Determining the optimal dosimetric leaf gap setting for rounded leaf-end multileaf collimator systems by simple test fields.

Individual QA for IMRT/VMAT plans is required by protocols. Sometimes plans cannot pass the institute's QA criteria. For the Eclipse treatment planning system (TPS) with rounded leaf-end multileaf collimator (MLC), one practical way to improve the agreement of planned and delivered doses is to tune the value of dosimetric leaf gap (DLG) in the TPS from the measured DLG. We propose that this step may be necessary due to the complexity of the MLC system, including dosimetry of small fields and the tongue-and-groove (T&G) effects, and report our use of test fields to obtain linac-specific optimal DLGs in TPSs. More than 20 original patient plans were reoptimized with the linac-specific optimal DLG value. We examined the distribution of gaps and T&G extensions in typical patient plans and the effect of using the optimal DLG on the distribution. The QA pass rate of patient plans using the optimal DLG was investigated. The dose-volume histograms (DVHs) of targets and organs at risk were checked. We tested three MLC systems (Varian millennium 120 MLC, high-definition 120 MLC, and Siemens 160 MLC) installed in four Varian linear accelerators (linacs) (TrueBEAM STx, Trilogy, Clinac 2300 iX, and Clinac 21 EX) and 1 Siemens linac (Artiste). With an optimal DLG, the individual QA for all those patient plans passed the institute's criteria (95% in DTA test or gamma test with 3%/3 mm/10%), even though most of these plans had failed to pass QA when using original DLGs optimized from typical patient plans or from the optimization process (automodeler) of Pinnacle TPS. Using either our optimal DLG or one optimized from typical patient plans or from the Pinnacle optimization process yielded similar DVHs.

Proton beam therapy: a fad or a new standard of care.

PURPOSE OF REVIEW: Newer methods and advances in radiation therapy promise to reduce the risk of complications in children who require irradiation. They have secured the role of radiation therapy in the treatment of a variety of pediatric central nervous system and solid tumors and for young patients enrolled on clinical trials. RECENT FINDINGS: Proton therapy is the latest advancement in radiation therapy. Its availability is increasing as new centers are built throughout the United States. Pediatric specialists should understand that proton therapy is in its pioneering stage of development and that advantages have not been quantitatively demonstrated. Proton therapy clearly reduces collateral radiation dose to normal tissue when compared with photon (X-ray)-based methods of irradiation and has the potential to selectively and safely escalate dose to high-risk tumors; however, research results are lacking in both of these areas, leading to some confusion among pediatric specialists with regard to indications and the need to refer patients for this limited resource and expensive form of radiation therapy. SUMMARY: This review highlights a number of issues surrounding proton therapy in children and supports the use of proton therapy in clinical trials.

Cyclotron and linear accelerator generated scanning proton beams for lung cancer SBRT: Interplay effects and mitigations.

BACKGROUND: Pencil beam scanning (PBS) proton therapy for moving targets is known to be impacted by interplay effects between the scanning beam and organ motion. While respiratory motion in the thoracic region is the major cause for organ motion, interplay effects depend on the delivery characteristics of proton accelerators. PURPOSE: To evaluate the impact of different types of PBS proton accelerators and spot sizes on interplay effects, mitigations, and plan quality for Stereotactic Body Radiation Therapy (SBRT) treatment of non-small cell lung cancer (NSCLC). METHODS: Twenty NSCLC patients treated with photon SBRT were selected to represent varying tumor volumes and respiratory motion amplitudes (median: 0.6 cm with abdominal compression) for this retrospective study. For each patient, plans were created using: (1) cyclotron-generated proton beams (CPB) with spot sizes of σ = 2.7-7.0 mm; (2) linear accelerator proton beams (LPB) (σ = 2.9-5.5 mm); and (3) linear accelerator proton minibeams (LPMB) (σ = 0.9-3.9 mm). The energy switching time is one second for CPB, and 0.005 s for LPMB and LPB. Plans were robustly optimized on the gross tumor volume (GTV) using each individual phase of four-dimensional computed tomography (4DCT) scans. Initially, single-field optimization (SFO) plans were evaluated; if the plan quality did not meet the dosimetric requirement, multi-field optimization (MFO) was used. MFO plans were created for all patients for comparisons. For each patient, all plans were normalized to have the same dose received by 99% of the GTV. Interplay effects were evaluated by computing the dose on 10 breathing phases, based on the spot distribution. Volumetric repainting (VR) was performed 2-6 times for each plan. We compared volume receiving 100% of the prescribed dose (V100%RX) of the GTV, and normal lung V20Gy. RESULTS: Twelve of 20 plans can be optimized sufficiently with SFO. SFO plans were less sensitive to the interplay effect compared to MFO plans in terms of target coverage for both LPB and LPMB. The following comparisons showed results utilizing the MFO technique. In the interplay evaluation without repainting, the mean V100%RX of the GTV were 99.42 ± 0.6%, 97.52 ± 3.9%, and 94.49 ± 7.3% for CPB, LPB, and LPMB plans, respectively. Following VR (2 × for CPB; 3 × for LPB; 5 × for LPMB), V100%RX of the GTV were improved (on average) by 0.13%, 1.84%, and 4.63%, respectively, achieving the acceptance criteria of V100%RX > 95%. Because of fast energy switch in linear accelerator proton machines, the delivery time for VR plans was the lowest for LPB plans, while delivery time for LPMB was on average 1 min longer than CPB plans. The advantage of small spot machines was better sparing in normal lung V20Gy, even when VR was applied. CONCLUSION: In the absence of repainting, proton machines with large spot sizes generated more robust plans against interplay effects. The number of VR increased with decreasing spot sizes to achieve the acceptance criteria. VR improved the plan robustness against interplay effects for modalities with small spot sizes and fast energy changes, preserving the low dose sparing aspect of the LPMB, even when motion is included.

Technical note: Determination of proton linear energy transfer from the integral depth dose.

BACKGROUND: Proton linear energy transfer (LET) is associated with the relative biological effectiveness of radiation on tissues. Monte Carlo (MC) simulations have been known to be the preferred method to calculate LET. Detectors have also been built to measure LET, but they need to be calibrated with MC simulations. PURPOSE: To propose and test a MC-free method for determining LET from the measured integral depth dose (LFI) of the protons of interest. METHOD AND MATERIALS: LFI consists of three steps: (1) IDD measurements, (2) extraction of energy spectrum (ES) from the IDD, and (3) LET determination from the extracted ES and the stopping power of each energy. To validate the accuracy of the extraction of ES, we use Gaussian ES to synthesize IDD, extract ES from the synthesized IDD, and then compare the original (ground truth) and extracted ES. LETs calculated from the original and extracted ES are also compared. To obtain the LET of protons of interest, we measure IDDs by a large-area plane-parallel ionization chamber in water. Finally, TOPAS MC is employed to simulate IDDs, ES, and LETs. From the simulated IDD, the extracted ES and LET are compared with the simulations from TOPAS MC. RESULTS: From the synthesized IDDs, the LETs agreed excellently when the peak energies ≥10 and 1.25 MeV with depth resolutions 0.1 and 0.01 mm, respectively. For energy <1.25 MeV, even higher depth resolution than 0.01 mm is required. From the MC simulated IDDs, our track-averaged LET excellently agreed with MC simulation, but not the LETd . Our LETd was smaller than MC simulated LETd in the shallow region but larger in the distal Bragg peak region. CONCLUSION: LET can be accurately determined from the IDD. This method can be used in the clinic to commission or validate LETs from other measurement methods or a treatment planning system.

Lateral dose profile characterization in scanning particle therapy.

PURPOSE: In light-ion beam dose delivery with the scanning technique the spacing between adjacent spots is an important parameter during treatment planning. In order to study the effect of spot spacing on dose conformity and robustness for single field uniform dose configurations, fundamental geometrical properties of placement of Gaussian beamlets are explored. In particular, the dependence of penumbra width and flatness on spot width and spot spacing is investigated. METHODS: Infinitesimal calculus and analytical methods are used to derive simple expressions for the lateral penumbra and the flatness of one-dimensional dose profiles in continuous scanning and uniform discrete spot scanning. In the same way expressions for the fundamental modes of perturbation of the spot sequence are developed. A numerical, matrix-based approach is followed to optimize weights spot-by-spot. RESULTS: Generally the lateral penumbra widths lie between 1.13 sigma(b) and 1.68 sigma(b) with sigma(b) being the standard deviation of the beam spot profile. For regularly placed spots of equal weight with spot spacing lambda the lateral penumbra is given by 1.68 sigma' where sigma' results from quadratic subtraction of lambda/square root of 12 from sigma(b). The quantization error is identified as additional parameter describing the lateral dose conformity. It's variance is given by lambda2/12 for a bunch of spots with uniform weights. The matrix-based optimization of weights for a one-dimensional dose box results in a lateral penumbra of typically 1.4 sigma(b). This value reduces to about 1.3 sigma(b) if also the positions of the beam spots are optimized for the considered field size. The analytical formulas for uniform discrete scanning can be used as rough approximations of the best-case scenarios for weight-optimized dose profiles if the spot spacing is defined as effective spot spacing. CONCLUSIONS: The trade-off between flatness, quantization error, and robustness on the one side and penumbra width on the other side can be described analytically for equally weighted spots. Treatment planning systems often perform a least-squares optimization of the individual spot weights which results in smaller lateral penumbras and smaller quantization errors than for uniform discrete scanning. However, the benefit of this weight optimization decreases with increasing lambda (in the regime lambda > sigma(b)). The spot spacing, which is obtained from the scenario that the optimization objective is met by uniform discrete scanning, poses a sharp upper limit for the spot spacing lambda in weight optimization methods.

Technical note: Extraction of proton pencil beam energy spectrum from measured integral depth dose in a cyclotron proton beam system.

PURPOSE: Proton pencil beam energy spectrum is an essential parameter for calculations of dose and linear energy transfer. We extract the energy spectrum from measured integral depth dose (IDD). METHODS: A measured IDD (measIDD) in water is decomposed into many IDDs of mono-energetic pencil beams (monoIDDs) in water. A simultaneous iterative technique is used to do the decomposition that extracts the energy spectrum of protons from the measIDD. The monoIDDs are generated by our analytic random walk model-based proton dose calculation algorithm. The linear independence of the monoIDDs is considered and high spatial resolution monoIDDs are used to improve their linear independence. To validate the extraction, first we use synthesized IDDs (synIDD) with Gaussian energy spectrum and compare the extracted energy spectrum with the Gaussian; second, for the energy spectrum extracted from measIDDs, the accuracy of the extraction is validated by comparing the calculated IDD from the energy spectrum with the measIDD. The measIDDs are derived from commissioning of a cyclotron proton pencil beam system with a Bragg peak ionization chamber. The nominal energy of the pencil beams is from 70 to 245 MeV. The monoIDDs are generated for energies from 0.05 to 275 MeV in steps of 0.05 MeV with a spatial resolution of 1 mm. RESULTS: The difference of the extracted and original Gaussian energy spectrum peaked at 75 and 80 MeV was <1%. As the energy decreased, the difference increased but was reduced by using 0.1-mm monoIDDs. The difference was not sensitive to the energy interval of monoIDDs when the interval increased from 0.05 to 1 MeV. For the energy spectrum extraction from measIDDs, there was a main peak near the nominal energy but the spectrum was not in Gaussian distribution. In three example cases (70, 160, and 245 MeV), the relative differences of the measIDDs and calculated IDDs were within 3.4%, 2.9%, and 4.7% of the Bragg peak value, respectively. Fitting the spectrum by Gaussian distribution, we had σ = 0.87, 1.51, and 0.86 MeV, respectively, for these three examples, and the relative differences of the resultant calculated IDDs from the measIDDs were within 4.7%, 7.4%, and 4.5%, respectively. CONCLUSIONS: Our algorithm accurately extracted the energy spectrum from the synIDDs and measIDDs. High-resolution monoIDDs are necessary to extract low-energy spectrum. Energy spectrum extraction from measIDD reveals important information for beam modeling.

Clinical commissioning of intensity-modulated proton therapy systems: Report of AAPM Task Group 185.

Proton therapy is an expanding radiotherapy modality in the United States and worldwide. With the number of proton therapy centers treating patients increasing, so does the need for consistent, high-quality clinical commissioning practices. Clinical commissioning encompasses the entire proton therapy system's multiple components, including the treatment delivery system, the patient positioning system, and the image-guided radiotherapy components. Also included in the commissioning process are the x-ray computed tomography scanner calibration for proton stopping power, the radiotherapy treatment planning system, and corresponding portions of the treatment management system. This commissioning report focuses exclusively on intensity-modulated scanning systems, presenting details of how to perform the commissioning of the proton therapy and ancillary systems, including the required proton beam measurements, treatment planning system dose modeling, and the equipment needed.

Validation of dosimetric field matching accuracy from proton therapy using a robotic patient positioning system.

Large area, shallow fields are well suited to proton therapy. However, due to beam production limitations, such volumes typically require multiple matched fields. This is problematic due to the relatively narrow beam penumbra at shallow depths compared to electron and photon beams. Therefore, highly accurate dose planning and delivery is required. As the dose delivery includes shifting the patient for matched fields, accuracy at the 1-2 millimeter level in patient positioning is also required. This study investigates the dosimetric accuracy of such proton field matching by an innovative robotic patient positioner system (RPPS). The dosimetric comparisons were made between treatment planning system calculations, radiographic film and ionization chamber measurements. The results indicated good agreement amongst the methods and suggest that proton field matching by a RPPS is accurate and efficient.

Technical Note: Design and characterization of a large diameter parallel plate ionization chamber for accurate integral depth dose measurements with proton beams.

PURPOSE: The goal was to develop and test a large diameter parallel plate ionization chamber capable of intercepting at least 98% of the proton beamlets tested with the system. METHODS: A commercial synchrotron proton therapy system was used for the study (Hitachi, Ltd, Hitachi City, Japan; Model: Probeat-V). The energies investigated were in the range of 100 to 192 MeV. Three beam spot options available from the system were used. A PTW Bragg peak IC of diameter 84 mm (BP84) (Model PTW34070) was employed for comparison in a scanning water phantom. A prototype of 150 mm diameter was produced (PTW, Freiburg, Germany; model: T34089) and used for the testing. Monte Carlo calculations were also performed with FLUKA to guide the BP150 design and for comparison to the radiological measurements. For comparison, a 40 cm diameter ideal virtual detector was included in the Monte Carlo model. RESULTS: The measured proton range R90 agrees between the BP84 and BP150 ionization chambers within +0.06/-0.27 mm across the energies 100-192 MeV, which is less than the daily experimental setup uncertainty of 0.4 mm. The differences in the absolute integral depth dose curves (IDDs) between the BP84 and BP150 ranged from 0.3% to 1.0% for the spot sizes and beam energies tested. As predicted by the Monte Carlo modeling, the greatest differences were found in the plateau region of the IDDs. Also, the IDDs measured with the BP150 were very similar to those of the ideal 40 cm diameter detector Monte Carlo simulations. CONCLUSIONS: We conclude that the BP150 offers a small, but a useful reduction in uncertainty from the nuclear halo effect for the system under test.

Range and modulation dependencies for proton beam dose per monitor unit calculations.

Calculations of dose per monitor unit (D/MU) are required in addition to measurements to increase patient safety in the clinical practice of proton radiotherapy. As in conventional photon and electron therapy, the D/MU depends on several factors. This study focused on obtaining range and modulation dependence factors used in D/MU calculations for the double scattered proton beam line at the Midwest Proton Radiotherapy Institute. Three dependencies on range and one dependency on modulation were found. A carefully selected set of measurements was performed to discern these individual dependencies. Dependencies on range were due to: (1) the stopping power of the protons passing through the monitor chamber; (2) the reduction of proton fluence due to nuclear interactions within the patient; and (3) the variation of proton fluence passing through the monitor chamber due to different source-to-axis distances (SADs) for different beam ranges. Different SADs are produced by reconfigurations of beamline elements to provide different field sizes and ranges. The SAD effect on the D/MU varies smoothly as the beam range is varied, except at the beam range for which the first scatterers are exchanged and relocated to accommodate low and high beam ranges. A geometry factor was devised to model the SAD variation effect on the D/MU. The measured D/MU variation as a function of range can be predicted within 1% using the three modeled dependencies on range. Investigation of modulated beams showed that an analytical formula can predict the D/MU dependency as a function of modulation to within 1.5%. Special attention must be applied when measuring the D/MU dependence on modulation to avoid interplay between range and SAD effects.

Energy spectrum control for modulated proton beams.

In proton therapy delivered with range modulated beams, the energy spectrum of protons entering the delivery nozzle can affect the dose uniformity within the target region and the dose gradient around its periphery. For a cyclotron with a fixed extraction energy, a rangeshifter is used to change the energy but this produces increasing energy spreads for decreasing energies. This study investigated the magnitude of the effects of different energy spreads on dose uniformity and distal edge dose gradient and determined the limits for controlling the incident spectrum. A multilayer Faraday cup (MLFC) was calibrated against depth dose curves measured in water for nonmodulated beams with various incident spectra. Depth dose curves were measured in a water phantom and in a multilayer ionization chamber detector for modulated beams using different incident energy spreads. Some nozzle entrance energy spectra can produce unacceptable dose nonuniformities of up to +/-21% over the modulated region. For modulated beams and small beam ranges, the width of the distal penumbra can vary by a factor of 2.5. When the energy spread was controlled within the defined limits, the dose nonuniformity was less than +/-3%. To facilitate understanding of the results, the data were compared to the measured and Monte Carlo calculated data from a variable extraction energy synchrotron which has a narrow spectrum for all energies. Dose uniformity is only maintained within prescription limits when the energy spread is controlled. At low energies, a large spread can be beneficial for extending the energy range at which a single range modulator device can be used. An MLFC can be used as part of a feedback to provide specified energy spreads for different energies.

AAPM task group 224: Comprehensive proton therapy machine quality assurance.

PURPOSE:  Task Group (TG) 224 was established by the American Association of Physicists in Medicine's Science Council under the Radiation Therapy Committee and Work Group on Particle Beams. The group was charged with developing comprehensive quality assurance (QA) guidelines and recommendations for the three commonly employed proton therapy techniques for beam delivery: scattering, uniform scanning, and pencil beam scanning. This report supplements established QA guidelines for therapy machine performance for other widely used modalities, such as photons and electrons (TG 142, TG 40, TG 24, TG 22, TG 179, and Medical Physics Practice Guideline 2a) and shares their aims of ensuring the safe, accurate, and consistent delivery of radiation therapy dose distributions to patients. METHODS:  To provide a basis from which machine-specific QA procedures can be developed, the report first describes the different delivery techniques and highlights the salient components of the related machine hardware. Depending on the particular machine hardware, certain procedures may be more or less important, and each institution should investigate its own situation. RESULTS:  In lieu of such investigations, this report identifies common beam parameters that are typically checked, along with the typical frequencies of those checks (daily, weekly, monthly, or annually). The rationale for choosing these checks and their frequencies is briefly described. Short descriptions of suggested tools and procedures for completing some of the periodic QA checks are also presented. CONCLUSION:  Recommended tolerance limits for each of the recommended QA checks are tabulated, and are based on the literature and on consensus data from the clinical proton experience of the task group members. We hope that this and other reports will serve as a reference for clinical physicists wishing either to establish a proton therapy QA program or to evaluate an existing one.

Dosimetric impact of intrafraction motion for compensator-based proton therapy of lung cancer.

Compensator-based proton therapy of lung cancer using an un-gated treatment while allowing the patient to breathe freely requires a compensator design that ensures tumor coverage throughout respiration. Our investigation had two purposes: one is to investigate the dosimetric impact when a composite compensator correction is applied, or is not, and the other one is to evaluate the significance of using different respiratory phases as the reference computed tomography (CT) for treatment planning dose calculations. A 4D-CT-based phantom study and a real patient treatment planning study were performed. A 3D MIP dataset generated over all phases of the acquired 4D-CT scans was adopted to design the field-specific composite aperture and compensator. In the phantom study, the MIP-based compensator design plan named plan D was compared to the other three plans, in which average intensity projection (AIP) images in conjunction with the composite target volume contour copied from the MIP images were used. Relative electron densities within the target envelope were assigned either to original values from the AIP image dataset (plan A) or to predetermined values, 0.8 (plan B) and 0.9 (plan C). In the patient study, the dosimetric impact of a compensator design based on the MIP images (plan ITV(MIP)) was compared to designs based on end-of-inhale (EOI) (plan ITV(EOI)) and middle-of-exhale (MOE) CT images (plan ITV(MOE)). The dose distributions were recalculated for each phase. Throughout the ten phases, it shows that D(GTV)(min) changed slightly from 86% to 89% (SD = 0.9%) of prescribed dose (PD) in the MIP plan, while varying greatly from 10% to 79% (SD = 26.7%) in plan A, 17% to 73% (SD = 22.5%) in plan B and 53% to 73% (SD = 6.8%) in plan C. The same trend was observed for D(GTV)(mean) and V95 with less amplitude. In the MIP-based plan ITV(MIP), D(GTV)(mean) was almost identically equal to 95% in each phase (SD = 0.5%). The patient study verified that the MIP approach increased the minimum value of D99 of the clinical target volume (CTV) by 58.8% compared to plan ITV(EOI) and 12.9% compared to plan ITV(MOE). Minimum values of D99 were 37.60%, 83.50% and 96.40% for plan ITV(EOI), plan ITV(MOE) and plan ITV(MIP), respectively. Standard deviations of D99 were significantly decreased (SD = 0.5%) in the MIP plan as compared to plan ITV(EOI) (SD = 18.9%) or plan ITV(MOE) (SD = 4.0%). These studies demonstrate that the use of MIP images to design the patient-specific composite compensators provide superior and consistent tumor coverage throughout the entire respiratory cycle whilst maintaining a low average normal lung dose. The additional benefit of the MIP-based design approach is that the dose calculation can be implemented on any single phase as long as it uses the aperture and compensator optimized from the MIP images. This also reduces the requirement for contouring on all breathing phases down to just one.

New horizons in particle therapy systems.

Particle therapy is rapidly expanding and claiming its position as the treatment modality of choice in teletherapy. However, the rate of expansion continues to be restricted by the size and cost of the associated particle therapy systems and their operation. Additional technical limitations such as dose delivery rate, treatment process efficiency, and achievement of superior dose conformity potentially hinder the complete fulfillment of the promise of particle therapy. These topics are explored in this review considering the current state of particle therapy systems and what improvements are required to overcome the current challenges. Beam production systems (accelerators), beam transport systems including gantries and beam delivery systems are addressed explicitly in these regards.

Feasibility study of range-based registration using daily cone beam CT for intensity-modulated proton therapy.

PURPOSE: Proton dose coverage is sensitive to proton beam range. The current practice of CT number-based registration for patient positioning focuses on matching the target and is not sufficient for proton therapy because the proton range depends on the medium traversed by the beam. Patient body deformations and anatomical changes result in range deviation in the target. We propose proton range-based registration to minimize the range deviation. METHODS: The range was calculated from cone beam-computed tomography (CBCT) of the patient on couch, and the range deviation was the difference of the calculated range from that on the initial (day 1) CBCT. In the investigated prostate cases in which the main cause of range deviation was the rotation of femur bones, and in the investigated abdomen cases in which the main cause of range deviation was body growth and anatomic change, our range-based registration was used to obtain the optimal beam angle by minimizing the range deviation. The new angle was limited to be ±5° from that planned to prevent potentially increased dose to the organs at risk. To demonstrate the benefit of range-based registration, we investigated the range at the voxels on the surface of the target volume. The calculation error of range deviation due to CBCT scatter was investigated by using solid water phantoms with different thicknesses. Range-based registration using both CBCTs and CTs was performed in cases of two patients with pelvic rhabdomyosarcoma and one patient with upper abdominal tumor. The range was represented by the water-equivalent thickness to shorten the computation for online application purposes. RESULTS: In the phantom study, the calculation error of range deviation due to CBCT scatter was within 2 mm for a 1-cm thickness change (the mean range deviation was 0.8 mm). In the CT study of the prostate cases, the range deviation (mean ± root-mean-square deviation) on the contour in each slice was efficiently reduced from 3.6 ± 2.8 mm to 2.1 ± 1.4 mm, with most slices being within 3 mm; in the CT study of the abdomen cases, the range deviation of the whole set was reduced from 4.4 ± 1.9 mm to 3.5 ± 2.1 mm. Both the mean and root-mean-square deviation of the range deviation on each treatment day were decreased. The dose coverage on the target was improved and the dose on the OARs was only slightly changed. CONCLUSION: Range-based registration can efficiently mitigate range deviation due to patient positioning and anatomical changes. It can shorten patient positioning time and reduce the patient's dose from CBCT.

Scattered neutron dose equivalent from an active scanning proton beam delivery system.

A study of neutron production from a novel active scanning proton beam delivery system at the Midwest Proton Radiotherapy Institute (MPRI) has been performed. The neutron dose equivalent was determined using a neutron rem (roentgen equivalent in man) detector which has an upper energy limit of 10 MeV. Measurement were taken at 0, 45, and 90 degrees from the proton beam central axis and for various proton beam energies (127-208 MeV) and scanned field sizes (25-144 cm2). The maximum neutron dose observed was 0.43 mSv / (proton treatment Gy) at 90 degrees from the beam axis for a beam energy of 208.4 MeV and a scanned field size of 144 cm2. It is still possible to further mitigate this secondary neutron dose during treatment by optimizing parameters within the treatment nozzle and using shielding.

Premature Ovarian Insufficiency in Childhood Cancer Survivors: A Report From the St. Jude Lifetime Cohort.

Context: Long-term follow-up data on premature ovarian insufficiency (POI) in childhood cancer survivors are limited. Objective: To describe the prevalence of POI, its risk factors, and associated long-term adverse health outcomes. Design: Cross-sectional. Setting: The St. Jude Lifetime Cohort Study, an established cohort in a tertiary care center. Patients: Nine hundred twenty-one participants (median age, 31.7 years) were evaluated at a median of 24.0 years after cancer diagnosis. Main Outcome Measure: POI was defined by persistent amenorrhea combined with a follicle-stimulating hormone level >30 IU/L before age 40. Multivariable Cox regression was used to study associations between demographic or treatment-related risk factors and POI. Multivariable logistic regression was used to study associations between POI and markers for cardiovascular disease, bone mineral density (BMD), and frailty. Exposure to alkylating agents was quantified using the validated cyclophosphamide equivalent dose (CED). Results: The prevalence of POI was 10.9%. Independent risk factors for POI included ovarian radiotherapy at any dose and CED ≥8000 mg/m2. Patients with a body mass index ≥30 kg/m2 at the time of the St. Jude Lifetime Cohort assessment were less likely to have a diagnosis of POI. Low BMD and frailty were independently associated with POI. Conclusion: High-dose alkylating agents and ovarian radiotherapy at any dose are associated with POI. Patients at the highest risk should be offered fertility preservation whenever feasible. POI contributes to poor general health outcomes in childhood cancer survivors; further studies are needed to investigate the role of sex hormone replacement in improving such outcomes.

Neutron scattered dose equivalent to a fetus from proton radiotherapy of the mother.

Scattered neutron dose equivalent to a representative point for a fetus is evaluated in an anthropomorphic phantom of the mother undergoing proton radiotherapy. The effect on scattered neutron dose equivalent to the fetus of changing the incident proton beam energy, aperture size, beam location, and air gap between the beam delivery snout and skin was studied for both a small field snout and a large field snout. Measurements of the fetus scattered neutron dose equivalent were made by placing a neutron bubble detector 10 cm below the umbilicus of an anthropomorphic Rando phantom enhanced by a wax bolus to simulate a second trimester pregnancy. The neutron dose equivalent in milliSieverts (mSv) per proton treatment Gray increased with incident proton energy and decreased with aperture size, distance of the fetus representative point from the field edge, and increasing air gap. Neutron dose equivalent to the fetus varied from 0.025 to 0.450 mSv per proton Gray for the small field snout and from 0.097 to 0.871 mSv per proton Gray for the large field snout. There is likely to be no excess risk to the fetus of severe mental retardation for a typical proton treatment of 80 Gray to the mother since the scattered neutron dose to the fetus of 69.7 mSv is well below the lower confidence limit for the threshold of 300 mGy observed for the occurrence of severe mental retardation in prenatally exposed Japanese atomic bomb survivors. However, based on the linear no threshold hypothesis, and this same typical treatment for the mother, the excess risk to the fetus of radiation induced cancer death in the first 10 years of life is 17.4 per 10,000 children.

A simplified analytical random walk model for proton dose calculation.

We propose an analytical random walk model for proton dose calculation in a laterally homogeneous medium. A formula for the spatial fluence distribution of primary protons is derived. The variance of the spatial distribution is in the form of a distance-squared law of the angular distribution. To improve the accuracy of dose calculation in the Bragg peak region, the energy spectrum of the protons is used. The accuracy is validated against Monte Carlo simulation in water phantoms with either air gaps or a slab of bone inserted. The algorithm accurately reflects the dose dependence on the depth of the bone and can deal with small-field dosimetry. We further applied the algorithm to patients' cases in the highly heterogeneous head and pelvis sites and used a gamma test to show the reasonable accuracy of the algorithm in these sites. Our algorithm is fast for clinical use.