Publications by authors named "Caroline Chung"

107 Publications

A Prospective Phase II Randomized Trial of Proton Radiotherapy vs. Intensity Modulated Radiotherapy for Patients with Newly Diagnosed Glioblastoma.

Neuro Oncol 2021 Feb 27. Epub 2021 Feb 27.

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

Background: To determine if proton radiotherapy (PT), compared to intensity modulated radiotherapy (IMRT), delayed time to cognitive failure in patients with newly diagnosed glioblastoma.

Methods: Eligible patients were randomized unblinded to PT vs. IMRT. The primary endpoint was time to cognitive failure. Secondary endpoints included overall survival (OS), intracranial progression-free survival (PFS), toxicity, and patient-reported outcomes.

Results: A total of 90 patients were enrolled and 67 were evaluable with median follow-up of 48.7 months (range 7.1-66.7). There was no significant difference in time to cognitive failure between treatment arms (HR, 0.88; 95% CI, 0.45 to 1.75; P=0.74). PT was associated with a lower rate of fatigue (24% vs. 58%, P=0.05), but otherwise there were no significant differences in patient-reported outcomes at 6 months. There was no difference in PFS (HR, 0.74; 95% CI, 0.44 to 1.23; P=0.24) or OS (HR, 0.86; 95% CI, 0.49 to 1.50; P=0.60). However, PT significantly reduced the radiation dose for nearly all structures analyzed. The average number of grade 2 or higher toxicities was significantly higher in patients who received IMRT (mean 1.15, range 0-6) compared to PT (mean 0.35, range 0-3; P=0.02).

Conclusions: In this signal seeking phase II trial, PT was not associated with a delay in time to cognitive failure but did reduce toxicity and patient reported fatigue. Larger randomized trials are needed to determine the potential of PT such as dose escalation for glioblastoma and cognitive preservation in patients with lower grade gliomas with a longer survival time.
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http://dx.doi.org/10.1093/neuonc/noab040DOI Listing
February 2021

The COVID-19 & Cancer Consortium (CCC19) and Opportunities for Radiation Oncology.

Adv Radiat Oncol 2021 Jan-Feb;6(1):100614. Epub 2020 Dec 24.

Department of Radiation Oncology, George Washington University School of Medicine and Health Sciences, Washington, DC.

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http://dx.doi.org/10.1016/j.adro.2020.10.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834122PMC
December 2020

Evaluation of a multiview architecture for automatic vertebral labeling of palliative radiotherapy simulation CT images.

Med Phys 2020 Nov 15;47(11):5592-5608. Epub 2020 Sep 15.

Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.

Purpose: The purpose of this work was to evaluate the performance of X-Net, a multiview deep learning architecture, to automatically label vertebral levels (S2-C1) in palliative radiotherapy simulation CT scans.

Methods: For each patient CT scan, our automated approach 1) segmented spinal canal using a convolutional-neural network (CNN), 2) formed sagittal and coronal intensity projection pairs, 3) labeled vertebral levels with X-Net, and 4) detected irregular intervertebral spacing using an analytic methodology. The spinal canal CNN was trained via fivefold cross validation using 1,966 simulation CT scans and evaluated on 330 CT scans. After labeling vertebral levels (S2-C1) in 897 palliative radiotherapy simulation CT scans, a volume of interest surrounding the spinal canal in each patient's CT scan was converted into sagittal and coronal intensity projection image pairs. Then, intensity projection image pairs were augmented and used to train X-Net to automatically label vertebral levels using fivefold cross validation (n = 803). Prior to testing upon the final test set (n = 94), CT scans of patients with anatomical abnormalities, surgical implants, or other atypical features from the final test set were placed in an outlier group (n = 20), whereas those without these features were placed in a normative group (n = 74). The performance of X-Net, X-Net Ensemble, and another leading vertebral labeling architecture (Btrfly Net) was evaluated on both groups using identification rate, localization error, and other metrics. The performance of our approach was also evaluated on the MICCAI 2014 test dataset (n = 60). Finally, a method to detect irregular intervertebral spacing was created based on the rate of change in spacing between predicted vertebral body locations and was also evaluated using the final test set. Receiver operating characteristic analysis was used to investigate the performance of the method to detect irregular intervertebral spacing.

Results: The spinal canal architecture yielded centroid coordinates spanning S2-C1 with submillimeter accuracy (mean ± standard deviation, 0.399 ± 0.299 mm; n = 330 patients) and was robust in the localization of spinal canal centroid to surgical implants and widespread metastases. Cross-validation testing of X-Net for vertebral labeling revealed that the deep learning model performance (F score, precision, and sensitivity) improved with CT scan length. The X-Net, X-Net Ensemble, and Btrfly Net mean identification rates and localization errors were 92.4% and 2.3 mm, 94.2% and 2.2 mm, and 90.5% and 3.4 mm, respectively, in the final test set and 96.7% and 2.2 mm, 96.9% and 2.0 mm, and 94.8% and 3.3 mm, respectively, within the normative group of the final test set. The X-Net Ensemble yielded the highest percentage of patients (94%) having all vertebral bodies identified correctly in the final test set when the three most inferior and superior vertebral bodies were excluded from the CT scan. The method used to detect labeling failures had 67% sensitivity and 95% specificity when combined with the X-Net Ensemble and flagged five of six patients with atypical vertebral counts (additional thoracic (T13), additional lumbar (L6) or only four lumbar vertebrae). Mean identification rate on the MICCAI 2014 dataset using an X-Net Ensemble was increased from 86.8% to 91.3% through the use of transfer learning and obtained state-of-the-art results for various regions of the spine.

Conclusions: We trained X-Net, our unique convolutional neural network, to automatically label vertebral levels from S2 to C1 on palliative radiotherapy CT images and found that an ensemble of X-Net models had high vertebral body identification rate (94.2%) and small localization errors (2.2 ± 1.8 mm). In addition, our transfer learning approach achieved state-of-the-art results on a well-known benchmark dataset with high identification rate (91.3%) and low localization error (3.3 mm ± 2.7 mm). When we pre-screened radiotherapy CT images for the presence of hardware, surgical implants, or other anatomic abnormalities prior to the use of X-Net, it labeled the spine correctly in more than 97% of patients and 94% of patients when scans were not prescreened. Automatically generated labels are robust to widespread vertebral metastases and surgical implants and our method to detect labeling failures based on neighborhood intervertebral spacing can reliably identify patients with an additional lumbar or thoracic vertebral body.
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http://dx.doi.org/10.1002/mp.14415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756475PMC
November 2020

Simultaneous Truth and Performance Level Estimation Method for Evaluation of Target Contouring in Radiosurgery.

Anticancer Res 2021 Jan;41(1):279-288

The Skandion Clinic, Uppsala, Sweden.

Background/aim: The problem of lack of standardisation in target delineation and herewith the variability of target contours in Gamma Knife radiosurgery is as severe as in linac-based radiotherapy in general. The first aim of this study was to quantify the contouring variability for a group of five radiosurgery targets and estimate their true-volume based on multiple delineations using the Simultaneous Truth and Performance Level Estimation (STAPLE) algorithm. The second aim was to assess the robustness of the STAPLE method for the assessment of the true-volume, with respect to the number of contours available as input.

Patients And Methods: A multicentre analysis of the variability in contouring of five cases was performed. Twelve contours were provided for each case by experienced planners for Gamma Knife. To assess the robustness of the STAPLE method with respect to the number of contours used as input, sets of contours were randomly selected in the analysis.

Results: A high similarity was observed between the STAPLE generated true-volume and the 50%-agreement volume when all 12 available contours were used as input (90-100%). Lower similarity was observed with smaller sets of contours (10-70%).

Conclusion: If a high number of input contours is available, the STAPLE method provides a valuable tool in the estimation of the true volume of a target based on multiple contours as well as the sensitivity and specificity for each input contour relative to the true volume of that structure. The robustness of the STAPLE method for rendering the true target volume depends on the number of contours provided as input and their variability with respect to shape, size and position.
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http://dx.doi.org/10.21873/anticanres.14774DOI Listing
January 2021

In the Era of Deep Learning, Why Reconstruct an Image at All?

J Am Coll Radiol 2021 Jan;18(1 Pt B):170-173

Chief Technology and Digital Officer, The University of Texas MD Anderson Cancer Center, Houston, Texas.

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http://dx.doi.org/10.1016/j.jacr.2020.09.050DOI Listing
January 2021

The Provocative: A Glimpse Into Radiology's Future.

J Am Coll Radiol 2021 Jan;18(1 Pt B):137-139

Director, Northwest Screening and Cancer Outcomes Research Enterprise, Department of Radiology, University of Washington School of Medicine, Seattle, Washington. Electronic address:

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http://dx.doi.org/10.1016/j.jacr.2020.10.007DOI Listing
January 2021

A mathematical model for the quantification of a patient's sensitivity to checkpoint inhibitors and long-term tumour burden.

Nat Biomed Eng 2021 Jan 4. Epub 2021 Jan 4.

Mathematics in Medicine Program, Houston Methodist Research Institute, Houston, TX, USA.

A large proportion of patients with cancer are unresponsive to treatment with immune checkpoint blockade and other immunotherapies. Here, we report a mathematical model of the time course of tumour responses to immune checkpoint inhibitors. The model takes into account intrinsic tumour growth rates, the rates of immune activation and of tumour-immune cell interactions, and the efficacy of immune-mediated tumour killing. For 124 patients, four cancer types and two immunotherapy agents, the model reliably described the immune responses and final tumour burden across all different cancers and drug combinations examined. In validation cohorts from four clinical trials of checkpoint inhibitors (with a total of 177 patients), the model accurately stratified the patients according to reduced or increased long-term tumour burden. We also provide model-derived quantitative measures of treatment sensitivity for specific drug-cancer combinations. The model can be used to predict responses to therapy and to quantify specific drug-cancer sensitivities in individual patients.
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http://dx.doi.org/10.1038/s41551-020-00662-0DOI Listing
January 2021

Equivalent Efficacy and Safety of Radiosurgery for Cystic and Solid Vestibular Schwannomas: A Systematic Review.

World Neurosurg 2021 Feb 16;146:322-331.e1. Epub 2020 Nov 16.

Penn State Department of Neurosurgery, Hershey, Pennsylvania, USA; Penn State Cancer Institute, Hershey, Pennsylvania, USA. Electronic address:

Background: Cystic vestibular schwannomas (VS) are associated with unpredictable growth behavior and potentially worse surgical outcomes compared with their solid counterparts. Growth control and potential adverse effects of radiosurgery for cystic VS have created concerns surrounding this modality. We sought to compare the treatment efficacy and safety profile of radiosurgery between cystic and solid VS through a systematic review.

Methods: PubMed, EMBASE, Web of Science, and Cochrane were searched for related terms and studies reporting radiosurgical outcomes of cystic and solid VS. A meta-analysis was performed to compare the rates of tumor control. Random-effect models with generic inverse variance method was used to calculate overall pooled estimates. Study quality was assessed with the Newcastle Ottawa Criteria.

Results: In total, 2989 studies were retrieved, and 6 including 1358 VS (79.89% solid; 20.11% cystic, median follow-up range 31.8-150 months) were selected. The median maximal dose was 25 Gy (range, 13-36 Gy) and the median marginal tumor dose was 12 Gy (10-18 Gy). There was no difference between cystic and solid VS (risk ratio, 1.02; 95% confidence interval 0.94-1.10; P = 0.69; I = 78%). Transient enlargement of cystic tumors may be associated with trigeminal or facial neuropathy.

Conclusions: The evidence collected by this study suggests that radiosurgery for cystic VS exhibits effective tumor control probabilities similar to solid VS. Consensus definitions and standard criteria are needed in the future to better understand the patterns of tumor growth and response to treatment following radiosurgery for cystic VS, as well as long-term neurological and functional outcomes.
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http://dx.doi.org/10.1016/j.wneu.2020.11.040DOI Listing
February 2021

Unique Glioma Requiring Unique Management.

Authors:
Caroline Chung

Int J Radiat Oncol Biol Phys 2020 Nov;108(3):520-521

Radiation Oncology and Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

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http://dx.doi.org/10.1016/j.ijrobp.2019.09.021DOI Listing
November 2020

Glioma consensus contouring recommendations from a MR-Linac International Consortium Research Group and evaluation of a CT-MRI and MRI-only workflow.

J Neurooncol 2020 Sep 29;149(2):305-314. Epub 2020 Aug 29.

Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada.

Introduction: This study proposes contouring recommendations for radiation treatment planning target volumes and organs-at-risk (OARs) for both low grade and high grade gliomas.

Methods: Ten cases consisting of 5 glioblastomas and 5 grade II or III gliomas, including their respective gross tumor volume (GTV), clinical target volume (CTV), and OARs were each contoured by 6 experienced neuro-radiation oncologists from 5 international institutions. Each case was first contoured using only MRI sequences (MRI-only), and then re-contoured with the addition of a fused planning CT (CT-MRI). The level of agreement among all contours was assessed using simultaneous truth and performance level estimation (STAPLE) with the kappa statistic and Dice similarity coefficient.

Results: A high level of agreement was observed between the GTV and CTV contours in the MRI-only workflow with a mean kappa of 0.88 and 0.89, respectively, with no statistically significant differences compared to the CT-MRI workflow (p = 0.88 and p = 0.82 for GTV and CTV, respectively). Agreement in cochlea contours improved from a mean kappa of 0.39 to 0.41, to 0.69 to 0.71 with the addition of CT information (p < 0.0001 for both cochleae). Substantial to near perfect level of agreement was observed in all other contoured OARs with a mean kappa range of 0.60 to 0.90 in both MRI-only and CT-MRI workflows.

Conclusions: Consensus contouring recommendations for low grade and high grade gliomas were established using the results from the consensus STAPLE contours, which will serve as a basis for further study and clinical trials by the MR-Linac Consortium.
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http://dx.doi.org/10.1007/s11060-020-03605-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541359PMC
September 2020

Response to Letter to Editor.

Neuro Oncol 2020 11;22(11):1706-1707

UCLA Brain Tumor Imaging Laboratory, Center for Computer Vision and Imaging Biomarkers, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.

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http://dx.doi.org/10.1093/neuonc/noaa202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690353PMC
November 2020

Radiation for Glioblastoma in the Era of Coronavirus Disease 2019 (COVID-19): Patient Selection and Hypofractionation to Maximize Benefit and Minimize Risk.

Adv Radiat Oncol 2020 Jul-Aug;5(4):743-745. Epub 2020 May 27.

Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

We describe the institutional guidelines of a major tertiary cancer center with regard to using hypofractionated radiation regimens to treat glioblastoma as a measure to minimize exposure to coronavirus disease 2019 (COVID-19) while not sacrificing clinical outcomes. Our guidelines review level one evidence of various hypofractionated regimens, and recommend a multidisciplinary approach while balancing the risk of morbidity and mortality among individuals at high risk for severe illness from COVID-19 infection. We also briefly outline strategies our department is taking in mitigating risk among our cancer patients undergoing radiation.
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http://dx.doi.org/10.1016/j.adro.2020.04.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251361PMC
May 2020

Proton therapy reduces the likelihood of high-grade radiation-induced lymphopenia in glioblastoma patients: phase II randomized study of protons vs photons.

Neuro Oncol 2021 Feb;23(2):284-294

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

Background: We investigated differences in radiation-induced grade 3+ lymphopenia (G3+L), defined as an absolute lymphocyte count (ALC) nadir of <500 cells/µL, after proton therapy (PT) or X-ray (photon) therapy (XRT) for patients with glioblastoma (GBM).

Methods: Patients enrolled in a randomized phase II trial received PT (n = 28) or XRT (n = 56) concomitantly with temozolomide. ALC was measured before, weekly during, and within 1 month after radiotherapy. Whole-brain mean dose (WBMD) and brain dose-volume indices were extracted from planned dose distributions. Univariate and multivariate logistic regression analyses were used to identify independent predictive variables. The resulting model was evaluated using receiver operating characteristic (ROC) curve analysis.

Results: Rates of G3+L were lower in men (7/47 [15%]) versus women (19/37 [51%]) (P < 0.001), and for PT (4/28 [14%]) versus XRT (22/56 [39%]) (P = 0.024). G3+L was significantly associated with baseline ALC, WBMD, and brain volumes receiving 5‒40 Gy(relative biological effectiveness [RBE]) or higher (ie, V5 through V40). Stepwise multivariate logistic regression analysis identified being female (odds ratio [OR] 6.2, 95% confidence interval [CI]: 1.95‒22.4, P = 0.003), baseline ALC (OR 0.18, 95% CI: 0.05‒0.51, P = 0.003), and whole-brain V20 (OR 1.07, 95% CI: 1.03‒1.13, P = 0.002) as the strongest predictors. ROC analysis yielded an area under the curve of 0.86 (95% CI: 0.79-0.94) for the final G3+L prediction model.

Conclusions: Sex, baseline ALC, and whole-brain V20 were the strongest predictors of G3+L for patients with GBM treated with radiation and temozolomide. PT reduced brain volumes receiving low and intermediate doses and, consequently, reduced G3+L.
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http://dx.doi.org/10.1093/neuonc/noaa182DOI Listing
February 2021

Vascular Neurologists' Involvement in the Care of Medicare Patients With Ischemic Stroke.

Neurohospitalist 2020 Jul 11;10(3):181-187. Epub 2020 Feb 11.

Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute, New York, NY, USA.

Background And Purpose: We sought to determine the proportion of patients with ischemic stroke evaluated by vascular neurologists in the United States.

Methods: Using 2009 to 2015 claims from a 5% nationally representative sample of Medicare beneficiaries, we identified patients ≥65 years of age who were hospitalized for ischemic stroke. We ascertained the proportion of patients evaluated during the hospitalization or within 90 days of discharge by nonvascular and vascular neurologists. We assessed the relationship between county-level socioeconomic status and the likelihood of neurologist evaluation and between neurologist evaluation and diagnostic testing.

Results: Among 66 989 patients with ischemic stroke, 37 820 (56.5%) were evaluated by a nonvascular neurologist and 11 700 (17.5%) by a board-certified vascular neurologist. Across increasing quartiles of county socioeconomic advantage, the proportion of patients evaluated by a vascular neurologist was 12.2%, 16.5%, 19.8%, and 23.0%. Relative to evaluation by a nonvascular neurologist, evaluation by a vascular neurologist was associated with a higher likelihood of postdischarge heart rhythm monitoring (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.6-1.9), echocardiography (OR, 1.4; 95% CI, 1.3-1.4), cervical vessel imaging (OR, 1.3; 95% CI, 1.2-1.3), and intracranial vessel imaging (OR, 2.1; 95% CI, 2.0-2.2).

Conclusions: In a nationally representative cohort of Medicare beneficiaries, we found that about three quarters of patients with ischemic stroke were evaluated by a neurologist, and about one-sixth were evaluated by a vascular neurologist. Patients who were evaluated by a vascular neurologist were significantly more likely to undergo diagnostic testing.
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http://dx.doi.org/10.1177/1941874420902951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271626PMC
July 2020

A modular phantom and software to characterize 3D geometric distortion in MRI.

Phys Med Biol 2020 09 28;65(19):195008. Epub 2020 Sep 28.

Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States of America.

Magnetic resonance imaging (MRI) offers outstanding soft tissue contrast that may reduce uncertainties in target and organ-at-risk delineation and enable online adaptive image-guided treatment. Spatial distortions resulting from non-linearities in the gradient fields and non-uniformity in the main magnetic field must be accounted for across the imaging field-of-view to prevent systematic errors during treatment delivery. This work presents a modular phantom and software application to characterize geometric distortion (GD) within the large field-of-view MRI images required for radiation therapy simulation. The modular phantom is assembled from a series of rectangular foam blocks containing high-contrast fiducial markers in a known configuration. The modular phantom design facilitates transportation of the phantom between different MR scanners and MR-guided linear accelerators and allows the phantom to be adapted to fit different sized bores or coils. The phantom was evaluated using a 1.5 T MR-guided linear accelerator (MR-Linac) and 1.5 T and 3.0 T diagnostic scanners. Performance was assessed by varying acquisition parameters to induce image distortions in a known manner. Imaging was performed using T1 and T2 weighted pulse sequences with 2D and 3D distortion correction algorithms and the receiver bandwidth (BW) varied as 250-815 Hz pixel. Phantom set-up reproducibility was evaluated across independent set-ups. The software was validated by comparison with a non-modular phantom. Average geometric distortion was 0.94 ± 0.58 mm for the MR-Linac, 0.90 ± 0.53 mm for the 1.5 T scanner, and 1.15 ± 0.62 mm for the 3.0 T scanner, for a 400 mm diameter volume-of-interest. GD increased, as expected, with decreasing BW, and with the 2D versus 3D correction algorithm. Differences in GD attributed to phantom set-up were 0.13 mm or less. Differences in GD for the two software applications were less than 0.07 mm. A novel modular phantom was developed to evaluate distortions in MR images for radiation therapy applications.
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http://dx.doi.org/10.1088/1361-6560/ab9c64DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772054PMC
September 2020

Consensus recommendations for a dynamic susceptibility contrast MRI protocol for use in high-grade gliomas.

Neuro Oncol 2020 09;22(9):1262-1275

Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.

Despite the widespread clinical use of dynamic susceptibility contrast (DSC) MRI, DSC-MRI methodology has not been standardized, hindering its utilization for response assessment in multicenter trials. Recently, the DSC-MRI Standardization Subcommittee of the Jumpstarting Brain Tumor Drug Development Coalition issued an updated consensus DSC-MRI protocol compatible with the standardized brain tumor imaging protocol (BTIP) for high-grade gliomas that is increasingly used in the clinical setting and is the default MRI protocol for the National Clinical Trials Network. After reviewing the basis for controversy over DSC-MRI protocols, this paper provides evidence-based best practices for clinical DSC-MRI as determined by the Committee, including pulse sequence (gradient echo vs spin echo), BTIP-compliant contrast agent dosing (preload and bolus), flip angle (FA), echo time (TE), and post-processing leakage correction. In summary, full-dose preload, full-dose bolus dosing using intermediate (60°) FA and field strength-dependent TE (40-50 ms at 1.5 T, 20-35 ms at 3 T) provides overall best accuracy and precision for cerebral blood volume estimates. When single-dose contrast agent usage is desired, no-preload, full-dose bolus dosing using low FA (30°) and field strength-dependent TE provides excellent performance, with reduced contrast agent usage and elimination of potential systematic errors introduced by variations in preload dose and incubation time.
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http://dx.doi.org/10.1093/neuonc/noaa141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523451PMC
September 2020

Association Between Facility Volume and Overall Survival for Patients with Grade II Meningioma after Gross Total Resection.

World Neurosurg 2020 09 11;141:e133-e144. Epub 2020 May 11.

Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Department of Health Services Research, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Background: The role of adjuvant radiation after gross total resection (GTR) for grade II meningioma is evolving, prompting further evaluation in NRG-BN003, a phase 3 national trial. Furthermore, the relationship between facility volume and outcomes in patients with grade II meningioma after GTR has not been examined at a national level. We aim to assess overall survival (OS) of patients with grade II meningioma after GTR by surgical case volume and OS by receipt of adjuvant radiation.

Methods: We used the National Cancer Database to identity 2823 patients diagnosed with grade II meningioma who underwent GTR. Propensity score matching was applied to balance covariates in patients with grade II meningioma after GTR stratified by adjuvant radiation status. Multivariable logistic regression was used to assess factors associated with radiation receipt. Kaplan-Meier and log-rank tests were used to assess OS by facility volume.

Results: As facility volume increased, OS increased, with a 5-year OS of 72.8% for facilities with GTR grade II meningioma volumes of ≤8 cases per decade and 87.5% for >8 cases per decade (P < 0.0001). There was no difference in 5-year OS between GTR alone and GTR with adjuvant radiation (84.8% vs. 86.4%; P = 0.151). Covariates significantly associated with radiation receipt included facility location, facility volume, distance, and tumor size.

Conclusions: Treatment at higher surgical case volume facilities is associated with improved OS for GTR grade II meningioma. These facilities also have more patients receiving adjuvant radiation. However, we observed no difference in OS between adjuvant radiation and surgery alone.
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http://dx.doi.org/10.1016/j.wneu.2020.05.030DOI Listing
September 2020

A prospective parallel design study testing non-inferiority of customized oral stents made using 3D printing or manually fabricated methods.

Oral Oncol 2020 07 13;106:104665. Epub 2020 Apr 13.

Department of Head and Neck Surgery, Division of Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, United States.

Background And Purpose: Customized mouth-opening-tongue-depressing-stents (MOTDs) may reduce toxicity in patients with head and neck cancers (HNC) receiving radiotherapy (RT). However, making MOTDs requires substantial resources, which limits their utilization. Previously, we described a workflow for fabricating customized 3D-printed MOTDs. This study reports the results of a prospective trial testing the non-inferiority of 3D-printed to standard and commercially-available (TruGuard) MOTDs as measured by patient reported outcomes (PROs).

Materials And Methods: PROs were collected at 3 time points: (t1) simulation, (t2) prior to RT, (t3) between fractions 15-25 of RT. Study participants received a 3D-printed MOTDs (t1, t2, t3), a wax-pattern (t1), an acrylic-MOTDs (t2, t3) and an optional TruGuard (t1, t2, t3). Patients inserted the stents for 5-10 min and completed a PRO-questionnaire covering ease-of-insertion and removal, gagging, jaw-pain, roughness and stability. Inter-incisal opening and tongue-displacement were recorded. With 39 patients, we estimated 90% power to detect a non-inferiority margin of 2 at a significance level of 0.025. Matched pairs and t-test were used for statistics.

Results: 41 patients were evaluable. The 3D-printed MOTDs achieved a significantly better overall PRO score compared to the wax-stent (p = 0.0007) and standard-stent (p = 0.0002), but was not significantly different from the TruGuard (p = 0.41). There was no difference between 3D-printed and standard MOTDs in terms of inter-incisal opening (p = 0.4) and position reproducibility (p = 0.98). The average 3D-printed MOTDs turn-around time was 8 vs 48 h for the standard-stent.

Conclusions: 3D-printed stents demonstrated non-inferior PROs compared to TruGuard and standard-stents. Our 3D-printing process may expand utilization of MOTDs.
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http://dx.doi.org/10.1016/j.oraloncology.2020.104665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350149PMC
July 2020

Optimal Timing of Radiotherapy Following Gross Total or Subtotal Resection of Glioblastoma: A Real-World Assessment using the National Cancer Database.

Sci Rep 2020 03 18;10(1):4926. Epub 2020 Mar 18.

Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, United States.

Treatment for glioblastoma (GBM) includes surgical resection and adjuvant radiotherapy (RT) and chemotherapy. The optimal time interval between surgery and RT remains unclear. The National Cancer Database (NCDB) was queried for patients with GBM. Overall survival (OS) was estimated using Kaplan-Meier and log-rank tests. Univariate (UVA) and multivariable Cox regression (MVA) modeling was used to determine predictors of OS. A total of 45,942 patients were included. On MVA: younger age, female gender, black ethnicity, higher KPS, obtaining a gross total resection (GTR), MGMT promoter-methylated gene status, unifocal disease, higher RT dose, and RT delay of 4-8 weeks had improved OS. Patients who underwent a subtotal resection (STR) had worsened survival with RT delay ≤4 weeks and patients with GTR had worsened survival when RT was delayed >8 weeks. This analysis suggests that an interval of 4-8 weeks between resection and RT results in better survival. Delays >8 weeks in patients with a GTR and delays <4 weeks in patients with a STR/biopsy resulted in worse survival. This impact of time delay from surgery to RT, in conjunction with extent of resection, should be considered in the clinical management of patients and future designs of clinical trials.
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http://dx.doi.org/10.1038/s41598-020-61701-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080722PMC
March 2020

Detection of Glioblastoma Subclinical Recurrence Using Serial Diffusion Tensor Imaging.

Cancers (Basel) 2020 Feb 29;12(3). Epub 2020 Feb 29.

Department of Radiation Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Glioblastoma is an aggressive brain tumor with a propensity for intracranial recurrence. We hypothesized that tumors can be visualized with diffusion tensor imaging (DTI) before they are detected on anatomical magnetic resonance (MR) images. We retrospectively analyzed serial MR images from 30 patients, including the DTI and T1-weighted images at recurrence, at 2 months and 4 months before recurrence, and at 1 month after radiation therapy. The diffusion maps and T1 images were deformably registered longitudinally. The recurrent tumor was manually segmented on the T1-weighted image and then applied to the diffusion maps at each time point to collect mean FA, diffusivities, and neurite density index (NDI) values, respectively. Group analysis of variance showed significant changes in FA ( = 0.01) and NDI ( = 0.0015) over time. Pairwise t tests also revealed that FA and NDI at 2 months before recurrence were 11.2% and 6.4% lower than those at 1 month after radiation therapy ( < 0.05), respectively. Changes in FA and NDI were observed 2 months before recurrence, suggesting that progressive microstructural changes and neurite density loss may be detectable before tumor detection in anatomical MR images. FA and NDI may serve as non-contrast MR-based biomarkers for detecting subclinical tumors.
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http://dx.doi.org/10.3390/cancers12030568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139975PMC
February 2020

Consensus recommendations for a standardized brain tumor imaging protocol for clinical trials in brain metastases.

Neuro Oncol 2020 06;22(6):757-772

UCLA Brain Tumor Imaging Laboratory, Center for Computer Vision and Imaging Biomarkers, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.

A recent meeting was held on March 22, 2019, among the FDA, clinical scientists, pharmaceutical and biotech companies, clinical trials cooperative groups, and patient advocacy groups to discuss challenges and potential solutions for increasing development of therapeutics for central nervous system metastases. A key issue identified at this meeting was the need for consistent tumor measurement for reliable tumor response assessment, including the first step of standardized image acquisition with an MRI protocol that could be implemented in multicenter studies aimed at testing new therapeutics. This document builds upon previous consensus recommendations for a standardized brain tumor imaging protocol (BTIP) in high-grade gliomas and defines a protocol for brain metastases (BTIP-BM) that addresses unique challenges associated with assessment of CNS metastases. The "minimum standard" recommended pulse sequences include: (i) parameter matched pre- and post-contrast inversion recovery (IR)-prepared, isotropic 3D T1-weighted gradient echo (IR-GRE); (ii) axial 2D T2-weighted turbo spin echo acquired after injection of gadolinium-based contrast agent and before post-contrast 3D T1-weighted images; (iii) axial 2D or 3D T2-weighted fluid attenuated inversion recovery; (iv) axial 2D, 3-directional diffusion-weighted images; and (v) post-contrast 2D T1-weighted spin echo images for increased lesion conspicuity. Recommended sequence parameters are provided for both 1.5T and 3T MR systems. An "ideal" protocol is also provided, which replaces IR-GRE with 3D TSE T1-weighted imaging pre- and post-gadolinium, and is best performed at 3T, for which dynamic susceptibility contrast perfusion is included. Recommended perfusion parameters are given.
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http://dx.doi.org/10.1093/neuonc/noaa030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283031PMC
June 2020

Radiotherapy in Leptomeningeal Disease: A Systematic Review of Randomized and Non-randomized Trials.

Front Oncol 2019 15;9:1224. Epub 2019 Nov 15.

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

Leptomeningeal disease (LMD), also known as neoplastic meningitis, leptomeningeal carcinomatosis, or carcinomatous meningitis, is a rare cancer complication occurring in ~5% of cases and ultimately leads to significant morbidity and mortality. In the modern era, incidence of this condition continues to rise with longer survival of patients with advanced and even metastatic disease due to continued improvements in systemic therapies that are providing prolonged control of distant disease, but with limited effect in the central nervous system (CNS). Typical treatment strategies include optimal systemic therapy for the primary disease, as well as neuroaxis directed therapies, which may include intrathecal chemotherapy (ITC) or radiotherapy (RT). A systematic review of radiotherapy for LMD was performed. Medline, EMBASE, and Cochrane databases were searched from 1946 to 2018 for clinical trials, retrospective/prospective reviews, and case series with ≥2 human subjects that used radiation therapy techniques in the treatment of LMD. The outcome measures of interest included: characteristics of trial participants, inclusion/exclusion criteria, study type, number of participants, primary cancer histology, type of intervention for LMD, survival results if reported, length of follow up, and study conclusion. Of 547 unique citations, 62 studies met the pre-specified eligibility criteria. These studies included 36 retrospective cohorts, 11 prospective series, 12 case series, and a single citation of guidelines, NCDB analysis, and a randomized control trial. Owing to study heterogeneity, meta-analyses of the endpoint data could not be performed. LMD is a devastating complication of cancer with reported survivals ranging from 2 to 4 months. Based on this systematic review, the recommendation for the treatment of LMD is for multimodality discussion of cases and treatment, including the use of radiotherapy, for LMD. However, with continued advances in systemic therapy as well as imaging advances, the landscape of LMD is evolving rapidly and the role of RT will likely also continue to evolve and advance. There is limited high-quality evidence to guide the optimal use of RT for the treatment of LMD, and there is a great need for prospective, histology specific investigation of the role of radiotherapy for LMD in the era of modern systemic therapies.
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http://dx.doi.org/10.3389/fonc.2019.01224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6872542PMC
November 2019

Coronary Artery Dose-Volume Parameters Predict Risk of Calcification After Radiation Therapy.

J Cardiovasc Imaging 2019 Oct;27(4):268-279

Department of Diagnostic Imaging, MD Anderson Cancer Center, Houston, TX, USA.

Background: Radiation exposure increases the risk of coronary artery disease (CAD). We explored the association of CAD with coronary artery dose-volume parameters in patients treated with 3D-planned radiation therapy (RT).

Methods: Patients who received thoracic RT and were evaluated by cardiac computed tomography ≥ 1 year later were included. Demographic data and cardiac risk factors were retrospectively collected. Dosimetric data (mean heart dose, d, d, V - V₅) were collected for the whole heart and for each coronary artery. A coronary artery calcium (CAC) Agatston score was calculated on a per-coronary basis and as a total score. Multivariable generalized linear mixed models were generated. The predicted probabilities were used for receiver operating characteristic analyses.

Results: Twenty patients with a median age of 53 years at the time of RT were included. Nine patients (45%) had ≥ 3/6 conventional cardiac risk factors. Patients received RT for breast cancer (10, 50%), lung cancer (6, 30%), or lymphoma/myeloma (4, 20%) with a median dose of 60 Gy. CAC scans were performed a median of 32 months after RT. CAC score was significantly associated with radiation dose and presence of diabetes. In a multivariable model adjusted for diabetes, segmental coronary artery dosimetric parameters (d, d, V₅₀, V₄₀ V₃₀, V₂₀, V₁₀, and V₅) were significantly associated with CAC score > 0. V₅₀ had the highest area under the ROC curve (0.89, 95% confidence interval, 0.80-0.97).

Conclusions: Coronary artery radiation exposure is strongly correlated with subsequent segmental CAC score. Coronary calcification may occur soon after RT and in individuals with conventional cardiac risk factors.
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http://dx.doi.org/10.4250/jcvi.2019.27.e38DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6795565PMC
October 2019

Multi-institutional validation of brain metastasis velocity, a recently defined predictor of outcomes following stereotactic radiosurgery.

Radiother Oncol 2020 01 13;142:168-174. Epub 2019 Sep 13.

Department of Radiation Oncology, Wake Forest School of Medicine, USA.

Introduction: Brain metastasis velocity (BMV) is a prognostic metric that describes the recurrence rate of new brain metastases after initial treatment with radiosurgery (SRS). We have previously risk stratified patients into high, intermediate, and low-risk BMV groups, which correlates with overall survival (OS). We sought to externally validate BMV in a multi-institutional setting.

Methods: Patients from nine academic centers were treated with upfront SRS; the validation cohort consisted of data from eight institutions not previously used to define BMV. Patients were classified by BMV into low (<4 BMV), intermediate (4-13 BMV), and high-risk groups (>13 BMV). Time-to-event outcomes were estimated using the Kaplan-Meier method. Cox proportional hazards methods were used to estimate the effect of BMV and salvage modality on OS.

Results: Of 2829 patients, 2092 patients were included in the validation dataset. Of these, 921 (44.0%) experienced distant brain failure (DBF). Median OS from initial SRS was 11.2 mo. Median OS for BMV < 4, BMV 4-13, and BMV > 13 were 12.5 mo, 7.0 mo, and 4.6 mo (p < 0.0001). After multivariate regression modeling, melanoma histology (β: 10.10, SE: 1.89, p < 0.0001) and number of initial brain metastases (β: 1.52, SE: 0.34, p < 0.0001) remained predictive of BMV (adjusted R = 0.06).

Conclusions: This multi-institutional dataset validates BMV as a predictor of OS following initial SRS. BMV is being utilized in upcoming multi-institutional randomized controlled trials as a stratification variable for salvage whole brain radiation versus salvage SRS after DBF.
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http://dx.doi.org/10.1016/j.radonc.2019.08.011DOI Listing
January 2020

Creating customized oral stents for head and neck radiotherapy using 3D scanning and printing.

Radiat Oncol 2019 Aug 19;14(1):148. Epub 2019 Aug 19.

Department of Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0097, Houston, TX, 77030, USA.

Background: To evaluate and establish a digital workflow for the custom designing and 3D printing of mouth opening tongue-depressing (MOTD) stents for patients receiving radiotherapy for head and neck cancer.

Methods: We retrospectively identified 3 patients who received radiation therapy (RT) for primary head and neck cancers with MOTD stents. We compared two methods for obtaining the digital impressions of patients' teeth. The first method involved segmentation from computed tomography (CT) scans, as previously established by our group, and the second method used 3D scanning of the patients' articulated stone models that were made during the conventional stent fabrication process. Three independent observers repeated the process to obtain digital impressions which provided data to design customized MOTD stents. For each method, we evaluated the time efficiency, dice similarity coefficient (DSC) for reproducibility, and the 3D printed stents' accuracy. For the 3D scanning method, we evaluated the registration process using manual and automatic approaches.

Results: For all patients, the 3D scanning method demonstrated a significant advantage over the CT scanning method in terms of time efficiency with over 60% reduction in time consumed (p < 0.0001) and reproducibility with significantly higher DSC (p < 0.001). The printed stents were tested over the articulated dental stone models, and the trueness of fit and accuracy of dental anatomy was found to be significantly better for MOTD stents made using the 3D scanning method. The automated registration showed higher accuracy with errors < 0.001 mm compared to manual registration.

Conclusions: We developed an efficient workflow for custom designing and 3D-printing MOTD radiation stents. This workflow represents a considerable improvement over the CT-derived segmentation method. The application of this rapid and efficient digital workflow into radiation oncology practices can expand the use of these toxicity sparing devices to practices that do not currently have the support to make them.
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http://dx.doi.org/10.1186/s13014-019-1357-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6701083PMC
August 2019

Informational needs of brain metastases patients and their caregivers.

Neurooncol Pract 2019 Jan 20;6(1):47-60. Epub 2018 Apr 20.

Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.

Background: In response to a dearth of formal health information targeted towards patients with brain metastases and their caregivers, a formal informational and supportive care needs assessment was conducted.

Methods: Brain metastases patients and caregivers who attended a clinic focused on the treatment of brain metastases at a tertiary medical center completed a self-report survey to assess informational needs across 6 domains: medical, physical, practical, social, emotional, and spiritual informational needs. Univariate and multivariate analyses of associations between variables was conducted using linear regression models.

Results: A total of 109 patients and 77 caregivers participated. Patients and caregivers both prioritized medical and physical informational domains, with a large focus on symptoms and side-effect profiles, significance of brain metastases locations and their implications, available treatment options and their risks and benefits, prognoses and follow-ups if treatment is completed, and end-of-life experiences and supports. One-on-one counseling was preferred by both caregivers and patients for these domains, as well as for practical informational needs; while patients preferred pamphlets to address social, emotional and spiritual informational needs, caregivers preferred one-on-one counseling for the former two domains as well.

Conclusions: Brain metastases patients and their caregivers prioritize medical and physical informational needs, with one-on-one counseling and pamphlets being the most preferred modalities for information provision. Further exploration regarding existing non-validated resources and the development of tailored resources to address the unique needs of these patient and caregiver populations are warranted.
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http://dx.doi.org/10.1093/nop/npy008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668253PMC
January 2019

The joint effect of aging and HIV infection on microstructure of white matter bundles.

Hum Brain Mapp 2019 10 4;40(15):4370-4380. Epub 2019 Jul 4.

Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California.

Recent evidence suggests the aging process is accelerated by HIV. Degradation of white matter (WM) has been independently associated with HIV and healthy aging. Thus, WM may be vulnerable to joint effects of HIV and aging. Diffusion-weighted imaging (DWI) was conducted with HIV-seropositive (n = 72) and HIV-seronegative (n = 34) adults. DWI data underwent tractography, which was parcellated into 18 WM tracts of interest (TOIs). Functional Analysis of Diffusion Tensor Tract Statistics (FADTTS) regression was conducted assessing the joint effect of advanced age and HIV on fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) along TOI fibers. In addition to main effects of age and HIV on WM microstructure, the interactive effect of age and HIV was significantly related to lower FA and higher MD, AD, and RD across all TOIs. The location of findings was consistent with the clinical presentation of HIV-associated neurocognitive disorders. While older age is related to poorer WM microstructure, its detrimental effect on WM is stronger among HIV+ relative to HIV- individuals. Loss of WM integrity in the context of advancing age may place HIV+ individuals at increased risk for brain and cognitive compromise.
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http://dx.doi.org/10.1002/hbm.24708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865715PMC
October 2019