Hsiao-Ming Lu

Reduction of cardiac volume in left-breast treatment fields by respiratory maneuvers: a CT study

PURPOSE A previous study of healthy female volunteers suggested that deep inspiratory breath holding can reduce the cardiac volume in the treatment portals for left-breast cancer treatment. The reduction of irradiated cardiac volume may be important considering the reported late cardiac morbidity and mortality and the frequent coexistent use of potentially cardiotoxic chemotherapy in breast cancer patients. In the present study, we evaluated the heart volume in the fields and, thus, the true benefit of this respiratory maneuver in breast cancer patients undergoing CT simulation. MATERIALS AND METHODS Fifteen patients (median age, 53) were studied. For each patient, CT scans were performed both when the patient breathed normally (quiet respiration) and when the patient held her breath after a deep inspiration. Tangential fields were planned using the same medial, lateral, superior, and inferior borders on skin for the normal breathing and the breath-holding configurations. The cardiac and left-lung volumes within the tangential fields were calculated for both breathing configurations. Multiple scan series were performed for the breath-holding configuration to provide a more accurate delineation of the cardiac tissue and to study the reproducibility of the patients position between different cycles of deep inspiration. RESULTS None of the patients had difficulty holding her breath for 20 s. The cardiac volume in the field was reduced (-86 +/- 24%; p < 0.001) when patients held their breath after a deep inspiration compared to when breathing normally. For 7 patients (47%), deep inspiration moved the heart completely out of the radiation fields. The expansion of the lung tissue due to deep inspiration also increased the absolute lung volume in the tangential fields (183 cm(3) vs 97 cm(3), p < 0.001). However, the fractional volume of the left lung in the field was essentially unchanged. For all but 1 patient, the maximum difference between the external body contours from different breath holding cycles was 5 mm and occurred at the lateral aspect of the breast. At the medial aspect, as indicated by the position of the midline marker, the variations were well within the currently accepted tolerance for patient positioning during tangential treatment. CONCLUSIONS Deep-inspiration breath holding substantially reduces cardiac volume in the tangential fields for left-sided breast cancer treatment. The variation between patient positions at different cycles of breath holding was found to be reasonably small. Therefore, it appears feasible to reduce cardiac radiation by treating patients with intratreatment minifractions lasting 10-15 s while patients hold their breath.

Proton therapy for breast cancer after mastectomy: early outcomes of a prospective clinical trial.

PURPOSE Dosimetric planning studies have described potential benefits for the use of proton radiation therapy (RT) for locally advanced breast cancer. We report acute toxicities and feasibility of proton delivery for 12 women treated with postmastectomy proton radiation with or without reconstruction. METHODS AND MATERIALS Twelve patients were enrolled in an institutional review board-approved prospective clinical trial. The patients were assessed for skin toxicity, fatigue, and radiation pneumonitis during treatment and at 4 and 8 weeks after the completion of therapy. All patients consented to have photographs taken for documentation of skin toxicity. RESULTS Eleven of 12 patients had left-sided breast cancer. One patient was treated for right-sided breast cancer with bilateral implants. Five women had permanent implants at the time of RT, and 7 did not have immediate reconstruction. All patients completed proton RT to a dose of 50.4 Gy (relative biological effectiveness [RBE]) to the chest wall and 45 to 50.4 Gy (RBE) to the regional lymphatics. No photon or electron component was used. The maximum skin toxicity during radiation was grade 2, according to the Common Terminology Criteria for Adverse Events (CTCAE). The maximum CTCAE fatigue was grade 3. There have been no cases of RT pneumonitis to date. CONCLUSIONS Proton RT for postmastectomy RT is feasible and well tolerated. This treatment may be warranted for selected patients with unfavorable cardiac anatomy, immediate reconstruction, or both that otherwise limits optimal RT delivery using standard methods.

A Four-Dimensional Computed Tomography Analysis of Multiorgan Abdominal Motion

PURPOSE To characterize and quantify multiorgan respiration-induced motion in the abdomen in liver and pancreatic cancer patients. METHODS AND MATERIALS Four-dimensional computed tomography scans were acquired for 18 patients treated for abdominal tumors. Contours of multiple abdominal organs were drawn by the radiation oncologist at one respiratory phase; these contours were propagated to other respiratory phases by deformable registration. Three-dimensional organ models were generated from the resulting contours at each phase. Motions of the bounding box and center of mass were extracted and analyzed for the clinical target volume and organs at risk. RESULTS On average, the center of mass motion for liver clinical target volumes was 9.7 mm (SD 5 mm) in the superior-inferior direction, with a range of 3 to 18 mm; for pancreatic tumors, the average was 5 mm (SD 1 mm) m with a range of 3 to 7 mm. Abdominal organs move in unison, but with varying amplitudes. Gating near exhale (T40-T60) reduces the range of motion by a factor of ∼10. CONCLUSION We have used deformable registration to calculate the trajectories of abdominal organs in four dimensions, based on center of mass and bounding box motion metrics. Our results are compared with previously reported studies. Possible reasons for differences are discussed.

Interfractional Variations in the Setup of Pelvic Bony Anatomy and Soft Tissue, and Their Implications on the Delivery of Proton Therapy for Localized Prostate Cancer

PURPOSE To quantify daily variations in the anatomy of patients undergoing radiation therapy for prostate carcinoma, to estimate their effect on dose distribution, and to evaluate the effectiveness of current standard planning and setup approaches employed in proton therapy. METHODS We used series of computed tomography data, which included the pretreatment scan, and between 21 and 43 in-room scans acquired on different treatment days, from 10 patients treated with intensity-modulated radiation therapy at Morristown Memorial Hospital. Variations in femur rotation angles, thickness of subcutaneous adipose tissue, and physical depth to the distal surface of the prostate for lateral beam arrangement were recorded. Proton dose distributions were planned with the standard approach. Daily variations in the location of the prescription isodose were evaluated. RESULTS In all 10 datasets, substantial variation was observed in the lateral tissue thickness (standard deviation of 1.7-3.6 mm for individual patients, variations of >5 mm from the planning computed tomography observed in all series), and femur rotation angle (standard deviation between 1.3° and 4.8°, with the maximum excursion exceeding 10° in 6 of 10 datasets). Shifts in the position of treated volume (98% isodose) were correlated with the variations in the lateral tissue thickness. CONCLUSIONS Analysis suggests that, combined with image-guided setup verification, the range compensator expansion technique prevents loss of dose to target from femur rotation and soft-tissue deformation, in the majority of cases. Anatomic changes coupled with the uncertainties of particle penetration in tissue restrict possibilities for margin reduction in proton therapy of prostate cancer.

Optimization of current modulation function for proton spread-out Bragg peak fields

Proton treatments with spread-out Bragg peak (SOBP) fields often use a rotating modulation wheel of varying thickness to modulate the pristine Bragg peak in depth and intensity. The technique of modulating also the beam current independently over the wheel rotation provides an additional control over the intensities of the pulled-back Bragg peaks. As a result, a single wheel can be used over a large range of energies and SOBP parameters and field-specific wheels are no longer necessary. An essential task in commissioning a particular treatment depth is the determination of this current modulation function. We have developed a method for the optimization of the current modulation function. The basic idea is to treat the entire beam nozzle, housing the various beam scattering and modulating components, as a whole and to characterize its effect as a transformation from a modulating beam current to a depth-dose distribution. While this transformation is difficult to calculate theoretically due to the complex scattering paths in the nozzle and the phantom, it can, however, be determined by time-resolved dose measurements. Using this transformation, we can calculate SOBP depth-dose distributions for any current modulation function and optimize it by a simple numerical optimization. We have applied the new method to a number of proton beams with satisfactory results.

A respiratory-gated treatment system for proton therapy.

Proton therapy offers the potential for excellent dose conformity and reduction in integral dose. The superior dose distribution is, however, much more sensitive to changes in radiological depths along the beam path than for photon fields. Respiratory motion can cause such changes for treatments sites like lung, liver, and mediastinum and thus affect the proton dose distribution significantly. We have implemented and commissioned a respiratory-gated system for range-modulated treatment fields. The gating system was designed to ensure that each gate always contains complete modulation cycles so that for any beam segment the delivered dose has the planned depth-dose distribution. Measurements have been made to estimate the time delays for the various components of the system. The total delay between the actual motion and the beam on/off control is in the range of 65-195 ms. Time-resolved dose measurements and film tests were also conducted to examine the overall gating effect.

Intensity modulated proton therapy for postmastectomy radiation of bilateral implant reconstructed breasts: A treatment planning study

BACKGROUND AND PURPOSE Delivery of post-mastectomy radiation (PMRT) in women with bilateral implants represents a technical challenge, particularly when attempting to cover regional lymph nodes. Intensity modulated proton therapy (IMPT) holds the potential to improve dose delivery and spare non-target tissues. The purpose of this study was to compare IMPT to three-dimensional (3D) conformal radiation following bilateral mastectomy and reconstruction. MATERIALS AND METHODS Ten IMPT, 3D conformal photon/electron (P/E), and 3D photon (wide tangent) plans were created for 5 patients with breast cancer, all of whom had bilateral breast implants. Using RTOG guidelines, a physician delineated contours for both target volumes and organs-at-risk. Plans were designed to achieve 95% coverage of all targets (chest wall, IMN, SCV, axilla) to a dose of 50.4 Gy or Gy (RBE) while maximally sparing organs-at-risk. RESULTS IMPT plans conferred similar target volume coverage with enhanced homogeneity. Both mean heart and lung doses using IMPT were significantly decreased compared to both P/E and wide tangent planning. CONCLUSIONS IMPT provides improved homogeneity to the chest wall and regional lymphatics in the post-mastectomy setting with improved sparing of surrounding normal structures for woman with reconstructed breasts. IMPT may enable women with mastectomy to undergo radiation therapy without the need for delay in breast reconstruction.

Proton radiography and proton computed tomography based on time-resolved dose measurements

We present a proof of principle study of proton radiography and proton computed tomography (pCT) based on time-resolved dose measurements. We used a prototype, two-dimensional, diode-array detector capable of fast dose rate measurements, to acquire proton radiographic images expressed directly in water equivalent path length (WEPL). The technique is based on the time dependence of the dose distribution delivered by a proton beam traversing a range modulator wheel in passive scattering proton therapy systems. The dose rate produced in the medium by such a system is periodic and has a unique pattern in time at each point along the beam path and thus encodes the WEPL. By measuring the time dose pattern at the point of interest, the WEPL to this point can be decoded. If one measures the time–dose patterns at points on a plane behind the patient for a beam with sufficient energy to penetrate the patient, the obtained 2D distribution of the WEPL forms an image. The technique requires only a 2D dosimeter array and it uses only the clinical beam for a fraction of second with negligible dose to patient. We first evaluated the accuracy of the technique in determining the WEPL for static phantoms aiming at beam range verification of the brain fields of medulloblastoma patients. Accurate beam ranges for these fields can significantly reduce the dose to the cranial skin of the patient and thus the risk of permanent alopecia. Second, we investigated the potential features of the technique for real-time imaging of a moving phantom. Real-time tumor tracking by proton radiography could provide more accurate validations of tumor motion models due to the more sensitive dependence of proton beam on tissue density compared to x-rays. Our radiographic technique is rapid (~100 ms) and simultaneous over the whole field, it can image mobile tumors without the problem of interplay effect inherently challenging for methods based on pencil beams. Third, we present the reconstructed pCT images of a cylindrical phantom containing inserts of different materials. As for all conventional pCT systems, the method illustrated in this work produces tomographic images that are potentially more accurate than x-ray CT in providing maps of proton relative stopping power (RSP) in the patient without the need for converting x-ray Hounsfield units to proton RSP. All phantom tests produced reasonable results, given the currently limited spatial and time resolution of the prototype detector. The dose required to produce one radiographic image, with the current settings, is ~0.7 cGy. Finally, we discuss a series of techniques to improve the resolution and accuracy of radiographic and tomographic images for the future development of a full-scale detector.

Proton Radiotherapy for High-Risk Pediatric Neuroblastoma: Early Outcomes and Dose Comparison

PURPOSE To report the early outcomes for children with high-risk neuroblastoma treated with proton radiotherapy (RT) and to compare the dose distributions for intensity-modulated photon RT (IMRT), three-dimensional conformal proton RT (3D-CPT), and intensity-modulated proton RT to the postoperative tumor bed. METHODS AND MATERIALS All patients with high-risk (International Neuroblastoma Staging System Stage III or IV) neuroblastoma treated between 2005 and 2010 at our institution were included. All patients received induction chemotherapy, surgical resection of residual disease, high-dose chemotherapy with stem cell rescue, and adjuvant 3D-CPT to the primary tumor sites. The patients were followed with clinical examinations, imaging, and laboratory testing every 6 months to monitor disease control and side effects. IMRT, 3D-CPT, and intensity-modulated proton RT plans were generated and compared for a representative case of adjuvant RT to the primary tumor bed followed by a boost. RESULTS Nine patients were treated with 3D-CPT. The median age at diagnosis was 2 years (range 10 months to 4 years), and all patients had Stage IV disease. All patients had unfavorable histologic characteristics (poorly differentiated histologic features in 8, N-Myc amplification in 6, and 1p/11q chromosomal abnormalities in 4). The median tumor size at diagnosis was 11.4 cm (range 7-16) in maximal dimension. At a median follow-up of 38 months (range 11-70), there were no local failures. Four patients developed distant failure, and, of these, two died of disease. Acute side effects included Grade 1 skin erythema in 5 patients and Grade 2 anorexia in 2 patients. Although comparable target coverage was achieved with all three modalities, proton therapy achieved substantial normal tissue sparing compared with IMRT. Intensity-modulated proton RT allowed additional sparing of the kidneys, lungs, and heart. CONCLUSIONS Preliminary outcomes reveal excellent local control with proton therapy for high-risk neuroblastoma, although distant failures continu to occur. Dosimetric comparisons demonstrate the advantage of proton RT compared with IMRT in this setting, allowing more conformal treatment and better normal tissue sparing.

Optimized beam planning for linear accelerator-based stereotactic radiosurgery

PURPOSE Current treatment planning for linear accelerator-based stereotactic radiosurgery and radiotherapy is a lengthy and iterative procedure. The planner has to manually select the beam arcs and carefully consider many different selections to ensure target volume coverage while sparing dose to critical organs. In this article we report an optimization procedure that can automatically select the beam arcs based on geometric and dosimetric analysis of the treatment parameters. METHODS AND MATERIALS The optimization problem is introduced by using a Beams Eye View (BEV) map where a pattern of lines represents a beam arc combination for a treatment plan. The collection of all possible treatment plans is described by using the concept of phase space where each point corresponds to a particular configuration of the system under consideration, and in this case, a particular beam arc combination. A geometric reduction of the phase space is performed by excluding static beam ports that irradiate too much critical organs and too little target volume. The phase space is further reduced by excluding beam arc combinations that do not comply with treatment convenience considerations and established planning experiences. These reductions significantly reduces the number of beam arc combinations to be considered and thus dramatically simplifies the computational complexity. The method of simulated annealing is then used to the reduced phase space to select the set of beam arcs that provides the best surface dose distribution for the target volume. The optimization procedure is applied to a radiosurgery case to compare the optimized beam arcs with the previously manually planned beam arcs. The procedure is also applied to 10 randomly selected cases for a comparison in terms of tissue-volume ratio calculations. RESULTS The system is a highly automated beam arc planning tool for stereotactic radiosurgery and stereotactic radiotherapy. Its interactive nature allows the planner to rapidly consider many treatment plans to search for the best option. For the case presented, it is shown that the optimized beams substantially reduce the dose to the postrema. The tissue-volume ratio calculations demonstrate that the optimization often produces clinically superior treatment plans than the manual beam planning method. CONCLUSIONS Our method of phase space reduction proves to be very useful in approaching the complex problem of treatment planning optimization. Not only does it substantially reduce the number of beam arcs that need to be considered, but it also simplifies the evaluation of the beam arc options. Both of these greatly reduce the computational complexity of the optimization and make the procedure fast and efficient. Moreover, the reduction of phase space adds another layer of interaction between the user and the beam selection procedure, so that the optimization process is well controlled and thus very effective.