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This manuscript describes the structure, management and outcomes of a multi-institutional clinical and research medical physics residency program (Harvard Medical Physics Residency Program, or HMPRP) to provide potentially useful information to the centers considering a multi-institutional approach for their training programs.Data from the program documents and public records was used to describe HMPRP and obtain statistics about participating faculty, enrolled residents, and graduates. Challenges associated with forming and managing a multi-institutional program and developed solutions for effective coordination between several clinical centers are described.HMPRP was formed in 2009 and was accredited by the Commission on Accreditation of Medical Physics Education Programs (CAMPEP) in 2011. It is a 3-year therapy program, with a dedicated year of research and the 2 years of clinical training at three academic hospitals. A CAMPEP-accredited Certificate Program is embedded in HMPRP to allow enrolled residents to complete a formal didactic training in medical physics if necessary. The clinical training covers the material required by CAMPEP. In addition, training in protons, CyberKnife, MR-linac, and at network locations is included. The clinical training and academic record of the residents is outstanding. All graduates have found employment within clinical medical physics, mostly at large academic centers and graduates had a 100% pass rate at the oral American Board of Radiology exams. On average, three manuscripts per resident are published during residency, and multiple abstracts are presented at conferences.A multi-institutional medical physics residency program can be successfully formed and managed. With a collaborative administrative structure, the program creates an environment for high-quality clinical training of the residents and high productivity in research. The main advantage of such program is access to a wide variety of resources. The main challenge is creating a structure for efficient management of multiple resources at different locations. This report may provide valuable information to centers considering starting a multi-institutional residency program.

Objective. Monte Carlo (MC) codes are increasingly used for accurate radiotherapy dose calculation. In proton therapy, the accuracy of the dose calculation algorithm is expected to have a more significant impact than in photon therapy due to the depth-dose characteristics of proton beams. However, MC simulations come at a considerable computational cost to achieve statistically sufficient accuracy. There have been efforts to improve computational efficiency while maintaining sufficient accuracy. Among those, parallelizing particle transportation using graphic processing units (GPU) achieved significant improvements. Contrary to the central processing unit, a GPU has limited memory capacity and is not expandable. It is therefore challenging to score quantities with large dimensions requiring extensive memory. The objective of this study is to develop an open-source GPU-based MC package capable of scoring those quantities. Approach. We employed a hash-table, one of the key-value pair data structures, to efficiently utilize the limited memory of the GPU and score the quantities requiring a large amount of memory. With the hash table, only voxels interacting with particles will occupy memory, and we can search the data efficiently to determine their address. The hash-table was integrated with a novel GPU-based MC code, moqui. Main results. The developed code was validated against an MC code widely used in proton therapy, TOPAS, with homogeneous and heterogeneous phantoms. We also compared the dose calculation results of clinical treatment plans. The developed code agreed with TOPAS within 2%, except for the fall-off and regions, and the gamma pass rates of the results were >99% for all cases with a 2 mm/2% criteria. Significance. We can score dose-influence matrix and dose-rate on a GPU for a 3-field H&N case with 10 GB of memory using moqui, which would require more than 100 GB of memory with the conventionally used array data structure.

Pencil beam scanning (PBS) monitoring chambers use an ionization control signal, monitor units (MUs), or gigaprotons (Gp) to irradiate a pencil beam and normalize dose calculations. The nozzle deflects the beam from the nozzle axis by an angle subtended at the source-to-axis distance (τ) from the isocenter. If the angle is not correctly considered in calibrations or calculations, it can lead to systematic errors.Aspects to consider for machines of various τs are fourfold. First, for the machine, there is a pathlength change of proton tracks in the monitor chamber. Second, for measurements, a uniform-square irradiation over a plane, with constant Gp per spot, does not deliver uniform dose in a measurement plane. Third, for Monte Carlo (MC) simulations, Gp (and not MU) is proportional to simulating a number of protons. Fourth, for pencil beam algorithms (PBA), MU or Gp may be used for pencil beam weight, but usage needs to be consistent. Another consideration is the beam shape change from circular to oval in the projection onto voxels.Coordinate systems for PBS delivery are described.Users of intermediate-τ machines, corresponding to the onset of 1% pathlength corrections within the scanned field size, must not assume that MUs are proportional to the number of particles in MC simulations, and the PBA may need pathlength corrections. For a field size of 24 × 24 cmIdentifying corrections due to the pencil beam angle and their onset are important for reducing the outer diameter of proton therapy gantries. The use of Gp (or the number of protons) meterset standardizes data interchange and helps to reduce systematic errors due to the angle of the beam.

Background and purpose Scatter correction of cone-beam computed tomography (CBCT) projections may enable accurate online dose-delivery estimations in photon and proton-based radiotherapy. This study aimed to evaluate the impact of scatter correction in CBCT-based proton range/dose calculations, in scans acquired in both proton and photon gantries. Material and methods CBCT projections of a Catphan and an Alderson phantom were acquired on both a proton and a photon gantry. The scatter corrected CBCTs (corrCBCTs) and the clinical reconstructions (stdCBCTs) were compared against CTs rigidly registered to the CBCTs (rigidCTs). The CBCTs of the Catphan phantom were segmented by materials for CT number analysis. Water equivalent path length (WEPL) maps were calculated through the Alderson phantom while proton plans optimized on the rigidCT and recalculated on all CBCTs were compared in a gamma analysis. Results In medium and high-density materials, the corrCBCT CT numbers were much closer to those of the rigidCT than the stdCBCTs. E.g. in the 50% bone segmentations the differences were reduced from above 300 HU (with stdCBCT) to around 60–70 HU (with corrCBCT). Differences in WEPL from the rigidCT were typically well below 5 mm for the corrCBCTs, compared to well above 10 mm for the stdCBCTs with the largest deviations in the head and thorax regions. Gamma pass rates (2%/2mm) when comparing CBCT-based dose re-calculations to rigidCT calculations were improved from around 80% (with stdCBCT) to mostly above 90% (with corrCBCT). Conclusion Scatter correction leads to substantial artefact reductions, improving accuracy of CBCT-based proton range/dose calculations.

Purpose To investigate angular sensitivity of proton range variation due to anatomic change in patients and patient setup error via water equivalent path length (WEPL) calculations. Methods Proton range was estimated by calculating WEPL to the distal edge of target volume using planning CT (pCT) and weekly scatter-corrected cone-beam CT (CBCT) images of 11 head and neck patients. Range variation was estimated as the difference between the distal WEPLs calculated on pCT and scatter-corrected CBCT (cCBCT). This WEPL analysis was performed every five degrees ipsilaterally to the target. Statistics of the distal WEPL difference were calculated over the distal area to compare between different beam angles. Physician-defined contours were used for the WEPL calculation on both pCT and cCBCT, not considering local deformation of target volume. It was also tested if a couch kick (10°) can mitigate the range variation due to anatomic change and patient setup error. Results For most of the patients considered, median, 75% quantile, and 95% quantile of the distal WEPL difference were largest for posterior oblique angles, indicating a higher chance of overdosing normal tissues at distal edge with these angles. Using a couch kick resulted in decrease in the WEPL difference for some posterior oblique angles. Conclusions It was demonstrated that the WEPL change has angular dependency for the cohort of head and neck cancer patients. Selecting beam configuration robust to anatomic change in patient and patient setup error may improve the treatment outcome of head and neck proton therapy.

Purpose To automatically segment the diaphragm on individual lung cone-beam CT projection images, to enable real-time tracking of lung tumors using kilovoltage imaging. Methods The deep neural network Mask R-CNN was trained on 3500 raw cone-beam CT projection images from 10 lung cancer patients, with the diaphragm manually segmented on each image used as a ground truth label. Ground-truth breathing traces were extracted from each patient for both diaphragm hemispheres, and apex positions were compared against the predicted output of the neural network. Ten-fold cross-validation was used to evaluate the segmentation accuracy. Results The mean diaphragm apex prediction error was 4.4 mm. The mean percentage of projection images for which a successful prediction could me made was 87.3%. Prediction accuracy at some lateral gantry angles was worse due to overlap between diaphragm hemispheres, and the increased amount of fatty tissue. Conclusions The neural network was able to track the diaphragm apex position successfully. This allows accurate assessment of the breathing phase, which can be used to estimate the position of the lung tumor in real time.

Simple Summary The fast and accurate definition of structures is a main limiting factor in online adaptive proton therapy. In this study, different methods to include structure propagation uncertainties in the optimization were compared with adaptation using physician-drawn structures, uncorrected propagated structures, and no adaptation. While adaptation with physician-drawn structures resulted in the best adaptive plan quality and no adaptation in the worst, manual structure correction could be replaced by a fast 'plausibility check', and plans could be adapted with correction-free adaptation strategies. Currently, adaptive strategies require time- and resource-intensive manual structure corrections. This study compares different strategies: optimization without manual structure correction, adaptation with physician-drawn structures, and no adaptation. Strategies were compared for 16 patients with pancreas, liver, and head and neck (HN) cancer with 1-5 repeated images during treatment: 'reference adaptation', with structures drawn by a physician; 'single-DIR adaptation', using a single set of deformably propagated structures; 'multi-DIR adaptation', using robust planning with multiple deformed structure sets; 'conservative adaptation', using the intersection and union of all deformed structures; 'probabilistic adaptation', using the probability of a voxel belonging to the structure in the optimization weight; and 'no adaptation'. Plans were evaluated using reference structures and compared using a scoring system. The reference adaptation with physician-drawn structures performed best, and no adaptation performed the worst. For pancreas and liver patients, adaptation with a single DIR improved the plan quality over no adaptation. For HN patients, integrating structure uncertainties brought an additional benefit. If resources for manual structure corrections would prevent online adaptation, manual correction could be replaced by a fast 'plausibility check', and plans could be adapted with correction-free adaptation strategies. Including structure uncertainties in the optimization has the potential to make online adaptation more automatable., Cancers, 14 (16), ISSN:2072-6694

Background/purpose Setup variations and anatomical changes can severely affect the quality of head and neck intensity-modulated proton therapy (IMPT) treatments. The impact of these changes can be alleviated by increasing the plan’s robustness a priori, or by adapting the plan online. This work compares these approaches in the context of head and neck IMPT. Materials/methods A representative cohort of 10 head and neck squamous cell carcinoma (HNSCC) patients with daily cone-beam computed tomography (CBCT) was evaluated. For each patient, three IMPT plans were created: 1- a classical robust optimization (cRO) plan optimized on the planning CT, 2- an anatomical robust optimization (aRO) plan additionally including the two first daily CBCTs and 3- a plan optimized without robustness constraints, but online-adapted (OA) daily, using a constrained spot intensity re-optimization technique only. Results The cumulative dose following OA fulfilled the clinical objective of both the high-risk and low-risk clinical target volumes (CTV) coverage in all 10 patients, compared to 8 for aRO and 4 for cRO. aRO did not significantly increase the dose to most organs at risk compared to cRO, although the integral dose was higher. OA significantly reduced the integral dose to healthy tissues compared to both robust methods, while providing equivalent or superior target coverage. Conclusion Using a simple spot intensity re-optimization, daily OA can achieve superior target coverage and lower dose to organs at risk than robust optimization methods.

Background and purpose Scatter correction of cone-beam computed tomography (CBCT) projections may enable accurate online dose-delivery estimations in photon and proton-based radiotherapy. This study aimed to evaluate the impact of scatter correction in CBCT-based proton range/dose calculations, in scans acquired in both proton and photon gantries. Material and methods CBCT projections of a Catphan and an Alderson phantom were acquired on both a proton and a photon gantry. The scatter corrected CBCTs (corrCBCTs) and the clinical reconstructions (stdCBCTs) were compared against CTs rigidly registered to the CBCTs (rigidCTs). The CBCTs of the Catphan phantom were segmented by materials for CT number analysis. Water equivalent path length (WEPL) maps were calculated through the Alderson phantom while proton plans optimized on the rigidCT and recalculated on all CBCTs were compared in a gamma analysis. Results In medium and high-density materials, the corrCBCT CT numbers were much closer to those of the rigidCT than the stdCBCTs. E.g. in the 50% bone segmentations the differences were reduced from above 300 HU (with stdCBCT) to around 60–70 HU (with corrCBCT). Differences in WEPL from the rigidCT were typically well below 5 mm for the corrCBCTs, compared to well above 10 mm for the stdCBCTs with the largest deviations in the head and thorax regions. Gamma pass rates (2%/2mm) when comparing CBCT-based dose re-calculations to rigidCT calculations were improved from around 80% (with stdCBCT) to mostly above 90% (with corrCBCT). Conclusion Scatter correction leads to substantial artefact reductions, improving accuracy of CBCT-based proton range/dose calculations.

Radiation therapy treatments are typically planned based on a single image set, assuming that the patient’s anatomy and its position relative to the delivery system remains constant during the course of treatment. Similarly, the prescription dose assumes constant biological dose-response over the treatment course. However, variations can and do occur on multiple time scales. For treatment sites with significant intra-fractional motion, geometric changes happen over seconds or minutes, while biological considerations change over days or weeks. At an intermediate timescale, geometric changes occur between daily treatment fractions. Adaptive radiation therapy is applied to consider changes in patient anatomy during the course of fractionated treatment delivery. While traditionally adaptation has been done off-line with replanning based on new CT images, online treatment adaptation based on on-board imaging has gained momentum in recent years due to advanced imaging techniques combined with treatment delivery systems. Adaptation is particularly important in proton therapy where small changes in patient anatomy can lead to significant dose perturbations due to the dose conformality and finite range of proton beams. This review summarizes the current state-of-the-art of on-line adaptive proton therapy and identifies areas requiring further research.

Purpose Reirradiation has been proposed as an effective modality for recurrent central nervous system (CNS) malignancies in adults. We evaluated the toxicity and outcomes of CNS reirradiation in pediatric patients. Methods and Materials The data from pediatric patients Results Sixty-seven pediatric patients underwent CNS reirradiation. The primary diagnoses included medulloblastoma/primitive neuroectodermal tumor (n=20; 30%), ependymoma (n=19; 28%), germ cell tumor (n=8; 12%), high-grade glioma (n=9; 13%), low-grade glioma (n=5; 7%), and other (n=6; 9%). The median age at the first course of RT was 8.5 years (range 0.5-19.5) and was 12.3 years (range 3.3-30.2) at reirradiation. The median interval between RT courses was 2.0 years (range 0.3-16.5). The median radiation dose and fractionation in equivalent 2-Gy fractions was 63.7 Gy (range 27.6-74.8) for initial RT and 53.1 Gy (range 18.6-70.1) for repeat RT. The relapse location was infield in 52 patients (78%) and surrounding the initial RT field in 15 patients (22%). Thirty-seven patients (58%) underwent gross or subtotal resection at recurrence. The techniques used for reirradiation were intensity modulated RT (n=46), 3-dimensional conformal RT (n=9), stereotactic radiosurgery (n=4; 12-13 Gy × 1 or 5 Gy × 5), protons (n=4), combined modality (n=3), 2-dimensional RT (n=1), and brachytherapy (n=1). Radiation necrosis was detected in 2 patients after the first RT course and 1 additional patient after reirradiation. Six patients (9%) developed secondary neoplasms after initial RT (1 hematologic, 5 intracranial). One patient developed a secondary neoplasm identified shortly after repeat RT. The median overall survival after completion of repeat RT was 12.8 months for the entire cohort and 20.5 and 8.4 months for patients with recurrent ependymoma and medulloblastoma after reirradiation, respectively. Conclusions CNS reirradiation in pediatric patients could be a reasonable treatment option, with moderate survival noted after repeat RT. However, prospective data characterizing the rates of local control and toxicity are needed.

The high conformality of intensity-modulated proton therapy (IMPT) dose distributions causes treatment plans to be sensitive to geometrical changes during the course of a fractionated treatment. This can be addressed using adaptive proton therapy (APT). One important question in APT is the frequency of adaptations performed during a fractionated treatment, which is related to the question whether plan adaptation has to be done online or offline. The purpose of this work is to investigate the impact of weekly and daily online IMPT plan adaptation on the treatment quality for head and neck patients. A cohort of ten head and neck patients with daily acquired cone-beam CT (CBCT) images was evaluated retrospectively. Dose tracking of the IMPT treatment was performed for three scenarios: base plan with no adaptation (BP), weekly online adaptation (OAW), and daily online adaptation (OAD). Both adaptation schemes used an in-house developed online APT workflow, performing Monte Carlo dose calculations on scatter-corrected CBCTs. IMPT plan adaptation was achieved by only tuning the weights of a subset of beamlets, based on deformable image registration from the planning CT to each CBCT. Although OAD mitigated random delivery errors more effectively than OAW on a fraction per fraction basis, both OAW and OAD achieved the clinical goals for all ten patients, while BP failed for six cases. In the high-risk CTV, accumulated values of D 98% ranged between 97.15% and 99.73% of the prescription dose for OAD, with a median of 98.07%. For OAW, values between 95.02% and 99.26% were obtained, with a median of 97.61% of the prescription dose. Otherwise, the dose to most organs at risk was similar for all three scenarios. Globally, our results suggest that OAW could be used as an alternative approach to OAD for most patients in order to reduce the clinical workload.

Adaptive proton therapy (APT) is a promising approach for the treatment of head and neck cancers. One crucial element of APT is daily volumetric imaging of the patient in the treatment position. Such data can be acquired with cone-beam computed tomography (CBCT), although scatter artifacts make uncorrected CBCT images unsuitable for proton therapy dose calculation. The purpose of this work is to evaluate the performance of a U-shape deep convolutive neural network (U-Net) to perform projection-based scatter correction and enable fast and accurate dose calculation on CBCT images in the context of head and neck APT. CBCT projections are simulated for a cohort of 48 head and neck patients using a GPU accelerated Monte Carlo (MC) code . A U-Net is trained to reproduce MC projection-based scatter correction from raw projections. The accuracy of the scatter correction is experimentally evaluated using CT and CBCT images of an anthropomorphic head phantom. The potential of the method for head and neck APT is assessed by comparing proton therapy dose distributions calculated on scatter-free, uncorrected and scatter-corrected CBCT images. Finally, dose calculation accuracy is estimated in experimental patient images using a previously validated empirical scatter correction as reference. The mean and mean absolute HU differences between scatter-free and scatter-corrected images are -0.8 and 13.4 HU, compared to -28.6 and 69.6 HU for the uncorrected images. In the head phantom, the root-mean square difference of proton ranges calculated in the reference CT and corrected CBCT is 0.73 mm. The average 2%/2 mm gamma pass rate for proton therapy plans optimized in the scatter free images and re-calculated in the scatter-corrected ones is 98.89%. In experimental CBCT patient images, a 3%/3 mm passing rate of 98.72% is achieved between the proposed method and the reference one. All CBCT projection volume could be corrected in less than 5 seconds.

OBJECTIVE This study is a multi-institutional pooled analysis specific to imaging-based local control of spinal metastases in patients previously treated with conventional external beam radiation therapy (cEBRT) and then treated with re-irradiation stereotactic body radiotherapy (SBRT) to the spine as salvage therapy, the largest such study to date. METHODS The authors reviewed cases involving 215 patients with 247 spinal target volumes treated at 7 institutions. Overall survival was calculated on a patient basis, while local control was calculated based on the spinal target volume treated, both using the Kaplan-Meier method. Local control was defined as imaging-based progression within the SBRT target volume. Equivalent dose in 2-Gy fractions (EQD2) was calculated for the cEBRT and SBRT course using an α/β of 10 for tumor and 2 for both spinal cord and cauda equina. RESULTS The median total dose/number of fractions of the initial cEBRT was 30 Gy/10. The median SBRT total dose and number of fractions were 18 Gy and 1, respectively. Sixty percent of spinal target volumes were treated with single-fraction SBRT (median, 16.6 Gy and EQD2/10 = 36.8 Gy), and 40% with multiple-fraction SBRT (median 24 Gy in 3 fractions, EQD2/10 = 36 Gy). The median time interval from cEBRT to re-irradiation SBRT was 13.5 months, and the median duration of patient follow-up was 8.1 months. Kaplan-Meier estimates of 6- and 12-month overall survival rates were 64% and 48%, respectively; 13% of patients suffered a local failure, and the 6- and 12-month local control rates were 93% and 83%, respectively. Multivariate analysis identified Karnofsky Performance Status (KPS) < 70 as a significant prognostic factor for worse overall survival, and single-fraction SBRT as a significant predictive factor for better local control. There were no cases of radiation myelopathy, and the vertebral compression fracture rate was 4.5%. CONCLUSIONS Re-irradiation spine SBRT is effective in yielding imaging-based local control with a clinically acceptable safety profile. A randomized trial would be required to determine the optimal fractionation.

Purpose This work aims at investigating intensity corrected cone-beam x-ray computed tomography (CBCT) images for accurate dose calculation in adaptive intensity modulated proton therapy (IMPT) for prostate and head and neck (H&N) cancer. A deformable image registration (DIR)-based method and a scatter correction approach using the image data obtained from DIR as prior are characterized and compared on the basis of the same clinical patient cohort for the first time. Methods Planning CT (pCT) and daily CBCT data (reconstructed images and measured projections) of four H&N and four prostate cancer patients have been considered in this study. A previously validated Morphons algorithm was used for DIR of the planning CT to the current CBCT image, yielding a so-called virtual CT (vCT). For the first time, this approach was translated from H&N to prostate cancer cases in the scope of proton therapy. The warped pCT images were also used as prior for scatter correction of the CBCT projections for both tumor sites. Single field uniform dose and IMPT (only for H&N cases) treatment plans have been generated with a research version of a commercial planning system. Dose calculations on vCT and scatter corrected CBCT (CBCTcor) were compared by means of the proton range and a gamma-index analysis. For the H&N cases, an additional diagnostic replanning CT (rpCT) acquired within three days of the CBCT served as additional reference. For the prostate patients, a comprehensive contour comparison of CBCT and vCT, using a trained physician's delineation, was performed. Results A high agreement of vCT and CBCTcor was found in terms of the proton range and gamma-index analysis. For all patients and indications between 95% and 100% of the proton dose profiles in beam's eye view showed a range agreement of better than 3 mm. The pass rate in a (2%,2 mm) gamma-comparison was between 96% and 100%. For H&N patients, an equivalent agreement of vCT and CBCTcor to the reference rpCT was observed. However, for the prostate cases, an insufficient accuracy of the vCT contours retrieved from DIR was found, while the CBCTcor contours showed very high agreement to the contours delineated on the raw CBCT. Conclusions For H&N patients, no considerable differences of vCT and CBCTcor were found. For prostate cases, despite the high dosimetric agreement, the DIR yields incorrect contours, probably due to the more pronounced anatomical changes in the abdomen and the reduced soft-tissue contrast in the CBCT. Using the vCT as prior, these inaccuracies can be overcome and images suitable for accurate delineation and dose calculation in CBCT-based adaptive IMPT can be retrieved from scatter correction of the CBCT projections.

Purpose: Cone-beam CT (CBCT) imaging may enable image- and dose-guided proton therapy, but is challenged by image artefacts. The aim of this study was to demonstrate the general applicability of a previously developed a priori scatter correction algorithm to allow CBCT-based proton dose calculations. Methods: The a priori scatter correction algorithm used a plan CT (pCT) and raw cone-beam projections acquired with the Varian On-Board Imager. The projections were initially corrected for bow-tie filtering and beam hardening and subsequently reconstructed using the Feldkamp-Davis-Kress algorithm (rawCBCT). The rawCBCTs were intensity normalised before a rigid and deformable registration were applied on the pCTs to the rawCBCTs. The resulting images were forward projected onto the same angles as the raw CB projections. The two projections were subtracted from each other, Gaussian and median filtered, and then subtracted from the raw projections and finally reconstructed to the scatter-corrected CBCTs. For evaluation, water equivalent path length (WEPL) maps (from anterior to posterior) were calculated on different reconstructions of three data sets (CB projections and pCT) of three parts of an Alderson phantom. Finally, single beam spot scanning proton plans (0–360 deg gantry angle in steps of 5 deg; using PyTRiP) treating a 5 cm central spherical target in the pCT were re-calculated on scatter-corrected CBCTs with identical targets. Results: The scatter-corrected CBCTs resulted in sub-mm mean WEPL differences relative to the rigid registration of the pCT for all three data sets. These differences were considerably smaller than what was achieved with the regular Varian CBCT reconstruction algorithm (1–9 mm mean WEPL differences). Target coverage in the re-calculated plans was generally improved using the scatter-corrected CBCTs compared to the Varian CBCT reconstruction. Conclusion: We have demonstrated the general applicability of a priori CBCT scatter correction, potentially opening for CBCT-based image/dose-guided proton therapy, including adaptive strategies. Research agreement with Varian Medical Systems, not connected to the present project.

PURPOSE/OBJECTIVES There is little consensus regarding the application of stereotactic radiotherapy (SRT) in pediatrics. We evaluated patterns of pediatric SRT practice through an international research consortium. MATERIALS AND METHODS Eight international institutions with pediatric expertise completed a 124-item survey evaluating patterns of SRT use for patients 21 years old and younger. Frequencies of SRT use and median margins applied with and without SRT were evaluated. RESULTS Across institutions, 75% reported utilizing SRT in pediatrics. SRT was used in 22% of brain, 18% of spine, 16% of other bone, 16% of head and neck, and

Purpose To evaluate plan quality and delivery efficiency gains of volumetric modulated arc therapy (VMAT) versus a multicriteria optimization-based intensity modulated radiation therapy (MCO-IMRT) for stereotactic radiosurgery of spinal metastases. Methods and materials MCO-IMRT plans (RayStation V2.5; RaySearch Laboratories, Stockholm, Sweden) of 10 spinal radiosurgery cases using 7-9 beams were developed for clinical delivery, and patients were replanned using VMAT with partial arcs. The prescribed dose was 18 Gy, and target coverage was maximized such that the maximum dose to the planning organ-at-risk volume (PRV) of the spinal cord was 10 or 12 Gy. Dose-volume histogram (DVH) constraints from the clinically acceptable MCO-IMRT plans were utilized for VMAT optimization. Plan quality and delivery efficiency with and without collimator rotation for MCO-IMRT and VMAT were compared and analyzed based upon DVH, planning target volume coverage, homogeneity index, conformity number, cord PRV sparing, total monitor units (MU), and delivery time. Results The VMAT plans were capable of matching most DVH constraints from the MCO-IMRT plans. The ranges of MU were 4808-7193 for MCO-IMRT without collimator rotation, 3509-5907 for MCO-IMRT with collimator rotation, 4444-7309 for VMAT without collimator rotation, and 3277-5643 for VMAT with collimator of 90 degrees. The MU for the VMAT plans were similar to their corresponding MCO-IMRT plans, depending upon the complexity of the target and PRV geometries, but had a larger range. The delivery times of the MCO-IMRT and VMAT plans, both with collimator rotation, were 18.3 ± 2.5 minutes and 14.2 ± 2.0 minutes, respectively ( P Conclusions The MCO-IMRT and VMAT can create clinically acceptable plans for spinal radiosurgery. The MU for MCO-IMRT and VMAT can be reduced significantly by utilizing a collimator rotation following the orientation of the spinal cord. Plan quality for VMAT is similar to MCO-IMRT, with similar MU for both modalities. Delivery times can be reduced by nominally 25% with VMAT.

The differences between planning proton-beam therapy and photon-beam therapy derive from the differences in the physics of protons and photons, namely [1]: That protons have a finite and controllable (through choice of energy) penetration in depth with virtually no exit dose (Fig. 3.1). That the penetration of protons is strongly affected by the nature (e.g., density) of the tissues through which they pass, while photons are much less affected (density changes generally give rise to only small intensity changes, except for the lung). Therefore, heterogeneities are much more important in proton-beam therapy than in photon-beam therapy (Fig. 3.2). The apparatus for proton-beam delivery is different, and its details affect the dose distributions (Chap. 2).

Purpose Image guided radiation therapy (IGRT) has become common practice for both photon and proton radiation therapy, but there is little consensus regarding its application in the pediatric population. We evaluated clinical patterns of pediatric IGRT practice through an international pediatrics consortium comprised of institutions using either photon or proton radiation therapy. Methods and materials Seven international institutions with dedicated pediatric expertise completed a 53-item survey evaluating patterns of IGRT use in definitive radiation therapy for patients ≤21 years old. Two institutions use proton therapy for children and all others use IG photon therapy. Descriptive statistics including frequencies of IGRT use and means and standard deviations for planning target volume (PTV) margins by institution and treatment site were calculated. Results Approximately 750 pediatric patients were treated annually across the 7 institutions. IGRT was used in tumors of the central nervous system (98%), abdomen or pelvis (73%), head and neck (100%), lung (83%), and liver (69%). Photon institutions used kV cone beam computed tomography and kV- and MV-based planar imaging for IGRT, and all proton institutions used kV-based planar imaging; 57% of photon institutions used a specialized pediatric protocol for IGRT that delivers lower dose than standard adult protocols. Immobilization techniques varied by treatment site and institution. IGRT was utilized daily in 45% and weekly in 35% of cases. The PTV margin with use of IGRT ranged from 2 cm to 1 cm across treatment sites and institution. Conclusions Use of IGRT in children was prevalent at all consortium institutions. There was treatment site-specific variability in IGRT use and technique across institutions, although practices varied less at proton facilities. Despite use of IGRT, there was no consensus of optimum PTV margin by treatment site. Given the desire to restrict any additional radiation exposure in children to instances where the exposure is associated with measureable benefit, prospective studies are warranted to optimize IGRT protocols by modality and treatment site.

The purpose of this study was to determine the effects of geometric uncertainties of patient position on treatments of multiple nonisocentric intracranial lesions. The average distance between lesions in patients with multiple targets was determined by a retrospective survey of patients with multiple lesions. Retrospective patient imaging data from fractionated stereotactic patients were used to calculate interfractional and intrafractional patient position uncertainty. Three different immobilization devices were included in the positioning study. The interfractional and intrafractional patient positioning error data were used to calculate the geometric offset of a lesion located at varying distances from the mechanical isocenter for treatments of multiple lesions with a single arc, assuming that no intrafractional position correction is employed during an arc rotation. Dosimetric effects were studied using two representative lesions of two sizes, 6 mm and 13 mm maximum dimensions, and prescribed to 20 Gy and 18 Gy, respectively. Distances between lesions ranged from < 10 mm to 150 mm, which would correspond to a range of isocenter to lesion separations of < 10 mm to 75 mm, assuming an isocenter located at the geometric mean. In the presence of a full six degree of freedom patient correction system, the effects of the intrafractional patient positioning uncertainties were less than 1.8 mm (3.6 mm) for 1σ (2σ) deviations for lesion spacing up to 75 mm assuming a quadratic summation of 1σ and 2σ. Without the benefit of a six DOF correction device, only correcting for three translations, the effects of the intrafractional patient positioning uncertainties were within 3.1 mm (7.2 mm) for 1σ (2σ) deviations for distances up to 75 mm. 1σ and 2σ deviations along all six axes were observed in 3.6% and 0.3%, respectively, of 974 fractions analyzed. Dosimetric effects for 2 mm and 4 mm offsets were most significant for the small lesion with minimum dose (Dmin) decreasing from 20 Gy to 13.6 Gy and 5.7 Gy and volume receiving the prescription (V20Gy) reducing from 100% to 57% and 16%, respectively. The dosimetric effects on the larger lesion were less pronounced with Dmin reducing from 18 Gy to 17.5 Gy and 14.2 Gy, and V18Gy reducing from 100% to 98.3% and 85.4%, for 2 mm and 4 mm offsets, respectively. In the 1σ scenario (3.6% of patients) angular uncertainties in patient positioning can introduce 1.0 mm shifts in the location of the lesion position at distances of 75 mm, compared to an isocentric treatment even with a full six DOF correction. Without the ability to correct angular positioning errors, a lesion positioned 75 mm away from the mechanical isocenter can be located in 3.6% of patients > 3.0 mm distant from the planned position. Dosimetric results depend upon the distance from isocenter and the size of the target. Single isocenter treatments for multiple lesions should be considered only when full six DOF corrections can be applied, the intrafractional immobilization precision is well quantified, and a PTV expansion is included for more distant lesions to account for unavoidable residual patient positioning uncertainties. PACS number: 87.55.Qr, 87.53.Ly, 87.55.D‐

To promote accurate image-guided radiotherapy (IGRT) for a proton pencil beam scanning (PBS) system, a new quality assurance (QA) procedure employing a cone-shaped scintillator detector has been developed for multiple QA tasks in a semi-automatic manner. The cone-shaped scintillator detector (XRV-124, Logos Systems, CA) is sensitive to both x-ray and proton beams. It records scintillation on the cone surface as a 2D image, from which the geometry of the radiation field that enters and exits the cone can be extracted. Utilizing this feature, QA parameters that are essential to PBS IGRT treatment were measured and analyzed. The first applications provided coincidence checks of laser, imaging and radiation isocenters, and dependencies on gantry angle and beam energies. The analysis of the Winston-Lutz test was made available by combining the centricity measurements of the x-ray beam and the pencil beam. The accuracy of the gantry angle was validated against console readings provided by the digital encoder and an agreement of less than 0.2° was found. The accuracy of the position measurement was assessed with a robotic patient positioning system (PPS) and an agreement of less than 0.5 mm was obtained. The centricity of the two onboard x-ray imaging systems agreed well with that from the routinely used Digital Imaging Positioning System (DIPS), up to a consistent small shift of (-0.5 mm, 0.0 mm, -0.3 mm). The pencil beam spot size, in terms of σ of Gaussian fitting, agreed within 0.2 mm for most energies when compared to the conventional measurements by a 2D ion-chamber array (MatriXX-PT, IBA Dosimetry, Belgium). The cone-shaped scintillator system showed advantages in making multi-purpose measurements with a single setup. The in-house algorithms were successfully implemented to measure and analyze key QA parameters in a semi-automatic manner. This study presents an alternative and more efficient approach for IGRT QA for PBS and potentially for linear accelerators.

To develop an online plan adaptation algorithm for intensity modulated proton therapy (IMPT) based on fast Monte Carlo dose calculation and cone beam CT (CBCT) imaging. A cohort of ten head and neck cancer patients with an average of six CBCT scans were studied. To adapt the treatment plan to the new patient geometry, contours were propagated to the CBCTs with a vector field (VF) calculated with deformable image registration between the CT and the CBCTs. Within the adaptive planning algorithm, beamlets were shifted following the VF at their distal falloff and raytraced in the CBCT to adjust their energies, creating a geometrically adapted plan. Four geometric adaptation modes were studied: unconstrained geometric shifts (Free), isocenter shift (Iso), a range shifter (RS), or isocenter shift and range shifter (Iso-RS). After evaluation of the geometrical adaptation, the weights of a selected subset of beamlets were automatically tuned using MC-generated influence matrices to fulfill the original plan requirements. All beamlet calculations were done with a fast Monte Carlo running on a GPU (graphics processing unit). Geometrical adaptation alone only worked with small anatomy changes. The weight-tuned adaptation worked for every fraction, with the Free and Iso modes performing similarly and being superior than the two range shifters modes. The mean V95 and V107 were 99.4 ± 0.9 and 6.4% ± 4.7% in the Free mode with weight tuning. The calculation time per fraction was ~5 min, but further task parallelization could reduce it to ~1-2 min for delivery adaptation right after patient setup. An online adaptation algorithm was developed that significantly improved the treatment quality for inter-fractional geometry changes. Clinical implementation of the algorithm would allow delivery adaptation right before treatment and thus allow planning margin reductions for IMPT.

Purpose The purpose of this study is to evaluate the potential of using in-room positron emission tomography (PET) for treatment verification in proton therapy and for deriving suitable PET scan times. Methods and Materials Nine patients undergoing passive scattering proton therapy underwent scanning immediately after treatment with an in-room PET scanner. The scanner was positioned next to the treatment head after treatment. The Monte Carlo (MC) method was used to reproduce PET activities for each patient. To assess the proton beam range uncertainty, we designed a novel concept in which the measured PET activity surface distal to the target at the end of range was compared with MC predictions. The repositioning of patients for the PET scan took, on average, approximately 2 minutes. The PET images were reconstructed considering varying scan times to test the scan time dependency of the method. Results The measured PET images show overall good spatial correlations with MC predictions. Some discrepancies could be attributed to uncertainties in the local elemental composition and biological washout. For 8 patients treated with a single field, the average range differences between PET measurements and computed tomography (CT) image-based MC results were Conclusions Our first clinical trials in 9 patients using an in-room PET system demonstrated its potential for in vivo treatment monitoring in proton therapy. For a quantitative range prediction with arbitrary shape of target volume, we suggest using the distal PET activity surface.

Background/Objectives The practice of palliative radiation therapy (RT) is based on extrapolation from adult literature. We evaluated patterns of pediatric palliative RT to describe regimens used to identify opportunity for future pediatric-specific clinical trials. Design/Methods Six international institutions with pediatric expertise completed a 122-item survey evaluating patterns of palliative RT for patients ≤21 years old from 2010 to 2015. Two institutions use proton RT. Palliative RT was defined as treatment with the goal of symptom control or prevention of immediate life-threatening progression. Results Of 3,225 pediatric patients, 365 (11%) were treated with palliative intent to a total of 427 disease sites. Anesthesia was required in 10% of patients. Treatment was delivered to metastatic disease in 54% of patients. Histologies included neuroblastoma (30%), osteosarcoma (18%), leukemia/lymphoma (12%), rhabdomyosarcoma (12%), medulloblastoma/ependymoma (12%), Ewing sarcoma (8%), and other (8%). Indications included pain (43%), intracranial symptoms (23%), respiratory compromise (14%), cord compression (8%), and abdominal distention (6%). Sites included nonspine bone (35%), brain (16% primary tumors, 6% metastases), abdomen/pelvis (15%), spine (12%), head/neck (9%), and lung/mediastinum (5%). Re-irradiation comprised 16% of cases. Techniques employed three-dimensional conformal RT (41%), intensity-modulated RT (23%), conventional RT (26%), stereotactic body RT (6%), protons (1%), electrons (1%), and other (2%). The most common physician-reported barrier to consideration of palliative RT was the concern about treatment toxicity (83%). Conclusion There is significant diversity of practice in pediatric palliative RT. Combined with ongoing research characterizing treatment response and toxicity, these data will inform the design of forthcoming clinical trials to establish effective regimens and minimize treatment toxicity for this patient population.

Re-Irradiation for Recurrent Pediatric CNS Malignancies : A Multi-Institutional Retrospective Review

Purpose: To evaluate the effect of target trajectory shape on the optimal treatment margin. Methods: Intensity-modulated radiation therapy and volumetric modulated arc therapy plans were created for three spherical targets (3, 5, and 7 cm diameter) simulated in exhalation phases, each with margins of 2, 4, 6, 8, and 10 mm to account for motion. The plans were delivered to a stationary 2D ion chamber array, and dose movies were obtained of the delivered doses. The dose movie frames were then displaced to simulate different respiratory traces. Five traces were used: sin2, sin4, sin6, and two patient traces. The optimal margin was defined as the margin for which the dose delivered to 95% of the target was closest to that obtained with no margin or motion. The equivalent uniform dose was also investigated as an alternative cost function. Results: The optimal margin was always smaller than the peak-to-peak motion. When the respiratory trace spent less time in the inhale phases, the optimal margin was consistently smaller than when more time was spent in the inhale phases. The target size and treatment modality also affected the optimal margin. Conclusions: The necessary margin for targets that spend less time in the exhale phase (sin6) is 2–4 mm smaller than for targets that spend equal time in the inhale and exhale phases (sin).

Purpose: To design a fast Winston Lutz (fWL) algorithm for accurate analysis of radiation isocenter from images without edge detection or center of mass calculations. Methods: An algorithm has been developed to implement the Winston Lutz test for mechanical/radiation isocenter agreement using an electronic portal imaging device (EPID). The algorithm detects the position of the radiation shadow of a tungsten ball within a stereotactic cone. The fWL algorithm employs a double convolution to independently find the position of the sphere and cone centers. Subpixel estimation is used to achieve high accuracy. Results of the algorithm were compared to (1) a human observer with template guidance and (2) an edge detection/center of mass (edCOM) algorithm. Testing was performed with high resolution (0.05mm/px, film) and low resolution (0.78mm/px, EPID) image sets. Results: Sphere and cone center relative positions were calculated with the fWL algorithm for high resolution test images with an accuracy of 0.002{+-}0.061 mm compared to 0.042{+-}0.294 mm for the human observer, and 0.003{+-}0.038 mm for the edCOM algorithm. The fWL algorithm required 0.01 s per image compared to 5 s for the edCOM algorithm and 20 s for the human observer. For lower resolution images the fWL algorithm localized themore » centers with an accuracy of 0.083{+-}0.12 mm compared to 0.03{+-}0.5514 mm for the edCOM algorithm. Conclusions: A fast (subsecond) subpixel algorithm has been developed that can accurately determine the center locations of the ball and cone in Winston Lutz test images without edge detection or COM calculations.« less

Purpose: To compare the effect of respiration-induced motion on delivered dose (the interplay effect) for different treatment techniques under realistic clinical conditions. Methods: A flexible resin tumor model was created using rapid prototyping techniques based on a computed tomography (CT) image of an actual tumor. Twenty micro-MOSFETs were inserted into the tumor model and the tumor model was inserted into an anthropomorphic breathing phantom. Phantom motion was programed using the motion trajectory of an actual patient. A four-dimensional CT image was obtained and several treatment plans were created using different treatment techniques and planning systems: Conformal (Eclipse), step-and-shoot intensity-modulated radiation therapy (IMRT) (Pinnacle), step-and-shoot IMRT (XiO), dynamic IMRT (Eclipse), complex dynamic IMRT (Eclipse), hybrid IMRT [60% conformal, 40% dynamic IMRT (Eclipse)], volume-modulated arc therapy (VMAT) [single-arc (Eclipse)], VMAT [double-arc (Eclipse)], and complex VMAT (Eclipse). The complex plans were created by artificially pushing the optimizer to give complex multileaf collimator sequences. Each IMRT field was irradiated five times and each VMAT field was irradiated ten times, with each irradiation starting at a random point in the respiratory cycle. The effect of fractionation was calculated by randomly summing the measured doses. The maximum deviation for each measurement point per fraction and the more » probability that 95% of the model tumor had dose deviations less than 2% and 5% were calculated as a function of the number of fractions. Tumor control probabilities for each treatment plan were calculated and compared. Results: After five fractions, measured dose deviations were less than 2% for more than 95% of measurement points within the tumor model for all plans, except the complex dynamic IMRT, step-and-shoot IMRT (XiO), complex VMAT, and single-arc VMAT plans. Reducing the dose rate of the complex IMRT plans from 600 to 200 MU/min reduced the dose deviations to less than 2%. Dose deviations were less than 5% after five fractions for all plans, except the complex single-arc VMAT plan. Conclusions: Rapid prototyping techniques can be used to create realistic tumor models. For most treatment techniques, the dose deviations averaged out after several fractions. Treatments with unusually complicated multileaf collimator sequences had larger dose deviations. For IMRT treat-ments, dose deviations can be reduced by reducing the dose rate. For VMAT treatments, using two arcs instead of one is effective for reducing dose deviations. « less

PURPOSE To balance dose reduction and image registration accuracy in breast setup imaging. In particular, the authors demonstrate the relationship between scan angle and dose delivery for cone beam tomosynthesis (CBTS) when employed for setup verification of breast cancer patients with surgical clips. METHODS The dose measurements were performed in a female torso phantom for varying scan angles of CBTS. Setup accuracy was measured using three registration methods: Clip centroid localization accuracy and the accuracy of two semiautomatic registration algorithms. The dose to the organs outside of the ipsilateral breast and registration accuracy information were compared to determine the optimal scan angle for CBTS for breast patient setup verification. Isocenter positions at the center of the patient and at the breast-chest wall interface were considered. RESULTS Image registration accuracy was within 1 mm for the CBTS scan angles theta above 20 degrees for some scenarios and as large as 80 degrees for the worst case, depending on the imaged breast and registration algorithm. Registration accuracy was highest based on clip centroid localization. For left and right breast imaging with the isocenter at the chest wall, the dose to the contralateral side of the patient was very low (

Purpose: We have investigated the dosimetric errors caused by the interplay between the motions of the LINAC and the tumor during the delivery of a volume modulated arc therapy treatment. This includes the development of an IMRT QA technique, applied here to evaluate RapidArc plans of varying complexity. Methods: An IMRT QA technique was developed, which involves taking a movie of the delivered dose (0.2 s frames) using a 2D ion chamber array. Each frame of the movie is then moved according to a respiratory trace and the cumulative dose calculated. The advantage of this approach is that the impact of turning the beam on at different points in the respiratory trace, and of different types of motion, can be evaluated using data from a single irradiation. We evaluated this technique by comparing with the results when we actually moved the phantom during irradiation. RapidArc plans were created to treat a 62 cc spherical tumor in a lung phantom (16 plans) and a 454 cc irregular tumor in an actual patient (five plans). The complexity of each field was controlled by adjusting the MU (312-966 MU). Each plan was delivered to a phantom, and a movie of the delivered dosemore » taken using a 2D ion chamber array. Patient motion was modeled by shifting each dose frame according to a respiratory trace, starting the motion at different phases. The expected dose distribution was calculated by blurring the static dose distribution with the target motion. The dose error due to the interplay effect was then calculated by comparing the delivered dose with the expected dose distribution. Peak-to-peak motion of 0.5, 1.0, and 2.0 cm in the craniocaudal and right-left directions, with target periods of 3 and 5 s, were evaluated for each plan (252 different target motion/plan combinations). Results: The daily dose error due to the interplay effect was less than 10% for 98.4% of all pixels in the target for all plans investigated. The percentage of pixels for which the daily dose error could be larger than 5% increased with increasing plan complexity (field MU), but was less than 15% for all plans if the motion was 1 cm or less. For 2 cm motion, the dose error could be larger than 5% for 40% of pixels, but was less than 5% for more than 80% of pixels for MU

A systematic set of measurements is reported for evaluation of doses to critical organs resulting from cone-beam CT (CB-CT) and cone-beam tomosynthesis (CB-TS) as applied to breast setup for external beam irradiation. The specific focus of this study was on evaluation of doses from these modalities in a setting of volumetric breast imaging for target localization in radiotherapy treatments with the goal of minimizing radiation to healthy organs. Ion chamber measurements were performed in an anthropomorphic female thorax phantom at the center of each breast and lung and on the phantom surface at one anterior and two lateral locations (seven points total). The measurements were performed for three different isocenters located at the center of the phantom and at offset locations of the right and left breast. The dependence of the dose on angle selection for the CB-TS arc was also studied. For the most typical situation of centrally located CB-CT isocenter the measured doses ranged between 3 and 7 cGy, in good agreement with previous reports. Dose measurements were performed for a range of start/stop angles commonly used for CB-TS and the impact of direct and scatter dose on organs at risk was analyzed. All measured CB-TS doses were considerably lower than CB-CT doses, with greater decrease in dose for the organs outside of the beam (up to 98% decrease in dose). Remarkably, offsetting the isocenter towards the ipsilateral breast resulted on average to additional 46% dose reduction to organs at risk. The lowest doses to the contralateral breast and lung were less than 0.1 cGy when they were measured for the offset isocenter. The biggest reduction in dose was obtained by using CB-TS beams that completely avoid the critical organ. For points inside the CB-TS beam, the dose was reduced in a linear relation with distance from the center of the imaging arc. The data indicate that it is possible to reduce substantially radiation doses to the contralateral organs by proper selection of CB-TS angles and imaging field sizes. Our results provide the first systematic study on CB-TS doses from setup imaging for external breast irradiation and can be a useful resource for estimating anticipated radiation doses as a function of the conditions chosen for imaging breast setup.

Purpose: To demonstrate the feasibility of proton dose calculation on scatter-corrected cone-beam computed tomographic (CBCT) images for the purpose of adaptive proton therapy. Methods: CBCT projection images were acquired from anthropomorphic phantoms and a prostate patient using an on-board imaging system of an Elekta infinity linear accelerator. Two previously introduced techniques were used to correct the scattered x-rays in the raw projection images: uniform scatter correction (CBCT us) and a priori CT-based scatter correction (CBCT ap). CBCT images were reconstructed using a standard FDK algorithm and GPU-based reconstruction toolkit. Soft tissue ROI-based HU shifting was used to improve HU accuracy of the uncorrected CBCT images and CBCT us, while no HU change was applied to the CBCT ap. The degree of equivalence of the corrected CBCT images with respect to the reference CT image (CT ref) was evaluated by using angular profiles of water equivalent path length (WEPL) and passively scattered proton treatment plans. The CBCT ap was further evaluated in more realistic scenarios such as rectal filling and weight loss to assess the effect of mismatched prior information on the corrected images. Results: The uncorrected CBCT and CBCT us images demonstrated substantial WEPL discrepancies (7.3 ± 5.3 mm and 11.1 ± 6.6 mm, respectively) with respect to the CT ref, while the CBCT ap images showed substantially reduced WEPL errors (2.4 ± 2.0 mm). Similarly, the CBCT ap-based treatment plans demonstrated a high pass rate (96.0% ± 2.5% in 2 mm/2% criteria) in a 3D gamma analysis. Conclusions: A priori CT-based scatter correction technique was shown to be promising for adaptive proton therapy, as it achieved equivalent proton dose distributions and water equivalent path lengths compared to those of a reference CT in a selection of anthropomorphic phantoms.

Ultrasound-induced blood stasis has been observed for more than 30 years . Most of the literature has been focused on the health risks associated with this phenomenon and methods employed to prevent stasis from occurring during ultrasound imaging. To date, experimental observations have been either in vitro or invasive. The current work demonstrates ultrasound-induced blood stasis in murine normal leg muscle versus tumor-bearing legs, observed through noninvasive measurements of optical spectroscopy, and discusses possible diagnostic uses for this previously undesirable effect of ultrasound. We demonstrate that, using optical spectroscopy,effects of ultrasound can be used to differentiate tumor from normal leg muscletissue in mice. Finally, we propose a novel diagnostic algorithm that quantitatively differentiates tumor from nontumor with maximum specificity 0.83, maximum sensitivity 0.79, and area under receiver-operating-characteristics curve 0.90.

Purpose: We developed a knowledge-based model that can predict the patient-specific benefits of proton therapy based upon geometric considerations. The model could also aid patient selection in model-based clinical trials or help justify clinical decisions to insurance companies. Methods: The knowledge-based method trains a model upon existing proton treatment plans, exploiting correlations between dose and distance-to-target. Each OAR is split into concentric subvolumes surrounding the target volume, and a skew-normal PDF is fit to the dose distribution found within each shell. The model learns from shared trends in how the best-fit skew-normal parameters depend upon distance-to-target. It can then predict feasible OAR DVHs for a new patient (without a proton plan) based upon their geometry. The expected benefits of proton therapy are assessed by comparing the predicted DVHs to those of an IMRT plan, using a metric such as the equivalent uniform dose (EUD). Results: A model was trained for clival chordoma, owing to its geometric complexity and the multitude of nearby OARs. The model was trained using 20 patients and validated with a further 20 patients, and considers several different OARs. The predicted EUD was in good agreement with that of the actual proton plan. The coefficient of determination (R-squared) was 85% overall, 92% for cochleas, 80% for optic chiasm and 79% for spinal cord. The model exhibited no signs of bias or overfitting. When compared to an IMRT plan, the model could classify whether a patient will experience a gain or a loss with an accuracy between 75% and 95%, depending upon the OAR. Conclusion: We developed a model that can quickly and accurately predict the patient-specific benefits of proton therapy in clival chordoma patients, though models could be trained for other tumor sites. This work is funded by National Cancer Institute grant U19 CA 021239.

Purpose: An unpredictable movement of a patient can occur during SBRT even when immobilization devices are applied. In the SBRT treatments using a conventional linear accelerator detection of such movements relies heavily on human interaction and monitoring. This study aims to detect such positional abnormalities in real-time by assessing intra-fractional gantry mounted kV projection images of a patient's spine. Methods: We propose a self-CBCT image based spine tracking method consisting of the following steps: (1)Acquire a pre-treatment CBCT image; (2)Transform the CBCT volume according to the couch correction; (3)Acquire kV projections during treatment beam delivery; (4)Simultaneously with each acquisition generate a DRR from the CBCT volume based-on the current projection geometry; (5)Perform an intensity gradient-based 2D registration between spine ROI images of the projection and the DRR images; (6)Report an alarm if the detected 2D displacement is beyond a threshold value. To demonstrate the feasibility, retrospective simulations were performed on 1,896 projections from nine CBCT sessions of three patients who received lung SBRT. The unpredictable movements were simulated by applying random rotations and translations to the reference CBCT prior to each DRR generation. As the ground truth, the 3D translations and/or rotations causing >3 mm displacement of the midpoint of the thoracic spine were regarded as abnormal. In the measurements, different threshold values of 2D displacement were tested to investigate sensitivity and specificity of the proposed method. Results: A linear relationship between the ground truth 3D displacement and the detected 2D displacement was observed (R2 = 0.44). When the 2D displacement threshold was set to 3.6 mm the overall sensitivity and specificity were 77.7±5.7% and 77.9±3.5% respectively. Conclusion: In this simulation study, it was demonstrated that intrafractional kV projections from an on-board CBCT system have a potential to detect unpredictable patient movement during SBRT. This research is funded by Interfractional Imaging Research Grant from Elekta.