John Bayouth, PhD

John Bayouth, PhD


Department of Human Oncology

I am a tenured professor, the Bhudatt Paliwal endowed chair and the chief of the Radiation Oncology Physics Division in the Department of Human Oncology at the University of Wisconsin in Madison. It’s my honor to direct one of the nation’s premier radiation oncology physics programs, a group of 20 medical physics faculty and staff. I am also the director of the UW–Madison Medical Physics Residency Program in Radiation Therapy. Nationally, I have served in the presidential chain of both the American Association of Physics in Medicine (AAPM) and the Society of Directors of Academic Medical Physics Programs (SDAMPP) and within various committees of the American Society of Radiation Oncology (ASTRO), the Radiological Society of North America (RSNA) and the American Board of Radiology (ABR).

For several years, I have investigated the clinical impact of advanced treatment approaches in radiation oncology, including intensity modulation radiation therapy treatment (IMRT) planning, image-guided radiation therapy (IGRT), respiratory-gated imaging and radiation therapy and functional imaging for treatment planning and response to therapy. My primary area of research is acquisition and analysis of 4DCT images to quantify longitudinal pulmonary functional changes following radiation therapy, and I am currently the principle investigator (PI) of an NCI funded (R01 CA166703) Investigator Initiated Clinical Trial open at UW-Madison (UW16037), whose goal is to design and deliver radiation treatment plans that will improve pulmonary function of radiation therapy patients.

Beginning in 2013, I worked on the clinical development and implementation of MRI-guided Co-60 radiation therapy (ViewRay) at UW-Madison. This program is creating novel research in IGRT, as patients are imaged daily and during treatment delivery, demonstrating the indication for and enabling execution of online adaptation of treatment delivery and providing a wealth of tumor and normal tissue response information.


Research Fellow, MD Anderson, Houston, TX, Radiation Physics (1993-1994)

PhD, MD Anderson, Houston, TX, Radiation Physics (1993)

MS, Kansas State University, Manhattan, Kansas, Nuclear Engineering (1991)

BS, Kansas State University, Manhattan, Kansas, Nuclear Engineering (1988)

Academic Appointments

Professor and Chief of Physics, Human Oncology (2013)

Selected Honors and Awards

Fellow, American Association of Physicists in Medicine (2014)

Endowed Chair: Bhudatt Paliwal Professor of Human Oncology (Professorship) University of Wisconsin School of Medicine and Public Health (2013)

Boards, Advisory Committees and Professional Organizations

Member, American Board of Radiology (Therapeutic Radiological Physics) (1997-pres.)

Research Focus

Quantifying and minimizing normal tissue toxicities during and following radiation therapy

Enabling cancer patients to survive their disease with the highest possible quality of life


Our group uses medical images to quantitatively characterize tumors and normal tissues. Tissue characterization changes that occur during therapy provide an indication for adapting therapy; we hypothesize that this form of personalized medicine will lead to improved effectiveness of radiation therapy, measured by increased overall survival and reduced normal tissue toxicity.

Improving Pulmonary Function following Radiation Therapy

Radiation is highly damaging to healthy lung tissue. Our group is using information about the patient’s healthy lung tissue to design radiation treatments that may reduce the side effects of radiation therapy to lung tumors. We have established a clinical trial that is set out to determine if subjects who have been treated with radiation therapy plans designed to spare high ventilation regions have superior preservation of pulmonary function compared to those treated with standard radiation dose distributions. Four-dimensional computed tomographic imaging (4DCT) will be used to determine lung tissue elasticity, as required for ventilation. Lung tissue elasticity maps at three months after RT will be compared to those prior to RT and used to quantify the change in the lung elasticity maps. Reduced lung tissue elasticity is defined in this study as a >6 percent reduction in expansion when compared to the baseline; the amount of lung tissue showing a >6 percent reduction is the metric for our primary endpoint and will be tested for a significant difference between the two arms.

images from a 4DCT scan; one at inhale, one at exhale, and the subsequent ventilation map derived from those images

The figure shows images from a 4DCT scan; one at inhale, one at exhale and the subsequent ventilation map derived from those images. The ventilation map shows regions of the lung where lung function is high, so we hope to avoid these regions during treatment delivery.

MRI-guided Adaptive Radiation Therapy

MRI-guided radiation therapy provides a method by which we are able to observe daily changes in the patient’s internal anatomy. This can be caused by many factors, ranging from reduction in tumor size to differing amounts of content in the stomach, bladder and bowels. Consequently, radiation treatment plans based on an image acquired weeks prior to radiation delivery may not adequately represent the patient’s anatomy on a daily basis.


MRI-guided Adaptive Radiation Therapy is a process through which we can identify these anatomical changes and adapt the patient’s treatment on a daily basis, which can produce a substantial improvement in the radiation dose distribution. The image below shows a Dose Volume Histogram for two treatment plans, the original plan and an adaptive plan. The adaptive plan shows much better radiation dose delivery to the gross tumor volume (GTV) and planning tumor volume (PTV) when compared to the original plan. The doses to normal tissues are also reduced with the adaptive plan. We are investigating novel planning techniques to make this process robust and effective.

Dose Volume Histogram for two treatment plans, the original plan and an adaptive plan.


Tomotherapy Motion Compensation

Tumor and normal tissue motion during respiration creates many unique challenges in radiation therapy planning and treatment delivery. Most strategies to account for this motion assume the patient’s breathing pattern remains consistent during the entire course of treatment, which may be as long as eight weeks. Unfortunately, humans do not breath as consistently as mechanical phantoms that medical physicists like to use to simulate this behavior. The image below shows variation in tumor position during normal respiration. Note that the tumor motion is large (nearly 10 mm) but also changes substantially from one breath to the next.


Consequently, we require more sophisticated techniques for managing respiratory motion. Through collaborative research with Accuray, Inc., we intend to develop and validate a motion compensation system on the Tomotherapy delivery platform.graphical depiction of variation in patient breathing pattern during radiation treatment

MRI-guided Radiation Therapy

MRI is an excellent imaging modality for visualization of soft tissues. This is particularly useful for tumors of the abdomen, such as pancreatic cancer shown below.  The left image shows the patient’s anatomy during exhale, while the image on the right shows the anatomical change during a maximum inspiration breath hold (MIBH). In the MIBH image we can see motion of nearly all the soft tissue, providing us superior ability to align the tumor during our treatment delivery. We are analyzing the clinical impact of using these treatment planning and delivery techniques and our patient’s ability to comply with self-guided breathing maneuvers.

Pancreatic cancer shown here. The left image shows the patient’s anatomy during exhale, while the image on the right shows the anatomical change during a maximum inspiration breath hold (MIBH). 

Patient-Specific Response-Informed Treatment Planning

Changes to the patient occur during the course of radiation treatment, which can be eight weeks. Some of the changes are morphological (tumor size and/or position) and some are physiological (metabolic activity, inflammation, oxygenation, perfusion, etc.). We are developing imaging techniques to quantify these changes that occur during the patient’s treatment process. The results of these studies are then being used to design subsequent treatments that exploit the observed changes.  This enables a new type of precision radiation therapy that we hope will significantly improve patient outcomes.


The image below shows an example of patient-specific response-informed treatment planning. This patient has highly functioning lung tissue in the apex of the right upper lobe. While this is an uncommon region of the lung to demonstrate high levels of ventilation, this knowledge enables us to design radiation treatment plans to avoid delivering doses in the high functioning lung (as shown in the second row of images). We are imaging these patients after radiation treatment as well to determine how much improvement can be accomplished using this novel therapeutic approach.

The image shows an example of patient-specific response-informed treatment planning.

  • Responses to the 2018 and 2019 'One Big Discovery' Question: ASTRO membership's opinions on the most important research question facing radiation oncology…where are we headed? Int J Radiat Oncol Biol Phys
    Dominello MM, Sanders T, Anscher M, Bayouth J, Brock KK, Carlson DJ, Hugo G, Joseph S, Knisely J, Mendonca MS, Mian OY, Moros EG, Singh AK, Yu JB
    2020 Aug 13; :
  • Evaluation of radixact motion synchrony for 3D respiratory motion: Modeling accuracy and dosimetric fidelity. J Appl Clin Med Phys
    Ferris WS, Kissick MW, Bayouth JE, Culberson WS, Smilowitz JB
    2020 Jul 21; :
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      The Radixact® linear accelerator contains the motion Synchrony system, which tracks and compensates for intrafraction patient motion. For respiratory motion, the system models the motion of the target and synchronizes the delivery of radiation with this motion using the jaws and multi-leaf collimators (MLCs). It was the purpose of this work to determine the ability of the Synchrony system to track and compensate for different phantom motions using a delivery quality assurance (DQA) workflow. Thirteen helical plans were created on static datasets from liver, lung, and pancreas subjects. Dose distributions were measured using a Delta4® Phantom+ mounted on a Hexamotion® stage for the following three case scenarios for each plan: (a) no phantom motion and no Synchrony (M0S0), (b) phantom motion and no Synchrony (M1S0), and (c) phantom motion with Synchrony (M1S1). The LEDs were placed on the Phantom+ for the 13 patient cases and were placed on a separate one-dimensional surrogate stage for additional studies to investigate the effect of separate target and surrogate motion. The root-mean-square (RMS) error between the Synchrony-modeled positions and the programmed phantom positions was <1.5 mm for all Synchrony deliveries with the LEDs on the Phantom+. The tracking errors increased slightly when the LEDs were placed on the surrogate stage but were similar to tracking errors observed for other motion tracking systems such as CyberKnife Synchrony. One-dimensional profiles indicate the effects of motion interplay and dose blurring present in several of the M1S0 plans that are not present in the M1S1 plans. All 13 of the M1S1 measured doses had gamma pass rates (3%/2 mm/10%T) compared to the planned dose > 90%. Only two of the M1S0 measured doses had gamma pass rates > 90%. Motion Synchrony offers a potential alternative to the current, ITV-based motion management strategy for helical tomotherapy deliveries.

      View details for PubMedID 32691973
  • Modeling the impact of out-of-phase ventilation on normal lung tissue response to radiation dose. Med Phys
    Wallat EM, Flakus MJ, Wuschner AE, Shao W, Christensen GE, Reinhardt JM, Baschnagel AM, Bayouth JE
    2020 Mar 18; :
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      PURPOSE: To create a dose response model that predicts lung ventilation change following radiation therapy, and examine the effects of out-of-phase ventilation.

      METHODS: The dose response model was built using 27 human subjects who underwent radiation therapy (RT) from an IRB-approved trial. For each 4DCT, two ventilation maps were created by calculating the N-phase local expansion ratio (LERN ) using most or all breathing phases and the 2-phase LER (LER2 ) using only the end inspiration and end expiration breathing phases. A polynomial regression model was created using the LERN ventilation maps pre-RT and post-RT and dose distributions for each subject, and cross-validated with a leave-one-out method. Further validation of the model was performed using 15 additional human subjects using common statistical operating characteristics and gamma pass rates.

      RESULTS: For voxels receiving 20 Gy or greater, there was a significant increase from 52% to 59% (p=0.03) in the gamma pass rates of the LERN model predicted post-RT Jacobian maps to the actual post-RT Jacobian maps, relative to the LER2 model. Additionally, accuracy significantly increased (p=0.03) from 68% to 75% using the LERN model, relative to the LER2 model.

      CONCLUSIONS: The LERN model was significantly more accurate than the LER2 model at predicting post-RT ventilation maps. More accurate post-RT ventilation maps will aid in producing a higher quality functional avoidance treatment plan, allowing for potentially better normal tissue sparing.

      View details for PubMedID 32187683
  • Validation of an MR-guided online adaptive radiotherapy (MRgoART) program: Deformation accuracy in a heterogeneous, deformable, anthropomorphic phantom. Radiother Oncol
    Mittauer KE, Hill PM, Bassetti MF, Bayouth JE
    2020 Mar 05; 146: 97-109
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      BACKGROUND AND PURPOSE: To investigate deformable image registration (DIR) and multi-fractional dose accumulation accuracy of a clinical MR-guided online adaptive radiotherapy (MRgoART) program, utilizing clinically-based magnitudes of abdominal deformation vector fields (DVFs).

      MATERIALS AND METHODS: A heterogeneous anthropomorphic multi-modality abdominal deformable phantom was comprised of MR and CT anatomically-relevant materials. Thermoluminescent dosimeters (TLDs) were affixed within regions of interest (ROIs). CT and MR simulation scans were acquired. CT was deformed to MR for dose calculations. MRgoART was executed on a MR-linac (MRIdian) for 5 Gy/5 fractions. Before each fraction, a deformation was applied. Ground truth was known for ROI volume, TLD position, and TLD dose measured by an accredited dosimetry calibration laboratory. To validate the range of applied deformations, phantom DVFs were compared to DVFs of clinical abdominal MRgoART fractions. MR-MR deformation accuracy was quantified through dice similarity coefficient (DSC), Hausdorff distance (HD), mean distance-to-agreement (MDA), and as mean-absolute-error (MAE) for CT-MR-MR deformation. Arithmetic-summation of calculated dose at respective TLD positions and deform-accumulated dose (MIM) was compared to TLD measured dose, respectively. MR-MR deformation statistics were quantified for MRIdian and MIM.

      RESULTS: Mean phantom DVFs were 5.0 ± 2.9 mm compared to mean DVF of clinical abdominal patients at 5.2 ± 3.0 mm. Respective mean DSC, HD, MDA was 0.93 ± 0.03, 0.74 ± 0.80 cm, 0.08 ± 0.03 cm for MRIdian and 0.93 ± 0.03, 0.54 ± 0.27 cm, 0.08 ± 0.03 cm for MIM (N = 80 ROIs). Mean MAE was 20.5 HU. Respective mean and median dose differences were 0.3%, -0.3% for arithmetic-summation and 4.1%, 0.6% for deformed-accumulation. Maximum differences were 0.21 Gy (arithmetic-summation), 0.31 Gy (deformed-accumulation).

      CONCLUSIONS: MRgoART deformation and dosimetric accuracy has been benchmarked for mean fractional DVFs of 5 mm in a multiple-rigid-body deformable phantom. Deformation accuracy was within TG132 criteria and clinically acceptable end-to-end MRgoART dosimetric agreement was observed for this phantom. Further efforts are needed in validation of deform-accumulated dose.

      View details for PubMedID 32146260
  • N-Phase Local Expansion Ratio for Characterizing Out-of-Phase Lung Ventilation. IEEE Trans Med Imaging
    Shao W, Patton TJ, Gerard SE, Pan Y, Reinhardt JM, Durumeric OC, Bayouth JE, Christensen GE
    2019 Dec 30; :
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      Out-of-phase ventilation occurs when local regions of the lung reach their maximum or minimum volumes at breathing phases other than the global end inhalation or exhalation phases. This paper presents the N-phase local expansion ratio (LERN) as a surrogate for lung ventilation. A common approach to estimate lung ventilation is to use image registration to align the end exhalation and inhalation 3DCT images and then analyze the resulting correspondence map. This 2-phase local expansion ratio (LER2) is limited because it ignores out-of-phase ventilation and thus may underestimate local lung ventilation. To overcome this limitation, LERN measures the maximum ratio of local expansion and contraction over the entire breathing cycle. Comparing LER2 to LERN provides a means for detecting and characterizing locations of the lung that experience out-of-phase ventilation. We present a novel in-phase/out-of-phase ventilation (IOV) function plot to visualize and measure the amount of high-function IOV that occurs during a breathing cycle. Treatment planning 4DCT scans collected during coached breathing from 32 human subjects with lung cancer were analyzed in this study. Results show that out-of-phase breathing occurred in all subjects and that the spatial distribution of out-of-phase ventilation varied from subject to subject. For the 32 subjects analyzed, 50% of the out-of-phase regions on average were mislabeled as low-function by LER2 (high-function threshold of 1.1, IOV threshold of 1.05). 4DCT and Xenon-enhanced CT of four sheep showed that LER8 is more accurate than LER2 for measuring lung ventilation.

      View details for PubMedID 31899418
  • STAT-ART: The Promise and Practice of a Rapid Palliative Single Session of MR-Guided Online Adaptive Radiotherapy (ART). Front Oncol
    Mittauer KE, Hill PM, Geurts MW, De Costa AM, Kimple RJ, Bassetti MF, Bayouth JE
    2019; 9: 1013
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      This work describes a novel application of MR-guided online adaptive radiotherapy (MRgoART) in the management of patients whom urgent palliative care is indicated using statum-adaptive radiotherapy (STAT-ART). The implementation of STAT-ART, as performed at our institution, is presented including a discussion of the advantages and limitations compared to the standard of care for palliative radiotherapy on conventional c-arm linacs. MR-based treatment planning techniques of STAT-ART for density overrides and deformable image registration (DIR) of diagnostic CT to the treatment MR are also addressed.

      View details for PubMedID 31696053
  • Characterization of Positional Accuracy of a Double-Focused and Double-Stack Multileaf Collimator on an MR-Guided Radiotherapy (MRgRT) Linac using an IC-Profiler Array. Med Phys
    Mittauer KE, Yadav P, Paliwal B, Bayouth JE
    2019 Nov 04; :
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      PURPOSE: With advance MR-guided online adaptive radiotherapy (MRgoART) relying on calculation-based IMRT quality assurance (QA), accurate and sensitive QA of the multileaf collimator (MLC) becomes an increasingly essential component for routine machine QA. As such, it is important to assure compliance with the AAPM TG142 guidelines to supplement calculation-based QA methods for an online adaptive radiotherapy program. We have developed and implemented an efficient and highly sensitive QA procedure using an ionization chamber profiler (ICP) array to enable real-time characterization of the positional accuracy of a double-focused and double-stacked MLC on a clinical MR-guided radiotherapy (MRgRT) system and to supplement calculation-based QA for an MRgoART program.

      METHODS: An in-house MR-compatible jig was used to position the ICP (detector resolution 5 mm on X/Y axis) at an extended SDD of 108.4 cm to enable each MLC leaf (8.3 mm leaf width at isocenter) to be uniquely determined by two neighboring ion chambers. The MRgRT linac system utilizes a novel jawless, double-focused, and double-stacked MLC design such that the upper bank (MLC1) and lower bank (MLC2) are offset by half a leaf width. Positional accuracy was characterized by three methods: single bank half-beam block (HBB) at central axis, forward slash diagonal (FSD) and backslash diagonal (BSD) at off-axis. Measurements were performed for each bank in which each leaf occludes half of a detector. A corresponding reference field with the MLC retracted from occlusion was measured. The sensitivities of HBB, FSD, and BSD were evaluated by introducing 0.5-2.5 mm of known errors in 0.5 mm increments, in both positive and negative directions. The relationship between detector response and MLC error was established. Over a six-month longitudinal assessment, we have evaluated MLC performance with weekly QA of HBB among cardinal angles, and monthly QA of FSD and BSD.

      RESULTS: A strong correlation was found between detector response of percentage dose difference and MLC positional error introduced (N=350 introduced errors) for both HBB and FSD/BSD with coefficient of determination of 0.999 and 0.977, respectively. The relationship between detector response to MLC positional change was found to be 20.65%/mm for HBB and 11.14%/mm for FSD and BSD. At baseline the mean MLC positional accuracy averaged across all leaves was 0.06±0.27 mm (HBB), 0.04±0.52 mm (FSD), -0.06±0.51 mm (BSD). The mean MLC positional accuracy relative to baseline over the six-month assessment was found to be highly reproducible at 0.00±0.12 mm (HBB; N=28 weeks), -0.02±0.19 mm (FSD; N=6 months), -0.03±0.19 mm (BSD; N=6 months).

      CONCLUSIONS: Positional accuracy of a novel jawless, double-focused, double-stacked MLC has been characterized and monitored over six months with an efficient, highly sensitive and robust method using an ICP array. This routine QA method supplements calculation-based IMRT QA for an online adaptive radiotherapy program. Longitudinal assessment demonstrated no-drift in the MLC calibration. A highly reproducible jig setup allowed the validation of MLC positional accuracy to be within TG142 criteria of ±1mm for 99% of measurements (i.e.,100% HBB, 95% BSD, 95% FSD) over the six-month assessment.

      View details for PubMedID 31682018
  • Characterization and longitudinal assessment of daily quality assurance for an MR-guided radiotherapy (MRgRT) linac. J Appl Clin Med Phys
    Mittauer KE, Dunkerley DAP, Yadav P, Bayouth JE
    2019 Nov; 20 (11): 27-36
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      PURPOSE: To describe and characterize daily machine quality assurance (QA) for an MR-guided radiotherapy (MRgRT) linac system, in addition to reporting a longitudinal assessment of the dosimetric and mechanical stability over a 7-month period of clinical operation.

      METHODS: Quality assurance procedures were developed to evaluate MR imaging/radiation isocenter, imaging and patient handling system, and linear accelerator stability. A longitudinal assessment was characterized for safety interlocks, laser and imaging isocenter coincidence, imaging and radiation (RT) isocentricity, radiation dose rate and output, couch motion, and MLC positioning. A cylindrical water phantom and an MR-compatible A1SL detector were utilized. MR and RT isocentricity and MLC positional accuracy was quantified through dose measured with a 0.40 cm2  x 0.83 cm2 field at each cardinal angle. The relationship between detector response to MR/RT isocentricity and MLC positioning was established through introducing known errors in phantom position.

      RESULTS: Correlation was found between detector response and introduced positional error (N = 27) with coefficients of determination of 0.9996 (IEC-X), 0.9967 (IEC-Y), 0.9968 (IEC-Z) in each respective shift direction. The relationship between dose (DoseMR/RT+MLC ) and the vector magnitude of MLC and MR/RT positional error (Errormag ) was calculated to be a nonlinear response and resembled a quadratic function: DoseMR/RT+MLC [%] = -0.0253 Errormag [mm]2  - 0.0195 Errormag [mm]. For the temporal assessment (N = 7 months), safety interlocks were functional. Laser coincidence to MR was within ±2.0 mm (99.6%) and ±1.0 mm (86.8%) over the 7-month assessment. IGRT position-reposition shifts were within ±2.0 mm (99.4%) and ±1.0 mm (92.4%). Output was within ±3% (99.4%). Mean MLC and MR/RT isocenter accuracy was 1.6 mm, averaged across cardinal angles for the 7-month period.

      CONCLUSIONS: The linac and IGRT accuracy of an MR-guided radiotherapy system has been validated and monitored over seven months for daily QA. Longitudinal assessment demonstrated a drift in dose rate, but temporal assessment of output, MLC position, and isocentricity has been stable.

      View details for PubMedID 31633882
  • Dosimetric study for spine stereotactic body radiation therapy: magnetic resonance guided linear accelerator versus volumetric modulated arc therapy. Radiol Oncol
    Yadav P, Musunuru HB, Witt JS, Bassetti M, Bayouth J, Baschnagel AM
    2019 09 24; 53 (3): 362-368
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      Background Stereotactic body radiation therapy (SBRT) given in 1-5 fractions is an effective treatment for vertebral metastases. Real-time magnetic resonance-guided radiotherapy (MRgRT) improves soft tissue contrast, which translates into accurate delivery of spine SBRT. Here we report on clinical implementation of MRgRT for spine SBRT, the quality of MRgRT plans compared to TrueBeam based volumetric modulated arc therapy (VMAT) plans in the treatment of spine metastases and benefits of MRgRT MR scan. Patients and methods Ten metastatic lesions were included in this study for plan comparison. Lesions were spread across thoracic spine and lumbosacral spine. Three fraction spine SBRT plans: 27Gy to planning target volume (PTV) and 30Gy to gross tumor volume (GTV) were generated on the ViewRay MRIdian Linac system and compared to TrueBeamTM STx based VMAT plans. Plans were compared using metrics such as minimum dose, maximum dose, mean dose, ratio of the dose to 50% of the volume (R50), conformity index, homogeneity index and dose to the spinal cord. Results MRIdian plans achieved equivalent target coverage and spinal cord dose compared to VMAT plans. The maximum and minimum PTV doses and homogeneity index were equivalent for both planning systems. R50 was lower for MRIdian plans compared to VMAT plans, indicating a lower spread of intermediate doses with MRIdian system (5.16 vs. 6.11, p = 0.03). Conclusions MRgRT can deliver high-quality spine SBRT plans comparable to TrueBeam volumetric modulated arc therapy (VMAT) plans.

      View details for PubMedID 31553704
  • Task Group 174 Report: Utilization of [18 F]Fluorodeoxyglucose Positron Emission Tomography ([18 F]FDG-PET) in Radiation Therapy. Med Phys
    Das SK, McGurk R, Miften M, Mutic S, Bowsher J, Bayouth J, Erdi Y, Mawlawi O, Boellaard R, Bowen SR, Xing L, Bradley J, Schoder H, Yin FF, Sullivan DC, Kinahan P
    2019 Oct; 46 (10): e706-e725
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      The use of positron emission tomography (PET) in radiation therapy (RT) is rapidly increasing in the areas of staging, segmentation, treatment planning, and response assessment. The most common radiotracer is 18 F-fluorodeoxyglucose ([18 F]FDG), a glucose analog with demonstrated efficacy in cancer diagnosis and staging. However, diagnosis and RT planning are different endeavors with unique requirements, and very little literature is available for guiding physicists and clinicians in the utilization of [18 F]FDG-PET in RT. The two goals of this report are to educate and provide recommendations. The report provides background and education on current PET imaging systems, PET tracers, intensity quantification, and current utilization in RT (staging, segmentation, image registration, treatment planning, and therapy response assessment). Recommendations are provided on acceptance testing, annual and monthly quality assurance, scanning protocols to ensure consistency between interpatient scans and intrapatient longitudinal scans, reporting of patient and scan parameters in literature, requirements for incorporation of [18 F]FDG-PET in treatment planning systems, and image registration. The recommendations provided here are minimum requirements and are not meant to cover all aspects of the use of [18 F]FDG-PET for RT.

      View details for PubMedID 31230358
  • MRI-linac systems will replace conventional IGRT systems within 15 years. Med Phys
    Bayouth JE, Low DA, Zaidi H
    2019 Sep; 46 (9): 3753-3756
  • The Dosimetric and Temporal Effects of Respiratory-Gated, High-Dose-Rate Radiation Therapy in Patients With Lung Cancer. Technol Cancer Res Treat
    Rouabhi O, Gross B, Bayouth J, Xia J
    2019 01 01; 18: 1533033818816072
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      PURPOSE: To evaluate the dosimetric and temporal effects of high-dose-rate respiratory-gated radiation therapy in patients with lung cancer.

      METHODS: Treatment plans from 5 patients with lung cancer (3 nongated and 2 gated at 80EX-80IN) were retrospectively evaluated. Prescription dose for these patients varied from 8 to 18 Gy/fraction with 3 to 5 treatment fractions. Using the same treatment planning criteria, 4 new treatment plans, corresponding to 4 gating windows (20EX-20IN, 40EX-40IN, 60EX-60IN, and 80EX-80IN), were generated for each patient. Mean tumor dose, mean lung dose, and lung V20 were used to assess the dosimetric effects. A MATLAB algorithm was developed to compute treatment time.

      RESULTS: Mean lung dose and lung V20 were on average reduced between -16.1% to -6.0% and -20.0% to -7.2%, respectively, for gated plans when compared to the corresponding nongated plans, and between -5.8% to -4.2% and -7.0% to -5.4%, respectively, for plans with smaller gating windows when compared to the corresponding plans gated at 80EX-80IN. Treatment delivery times of gated plans using high-dose rate were reduced on average between -19.7% (-0.10 min/100 MU) and -27.2% (-0.13 min/100 MU) for original nongated plans and -15.6% (-0.15 min/100 MU) and -20.3% (-0.19 min/100 MU) for original 80EX-80IN-gated plans.

      CONCLUSION: Respiratory-gated radiation therapy in patients with lung cancer can reduce lung dose while maintaining tumor dose. Because treatment delivery during gated therapy is discontinuous, total treatment time may be prolonged. However, this increase in treatment time can be offset by increasing the dose delivery rate. Estimation of treatment time may be helpful in selecting patients for respiratory gating and choosing appropriate gating windows.

      View details for PubMedID 30803374
  • A Multi-Institutional Experience of MR-Guided Liver Stereotactic Body Radiation Therapy. Adv Radiat Oncol
    Rosenberg SA, Henke LE, Shaverdian N, Mittauer K, Wojcieszynski AP, Hullett CR, Kamrava M, Lamb J, Cao M, Green OL, Kashani R, Paliwal B, Bayouth J, Harari PM, Olsen JR, Lee P, Parikh PJ, Bassetti M
    2019 Jan-Mar; 4 (1): 142-149
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      Purpose: Daily magnetic resonance (MR)-guided radiation has the potential to improve stereotactic body radiation therapy (SBRT) for tumors of the liver. Magnetic resonance imaging (MRI) introduces unique variables that are untested clinically: electron return effect, MRI geometric distortion, MRI to radiation therapy isocenter uncertainty, multileaf collimator position error, and uncertainties with voxel size and tracking. All could lead to increased toxicity and/or local recurrences with SBRT. In this multi-institutional study, we hypothesized that direct visualization provided by MR guidance could allow the use of small treatment volumes to spare normal tissues while maintaining clinical outcomes despite the aforementioned uncertainties in MR-guided treatment.

      Methods and materials: Patients with primary liver tumors or metastatic lesions treated with MR-guided liver SBRT were reviewed at 3 institutions. Toxicity was assessed using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4. Freedom from local progression (FFLP) and overall survival were analyzed with the Kaplan-Meier method and χ2 test.

      Results: The study population consisted of 26 patients: 6 hepatocellular carcinomas, 2 cholangiocarcinomas, and 18 metastatic liver lesions (44% colorectal metastasis). The median follow-up was 21.2 months. The median dose delivered was 50 Gy at 10 Gy/fraction. No grade 4 or greater gastrointestinal toxicities were observed after treatment. The 1-year and 2-year overall survival in this cohort is 69% and 60%, respectively. At the median follow-up, FFLP for this cohort was 80.4%. FFLP for patients with hepatocellular carcinomas, colorectal metastasis, and all other lesions were 100%, 75%, and 83%, respectively.

      Conclusions: This study describes the first clinical outcomes of MR-guided liver SBRT. Treatment was well tolerated by patients with excellent local control. This study lays the foundation for future dose escalation and adaptive treatment for liver-based primary malignancies and/or metastatic disease.

      View details for PubMedID 30706022
  • The VAMPIRE challenge: A multi-institutional validation study of CT ventilation imaging. Med Phys
    Kipritidis J, Tahir BA, Cazoulat G, Hofman MS, Siva S, Callahan J, Hardcastle N, Yamamoto T, Christensen GE, Reinhardt JM, Kadoya N, Patton TJ, Gerard SE, Duarte I, Archibald-Heeren B, Byrne M, Sims R, Ramsay S, Booth JT, Eslick E, Hegi-Johnson F, Woodruff HC, Ireland RH, Wild JM, Cai J, Bayouth JE, Brock K, Keall PJ
    2019 Mar; 46 (3): 1198-1217
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      PURPOSE: CT ventilation imaging (CTVI) is being used to achieve functional avoidance lung cancer radiation therapy in three clinical trials (NCT02528942, NCT02308709, NCT02843568). To address the need for common CTVI validation tools, we have built the Ventilation And Medical Pulmonary Image Registration Evaluation (VAMPIRE) Dataset, and present the results of the first VAMPIRE Challenge to compare relative ventilation distributions between different CTVI algorithms and other established ventilation imaging modalities.

      METHODS: The VAMPIRE Dataset includes 50 pairs of 4DCT scans and corresponding clinical or experimental ventilation scans, referred to as reference ventilation images (RefVIs). The dataset includes 25 humans imaged with Galligas 4DPET/CT, 21 humans imaged with DTPA-SPECT, and 4 sheep imaged with Xenon-CT. For the VAMPIRE Challenge, 16 subjects were allocated to a training group (with RefVI provided) and 34 subjects were allocated to a validation group (with RefVI blinded). Seven research groups downloaded the Challenge dataset and uploaded CTVIs based on deformable image registration (DIR) between the 4DCT inhale/exhale phases. Participants used DIR methods broadly classified into B-splines, Free-form, Diffeomorphisms, or Biomechanical modeling, with CT ventilation metrics based on the DIR evaluation of volume change, Hounsfield Unit change, or various hybrid approaches. All CTVIs were evaluated against the corresponding RefVI using the voxel-wise Spearman coefficient r S , and Dice similarity coefficients evaluated for low function lung ( DSC low ) and high function lung ( DSC high ).

      RESULTS: A total of 37 unique combinations of DIR method and CT ventilation metric were either submitted by participants directly or derived from participant-submitted DIR motion fields using the in-house software, VESPIR. The r S and DSC results reveal a high degree of inter-algorithm and intersubject variability among the validation subjects, with algorithm rankings changing by up to ten positions depending on the choice of evaluation metric. The algorithm with the highest overall cross-modality correlations used a biomechanical model-based DIR with a hybrid ventilation metric, achieving a median (range) of 0.49 (0.27-0.73) for r S , 0.52 (0.36-0.67) for DSC low , and 0.45 (0.28-0.62) for DSC high . All other algorithms exhibited at least one negative r S value, and/or one DSC value less than 0.5.

      CONCLUSIONS: The VAMPIRE Challenge results demonstrate that the cross-modality correlation between CTVIs and the RefVIs varies not only with the choice of CTVI algorithm but also with the choice of RefVI modality, imaging subject, and the evaluation metric used to compare relative ventilation distributions. This variability may arise from the fact that each of the different CTVI algorithms and RefVI modalities provides a distinct physiologic measurement. Ultimately this variability, coupled with the lack of a "gold standard," highlights the ongoing importance of further validation studies before CTVI can be widely translated from academic centers to the clinic. It is hoped that the information gleaned from the VAMPIRE Challenge can help inform future validation efforts.

      View details for PubMedID 30575051
  • FissureNet: A Deep Learning Approach For Pulmonary Fissure Detection in CT Images. IEEE Trans Med Imaging
    Gerard SE, Patton TJ, Christensen GE, Bayouth JE, Reinhardt JM
    2019 01; 38 (1): 156-166
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      Pulmonary fissure detection in computed tomography (CT) is a critical component for automatic lobar segmentation. The majority of fissure detection methods use feature descriptors that are hand-crafted, low-level, and have local spatial extent. The design of such feature detectors is typically targeted toward normal fissure anatomy, yielding low sensitivity to weak, and abnormal fissures that are common in clinical data sets. Furthermore, local features commonly suffer from low specificity, as the complex textures in the lung can be indistinguishable from the fissure when the global context is not considered. We propose a supervised discriminative learning framework for simultaneous feature extraction and classification. The proposed framework, called FissureNet, is a coarse-to-fine cascade of two convolutional neural networks. The coarse-to-fine strategy alleviates the challenges associated with training a network to segment a thin structure that represents a small fraction of the image voxels. FissureNet was evaluated on a cohort of 3706 subjects with inspiration and expiration 3DCT scans from the COPDGene clinical trial and a cohort of 20 subjects with 4DCT scans from a lung cancer clinical trial. On both data sets, FissureNet showed superior performance compared with a deep learning approach using the U-Net architecture and a Hessian-based fissure detection method in terms of area under the precision-recall curve (PR-AUC). The overall PR-AUC for FissureNet, U-Net, and Hessian on the COPDGene (lung cancer) data set was 0.980 (0.966), 0.963 (0.937), and 0.158 (0.182), respectively. On a subset of 30 COPDGene scans, FissureNet was compared with a recently proposed advanced fissure detection method called derivative of sticks (DoS) and showed superior performance with a PR-AUC of 0.991 compared with 0.668 for DoS.

      View details for PubMedID 30106711
  • Quantifying ventilation change due to radiation therapy using 4DCT Jacobian calculations. Med Phys
    Patton TJ, Gerard SE, Shao W, Christensen GE, Reinhardt JM, Bayouth JE
    2018 Oct; 45 (10): 4483-4492
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      PURPOSE: Regional ventilation and its response to radiation dose can be estimated using four-dimensional computed tomography (4DCT) and image registration. This study investigated the impact of radiation therapy (RT) on ventilation and the dependence of radiation-induced ventilation change on pre-RT ventilation derived from 4DCT.

      METHODS AND MATERIALS: Three 4DCT scans were acquired from each of 12 subjects: two scans before RT and one scan 3 months after RT. The 4DCT datasets were used to generate the pre-RT and post-RT ventilation maps by registering the inhale phase image to the exhale phase image and computing the Jacobian determinant of the resulting transformation. The ventilation change between pre-RT and post-RT was calculated by taking a ratio of the post-RT Jacobian map to the pre-RT Jacobian map. The voxel-wise ventilation change between pre- and post-RT was investigated as a function of dose and pre-RT ventilation.

      RESULTS: Lung regions receiving over 20 Gy exhibited a significant decrease in function (3.3%, P < 0.01) compared to those receiving less than 20 Gy. When the voxels were stratified into high and low pre-RT function by thresholding the Jacobian map at 10% volume expansion (Jacobian = 1.1), high-function voxels exhibited 4.8% reduction in function for voxels receiving over 20 Gy, a significantly greater decline (P = 0.037) than the 2.4% reduction in function for low-function voxels. Ventilation decreased linearly with dose in both high-function and low-function regions. High-function regions showed a significantly larger decline in ventilation (P ≪ 0.001) as dose increased (1.4% ventilation reduction/10 Gy) compared to low-function regions (0.3% ventilation reduction/10 Gy). With further stratification of pre-RT ventilation, voxels exhibited increasing dose-dependent ventilation reduction with increasing pre-RT ventilation, with the largest pre-RT Jacobian bin (pre-RT Jacobian between 1.5 and 1.6) exhibiting a ventilation reduction of 4.8% per 10 Gy.

      CONCLUSIONS: Significant ventilation reductions were measured after radiation therapy treatments, and were dependent on the dose delivered to the tissue and the pre-RT ventilation of the tissue. For a fixed radiation dose, lung tissue with high pre-RT ventilation experienced larger decreases in post-RT ventilation than lung tissue with low pre-RT ventilation.

      View details for PubMedID 30047588
  • Responses to the 2017 "1 Million Gray Question": ASTRO Membership's Opinions on the Most Important Research Question Facing Radiation Oncology. Int J Radiat Oncol Biol Phys
    Dominello MM, Keen JC, Beck TF, Bayouth J, Knisely J, Carlson DJ, Mendonca MS, Mian O, Brock KK, Anscher M, Hugo G, Moros EG, Singh AK, Yu JB
    2018 10 01; 102 (2): 249-250
  • A New Era of Image Guidance with Magnetic Resonance-guided Radiation Therapy for Abdominal and Thoracic Malignancies. Cureus
    Mittauer K, Paliwal B, Hill P, Bayouth JE, Geurts MW, Baschnagel AM, Bradley KA, Harari PM, Rosenberg S, Brower JV, Wojcieszynski AP, Hullett C, Bayliss RA, Labby ZE, Bassetti MF
    2018 Apr 04; 10 (4): e2422
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      Magnetic resonance-guided radiation therapy (MRgRT) offers advantages for image guidance for radiotherapy treatments as compared to conventional computed tomography (CT)-based modalities. The superior soft tissue contrast of magnetic resonance (MR) enables an improved visualization of the gross tumor and adjacent normal tissues in the treatment of abdominal and thoracic malignancies. Online adaptive capabilities, coupled with advanced motion management of real-time tracking of the tumor, directly allow for high-precision inter-/intrafraction localization. The primary aim of this case series is to describe MR-based interventions for localizing targets not well-visualized with conventional image-guided technologies. The abdominal and thoracic sites of the lung, kidney, liver, and gastric targets are described to illustrate the technological advancement of MR-guidance in radiotherapy.

      View details for PubMedID 29872602
  • An analysis of the ArcCHECK-MR diode array's performance for ViewRay quality assurance. J Appl Clin Med Phys
    Ellefson ST, Culberson WS, Bednarz BP, DeWerd LA, Bayouth JE
    2017 Jul; 18 (4): 161-171
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      The ArcCHECK-MR diode array utilizes a correction system with a virtual inclinometer to correct the angular response dependencies of the diodes. However, this correction system cannot be applied to measurements on the ViewRay MR-IGRT system due to the virtual inclinometer's incompatibility with the ViewRay's multiple simultaneous beams. Additionally, the ArcCHECK's current correction factors were determined without magnetic field effects taken into account. In the course of performing ViewRay IMRT quality assurance with the ArcCHECK, measurements were observed to be consistently higher than the ViewRay TPS predictions. The goals of this study were to quantify the observed discrepancies and test whether applying the current factors improves the ArcCHECK's accuracy for measurements on the ViewRay. Gamma and frequency analysis were performed on 19 ViewRay patient plans. Ion chamber measurements were performed at a subset of diode locations using a PMMA phantom with the same dimensions as the ArcCHECK. A new method for applying directionally dependent factors utilizing beam information from the ViewRay TPS was developed in order to analyze the current ArcCHECK correction factors. To test the current factors, nine ViewRay plans were altered to be delivered with only a single simultaneous beam and were measured with the ArcCHECK. The current correction factors were applied using both the new and current methods. The new method was also used to apply corrections to the original 19 ViewRay plans. It was found the ArcCHECK systematically reports doses higher than those actually delivered by the ViewRay. Application of the current correction factors by either method did not consistently improve measurement accuracy. As dose deposition and diode response have both been shown to change under the influence of a magnetic field, it can be concluded the current ArcCHECK correction factors are invalid and/or inadequate to correct measurements on the ViewRay system.

      View details for PubMedID 28681448
  • Genomics, functional and molecular imaging will pave the road to individualized radiation therapy. Med Phys
    Stancanello J, Bayouth JE, Orton CG
    2008 Nov; 35 (11): 4769-4772
  • The effect of Optune™ Tumor Treating Fields transducer arrays on skin radiation dose during radiotherapy. J Clin Neurosci
    Bender E, Kozak K, Howard S, Hayes L, Bayouth J, Robins HI
    2017 Aug; 42: 172-175
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      A Phase 3 clinical study demonstrated that the addition of 200kHz Tumor Treating Fields (TTF) to temozolomide in the post-radiation (RT) phase of therapy in newly diagnosed glioblastoma increases progression free and overall survival (resulting in FDA and European Union approval). Preclinical studies have demonstrated the ability of TTF to act as a radiosensitizer, suggesting concurrent TTF and RT may have clinical utility. The removal and replacement of TTF transducer arrays from the scalps of patients on a daily basis, i.e., just before and after RT treatments, would be extremely cumbersome. Based on these considerations, phantom studies of the effect of Optune (TM) transducer arrays on radiation dose distribution were performed to evaluate the feasibility of leaving arrays in place during RT. Film measurements were performed using Gafchromic EBT3 film and an Epson 11000XL scanner. Film calibration was done based on the ratio of the red to blue color channel data. A Siemens Oncor linear accelerator operating at 6MV, 10cm×10cm field size, and 100cm source-to-film distance was used for all measurements. For each exposure, two films were stacked, providing planes of measurement that were ∼0.1 and 0.4mm in depth. Data accrued demonstrated that radiation attenuation should not be a clinically significant issue. However, TTF transducer arrays were found to cause both a radiation bolus effect, as well as an increased exit dose effect. These studies predict increased skin toxicity, which merits significant caution for further clinical development of this combination.

      View details for PubMedID 28427800
  • Dosimetric Comparison of Real-Time MRI-Guided Tri-Cobalt-60 Versus Linear Accelerator-Based Stereotactic Body Radiation Therapy Lung Cancer Plans. Technol Cancer Res Treat
    Wojcieszynski AP, Hill PM, Rosenberg SA, Hullett CR, Labby ZE, Paliwal B, Geurts MW, Bayliss RA, Bayouth JE, Harari PM, Bassetti MF, Baschnagel AM
    2017 Jun; 16 (3): 366-372
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      PURPOSE: Magnetic resonance imaging-guided radiation therapy has entered clinical practice at several major treatment centers. Treatment of early-stage non-small cell lung cancer with stereotactic body radiation therapy is one potential application of this modality, as some form of respiratory motion management is important to address. We hypothesize that magnetic resonance imaging-guided tri-cobalt-60 radiation therapy can be used to generate clinically acceptable stereotactic body radiation therapy treatment plans. Here, we report on a dosimetric comparison between magnetic resonance imaging-guided radiation therapy plans and internal target volume-based plans utilizing volumetric-modulated arc therapy.

      MATERIALS AND METHODS: Ten patients with early-stage non-small cell lung cancer who underwent radiation therapy planning and treatment were studied. Following 4-dimensional computed tomography, patient images were used to generate clinically deliverable plans. For volumetric-modulated arc therapy plans, the planning tumor volume was defined as an internal target volume + 0.5 cm. For magnetic resonance imaging-guided plans, a single mid-inspiratory cycle was used to define a gross tumor volume, then expanded 0.3 cm to the planning tumor volume. Treatment plan parameters were compared.

      RESULTS: Planning tumor volumes trended larger for volumetric-modulated arc therapy-based plans, with a mean planning tumor volume of 47.4 mL versus 24.8 mL for magnetic resonance imaging-guided plans ( P = .08). Clinically acceptable plans were achievable via both methods, with bilateral lung V20, 3.9% versus 4.8% ( P = .62). The volume of chest wall receiving greater than 30 Gy was also similar, 22.1 versus 19.8 mL ( P = .78), as were all other parameters commonly used for lung stereotactic body radiation therapy. The ratio of the 50% isodose volume to planning tumor volume was lower in volumetric-modulated arc therapy plans, 4.19 versus 10.0 ( P < .001). Heterogeneity index was comparable between plans, 1.25 versus 1.25 ( P = .98).

      CONCLUSION: Magnetic resonance imaging-guided tri-cobalt-60 radiation therapy is capable of delivering lung high-quality stereotactic body radiation therapy plans that are clinically acceptable as compared to volumetric-modulated arc therapy-based plans. Real-time magnetic resonance imaging provides the unique capacity to directly observe tumor motion during treatment for purposes of motion management.

      View details for PubMedID 28168936
  • Using [(18)F]Fluorothymidine Imaged With Positron Emission Tomography to Quantify and Reduce Hematologic Toxicity Due to Chemoradiation Therapy for Pelvic Cancer Patients. Int J Radiat Oncol Biol Phys
    McGuire SM, Bhatia SK, Sun W, Jacobson GM, Menda Y, Ponto LL, Smith BJ, Gross BA, Bayouth JE, Sunderland JJ, Graham MM, Buatti JM
    2016 Sep 01; 96 (1): 228-39
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      PURPOSE: The purpose of the present prospective clinical trial was to determine the efficacy of [(18)F]fluorothymidine (FLT)-identified active bone marrow sparing for pelvic cancer patients by correlating the FLT uptake change during and after chemoradiation therapy with hematologic toxicity.

      METHODS AND MATERIALS: Simulation FLT positron emission tomography (PET) images were used to spare pelvic bone marrow using intensity modulated radiation therapy (IMRT BMS) for 32 patients with pelvic cancer. FLT PET scans taken during chemoradiation therapy after 1 and 2 weeks and 30 days and 1 year after completion of chemoradiation therapy were used to evaluate the acute and chronic dose response of pelvic bone marrow. Complete blood counts were recorded at each imaging point to correlate the FLT uptake change with systemic hematologic toxicity.

      RESULTS: IMRT BMS plans significantly reduced the dose to the pelvic regions identified with FLT uptake compared with control IMRT plans (P<.001, paired t test). Radiation doses of 4 Gy caused an ∼50% decrease in FLT uptake in the pelvic bone marrow after either 1 or 2 weeks of chemoradiation therapy. Additionally, subjects with more FLT-identified bone marrow exposed to ≥4 Gy after 1 week developed grade 2 leukopenia sooner than subjects with less marrow exposed to ≥4 Gy (P<.05, Cox regression analysis). Apparent bone marrow recovery at 30 days after therapy was not maintained 1 year after chemotherapy. The FLT uptake in the pelvic bone marrow regions that received >35 Gy was 18.8% ± 1.8% greater at 30 days after therapy than at 1 year after therapy. The white blood cell, platelet, lymphocyte, and neutrophil counts at 1 year after therapy were all lower than the pretherapy levels (P<.05, paired t test).

      CONCLUSIONS: IMRT BMS plans reduced the dose to FLT-identified pelvic bone marrow for pelvic cancer patients. However, reducing hematologic toxicity is challenging owing to the acute radiation sensitivity (∼4 Gy) and chronic suppression of activity in bone marrow receiving radiation doses >35 Gy, as measured by the FLT uptake change correlated with the complete blood cell counts.

      View details for PubMedID 27319286
  • Impact of temporal probability in 4D dose calculation for lung tumors. J Appl Clin Med Phys
    Rouabhi O, Ma M, Bayouth J, Xia J
    2015 11 08; 16 (6): 110-118
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      The purpose of this study was to evaluate the dosimetric uncertainty in 4D dose calculation using three temporal probability distributions: uniform distribution, sinusoidal distribution, and patient-specific distribution derived from the patient respiratory trace. Temporal probability, defined as the fraction of time a patient spends in each respiratory amplitude, was evaluated in nine lung cancer patients. Four-dimensional computed tomography (4D CT), along with deformable image registration, was used to compute 4D dose incorporating the patient's respiratory motion. First, the dose of each of 10 phase CTs was computed using the same planning parameters as those used in 3D treatment planning based on the breath-hold CT. Next, deformable image registration was used to deform the dose of each phase CT to the breath-hold CT using the deformation map between the phase CT and the breath-hold CT. Finally, the 4D dose was computed by summing the deformed phase doses using their corresponding temporal probabilities. In this study, 4D dose calculated from the patient-specific temporal probability distribution was used as the ground truth. The dosimetric evaluation matrix included: 1) 3D gamma analysis, 2) mean tumor dose (MTD), 3) mean lung dose (MLD), and 4) lung V20. For seven out of nine patients, both uniform and sinusoidal temporal probability dose distributions were found to have an average gamma passing rate > 95% for both the lung and PTV regions. Compared with 4D dose calculated using the patient respiratory trace, doses using uniform and sinusoidal distribution showed a percentage difference on average of -0.1% ± 0.6% and -0.2% ± 0.4% in MTD, -0.2% ± 1.9% and -0.2% ± 1.3% in MLD, 0.09% ± 2.8% and -0.07% ± 1.8% in lung V20, -0.1% ± 2.0% and 0.08% ± 1.34% in lung V10, 0.47% ± 1.8% and 0.19% ± 1.3% in lung V5, respectively. We concluded that four-dimensional dose computed using either a uniform or sinusoidal temporal probability distribution can approximate four-dimensional dose computed using the patient-specific respiratory trace.

      View details for PubMedID 26699562
  • Characterization of a 0.35T MR system for phantom image quality stability and in vivo assessment of motion quantification. J Appl Clin Med Phys
    Saenz DL, Yan Y, Christensen N, Henzler MA, Forrest LJ, Bayouth JE, Paliwal BR
    2015 11 08; 16 (6): 30-40
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      ViewRay is a novel MR-guided radiotherapy system capable of imaging in near real-time at four frames per second during treatment using 0.35T field strength. It allows for improved gating techniques and adaptive radiotherapy. Three cobalt-60 sources (~ 15,000 Curies) permit multiple-beam, intensity-modulated radiation therapy. The primary aim of this study is to assess the imaging stability, accuracy, and automatic segmentation algorithm capability to track motion in simulated and in vivo targets. Magnetic resonance imaging (MRI) characteristics of the system were assessed using the American College of Radiology (ACR)-recommended phantom and accreditation protocol. Images of the ACR phantom were acquired using a head coil following the ACR scanning instructions. ACR recommended T1- and T2-weighted sequences were evaluated. Nine measurements were performed over a period of seven months, on just over a monthly basis, to establish consistency. A silicon dielectric gel target was attached to the motor via a rod. 40 mm total amplitude was used with cycles of 3 to 9 s in length in a sinusoidal trajectory. Trajectories of six moving clinical targets in four canine patients were quantified and tracked. ACR phantom images were analyzed, and the results were compared with the ACR acceptance levels. Measured slice thickness accuracies were within the acceptance limits. In the 0.35 T system, the image intensity uniformity was also within the ACR acceptance limit. Over the range of cycle lengths, representing a wide range of breathing rates in patients imaged at four frames/s, excellent agreement was observed between the expected and measured target trajectories. In vivo canine targets, including the gross target volume (GTV), as well as other abdominal soft tissue structures, were visualized with inherent MR contrast, allowing for preliminary results of target tracking.

      View details for PubMedID 26699552
  • Gadoxetate for direct tumor therapy and tracking with real-time MRI-guided stereotactic body radiation therapy of the liver. Radiother Oncol
    Wojcieszynski AP, Rosenberg SA, Brower JV, Hullett CR, Geurts MW, Labby ZE, Hill PM, Bayliss RA, Paliwal B, Bayouth JE, Harari PM, Bassetti MF
    2016 Feb; 118 (2): 416-8
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      SBRT is increasingly utilized in liver tumor treatment. MRI-guided RT allows for real-time MRI tracking during therapy. Liver tumors are often poorly visualized and most contrast agents are transient. Gadoxetate may allow for sustained tumor visualization. Here, we report on the first use of gadoxetate during real-time MRI-guided SBRT.

      View details for PubMedID 26627702
  • Flattening filter-free accelerators: a report from the AAPM Therapy Emerging Technology Assessment Work Group. J Appl Clin Med Phys
    Xiao Y, Kry SF, Popple R, Yorke E, Papanikolaou N, Stathakis S, Xia P, Huq S, Bayouth J, Galvin J, Yin FF
    2015 May 08; 16 (3): 5219
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      This report describes the current state of flattening filter-free (FFF) radiotherapy beams implemented on conventional linear accelerators, and is aimed primarily at practicing medical physicists. The Therapy Emerging Technology Assessment Work Group of the American Association of Physicists in Medicine (AAPM) formed a writing group to assess FFF technology. The published literature on FFF technology was reviewed, along with technical specifications provided by vendors. Based on this information, supplemented by the clinical experience of the group members, consensus guidelines and recommendations for implementation of FFF technology were developed. Areas in need of further investigation were identified. Removing the flattening filter increases beam intensity, especially near the central axis. Increased intensity reduces treatment time, especially for high-dose stereotactic radiotherapy/radiosurgery (SRT/SRS). Furthermore, removing the flattening filter reduces out-of-field dose and improves beam modeling accuracy. FFF beams are advantageous for small field (e.g., SRS) treatments and are appropriate for intensity-modulated radiotherapy (IMRT). For conventional 3D radiotherapy of large targets, FFF beams may be disadvantageous compared to flattened beams because of the heterogeneity of FFF beam across the target (unless modulation is employed). For any application, the nonflat beam characteristics and substantially higher dose rates require consideration during the commissioning and quality assurance processes relative to flattened beams, and the appropriate clinical use of the technology needs to be identified. Consideration also needs to be given to these unique characteristics when undertaking facility planning. Several areas still warrant further research and development. Recommendations pertinent to FFF technology, including acceptance testing, commissioning, quality assurance, radiation safety, and facility planning, are presented. Examples of clinical applications are provided. Several of the areas in which future research and development are needed are also indicated.

      View details for PubMedID 26103482
  • Interobserver and intermodality variability in GTV delineation on simulation CT, FDG-PET, and MR Images of Head and Neck Cancer. Jacobs J Radiat Oncol
    Anderson CM, Sun W, Buatti JM, Maley JE, Policeni B, Mott SL, Bayouth JE
    2014 Sep; 1 (1): 006
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      PURPOSE: To compare the interobserver and intermodality differences in image-based identification of head and neck primary site gross tumor volumes (GTV). Modalities compared include: contrast-enhanced CT, F-18 fluorodeoxyglucose positron emission tomography (PET/CT) and contrast-enhanced MRI.

      METHODS AND MATERIALS: Fourteen patients were simulated after immobilization for all 3 imaging modalities (CT, PET/CT, MRI). Three radiation oncologists (RO) contoured GTVs as seen on each modality. The GTV was contoured first on the contrast-enhanced CT (considered the standard), then on PET/CT, and finally on post-contrast T1 MRI. Interobserver and intermodality variability were analyzed by volume, intersection, union, and volume overlap ratio (VOR).

      RESULTS: Analysis of RO contours revealed the average volume for CT-, PET/CT-, and MRI-derived GTVs were 45cc, 35cc and 49cc, respectively. In 93% of cases PET/CT-derived GTVs had the smallest volume and in 57% of cases MRI-derived GTVs had the largest volume. CT showed the largest variation in target definition (standard deviation amongst observers 35%) compared to PET/CT (28%) and MRI (27%). The VOR was largest (indicating greatest interobserver agreement) in PET/CT (46%), followed by MRI (36%), followed by CT (34%). For each observer, the least agreement in GTV definition occurred between MRI & PET/CT (average VOR = 41%), compared to CT & PET/CT (48%) and CT & MRI (47%).

      CONCLUSIONS: A nonsignificant interobserver difference in GTVs for each modality was seen. Among three modalities, CT was least consistent, while PET/CT-derived GTVs had the smallest volumes and were most consistent. MRI combined with PET/CT provided the least agreement in GTVs generated. The significance of these differences for head & neck cancer is important to explore as we move to volume-based treatment planning based on multi-modality imaging as a standard method for treatment delivery.

      View details for PubMedID 25568889
  • Impact of spot size on plan quality of spot scanning proton radiosurgery for peripheral brain lesions. Med Phys
    Wang D, Dirksen B, Hyer DE, Buatti JM, Sheybani A, Dinges E, Felderman N, TenNapel M, Bayouth JE, Flynn RT
    2014 Dec; 41 (12): 121705
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      PURPOSE: To determine the plan quality of proton spot scanning (SS) radiosurgery as a function of spot size (in-air sigma) in comparison to x-ray radiosurgery for treating peripheral brain lesions.

      METHODS: Single-field optimized (SFO) proton SS plans with sigma ranging from 1 to 8 mm, cone-based x-ray radiosurgery (Cone), and x-ray volumetric modulated arc therapy (VMAT) plans were generated for 11 patients. Plans were evaluated using secondary cancer risk and brain necrosis normal tissue complication probability (NTCP).

      RESULTS: For all patients, secondary cancer is a negligible risk compared to brain necrosis NTCP. Secondary cancer risk was lower in proton SS plans than in photon plans regardless of spot size (p = 0.001). Brain necrosis NTCP increased monotonically from an average of 2.34/100 (range 0.42/100-4.49/100) to 6.05/100 (range 1.38/100-11.6/100) as sigma increased from 1 to 8 mm, compared to the average of 6.01/100 (range 0.82/100-11.5/100) for Cone and 5.22/100 (range 1.37/100-8.00/100) for VMAT. An in-air sigma less than 4.3 mm was required for proton SS plans to reduce NTCP over photon techniques for the cohort of patients studied with statistical significance (p = 0.0186). Proton SS plans with in-air sigma larger than 7.1 mm had significantly greater brain necrosis NTCP than photon techniques (p = 0.0322).

      CONCLUSIONS: For treating peripheral brain lesions--where proton therapy would be expected to have the greatest depth-dose advantage over photon therapy--the lateral penumbra strongly impacts the SS plan quality relative to photon techniques: proton beamlet sigma at patient surface must be small (<7.1 mm for three-beam single-field optimized SS plans) in order to achieve comparable or smaller brain necrosis NTCP relative to photon radiosurgery techniques. Achieving such small in-air sigma values at low energy (<70 MeV) is a major technological challenge in commercially available proton therapy systems.

      View details for PubMedID 25471952
  • Patient-specific biomechanical model for the prediction of lung motion from 4-D CT images. IEEE Trans Med Imaging
    Fuerst B, Mansi T, Carnis F, Salzle M, Zhang J, Declerck J, Boettger T, Bayouth J, Navab N, Kamen A
    2015 Feb; 34 (2): 599-607
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      This paper presents an approach to predict the deformation of the lungs and surrounding organs during respiration. The framework incorporates a computational model of the respiratory system, which comprises an anatomical model extracted from computed tomography (CT) images at end-expiration (EE), and a biomechanical model of the respiratory physiology, including the material behavior and interactions between organs. A personalization step is performed to automatically estimate patient-specific thoracic pressure, which drives the biomechanical model. The zone-wise pressure values are obtained by using a trust-region optimizer, where the estimated motion is compared to CT images at end-inspiration (EI). A detailed convergence analysis in terms of mesh resolution, time stepping and number of pressure zones on the surface of the thoracic cavity is carried out. The method is then tested on five public datasets. Results show that the model is able to predict the respiratory motion with an average landmark error of 3.40 ±1.0 mm over the entire respiratory cycle. The estimated 3-D lung motion may constitute as an advanced 3-D surrogate for more accurate medical image reconstruction and patient respiratory analysis.

      View details for PubMedID 25343757
  • Spatial mapping of functional pelvic bone marrow using FLT PET. J Appl Clin Med Phys
    McGuire SM, Menda Y, Ponto LLB, Gross B, TenNapel M, Smith BJ, Bayouth JE
    2014 07 08; 15 (4): 129–136
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      The purpose of this study was to determine the ability of regions identified with bony landmarks on CT imaging to accurately represent active bone marrow when compared to FLT PET imaging. These surrogate regions could then be used to create a bone marrow sparing radiation therapy plan when FLT PET imaging is not available. Whole body (WB) FLT PET images were obtained of 18 subjects prior to chemoradiation therapy. The FLT image of each subject was registered to a CT image acquired for that subject to obtain anatomic information of the pelvis. Seventeen regions were identified based on features of the pelvic bones, sacrum, and femoral heads. The probability of FLT uptake being located in each of 17 different CT-based regions of the bony pelvis was calculated using Tukey's multiple comparison test. Statistical analysis of FLT uptake in the pelvis indicated four distinct groups within the 17 regions that had similar levels of activity. Regions located in the central part of the pelvis, including the superior part of the sacrum, the inner halves of the iliac crests, and the L5 vertebral body, had greater FLT uptake than those in the peripheral regions (p-value < 0.05). We have developed a method to use CT-defined pelvic bone regions to represent FLT PET-identified functional bone marrow. Individual regions that have a statistically significant probability of containing functional bone marrow can be used as avoidance regions to reduce radiation dose to functional bone marrow in radiation therapy planning. However, because likely active bone marrow regions and pelvic targets typically overlap, patient-specific spatial detail may be advantageous in IMRT planning scenarios and may best be provided using FLT PET imaging.

      View details for PubMedID 25207403
  • An Almost Linear Time Algorithm for Field Splitting in Radiation Therapy. Comput Geom
    Wu X, Dou X, Bayouth JE, Buatti JM
    2013 Aug 01; 46 (6): 673-687
    • More

      In this paper, we study an interesting geometric partition problem, called optimal field splitting, which arises in Intensity-Modulated Radiation Therapy (IMRT). In current clinical practice, a multi-leaf collimator (MLC) with a maximum leaf spread constraint is used to deliver the prescribed intensity maps (IMs). However, the maximum leaf spread of an MLC may require to split a large intensity map into several overlapping sub-IMs with each being delivered separately. We develop a close-to-linear time algorithm for solving the field splitting problem while minimizing the total complexity of the resulting sub-IMs, thus improving the treatment delivery efficiency. Meanwhile, our algorithm strives to minimize the maximum beam-on time of those sub-IMs. Our basic idea is to formulate the field splitting problem as computing a shortest path in a directed acyclic graph, which expresses a special "layered" structure. The edge weights of the graph satisfy the Monge property, which enables us to solve this shortest path problem by examining only a small portion of the graph, yielding a close-to-linear time algorithm. To minimize the maximum beam-on time of the resulting sub-IMs, we consider an interesting min-max slope path problem in a monotone polygon which is solvable in linear time. The min-max slope path problem may be of interest in its own right. Experimental results based on real medical data and computer generated IMs showed that our new algorithm runs fast and produces high quality field splitting results.

      View details for PubMedID 24999294
  • 3-Dimensional magnetic resonance spectroscopic imaging at 3 Tesla for early response assessment of glioblastoma patients during external beam radiation therapy. Int J Radiat Oncol Biol Phys
    Muruganandham M, Clerkin PP, Smith BJ, Anderson CM, Morris A, Capizzano AA, Magnotta V, McGuire SM, Smith MC, Bayouth JE, Buatti JM
    2014 Sep 01; 90 (1): 181-9
    • More

      PURPOSE: To evaluate the utility of 3-dimensional magnetic resonance (3D-MR) proton spectroscopic imaging for treatment planning and its implications for early response assessment in glioblastoma multiforme.

      METHODS AND MATERIALS: Eighteen patients with newly diagnosed, histologically confirmed glioblastoma had 3D-MR proton spectroscopic imaging (MRSI) along with T2 and T1 gadolinium-enhanced MR images at simulation and at boost treatment planning after 17 to 20 fractions of radiation therapy. All patients received standard radiation therapy (RT) with concurrent temozolomide followed by adjuvant temozolomide. Imaging for response assessment consisted of MR scans every 2 months. Progression-free survival was defined by the criteria of MacDonald et al. MRSI images obtained at initial simulation were analyzed for choline/N-acetylaspartate ratios (Cho/NAA) on a voxel-by-voxel basis with abnormal activity defined as Cho/NAA ≥2. These images were compared on anatomically matched MRSI data collected after 3 weeks of RT. Changes in Cho/NAA between pretherapy and third-week RT scans were tested using Wilcoxon matched-pairs signed rank tests and correlated with progression-free survival, radiation dose and location of recurrence using Cox proportional hazards regression.

      RESULTS: After a median follow-up time of 8.6 months, 50% of patients had experienced progression based on imaging. Patients with a decreased or stable mean or median Cho/NAA values had less risk of progression (P<.01). Patients with an increase in mean or median Cho/NAA values at the third-week RT scan had a significantly greater chance of early progression (P<.01). An increased Cho/NAA at the third-week MRSI scan carried a hazard ratio of 2.72 (95% confidence interval, 1.10-6.71; P=.03). Most patients received the prescription dose of RT to the Cho/NAA ≥2 volume, where recurrence most often occurred.

      CONCLUSION: Change in mean and median Cho/NAA detected at 3 weeks was a significant predictor of early progression. The potential impact for risk-adaptive therapy based on early spectroscopic findings is suggested.

      View details for PubMedID 24986746
  • A dose homogeneity and conformity evaluation between ViewRay and pinnacle-based linear accelerator IMRT treatment plans. J Med Phys
    Saenz DL, Paliwal BR, Bayouth JE
    2014 Apr; 39 (2): 64-70
    • More

      ViewRay, a novel technology providing soft-tissue imaging during radiotherapy is investigated for treatment planning capabilities assessing treatment plan dose homogeneity and conformity compared with linear accelerator plans. ViewRay offers both adaptive radiotherapy and image guidance. The combination of cobalt-60 (Co-60) with 0.35 Tesla magnetic resonance imaging (MRI) allows for magnetic resonance (MR)-guided intensity-modulated radiation therapy (IMRT) delivery with multiple beams. This study investigated head and neck, lung, and prostate treatment plans to understand what is possible on ViewRay to narrow focus toward sites with optimal dosimetry. The goal is not to provide a rigorous assessment of planning capabilities, but rather a first order demonstration of ViewRay planning abilities. Images, structure sets, points, and dose from treatment plans created in Pinnacle for patients in our clinic were imported into ViewRay. The same objectives were used to assess plan quality and all critical structures were treated as similarly as possible. Homogeneity index (HI), conformity index (CI), and volume receiving <20% of prescription dose (DRx) were calculated to assess the plans. The 95% confidence intervals were recorded for all measurements and presented with the associated bars in graphs. The homogeneity index (D5/D95) had a 1-5% inhomogeneity increase for head and neck, 3-8% for lung, and 4-16% for prostate. CI revealed a modest conformity increase for lung. The volume receiving 20% of the prescription dose increased 2-8% for head and neck and up to 4% for lung and prostate. Overall, for head and neck Co-60 ViewRay treatments planned with its Monte Carlo treatment planning software were comparable with 6 MV plans computed with convolution superposition algorithm on Pinnacle treatment planning system.

      View details for PubMedID 24872603
  • Feasibility of using nonflat photon beams for whole-breast irradiation with breath hold. J Appl Clin Med Phys
    Wang Y, Vassil A, Tendulkar R, Bayouth J, Xia P
    2014 Jan 06; 15 (1): 4397
    • More

      Removing a flattening filter or replacing it with a thinner filter alters the characteristics of a photon beam, creating a forward peaked intensity profile to make the photon beam nonflat. This study is to investigate the feasibility of applying nonflat photon beams to the whole-breast irradiation with breath holds for a potential of delivery time reduction during the gated treatment. Photon beams of 6 MV with flat and nonflat intensity profiles were commissioned. Fifteen patients with early-stage breast cancer, who received whole-breast radiation without breathing control, were retrospectively selected for this study. For each patient, three plans were created using a commercial treatment planning system: (a) the clinically approved plan using forward planning method (FP); (b) a hybrid intensity-modulated radiation therapy (IMRT) plan where the flat beam open fields were combined with the nonflat beam IMRT fields using direct aperture optimization method (mixed DAO); (c) a hybrid IMRT plan where both open and IMRT fields were from nonflat beams using direct aperture optimization (nonflat DAO). All plans were prescribed for ≥ 95% of the breast volume receiving the prescription dose of 50 Gy (2.0 Gy per fraction). In comparison, all plans achieved a similar dosimetric coverage to the targeted volume. The average homogeneity index of the FP, mixed DAO, and nonflat DAO plans were 0.882 ± 0.024, 0.879 ± 0.023, and 0.867 ± 0.027, respectively. The average percentage volume of V105 was 57.66% ± 5.21%, 34.67% ± 4.91%, 41.64% ± 5.32% for the FP, mixed, and nonflat DAO plans, respectively. There was no significant difference (p &gt; 0.05) observed for the defined endpoint doses in organs at risk (OARs). In conclusion, both mixed DAO and nonflat DAO plans can achieve similar plan quality as the clinically approved FP plan, measured by plan homogeneity and endpoint doses to the ORAs. Nonflat beam plans may reduce treatment time in breath-hold treatment, especially for hypofractionated treatment.

      View details for PubMedID 24423835
  • A computer aided treatment event recognition system in radiation therapy. Med Phys
    Xia J, Mart C, Bayouth J
    2014 Jan; 41 (1): 011713
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      PURPOSE: To develop an automated system to safeguard radiation therapy treatments by analyzing electronic treatment records and reporting treatment events.

      METHODS: CATERS (Computer Aided Treatment Event Recognition System) was developed to detect treatment events by retrieving and analyzing electronic treatment records. CATERS is designed to make the treatment monitoring process more efficient by automating the search of the electronic record for possible deviations from physician's intention, such as logical inconsistencies as well as aberrant treatment parameters (e.g., beam energy, dose, table position, prescription change, treatment overrides, etc). Over a 5 month period (July 2012-November 2012), physicists were assisted by the CATERS software in conducting normal weekly chart checks with the aims of (a) determining the relative frequency of particular events in the authors' clinic and (b) incorporating these checks into the CATERS. During this study period, 491 patients were treated at the University of Iowa Hospitals and Clinics for a total of 7692 fractions.

      RESULTS: All treatment records from the 5 month analysis period were evaluated using all the checks incorporated into CATERS after the training period. About 553 events were detected as being exceptions, although none of them had significant dosimetric impact on patient treatments. These events included every known event type that was discovered during the trial period. A frequency analysis of the events showed that the top three types of detected events were couch position override (3.2%), extra cone beam imaging (1.85%), and significant couch position deviation (1.31%). The significant couch deviation is defined as the number of treatments where couch vertical exceeded two times standard deviation of all couch verticals, or couch lateral/longitudinal exceeded three times standard deviation of all couch laterals and longitudinals. On average, the application takes about 1 s per patient when executed on either a desktop computer or a mobile device.

      CONCLUSIONS: CATERS offers an effective tool to detect and report treatment events. Automation and rapid processing enables electronic record interrogation daily, alerting the medical physicist of deviations potentially days prior to performing weekly check. The output of CATERS could also be utilized as an important input to failure mode and effects analysis.

      View details for PubMedID 24387505
  • Respiratory effort correction strategies to improve the reproducibility of lung expansion measurements. Med Phys
    Du K, Reinhardt JM, Christensen GE, Ding K, Bayouth JE
    2013 Dec; 40 (12): 123504
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      PURPOSE: Four-dimensional computed tomography (4DCT) can be used to make measurements of pulmonary function longitudinally. The sensitivity of such measurements to identify change depends on measurement uncertainty. Previously, intrasubject reproducibility of Jacobian-based measures of lung tissue expansion was studied in two repeat prior-RT 4DCT human acquisitions. Difference in respiratory effort such as breathing amplitude and frequency may affect longitudinal function assessment. In this study, the authors present normalization schemes that correct ventilation images for variations in respiratory effort and assess the reproducibility improvement after effort correction.

      METHODS: Repeat 4DCT image data acquired within a short time interval from 24 patients prior to radiation therapy (RT) were used for this analysis. Using a tissue volume preserving deformable image registration algorithm, Jacobian ventilation maps in two scanning sessions were computed and compared on the same coordinate for reproducibility analysis. In addition to computing the ventilation maps from end expiration to end inspiration, the authors investigated the effort normalization strategies using other intermediated inspiration phases upon the principles of equivalent tidal volume (ETV) and equivalent lung volume (ELV). Scatter plots and mean square error of the repeat ventilation maps and the Jacobian ratio map were generated for four conditions: no effort correction, global normalization, ETV, and ELV. In addition, gamma pass rate was calculated from a modified gamma index evaluation between two ventilation maps, using acceptance criterions of 2 mm distance-to-agreement and 5% ventilation difference.

      RESULTS: The pattern of regional pulmonary ventilation changes as lung volume changes. All effort correction strategies improved reproducibility when changes in respiratory effort were greater than 150 cc (p < 0.005 with regard to the gamma pass rate). Improvement of reproducibility was correlated with respiratory effort difference (R = 0.744 for ELV in the cohort with tidal volume difference greater than 100 cc). In general for all subjects, global normalization, ETV and ELV significantly improved reproducibility compared to no effort correction (p = 0.009, 0.002, 0.005 respectively). When tidal volume difference was small (less than 100 cc), none of the three effort correction strategies improved reproducibility significantly (p = 0.52, 0.46, 0.46 respectively). For the cohort (N = 13) with tidal volume difference greater than 100 cc, the average gamma pass rate improves from 57.3% before correction to 66.3% after global normalization, and 76.3% after ELV. ELV was found to be significantly better than global normalization (p = 0.04 for all subjects, and p = 0.003 for the cohort with tidal volume difference greater than 100 cc).

      CONCLUSIONS: All effort correction strategies improve the reproducibility of the authors' pulmonary ventilation measures, and the improvement of reproducibility is highly correlated with the changes in respiratory effort. ELV gives better results as effort difference increase, followed by ETV, then global. However, based on the spatial and temporal heterogeneity in the lung expansion rate, a single scaling factor (e.g., global normalization) appears to be less accurate to correct the ventilation map when changes in respiratory effort are large.

      View details for PubMedID 24320544
  • Continuous localization technologies for radiotherapy delivery: Report of the American Society for Radiation Oncology Emerging Technology Committee. Pract Radiat Oncol
    D'Ambrosio DJ, Bayouth J, Chetty IJ, Buyyounouski MK, Price RA, Correa CR, Dilling TJ, Franklin GE, Xia P, Harris EE, Konski A
    2012 Apr-Jun; 2 (2): 145-50
  • Equivalent-quality unflattened photon beam modeling, planning, and delivery. J Appl Clin Med Phys
    Huang Y, Flynn RT, Siochi RA, Bayouth JE
    2013 Jul 08; 14 (4): 4211
    • More

      The clinical application of the flattening filter-free photon beam (FFF) has enjoyed greater use due to its advantage of reduced treatment time because of the increased dose rate. Its unique beam characteristics, along with the very high-dose rate, require a thorough knowledge of the capability and accuracy in FFF beam modeling, planning, and delivery. This work verifies the feasibility of modeling an equivalent quality unflattened photon beam (eqUF), and the dosimetric accuracy in eqUF beam planning and delivery. An eqUF beam with a beam quality equivalent to a conventional 6 MV photon beam with the filter in place (WF) was modeled for the Pinnacle3 TPS and the beam model quality was evaluated by gamma index test. Results showed that the eqUF beam modeling was similar to that of the WF beam, as the overall passing rate of the 2%/2 mm gamma index test was 99.5% in the eqUF beam model and 96% in the WF beam model. Hypofractionated IMRT plans were then generated with the same constraints using both WF and eqUF beams, and the similarity was evaluated by DVH comparison and generalized 3D gamma index test. The WF and eqUF plans showed no clinically significant differences in DVH comparison and, on average &gt; 98% voxels passed the 3%/3 mm 3D gamma index test. Dosimetric accuracy in gated phantom delivery was verified by ion chamber and film measurements. All ion chamber measurements at the isocenter were within 1% of calculated values and film measurements passed the 3 mm/3% gamma index test with an overall passing rate &gt; 95% in the high-dose and low-gradient region in both WF and eqUF cases. Treatment plan quality assurance (QA), using either measurement-based or independent calculation-based methods of ten clinically treated eqUF IMRT plans were analyzed. In both methods, the point dose differences were all within 2% difference. In the relative 2D dose distribution comparison, &gt;95% points were within 3% dose difference or 3 mm DTA.

      View details for PubMedID 23835385
  • Reproducibility of intensity-based estimates of lung ventilation. Med Phys
    Du K, Bayouth JE, Ding K, Christensen GE, Cao K, Reinhardt JM
    2013 Jun; 40 (6): 063504
    • More

      PURPOSE: Lung function depends on lung expansion and contraction during the respiratory cycle. Respiratory-gated CT imaging and image registration can be used to estimate the regional lung volume change by observing CT voxel density changes during inspiration or expiration. In this study, the authors examine the reproducibility of intensity-based estimates of lung tissue expansion and contraction in three mechanically ventilated sheep and ten spontaneously breathing humans. The intensity-based estimates are compared to the estimates of lung function derived from image registration deformation field.

      METHODS: 4DCT data set was acquired for a cohort of spontaneously breathing humans and anesthetized and mechanically ventilated sheep. For each subject, two 4DCT scans were performed with a short time interval between acquisitions. From each 4DCT data set, an image pair consisting of a volume reconstructed near end inspiration and a volume reconstructed near end exhalation was selected. The end inspiration and end exhalation images were registered using a tissue volume preserving deformable registration algorithm. The CT density change in the registered image pair was used to compute intensity-based specific air volume change (SAC) and the intensity-based Jacobian (IJAC), while the transformation-based Jacobian (TJAC) was computed directly from the image registration deformation field. IJAC is introduced to make the intensity-based and transformation-based methods comparable since SAC and Jacobian may not be associated with the same physiological phenomenon and have different units. Scan-to-scan variations in respiratory effort were corrected using a global scaling factor for normalization. A gamma index metric was introduced to quantify voxel-by-voxel reproducibility considering both differences in ventilation and distance between matching voxels. The authors also tested how different CT prefiltering levels affected intensity-based ventilation reproducibility.

      RESULTS: Higher reproducibility was found for anesthetized mechanically ventilated animals than for the humans for both the intensity-based (IJAC) and transformation-based (TJAC) ventilation estimates. The human IJAC maps had scan-to-scan correlation coefficients of 0.45 ± 0.14, a gamma pass rate 70 ± 8 without normalization and 75 ± 5 with normalization. The human TJAC maps had correlation coefficients 0.81 ± 0.10, a gamma pass rate 86 ± 11 without normalization and 93 ± 4 with normalization. The gamma pass rate and correlation coefficient of the IJAC maps gradually increased with increased smoothing, but were still much lower than those of the TJAC maps.

      CONCLUSIONS: The transformation-based ventilation maps show better reproducibility than the intensity-based maps, especially in human subjects. Reproducibility was also found to depend on variations in respiratory effort; all techniques were better when applied to images from mechanically ventilated sheep compared to spontaneously breathing human subjects. Nevertheless, intensity-based techniques applied to mechanically ventilated sheep were less reproducible than the transformation-based applied to spontaneously breathing humans, suggesting the method used to determine ventilation maps is important. Prefiltering of the CT images may help to improve the reproducibility of the intensity-based ventilation estimates, but even with filtering the reproducibility of the intensity-based ventilation estimates is not as good as that of transformation-based ventilation estimates.

      View details for PubMedID 23718615
  • Optimal co-segmentation of tumor in PET-CT images with context information. IEEE Trans Med Imaging
    Song Q, Bai J, Han D, Bhatia S, Sun W, Rockey W, Bayouth JE, Buatti JM, Wu X
    2013 Sep; 32 (9): 1685-97
    • More

      Positron emission tomography (PET)-computed tomography (CT) images have been widely used in clinical practice for radiotherapy treatment planning of the radiotherapy. Many existing segmentation approaches only work for a single imaging modality, which suffer from the low spatial resolution in PET or low contrast in CT. In this work, we propose a novel method for the co-segmentation of the tumor in both PET and CT images, which makes use of advantages from each modality: the functionality information from PET and the anatomical structure information from CT. The approach formulates the segmentation problem as a minimization problem of a Markov random field model, which encodes the information from both modalities. The optimization is solved using a graph-cut based method. Two sub-graphs are constructed for the segmentation of the PET and the CT images, respectively. To achieve consistent results in two modalities, an adaptive context cost is enforced by adding context arcs between the two sub-graphs. An optimal solution can be obtained by solving a single maximum flow problem, which leads to simultaneous segmentation of the tumor volumes in both modalities. The proposed algorithm was validated in robust delineation of lung tumors on 23 PET-CT datasets and two head-and-neck cancer subjects. Both qualitative and quantitative results show significant improvement compared to the graph cut methods solely using PET or CT.

      View details for PubMedID 23693127
  • Image guided radiation therapy (IGRT) technologies for radiation therapy localization and delivery. Int J Radiat Oncol Biol Phys
    De Los Santos J, Popple R, Agazaryan N, Bayouth JE, Bissonnette JP, Bucci MK, Dieterich S, Dong L, Forster KM, Indelicato D, Langen K, Lehmann J, Mayr N, Parsai I, Salter W, Tomblyn M, Yuh WT, Chetty IJ
    2013 Sep 01; 87 (1): 33-45
  • Optimal field-splitting algorithm in intensity-modulated radiotherapy: evaluations using head-and-neck and female pelvic IMRT cases. Med Dosim
    Dou X, Kim Y, Bayouth JE, Buatti JM, Wu X
    2013; 38 (1): 12-7
    • More

      To develop an optimal field-splitting algorithm of minimal complexity and verify the algorithm using head-and-neck (H&N) and female pelvic intensity-modulated radiotherapy (IMRT) cases. An optimal field-splitting algorithm was developed in which a large intensity map (IM) was split into multiple sub-IMs (≥2). The algorithm reduced the total complexity by minimizing the monitor units (MU) delivered and segment number of each sub-IM. The algorithm was verified through comparison studies with the algorithm as used in a commercial treatment planning system. Seven IMRT, H&N, and female pelvic cancer cases (54 IMs) were analyzed by MU, segment numbers, and dose distributions. The optimal field-splitting algorithm was found to reduce both total MU and the total number of segments. We found on average a 7.9 ± 11.8% and 9.6 ± 18.2% reduction in MU and segment numbers for H&N IMRT cases with an 11.9 ± 17.4% and 11.1 ± 13.7% reduction for female pelvic cases. The overall percent (absolute) reduction in the numbers of MU and segments were found to be on average -9.7 ± 14.6% (-15 ± 25 MU) and -10.3 ± 16.3% (-3 ± 5), respectively. In addition, all dose distributions from the optimal field-splitting method showed improved dose distributions. The optimal field-splitting algorithm shows considerable improvements in both total MU and total segment number. The algorithm is expected to be beneficial for the radiotherapy treatment of large-field IMRT.

      View details for PubMedID 22835649
  • Dosimetric properties of a beam quality-matched 6 MV unflattened photon beam. J Appl Clin Med Phys
    Huang Y, Siochi RA, Bayouth JE
    2012 Jul 05; 13 (4): 3701
    • More

      The purpose of this study was to report the characteristics of an equivalent quality unflattened (eqUF) photon beam in clinical implementation and to provide a generalized method to describe unflattened (UF) photon beam profiles. An unflattened photon beam with a beam quality equivalent to the corresponding flat 6 MV photon beam (WF) was obtained by removing the flattening filter from a Siemens ONCOR Avant-Garde linear accelerator and adjusting the photon energy. A method independent from the WF beam profile was presented to describe UF beam profiles and other selected beam characteristics were examined. The short-term beam stability was examined by dynamic beam profiles, recorded every 0.072 s in static and gated delivery, and the long-term stability was evidenced by the five-year clinical quality assurance records. The dose rate was raised fivefold using the eqUF beam. The depth of maximum dose (d(max)) shifted 3 mm deeper, but the percent depth dose beyond d(max) was very similar to that of the WF beam. The surface dose and out-of-field dose were lower, but the penumbra was slightly wider. The variation in head scatter and phantom scatter with changes in field size was smaller; the variation in the profile shape with change in depth was also smaller. The eqUF beam is stable 0.072 s after the beam is turned on, and the five-year beam stability was comparable to that of the WF beam. A fivefold dose rate increase was observed in the eqUF beam with similar beam characteristics to other reported UF beam data except for a deeper dmax and a slightly wider penumbra. The initial and long-term stability of the eqUF beam profile is on parity with the WF beam. The UF beam profile can be described in the generalized method independently without relying on the WF beam profile.

      View details for PubMedID 22766941
  • Reproducibility of registration-based measures of lung tissue expansion. Med Phys
    Du K, Bayouth JE, Cao K, Christensen GE, Ding K, Reinhardt JM
    2012 Mar; 39 (3): 1595-608
    • More

      PURPOSE: Lung function depends on lung expansion and contraction during the respiratory cycle. Respiratory-gated CT imaging and 3D image registration can be used to locally estimate lung tissue expansion and contraction (regional lung volume change) by computing the determinant of the Jacobian matrix of the image registration deformation field. In this study, the authors examine the reproducibility of Jacobian-based measures of lung tissue expansion in two repeat 4DCT acquisitions of mechanically ventilated sheep and free-breathing humans.

      METHODS: 4DCT image data from three white sheep and nine human subjects were used for this analysis. In each case, two 4DCT studies were acquired for each subject within a short time interval. The animal subjects were anesthetized and mechanically ventilated, while the humans were awake and spontaneously breathing based on respiratory pacing audio cues. From each 4DCT data set, an image pair consisting of a volume reconstructed near end inspiration and a volume reconstructed near end exhalation was selected. The end inspiration and end exhalation images were registered using a tissue volume preserving deformable registration algorithm and the Jacobian of the registration deformation field was used to measure regional lung expansion. The Jacobian map from the baseline data set was compared to the Jacobian map from the followup data by measuring the voxel-by-voxel Jacobian ratio.

      RESULTS: In the animal subjects, the mean Jacobian ratio (baseline scan Jacobian divided by followup scan Jacobian, voxel-by-voxel) was 0.9984±0.021 (mean ± standard deviation, averaged over the entire lung region). The mean Jacobian ratio was 1.0224±0.058 in the human subjects. The reproducibility of the Jacobian values was found to be strongly dependent on the reproducibility of the subject's respiratory effort and breathing pattern.

      CONCLUSIONS: Lung expansion, a surrogate for lung function, can be assessed using two or more respiratory-gated CT image acquisitions. The results show that good reproducibility can be obtained in anesthetized, mechanically ventilated animals, but variations in respiratory effort and breathing patterns reduce reproducibility in spontaneously-breathing humans. The global linear normalization can globally compensate for breathing effort differences, but a homogeneous scaling does not account for differences in regional lung expansion rates. Additional work is needed to develop compensation procedures or normalization schemes that can account for local variations in lung expansion during respiration.

      View details for PubMedID 22380392
  • Feature Guided Motion Artifact Reduction with Structure-Awareness in 4D CT Images. Proc IEEE Comput Soc Conf Comput Vis Pattern Recognit
    Han D, Bayouth J, Song Q, Bhatia S, Sonka M, Wu X
    2011 Jun 20; 2011: 1057-1064
    • More

      In this paper, we propose a novel method to reduce the magnitude of 4D CT artifacts by stitching two images with a data-driven regularization constrain, which helps preserve the local anatomy structures. Our method first computes an interface seam for the stitching in the overlapping region of the first image, which passes through the "smoothest" region, to reduce the structure complexity along the stitching interface. Then, we compute the displacements of the seam by matching the corresponding interface seam in the second image. We use sparse 3D features as the structure cues to guide the seam matching, in which a regularization term is incorporated to keep the structure consistency. The energy function is minimized by solving a multiple-label problem in Markov Random Fields with an anatomical structure preserving regularization term. The displacements are propagated to the rest of second image and the two image are stitched along the interface seams based on the computed displacement field. The method was tested on both simulated data and clinical 4D CT images. The experiments on simulated data demonstrated that the proposed method was able to reduce the landmark distance error on average from 2.9 mm to 1.3 mm, outperforming the registration-based method by about 55%. For clinical 4D CT image data, the image quality was evaluated by three medical experts, and all identified much fewer artifacts from the resulting images by our method than from those by the compared method.

      View details for PubMedID 22058647
  • Point/counterpoint. Medical physics graduate programs should adjust enrollment to achieve equilibrium between graduates and residents. Med Phys
    Bayouth JE, Burmeister JW, Orton CG
    2011 Aug; 38 (8): ii-iv
  • Globally optimal tumor segmentation in PET-CT images: a graph-based co-segmentation method. Inf Process Med Imaging
    Han D, Bayouth J, Song Q, Taurani A, Sonka M, Buatti J, Wu X
    2011; 22: 245-56
    • More

      Tumor segmentation in PET and CT images is notoriously challenging due to the low spatial resolution in PET and low contrast in CT images. In this paper, we have proposed a general framework to use both PET and CT images simultaneously for tumor segmentation. Our method utilizes the strength of each imaging modality: the superior contrast of PET and the superior spatial resolution of CT. We formulate this problem as a Markov Random Field (MRF) based segmentation of the image pair with a regularized term that penalizes the segmentation difference between PET and CT. Our method simulates the clinical practice of delineating tumor simultaneously using both PET and CT, and is able to concurrently segment tumor from both modalities, achieving globally optimal solutions in low-order polynomial time by a single maximum flow computation. The method was evaluated on clinically relevant tumor segmentation problems. The results showed that our method can effectively make use of both PET and CT image information, yielding segmentation accuracy of 0.85 in Dice similarity coefficient and the average median hausdorff distance (HD) of 6.4 mm, which is 10% (resp., 16%) improvement compared to the graph cuts method solely using the PET (resp., CT) images.

      View details for PubMedID 21761661
  • Characterization and identification of spatial artifacts during 4D-CT imaging. Med Phys
    Han D, Bayouth J, Bhatia S, Sonka M, Wu X
    2011 Apr; 38 (4): 2074-87
    • More

      PURPOSE: The purpose of this work is twofold: First, to characterize the artifacts occurring in helical 4D-CT imaging; second, to propose a method that can automatically identify the artifacts in 4D-CT images. The authors have designed a process that can automatically identify the artifacts in 4D-CT images, which may be invaluable in quantifying the quality of 4D-CT images and reducing the artifacts from the reconstructed images on a large dataset.

      METHODS: Given two adjacent stacks obtained from the same respiration phase, the authors determine if there are artifacts between them. The proposed method uses a "bridge" stack strategy to connect the two stacks. Using normalized cross correlation convolution (NCCC), the two stacks are mapped to the bridge stack and the best matching positions can be located. Using this position information, the authors can then determine if there are artifacts between the two stacks. By combining the matching positions with NCCC values, the performance can be improved.

      RESULTS: To validate the method, three expert observers independently labeled over 600 stacks on five patients. The results confirmed that high performance was obtained using the proposed method. The average sensitivity was about 0.87 and the average specificity was 0.82. The proposed method also outperformed the method of using respiratory signal (sensitivity increased from 0.50 to 0.87 and specificity increased from 0.70 to 0.82).

      CONCLUSIONS: This study shows that the spatial artifacts during 4D-CT imaging are characterized and can be located automatically by the proposed method. The method is relatively simple but effective. It provides a way to evaluate the artifacts more objectively and accurately. The reported approach has promising potential for automatically identifying the types and frequency of artifacts on large scale 4D-CT image dataset.

      View details for PubMedID 21626940
  • A methodology for incorporating functional bone marrow sparing in IMRT planning for pelvic radiation therapy. Radiother Oncol
    McGuire SM, Menda Y, Ponto LL, Gross B, Juweid M, Bayouth JE
    2011 Apr; 99 (1): 49-54
    • More

      BACKGROUND AND PURPOSE: The purpose of this study was to design a radiation therapy treatment planning approach that would spare hematopoietically active bone marrow using [(18)F]FLT PET imaging.

      MATERIALS AND METHODS: We have developed an IMRT planning methodology to incorporate functional PET imaging using [(18)F]FLT scans. Plans were generated for two simulated cervical cancer patients, where pelvic active bone marrow regions were incorporated as avoidance regions based on the ranges: SUV4 ≥ 4; 4>SUV3 ≥ 3; and 3 > SUV2 ≥ 2. Dose objectives were set to reduce bone marrow volume that received 10 (V(10)) and 20 (V(20))Gy.

      RESULTS: Active bone marrow regions identified by [(18)F]FLT with an SUV ≥ 2, SUV ≥ 3, and SUV ≥ 4 represented an average of 43.0%, 15.3%, and 5.8%, respectively of the total osseous pelvis for the two cases studied. Improved dose-volume histograms for all identified bone marrow SUV volumes and decreases in V(10), and V(20) were achieved without clinically significant changes to PTV or OAR doses.

      CONCLUSIONS: Incorporation of [(18)F]FLT PET in IMRT planning provides a methodology to reduce radiation dose to active bone marrow without compromising PTV or OAR dose objectives in pelvic malignancies.

      View details for PubMedID 21397965
  • Image-based biomarkers in clinical practice. Semin Radiat Oncol
    Bayouth JE, Casavant TL, Graham MM, Sonka M, Muruganandham M, Buatti JM
    2011 Apr; 21 (2): 157-66
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      The growth of functional and metabolically informative imaging is eclipsing anatomic imaging alone in clinical practice. The recognition that magnetic resonance (MR) and positron emission tomography (PET)-based treatment planning and response assessment are essential components of clinical practice and furthermore offer the potential of quantitative analysis being important. Extracting the greatest benefit from these imaging techniques will require refining the best combinations of multimodality imaging through well-designed clinical trials that use robust image-analysis tools and require substantial computer based infrastructure. Through these changes and enhancements, image-based biomarkers will enhance clinical decision making and accelerate the progress that is made through clinical trial research.

      View details for PubMedID 21356483
  • 3'-deoxy-3'-[¹⁸F]fluorothymidine PET quantification of bone marrow response to radiation dose. Int J Radiat Oncol Biol Phys
    McGuire SM, Menda Y, Boles Ponto LL, Gross B, Buatti J, Bayouth JE
    2011 Nov 01; 81 (3): 888-93
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      PURPOSE: The purpose of this study was to quantify the relationship of bone marrow response to radiation dose, using 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT)-labeled uptake quantified in positron-emission tomography (PET) scans.

      METHODS AND MATERIALS: Pre- and post-Week 1 treatment [(18)F]FLT PET images were registered to the CT images used to create the radiation treatment plan. Changes in [(18)F]FLT uptake values were measured using profile data of standardized uptake values (SUVs) and doses along the vertebral bodies located at a field border where a range of radiation doses were present for 10 patients. Data from the profile measurements were grouped into 1 Gy dose bins from 1 to 9 Gy to compare SUV changes for all patients. Additionally, the maximum pretreatment, the post-Week 1 treatment, and the dose values located within the C6-T7 vertebrae that straddled the field edge were measured for all patients.

      RESULTS: Both the profile and the individual vertebral data showed a strong correlation between SUV change and radiation dose. Relative differences in SUVs between bins >1 Gy and <7 Gy were statistically significant (p < 0.01, two-sample t test). The reduction in SUV was approximately linear until it reached a reduction threshold of 75%-80% in SUV for doses greater than 6 Gy/week for both the dose-binned data and the vertebral maximum SUVs.

      CONCLUSIONS: The change in SUV observed in head and neck cancer patients treated with chemoradiation shows the potential for using [(18)F]FLT PET images for identifying active bone marrow and monitoring changes due to radiation dose. Additionally, the change in [(18)F]FLT uptake observed in bone marrow for different weekly doses suggests potential dose thresholds for reducing bone marrow toxicity.

      View details for PubMedID 21300484
  • Evaluation of artifacts and distortions of titanium applicators on 3.0-Tesla MRI: feasibility of titanium applicators in MRI-guided brachytherapy for gynecological cancer. Int J Radiat Oncol Biol Phys
    Kim Y, Muruganandham M, Modrick JM, Bayouth JE
    2011 Jul 01; 80 (3): 947-55
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      PURPOSE: The aim of this study was to characterize the levels of artifacts and distortions of titanium applicators on 3.0-Tesla magnetic resonance imaging (MRI).

      METHODS AND MATERIALS: Fletcher-Suit-Delclos-style tandem and ovoids (T&O) and tandem and ring applicator (T&R) were examined. The quality assurance (QA) phantoms for each applicator were designed and filled with copper sulphate solution (1.5 g/l). The artifacts were quantified with the registration of corresponding computed tomography (CT) images. A favorable MR sequence was searched in terms of artifacts. Using the sequence, the artifacts were determined. The geometric distortions induced by the applicators were quantified through each registration of CT and MRI without applicators. The artifacts of T&O were also evaluated on in vivo MRI datasets of 5 patients.

      RESULTS: T1-weighted MRI with 1-mm slice thickness was found as a favorable MR sequence. Applying the sequence, the artifacts at the tandem tip of T&O and T&R were determined as 1.5 ± 0.5 mm in a superior direction in phantom studies. In the ovoids of T&O, we found artifacts less than 1.5 ± 0.5 mm. The artifacts of a T&O tandem in vivo were found as less than 2.6 ± 1.3 mm on T1-weighted MRI, whereas less than 6.9 ± 3.4 mm on T2-weighted MRI. No more than 1.2 ± 0.6 mm (3.0 ± 1.5 mm) of distortions, due to a titanium applicator, were measured on T1-weighted MRI (T2-).

      CONCLUSION: In 3.0-Tesla MRI, we found the artifact widths at the tip of tandem were less than 1.5 ± 0.5 mm for both T&O and T&R when using T1-weighted MRI in phantom studies. However, exclusive 3.0-Tesla MRI-guided brachytherapy planning with a titanium applicator should be cautiously implemented.

      View details for PubMedID 20934275
  • 4DCT-based measurement of changes in pulmonary function following a course of radiation therapy. Med Phys
    Ding K, Bayouth JE, Buatti JM, Christensen GE, Reinhardt JM
    2010 Mar; 37 (3): 1261-72
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      PURPOSE: Radiation therapy (RT) for lung cancer is commonly limited to subtherapeutic doses due to unintended toxicity to normal lung tissue. Reducing the frequency of occurrence and magnitude of normal lung function loss may benefit from treatment plans that incorporate the regional lung and radiation dose information. In this article, the authors propose a method that quantitatively measures the regional changes in lung tissue function following a course of radiation therapy by using 4DCT and image registration techniques.

      METHODS: 4DCT data sets before and after RT from two subjects are used in this study. Nonlinear 3D image registration is applied to register an image acquired near end inspiration to an image acquired near end expiration to estimate the pulmonary function. The Jacobian of the image registration transformation, indicating local lung expansion or contraction, serves as an index of regional pulmonary function. Approximately 120 annotated vascular bifurcation points are used as landmarks to evaluate registration accuracy. The authors compare regional pulmonary function before and after RT to the planned radiation dose at different locations of the lung.

      RESULTS: In all registration pairs, the average landmark distances after registration are on the order of 1 mm. The pulmonary function change as indicated by the Jacobian change ranges from -0.15 to 0.1 in the contralateral lung and -0.22 to 0.23 in the ipsilateral lung for subject A, and ranges from -0.4 to 0.39 in the contralateral lung and -0.25 to 0.5 in the ipsilateral lung for subject B. Both of the subjects show larger range of the increase in the pulmonary function in the ipsilateral lung than the contralateral lung. For lung tissue regions receiving a radiation dose larger than 24 Gy, a decrease in pulmonary function was observed. For regions receiving a radiation dose smaller than 24 Gy, either an increase or a decrease in pulmonary function was observed. The relationship between the pulmonary function change and the radiation dose varies at different locations.

      CONCLUSIONS: With the use of 4DCT and image registration techniques, the pulmonary function prior to and following a course of radiation therapy can be measured. In the preliminary application of this approach for two subjects, changes in pulmonary function were observed with a weak correlation between the dose and pulmonary function change. In certain sections of the lung, detected locally compromised pulmonary function may have resulted from radiation injury.

      View details for PubMedID 20384264
  • Assessment of three dead detector correction methods for cone-beam computed tomography. Med Phys
    Nelms DW, Shukla HI, Nixon E, Bayouth JE, Flynn RT
    2009 Oct; 36 (10): 4569-76
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      PURPOSE: Dead detectors due to manufacturing defects or radiation damage in the electronic portal imaging devices (EPIDs) used for cone-beam computed tomography (CBCT) can lead to image degradation and ring artifacts. In this work three dead detector correction methods were assessed using megavoltage CBCT (MVCBCT) as a test system, with the goals of assessing the relative effectiveness of the three methods and establishing the conditions for which they fail.

      METHODS: MVCBCT projections acquired with four linacs at 8 and 60 MU (monitor units) were degraded with varying percentages (2%-95%) of randomly distributed dead single detectors (RDSs), randomly distributed dead detector clusters (RDCs) of 2 mm diameter, and nonrandomly distributed dead detector disks (NRDDs) of varying diameter (4-16 mm). Correction algorithms were bidirectional linear interpolation (BLI), quad-directional linear interpolation (QLI), and a Laplacian solution (LS) method. Correction method failure was defined to occur if ring artifacts were present in the reconstructed phantom images from any linac or if the modulation transfer function (MTF) for any linac dropped below baseline with a p value, calculated with the two sample t test, of less than 0.01.

      RESULTS: All correction methods failed at the same or lower RDC/RDS percentages and NRDD diameters for the 60 MU as for the 8 MU cases. The LS method tended to outperform or match the BLI and QLI methods. If ring artifacts anywhere in the images were considered unacceptable, the LS method failed for 60 MU at >33% RDS, >2% RDC, and >4 mm NRDD. If ring artifacts within 4 mm longitudinally of the phantom section interfaces were considered acceptable, the LS method failed for 60 MU at >90% RDS, >80% RDC, and >4 mm NRDD. LS failed due to MTF drop for 60 MU at >50% RDS, >25% RDC, and >4 mm NRDD.

      CONCLUSIONS: The LS method is superior to the BLI and QLI methods, and correction algorithm effectiveness decreases as imaging dose increases. All correction methods failed first due to ring artifacts and second due to MTF drop. If ring artifacts in axial slices within a 4 mm longitudinal distance from phantom section interfaces are acceptable, statistically significant loss in spatial resolution does not occur until over 25% of the EPID is covered in randomly distributed dead detectors, or NRDDs of 4 mm diameter are present.

      View details for PubMedID 19928088
  • Task Group 142 report: quality assurance of medical accelerators. Med Phys
    Klein EE, Hanley J, Bayouth J, Yin FF, Simon W, Dresser S, Serago C, Aguirre F, Ma L, Arjomandy B, Liu C, Sandin C, Holmes T, Task Group 142, American Association of Physicists in Medicine
    2009 Sep; 36 (9): 4197-212
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      The task group (TG) for quality assurance of medical accelerators was constituted by the American Association of Physicists in Medicine's Science Council under the direction of the Radiation Therapy Committee and the Quality Assurance and Outcome Improvement Subcommittee. The task group (TG-142) had two main charges. First to update, as needed, recommendations of Table II of the AAPM TG-40 report on quality assurance and second, to add recommendations for asymmetric jaws, multileaf collimation (MLC), and dynamic/virtual wedges. The TG accomplished the update to TG-40, specifying new test and tolerances, and has added recommendations for not only the new ancillary delivery technologies but also for imaging devices that are part of the linear accelerator. The imaging devices include x-ray imaging, photon portal imaging, and cone-beam CT. The TG report was designed to account for the types of treatments delivered with the particular machine. For example, machines that are used for radiosurgery treatments or intensity-modulated radiotherapy (IMRT) require different tests and/or tolerances. There are specific recommendations for MLC quality assurance for machines performing IMRT. The report also gives recommendations as to action levels for the physicists to implement particular actions, whether they are inspection, scheduled action, or immediate and corrective action. The report is geared to be flexible for the physicist to customize the QA program depending on clinical utility. There are specific tables according to daily, monthly, and annual reviews, along with unique tables for wedge systems, MLC, and imaging checks. The report also gives specific recommendations regarding setup of a QA program by the physicist in regards to building a QA team, establishing procedures, training of personnel, documentation, and end-to-end system checks. The tabulated items of this report have been considerably expanded as compared with the original TG-40 report and the recommended tolerances accommodate differences in the intended use of the machine functionality (non-IMRT, IMRT, and stereotactic delivery).

      View details for PubMedID 19810494
  • Dosimetric characterization and application of an imaging beam line with a carbon electron target for megavoltage cone beam computed tomography. Med Phys
    Flynn RT, Hartmann J, Bani-Hashemi A, Nixon E, Alfredo R, Siochi C, Pennington EC, Bayouth JE
    2009 Jun; 36 (6): 2181-92
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      Imaging dose from megavoltage cone beam computed tomography (MVCBCT) can be significantly reduced without loss of image quality by using an imaging beam line (IBL), with no flattening filter and a carbon, rather than tungsten, electron target. The IBL produces a greater keV-range x-ray fluence than the treatment beam line (TBL), which results in a more optimal detector response. The IBL imaging dose is not necessarily negligible, however. In this work an IBL was dosimetrically modeled with the Philips Pinnacle3 treatment planning system (TPS), verified experimentally, and applied to clinical cases. The IBL acquisition dose for a 200 degrees gantry rotation was verified in a customized acrylic cylindrical phantom at multiple imaging field sizes with 196 ion chamber measurements. Agreement between the measured and calculated IBL dose was quantified with the 3D gamma index. Representative IBL and TBL imaging dose distributions were calculated for head and neck and prostate patients and included in treatment plans using the imaging dose incorporation (IDI) method. Surface dose was measured for the TBL and IBL for four head and neck cancer patients with MOSFETs. The IBL model, when compared to the percentage depth dose and profile measurements, had 97% passing gamma indices for dosimetric and distance acceptance criteria of 3%, 3 mm, and 100% passed for 5.2%, 5.2 mm. For the ion chamber measurements of phantom image acquisition dose, the IBL model had 93% passing gamma indices for acceptance criteria of 3%, 3 mm, and 100% passed for 4%, 4 mm. Differences between the IBL- and TBL-based IMRT treatment plans created with the IDI method were dosimetrically insignificant for both the prostate and head and neck cases. For IBL and TBL beams with monitor unit values that would result in the delivery of the same dose to the depth of maximum dose under standard calibration conditions, the IBL imaging surface dose was higher than the TBL imaging surface dose by an average of 18%, with a standard deviation of 8% (p = 2 x 10(-6)). The IBL can be modeled with acceptable accuracy using a standard TPS, and accounting for IBL dose in treatment plans with the IDI method is straightforward. The resulting composite dose distributions, assuming similar imaging doses, are negligibly different from those of the TBL. The increased IBL surface dose relative to the TBL is likely clinically insignificant.

      View details for PubMedID 19610307
  • Radiation therapy plan checks in a paperless clinic. J Appl Clin Med Phys
    Siochi RA, Pennington EC, Waldron TJ, Bayouth JE
    2009 Jan 27; 10 (1): 2905
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      Traditional quality assurance checks of a patient's radiation therapy plan involve printing out treatment parameters from the treatment planning system and the "record and verify" (R&V) system and visually checking the information for one-to-one correspondence. In a paperless environment, one can automate this process through independent software that can read the treatment planning data directly and compare it against the parameters in the R&V system's database. In addition to verifying the data integrity, it is necessary to check the logical consistency of the data and the accuracy of various calculations. The results are then imported into the patient's electronic medical record. Appropriate workflows must be developed to ensure that no steps of the QA process are missed. This paper describes our electronic QA system (EQS), consisting of in-house software and workflows. The EQS covers 3D conformal and intensity modulated radiation therapy, electrons, stereotactic radiosurgery, total body irradiation, and clinical set ups with and without virtual simulation. The planning systems handled by our EQS are ADAC Pinnacle and Varian FASTPLAN, while the R&V systems are LANTIS and VARIS. The improvement in our plan check process over the paperless system is described in terms of the types of detected errors. The potential problems with the implementation and use of the EQS, as well as workarounds for data that are not easily accessible through electronic means, are described.

      View details for PubMedID 19223840
  • Point/counterpoint. Genomics, functional and molecular imaging will pave the road to individualized radiation therapy. Med Phys
    Stancanello J, Bayouth JE, Orton CG
    2008 Nov; 35 (11): 4769-72
  • Analysis of interfraction prostate motion using megavoltage cone beam computed tomography. Int J Radiat Oncol Biol Phys
    Bylund KC, Bayouth JE, Smith MC, Hass AC, Bhatia SK, Buatti JM
    2008 Nov 01; 72 (3): 949-56
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      PURPOSE: Determine the degree of interfraction prostate motion and its components measured by using daily megavoltage (MV) cone beam computed tomography (CBCT) imaging.

      METHODS AND MATERIALS: A total of 984 daily MV CBCT images from 24 patients undergoing definitive intensity-modulated radiotherapy for localized prostate cancer were analyzed retrospectively. Pretreatment couch shifts, based on physician registration of MV CBCT to planning CT data sets, were used as a measure of daily interfraction motion. Off-line bony registration was performed to separate bony misalignment from internal organ motion. Interobserver and intraobserver variation studies were performed on 20 MV CBCT images.

      RESULTS: Mean interfraction prostate motion was 6.7 mm, with the greatest single-axis deviation in the anterior-posterior (AP) direction. The largest positional inaccuracy was accounted for by systematic deviations in bony misalignment, whereas random deviations occurred from bony misalignment and internal prostate motion. In the aggregate, AP motion did not correlate with days elapsed since beginning therapy or on average with rectal size at treatment planning. Interobserver variation was greatest in the AP direction, decreased in experienced observers, and further decreased in intraobserver studies. Mean interfraction motion during the first 6 days of therapy, when used as a subsequent offset, reduced acceptable AP planning target volume margins by 50%.

      CONCLUSION: The MV CBCT is a practical direct method of daily localization that shows significant interfraction motion with respect to conventional three-dimensional conformal and intensity-modulated radiotherapy margins, similar to that measured in other modalities.

      View details for PubMedID 19014783
  • Feasibility of IMRT to cover pelvic nodes while escalating the dose to the prostate gland: dosimetric data on 35 consecutive patients. Med Dosim
    Bayouth JE, Pena J, Culp L, Brack C, Sanguineti G
    2008; 33 (3): 180-90
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      Utilizing available dosimetric and acute toxicity data, we confirm the feasibility of intensity modulated radiotherapy (IMRT) to include treatment of the pelvic nodes (PN) while escalating the dose to the prostate. Data were obtained from 35 consecutive patients with prostate cancer with > or =15% risk of PN involvement. Patients received an initial boost to the prostate, delivering 16 Gy over 8 fractions using a 6-field conformal technique, followed by an 8-field coplanar inverse planning IMRT technique delivering an additional 60 Gy over 30 fractions to the prostate (76 Gy total) and 54 Gy over 30 fractions to the seminal vesicles (SV) and PN. Dose-volume histogram analysis was performed for planning target volumes and organs at risk. Acute toxicity (RTOG/EORTC scale) was prospectively and independently scored weekly for each patient. The maximum, mean, minimum dose, and D95 to each planning target volume is provided: prostate (82.2, 78.2, 72.6, 75.2 Gy), SV (79.0, 72.5, 56.9, 61.1 Gy), and PN (80.4, 59.7, 46.5, 53.3 Gy), respectively. The percent volume receiving a dose at or above "x" Gy (Vx) was recorded for V75, V70, V65, V60, and V50 as: bladder (14%, 24%, 32%, 39%, and 54%) and rectum (3%, 18%, 26%, 34%, and 51%), respectively. Acute toxicity was as follows: 54% grade 2+ GI (n = 19), 25% grade 2+ GU (n = 9). IMRT enables treatment of pelvic nodes while escalating dose to the prostate and is clinically feasible with acute toxicity within expected ranges.

      View details for PubMedID 18674682
  • Siemens multileaf collimator characterization and quality assurance approaches for intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys
    Bayouth JE
    2008; 71 (1 Suppl): S93-7
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      Application of the multileaf collimator (MLC) has evolved from replacing blocks to create treatment fields to creating photon fluence modulation for intensity-modulated radiotherapy (IMRT). Multileaf collimator system performance requirements are far more stringent for such applications and will require increased performance for future applications, such as motion tracking. This article reviews Siemens MLC systems, including a technical description and dosimetric characteristics of 56-, 82-, and 160-leaf designs. Routine quality assurance of MLC for IMRT necessitates frequent and critical assessment of MLC leaf position calibration errors that can present in many different ways (e.g., accuracy, reproducibility, longevity, hysteresis, and collimator/gantry angle dependencies). Several techniques for measuring these errors are presented, along with qualitative and quantitative techniques for analyzing results. In particular, increased accuracy of leaf position measurement at variable gantry angles is enabled by spatial transformations to electronic portal imaging device position quantified by calibration protocols introduced with megavoltage cone beam. Measured values of X-ray transmission (intra-leaf, inter-leaf, and through abutting leaf pairs) and penumbra (leaf end, leaf tongue, leaf groove) are presented with an evaluation of their characterization by a treatment-planning system. The dosimetric impact of planning system model inadequacies is demonstrated for collimator scatter, dose profile values within 30 mm of the field edge, and the resultant effect demonstrated on clinical cases. Finally, a description of automated quality assurance delivery, analysis, and calibration protocols applicable for the specific vendor's system is provided.

      View details for PubMedID 18406947
  • Image-guided stereotactic radiosurgery using a specially designed high-dose-rate linac. Med Dosim
    Bayouth JE, Kaiser HS, Smith MC, Pennington EC, Anderson KM, Ryken TC, Buatti JM
    2007; 32 (2): 134-41
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      Stereotactic radiosurgery and image-guided radiotherapy (IGRT) place enhanced demands on treatment delivery machines. In this study, we describe a high-dose-rate output accelerator as a part of our stereotactic IGRT delivery system. The linac is a Siemens Oncor without a flattening filter, and enables dose rates to reach 1000 monitor units (MUs) per minute. Even at this high-dose-rate, the linac dosimetry system remains robust; constancy, linearity, and beam energy remain within 1% for 3 to 1000 MU. Dose profiles for larger field sizes are not flat, but they are radially symmetric and, as such, able to be modeled by a treatment planning system. Target localization is performed via optical guidance utilizing a 3-dimensional (3D) ultrasound probe coupled to an array of 4 infrared light-emitting diodes. These diodes are identified by a fixed infrared camera system that determines diode position and, by extension, all objects imaged in the room coordinate system. This system provides sub-millimeter localization accuracy for cranial applications and better than 1.5 mm for extracranial applications. Because stereotactic IGRT can require significantly longer times for treatment delivery, the advantages of the high-dose-rate design and its direct impact on IGRT are discussed.

      View details for PubMedID 17472892
  • Changing failure patterns in oropharyngeal squamous cell carcinoma treated with intensity modulated radiotherapy and implications for future research. Am J Clin Oncol
    Yao M, Nguyen T, Buatti JM, Dornfeld KJ, Tan H, Wacha J, Bayouth JE, Clamon GH, Funk GF, Smith RB, Chang K, Hoffman HT
    2006 Dec; 29 (6): 606-12
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      OBJECTIVE: Review the University of Iowa experience with intensity modulated radiation treatment (IMRT) in oropharyngeal squamous cell carcinoma.

      METHODS: From January 2000 to July 2004, 66 patients with oropharyngeal cancer were treated with IMRT, 62 with definitive IMRT and 4 postoperative IMRT. Three target volumes (CTV1, CTV2, and CTV3) were defined. The prescribed doses to CTV1, CTV2, and CTV3 were 70 to 74 Gy, 60 Gy, and 54 Gy, respectively, for definitive IMRT, and 60 to 66 Gy, 60 Gy, and 54 Gy, respectively, for postoperative IMRT.

      RESULTS: Median follow-up was 27.3 months and all living patients had a follow-up of at least 11.5 months. The 3-year estimate of locoregional progression free survival was 98.8%. However, there is a high incidence of distant metastasis with a 3-year estimate of distant metastasis-free survival of 80.4%. In addition, there is a high incidence of second primary tumor. The 3-year overall survival and 3-year disease-free survival were 78.1% and 64.4%, respectively. Treatment was well tolerated with 1 death resulting from treatment toxicity.

      CONCLUSIONS: IMRT offers an excellent locoregional control for oropharyngeal cancer patients. Failure patterns have changed with an increased portion of patients who failed distantly, either with metastasis or second primary tumor. Therefore, survival for these patients is still poor. Future research should focus on identifying patients at high risk of distant diseases and developing effective systemic treatment and prevention for distant diseases.

      View details for PubMedID 17148999
  • Is IMRT needed to spare the rectum when pelvic lymph nodes are part of the initial treatment volume for prostate cancer? Int J Radiat Oncol Biol Phys
    Sanguineti G, Cavey ML, Endres EJ, Brandon GG, Bayouth JE
    2006 Jan 01; 64 (1): 151-60
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      PURPOSE: To assess whether a 4-field box technique (4FBT), along with its technical refinements, is an adequate approach in terms of rectal sparing and target coverage for patients with localized prostate cancer undergoing whole-pelvic radiotherapy followed by a prostate boost and whether or not intensity-modulated radiotherapy (IMRT) is needed.

      METHODS AND MATERIALS: For 8 patients, 31 plans were generated, each of them differing in one or more features, including prescription (dose/volume) and/or technical factors. For the latter, several "solutions" to try to reduce the amount of irradiated rectal volume were addressed, including modifications of the 4FBT and the use of sequential IMRT. We constructed a database with 248 plans that were tested for their ability to meet a series of rectal dose-volume constraints at V50, V60, V65, V70, V75, and V75.6. Multivariate logistic regression was used to identify factors independently associated with the end point. Successful solutions were also compared in terms of coverage of both pelvic node and prostate planning target volume (PTV) by isodose 95%.

      RESULTS: At multivariate logistic regression, both rectal blocking and IMRT were independent predictors of the probability of meeting rectal dose-volume constraints during the pelvic and boost phases of treatment with close relative risks. However, on average, partial rectal blocking on lateral fields of 4FBT during whole-pelvic radiotherapy resulted in about 3% of pelvic node PTV being outside isodose 95%; only 2 of 8 patients had the pelvic nodal PTV covered similarly to what was achieved by whole-pelvis IMRT. Conversely, blocking the rectum during the last 3 fractions of the conformal boost showed a dosimetric coverage of prostate PTV similar to that achieved by IMRT boost. Interestingly, patient anatomic configuration was the strongest predictor of rectal sparing. Finally, the size of prostate margins to generate PTV was also independently associated with the probability of meeting rectal dose-volume constraints.

      CONCLUSION: In the dose range of 70-76 Gy to the prostate, IMRT and standard techniques are equally effective in meeting rectal dose-volume constraints. However, whole-pelvis IMRT might be preferable to standard techniques for its slightly superior PTV coverage.

      View details for PubMedID 16198066
  • Intensity-modulated radiation treatment for head-and-neck squamous cell carcinoma--the University of Iowa experience. Int J Radiat Oncol Biol Phys
    Yao M, Dornfeld KJ, Buatti JM, Skwarchuk M, Tan H, Nguyen T, Wacha J, Bayouth JE, Funk GF, Smith RB, Graham SM, Chang K, Hoffman HT
    2005 Oct 01; 63 (2): 410-21
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      PURPOSE: To review the University of Iowa experience with intensity-modulated radiotherapy (IMRT) in the treatment of head-and-neck squamous cell carcinoma.

      METHODS AND MATERIALS: From October 1999 to April 2004, 151 patients with head-and-neck squamous cell carcinoma were treated with IMRT for curative intent. One patient was lost to follow-up 2 months after treatment and therefore excluded from analysis. Of the remaining 150 patients, 99 were treated with definitive IMRT, and 51 received postoperative IMRT. Sites included were nasopharynx, 5; oropharynx, 56; larynx, 33; oral cavity, 29; hypopharynx, 8; nasal cavity/paranasal sinus, 8; and unknown primary, 11. None of the patients treated with postoperative IMRT received chemotherapy. Of 99 patients who had definitive IMRT, 68 patients received concurrent cisplatin-based chemotherapy. One patient received induction cisplatin-based chemotherapy, but no concurrent chemotherapy was given. Three clinical target volumes (CTV1, CTV2, and CTV3) were defined. The prescribed doses to CTV1, CTV2, and CTV3 in the definitive cohort were 70-74 Gy, 60 Gy, and 54 Gy, respectively. For high-risk postoperative IMRT, the prescribed doses to CTV1, CTV2, and CTV3 were 64-66 Gy, 60 Gy, and 54 Gy, respectively. For intermediate-risk postoperative IMRT, the prescribed doses to CTV1, CTV2, and CTV3 were 60 Gy, 60 Gy, and 54 Gy.

      RESULTS: The median follow-up was 18 months (range, 2-60 months). All living patients were followed for at least 6 months. There were 11 local-regional failures: 7 local failures, 3 regional failures, and 1 failure both in the primary tumor and regional lymph node. There were 16 patients who failed distantly, either with distant metastasis or new lung primaries. The 2-year overall survival, local progression-free survival, locoregional progression-free survival, and distant disease-free survival rates were 85%, 94%, 92%, and 87%, respectively. The median time from treatment completion to local-regional recurrence was 4.7 months (range, 1.8 to 15.6 months). Only one marginal failure was noted in a patient who had extensive tonsil cancer with tumor extension into the orbit and cavernous sinus. Patients with oropharyngeal cancer did significantly better than patients with oral cavity and laryngeal cancer, with a 2-year local-regional control rate of 98%, compared with 78% for oral cavity cancer and 85% for laryngeal cancer (p = 0.005). There was no significant difference in local-regional control for patients who received postoperative radiation or definitive radiation (p = 0.339) and for patients who had chemotherapy or not (p = 0.402). Neither T stage nor N stage had a significant effect on local-regional control (p = 0.722 and 0.712, respectively).

      CONCLUSIONS: Our results have confirmed the effectiveness of IMRT in head-and-neck cancer. It offers excellent outcomes in local-regional control and overall survival. More studies are necessary to further improve the outcomes of laryngeal cancer as well as oral cavity cancer.

      View details for PubMedID 16168834
  • IMRT to escalate the dose to the prostate while treating the pelvic nodes. Strahlenther Onkol
    Cavey ML, Bayouth JE, Colman M, Endres EJ, Sanguineti G
    2005 Jul; 181 (7): 431-41
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      BACKGROUND AND PURPOSE: To assess and quantify the benefit of introducing intensity-modulated radiotherapy (IMRT) over conventional approaches to cover the pelvic nodes while escalating the dose to the prostate gland.

      MATERIAL AND METHODS: The pelvic lymphatics were planned to receive 50 Gy at 2 Gy per fraction by four-field box (4FB) technique and standard field blocks drawn on digitally reconstructed radiographs (DRR), 4FB with field blocks according to the position of pelvic nodes as contoured on serial planning CT slices, or IMRT. The lateral fields included three different variations of field blocks to assess the role of various degrees of rectal shielding. The boost consisted in 26 Gy in 13 fractions delivered via six-field three-dimensional conformal radiotherapy (3DCRT) or IMRT. By the combination of a pelvic treatment and boost, several plans were obtained for each patient, all normalized to be isoeffective with regard to prostate-planning target volume (PTV-P) coverage. Plans were compared with respect to dose-volume histogram (DVH) of pelvic nodes/seminal vesicles-PTV (PTV-PN/SV), rectum, bladder and intestinal cavity. Reported are the results obtained in eight patients.

      RESULTS: Pelvic IMRT with a conformal boost provided superior sparing of both bladder and rectum over any of the 4FB plans with the same boost. For the rectum the advantage was around 10% at V70 and even larger for lower doses. Coverage of the pelvic nodes was adequate with initial IMRT with about 98% of the volume receiving 100% of the prescribed dose. An IMRT boost provided a gain in rectal sparing as compared to a conformal boost. However, the benefit was always greater with pelvic IMRT followed by a conformal boost as compared to 4FB with IMRT boost. Finally, the effect of utilizing an IMRT boost with initial pelvic IMRT was greater for the bladder than for the rectum (at V70, about 9% and 3% for the bladder and rectum, respectively).

      CONCLUSION: IMRT to pelvic nodes with a conformal boost allows dose escalation to the prostate while respecting current dose objectives in the majority of patients and it is dosimetrically superior to 4FB. An IMRT boost should be considered for patients who fail to meet bladder dose objectives.

      View details for PubMedID 15995836
  • Dosimetric comparison of conventional and forward-planned intensity-modulated techniques for comprehensive locoregional irradiation of post-mastectomy left breast cancers. Med Dosim
    Cavey ML, Bayouth JE, Endres EJ, Pena JM, Colman M, Hatch S
    2005; 30 (2): 107-16
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      Three recently published randomized trials have shown a survival benefit to postoperative radiation therapy when the internal mammary chain (IMC), supraclavicular (SCV), and axillary lymphatics are treated. When treating the IMC, techniques that minimize dose to the heart and lungs may be utilized to prevent excess morbidity and mortality and achieve the survival benefit reported. The purpose of this study was to dosimetrically compare forward-planned intensity-modulated radiation therapy (fIMRT) with conventional techniques for comprehensive irradiation of the chest wall and regional lymphatics. For irradiation of the chest wall and IMC, 3 treatment plans, (1) fIMRT, (2) partially-wide tangent (PWT) fields, and (3) a photon-electron (PE) technique, were compared for 12 patients previously treated at our institution with fIMRT to the left chest wall and regional lymphatics. Additionally, the SCV and infraclavicular lymphatics were irradiated and 4 methods were compared: 2 with anterior fields only (dose prescribed to 3 and 5 cm [SC3cm, SC5cm]) and 2 with anterior and posterior fields (fIMRT, 3DCRT). Each patient was planned to receive 50 Gy in 25 fractions. Regions of interest (ROIs) created for each patient included chest wall (CW) planning target volume (PTV), IMC PTV, and SCV PTV. Additionally, the following organs at risk (OAR) volumes were created: contralateral breast, heart, and lungs. For each plan and ROI, target volume coverage (V(95-107)) and dose homogeneity (D(95-5)) were evaluated. Additionally, the mean OAR dose and normal tissue complication probability (NTCP) were computed. For irradiation of the CW, target volume coverage and dose homogeneity were improved for the fIMRT technique as compared to PE (p < 0.001, p = 0.023, respectively). Similar improvements were seen with respect to IMC PTV (p = 0.012, p = 0.064). These dosimetric parameters were also improved as compared to PWT, but not to the same extent (p = 0.011, p = 0.095 for CW PTV, and p = 0.164, p > 0.2 for IMC PTV). The PE technique resulted in the lowest heart V30, although this difference was not significant (p > 0.2). The NTCP values for excess cardiac mortality for fIMRT and PE were equivalent (1.9%) and lower than with PWT (2.8%, p > 0.2). The fIMRT technique was able to reduce heart dose and NTCP for each patient as compared to PWT. When comparing the anterior field techniques of treating SCV PTV, prescribing dose to 5 cm resulted in a improved V50 (p = 0.089). However, when compared to fIMRT, the SC3cm and SC5cm had inferior target volume coverage (p = 0.055, p = 0.014) and significantly greater dose heterogeneity (p = 0.031, p = 0.043). The addition of a posterior field increased the volume of lung receiving 40 and 50 Gy, but not significantly (p > 0.2). For complex breast treatments that irradiate the chest wall, IMC, and SCV, fIMRT resulted in improved dose homogeneity and target volume coverage as compared to conventional techniques. Furthermore, the dosimetric gains in target volume coverage with fIMRT came at no significant increase in dose to OAR. The fIMRT technique demonstrated the ability to maintain the advantage of each of the other 2 techniques: reducing the dose to OARs, as with PE, and providing superior target volume coverage, as with PWT.

      View details for PubMedID 15922178
  • Are neck nodal volumes drawn on CT slices covered by standard three-field technique? Int J Radiat Oncol Biol Phys
    Sanguineti G, Culp LR, Endres EJ, Bayouth JE
    2004 Jul 01; 59 (3): 725-42
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      PURPOSE: Several definitions have been proposed in the past few years on how to contour the various neck nodal levels on CT slices. However, whether the resulting nodal volumes would have been covered by standard techniques is unknown. The purpose of this study was to clarify this issue.

      METHODS AND MATERIALS: Eight patients (N0-N1) with head-and-neck cancer from various primary sites referred to us for definitive radiotherapy were included in this study. Two observers contoured the level Ib-V neck nodal volumes on planning CT according to seven reported definitions. Each observer also drew blocks on digitally reconstructed radiographs for the initial (on-cord) phase of a standard three-field technique (parallel opposed lateral fields and AP supraclavicular field) for three different clinical settings: "medium" larynx (to cover upper, mid, and low jugular nodes), "big" larynx (same as for medium, plus posterior cervical nodes), and "tonsil" (same as for big plus retropharyngeal nodes). Fields blocks were concentrically reduced 5 mm in all directions as a surrogate for the clinical target volume to planning target volume expansion. A plan was created for each of the clinical settings, delivering 2 Gy to the International Commission on Radiation Units and Measurements reference point. The coverage of the nodal levels according to the various definitions was investigated throughout the analysis of the volume receiving 50%, 80%, and 95% of the prescribed dose (V(50), V(80), and V(95), respectively) and dose covering at least 95% of the volume (D(95)) values extracted from their cumulative dose-volume histograms in the three clinical settings.

      RESULTS: The V(50) coverage of levels III and IV was adequate for all definitions and trials. For level V, about 3-5% of the volume was outside the 50% isodose of those trials that targeted the posterior cervical chain. Coverage of level Ib was highly dependent on the definition, with up to 21% of the volume outside the standard tonsillar fields. For level II, although the 50% isodose from the tonsillar fields seemed to encompass all definitions, this was not the case for the laryngeal trials. Overall, we found 20-30% of the volumes to be outside the 95% isodose, with larger percentages for levels II and V. Similarly the D(95) results showed all volumes to be underdosed; only about 45% and 65% of levels II and V, on average, received 95% of the prescription dose.

      CONCLUSION: Within three different clinical settings, we showed that the current definitions provide nodal neck volumes that often fall outside the 50% and 95% isodose lines of the standard three-field technique. Because these volumes are routinely used to define nodal neck volumes for intensity-modulated radiotherapy, the dose-volume objectives of intensity-modulated radiotherapy may not be consistent with those traditionally achieved by the standard three-field technique.

      View details for PubMedID 15183476
  • A case of radiation recall mucositis associated with docetaxel. Head Neck
    Culp LR, Pou AM, Jones DV, Bayouth J, Sanguineti G
    2004 Feb; 26 (2): 197-200
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      BACKGROUND: Radiation recall reactions, in particular dermatitis, are well documented in the literature. However, radiation recall mucositis is a rare clinical phenomenon.

      METHODS: We report a case of a 45-year-old man diagnosed with squamous cell carcinoma of the base of tongue. He was treated with surgery followed by chemotherapy and radiation therapy. Several months after completing treatment, he had a recurrence develop outside of the previously irradiated field. He was offered radiation therapy concurrent with docetaxel as salvage therapy.

      RESULTS: During salvage therapy, acute recall mucositis developed corresponding to his previously irradiated fields. His chemotherapy with docetaxel was withheld, and his symptoms rapidly improved.

      CONCLUSIONS: This case describes radiation recall mucositis associated with docetaxel, a rare but potentially serious clinical situation. Given the potential severity of the reaction and increasing use of docetaxel as second-line treatment of recurrent head and neck cancers, it is important to be aware of this phenomenon.

      View details for PubMedID 14762890

Contact Information

John Bayouth, PhD

600 Highland Avenue, K4/B78
Madison, WI 53792-0600