101 results on '"Soltys S"'
Search Results
2. DSC Perfusion MRI–Derived Fractional Tumor Burden and Relative CBV Differentiate Tumor Progression and Radiation Necrosis in Brain Metastases Treated with Stereotactic Radiosurgery.
- Author
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Kuo, F., Ng, N. N., Nagpal, S., Pollom, E. L., Soltys, S., Hayden-Gephart, M., Li, G., Born, D. E., and Iv, M.
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- 2022
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3. Esophageal tolerance to high-dose stereotactic ablative radiotherapy
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Abelson, J. A., Murphy, J. D., Loo, B. W., Jr, Chang, D. T., Daly, M. E., Wiegner, E. A., Hancock, S., Chang, S. D., Le, Q.-T., Soltys, S. G., and Gibbs, I. C.
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- 2012
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4. WE-F-304-04: Radiosurgery for Vestibular Schwannomas: Tumor Control Probability Analyses and Recommended Reporting Standards
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Soltys, S., primary
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- 2015
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5. NT-34 * COMPLETE RESPONSE TO VEMURAFINIB IN A PATIENT WITH METASTATIC ANAPLASTIC XANTHROASTROCYTOMA
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Thomas, R., primary, Ajlan, A., additional, Ziskin, J., additional, Soltys, S., additional, Reddy, S., additional, Recht, L., additional, and Nagpal, S., additional
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- 2014
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6. SU-E-T-236: Monte Carlo Calculations for Radiosurgery of the Clivus
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Ho, A, primary, Gibbs, I, additional, Chang, S, additional, and Soltys, S, additional
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- 2014
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7. SU‐E‐T‐603: Evaluation of MLC‐Based Robotic Radiotherapy
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Fahimian, B, primary, Soltys, S, additional, Xing, L, additional, Gibbs, I, additional, Chang, S, additional, and Wang, L, additional
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- 2013
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8. Impact of Dose Hot Spots on Spinal Cord Tolerance following Stereotactic Body Radiotherapy: A Generalized Biological Effective Dose Analysis
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Sahgal, A., primary, Ma, L., additional, Fowler, J., additional, Weinberg, V., additional, Gibbs, I., additional, Gerszten, P. C., additional, Ryu, S., additional, Soltys, S., additional, Chang, E., additional, Wong, C. S., additional, and Larson, D. A., additional
- Published
- 2012
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- View/download PDF
9. Esophageal tolerance to high-dose stereotactic ablative radiotherapy
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Abelson, J. A., primary, Murphy, J. D., additional, Loo Jr, B. W., additional, Chang, D. T., additional, Daly, M. E., additional, Wiegner, E. A., additional, Hancock, S., additional, Chang, S. D., additional, Le, Q.-T., additional, Soltys, S. G., additional, and Gibbs, I. C., additional
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- 2011
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10. Transitioning Between Clerkship Directors
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Soltys, S. M., primary, Pary, R. J., additional, Robinson, S. W., additional, and Markwell, S. J., additional
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- 2011
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11. Primer for the Interim Chair
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Soltys, S. M., primary
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- 2011
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12. Can Temporal Lobe Necrosis be Prevented in Patients with Nasopharyngeal/Skull Base Tumors Undergoing a Stereotactic Radiosurgery Boost? A Dose Volume Analysis
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Hara, W., primary, Yun, S., additional, Hsu, A., additional, Soltys, S., additional, Adler, J., additional, Le, Q., additional, and Loo, B.W., additional
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- 2010
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13. Clinical Management of Patients with Temporal Lobe Necrosis
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Krakow, T.E., primary, Hara, W., additional, Yun, S., additional, Soltys, S., additional, Chang, S., additional, Fischbein, N., additional, Loo, B., additional, and Le, Q., additional
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- 2010
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14. SU-GG-T-152: Pediatric Craniospinal Irradiation with RapidArc: A Feasibility Study and Dosimetric Comparison
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Atwood, T, primary, Soltys, S, additional, and Xing, L, additional
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- 2010
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15. Re-treatment Spinal Cord Tolerance for Spine Stereotactic Body Radiotherapy
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Sahgal, A., primary, Ma, L., additional, Gibbs, I., additional, Chao, S., additional, Chang, U., additional, Weinberg, V., additional, Soltys, S., additional, Fowler, J., additional, Wong, S., additional, and Larson, D., additional
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- 2009
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16. Preliminary Guidelines for Avoidance of Radiation-induced Myelopathy Following Spine Stereotactic Body Radiosurgery (SBRS)
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Sahgal, A., primary, Gibbs, I., additional, Ryu, S., additional, Ma, L., additional, Gerszten, P., additional, Soltys, S., additional, Weinberg, V., additional, Fowler, J., additional, Chang, E., additional, and Larson, D., additional
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- 2008
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17. Is a planned neck dissection necessary after chemoradiotherapy in head and neck cancer patients with advanced nodal stage
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SOLTYS, S, primary, SUEN, A, additional, FEE, W, additional, PINTO, H, additional, SIVANANDAN, R, additional, GOODE, R, additional, GOFFINET, D, additional, and LE, Q, additional
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- 2004
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18. A proteomics approach to the identification of novel hypoxia regulated endoplasmic reticulum (ER) proteins by 2D gel electrophoresis and mass spectroscopy
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Chen, Y, primary, Shi, G, additional, Soltys, S, additional, Le, Q.T, additional, and Koong, A.C, additional
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- 2002
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19. Fighting fire with fire
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Slaughter, J, primary, Soltys, S, additional, and Eppright, T, additional
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- 1998
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20. Myocardial adeno-associated virus serotype 6-betaARKct gene therapy improves cardiac function and normalizes the neurohormonal axis in chronic heart failure.
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Rengo G, Lymperopoulos A, Zincarelli C, Donniacuo M, Soltys S, Rabinowitz JE, Koch WJ, Rengo, Giuseppe, Lymperopoulos, Anastasios, Zincarelli, Carmela, Donniacuo, Maria, Soltys, Stephen, Rabinowitz, Joseph E, and Koch, Walter J
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- 2009
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21. Nonverbal learning disabilities and sensory processing disorders.
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Dobbins M, Sunder T, and Soltys S
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- 2007
22. Stable myocardial-specific AAV6-S100A1 gene therapy results in chronic functional heart failure rescue.
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Pleger ST, Most P, Boucher M, Soltys S, Chuprun JK, Pleger W, Gao E, Dasgupta A, Rengo G, Remppis A, Katus HA, Eckhart AD, Rabinowitz JE, and Koch WJ
- Published
- 2007
23. Risk of leptomeningeal disease in patients treated with stereotactic radiosurgery targeting the post-operative resection cavity for brain metastases.
- Author
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Soltys, S. G., Modlin, L. A., Atalar, B., Gibbs, I. C., S. D. Chang, Harsh, G. R., Adler, J. R., and C. Y. Choi
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- *
MENINGEAL cancer , *STEREOTACTIC radiosurgery , *BRAIN metastasis , *IRRADIATION , *CANCER patients , *THERAPEUTICS - Abstract
Objective: We sought to determine the risk of leptomeningeal disease (LMD) in patients treated with stereotactic radiosurgery (SRS) targeting the postoperative cavity following surgical resection of a brain metastasis, deferring whole brain irradiation (WBRT) in all patients. Methods: We retrospectively reviewed 175 brain metastasis resection cavities in 165 patients with evaluable follow-up imaging treated with post-operative SRS from 1998 to 2011. No patient had WBRT. LMD was defined through radiologic and/or pathologic findings. The local cavity, distant parenchymal brain, and leptomeningeal brain failure rates were calculated using the competing risk analyses, with death as a competing risk. Control rates were censored at the time of last follow-up or at the time of salvage WBRT. Factors associated with LMD were determined through univariate analysis. The overall survival rate was calculated using Kaplan-Meier estimates. Results: Median follow-up duration was 12 months (range, 1 - 156 months). Median overall survival was 18 months. The cumulative incidence rates of local cavity failure at 1- and 2- years were 10% and 14%, respectively. Twenty-one patients (13% crude rate) developed LMD at a median of 5 months (range, 2-33 months) following SRS. The 1- and 2- year cumulative incidence rates of LMD were 11% and 13%, respectively. Posterior fossa (p=0.5) or pial (p=0.2) location was not associated with LMD. The factors predictive for LMD on univariate analysis were new parenchymal metastases (p=0.009) and breast cancer histology (p=0.004). Both continued to be significant on multivariate analysis (p=0.03 and 0.007, respectively). The 1 year rate of LMD was 24% for breast (n=26 patients) vs. 9% for non-breast (n=139) histology. The receptor status of breast cancer patients did not correlate with risk of LMD. All LMD patients were subsequently treated with WBRT. Median survival following the diagnosis of LMD was 7 months (range, 1 - 37 months). Conclusions: Patients treated with SRS targeting the post-operative cavity following resection of breast cancer metastases have a higher risk of LMD in this series. Whether the inclusion of WBRT would decrease the rate of LMD or if the biology of breast cancer brain metastases places patients at higher risk irrespective of the treatment choice is unknown. We encourage all future reports on SRS cavity boost to include the risk of LMD. Disclosure: No significant relationships. [ABSTRACT FROM AUTHOR]
- Published
- 2013
24. Estimated risk level of unified SbRT dose tolerance limits for spinal cord.
- Author
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Gibbs, I. C., Grimm, J., Luxton, G., Soltys, S. G., Sahgal, A., Patel, A., Herbert, S., J. Xue, L. Ma, and Adler, J. R.
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STEREOTACTIC radiotherapy ,SPINAL cord tumors ,RADIOTHERAPY ,SPINAL muscular atrophy - Abstract
Objectives: A variety of guidelines have been reported to estimate spinal cord dose tolerance for patients treated with stereotactic body radiation therapy (SBRT). The purpose of this work is to comprehensively analyze dose-volume data of a cohort of patients treated by SBRT in order to estimate the complication probability and compare these probabilities to dose tolerance limits currently in clinical use. Methods: An extensive literature review of English-language publications identified 59 spinal cord dose tolerance limits suggested for clinical use. These guidelines were partitioned into a unified format of high-risk and low-risk dose tolerance limits. A dataset of spinal cord dose-volume points were interpolated from a previously published cohort of 74 patients with 102 spinal metastases in whom 3 patients developed treatment-related severe myelopathy. Seventy-four percent (50/68) of previously treated patients had prior radiation. Dose-volume data was digitized into the DVH Evaluator software tool where the rest of the DVH was approximated and parameters of the probit dose response model were fitted to the data using the maximum likelihood approach. We estimated risk levels for spinal cord dose-volume parameters including maximum dose, D1cc, and D0.1cc, and compared the corresponding risk level with the published suggested guidelines for spinal cord tolerance. Results: Based on the risk model generated from this limited dataset, the Accuray STARS 20Gy to 1 cc limit and the RTOG 0813 30Gy maximum limit had the highest risk levels, at about 5%, and most of the other unified dose tolerance limits had 1-3% risk. Only one of the unified low-risk limits had higher than 3% risk. Two thirds of patients in this study had prior irradiation so it is likely that in other patient populations the risk level of these limits will be lower. Conclusion: While severe myelopathy is an unacceptable complication, no clinical procedure is without risk. Guidelines, therefore, should aim to minimize the risk of injury to 1-3% or less. No single dose-volume parameter can be relied on to predict this complication, however, it is likely that the use of multiple dose-volume-based guidelines may improve safety. Based on the findings of this study, the current guidelines for D
0. 1cc as well as the low-risk guidelines for maximum dose (Dmax ) may be useful to establish the lower limits of tolerance. Longer follow-up with more patients from more institutions is required to improve the risk estimates. Disclosure: No significant relationships. [ABSTRACT FROM AUTHOR]- Published
- 2013
25. SBRT for cardiac arrhythmia ablation.
- Author
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A. Lo, B. Loo, Maguire, P., Soltys, S. G., L. Wang, and P. Zei
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CATHETER ablation ,VENTRICULAR tachycardia ,CARDIAC pacemakers ,CARDIAC research ,CARDIAC patients - Abstract
Purpose: Stereotactic Body Radiation Therapy (SBRT) for cardiac ablation of ventricular tachycardia (VT) represents an alternative to standard catheter-based methods for treating VT. This study reports the steps and considerations for treatment setup, target definition, treatment planning and treatment delivery with CardioPlan 3-D contouring software (CyberHeart) and Cyberknife (Accuray). Methods: A selected patient was observed under fluoroscopy to visualize his existing pacemaker lead. Because of extensive metallic components it was not suitable for Synchrony (Accuray) tracking. A dummy lead with a single metal end was implanted via percutaneous right axillary vein access for tracking purpose. Cardiac motion about 1 cm was observed with breathe hold. FHS 4D-CT, breathe hold CT were performed with patient rolled about 15 degree to the right so the dummy lead could be identified clearly by Synchrony tracking. CT images were loaded into CardioPlan 3-D contouring software. The cardiologist visualized the heart in 3D, segmented to show various volumes and contoured a 3D target that was projected into CT slices. The SS (structure set) was transferred to Multiplan (Accuray). The radiation oncologist refined a composite target incorporating cardiac motion and PET uptake and a PTV (planning target volume) that allows dose to extend to the interior wall and chamber. Adjacent critical organs were also contoured. Special shells were created during planning to create a conformal dose distribution around the PTV while keeping dose to critical organs to minimum. Results: A Synchrony treatment plan with Iris collimator of 25 Gy in 1 fraction to 75% isodose line, 175 non zero beams and 27671 MU was created that covered 97% of PTV, doses to critical organ were all acceptable. Patient setup took half an hour including placing monitors to monitor vital signs, identified the dummy lead and built Synchrony tracking model. Actual radiation delivery with Synchrony took 90 minutes with a 30 minute rest period in between that the patient requested. Total elapsed time was under 3 hours. The cardiologist then removed the dummy lead. Patient was admitted under observation overnight and discharged next day. Conclusions: The first Cyberknife SBRT cardiac ablation of ventricular tachycardia was performed successfully. 25 Gy was high enough based on success with animal testing and low enough to be safe based on other SBRT experience. This procedure combines complex target definition and tracking strategy that represents a new and less invasive option to treat VT. Disclosure: No significant relationships. [ABSTRACT FROM AUTHOR]
- Published
- 2013
26. CyberKnife Stereotactic Radiosurgery for Recurrent, Metastatic, and Residual Hemangiopericytomas
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Soltys Scott G, Lee Marco, Patil Chirag G, Jiang Bowen, Veeravagu Anand, Gibbs Iris C, and Chang Steven D
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Diseases of the blood and blood-forming organs ,RC633-647.5 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Objective Hemangiopericytoma is a rare and aggressive meningeal tumor. Although surgical resection is the standard treatment, hemangiopericytomas often recur with high incidences of metastasis. The purpose of this study was to evaluate the role of CyberKnife stereotactic radiosurgery (CK) in the management of recurrent, metastatic, and residual hemangiopericytomas. Methods In a review of the Stanford radiosurgery database between 2002 and 2009, the authors found 14 patients who underwent CK therapy for recurrent, metastatic, and residual hemangiopericytomas. A total of 24 tumors were treated and the median patient age was 52 years (range 29-70 years) at the time of initial CK therapy. The median follow-up period was 37 months (10-73 months) and all patients had been previously treated with surgical resection. Mean tumor volume was 9.16 cm3 and the mean marginal and maximum radiosurgical doses to the tumors were 21.2 Gy and 26.8 Gy, respectively. Results Of the 24 tumors treated, 22 have clinical follow-up data at this time. Of those 22 tumors, 12 decreased in size (54.5%), 6 remained unchanged (27.3%), and 4 showed recurrence (18.2%) after CK therapy. Progression-free survival rate was 95%, 71.5%, and 71.5% at 1, 3, and 5 years after multiple CK treatments. The 5-year survival rate after CK was 81%. Conclusions CK is an effective and safe management option for hemangiopericytomas. The current series demonstrates a tumor control of 81.8%. Other institutions have demonstrated similar outcomes with stereotactic radiosurgery, with tumor control ranging from 46.4% to 100%.
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- 2011
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- View/download PDF
27. Is it important to use monte carlo calculations for radiosurgery of the clivus?
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Ho, A. K., Soltys, S. G., and Chang, S. D.
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RADIOSURGERY , *CANCER radiotherapy research , *RADIATION dosimetry , *RADIATION doses , *CANCER treatment ,REPORTING - Abstract
Objectives: We sought to determine if dosimetric differences exist between Ray-Trace (RT) and Monte- Carlo (MC) calculation algorithms for radiosurgery for tumors of the clivus, given their proximity to air-tissue inhomogeneity. Methods: We retrospectively identified 6 patients with a tumor of the clivus where the target was located near an air-tissue interface. CyberKnife treatment was delivered in 1 to 5 fractions. Plans originally calculated with the RT algorithm were re-calculated with the same monitor units (MU) with the MC algorithm. Similarly, plans originally calculated with MC were recalculated with RT. MC calculations were performed using High Resolution with 2% uncertainty on the MultiPlan 4.6 planning system. If the RT plans were originally calculated using water- air density model, they were re-calculated with Body standard density model, and then compared with MC plans computed with Body standard density model. The maximum dose (Dmax) to the planning target volumes (PTV) and critical structures, minimum dose (Dmin) and coverage percentage for the PTV were calculated. Results: For the PTV, MC target coverage was a median of 4% (range, 0-13%) less than for RT. MC PTV Dmin was a median 6% (range, 1-10%) and Dmax a median 6% (range, 4-9%) higher than for RT. Similarly, the dose to critical structures (optic pathways and brainstem) was a median 9% (range, 3-27%) higher with MC as compared to RT. The degree of differences depends on the location of the target relative to the air-tissue inhomogeneity. Conclusion: Monte Carlo dose calculations are recommended for targets near tissue homogeneity such as the clivus. Assuming that Monte Carlo more closely approximates the true dosimetry, the use of Ray Trace could both overestimate target coverage and underestimate dose to critical structures. Analysis of the clinical correlates of worse tumor control and higher toxicity is ongoing. Disclosure: No significant relationships. [ABSTRACT FROM AUTHOR]
- Published
- 2013
28. SU-E-T-236: Monte Carlo Calculations for Radiosurgery of the Clivus
- Author
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Soltys, S [Stanford University Hospital, Stanford, CA (United States)]
- Published
- 2014
- Full Text
- View/download PDF
29. Impact of receptor status on prognosis among breast cancer patients with brain metastases treated with Cyberknife radiosurgery.
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Fasola, C. E., Gibbs, I. C., Soltys, S. G., and Horst, K. C.
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STEREOTAXIC techniques , *BRAIN metastasis , *CANCER in women , *BREAST cancer patients , *RADIOSURGERY - Abstract
Purpose: Stereotactic radiosurgery (SRS) is increasingly used in the management of brain metastases. Receptor status is an important prognostic factor among women with breast cancer. The aim of this study was to evaluate the effect of receptor status on clinical outcomes in breast cancer patients with brain metastases treated with SRS. Materials and Methods: We performed a retrospective review of 102 primary breast cancer patients with brain metastases treated with Cyberknife radiosurgery at Stanford University Medical Center between 2004 and 2011. The clinical characteristics, pathologic features, treatment details and clinical outcomes were reviewed. Median follow-up time was 18 months from the date of treatment with Cyberknife radiosurgery. All analyses were performed using SAS software, version 9.3 (SAS Institute, Cary, NC). Results: Patients with Her-2/neu positive receptor status treated with trastuzumab had a significantly improved median overall survival after treatment with stereotactic radiosurgery compared to patients with Her-2/neu negative receptor status (27 months vs 7 months, p = 0.002) or patients with Her-2/neu positive receptor status who did not receive trastuzumab (27 months vs 12 months, p = 0.04). In contrast, patients with estrogen receptor, progesterone receptor and Her-2/neu negative receptor status had significantly worse median overall survival after treatment with stereotactic radiosurgery compared to patients with at least one positive receptor (8 months vs 17 months, p = 0.02). On multivariable analysis, Her-2/neu status emerged as the only significant predictor of survival (p = 0.01). Conclusions: Her-2/neu receptor status was found to be a significant prognostic factor influencing survival among breast cancer patients with brain metastases treated with SRS. Importantly, the addition of treatment with trastuzumab among Her-2 neu positive patients significantly improved clinical outcomes. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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30. Comparative Cardiac Gene Delivery of Adeno-Associated Virus Serotypes 1-9 reveals that AAV6 Mediates the Most Efficient Transduction in Mouse Heart
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Joseph E. Rabinowitz, Carmela Zincarelli, Walter J. Koch, Giuseppe Rengo, Stephen Soltys, Zincarelli, C., Soltys, S., Rengo, G., Koch, W. J., and Rabinowitz, J. E.
- Subjects
Cardiac function curve ,Genetic enhancement ,Transgene ,Gene Dosage ,AAV cardiac tropism ,Genome, Viral ,Gene delivery ,Biology ,medicine.disease_cause ,Gene dosage ,General Biochemistry, Genetics and Molecular Biology ,Electrocardiography ,Mice ,Transduction (genetics) ,Gene therapy ,Imaging, Three-Dimensional ,Adeno-associated viru ,Transduction, Genetic ,medicine ,Animals ,Tissue Distribution ,Transgenes ,Serotyping ,General Pharmacology, Toxicology and Pharmaceutics ,Luciferases ,Adeno-associated virus ,Research Articles ,Tropism ,Kinetic ,Animal ,Myocardium ,General Neuroscience ,Heart Function Test ,General Medicine ,Dependovirus ,Dependoviru ,Virology ,Kinetics ,Indirect intracoronary gene delivery ,Heart Function Tests ,Immunology ,Luciferase - Abstract
Cardiac gene transfer is an attractive tool for developing novel heart disease treatments. Adeno-associated viral (AAV) vectors are widely used to mediate transgene expression in animal models and are being evaluated for human gene therapy. However, it is not clear which serotype displays the best cardiac tropism. Therefore, we curried out this study to directly compare AAV serotypes 1-9 heart transduction efficiency after indirect intracoronary injection. AAV-cytomegalovirus immediate early enhancer promoter (CMV)-luciferase serotypes 1-9 were injected in the left ventricular cavity of adult mice, after cross-clamping the ascending aorta and pulmonary artery. An imaging system was used to visualize luciferase expression at 3, 7, 21, 70, and 140 days postinjection. Echocardiography was performed to evaluate cardiac function on day 140. At the end of the study, luciferase enzyme activity and genome copies of the different AAV serotypes were assessed in several tissues and potential AAV immunogenicity was evaluated on heart sections by staining for macrophage and lymphocyte antigens. Among AAV serotypes 1-9, AAV6 showed the best capability of achieving high transduction levels in the myocardium in a tissue-specific manner, whereas the other serotypes had less cardiac transduction and more extracardiac expression, especially in the liver. Importantly, none of the serotypes tested with this marker gene affected cardiac function nor was associated with inflammation.
- Published
- 2010
31. Stable Myocardial-Specific AAV6-S100A1 Gene Therapy Results in Chronic Functional Heart Failure Rescue
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Walter J. Koch, Hugo A. Katus, Joseph E. Rabinowitz, Patrick Most, Erhe Gao, Abhijit Dasgupta, Andrew Remppis, J. Kurt Chuprun, Wiebke Pleger, Sven T. Pleger, Andrea D. Eckhart, Giuseppe Rengo, Matthieu Boucher, Stephen Soltys, Pleger, S. T., Most, P., Boucher, M., Soltys, S., Chuprun, J. K., Pleger, W., Gao, E., Dasgupta, A., Rengo, G., Remppis, A., Katus, H. A., Eckhart, A. D., Rabinowitz, J. E., and Koch, W. J.
- Subjects
Heart disease ,Genetic enhancement ,Myocardial Infarction ,Mice ,Genes, Reporter ,Vector (molecular biology) ,Promoter Regions, Genetic ,Heart Function Test ,S100 Proteins ,Dependovirus ,Dependoviru ,Enhancer Elements, Genetic ,Lac Operon ,S100 Protein ,Organ Specificity ,Heart Function Tests ,Cardiology ,Genetic Vector ,Cardiology and Cardiovascular Medicine ,Human ,medicine.medical_specialty ,S100A1 protein ,Recombinant Fusion Proteins ,Transgene ,Genetic Vectors ,Green Fluorescent Proteins ,Cardiomegaly ,Green Fluorescent Protein ,Long-term care ,Gene therapy ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,Humans ,Clinical significance ,Calcium Signaling ,Enhancer ,Ventricular remodeling ,Actin ,Heart Failure ,Binding Sites ,Animal ,business.industry ,Binding Site ,Genetic Therapy ,medicine.disease ,Myocardial Contraction ,Actins ,Rats ,Mice, Inbred C57BL ,Endocrinology ,Heart failure ,Rat ,business ,Recombinant Fusion Protein - Abstract
Background— The incidence of heart failure is ever-growing, and it is urgent to develop improved treatments. An attractive approach is gene therapy; however, the clinical barrier has yet to be broken because of several issues, including the lack of an ideal vector supporting safe and long-term myocardial transgene expression. Methods and Results— Here, we show that the use of a recombinant adeno-associated viral (rAAV6) vector containing a novel cardiac-selective enhancer/promoter element can direct stable cardiac expression of a therapeutic transgene, the calcium (Ca 2+ )-sensing S100A1, in a rat model of heart failure. The chronic heart failure–rescuing properties of myocardial S100A1 expression, the result of improved sarcoplasmic reticulum Ca 2+ handling, included improved contractile function and left ventricular remodeling. Adding to the clinical relevance, long-term S100A1 therapy had unique and additive beneficial effects over β-adrenergic receptor blockade, a current pharmacological heart failure treatment. Conclusions— These findings demonstrate that stable increased expression of S100A1 in the failing heart can be used for long-term reversal of LV dysfunction and remodeling. Thus, long-term, cardiac-targeted rAAV6-S100A1 gene therapy may be of potential clinical utility in human heart failure.
- Published
- 2007
32. An adrenal β-arrestin 1-mediated signaling pathway underlies angiotensin II-induced aldosterone production in vitro and in vivo
- Author
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Carmela Zincarelli, Giuseppe Rengo, Anastasios Lymperopoulos, Stephen Soltys, Walter J. Koch, Jihee Kim, Lymperopoulos, A., Rengo, G., Zincarelli, C., Kim, J., Soltys, S., and Koch, W. J.
- Subjects
medicine.medical_specialty ,Arrestins ,Adrenal Gland ,Biology ,Biased agonism ,Receptor, Angiotensin, Type 1 ,chemistry.chemical_compound ,Internal medicine ,Adrenal Glands ,Renin–angiotensin system ,medicine ,Animals ,Extracellular Signal-Regulated MAP Kinases ,Aldosterone ,beta-Arrestins ,Adrenal steroid hormone ,Multidisciplinary ,Arrestin ,Beta-Arrestins ,Animal ,Extracellular Signal-Regulated MAP Kinase ,beta-Arrestin ,Steroidogenic acute regulatory protein ,Angiotensin II ,G protein-coupled receptor angiotensin II receptor type I ,Biological Sciences ,Phosphoproteins ,medicine.disease ,Hyperaldosteronism ,Adrenocortical zona glomerulosa cell ,Rats ,medicine.anatomical_structure ,Endocrinology ,beta-Arrestin 1 ,chemistry ,Zona glomerulosa ,Phosphoprotein ,Rat ,Zona Glomerulosa ,Signal transduction ,Signal Transduction - Abstract
Aldosterone produces a multitude of effects in vivo, including promotion of postmyocardial infarction adverse cardiac remodeling and heart failure progression. It is produced and secreted by the adrenocortical zona glomerulosa (AZG) cells after angiotensin II (AngII) activation of AngII type 1 receptors (AT 1 Rs). Until now, the general consensus for AngII signaling to aldosterone production has been that it proceeds via activation of G q/11 -proteins, to which the AT 1 R normally couples. Here, we describe a novel signaling pathway underlying this AT 1 R-dependent aldosterone production mediated by β-arrestin-1 (βarr1), a universal heptahelical receptor adapter/scaffolding protein. This pathway results in sustained ERK activation and subsequent up-regulation of steroidogenic acute regulatory protein, a steroid transport protein regulating aldosterone biosynthesis in AZG cells. Also, this βarr1-mediated pathway appears capable of promoting aldosterone turnover independently of G protein activation, because treatment of AZG cells with SII, an AngII analog that induces βarr, but not G protein coupling to the AT 1 R, recapitulates the effects of AngII on aldosterone production and secretion. In vivo, increased adrenal βarr1 activity, by means of adrenal-targeted adenoviral-mediated gene delivery of a βarr1 transgene, resulted in a marked elevation of circulating aldosterone levels in otherwise normal animals, suggesting that this adrenocortical βarr1-mediated signaling pathway is operative, and promotes aldosterone production and secretion in vivo, as well. Thus, inhibition of adrenal βarr1 activity on AT 1 Rs might be of therapeutic value in pathological conditions characterized and aggravated by hyperaldosteronism.
- Published
- 2009
33. Myocardial adeno-associated virus serotype 6-βARKct gene therapy improves cardiac function and normalizes the neurohormonal axis in chronic heart failure
- Author
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Carmela Zincarelli, Stephen Soltys, Joseph E. Rabinowitz, Anastasios Lymperopoulos, Walter J. Koch, Maria Donniacuo, Giuseppe Rengo, Rengo, Giuseppe, Lymperopoulos, Anastasio, Zincarelli, Carmela, Donniacuo, Maria, Soltys, Stephen, Rabinowitz, Joseph E., Koch, Walter J., Rengo, G., Lymperopoulos, A., Zincarelli, C., Donniacuo, M., Soltys, S., Rabinowitz, J. E., and Koch, W. J.
- Subjects
medicine.disease_cause ,Catecholamines ,Neurohormone ,Transgenes ,Adeno-associated virus ,Aldosterone ,Metoprolol ,Ultrasonography ,Ventricular Remodeling ,Dependovirus ,Recombinant Protein ,Dependoviru ,Recombinant Proteins ,medicine.anatomical_structure ,Peptide ,Cardiology ,Catecholamine ,Rats, Transgenic ,Cardiology and Cardiovascular Medicine ,medicine.drug ,Cardiac function curve ,medicine.medical_specialty ,Adrenergic beta-Antagonists ,Green Fluorescent Proteins ,Gene delivery ,Green Fluorescent Protein ,Article ,Contractility ,Transgene ,Gene therapy ,Internal medicine ,Physiology (medical) ,Receptors, Adrenergic, beta ,medicine ,Animals ,Ventricular remodeling ,Cardiac remodeling ,Heart Failure ,business.industry ,Animal ,Ventricular ,Adrenergic beta-Antagonist ,Genetic Therapy ,medicine.disease ,Rats ,Disease Models, Animal ,Ventricle ,Heart failure ,Chronic Disease ,Rat ,Peptides ,business - Abstract
Background— The upregulation of G protein–coupled receptor kinase 2 in failing myocardium appears to contribute to dysfunctional β-adrenergic receptor (βAR) signaling and cardiac function. The peptide βARKct, which can inhibit the activation of G protein–coupled receptor kinase 2 and improve βAR signaling, has been shown in transgenic models and short-term gene transfer experiments to rescue heart failure (HF). This study was designed to evaluate long-term βARKct expression in HF with the use of stable myocardial gene delivery with adeno-associated virus serotype 6 (AAV6). Methods and Results— In HF rats, we delivered βARKct or green fluorescent protein as a control via AAV6-mediated direct intramyocardial injection. We also treated groups with concurrent administration of the β-blocker metoprolol. We found robust and long-term transgene expression in the left ventricle at least 12 weeks after delivery. βARKct significantly improved cardiac contractility and reversed left ventricular remodeling, which was accompanied by a normalization of the neurohormonal (catecholamines and aldosterone) status of the chronic HF animals, including normalization of cardiac βAR signaling. Addition of metoprolol neither enhanced nor decreased βARKct-mediated beneficial effects, although metoprolol alone, despite not improving contractility, prevented further deterioration of the left ventricle. Conclusions— Long-term cardiac AAV6-βARKct gene therapy in HF results in sustained improvement of global cardiac function and reversal of remodeling at least in part as a result of a normalization of the neurohormonal signaling axis. In addition, βARKct alone improves outcomes more than a β-blocker alone, whereas both treatments are compatible. These findings show that βARKct gene therapy can be of long-term therapeutic value in HF.
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- 2009
34. Analysis of AAV serotypes 1-9 mediated gene expression and tropism in mice after systemic injection
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Carmela Zincarelli, Stephen Soltys, Joseph E. Rabinowitz, Giuseppe Rengo, Zincarelli, C., Soltys, S., Rengo, G., and Rabinowitz, J. E.
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Male ,Biodistribution ,Time Factors ,Time Factor ,Transgene ,Biology ,HeLa Cell ,Genome ,Virus ,Mice ,Gene expression ,Drug Discovery ,Genetics ,Bioluminescence imaging ,Animals ,Humans ,Transgenes ,Molecular Biology ,Tropism ,Regulation of gene expression ,Kinetic ,Pharmacology ,Models, Genetic ,Animal ,Gene Transfer Techniques ,Genetic Therapy ,Gene Transfer Technique ,Dependovirus ,Dependoviru ,Virology ,Molecular biology ,Kinetics ,Gene Expression Regulation ,Echocardiography ,Molecular Medicine ,Human ,HeLa Cells - Abstract
This study examines transgene expression and biodistribution of adeno-associated virus (AAV) pseudotyped 1–9 after tail vein (TV) injection in male mice. Using a cytomegalovirus (CMV)-luciferase transgene, the time-course of expression in each animal was tracked throughout the experiment. The animals were imaged at 7, 14, 29, 56, and 100 days after the TV injection. The total number of photons emitted from each animal was recorded, allowing examination of expression level and kinetics for each pseudotyped virus. The bioluminescence imaging revealed three expression levels (i) low-expression group, AAV2, 3, 4, and 5; (ii) moderate-expression group, AAV1, 6, and 8; and (iii) high-expression group, AAV7 and 9. In addition, imaging revealed two classes of kinetics (i) rapid-onset, for AAV1, 6, 7, 8, and 9; and (ii) slow-onset, for AAV2, 3, 4, and 5. We next evaluated protein expression and viral genome copy numbers in dissected tissues. AAV9 had the best viral genome distribution and highest protein levels. The AAV7 protein and genome copy numbers were comparable to those of AAV9 in the liver. Most surprisingly, AAV4 showed the greatest number of genome copies in lung and kidney, and a high copy number in the heart. AAV6 expression was observed in the heart, liver, and skeletal muscle, and the genome distribution corroborated these observations.
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- 2008
35. Modulation of adrenal catecholamine secretion by in vivo gene transfer and manipulation of G protein-coupled receptor kinase-2 activity
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Anastasios Lymperopoulos, Walter J. Koch, Carmela Zincarelli, Giuseppe Rengo, Stephen Soltys, Lymperopoulos, A., Rengo, G., Zincarelli, C., Soltys, S., and Koch, W. J.
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medicine.medical_specialty ,G-Protein-Coupled Receptor Kinase 2 ,Chromaffin Cells ,Adrenal Gland ,Genetic Vectors ,Blotting, Western ,Gene delivery ,Biology ,Adenoviridae ,Catecholamines ,Chromaffin Cell ,Downregulation and upregulation ,In vivo ,Receptors, Adrenergic, alpha-2 ,Internal medicine ,Drug Discovery ,Adrenal Glands ,Genetics ,medicine ,Animals ,Secretion ,Transgenes ,Receptor ,Molecular Biology ,Cells, Cultured ,Pharmacology ,G protein-coupled receptor kinase ,Adrenal gland ,Animal ,Rats ,medicine.anatomical_structure ,Endocrinology ,Catecholamine ,Molecular Medicine ,Rat ,Genetic Vector ,medicine.drug ,Signal Transduction - Abstract
We recently reported that the upregulation of adrenal G protein-coupled receptor kinase-2 (GRK2) causes enhanced catecholamine (CA) secretion by desensitizing sympatho-inhibitory alpha (2)-adrenergic receptors (alpha (2)ARs) of chromaffin cells, and thereby aggravating heart failure (HF). In this study, we sought to develop an efficient and reproducible in vivo adrenal gene transfer method to determine whether manipulation of adrenal GRK2 levels/activity regulates physiological CA secretion in rats. We specifically investigated two different in vivo gene delivery methods: direct injection into the suprarenal glands, and retrograde delivery through the suprarenal veins. We delivered adenoviral (Ad) vectors containing either GRK2 or an inhibitor of GRK2 activity, the beta ARKct. We found both delivery approaches equally effective at supporting robust (>80% of the whole organ) and adrenal-restricted transgene expression, in the cortical region as well as in the medullar region. Additionally, rats with AdGRK2-infected adrenals exhibit enhanced plasma CA levels when compared with control rats (AdGFP-injected adrenals), whereas plasma CA levels after Ad beta ARKct infection were significantly lower. Finally, in isolated chromaffin cells, alpha (2)ARs of AdGRK2-infected cells failed to inhibit CA secretion whereas Ad beta ARKct-infected cells showed normal alpha (2)AR responsiveness. These results not only indicate that in vivo adrenal gene transfer is an effective way of manipulating adrenal gland signalling, but also identify GRK2 as a critically important molecule involved in CA secretion.
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- 2008
36. Effect of Language Barriers and Use of Interpreters on Hope Among Patients With Central Nervous System Malignancies and Bone Metastases.
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Hui C, Hall J, Fang Z, Lefebvre S, Hayden-Gephart M, Li G, Meola A, Nagpal S, Soltys S, and Pollom E
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- Humans, Male, Middle Aged, Female, Aged, Adult, Aged, 80 and over, Young Adult, Adolescent, Quality of Life, Surveys and Questionnaires, Prospective Studies, Language, Bone Neoplasms secondary, Bone Neoplasms radiotherapy, Communication Barriers, Central Nervous System Neoplasms secondary, Central Nervous System Neoplasms radiotherapy, Hope
- Abstract
Purpose: Hope is important in serious illnesses, as it has been linked to patient quality of life. We aimed to determine factors associated with lower hope scores among patients with central nervous system disease or bone metastases., Methods and Materials: The Adult Dispositional Hope Scale (AHS) is a 12-item questionnaire that measures hope through 2 qualities: agency (goal-directed energy) and pathways (plan to meet goals). Total scores range from 8 to 64, with higher scores reflecting higher agency and pathways thinking. We prospectively collected scores from patients seen in 2 radiation oncology clinics at our institution from October 2022 to April 2023. The method of least squares to fit general linear models and Pearson's correlation coefficients was used to determine relationships between AHS score and socioeconomic and disease factors., Results: Of the 197 patients who responded, the median age was 60.5 years (range, 16.9-92.5 years) and most patients were male (60.9%), were White (59.4%), and had malignant disease (59.4%). The median overall AHS score was 54 (range, 8-64), and median pathway and agency thinking scores were 27 (range, 4-32) and 27 (range, 4-32), respectively. Patients who needed an interpreter compared with those who did not had significantly lower overall AHS scores (mean score, 45.4 vs 51.2, respectively; P = .0493) and pathway thinking scores (mean score, 21.5 vs 25.7, respectively; P = .0085), and patients with poorer performance status had significantly worse overall AHS scores (Pearson's correlation coefficient = -0.2703, P = .0003)., Conclusions: Patients with central nervous system disease or bone metastases requiring the use of an interpreter had lower AHS scores, highlighting the possible association of language barriers to hope. Addressing patient language barriers and further studies on the possible association of language barriers to hope may improve hope, quality of life, and outcomes among these patients., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2024
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37. Where Does Auto-Segmentation for Brain Metastases Radiosurgery Stand Today?
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Kim M, Wang JY, Lu W, Jiang H, Stojadinovic S, Wardak Z, Dan T, Timmerman R, Wang L, Chuang C, Szalkowski G, Liu L, Pollom E, Rahimy E, Soltys S, Chen M, and Gu X
- Abstract
Detection and segmentation of brain metastases (BMs) play a pivotal role in diagnosis, treatment planning, and follow-up evaluations for effective BM management. Given the rising prevalence of BM cases and its predominantly multiple onsets, automated segmentation is becoming necessary in stereotactic radiosurgery. It not only alleviates the clinician's manual workload and improves clinical workflow efficiency but also ensures treatment safety, ultimately improving patient care. Recent strides in machine learning, particularly in deep learning (DL), have revolutionized medical image segmentation, achieving state-of-the-art results. This review aims to analyze auto-segmentation strategies, characterize the utilized data, and assess the performance of cutting-edge BM segmentation methodologies. Additionally, we delve into the challenges confronting BM segmentation and share insights gleaned from our algorithmic and clinical implementation experiences.
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- 2024
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38. The Assistant Clinical Research Coordinator Program: A Pathway for Recruitment in Radiation Oncology.
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Aboytes M, Cody M, Laseinde E, Hall J, Soltys S, Beadle B, Kidd E, Qian Y, Koong AC, Chang D, Le QT, and Pollom EL
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Purpose: Recruiting prospective physicians to radiation oncology can be challenging, because of limited familiarity with the field. The Assistant Clinical Research Coordinator (ACRC) program can help provide trainees early exposure to radiation oncology., Methods and Materials: The ACRC program involves hiring a college graduate to provide administrative and research support for faculty members. The program was developed with our institution's clinical trials office, which provided guidance on regulatory compliance and training. A structured selection process identifies top candidates, and a rigorous onboarding process ensures smooth transitions between ACRCs. We report characteristics and outcomes of ACRC employees and surveyed them to assess their program experience using a Likert scale., Results: From 2005 to 2023, the ACRC program paired 73 ACRCs with faculty. Most faculty (68%) are currently supported by ACRCs. In 2023, 113 applications were received for 4 positions. ACRCs have contributed to research publications (293 as coauthors and 43 as first authors) and taken on leadership roles in the department. Most program alumni have attended medical school (34 of 64 program graduates; 53%). Eight have chosen to specialize in radiation oncology (13%; 2 applying into radiation oncology, 1 in residency, and 5 attendings). Of the 25% of alumni who responded to our survey, 77% responded that the mentorship provided by the ACRC program was very or extremely effective in guiding their academic development. All respondents rated the research opportunities as good or excellent, and 77% rated the clinical experience opportunities as good or excellent. Most (77%) reported that the ACRC program had substantial or significant influence on their choice of career path., Conclusions: The ACRC program provides an opportunity to address recruitment challenges in radiation oncology by offering early exposure to the field, clinical research skills, and mentorship. With the strong interest in our job posting this year, there is potential to expand this program to other institutions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)
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- 2024
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39. Surgery and stereotactic radiosurgery for spinal leiomyosarcoma: a single-institution retrospective series and systematic review.
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Zamarud A, Marianayagam NJ, Sekar V, Testa S, Park DJ, Yener U, McCleary TL, Yoo KH, Emrich S, Tayag A, Ustrzynski L, Pollom E, Soltys S, Wang L, Charville G, Ganjoo K, Chang SD, and Meola A
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- Humans, Middle Aged, Aged, Female, Adult, Retrospective Studies, Male, Aged, 80 and over, Treatment Outcome, Leiomyosarcoma surgery, Leiomyosarcoma pathology, Radiosurgery methods, Spinal Neoplasms surgery, Spinal Neoplasms radiotherapy
- Abstract
Objective: Leiomyosarcoma (LMS) is a rare, aggressive soft-tissue sarcoma that seldom spreads to the bone. The spine can be either the site of LMS osseous metastases or the primary tumor site. The optimal treatment option for spinal LMS is still unclear. The authors present a cohort of patients with spinal LMS treated with either upfront surgery or upfront CyberKnife stereotactic radiosurgery (SRS)., Methods: The authors retrospectively studied the clinical and radiological outcomes of 17 patients with spinal LMS treated at their institution between 2004 and 2020. Either surgery or SRS was used as the upfront treatment. The clinical and radiological outcomes were assessed. A systematic review of the literature was also conducted., Results: Of the 17 patients (20 spinal lesions), 12 (70.6%) were female. The median patient age was 61 years (range 41-80 years). Ten patients had upfront surgery for their spinal lesions, and 7 had upfront CyberKnife radiosurgery. The median follow-up was 11 months (range 0.3-130 months). The median overall survival (OS) for the entire cohort was 13 months (range 0.3-97 months). In subgroup analysis, the median OS was lower for the surgical group (13 months, range 0.3-50 months), while the median OS for the SRS group was 15 months (range 5-97 months) (p = 0.5). Forty percent (n = 4) of those treated with surgery presented with local recurrence at a median of 6.7 months (range 0.3-36 months), while only 14% (n = 1) of those treated with CyberKnife radiosurgery had local recurrence after 5 months. Local tumor control (LTC) rates at the 6-, 12-, and 18-month follow-ups were 72%, 58%, and 43%, respectively, for the SRS group and 40%, 30%, and 20%, respectively, for the surgery group (p < 0.05). The literature review included 35 papers with 70 patients harboring spinal LMS; only 2 patients were treated with SRS. The literature review confirms the clinical and radiological outcomes of the surgical group, while data on SRS are anecdotal., Conclusions: The authors present the largest series in the literature of spinal LMS and the first on SRS for spinal LMS. This study shows that LTC is statistically significantly better in patients receiving upfront SRS instead of surgery. The OS does not appear different between the two groups.
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- 2023
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40. Stereotactic radiosurgery for distant brain metastases secondary to esthesioneuroblastoma: a single-institution series.
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Zamarud A, Yener U, Yoo KH, Park DJ, Marianayagam NJ, Ho QA, Pollom E, Soltys S, Wang L, Chang SD, and Meola A
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- Humans, Middle Aged, Aged, Retrospective Studies, Nasal Cavity surgery, Treatment Outcome, Radiosurgery adverse effects, Esthesioneuroblastoma, Olfactory radiotherapy, Esthesioneuroblastoma, Olfactory surgery, Esthesioneuroblastoma, Olfactory etiology, Brain Neoplasms radiotherapy, Brain Neoplasms surgery, Brain Neoplasms pathology, Nose Neoplasms radiotherapy, Nose Neoplasms surgery, Nose Neoplasms etiology
- Abstract
Objective: Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, is a rare, malignant tumor of neuroectodermal origin that arises from the olfactory neuroepithelium. In this study the authors present the first series in the literature on distant brain metastases (BMs) secondary to ENB that were treated with stereotactic radiosurgery (SRS), to evaluate the safety and effectiveness of SRS for this indication., Methods: A retrospective analysis of clinical and radiological outcomes of patients with ENB who underwent CyberKnife (CK) SRS at a single center was conducted. The clinical and radiological outcomes of patients, including progression-free survival, overall survival, and local tumor control (LTC) were reported., Results: Between 2003 and 2022, 32 distant BMs in 8 patients were treated with CK SRS at Stanford University. The median patient age at BM diagnosis was 62 years (range 47-75 years). Among 32 lesions, 2 (6%) had previously been treated with surgery, whereas for all other lesions (30 [94%]), CK SRS was used as their primary treatment modality. The median target volume was 1.5 cm3 (range 0.09-21.54 cm3). CK SRS was delivered by a median marginal dose of 23 Gy (range 15-30 Gy) and a median of 3 fractions (range 1-5 fractions) to a median isodose line of 77% (range 70%-88%). The median biologically effective dose was 48 Gy (range 21-99.9 Gy) and the median follow-up was 30 months (range 3-95 months). The LTC at 1-, 2-, and 3-year follow-up was 86%, 65%, and 50%, respectively. The median progression-free survival and overall survival were 29 months (range 11-79 months) and 51 months (range 15-79 months), respectively. None of the patients presented adverse radiation effects., Conclusions: In the authors' experience, SRS provided excellent LTC without any adverse radiation effects for BMs secondary to ENB.
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- 2023
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41. Stereotactic radiosurgery for sarcoma metastases to the brain: a single-institution experience.
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Zamarud A, Park DJ, Dadey DYA, Yoo KH, Marianayagam NJ, Yener U, Szalkowski GA, Pollom E, Soltys S, Chang SD, and Meola A
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- Female, Humans, Child, Preschool, Child, Adolescent, Young Adult, Adult, Middle Aged, Aged, Retrospective Studies, Treatment Outcome, Brain pathology, Radiosurgery methods, Brain Neoplasms radiotherapy, Brain Neoplasms surgery, Brain Neoplasms pathology, Sarcoma radiotherapy, Sarcoma surgery
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Objective: Brain metastases (BMs) secondary to sarcoma are rare, and their incidence ranges from 1% to 8% of all bone and soft tissue sarcomas. Although stereotactic radiosurgery (SRS) is widely used for BMs, only a few papers have reported on SRS for sarcoma metastasizing to the brain. The purpose of this study was to evaluate the safety and effectiveness of SRS for sarcoma BM., Methods: The authors retrospectively reviewed the clinical and radiological outcomes of patients with BM secondary to histopathologically confirmed sarcoma treated with SRS, either as primary treatment or as adjuvant therapy after surgery, at their institution between January 2005 and September 2022. They also compared the outcomes of patients with hemorrhagic lesions and of those without., Results: Twenty-three patients (9 females) with 150 BMs secondary to sarcoma were treated with CyberKnife SRS. Median age at the time of treatment was 48.22 years (range 4-76 years). The most common primary tumor sites were the heart, lungs, uterus, upper extremities, chest wall, and head and neck. The median Karnofsky Performance Status on presentation was 73.28 (range 40-100). Eight patients underwent SRS as a primary treatment and 15 as adjuvant therapy to the resection cavity. The median tumor volume was 24.1 cm3 (range 0.1-150.3 cm3), the median marginal dose was 24 Gy (range 18-30 Gy) delivered in a median of 1 fraction (range 1-5) to a median isodose line of 76%. The median follow-up was 8 months (range 2-40 months). Median progression-free survival and overall survival were 5.3 months (range 0.4-32 months) and 8.2 months (range 0.1-40), respectively. The 3-, 6-, and 12-month local tumor control (LTC) rates for all lesions were respectively 78%, 52%, and 30%. There were no radiation-induced adverse effects. LTC at the 3-, 6-, and 12-month follow-ups was better in patients without hemorrhagic lesions (100%, 70%, and 40%, respectively) than in those with hemorrhagic lesions (68%, 38%, and 23%, respectively)., Conclusions: SRS, both as a primary treatment and as adjuvant therapy to the resection cavity after surgery, is a safe and relatively effective treatment modality for sarcoma BMs. Nonhemorrhagic lesions show better LTC than hemorrhagic lesions. Larger studies aiming to validate these results are encouraged.
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- 2023
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42. SUPPORT: SUrvey of Parental Leave POlicies of RadiaTion Oncology Programs and Residency Applicants.
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Baniel CC, Qu V, Ponce SB, Taparra K, Beadle B, Currey A, Lichter KE, Frank J, Bagshaw H, Soltys S, and Pollom E
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Purpose: Recruitment to radiation oncology training programs has recently declined, and gender inequities persist in radiation oncology. Policies that promote inclusivity, such as the updated American College of Graduate Medical Education parental leave policy establishing minimum parental leave requirements, may support recruitment to radiation oncology., Methods and Materials: We surveyed 2021-2022 radiation oncology residency applicants and program directors (PDs) about program-specific parental leave policies, transparency of parental leave information during the residency application and interview process, and perceptions of the effect of parenthood on residency training, career advancement, and well-being., Results: Of 89 radiation oncology PDs, 29 (33%) completed the survey. Of 154 residency applicants (current fourth-year medical students, international applicants, or postdoctoral fellows) surveyed, 62 (40%) completed the survey. Most applicants planned to start a family during residency (53%) and reported perceived flexibility to start a family influenced their decision to pursue radiation oncology over other career specialties (55%). Many applicants viewed time in residency (nonresearch, 22%), in research (33%), and as early career faculty (24%) as the best time to start a family. A small number of applicants used program-specific parental leave policy information in determining their rank list (11%), and many applicants sought information regarding fertility health care benefits (55%). Many applicants obtained parental leave information verbally, despite expressing a preference for objective means (slide deck, 63%; website, 50%; or handout, 42%) of information sharing. PDs were all supportive of a 6-week maternity leave policy (100% agree or strongly agree with the policy) and did not feel parental leave would negatively affect a resident's ability to pursue an academic (100%) or private practice career (100%)., Conclusions: Many radiation oncology residency applicants plan to start families during training, seek and value program-specific parental leave information and health benefits, and prefer objective means of information sharing. These findings likely reflect those who have strong views of parental leave policies., (© 2023 The Author(s).)
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- 2023
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43. Practical Guideline for Prevention of Patchy Hair Loss following CyberKnife Stereotactic Radiosurgery for Calvarial or Scalp Tumors: Retrospective Analysis of a Single Institution Experience.
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Park DJ, Marianayagam NJ, Yener U, Tayag A, Ustrzynski L, Emrich SC, Pollom E, Soltys S, Meola A, and Chang SD
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Introduction: Patchy alopecia is a common adverse effect of stereotactic radiosurgery (SRS) on the calvarium and/or scalp, yet no guidelines exist for its prevention. This study aims to investigate the incidence and outcomes of patchy alopecia following SRS for patients with calvarial or scalp lesions and establish preventive guidelines., Methods: The study included 20 patients who underwent CyberKnife SRS for calvarial or scalp lesions, resulting in a total of 30 treated lesions. SRS was administered as a single fraction for 8 lesions and hypofractionated for 22 lesions. The median SRS target volume was 9.85 cc (range: 0.81-110.7 cc), and the median prescription dose was 27 Gy (range: 16-40 Gy), delivered in 1-5 fractions (median: 3). The median follow-up was 15 months., Results: Among the 30 treated lesions, 11 led to patchy alopecia, while 19 did not. All cases of alopecia resolved within 12 months, and no patients experienced other adverse radiation effects. Lesions resulting in alopecia exhibited significantly higher biologically effective dose (BED) and single-fraction equivalent dose (SFED) on the overlying scalp compared to those without alopecia. Patients with BED and SFED exceeding 60 Gy and 20 Gy, respectively, were 9.3 times more likely to experience patchy alopecia than those with lower doses. The 1-year local tumor control rate for the treated lesions was 93.3%. Chemotherapy was administered for 26 lesions, with 11 lesions receiving radiosensitizing agents. However, no statistically significant difference was found., Conclusion: In summary, SRS is a safe and effective treatment for patients with calvarial/scalp masses regarding patchy alopecia near the treated area. Limiting the BED under 60 Gy and SFED under 20 Gy for the overlying scalp can help prevent patchy alopecia during SRS treatment of the calvarial/scalp mass. Clinicians can use this information to inform patients about the risk of alopecia and the contributing factors., (© 2023 The Author(s). Published by S. Karger AG, Basel.)
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- 2023
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44. Local control of brain metastases with osimertinib alone in patients with EGFR-mutant non-small cell lung cancer.
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Hui C, Qu V, Wang JY, von Eyben R, Chang YC, Chiang PL, Liang CH, Lu JT, Li G, Hayden-Gephart M, Wakelee H, Neal J, Ramchandran K, Das M, Nagpal S, Soltys S, Myall N, and Pollom E
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- Humans, Aniline Compounds therapeutic use, ErbB Receptors genetics, Mutation, Retrospective Studies, Brain Neoplasms drug therapy, Brain Neoplasms secondary, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung pathology, Lung Neoplasms drug therapy, Lung Neoplasms pathology, Protein Kinase Inhibitors therapeutic use
- Abstract
Purpose: Although osimertinib has excellent intracranial activity in metastatic non-small cell lung cancer (NSCLC) with exon 19 deletion or L858R EGFR alterations, measures of local control of brain metastases are less well-reported. We describe lesion-level outcomes of brain metastases treated with osimertinib alone., Methods: We retrospectively reviewed patients with EGFR-mutant NSCLC with untreated brain metastasis measuring ≥ 5 mm at the time of initiating osimertinib. Cumulative incidence of local recurrence in brain (LRiB) was calculated with death as a competing risk, and univariable and multivariable analyses were conducted to identify factors associated with LRiB., Results: We included 284 brain metastases from 37 patients. Median follow-up was 20.1 months. On initial MRI after starting osimertinib, patient-level response was complete response (CR) in 11 (15%), partial response (PR) in 33 (45%), stable disease (SD) in 18 (25%) and progressive disease (PD) in 11 (15%). The 1-year cumulative incidence of LRiB was 14% (95% CI 9.9-17.9) and was significantly different in patients with a CR (0%), PR (4%), and SD (11%; p = 0.02). Uncontrolled primary tumor (adjusted hazard ratio [aHR] 3.78, 95% CI 1.87-7.66; p < 0.001), increasing number of prior systemic therapies (aHR 2.12, 95% CI 1.49-3.04; p < 0.001), and higher ECOG score (aHR 7.8, 95% CI 1.99-31.81; p = 0.003) were associated with LRiB., Conclusions: Although 1-year cumulative incidence of LRiB is < 4% with a CR or PR, 1-year cumulative incidence of LRiB is over 10% for patients with less than a PR to osimertinib on initial MRI. These patients should be followed closely for need for additional treatment such as stereotactic radiosurgery., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2022
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45. Radiotherapy for Brain Metastases from Thyroid Cancer: An Institutional and National Retrospective Cohort Study.
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Blomain E, Berta S, Hug N, Giao D, Meola A, Binkley M, Hui C, Churilla T, Shahsavari N, Desai K, Chang S, Soltys S, and Pollom E
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- Cohort Studies, Humans, Necrosis etiology, Necrosis surgery, Retrospective Studies, Treatment Outcome, Brain Neoplasms radiotherapy, Brain Neoplasms secondary, Brain Neoplasms surgery, Radiation Injuries etiology, Radiosurgery methods, Thyroid Neoplasms surgery
- Abstract
Background: Stereotactic radiosurgery (SRS) is the standard of care for patients with a limited number of brain metastases. Despite the fact that the seminal studies regarding SRS for brain metastases were largely tissue agnostic, several current national guidelines do not uniformly recommend SRS in thyroid cancer. We therefore investigated oncological outcomes in a cohort of patients with brain metastases from thyroid cancer who received radiotherapy (RT) at our institution as well as those in a nationally representative cancer cohort, the National Cancer Database (NCDB). Materials and Methods: We identified patients with thyroid cancer and brain metastases treated with RT at our institution from 2002 through 2020. For the NCDB cohort, the national database of patients with thyroid cancer was screened on the basis of brain-directed RT or brain metastases. For the institutional cohort, the cumulative risk of local failure (LF), distant intracranial failure, and radiation necrosis were calculated, adjusted for the competing risk of death. Overall survival (OS) in both cohorts was analyzed using the Kaplan-Meier method. Univariate analysis was accomplished via clustered competing risks regression. Results: For the institutional cohort, we identified 33 patients with 212 treated brain metastases. OS was 6.6 months. The 1-year cumulative incidences of LF and distant intracranial failures were 7.0% and 38%, respectively. The 1-year risk of radiation necrosis was 3.3%. In the NCDB cohort, there were 289 patients, and the median survival was 10.2 months. NCDB national practice patterns analysis showed an increasing use of SRS over time in both the entire cohort and the subset of anaplastic patients. Univariate analysis was performed for OS, risk of LF, risk of regional intracranial failure, and risk of radiation necrosis. Conclusions: SRS is a safe, effective, and increasingly utilized treatment for thyroid cancer brain metastases of any histology and should be the standard of care treatment.
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- 2022
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46. DSC Perfusion MRI-Derived Fractional Tumor Burden and Relative CBV Differentiate Tumor Progression and Radiation Necrosis in Brain Metastases Treated with Stereotactic Radiosurgery.
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Kuo F, Ng NN, Nagpal S, Pollom EL, Soltys S, Hayden-Gephart M, Li G, Born DE, and Iv M
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- Humans, Magnetic Resonance Imaging methods, Necrosis diagnostic imaging, Perfusion, Retrospective Studies, Tumor Burden, Brain Neoplasms diagnostic imaging, Brain Neoplasms radiotherapy, Brain Neoplasms surgery, Radiation Injuries diagnostic imaging, Radiation Injuries etiology, Radiosurgery methods
- Abstract
Background and Purpose: Differentiation between tumor and radiation necrosis in patients with brain metastases treated with stereotactic radiosurgery is challenging. We hypothesized that MR perfusion and metabolic metrics can differentiate radiation necrosis from progressive tumor in this setting., Materials and Methods: We retrospectively evaluated MRIs comprising DSC, dynamic contrast-enhanced, and arterial spin-labeling perfusion imaging in subjects with brain metastases previously treated with stereotactic radiosurgery. For each lesion, we obtained the mean normalized and standardized relative CBV and fractional tumor burden, volume transfer constant, and normalized maximum CBF, as well as the maximum standardized uptake value in a subset of subjects who underwent FDG-PET. Relative CBV thresholds of 1 and 1.75 were used to define low and high fractional tumor burden., Results: Thirty subjects with 37 lesions (20 radiation necrosis, 17 tumor) were included. Compared with radiation necrosis, tumor had increased mean normalized and standardized relative CBV ( P = .002) and high fractional tumor burden (normalized, P = .005; standardized, P = .003) and decreased low fractional tumor burden (normalized, P = .03; standardized, P = .01). The area under the curve showed that relative CBV (normalized = 0.80; standardized = 0.79) and high fractional tumor burden (normalized = 0.77; standardized = 0.78) performed the best to discriminate tumor and radiation necrosis. For tumor prediction, the normalized relative CBV cutoff of ≥1.75 yielded a sensitivity of 76.5% and specificity of 70.0%, while the standardized cutoff of ≥1.75 yielded a sensitivity of 41.2% and specificity of 95.0%. No significance was found with the volume transfer constant, normalized CBF, and standardized uptake value., Conclusions: Increased relative CBV and high fractional tumor burden (defined by a threshold relative CBV of ≥1.75) best differentiated tumor from radiation necrosis in subjects with brain metastases treated with stereotactic radiosurgery. Performance of normalized and standardized approaches was similar., (© 2022 by American Journal of Neuroradiology.)
- Published
- 2022
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47. Current status and recent advances in resection cavity irradiation of brain metastases.
- Author
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Minniti G, Niyazi M, Andratschke N, Guckenberger M, Palmer JD, Shih HA, Lo SS, Soltys S, Russo I, Brown PD, and Belka C
- Subjects
- Cranial Irradiation, Disease Progression, Dose Fractionation, Radiation, Humans, Neoplasm Metastasis, Neoplasm Recurrence, Local mortality, Radiotherapy, Radiotherapy, Adjuvant, Risk, Treatment Outcome, Brain radiation effects, Brain Neoplasms radiotherapy, Brain Neoplasms secondary, Brain Neoplasms surgery, Necrosis etiology, Radiosurgery methods
- Abstract
Despite complete surgical resection brain metastases are at significant risk of local recurrence without additional radiation therapy. Traditionally, the addition of postoperative whole brain radiotherapy (WBRT) has been considered the standard of care on the basis of randomized studies demonstrating its efficacy in reducing the risk of recurrence in the surgical bed as well as the incidence of new distant metastases. More recently, postoperative stereotactic radiosurgery (SRS) to the surgical bed has emerged as an effective and safe treatment option for resected brain metastases. Published randomized trials have demonstrated that postoperative SRS to the resection cavity provides superior local control compared to surgery alone, and significantly decreases the risk of neurocognitive decline compared to WBRT, without detrimental effects on survival. While studies support the use of postoperative SRS to the resection cavity as the standard of care after surgery, there are several issues that need to be investigated further with the aim of improving local control and reducing the risk of leptomeningeal disease and radiation necrosis, including the optimal dose prescription/fractionation, the timing of postoperative SRS treatment, and surgical cavity target delineation. We provide a clinical overview on current status and recent advances in resection cavity irradiation of brain metastases, focusing on relevant strategies that can improve local control and minimize the risk of radiation-induced toxicity.
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- 2021
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48. Stereotactic radiosurgery for head and neck paragangliomas: a systematic review and meta-analysis.
- Author
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Fatima N, Pollom E, Soltys S, Chang SD, and Meola A
- Subjects
- Adult, Aged, Female, Head and Neck Neoplasms diagnostic imaging, Humans, Male, Middle Aged, Paraganglioma diagnostic imaging, Radiosurgery trends, Treatment Outcome, Head and Neck Neoplasms surgery, Paraganglioma surgery, Radiosurgery methods
- Abstract
Head and neck paragangliomas (HNPs) are rare, usually benign hyper vascularized neuroendocrine tumors that traditionally have been treated by surgery, with or without endovascular embolization, or, more recently stereotactic radiosurgery (SRS). The aim of our study is to determine the clinical and radiographic effectiveness of SRS for treatment of HNPs. A systematic search of electronic databases was performed, and 37 articles reporting 11,174 patients (1144 tumors) with glomus jugulare (GJT: 993, 86.9%), glomus tympanicum (GTT: 94, 8.2%), carotid body tumors (CBTs: 28, 2.4%), and glomus vagale (GVT: 16, 1.4%) treated with SRS definitively or adjuvantly were included. The local control (LC) was estimated from the pooled analysis of the series, and its association with SRS technique as well as demographic and clinical factors was analyzed. The median age was 56 years (44-69 years). With a median clinical and radiological follow-up of 44 months (9-161 months), LC was 94.2%. Majority of the patients (61.0%) underwent Gamma Knife Radiosurgery (GKS), but there was no statistically significant difference in LC depending upon the SRS technique (p = 0.9). Spearmen's correlation showed that LC was strongly and negatively correlated with multiple parameters, which included female gender (r = - 0.4, p = 0.001), right-sided tumor (r = - 0.3, p = 0.03), primary SRS (r = - 0.5, p ≤ 0.001), and initial clinical presentation of hearing loss (r = - 0.4, p = 0.001). To achieve a LC ≥ 90%, a median marginal dose (Gy) of 15 (range, 12-30 Gy) was required. The results corroborate that SRS in HNPs is associated with good clinical and radiological outcome.
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- 2021
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49. Virtual Radiation Oncology Clerkship During the COVID-19 Pandemic and Beyond.
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Sandhu N, Frank J, von Eyben R, Miller J, Obeid JP, Kastelowitz N, Panjwani N, Soltys S, Bagshaw HP, Donaldson SS, Horst K, Beadle BM, Chang DT, Gibbs IC, and Pollom E
- Subjects
- Adult, COVID-19, Female, Health Knowledge, Attitudes, Practice, Humans, Male, User-Computer Interface, Young Adult, Clinical Clerkship methods, Coronavirus Infections epidemiology, Pandemics, Pneumonia, Viral epidemiology, Radiation Oncology education
- Abstract
Purpose: We evaluated the impact of a virtual radiation oncology clerkship., Methods and Materials: We developed a 2-week virtual radiation oncology clerkship that launched on April 27, 2020. Clerkship components included a virtual clinic with radiation oncology faculty and residents, didactic lectures, student talks, and supplemental sessions such as tumor boards and chart rounds. Medical students completed pre- and post-clerkship self-assessments. Faculty and resident participants also completed surveys on their experience with virtual lectures and clinics. Pre- and post-clerkship results were compared using a 2-sided paired t test. An analysis of variance model was used to analyze the clerkship components., Results: Twenty-six medical students, including 4 visiting students, enrolled over 2 clerkship periods (4 weeks). All students completed the pre- and post-clerkship self-assessments and agreed that the clerkship improved their understanding of radiation oncology. Compared with 3 (11.5%) students who agreed that they understood the daily responsibilities of a radiation oncologist before the clerkship, 22 (84.6%) students agreed and 3 (11.5%) strongly agreed that they understood the daily responsibilities of a radiation oncologist after the clerkship (P < .0001). Although 15 students (57.7%) reported an increased interest in radiation oncology because of the clerkship, the mean level of interest in radiation oncology as a career remained the same, with pre- and post-clerkship scores of 3.0 (±0.9) and 3.0 (±1.1) on a 5-point scale, respectively (P = .7). Students found virtual clinic and didactic lectures to be the most valuable components of the clerkship. Most respondents agreed (30.8%) or strongly agreed (65.4%) to recommend the clerkship to their classmates., Conclusions: Our virtual clerkship was effective in increasing medical student interest in and knowledge about radiation oncology. These data will help optimize a new paradigm of virtual radiation oncology education for medical students during COVID-19 and beyond., (Copyright © 2020 Elsevier Inc. All rights reserved.)
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- 2020
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50. Stereotactic Radiosurgery for Benign Spinal Tumors.
- Author
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Meola A, Soltys S, Schmitt A, Gerszten PC, and Chang SD
- Subjects
- Humans, Meningeal Neoplasms radiotherapy, Meningioma surgery, Neurosurgical Procedures methods, Spinal Cord Neoplasms surgery, Spinal Neoplasms surgery, Meningeal Neoplasms surgery, Meningioma radiotherapy, Radiosurgery, Spinal Cord Neoplasms radiotherapy, Spinal Neoplasms radiotherapy
- Abstract
Benign spinal tumors are rare clinical conditions, including meningiomas, schwannomas, and neurofibromas. Although these tumors are usually treated with open surgical resection, spinal stereotactic radiosurgery may be a safe and effective alternative to surgery in selected patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2020
- Full Text
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