Bio


Education:

1990-B.S., Bioelectrical Engineering (6-1B), Massachusetts Institute of Technology, Cambridge, MA

1992-M.S., Bioengineering, University of Pennsylvania, Philadelphia, PA

1994-M.S., Nuclear Engineering (NMR Spectroscopy), Massachusetts Institute of Technology, Cambridge, MA

1999-Ph.D., Nuclear Engineering (Boron Neutron Capture Therapy), Massachusetts Institute of Technology, Cambridge, MA

2001-Postdoctoral Fellowship (Peregrine Project), Lawrence Livermore National Laboratory

2003-Medical Physics Residency, University of California, San Francisco (joint 3.5-year postdoctoral and residency program)


Academic Appointments:

2003 - 2005-Clinical Instructor, Radiation Oncology, University of California, San Francisco, San Francisco, California

2005 - 2009-Assistant Adjunct Professor, Radiation Oncology, University of California, San Francisco, San Francisco, California

2009 - 2013-Assistant Professor In Residence, Radiation Oncology, University of California, San Francisco, San Francisco, California

2013 - 2017-Associate Professor In Residence, Radiation Oncology, University of California, San Francisco, San Francisco, California

2017 - 2018-Associate Professor of Clinical Radiation Oncology, University of California, San Francisco, San Francisco, California

2019 - 2023-Clinical Associate Professor, Department of Radiation Oncology, Clinical Educator Line, Stanford University, Stanford, CA

2024 - Present-Clinical Professor, Department of Radiation Oncology, Clinical Educator Line, Stanford University, Stanford, CA

Academic Appointments


Honors & Awards


  • The Fairchild Award for Young Researchers, International Society for Neutron Capture Therapy (1998)
  • Travel Grant Award Recipient, AAPM (2004)
  • Best of Physics presentation (2nd author), 54th Annual AAPM Meeting (2012)

Boards, Advisory Committees, Professional Organizations


  • Member, American Nuclear Society (1993 - 1999)
  • Member, American Association of Physicists in Medicine (1999 - Present)
  • Member, American Society of Radiation Oncology (2006 - Present)
  • Medical Physics Co-Chair, NRG HN-008, NRG (2020 - Present)
  • Chair, AAPM Practice Environment Subcommittee (CCGSC), American Association of Physicists in Medicine (2023 - Present)
  • Chair, AAPM Quality Assurance and Outcome Improvement Subcommittee (QASC), Member, American Association of Physicists in Medicine (2023 - Present)

All Publications


  • A time- and space-saving Monte Carlo simulation method using post-collimation generative adversarial network for dose calculation of an O-ring gantry Linac. Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB) Shi, M., Cui, S., Chuang, C., Oderinde, O., Kovalchuk, N., Surucu, M., Xing, L., Han, B. 2024; 119: 103318

    Abstract

    This study explores the feasibility of employing Generative Adversarial Networks (GANs) to model the RefleXion X1 Linac. The aim is to investigate the accuracy of dose simulation and assess the potential computational benefits.The X1 Linac is a new radiotherapy machine with a binary multi-leaf collimation (MLC) system, facilitating innovative biology-guided radiotherapy. A total of 34 GAN generators, each representing a desired MLC aperture, were developed. Each generator was trained using a phase space file generated underneath the corresponding aperture, enabling the generation of particles and serving as a beam source for Monte Carlo simulation. Dose distributions in water were simulated for each aperture using both the GAN and phase space sources. The agreement between dose distributions was evaluated. The computational time reduction from bypassing the collimation simulation and storage space savings were estimated.The percentage depth dose at 10 cm, penumbra, and full-width half maximum of the GAN simulation agree with the phase space simulation, with differences of 0.4 % ± 0.2 %, 0.32 ± 0.66 mm, and 0.26 ± 0.44 mm, respectively. The gamma passing rate (1 %/1mm) for the planar dose exceeded 90 % for all apertures. The estimated time-saving for simulating an plan using 5766 beamlets was 530 CPU hours. The storage usage was reduced by a factor of 102.The utilization of the GAN in simulating the X1 Linac demonstrated remarkable accuracy and efficiency. The reductions in both computational time and storage requirements make this approach highly valuable for future dosimetry studies and beam modeling.

    View details for DOI 10.1016/j.ejmp.2024.103318

    View details for PubMedID 38382210

  • Angular correction methodology and characterization of a high-resolution CMOS array for patient specific quality assurance on a robotic arm linac. Journal of applied clinical medical physics Ashraf, M. R., Krimmer, J., Zalavri, L., Gu, X., Wang, L., Chuang, C. F. 2023: e14110

    Abstract

    PURPOSE: To develop an angular correction methodology and characterize a high-resolution complementary metal-oxide-semiconductor (CMOS) array for patient specific quality assurance on a robotic arm linear accelerator.METHODS: Beam path files from the treatment planning software (TPS) were used to calculate the angle of radiation beam with respect to the detector plane. Beams from multiple discrete angles were delivered to the CMOS detector array and an angular dependency look up table (LUT) was created. The LUT was then used to correct for the angular dependency of the detector. An iso-centric 5mm fixed cone, non iso-centric multi-target fixed cone, 10mm Iris and a multi-leaf collimator (MLC) based collimated plan were delivered to the phantom and compared to the TPS with and without angular correction applied. Additionally, the CMOS array was compared to gafchromic film and a diode array.RESULTS: Large errors of up to 30% were observed for oblique angles. When angular correction was applied, the gamma passing rate increased from 99.2% to 100% (average gamma value decreased from 0.29 to 0.14) for the 5-mm iso-centric cone plan. Similarly, the passing rate increased from 84.0% to 100% for the Iris plan and from 49.98% to 98.4% for the MLC plan when angular correction was applied. For the multi-target plan, applying angular correction improved the gamma passing rate from 94% to 99.6%. The 5mm iso-centric fixed cone plan was also delivered to film, and the gamma passing rate was 91.3% when using gafchromic film as the reference dataset, whereas the diode array provided insufficient sampling for this plan.CONCLUSION: A methodology of calculating the beam angle based on the beam path files was developed and validated. The array was demonstrated to be superior to other quality assurance tools because of its sub-millimeter spatial resolution and immediate read out of the results.

    View details for DOI 10.1002/acm2.14110

    View details for PubMedID 37528747

  • Stereotactic Radiosurgery for Contrast-Enhancing Satellite Nodules in Recurrent Glioblastoma: A Rare Case Series From a Single Institution. Cureus Park, D. J., Persad, A. R., Yoo, K. H., Marianayagam, N. J., Yener, U., Tayag, A., Ustrzynski, L., Emrich, S. C., Chuang, C., Pollom, E., Soltys, S. G., Meola, A., Chang, S. D. 2023; 15 (8): e44455

    Abstract

    Introduction Glioblastoma (GBM) is the most common malignant adult brain tumor and is invariably fatal. The standard treatment for GBM involves resection where possible, followed by chemoradiation per Stupp's protocol. We frequently use stereotactic radiosurgery (SRS) as a single-fraction treatment for small (volume ≤ 1cc) nodular recurrent GBM to the contrast-enhancing target on T1 MRI scan. In this paper, we aimed to evaluate the safety and efficacy of SRS for patients with contrast-enhancing satellite nodules in recurrent GBM. Methods This retrospective study analyzed the clinical and radiological outcomes of five patients who underwent CyberKnife (Accuray Inc., Sunnyvale, California) SRS at the institute between 2013 and 2022. Results From 96 patients receiving SRS for GBM, five (four males, one female; median age 53) had nine distinct new satellite lesions on MRI, separate from their primary tumor beds. Those nine lesions were treated with a median margin dose of 20 Gy in a single fraction. The three-, six, and 12-month local tumor control rates were 77.8%, 66.7%, and 26.7%, respectively. Median progression-free survival (PFS) was seven months, median overall survival following SRS was 10 months, and median overall survival (OS) was 35 months. Interestingly, the only lesion that did not show radiological progression was separate from the T2-fluid attenuated inversion recovery (FLAIR) signal of the main tumor. Conclusion Our SRS treatment outcomes for recurrent GBM satellite lesions are consistent with existing findings. However, in a unique case, a satellite nodule distinct from the primary tumor's T2-FLAIR signal and treated with an enlarged target volume showed promising control until the patient's demise. This observation suggests potential research avenues, given the limited strategies for 'multicentric' GBM lesions.

    View details for DOI 10.7759/cureus.44455

    View details for PubMedID 37664337

    View details for PubMedCentralID PMC10470661

  • Physics of Stereotactic Radiosurgery and Stereotactic Body Radiotherapy Handbook of Evidence-Based Stereotactic Radiosurgery and Stereotactic Body Radiotherapy Perez-Andujar, A., Descovich, M., Chuang, C. Springer Cham. 2023; 2
  • Stereotactic radiosurgery for trigeminal neuralgia secondary to tumor: a single-institution retrospective series. Neurosurgical focus Hall, J. C., Ung, T. H., McCleary, T. L., Chuang, C., Gibbs, I. C., Soltys, S. G., Hayden Gephart, M., Li, G., Pollom, E. L., Chang, S. D., Meola, A. 2022; 53 (5): E3

    Abstract

    Trigeminal neuralgia (TN) secondary to tumor represents a rare and diverse entity, and treatment for secondary TN remains controversial. This report reviews a single institution's experience in treating secondary TN with stereotactic radiosurgery (SRS) and focuses on the durability of pain relief with respect to various treatment targets, i.e., the trigeminal nerve, offending tumor, or both.Between the years 2009 and 2021, 21 patients with TN secondary to benign (n = 13) or malignant (n = 8) tumors underwent SRS. Barrow Neurological Institute (BNI) pain intensity scale scores were collected from patient electronic medical records at baseline, initial follow-up, and 1 and 3 years post-SRS. The interval change in BNI scale score (ΔBNI) at the various follow-up time points was also calculated to assess the durability of pain relief following SRS.The median follow-up period was 24 (range 0.5-155) months. Five patients (24%) received treatment to the trigeminal nerve only, 10 (48%) received treatment to the tumor only, and 6 (29%) had treatment to both the nerve and tumor. The overall radiation dosage ranged from 14 to 60 Gy delivered in 1-5 fractions, with a median overall dose of 26 Gy. The median dose to the tumor was 22.5 (range 14-35) Gy, delivered in 1-5 fractions. Of the treatments targeting the tumor, 25% were delivered in a single fraction with doses ranging from 14 to 20 Gy, 60% were delivered in 3 fractions with doses ranging from 18 to 27 Gy, and 15% were delivered in 5 fractions with doses ranging from 25 to 35 Gy. The most common dose regimen for tumor treatment was 24 Gy in 3 fractions. The median biologically effective dose (with an assumed alpha/beta ratio of 10 [BED10]) for tumor treatments was 43.1 (range 13.3-60.0) Gy. There was a significant difference in the proportion of patients with recurrent pain (ΔBNI score ≥ 0) at the time of last follow-up across the differing SRS treatment targets: trigeminal nerve only, tumor only, or both (p = 0.04). At the time of last follow-up, the median ΔBNI score after SRS to the nerve only was -1, 0 after SRS to tumor only, and -2 after SRS to both targets.SRS offers clinical symptomatic benefit to patients with TN secondary to tumor. For optimal pain relief and response durability, treatment targeting both the tumor and the trigeminal nerve appears to be most advantageous.

    View details for DOI 10.3171/2022.8.FOCUS22381

    View details for PubMedID 36321284

  • Mitigating the uncertainty in small field dosimetry by leveraging machine learning strategies. Physics in medicine and biology Zhao, W., Yang, Y., Xing, L., Chuang, C. F., Schüler, E. 2022

    Abstract

    Small field dosimetry is significantly different from the dosimetry of broad beams due to loss of electron side scatter equilibrium, source occlusion, and effects related to the choice of detector. However, use of small fields is increasing with the increase in indications for intensity-modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT), and thus the need for accurate dosimetry is ever more important. Here we propose to leverage machine learning (ML) strategies to reduce the uncertainties and increase the accuracy in determining small field output factors (OFs). Linac OFs from a Varian TrueBeam STx were calculated either by the treatment planning system (TPS) or measured with a W1 scintillator detector at various multi-leaf collimator (MLC) positions, jaw positions, and with and without contribution from leaf-end transmission. The fields were defined by the MLCs with the jaws at various positions. Field sizes between 5 and 100 mm were evaluated. Separate ML regression models were generated based on the TPS calculated or the measured datasets. Accurate predictions of small field OFs at different field sizes (FSs) were achieved independent of jaw and MLC position. A mean and maximum % relative error (RE) of 0.380.39% and 3.62%, respectively, for the best-performing models based on the measured datasets were found. The prediction accuracy was independent of contribution from leaf-end transmission. Several ML models for predicting small field OFs were generated, validated, and tested. Incorporating these models into the dose calculation workflow could greatly increase the accuracy and robustness of dose calculations for any radiotherapy delivery technique that relies heavily on small fields.

    View details for DOI 10.1088/1361-6560/ac7fd6

    View details for PubMedID 35803256

  • Implicit neural representation for radiation therapy dose distribution. Physics in medicine and biology Vasudevan, V., Shen, L., Huang, C., Chuang, C. F., Islam, M. T., Ren, H., Yang, Y., Dong, P., Xing, L. 2022

    Abstract

    OBJECTIVE: Dose distribution data plays a pivotal role in radiotherapy treatment planning. The data is typically represented using voxel grids, and its size ranges from 10^6--10^8. A concise representation of the treatment plan is of great value in facilitating treatment planning and downstream applications. This work aims to develop an implicit neural representation of 3D dose distribution data.APPROACH: Instead of storing the dose values at each voxel, in the proposed approach, the weights of a multilayer perceptron (MLP) are employed to characterize the dosimetric data for plan representation and subsequent applications. We train a coordinate-based MLP with sinusoidal activations to map the voxel spatial coordinates to the corresponding dose values. We identify the best architecture for a given parameter budget and use that to train a model for each patient. The trained MLP is evaluated at each voxel location to reconstruct the dose distribution. We perform extensive experiments on dose distributions of prostate, spine, and head and neck tumor cases to evaluate the quality of the proposed representation. We also study the change in representation quality by varying model size and activation function.MAIN RESULTS: Using coordinate-based MLPs with sinusoidal activations, we can learn implicit representations that achieve a mean-squared error of 10^{-6} and peak signal-to-noise ratio greater than 50 dB at a target bitrate of ~1 across all the datasets, with a compression ratio of ~32. Our results also show that model sizes with a bitrate of 1--2 achieve optimal accuracy. For smaller bitrates, performance starts to drop significantly.SIGNIFICANCE: The proposed model provides a low-dimensional, implicit, and continuous representation of 3D dose data. In summary, given a dose distribution, we systematically show how to find a compact model to fit the data accurately. This study lays the groundwork for future applications of neural representations of dose data in radiation oncology.

    View details for DOI 10.1088/1361-6560/ac6b10

    View details for PubMedID 35477171

  • Small field measurement and monte carlo model validation of a novel image-guided radiotherapy system. Medical physics Shi, M., Chuang, C. F., Kovalchuk, N., Bush, K. K., Zaks, D., Xing, L., Surucu, M., Han, B. 2021

    Abstract

    PURPOSE: The RefleXionTM X1 is a novel radiotherapy system that is designed for image-guided radiotherapy and, eventually, biology-guided radiotherapy (BgRT). BgRT is a treatment paradigm that tracks tumor motion using real-time positron emission signals. This study reports the small field measurement results and the validation of a Monte Carlo (MC) model of the first clinical RefleXion unit.METHODS: The RefleXion linear accelerator (linac) produces a 6 MV flattening filter free (FFF) photon beam and consists of a binary multi-leaf collimator (MLC) system with 64 leaves and two pairs of y-jaws. The maximum clinical field size achievable is 400 * 20 mm2 . The y-jaws provide either a 10 mm or 20 mm opening at source-to-axis distance (SAD) of 850 mm. The width of each MLC leaf at SAD is 6.25 mm. Percentage depth doses (PDDs) and relative beam profiles were acquired using an Edge diode detector in a water tank for field sizes from 12.5 * 10 mm2 to 100 * 20 mm2 . Beam profiles were also measured using films. Output factors of fields ranging from 6.25 * 10 mm2 to 100 * 20 mm2 were measured using W2 scintillator detector, Edge detector, and films. Output correction factors k of the Edge detector for RefleXion were calculated. A MC model of the linac including pre-MLC beam sources and detailed structures of MLC and lower y-jaws was validated against the measurements. Simulation codes BEAMnrc and GATE were utilized.RESULTS: The diode measured PDD at 10 cm depth (PDD10) increases from 53.6% to 56.9% as the field opens from 12.5 * 10 mm2 to 100 * 20 mm2 . The W2-measured output factor increases from 0.706 to 1 as the field opens from 6.25 * 10 mm2 to 100 * 20 mm2 (reference field size). The output factors acquired by diode and film differ from the W2 results by 1.65% (std = 1.49%) and 2.09% (std = 1.41%) on average, respectively. The profile penumbra and full width half maximum (FWHM) measured by diode agree well with the film results with a deviation of 0.60 mm and 0.73% on average, respectively. The averaged beam profile consistency calculated between the diode and film measured profiles among different depths is within 1.72%. By taking the W2 measurements as the ground truth, the output correction factors k for Edge detector ranging from 0.958 to 1 were reported. For the MC model validation, the simulated PDD10 agreed within 0.6% to the diode measurement. The MC simulated output factor differed from the W2 results by 2.3% on average (std = 3.7%) while the MC simulated beam penumbra differed from the diode results by 0.67 mm on average (std = 0.42 mm). The MC FWHM agreed with the diode results to within 1.40% on average. The averaged beam profile consistency calculated between the diode and MC profiles among different depths is less than 1.29%.CONCLUSIONS: This study represents the first small field dosimetry of a clinical RefleXion system. A complete and accurate MC model of the RefleXion linac has been validated. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1002/mp.15273

    View details for PubMedID 34628666

  • Deep learning-enabled EPID-based 3D dosimetry for dose verification of step-and-shoot radiotherapy. Medical physics Jia, M., Wu, Y., Yang, Y., Wang, L., Chuang, C., Han, B., Xing, L. 2021

    Abstract

    PURPOSE: The study aims at a novel dosimetry methodology to reconstruct a 3D dose distribution as imparted to a virtual cylindrical phantom using an electronic portal imaging device (EPID).METHODS: A deep learning-based signal processing strategy, referred to as 3DosiNet, is utilized to learn a mapping from an EPID image to planar dose distributions at given depths. The network was trained with the volumetric dose exported from the clinical treatment planning system (TPS). Given the latent inconsistency between measurements and corresponding TPS calculations, unsupervised learning is formulated in 3DosiNet to capture abstractive image features that are less sensitive to the potential variations.RESULTS: Validation experiments were performed using five regular fields and three clinical IMRT cases. The measured dose profiles and percentage depth dose (PDD) curves were compared with those measured using standard tools in terms of the 1D gamma index. The mean gamma pass rates (2%/2mm) over the regular fields are 100% and 97.3% for the dose profile and PDD measurements, respectively. The measured volumetric dose was compared to corresponding TPS calculation in terms of the 3D gamma index. The mean 2% / 2mm gamma pass rates are 97.9% for square fields and 94.9% for the IMRT fields.CONCLUSIONS: The system promises to be a practical 3D dosimetric tool for pre-treatment patient-specific quality assurance and further developed for in-treatment patient dose monitoring. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1002/mp.15218

    View details for PubMedID 34519365

  • Medical Physics Practice Guideline (MPPG) 11.a: Plan and chart review in external beam radiotherapy and brachytherapy. Journal of applied clinical medical physics Xia, P., Sintay, B. J., Colussi, V. C., Chuang, C., Lo, Y., Schofield, D., Wells, M., Zhou, S. 2021

    Abstract

    A therapeutic medical physicist is responsible for reviewing radiation therapy treatment plans and patient charts, including initial treatment plans and new chart review, on treatment chart (weekly) review, and end of treatment chart review for both external beam radiation and brachytherapy. Task group report TG 275 examined this topic using a risk-based approach to provide a thorough analysis and guidance for best practice. Considering differences in resources and workflows of various clinical practice settings, the Professional Council of the American Association of Physicists in Medicine assembled this task group to develop a practice guideline on the same topic to provide a minimum standard that balances an appropriate level of safety and resource utilization. This medical physics practice guidelines (MPPG) thus provides a concise set of recommendations for medical physicists and other clinical staff regarding the review of treatment plans and patient charts while providing specific recommendations about who to be involved, and when/what to check in the chart review process. The recommendations, particularly those related to the initial plan review process, are critical for preventing errors and ensuring smooth clinical workflow. We believe that an effective review process for high-risk items should include multiple layers with collective efforts across the department. Therefore, in this report, we make specific recommendations for various roles beyond medical physicists. The recommendations of this MPPG have been reviewed and endorsed by the American Society of Radiologic Technologists and the American Association of Medical Dosimetrists.

    View details for DOI 10.1002/acm2.13366

    View details for PubMedID 34342124

  • The Stanford stereotactic radiosurgery experience on 7000 patients over 2 decades (1999-2018): looking far beyond the scalpel. Journal of neurosurgery Fatima, N., Meola, A., Ding, V. Y., Pollom, E., Soltys, S. G., Chuang, C. F., Shahsavari, N., Hancock, S. L., Gibbs, I. C., Adler, J. R., Chang, S. D. 2021: 1–17

    Abstract

    OBJECTIVE: The CyberKnife (CK) has emerged as an effective frameless and noninvasive method for treating a myriad of neurosurgical conditions. Here, the authors conducted an extensive retrospective analysis and review of the literature to elucidate the trend for CK use in the management paradigm for common neurosurgical diseases at their institution.METHODS: A literature review (January 1990-June 2019) and clinical review (January 1999-December 2018) were performed using, respectively, online research databases and the Stanford Research Repository of patients with intracranial and spinal lesions treated with CK at Stanford. For each disease considered, the coefficient of determination (r2) was estimated as a measure of CK utilization over time. A change in treatment modality was assessed using a t-test, with statistical significance assessed at the 0.05 alpha level.RESULTS: In over 7000 patients treated with CK for various brain and spinal lesions over the past 20 years, a positive linear trend (r2 = 0.80) in the system's use was observed. CK gained prominence in the management of intracranial and spinal arteriovenous malformations (AVMs; r2 = 0.89 and 0.95, respectively); brain and spine metastases (r2 = 0.97 and 0.79, respectively); benign tumors such as meningioma (r2 = 0.85), vestibular schwannoma (r2 = 0.76), and glomus jugulare tumor (r2 = 0.89); glioblastoma (r2 = 0.54); and trigeminal neuralgia (r2 = 0.81). A statistically significant difference in the change in treatment modality to CK was observed in the management of intracranial and spinal AVMs (p < 0.05), and while the treatment of brain and spine metastases, meningioma, and glioblastoma trended toward the use of CK, the change in treatment modality for these lesions was not statistically significant.CONCLUSIONS: Evidence suggests the robust use of CK for treating a wide range of neurological conditions.

    View details for DOI 10.3171/2020.9.JNS201484

    View details for PubMedID 33799297

  • A robotically assisted 3D printed quality assurance lung phantom for Calypso. Physics in medicine and biology Capaldi, D. P., Skinner, L. B., Dubrowski, P. n., Zhang, H. n., Xing, L. n., Chuang, C. F., Loo, B. W., Bush, K. K., Fahimian, B. P., Yu, A. S. 2021

    Abstract

    Purpose:Radiation dose delivered to targets located near the upper-abdomen or in the thorax are significantly affected by respiratory-motion. Relatively large-margins are commonly added to compensate for this motion, limiting radiation-dose-escalation. Internal-surrogates of target motion, such as a radiofrequency (RF) tracking system, i.e. Calypso® System, are used to overcome this challenge and improve normal-tissue sparing. RF tracking systems consist of implanting transponders in the vicinity of the tumor to be tracked using radiofrequency-waves. Unfortunately, although the manufacture provides a universal quality-assurance (QA) phantom, QA-phantoms specifically for lung-applications are limited, warranting the development of alternative solutions to fulfil the tests mandated by AAPM's TG142. Accordingly, our objective was to design and develop a motion-phantom to evaluate Calypso for lung-applications that allows the Calypso® Beacons to move in different directions to better simulate true lung-motion.Methods and Materials:A Calypso lung QA-phantom was designed, and 3D-printed. The design consists of three independent arms where the transponders were attached. A pinpoint-chamber with a buildup-cap was also incorporated. A 4-axis robotic arm was programmed to drive the motion-phantom to mimic breathing. After acquiring a four-dimensional-computed-tomography (4DCT) scan of the motion-phantom, treatment-plans were generated and delivered on a Varian TrueBeam® with Calypso capabilities. Stationary and gated-treatment plans were generated and delivered to determine the dosimetric difference between gated and non-gated treatments. Portal cine-images were acquired to determine the temporal-accuracy of delivery by calculating the difference between the observed versus expected transponders locations with the known speed of the transponders' motion.Results:Dosimetric accuracy is better than TG142 tolerance of 2%. Temporal accuracy is greater than, TG142 tolerance of 100ms for beam-on, but less than 100ms for beam-hold.Conclusions:The robotic QA-phantom designed and developed in this study provides an independent phantom for performing Calypso lung-QA for commissioning and acceptance testing of Calypso for lung treatments.

    View details for DOI 10.1088/1361-6560/abebaa

    View details for PubMedID 33657537

  • Cyberknife Image-Guided Hypofractionated Stereotactic Radiotherapy Image-Guided Hypofractionated Stereotactic Radiosurgery: A Practical Approach to Guide Treatment of Brain and Spine Tumors McGuinness, C., Descovich, M., Chuang, C. CRC Press. 2021; 2
  • ZAP-X: A Novel Radiosurgical Device for the Treatment of Trigeminal Neuralgia CUREUS Romanelli, P., Chuang, C., Meola, A., Bodduluri, R. M., Adler, J. R. 2020; 12 (5)
  • Clinical impact of the VOLO optimizer on treatment plan quality and clinical treatment efficiency for CyberKnife. Journal of applied clinical medical physics Schuler, E., Lo, A., Chuang, C. F., Soltys, S. G., Pollom, E. L., Wang, L. 2020

    Abstract

    With the recent CyberKnife treatment planning system (TPS) upgrade from Precision 1.0 to Precision 2.0, the new VOLO optimizer was released for plan optimization. The VOLO optimizer sought to overcome some of the limitations seen with the Sequential optimizer from previous TPS versions. The purpose of this study was to investigate the clinical impact of the VOLO optimizer on treatment plan quality and clinical treatment efficiency as compared to the Sequential optimizer. Treatment plan quality was evaluated in four categories of patients: Brain Simple (BS), Brain Complex (BC), Spine Complex (SC), and Prostate (PC). A total of 60 treatment plans were compared using both the Sequential and VOLO optimizers with Iris and MLC collimation with the same clinical constraints. Metrics evaluated included estimated treatment time, monitor units (MUs) delivered, conformity index (CI), and gradient index (GI). Furthermore, the clinical impact of the VOLO optimizer was evaluated through statistical analysis of the patient population treated during the 4months before (n=297) and 4months after (n=285) VOLO introduction. Significant MU and time reductions were observed for all four categories planned. MU reduction ranged from -14% (BS Iris) to -52% (BC MLC), and time reduction ranged from -11% (BS Iris) to -22% (BC MLC). The statistical analysis of patient population before and after VOLO introduction for patients using 6D Skull tracking with fixed cone, 6D Skull tracking with Iris, and Xsight Spine tracking with Iris were -4.6%, -22.2%, and -17.8% for treatment time reduction, -1.1%, -22.0%, and -28.4% for beam reduction and -3.2%, -21.8%, and -28.1% for MU reduction, respectively. The VOLO optimizer maintains or improves the plan quality while decreases the plan complexity and improves treatment efficiency. We anticipate an increase in patient throughput with the introduction of the VOLO optimizer.

    View details for DOI 10.1002/acm2.12851

    View details for PubMedID 32212374

  • Technical Note: Performance of CyberKnife® Tracking Using Low-Dose CT and kV Imaging. Medical physics Nano, T. F., Capaldi, D. P., Yeung, T. n., Chuang, C. F., Wang, L. n., Descovich, M. n. 2020

    Abstract

    To investigate the effects of CT protocol and in-room x-ray technique on CyberKnife® (Accuray Inc.) tracking accuracy by evaluating end-to-end tests.End-to-end (E2E) tests were performed for the different tracking methods (6D skull, fiducial, spine and lung) using an anthropomorphic head phantom (Accuray Inc.) and thorax phantom (CIRS Inc.). Bolus was added to the thorax phantom to simulate a large patient and to evaluate the performance of lung tracking in a more realistic condition. The phantoms were scanned with a Siemens Sensation Open 24 slice CT at low-dose (120kV, 70mAs, 1.5mm slice thickness) and high-dose (120kV, 700mAs, 1.5mm slice thickness) to generate low-dose and high-dose digitally reconstructed radiographs (DRRs). The difference in initial phantom alignment, Δ(Align), and in total targeting accuracy, E2E, were obtained for all tracking methods with low and high dose DRRs. Additionally, Δ(Align) was determined for different in-room x-ray imaging techniques (0.5 to 50mAs and 100 to 140kV) using a low-dose lung tracking plan.Low-dose CT scans produced images with high noise, however, for these phantoms the targets could be easily delineated on all scans. End-to-end results were less than 0.95mm for all tracking methods and all plans. The greatest difference in initial alignment Δ(Align) and E2E results between low and high dose CT protocols was 0.32mm and 0.24mm, respectively. Similar results were observed with a large thorax phantom. Tracking using di_erent in-room x-ray imaging techniques (mAs) corresponding to low exposures (resulting in high image noise) or high exposure (resulting in image saturation) had alignment accuracy Δ(Align) greater than 1mm.End-to-end targeting accuracy within tolerance (<0.95mm) was obtained for all tracking methods using low-dose CT protocols, suggesting that CT protocol should be set by target contouring needs. Additionally, high tracking accuracy was achieved for in in-room x-ray imaging techniques that produce high quality images.

    View details for DOI 10.1002/mp.14537

    View details for PubMedID 33064863

  • Stereotaxis: Principles and Techniques Stereotactic Radiosurgery (SRS): Procedures, Results and Risks Ma, L., Perez-Andujar, A., Chuang, C. 2020
  • Successful Use of Frameless Stereotactic Radiosurgery for Treatment of Recurrent Brain Metastases in an 18 Month Old Child. The International journal of neuroscience Rahimy, E., Chuang, C., Spunt, S. L., Mahaney, K., Donaldson, S. S., Gibbs, I. C., Soltys, S. G., Pollom, E., Hiniker, S. M. 2019: 1–6

    Abstract

    There are very few reported cases of stereotactic radiosurgery delivered in children under 3 years of age. We report an 18 month old boy with metastatic recurrence of undifferentiated round cell sarcoma to the brain which was treated with chemotherapy, resection, and robotic frameless stereotactic radiosurgery (SRS). Frameless SRS was delivered without technical difficulties, acute adverse events, or clinical sequelae 1.5 months post-radiation. Longer term follow-up will be needed to evaluate local tumor control and effects on neurocognitive development, endocrine function, and growth. This report adds to the literature of the few reported cases of successfully attempted SRS in very young children.

    View details for DOI 10.1080/00207454.2019.1655015

    View details for PubMedID 31401906

  • Optimizing beam models for dosimetric accuracy over a wide range of treatments. Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB) Chen, J., Morin, O., Weethee, B., Perez-Andujar, A., Phillips, J., Held, M., Kearney, V., Han, D. Y., Cheung, J., Chuang, C., Valdes, G., Sudhyadhom, A., Solberg, T. 2019; 58: 47-53

    Abstract

    This work presents a systematic approach for testing a dose calculation algorithm over a variety of conditions designed to span the possible range of clinical treatment plans. Using this method, a TrueBeam STx machine with high definition multi-leaf collimators (MLCs) was commissioned in the RayStation treatment planning system (TPS). The initial model parameters values were determined by comparing TPS calculations with standard measured depth dose and profile curves. The MLC leaf offset calibration was determined by comparing measured and calculated field edges utilizing a wide range of MLC retracted and over-travel positions. The radial fluence was adjusted using profiles through both the center and corners of the largest field size, and through measurements of small fields that were located at highly off-axis positions. The flattening filter source was adjusted to improve the TPS agreement for the output of MLC-defined fields with much larger jaw openings. The MLC leaf transmission and leaf end parameters were adjusted to optimize the TPS agreement for highly modulated intensity-modulated radiotherapy (IMRT) plans. The final model was validated for simple open fields, multiple field configurations, the TG 119 C-shape target test, and a battery of clinical IMRT and volumetric-modulated arc therapy (VMAT) plans. The commissioning process detected potential dosimetric errors of over 10% and resulted in a final model that provided in general 3% dosimetric accuracy. This study demonstrates the importance of using a variety of conditions to adjust a beam model and provides an effective framework for achieving high dosimetric accuracy.

    View details for DOI 10.1016/j.ejmp.2019.01.011

    View details for PubMedID 30824149

  • Fast calculation of nanodosimetric quantities in treatment planning of proton and ion therapy. Physics in medicine and biology Ramos-Méndez, J., Burigo, L. N., Schulte, R., Chuang, C., Faddegon, B. 2018; 63 (23): 235015

    Abstract

    Details of the pattern of ionization formed by particle tracks extends knowledge of dose effects on the nanometer scale. Ionization detail (ID), frequently characterized by ionization cluster size distributions (ICSD), is obtained through time-consuming Monte Carlo (MC) track-structure simulations. In this work, TOPAS-nBio was used to generate a highly precise database of biologically significant ID quantities, sampled with randomly oriented 2.3 nm diameter cylinders, 3.4 nm (10 base pairs) long, inside a chromatin-size cylinder, irradiated by 1-1000 MeV/u ions of Z  =  1-8. A macroscopic method developed to utilize the database using condensed-history MC was used to calculate distributions of the ICSD first moment [Formula: see text] and cumulative probability [Formula: see text] in a 20  ×  20  ×  40 cm3 water phantom irradiated with proton and carbon spread-out Bragg peak (SOBP) of 10.5 cm range, 2 cm width. Results were verified against detailed MC track-structure simulations using phase space scored at several depths. ID distributions were then obtained for intensity modulated proton and carbon radiotherapy plans in a digitized anthropomorphic phantom of a base of skull tumor to demonstrate clinical application of this approach. The database statistical uncertainties were 0.5% (3 standard deviations). Fluence-averaged ID as implemented proved unsuitable for macroscopic calculation. E dep-averaged ID agreed with track-structure results within 0.8% for protons. For carbon, maximum absolute differences of 2.9%  ±  1.6% and 5.6%  ±  1.9% for [Formula: see text], 1.7%  ±  0.8% and 1.9%  ±  0.4% (1 standard deviation) for [Formula: see text], were found in the plateau and SOBP, respectively, up to 11.5%  ±  5.6% in the tail region. Macroscopic ID calculation was demonstrated for a realistic treatment plan. Computation times with or without ID calculation were comparable in all cases. Pre-calculated nanodosimetric data may be used for condensed-history MC for nanodosimetric ID-based treatment planning in ion radiotherapy in the future. The macroscopic approach developed has the calculation speed of condensed-history MC while approaching the accuracy of full track structure simulations.

    View details for DOI 10.1088/1361-6560/aaeeee

    View details for PubMedID 30484432

    View details for PubMedCentralID PMC8691449

  • Correcting TG 119 confidence limits. Medical physics Kearney, V., Solberg, T., Jensen, S., Cheung, J., Chuang, C., Valdes, G. 2018; 45 (3): 1001-1008

    Abstract

    Task Group 119 (TG-119) has been adopted for evaluating the adequacy of intensity-modulated radiation therapy (IMRT) commissioning and for establishing patient-specific IMRT quality assurance (QA) passing criteria in clinical practice. TG-119 establishes 95% confidence limits (CLs), which help clinics identify systematic IMRT QA errors and identify outliers. In TG-119, the 95% CLs are established by fitting the Gamma Γ analysis passing rate results to an assumed distribution, then calculating the limit in which 95% of the data fall. CLs for a given dataset will depend greatly on the type of distribution used, and those determined by following the TG-119 guidelines are only valid if the underlying data follows a Gaussian distribution. Gaussian distributions assume symmetry about the mean, which would imply the possibility of negative Γ analysis failing rates. This study demonstrates that the gamma distribution is a more reasonable assumption for establishing CLs than the Gaussian distribution used in TG-119. Thus, the gamma distribution is suggested as a replacement to the conventional Gaussian statistical model used in TG-119.The moments estimator (ME) for the gamma family is used to obtain the CLs of the failing rates for all Γ analysis criteria. To demonstrate the congruence of the gamma distribution, the root mean squared error and the CL values for the MEs of the gamma and the Gaussian families were compared.In this study, the empirical 95% CLs generated using 302 plans represent the ground truth, which resulted in a 91.83% passing rate using 3%/3 mm error local criteria. The gamma distribution underestimates the 95% CL by 0.09%, while the Gaussian distribution overestimates the 95% CL by 4.12%.Although IMRT QA equipment may vary between clinics, the mathematical formalism presented in this study applies to any combination of planning and delivery systems. This study has demonstrated that a gamma distribution should be favored over a Gaussian distribution when establishing CLs for IMRT QA.

    View details for DOI 10.1002/mp.12759

    View details for PubMedID 29360150

  • Non-local total-variation (NLTV) minimization combined with reweighted L1-norm for compressed sensing CT reconstruction PHYSICS IN MEDICINE AND BIOLOGY Kim, H., Chen, J., Wang, A., Chuang, C., Held, M., Pouliot, J. 2016; 61 (18): 6878–91

    Abstract

    The compressed sensing (CS) technique has been employed to reconstruct CT/CBCT images from fewer projections as it is designed to recover a sparse signal from highly under-sampled measurements. Since the CT image itself cannot be sparse, a variety of transforms were developed to make the image sufficiently sparse. The total-variation (TV) transform with local image gradient in L1-norm was adopted in most cases. This approach, however, which utilizes very local information and penalizes the weight at a constant rate regardless of different degrees of spatial gradient, may not produce qualified reconstructed images from noise-contaminated CT projection data. This work presents a new non-local operator of total-variation (NLTV) to overcome the deficits stated above by utilizing a more global search and non-uniform weight penalization in reconstruction. To further improve the reconstructed results, a reweighted L1-norm that approximates the ideal sparse signal recovery of the L0-norm is incorporated into the NLTV reconstruction with additional iterates. This study tested the proposed reconstruction method (reweighted NLTV) from under-sampled projections of 4 objects and 5 experiments (1 digital phantom with low and high noise scenarios, 1 pelvic CT, and 2 CBCT images). We assessed its performance against the conventional TV, NLTV and reweighted TV transforms in the tissue contrast, reconstruction accuracy, and imaging resolution by comparing contrast-noise-ratio (CNR), normalized root-mean square error (nRMSE), and profiles of the reconstructed images. Relative to the conventional NLTV, combining the reweighted L1-norm with NLTV further enhanced the CNRs by 2-4 times and improved reconstruction accuracy. Overall, except for the digital phantom with low noise simulation, our proposed algorithm produced the reconstructed image with the lowest nRMSEs and the highest CNRs for each experiment.

    View details for DOI 10.1088/0031-9155/61/18/6878

    View details for Web of Science ID 000384317800002

    View details for PubMedID 27589006

  • Performance variations among clinically available deformable image registration tools in adaptive radiotherapy - how should we evaluate and interpret the result? Journal of applied clinical medical physics Nie, K., Pouliot, J., Smith, E., Chuang, C. 2016; 17 (2): 328-340

    Abstract

    The purpose of this study is to evaluate the performance variations in commercial deformable image registration (DIR) tools for adaptive radiation therapy and further to interpret the differences using clinically available terms. Three clinical examples (prostate, head and neck (HN), and cranial spinal irradiation (CSI) with L-spine boost) were evaluated in this study. Firstly, computerized deformed CT images were generated using simulation QA software with virtual deformations of bladder filling (prostate), neck flexion/bite-block repositioning/tumor shrinkage (HN), and vertebral body rotation (CSI). The corresponding transformation matrices served as a "reference" for the following comparisons. Three commercialized DIR algorithms: the free-form deformation from MIMVista 5.5 and the RegRefine from MIMMaestro 6.0, the multipass B-spline from VelocityAI v3.0.1, and the adap-tive demons from OnQ rts 2.1.15, were applied between the initial images and the deformed CT sets. The generated adaptive contours and dose distributions were compared with the "reference" and among each other. The performance in transfer-ring contours was comparable among all three tools with an average Dice similarity coefficient of 0.81 for all the organs. However, the dose warping accuracy appeared to rely on the evaluation end points and methodologies. Point-dose differences could show a difference of up to 23.3 Gy inside the PTVs and to overestimate up to 13.2 Gy for OARs, which was substantial for a 72 Gy prescription dose. Dose-volume histogram-based evaluation might not be sensitive enough to illustrate all the detailed variations, while isodose assessment on a slice-by-slice basis could be tedious. We further explored the possibility of using 3D gamma index analysis for warping dose variation assessment, and observed differences in dose warping using different DIR tools. Overall, our results demonstrated that evaluation based only on the performance of contour transformation could not guarantee the accuracy in dose warping, while dose-transferring validation strongly relied on the evaluation endpoint. As dose-transferring errors could cause misinterpretations when attempting to accumulate dose for adaptive radiation therapy and more DIR tools are available for clinical use, a standard and clinically meaningful quality assurance criterion should be established for DIR QA in the near future.

    View details for DOI 10.1120/jacmp.v17i2.5778

    View details for PubMedID 27074457

    View details for PubMedCentralID PMC5874855

  • Technical Note: Preferred dosimeter size and associated correction factors in commissioning high dose per pulse, flattening filter free x-ray beams. Medical physics Sudhyadhom, A., Kirby, N., Faddegon, B., Chuang, C. F. 2016; 43 (3): 1507-13

    Abstract

    High dose rate flattening filter free (FFF) beams pose new challenges and considerations for accurate reference and relative dosimetry. The authors report errors associated with commonly used ion chambers and introduce simple methods to mitigate them.Dosimetric errors due to (1) ion recombination effects of high dose per pulse (DPP) FFF beams and (2) volume-averaging effects of the radial profile were examined on a TrueBeam STx. Four commonly used cylindrical ion chambers spanning a range of lengths (0.29-2.3 cm) and volumes (0.016-0.6 cm(3)) were used to determine the magnitude of these effects for 6 and 10 MV unflattened x-ray beams (6XFFF and 10XFFF, respectively). Two methods were used to determine the magnitude of ion collection efficiency: (1) direct measurement of the percent depth dose (PDD) for the clinical, high DPP beam in comparison to that obtained after reducing the DPP and (2) measurement of Pion as a function of depth. Two methods were used to quantify the magnitude of volume-averaging: (1) direct measurement of volume-averaging via cross-calibration and (2) calculation of volume-averaging from radial profiles of the beam. Finally, a simple analytical expression for the radial profile volume-averaging correction factor, Prp = [OAR(0.29L)](-1), or the inverse of the off-axis ratio of dose at 0.29L, where L is the length of the chamber's sensitive volume, is introduced to mitigate the volume-averaging effect in Farmer-type chambers.Errors in measured PDD for the clinical beams were 1.3% ± 0.07% and 1.6% ± 0.07% at 35 cm depth for the 6XFFF and 10XFFF beam, respectively, using an IBA CC13 ion chamber, due to charge recombination with a high DPP. Volume-averaging effects were 0.4% and 0.7% for the 6XFFF and 10XFFF beam, respectively, when measured with a Farmer-type chamber. For the application of TG-51, these errors combine when using a CC13 to measure the PDD and a Farmer for absolute output dosimetry for a total error of up to 2% at dmax for the 10XFFF beam.Relative and absolute dosimetry in high DPP, unflattened x-ray beams of 10 MV or higher requires corrections for charge recombination and/or volume-averaging when dosimeters with certain geometries are used. Chambers used for PDD measurement are available that do not require a correction for charge recombination. A simple analytical expression of the correction factor Prp was introduced in this work to account for volume-averaging effects in Farmer chambers. Choice of an appropriate dosimeter coupled with application of the established correction factors Pion and Prp reduces the uncertainty in the PDD measurement and the reference dose measurement.

    View details for DOI 10.1118/1.4941691

    View details for PubMedID 26936734

  • Physics of Stereotactic Radiosurgery and Stereotactic Body Radiotherapy Handbook of Evidence-Based Stereotactic Radiosurgery and Stereotactic Body Radiotherapy Perez-Andujar, A., Descovich, M., Chuang, C. Springer Cham. 2016; 1
  • Use of TrueBeam developer mode for imaging QA. Journal of applied clinical medical physics Valdes, G., Morin, O., Valenciaga, Y., Kirby, N., Pouliot, J., Chuang, C. 2015; 16 (4): 322–333

    Abstract

    The purpose of this study was to automate regular Imaging QA procedures to become more efficient and accurate. Daily and monthly imaging QA for SRS and SBRT protocols were fully automated on a Varian linac. A three-step paradigm where the data are automatically acquired, processed, and analyzed was defined. XML scripts were written and used in developer mode in a TrueBeam linac to automatically acquire data. MATLAB R013B was used to develop an interface that could allow the data to be processed and analyzed. Hardware was developed that allowed the localization of several phantoms simultaneously on the couch. 14 KV CBCTs from the Emma phantom were obtained using a TrueBeam onboard imager as example of data acquisition and analysis. The images were acquired during two months. Artifacts were artificially introduced in the images during the reconstruction process using iTool reconstructor. Support vector machine algorithms to automatically identify each artifact were written using the Machine Learning MATLAB R2011 Toolbox. A daily imaging QA test could be performed by an experienced medical physicist in 14.3 ± 2.4 min. The same test, if automated using our paradigm, could be performed in 4.2 ± 0.7 min. In the same manner, a monthly imaging QA could be performed by a physicist in 70.7 ± 8.0 min and, if fully automated, in 21.8 ± 0.6 min. Additionally, quantitative data analysis could be automatically performed by Machine Learning Algorithms that could remove the subjectivity of data interpretation in the QA process. For instance, support vector machine algorithms could correctly identify beam hardening, rings and scatter artifacts. Traditional metrics, as well as metrics that describe texture, are needed for the classification. Modern linear accelerators are equipped with advanced 2D and 3D imaging capabilities that are used for patient alignment, substantially improving IGRT treatment accuracy. However, this extra complexity exponentially increases the number of QA tests needed. Using the new paradigm described above, not only the bare minimum — but also best practice — QA programs could be implemented with the same manpower.

    View details for DOI 10.1120/jacmp.v16i4.5363

    View details for PubMedID 26219002

    View details for PubMedCentralID PMC5690025

  • Physics of Stereotactic Body Radiotherapy - Commissioning, Quality Assurance, and Treatment Planning Stereotactic Body Radiotherapy : A Practical Guide Chuang, C. F., D'Souza, M. F., Rossman, J. A. Springer London. 2015; 1
  • Evaluation of ray tracing and Monte Carlo algorithms in dose calculation and clinical outcomes for robotic stereotactic body radiotherapy of lung cancers. Journal of radiosurgery and SBRT Braunstein, S. E., Dionisio, S. A., Lometti, M. W., Pinnaduwage, D. S., Chuang, C. F., Yom, S. S., Gottschalk, A. R., Descovich, M. 2014; 3 (1): 67-79

    Abstract

    Dose calculation in treatment planning must account for tissue heterogeneity, especially for tumors within low-density lung tissues. While Monte Carlo (MC) calculation methods are the most accurate, Ray Tracing (RT) methods are also commonly employed. We evaluated dose calculation differences between the RT and MC algorithms in central and peripheral lung tumors treated with CyberKnife SBRT to determine which planning parameters may predict dose differences. We also examined clinical outcomes of local-regional control (LRC) and long-term treatment-related toxicity as a function of calculation method.A retrospective series of 70 patient plans (19 central and 51 peripheral lung lesions) treated between 2009 and 2011 were analyzed. Among those, 33 were primary lung cancer and 37 were metastatic lesions. Thirty-three treatment plans were developed with the RT method, and 37 plans used MC. Groups were recalculated with the reciprocal method for dose comparison. Parameters examined to quantify dose differences between the two algorithms included: dose delivered to 95% (D95) of the planning target volume (PTV), dose heterogeneity, and dose to organs at risk (OAR). Dose differences were analyzed as a function of target volume, distance to soft tissue, and fraction of target overlap with soft tissue. For the subset of primary lung tumors, LRC was assessed radiographically at a median follow-up of 19 months (mo) (range, 2 to 41 mo).Compared to MC, the RT algorithm largely overestimated the dose delivered to the PTV. The dose difference between RT and MC plans correlated to the volume of PTV overlapping with soft tissue; the smaller the overlap volume, the larger the dose differences between RT and MC. Compared to MC, the RT algorithm overestimated the dose delivered to 10% of the ipsilateral lung (D10%). Evidence of local progression was noted in only one of the 31 patients treated for primary lung malignancy. DFS and OS were not significantly different between RT and MC plans.There is a significant range of discordance between MC and RT dose calculations for SBRT treated peripheral lung tumors. While variation is correlated to target size and proximity to soft tissue, no single parameter can reliably predict dose differences. Ultimately, local control and long-term toxicity appear independent of the dose calculation method.

    View details for PubMedID 29296387

    View details for PubMedCentralID PMC5725332

  • Site-specific deformable imaging registration algorithm selection using patient-based simulated deformations. Medical physics Nie, K., Chuang, C., Kirby, N., Braunstein, S., Pouliot, J. 2013; 40 (4): 041911

    Abstract

    The accuracy of deformable image registration could have a significant dosimetric impact in radiation treatment planning. Various image registration algorithms have been developed for clinical application. However, validation of these algorithms in the current clinical setting remains subjective, relying on visual assessment and lacking a comparison to the ground-truth deformation. In this study, the authors propose a framework to quantitatively validate various image registration solutions by using patient-based synthetic quality assurance (QA) phantoms, which can be applied on a site-by-site basis.The computer-simulated deformation was first generated with virtual deformation QA software and further benchmarked using a physical pelvic phantom that was modeled after real patient CT images. After the validity of the virtual deformation was confirmed, a set of synthetic deformable images was produced to simulate various anatomical movements during radiotherapy based on real patient CT images. Three patients with head-and-neck, prostate, and spine cancer were included. The transformations included bladder filling, soft tissue deformation, mandible, and vertebral body movement, etc., which provided various ground-truth images to validate deformable registration. Several clinically available deformable registration algorithms were tested on these images with multiple registration setups, such as global or regional and single-pass or multipass optimization. The generated deformation fields and the ground-truth deformation are compared using voxel-by-voxel based analysis as well as regional based analysis.Performance of registration algorithms varies with clinical sites. The voxel-by-voxel analysis showed the intensity-based free-form deformation by MIM generated the greatest accuracy for low-contrast small regions that underwent significant deformation, such as bladder expansion for prostate. However, for large field deformations with strong contrast, this approach may increase errors, which is especially evident in the cranial spinal irradiation (CSI) case. Both single-pass and multipass B-spline registrations performed well for the head-and-neck patient and CSI patients.QA for deformable image registration is essential to verify the cumulated dose for accurate adaptive radiotherapy. In this study, the authors develop a workflow that can validate image registration techniques for several different clinical sites and for various types of deformations using patient-based simulated deformations. This work could provide a reference for clinicians and radiation physicists on how to choose appropriate image registration algorithms for different situations.

    View details for DOI 10.1118/1.4793723

    View details for PubMedID 23556905

  • The need for application-based adaptation of deformable image registration. Medical physics Kirby, N., Chuang, C., Ueda, U., Pouliot, J. 2013; 40 (1): 011702

    Abstract

    To utilize a deformable phantom to objectively evaluate the accuracy of 11 different deformable image registration (DIR) algorithms.The phantom represents an axial plane of the pelvic anatomy. Urethane plastic serves as the bony anatomy and urethane rubber with three levels of Hounsfield units (HU) is used to represent fat and organs, including the prostate. A plastic insert is placed into the phantom to simulate bladder filling. Nonradiopaque markers reside on the phantom surface. Optical camera images of these markers are used to measure the positions and determine the deformation from the bladder insert. Eleven different DIR algorithms are applied to the full and empty-bladder computed tomography images of the phantom (fixed and moving volumes, respectively) to calculate the deformation. The algorithms include those from MIM Software (MIM) and Velocity Medical Solutions (VEL) and nine different implementations from the deformable image registration and adaptive radiotherapy toolbox for Matlab. These algorithms warp one image to make it similar to another, but must utilize a method for regularization to avoid physically unrealistic deformation scenarios. The mean absolute difference (MAD) between the HUs at the marker locations on one image and the calculated location on the other serves as a metric to evaluate the balance between image similarity and regularization. To demonstrate the effect of regularization on registration accuracy, an additional beta version of MIM was created with a variable smoothness factor that controls the emphasis of the algorithm on regularization. The distance to agreement between the measured and calculated marker deformations is used to compare the overall spatial accuracy of the DIR algorithms. This overall spatial accuracy is also utilized to evaluate the phantom geometry and the ability of the phantom soft-tissue heterogeneity to represent patient data. To evaluate the ability of the DIR algorithms to accurately transfer anatomical contours, the rectum is delineated on both the fixed and moving images. A Dice similarity coefficient is then calculated between the contour on the fixed image and that transferred, via the calculated deformation, from the moving to the fixed image.The phantom possesses sufficient soft-tissue heterogeneity to act as a proxy for patient data. Large discrepancies appear between the algorithms and the measured ground-truth deformation. VEL yields the smallest mean spatial error and a Dice coefficient of 0.90. MIM produces the lowest MAD value and the highest Dice coefficient of 0.96, but creates the largest spatial errors. Increasing the MIM smoothness factor above the default value improves the overall spatial accuracy, but the factor associated with the lowest mean error decreases the Dice coefficient to 0.85.Different applications of DIR require disparate balances between image similarity and regularization. A DIR algorithm that is optimized only for its ability to transfer anatomical contours will yield large deformation errors in homogeneous regions, which is problematic for dose mapping. For this reason, these algorithms must be tested for their overall spatial accuracy. The developed phantom is an objective tool for this purpose.

    View details for DOI 10.1118/1.4769114

    View details for PubMedID 23298072

  • Management of vestibular schwannoma: focus on vertigo. CNS oncology Dayal, M., Perez-Andujar, A., Chuang, C., Parsa, A. T., Barani, I. J. 2013; 2 (1): 99-104

    Abstract

    This article reviews published literature on vertigo and a 'sense of imbalance' affecting patients who are treated with radiosurgery (RS) for vestibular schwannoma. This is a relatively understudied complaint, along with tinnitus, in this patient population, despite its significant impact on quality of life. It is also a symptom that is most inconsistently impacted by either RS or surgery. This article aims to highlight the importance of this symptom in patients managed for vestibular schwannoma primarily with RS to encourage a more systematic study of vertigo as an outcome measure and to help elucidate its potential etiology.

    View details for DOI 10.2217/cns.12.30

    View details for PubMedID 25054360

    View details for PubMedCentralID PMC6169458

  • Comparison between prone and supine patient setup for spine stereotactic body radiosurgery. Technology in cancer research & treatment Descovich, M., Ma, L., Chuang, C. F., Larson, D. A., Barani, I. J. 2012; 11 (3): 229-36

    Abstract

    This paper investigates the dosimetric characteristics of stereotactic body radiotherapy (SBRT) treatment plans of spine patients in the prone position compared to the supine position. A feasibility study for treating spine patients in the prone position using a fiducial-less tracking method is presented. One patient with a multilevel spinal metastasis was simulated for SBRT treatment in both the supine and prone position. CT scans of the patient were acquired, and treatment plans were created using the CyberKnife® planning platform. The potential advantage of the prone setup as a function of lesion location and number of vertebral bodies involved was studied for targets extending over 1, 2 and 3 consecutive vertebral bodies in the thoracic and lumbar spine. The same process was repeated on an anthropomorphic phantom. A dose of 30 Gy in 5 fractions was prescribed to 95% of the tumor volume and the dose to the cord was limited to 25 Gy. To investigate the feasibility of a fiducial-less tracking method in the prone setup, the patient was positioned prone on the treatment table and the spine motion was monitored as a function of time. Patient movement with the respiratory cycle was reduced by means of a belly-board. Plans in the prone and supine position achieved similar tumor coverage and sparing of the critical structures immediately adjacent to the spine (such as cord and esophagus). However, the prone plans systematically resulted in a lower dose to the normal structures located in the anterior part of the body (such as heart for thoracic cases; stomach, lower gastrointestinal tract and liver for lumbar cases). In addition, prone plans resulted in a lower number of monitor units compared to supine plans.

    View details for DOI 10.7785/tcrt.2012.500291

    View details for PubMedID 22468994

  • 7-Tesla Susceptibility-Weighted Imaging to Assess the Effects of Radiotherapy on Normal-Appearing Brain in Patients With Glioma INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Lupo, J. M., Chuang, C. F., Chang, S. M., Barani, I. J., Jimenez, B., Hess, C. P., Nelson, S. J. 2012; 82 (3): E493-E500

    Abstract

    To evaluate the intermediate- and long-term imaging manifestations of radiotherapy on normal-appearing brain tissue in patients with treated gliomas using 7T susceptibility-weighted imaging (SWI).SWI was performed on 25 patients with stable gliomas on a 7 Tesla magnet. Microbleeds were identified as discrete foci of susceptibility that did not correspond to vessels. The number of microbleeds was counted within and outside of the T2-hyperintense lesion. For 3 patients, radiation dosimetry maps were reconstructed and fused with the 7T SWI data.Multiple foci of susceptibility consistent with microhemorrhages were observed in patients 2 years after chemoradiation. These lesions were not present in patients who were not irradiated. The prevalence of microhemorrhages increased with the time since completion of radiotherapy, and these lesions often extended outside the boundaries of the initial high-dose volume and into the contralateral hemisphere.High-field SWI has potential for visualizing the appearance of microbleeds associated with long-term effects of radiotherapy on brain tissue. The ability to visualize these lesions in normal-appearing brain tissue may be important in further understanding the utility of this treatment in patients with longer survival.

    View details for DOI 10.1016/j.ijrobp.2011.05.046

    View details for Web of Science ID 000300423500021

    View details for PubMedID 22000750

    View details for PubMedCentralID PMC3268881

  • Stereotactic body radiotherapy as monotherapy or post-external beam radiotherapy boost for prostate cancer: technique, early toxicity, and PSA response. International journal of radiation oncology, biology, physics Jabbari, S., Weinberg, V. K., Kaprealian, T., Hsu, I. C., Ma, L., Chuang, C., Descovich, M., Shiao, S., Shinohara, K., Roach, M., Gottschalk, A. R. 2012; 82 (1): 228-34

    Abstract

    High dose rate (HDR) brachytherapy has been established as an excellent monotherapy or after external-beam radiotherapy (EBRT) boost treatment for prostate cancer (PCa). Recently, dosimetric studies have demonstrated the potential for achieving similar dosimetry with stereotactic body radiotherapy (SBRT) compared with HDR brachytherapy. Here, we report our technique, PSA nadir, and acute and late toxicity with SBRT as monotherapy and post-EBRT boost for PCa using HDR brachytherapy fractionation.To date, 38 patients have been treated with SBRT at the University of California-San Francisco with a minimum follow-up of 12 months. Twenty of 38 patients were treated with SBRT monotherapy (9.5 Gy × 4 fractions), and 18 were treated with SBRT boost (9.5 Gy × 2 fractions) post-EBRT and androgen deprivation therapy. PSA nadir to date for 44 HDR brachytherapy boost patients with disease characteristics similar to the SBRT boost cohort was also analyzed as a descriptive comparison.SBRT was well tolerated. With a median follow-up of 18.3 months (range, 12.6-43.5), 42% and 11% of patients had acute Grade 2 gastrourinary and gastrointestinal toxicity, respectively, with no Grade 3 or higher acute toxicity to date. Two patients experienced late Grade 3 GU toxicity. All patients are without evidence of biochemical or clinical progression to date, and favorably low PSA nadirs have been observed with a current median PSA nadir of 0.35 ng/mL (range, <0.01-2.1) for all patients (0.47 ng/mL, range, 0.2-2.1 for the monotherapy cohort; 0.10 ng/mL, range, 0.01-0.5 for the boost cohort). With a median follow-up of 48.6 months (range, 16.4-87.8), the comparable HDR brachytherapy boost cohort has achieved a median PSA nadir of 0.09 ng/mL (range, 0.0-3.3).Early results with SBRT monotherapy and post-EBRT boost for PCa demonstrate acceptable PSA response and minimal toxicity. PSA nadir with SBRT boost appears comparable to those achieved with HDR brachytherapy boost.

    View details for DOI 10.1016/j.ijrobp.2010.10.026

    View details for PubMedID 21183287

  • Temporal compartmental dosing effects for robotic prostate stereotactic body radiotherapy. Physics in medicine and biology Shiao, S. L., Sahgal, A., Hu, W., Jabbari, S., Chuang, C., Descovich, M., Hsu, I. C., Gottschalk, A. R., Roach, M., Ma, L. 2011; 56 (24): 7767-75

    Abstract

    The rate of dose accumulation within a given area of a target volume tends to vary significantly for non-isocentric delivery systems such as Cyberknife stereotactic body radiotherapy. In this study, we investigated whether intra-target temporal dose distributions produce significant variations in the biological equivalent dose. For the study, time courses of ten patients were reconstructed and calculation of a biologically equivalent uniform dose (EUD) was performed using a formula derived from the linear quadratic model (α/β = 3 for prostate cancer cells). The calculated EUD values obtained for the actual patient treatments were then compared with theoretical EUD values for delivering the same physical dose distribution except that the whole target being irradiated continuously (e.g. large-field 'dose-bathing' type of delivery). For all the case, the EUDs for the actual treatment delivery were found to correlate strongly with the EUDs for the large-field delivery: a linear correlation coefficient of R² = 0.98 was obtained and the average EUD for the actual Cyberknife delivery was somewhat higher (5.0 ± 4.7%) than that for the large-field delivery. However, no statistical significance was detected between the two types of delivery (p = 0.21). We concluded that non-isocentric small-field Cyberknife delivery produced consistent biological dosing that tracked well with the constant-dose-rate, large-field-type delivery for prostate stereotactic body radiotherapy.

    View details for DOI 10.1088/0031-9155/56/24/006

    View details for PubMedID 22107791

  • Physics strategies for sparing neural stem cells during whole-brain radiation treatments. Medical physics Kirby, N., Chuang, C., Pouliot, J., Hwang, A., Barani, I. J. 2011; 38 (10): 5338-44

    Abstract

    Currently, there are no successful long-term treatments or preventive strategies for radiation-induced cognitive impairments, and only a few possibilities have been suggested. One such approach involves reducing the dose to neural stem cell compartments (within and outside of the hippocampus) during whole-brain radiation treatments for brain metastases. This study investigates the fundamental physics issues associated with the sparing of neural stem cells during photon radiotherapy for brain metastases.Several factors influence the stem cell dose: intracranial scattering, collimator leakage, beam energy, and total number of beams. The relative importance of these factors is investigated through a set of radiation therapy plans, which are all variations of an initial 6 MV intensity-modulated radiation therapy (IMRT) plan designed to simultaneously deliver a whole-brain dose of 30 Gy and maximally reduce stem cell compartment dose. Additionally, an in-house leaf segmentation algorithm was developed that utilizes jaw motion to minimize the collimator leakage.The plans are all normalized such that 50% of the PTV receives 30 Gy. For the initial 6 MV IMRT plan, 50% of the stem cells receive a dose greater than 6.3 Gy. Calculations indicate that 3.6 Gy of this dose originates from intracranial scattering. The jaw-tracking segmentation algorithm, used in conjunction with direct machine parameter optimization, reduces the 50% stem cell dose to 4.3 and 3.7 Gy for 6 and 10 MV treatment beams, respectively.Intracranial scattering alone is responsible for a large dose contribution to the stem cell compartment. It is, therefore, important to minimize other contributing factors, particularly the collimator leakage, to maximally reduce dose to these critical structures. The use of collimator jaw tracking in conjunction with modern collimators can minimize this leakage.

    View details for DOI 10.1118/1.3633946

    View details for PubMedID 21992352

  • Erratum: "Report of AAPM TG 135: Quality assurance for robotic radiosurgery". Medical physics Dieterich, S., Cavedon, C., Chuang, C. F., Cohen, A. B., Garrett, J. A., Lee, C. L., Lowenstein, J. R., D'Souza, M. F., Taylor, D. D., Wu, X., Yu, C. 2011; 38 (9): 5264

    View details for DOI 10.1118/1.3626480

    View details for PubMedID 28524974

  • Report of AAPM TG 135: Quality assurance for robotic radiosurgery (vol 38, pg 2914, 2011) MEDICAL PHYSICS Dieterich, S., Cavedon, C., Chuang, C. F., Cohen, A. B., Garrett, J. A., Lee, C. L., Lowenstein, J. R., d'Souza, M. F., Taylor, D. D., Wu, X., Yu, C. 2011; 38 (9): 5264-5264

    View details for DOI 10.1118/1.3626480

    View details for Web of Science ID 000294482900036

  • A two-dimensional deformable phantom for quantitatively verifying deformation algorithms. Medical physics Kirby, N., Chuang, C., Pouliot, J. 2011; 38 (8): 4583-6

    Abstract

    The incorporation of deformable image registration into the treatment planning process is rapidly advancing. For this reason, the methods used to verify the underlying deformation algorithms must evolve equally fast. This manuscript proposes a two-dimensional deformable phantom, which can objectively verify the accuracy of deformation algorithms, as the next step for improving these techniques.The phantom represents a single plane of the anatomy for a head and neck patient. Inflation of a balloon catheter inside the phantom simulates tumor growth. CT and camera images of the phantom are acquired before and after its deformation. Nonradiopaque markers reside on the surface of the deformable anatomy and are visible through an acrylic plate, which enables an optical camera to measure their positions; thus, establishing the ground-truth deformation. This measured deformation is directly compared to the predictions of deformation algorithms, using several similarity metrics. The ratio of the number of points with more than a 3 mm deformation error over the number that are deformed by more than 3 mm is used for an error metric to evaluate algorithm accuracy.An optical method of characterizing deformation has been successfully demonstrated. For the tests of this method, the balloon catheter deforms 32 out of the 54 surface markers by more than 3 mm. Different deformation errors result from the different similarity metrics. The most accurate deformation predictions had an error of 75%.The results presented here demonstrate the utility of the phantom for objectively verifying deformation algorithms and determining which is the most accurate. They also indicate that the phantom would benefit from more electron density heterogeneity. The reduction of the deformable anatomy to a two-dimensional system allows for the use of nonradiopaque markers, which do not influence deformation algorithms. This is the fundamental advantage of this verification technique.

    View details for DOI 10.1118/1.3597881

    View details for PubMedID 21928631

  • A two-step optimization method for improving multiple brain lesion treatments with robotic radiosurgery. Technology in cancer research & treatment Ma, L., Sahgal, A., Hwang, A., Hu, W., Descovich, M., Chuang, C., Barani, I., Sneed, P. K., McDermott, M., Larson, D. A. 2011; 10 (4): 331-8

    Abstract

    Planning robotic radiosurgery treatments for multiple (n > 3) metastatic brain lesions is challenging due to the need of satisfying a large number of dose-volume constraints and the requirement of prescribing different dose levels to individual targets. In this study, we developed a sequential two-step optimization technique to improve the planning quality of such treatments. In contrast to the conventional approach of where all targets are simultaneously planned, we have developed a two-step optimization method. In this method, the first step was to create treatment plans for individual targets. In the second step, the 3D dose matrices associated with each plan were exported to Dicom-RT digital files and subsequently optimized. For the optimization, a singular-value-decomposition (SVD) algorithm was implemented to minimize the dose interferences among different targets. Finally, we compared the optimized treatment plans with the treatment plans created using the conventional method to determine the effectiveness of the new method. Large improvements in target dose distributions as well as normal brain sparing were found for the two-step optimization treatment plans as compared with the conventional treatment plans. The two-step optimization significantly lowered the volume of normal brain receiving relatively low doses. For example, the normal brain volume receiving 12-Gy was reduced by averaged 42% (range 34%-47%) with the two-step optimization. Such improvements generally enlarged with increasing number of targets being treated regardless of target sizes. Of note, normal brain dose was found to increase non-linearly with increasing number of targets. In summary, a two-step optimization technique is demonstrated to significantly improve the treatment plan quality as well as reduce the planning effort for multi-target robotic radiosurgery.

    View details for DOI 10.7785/tcrt.2012.500210

    View details for PubMedID 21728390

  • Apparatus dependence of normal brain tissue dose in stereotactic radiosurgery for multiple brain metastases. Journal of neurosurgery Ma, L., Petti, P., Wang, B., Descovich, M., Chuang, C., Barani, I. J., Kunwar, S., Shrieve, D. C., Sahgal, A., Larson, D. A. 2011; 114 (6): 1580-4

    Abstract

    Technical improvements in commercially available radiosurgery platforms have made it practical to treat a large number of intracranial targets. The goal of this study was to investigate whether the dose to normal brain when planning radiosurgery to multiple targets is apparatus dependent.The authors selected a single case involving a patient with 12 metastatic lesions widely distributed throughout the brain as visualized on contrast-enhanced CT. Target volumes and critical normal structures were delineated with Leksell Gamma Knife Perfexion software. The imaging studies including the delineated contours were digitally exported into the CyberKnife and Novalis multileaf collimator-based planning systems for treatment planning using identical target dose goals and dose-volume constraints. Subsets of target combinations (3, 6, 9, or 12 targets) were planned separately to investigate the relationship of number of targets and radiosurgery platform to the dose to normal brain.Despite similar target dose coverage and dose to normal structures, the dose to normal brain was strongly apparatus dependent. A nonlinear increase in dose to normal brain volumes with increasing number of targets was also noted.The dose delivered to normal brain is strongly dependent on the radiosurgery platform. How general this conclusion is and whether apparatus-dependent differences are related to differences in hardware design or differences in dose-planning algorithms deserve further investigation.

    View details for DOI 10.3171/2011.1.JNS101056

    View details for PubMedID 21375377

  • Impact of dose compartmentalization effect for Cyberknife prostate cancer SBRT Annual Cyberknife Society Summit Meeting Ma, L., Shiao, S. L., Jabbari, S., Hossain, S., Chuang, C., Descovich, M., Huang, K., Hsu, I., Gottschalk, A., Roach III, M. 2011
  • A dosimetric comparison between Gamma Knife and CyberKnife treatment plans for trigeminal neuralgia. Journal of neurosurgery Descovich, M., Sneed, P. K., Barbaro, N. M., McDermott, M. W., Chuang, C. F., Barani, I. J., Nakamura, J. L., Lijun, M. 2010; 113 Suppl: 199-206

    Abstract

    The Leksell Gamma Knife and the Accuray CyberKnife systems have been used in the radio surgical treatment of trigeminal neuralgia. The 2 techniques use different delivery methods and different treatment parameters. In the past, CyberKnife treatments have been associated with an increased incidence of treatment-related complications, such as facial numbness. The goal of this study was to develop a method for planning a CyberKnife treatment for trigeminal neuralgia that would reproduce the dosimetric characteristics of a Gamma Knife plan. A comparison between Gamma Knife and CyberKnife treatment plans obtained with this method is presented.Five patients treated using the Gamma Knife Perfexion Unit were selected for this study. All patients underwent CT cisternography to accurately identify the position of the trigeminal nerve. The Gamma Knife plans used either one 4-mm-diameter collimator or two coincident 4-mm collimators (one open and one with sector blocking) placed at identical isocenter coordinates. A maximum local dose of 80 Gy was prescribed. Critical structures and representative isodose lines were outlined in GammaPlan and exported to the CyberKnife treatment planning platform. CyberKnife treatments were developed using the 5-mm-diameter cone and the trigeminal node set, which provides an effective collimation diameter of 4 mm at the isocenter. The 60-Gy isodose volume imported from GammaPlan was used as the target in the CyberKnife plans. The CyberKnife treatments were optimized to achieve target dose and critical structure sparing similar to the Gamma Knife plans. Isocentric and nonisocentric delivery techniques were investigated. Treatment plans were compared in terms of dosimetric characteristics, delivery, and planning efficiency.CyberKnife treatments using the 5-mm cone and the trigeminal node set can closely reproduce the dose distribution of Gamma Knife plans. CyberKnife isocentric and nonisocentric plans provide comparable results. The average length of the trigeminal nerve receiving a dose of 60 Gy was 4.5, 4.5, and 4.4 mm for Gamma Knife, nonisocentric CyberKnife, and isocentric CyberKnife, respectively. However, minimizing the dose to the critical structures was more difficult with the CyberKnife and required the use of tuning structures. In addition, the dose fall off away from the target was steeper in Gamma Knife plans, probably due to the larger number of beams (192 beams for perfexion vs ~ 100 beams for cyberknife). While the treatment time with the cyberknife is generally shorter, the planning time is significantly longer.CyberKnife radiosurgical parameters can be optimized to mimic the dose distribution of Gamma Knife plans. However, Gamma Knife plans result in superior sparing of critical structures (brainstem, temporal lobe,and cranial nerves VII and VIII) and in steeper dose fall off away from the target. The clinical significance of these effects is unknown. (DOI: 10.3171/2010.8.GKS101002)

    View details for PubMedID 21222296

  • Dose gradient near target-normal structure interface for nonisocentric CyberKnife and isocentric intensity-modulated body radiotherapy for prostate cancer. International journal of radiation oncology, biology, physics Hossain, S., Xia, P., Huang, K., Descovich, M., Chuang, C., Gottschalk, A. R., Roach, M., Ma, L. 2010; 78 (1): 58-63

    Abstract

    The treatment planning quality between nonisocentric CyberKnife (CK) and isocentric intensity modulation treatment was studied for hypofractionated prostate body radiotherapy. In particular, the dose gradient across the target and the critical structures such as the rectum and bladder was characterized.In the present study, patients treated with CK underwent repeat planning for nine fixed-field intensity-modulated radiotherapy (IMRT) using identical contour sets and dose-volume constraints. To calculate the dose falloff, the clinical target volume contours were expanded 30 mm anteriorly and posteriorly and 50 mm uniformly in other directions for all patients in the CK and IMRT plans.We found that all the plans satisfied the dose-volume constraints, with the CK plans showing significantly better conformity than the IMRT plans at a relative greater dose inhomogeneity. The rectal and bladder volumes receiving a low dose were also lower for CK than for IMRT. The average conformity index, the ratio of the prescription isodose volume and clinical target volume, was 1.18 +/- 0.08 for the CK plans vs. 1.44 +/- 0.11 for the IMRT plans. The average homogeneity index, the ratio of the maximal dose and the prescribed dose to the clinical target volume, was 1.45 +/- 0.12 for the CK plans vs. 1.28 +/- 0.06 for the IMRT plans. The average percentage of dose falloff was 2.9% +/- 0.8%/mm for CK and 3.1% +/- 1.0%/mm for IMRT in the anterior direction, 3.8% +/- 1.6%/mm for CK and 3.2% +/- 1.9%/mm for IMRT in the posterior direction, and 3.6% +/- 0.4% for CK and 3.6% +/- 0.4% for IMRT in all directions.Nonisocentric CK was as capable of producing equivalent fast dose falloff as high-number fixed-field IMRT delivery.

    View details for DOI 10.1016/j.ijrobp.2009.07.1752

    View details for PubMedID 20133073

  • Equivalence in dose fall-off for isocentric and nonisocentric intracranial treatment modalities and its impact on dose fractionation schemes. International journal of radiation oncology, biology, physics Ma, L., Sahgal, A., Descovich, M., Cho, Y. B., Chuang, C., Huang, K., Laperriere, N. J., Shrieve, D. C., Larson, D. A. 2010; 76 (3): 943-8

    Abstract

    To investigate whether dose fall-off characteristics would be significantly different among intracranial radiosurgery modalities and the influence of these characteristics on fractionation schemes in terms of normal tissue sparing.An analytic model was developed to measure dose fall-off characteristics near the target independent of treatment modalities. Variations in the peripheral dose fall-off characteristics were then examined and compared for intracranial tumors treated with Gamma Knife, Cyberknife, or Novalis LINAC-based system. Equivalent uniform biologic effective dose (EUBED) for the normal brain tissue was calculated. Functional dependence of the normal brain EUBED on varying numbers of fractions (1 to 30) was studied for the three modalities.The derived model fitted remarkably well for all the cases (R(2) > 0.99). No statistically significant differences in the dose fall-off relationships were found between the three modalities. Based on the extent of variations in the dose fall-off curves, normal brain EUBED was found to decrease with increasing number of fractions for the targets, with alpha/beta ranging from 10 to 20. This decrease was most pronounced for hypofractionated treatments with fewer than 10 fractions. Additionally, EUBED was found to increase slightly with increasing number of fractions for targets with alpha/beta ranging from 2 to 5.Nearly identical dose fall-off characteristics were found for the Gamma Knife, Cyberknife, and Novalis systems. Based on EUBED calculations, normal brain sparing was found to favor hypofractionated treatments for fast-growing tumors with alpha/beta ranging from 10 to 20 and single fraction treatment for abnormal tissues with low alpha/beta values such as alpha/beta = 2.

    View details for DOI 10.1016/j.ijrobp.2009.07.1721

    View details for PubMedID 20159366

  • Functional Relationship between the Volume of a Near-Target Peripheral Isodose Line and Its Isodose Value for Gamma Knife® Radiosurgery Ma, L., Sahgal, A., Chuang, C., Descovich, M., Petti, P., Smith, V., Verhey, L., Barbaro, N., McDermott, M., Huang, K., Nakamura, J., Sneed, P., Larson, D., McDermott, M. W. KARGER. 2010: 75-83

    View details for DOI 10.1159/000288720

    View details for Web of Science ID 000288517800007

  • A treatment planning optimization technique for improving multiple metastatic brain lesion treatment with Cyberknife radiosurgery 1st International Cyberknife Society Scientific Conference Ma, L., Sahgal, A., Hu, W., Descovich, M., Chuang, C., Barani, I., Sneed, P., McDermott, M., Larson, D. 2010
  • Comparisons of Novalis and CyberKnife® Spinal Stereotactic Body Radiotherapy Treatment Planning Based on Physical and Biological Modeling Parameters Sahgal, A., Chuang, C., Hossain, S., Petti, P., Larson, D. A., Shrieve, D. C., Ma, L., McDermott, M. W. KARGER. 2010: 366-377

    View details for DOI 10.1159/000288747

    View details for Web of Science ID 000288517800033

  • Nonrandom intrafraction target motions and general strategy for correction of spine stereotactic body radiotherapy. International journal of radiation oncology, biology, physics Ma, L., Sahgal, A., Hossain, S., Chuang, C., Descovich, M., Huang, K., Gottschalk, A., Larson, D. A. 2009; 75 (4): 1261-5

    Abstract

    To characterize nonrandom intrafraction target motions for spine stereotactic body radiotherapy and to develop a method of correction via image guidance. The dependence of target motions, as well as the effectiveness of the correction strategy for lesions of different locations within the spine, was analyzed.Intrafraction target motions for 64 targets in 64 patients treated with a total of 233 fractions were analyzed. Based on the target location, the cases were divided into three groups, i.e., cervical (n = 20 patients), thoracic (n = 20 patients), or lumbar-sacrum (n = 24 patients) lesions. For each case, time-lag autocorrelation analysis was performed for each degree of freedom of motion that included both translations (x, y, and z shifts) and rotations (roll, yaw, and pitch). A general correction strategy based on periodic interventions was derived to determine the time interval required between two adjacent interventions, to overcome the patient-specific target motions.Nonrandom target motions were detected for 100% of cases regardless of target locations. Cervical spine targets were found to possess the highest incidence of nonrandom target motion compared with thoracic and lumbar-sacral lesions (p < 0.001). The average time needed to maintain the target motion to within 1 mm of translation or 1 degrees of rotational deviation was 5.5 min, 5.9 min, and 7.1 min for cervical, thoracic, and lumbar-sacrum locations, respectively (at 95% confidence level).A high incidence of nonrandom intrafraction target motions was found for spine stereotactic body radiotherapy treatments. Periodic interventions at approximately every 5 minutes or less were needed to overcome such motions.

    View details for DOI 10.1016/j.ijrobp.2009.04.027

    View details for PubMedID 19647951

  • Stereotactic body radiotherapy is effective salvage therapy for patients with prior radiation of spinal metastases. International journal of radiation oncology, biology, physics Sahgal, A., Ames, C., Chou, D., Ma, L., Huang, K., Xu, W., Chin, C., Weinberg, V., Chuang, C., Weinstein, P., Larson, D. A. 2009; 74 (3): 723-31

    Abstract

    To provide actuarial outcomes and dosimetric data for spinal/paraspinal metastases, with and without prior radiation, treated with stereotactic body radiotherapy (SBRT).A total of 39 consecutive patients (60 metastases) were treated with SBRT between April 2003 and August 2006 and retrospectively reviewed. In all, 23 of 60 tumors had no previous radiation (unirradiated) and 37/60 tumors had previous irradiation (reirradiated). Of 37 reirradiated tumors, 31 were treated for "salvage" given image-based tumor progression. Local failure was defined as progression by imaging and/or clinically.At last follow-up, 19 patients were deceased. Median patient survival time measured was 21 months (95% CI = 8-27 months), and the 2-year survival probability was 45%. The median total dose prescribed was 24 Gy in three fractions prescribed to the 67% and 60% isodose for the unirradiated and reirradiated cohorts, respectively. The median tumor follow-up for the unirradiated and reirradiated group was 9 months (range, 1-26) and 7 months (range, 1-48) respectively. Eight of 60 tumors have progressed, and the 1- and 2-year progression-free probability (PFP) was 85% and 69%, respectively. For the salvage group the 1 year PFP was 96%. There was no significant difference in overall survival or PFP between the salvage reirradiated vs. all other tumors treated (p = 0.08 and p = 0.31, respectively). In six of eight failures the minimum distance from the tumor to the thecal sac was or=6 months follow-up and no radiation-induced myelopathy or radiculopathy has occurred.Spine SBRT has shown preliminary efficacy and safety in patients with image-based progression of previously irradiated metastases.

    View details for DOI 10.1016/j.ijrobp.2008.09.020

    View details for PubMedID 19095374

  • Effect of composite sector collimation on average dose fall-off for Gamma Knife Perfexion. Journal of neurosurgery Ma, L., Verhey, L., Chuang, C., Descovich, M., Smith, V., Huang, K., McDermott, M., Sneed, P. 2008; 109 Suppl: 15-20

    Abstract

    The new capability of composite sector collimation in Gamma Knife Perfexion produces complex, nonspherical, and nonelliptical dose distributions. In this study, the authors investigated the effect of composite sector collimation on average dose fall-off compared with the previous Gamma Knife model.A general formalism was derived to describe the peripheral dose distribution of all Gamma Knife models in the form of (V/V(0)) = (D/D(0))(gamma), where V is the volume of the peripheral isodose line with the value of D, V(0) is the reference prescription isodose volume, D(0) is the prescription dose, and gamma is the fitting parameter that determines how fast the dose falls off near the target. Based on this formula, the authors compared 40 cases involving patients treated with Gamma Knife Perfexion with 40 similar cases involving patients treated with Gamma Knife model 4C. The cases were grouped based on the use of the sector collimators in the treatment planning process. For each group as well as all cases combined, the mean gamma values were compared by means of the Student t-test for varying ranges of the peripheral dose distribution-from 100% of the prescription dose to 75, 50, and 25% of the prescription dose.The fit of general formula to the data was excellent for both Gamma Knife Perfexion and Gamma Knife 4C with R(2)> 0.99 for all the cases. The overall gamma values (mean +/- 2 standard deviations) were as follows: gamma = -1.74 +/- 0.47 (Model 4C) versus -1.77 +/- 0.40 (Perfexion) within 100-75% of the prescription dose; gamma = -1.57 +/- 0.26 (Model 4C) versus -1.58 +/- 0.25 (Perfexion) within 100-50% of the prescription dose; gamma = -1.47 +/- 0.18 (Model 4C) versus -1.50 +/- 0.16 (Perfexion) within 100-25% of the prescription dose. No statistical significance between the mean differences for Gamma Knife Perfexion and Model 4C was found within these ranges. The probability values were 0.65, 0.84, and 0.22, respectively.The use of composite sector collimators in Gamma Knife Perfexion demonstrated no statistically significant effects on the volume-averaged dose fall-off near a target periphery for typical treatment cases.

    View details for DOI 10.3171/JNS/2008/109/12/S4

    View details for PubMedID 19123883

  • Whole-procedure clinical accuracy of Gamma Knife treatments of large lesions Ma, L., Chuang, C., Descovich, M., Petti, P., Smith, V., Verhey, L. WILEY. 2008: 5110-5114

    Abstract

    The mechanical accuracy of Gamma Knife radiosurgery based on single-isocenter measurement has been established to within 0.3 mm. However, the full delivery accuracy for Gamma Knife treatments of large lesions has only been estimated via the quadrature-sum analysis. In this study, the authors directly measured the whole-procedure accuracy for Gamma Knife treatments of large lesions to examine the validity of such estimation. The measurements were conducted on a head-phantom simulating the whole treatment procedure that included frame placement, computed tomography imaging, treatment planning, and treatment delivery. The results of the measurements were compared with the dose calculations from the treatment planning system. Average agreements of 0.1-1.6 mm for the isodose lines ranging from 25% to 90% of the maximum dose were found despite potentially large contributing uncertainties such as 3-mm imaging resolution, 2-mm dose grid size, 1-mm frame registration, multi-isocenter deliveries, etc. The results of our measurements were found to be significantly smaller (>50%) than the calculated value based on the quadrature-sum analysis. In conclusion, Gamma Knife treatments of large lesions can be delivered much more accurately than predicted from the quadrature-sum analysis of major sources of uncertainties from each step of the delivery chain.

    View details for DOI 10.1118/1.2987669

    View details for Web of Science ID 000260484400038

    View details for PubMedID 19070245

  • Simulated real time image guided intrafraction tracking-delivery for hypofractionated prostate IMRT MEDICAL PHYSICS Hossain, S., Xia, P., Chuang, C., Verhey, L., Gottschalk, A. R., Mu, G., Ma, L. 2008; 35 (9): 4041-4048

    Abstract

    Hypofractionated stereotactic body radiotherapy (SBRT) has been tested for prostate cancer radiotherapy. This study aims to investigate the dosimetric effects of intrafraction prostate motion on the target and the normal structures for SBRT. For prostate cancer patients treated with an image-tracking CyberKnife system, the intrafraction prostate movements were recorded during 50-70 min treatment time. Based on the recorded intrafraction prostate movements, treatment plans were created for these cases using intensity modulated beams while scaling the average time patterns from the CyberKnife treatment to simulate hypofractionated intensity modulated radiotherapy (IMRT) delivery. The effect of delivery time on the intrafraction organ motion was investigated. For a nominal single fraction delivery of 9.5 Gy with IMRT, we found that the dosimetric effect of the intrafraction prostate movement is case dependent. For most cases, the dose volume histograms exhibited very small changes from the treatment plans that assumed no intrafractional prostate motion when the maximum intrafraction movements were within +/-5 mm. However, when sporadic prostate movements greater than 5 mm were present in any one direction, significant changes were found. For example, the V100, for the prostate could be reduced by more than 10% to less than 85% of the prostate volume coverage. If these large movements could be excluded by some active correction strategies, then the average V100% for the simulated plan could be restored to within approximately 2% of the ideal treatment plans. On average, the sporadic intrafraction motion has less dosimetric impact on the prolonged treatment delivery versus fast treatment delivery. For example, the average V100% for the clinical target volume was reduced from the original 95.1% to 92.1 +/- 3.7% for prolonged treatment, and to 91.3 +/- 5.4% when the treatment time was shortened by 50%. Due to the observed large sporadic prostate motions, we conclude that an on-line target motion monitoring and correction strategy is necessary to implement hypofractionated SBRT with intensity modulated beams for prostate cancer treatments.

    View details for DOI 10.1118/1.2968333

    View details for Web of Science ID 000258773000025

    View details for PubMedID 18841856

  • Split-volume treatment planning of multiple consecutive vertebral body metastases for Cyberknife image-guided robotic radiosurgery Sahgal, A., Chuang, C., Larson, D., Huang, K., Petti, P., Weinstein, P., Ma, L. ELSEVIER SCIENCE INC. 2008: 175-179

    Abstract

    Cyberknife treatment planning of multiple consecutive vertebral body metastases is challenging due to large target volumes adjacent to critical normal tissues. A split-volume treatment planning technique was developed to improve the treatment plan quality of such lesions. Treatment plans were generated for 1 to 5 consecutive thoracic vertebral bodies (CVBM) prescribing a total dose of 24 Gy in 3 fractions. The planning target volume (PTV) consisted of the entire vertebral body(ies). Treatment plans were generated considering both the de novo clinical scenario (no prior radiation), imposing a dose limit of 8 Gy to 1 cc of spinal cord, and the retreatment scenario (prior radiation) with a dose limit of 3 Gy to 1 cc of spinal cord. The split-volume planning technique was compared with the standard full-volume technique only for targets ranging from 2 to 5 CVBM in length. The primary endpoint was to obtain best PTV coverage by the 24 Gy prescription isodose line. A total of 18 treatment plans were generated (10 standard and 8 split-volume). PTV coverage by the 24-Gy isodose line worsened consistently as the number of CVBM increased for both the de novo and retreatment scenario. Split-volume planning was achieved by introducing a 0.5-cm gap, splitting the standard full-volume PTV into 2 equal length PTVs. In every case, split-volume planning resulted in improved PTV coverage by the 24-Gy isodose line ranging from 4% to 12% for the de novo scenario and, 8% to 17% for the retreatment scenario. We did not observe a significant trend for increased monitor units required, or higher doses to spinal cord or esophagus, with split-volume planning. Split-volume treatment planning significantly improves Cyberknife treatment plan quality for CVBM, as compared to the standard technique. This technique may be of particular importance in clinical situations where stringent spinal cord dose limits are required.

    View details for DOI 10.1016/j.meddos.2007.04.010

    View details for Web of Science ID 000258568400002

    View details for PubMedID 18674681

  • Intensity-modulated chemoradiation for treatment of stage III and IV oropharyngeal carcinoma - The University of California-San Francisco experience CANCER Huang, K., Xia, P., Chuang, C., Weinberg, V., Glastonbury, C. M., Eisele, D. W., Lee, N. Y., Yom, S. S., Phillips, T. L., Quivey, J. M. 2008; 113 (3): 497-507

    Abstract

    Treatment outcomes for stage III and IV oropharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy without prior surgical resection were reviewed.Between April 2000 and September 2004, 71 patients underwent IMRT concurrent with chemotherapy without prior surgical resection for stage III and IV oropharyngeal carcinoma. Chemotherapy was platinum based. The gross tumor volume (GTV) received 70 Gy in 2.12 Gy per fraction. The high-risk clinical tumor volume (CTV) received 59.4 Gy in 1.80 Gy per fraction, and the low-risk CTV received 54 Gy in 1.64 Gy per fraction.With a median follow-up of 33 months, the 3-year local, regional, and locoregional progression-free probabilities were 94%, 94%, and 90%, respectively. The 3-year overall survival estimate was 83%. Locoregional failures occurred in the GTV in 7 patients. Acute grade 3 or 4 toxicity developed in 35 patients. A feeding gastrostomy was placed in 25 patients. Late xerostomia was grade 0 in 16 patients, grade 1 in 31 patients, and grade 2 in 24 patients at last follow-up. No patients experienced grade 3 or 4 late toxicity, except for 1 who developed osteoradionecrosis of the mandible.Excellent local and regional control was achieved with IMRT and concurrent chemotherapy without prior surgical resection in the treatment of stage III and IV oropharyngeal carcinoma. Significant sparing of the parotid glands and other critical normal tissues was possible using IMRT with moderate acute toxicities and minimal severe late effects.

    View details for DOI 10.1002/cncr.23578

    View details for Web of Science ID 000257825700008

    View details for PubMedID 18521908

  • Peripheral dose measurement for CyberKnife radiosurgery with upgraded linac shielding MEDICAL PHYSICS Chuang, C. F., Larson, D. A., Zytkovicz, A., Smith, V., Petti, P. L. 2008; 35 (4): 1494-1496

    Abstract

    The authors investigated the peripheral dose reduction for CyberKnife radiosurgery treatments after the installation of a linac shielding upgrade. As in a previous investigation, the authors considered two treatment plans, one for a hypothetical target in the brain and another for a target in the thorax, delivered to an anthropomorphic phantom. The results of the prior investigation showed that the CyberKnife delivered significantly higher peripheral doses than comparable model C Gamma Knife or IMRT treatments. Current measurements, after the linac shielding upgrade, demonstrate that the additional shielding decreased the peripheral dose, expressed as a percentage of the delivered monitor units (MU), by a maximum of 59%. The dose reduction was greatest for cranial-caudal distances from the field edge less than 30 cm, and at these distances, the CyberKnife peripheral dose, expressed as a percentage of the delivered MU, is now comparable to that measured for the other treatment modalities in our previous investigation. For distances between 30 and 70 cm from the field edge, the additional shielding reduced the peripheral dose by between 20% and 55%. At these distances, the CyberKnife peripheral dose remains higher than doses measured in our previous study for the model C Gamma Knife and IMRT.

    View details for DOI 10.1118/1.2889620

    View details for Web of Science ID 000254510700038

    View details for PubMedID 18491544

  • Image-guided robotic stereotactic body radiotherapy for benign spinal tumors: The University of California San Francisco preliminary experience TECHNOLOGY IN CANCER RESEARCH & TREATMENT Sahgal, A., Chou, D., Ames, C., Ma, L., Lamborn, K., Huang, K., Chuang, C., Aiken, A., Petti, P., Weinstein, P., Larson, D. 2007; 6 (6): 595-603

    Abstract

    We evaluate our preliminary experience using the Cyberknife Radiosurgery System in treating benign spinal tumors. A retrospective review of 16 consecutively treated patients, comprising 19 benign spinal tumors, was performed. Histologic types included neurofibroma [11], chordoma [4], hemangioma [2], and meningioma [2]. Three patients had Neurofibromatosis Type 1 (NF1). Only one tumor, recurrent chordoma, had been previously irradiated, and as such not considered in the local failure analysis. Local failure, for the remaining 18 tumors, was based clinically on symptom progression and/or tumor enlargement based on imaging. Indications for spine stereotactic body radiotherapy (SBRT) consisted of either adjuvant to subtotal resection (5/19), primary treatment alone (12/19), boost following external beam radiotherapy (1/19), and salvage following previous radiation (1/19). Median tumor follow-up is 25 months (2-37), and one patient (with NF1) died at 12 months from a stroke. The median total dose, number of fractions, and prescription isodose was 21 Gy (10-30 Gy), 3 fx (1-5 fx), 80% (42-87%). The median tumor volume was 7.6 cc (0.2-274.1 cc). The median V100 (volume V receiving 100% of the prescribed dose) and maximum tumor dose was 95% (77-100%) and 26.7 Gy (15.4-59.7 Gy), respectively. Three tumors progressed at 2, 4, and 36 months post-SR (n=18). Two tumors were neurofibromas (both in NF1 patients), and the third was an intramedullary hemangioblastoma. Based on imaging, two tumors had MRI documented progression, three had regressed, and 13 were unchanged (n=18). With short follow-up, local control following Cyberknife spine SBRT for benign spinal tumors appear acceptable.

    View details for DOI 10.1177/153303460700600602

    View details for Web of Science ID 000251949300002

    View details for PubMedID 17994789

  • Effects of residual target motion for image-tracked spine radiosurgery. Medical physics Chuang, C., Sahgal, A., Lee, L., Larson, D., Huang, K., Petti, P., Verhey, L., Ma, L. 2007; 34 (11): 4484-90

    Abstract

    A quality assurance method was developed to investigate the effects of residual target motion for hypofractionated spine radiosurgery. The residual target motion (target movement between successive image-guided corrections) was measured on-line via dual x-ray imagers for patients treated with CyberKnife (Accuray, Inc., Sunnyvale, CA), a robotic linear accelerator with intrafractional image-tracking capability. The six degree-of-freedom characteristics of the residual target motion were analyzed, the effects of such motion on patient treatment delivery were investigated by incorporating the probability distribution of the residual motion into the treatment planning dose calculations, and deviations of the doses from those originally planned were calculated. Measurements using a programmable motion phantom were also carried out and compared with the static treatment plan calculations. It was found that the residual target motions were patient specific and typically on the order of 2 mm. The measured dose distributions incorporating the residual target motion also exhibited 2.0 mm discrepancy at the prescription isodose level when compared with the static treatment plan calculations. For certain patients, residual errors introduced significant uncertainties (-1 Gy) for the dose delivered to the spinal cord, especially at the high dose levels covering a small volume of the spinal cord (e.g., 0.1 cc). In such cases, stringent cord constraints and frequent monitoring of the target position should be implemented.

    View details for DOI 10.1118/1.2790587

    View details for PubMedID 18072513

  • Peripheral dose in ocular treatments with CyberKnife and Gamma Knife radiosurgery compared to proton radiotherapy. Physics in medicine and biology Zytkovicz, A., Daftari, I., Phillips, T. L., Chuang, C. F., Verhey, L., Petti, P. L. 2007; 52 (19): 5957-71

    Abstract

    Peripheral radiation can have deleterious effects on normal tissues throughout the body, including secondary cancer induction and cataractogenesis. The aim of this study is to evaluate the peripheral dose received by various regions of the body after ocular treatment delivered with the Model C Gamma Knife, proton radiotherapy with a dedicated ocular beam employing no passive-scattering system, or a CyberKnife unit before and after supplemental shielding was introduced. TLDs were used for stray gamma and x-ray dosimetry, whereas CR-39 dosimeters were used to measure neutron contamination in the proton experiments. Doses to the contralateral eye, neck, thorax and abdomen were measured on our anthropomorphic phantom for a 56 Gy treatment to a 588 mm(3) posterior ocular lesion. Gamma Knife (without collimator blocking) delivered the highest dose in the contralateral eye, with 402-2380 mSv, as compared with 118-234 mSv for CyberKnife pre-shielding, 46-255 mSv for CyberKnife post-shielding and 9-12 mSv for proton radiotherapy. Gamma Knife and post-shielding CyberKnife delivered comparable doses proximal to the treatment site, with 190 versus 196 mSv at the thyroid, whereas protons doses at these locations were less than 10 mSv. Gamma Knife doses decreased dramatically with distance from the treatment site, delivering only 13 mSv at the lower pelvis, comparable to the proton result of 4 to 7 mSv in this region. In contrast, CyberKnife delivered between 117 and 132 mSv to the lower pelvis. In conclusion, for ocular melanoma treatments, a proton beam employing no double scattering system delivers the lowest peripheral doses proximally to the contralateral eye and thyroid when compared to radiosurgery with the Model C Gamma Knife or CyberKnife. At distal locations in the pelvis, peripheral doses delivered with proton and Gamma Knife are of an order of magnitude smaller than those delivered with CyberKnife.

    View details for DOI 10.1088/0031-9155/52/19/016

    View details for PubMedID 17881812

  • Patterns of recurrence analysis in newly diagnosed glioblastoma multiforme after three-dimensional conformal radiation therapy with respect to pre-radiation therapy magnetic resonance spectroscopic findings 13th Annual Meeting of the International-Society-for-Magnetic-Resonance-in-Medicine Park, I., Tamai, G., Lee, M. C., Chuang, C. F., Chang, S. M., Berger, M. S., Nelson, S. J., Pirzkall, A. ELSEVIER SCIENCE INC. 2007: 381–89

    Abstract

    To determine whether the combined magnetic resonance imaging (MRI) and magnetic resonance spectroscopy imaging (MRSI) before radiation therapy (RT) is valuable for RT target definition, and to evaluate the feasibility of replacing the current definition of uniform margins by custom-shaped margins based on the information from MRI and MRSI.A total of 23 glioblastoma multiforme (GBM) patients underwent MRI and MRSI within 4 weeks after surgery but before the initiation of RT and at 2-month follow-up intervals thereafter. The MRSI data were quantified on the basis of a Choline-to-NAA Index (CNI) as a measure of spectroscopic abnormality. A combined anatomic and metabolic region of interest (MRI/S) consisting of T2-weighted hyperintensity, contrast enhancement (CE), resection cavity, and CNI2 (CNI >or= 2) based on the pre-RT imaging was compared to the extent of CNI2 and the RT dose distribution. The spatial relationship of the pre-RT MRI/S and the RT dose volume was compared with the extent of CE at each follow-up.Nine patients showed new or increased CE during follow-up, and 14 patients were either stable or had decreased CE. New or increased areas of CE occurred within CNI2 that was covered by 60 Gy in 6 patients and within the CNI2 that was not entirely covered by 60 Gy in 3 patients. New or increased CE resided within the pre-RT MRI/S lesion in 89% (8/9) of the patients with new or increased CE.These data indicate that the definition of RT target volumes according to the combined morphologic and metabolic abnormality may be sufficient for RT targeting.

    View details for DOI 10.1016/j.ijrobp.2007.03.019

    View details for Web of Science ID 000249796100010

    View details for PubMedID 17513061

    View details for PubMedCentralID PMC2377157

  • Potential value of MR spectroscopic imaging for the radiosurgical management of patients with recurrent high-grade gliomas. Technology in cancer research & treatment Chuang, C. F., Chan, A. A., Larson, D., Verhey, L. J., McDermott, M., Nelson, S. J., Pirzkall, A. 2007; 6 (5): 375-82

    Abstract

    Previous studies have shown that metabolic information provided by 3D Magnetic Resonance Spectroscopy Imaging (MRSI) could affect the definition of target volumes for radiation treatments (RT). This study aimed to (i) investigate the effect of incorporating spectroscopic volumes as determined by MRSI on target volume definition, patient selection eligibility, and dose prescription for stereotactic radiosurgery treatment planning; (ii) correlate the spatial extent of pre-SRS spectroscopic abnormality and treatment volumes with areas of focal recurrence as defined by changes in contrast enhancement; and (iii) examine the metabolic changes following SRS to assess treatment response. Twenty-six patients treated with Gamma Knife radiosurgery for recurrent glioblastoma multiforme (GBM) were retrospectively evaluated. All patients underwent both MRI and MRSI studies prior to SRS. Follow-up MRI exams were available for all 26 patients, with MRI/MRSI available in only 15/26 patients. We observed that the initial CNI 2 contours extended beyond the pre-SRS CE in 25/26 patients ranging in volume from 0.8 cc to 18.8 cc (median 5.6 cc). The inclusion of the volume of CNI 2 extending beyond the CE would have increased the SRS target volume by 5-165% (median 23.4%). This would have necessitated decreasing the SRS prescription dose in 19/26 patients to avoid increased toxicity; the resultant treatment volume would have exceeded 20cc in five patients, thus possibly excluding those from RS treatment per our institutional practice. MRSI follow-up studies showed a decrease in Choline, stable Creatine, and increased NAA indicative of response to SRS in the majority of patients. When combined with patient survival data, metabolic information obtained during follow-up MRSI studies seemed to indicate the potential to help to distinguish necrosis from new/recurrent tumor; however, this should be further verified by biopsy studies.

    View details for DOI 10.1177/153303460700600502

    View details for PubMedID 17877425

  • Boosting central target dose by optimizing embedded dose hot spots for gamma knife radiosurgery. Stereotactic and functional neurosurgery Ma, L., Larson, D., Petti, P., Chuang, C., Verhey, L. 2007; 85 (6): 259-63

    Abstract

    To develop a boost technique for Gamma Knife radiosurgery by embedding and optimizing dose hot spots inside a conventional Gamma Knife plan.An optimization algorithm was developed to automatically arrange the pattern and adjust the intensities of the embedded dose hot spots. We compared the treatment plans of the optimized boost technique with the conventional Gamma Knife treatment plans, where dose hot spots were scattered randomly within the target volume.We found the embedded boost plans significantly increased the maximum dose of the target (on average 31% or 5-6 Gy). The mean dose to the target was increased by an averaged 7.1% (1.5-2 Gy). In contrast, the dose to the adjacent normal brain was strictly maintained with the dose volume histograms differing less than 0.5% between the boost treatment plans and the conventional treatment plans. The planning effort and treatment time was comparable between the two techniques.We have demonstrated a simple and an effective technique for increasing the central target dose without affecting the normal brain sparing for Gamma Knife radiosurgery.

    View details for DOI 10.1159/000107357

    View details for PubMedID 17709977

  • The cyberknife: Practical experience with treatment planning and delivery Smith, V., Chuang, C. F., Meyer, J. L., Kavanagh, B. D., Purdy, J. A., Timmerman, R. KARGER. 2007: 143-161

    Abstract

    The Cyberknife Robotic Radiosurgery System is used at the University of California at San Francisco to provide stereotactic treatments to a range of lesions throughout the body. Image guidance is an integral part of this system and is used in every treatment to provide adaptive control during the treatment. Clinical examples are given for various types of lesions using the different image guidance techniques that are available with this technology.

    View details for DOI 10.1159/000106033

    View details for Web of Science ID 000248596600009

    View details for PubMedID 17641507

  • Dose-guided radiation therapy with megavoltage cone-beam CT. The British journal of radiology Chen, J., Morin, O., Aubin, M., Bucci, M. K., Chuang, C. F., Pouliot, J. 2006; 79 Spec No 1: S87-98

    Abstract

    Recent advances in fractionated external beam radiation therapy have increased our ability to deliver radiation doses that conform more tightly to the tumour volume. The steeper dose gradients delivered in these treatments make it increasingly important to set precisely the positions of the patient and the internal organs. For this reason, considerable research now focuses on methods using three-dimensional images of the patient on the treatment table to adapt either the patient position or the treatment plan, to account for variable organ locations. In this article, we briefly review the different adaptive methods being explored and discuss a proposed dose-guided radiation therapy strategy that adapts the treatment for future fractions to compensate for dosimetric errors from past fractions. The main component of this strategy is a procedure to reconstruct the dose delivered to the patient based on treatment-time portal images and pre-treatment megavoltage cone-beam computed tomography (MV CBCT) images of the patient. We describe the work to date performed to develop our dose reconstruction procedure, including the implementation of a MV CBCT system for clinical use, experiments performed to calibrate MV CBCT for electron density and to use the calibrated MV CBCT for dose calculations, and the dosimetric calibration of the portal imager. We also present an example of a reconstructed patient dose using a preliminary reconstruction program and discuss the technical challenges that remain to full implementation of dose reconstruction and dose-guided therapy.

    View details for DOI 10.1259/bjr/60612178

    View details for PubMedID 16980688

  • Peripheral doses in CyberKnife radiosurgery. Medical physics Petti, P. L., Chuang, C. F., Smith, V., Larson, D. A. 2006; 33 (6): 1770-9

    Abstract

    The purpose of this work is to measure the dose outside the treatment field for conformal CyberKnife treatments, to compare the results to those obtained for similar treatments delivered with gamma knife or intensity-modulated radiation therapy (IMRT), and to investigate the sources of peripheral dose in CyberKnife radiosurgery. CyberKnife treatment plans were developed for two hypothetical lesions in an anthropomorphic phantom, one in the thorax and another in the brain, and measurements were made with LiF thermoluminescent dosimeters (TLD-100 capsules) placed within the phantom at various depths and distances from the irradiated volume. For the brain lesion, gamma knife and 6-MV IMRT treatment plans were also developed, and peripheral doses were measured at the same locations as for the CyberKnife plan. The relative contribution to the CyberKnife peripheral dose from inferior- or superior-oblique beams entering or exiting through the body, internally scattered radiation, and leakage radiation was assessed through additional experiments using the single-isocenter option of the CyberKnife treatment-planning program with different size collimators. CyberKnife peripheral doses (in cGy) ranged from 0.16 to 0.041% (+/- 0.003%) of the delivered number of monitor units (MU) at distances between 18 and 71 cm from the field edge. These values are two to five times larger than those measured for the comparable gamma knife brain treatment, and up to a factor of four times larger those measured in the IMRT experiment. Our results indicate that the CyberKnife peripheral dose is due largely to leakage radiation, however at distances less than 40 cm from the field edge, entrance, or exit dose from inferior- or superior-oblique beams can also contribute significantly. For distances larger than 40 cm from the field edge, the CyberKnife peripheral dose is directly related to the number of MU delivered, since leakage radiation is the dominant component.

    View details for DOI 10.1118/1.2198173

    View details for PubMedID 16872084

  • Calibration of an amorphous-silicon flat panel portal imager for exit-beam dosimetry. Medical physics Chen, J., Chuang, C. F., Morin, O., Aubin, M., Pouliot, J. 2006; 33 (3): 584-94

    Abstract

    Amorphous-silicon flat panel detectors are currently used to acquire digital portal images with excellent image quality for patient alignment before external beam radiation therapy. As a first step towards interpreting portal images acquired during treatment in terms of the actual dose delivered to the patient, a calibration method is developed to convert flat panel portal images to the equivalent water dose deposited in the detector plane and at a depth of 1.5 cm. The method is based on empirical convolution models of dose deposition in the flat panel detector and in water. A series of calibration experiments comparing the response of the flat panel imager and ion chamber measurements of dose in water determines the model parameters. Kernels derived from field size measurements account for the differences in the production and detection of scattered radiation in the two systems. The dissimilar response as a function of beam energy spectrum is characterized from measurements performed at various off-axis positions and for increasing attenuator thickness in the beam. The flat panel pixel inhomogeneity is corrected by comparing a large open field image with profiles measured in water. To verify the accuracy of the calibration method, calibrated flat panel profiles were compared with measured dose profiles for fields delivered through solid water slabs, a solid water phantom containing an air cavity, and an anthropomorphic head phantom. Open rectangular fields of various sizes and locations as well as a multileaf collimator-shaped field were delivered. For all but the smallest field centered about the central axis, the calibrated flat panel profiles matched the measured dose profiles with little or no systematic deviation and approximately 3% (two standard deviations) accuracy for the in-field region. The calibrated flat panel profiles for fields located off the central axis showed a small -1.7% systematic deviation from the measured profiles for the in-field region. Out of the field, the differences between the calibrated flat panel and measured profiles continued to be small, approximately 0%-2% of the mean in-field dose. Further refinement of the calibration model should increase the accuracy of the procedure. This calibration method for flat panel portal imagers may be used as part of a validation scheme to verify the dose delivered to the patient during treatment.

    View details for DOI 10.1118/1.2168294

    View details for PubMedID 16878562

  • Magnetic Resonance Imaging for IMRT Image-Guided IMRT Verhey, L., Chuang, C., Pirzkall, A. Springer Berlin, Heidelberg. 2006; 1
  • Pretreatment Quality Assurance of Image-Tracked Lung Tumor Treatments Ma, L., Chuang, C., Huang, K., Petti, P., Sahgal, A., Larson, D., Verhey, L. 2006
  • A critical examination of the results from the Harvard-MIT NCT program phase I clinical trial of neutron capture therapy for intracranial disease. Journal of neuro-oncology Busse, P. M., Harling, O. K., Palmer, M. R., Kiger, W. S., Kaplan, J., Kaplan, I., Chuang, C. F., Goorley, J. T., Riley, K. J., Newton, T. H., Santa Cruz, G. A., Lu, X. Q., Zamenhof, R. G. 2003; 62 (1-2): 111-21

    Abstract

    A phase I trial was designed to evaluate normal tissue tolerance to neutron capture therapy (NCT); tumor response was also followed as a secondary endpoint. Between July 1996 and May 1999, 24 subjects were entered into a phase I trial evaluating cranial NCT in subjects with primary or metastatic brain tumors. Two subjects were excluded due to a decline in their performance status and 22 subjects were irradiated at the MIT Nuclear Reactor Laboratory. The median age was 56 years (range 24-78). All subjects had a pathologically confirmed diagnosis of either glioblastoma (20) or melanoma (2) and a Karnofsky of 70 or higher. Neutron irradiation was delivered with a 15 cm diameter epithermal beam. Treatment plans varied from 1 to 3 fields depending upon the size and location of the tumor. The 10B carrier, L-p-boronophenylalanine-fructose (BPA-f), was infused through a central venous catheter at doses of 250 mg kg(-1) over 1 h (10 subjects), 300 mg kg(-1) over 1.5 h (two subjects), or 350 mg kg(-1) over 1.5-2 h (10 subjects). The pharmacokinetic profile of 10B in blood was very reproducible and permitted a predictive model to be developed. Cranial NCT can be delivered at doses high enough to exhibit a clinical response with an acceptable level of toxicity. Acute toxicity was primarily associated with increased intracranial pressure; late pulmonary effects were seen in two subjects. Factors such as average brain dose, tumor volume, and skin, mucosa, and lung dose may have a greater impact on tolerance than peak dose alone. Two subjects exhibited a complete radiographic response and 13 of 17 evaluable subjects had a measurable reduction in enhanced tumor volume following NCT.

    View details for DOI 10.1007/BF02699938

    View details for PubMedID 12749707

  • Patient Specific Quality Assurance in IMRT Intensity-Modulated Radiation Therapy: The State of the Art Xia, P., Chuang, C. Medical Physics Publishing. 2003; 1
  • Skin toxicity due to intensity-modulated radiotherapy for head-and-neck carcinoma. International journal of radiation oncology, biology, physics Lee, N., Chuang, C., Quivey, J. M., Phillips, T. L., Akazawa, P., Verhey, L. J., Xia, P. 2002; 53 (3): 630-7

    Abstract

    To investigate the cause of acute skin toxicity observed in the treatment of head-and-neck cancer with extended-field intensity-modulated radiotherapy (EF-IMRT).EF-IMRT was used to treat head-and-neck cancer, with the gross target volume receiving 70 Gy and the clinical target volume 60 Gy. A thermoplastic mask covering the head, neck, and shoulder was used for immobilization. Dosimetric studies were conducted to investigate the possible causes of the skin reactions, such as the bolus effect of the mask, the use of multiple tangential beams with IMRT plans, and the way in which the physicians contoured the lymph nodes. The dose-volume histograms of conventional opposed-lateral fields were compared with that of the multiple tangential EF-IMRT fields. IMRT plans with neck nodes contoured up to and including the skin surface were compared with plans that contoured the neck nodes 5 mm away from the skin surface. In addition, IMRT plans defining the skin as a sensitive structure were compared with plans that did not define the skin as a sensitive structure. All plans were created using an anthropomorphic Rando phantom, and the skin doses were measured with and without the mask. In each measurement, 6 thermoluminescent dosimeters (TLDs) were placed at the lateral and medial surfaces of the neck.For all four plans, the measured skin doses with the mask were consistently higher than those without the mask. The average dose increase was about 18% owing to the bolus effect of the mask. Multiple tangential fields used in IMRT plans contributed to an increase in skin dose by about 19% and 27%, with and without the mask, respectively. If the skin of the neck was contoured as a sensitive structure for dose optimization, the volume of skin that received >45 Gy was further reduced by about 20%. Five patients immobilized with head and shoulder masks were treated with EF-IMRT plans with the neck nodes carefully delineated away from the skin surface. The neck skin was identified as a sensitive structure for dose optimization. Grade 1 toxicity was observed in 3 patients, Grade 2 in 1 patient, and Grade 3 in 1 patient toward the end of treatment.Multiple factors contributed to the observed acute skin reaction for head-and-neck cancer patients treated with EF-IMRT. By taking into consideration the skin as a sensitive structure during inverse planning, it was possible to reduce the skin dose to a tolerable level without compromising tumor target coverage.

    View details for DOI 10.1016/s0360-3016(02)02756-6

    View details for PubMedID 12062606

  • Investigation of the use of MOSFET for clinical IMRT dosimetric verification. Medical physics Chuang, C. F., Verhey, L. J., Xia, P. 2002; 29 (6): 1109-15

    Abstract

    (Received 22 October 2001; accepted for publication 26 March 2002; published 22 May 2002) With advanced conformal radiotherapy using intensity modulated beams, it is important to have radiation dose verification measurements prior to treatment. Metal oxide semiconductor field effect transistors (MOSFET) have the advantage of a faster and simpler reading procedure compared to thermoluminescent dosimeters (TLD), and with the commercial MOSFET system, multiple detectors can be used simultaneously. In addition, the small size of the detector could be advantageous, especially for point dose measurements in small homogeneous dose regions. To evaluate the feasibility of MOSFET for routine IMRT dosimetry, a comprehensive set of experiments has been conducted, to investigate the stability, linearity, energy, and angular dependence. For a period of two weeks, under a standard measurement setup, the measured dose standard deviation using the MOSFETs was +/- 0.015 Gy with the mean dose being 1.00 Gy. For a measured dose range of 0.3 Gy to 4.2 Gy, the MOSFETs present a linear response, with a linearity coefficient of 0.998. Under a 10 x 10 cm2 square field, the dose variations measured by the MOSFETs for every 10 degrees from 0 to 180 degrees is +/- 2.5%. The percent depth dose (PDD) measurements were used to verify the energy dependence. The measured PDD using the MOSFETs from 0.5 cm to 34 cm depth agreed to within +/- 3% when compared to that of the ionization chamber. For IMRT dose verification, two special phantoms were designed. One is a solid water slab with 81 possible MOSFET placement holes, and another is a cylindrical phantom with 48 placement holes. For each IMRT phantom verification, an ionization chamber and 3 to 5 MOSFETs were used to measure multiple point doses at different locations. Preliminary results show that the agreement between dose measured by MOSFET and that calculated by Corvus is within 5% error, while the agreement between ionization chamber measurement and the calculation is within 3% error. In conclusion, MOSFET detectors are suitable for routine IMRT dose verification.

    View details for DOI 10.1118/1.1481520

    View details for PubMedID 12094980

  • Communication and sampling rate limitations in IMRT delivery with a dynamic multileaf collimator system. Medical physics Xia, P., Chuang, C. F., Verhey, L. J. 2002; 29 (3): 412-23

    Abstract

    The delivery of an intensity modulated radiation field with a dynamic multileaf collimator (MLC) requires precise correlation between MLC positions and cumulative monitor units (MUs). The purpose of this study is to investigate the precision of this correlation as a function of delivered MUs and dose rate. A semi-Gaussian shaped intensity profile and a simple geometric intensity pattern consisting of four square segments were designed to deliver a total of 1, 4, 16, 64, and 100 MUs at three different dose rates of 100, 400, and 600 MU/min. The semi-Gaussian intensity pattern was delivered using both sliding window and step and shoot techniques. The dose profiles of this intensity pattern were measured with films. The four square intensity pattern was delivered using step and shoot and conventional delivery techniques for comparison. Because of geometrical symmetry, the dose to each segment in this intensity pattern is expected to be the same when the same MU is assigned to each segment. An ionization chamber was used to measure the dose in the center of each of the four square segments. For the semi-Gaussian shaped profile, significant artifacts were observed when the profile was delivered with small MUs and/or at a high dose rate. For the four square intensity pattern, the dose measured in each segment presented a large variation when delivered with small MUs and a high dose rate. The variation increases as the MU/segment decreases and as the dose rate increases. These MU and dose rate dependencies were not observed when the intensity pattern was delivered using a conventional delivery technique. The observed distortion of the semi-Gaussian profile and dose variations among the segments of the four square intensity pattern are explained by considering the sampling rate and the communication time lag between the control systems. Finally, clinical significance is discussed.

    View details for DOI 10.1118/1.1449496

    View details for PubMedID 11929023

  • Pharmacokinetic Analysis and Modeling of BPA-F in Murine Glioma and Melanoma Models for NCT Tenth International Congress on Neutron Capture Therapy for Cancer Kiger, W. S., Chuang, C. F., Palmer, M. R., Zamenhof, R. G., Busse, P. M. 2002
  • Creation of a reference image with Monte Carlo simulations for online EPID verification of daily patient setup SPIE Medical imaging Descalle, M. A., Chuang, C., Pouliot, J. 2002
  • Description and dosimetric verification of the PEREGRINE Monte Carlo dose calculation system for photon beams incident on a water phantom. Medical physics Hartmann Siantar, C. L., Walling, R. S., Daly, T. P., Faddegon, B., Albright, N., Bergstrom, P., Bielajew, A. F., Chuang, C., Garrett, D., House, R. K., Knapp, D., Wieczorek, D. J., Verhey, L. J. 2001; 28 (7): 1322-37

    Abstract

    PEREGRINE is a three-dimensional Monte Carlo dose calculation system written specifically for radiotherapy. This paper describes the implementation and overall dosimetric accuracy of PEREGRINE physics algorithms, beam model, and beam commissioning procedure. Particle-interaction data, tracking geometries, scoring, variance reduction, and statistical analysis are described. The BEAM code system is used to model the treatment-independent accelerator head, resulting in the identification of primary and scattered photon sources and an electron contaminant source. The magnitude of the electron source is increased to improve agreement with measurements in the buildup region in the largest fields. Published measurements provide an estimate of backscatter on monitor chamber response. Commissioning consists of selecting the electron beam energy, determining the scale factor that defines dose per monitor unit, and describing treatment-dependent beam modifiers. We compare calculations with measurements in a water phantom for open fields, wedges, blocks, and a multileaf collimator for 6 and 18 MV Varian Clinac 2100C photon beams. All calculations are reported as dose per monitor unit. Aside from backscatter estimates, no additional, field-specific normalization is included in comparisons with measurements. Maximum discrepancies were less than either 2% of the maximum dose or 1.2 mm in isodose position for all field sizes and beam modifiers.

    View details for DOI 10.1118/1.1381551

    View details for PubMedID 11488562

  • Selective tumor uptake of Boronophenylalanine-fructose (BPA-f) in animal model of hepatic colorectal metastases Frontiers in Neutron Capture Therapy: Vol. 2 Chuang, C., Busse, P., Palmer, M., Thomas, P., Zamenhof, R. Kluwer Academic/Plenum Publishers. 2001; 1
  • Time-dependent biodistribution of BAP-f in normal and tumor brain tissues in mice Frontiers in Neutron Capture Therapy: Vol. 2 Chuang, C., Palmer, M., Zamenhof, R., Busse, P. Kluwer Academic/Plenum Publishers. 2001; 1
  • Predicting boron-10 concentrations in normal brain and GBM from blood measurements Frontiers in Neutron Capture Therapy: Vol Palmer, M. R., Chuang, C., Kiger, W. S., Busse, P. M., Zamenhof, R. G. Kluwer Academic/Plenum Publishers. 2001; 1
  • The Harvard-MIT BCNT Program: Overview of the clinical trials and translational research Frontiers in Neutron Capture Therapy: Vol. 1 Busse, P. M., Zamenhof, R. G., Harling, O. K., Kaplan, I., Kaplan, J., Chuang, C., Goorley, J. T., Kiger, W. S., Riley, K. J., Tang, L., Solares, G. R., Palmer, M. R. Kluwer Academic/Plenum Publishers. 2001; 1
  • Computer simulated patient motion and setup uncertainties in intensity modulated radiotherapy XIII International Conference on the Use of Computers in Radiation Therapy Xia, P., Chuang, C., Nguyen-Tan, F., Fu, K. K., Verhey, L. 2000
  • A Phase-I clinical trial for cranial BNCT at Harvard-MIT the Ninth International Symposium on Neutron Capture Therapy for Cancer Busse, P. M., Harling, O. K., Palmer, M. R., Kaplan, I., Newton, T. H., Kaplan, J., Chuang, C. F., Kiger, W. S., Riley, K. J., Goorley, J. T., Zamenhof, R. G. 2000
  • The Harvard-MIT BNCT program: overview of the clinical trials and translational research the Eleventh International Congress of Radiation Research Busse, P. M., Zamenhof, R. G., Harling, O. K., Kaplan, I., Kaplan, J., Chuang, C. F., Goorley, J. T., Kiger, W. S., Riely, K. J., Tang, L., Solares, G. R., Palmer, M. R. 1999
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