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Abstract: Due to the rarity of solitary bone plasmacytoma (SBP), few studies reported the prognosis and survival predictors of SBP, especially for patients with extremity SBP.A total of 552 patients with extremity SBP were identified from the Surveillance Epidemiology and Ends Results (SEER) database between 1973 and 2016. In order to obtain independent predictors of survival, we performed both univariate and multivariate analysis via Cox proportional hazards model. Additionally, we used the Kaplan-Meier method to construct survival curves.The mean and median age at diagnosis of all patients were 64 and 65 years, respectively. The ratio of male versus women was 1.3:1. Overall survival for this special population was 51.2% and 34.9% at 5 and 10 years, respectively. Cancer-specific survival (CSS) for this special population was 63.5% and 47.5% at 5 and 10 years, respectively. Age at diagnosis and radiotherapy treatment were found to be significant independent predictors of both overall survival and CSS. Additionally, multivariate analysis showed that year of diagnosis and marital status were significantly correlated with CSS.This is the first study to identify prognostic factors of extremity SBP by using the SEER database. Our findings highlight that radiotherapy is the mainstream treatment for extremity SBP. Additionally, age, year of diagnosis, and marital status were significant independent predictors of survival. Knowledge of these survival predictors may help clinicians provide appropriate management for extremity SBP patients., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Gut microbiota have close interactions with the host. It can affect cancer progression and the outcomes of cancer therapy, including chemotherapy, immunotherapy, and radiotherapy. Therefore, approaches toward the modulation of gut microbiota will enhance cancer prevention and treatment. Modern drug delivery systems (DDS) are emerging as rational and promising tools for microbiota intervention. These delivery systems have compensated for the obstacles associated with traditional treatments. In this review, the essential roles of gut microbiota in carcinogenesis, cancer progression, and various cancer therapies are first introduced. Next, advances in DDS that are aimed at enhancing the efficacy of cancer therapy by modulating or engineering gut microbiota are highlighted. Finally, the challenges and opportunities associated with the application of DDS targeting gut microbiota for cancer prevention and treatment are briefly discussed., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

The physical properties of particles used in radiation therapy, such as protons, have been well characterized, and their dose distributions are superior to photon-based treatments. However, proton therapy may also have inherent biologic advantages that have not been capitalized on. Unlike photon beams, the linear energy transfer (LET) and hence biologic effectiveness of particle beams varies along the beam path. Selective placement of areas of high effectiveness could enhance tumor cell kill and simultaneously spare normal tissues. However, previous methods for mapping spatial variations in biologic effectiveness are time-consuming and often yield inconsistent results with large uncertainties. Thus the data needed to accurately model relative biological effectiveness to guide novel treatment planning approaches are limited. We used Monte Carlo modeling and high-content automated clonogenic survival assays to spatially map the biologic effectiveness of scanned proton beams with high accuracy and throughput while minimizing biological uncertainties. We found that the relationship between cell kill, dose, and LET, is complex and non-unique. Measured biologic effects were substantially greater than in most previous reports, and non-linear surviving fraction response was observed even for the highest LET values. Extension of this approach could generate data needed to optimize proton therapy plans incorporating variable RBE.

Objectives: Intractable aspiration pneumonia in patients with post-radiotherapeutic nasopharyngeal carcinoma (PNC) is a formidable complication, but has not attracted enough attention in clinical practice. Modified laryngotracheal separation (MLTS) was applied for these patients in our hospital, the surgical effects of which were assessed., Patients and Methods: Retrospective analysis of 9 PNC cases complicated by intractable aspiration pneumonia in our hospital was carried out. All cases were diagnosed as lower cranial nerve palsy. Their aspiration pneumonia was not effectively prevented or controlled after a series of previous treatments, including active anti-infectives, neurotrophy, acupuncture, nutrition support, nasogastric feeding and tracheotomy. Ultimately all of them received modified laryngotracheal separation (MLTS) surgery. Efficacy of the operation was assessed., Results: In all patients, aspiration pneumonia was effectively controlled after the operation, body weights increased more than 6kg six months later, and nutrition status, swallowing function and quality of life were all improved., Conclusions: Intractable post-radiotherapeutic aspiration pneumonia in patients with nasopharyngeal carcinoma was possibly caused by lower cranial nerve palsy, which might be related to radiation fields overlapped. Modified laryngotracheal separation is effective in eliminating intractable aspiration in PNC. Suitable patients should be carefully selected although the procedure is potentially reversible., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Beam angle optimization (BAO) by far remains an important and challenging problem in external beam radiation therapy treatment planning. Conventional BAO algorithms discussed in previous studies all focused on photon-based therapies. Impact of BAO on proton therapy is important while proton therapy increasingly receives great interests. This study focuses on potential benefits of BAO on intensity-modulated proton therapy (IMPT) that recently began available to clinical cancer treatment., Methods: The authors have developed a novel uncertainty incorporated BAO algorithm for IMPT treatment planning in that IMPT plan quality is highly sensitive to uncertainties such as proton range and setup errors. A linear programming was used to optimize robust intensity maps to scenario-based uncertainties for an incident beam angle configuration. Unlike conventional intensity-modulated radiation therapy with photons (IMXT), the search space for IMPT treatment beam angles may be relatively small but optimizing an IMPT plan may require higher computational costs due to larger data size. Therefore, a deterministic local neighborhood search algorithm that only needs a very limited number of plan objective evaluations was used to optimize beam angles in IMPT treatment planning., Results: Three prostate cancer cases and two skull base chordoma cases were studied to demonstrate the dosimetric advantages and robustness of optimized beam angles from the proposed BAO algorithm. Two- to four-beam plans were optimized for prostate cases, and two- and three-beam plans were optimized for skull base cases. By comparing plans with conventional two parallel-opposed angles, all plans with optimized angles consistently improved sparing at organs at risks, i.e., rectum and femoral heads for prostate, brainstem for skull base, in either nominal dose distribution or uncertainty-based dose distributions. The efficiency of the BAO algorithm was demonstrated by comparing it with alternative methods including simulated annealing and genetic algorithm. The numbers of IMPT plan objective evaluations required were reduced by up to a factor of 5 while the same optimal angle plans were converged in selected comparisons., Conclusions: Uncertainty incorporated BAO may introduce pronounced improvement of IMPT plan quality including dosimetric benefits and robustness over uncertainties, based on the five clinical studies in this paper. In addition, local search algorithms may be more efficient in finding optimal beam angles than global optimization approaches for IMPT BAO.

Image guidance using implanted fiducial markers is commonly used to ensure accurate and reproducible target positioning in radiation therapy for prostate cancer. The ideal fiducial marker is clearly visible in kV imaging, does not perturb the therapeutic dose in the target volume and does not cause any artifacts on the CT images used for treatment planning. As yet, ideal markers that fully meet all three of these criteria have not been reported. In this study, 12 fiducial markers were evaluated for their potential clinical utility in proton radiation therapy for prostate cancer. In order to identify the good candidates, each fiducial was imaged using a CT scanner as well as a kV imaging system. Additionally, the dose perturbation caused by each fiducial was quantified using radiochromic film and a clinical proton beam. Based on the results, three fiducials were identified as good candidates for use in proton radiotherapy of prostate cancer.

We used a mobile positron emission tomography (PET) scanner positioned within the proton therapy treatment room to study the feasibility of proton range verification with an in-room, stand-alone PET system, and compared with off-line equivalent studies. Two subjects with adenoid cystic carcinoma were enrolled into a pilot study in which in-room PET scans were acquired in list-mode after a routine fractionated treatment session. The list-mode PET data were reconstructed with different time schemes to generate in-room short, in-room long and off-line equivalent (by skipping coincidences from the first 15 min during the list-mode reconstruction) PET images for comparison in activity distribution patterns. A phantom study was followed to evaluate the accuracy of range verification for different reconstruction time schemes quantitatively. The in-room PET has a higher sensitivity compared to the off-line modality so that the PET acquisition time can be greatly reduced from 30 to <5 min. Features in deep-site, soft-tissue regions were better retained with in-room short PET acquisitions because of the collection of (15)O component and lower biological washout. For soft tissue-equivalent material, the distal fall-off edge of an in-room short acquisition is deeper compared to an off-line equivalent scan, indicating a better coverage of the high-dose end of the beam. In-room PET is a promising low cost, high sensitivity modality for the in vivo verification of proton therapy. Better accuracy in Monte Carlo predictions, especially for biological decay modeling, is necessary.

The transfer of radiation therapy data among the various subsystems required for external beam treatments is subject to error. Hence, the establishment and management of a data transfer quality assurance program is strongly recommended. It should cover the QA of data transfers of patient specific treatments, imaging data, manually handled data and historical treatment records. QA of the database state (logical consistency and information integrity) is also addressed to ensure that accurate data are transferred.

We have developed a quantitative computed tomography (CT)-based quality assurance (QA) tool for evaluating the accuracy of manufactured compensators used in passively scattered proton therapy. The thickness of a manufactured compensator was measured from its CT images and compared with the planned thickness defined by the treatment planning system. The difference between the measured and planned thicknesses was calculated with use of the Euclidean distance transformation and the kd-tree search method. Compensator accuracy was evaluated by examining several parameters including mean distance, maximum distance, global thickness error and central axis shifts. Two rectangular phantoms were used to validate the performance of the QA tool. Nine patients and 20 compensators were included in this study. We found that mean distances, global thickness errors and central axis shifts were all within 1 mm for all compensators studied, with maximum distances ranging from 1.1 to 3.8 mm. Although all compensators passed manual verification at selected points, about 5% of the pixels still had maximum distances of >2 mm, most of which correlated with large depth gradients. The correlation between the mean depth gradient of the compensator and the percentage of pixels with mean distance <1 mm is -0.93 with p < 0.001, which suggests that the mean depth gradient is a good indicator of compensator complexity. These results demonstrate that the CT-based compensator QA tool can be used to quantitatively evaluate manufactured compensators.

Purpose: The purposes of this study were to validate a discrete spot scanning proton beam nozzle using the Monte Carlo (MC) code MCNPX and use the MC validated model to investigate the effects of a low-dose envelope, which surrounds the beam's central axis, on measurements of integral depth dose (IDD) profiles., Methods: An accurate model of the discrete spot scanning beam nozzle from The University of Texas M. D. Anderson Cancer Center (Houston, Texas) was developed on the basis of blueprints provided by the manufacturer of the nozzle. The authors performed simulations of single proton pencil beams of various energies using the standard multiple Coulomb scattering (MCS) algorithm within the MCNPX source code and a new MCS algorithm, which was implemented in the MCNPX source code. The MC models were validated by comparing calculated in-air and in-water lateral profiles and percentage depth dose profiles for single pencil beams with their corresponding measured values. The models were then further tested by comparing the calculated and measured three-dimensional (3-D) dose distributions. Finally, an IDD profile was calculated with different scoring radii to determine the limitations on the use of commercially available plane-parallel ionization chambers to measure IDD., Results: The distance to agreement, defined as the distance between the nearest positions of two equivalent distributions with the same value of dose, between measured and simulated ranges was within 0.13 cm for both MCS algorithms. For low and intermediate pencil beam energies, the MC simulations using the standard MCS algorithm were in better agreement with measurements. Conversely, the new MCS algorithm produced better results for high-energy single pencil beams. The IDD profile calculated with cylindrical tallies with an area equivalent to the area of the largest commercially available ionization chamber showed up to 7.8% underestimation of the integral dose in certain depths of the IDD profile., Conclusions: The authors conclude that a combination of MCS algorithms is required to accurately reproduce experimental data of single pencil beams and 3-D dose distributions for the scanning beam nozzle. In addition, the MC simulations showed that because of the low-dose envelope, ionization chambers with radii as large as 4.08 cm are insufficient to accurately measure IDD profiles for a 221.8 MeV pencil beam in the scanning beam nozzle.

This paper reports an inverse arc-modulated radiation therapy planning technique based on linear models. It is implemented with a two-step procedure. First, fluence maps for 36 fixed-gantry beams are generated using a linear model-based intensity-modulated radiation therapy (IMRT) optimization algorithm. The 2D fluence maps are decomposed into 1D fluence profiles according to each leaf pair position. Second, a mixed integer linear model is used to construct the leaf motions of an arc delivery that reproduce the 1D fluence profile previously derived from the static gantry IMRT optimization. The multi-leaf collimator (MLC) sequence takes into account the starting and ending leaf positions in between the neighbouring apertures, such that the MLC segments of the entire treatment plan are deliverable in a continuous arc. Since both steps in the algorithm use linear models, implementation is simple and straightforward. Details of the algorithm are presented, and its conceptual correctness is verified with clinical cases representing prostate and head-and-neck treatments.

Scanned proton pencil beams carry a low-dose envelope that extends several centimeters from the individual beam's central axis. Thus, the total delivered dose depends on the size of the target volume and the corresponding number and intensity of beams necessary to cover the target volume uniformly. This dependence must be considered in dose calculation algorithms used by treatment planning systems. In this work, we investigated the sources of particles contributing to the low-dose envelope using the Monte Carlo technique. We used a validated model of our institution's scanning beam line to determine the contributions to the low-dose envelope from secondary particles created in a water phantom and particles scattered in beam line components. Our results suggested that, for high-energy beams, secondary particles produced by nuclear interactions in the water phantom are the major contributors to the low-dose envelope. For low-energy beams, the low-dose envelope is dominated by particles undergoing multiple Coulomb scattering in the beam line components and water phantom. Clearly, in the latter situation, the low-dose envelope depends directly on beam line design features. Finally, we investigated the dosimetric consequences of the low-dose envelope. Our results showed that if not modeled properly the low-dose envelope may cause clinically relevant dose disturbance in the target volume. This work suggested that this low-dose envelope is beam line specific for low-energy beams, should be thoroughly experimentally characterized and validated during commissioning of the treatment planning system, and therefore is of great concern for accurate delivery of proton scanning beam doses.

This study investigated the integration of the Calypso real-time tracking system, based on implanted ferromagnetic transponders and a detector array, into the current process for image-guided radiation treatment (IGRT) of prostate cancer at our institution. The current IGRT process includes magnetic resonance imaging (MRI) for prostate delineation, CT simulation for treatment planning, daily on-board kV and CBCT imaging for target alignment, and MRI/MRS for post-treatment assessment. This study assesses (1) magnetic-field-induced displacement and radio-frequency (RF)-induced heating of transponders during MRI at 1.5 T and 3 T, and (2) image artifacts caused by transponders and the detector array in phantom and patient cases with the different imaging systems. A tissue-equivalent phantom mimicking prostate tissue stiffness was constructed and implanted with three operational transponders prior to phantom solidification. The measurements show that the Calypso system is safe with all the imaging systems. Transponder position displacements due to the MR field are minimal (<1.0 mm) for both 1.5 T and 3 T MRI scanners, and the temperature variation due to MRI RF heating is <0.2 degrees C. The visibility of transponders and bony anatomy was not affected on the OBI kV and CT images. Image quality degradation caused by the detector antenna array is observed in the CBCT image. Image artifacts are most significant with the gradient echo sequence in the MR images, producing null signals surrounding the transponders with radii approximately 1.5 cm and length approximately 4 cm. Thus, Calypso transponders can preclude the use of MRI/MRS in post-treatment assessment. Modifications of the clinical flow are required to accommodate and minimize the substantial MRI artifacts induced by the Calypso transponders.

Purpose: The purpose of this study is to describe the University of Texas M. D. Anderson proton therapy system (PTC-H) including the accelerator, beam transport, and treatment delivery systems, the functionality and clinical parameters for passive scattering and pencil beam scanning treatment modes, and the results of acceptance tests., Methods: The PTC-H has a synchrotron (70-250 MeV) and four treatment rooms. An overall control system manages the treatment, physics, and service modes of operation. An independent safety system ensures the safety of patients, staff, and equipment. Three treatment rooms have isocentric gantries and one room has two fixed horizontal beamlines, which include a large-field treatment nozzle, used primarily for prostate treatments, and a small-field treatment nozzle for ocular treatments. Two gantry treatment rooms and the fixed-beam treatment room have passive scattering nozzles. The third gantry has a pencil beam scanning nozzle for the delivery of intensity modulated proton treatments (IMPT) and single field uniform dose (SFUD) treatments. The PTC-H also has an experimental room with a fixed horizontal beamline and a passive scattering nozzle. The equipment described above was provided by Hitachi, Ltd. Treatment planning is performed using the Eclipse system from Varian Medical Systems and data management is handled by the MOSAIQ system from IMPAC Medical Systems, Inc. The large-field passive scattering nozzles use double scattering systems in which the first scatterers are physically integrated with the range modulation wheels. The proton beam is gated on the rotating range modulation wheels at gating angles designed to produce spread-out-Bragg peaks ranging in size from 2 to 16 g/cm2. Field sizes of up to 25 x 25 cm2 can be achieved with the double scattering system. The IMPT delivery technique is discrete spot scanning, which has a maximum field size of 30 x 30 cm2. Depth scanning is achieved by changing the energy extracted from the synchrotron (energy can be changed pulse to pulse). The PTC-H is fully integrated with DICOM-RT ION interfaces for imaging, treatment planning, data management, and treatment control functions., Results: The proton therapy system passed all acceptance tests for both passive scattering and pencil beam scanning. Treatments with passive scattering began in May 2006 and treatments with the scanning system began in May 2008. The PTC-H was the first commercial system to demonstrate capabilities for IMPT treatments and the first in the United States to treat using SFUD techniques. The facility has been in clinical operation since May 2006 with up-time of approximately 98%., Conclusions: As with most projects for which a considerable amount of new technology is developed and which have duration spanning several years, at project completion it was determined that several upgrades would improve the overall system performance. Some possible upgrades are discussed. Overall, the system has been very robust, accurate, reproducible, and reliable. The authors found the pencil beam scanning system to be particularly satisfactory; prostate treatments can be delivered on the scanning nozzle in less time than is required on the passive scattering nozzle.

Objective: In order to observe the long-term curative effect of microwave to treat the choanal atresia after radiotherapy under nasal endoscope., Method: Twenty-one cases of choanal atresia after radiotherapy were treated by microwave under nasal endoscope., Result: Following-up more than 3 years after operation, all the 21 cases were cured(100%) with no relapse., Conclusion: This method is simple with mild damage to normal tissues, clear operation visual field, less postoperation pain, stadle long-term therapeutical effect and good way to treat choanal atresia in NPC after radiotherapy.

A method has been developed to estimate potential dose errors due to linear accelerator angular setting misalignments of Intensity Modulated Radiation Therapy (IMRT) treatments. A first-order approximation to the dose error at a point is modeled as the dot product of the dose gradient and the shift vector of the point due to the rotational error. The analysis method is applied to a previously published set of optimized fluences for a 50 MV IMRT pelvis irradiation. Three of the published cases exhibiting a wide range of modulation are presented; a rectangular open field, a field optimized for a static multileaf collimator defining the portal outline coupled with a single broad bremsstrahlung profile modulation, and a fully modulated field using a physical modulator. To examine the energy dependence of angle setting errors, the study is repeated using the same fluence distributions, but with a dose-spread kernel appropriate for a 6 MV photon beam. The collimator angle error is set to 2 degree, and the dose error determined with both a centrally located isocenter and an isocenter chosen to model a split-field geometry. The dose error due to a 2 degree gantry setting error is assessed at a plane 10 cm distal to the isocenter. The mathematical form of the dose error due to couch motion is similar to the other two errors, so the dose error resulting from a couch angle missetting is not presented. The magnitude of the errors is largest for the 6 MV beam, while the volume encompassed by the errors is greater for the 50 MV beam. The gantry error yields the largest dose error values, with the 6 MV modulated case presenting dose errors of greater than 40%.

Purpose: The main purpose of this work was to generate and validate the dosimetric accuracy of proton beams of dimensions that are appropriate for in vivo small animal and in vitro ultrahigh dose rate (FLASH) radiotherapy experiments using a synchrotron‐based treatment delivery system. This study was performed to enable future investigations of the relevance of a spread‐out Bragg peak (SOBP) under FLASH conditions. Methods: The spill characteristics of the small field fixed horizontal beam line were modified to deliver accelerated protons in times as short as 2 ms and to control the dose delivered. A Gaussian‐like transverse beam profile was transformed into a square uniform one at FLASH dose rates, while avoiding low‐dose regions, a crucial requirement to protect normal tissue during FLASH irradiation. Novel beam‐shaping devices were designed using Monte Carlo techniques to produce up to about 6 cm3 of uniform dose in SOBPs while maximizing the dose rate. These included a scattering foil, a conical flattening filter to maximize the flux of protons into the region of interest, energy filters, range compensators, and collimators. The shapes, sizes, and positions of the components were varied to provide the required field sizes and SOBPs. Results: The designed and fabricated devices were used to produce 10‐, 15‐, and 20‐mm diameter, circular field sizes and 10‐, 15‐, and 20‐mm SOBP modulation widths at uniform physical dose rates of up to 375 Gy/s at the center of the SOBP and a minimum dose rate of about 255 Gy/s at the entrance, respectively, in cylindrical volumes. The flatness of lateral dose profiles at the center could be adjusted to within ±1.5% at the center of the SOBP. Assessment of systematic uncertainties, such as impact of misalignments and positioning uncertainties, was performed using simulations, and the results were used to provide appropriate adjustments to ensure high‐accuracy FLASH beam delivery for both in vitro and in vivo preclinical experiments. Conclusions: It is feasible to use synchrotron‐generated proton beams of sufficient dimensions for FLASH radiobiology experiments. We expect to use the system we developed to acquire in vitro and in vivo small animal FLASH radiobiology data as a function of dose, dose rate, oxygen content, and linear energy transfer to help us understand the underlying mechanisms of the FLASH phenomenon. [ABSTRACT FROM AUTHOR]

Opinion Statement: The rise in the incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPC), the relatively young age at which it is diagnosed, and its favorable prognosis necessitate the use of treatment techniques that reduce the likelihood of side effects during and after curative treatment. Intensity-modulated proton therapy (IMPT) is a form of radiotherapy that de-intensifies treatment through dose de-escalation to normal tissues without compromising dose to the primary tumor and involved, regional lymph nodes. Preclinical studies have demonstrated that HPV-positive squamous cell carcinoma is more sensitive to proton radiation than is HPV-negative squamous cell carcinoma. Retrospective studies comparing intensity-modulated photon (X-ray) radiotherapy to IMPT for OPC suggest comparable rates of disease control and lower rates of pain, xerostomia, dysphagia, dysgeusia, gastrostomy tube dependence, and osteoradionecrosis with IMPT-all of which meaningfully affect the quality of life of patients treated for HPV-associated OPC. Two phase III trials currently underway-the "Randomized Trial of IMPT versus IMRT for the Treatment of Oropharyngeal Cancer of the Head and Neck" and the "TOxicity Reduction using Proton bEam therapy for Oropharyngeal cancer (TORPEdO)" trial-are expected to provide prospective, level I evidence regarding the effectiveness of IMPT for such patients. [ABSTRACT FROM AUTHOR]

Purpose: To develop and validate a novel delivery strategy for reducing the respiratory motion-induced dose uncertainty of spot-scanning proton therapy.Methods and Materials: The spot delivery sequence was optimized to reduce dose uncertainty. The effectiveness of the delivery sequence optimization was evaluated using measurements and patient simulation. One hundred ninety-one 2-dimensional measurements using different delivery sequences of a single-layer uniform pattern were obtained with a detector array on a 1-dimensional moving platform. Intensity modulated proton therapy plans were generated for 10 lung cancer patients, and dose uncertainties for different delivery sequences were evaluated by simulation.Results: Without delivery sequence optimization, the maximum absolute dose error can be up to 97.2% in a single measurement, whereas the optimized delivery sequence results in a maximum absolute dose error of ≤11.8%. In patient simulation, the optimized delivery sequence reduces the mean of fractional maximum absolute dose error compared with the regular delivery sequence by 3.3% to 10.6% (32.5-68.0% relative reduction) for different patients.Conclusions: Optimizing the delivery sequence can reduce dose uncertainty due to respiratory motion in spot-scanning proton therapy, assuming the 4-dimensional CT is a true representation of the patients' breathing patterns. [ABSTRACT FROM AUTHOR]

Purpose: This study investigates potential gains of an improved beam angle arrangement compared to a conventional fixed gantry setup in intensity modulated proton therapy (IMPT) treatment for localized prostate cancer patients based on a proof of principle study. Materials and Methods: Three patients with localized prostate cancer retrospectively selected from our institution were studied. For each patient, IMPT plans were designed using two, three and four beam angles, respectively, obtained from a beam angle optimization algorithm. Those plans were then compared with ones using two lateral parallel-opposed beams according to the conventional planning protocol for localized prostate cancer adopted at our institution. Results: IMPT plans with two optimized angles achieved significant improvements in rectum sparing and moderate improvements in bladder sparing against those with two lateral angles. Plans with three optimized angles further improved rectum sparing significantly over those two-angle plans, whereas four-angle plans found no advantage over three-angle plans. A possible three-beam class solution for localized prostate patients was suggested and demonstrated with preserved dosimetric benefits because individually optimized three-angle solutions were found sharing a very similar pattern. Conclusions: This study has demonstrated the potential of using an improved beam angle arrangement to better exploit the theoretical dosimetric benefits of proton therapy and provided insights of selecting quality beam angles for localized prostate cancer treatment. [ABSTRACT FROM AUTHOR]

Injectable spacers placed between the prostate and rectum before radiation therapy (RT) for prostate cancer can reduce the dose to the adjacent rectum. While this method has been studied extensively with external beam RT, there is limited data for its use in high-dose-rate brachytherapy (HDR-BT). Additionally, a new formulation using non-animal stabilized hyaluronic acid (NASHA) allows for improved anatomic visibility and thus may better facilitate accurate spacer placement, minimizing complications. This study aims to assess the feasibility and dosimetry of NASHA rectal spacer utilization during HDR-BT. This single-center study retrospectively reviewed consecutive patients with prostate cancer who received HDR-BT from 2021-2024. A subset received a NASHA rectal spacer via a transperineal approach under transrectal ultrasound guidance and returned 2-4 weeks after placement to undergo HDR-BT. Dosimetric variables were compared between patients with and without spacers using two sample t-tests. 76 patients received HDR-BT, 13 with a spacer and 63 without a spacer, including two patients for whom spacer implantation was intended but unachievable due to a small rectal-prostate interface. Median age was 67 years. Prostate cancer stage included low risk (n=1), favorable intermediate risk (n=23), unfavorable intermediate risk (n=22), high risk (n=21), very high risk (n=8), and node-positive (n=1). Median baseline PSA was 7.05 ng/mL (range 1.93 – 292). A total of 107 HDR-BT treatments were administered (21 spacer, 86 non-spacer). 23 patients (6 spacer, 17 non-spacer) were treated with prostate monotherapy (27 Gy in 2 fractions), 2 patients (1 spacer, 1 non-spacer), with salvage brachytherapy, and 51 patients (6 spacer, 45 non-spacer) with HDR brachytherapy boost and external beam RT. Mean prostate volume was 48.1cc. Use of a rectal spacer resulted in a reduction in mean rectal D0.1cc and V75% (80.0% vs 84.7%, p<0.0001; 0.69cc vs 0.93cc, p=0.0170, respectively). Patients treated with a rectal spacer had a higher mean prostate V125% (60.9% vs. 58.7%, p=0.0167). There were no differences in prostate V100% and V200%, urethra D0.1cc, and bladder D0.1cc between groups (p>0.05). Rectal spacer did not negatively impact the feasibility of HDR-BT catheter placement under ultrasound guidance, nor were there complications from placement. A NASHA rectal spacer can be placed prior to prostate HDR-BT to successfully increase the distance between the rectum and prostate without interfering with visibility and technical delivery of HDR-BT. Use of a rectal spacer effectively reduces dose to the rectum, while maintaining appropriate target coverage to the prostate. Future investigations will be performed to assess the impact of rectal spacer use on acute and late gastrointestinal toxicity. [ABSTRACT FROM AUTHOR]

Purpose: The measurement of percentage depth-dose (PDD) distributions for the quality assurance of clinical proton beams is most commonly performed with a computerized water tank dosimetry system with ionization chamber, commonly referred to as water tank. Although the accuracy and reproducibility of this method is well established, it can be time-consuming if a large number of measurements are required. In this work the authors evaluate the linearity, reproducibility, sensitivity to field size, accuracy, and time-savings of another system: the Zebra, a multilayer ionization chamber system. Methods: The Zebra, consisting of 180 parallel-plate ionization chambers with 2 mm resolution, was used to measure depth-dose distributions. The measurements were performed for scattered and scanned proton pencil beams of multiple energies delivered by the Hitachi PROBEAT synchrotron-based delivery system. For scattered beams, the Zebra-measured depth-dose distributions were compared with those measured with the water tank. The principal descriptors extracted for comparisons were: range, the depth of the distal 90% dose; spread-out Bragg peak (SOBP) length, the region between the proximal 95% and distal 90% dose; and distal-dose fall off (DDF), the region between the distal 80% and 20% dose. For scanned beams, the Zebra-measured ranges were compared with those acquired using a Bragg peak chamber during commissioning. Results: The Zebra demonstrated better than 1% reproducibility and monitor unit linearity. The response of the Zebra was found to be sensitive to radiation field sizes greater than 12.5 × 12.5 cm; hence, the measurements used to determine accuracy were performed using a field size of 10 × 10 cm. For the scattered proton beams, PDD distributions showed 1.5% agreement within the SOBP, and 3.8% outside. Range values agreed within -0.1 ± 0.4 mm, with a maximum deviation of 1.2 mm. SOBP length values agreed within 0 ± 2 mm, with a maximum deviation of 6 mm. DDF values agreed within 0.3 ± 0.1 mm, with a maximum deviation of 0.6 mm. For the scanned proton pencil beams, Zebra and Bragg peak chamber range values demonstrated agreement of 0.0 ± 0.3 mm with a maximum deviation of 1.3 mm. The setup and measurement time for all Zebra measurements was 3 and 20 times less, respectively, compared to the water tank measurements. Conclusions: Our investigation shows that the Zebra can be useful not only for fast but also for accurate measurements of the depth-dose distributions of both scattered and scanned proton beams. The analysis of a large set of measurements shows that the commonly assessed beam quality parameters obtained with the Zebra are within the acceptable variations specified by the manufacturer for our delivery system. [ABSTRACT FROM AUTHOR]

Background: For treatment of the entire cranium using passive scattering proton therapy (PSPT) compensators are often employed in order to reduce lens and cochlear exposure. We sought to assess the advantages and consequences of utilizing compensators for the treatment of the whole brain as a component of craniospinal radiation (CSI) with PSPT. Moreover, we evaluated the potential benefits of spot scanning beam delivery in comparison to PSPT.Methods: Planning computed tomography scans for 50 consecutive CSI patients were utilized to generate passive scattering proton therapy treatment plans with and without Lucite compensators (PSW and PSWO respectively). A subset of 10 patients was randomly chosen to generate scanning beam treatment plans for comparison. All plans were generated using an Eclipse treatment planning system and were prescribed to a dose of 36 Gy(RBE), delivered in 20 fractions, to the whole brain PTV. Plans were normalized to ensure equal whole brain target coverage. Dosimetric data was compiled and statistical analyses performed using a two-tailed Student's t-test with Bonferroni corrections to account for multiple comparisons.Results: Whole brain target coverage was comparable between all methods. However, cribriform plate coverage was superior in PSWO plans in comparison to PSW (V95%; 92.9 ± 14 vs. 97.4 ± 5, p < 0.05). As predicted, PSWO plans had significantly higher lens exposure in comparison to PSW plans (max lens dose Gy(RBE): left; 24.8 ± 0.8 vs. 22.2 ± 0.7, p < 0.05, right; 25.2 ± 0.8 vs. 22.8 ± 0.7, p < 0.05). However, PSW plans demonstrated no significant cochlear sparing vs. PSWO (mean cochlea dose Gy(RBE): 36.4 ± 0.2 vs. 36.7 ± 0.1, p = NS). Moreover, dose homogeneity was inferior in PSW plans in comparison to PSWO plans as reflected by significant alterations in both whole brain and brainstem homogeneity index (HI) and inhomogeneity coefficient (IC). In comparison to both PSPT techniques, multi-field optimized intensity modulated (MFO-IMPT) spot scanning treatment plans displayed superior sparing of both lens and cochlea (max lens: 12.5 ± 0.6 and 12.9 ± 0.7 right and left respectively; mean cochlea 28.6 ± 0.5 and 27.4 ± 0.2), although heterogeneity within target volumes was comparable to PSW plans.Conclusions: For PSPT treatments, the addition of a compensator imparts little clinical advantage. In contrast, the incorporation of spot scanning technology as a component of CSI treatments, offers additional normal tissue sparing which is likely of clinical significance. [ABSTRACT FROM AUTHOR]

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

An elevated DNA-repair capacity in cancer cells leads to radiation resistance and severely limits the efficacy of radiation therapy. Activation of Akt is tightly associated with resistance to radiotherapy, and Mre11 protein has important role during the repair of DNA double-strand breaks (DSBs). In this report, our results showed that inhibition of Akt activity impaired the repair of DSBs in CNE2 cells, whereas activated Akt promoted the repair of DSBs in HeLa cells. Knockdown of Mre11 also impaired the process of DSB repair in both these two cell lines. More importantly, we found that Akt could regulate Mre11 expression. Inhibition of Akt activity by small interfering RNA or LY294002 efficiently downregulated the Mre11 expression in CNE2 cells, and transfection with myr-Akt plasmid in HeLa cells upregulated the Mre11 expression. In addition, luciferase reporter analysis revealed that Mre11 reporter activity increased after transfection with myr-Akt1 plasmids, and this myr-Akt1-induced transcriptional activity was blocked in the presence of LY294002. Further study showed GSK3β/β-catenin/LEF-1 pathway was involved in this regulation. Knockdown of β-catenin or LEF-1 led to the downregulation of Mre11, whereas overexpression of β-catenin led to upregulation of Mre11. The chromatin immunoprecipitation assay assay showed β-catenin/LEF-1 heterodimer could directly bind to the promoter of Mre11 in vivo. And the luciferase activity of the pGL3-Mre11 and pGL3-Lef increased in HeLa cells following β-catenin plasmid co-transfected, but was abolished when the LEF-1-binding conserved sequences of Mre11 promoter were mutated. These results together support Akt can upregulate the expression of Mre11 through GSK3β/ β-catenin/LEF pathway to elevate DSB-repair capacity in cancer cells. [ABSTRACT FROM AUTHOR]

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

Purpose: To assess the positioning accuracy using two-dimensional kilovoltage (2DkV) imaging and three-dimensional cone beam CT (CBCT) in patients with head and neck (H&N) cancer receiving radiation therapy. To assess the benefit of patient-specific headrest. Materials and Methods: All 21 patients studied were immobilized using thermoplastic masks with either a patient-specific vacuum bag (11 of 21, IMA) or standard clear plastic (10 of 21, IMB) headrests. Each patient was imaged with a pair of orthogonal 2DkV images in treatment position using onboard imaging before the CBCT procedure. The 2DkV and CBCT images were acquired weekly during the same session. The 2DkV images were reviewed by oncologists and also analyzed by a software tool based on mutual information (MI). Results: Ninety-eight pairs of assessable 2DkV-CBCT alignment sets were obtained. Systematic and random errors were <1.6 mm for both 2DkV and CBCT alignments. When we compared shifts determined by CBCT and 2DkV for the same patient setup, statistically significant correlations were observed in all three major directions. Among all CBCT couch shifts, 4.1% ≥ 0.5 cm and 18.7% ≥ 0.3 cm, whereas among all 2DkV (MI) shifts, 1.7% ≥ 0.5 cm and 11.2% ≥ 0.3 cm. Statistically significant difference was found on anteroposterior direction between IMA and IMB with the CBCT alignment only. Conclusions: The differences between 2D and 3D alignments were mainly caused by the relative flexibility of certain H&N structures and possibly by rotation. Better immobilization of the flexible neck is required to further reduce the setup errors for H&N patients receiving radiotherapy. [Copyright &y& Elsevier]

We have developed a new four-dimensional cone beam CT (4D-CBCT) on a Varian image-guided radiation therapy system, which has radiation therapy treatment and cone beam CT imaging capabilities. We adapted the speed of gantry rotation time of the CBCT to the average breath cycle of the patient to maintain the same level of image quality and adjusted the data sampling frequency to keep a similar level of radiation exposure to the patient. Our design utilized the real-time positioning and monitoring system to record the respiratory signal of the patient during the acquisition of the CBCT data. We used the full-fan bowtie filter during data acquisition, acquired the projection data over 200 deg of gantry rotation, and reconstructed the images with a half-scan cone beam reconstruction. The scan time for a 200-deg gantry rotation per patient ranged from 3.3 to 6.6 min for the average breath cycle of 3–6 s. The radiation dose of the 4D-CBCT was about 1–2 times the radiation dose of the 4D-CT on a multislice CT scanner. We evaluated the 4D-CBCT in scanning, data processing and image quality with phantom studies. We demonstrated the clinical applicability of the 4D-CBCT and compared the 4D-CBCT and the 4D-CT scans in four patient studies. The contrast-to-noise ratio of the 4D-CT was 2.8–3.5 times of the contrast-to-noise ratio of the 4D-CBCT in the four patient studies. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to quantify respiratory motion-induced dose uncertainty at the planning stage for step-and-shoot intensity-modulated radiation therapy (IMRT) using an analytical technique. Methods: Ten patients with stage II/III lung cancer who had undergone a planning four-dimensional (4D) computed tomographic scan and step-and-shoot IMRT planning were selected with a mix of motion and tumor size for this retrospective study. A step-and-shoot IMRT plan was generated for each patient. The maximum and minimum doses with respiratory motion were calculated for each plan, and the mean deviation from the 4D dose was calculated, taking delivery time, fractionation, and patient breathing cycle into consideration. Results: For all patients evaluated in this study, the mean deviation from the 4D dose in the planning target volume (PTV) was <2.5%, with a standard deviation <1.2%, and maximum point dose variation from the 4D dose was <6.2% in the PTV assuming delivery dose rate of 200 MU/min and patient breathing cycle of 8 s. The motion-induced dose uncertainty is a function of motion, fractionation, MU (plan modulation), dose rate, and patient breathing cycle. Conclusions: Respiratory motion-induced dose uncertainty varies from patient to patient. Therefore, it is important to evaluate the dose uncertainty on a patient-specific basis, which could be useful for plan evaluation and treatment strategy determination for selected patients. [ABSTRACT FROM AUTHOR]

Purpose: To present our method and experience in commissioning dose models in water for spot scanning proton therapy in a commercial treatment planning system (TPS). Methods: The input data required by the TPS included in-air transverse profiles and integral depth doses (IDDs). All input data were obtained from Monte Carlo (MC) simulations that had been validated by measurements. MC-generated IDDs were converted to units of Gy mm2/MU using the measured IDDs at a depth of 2 cm employing the largest commercially available parallel-plate ionization chamber. The sensitive area of the chamber was insufficient to fully encompass the entire lateral dose deposited at depth by a pencil beam (spot). To correct for the detector size, correction factors as a function of proton energy were defined and determined using MC. The fluence of individual spots was initially modeled as a single Gaussian (SG) function and later as a double Gaussian (DG) function. The DG fluence model was introduced to account for the spot fluence due to contributions of large angle scattering from the devices within the scanning nozzle, especially from the spot profile monitor. To validate the DG fluence model, we compared calculations and measurements, including doses at the center of spread out Bragg peaks (SOBPs) as a function of nominal field size, range, and SOBP width, lateral dose profiles, and depth doses for different widths of SOBP. Dose models were validated extensively with patient treatment field-specific measurements. Results: We demonstrated that the DG fluence model is necessary for predicting the field size dependence of dose distributions. With this model, the calculated doses at the center of SOBPs as a function of nominal field size, range, and SOBP width, lateral dose profiles and depth doses for rectangular target volumes agreed well with respective measured values. With the DG fluence model for our scanning proton beam line, we successfully treated more than 500 patients from March 2010 through June 2012 with acceptable agreement between TPS calculated and measured dose distributions. However, the current dose model still has limitations in predicting field size dependence of doses at some intermediate depths of proton beams with high energies. Conclusions: We have commissioned a DG fluence model for clinical use. It is demonstrated that the DG fluence model is significantly more accurate than the SG fluence model. However, some deficiencies in modeling the low-dose envelope in the current dose algorithm still exist. Further improvements to the current dose algorithm are needed. The method presented here should be useful for commissioning pencil beam dose algorithms in new versions of TPS in the future. [ABSTRACT FROM AUTHOR]

Purpose To compare field junction robustness and sparing of organs at risk (OARs) during craniospinal irradiation (CSI) using intensity modulated proton therapy (IMPT) to conventional passively scattered proton therapy (PSPT). Methods and Materials Ten patients, 5 adult and 5 pediatric patients, previously treated with PSPT-based CSI were selected for comparison. Anterior oblique cranial fields, using a superior couch rotation, and posterior spinal fields were used for IMPT planning. To facilitate low-gradient field junctioning along the spine, the inverse-planning IMPT technique was divided into 3 stages. Dose indices describing target coverage and normal tissue dose, in silico error modeling, and film dosimetry were used to assess plan quality. Results Field junction robustness along the spine was improved using the staged IMPT planning technique, reducing the worst case impact of a 4-mm setup error from 25% in PSPT to <5% of prescription dose. This was verified by film dosimetry for clinical delivery. Exclusive of thyroid dose in adult patients, IMPT plans demonstrated sparing of organs at risk as good or better than PSPT. Coverage of the cribriform plate for pediatric (V95% [percentage of volume of the target receiving at least 95% of the prescribed dose]; 87 ± 11 vs 92 ± 7) and adult (V95%; 94 ± 7 vs 100 ± 1) patients and the clinical target in pediatric (V95%; 98 ± 2 vs 100 ± 1) and adult (V95%; 100 ± 1 vs 100 ± 1) patients for PSPT and IMPT plans, respectively, were comparable or improved. For adult patients, IMPT target dose inhomogeneity was increased, as determined by heterogeneity index (HI) and inhomogeneity coefficient (IC). IMPT lowered maximum spinal cord dose, improved spinal dose homogeneity, and reduced exposure to other OARs. Conclusions IMPT has the potential to improve CSI plan quality and the homogeneity of intrafractional dose at match lines. The IMPT approach developed may also simplify treatments and reduce workload per patient relative to PSPT. [ABSTRACT FROM AUTHOR]

Abstract: In the region of high-dose gradients at the end of the proton range, the stopping power ratio of the protons undergoes significant changes, allowing for a broad spectrum of proton energies to be deposited within a relatively small volume. Because of the potential linear energy transfer dependence of LiF TLD-100 (thermolumescent dosimeter), dose measurements made in the distal fall-off region of a proton beam may be less accurate than those made in regions of low-dose gradients. The purpose of this study is to determine the accuracy and precision of dose measured using TLD-100 for a pristine Bragg peak, particularly in the distal fall-off region. All measurements were made along the central axis of an unmodulated 200-MeV proton beam from a Probeat passive beam-scattering proton accelerator (Hitachi, Ltd., Tokyo, Japan) at varying depths along the Bragg peak. Measurements were made using TLD-100 powder flat packs, placed in a virtual water slab phantom. The measurements were repeated using a parallel plate ionization chamber. The dose measurements using TLD-100 in a proton beam were accurate to within ±5.0% of the expected dose, previously seen in our past photon and electron measurements. The ionization chamber and the TLD relative dose measurements agreed well with each other. Absolute dose measurements using TLD agreed with ionization chamber measurements to within ± 3.0 cGy, for an exposure of 100 cGy. In our study, the differences in the dose measured by the ionization chamber and those measured by TLD-100 were minimal, indicating that the accuracy and precision of measurements made in the distal fall-off region of a pristine Bragg peak is within the expected range. Thus, the rapid change in stopping power ratios at the end of the range should not affect such measurements, and TLD-100 may be used with confidence as an in vivo dosimeter for proton beam therapy. [Copyright &y& Elsevier]

Purpose: A single-institution prospective study was conducted to assess disease control and toxicity of proton therapy for patients with head and neck cancer.Methods and Materials: Disease control, toxicity, functional outcomes, and patterns of failure for the initial cohort of patients with oropharyngeal squamous carcinoma (OPC) treated with intensity modulated proton therapy (IMPT) were prospectively collected in 2 registry studies at a single institution. Locoregional failures were analyzed by using deformable image registration.Results: Fifty patients with OPC treated from March 3, 2011, to July 2014 formed the cohort. Eighty-four percent were male, 50% had never smoked, 98% had stage III/IV disease, 64% received concurrent therapy, and 35% received induction chemotherapy. Forty-four of 45 tumors (98%) tested for p16 were positive. All patients received IMPT (multifield optimization to n=46; single-field optimization to n=4). No Common Terminology Criteria for Adverse Events grade 4 or 5 toxicities were observed. The most common grade 3 toxicities were acute mucositis in 58% of patients and late dysphagia in 12%. Eleven patients had a gastrostomy (feeding) tube placed during therapy, but none had a feeding tube at last follow-up. At a median follow-up time of 29 months, 5 patients had disease recurrence: local in 1, local and regional in 1, regional in 2, and distant in 1. The 2-year actuarial overall and progression-free survival rates were 94.5% and 88.6%.Conclusions: The oncologic, toxicity, and functional outcomes after IMPT for OPC are encouraging and provide the basis for ongoing and future clinical studies. [ABSTRACT FROM AUTHOR]

Purpose Computed tomography (CT) artifacts can severely degrade dose calculation accuracy in proton therapy. Prompted by the recently increased popularity of magnetic resonance imaging (MRI) in the radiation therapy clinic, we developed an MRI-based CT artifact correction method for improving the accuracy of proton range calculations. Methods and Materials The proposed method replaces corrupted CT data by mapping CT Hounsfield units (HU number) from a nearby artifact-free slice, using a coregistered MRI. MRI and CT volumetric images were registered with use of 3-dimensional (3D) deformable image registration (DIR). The registration was fine-tuned on a slice-by-slice basis by using 2D DIR. Based on the intensity of paired MRI pixel values and HU from an artifact-free slice, we performed a comprehensive analysis to predict the correct HU for the corrupted region. For a proof-of-concept validation, metal artifacts were simulated on a reference data set. Proton range was calculated using reference, artifactual, and corrected images to quantify the reduction in proton range error. The correction method was applied to 4 unique clinical cases. Results The correction method resulted in substantial artifact reduction, both quantitatively and qualitatively. On respective simulated brain and head and neck CT images, the mean error was reduced from 495 and 370 HU to 108 and 92 HU after correction. Correspondingly, the absolute mean proton range errors of 2.4 cm and 1.7 cm were reduced to less than 2 mm in both cases. Conclusions Our MRI-based CT artifact correction method can improve CT image quality and proton range calculation accuracy for patients with severe CT artifacts. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to evaluate the impact of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) fused with planning computed tomography (CT) on tumor localization, which guided intensity-modulated radiotherapy (IMRT) of patients with head-and-neck carcinoma. Methods and Materials: From October 2002 through April 2005, we performed FDG-PET/CT guided IMRT for 28 patients with head-and-neck carcinoma. Patients were immobilized with face masks that were attached with five fiducial markers. FDG-PET and planning CT scans were performed on the same flattop table in one session and were then fused. Target volumes and critical organs were contoured, and IMRT plans were generated based on the fused images. Results: All 28 patients had abnormal increased uptake in FDG-PET/CT scans. PET/CT resulted in CT-based staging changes in 16 of 28 (57%) patients. PET/CT fusions were successfully performed and were found to be accurate with the use of the two commercial planning systems. Volume analysis revealed that the PET/CT-based gross target volumes (GTVs) were significantly different from those contoured from the CT scans alone in 14 of 16 patients. In addition, 16 of 28 patients who were followed for more than 6 months did not have any evidence of locoregional recurrence in the median time of 17 months. Conclusion: Fused images were found to be useful to delineate GTV required in IMRT planning. PET/CT should be considered for both initial staging and treatment planning in patients with head-and-neck carcinoma. [ABSTRACT FROM AUTHOR]