Publications by authors named "Nzhde Agazaryan"

59 Publications

Clinical outcomes of stereotactic magnetic resonance image-guided adaptive radiotherapy for primary and metastatic tumors in the abdomen and pelvis.

Cancer Med 2021 Jul 20. Epub 2021 Jul 20.

Department of Radiation Oncology, MD Anderson Cancer Center, University of Texas, Houston, TX, USA.

Purpose: Stereotactic body radiotherapy (SBRT) delivers ablative doses with excellent local control. However, implementing SBRT for abdominal and pelvic tumors has been limited by the risk for treatment-related gastrointestinal toxicity. MRI-guided radiotherapy may ameliorate these risks and increase the therapeutic ratio. We report the clinical outcomes of stereotactic MRI-guided adaptive radiotherapy (SMART) for primary and metastatic tumors in the abdomen and pelvis.

Methods: From November 2014 to August 2017, the first 106 consecutive patients with 121 tumors in the abdomen and pelvis were treated with SMART at a single institution. Of the cohort, 41.5%, 15.1%, and 43.4% had primary, locally recurrent, and oligometastatic tumors, respectively. SMART was delivered using a tri-cobalt-60 gantry with on-board 0.35 Tesla MRI with respiratory breath-hold and daily adaptive re-planning when anatomically necessary. A median of 40Gy in five fractions was prescribed. The Common Terminology Criteria for Adverse Events v.4.03 was used to score treatment-related toxicities. Local control (LC), progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan-Meier method.

Results: Of the 510 treatments, seventy-one (13.9%) were adapted. Fatigue, nausea, and pain were the most common acute toxicities. 0.9 and 0% of patients experienced acute grade three and four toxicities, respectively. 5.2 and 2.1% of patients experienced late grade three and four toxicities, respectively. After a median follow-up of 20.4 months, the 2-year LC rate was 74% on a per-lesion basis. Two-year LC was 96% for lesions that were treated with BED ≥100 versus 69% for BED <100 (p = 0.02). PFS was significantly different between patients with and without locally controlled tumors (2-year PFS 21 vs. 8%, p = 0.03). Two-year OS was 57% for the entire cohort.

Conclusions: Favorable LC and PFS outcomes were observed with minimal morbidity for tumors in the abdomen and pelvis treated with SMART. Future prospective clinical trials to validate these findings are warranted.
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http://dx.doi.org/10.1002/cam4.4139DOI Listing
July 2021

Intra-Fraction Motion Management for Radiosurgical Treatments of Trigeminal Neuralgia: Clinical Experience, Imaging Frequency, and Motion Analysis.

Cureus 2021 Apr 21;13(4):e14616. Epub 2021 Apr 21.

Radiation Oncology, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, USA.

Purpose The aim of this study is to evaluate the patient positioning and intra-fraction motion management performance of an image-guidance protocol established for radiosurgical treatments of trigeminal neuralgia patients. Specifically, it also aims to analyze patient motion data for the evaluation of current motion tolerance levels and imaging frequency utilized for repositioning patients. Methods A linear accelerator equipped with ExacTrac is used for patient positioning with stereoscopic imaging and treatments. Treatments are delivered with 4-mm conical collimators using seven equally spaced arcs. Arcs are 20 degrees apart and span 100 arc degrees each. Following initial ExacTrac positioning, cone beam computed tomography (CBCT) is obtained for independent confirmation of patient position. Patients are then stereoscopically imaged prior to the delivery of each arc and repositioned when 0.5-mm translational tolerance in any direction is exceeded. After the patient has been repositioned, verification stereoscopic images are obtained. Data from 48 patients with 607 image pairs were analyzed for this study. Results Over the course of 48 patient treatments, the mean magnitude of mean 3D deviations was 0.64 mm ± 0.12 mm (range: 0.07-2.74 mm). With the current 0.50-mm tolerance level for repositioning, patients exceeded the tolerance 51.4% of the time considering only images following an arc segment. For those instances, patients were repositioned with a mean magnitude of 0.85 mm ± 0.15 mm (1 SD). For a 0.25-mm tolerance level, 86.1% of arc segments would have required repositioning following the delivery of an arc segment, with a mean magnitude of 0.68 mm ± 0.12 mm. Conversely, for 0.75-mm and 1.00-mm tolerance levels, the tolerance would have been exceeded only 21.5% and 6.6% of instances following the delivery of an arc segment, with a mean magnitude of 1.08 mm ± 0.21 mm and 1.34 mm ± 0.24 mm, respectively. Each repositioning adds approximately 2 minutes to treatment time, which accounts for parts of the variability in patient treatment times. Following the initial ExacTrac and CBCT, the mean treatment time from first arc to treatment end was 57 minutes (range: 33-63 minutes). Discussions The current 0.50-mm tolerance level results in a clinically manageable but significant number of patient repositions during trigeminal neuralgia treatments. Frequent patient repositioning can result from actual patient motion convolved with the accuracy and precision limitations of the image analysis. Increasing the repositioning tolerance could more selectively correct for actual patient motion and shorten the treatment time at the expense of more variations in patient position. A more lenient tolerance level of 0.75 mm would decrease the repositioning rate by approximately a factor of 2; however, the permissible magnitude of motion will increase, leading to possible dosimetric consequences. Once treatment begins, there was no trend as to when patients exceeded the tolerance. Conclusions Current imaging protocol for patient positioning and intra-fraction motion management fits the clinical workflow with clinically acceptable residual patient motion. The next important step would be to assess how the number of repositions and magnitude of residual movements affect treatment outcomes.
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http://dx.doi.org/10.7759/cureus.14616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139874PMC
April 2021

Magnetic resonance imaging-guided stereotactic body radiotherapy for prostate cancer (mirage): a phase iii randomized trial.

BMC Cancer 2021 May 11;21(1):538. Epub 2021 May 11.

Department of Radiation Oncology, University of California Los Angeles, 200 Medical Plaza Driveway, Suite # B265, Medical Plaza Driveway, Los Angeles, CA, 90095, USA.

Background: Stereotactic body radiotherapy (SBRT) is becoming increasingly used in treating localized prostate cancer (PCa), with evidence showing similar toxicity and efficacy profiles when compared with longer courses of definitive radiation. Magnetic resonance imaging (MRI)-guided radiotherapy has multiple potential advantages over standard computed tomography (CT)-guided radiotherapy, including enhanced prostate visualization (abrogating the need for fiducials and MRI fusion), enhanced identification of the urethra, the ability to track the prostate in real-time, and the capacity to perform online adaptive planning. However, it is unknown whether these potential advantages translate into improved outcomes. This phase III randomized superiority trial is designed to prospectively evaluate whether toxicity is lower after MRI-guided versus CT-guided SBRT.

Methods: Three hundred men with localized PCa will be randomized in a 1:1 ratio to SBRT using CT or MRI guidance. Randomization will be stratified by baseline International Prostate Symptom Score (IPSS) (≤15 or > 15) and prostate gland volume (≤50 cc or > 50 cc). Five fractions of 8 Gy will be delivered to the prostate over the course of fourteen days, with or without hormonal therapy and elective nodal radiotherapy (to a dose of 5 Gy per fraction) as per the investigator's discretion. The primary endpoint is the incidence of physician-reported acute grade ≥ 2 genitourinary (GU) toxicity (during the first 90 days after SBRT), as assessed by the CTCAE version 4.03 scale. Secondary clinical endpoints include incidence of acute grade ≥ 2 gastrointestinal (GI) toxicity, 5-year cumulative incidences of physician-reported late grade ≥ 2 GU and GI toxicity, temporal changes in patient-reported quality of life (QOL) outcomes, 5-year biochemical recurrence-free survival and the proportion of fractions of MRI-guided SBRT in which online adaptive radiotherapy is used.

Discussion: The MIRAGE trial is the first randomized trial comparing MRI-guided with standard CT-guided SBRT for localized PCa. The primary hypothesis is that MRI-guided SBRT will lead to an improvement in the cumulative incidence of acute grade ≥ 2 GU toxicity when compared to CT-guided SBRT. The pragmatic superiority design focused on an acute toxicity endpoint will allow an early comparison of the two technologies.

Trial Registration: Clinicaltrials.gov identifier: NCT04384770. Date of registration: May 12, 2020. https://clinicaltrials.gov/ct2/show/NCT04384770 PROTOCOL VERSION: Version 2.1, Aug 28, 2020.
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http://dx.doi.org/10.1186/s12885-021-08281-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114498PMC
May 2021

Dosimetric Quality of Online Adapted Pancreatic Cancer Treatment Plans on an MRI-Guided Radiation Therapy System.

Adv Radiat Oncol 2021 May-Jun;6(3):100682. Epub 2021 Mar 3.

David Geffen School of Medicine at the University of California, Los Angeles, California.

Purpose: Stereotactic magnetic resonance image-guided adaptive radiation therapy (SMART) is an emerging technique that shows promise in the treatment of pancreatic cancer and other abdominopelvic malignancies. However, it is unknown whether the time-limited nature of on-table adaptive planning may result in dosimetrically suboptimal plans. The purpose of this study was to quantitatively address that question through systemic retrospective replanning of treated on-table adaptive pancreatic cancer cases.

Methods And Materials: Of 74 consecutive adapted fractions, 30 were retrospectively replanned based on deficiencies in planning target volume (PTV) and gross tumor volume (GTV) coverage or doses to organs-at-risk (OARs) that exceeded ideal constraints. Retrospective plans were created by adjusting dose-volume objectives in an iterative fashion until deemed optimized. The goal of replanning was to improve PTV/GTV coverage while keeping the dose to gastrointestinal OARs the same or lower or to reduce OAR doses while keeping PTV coverage the same or higher. The global maximum dose was required to be maintained within 2% of that of the treated adaptive plan to eliminate it as a confounding factor. A threshold of 5% improvement in PTV coverage or 5% decrease in OAR dose was used to define a clinically significant improvement.

Results: Of the 30 replans, 7 obtained at least 5% PTV coverage improvement. The average increase in PTV coverage for these plans was 11%. No plans were clinically significantly improved in terms of OAR sparing. Changes in beam-on time did not show any correlation. Statistical analysis via a linear mixed-effects model with a nested random effect suggested that both GTV and PTV coverage were improved over SMART process plans by 0.91 cc ( = .02) and 2.03 cc ( < .001), respectively.

Conclusions: Dosimetric plan quality of at least 10% of SMART fractions may be improved through more extensive replanning than is currently performed on-table. Further work is needed to develop an automated replanning workflow to streamline the in-depth replanning process to better fit into an on-table adaptive workflow.
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http://dx.doi.org/10.1016/j.adro.2021.100682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056223PMC
March 2021

A Framework for Sharing Radiation Dose Distribution Maps in the Electronic Medical Record for Improving Multidisciplinary Patient Management.

Radiol Imaging Cancer 2021 03 12;3(2):e200075. Epub 2021 Mar 12.

Departments of Radiation Oncology (R.R.S., J.D., M.M., S.T., N.A., J.H., T.K.) and Radiology (N.S.), UCLA David Geffen School of Medicine, 200 UCLA Medical Plaza, Suite B265, Los Angeles, CA 90095.

Radiation oncology practices use a suite of dedicated software and hardware that are not common to other medical subspecialties, making radiation treatment history inaccessible to colleagues. A radiation dose distribution map is generated for each patient internally that allows for visualization of the dose given to each anatomic structure volumetrically; however, this crucial information is not shared systematically to multidisciplinary medical, surgery, and radiology colleagues. A framework was developed in which dose distribution volumes are uploaded onto the medical center's picture archiving and communication system (PACS) to rapidly retrieve and review exactly where, when, and to what dose a lesion or structure was treated. The ability to easily visualize radiation therapy information allows radiology clinics to incorporate radiation dose into image interpretation without direct access to radiation oncology planning software and data. Tumor board discussions are simplified by incorporating radiation therapy information collectively in real time, and daily onboard imaging can also be uploaded while a patient is still undergoing radiation therapy. Placing dose distribution information into PACS facilitates central access into the electronic medical record and provides a succinct visual summary of a patient's radiation history for all medical providers. More broadly, the radiation dose map provides greater visibility and facilitates incorporation of a patient's radiation history to improve oncologic decision making and patient outcomes. Brain/Brain Stem, CNS, MRI, Neuro-Oncology, Radiation Effects, Radiation Therapy, Radiation Therapy/Oncology, Radiosurgery, Skull Base, Spine, Technology Assessment © RSNA, 2021 See also commentary by Khandelwal and Scarboro in this issue.
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http://dx.doi.org/10.1148/rycan.2021200075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011443PMC
March 2021

Resilience vs. Vulnerability: Psychological Safety and Reporting of Near Misses with Varying Proximity to Harm in Radiation Oncology.

Jt Comm J Qual Patient Saf 2020 Sep 20. Epub 2020 Sep 20.

Background: Psychological safety, a shared belief that interpersonal risk taking is safe, is an important determinant of incident reporting. However, how psychological safety affects near-miss reporting is unclear, as near misses contain contrasting cues that highlight both resilience ("we avoided failure") and vulnerability ("we nearly failed"). Near misses offer learning opportunities for addressing underlying causes of potential incidents, and it is crucial to understand what facilitates near-miss reporting.

Methods: A survey of radiation oncology department staff in an academic hospital assessed psychological safety and presented five scenarios with varying proximity to patient harm: "standard care" involving no harm, three near misses with varying proximity to harm ("could have happened," "fortuitous catch," "almost happened"), and one "hit" involving harm. Respondents evaluated each event as success or failure and reported willingness to report on a seven-point Likert scale. The analysis employed ordered logistic regression models.

Results: A total of 78 staff (61.4%) completed the survey. The odds of reporting "hit" (odds ratio [OR]: 1.96, 95% confidence interval [CI]: 1.19-3.23), "almost happened" (OR: 1.60, 95% CI: 1.07-2.37), and "fortuitous catch" (OR: 1.60, 95% CI: 1.10-2.33) improved with an increase in psychological safety. The relationship of psychological safety to reporting "standard care" and "could have happened" was not statistically significant. The odds of reporting were higher when a near miss was discerned as failure (vs. success).

Conclusion: Near misses are not processed and reported equally. The effect of psychological safety on reporting near misses becomes stronger with their increasing proximity to a negative outcome. Educating health care workers to properly identify near misses and fostering psychological safety may increase near-miss reporting and improve patient safety.
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http://dx.doi.org/10.1016/j.jcjq.2020.09.005DOI Listing
September 2020

The Timeliness Initiative: Continuous Process Improvement for Prompt Initiation of Radiation Therapy Treatment.

Adv Radiat Oncol 2020 Sep-Oct;5(5):1014-1021. Epub 2020 Mar 10.

Department of Radiation Oncology, UCLA, Los Angeles, California.

Purpose: The ambulatory patient experience is heavily influenced by wait times for provider care. Delayed patient visit start times may negatively affect overall satisfaction, and increased wait times affect the perception of the information, instructions, and treatment given by health care providers. Improving institutional practices overall requires the determination of the essential quality metrics that will make such an achievement possible. A protracted time leading up to the initiation of radiation therapy may promote poor satisfaction and perceived quality of care for both patients and referring providers alike, which may then create a barrier to patients being treated with radiation therapy. This institution piloted and sucessfully completed a study into improving the timeliness of initiation of patient radiation therapy for our patients.

Methods And Materials: This work sought to identify inefficiencies in radiation therapy treatment planning to shorten the time each patient waited for treatment. We examined the time between simulation to the start of the first fraction of treatment. This period includes simulation, contouring, treatment planning, and quality assurance of the plan.

Results: Before the study, the planning process would typically take 2 weeks. Target and organs-at-risk contouring were found to be the main inefficiency delaying treatment start dates. This delineating process includes drawing contours on radiologic images, typically computed tomography and magnetic resonance imaging. We focused on the time needed for the contouring process to be completed and took steps to increase efficiency. The length of time from simulation to contour approval was decreased by more than 60%, a reduction from an average of more than 4 days to less than 1.5 days. Overall planning time dropped from 2 weeks to less than 5 days.

Conclusions: Process improvements and implementation of task-specific tools improved the timeliness of patient treatments, reducing the overall planning time from simulation to treatments to less than 5 days. Continuous monitoring and modification of these processes revealed that the successes achieved toward better quality of care have been sustained.
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http://dx.doi.org/10.1016/j.adro.2020.01.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557132PMC
March 2020

Dose-response with stereotactic body radiotherapy for prostate cancer: A multi-institutional analysis of prostate-specific antigen kinetics and biochemical control.

Radiother Oncol 2021 01 7;154:207-213. Epub 2020 Oct 7.

Department of Radiation Oncology, University of California, Los Angeles, USA.

Background And Purpose: The optimal dose for prostate stereotactic body radiotherapy (SBRT) is still unknown. This study evaluated the dose-response relationships for prostate-specific antigen (PSA) decay and biochemical recurrence (BCR) among 4 SBRT dose regimens.

Materials And Methods: In 1908 men with low-risk (50.0%), favorable intermediate-risk (30.9%), and unfavorable intermediate-risk (19.1%) prostate cancer treated with prostate SBRT across 8 institutions from 2003 to 2018, we examined 4 regimens (35 Gy/5 fractions [35/5, n = 265, 13.4%], 36.25 Gy/5 fractions [36.25/5, n = 711, 37.3%], 40 Gy/5 fractions [40/5, n = 684, 35.8%], and 38 Gy/4 fractions [38/4, n = 257, 13.5%]). Between dose groups, we compared PSA decay slope, nadir PSA (nPSA), achievement of nPSA ≤0.2 and ≤0.5 ng/mL, and BCR-free survival (BCRFS).

Results: Median follow-up was 72.3 months. Median nPSA was 0.01 ng/mL for 38/4, and 0.17-0.20 ng/mL for 5-fraction regimens (p < 0.0001). The 38/4 cohort demonstrated the steepest PSA decay slope and greater odds of nPSA ≤0.2 ng/mL (both p < 0.0001 vs. all other regimens). BCR occurred in 6.25%, 6.75%, 3.95%, and 8.95% of men treated with 35/5, 36.25/5, 40/5, and 38/4, respectively (p = 0.12), with the highest BCRFS after 40/5 (vs. 35/5 hazard ratio [HR] 0.49, p = 0.026; vs. 36.25/5 HR 0.42, p = 0.0005; vs. 38/4 HR 0.55, p = 0.037) including the entirety of follow-up, but not for 5-year BCRFS (≥93% for all regimens, p ≥ 0.21).

Conclusion: Dose-escalation was associated with greater prostate ablation and PSA decay. Dose-escalation to 40/5, but not beyond, was associated with improved BCRFS. Biochemical control remains excellent, and prospective studies will provide clarity on the benefit of dose-escalation.
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http://dx.doi.org/10.1016/j.radonc.2020.09.053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956167PMC
January 2021

Missing the Near Miss: Recognizing Valuable Learning Opportunities in Radiation Oncology.

Pract Radiat Oncol 2021 May-Jun;11(3):e256-e262. Epub 2020 Sep 22.

Department of Radiation Oncology, University of California Los Angeles, Los Angeles, California.

Purpose: "Near miss" events are valuable low-cost learning opportunities in radiation oncology as they do not result in patient harm and are more pervasive than adverse events that do. Near misses vary depending on the presence of a latent error of behavior or process, and the presence of an enabling condition predisposing the patient to harm. These nuanced distinctions across near miss types can elicit different cognitive biases affecting the recognition of near misses as learning opportunities. We define near miss types in radiation oncology and explore the differential perceptions among radiation oncology staff.

Methods And Materials: Six event types were defined based on attributes of latent error and enabling conditions: "hit," "potential hit," "almost happened," "fortuitous catch," "could have happened," and "process-based catch." These events were illustrated with an example of a patient receiving pacemaker cardiac clearance before radiation treatment. A survey assessing (1) success versus failure of an event and (2) willingness to report the event was administered to a radiation oncology department using the pacemaker example. Mean scores for each near miss type were compared.

Results: Ninety-five staff members (74%) completed the survey. Perceived success scores and willing-to-report scores significantly differed by near miss type (P = .042 for success ratings; P < .0001 for willingness to report). "Could have happened" events were viewed as less successful and were more likely to be reported than "almost happened" events (P < .0001).

Conclusions: Cognitive biases appear to influence whether and how near miss types are recognized as report-worthy. Education of near miss types and engaging staff for quality improvement may improve recognition.
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http://dx.doi.org/10.1016/j.prro.2020.09.007DOI Listing
September 2020

Time-Driven Activity-Based Costing Comparison of Stereotactic Radiosurgery to Multiple Brain Lesions Using Single-Isocenter Versus Multiple-Isocenter Technique.

Int J Radiat Oncol Biol Phys 2020 11 27;108(4):999-1007. Epub 2020 Jun 27.

Department of Radiation Oncology, University of California Los Angeles, Los Angeles, California. Electronic address:

Purpose: Stereotactic radiosurgery (SRS) historically has been used to treat multiple brain lesions using a multiple-isocenter technique-frequently associated with significant complexity in treatment planning and long treatment times. Recently, given innovations in planning algorithms, patients with multiple brain lesions may now be treated with a single-isocenter technique using fewer total arcs and less time spent during image guidance (though with stricter image guided radiation therapy tolerances). This study used time-driven activity-based costing to determine the difference in cost to a provider for delivering SRS to multiple brain lesions using single-isocenter versus multiple-isocenter techniques.

Methods And Materials: Process maps, consisting of discrete steps, were created for each phase of the SRS care cycle and were based on interviews with department personnel. Actual treatment times (including image guidance) were extracted from treatment record and verify software. Additional sources of data to determine costs included salary/benefit data of personnel and average list price/maintenance costs for equipment.

Results: Data were collected for 22 patients who underwent single-isocenter SRS (mean lesions treated, 5.2; mean treatment time, 30.2 minutes) and 51 patients who underwent multiple-isocenter SRS (mean lesions treated, 4.4; mean treatment time, 75.2 minutes). Treatment time for multiple-isocenter SRS varied substantially with increasing number of lesions (11.8 minutes/lesion; P < .001), but to a much lesser degree in single-isocenter SRS (1.8 minutes/lesion; P = .029). The resulting cost savings from single-isocenter SRS based on number of lesions treated ranged from $296 to $3878 for 2 to 10 lesions treated. The 2-mm planning treatment volume margin used with single-isocenter SRS resulted in a mean 43% increase of total volume treated compared with a 1-mm planning treatment volume expansion.

Conclusions: In a comparison of time-driven activity-based costing assessment of single-isocenter versus multiple-isocenter SRS for multiple brain lesions, single-isocenter SRS appears to save time and resources for as few as 2 lesions, with incremental benefits for additional lesions treated.
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http://dx.doi.org/10.1016/j.ijrobp.2020.06.035DOI Listing
November 2020

Time-Driven Activity-Based Costing Comparison of CT-Guided Versus MR-Guided SBRT.

JCO Oncol Pract 2020 11 15;16(11):e1378-e1385. Epub 2020 Jun 15.

Department of Radiation Oncology, University of California, Los Angeles, CA.

Purpose: Magnetic resonance-guided radiation therapy (MRgRT) has recently become commercially available, offering the opportunity to accurately image and target moving tumors as compared with computed tomography-guided radiation therapy (CTgRT) systems. However, the costs of delivering care with these 2 modalities remain poorly described. With localized unresectable hepatocellular carcinoma as an example, we were able to use time-driven activity-based costing to determine the cost of treatment on linear accelerators with CTgRT compared with MRgRT.

Materials And Methods: Process maps, informed via interviews with departmental personnel, were created for each phase of the care cycle. Stereotactic body radiation therapy was delivered at 50 Gy in 5 fractions, either with CTgRT using fiducial placement, deep inspiration breath-hold (DIBH) with real-time position management, and volumetric-modulated arc therapy, or with MRgRT using real-time tumor gating, DIBH, and static-gantry intensity-modulated radiation therapy.

Results: Direct clinical costs were $7,306 for CTgRT and $8,622 for MRgRT comprising personnel costs ($3,752 $3,603), space and equipment costs ($2,912 $4,769), and materials costs ($642 $250). Increased MRgRT costs may be mitigated by forgoing CT simulation ($322 saved) or shortening treatment to 3 fractions ($1,815 saved). Conversely, adaptive treatment with MRgRT would result in an increase in cost of $529 per adaptive treatment.

Conclusion: MRgRT offers real-time image guidance, avoidance of fiducial placement, and ability to use adaptive treatments; however, it is 18% more expensive than CTgRT under baseline assumptions. Future studies that elucidate the magnitude of potential clinical benefits of MRgRT are warranted to clarify the value of using this technology.
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http://dx.doi.org/10.1200/JOP.19.00605DOI Listing
November 2020

Comparison of Clinical Outcomes Stratified by Target Delineation for Patients Undergoing Stereotactic Body Radiotherapy for Spinal Metastases.

World Neurosurg 2020 Apr 13;136:e68-e74. Epub 2019 Nov 13.

Department of Neurosurgery, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California, USA; Department of Radiation Oncology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California, USA. Electronic address:

Objective: Stereotactic body radiotherapy (SBRT) is an effective treatment of spinal metastases in the vertebral body. However, variation has existed between practitioners regarding the appropriate target delineation. As such, we compared the tumor control, rates of compression fractures, and pain control for patients who had undergone SBRT for spinal metastases to either the lesion only (LO) or the full vertebral body (FVB).

Methods: A total of 126 spinal metastases in 84 patients had received single-fraction SBRT from January 2009 to February 2015. Of the 126 lesions, 36 (29%) were in the FVB group and 90 were in the LO group. The SBRT plans were reviewed to determine the treatment volume. Odds ratios were used to compare the rates of compression fracture and local failure. Regression analysis was performed to identify the predictors of outcome.

Results: A total of 5 failures had occurred in the FVB group and 14 in the LO group; however, the difference was not statistically significant (P = 0.5). No difference was found in pain reduction between the 2 groups (P = 0.9). Seven post-treatment compression fractures occurred in the LO group and four in the FVB group; however, the difference was not statistically significant (P = 0.6). The minimum dose to the planning target volume, patient age, and planning target volume size were the only significant factors predicting for local failure, vertebral body fracture, and pain control, respectively.

Conclusions: Given that we found no difference in tumor control, pain reduction, or fracture rate between patients treated to the FVB versus the. LO, it might be reasonable to consider SBRT to the LO for select patients.
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http://dx.doi.org/10.1016/j.wneu.2019.10.094DOI Listing
April 2020

Immediate Pain Relief Elicited After Radiosurgery for Classical and Symptomatic Trigeminal Neuralgia.

Cureus 2019 May 30;11(5):e4777. Epub 2019 May 30.

Neurosurgery, University of California, Los Angeles, USA.

Background Immediate relief following radiosurgery for trigeminal neuralgia (TN) has been observed in a minority of cases. Objective Our goals were to determine the occurrence of immediate pain relief as real vs. placebo effect and to search for factors associated with this desirable outcome. Methods Between January 2003 and June 2008, 150 patients were treated with radiosurgery for classical or symptomatic TN. A commercially available linear accelerator (Novalis®, BrainLab) device was used to deliver 90 Gy to the root-entry zone with a 4- or 5-mm collimator. Pain outcomes were graded using a four-point scale. Complications were recorded through standardized follow-up evaluations. Treatment plans were retrieved and brainstem/trigeminal nerves were retrospectively re-contoured using standard anatomical landmarks. Dose-volume histograms were used to calculate the volume of brainstem/trigeminal nerve receiving 20%, 30%, and 50% of the prescribed radiation doses. Results Twenty-five (19.84%) patients presented with immediate pain relief, defined as pain cessation within 48 hours post-radiosurgery. Kaplan-Meier analysis showed that good/excellent pain outcomes were sustained and significantly better in the immediate pain relief group (= 0.006) compared to non-immediate relief. Univariate and multivariate logistic regression analyses failed to show the correlation between brainstem/trigeminal nerve volumes, trigeminal nerve-pontine angle, prior surgical procedures, TN etiology, age, gender, and immediate pain relief. Neither post-radiosurgery complications nor recurrence rates were different between groups. Conclusion Immediate pain relief leads to sustained relief and patients present significantly better pain outcomes in comparison to those without immediate relief. The mechanism triggering immediate relief is still unknown and did not correlate with the volume of brainstem/trigeminal nerve receiving pre-specified doses of radiation.
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http://dx.doi.org/10.7759/cureus.4777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6666916PMC
May 2019

Safety-oriented design of in-house software for new techniques: A case study using a model-based 4DCT protocol.

Med Phys 2019 Apr 18;46(4):1523-1532. Epub 2019 Feb 18.

Department of Radiation Oncology, University of California, Los Angeles, 200 Medical Plaza Suite B265, Los Angeles, California, 90095, USA.

Purpose: In-house software is commonly employed to implement new imaging and therapy techniques before commercial solutions are available. Risk analysis methods, as detailed in the TG-100 report of the American Association of Physicists in Medicine, provide a framework for quality management of processes but offer little guidance on software design. In this work, we examine a novel model-based four-dimensional computed tomography (4DCT) protocol using the TG-100 approach and describe two additional methods for promoting safety of the associated in-house software.

Methods: To implement a previously published model-based 4DCT protocol, in-house software was necessary for tasks such as synchronizing a respiratory signal to computed tomography images, deformable image registration (DIR), model parameter fitting, and interfacing with a treatment planning system. A process map was generated detailing the workflow. Failure modes and effects analysis (FMEA) was performed to identify critical steps and guide quality interventions. Software system safety was addressed through writing "use cases," narratives that characterize the behavior of the software, for all major operations to elicit safety requirements. Safety requirements were codified using the easy approach to requirements syntax (EARS) to ensure testability and eliminate ambiguity.

Results: Sixty-one failure modes were identified and assigned risk priority numbers using FMEA. Resultant quality management interventions include integration of a comprehensive reporting and logging system into the software, mandating daily and monthly equipment quality assurance procedures, and a checklist to be completed at image acquisition. Use cases and resulting safety requirements informed the design of needed in-house software as well as a suite of tests performed during the image generation process.

Conclusions: TG-100 methods were used to construct a process-level quality management program for a 4DCT imaging protocol. Two supplemental tools from the field of requirements engineering facilitated elicitation and codification of safety requirements that informed the design and testing of in-house software necessary to implement the protocol. These general tools can be applied to promote safety when in-house software is needed to bring new techniques to the clinic.
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http://dx.doi.org/10.1002/mp.13386DOI Listing
April 2019

Image-guided radiotherapy for prostate cancer.

Transl Androl Urol 2018 Jun;7(3):308-320

Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.

Intensity-modulated radiotherapy (IMRT) has become the standard radiotherapy technology utilized for the treatment of prostate cancer, as it permits the delivery of highly conformal radiation dose distributions. Image-guided radiotherapy (IGRT) is an essential companion to IMRT that allows the treatment team to account for daily changes in target anatomy and positioning. In the present review, we will discuss the different sources of geometric uncertainty and review the rationale behind using IGRT in the treatment of prostate cancer. We will then describe commonly employed IGRT techniques and review their benefits and drawbacks. Additionally, we will review the evidence suggesting a potential clinical benefit to utilizing IGRT.
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http://dx.doi.org/10.21037/tau.2017.12.37DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043755PMC
June 2018

A Prospective Phase 2 Study Evaluating Safety and Efficacy of Combining Stereotactic Body Radiation Therapy With Heat-based Ablation for Centrally Located Lung Tumors.

Int J Radiat Oncol Biol Phys 2018 07 21;101(3):564-573. Epub 2018 Mar 21.

Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California. Electronic address:

Purpose: Stereotactic body radiation therapy (SBRT) and heat-based ablation (HBA) are both potentially safe and effective treatments for primary and metastatic lung tumors. Both are suboptimal for centrally located tumors, with SBRT having a higher risk of significant toxicity and HBA having lower efficacy. This study evaluates the safety and efficacy of combination SBRT-HBA to determine whether combined treatment can result in superior outcomes to each treatment alone.

Methods And Materials: Patients with 1 or 2 primary or metastatic lung tumors ≤ 5 cm in size were enrolled in a prospective phase 2 trial and treated with SBRT in 3 fractions followed by HBA. Tumors < 1 cm from the central bronchial tree received a total of 36 Gy, and tumors 1 to 2 cm away received 42 Gy. HBA was delivered within 10 days after SBRT. The primary endpoints were local control, toxicity, and degree of decline in lung function. The secondary endpoints were progression-free survival and overall survival.

Results: We treated 16 patients with 17 tumors. The median follow-up time was 26 months. Fifteen tumors were evaluable for local control. The 1- and 2-year actuarial local control rates were 93% and 81%, respectively. Three patients had grade ≥ 3 toxicity: bronchial stenosis, pain, and pulmonary hemorrhage. The percent predicted forced expiratory volume in 1 second and functional vital capacity decreased by 8% and 8.5%, respectively, at 3 months after treatment (P < .001 for both).

Conclusions: Combining SBRT and HBA for centrally located lung tumors offers reasonable local control and toxicity despite the anatomic challenges of this location. HBA may be a reasonable supplement to SBRT when trachea and bronchus, large vessel, or esophageal constraints cannot be met with full-dose SBRT and a biologically effective dose < 100 Gy is delivered because of an ultra-central location or large tumor size.
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http://dx.doi.org/10.1016/j.ijrobp.2018.03.011DOI Listing
July 2018

Initial clinical observations of intra- and interfractional motion variation in MR-guided lung SBRT.

Br J Radiol 2018 Feb 22;91(1083):20170522. Epub 2018 Jan 22.

2 Department of Radiation Oncology, University of California , Los Angeles, CA , USA.

Objective: To evaluate variations in intra- and interfractional tumour motion, and the effect on internal target volume (ITV) contour accuracy, using deformable image registration of real-time two-dimensional-sagittal cine-mode MRI acquired during lung stereotactic body radiation therapy (SBRT) treatments.

Methods: Five lung tumour patients underwent free-breathing SBRT treatments on the ViewRay system, with dose prescribed to a planning target volume (defined as a 3-6 mm expansion of the 4DCT-ITV). Sagittal slice cine-MR images (3.5 × 3.5 mm pixels) were acquired through the centre of the tumour at 4 frames per second throughout the treatments (3-4 fractions of 21-32 min). Tumour gross tumour volumes (GTVs) were contoured on the first frame of the MR cine and tracked for the first 20 min of each treatment using offline optical-flow based deformable registration implemented on a GPU cluster. A ground truth ITV (MR-ITV) was formed by taking the union of tracked GTV contours. Pseudo-ITVs were generated from unions of the GTV contours tracked over 10 s segments of image data (MR-ITV).

Results: Differences were observed in the magnitude of median tumour displacement between days of treatments. MR-ITV areas were as small as 46% of the MR-ITV.

Conclusion: An ITV offers a "snapshot" of breathing motion for the brief period of time the tumour is imaged on a specific day. Real-time MRI over prolonged periods of time and over multiple treatment fractions shows that ITV size varies. Further work is required to investigate the dosimetric effect of these results. Advances in knowledge: Five lung tumour patients underwent free-breathing MRI-guided SBRT treatments, and their tumours tracked using deformable registration of cine-mode MRI. The results indicate that variability of both intra- and interfractional breathing amplitude should be taken into account during planning of lung radiotherapy.
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http://dx.doi.org/10.1259/bjr.20170522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5965474PMC
February 2018

Online Adaptive Radiation Therapy: Implementation of a New Process of Care.

Cureus 2017 Aug 27;9(8):e1618. Epub 2017 Aug 27.

Department of Radiation Oncology, University of California, Los Angeles.

Onboard magnetic resonance imaging (MRI) guided radiotherapy is now clinically available in nine centers in the world. This technology has facilitated the clinical implementation of online adaptive radiotherapy (OART), or the ability to alter the daily treatment plan based on tumor and anatomical changes in real-time while the patient is on the treatment table. However, due to the time sensitive nature of OART, implementation in a large and busy clinic has many potential obstacles as well as patient-related safety considerations. In this work, we have described the implementation of this new process of care in the Department of Radiation Oncology at the University of California, Los Angeles (UCLA). We describe the rationale, the initial challenges such as treatment time considerations, technical issues during the process of re-contouring, re-optimization, quality assurance, as well as our current solutions to overcome these challenges. In addition, we describe the implementation of a coverage system with a physician of the day as well as online planners (physicists or dosimetrists) to oversee each OART treatment with patient-specific 'hand-off' directives from the patient's treating physician. The purpose of this effort is to streamline the process without compromising treatment quality and patient safety. As more MRI-guided radiotherapy programs come online, we hope that our experience can facilitate successful adoption of OART in a way that maximally benefits the patient.
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http://dx.doi.org/10.7759/cureus.1618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5663325PMC
August 2017

Magnetic resonance imaging guided reirradiation of recurrent and second primary head and neck cancer.

Adv Radiat Oncol 2017 Apr-Jun;2(2):167-175. Epub 2017 Feb 21.

Department of Radiation Oncology, University of California, David Geffen School of Medicine, Los Angeles, California.

Purpose: To report a single-institutional experience using magnetic resonance imaging (MRI) guided radiation therapy for the reirradiation of recurrent and second cancers of the head and neck.

Methods And Materials: Between October 2014 and August 2016, 13 consecutive patients with recurrent or new primary cancers of the head and neck that occurred in a previously irradiated field were prospectively enrolled in an institutional registry trial to investigate the feasibility and efficacy of MRI guided radiation therapy using a 0.35-T MRI scanner with a cobalt-60 radiation therapy source called the ViewRay system (ViewRay Inc., Cleveland, OH). Eligibility criteria included biopsy-proven evidence of recurrent or new primary squamous cell carcinoma of the head and neck, measurable disease, and previous radiation to >60 Gy. MRI guided reirradiation was delivered either using intensity modulated radiation therapy with conventional fractionation to a median dose of 66 Gy or stereotactic body radiation therapy (SBRT) using 7 to 8 Gy fractions on nonconsecutive days to a median dose of 40 Gy. Two patients (17%) received concurrent chemotherapy.

Results: The 1- and 2-year estimates of in-field control were 72% and 72%, respectively. A total of 227 daily MRI scans were obtained to guide reirradiation. The 2-year estimates of overall survival and progression-free survival were 53% and 59%, respectively. There were no treatment-related fatalities or hospitalizations. Complications included skin desquamation, odynophagia, otitis externa, keratitis and/or conjunctivitis, and 1 case of aspiration pneumonia.

Conclusions: Our preliminary findings show that reirradiation with MRI guided radiation therapy results in effective disease control with relatively low morbidity for patients with recurrent and second primary cancers of the head and neck. The superior soft tissue resolution of the MRI scans that were used for planning and delivery has the potential to improve the therapeutic ratio.
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http://dx.doi.org/10.1016/j.adro.2017.02.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5514244PMC
February 2017

Dosimetric validation of a magnetic resonance image gated radiotherapy system using a motion phantom and radiochromic film.

J Appl Clin Med Phys 2017 May 24;18(3):163-169. Epub 2017 Apr 24.

Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.

Purpose: Magnetic resonance image (MRI) guided radiotherapy enables gating directly on the target position. We present an evaluation of an MRI-guided radiotherapy system's gating performance using an MRI-compatible respiratory motion phantom and radiochromic film. Our evaluation is geared toward validation of our institution's clinical gating protocol which involves planning to a target volume formed by expanding 5 mm about the gross tumor volume (GTV) and gating based on a 3 mm window about the GTV.

Methods: The motion phantom consisted of a target rod containing high-contrast target inserts which moved in the superior-inferior direction inside a body structure containing background contrast material. The target rod was equipped with a radiochromic film insert. Treatment plans were generated for a 3 cm diameter spherical planning target volume, and delivered to the phantom at rest and in motion with and without gating. Both sinusoidal trajectories and tumor trajectories measured during MRI-guided treatments were used. Similarity of the gated dose distribution to the planned, motion-frozen, distribution was quantified using the gamma technique.

Results: Without gating, gamma pass rates using 4%/3 mm criteria were 22-59% depending on motion trajectory. Using our clinical standard of repeated breath holds and a gating window of 3 mm with 10% target allowed outside the gating boundary, the gamma pass rate was 97.8% with 3%/3 mm gamma criteria. Using a 3 mm window and 10% allowed excursion, all of the patient tumor motion trajectories at actual speed resulting in at least 95% gamma pass rate at 4%/3 mm.

Conclusions: Our results suggest that the device can be used to compensate respiratory motion using a 3 mm gating margin and 10% allowed excursion results in conjunction with repeated breath holds. Full clinical validation requires a comprehensive evaluation of tracking performance in actual patient images, outside the scope of this study.
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http://dx.doi.org/10.1002/acm2.12088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5689863PMC
May 2017

Characterization of spatial distortion in a 0.35 T MRI-guided radiotherapy system.

Phys Med Biol 2017 06 20;62(11):4525-4540. Epub 2017 Apr 20.

Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, United States of America.

Spatial distortion results in image deformation that can degrade accurate targeting and dose calculations in MRI-guided adaptive radiotherapy. The authors present a comprehensive assessment of a 0.35 T MRI-guided radiotherapy system's spatial distortion using two commercially-available phantoms with regularly spaced markers. Images of the spatial integrity phantoms were acquired using five clinical protocols on the MRI-guided radiotherapy machine with the radiotherapy gantry positioned at various angles. Software was developed to identify and localize all phantom markers using a template matching approach. Rotational and translational corrections were implemented to account for imperfect phantom alignment. Measurements were made to assess uncertainties arising from susceptibility artifacts, image noise, and phantom construction accuracy. For a clinical 3D imaging protocol with a 1.5 mm reconstructed slice thickness, 100% of spheres within a 50 mm radius of isocenter had a 3D deviation of 1 mm or less. Of the spheres within 100 mm of isocenter, 99.9% had a 3D deviation less than 1 mm. 94.8% and 100% of the spheres within 175 mm were found to be within 1 mm and 2 mm of the expected positions in 3D respectively. Maximum 3D distortions within 50 mm, 100 mm and 175 mm of isocenter were 0.76 mm, 1.15 mm and 1.88 mm respectively. Distortions present in images acquired using the real-time imaging sequence were less than 1 mm for 98.1% and 95.0% of the cylinders within 50 mm and 100 mm of isocenter. The corresponding maximum distortion in these regions was 1.10 mm and 1.67 mm. These results may be used to inform appropriate planning target volume (PTV) margins for 0.35 T MRI-guided radiotherapy. Observed levels of spatial distortion should be explicitly considered when using PTV margins of 3 mm or less or in the case of targets displaced from isocenter by more than 50 mm.
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http://dx.doi.org/10.1088/1361-6560/aa6e1aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6061953PMC
June 2017

Diffusion tractography imaging-guided frameless linear accelerator stereotactic radiosurgical thalamotomy for tremor: case report.

J Neurosurg 2018 01 24;128(1):215-221. Epub 2017 Feb 24.

Departments of1Neurosurgery.

Essential tremor and Parkinson's disease-associated tremor are extremely prevalent within the field of movement disorders. The ventral intermediate (VIM) nucleus of the thalamus has been commonly used as both a neuromodulatory and neuroablative target for the treatment of these forms of tremor. With both deep brain stimulation and Gamma Knife radiosurgery, there is an abundance of literature regarding the surgical planning, targeting, and outcomes of these methodologies. To date, there have been no reports of frameless, linear accelerator (LINAC)-based thalomotomies for tremor. The authors report the case of a patient with tremor-dominant Parkinson's disease, with poor tremor improvement with medication, who was offered LINAC-based thalamotomy. High-resolution 0.9-mm isotropic MR images were obtained, and simulation was performed via CT with 1.5-mm contiguous slices. The VIM thalamic nucleus was determined using diffusion tensor imaging (DTI)-based segmentation on FSL using probabilistic tractography. The supplemental motor and premotor areas were the cortical target masks. The authors centered their isocenter within the region of the DTI-determined target and treated the patient with 140 Gy in a single fraction. The DTI-determined target had coordinates of 14.2 mm lateral and 8.36 mm anterior to the posterior commissure (PC), and 3 mm superior to the anterior commissure (AC)-PC line, which differed by 3.30 mm from the original target determined by anatomical considerations (15.5 mm lateral and 7 mm anterior to the PC, and 0 mm superior to the AC-PC line). There was faint radiographic evidence of lesioning at the 3-month follow-up within the target zone, which continued to consolidate on subsequent scans. The patient experienced continued right upper-extremity resting tremor improvement starting at 10 months until it was completely resolved at 22 months of follow-up. Frameless LINAC-based thalamotomy guided by DTI-based thalamic segmentation is a feasible method for achieving radiosurgical lesions of the VIM thalamus to treat tremor.
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http://dx.doi.org/10.3171/2016.10.JNS161603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5568966PMC
January 2018

Feasibility evaluation of diffusion-weighted imaging using an integrated MRI-radiotherapy system for response assessment to neoadjuvant therapy in rectal cancer.

Br J Radiol 2017 Mar 12;90(1071):20160739. Epub 2017 Jan 12.

1 Department of Radiation Oncology, University of California, Los Angeles, CA, USA.

Objective: To evaluate the feasibility of on-board diffusion-weighted imaging (DWI) with an integrated low-field MRI radiotherapy system to assess responses to neoadjuvant chemoradiation (NAC) in rectal cancer.

Methods: A spin echo-based planar imaging diffusion sequence on a 0.35-T MRI radiotherapy system was acquired over the course of NAC. The apparent diffusion coefficients (ADCs) from the tumour regions of interest (ROIs) were calculated. A functional diffusion map (fDM) was created showing a pixelwise ADC analysis of the ROI over the course of treatment. Surgical pathology was correlated with ADC data.

Results: Consecutive patients treated on a 0.35-T MRI radiotherapy system were evaluated. Patient A had the worst pathological response to NAC with a tumour regression score of 1 and was the only patient with a negative slope in the change of ADC values over the entire course of NAC, and during both the first and second half of NAC. The fDM from the first half of NAC for Patient A showed discrete dark areas in the tumour ROI, reflecting subregions with decreasing ADC values during NAC. Patient C had the most favourable pathological response to NAC with a Grade 3 response and was the only patient who had an increase in the slope in the change of ADC values from the first to the second half of NAC.

Conclusion: DWI using a low-field MRI radiotherapy system for evaluating the responses to NAC is feasible. Advances in knowledge: ADC values obtained using a 0.35-T MRI radiotherapy system over the course of NAC for rectal cancer correlate with pathological responses.
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http://dx.doi.org/10.1259/bjr.20160739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5601527PMC
March 2017

Technical Note: Dosimetric effects of couch position variability on treatment plan quality with an MRI-guided Co-60 radiation therapy machine.

Med Phys 2016 Aug;43(8):4514

Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California 90095.

Purpose: Magnetic resonance imaging (MRI) guidance in radiation therapy brings real-time imaging and adaptive planning into the treatment vault where it can account for interfraction and intrafraction movement of soft tissue. The only commercially available MRI-guided radiation therapy device is a three-head (60)Co and MRI system with an integrated treatment planning system (TPS). Couch attenuation of the beam of up to 20% is well modeled in the TPS. Variations in the patient's day-to-day position introduce discrepancies in the actual couch attenuation as modeled in the treatment plan. For this reason, the authors' institution avoids plans with beams that pass through or near the couch edges. This study investigates the effects of differential beam attenuation by the couch due to couch shifts in order to determine whether couch edge avoidance restrictions can be lifted. Couch shifts were simulated using a Monte Carlo treatment planning system and ion chamber measurements performed for validation.

Methods: A total of 27 plans from 23 patients were investigated. Couch shifts of 1 and 2 cm were introduced in combinations of lateral and vertical directions to simulate patient position variations giving 16 shifted plans per reference plan. The 1 and 2 cm shifts were based on shifts recorded in 320 treatment fractions.

Results: Following TG176 recommendations for measurement methods, couch attenuation measurements agreed with TPS modeled attenuation to within 2.1%. Planning target volume D95 changed less than 1% for 1 and 2 cm couch shifts in only the x-direction and less than 3% for all directions.

Conclusions: Dosimetry of all plans tested was robust to couch shifts up to ±2 cm. In general, couch shifts resulted in clinically insignificant dosimetric deviations. It is conceivable that in certain cases with large systematic couch shifts and plans that are particularly sensitive to shifts, dosimetric changes might rise to a clinically significant level.
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http://dx.doi.org/10.1118/1.4955116DOI Listing
August 2016

Longitudinal diffusion MRI for treatment response assessment: Preliminary experience using an MRI-guided tri-cobalt 60 radiotherapy system.

Med Phys 2016 Mar;43(3):1369-73

Department of Radiological Sciences, University of California, Los Angeles, California 90095.

Purpose: To demonstrate the preliminary feasibility of a longitudinal diffusion magnetic resonance imaging (MRI) strategy for assessing patient response to radiotherapy at 0.35 T using an MRI-guided radiotherapy system (ViewRay).

Methods: Six patients (three head and neck cancer, three sarcoma) who underwent fractionated radiotherapy were enrolled in this study. A 2D multislice spin echo single-shot echo planar imaging diffusion pulse sequence was implemented on the ViewRay system and tested in phantom studies. The same pulse sequence was used to acquire longitudinal diffusion data (every 2-5 fractions) on the six patients throughout the entire course of radiotherapy. The reproducibility of the apparent diffusion coefficient (ADC) measurements was assessed using reference regions and the temporal variations of the tumor ADC values were evaluated.

Results: In diffusion phantom studies, the ADC values measured on the ViewRay system matched well with reference ADC values with <5% error for a range of ground truth diffusion coefficients of 0.4-1.1 × 10(-3) mm(2)/s. The remote reference regions (i.e., brainstem in head and neck patients) had consistent ADC values throughout the therapy for all three head and neck patients, indicating acceptable reproducibility of the diffusion imaging sequence. The tumor ADC values changed throughout therapy, with the change differing between patients, ranging from a 40% drop in ADC within the first week of therapy to gradually increasing throughout therapy. For larger tumors, intratumoral heterogeneity was observed. For one sarcoma patient, postradiotherapy biopsy showed less than 10% necrosis score, which correlated with the observed 40% decrease in ADC from the fifth fraction to the eighth treatment fraction.

Conclusions: This pilot study demonstrated that longitudinal diffusion MRI is feasible using the 0.35 T ViewRay MRI. Larger patient cohort studies are warranted to correlate the longitudinal diffusion measurements to patient outcomes. Such an approach may enable response-guided adaptive radiotherapy.
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http://dx.doi.org/10.1118/1.4942381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961701PMC
March 2016

The significance of PTV dose coverage on cancer control outcomes in early stage non-small cell lung cancer patients treated with highly ablative stereotactic body radiation therapy.

Br J Radiol 2016 14;89(1059):20150963. Epub 2016 Jan 14.

Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA, USA.

Objective: We evaluated whether patients with early-stage non-small-cell lung cancers (NSCLCs) treated with stereotactic body radiation therapy (SBRT) without full prescription dose coverage of the planning target volume (PTV) had inferior outcomes.

Methods: The SBRT regimen was 54 Gy in three fractions. Dosimetric constraints were as per the Radiation Therapy Oncology Group 0236 guidelines. All patients underwent four-dimensional CT (4D-CT) simulation. The internal target volume (ITV) was defined using 4D-CT, and the PTV was defined as a 6-mm longitudinal and a 3-mm axial expansion from the ITV. If normal tissue constraints were beyond tolerance, ITV-based dosing was employed where priority was made for full ITV coverage at the expense of PTV coverage. Patients with and without full PTV dose coverage were compared, and control rates were estimated using Kaplan-Meier analysis.

Results: 120 NSCLC cases were evaluated with 81% having adequate PTV dose coverage. ITV and PTV were significantly larger in the cohort with inadequate PTV dose coverage (p = 0.0085 and p = 0.0038, respectively), and the mean ITV and PTV doses were higher in patients with adequate PTV dose coverage (p = 0.002 and p < 0.0001, respectively). The 3-year local control rate was 100% for both cohorts. There was no difference in 3-year regional control (p = 0.36), disease-specific survival (p = 0.79) or overall survival (p = 0.73).

Conclusion: When delivering a highly ablative SBRT regimen for early-stage NSCLC, full-dose coverage of the ITV is sufficient for local control.

Advances In Knowledge: Our data are among the first to evaluate the utility of PTV margins in a highly ablative SBRT regimen and suggest that when dosing constraints cannot be met, full tumouricidal dose coverage of the ITV is sufficient for local control.
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http://dx.doi.org/10.1259/bjr.20150963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4986505PMC
July 2016

A treatment planning comparison between modulated tri-cobalt-60 teletherapy and linear accelerator-based stereotactic body radiotherapy for central early-stage non-small cell lung cancer.

Med Dosim 2016 2;41(1):87-91. Epub 2016 Jan 2.

Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA. Electronic address:

We evaluated the feasibility of planning stereotactic body radiotherapy (SBRT) for large central early-stage non-small cell lung cancer with a tri-cobalt-60 (tri-(60)Co) system equipped with real-time magnetic resonance imaging (MRI) guidance, as compared to linear accelerator (LINAC)-based SBRT. In all, 20 patients with large central early-stage non-small cell lung cancer who were treated between 2010 and 2015 with LINAC-based SBRT were replanned using a tri-(60)Co system for a prescription dose of 50Gy in 4 fractions. Doses to organs at risk were evaluated based on established MD Anderson constraints for central lung SBRT. R100 values were calculated as the total tissue volume receiving 100% of the dose (V100) divided by the planning target volume and compared to assess dose conformity. Dosimetric comparisons between LINAC-based and tri-(60)Co SBRT plans were performed using Student׳s t-test and Wilcoxon Ranks test. Blinded reviews by radiation oncologists were performed to assess the suitability of both plans for clinical delivery. The mean planning target volume was 48.3cc (range: 12.1 to 139.4cc). Of the tri-(60)Co SBRT plans, a mean 97.4% of dosimetric parameters per patient met MD Anderson dose constraints, whereas a mean 98.8% of dosimetric parameters per patient were met with LINAC-based SBRT planning (p = 0.056). R100 values were similar between both plans (1.20 vs 1.21, p = 0.79). Upon blinded review by 4 radiation oncologists, an average of 90% of the tri-(60)Co SBRT plans were considered acceptable for clinical delivery compared with 100% of the corresponding LINAC-based SBRT plans (p = 0.17). SBRT planning using the tri-(60)Co system with built-in MRI is feasible and achieves clinically acceptable plans for most central lung patients, with similar target dose conformity and organ at risk dosimetry. The added benefit of real-time MRI-guided therapy may further optimize tumor targeting while improving normal tissue sparing, which warrants further investigation in a prospective feasibility clinical trial.
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http://dx.doi.org/10.1016/j.meddos.2015.09.002DOI Listing
December 2016

Accuracy of UTE-MRI-based patient setup for brain cancer radiation therapy.

Med Phys 2016 Jan;43(1):262

Department of Radiological Sciences, University of California, Los Angeles, California 90095.

Purpose: Radiation therapy simulations solely based on MRI have advantages compared to CT-based approaches. One feature readily available from computed tomography (CT) that would need to be reproduced with MR is the ability to compute digitally reconstructed radiographs (DRRs) for comparison against on-board radiographs commonly used for patient positioning. In this study, the authors generate MR-based bone images using a single ultrashort echo time (UTE) pulse sequence and quantify their 3D and 2D image registration accuracy to CT and radiographic images for treatments in the cranium.

Methods: Seven brain cancer patients were scanned at 1.5 T using a radial UTE sequence. The sequence acquired two images at two different echo times. The two images were processed using an in-house software to generate the UTE bone images. The resultant bone images were rigidly registered to simulation CT data and the registration error was determined using manually annotated landmarks as references. DRRs were created based on UTE-MRI and registered to simulated on-board images (OBIs) and actual clinical 2D oblique images from ExacTrac™.

Results: UTE-MRI resulted in well visualized cranial, facial, and vertebral bones that quantitatively matched the bones in the CT images with geometric measurement errors of less than 1 mm. The registration error between DRRs generated from 3D UTE-MRI and the simulated 2D OBIs or the clinical oblique x-ray images was also less than 1 mm for all patients.

Conclusions: UTE-MRI-based DRRs appear to be promising for daily patient setup of brain cancer radiotherapy with kV on-board imaging.
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http://dx.doi.org/10.1118/1.4938266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961699PMC
January 2016

Visual Acuity, Contrast Sensitivity and Color Vision Three Years After Iodine-125 Brachytherapy for Choroidal and Ciliary Body Melanoma.

Open Ophthalmol J 2015 26;9:131-5. Epub 2015 Jun 26.

Department of Ophthalmology and Jules Stein Eye Institute, University of California, Los Angeles, Los Angeles, CA, USA.

Purpose: To report visual acuity, contrast sensitivity and color vision prior to, 1 year after, 2 years after and 3 years after iodine-125 brachytherapy for choroidal and ciliary body melanoma (CCM).

Design: Prospective interventional case series.

Participants: Thirty-seven patients (37 eyes) with CCM.

Methods: Patients had best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity, Pelli-Robson contrast sensitivity and Hardy-Rand-Rittler color vision measurement; comprehensive ophthalmology examination; optical coherence tomography; and ultrasonography at baseline prior to, 1 year after, 2 years after and 3 years after I-125 brachytherapy.

Main Outcome Measures: Visual acuity, contrast sensitivity and color vision prior to, 1 year after, 2 years after and 3 years after brachytherapy.

Results: Nineteen (19) men and 18 women with mean age of 58 years (SD 13, range 30-78) prior to, 1 year after, 2 years after and 3 years after brachytherapy had mean best-corrected visual acuity of 77 letters (20/32), 65 letters (20/50), 56 letters (20/80) and 47 letters (20/125); contrast sensitivity of 30, 26, 22 and 19 letters; color vision of 26, 20, 17 and 14 test figures, respectively. Decrease in visual acuity, contrast sensitivity and color vision was statistically significant from baseline at 1 year, 2 years, and 3 years after brachytherapy. Decreased acuity at 3 years was associated with mid-choroid and macula melanoma location, ≥ 4.1 mm melanoma height, radiation maculopathy and radiation optic neuropathy.

Conclusion: 1, 2 and 3 years after brachytherapy, eyes with CCM had significantly decreased visual acuity, contrast sensitivity and color vision.
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http://dx.doi.org/10.2174/1874364101509010131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4541296PMC
August 2015

Safety and efficacy of stereotactic body radiation therapy in the treatment of pulmonary metastases from high grade sarcoma.

Sarcoma 2013 1;2013:360214. Epub 2013 Oct 1.

Department of Radiation Oncology, David Geffen School of Medicine at UCLA, 200 UCLA Medical Plaza, B265, Los Angeles, CA 90095, USA.

Introduction. Patients with high-grade sarcoma (HGS) frequently develop metastatic disease thus limiting their long-term survival. Lung metastases (LM) have historically been treated with surgical resection (metastasectomy). A potential alternative for controlling LM could be stereotactic body radiation therapy (SBRT). We evaluated the outcomes from our institutional experience utilizing SBRT. Methods. Sixteen consecutive patients with LM from HGS were treated with SBRT between 2009 and 2011. Routine radiographic and clinical follow-up was performed. Local failure was defined as CT progression on 2 consecutive scans or growth after initial shrinkage. Radiation pneumonitis and radiation esophagitis were scored using Common Toxicity Criteria (CTC) version 3.0. Results. All 16 patients received chemotherapy, and a subset (38%) also underwent prior pulmonary metastasectomy. Median patient age was 56 (12-85), and median follow-up time was 20 months (range 3-43). A total of 25 lesions were treated and evaluable for this analysis. Most common histologies were leiomyosarcoma (28%), synovial sarcoma (20%), and osteosarcoma (16%). Median SBRT prescription dose was 54 Gy (36-54) in 3-4 fractions. At 43 months, local control was 94%. No patient experienced G2-4 radiation pneumonitis, and no patient experienced radiation esophagitis. Conclusions. Our retrospective experience suggests that SBRT for LM from HGS provides excellent local control and minimal toxicity.
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http://dx.doi.org/10.1155/2013/360214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3807836PMC
November 2013
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