Publications by authors named "Anthony Cmelak"

93 Publications

Targeting for stereotactic radiosurgical thalamotomy based on tremor treatment response.

J Neurosurg 2021 Oct 29:1-8. Epub 2021 Oct 29.

Departments of1Radiation Oncology.

Objective: Stereotactic radiosurgery (SRS) treats severe, medically refractory essential tremor and tremor-dominant Parkinson disease. However, the optimal target for SRS treatment within the thalamic ventral intermediate nucleus (VIM) is not clearly defined. This work evaluates the precision of the physician-selected VIM target, and determines the optimal SRS target within the VIM by correlation between early responders and nonresponders.

Methods: Early responders and nonresponders were assessed retrospectively by Elements Basal Ganglia Atlas autocontouring of the VIM on the pre-SRS-treatment 1-mm slice thickness T1-weighted MRI and correlating the center of the post-SRS-treatment lesion. Using pre- and posttreatment diffusion tensor imaging, the fiber tracking package in the Elements software generated tremor-related tracts from autosegmented motor cortex, thalamus, red nucleus, and dentate nucleus. Autocontouring of the VIM was successful for all patients.

Results: Among 23 patients, physician-directed SRS targets had a medial-lateral target range from +2.5 mm to -2.0 mm from the VIM center. Relative to the VIM center, the SRS isocenter target was 0.7-0.9 mm lateral for 6 early responders and 0.9-1.1 mm medial for 4 nonresponders (p = 0.019), and without differences in the other dimensions: 0.2 mm posterior and 0.6 mm superior. Dose-volume histogram analyses for the VIM had no significant differences between responders and nonresponders between 20 Gy and 140 Gy, mean or maximum dose, and dose to small volumes. Tractography data was obtained for 4 patients.

Conclusions: For tremor control in early responders, the Elements Basal Ganglia Atlas autocontour for the VIM provides the optimal SRS target location that is 0.7-0.9 mm lateral to the VIM center.
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http://dx.doi.org/10.3171/2021.7.JNS21160DOI Listing
October 2021

Impact of COVID-19 on presentation, staging, and treatment of head and neck mucosal squamous cell carcinoma.

Am J Otolaryngol 2021 Oct 8;43(1):103263. Epub 2021 Oct 8.

Department of Otolaryngology Head and Neck Surgery, Vanderbilt University Medical Center, 7th floor 1215 21st Ave S, Nashville, TN 37232, USA.

Objectives: During the COVID-19 pandemic, maintenance of safe and timely oncologic care has been challenging. The goal of this study is to compare presenting symptoms, staging, and treatment of head and neck mucosal squamous cell carcinoma during the pandemic with an analogous timeframe one year prior.

Materials And Methods: Retrospective cohort study at a single tertiary academic center of new adult patients evaluated in a head and neck surgical oncology clinic from March -July 2019 (pre-pandemic control) and March - July 2020 (COVID-19 pandemic).

Results: During the pandemic, the proportion of patients with newly diagnosed malignancies increased by 5%, while the overall number of new patients decreased (n = 575) compared to the control year (n = 776). For patients with mucosal squamous cell carcinoma (SCC), median time from referral to initial clinic visit decreased from 11 days (2019) to 8 days (2020) (p = 0.0031). There was no significant difference in total number (p = 0.914) or duration (p = 0.872) of symptoms. During the pandemic, patients were more likely to present with regional nodal metastases (adjusted odds ratio (OR) 2.846, 95% CI 1.072-3.219, p = 0.028) and more advanced clinical nodal (N) staging (p = 0.011). No significant difference was seen for clinical tumor (T) (p = 0.502) or metastasis (M) staging (p = 0.278). No significant difference in pathologic T (p = 0.665), or N staging (p = 0.907) was found between the two periods.

Conclusion: Head and neck mucosal SCC patients presented with more advanced clinical nodal disease during the early months of the COVID-19 pandemic despite no change in presenting symptoms.
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http://dx.doi.org/10.1016/j.amjoto.2021.103263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500684PMC
October 2021

Effects of cone versus multi-leaf collimation on dosimetry and neurotoxicity in patients with small arteriovenous malformations treated by stereotactic radiosurgery.

J Radiosurg SBRT 2021 ;7(4):287-294

Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN, USA.

Purpose/objective: Linear accelerator (LINAC) based stereotactic radiosurgery (SRS) for arteriovenous malformations (AVMs) is delivered with cone or multileaf collimators (MLCs), and favorable dosimetry is associated with reduced radionecrosis in normal brain tissue. This study aims to determine whether cones or MLCs has better dosimetric characteristics, to predict differences in toxicity.

Methods: All patients treated for AVMs using LINAC SRS from 2003-2017 were examined retrospectively. Demographic data, volumes of normal tissue exposed to 12Gy (V12Gy[cc]) and 4Gy (V4Gy[cc]), maximal dose, and dose gradient were analyzed. Univariate and multivariate analyses were used to evaluate relationships between collimator type, dosimetric parameters, and toxicity. Propensity score matching was used to adjust for AVM size.

Results: Compared to MLC, cones were independently associated with reduced V12Gy[cc] after propensity score matching (p=0.008) and reduced neurotoxicity (p=0.016). Higher V12Gy[cc] (p=0.0008) and V4Gy[cc] (p=0.002) were associated with increased neurotoxicity.

Conclusions: Treating AVMs with cone-based SRS over MLC-based SRS may improve dosimetry and reduce toxicities.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492055PMC
January 2021

Noninvasive Thalamotomy for Refractory Tremor by Frameless Radiosurgery.

Int J Radiat Oncol Biol Phys 2021 Aug 25. Epub 2021 Aug 25.

Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN.

Objective: We sought to determine whether a more widely accessible, non-invasive frameless approach to radiosurgical thalamotomy would improve objective measures of refractory essential or parkinsonian tremor without added toxicity compared to reports of frame-based radiosurgery.

Methods: We conducted a single-arm pilot observational prospective trial of adult patients with essential or parkinsonian tremor from 2013 to 2019 and report results at one-year follow-up. Patients were treated with frameless unilateral radiosurgical ablation of the thalamic ventral intermediate nucleus to a maximum dose of 160 Gy. Treatment response was measured by the Fahn-Tolosa-Marin (FTM) tremor rating scale and the Quality of Life in Essential Tremor or Parkinson's Disease Questionnaire obtained prior to treatment and at 3, 6, 9, and 12 months.

Results: Thirty-three patients, including 23 with essential tremor and 10 with Parkinson's disease, were enrolled. Overall treatment response rate per FTM was 83% (n=15/18) at 6 months. There was a marked improvement in tremor, with average total FTM reduction of 21% at 3 months (from 46 to 30 points, p=0.003) and 41% at 6 months (from 46 to 24 points, p=0.001). At 6 months, functional decline had regressed by 54% (from 15 to 7 points, p=0.001). Quality of life improved by 57% (p=0.001) at 6 months in patients with essential tremor, and patients with Parkinson's Disease had unchanged quality of life. At one-year follow-up, grade 2 neurologic adverse events were observed in 6% (n=2/33) of patients without any grade ≥ 3 events.

Conclusion: Noninvasive, frameless radiosurgical thalamotomy may be a feasible treatment for patients with refractory tremor and demonstrates short-term safety at one-year follow-up. This pilot study provides promising preliminary descriptions of efficacy, and definitive estimates of long-term safety and benefit require further study with longer follow-up.
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http://dx.doi.org/10.1016/j.ijrobp.2021.08.021DOI Listing
August 2021

Stereotactic Radiosurgery and Hypofractionated Stereotactic Radiotherapy for Nonfunctioning Pituitary Adenoma.

J Neurol Surg B Skull Base 2021 Jul 5;82(Suppl 3):e51-e58. Epub 2020 May 5.

Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, Tennessee, United States.

 Hypofractionated stereotactic radiotherapy (HSRT) in two to five fractions may offer patients with large nonfunctioning pituitary adenomas (NFPAs) with chiasm involvement a safe and effective treatment over a single week. However, little has been reported regarding this novel approach.  We compared the feasibility, outcomes, and toxicity of single-fraction stereotactic radiosurgery and HSRT.  This study was conducted at a tertiary academic referral center.  After approval by the institutional review board, we performed a retrospective cohort study of patients treated at our institution with stereotactic radiosurgery (SRS) and HSRT for NFPA. Selection for SRS or HSRT was based on clinicopathologic factors including tumor size and cavernous sinus invasion at the discretion of the treating physician.  Local control, endocrinopathy, and radiation-associated toxicity were evaluated by binary logistic regression and Cox's proportional hazards regression.  A total of 45 patients with mean follow-up of 5 years were enrolled including 26 patients treated by HSRT with mean follow-up of 3 years and 19 patients treated by SRS with median follow-up of 6 years. Clinicopathologic characteristics were balanced between cohorts. Local failure at last follow-up was 5% in the SRS cohort and 8% in the HSRT cohort, and rates of post-SRS endocrinopathy were similar between each cohort. Late complications including radionecrosis, visual deficit, and secondary malignancy were minimal in either cohort.  HSRT is an appropriate treatment strategy for patients with NFPAs, particularly for optic pathway preservation in the setting of large tumors with chiasm involvement. Further studies are needed to optimize fractionated approaches and patient selection.
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http://dx.doi.org/10.1055/s-0040-1710518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289501PMC
July 2021

Progressive Vestibular Schwannoma following Subtotal or Near-Total Resection: Dose-Escalated versus Standard-Dose Salvage Stereotactic Radiosurgery.

J Neurol Surg B Skull Base 2021 Jul 26;82(Suppl 3):e9-e14. Epub 2020 May 26.

Department of Radiation Oncology, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, United States.

 Local failure of incompletely resected vestibular schwannoma (VS) following salvage stereotactic radiosurgery (SRS) using standard doses of 12 to 13 Gy is common. We hypothesized that dose-escalated SRS, corrected for biologically effective dose, would have superior local control of high-grade VS progressing after subtotal or near-total resection compared with standard-dose SRS.  Retrospective cohort study.  Tertiary academic referral center.  Adult patients treated with linear accelerator-based SRS for progressive VS following subtotal or near-total resection.  Dose-escalated SRS was defined by a biologically effective dose exceeding a single-fraction 13-Gy regimen. Study outcomes were local control and neurologic sequelae of SRS. Binary logistic regression was used to evaluate predictors of study outcomes.  A total of 18 patients with progressive disease following subtotal (71%) and near-total (39%) resection of Koos grade IV disease (94%) were enrolled. Of the 18 patients, 7 were treated with dose-escalated SRS and 11 with standard-dose SRS. Over a median follow-up of 32 months after SRS, local control was 100% in the dose-escalated cohort and 91% in the standard-dose cohort (  = 0.95). Neurologic sequelae occurred in 28% of patients, including 60% of dose-escalated cohort and 40% of the standard-dose cohort (  = 0.12), although permanent neurologic sequelae were low at 6%.  Dose-escalated SRS has similar local control of recurrent VS following progression after subtotal or near-total resection and does not appear to have higher neurologic sequalae. Larger studies are needed.
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http://dx.doi.org/10.1055/s-0040-1712462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289534PMC
July 2021

Diameter-Based Volumetric Models May Inadequately Calculate Jugular Paraganglioma Volume Following Sub-Total Resection.

Otol Neurotol 2021 10;42(9):e1339-e1345

Department of Radiology, Vanderbilt University Medical Center, Nashville, Tennessee.

Background: As gross total resection of jugular paragangliomas (JPs) may result in cranial nerve deficits, JPs are increasingly managed with subtotal resection (STR) with postoperative radiological monitoring. However, the validity of commonly used diameter-based models that calculate postoperative volume to determine residual tumor growth is dubious. The purpose of this study was to assess the accuracy of these models compared to manual volumetric slice-by-slice segmentation.

Methods: A senior neuroradiologist measured volumes via slice-by-slice segmentation of JPs pre- and postoperatively from patients who underwent STR from 2007 to 2019. Volumes from three linear-based models were calculated. Models with absolute percent error (APE) > 20% were considered unsatisfactory based on a common volumetric definition for residual growth. Bland-Altman plots were used to evaluate reproducibility, and Wilcoxon matched-pairs signed rank test evaluated model bias.

Results: Twenty-one patients were included. Median postoperative APE exceeded the established 20% threshold for each of the volumetric models as cuboidal, ellipsoidal, and spherical model APE were 63%, 28%, and 27%, respectively. The postoperative cuboidal model had significant systematic bias overestimating volume (p = 0.002) whereas the postoperative ellipsoidal and spherical models lacked systematic bias (p = 0.11 and p = 0.82).

Conclusion: Cuboidal, ellipsoidal, and spherical models do not provide accurate assessments of postoperative JP tumor volume and may result in salvage therapies that are unnecessary or inappropriately withheld due to inaccurate assessment of residual tumor growth. While more time-consuming, slice-by-slice segmentation by an experienced neuroradiologist provides a substantially more accurate and precise measurement of tumor volume that may optimize clinical management.
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http://dx.doi.org/10.1097/MAO.0000000000003226DOI Listing
October 2021

Treatment De-intensification for HPV-Positive Oropharynx Cancer: What Is Currently Acceptable?

J Clin Oncol 2021 08 27;39(24):2732-2733. Epub 2021 May 27.

Anthony J. Cmelak, MD, Vanderbilt University Medical Center, Nashville, TN; Robert L. Ferris, MD, PhD, UPMC Hillman Cancer Center, Pittsburgh, PA; Allen M. Chen, MD, University of California Irvine, Irvine, CA; Tanguy Seiwert, MD, Johns Hopkins Medical Institutions, Johns Hopkins Medical Center, Baltimore, MD; and Barbara Burtness, MD, Yale School of Medicine, Yale University, New Haven, CT.

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http://dx.doi.org/10.1200/JCO.21.00594DOI Listing
August 2021

ECOG-ACRIN 2399: analysis of patient related outcomes after Chemoradiation for locally advanced head and neck Cancer.

Cancers Head Neck 2020 Dec 22;5(1):12. Epub 2020 Dec 22.

Department of Radiation Oncology, Vanderbilt University, B-1003 Preston Research Building, 2220 Pierce Avenue, Nashville, TN, 37232-5671, USA.

Background: We conducted a correlative study for E2399, a function preservation trial for resectable locally advanced oropharynx and larynx cancer, to prospectively assess effects of chemoradiation (CCR) on quality of life (QOL), swallowing and voice. We correlated the results of swallow assessments done via questionnaires and objective assessments by modified barium swallow (MBS).

Methods: The Functional Assessment of Cancer-HN (FACT-HN), the Performance Status Scale - Head and Neck (PSS-HN), swallow assessments (including modified barium swallow studies), and voice assessments: Voice Handicap Index (VHI), the Voice Disability Assessment (VDA), and American Speech-Language Hearing Association's Functional Communication Measure (FCM) were conducted at baseline and periodically post-treatment for 2 years.

Results: Baseline QOL and swallowing function predicted overall survival. Patients experienced a marked decrease in QOL, swallowing, and speech post CCR although the decrease in vocal function was modest. Function and QOL returned towards baseline in the majority of patients by 12 months post treatment. Less than 10% of patients had severe dysphagia and were PEG dependent at 12 months post treatment. There was a high degree of correlation between the FACT-HN and PSS-HN swallow items. Statistically significant correlations were found between subjective and objective measures of swallow function.

Conclusions: Patients experience marked loss in swallowing function post CCR which returned to baseline in the majority of patients. The correlations between the FCM and self-report swallow items on the PSS and FACT-HN appear to be sufficiently strong to justify their use as a surrogate marker for swallowing disability in large therapeutic trials.
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http://dx.doi.org/10.1186/s41199-020-00059-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756946PMC
December 2020

Transient Subacute Facial Nerve Dysfunction After Dual Modality Treatment of Large Vestibular Schwannomas.

Otol Neurotol 2021 02;42(2):e209-e215

Department of Otolaryngology-Head and Neck Surgery.

Objectives: 1: Describe subacute facial nerve paralysis after salvage stereotactic radiosurgery (SRS). 2: To analyze predictors of facial nerve weakness after dual modality treatment.

Patients: Adult patients with Vestibular Schwannoma who underwent sub-total resection (STR) followed by salvage radiation.

Interventions: Microsurgical resection of VS, stereotactic radiosurgery, intensity-modulated radiotherapy, proton radiotherapy.

Main Outcome Measures: Serial facial nerve function (House-Brackmann scale).

Results: Thirteen patients who underwent dual modality treatment for large VS were included (mean age = 43.6 years, 77% females). The mean pre-operative tumor volume was 11.7 cm3 (SD = 6.5) and the immediate mean post-operative remnant volume was 1.5 cm3 (SD = 1.4) with a mean extent of resection of 86.7% (SD = 9.5). The mean salvage-free interval was 20.8 months (SD = 13.3). All patients had excellent one-year FN outcome (HB grade 1, 2) after resection. Three patients developed subacute facial nerve weakness after salvage SRS (4.2-9.4 months after SRS). This paralysis responded to high dose systemic steroids and no surgical interventions for facial rehabilitation were required. At last follow up (mean 61.6 months, SD = 28.5), facial nerve function was favorable (HB grade 1-2 in 12 patients and HB grade 3 in 1 patient). There were no significant associations between various predictors and subacute deterioration of facial nerve function after SRS.

Conclusions: Sub-acute transient facial nerve dysfunction can develop infrequently over a variable time frame after post-operative salvage SRS and usually responds to steroids. Patients should be adequately counseled about potential of transient deterioration of facial nerve function after salvage SRS.
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http://dx.doi.org/10.1097/MAO.0000000000002893DOI Listing
February 2021

Chronic Electroconvulsive Therapy May Induce Calvarial Hyperemia and Marrow Replacement.

J ECT 2021 Jun;37(2):e13-e16

From the Department of Radiation Oncology, Vanderbilt University Medical Center.

Abstract: Electroconvulsive therapy (ECT) is a treatment option for a number of psychiatric disorders, including refractory major depression and obsessive compulsive disorder. There are no known structural sequelae of ECT. Here we present a patient with severe refractory obsessive compulsive disorder and major depression treated over 2 years with ECT every 2 weeks. Planning magnetic resonance imaging intended for a potential procedural intervention for her psychiatric disease incidentally demonstrated a new area of increased enhancement and loss of marrow signal within the right frontal bone. Imaging findings were suggestive of underlying bone marrow or bone changes, although there was no evidence of bone destruction on bone-windowed computed tomography (CT) and there was no uptake on nuclear bone scan. The CT chest/abdomen/pelvis were also reassuring that this did not represent metastatic disease, and findings were unchanged on repeat magnetic resonance imaging 4 months later. Thus, this area corresponded to the site directly underlying the unilateral ECT electrode placement, suggestive of never-before described ECT-induced hyperemia. We report for the first time that frequent, chronic ECT may induce asymptomatic skull bone marrow hyperemia with radiologic findings. This appears to be a direct consequence of electrical current leading to chronic inflammatory and edematous marrow replacement. Electroconvulsive therapy should be added to the neuroradiological differential diagnosis of calvarial enhancement and loss of marrow signal. Psychiatrists should counsel patients on the possibility of this rare radiological finding, which may be confused for other processes.
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http://dx.doi.org/10.1097/YCT.0000000000000728DOI Listing
June 2021

Refinement and Validation of the Head and Neck Lymphedema and Fibrosis Symptom Inventory.

Int J Radiat Oncol Biol Phys 2021 03 14;109(3):747-755. Epub 2020 Oct 14.

Vanderbilt-Ingram Cancer Center, Vanderbilt Medical Center, Nashville, Tennessee.

Purpose: Lymphedema and fibrosis (LEF) are common yet overlooked late effects of head and neck cancer and its therapy. Lack of reliable and valid measures of head and neck LEF is a critical barrier to the timely identification and management of head and neck LEF. To fill this gap, we developed and pilot tested a 64-item patient-reported outcome measure ( Lymphedema Symptom Intensity and Distress Survey-Head and Neck, LSIDS-H&N). This article aims to report the process of further validation and refinement of the tool.

Methods And Materials: A prospective, longitudinal study was conducted, and 120 patients with oral cavity and oropharyngeal cancer were recruited. Participants completed the LSIDS-H&N at pretreatment, end of treatment, and every 3 months up to 12 months after treatment. SAS PROC VARCLUS was used to generate preliminary clusters of item responses. Internal consistency of the item responses within each cluster was assessed using Cronbach's alpha.

Results: A total of 117 patients completed the study. The participants reported that the LSIDS-H&N was easy to understand and captured their symptoms and medical conditions. However, >50% of participants indicated that the survey was burdensome due to length. Thus, we proceeded with item reduction, and the shortened tool (33-item) was named Head and Neck Lymphedema and Fibrosis Symptom Inventory (HN-LEF Symptom Inventory). The subsequent exploration of symptom clusters identified 7 symptom domain clusters (eg, soft tissue and neurologic toxicity), all of which demonstrated good internal consistency.

Conclusions: The HN-LEF Symptom Inventory has been carefully developed and refined to allow clinicians and researchers to capture LEF-associated symptom burden and function impairments. Additional rigorous psychometric testing of the tool is ongoing to further validate the strength and internal validity of this tool.
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http://dx.doi.org/10.1016/j.ijrobp.2020.10.003DOI Listing
March 2021

Preventive use of gabapentin to decrease pain and systemic symptoms in patients with head and neck cancer undergoing chemoradiation.

Head Neck 2020 12 7;42(12):3497-3505. Epub 2020 Aug 7.

Department of Medicine, Oncology Division, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Background: Radiation for patients with head and neck cancer (HNC) is associated with painful mucositis that impacts the delivery of treatment and contributes to high symptom burden.

Methods: This was a prospective, randomized pilot trial. Eligible patients received primary or adjuvant chemoradiation. Patients were randomized to usual care vs usual care plus gabapentin titrated to drug tolerance during radiation. Patients completed a symptom survey at baseline and weekly during therapy.

Results: Seventy-nine patients were enrolled in the study (38 control, 41 treatment). At interim analysis, gabapentin use resulted in a decrease in pain (P = .004), with the biggest decreases being in the latter weeks of therapy. By week 7, the median pain score in the treatment group was below the 0.25 quantile of the control group.

Conclusion: Prophylactic use of gabapentin during chemoradiation for HNC patients resulted in a decrease in pain, neurosensory symptoms, and general systemic symptoms.
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http://dx.doi.org/10.1002/hed.26407DOI Listing
December 2020

Improved Cerebral Arteriovenous Malformation Obliteration With 3-Dimensional Rotational Digital Subtraction Angiography for Radiosurgical Planning: A Retrospective Cohort Study.

Neurosurgery 2020 12;88(1):122-130

Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, Tennessee.

Background: Stereotactic radiosurgery (SRS) for cerebral arteriovenous malformations (AVMs) is well-established. Radiographic advantages exist for 3-dimensional rotational digital subtraction angiography (3DRA) over 2-dimensional digital subtraction angiography (2D DSA) in delineating AVM nidus structure for SRS treatment planning. However, currently there is limited to no data directly comparing 2D DSA versus 3DRA in terms of patient outcomes.

Objective: To investigate whether the use of 3DRA over 2D DSA in radiosurgical treatment planning for AVMs associates with improved clinical outcomes.

Methods: All AVM patients treated with SRS at our institution between the years 2000 and 2018 were identified. Primary outcomes were obliteration rates and time to obliteration (TTO); secondary outcomes included rates of post-SRS hemorrhage, salvage therapy, and symptomatic radionecrosis. A minimum of 12 mo of follow-up imaging/angiogram post-SRS was required, or alternatively evidence of obliteration on angiogram prior to 12 mo post-SRS. Single predictor and multivariable Cox regression and logistic regression models were constructed to test for association between radiographic, clinical, and treatment factors with outcomes.

Results: A total of 75 patients were included. Total 17 patients received 3DRA and 58 patients received 2D DSA, with a median follow-up of 3.29 yr. The 3DRA is significantly associated with improved TTO on single predictor (HR 2.87, 1.29-6.12; P = .0109) and multivariable analysis (HR 2.448, 1.076-5.750; P = .0330) and increased odds of achieving obliteration by 3 yr post-SRS on single predictor analysis (OR 6.044, 1.405-26.009; P = .0157).

Conclusion: The 3DRA over 2D DSA in SRS treatment planning for AVMs may result in improved TTO and 3-yr obliteration rates. Further investigation and prospective study are warranted.
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http://dx.doi.org/10.1093/neuros/nyaa321DOI Listing
December 2020

Contemporary Management of Jugular Paragangliomas With Neural Preservation.

Otolaryngol Head Neck Surg 2021 02 14;164(2):391-398. Epub 2020 Jul 14.

Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Objectives: Management of jugular paragangliomas (PGL) has evolved toward subtotal resection (STR). The purpose of this study is to analyze neural preservation and adjuvant treatment for long-term local control.

Study Design: Retrospective chart review.

Settings: Tertiary neurotology practice.

Subjects And Methods: Adults undergoing surgical treatment of jugular PGL between 2006 and 2019. Patients, disease, and treatment variables were collected retrospectively. Single predictor logistic regression was used to ascertain predictors of regrowth or need for salvage radiation.

Results: A total of 41 patients (median age, 47 years; 76% female) were identified. Most patients presented with advanced-stage disease (Glasscock-Jackson stage III-IV = 76%). Subtotal resection (STR) was performed in 32 (78%) patients. Extended STR (type 1) was the most commonly performed conservative procedure (n = 19, 59%). Postoperative new low cranial neuropathy (LCN) involving CN X and XII was rare (n = 3 and n = 1, respectively). Seventeen patients (41%) underwent postsurgical therapy for tumor regrowth or recurrence, including 15 patients who underwent adjuvant (n = 4) or salvage (n = 11) radiation. Overall tumor control of 94.7% was achieved at a mean follow-up of 35 months. All patients treated with combined modality treatment had local control at last follow-up. Logistic regression identified no single predictor for postsurgical radiation treatment or salvage-free survival.

Conclusion: Management of jugular PGL with a conservative approach is safe and effective with a low rate of new LCN deficit. Active surveillance of residual tumor with salvage radiation for growth results in excellent long-term tumor control.
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http://dx.doi.org/10.1177/0194599820938660DOI Listing
February 2021

Head and Neck Cancers, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology.

J Natl Compr Canc Netw 2020 07;18(7):873-898

16The University of Texas MD Anderson Cancer Center.

Treatment is complex for patients with head and neck (H&N) cancers with specific site of disease, stage, and pathologic findings guiding treatment decision-making. Treatment planning for H&N cancers involves a multidisciplinary team of experts. This article describes supportive care recommendations in the NCCN Guidelines for Head and Neck Cancers, as well as the rationale supporting a new section on imaging recommendations for patients with H&N cancers. This article also describes updates to treatment recommendations for patients with very advanced H&N cancers and salivary gland tumors, specifically systemic therapy recommendations.
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http://dx.doi.org/10.6004/jnccn.2020.0031DOI Listing
July 2020

Longitudinal Radiographic Outcomes of Vestibular Schwannoma in Single and Fractionated Stereotactic Radiosurgery: A Retrospective Cohort Study.

J Neurol Surg B Skull Base 2020 Jun 12;81(3):308-316. Epub 2019 Jun 12.

Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, Tennessee, United States.

Management of vestibular schwannoma (VS) includes stereotactic radiosurgery (SRS) in single or fractionated treatments. There is a paucity of literature on the three-dimensional (3D) volumetric kinetics and radiological changes following SRS and no consensus on appropriate post-SRS surveillance imaging timeline. This is a retrospective cohort study with institutional review board approval. A total of 55 patients met study criteria. We collected volumetric kinetic data in VS treated with SRS over time using a target volume contouring software. We also tracked radiographic phenomena such as pseudoprogression and necrosis. A secondary objective was to describe our overall treatment success rate and any failures. For all treatments groups, pseudoprogression most typically occurred within 12 months post-SRS, after which tumor volumes on average normalized and then decreased from pretreatment size at the last follow-up. Only two patients required salvage therapy post-SRS and were considered SRS treatment failures. Both patients were in the five-fraction cohort but with a lower biologically equivalent dose. Our study is first to collect 3D volumetric kinetics of VS following single and fractionated SRS in contrast to extrapolations from single and two-dimensional measurements. Our longitudinal data also show initial increases in volume in the first 12 months post-SRS followed by later declines, setting up interesting questions regarding the utility of early posttreatment surveillance imaging in the asymptomatic patient. Finally, we show low rates of treatment failure (3.6%) and show in our cohort that SRS dose de-escalation posed a risk of treatment failure.
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http://dx.doi.org/10.1055/s-0039-1692642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253303PMC
June 2020

Radiotherapy and Radiosurgery for Treatment of Residual or Recurrent Endolymphatic Sac Tumor Following Previous Microsurgical Resection.

Otol Neurotol 2020 07;41(6):e759-e762

Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, Tennessee.

Objective: To report and discuss the effectiveness of stereotactic radiosurgery (SRS) or fractionated radiotherapy (FRT) for tumor control following surgical resection of endolymphatic sac tumors (ELST).

Study Design: Retrospective case series.

Setting: Multi-institutional academic referral centers.

Patients: Patients undergoing surgical resection for ELST followed by SRS or FRT.

Intervention(s): Surgical resection followed by radiotherapy.

Main Outcome Measures: Local tumor control.

Results: Two of the five patients experienced tumor recurrence after gross total microsurgical at 78 and 11 months, respectively. The former patient received salvage 3D conformal radiotherapy (3D-CRT) and while the latter patient underwent three courses of salvage SRS for recurrence, two of which were in-field and was disease-free at last follow up. Two additional patients underwent subtotal tumor resection (STR) followed by intensity-modulated radiation therapy (IMRT) and are currently without disease. One patient underwent STR followed by proton-beam therapy (PBT) and was free of disease at most recent follow-up.

Conclusion: SRS/FRT remains a useful adjuvant for treatment of residual or recurrent ELSTs, where the risk of revision microsurgical resection is high.
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http://dx.doi.org/10.1097/MAO.0000000000002639DOI Listing
July 2020

Secondary malignancy following stereotactic radiosurgery for benign neurologic disease: A cohort study and review of the literature.

J Radiosurg SBRT 2020 ;6(4):287-294

Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN, USA.

Radiation-associated malignancy and malignant transformation are risks associated with stereotactic radiosurgery (SRS); however, incidence is uncertain. The purpose of our study is to present the rate of radiation-associated malignancy and malignant transformation at our institution. After IRB approval, we undertook a retrospective cohort study evaluating patients treated with Gamma Knife® or linac-based SRS between 1990 and 2014 for benign CNS pathology with at least 5 years of clinical follow-up. Risk of transformation was calculated using the Kaplan-Meier method. A total of 273 patients met selection criteria. Median clinical follow-up after SRS was 11 years (range 5-27). Over 3,216 patient-years following SRS, we found zero cases of radiation-associated malignancy and two cases of radiation-associated malignant transformation for a crude rate of 0.73% or case rate of 0.62 per 1,000 patient-years. The Kaplan-Meier risk of malignant transformation at 5, 10, and 15 years was 0.4% (95% CI 0.05% 2.6%). These data support the continued use of SRS for benign intracranial pathology without significant concern for secondary malignancy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065897PMC
January 2020

Body mass index and response to stereotactic radiosurgery in the treatment of refractory trigeminal neuralgia: A retrospective cohort study.

J Radiosurg SBRT 2020 ;6(4):253-261

Department of Radiation Oncology, Vanderbilt University Medical Center, 2220 Pierce Avenue, PRB-B1003, Nashville, TN 37232, USA.

Stereotactic radiosurgery (SRS) is used as a noninvasive treatment option for patients with trigeminal neuralgia (TN), but the effect of obesity on pain relief post SRS, if any, is unknown. The primary goal of our study was to evaluate the association between obesity and response to SRS in patients with TN. We conducted an IRB-approved retrospective review of patients treated with SRS for TN between 2010 and 2017. Barrow Neurologic Institute (BNI) Score was assigned pre-and post-SRS to quantify pain level. Thirty-two patients (65% female) between the ages of 24 and 96 were studied with a median follow-up time of 11 months. Patients with BMI >25 were significantly less likely to have improvement in their symptoms with SRS (p = 0.005). Elevated BMI may be associated with worsened response to SRS in the treatment of TN.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065898PMC
January 2020

Long-term Outcomes for the Treatment of Paragangliomas in the Upfront, Adjuvant, and Salvage Settings With Stereotactic Radiosurgery and Intensity-modulated Radiotherapy.

Otol Neurotol 2020 01;41(1):133-140

Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, Tennessee.

Objective: To analyze local control (LC) and toxicity rates between stereotactic radiosurgery (SRS) and intensity-modulated radiotherapy (IMRT) in relation to reported surgical rates in the treatment of paragangliomas (PG) in the upfront, adjuvant, and salvage settings, and to explore factors affecting tumor size reduction, toxicity rates, and symptom control.

Study Design: Retrospective cohort analysis.

Setting: Tertiary referral center.

Patients And Interventions: Thirty patients treated with either linear accelerator-based SRS or IMRT in the definitive, planned adjuvant, or unplanned salvage postsurgery settings.

Main Outcome Measures: Local control, toxicities, symptom control, tumor size reduction, and factors affecting each.

Results: Median follow-up was 4.16 years. LC rates were 100%. Acute grade >3 toxicity rate was 6.7%, 86.7% of tumors had a reduction in volume, and 76.7% of patients had improvement in at least one tumor-induced symptom by last follow-up. Larger tumor size at presentation and longer time to last follow-up were significantly associated with greater tumor size reduction on multivariate analysis.

Conclusions: SRS and IMRT are safe and effective treatment for PG with high efficacy and low morbidity rates in the upfront, planned adjuvant, and unplanned salvage settings.
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http://dx.doi.org/10.1097/MAO.0000000000002461DOI Listing
January 2020

Current Volumetric Models Overestimate Vestibular Schwannoma Size Following Stereotactic Radiosurgery.

Otol Neurotol 2020 02;41(2):e262-e267

Department of Radiation Oncology.

Objective: Accurate volume assessment is essential for the management of vestibular schwannoma after stereotactic radiosurgery (SRS). A cuboidal approximation for volume is the standard surveillance method; however, this may overestimate tumor volume. We sought to evaluate several volumetric models and their suitability for post-SRS surveillance.

Study Design: Retrospective cohort study.

Setting: Tertiary referral center.

Patients: We evaluated 54 patients with vestibular schwannoma before and after SRS.

Intervention(s): Gold-standard volumes were obtained by a radiation oncologist using contouring software. Volume was also calculated by cuboidal, ellipsoidal, and spherical formulae using tumor diameters obtained by a neuroradiologist.

Main Outcome Measure(s): Percent error (PE) and absolute percent error (APE) were calculated. Paired t test evaluated bias, and the Bland-Altman method evaluated reproducibility. Linear regression evaluated predictors of model error.

Results: All models overestimated volume compared with the gold standard. The cuboidal model was not reproducible before SRS (p < 0.001), and no model was reproducible after SRS (cuboidal p < 0.001; ellipsoidal p = 0.02; spherical p = 0.02). Significant bias was present before SRS for the cuboidal model (p < 0.001), and post-SRS for all models [cuboidal (p < 0.001), ellipsoidal (p < 0.02), and spherical (p = 0.005)]. Model error was negatively associated with pretreatment volume for the cuboidal (PE p = 0.03; APE p = 0.03), ellipsoidal (PE p = 0.03; APE p = 0.04), and spherical (PE p = 0.02; APE p = 0.03) methods and lost linearity post-SRS.

Conclusions: The standard cuboidal practice for following vestibular schwannoma tumor volume after SRS overestimates size. Ellipsoidal and spherical estimations have improved performance but also overestimate volume and lack reliability post-SRS. The development of other volumetric models or application of contouring software should be investigated.
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http://dx.doi.org/10.1097/MAO.0000000000002488DOI Listing
February 2020

Outcomes of stereotactic radiosurgery and hypofractionated stereotactic radiotherapy for refractory Cushing's disease.

Pituitary 2019 Dec;22(6):607-613

Department of Radiation Oncology, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, 2220 Pierce Avenue, Preston Research Building, Rm B-1003, Nashville, TN, 37232-5671, USA.

Purpose: Hypofractionated stereotactic radiotherapy (HSRT) for refractory Cushing's disease may offer a condensed treatment schedule for patients with large tumors abutting the optic chiasm unsuitable for stereotactic radiosurgery (SRS). To-date only four patients have been treated by HSRT in the published literature. We investigated the feasibility, toxicity, and efficacy of HSRT compared to SRS.

Methods: After approval, we retrospectively evaluated patients treated at our institution for refractory Cushing's disease with SRS or HSRT. Study outcomes included biochemical control, time to biochemical control, local control, and late complications. Binary logistic regression and Cox proportional hazards regression evaluated predictors of outcomes.

Results: Patients treated with SRS (n = 9) and HSRT (n = 9) were enrolled with median follow-up of 3.4 years. Clinicopathologic details were balanced between the cohorts. Local control was 100% in both cohorts. Time to biochemical control was 6.6. and 9.5 months in the SRS and HSRT cohorts, respectively (p = 0.6258). Two patients in each cohort required salvage bilateral adrenalectomy. Late complications including secondary malignancy, radionecrosis, cranial nerve neuropathy, and optic pathway injury were minimal for either cohort.

Conclusions: HSRT is an appropriate treatment approach for refractory Cushing's disease, particularly for patients with large tumors abutting the optic apparatus. Prospective studies are needed to validate these findings and identify factors suggesting optimal fractionation approaches.
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http://dx.doi.org/10.1007/s11102-019-00992-6DOI Listing
December 2019

In Reply: A Retrospective Cohort Study of Longitudinal Audiologic Assessment in Single and Fractionated Stereotactic Radiosurgery for Vestibular Schwannoma.

Neurosurgery 2019 12;85(6):E1127-E1129

Department of Radiation Oncology Vanderbilt University Medical Center Nashville, Tennessee.

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http://dx.doi.org/10.1093/neuros/nyz373DOI Listing
December 2019

A Retrospective Cohort Study of Longitudinal Audiologic Assessment in Single and Fractionated Stereotactic Radiosurgery for Vestibular Schwannoma.

Neurosurgery 2019 12;85(6):E1078-E1083

Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, Tennessee.

Background: Fractionated stereotactic radiosurgery (SRS) for vestibular schwannomas (VS) has been theorized to allow for tumor control with higher rates of hearing preservation in selected patients with useful hearing. However, there is a paucity of literature with formal audiologic measures of hearing preservation to support the standard use of fractionated SRS in VS. We hypothesized that fractionation would diminish the amount of hearing damage.

Objective: To evaluate the relationship between audiologic performance and SRS fractionation scheme.

Methods: We performed an IRB-approved retrospective review of patients treated with 1, 3, or 5 fraction SRS for VS at our institution from 1998 to 2016. Pre- and post-SRS audiograms with speech awareness threshold (SAT) in treated and contralateral ears were obtained. Contralateral ear measurements were used for hearing normalization to account for presbycusis.

Results: Fifty-six patients with median audiologic follow-up 2.0 yr (mean 2.66 yr, min-max 0.50-9.45 yr) were included. Patients treated with single fractionation had a significantly worsened SAT (dB) compared to patients treated with 5 fractions (P = .008) and compared to all multifraction patients (P = .009) at 12 to 24 mo follow-up.

Conclusion: This retrospective analysis supports the use of fractionated SRS to preserve hearing in patients with VS. SAT can be used as an objective metric of hearing response to radiosurgery.
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http://dx.doi.org/10.1093/neuros/nyz219DOI Listing
December 2019

Evolving Treatment Paradigms for Oropharyngeal Squamous Cell Carcinoma.

J Glob Oncol 2018 09 9;4:1-9. Epub 2016 Nov 9.

Ryan K. Cleary and Anthony J. Cmelak, Vanderbilt University Medical Center, Nashville, TN.

Oropharyngeal squamous cell carcinoma (OPSCC) is increasing in incidence in the United States and in many countries worldwide primarily as a result of increasing rates of human papillomavirus (HPV) infection. HPV-positive OPSCC represents a distinct disease entity from head and neck squamous cell carcinoma caused by traditional risk factors such as tobacco and alcohol, with different epidemiology, patterns of failure, and expected outcomes. Because patients with HPV-positive OPSCC have a younger median age and superior prognosis compared with their HPV-negative counterparts, they live longer with the morbidity of treatment, which can be severe. Therefore, efforts are under way to de-escalate therapy in favorable-risk patients while maintaining treatment efficacy. Additional work is being undertaken to discover new therapies that may benefit both HPV-positive and HPV-negative patient subsets. Herein, we will review the available data for the evolving treatment paradigms in OPSCC as well as discuss ongoing clinical trials.
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http://dx.doi.org/10.1200/JGO.2016.006304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6223382PMC
September 2018

NCCN Guidelines Insights: Head and Neck Cancers, Version 1.2018.

J Natl Compr Canc Netw 2018 05;16(5):479-490

The NCCN Guidelines for Head and Neck (H&N) Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the H&N, and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding evaluation and treatment of nasopharyngeal carcinoma.
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http://dx.doi.org/10.6004/jnccn.2018.0026DOI Listing
May 2018

A simple technique to improve calculated skin dose accuracy in a commercial treatment planning system.

J Appl Clin Med Phys 2018 Mar 6;19(2):191-197. Epub 2018 Feb 6.

Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.

Radiation dermatitis during radiotherapy is correlated with skin dose and is a common clinical problem for head and neck and thoracic cancer patients. Therefore, accurate prediction of skin dose during treatment planning is clinically important. The objective of this study is to evaluate the accuracy of skin dose calculated by a commercial treatment planning system (TPS). We evaluated the accuracy of skin dose calculations by the anisotropic analytical algorithm (AAA) implemented in Varian Eclipse (V.11) system. Skin dose is calculated as mean dose to a contoured structure of 0.5 cm thickness from the surface. The EGSnrc Monte Carlo (MC) simulations are utilized for the evaluation. The 6, 10 and 15 MV photon beams investigated are from a Varian TrueBeam linear accelerator. The accuracy of the MC dose calculations was validated by phantom measurements with optically stimulated luminescence detectors. The calculation accuracy of patient skin doses is studied by using CT based radiotherapy treatment plans including 3D conformal, static gantry IMRT, and VMAT treatment techniques. Results show the Varian Eclipse system underestimates skin doses by up to 14% of prescription dose for the patients studied when external body contour starts at the patient's skin. The external body contour is used in a treatment planning system to calculate dose distributions. The calculation accuracy of skin dose with Eclipse can be considerably improved to within 4% of target dose by extending the external body contour by 1 to 2 cm from the patient's skin. Dose delivered to deeper target volumes or organs at risk are not affected. Although Eclipse treatment planning system has its limitations in predicting patient skin dose, this study shows the calculation accuracy can be considerably improved to an acceptable level by extending the external body contour without affecting the dose calculation accuracy to the treatment target and internal organs at risk. This is achieved by moving the calculation entry point away from the skin.
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http://dx.doi.org/10.1002/acm2.12275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5849836PMC
March 2018

Long-term Outcomes after Salvage Stereotactic Radiosurgery (SRS) following In-Field Failure of Initial SRS for Brain Metastases.

Front Oncol 2017 23;7:279. Epub 2017 Nov 23.

Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN, United States.

Purpose: The optimal treatment strategy following local recurrence after stereotactic radiosurgery (SRS) remains unclear. While upfront SRS has been extensively studied, few reports focus on outcomes after retreatment. Here, we report the results following a second course of SRS for local recurrence of brain metastases previously treated with SRS.

Methods: Using institutional database, patients who received salvage SRS (SRS2) following in-field failure of initial SRS (SRS1) for brain metastases were identified. Radionecrosis and local failure were defined radiographically by MRI following SRS2. The primary endpoint was defined as the time from SRS2 to the date of all-cause death or last follow-up [overall survival (OS)]. The secondary endpoints included local failure-free survival (LFFS) and radionecrosis-free survival, defined as the time from SRS2 to the date of local failure or radionecrosis, or last follow-up, respectively.

Results: Twenty-eight patients with 32 brain metastases were evaluated between years 2004 and 2015. The median interval between SRS1 and SRS2 was 9.7 months. Median OS was 22.0 months. Median LFFS time after SRS2 was 13.6 months. The overall local control rate following SRS2 was 84.4%. The 1- and 2-year local control rates are 88.3% (95% CI, 76.7-100%) and 80.3% (95% CI, 63.5-100%), respectively. The overall rate of radionecrosis following SRS2 was 18.8%. On univariate analysis, higher prescribed isodose line ( = 0.033) and higher gross tumor volume ( = 0.015) at SRS1 were associated with radionecrosis. Although not statistically significant, there was a trend toward lower risk of radionecrosis with interval surgical resection, fractionated SRS, lower total EQD2 (<50 Gy), and lack of concurrent systemic therapy at SRS2.

Conclusion: In select patients, repeat LINAC-based SRS following recurrence remains a reasonable option leading to long-term survival and local control. Radionecrosis approaches 20% for high risk individuals and parallels historic values.
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http://dx.doi.org/10.3389/fonc.2017.00279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703829PMC
November 2017

Postoperative Fractionated Stereotactic Radiosurgery to the Tumor Bed for Surgically Resected Brain Metastases.

Cureus 2017 May 26;9(5):e1279. Epub 2017 May 26.

Department of Radiation Oncology, Vanderbilt University Medical Center.

Introduction Stereotactic radiosurgery (SRS) is increasingly used as an alternative to whole brain radiotherapy (WBRT) following surgical resection of brain metastases. We analyzed the outcomes of postoperative frameless fractionated stereotactic radiosurgery (fSRS) cases for surgically resected brain metastases at our institution. Materials and Methods We performed a retrospective review of 85 patients who underwent fSRS to 87 resection beds from 2006 - 2014 with a median follow-up of 6.4 months. Clinically relevant outcomes were assessed with analysis to determine predictors of these outcomes. Results The median target volume was 9.8 cm- (1.1 - 43.1 cm-). The most frequently used fractionation scheme was 3,000 cGy in five fractions. The rates of local control (LC), distant brain failure (DBF), and overall survival (OS) at one-year were 87%, 52%, and 52%, respectively. Five patients (5.9%) experienced Grade >2 toxicity related to fSRS, including seizures (two), symptomatic radionecrosis (two), and potential treatment-related death (one). A multivariable analysis revealed that tumor volume (p < 0.001) and number of fractions (p < 0.001) were associated with LC, while recursive partitioning analysis (RPA) class (< .0001), tumor volume (= .0181), and the number of fractions (.0181) were associated with OS. Conclusions Postoperative fSRS for surgically resected brain metastases is well-tolerated and achieves durable LC. Further studies are needed to determine the optimal dose and fractionation for fSRS as well as to compare outcomes with WBRT.
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http://dx.doi.org/10.7759/cureus.1279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5484602PMC
May 2017
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