Spot scanning proton therapy minimizes neutron dose in the setting of radiation therapy administered during pregnancy.

This is a real case study to minimize the neutron dose equivalent (H) to a fetus using spot scanning proton beams with favorable beam energies and angles. Minimum neutron dose exposure to the fetus was achieved with iterative planning under the guidance of neutron H measurement. Two highly conformal treatment plans, each with three spot scanning beams, were planned to treat a 25-year-old pregnant female with aggressive recurrent chordoma of the base of skull who elected not to proceed with termination. Each plan was scheduled for delivery every other day for robust target coverage. Neutron H to the fetus was measured using a REM500 neutron survey meter placed at the fetus position of a patient simulating phantom. 4.1 and 44.1 µSv/fraction were measured for the two initial plans. A vertex beam with higher energy and the fetal position closer to its central axis was the cause for the plan that produced an order higher neutron H. Replacing the vertex beam with a lateral beam reduced neutron H to be comparable with the other plan. For a prescription of 70 Gy in 35 fractions, the total neutron H to the fetus was estimated to be 0.35 mSv based on final measurement in single fraction. In comparison, the passive scattering proton plan and photon plan had an estimation of 26 and 70 mSv, respectively, for this case. While radiation therapy in pregnant patients should be avoided if at all possible, our work demonstrated spot scanning beam limited the total neutron H to the fetus an order lower than the suggested 5 mSv regulation threshold. It is far superior than passive scattering beam and careful beam selection with lower energy and keeping fetus further away from beam axis are essential in minimizing the fetus neutron exposure.

A procedure for calculation of monitor units for passively scattered proton radiotherapy beams.

The purpose of this study is to validate a monitor unit (MU) calculation procedure for passively scattered proton therapy beams. The output dose per MU (d/MU) of a therapeutic radiation beam is traditionally calibrated under specific reference conditions. These conditions include beam energy, field size, suitable depth in water or water equivalent phantom in a low dose gradient region with known relative depth dose, and source to point of calibration distance. Treatment field settings usually differ from these reference conditions leading to a different d/MU that needs to be determined for delivering the prescribed dose. For passively scattered proton beams, the proton specific parameters, which need to be defined, are related to the energy, lateral scatterers, range modulating wheel, spread out Bragg peak (SOBP) width, thickness of any range shifter, the depth dose value relative to the normalization point in the SOBP, and scatter both from the range compensator and inhomogeneity in the patient. Following the custom for photons or electrons, a set of proton dosimetry factors, representing the changes in the d/MU relative to a reference condition, can be defined as the relative output factor (ROF), SOBP factor (SOBPF), range shifter factor (RSF), SOBP off-center factor (SOBPOCF), off-center ratio (OCR), inverse square factor (ISF), field size factor (FSF), and compensator and patient scatter factor (CPSF). The ROF, SOBPF, and RSF are the major contributors to the d/MU and were measured using an ion chamber in water tank during the clinical commissioning of each beam to create a dosimetry beam data table to be used for calculating the monitor units. The following simple formula is found to provide an independent method to determine the d/MU at the point of interest (POI) in the patient, namely, (d/MU) = ROF SOBPF. RSF SOBPOCF.OCR.FSF.ISF.CPSF. The monitor units for delivering the intended dose (D) to the POI can be obtained from MU = D / (d/MU). The accuracy and robustness of the above formula were validated by calculating the d/MU in water for many different combinations of beam parameters and comparing it with the corresponding measured d/MU by an ion chamber in a water or water/plastic phantom. This procedure has been in use for MU calculation for patient treatment fields at our facility since May 2006. The differences in the calculated and measured values of the d/MU for 623 distinct fields used for patient treatment during the period of May 2006 to February 2007 are within 2% for 99% of these fields. The authors conclude that an intuitive formula similar to the one used for monitor unit calculation of therapeutic photon beams can be used to compute the monitor units of passively scattered proton therapy beams.

Incorporating partial shining effects in proton pencil-beam dose calculation.

A range modulator wheel (RMW) is an essential component in passively scattered proton therapy. We have observed that a proton beam spot may shine on multiple steps of the RMW. Proton dose calculation algorithms normally do not consider the partial shining effect, and thus overestimate the dose at the proximal shoulder of spread-out Bragg peak (SOBP) compared with the measurement. If the SOBP is adjusted to better fit the plateau region, the entrance dose is likely to be underestimated. In this work, we developed an algorithm that can be used to model this effect and to allow for dose calculations that better fit the measured SOBP. First, a set of apparent modulator weights was calculated without considering partial shining. Next, protons spilled from the accelerator reaching the modulator wheel were simplified as a circular spot of uniform intensity. A weight-splitting process was then performed to generate a set of effective modulator weights with the partial shining effect incorporated. The SOBPs of eight options, which are used to label different combinations of proton-beam energy and scattering devices, were calculated with the generated effective weights. Our algorithm fitted the measured SOBP at the proximal and entrance regions much better than the ones without considering partial shining effect for all SOBPs of the eight options. In a prostate patient, we found that dose calculation without considering partial shining effect underestimated the femoral head and skin dose.

Intensity-modulated radiotherapy (IMRT) and conventional three-dimensional conformal radiotherapy for high-grade gliomas: does IMRT increase the integral dose to normal brain?

PURPOSE: To determine whether intensity-modulated radiotherapy (IMRT) treatment increases the total integral dose of nontarget tissue relative to the conventional three-dimensional conformal radiotherapy (3D-CRT) technique for high-grade gliomas. METHODS AND MATERIALS: Twenty patients treated with 3D-CRT for glioblastoma multiforme were selected for a comparative dosimetric evaluation with IMRT. Original target volumes, organs at risk (OAR), and dose-volume constraints were used for replanning with IMRT. Predicted isodose distributions, cumulative dose-volume histograms of target volumes and OAR, normal tissue integral dose, target coverage, dose conformity, and normal tissue sparing with 3D-CRT and IMRT planning were compared. Statistical analyses were performed to determine differences. RESULTS: In all 20 patients, IMRT maintained equivalent target coverage, improved target conformity (conformity index [CI] 95% 1.52 vs. 1.38, p < 0.001), and enabled dose reductions of normal tissues, including brainstem (D(mean) by 19.8% and D(max) by 10.7%), optic chiasm (D(mean) by 25.3% and D(max) by 22.6%), right optic nerve (D(mean) by 37.3% and D(max) by 28.5%), and left optic nerve (D(mean) by 40.6% and D(max) by 36.7%), p < or = 0.01. This was achieved without increasing the total nontarget integral dose by greater than 0.5%. Overall, total integral dose was reduced by 7-10% with IMRT, p < 0.001, without significantly increasing the 0.5-5 Gy low-dose volume. CONCLUSIONS: These results indicate that IMRT treatment for high-grade gliomas allows for improved target conformity, better critical tissue sparing, and importantly does so without increasing integral dose and the volume of normal tissue exposed to low doses of radiation.

Automatic target localization and verification for on-line image-guided stereotactic body radiotherapy of the spine.

To facilitate image-guided stereotactic body radiotherapy (IG-SBRT) of spinal and paraspinal tumors, the authors have developed an on-line image registration system for automated target localization and patient position verification with high precision. When rotations are present in a patient's daily setup position, a setup error of a few millimeters can be introduced in localization of the isocenter by using surrounding bony structures. This setup error not only will deteriorate the dose coverage of the tumor, more importantly it will overdose the spinal cord. To resolve this issue, the image registration program developed by the authors detects translational shifts as well as rotational shifts using 3D CT image registration. Unacceptable rotations were corrected by either repositioning the patient or adjusting the treatment couch that was capable of rotational corrections when such a couch was available for clinical use. One pair of orthogonal digitally reconstructed radiographs (DRR) were generated from the daily pretreatment CT scan to compare with the corresponding DRRs generated from the planning CT scan to confirm the target shift correction. After the patient's position was corrected a pair of orthogonal portal images were taken for final verification. The accuracy of the image registration result was found to be within 0.1 mm on a head and neck phantom. Target shifts of a fraction of a millimeter were readily visible in our DRR comparison and portal image verification. The time needed to complete the image registration and DRR comparison was about 3 minutes. An integrated system that combines a high-speed CT scanner and a linear accelerator was used for imaging and treatment delivery. Application of the program in actual IG-SBRT cases demonstrated that it was accurate, fast, and reliable. It serves as a useful tool for image-guided radiotherapy where high precision of target localization is required.

Dosimetric Characteristics of a Two-Dimensional Diode Array Detector Irradiated with Passively Scattered Proton Beams.

PURPOSE: To evaluate the dosimetric characteristics of a two-dimensional (2D) diode array detector irradiated with passively scattered proton beams. MATERIALS AND METHODS: A diode array detector, MapCHECK (Model 1175, Sun Nuclear, Melbourne, FL, USA) was characterized in passive-scattered proton beams. The relative sensitivity of the diodes and absolute dose calibration were determined using a 250 MeV beam. The pristine Bragg curves (PBCs) measured by MapCHECK diodes were compared with those of an ion chamber using a range shift method. The water-equivalent thickness (WET) of the diode array detector's intrinsic buildup also was determined. The inverse square dependence, linearity, and other proton dosimetric quantities measured by MapCHECK were also compared with those of the ion chambers. The change in the absolute dose response of the MapCHECK as a function of accumulated radiation dose was used as an indicator of radiation damage to the diodes. 2D dose distribution with and without the compensator were measured and compared with the treatment planning system (TPS) calculations. RESULTS: The WET of the MapCHECK diode's buildup was determined to be 1.7 cm. The MapCHECK-measured PBC were virtually identical to those measured by a parallel-plate ion chamber for 160, 180, and 250 MeV proton beams. The inverse square results of the MapCHECK were within ±0.4% of the ion chamber results. The linearity of MapCHECK results was within 1% of those from the ion chamber as measured in the range between 10 and 300 MU. All other dosimetric quantities were within 1.3% of the ion chamber results. The 2D dose distributions for non-clinical fields without compensator and the patient treatment fields with the compensator were consistent with the TPS results. The absolute dose response of the MapCHECK was changed by 7.4% after an accumulated dose increased by 170 Gy. CONCLUSIONS: The MapCHECK is a convenient and useful tool for 2D dose distribution measurements using passively scattered proton beams. Variations in MapCHECK's dose response with increasing levels of total accumulated radiation dose should be carefully monitored.

Erectile dysfunction and radiation dose to penile base structures: a lack of correlation.

PURPOSE: To evaluate the relationship between the dose and volume of radiation to proximal penile structures and the development of erectile dysfunction after external beam radiotherapy (RT) for localized prostate adenocarcinoma. METHODS AND MATERIALS: The study cohort comprised 28 patients who were enrolled our in-house three-dimensional conformal RT dose escalation protocol. The patients were treated to 78 Gy between 1995 and 1998. This protocol included a planned quality-of-life questionnaire to assess sexual function 2 years after completing RT. All the study patients were potent before RT. The median follow-up was 66 months (range 39-95). Penile base contents were outlined retrospectively in restored treatment plans. The dose-volume histograms (DVHs) for the corpus spongiosum (penile bulb), corpora cavernosum and crura, and total penile structure (corpus spongiosum plus corpora cavernosum and crura) were calculated. Statistical significance was defined as p < 0.05. The Bonferroni correction was used to adjust for multiple comparisons. Power calculations showed that our study sample would detect radiation- induced impotence with a very high power. We also estimated that a relatively small difference of 10-15% in the DVHs between the potent and impotent patients could be detected. RESULTS: At 2 years after RT, 10 patients (35.7%) reported new-onset erectile dysfunction and were unable to attain firm enough erections to have intercourse. Only hypertension was observed to affect erectile dysfunction after external beam RT. We found no statistically significant correlation among age, diabetes, or heavy alcohol consumption and post-RT potency. The mean radiation dose +/- standard deviation delivered to the corpus spongiosum, corpora cavernosa and crura, and total penile structure was, respectively, 42.2 +/- 8.4 Gy, 36.3 +/- 8.0 Gy, and 38.2 +/- 7.5 Gy. t test comparisons were performed between DVHs of post-RT potent and impotent patients on multiple cutpoints. No dose-volume effect was found. Analysis of the DVHs when the patients were subdivided into normotensive and hypertensive groups also showed no dose-volume response. CONCLUSION: Our analysis did not show statistically significant correlations between potency preservation and radiation dose to the proximal penis. The entire etiology of radiation- induced erectile dysfunction remains unclear and further research is needed.

Phase I clinical evaluation of near-simultaneous computed tomographic image-guided stereotactic body radiotherapy for spinal metastases.

PURPOSE: To evaluate in a Phase I study the safety, feasibility, and patient-positioning accuracy of treating patients with intensity-modulated, near-simultaneous, computed tomographic (CT) image-guided stereotactic body radiotherapy (SBRT). PATIENTS AND METHODS: Fifteen consecutive patients with metastatic spinal disease who met protocol eligibility criteria were entered into a Phase I clinical trial. Each patient received five treatments of intensity-modulated, near-simultaneous CT image-guided SBRT, for a total of 75 treatments with 90 isocenter setups during the course of the study. Patients uniformly received 30 Gy (if possible) of radiotherapy in 5 fractions to the clinical target volume. The total dose was constrained by limiting the spinal cord to a maximum dose of 10 Gy. To verify correct daily patient positioning before each treatment and to determine the daily treatment setup error after radiation delivery, axial CT scans were taken before and immediately after each treatment without moving the patient from the treatment position, for comparison with the planning CT scan. Toxicity was measured using the Common Toxicity Criteria, the Late Effects of Normal Tissue scoring system and a neurologic function scale. Follow-up was conducted 4 weeks after completion of SBRT, and then 2, 3, 6, 9, 12, and every 6 months thereafter. RESULTS: The procedure was technically feasible to perform in all patients. No neurologic toxicity was observed in any patient. The median follow-up time was 9 months (range 6-16). The Clopper-Pearson upper bound on the probability of paralysis with 95% confidence is no greater than 0.181. The positional setup error was determined to be within 1 mm of planning isocenter. CONCLUSIONS: This Phase I study shows that intensity-modulated, near simultaneous, CT image-guided SBRT is a feasible, and highly precise technique for the noninvasive treatment of spinal metastases. Although no paralysis has developed in the 15 patients treated, continued monitoring for spinal cord toxicity is warranted, as larger numbers of patients will be needed to more precisely define the upper bound on the probability of spinal cord myelopathy.

Near simultaneous computed tomography image-guided stereotactic spinal radiotherapy: an emerging paradigm for achieving true stereotaxy.

PURPOSE: To report treatment setup data from an emerging technique using near-simultaneous computed tomography (CT) image-guided stereotactic radiotherapy for the treatment of spinal and paraspinal tumors. METHODS AND MATERIALS: A targeting system that integrates a CT-on-rails scanner with a linear accelerator (LINAC) was evaluated in the lead-in portion of a Phase I/II protocol for treating patients with paraspinal metastases. Patients were immobilized in supine position by a moldable body cushion vacuum wrapped with a plastic fixation sheet. Planning CT and immediately repeated CT were performed on the LINAC/CT-on-rails unit to assess respiratory-related vertebral body motion. Coplanar intensity-modulated radiotherapy (IMRT) using 7-9 beams was used to deliver 30 Gy in five fractions to the target volume, while limiting the spinal cord dose to <10 Gy. Pretreatment CT scans were fused with the planning CT scans to determine the correct target isocenter by accounting for any translational and roll (axial) rotational discrepancies from the planning CT. (Corrections caused by yaw and pitch rotations have not yet been implemented.) The reproducibility of the treatment isocenter as compared with the planned isocenter was measured with digitally reconstructed radiographs (DRRs), portal film imaging, and immediate post-treatment verification CT scans. Phantom measurements were taken for dose verification for each IMRT plan. RESULTS: Based on a total of 36 CT scans (3 for planning, 3 for respiration study, 15 pretreatment, and 15 post-treatment) from 3 patients, no respiration-associated vertebral body motion was seen. A comparison of the corrected daily anterior-posterior (AP) and lateral (LAT) digital portal images with the planning AP and LAT DRRs confirmed that the isocenter setup accuracy for the 15 treatments was within 1 mm of the planning isocenter. The results from the immediate post-treatment CT scans reconfirmed the findings from the portal images and verified the absence of spinal movement during the treatment. The ion-chamber measurement for the high-dose region was within 2% of the planning dose for three patient treatment plans. Film dose measurement in an IMRT quality assurance phantom demonstrated good agreement from 90% to 30% isodose lines between the planned and measured results. CONCLUSION: Preliminary experience suggests that the near-simultaneous CT image-guided verification technique can be used as a new platform technology for extracranial applications of stereotactic radiotherapy and radiosurgery to spinal and paraspinal tumors.

Patient-specific quality assurance for prostate cancer patients receiving spot scanning proton therapy using single-field uniform dose.

PURPOSE: To describe our experiences with patient-specific quality assurance (QA) for patients with prostate cancer receiving spot scanning proton therapy (SSPT) using single-field uniform dose (SFUD). METHODS AND MATERIALS: The first group of 249 patients with prostate cancer treated with SSPT using SFUD was included in this work. The scanning-beam planning target volume and number of monitor units were recorded and checked for consistency. Patient-specific dosimetric measurements were performed, including the point dose for each plan, depth doses, and two-dimensional (2D) dose distribution in the planes perpendicular to the incident beam direction for each field at multiple depths. The γ-index with 3% dose or 3-mm distance agreement criteria was used to evaluate the 2D dose distributions. RESULTS: We observed a linear relationship between the number of monitor units and scanning-beam planning target volume. The difference between the measured and calculated point doses (mean ± SD) was 0.0% ± 0.7% (range, -2.9% to 1.8%). In general, the depth doses exhibited good agreement except at the distal end of the spread-out Bragg peak. The pass rate of γ-index (mean ± SD) for 2D dose comparison was 96.2% ± 2.6% (range, 90-100%). Discrepancies between the measured and calculated dose distributions primarily resulted from the limitation of the model used by the treatment planning system. CONCLUSIONS: We have established a patient-specific QA program for prostate cancer patients receiving SSPT using SFUD.

Optimal treatment planning for skull base chordoma: photons, protons, or a combination of both?

PURPOSE: We compared dosimetry of proton (PR), intensity modulated radiation therapy (IMRT) photon (PH), and combined PR and IMRT PH (PP) irradiation of skull base chordomas to determine the most optimal technique. METHODS AND MATERIALS: Computed tomography simulation scans of 5 patients with skull base chordoma were used to generate four treatment plans: an IMRT PH plan with 1-mm planning target volume (PTV; PH1) for stereotactic treatment, an IMRT PH plan with 3-mm PTV (PH3) for routine treatment, a PR plan with beam-specific expansion margins on the clinical target volume, and a PP plan combining PR and PH treatment. All plans were prescribed 74 Gy/Cobalt Gray equivalents (CGE) to the PTV. To facilitate comparison, the primary objective of all plans was 95% or greater PTV prescribed dose coverage. Plans then were optimized to limit dose to normal tissues. RESULTS: PTVs ranged from 4.4 to 36.7 cc in size (mean, 21.6 cc). Mean % PTV receiving 74 Gy was highest in the PP plans (98.4%; range, 96.5-99.2%) and lowest in the PH3 plans (96.1%; range, 95.1-96.7%). PR plans were the least homogeneous and conformal. PH3 plans had the highest mean % volume (V) of brain, brainstem, chiasm, and temporal lobes greater than tolerance doses. The PH1 plans had the lowest brainstem mean % V receiving 67 Gy (V(67Gy); 2.3 Gy; range, 0-7.8 Gy) and temporal lobe mean % V(65Gy) (4.3 Gy; range, 0.1-7.7 Gy). Global evaluation of the plans based on objective parameters revealed that PH1 and PP plans were more optimal than either single-modality PR or PH3 plans. CONCLUSIONS: There are dosimetric advantages to using either PH1 or PP plans, with the latter yielding the best target coverage and conformality.