Publications by authors named "Lauren Henke"

35 Publications

MR-Guided Radiotherapy for Liver Malignancies.

Front Oncol 2021 1;11:616027. Epub 2021 Apr 1.

Radiation Medicine Program, Princess Margaret Cancer Centre, Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada.

MR guided radiotherapy represents one of the most promising recent technological innovations in the field. The possibility to better visualize therapy volumes, coupled with the innovative online adaptive radiotherapy and motion management approaches, paves the way to more efficient treatment delivery and may be translated in better clinical outcomes both in terms of response and reduced toxicity. The aim of this review is to present the existing evidence about MRgRT applications for liver malignancies, discussing the potential clinical advantages and the current pitfalls of this new technology.
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http://dx.doi.org/10.3389/fonc.2021.616027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047407PMC
April 2021

Sensible Introduction of MR-Guided Radiotherapy: A Warm Plea for the RCT.

Front Oncol 2021 19;11:652889. Epub 2021 Mar 19.

Department of Radiation Oncology, Washington University School of Medicine in St. Louis, St Louis, MO, United States.

Magnetic resonance guided radiotherapy (MRgRT) is the newest face of technology within a field long-characterized by continual technologic advance. MRgRT may offer improvement in the therapeutic index of radiation by offering novel planning types, like online adaptation, and improved image guidance, but there is a paucity of randomized data or ongoing randomized controlled trials (RCTs) to demonstrate clinical gains. Strong clinical evidence is needed to confirm the theoretical advantages of MRgRT and for the rapid dissemination of (and reimbursement for) appropriate use. Although some future evidence for MRgRT may come from large registries and non-randomized studies, RCTs should make up the core of this future data, and should be undertaken with thoughtful preconception, endpoints that incorporate patient-reported outcomes, and warm collaboration across existing MRgRT platforms. The advance and future success of MRgRT hinges on collaborative pursuit of the RCT.
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http://dx.doi.org/10.3389/fonc.2021.652889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017276PMC
March 2021

Technical Note: Self-shielding evaluation and radiation leakage measurement of a jawless ring gantry linac with a beam stopper.

Med Phys 2021 Mar 24. Epub 2021 Mar 24.

Department of Radiation Oncology, Washington University, St. Louis, MO, 63110, USA.

Purpose: To characterize the shielding design and leakage radiation from a newly released ring gantry linac (Halcyon, Varian Medical Systems).

Methods: To assess the radiation leakage surrounding headshield and the radiation level after the beam stopper, measurements were made with GafChromic films. To evaluate the in-room radiation levels, the radiation leakage in the isocenter plane was measured with a large volume spherical ionization chamber (Exradin A6, Standard Imaging). A lead enclosure was constructed to shield the chamber from the low energy scatter radiation from the room. The radiation level at multiple locations was measured with the MLC fully closed and gantry at 0, 45, 90, 135, 180, 225, 270, and 315 degrees. The leakage radiation passing through multiple concrete slabs with various thickness was recorded in a narrow beam geometry to determine the tenth value layer (TVL).

Results: A uniform leakage (<0.05%) at 1 m from electron beam line was measured surrounding the linac head with the maximum leakage measured at the top of the head enclosure. The highest radiation level (<0.08%) was measured near the edge of the beam stopper when projected to the measurement plane. The maximum radiation levels due to the head leakage at 15 locations inside the treatment room were recorded and a radiation map was plotted. The maximum leakage was measured at points that along the electron beam line while the gantry at 90 or 270 degree and at the end of head enclosure (0.314%, 0.4 m from electron beamline). The leakage TVL value is found to be 226 mm in a narrow beam geometry with the concrete density of 2.16 g/cm or 134.6 lb/cu.ft.

Conclusion: An overall uniform leakage was measured surrounding linac head. The beam stopper shields the primary radiation with the highest valued measured near the edge of beam stopper. The leakage TVL values are derived and less than the values reported for conventional C-arm linac.
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http://dx.doi.org/10.1002/mp.14858DOI Listing
March 2021

Ablative Five-Fraction Stereotactic Body Radiation Therapy for Inoperable Pancreatic Cancer Using Online MR-Guided Adaptation.

Adv Radiat Oncol 2021 Jan-Feb;6(1):100506. Epub 2020 Jun 25.

Department of Radiation Oncology, Washington University School of Medicine and Alvin J. Siteman Comprehensive Cancer Center, St. Louis, Missouri.

Purpose: Patients with inoperable pancreatic adenocarcinoma have limited options, with traditional chemoradiation providing modest clinical benefit and an otherwise poor prognosis. Stereotactic body radiation therapy for pancreatic cancer is limited by proximity to organs-at-risk (OAR). However, stereotactic magnetic resonance-guided adaptive radiation therapy (SMART) has shown promise in delivering ablative doses safely. We sought to demonstrate the benefits of SMART using a 5-fraction approach with daily on-table adaptation.

Methods And Materials: Patients with locally advanced, nonmetastatic pancreatic adenocarcinoma were treated with 50 Gy in 5 fractions (biologically effective dose 100 Gy) with a prescribed goal of 95% planning target volume coverage by 95% of prescription, prioritizing hard OAR constraints. Daily online adaptation was performed using magnetic resonance-guidance and on-table reoptimization. Patient outcomes, treatment factors, and daily adaptation were evaluated.

Results: Forty-four patients were treated with SMART at our institution from 2014 to 2019. Median follow-up from date of diagnosis was 16 months (range, 6.7-51.6). Late toxicity was limited to 2 (4.6%) grade 3 (gastrointestinal ulcers) and 3 (6.8%) grade 2 toxicities (duodenal perforation, antral ulcer, and gastric bleed). Tumor abutted OARs in 35 patients (79.5%) and tumor invaded OARs in 5 patients (11.1%). Reoptimization was performed for 93% of all fractions. Median overall survival was 15.7 months (95% confidence interval, 10.2-21.2), while 1-year and 2-year overall survival rates were 68.2% and 37.9%, respectively. One-year local control was 84.3%.

Conclusions: This is the first reported experience using 50 Gy in 5 fractions for inoperable pancreatic cancer. SMART allows this ablative dose with promising outcomes while minimizing toxicity. Additional prospective trials evaluating efficacy and safety are warranted.
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http://dx.doi.org/10.1016/j.adro.2020.06.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897757PMC
June 2020

Evaluation of interim MRI changes during limited-field radiation therapy for glioblastoma and implications for treatment planning.

Radiother Oncol 2021 May 13;158:237-243. Epub 2021 Feb 13.

Department of Radiation Oncology, Washington University School of Medicine, St. Louis, United States. Electronic address:

Background And Purpose: Consensus for defining gross tumor volume (GTV) and clinical target volume (CTV) for limited-field radiation therapy (LFRT) of GBM are not well established. We leveraged a department MRI simulator to image patients before and during LFRT to address these questions.

Materials And Methods: Supratentorial GBM patients receiving LFRT (46 Gy + boost to 60 Gy) underwent baseline MRI (MRI1) and interim MRI during RT (MRI2). GTV1 was defined as T1 enhancement + surgical cavity on MRI1 without routine inclusion of T2 abnormality (unless tumor did not enhance). The initial CTV margin was 15 mm from GTV1, and the boost CTV margin was 5-7 mm. The GTV1 characteristics were categorized into three groups: identical T1 and T2 abnormality (Group A), T1 only with larger T2 abnormality not included (Group B), and T2 abnormality when tumor lacked enhancement (Group C). GTV2 was contoured on MRI2 and compared with GTV1 plus 5-15 mm expansions.

Results: Among 120 patients treated from 2014-2019, 29 patients (24%) underwent replanning based on MRI2. On MRI2, 84% of GTV2 were covered by GTV1 + 5 mm, 93% by GTV1 + 7 mm, and 98% by GTV1 + 15 mm. On MRI1, 43% of GTV1 could be categorized into Group A, 39% Group B, and 18% Group C. Group B's patterns of failure, local control, or progression-free survival were similar to Group A/C.

Conclusions: Initial CTV margin of 15 mm followed by a boost CTV margin of 7 mm is a reasonable approach for LFRT of GBM. Omitting routine inclusion of T2 abnormality from GTV delineation may not jeopardize disease control.
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http://dx.doi.org/10.1016/j.radonc.2021.01.040DOI Listing
May 2021

Direct tumor visual feedback during free breathing in 0.35T MRgRT.

J Appl Clin Med Phys 2020 Oct 15;21(10):241-247. Epub 2020 Sep 15.

Department of Radiation Oncology, Washington University School of Medicine, St Louis, MO, 63110, USA.

To present a tumor motion control system during free breathing using direct tumor visual feedback to patients in 0.35 T magnetic resonance-guided radiotherapy (MRgRT). We present direct tumor visualization to patients by projecting real-time cine MR images on an MR-compatible display system inside a 0.35 T MRgRT bore. The direct tumor visualization included anatomical images with a target contour and an auto-segmented gating contour. In addition, a beam-status sign was added for patient guidance. The feasibility was investigated with a six-patient clinical evaluation of the system in terms of tumor motion range and beam-on time. Seven patients without visual guidance were used for comparison. Positions of the tumor and the auto-segmented gating contour from the cine MR images were used in probability analysis to evaluate tumor motion control. In addition, beam-on time was recorded to assess the efficacy of the visual feedback system. The direct tumor visualization system was developed and implemented in our clinic. The target contour extended 3 mm outside of the gating contour for 33.6 ± 24.9% of the time without visual guidance, and 37.2 ± 26.4% of the time with visual guidance. The average maximum motion outside of the gating contour was 14.4 ± 11.1 mm without and 13.0 ± 7.9 mm with visual guidance. Beam-on time as a percentage was 43.9 ± 15.3% without visual guidance, and 48.0 ± 21.2% with visual guidance, but was not significantly different (P = 0.34). We demonstrated the clinical feasibility and potential benefits of presenting direct tumor visual feedback to patients in MRgRT. The visual feedback allows patients to visualize and attempt to minimize tumor motion in free breathing. The proposed system and associated clinical workflow can be easily adapted for any type of MRgRT.
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http://dx.doi.org/10.1002/acm2.13016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592976PMC
October 2020

Evaluation of the Metastatic Spine Disease Multidisciplinary Working Group Algorithms as Part of a Multidisciplinary Spine Tumor Conference.

Global Spine J 2020 Oct 16;10(7):888-895. Epub 2019 Oct 16.

7548Washington University, St Louis, MO, USA.

Study Design: Retrospective cohort study.

Objective: The Metastatic Spine Disease Multidisciplinary Working Group Algorithms are evidence and expert opinion-based strategies for utilizing radiation therapy, interventional radiology procedures, and surgery to treat 5 types of spine metastases: asymptomatic spinal metastases, uncomplicated spinal metastases, stable vertebral compression fractures (VCF), unstable VCF, and metastatic epidural spinal cord compression (MESCC). Evaluation of this set of algorithms in a clinical setting is lacking. The authors aimed to identify rate of treatment adherence to the Working Group Algorithms and, subsequently, update these algorithms based on actual patient management decisions made at a single-institution, multidisciplinary, spine tumor conference.

Methods: Patients with metastatic spine disease from primary non-hematologic malignancies discussed at an institutional spine tumor conference from 2013 to 2016 were evaluated. Rates of Working Group Algorithms adherence were calculated for each type of metastasis. Based on the reasons for algorithm nonadherence, and patient outcomes in such cases, updated Working Group Algorithms recommendations were proposed.

Results: In total, 154 eligible patients with 171 spine metastases were evaluated. Rates of algorithm adherence were as follows: asymptomatic (67%), uncomplicated (73%), stable VCF (20%), unstable VCF (32%), and MESCC (41%). The most common deviation from the Working Group Algorithms was surgery for MESCC despite poor prognostic factors, but this treatment strategy was supported based on median survival surpassing 6 months in these patients.

Conclusions: Adherence to the Working Group Algorithm was lowest for MESCC and VCF patients, but many nonadherent treatments were supported by patient survival outcomes. We proposed updates to the Working Group Algorithm based on these findings.
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http://dx.doi.org/10.1177/2192568219882649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485068PMC
October 2020

Implementing a Novel Remote Physician Treatment Coverage Practice for Adaptive Radiation Therapy During the Coronavirus Pandemic.

Adv Radiat Oncol 2020 Jul-Aug;5(4):737-742. Epub 2020 May 24.

Department of Radiation Oncology, Washington University in St Louis School of Medicine, St. Louis, Missouri.

Purpose: The 2019 coronavirus disease pandemic has placed an increased importance on physical distancing to minimize the risk of transmission in radiation oncology departments. The pandemic has also increased the use of hypofractionated treatment schedules where magnetic resonance-guided online adaptive radiation therapy (ART) can aid in dose escalation. This specialized technique requires increased staffing in close proximity, and thus the need for novel coverage practices to increase physical distancing while still providing specialty care.

Methods And Materials: A remote-physician ART coverage practice was developed and described using commercially available software products. Our remote-physician coverage practice provided control to the physician to contour and review of the images and plans. The time from completion of image registration to the beginning of treatment was recorded for 20 fractions before remote-physician ART coverage and 14 fractions after implementation of remote-physician ART coverage. Visual quality was calculated using cross-correlation between the treatment delivery and remote-physician computer screens.

Results: For the 14 fractions after implementation, the average time from image registration to the beginning of treatment was 24.9 ± 6.1 minutes. In comparison, the 20 fractions analyzed without remote coverage had an average time of 29.2 ± 9.8 minutes. The correlation between the console and remote-physician screens was = .95.

Conclusions: Our novel remote-physician ART coverage practice is secure, interactive, timely, and of high visual quality. When using remote physicians for ART, our department was able to increase physical distancing to lower the risk of virus transmission while providing specialty care to patients in need.
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http://dx.doi.org/10.1016/j.adro.2020.05.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246005PMC
May 2020

Taking Guatemala From Cobalt to IMRT: A Tale of US Agency Collaboration With Academic Institutions and Industry.

Int J Radiat Oncol Biol Phys 2020 08;107(5):867-872

Global Health Center, Institute for Public Health, Washington University in St Louis, St Louis, Missouri. Electronic address:

The not-for-profit organization La LIGA Nacional Contra el Cáncer, with its hospital Instituto de Cancerología (INCAN), is responsible for cancer treatment of much of the indigent population in Guatemala, a country with a population of 16 million. Annually, approximately 70% of patients at INCAN are seen in late stages of cancer, which places a great strain on the hospital's limited resources. Private clinics account for 75% of radiation therapy centers in Guatemala and have considerable resources. However, private facilities are fee-based, which creates a barrier for low-income patients; this is an especially significant problem in Guatemala, which has the highest income inequalities and poverty rates in Latin America. This article describes a project on the transition from cobalt to a Halcyon radiation therapy system at INCAN through a partnership with the US Agency for International Development's Office of American Schools and Hospitals Abroad (USAID/ASHA), Washington University in St. Louis (WUSTL), industry partner Varian Medical Systems, and the US National Nuclear Security Administration to provide access to state-of-the-art radiation therapy technology while increasing the overall treatment capacity for the underserved population of Guatemala.
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http://dx.doi.org/10.1016/j.ijrobp.2020.04.001DOI Listing
August 2020

Intracranial Stereotactic Radiation Therapy With a Jawless Ring Gantry Linear Accelerator Equipped With New Dual Layer Multileaf Collimator.

Adv Radiat Oncol 2020 May-Jun;5(3):482-489. Epub 2020 Jan 28.

Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.

Purpose: To test the feasibility of a simplified, robust, workflow for intracranial stereotactic radiation therapy (SRT) using a ring gantry linear accelerator (RGLA) equipped with a dual-layer stacked, staggered, and interdigitating multileaf collimator.

Materials And Methods: Twenty recent clinical SRT cases treated using a radiosurgery c-arm linear accelerator were anonymized. From these data sets, a new planning workflow was developed and used to replan these cases, which then were compared to their clinical counterparts. Population-based dose-volume histograms were analyzed for target coverage and sparing of healthy brain. All plans underwent plan review and quality assurance and were delivered on an end-to-end verification phantom using image guidance to simulate treatment.

Results: The RGLA plans were able to meet departmental standards for target coverage and organ-at-risk sparing and showed plan quality similar to the clinical plans. RGLA plans showed increases in the 50% isodose in the axial plane but decreases in the sagittal and coronal planes. There were no statistically significant differences in the homogeneity index or number of monitor units between the 2 systems. There were statistically significant increases in conformity and gradient indices, with median values of 1.09 versus 1.11 and 2.82 versus 3.13, respectively, for the c-arm versus RGLA plans. These differences were not believed to be clinically significant because they met clinical goals. The population-based dose-volume histograms showed target coverage and organ-at-risk sparing similar to that of the clinical plans. All plans were able to meet the departmental quality assurance requirements and were delivered under image guidance on an end-to-end phantom with measurements agreeing within 3% of the expected value. RGLA plans showed a median reduction in delivery time of ≈50%.

Conclusions: This work describes a simplified and efficient workflow that could reduce treatment times and expand access to SRT to centers using an RGLA.
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http://dx.doi.org/10.1016/j.adro.2020.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276691PMC
January 2020

Implementation of a Novel Remote Physician Stereotactic Body Radiation Therapy Coverage Process during the Coronavirus Pandemic.

Adv Radiat Oncol 2020 Jul-Aug;5(4):690-696. Epub 2020 Apr 28.

Department of Radiation Oncology, Washington University in St Louis School of Medicine, St. Louis, Missouri.

Purpose: During the coronavirus 2019 disease (COVID-19) pandemic, alternative methods of care are needed to reduce the relative risk of transmission in departments. Also needed is the ability to provide vital radiation oncological care if radiation oncologists (RO) are reallocated to other departments. We implemented a novel remote RO stereotactic body radiation therapy (SBRT) coverage practice, requiring it to be reliable, of high audio and visual quality, timely, and the same level of specialty care as our current in-person treatment coverage practice.

Methods And Materials: All observed failure modes were recorded during implementation over the first 15 sequential fractions. The time from cone beam computed tomography to treatment was calculated before and after implementation to determine timeliness of remote coverage. Image quality metrics were calculated between the imaging console screen and the RO's shared screen. Comfort levels with audio and visual communication as well as overall comfort in comparison to in-person RO coverage was evaluated using Likert scale surveys after treatment.

Results: Remote RO SBRT coverage was successfully implemented in 14 of 15 fractions with 3 observed process failures that were all corrected before treatment. Average times of pretreatment coverage before and after implementation were 8.74 and 8.51 minutes, respectively. The cross correlation between the imaging console screen and RO's shared screen was r = 0.96 and lag was 0.05 seconds. The average value for all survey questions was more than 4.5, approaching in-person RO coverage comfort levels.

Conclusion: Our novel method of remote RO SBRT coverage permits reduced personnel and patient interactions surrounding radiation therapy procedures. This may help to reduce transmission of COVID-19 in our department and provides a means for SBRT coverage if ROs are reallocated to other areas of the hospital for COVID-19 support.
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http://dx.doi.org/10.1016/j.adro.2020.04.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186133PMC
April 2020

MRI-Based Upper Abdominal Organs-at-Risk Atlas for Radiation Oncology.

Int J Radiat Oncol Biol Phys 2020 03 14;106(4):743-753. Epub 2020 Jan 14.

Department of Radiation Oncology, University of Toronto, Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. Electronic address:

Purpose: The purpose of our study was to provide a guide for identification and contouring of upper abdominal organs-at-risk (OARs) in the setting of online magnetic resonance imaging (MRI)-guided radiation treatment planning and delivery.

Methods And Materials: After a needs assessment survey, it was determined that an upper abdominal MRI-based atlas of normal OARs would be of benefit to radiation oncologists and radiation therapists. An anonymized diagnostic 1.5T MRI from a patient with typical upper abdominal anatomy was used for atlas development. Two MRI sequences were selected for contouring, a T1-weighted gadoxetic acid contrast-enhanced MRI acquired in the hepatobiliary phase and axial fast imaging with balanced steady-state precession. Two additional clinical MRI sequences from commercial online MRI-guided radiation therapy systems were selected for contouring and were included in the final atlas. Contours from each data set were completed and reviewed by radiation oncologists, along with a radiologist who specializes in upper abdominal imaging, to generate a consensus upper abdominal MRI-based OAR atlas.

Results: A normal OAR atlas was developed, including recommendations for contouring. The atlas and contouring guidance are described, and high-resolution MRI images and contours are displayed. OARs, such as the bile duct and biliary tree, which may be better seen on MRI than on computed tomography, are highlighted. The full DICOM/DICOM-RT MRI images from both the diagnostic and clinical online MRI-guided radiation therapy systems data sets have been made freely available, for educational purposes, at econtour.org.

Conclusions: This MRI contouring atlas for upper abdominal OARs should provide a useful reference for contouring and education. Its routine use may help to improve uniformity in contouring in radiation oncology planning and OAR dose calculation. Full DICOM/DICOM-RT images are available online and provide a valuable educational resource for upper abdominal MRI-based radiation therapy planning and delivery.
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http://dx.doi.org/10.1016/j.ijrobp.2019.12.003DOI Listing
March 2020

Feasibility and safety assessment of magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU)-mediated mild hyperthermia in pelvic targets evaluated using an porcine model.

Int J Hyperthermia 2019 ;36(1):1147-1159

Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, USA.

To evaluate the feasibility and assess safety parameters of magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU)-mediated hyperthermia (HT; heating to 40-45 °C) in various pelvic targets in a porcine model . Thirteen HT treatments were performed in six pigs with a commercial MRgHIFU system (Sonalleve V2, Profound Medical Inc., Mississauga, Canada) to muscle adjacent to the ventral/dorsal bladder wall and uterus to administer 42 °C (±1°) for 30 min (±5%) using an 18-mm target diameter and 100 W power. Feasibility was assessed using accuracy, uniformity, and MR-thermometry performance-based metrics. Safety parameters were assessed for tissues in the targets and beam-path by contrast-enhanced MRI, gross-pathology and histopathology. Across all HT sessions, the mean difference between average temperature (T) and the target temperature within the target region-of-interest (tROI, the cross-section of the heated volume at focal depth) was 0.51 ± 0.33 °C. Within the tROI, the temperature standard deviation averaged 1.55 ± 0.31 °C, the average 30-min T variation was 0.80 ± 0.17 °C, and the maximum difference between T and the 10th- or 90th-percentile temperature averaged 2.01 ± 0.44 °C. The average time to reach ≥41 °C and cool to ≤40 °C within the tROI at the beginning and end of treatment was 47.25 ± 27.47 s and 66.37 ± 62.68 s, respectively. Compared to unheated controls, no abnormally-perfused tissue or permanent damage was evident in the MR images, gross pathology or histological analysis. MRgHIFU-mediated HT is feasible and safety assessment is satisfactory for treating an array of clinically-mimicking pelvic geometries in a porcine model , implying the technique may have utility in treating pelvic targets in human patients.
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http://dx.doi.org/10.1080/02656736.2019.1685684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105895PMC
April 2020

Eliminating Postoperative Radiation to the Pathologically Node-Negative Neck: Long-Term Results of a Prospective Phase II Study.

J Clin Oncol 2019 10 27;37(28):2548-2555. Epub 2019 Jun 27.

Washington University, St Louis, MO.

Purpose: The volume treated with postoperative radiation therapy (PORT) is a mediator of toxicity, and reduced volumes result in improved quality of life (QOL). In this phase II trial, treatment volumes were reduced by omitting PORT to the pathologically negative (PN0) neck in patients with primary head and neck squamous cell carcinoma.

Methods: Patients with head and neck squamous cell carcinoma who underwent surgical resection and neck dissection with a PN0 neck and high-risk features mandating PORT to the primary and/or involved neck were eligible. The primary end point was greater than 90% disease control in the unirradiated neck. QOL was evaluated using the MD Anderson Dysphagia Inventory and the University of Michigan patient-reported xerostomia questionnaire.

Results: Seventy-three patients were enrolled, and 72 were evaluable. Median age was 56 years (range, 31 to 81 years); 58 patients were male, and 47 (65%) had a smoking history. Sites included oral cavity (n = 14), oropharynx (n = 37), hypopharynx (n = 4), larynx (n = 16), and unknown primary tumor (n = 1). According to the American Joint Committee on Cancer Staging Manual (7 edition), 67 patients (93%) had stage III/IV disease, and 71% of tumors involved or crossed midline. No patient had contralateral neck PORT. In 17 patients (24%), only the primary site was treated. At a median follow-up of 53 months, two patients experienced treatment failure of the PN0 unirradiated neck; they also experienced treatment failure locally. Unirradiated neck control was 97% (95% CI, 93.4% to 100.0%). Five-year rates of local control, regional control, progression-free survival, and overall survival were 84%, 93%, 60%, and 64%, respectively. QOL measures were not significantly different from baseline at 12 and 24 months post-PORT ( > .05).

Conclusion: Eliminating PORT to the PN0 neck resulted in excellent control rates in the unirradiated neck without long-term adverse effects on global QOL.
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http://dx.doi.org/10.1200/JCO.19.00186DOI Listing
October 2019

Practical Clinical Workflows for Online and Offline Adaptive Radiation Therapy.

Semin Radiat Oncol 2019 07;29(3):219-227

Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO. Electronic address:

Adaptive radiotherapy emerged over 20 years ago and is now an established clinical practice in a number of organ sites. No one solution for adaptive therapy exists. Rather, adaptive radiotherapy is a process which combines multiple tools for imaging, assessment of need for adaptation, treatment planning, and quality assurance of this process. Workflow is therefore a critical aspect to ensure safe, effective, and efficient implementation of adaptive radiotherapy. In this work, we discuss the tools for online and offline adaptive radiotherapy and introduce workflow concepts for these types of adaptive radiotherapy. Common themes and differences between the workflows are introduced and controversies and areas of active research are discussed.
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http://dx.doi.org/10.1016/j.semradonc.2019.02.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6487881PMC
July 2019

First Reported Case of Pediatric Radiation Treatment With Magnetic Resonance Image Guided Radiation Therapy.

Adv Radiat Oncol 2019 Apr-Jun;4(2):233-236. Epub 2019 Jan 31.

Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.

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http://dx.doi.org/10.1016/j.adro.2019.01.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460231PMC
January 2019

MRI safety risks in the obese: The case of the disposable lighter stored in the pannus.

Radiol Case Rep 2019 May 15;14(5):634-638. Epub 2019 Mar 15.

Department of Radiation Oncology, Washington University School of Medicine, 4921 Parkview Place, St. Louis, MO 63110, US.

Obese patients constitute 40% of the adult population. MRIs of obese patients are typically challenging because of the effects of a large field of view on image quality and the increased risk of thermal burns from contact with the bore. In this case report, the impacts of obesity on MRI procedures and safety are introduced. Then a case is presented of a 30-year old female cervical cancer patient who received an MRI simulation to verify the placement of a titanium tandem and colpostats for brachytherapy. A large magnetic susceptibility artifact was detected near the right pelvis during the MRI scout indicating the presence of ferrous material. The source of the artifact turned out to be a disposable lighter that was stored inside the patient's pannus. The finding highlights an unanticipated risk to MRI safety and image quality associated with large body habitus.
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http://dx.doi.org/10.1016/j.radcr.2019.02.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6424094PMC
May 2019

Stereotactic MR-Guided Online Adaptive Radiation Therapy (SMART) for Ultracentral Thorax Malignancies: Results of a Phase 1 Trial.

Adv Radiat Oncol 2019 Jan-Mar;4(1):201-209. Epub 2018 Oct 18.

Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri.

Purpose: Stereotactic body radiation therapy (SBRT) is an effective treatment for oligometastatic or unresectable primary malignancies, although target proximity to organs at risk (OARs) within the ultracentral thorax (UCT) limits safe delivery of an ablative dose. Stereotactic magnetic resonance (MR)-guided online adaptive radiation therapy (SMART) may improve the therapeutic ratio using reoptimization to account for daily variation in target and OAR anatomy. This study assessed the feasibility of UCT SMART and characterized dosimetric and clinical outcomes in patients treated for UCT lesions on a prospective phase 1 trial.

Methods And Materials: Five patients with oligometastatic (n = 4) or unresectable primary (n = 1) UCT malignancies underwent SMART. Initial plans prescribed 50 Gy in 5 fractions with goal 95% planning target volume (PTV) coverage by 95% of prescription, subject to strict OAR constraints. Daily real-time online adaptive plans were created as needed to preserve hard OAR constraints, escalate PTV dose, or both, based on daily setup MR image set anatomy. Treatment times, patient outcomes, and dosimetric comparisons were prospectively recorded.

Results: All initial and daily adaptive plans met strict OAR constraints based on simulation and daily setup MR imaging anatomy, respectively. Four of the 5 patients received ≥1 adapted fraction. Ten of the 25 total delivered fractions were adapted. A total of 30% of plan adaptations were performed to improve PTV coverage; 70% were for reversal of ≥1 OAR violation. Local control by Response Evaluation Criteria in Solid Tumors was 100% at 3 and 6 months. No grade ≥3 acute (within 6 months of radiation completion) treatment-related toxicities were identified.

Conclusions: SMART may allow PTV coverage improvement and/or OAR sparing compared with nonadaptive SBRT and may widen the therapeutic index of UCT SBRT. In this small prospective cohort, we found that SMART was clinically deliverable to 100% of patients, although treatment delivery times surpassed our predefined, timing-based feasibility endpoint. This technique is well tolerated, offering excellent local control with no identified acute grade ≥3 toxicity.
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http://dx.doi.org/10.1016/j.adro.2018.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6349650PMC
October 2018

A Multi-Institutional Experience of MR-Guided Liver Stereotactic Body Radiation Therapy.

Adv Radiat Oncol 2019 Jan-Mar;4(1):142-149. Epub 2018 Aug 23.

Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.

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 χ 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.
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http://dx.doi.org/10.1016/j.adro.2018.08.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6349638PMC
August 2018

Characterization of a prototype rapid kilovoltage x-ray image guidance system designed for a ring shape radiation therapy unit.

Med Phys 2019 Mar 13;46(3):1355-1370. Epub 2019 Feb 13.

Department of Radiation Oncology, Washington University, St. Louis, MO, 63110, USA.

Purpose: This study aims to characterize the performance of a prototype rapid kilovoltage (kV) x-ray image guidance system onboard the newly released Halcyon 2.0 linear accelerator (Varian Medical Systems, Palo Alto, CA) by use of conventional and innovatively designed testing procedures.

Methods: Basic imaging system performance tests and radiation dose measurements were performed for all eleven kV-cone beam computed tomography (CBCT) imaging protocols available on a preclinical Halcyon 2.0 LINAC. Both conventional CBCT reconstruction using the Feldkamp-Davis-Kress (FDK) algorithm and a novel, advanced iterative reconstruction (iCBCT) available on this platform were evaluated. Standard image quality metrics, including slice thickness accuracy, high-contrast resolution, low-contrast resolution, regional uniformity and noise, and CT Hounsfield unit (HU) number accuracy and linearity were evaluated using a manufacturer-supplied QUART phantom (GmbH, Zorneding, Germany) and an independent image quality phantom (Catphan 500, The Phantom Laboratory, New York, NY). Due to the simplified design of the QUART phantom, we developed surrogate and clinically feasible strategies for measuring slice thickness and high- and low-contrast resolution. Imaging dose delivered by these eleven protocols was measured using a computed tomography dose index phantom and pencil chamber with commonly accepted methods and procedures. A subset of measurements were repeated on a conventional C-arm LINAC (TrueBeam and Trilogy, Varian Medical System) for comparison. Clinical patient images of pelvic and abdominal regions are also presented for qualitative assessment as part of a feasibility study for clinical implementation.

Results: Image acquisition time was 17-42 s on the Halcyon system compared with 60 s on the C-arm LINAC systems. The kV imager projection offset, imaging and treatment isocenter coincidence and the couch three-dimensional match movement all achieved less than1 mm mechanical accuracy. All major image quality metrics were within either the national guideline or vendor-recommended tolerances. The designed surrogate approach with the QUART phantom showed a range of 0.24-0.35 cycles/mm for spatial resolution, a contrast-to-noise ratio (CNR) of 2-20 for FDK reconstruction and a tolerance of 0.5 mm for slice thickness. Other metrics derived from the Catphan images obtained on the Halcyon and C-arm LINACs showed comparable values for the FDK reconstruction. The iterative reconstruction tended to reduce noise, as evidenced by a higher CNR ratio. The fast scan pelvis protocols for Halcyon resulted in 50% lower dose compared to the standard scans, and the thorax fast protocol similarly delivered 10% lower dose than the standard thoracic scan. Preliminary patient images indicated that rapid kV CBCT with breath-hold is feasible, with improved imaging quality compared to free-breathing scans.

Conclusion: Independent and comprehensive characterization of the kV imaging guidance system on the Halcyon 2.0 system demonstrated acceptable image quality for clinical use. The imaging unit onboard the Halcyon meets vendor specifications and satisfies requirements for routine clinical use. The fast kV imaging system enables the potential for volumetric CBCT acquisition during a single breath-hold and the iterative reconstruction tends to reduce the noise therefore has the potential to improve the CNR for normal size patient.
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http://dx.doi.org/10.1002/mp.13396DOI Listing
March 2019

Delineation of a Cardiac Planning Organ-At-Risk Volume Using Real-Time Magnetic Resonance Imaging for Cardiac Protection in Thoracic and Breast Radiation Therapy.

Pract Radiat Oncol 2019 May 18;9(3):e298-e306. Epub 2018 Dec 18.

Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri. Electronic address:

Purpose: Cardiac radiation is associated with cardiotoxicity in patients with thoracic and breast malignancies. We conducted a prospective study using cine magnetic resonance imaging (MRI) scans to evaluate heart motion. We hypothesized that cine MRI could be used to define population-based cardiac planning organ-at-risk volumes (PRV).

Methods And Materials: A total of 16 real-time acquisitions were obtained per subject on a 1.5 Tesla MRI (Philips Ingenia). Planar cine MRI was performed in 4 sequential sagittal and coronal planes at free-breathing (FB) and deep-inspiratory breath hold (DIBH). In-plane cardiac motion was assessed using a scale-invariant feature transformation-based algorithm. Subject-specific pixel motion ranges were defined in anteroposterior (AP), left-right (LR), and superoinferior (SI) planes. Averages of the 98% and 67% of the maximum ranges of pixel displacement were defined by subject, then averaged across the cohort to calculate PRV expansions at FB and DIBH.

Results: Data from 20 subjects with a total of 3120 image frames collected per subject in coronal and sagittal planes at DIBH and FB, and 62,400 total frames were analyzed. Cohort averages of 98% of the maximum cardiac motion ranges comprised margin expansions of 12.5 ± 1.1 mm SI, 5.8 ± 1.2 mm AP, and 6.6 ± 1.0 mm LR at FB and 6.7 ± 1.5 mm SI, 4.7 ± 1.3 mm AP, and 5.3 ± 1.3 mm LR at DIBH. Margins for 67% of the maximum range comprised 7.7 ± 0.7 mm SI, 3.2 ± 0.6 mm AP, and 3.7 ± 0.6 mm LR at FB and 4.1 ± 0.9 mm SI, 2.7 ± 0.8 mm AP, and 3.2 ± 0.8 mm LR at DIBH. Subsequently, these margins were simplified to form PRVs for treatment planning.

Conclusions: We implemented scale-invariant feature transformation-based motion tracking for analysis of the cardiac cine MRI scans to quantify motion and create cohort-based cardiac PRVs to improve cardioprotection in breast and thoracic radiation.
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http://dx.doi.org/10.1016/j.prro.2018.12.004DOI Listing
May 2019

A molecular approach combined with American Thyroid Association classification better stratifies recurrence risk of classic histology papillary thyroid cancer.

Cancer Med 2019 01 14;8(1):437-446. Epub 2018 Dec 14.

Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.

Background: Prognosis among patients with differentiated thyroid cancer is widely variable. Better understanding of biologic subtypes is necessary to stratify patients and improve outcomes.

Methods: In patients diagnosed with classic histology papillary thyroid cancer treated from 1973 to 2009, BRAF V600E mutation status was determined on surgical tumor specimens by restriction fragment length polymorphism analysis. A tissue microarray (TMA) was constructed from tumor specimens in triplicate and stained by immunohistochemistry for RET, phospho-MEK, MAPK(dpERK), PPARγ, and phospho-AKT(pAKT). Stained slides were scored independently and blindly by two investigators and compared to tumor and patient characteristics and outcomes.

Results: A total of 231 patients had archived formalin-fixed, paraffin-embedded tumor tissue available and were included on the TMA. Mean age at diagnosis was 44 years (range 6-82 years); proportion of patients with female sex was (72%); 2015 American Thyroid Association (ATA) risk stratification was low (26%), intermediate (32%), and high (42%). BRAF V600E mutation was found in 74% of specimens, and IHC was scored as positive for RET (61%), MAPK (dpERK) (14%), PPARγ (27%), and pAKT (39%). Positive RET staining was associated with a lower risk of recurrence (HR = 0.46, 95% CI 0.22-0.96). No other molecular biomarkers were independent predictors of recurrence on univariable analysis. On RPA, patients with RET-negative and either MAPK(dpERK)-positive or pAKT-positive tumors were identified to have a high risk of recurrence (HR = 5.4, 95%CI 2.5-11.7). This profile remained associated with recurrence in a multivariable model including ATA risk stratification (HR = 2.8, 95% CI 1.3-6.0).

Conclusion: Characterization of molecular pathways involved in cPTC tumorigenesis may add further risk stratification for recurrence beyond the 2015 ATA risk categories alone.
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http://dx.doi.org/10.1002/cam4.1857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6346248PMC
January 2019

Long-term outcomes of follicular variant vs classic papillary thyroid carcinoma.

Endocr Connect 2018 Dec;7(12):1226-1235

Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.

The majority of papillary thyroid carcinoma (PTC) cases comprise classic papillary (C-PTC) and follicular variant (FV-PTC) histologic sub-types. Historically, clinical equivalency was assumed, but recent data suggest C-PTC may have poorer outcomes. However, large single-institution series with long-term outcomes of C-PTC and FV-PTC, using modern pathologic criteria for FV-PTC, are needed. Our objective was to compare prevalence and impact of clinicopathologic factors, including BRAF mutation status, on long-term outcomes of C-PTC and FV-PTC. We hypothesized that patients with C-PTC would have higher risk disease features and worse survival outcomes. This retrospective study included 1293 patients treated at a single, US academic institution between 1943 and 2009 with mean follow-up of 8.6 years. All patients underwent either partial or total thyroidectomy and had invasive C-PTC or FV-PTC per modern pathology criteria. Primary study measurements included differences in recurrence-free survival (RFS), disease-specific survival (DSS) and associations with clinicopathologic factors including the BRAF mutation. Compared to FV-PTC, C-PTC was associated with multiple features of high-risk disease (P < 0.05) and significantly reduced RFS and DSS. Survival differences were consistent across univariate, multivariate and Kaplan-Meier analyses. BRAF mutations were more common in C-PTC (P = 0.002). However, on Kaplan-Meier analysis, mutational status did not significantly impact RFS or DSS for patients with either histologic sub-type. C-PTC therefore indicates higher-risk disease and predicts for significantly poorer long-term outcomes when compared to FV-PTC. The nature of this difference in outcome is not explained by traditional histopathologic findings or by the BRAF mutation.
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http://dx.doi.org/10.1530/EC-18-0264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240143PMC
December 2018

A novel MRI segmentation method using CNN-based correction network for MRI-guided adaptive radiotherapy.

Med Phys 2018 Nov 28;45(11):5129-5137. Epub 2018 Oct 28.

Department of Radiation Oncology, School of Medicine, Washington University in Saint Louis, St.Louis, MO, 63110, USA.

Purpose: The purpose of this study was to expedite the contouring process for MRI-guided adaptive radiotherapy (MR-IGART), a convolutional neural network (CNN) deep-learning (DL) model is proposed to accurately segment the liver, kidneys, stomach, bowel and duodenum in 3D MR images.

Methods: Images and structure contours for 120 patients were collected retrospectively. Treatment sites included pancreas, liver, stomach, adrenal gland, and prostate. The proposed DL model contains a voxel-wise label prediction CNN and a correction network which consists of two sub-networks. The prediction CNN and sub-networks in the correction network each includes a dense block which consists of twelve densely connected convolutional layers. The correction network was designed to improve the voxel-wise labeling accuracy of a CNN by learning and enforcing implicit anatomical constraints in the segmentation process. Its sub-networks learn to fix the erroneous classification of its previous network by taking as input both the original images and the softmax probability maps generated from its previous sub-network. The parameters of each sub-network were trained independently using piecewise training. The model was trained on 100 datasets, validated on 10 datasets and tested on the remaining 10 datasets. Dice coefficient, Hausdorff distance (HD) were calculated to evaluate the segmentation accuracy.

Results: The proposed DL model was able to segment the organs with good accuracy. The correction network outperformed the conditional random field (CRF), a most comparable method that is usually applied as a post-processing step. For the 10 testing patients, the average Dice coefficients were 95.3 ± 0.73, 93.1 ± 2.22, 85.0 ± 3.75, 86.6 ± 2.69, and 65.5 ± 8.90 for liver, kidneys, stomach, bowel, and duodenum, respectively. The mean Hausdorff Distance (HD) were 5.41 ± 2.34, 6.23 ± 4.59, 6.88 ± 4.89, 5.90 ± 4.05, and 7.99 ± 6.84 mm, respectively. Manual contouring, as to correct the automatic segmentation results, was four times as fast as manual contouring from scratch.

Conclusion: The proposed method can automatically segment the liver, kidneys, stomach, bowel, and duodenum in 3D MR images with good accuracy. It is useful to expedite the manual contouring for MR-IGART.
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http://dx.doi.org/10.1002/mp.13221DOI Listing
November 2018

Palliative radiation therapy (RT) for prostate cancer patients with bone metastases at diagnosis: A hospital-based analysis of patterns of care, RT fractionation scheme, and overall survival.

Cancer Med 2018 09 17;7(9):4240-4250. Epub 2018 Aug 17.

Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA.

Prostate cancer (PCa) is one of the most common malignancies associated with bone metastases, and palliative radiation therapy (RT) is an effective treatment option. A total of 2641 patients were identified with PCa and bone metastases at diagnosis from 2010 to 2014 in the NCDB. Fractionation scheme was designated as short course ([SC-RT]: 8 Gy in 1 fraction and 20 Gy in 5 fractions) vs long course ([LC-RT]: 30 Gy in 10 fractions and 37.5 Gy in 15 fractions). Patient characteristics were correlated with fractionation scheme using logistic regression. Overall survival was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, and propensity score-matched analyses. A total of 2255 (85.4%) patients were included in the LC-RT group and 386 (14.6%) patients in the SC-RT group. SC-RT was more common in patients over 75 years age (odds ratio [OR]: 1.70, 95% confidence interval [CI] 1.32-2.20), treatment at an academic center (OR: 1.76, 1.20-2.57), living greater than 15 miles distance to treatment facility (OR: 1.38, 1.05-1.83), treatment to the rib (OR: 2.99, 1.36-6.60), and in 2014 (OR: 1.73, 1.19-2.51). RT to the spine was more commonly long course (P < .0001). In the propensity-matched cohort, LC-RT was associated with improved OS (P < .0001), but no OS difference was observed between 37.5 Gy and either 8 Gy in one fraction or 20 Gy in 5 fractions (P > .5). LC-RT remains the most common treatment fractionation scheme for palliative bone metastases in PCa patients. Use of palliative SC-RT is increasing, particularly in more recent years, for older patients, treatment at academic centers, and with increasing distance from a treatment center.
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http://dx.doi.org/10.1002/cam4.1655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6144149PMC
September 2018

In Silico Trial of MR-Guided Midtreatment Adaptive Planning for Hypofractionated Stereotactic Radiation Therapy in Centrally Located Thoracic Tumors.

Int J Radiat Oncol Biol Phys 2018 11 25;102(4):987-995. Epub 2018 Jun 25.

Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri. Electronic address:

Purpose: Hypofractionated (>5 fraction) stereotactic radiation therapy (HSRT) may allow for ablative biologically equivalent dose to tumors with a lower risk of organ-at-risk (OAR) toxicity in central thoracic tumors. Adaptive planning may further improve OAR sparing while maintaining planning target volume (PTV) coverage. We hypothesized that midtreatment adaptive replanning would offer dosimetric advantages during HSRT for central thorax malignancies using magnetic resonance imaging (MRI)-guided radiation therapy.

Methods And Materials: Twelve patients with central thorax tumors received HSRT using MRI-guided radiation therapy. Clinically delivered regimens were 60 Gy in 12 fractions or 62.5 Gy in 10 fractions, with low-field magnetic resonance (0.35 T) volumetric setup imaging acquired at each fraction. Daily gross tumor volume (GTV) and OARs were retrospectively redefined on fraction 1, 6, and 10 MRIs, and GTV response was recorded. Simulated initial plans prescribed a dose of 60 Gy in 12 fractions based on fraction 1 MRI. Midtreatment adaptive plans were created based on fraction 6 anatomy-of-the-day. All plans were created using an isotoxicity approach with a goal of 95% PTV coverage, subject to hard OAR constraints, to represent clinically ideal OAR sparing. Plans were then compared for projected OAR sparing and PTV coverage.

Results: Patients demonstrated significant on-treatment MRI-defined GTV reduction (median 41.8%; range 16.7%-65.7%). At fraction 6, median reduction was 26.7%. All initial plans met OAR constraints. Initial plan application to fraction 6 and fraction 10 anatomy resulted in 8 OAR violations (5 of 13 patients) and 10 OAR violations (6 of 13 patients). All fraction 6 violations persisted at fraction 10. Midpoint adaptive planning reversed 100% of midpoint OAR violations and tended to reduce the magnitude of OAR violations incurred at fraction 10. In 40% of fractions (2 of 5) in which OAR violation resulted from initial plan application to fraction 6 anatomy, PTV coverage was increased concomitant with violation reversal.

Conclusions: Midtreatment adaptive planning based on tumor response may be dosimetrically advantageous for sparing of surrounding critical structures in HSRT for central thorax malignancies and could be applied using either an online or offline paradigm.
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http://dx.doi.org/10.1016/j.ijrobp.2018.06.022DOI Listing
November 2018

Practical Implications of Ferromagnetic Artifacts in Low-field MRI-guided Radiotherapy.

Cureus 2018 Mar 22;10(3):e2359. Epub 2018 Mar 22.

Radiation Oncology, Washington University School of Medicine, Barnes-Jewish Hospital.

Fractionated radiotherapy presents a new challenge in the screening of patients undergoing magnetic resonance imaging-guided radiotherapy (MR-IGRT). In our institution, patients are evaluated at the time of consult, simulation, and first fraction using a thorough MRI questionnaire identical to the one used for diagnostic radiology patients. For each subsequent fraction, the therapists are trained to inquire about any procedures the patient may have had between the last and current fractions. Patients are also advised to avoid food and fluid intake at least two but not beyond four hours prior to treatment. Despite these screening efforts, we have observed several non-permanent imaging artifacts that, while not harmful to the patient, prevent the accurate delivery of MR-IGRT when using online adaptive radiotherapy due to interference with the identification of relevant anatomy. Two such cases are presented here: (1) an imaging artifact due to iron-enriched breakfast cereal that precluded treatment for that day, and (2) an imaging artifact due to an iron-containing multivitamin that necessitated a creative solution to enable the accurate visualization of the area to be treated.
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http://dx.doi.org/10.7759/cureus.2359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5963946PMC
March 2018

Phase I trial of stereotactic MR-guided online adaptive radiation therapy (SMART) for the treatment of oligometastatic or unresectable primary malignancies of the abdomen.

Radiother Oncol 2018 Mar 23;126(3):519-526. Epub 2017 Dec 23.

Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, United States.

Purpose/objectives: SBRT is used to treat oligometastatic or unresectable primary abdominal malignancies, although ablative dose delivery is limited by proximity of organs-at-risk (OAR). Stereotactic, magnetic resonance (MR)-guided online-adaptive radiotherapy (SMART) may improve SBRT's therapeutic ratio. This prospective Phase I trial assessed feasibility and potential advantages of SMART to treat abdominal malignancies.

Materials/methods: Twenty patients with oligometastatic or unresectable primary liver (n = 10) and non-liver (n = 10) abdominal malignancies underwent SMART. Initial plans prescribed 50 Gy/5 fractions (BED 100 Gy) with goal 95% PTV coverage by 95% of prescription, subject to hard OAR constraints. Daily real-time online-adaptive plans were created as needed, based on daily setup MR-image-set tumor/OAR "anatomy-of-the-day" to preserve hard OAR constraints, escalate PTV dose, or both. Treatment times, patient outcomes, and dosimetric comparisons between initial and adaptive plans were prospectively recorded.

Results: Online adaptive plans were created at time of treatment for 81/97 fractions, due to initial plan violation of OAR constraints (61/97) or observed opportunity for PTV dose escalation (20/97). Plan adaptation increased PTV coverage in 64/97 fractions. Zero Grade ≥ 3 acute (<6 months) treatment-related toxicities were observed.

Discussion: SMART is clinically deliverable and safe, allowing PTV dose escalation and/or simultaneous OAR sparing compared to non-adaptive abdominal SBRT.
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http://dx.doi.org/10.1016/j.radonc.2017.11.032DOI Listing
March 2018

Two-and-a-half-year clinical experience with the world's first magnetic resonance image guided radiation therapy system.

Adv Radiat Oncol 2017 Jul-Sep;2(3):485-493. Epub 2017 Jun 1.

Washington University, Department of Radiation Oncology, St. Louis, Missouri.

Purpose: Magnetic resonance image guided radiation therapy (MR-IGRT) has been used at our institution since 2014. We report on more than 2 years of clinical experience in treating patients with the world's first MR-IGRT system.

Methods And Materials: A clinical service was opened for MR-IGRT in January 2014 with an MR-IGRT system consisting of a split 0.35T magnetic resonance scanner that straddles a ring gantry with 3 multileaf collimator-equipped Co heads. The service was expanded to include online adaptive radiation therapy (ART) MR-IGRT and cine gating after 6 and 9 months, respectively. Patients selected for MR-IGRT were enrolled in a prospective registry between January 2014 and June 2016. Patients were treated with a variety of radiation therapy techniques including intensity modulated radiation therapy and stereotactic body radiation therapy (SBRT). When applicable, online ART was performed and gating on sagittal 2-dimensional cine MR was used. The charts of patients treated with MR-IGRT were reviewed to report on the clinical and treatment characteristics of the initial patients who were treated with this novel technique.

Results: A total of 316 patients have been treated with the MR-IGRT system, which has been integrated into a high-volume clinic. The cases were most commonly selected for improved soft tissue visualization, ART, and cine gating. Seventy-six patients were treated with 3-dimensional conformal radiation therapy, 146 patients with intensity modulated radiation therapy, and 94 patients with SBRT. The most commonly treated disease sites were the abdomen (28%), breast (26%), pelvis (22%), thorax (19%), and head and neck (5%). Sixty-seven patients were treated with online ART over a total of 244 adapted fractions. Cine treatment gating was used for a total of 81 patients.

Conclusions: MR-IGRT has been successfully implemented in a high-volume radiation clinic and provides unique advantages in the treatment of a variety of malignancies. Additional clinical trials are in development to formally evaluate MR-IGRT in the treatment of multiple disease sites with techniques such as SBRT and ART.
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http://dx.doi.org/10.1016/j.adro.2017.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605309PMC
June 2017

Serum squamous cell carcinoma antigen as an early indicator of response during therapy of cervical cancer.

Br J Cancer 2018 01 7;118(1):72-78. Epub 2017 Nov 7.

Department of Radiation Oncology, Washington University School of Medicine, St Louis, MO 63110, USA.

Background: Pretreatment serum squamous cell carcinoma antigen (SCCA) is a prognostic biomarker in women with cervical cancer. SCCA has not been evaluated as an early indicator of response to chemoradiation therapy (CRT). The molecular role of the two SCCA isoforms, SCCA1 (SERPINB3) and SCCA2 (SERPINB4), in cervical cancer is unknown. We hypothesised that changes in serum SCCA during definitive CRT predicts treatment response, and that SCCA1 mediates radiation resistance.

Methods: Patients treated with definitive CRT for cervical squamous carcinoma with serum SCCA measured were included. SCCA immunohistochemistry was performed on tumour biopsies. Post-treatment FDG-PET/CT, recurrence, and overall survival were recorded. Radiation response of cervical tumour cell lines after SCCA1 expression or CRISPR/Cas9 knockout was evaluated by clonogenic survival assay.

Results: Persistently elevated serum SCCA during definitive CRT was an independent predictor of positive post-therapy FDG-PET/CT (P=0.043), recurrence (P=0.0046) and death (P=0.015). An SCCA1-expressing vector increased radioresistance, while SCCA knock out increased radiosensitivity of cervical tumour cell lines in vitro.

Conclusions: Early response assessment with serum SCCA is a powerful prognostic tool. These findings suggest that escalation of therapy in patients with elevated or sustained serum SCCA and molecular targeting of SCCA1 should be considered.
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http://dx.doi.org/10.1038/bjc.2017.390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765231PMC
January 2018