifications as fiducials were evaluated. Patients were initially positioned according to skin marks and after this according to bony structures based on CBCT. Prostate position correction was then performed with BAT. Residual error after repositioning based on skin marks, bony anatomy, and BAT was estimated by a second CBCT based on user-independent automatic fiducial registration. Results: Overall mean value (MV ± SD) residual error after BAT based on fiducial registration by CBCT was 0.7 ± 1.7 mm in x (group systematic error [M] = 0.5 mm; SD of systematic error [Σ] = 0.8 mm; SD of random error [σ] = 1.4 mm), 0.9 ± 3.3 mm in y (M = 0.5 mm, Σ = 2.2 mm, σ = 2.8 mm), and −1.7 ± 3.4 mm in z (M = −1.7 mm, Σ = 2.3 mm, σ = 3.0 mm) directions, whereas residual error relative to positioning based on skin marks was 2.1 ± 4.6 mm in x (M = 2.6 mm, Σ = 3.3 mm, σ = 3.9 mm), −4.8 ± 8.5 mm in y (M = −4.4 mm, Σ = 3.7 mm, σ = 6.7 mm), and −5.2 ± 3.6 mm in z (M = −4.8 mm, Σ = 1.7 mm, σ = 3.5mm) directions and relative to positioning based on bony anatomy was 0 ± 1.8 mm in x (M = 0.2 mm, Σ = 0.9 mm, σ = 1.1 mm), −3.5 ± 6.8 mm in y (M = −3.0 mm, Σ = 1.8 mm, σ = 3.7 mm), and −1.9 ± 5.2 mm in z (M = −2.0 mm, Σ = 1.3 mm, σ = 4.0 mm) directions. Conclusions: BAT improved the daily repositioning accuracy over skin marks or even bony anatomy. The results obtained with BAT are within the precision of extracranial stereotactic procedures and represent values that can be achieved with several users with different education levels. If sonographic visibility is insufficient, CBCT or kV/MV portal imaging with implanted fiducials are recommended. [Copyright &y& Elsevier]

Purpose: External beam accelerated partial breast irradiation requires accurate localization of the target volume for each treatment fraction. Using the concept of target registration error (TRE), the performance of several methods of target localization was compared. Methods and Materials: Twelve patients who underwent external beam accelerated partial breast irradiation were included in this study. TRE was quantified for four methods of image guidance: standard laser-based setup, kilovoltage imaging of the chest wall, kilovoltage imaging of surgically implanted clips, and three-dimensional surface imaging of the breast. The use of a reference surface created from a free-breathing computed tomography scan and a reference surface directly captured with three-dimensional video imaging were compared. The effects of respiratory motion were also considered, and gating was used for 8 of 12 patients. Results: The median value of the TRE for the laser, chest wall, and clip alignment was 7.1 mm (n = 94), 5.4 mm (n = 81), and 2.4 mm (n = 93), respectively. The median TRE for gated surface imaging based on the first fraction reference surface was 3.2 mm (n = 49), and the TRE for gated surface imaging using the computed tomography-based reference surface was 4.9 mm (n = 56). The TRE for nongated surface imaging using the first fraction reference surface was 6.2 mm (n = 25). Conclusions: The TRE of surface imaging using a reference surface directly captured with three-dimensional video and the TRE for clip-based setup were within 1 mm. Gated capture is important for surface imaging to reduce the effects of respiratory motion in accelerated partial breast irradiation. [Copyright &y& Elsevier]

Purpose: To compare different image-guidance strategies in the alignment of prostate cancer patients. Using data from patients treated using daily image guidance, the remaining setup errors for several different strategies were retrospectively calculated. Methods and Materials: The alignment data from 74 patients treated with helical tomotherapy were analyzed, resulting in a data set of 2,252 fractions during which a megavoltage computed tomography image was used for image guidance with intraprostatic metallic fiducials. Given the daily positional adjustments, a variety of protocols, differing in imaging frequency and method, were retrospectively studied. The residual setup errors were determined for each protocol. Results: As expected, the systematic errors were effectively reduced with imaging. However, the random errors were unaffected. Even when image guidance was performed every other day with a running mean of the previous displacements, residual setup errors >5 mm occurred in 24% of all fractions. This frequency increased to about 40% if setup errors >3 mm were scored. Conclusion: Setup errors increased with decreasing frequency of image guidance. However, residual errors were still significant at the 5-mm level, even with imaging was performed every other day. This suggests that localizations must be performed daily in the set up of prostate cancer patients during a course of external beam radiotherapy. [Copyright &y& Elsevier]

Purpose: The aim of this study is to implement augmented reality in real-time image-guided interstitial brachytherapy to allow an intuitive real-time intraoperative orientation. Methods and Materials: The developed system consists of a common video projector, two high-resolution charge coupled device cameras, and an off-the-shelf notebook. The projector was used as a scanning device by projecting coded-light patterns to register the patient and superimpose the operating field with planning data and additional information in arbitrary colors. Subsequent movements of the nonfixed patient were detected by means of stereoscopically tracking passive markers attached to the patient. Results: In a first clinical study, we evaluated the whole process chain from image acquisition to data projection and determined overall accuracy with 10 patients undergoing implantation. The described method enabled the surgeon to visualize planning data on top of any preoperatively segmented and triangulated surface (skin) with direct line of sight during the operation. Furthermore, the tracking system allowed dynamic adjustment of the data to the patient''s current position and therefore eliminated the need for rigid fixation. Because of soft-part displacement, we obtained an average deviation of 1.1 mm by moving the patient, whereas changing the projector''s position resulted in an average deviation of 0.9 mm. Mean deviation of all needles of an implant was 1.4 mm (range, 0.3–2.7 mm). Conclusions: The developed low-cost augmented-reality system proved to be accurate and feasible in interstitial brachytherapy. The system meets clinical demands and enables intuitive real-time intraoperative orientation and monitoring of needle implantation. [Copyright &y& Elsevier]

Purpose: To compare localization of the lumpectomy cavity by using breast surface matching vs. clips for image-guided external beam accelerated partial breast irradiation. Methods and Materials: Twenty-seven patients with breast cancer with two computed tomography (CT) scans each had three CT registrations performed: (1) to bony anatomy, (2) to the center of mass (COM) of surgical clips, and (3) to the breast surface. The cavity COM was defined in both the initial and second CT scans after each type of registration, and distances between COMs (ΔCOMBone, ΔCOMClips, and ΔCOMSurface) were determined. Smaller ΔCOMs were interpreted as better localizations. Correlation coefficients were calculated for ΔCOM vs. several variables. Results: The ΔCOMBone (mean, 7 ± 2 [SD] mm) increased with breast volume (r = 0.4; p = 0.02) and distance from the chest wall (r = 0.5; p = 0.003). Relative to bony registration, clip registration provided better localization (ΔCOMClips < ΔCOMBone) in 25 of 27 cases. Breast surface matching improved cavity localization (ΔCOMSurface < ΔCOMBone) in 19 of 27 cases. Mean improvements (ΔCOMBone − ΔCOMClips or Surface) were 4 ± 3 and 2 ± 4 mm, respectively. In terms of percentage of improvement ([ΔCOMBone − ΔCOMClips or Surface]/ΔCOMBone), only surface matching showed a correlation with breast volume. Clip localization outperformed surface registration for cavities located superior to the breast COM. Conclusions: Use of either breast surface or surgical clips as surrogates for the cavity results in improved localization in most patients compared with bony registration and may allow smaller planning target volume margins for external beam accelerated partial breast irradiation. Compared with surface registration, clip registration may be less sensitive to anatomic characteristics and therefore more broadly applicable. [Copyright &y& Elsevier]

Purpose: There are no accepted guidelines for target volume definition for online image-guided radiation therapy (IGRT) after radical prostatectomy (RP). This study used cone beam CT (CBCT) imaging to generate information for use in post-RP IGRT. Methods and Materials: The pelvic anatomy of 10 prostate cancer patients undergoing post-RP radiation therapy (RT) to 68.4 Gy was studied using CBCT images obtained immediately before treatment. Contoured bladder and rectal volumes on CBCT images were compared with planning CT (CTref) volumes from seminal vesicle stump (SVS) to bladder–urethral junction. This region was chosen to approximate the prostatic fossa (PF) during a course of post-RP RT. Anterior and posterior planning target volume margins were calculated using ICRU report 71 guidelines, accounting for systematic and random error based on bladder and rectal motion, respectively. Results: A total of 176 CBCT study sets obtained 2 to 5 times weekly were analyzed. The rectal and bladder borders were reliably identified in 166 of 176 (94%) of CBCT images. Relative to CTref, mean posterior bladder wall position was anterior by 0.1 to 1.5 mm, and mean anterior rectum wall position was posterior by 1.6 to 2.7 mm. Calculated anterior margin as derived from bladder motion ranged from 5.9 to 7.1 mm. Calculated posterior margin as derived from rectal motion ranged from 8.6 to 10.2 mm. Conclusions: Normal tissue anatomy was definable by CBCT imaging throughout the course of post-RP RT, and the interfraction anteroposterior motion of the bladder and rectum was studied. This information should be considered in devising post-RP RT techniques using image guidance. [Copyright &y& Elsevier]

Purpose: To compare two “four-dimensional” methods for image-guided target localization in the presence of respiration. Methods and Materials: Four-dimensional image guidance was performed with two methods. A respiration-correlated computed tomography (RCCT) was acquired on a CT simulator, and an average CT (AVG-CT) image was generated from the RCCT. A respiration-correlated cone-beam CT (RC-CBCT) and a free-breathing cone-beam CT (FB-CBCT) were acquired. The “RCCT method” consisted of calculating the mean target position on both the RCCT and RC-CBCT, registering the RCCT to the RC-CBCT, and determining the shift in the mean target position from the planned mean position. The “AVG-CT method” consisted of registering the AVG-CT to the FB-CBCT. The ability of each to measure the shift in the mean target position was compared, both in a respiratory phantom and in 8 patients. Results: In phantom, the RCCT and AVG-CT methods were able to measure the true mean target position to within 0.15 cm and 0.10 cm, respectively. In the patient study, the mean error between the methods was 0.13 cm (left–right), 0.14 cm (anterior–posterior), and 0.10 cm (cranio–caudal). The error was not observed to vary with tumor position or magnitude of tumor motion. Conclusions: Respiration may impact the on-line image guidance process. The RCCT method enables localization of the mean tumor position and measurement of changes in the motion pattern, whereas the AVG-CT method is simple, fast, and easily implemented. We found the methods to be nearly equivalent in detecting shifts in the mean tumor position. [Copyright &y& Elsevier]

Purpose: To present an on-line image guidance procedure for external beam accelerated partial breast irradiation based on cone-beam computed tomography (CBCT) imaging of surgical clips; and to estimate the possible clinical target volume (CTV) to planning target volume (PTV) margin reduction allowed by this technique. Methods and Materials: Clips in the CBCT image are detected automatically using in-house software. The treatment couch is translated according to the shift in the clips' center of mass between the planning and CBCT images. Three components for the PTV margin are considered: (1) breathing, (2) surrogate error (i.e., error in cavity position after perfect setup to clips), and (3) residual error (i.e., error arising from the inability to execute a perfect setup to clips due to technological limitations, such as couch travel precision). These factors were input into a standard formula for CTV-to-PTV margin calculation. Results: The average magnitude of clip-based corrections was 7 +/- 2 mm (10 patients, 44 fractions). After localization, the residual error magnitude was 1.6 +/- 1.3 mm, justifying an isotropic CTV-to-PTV margin of approximately 6 mm, including breathing and surrogate error. Conclusions: On-line localization of the lumpectomy cavity using surgical clips is technically feasible from the standpoint of equipment, time, and process, making possible a decreased CTV-to-PTV margin for accelerated partial breast irradiation. Because the procedure is exclusively target based, additional monitoring of critical structures may be advisable. [ABSTRACT FROM AUTHOR]

Purpose: To assess in a prospective trial the feasibility and late toxicity of hypofractionated radiotherapy (RT) for prostate cancer. Methods and Materials: Eligible patients had clinical stage T1c–2cNXM0 disease. They received 60 Gy in 20 fractions over 4 weeks with intensity-modulated radiotherapy including daily on-line image guidance with intraprostatic fiducial markers. Results: Between June 2001 and March 2004, 92 patients were treated with hypofractionated RT. The cohort had a median prostate-specific antigen value of 7.06 ng/mL. The majority had Gleason grade 5–6 (38%) or 7 (59%) disease, and 82 patients had T1c–T2a clinical staging. Overall, 29 patients had low-risk, 56 intermediate-risk, and 7 high-risk disease. Severe acute toxicity (Grade 3–4) was rare, occurring in only 1 patient. Median follow-up was 38 months. According to the Phoenix definition for biochemical failure, the rate of biochemical control at 14 months was 97%. According to the previous American Society for Therapeutic Radiology and Oncology definition, biochemical control at 3 years was 76%. The incidence of late toxicity was low, with no severe (Grade ≥3) toxicity at the most recent assessment. Conclusions: Hypofractionated RT using 60 Gy in 20 fractions over 4 weeks with image guidance is feasible and is associated with low rates of late bladder and rectal toxicity. At early follow-up, biochemical outcome is comparable to that reported for conventionally fractionated controls. The findings are being tested in an ongoing, multicenter, Phase III trial. [Copyright &y& Elsevier]

Purpose: To report and describe implantation techniques and stability of metallic fiducials in lung lesions to be treated with external beam radiotherapy. Methods and Materials: Patients undergoing radiation therapy for small early-stage lung cancer underwent implantation with small metallic markers. Implantation was either transcutaneous under computed tomographic (CT) or fluoroscopic guidance or transbronchial with the superDimension/Bronchus system (radiofrequency signal–based bronchoscopy guidance related to CT images). Results: Implantation was performed transcutaneously in 15 patients and transbronchially in 8 patients. Pneumothorax occurred with eight of the 15 transcutaneous implants, six of which required chest tube placement. None of the patients who underwent transbronchial implantation developed pneumothorax. Successfully inserted markers were all usable during gated image–guided radiotherapy. Marker stability was determined by observing the variation in gross target volume (GTV) centroid relative to the marker on repeated CT scans. Average three-dimensional variation in the GTV center relative to the marker was 2.6 ± 1.3 (SD) mm, and the largest variation along any anatomic axis for any patient was <5 mm. Average GTV volume decrease during the observation period was 34% ± 23%. Gross tumor volumes do not appear to shrink uniformly about the center of the tumor, but rather the tumor shapes deform substantially throughout treatment. Conclusions: Transbronchial marker placement is less invasive than transcutaneous placement, which is associated with high pneumothorax rates. Although marker geometry can be affected by tumor shrinkage, implanted markers are stable within tumors throughout the treatment duration regardless of implantation method. [Copyright &y& Elsevier]

Purpose: To evaluate the role of cone-beam CT (CBCT) guidance for setup error reduction and soft tissue visualization in accelerated partial breast irradiation (APBI). Methods and Materials: Twenty patients were recruited for the delivery of radiotherapy to the postoperative cavity (3850 cGy in 10 fractions over 5 days) using an APBI technique. Cone-beam CT data sets were acquired after an initial skin-mark setup and before treatment delivery. These were registered online using the ipsilateral lung and external contours. Corrections were executed for translations exceeding 3 mm. The random and systematic errors associated with setup using skin-marks and setup using CBCT guidance were calculated and compared. Results: A total of 315 CBCT data sets were analyzed. The systematic errors for the skin-mark setup were 2.7, 1.7, and 2.4 mm in the right-left, anterior-posterior, and superior-inferior directions, respectively. These were reduced to 0.8, 0.7, and 0.8 mm when CBCT guidance was used. The random errors were reduced from 2.4, 2.2, and 2.9 mm for skin-marks to 1.5, 1.5, and 1.6 mm for CBCT guidance in the right-left, anterior-posterior, and superior-inferior directions, respectively. Conclusion: A skin-mark setup for APBI patients is sufficient for current planning target volume margins for the population of patients studied here. Online CBCT guidance minimizes the occurrence of large random deviations, which may have a greater impact for the accelerated fractionation schedule used in APBI. It is also likely to permit a reduction in planning target volume margins and provide skin-line visualization and dosimetric evaluation of cardiac and lung volumes. [ABSTRACT FROM AUTHOR]

Purpose: Cone-beam computed tomography (CBCT) in-room imaging allows accurate inter- and intrafraction target localization in stereotactic body radiotherapy of lung tumors. Methods and Materials: Image-guided stereotactic body radiotherapy was performed in 28 patients (89 fractions) with medically inoperable Stage T1-T2 non-small-cell lung carcinoma. The targets from the CBCT and planning data set (helical or four-dimensional CT) were matched on-line to determine the couch shift required for target localization. Matching based on the bony anatomy was also performed retrospectively. Verification of target localization was done using either megavoltage portal imaging or CBCT imaging; repeat CBCT imaging was used to assess the intrafraction tumor position. Results: The mean three-dimensional tumor motion for patients with upper lesions (n = 21) and mid-lobe or lower lobe lesions (n = 7) was 4.2 and 6.7 mm, respectively. The mean difference between the target and bony anatomy matching using CBCT was 6.8 mm (SD, 4.9, maximum, 30.3); the difference exceeded 13.9 mm in 10% of the treatment fractions. The mean residual error after target localization using CBCT imaging was 1.9 mm (SD, 1.1, maximum, 4.4). The mean intrafraction tumor deviation was significantly greater (5.3 mm vs. 2.2 mm) when the interval between localization and repeat CBCT imaging (n = 8) exceeded 34 min. Conclusion: In-room volumetric imaging, such as CBCT, is essential for target localization accuracy in lung stereotactic body radiotherapy. Imaging that relies on bony anatomy as a surrogate of the target may provide erroneous results in both localization and verification. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to assess the residual setup error of different image-guidance (IG) protocols in the alignment of patients with head and neck cancer. The protocols differ in the percentage of treatment fractions that are associated with image guidance. Using data from patients who were treated with daily IG, the residual setup errors for several different protocols are retrospectively calculated. Methods and Materials: Alignment data from 24 patients (802 fractions) treated with daily IG on a helical tomotherapy unit were analyzed. The difference between the daily setup correction and the setup correction that would have been made according to a specific protocol was used to calculate the residual setup errors for each protocol. Results: The different protocols are generally effective in reducing systematic setup errors. Random setup errors are generally not reduced for fractions that are not image guided. As a consequence, if every other treatment is image guided, still about 11% of all treatments (IG and not IG) are subject to three-dimensional setup errors of at least 5 mm. This frequency increases to about 29% if setup errors >3 mm are scored. For various protocols that require 15% to 31% of the treatments to be image guided, from 50% to 60% and from 26% to 31% of all fractions are subject to setup errors >3 mm and >5 mm, respectively. Conclusion: Residual setup errors reduce with increasing frequency of IG during the course of external-beam radiotherapy for head-and-neck cancer patients. The inability to reduce random setup errors for fractions that are not image guided results in notable residual setup errors. [Copyright &y& Elsevier]

Purpose: The aim of this study was to compare the dosimetric consequences of 4 treatment delivery techniques for prostate cancer patients treated with intensity-modulated radiotherapy (IMRT). Methods and Materials: During an 8-week course of radiotherapy, 10 patients underwent computed tomography (CT) scans 3 times per week (243 total) before daily treatment with a CT-linear accelerator. Treatment delivery was simulated by realigning a fixed-margin treatment plan on each CT scan and calculating doses. The alignment methods were those based on the following: skin marks, bony registration, ultrasonography (US), and in-room CT. For the last two methods, prostate was the alignment target. The dosimetric effects of these alignment methods on the prostate, seminal vesicles, rectum, and bladder were compared. The average daily minimum dose to 0.1 cm3 was used as the metric for target coverage. Results: Skin and bone alignments provided acceptable prostate coverage for only 70% of patients, US alignment for 90%, and CT alignment for 100%. CT-based alignment of the prostate provided seminal vesicle (SV) coverage of > or = 69 Gy for all patients; US and bone alignments provided SV coverage of > or = 60 Gy. This SV coverage may be acceptable for early-stage cancer (equivalent SV dose = 55.8 Gy at 1.8 Gy per fraction), but unacceptable for late-stage cancer (SV dose = 75.6 Gy). At 75.6 Gy, the acceptable rate for SV coverage was 40% for skin and bone alignments, 70% for US, and 80% for CT. Conclusions: Direct target alignment methods (US and CT) provided better target coverage. CT-guided alignment provided the best and most consistent dosimetric coverage. A larger planning target volume margin is needed for SV coverage when the alignment target is the prostate. [ABSTRACT FROM AUTHOR]

Purpose: A six-fraction, high-precision radiotherapy protocol for unresectable liver cancer has been developed in which active breathing control (ABC) is used to immobilize the liver and daily megavoltage (MV) imaging and repositioning is used to decrease geometric uncertainties. We report the accuracy of setup in the first 20 patients consecutively treated using this approach. Methods and Materials: After setup using conventional skin marks and lasers, orthogonal MV images were acquired with the liver immobilized using ABC. The images were aligned to reference digitally reconstructed radiographs using the diaphragm for craniocaudal (CC) alignment and the vertebral bodies for anterior-posterior (AP) and mediolateral (ML) alignment. Adjustments were made for positioning errors >3 mm. Verification imaging was repeated after repositioning to assess for residual positioning error. Offline image matching was conducted to determine the setup accuracy using this approach compared with the initial setup error before repositioning. Real-time beam's-eye-view MV movies containing an air-diaphragm interface were also evaluated. Results: A total of 405 images were evaluated from 20 patients. Repositioning occurred in 109 of 120 fractions because of offsets >3 mm. Three to eight beam angles, with up to four segments per field, were used for each isocenter. Breath holds of up to 27 s were used for imaging and treatment. The average time from the initial verification image to the last treatment beam was 21 min. Image guidance and repositioning reduced the population random setup errors (sigma) from 6.5 mm (CC), 4.2 mm (ML), and 4.7 mm (AP) to 2.5 mm (CC), 2.8 mm (ML), and 2.9 mm (AP). The average individual random setup errors (sigma) were reduced from 4.5 mm (CC), 3.2 mm (AP), and 2.5 mm (ML) to 2.2 mm (CC), 2.0 mm (AP), and 2.0 mm (ML). The standard deviation of the distribution of systematic deviations (Sigma) was also reduced from 5.1 mm (CC), 3.4 mm (ML), and 3.1 mm (AP) to 1.4 mm (CC), 2.0 mm (ML), and 1.9 mm (AP) with image guidance and repositioning. The average absolute systematic errors were reduced from 4.1 mm (CC), 2.4 mm (AP), and 3.1 (ML) to 1.1 mm (CC), 1.3 mm (AP), and 1.6 mm (ML). Analysis of 52 real-time beam's-eye-view MV movies revealed an average absolute CC offset in diaphragm position of 1.9 mm. Conclusion: Image guidance with orthogonal MV imaging and ABC for stereotactic body radiotherapy for liver cancer is feasible, improving setup accuracy compared with ABC without daily imaging and repositioning. [ABSTRACT FROM AUTHOR]

Purpose: We hypothesize that surgical clips placed in the biopsy cavity during lumpectomy can be used as radiographic markers to facilitate image-guided external beam accelerated partial breast irradiation. Methods and Materials: We evaluated 28 patients with surgically placed clips in the lumpectomy cavity and two CT scans on different days. To establish whether the clips remain predictive of the lumpectomy cavity throughout therapy, we analyzed the motion of both cavities with repeat volumetric CT scans. The three-dimensional (3D) locations of each lumpectomy cavity and the associated clips were defined as individual regions of interest (ROIs). A single point of interest (POI) was defined for each ROI. The calculated movements of the lumpectomy cavity POIs between different scans were compared to those of the clip POIs. The second CT data set was then moved in accordance to the calculated clip POI's movement. The volume of the (second) lumpectomy cavity associated with the second scan outside of the (first) cavity of the first scan was measured. In addition, the required amount of a radial margin expansion around the first lumpectomy cavity to ensure coverage of the second lumpectomy cavity both before and after moving the second lumpectomy according to the clip POI movement was calculated. Results: The two CT scans were obtained on average 27 days apart, and the mean lumpectomy size decreased from 35 to 16 cc. The clip and lumpectomy cavity POIs moved a mean of 3 mm along the three principal Cartesian axes. In moving the second lumpectomy cavity according to the clip POI displacement from its original position, the volume of the second lumpectomy cavity outside of the volume of the first decreased from 2.6 cc to 1.0 cc after correction, and the required radial margin on the first lumpectomy cavity to include the second lumpectomy cavity decreased from 5.5 mm vs. 3.8 mm. Conclusion: The surgically placed clips after lumpectomy are strong radiographic surrogates for the biopsy cavity. If the clips were used to guide accelerated partial breast irradiation, a planning target volume margin of the order of 5 mm could be used, significantly smaller than the 10-mm margin currently employed. [ABSTRACT FROM AUTHOR]

Purpose: Magnetic resonance imaging (MRI) provides superior visualization of the prostate and surrounding anatomy, making it the modality of choice for imaging the prostate gland. This pilot study was performed to determine the feasibility and dosimetric quality achieved when placing high-dose-rate prostate brachytherapy catheters under MRI guidance in a standard “closed-bore” 1.5T scanner.Methods and materials: Patients with intermediate-risk and high-risk localized prostate cancer received MRI-guided high-dose-rate brachytherapy boosts before and after a course of external beam radiotherapy. Using a custom visualization and targeting program, the brachytherapy catheters were placed and adjusted under MRI guidance until satisfactory implant geometry was achieved. Inverse treatment planning was performed using high-resolution T2-weighted MRI.Results: Ten brachytherapy procedures were performed on 5 patients. The median percentage of volume receiving 100% of prescribed minimal peripheral dose (V100) achieved was 94% (mean, 92%; 95% confidence interval, 89–95%). The urethral V125 ranged from 0% to 18% (median, 5%), and the rectal V75 ranged from 0% to 3.1% (median, 0.3%). In all cases, lesions highly suspicious for malignancy could be visualized on the procedural MRI, and extracapsular disease was identified in 2 patients.Conclusion: High-dose-rate prostate brachytherapy in a standard 1.5T MRI scanner is feasible and achieves favorable dosimetry within a reasonable period with high-quality image guidance. Although the procedure was well tolerated in the acute setting, additional follow-up is required to determine the long-term safety and efficacy of this approach. [Copyright &y& Elsevier]

: PurposeImage-guided radiosurgery aligns the treatment beam to the target site by using a radiographic imaging system to locate anatomic landmarks associated with the treatment target. Because the procedure is performed without a rigid frame, the precision of dose alignment can be affected by patient movement. Movement is limited by noninvasive restraints and compensated by remeasuring the target position at short intervals throughout treatment and then realigning the beam. Frameless image-guided radiosurgery has been used at our institution to treat 250 cranial, 23 spinal, 9 lung, and 3 pancreas cases involving malignant and benign tumors as well as vascular malformations. We have analyzed the target position records for all of these cases to assess the frequency, magnitude, and case-by-case patterns of patient movement.: Methods and materialsThe position of the treatment site during image-guided radiosurgery was measured at approximately 1–2-min intervals, on average, using orthogonal amorphous silicon X-ray cameras and an image registration process that determined all six degrees of freedom in the target’s position. The change in position from one measurement to the next was indicative of patient movement.: ResultsThe treatment site position along each axis of translation was observed to vary by an average of 0.45 mm for the cranium, 0.53 mm for the cervical spine, 0.53 mm for the lumbar and thoracic spine, 1.06 mm for the lung, and 1.50 mm for the pancreas. Half of all cranial cases showed systematic drifting of the target away from the initial setup position.: ConclusionsUsing noninvasive restraints and supports, short-term movement of the head and spine during image-guided radiosurgery was limited to a radius of 0.8 mm, which satisfies the prevailing standard for radiosurgical dose alignment precision, but maintaining this margin of error throughout a treatment fraction requires regular monitoring of the target site’s position. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Purpose: Geometric uncertainties in the process of radiation planning and delivery constrain dose escalation and induce normal tissue complications. An imaging system has been developed to generate high-resolution, soft-tissue images of the patient at the time of treatment for the purpose of guiding therapy and reducing such uncertainties. The performance of the imaging system is evaluated and the application to image-guided radiation therapy is discussed.Methods and Materials: A kilovoltage imaging system capable of radiography, fluoroscopy, and cone-beam computed tomography (CT) has been integrated with a medical linear accelerator. Kilovoltage X-rays are generated by a conventional X-ray tube mounted on a retractable arm at 90° to the treatment source. A 41 × 41 cm2 flat-panel X-ray detector is mounted opposite the kV tube. The entire imaging system operates under computer control, with a single application providing calibration, image acquisition, processing, and cone-beam CT reconstruction. Cone-beam CT imaging involves acquiring multiple kV radiographs as the gantry rotates through 360° of rotation. A filtered back-projection algorithm is employed to reconstruct the volumetric images. Geometric nonidealities in the rotation of the gantry system are measured and corrected during reconstruction. Qualitative evaluation of imaging performance is performed using an anthropomorphic head phantom and a coronal contrast phantom. The influence of geometric nonidealities is examined.Results: Images of the head phantom were acquired and illustrate the submillimeter spatial resolution that is achieved with the cone-beam approach. High-resolution sagittal and coronal views demonstrate nearly isotropic spatial resolution. Flex corrections on the order of 0.2 cm were required to compensate gravity-induced flex in the support arms of the source and detector, as well as slight axial movements of the entire gantry structure. Images reconstructed without flex correction suffered from loss of detail, misregistration, and streak artifacts. Reconstructions of the contrast phantom demonstrate the soft-tissue imaging capability of the system. A contrast of 47 Hounsfield units was easily detected in a 0.1-cm-thick reconstruction for an imaging exposure of 1.2 R (in-air, in absence of phantom). The comparison with a conventional CT scan of the phantom further demonstrates the spatial resolution advantages of the cone-beam CT approach.Conclusions: A kV cone-beam CT imaging system based on a large-area, flat-panel detector has been successfully adapted to a medical linear accelerator. The system is capable of producing images of soft tissue with excellent spatial resolution at acceptable imaging doses. Integration of this technology with the medical accelerator will result in an ideal platform for high-precision, image-guided radiation therapy. [Copyright &y& Elsevier]