Martina Descovich

Patient dose considerations for routine megavoltage cone-beam CT imaging.

Megavoltage cone-beam CT (MVCBCT), the recent addition to the family of in-room CT imaging systems for image-guided radiation therapy (IGRT), uses a conventional treatment unit equipped with a flat panel detector to obtain a three-dimensional representation of the patient in treatment position. MVCBCT has been used for more than two years in our clinic for anatomy verification and to improve patient alignment prior to dose delivery. The objective of this research is to evaluate the image acquisition dose delivered to patients for MVCBCT and to develop a simple method to reduce the additional dose resulting from routine MVCBCT imaging. Conventional CT scans of phantoms and patients were imported into a commercial treatment planning system (TPS: Phillips, Pinnacle) and an arc treatment mimicking the MVCBCT acquisition process was generated to compute the delivered acquisition dose. To validate the dose obtained from the TPS, a simple water-equivalent cylindrical phantom with spaces for MOSFETs and an ion chamber was used to measure the MVCBCT image acquisition dose. Absolute dose distributions were obtained by simulating MVCBCTs of 9 and 5 monitor units (MU) on pelvis and head and neck patients, respectively. A compensation factor was introduced to generate composite plans of treatment and MVCBCT imaging dose. The article provides a simple equation to compute the compensation factor. The developed imaging compensation method was tested on routinely used clinical plans for prostate and head and neck patients. The quantitative comparison between the calculated dose by the TPS and measurement points on the cylindrical phantom were all within 3%. The dose percentage difference for the ion chamber placed in the center of the phantom was only 0.2%. For a typical MVCBCT, the dose delivered to patients forms a small anterior-posterior gradient ranging from 0.6 to 1.2 cGy per MVCBCT MU. MVCBCT acquisitions in the pelvis and head and neck areas deliver slightly more dose than current portal imaging but render soft tissue information for positioning. Overall, the additional dose from daily 9 MU MVCBCTs of prostate patients is small compared to the treatment dose (<4%). Dose-volume histograms of compensated plans for pelvis and head and neck patients imaged daily with MVCBCT showed no additional dose to the target and small increases at low doses. The results indicate that the dose delivered for MVCBCT imaging can be precisely calculated in the TPS and therefore included in the treatment plan. This allows simple plan compensations, such as slightly reducing the treatment dose, to minimize the total dose received by critical structures from daily positioning with MVCBCT. The proposed compensation factor reduces the number of MU per treatment beam per fraction. Both the number of fractions and the beam arrangement are kept unchanged. Reducing the imaging volume in the cranio-caudal direction can further reduce the dose delivered for MVCBCT. This is a useful feature to eliminate the imaging dose to the eyes or to focus on a specific region of interest for alignment.

Stereotactic Body Radiotherapy as Monotherapy or Post–External Beam Radiotherapy Boost for Prostate Cancer: Technique, Early Toxicity, and PSA Response

PURPOSE High dose rate (HDR) brachytherapy has been established as an excellent monotherapy or after external-beam radiotherapy (EBRT) boost treatment for prostate cancer (PCa). Recently, dosimetric studies have demonstrated the potential for achieving similar dosimetry with stereotactic body radiotherapy (SBRT) compared with HDR brachytherapy. Here, we report our technique, PSA nadir, and acute and late toxicity with SBRT as monotherapy and post-EBRT boost for PCa using HDR brachytherapy fractionation. PATIENTS AND METHODS To date, 38 patients have been treated with SBRT at the University of California-San Francisco with a minimum follow-up of 12 months. Twenty of 38 patients were treated with SBRT monotherapy (9.5 Gy × 4 fractions), and 18 were treated with SBRT boost (9.5 Gy × 2 fractions) post-EBRT and androgen deprivation therapy. PSA nadir to date for 44 HDR brachytherapy boost patients with disease characteristics similar to the SBRT boost cohort was also analyzed as a descriptive comparison. RESULTS SBRT was well tolerated. With a median follow-up of 18.3 months (range, 12.6-43.5), 42% and 11% of patients had acute Grade 2 gastrourinary and gastrointestinal toxicity, respectively, with no Grade 3 or higher acute toxicity to date. Two patients experienced late Grade 3 GU toxicity. All patients are without evidence of biochemical or clinical progression to date, and favorably low PSA nadirs have been observed with a current median PSA nadir of 0.35 ng/mL (range, <0.01-2.1) for all patients (0.47 ng/mL, range, 0.2-2.1 for the monotherapy cohort; 0.10 ng/mL, range, 0.01-0.5 for the boost cohort). With a median follow-up of 48.6 months (range, 16.4-87.8), the comparable HDR brachytherapy boost cohort has achieved a median PSA nadir of 0.09 ng/mL (range, 0.0-3.3). CONCLUSIONS Early results with SBRT monotherapy and post-EBRT boost for PCa demonstrate acceptable PSA response and minimal toxicity. PSA nadir with SBRT boost appears comparable to those achieved with HDR brachytherapy boost.

Nonrandom Intrafraction Target Motions and General Strategy for Correction of Spine Stereotactic Body Radiotherapy

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 degrees 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.

Apparatus dependence of normal brain tissue dose in stereotactic radiosurgery for multiple brain metastases

OBJECT Technical improvements in commercially available radiosurgery platforms have made it practical to treat a large number of intracranial targets. The goal of this study was to investigate whether the dose to normal brain when planning radiosurgery to multiple targets is apparatus dependent. METHODS The authors selected a single case involving a patient with 12 metastatic lesions widely distributed throughout the brain as visualized on contrast-enhanced CT. Target volumes and critical normal structures were delineated with Leksell Gamma Knife Perfexion software. The imaging studies including the delineated contours were digitally exported into the CyberKnife and Novalis multileaf collimator-based planning systems for treatment planning using identical target dose goals and dose-volume constraints. Subsets of target combinations (3, 6, 9, or 12 targets) were planned separately to investigate the relationship of number of targets and radiosurgery platform to the dose to normal brain. RESULTS Despite similar target dose coverage and dose to normal structures, the dose to normal brain was strongly apparatus dependent. A nonlinear increase in dose to normal brain volumes with increasing number of targets was also noted. CONCLUSIONS The dose delivered to normal brain is strongly dependent on the radiosurgery platform. How general this conclusion is and whether apparatus-dependent differences are related to differences in hardware design or differences in dose-planning algorithms deserve further investigation.

Equivalence in Dose Fall-Off for Isocentric and Nonisocentric Intracranial Treatment Modalities and Its Impact on Dose Fractionation Schemes

PURPOSE To investigate whether dose fall-off characteristics would be significantly different among intracranial radiosurgery modalities and the influence of these characteristics on fractionation schemes in terms of normal tissue sparing. METHODS AND MATERIALS An analytic model was developed to measure dose fall-off characteristics near the target independent of treatment modalities. Variations in the peripheral dose fall-off characteristics were then examined and compared for intracranial tumors treated with Gamma Knife, Cyberknife, or Novalis LINAC-based system. Equivalent uniform biologic effective dose (EUBED) for the normal brain tissue was calculated. Functional dependence of the normal brain EUBED on varying numbers of fractions (1 to 30) was studied for the three modalities. RESULTS The derived model fitted remarkably well for all the cases (R(2) > 0.99). No statistically significant differences in the dose fall-off relationships were found between the three modalities. Based on the extent of variations in the dose fall-off curves, normal brain EUBED was found to decrease with increasing number of fractions for the targets, with alpha/beta ranging from 10 to 20. This decrease was most pronounced for hypofractionated treatments with fewer than 10 fractions. Additionally, EUBED was found to increase slightly with increasing number of fractions for targets with alpha/beta ranging from 2 to 5. CONCLUSION Nearly identical dose fall-off characteristics were found for the Gamma Knife, Cyberknife, and Novalis systems. Based on EUBED calculations, normal brain sparing was found to favor hypofractionated treatments for fast-growing tumors with alpha/beta ranging from 10 to 20 and single fraction treatment for abnormal tissues with low alpha/beta values such as alpha/beta = 2.

Dose Gradient Near Target–Normal Structure Interface for Nonisocentric CyberKnife and Isocentric Intensity-Modulated Body Radiotherapy for Prostate Cancer

PURPOSE The treatment planning quality between nonisocentric CyberKnife (CK) and isocentric intensity modulation treatment was studied for hypofractionated prostate body radiotherapy. In particular, the dose gradient across the target and the critical structures such as the rectum and bladder was characterized. METHODS AND MATERIALS In the present study, patients treated with CK underwent repeat planning for nine fixed-field intensity-modulated radiotherapy (IMRT) using identical contour sets and dose-volume constraints. To calculate the dose falloff, the clinical target volume contours were expanded 30 mm anteriorly and posteriorly and 50 mm uniformly in other directions for all patients in the CK and IMRT plans. RESULTS We found that all the plans satisfied the dose-volume constraints, with the CK plans showing significantly better conformity than the IMRT plans at a relative greater dose inhomogeneity. The rectal and bladder volumes receiving a low dose were also lower for CK than for IMRT. The average conformity index, the ratio of the prescription isodose volume and clinical target volume, was 1.18 +/- 0.08 for the CK plans vs. 1.44 +/- 0.11 for the IMRT plans. The average homogeneity index, the ratio of the maximal dose and the prescribed dose to the clinical target volume, was 1.45 +/- 0.12 for the CK plans vs. 1.28 +/- 0.06 for the IMRT plans. The average percentage of dose falloff was 2.9% +/- 0.8%/mm for CK and 3.1% +/- 1.0%/mm for IMRT in the anterior direction, 3.8% +/- 1.6%/mm for CK and 3.2% +/- 1.9%/mm for IMRT in the posterior direction, and 3.6% +/- 0.4% for CK and 3.6% +/- 0.4% for IMRT in all directions. CONCLUSION Nonisocentric CK was as capable of producing equivalent fast dose falloff as high-number fixed-field IMRT delivery.

Physical performance and image optimization of megavoltage cone-beam CT.

Megavoltage cone-beam CT (MVCBCT) is the most recent addition to the in-room CT systems developed for image-guided radiation therapy. The first generation MVCBCT system consists of a 6 MV treatment x-ray beam produced by a conventional linear accelerator equipped with a flat panel amorphous silicon detector. The objective of this study was to evaluate the physical performance of MVCBCT in order to optimize the system acquisition and reconstruction parameters for image quality. MVCBCT acquisitions were performed with the clinical system but images were reconstructed and analyzed with a separate research workstation. The geometrical stability and the positioning accuracy of the system were evaluated by comparing geometrical calibrations routinely performed over a period of 12 months. The beam output and detector intensity stability during MVCBCT acquisition were also evaluated by analyzing in-air acquisitions acquired at different exposure levels. Several system parameters were varied to quantify their impact on image quality including the exposure (2.7, 4.5, 9.0, 18.0, and 54.0 MU), the craniocaudal imaging length (2, 5, 15, and 27.4 cm), the voxel size (0.5, 1, and 2 mm), the slice thickness (1, 3, and 5 mm), and the phantom size. For the reconstruction algorithm, the study investigated the effect of binning, averaging and diffusion filtering of raw projections as well as three different projection filters. A head-sized water cylinder was used to measure and improve the uniformity of MVCBCT images. Inserts of different electron densities were placed in a water cylinder to measure the contrast-to-noise ratio (CNR). The spatial resolution was obtained by measuring the point-spread function of the system using an iterative edge blurring technique. Our results showed that the geometric stability and accuracy of MVCBCT were better than 1 mm over a period of 12 months. Beam intensity variations per projection of up to 35.4% were observed for a 2.7 MU MVCBCT acquisition. These variations did not cause noticeable reduction in the image quality. The results on uniformity suggest that the cupping artifact occurring with MVCBCT is mostly due to off-axis response of the detector and not scattered radiation. Simple uniformity correction methods were developed to nearly eliminate this cupping artifact. The spatial resolution of the baseline MVCBCT reconstruction protocol was approximately 2 mm. An optimized reconstruction protocol was developed and showed an improvement of 75% in CNR with a penalty of only 8% in spatial resolution. Using this new reconstruction protocol, large adipose and muscular structures were differentiated at an exposure of 9 MU. A reduction of 36% in CNR was observed on a larger (pelvic-sized) phantom. This study demonstrates that soft-tissue visualization with MVCBCT can be substantially improved with proper system settings. Further improvement is expected from the next generation MVCBCT system with an optimized megavoltage imaging beamline.

Whole-procedure clinical accuracy of gamma knife treatments of large lesions.

The mechanical accuracy of Gamma Knife radiosurgery based on single-isocenter measurement has been established to within 0.3mm. However, the full delivery accuracy for Gamma Knife treatments of large lesions has only been estimated via the quadrature-sum analysis. In this study, the authors directly measured the whole-procedure accuracy for Gamma Knife treatments of large lesions to examine the validity of such estimation. The measurements were conducted on a head-phantom simulating the whole treatment procedure that included frame placement, computed tomography imaging, treatment planning, and treatment delivery. The results of the measurements were compared with the dose calculations from the treatment planning system. Average agreements of 0.1-1.6mm for the isodose lines ranging from 25% to 90% of the maximum dose were found despite potentially large contributing uncertainties such as 3-mm imaging resolution, 2-mm dose grid size, 1-mm frame registration, multi-isocenter deliveries, etc. The results of our measurements were found to be significantly smaller (>50%) than the calculated value based on the quadrature-sum analysis. In conclusion, Gamma Knife treatments of large lesions can be delivered much more accurately than predicted from the quadrature-sum analysis of major sources of uncertainties from each step of the delivery chain.

Investigating the clinical advantages of a robotic linac equipped with a multileaf collimator in the treatment of brain and prostate cancer patients

The purpose of this study was to evaluate the performance of a commercially available CyberKnife system with a multileaf collimator (CK‐MLC) for stereotactic body radiotherapy (SBRT) and standard fractionated intensity‐modulated radiotherapy (IMRT) applications. Ten prostate and ten intracranial cases were planned for the CK‐MLC. Half of these cases were compared with clinically approved SBRT plans generated for the CyberKnife with circular collimators, and the other half were compared with clinically approved standard fractionated IMRT plans generated for conventional linacs. The plans were compared on target coverage, conformity, homogeneity, dose to organs at risk (OAR), low dose to the surrounding tissue, total monitor units (MU), and treatment time. CK‐MLC plans generated for the SBRT cases achieved more homogeneous dose to the target than the CK plans with the circular collimators, for equivalent coverage, conformity, and dose to OARs. Total monitor units were reduced by 40% to 70% and treatment time was reduced by half. The CK‐MLC plans generated for the standard fractionated cases achieved prescription isodose lines between 86% and 93%, which was 2%–3% below the plans generated for conventional linacs. Compared to standard IMRT plans, the total MU were up to three times greater for the prostate (whole pelvis) plans and up to 1.4 times greater for the intracranial plans. Average treatment time was 25 min for the whole pelvis plans and 19 min for the intracranial cases. The CK‐MLC system provides significant improvements in treatment time and target homogeneity compared to the CK system with circular collimators, while maintaining high conformity and dose sparing to critical organs. Standard fractionated plans for large target volumes (>100 cm3) were generated that achieved high prescription isodose levels. The CK‐MLC system provides more efficient SRS and SBRT treatments and, in select clinical cases, might be a potential alternative for standard fractionated treatments. PACS numbers: 87.56.nk, 87.56.bd

Comparison Between Hybrid Direct Aperture Optimized Intensity-Modulated Radiotherapy and Forward Planning Intensity-Modulated Radiotherapy for Whole Breast Irradiation

PURPOSE To investigate the planning efficiency and dosimetric characteristics of hybrid direct aperture optimized (hDAO) intensity-modulated radiotherapy (IMRT) compared with forward planning (FP)-IMRT for whole breast irradiation with two tangential beams. METHODS AND MATERIALS A total of 15 patients with left-sided breast cancer, categorized with three different breast volumes, were selected for this study. All patients were treated with FP plans to 50 Gy in 25 fractions. The hDAO plans were created by combining two open fields with eight segments in two tangential beam directions and were inversely optimized. RESULTS The FP and hDAO plans achieved similar breast coverage and sparing of critical organs. The volume of breast receiving 105% of the prescription dose was significantly smaller in the hDAO than in the FP plans: 25% vs. 63% (p = .008) for small, 22% vs. 57% (p = .005) for medium, and 28% vs. 53% (p = .005) for large breasts. Furthermore, the tumor cavity coverage was slightly better in the hDAO plans (92.4% vs. 90.9%). CONCLUSION Compared with FP-IMRT, hDAO-IMRT provided dosimetric advantages, significantly reducing the size of the hot spot and slightly improving the coverage of the tumor cavity. In addition, hDAO-IMRT required less planning time and was less dependent on the planners ability.