Publications by authors named "Daniel M Trifiletti"

147 Publications

Letter regarding "Contribution of PET imaging to radiotherapy planning and monitoring in glioma patients-a report of the PET/RANO group": 18F-fluciclovine and target volume delineation.

Neuro Oncol 2021 Jun 3. Epub 2021 Jun 3.

Department of Radiation Oncology, Rose Ella Burkhart Brain Tumor and Neuro-Oncology Center, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University Cleveland Clinic, Cleveland, Ohio, USA.

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http://dx.doi.org/10.1093/neuonc/noab097DOI Listing
June 2021

Dose Escalated Radiotherapy for Glioblastoma Multiforme: An International Systematic Review and Meta-Analysis of 22 Prospective Trials.

Int J Radiat Oncol Biol Phys 2021 May 12. Epub 2021 May 12.

Department of Radiation Oncology and Neurosurgery, The James Cancer Hospital at the Ohio State University Wexner Medical Center, Columbus, OH, USA. Electronic address:

Background: Limited evidence is available on the utility of dose-escalated radiation therapy (DE-RT) +/- (TMZ) vs. standard-of-care RT (SoC-RT) for patients with newly diagnosed glioblastoma multiforme (GBM). We performed a systematic review/meta-analysis to compare overall survival (OS) and progression-free survival (PFS) between DE-RT and SoC-RT.

Methods: We utilized a PICOS/PRISMA/MOOSE selection criterion to identify studies. The primary and secondary outcomes were 1-year OS and 1-year PFS, respectively. Outcomes and comparisons were subdivided based on receipt of TMZ and MGMT status. DE-RT was defined based on equivalent dose (EQD) calculations. Random effects meta-analyses using the Knapp-Hartung correction, arcsine transformation, and restricted maximum likelihood method were conducted. Meta-regression was used to compare therapeutic (e.g. DE-RT and/or TMZ) and pathologic characteristics (e.g. MGMT methylation status) using the Wald-type test RESULTS: Across 22 published studies, 2,198 patients with GBM were included; 507 received DE-RT. One-year OS following DE-RT alone was higher than SoC-RT alone (46.3% vs. 23.4%; p=0.02) as was 1-year PFS (17.9% vs. 5.3%; p=0.02). No significant difference in 1-year OS (73.2% vs. 64.4%; p=0.23) or 1-year PFS (44.5% vs. 44.3%; p=0.33) between DE-RT+TMZ and SoC-RT+TMZ was noted. No difference in 1-year OS was noted between DE-RT+TMZ and SoC-RT+TMZ in either MGMT methylated (83.2% vs. 73.2%; p=0.23) or MGMT unmethylated (72.6% vs. 50.6%; p=0.16) patients.

Conclusions: DE-RT alone resulted in superior PFS and OS vs. SoC-RT alone. DE-RT+TMZ did not lead to improved outcomes vs. SoC-RT+TMZ. No differential benefit based on MGMT status was found. Future studies are warranted to define which subgroups benefit most from DE-RT.
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http://dx.doi.org/10.1016/j.ijrobp.2021.05.001DOI Listing
May 2021

Stereotactic Radiosurgery for Differentiated Thyroid Cancer Brain Metastases: An International, Multicenter Study.

Thyroid 2021 May 11. Epub 2021 May 11.

Department of Neurosurgery, University of Virginia, Charlottesville, Virginia, USA.

Brain metastases (BM) from differentiated thyroid cancer are rare. Stereotactic radiosurgery (SRS) is commonly used for the treatment of BMs; however, the experience with SRS for thyroid cancer BMs remains limited. The goal of this international, multi-centered study was to evaluate the efficacy and safety of SRS for thyroid cancer BMs. From 10 institutions participating in the International Radiosurgery Research Foundation, we pooled patients with established papillary or follicular thyroid cancer diagnosis who underwent SRS for histologically confirmed or radiologically suspected BMs. We investigated patient overall survival (OS), local tumor control, and adverse radiation events (AREs). We studied 42 (52% men) patients who underwent SRS for 122 papillary (83%) or follicular (17%) thyroid cancer BMs. The mean age at SRS was 59.86 ± 12.69 years. The mean latency from thyroid cancer diagnosis to SRS for BMs was 89.05 ± 105.49 months. The median number of BMs per patient was 2 (range: 1-10 BMs). The median SRS treatment volume was 0.79 cm (range: 0.003-38.18 cm), and the median SRS prescription dose was 20 Gy (range: 8-24 Gy). The median survival after SRS for BMs was 14 months (range: 3-58 months). The OS was significantly shorter in patients harboring ≥2 BMs, when compared with patients with one BM (Log-rank = 5.452,  = 0.02). Two or more BMs (odds ratio [OR] = 3.688; confidence interval [CI]: 1.143-11.904;  = 0.03) and lower Karnofsky performance score at the time of SRS (OR = 0.807; CI: 0.689-0.945;  = 0.008) were associated with shorter OS. During post-SRS imaging follow-up of 25.21 ± 30.49 months, local failure (progression and/or radiation necrosis) of BMs treated with SRS was documented in five (4%) BMs at 7.2 ± 7.3 months after the SRS. At the last imaging follow-up, the majority of patients with available imaging data had stable intracranial disease (33%) or achieved complete (26%) or partial (24%) response. There were no clinical AREs. Post-SRS peritumoral T2/fluid attenuated inversion recovery signal hyperintensity was noted in 7% BMs. The SRS allows durable local control of papillary and follicular thyroid cancer BMs in the vast majority of patients. Higher number of BMs and worse functional status at the time of SRS are associated with shorter OS in patients with thyroid cancer BMs. The SRS is safe and is associated with a low risk of AREs.
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http://dx.doi.org/10.1089/thy.2020.0947DOI Listing
May 2021

Boron Neutron Capture Therapy: A Review of Clinical Applications.

Front Oncol 2021 26;11:601820. Epub 2021 Feb 26.

Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL, United States.

Boron neutron capture therapy (BNCT) is an emerging treatment modality aimed at improving the therapeutic ratio for traditionally difficult to treat tumors. BNCT utilizes boronated agents to preferentially deliver boron-10 to tumors, which, after undergoing irradiation with neutrons, yields litihium-7 and an alpha particle. The alpha particle has a short range, therefore preferentially affecting tumor tissues while sparing more distal normal tissues. To date, BNCT has been studied clinically in a variety of disease sites, including glioblastoma multiforme, meningioma, head and neck cancers, lung cancers, breast cancers, hepatocellular carcinoma, sarcomas, cutaneous malignancies, extramammary Paget's disease, recurrent cancers, pediatric cancers, and metastatic disease. We aim to provide an up-to-date and comprehensive review of the studies of each of these disease sites, as well as a review on the challenges facing adoption of BNCT.
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http://dx.doi.org/10.3389/fonc.2021.601820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952987PMC
February 2021

Reducing Radiation-Induced Cognitive Toxicity: Sparing the Hippocampus and Beyond.

Int J Radiat Oncol Biol Phys 2021 Apr;109(5):1131-1136

Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California.

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http://dx.doi.org/10.1016/j.ijrobp.2021.01.001DOI Listing
April 2021

Cognitive outcomes in patients with low-grade glioma.

Neuro Oncol 2021 05;23(5):709-710

Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA.

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http://dx.doi.org/10.1093/neuonc/noab033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099460PMC
May 2021

The evolution of stereotactic radiosurgery in neurosurgical practice.

J Neurooncol 2021 Feb 21;151(3):451-459. Epub 2021 Feb 21.

Department of Neurological Surgery, University of Virginia, Charlottesville, VA, USA.

Introduction: Stereotactic radiosurgery (SRS) was born in an attempt to treat complex intracranial pathologies in a fashion whereby open surgery would create unnecessary or excessive risk. To create this innovation, it was necessary to harness advances in other fields such as engineering, physics, radiology, and computer science.

Methods: We review the history of SRS to provide context to today's current state, as well as guide future advancement in the field.

Results: Since time of Lars Leksell, the young Swedish neurosurgeon who pioneered the development of the SRS, the collegial and essential partnership between neurosurgeons, radiation oncologists and physicists has given rise to radiosurgery as a prominent and successful tool in neurosurgical practice.

Conclusion: We examine how neurosurgeons have helped foster the SRS evolution and how this evolution has impacted neurosurgical practice as well as that of radiation oncology and neuro-oncology.
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http://dx.doi.org/10.1007/s11060-020-03392-0DOI Listing
February 2021

Impact of Facility Surgical Volume on Survival in Patients With Cancer.

J Natl Compr Canc Netw 2021 05 9;19(5):495-503. Epub 2021 Feb 9.

1Department of Radiation Oncology, Penn State Cancer Institute, and.

Background: Increased facility surgical treatment volume is sometimes associated with improved survival in patients with cancer; however, published studies evaluating volume are heterogeneous and disparate in their patient inclusion and definition of volume. The purpose of this work was to evaluate uniformly the impact of surgical facility volume on survival in patients with cancer.

Methods: The National Cancer Database was searched for patients diagnosed in 2004 through 2013 with the 12 cancers most commonly treated surgically. Facilities were stratified by 4 categories using the overall population (low, intermediate, high, and very high), each including 25% of patients, and then stratified by each individual disease site. Five-year postsurgery survival was estimated using both the Kaplan-Meier method and corresponding log-rank tests for group comparisons. Cox proportional hazard models were used to evaluate the effects of facility volume on 5-year postsurgery survival further, adjusted for multiple covariates.

Results: A total of 3,923,618 patients who underwent surgery were included from 1,139 facilities. Of these, 40.4% had breast cancer, 12.8% prostate cancer, and 10.0% colon cancer. Most patients were female (65.0%), White (86.4%), and privately insured (51.6%) with stage 0-III disease (64.8%). For all cancers, the risk of death for patients undergoing surgery at very high-volume facilities was 88% of that for those treated at low-volume facilities. Hazard ratios (HRs) were greatest (very high vs low volume) for cancer of the prostate (HR, 0.66; 95% CI, 0.63-0.69), pancreas (HR, 0.75; 95% CI, 0.71-0.78), and esophagus (HR, 0.78; 95% CI, 0.73-0.83), and for melanoma (HR, 0.81; 95% CI, 0.78-0.84); differences were smallest for uterine and non-small cell lung cancers. Overall survival differences were greatest for cancers of the brain, pancreas, and esophagus.

Conclusions: Patients treated surgically at higher-volume facilities consistently had improved overall survival compared with those treated at low-volume centers, although the magnitude of difference was cancer-specific.
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http://dx.doi.org/10.6004/jnccn.2020.7644DOI Listing
May 2021

Treatment of WHO Grade 2 Meningiomas With Stereotactic Radiosurgery: Identification of an Optimal Group for SRS Using RPA.

Int J Radiat Oncol Biol Phys 2021 Jul 3;110(3):804-814. Epub 2021 Feb 3.

Department of Neurologic Surgery, University of Virginia Health System, Charlottesville, Virginia.

Purpose: This study assesses a large multi-institutional database to present the outcomes of World Health Organization grade 2 meningiomas treated with stereotactic radiosurgery (SRS). We also compare the 3-year progression-free survival (PFS) to that reported in the Radiation Therapy Oncology Group 0539 phase 2 cooperative group meningioma trial.

Methods And Materials: From an international, multicenter group, data were collected for grade 2 meningioma patients treated with SRS for demonstrable tumor from 1994 to 2019. Statistical methods used included the Kaplan-Meier method, Cox proportional hazards analysis, and recursive partitioning analysis.

Results: Two hundred thirty-three patients treated at 12 institutions were included. Patients presented at a median age of 60 years (range, 13-90), and many had at least 2 prior resections (30%) or radiation therapy (22%). Forty-eight percent of patients had prior gross total resection. At SRS, the median treatment volume was 6.1 cm (0.1-97.6). A median 15 Gy (10-30) was delivered to a median percent isodose of 50 (30-80), most commonly in 1 fraction (95%). A model was developed using recursive partitioning analysis, with one point attributed to age >50 years, treatment volume >11.5 cm, and prior radiation therapy or multiple surgeries. The good-prognostic group (score, 0-1) had improved PFS (P < .005) and time to local failure (P < .005) relative to the poor-prognostic group (score, 2-3). Age >50 years (hazard ratio = 1.85 [95% confidence interval, 1.09-3.14]) and multiple prior surgeries (hazard ratio = 1.80 [1.09-2.99]) also portended reduced PFS in patients without prior radiation therapy. Two hundred eighteen of 233 patients in this study qualified for the high-risk group of Radiation Therapy Oncology Group 0539, and they demonstrated similar outcomes (3-year PFS: 53.9% vs 58.8%). The good-prognostic group of SRS patients demonstrated slightly improved outcomes (3-year PFS: 63.1% vs 58.8%).

Conclusions: SRS should be considered in carefully selected patients with atypical meningiomas. We suggest the use of our good-prognostic group to optimize patient selection, and we strongly encourage the initiation of a clinical trial to prospectively validate these outcomes.
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http://dx.doi.org/10.1016/j.ijrobp.2021.01.048DOI Listing
July 2021

Proton and Heavy Particle Intracranial Radiosurgery.

Biomedicines 2021 Jan 3;9(1). Epub 2021 Jan 3.

Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL 32224, USA.

Stereotactic radiosurgery (SRS) involves the delivery of a highly conformal ablative dose of radiation to both benign and malignant targets. This has traditionally been accomplished in a single fraction; however, fractionated approaches involving five or fewer treatments have been delivered for larger lesions, as well as lesions in close proximity to radiosensitive structures. The clinical utilization of SRS has overwhelmingly involved photon-based sources via dedicated radiosurgery platforms (e.g., Gamma Knife and Cyberknife) or specialized linear accelerators. While photon-based methods have been shown to be highly effective, advancements are sought for improved dose precision, treatment duration, and radiobiologic effect, among others, particularly in the setting of repeat irradiation. Particle-based techniques (e.g., protons and carbon ions) may improve many of these shortcomings. Specifically, the presence of a Bragg Peak with particle therapy at target depth allows for marked minimization of distal dose delivery, thus mitigating the risk of toxicity to organs at risk. Carbon ions also exhibit a higher linear energy transfer than photons and protons, allowing for greater relative biological effectiveness. While the data are limited, utilization of proton radiosurgery in the setting of brain metastases has been shown to demonstrate 1-year local control rates >90%, which are comparable to that of photon-based radiosurgery. Prospective studies are needed to further validate the safety and efficacy of this treatment modality. We aim to provide a comprehensive overview of clinical evidence in the use of particle therapy-based radiosurgery.
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http://dx.doi.org/10.3390/biomedicines9010031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823941PMC
January 2021

Stereotactic radiosurgery training patterns across neurosurgical programs: a multi-national survey.

J Neurooncol 2021 Jan 4;151(2):325-330. Epub 2021 Jan 4.

Department of Neurological Surgery, University of Virginia, Box 800212, Charlottesville, VA, 22908, USA.

Introduction: The field of neurosurgery has witnessed a dramatic increase in the use of stereotactic radiosurgery (SRS) as a modality to treat various cranial and spinal pathologies. However, studies have consistently demonstrated disparities in SRS training. Accordingly, the present study represents a cross-sectional analysis of current SRS training and practice patterns.

Methods: An online survey was utilized to collect data from participants. Two-sided t-tests were used in order to compare frequency tables for statistically significant differences between groups. Qualitative analyses were performed by modified thematic analyses, employing open and axial coding.

Results: A total of 67 participants completed the online survey (16.4% response rate). The majority of participants were neurosurgery attendings (58.2%), followed by neurosurgery residents (25.4%). The majority of participants reported that resident exposure to SRS was gained primarily through non-SRS focused rotations (52.2%). The survey found that exposure to tumor cases was most frequent, followed by functional, vascular, and spine indications. The majority of participants (49.3%) indicate that residents are not competent or exhibit a low level of competency in SRS at the completion of neurosurgical residency. Qualitative analyses demonstrated that respondents believe SRS is a critical modality in current cranial neurosurgical care and that increased training is needed.

Conclusions: This study provides a multi-national analysis of SRS residency training and practice patterns, and aims to stimulate improvement in SRS in training worldwide. Enhanced resident training in SRS must include wider exposure to vascular, neoplastic, functional and pediatric indications for SRS.
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http://dx.doi.org/10.1007/s11060-020-03670-xDOI Listing
January 2021

Stereotactic radiosurgery for treatment of radiation-induced meningiomas: a multiinstitutional study.

J Neurosurg 2021 Jan 1:1-9. Epub 2021 Jan 1.

1Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia.

Objective: Radiation-induced meningiomas (RIMs) are associated with aggressive clinical behavior. Stereotactic radiosurgery (SRS) is sometimes considered for selected RIMs. The authors investigated the effectiveness and safety of SRS for the management of RIMs.

Methods: From 12 institutions participating in the International Radiosurgery Research Foundation, the authors pooled patients who had prior cranial irradiation and were subsequently clinically diagnosed with WHO grade I meningiomas that were managed with SRS.

Results: Fifty-two patients underwent 60 SRS procedures for histologically confirmed or radiologically suspected WHO grade I RIMs. The median ages at initial cranial radiation therapy and SRS for RIM were 5.5 years and 39 years, respectively. The most common reasons for cranial radiation therapy were leukemia (21%) and medulloblastoma (17%). There were 39 multiple RIMs (35%), the mean target volume was 8.61 ± 7.80 cm3, and the median prescription dose was 14 Gy. The median imaging follow-up duration was 48 months (range 4-195 months). RIM progressed in 9 patients (17%) at a median duration of 30 months (range 3-45 months) after SRS. Progression-free survival at 5 years post-SRS was 83%. Treatment volume ≥ 5 cm3 predicted progression (HR 8.226, 95% CI 1.028-65.857, p = 0.047). Seven patients (14%) developed new neurological symptoms or experienced SRS-related complications or T2 signal change from 1 to 72 months after SRS.

Conclusions: SRS is associated with durable local control of RIMs in the majority of patients and has an acceptable safety profile. SRS can be considered for patients and tumors that are deemed suboptimal, poor surgical candidates, and those whose tumor again progresses after removal.
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http://dx.doi.org/10.3171/2020.7.JNS202064DOI Listing
January 2021

Nanoparticles for Stem Cell Therapy Bioengineering in Glioma.

Front Bioeng Biotechnol 2020 7;8:558375. Epub 2020 Dec 7.

Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL, United States.

Gliomas are a dismal disease associated with poor survival and high morbidity. Current standard treatments have reached a therapeutic plateau even after combining maximal safe resection, radiation, and chemotherapy. In this setting, stem cells (SCs) have risen as a promising therapeutic armamentarium, given their intrinsic tumor homing as well as their natural or bioengineered antitumor properties. The interplay between stem cells and other therapeutic approaches such as nanoparticles holds the potential to synergize the advantages from the combined therapeutic strategies. Nanoparticles represent a broad spectrum of synthetic and natural biomaterials that have been proven effective in expanding diagnostic and therapeutic efforts, either used alone or in combination with immune, genetic, or cellular therapies. Stem cells have been bioengineered using these biomaterials to enhance their natural properties as well as to act as their vehicle when anticancer nanoparticles need to be delivered into the tumor microenvironment in a very precise manner. Here, we describe the recent developments of this new paradigm in the treatment of malignant gliomas.
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http://dx.doi.org/10.3389/fbioe.2020.558375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750507PMC
December 2020

Mask-based immobilization in Gamma Knife stereotactic radiosurgery.

J Clin Neurosci 2021 Jan 15;83:37-42. Epub 2020 Dec 15.

Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL, USA; Department of Neurological Surgery, Mayo Clinic, Jacksonville, FL, USA.

The Gamma Knife Icon (Elekta AB, Stockholm) is a cobalt-based stereotactic radiosurgery (SRS) unit to support the use of a thermoplastic mask in lieu of a rigid frame, using an onboard cone-beam CT (CBCT) and an intrafraction motion management system (IFMM). We retrospectively reviewed 124 patients treated with Gamma Knife SRS from January 2018 to December 2019 at our institution using a mask-based immobilization system. Patient and treatment characteristics were collected and summarized as well as interfraction shifts and treatment-related outcomes. This dataset includes 124 patients with an associated 358 intracranial tumors. Twenty-four patients presented with primary brain tumors, which included 14 meningiomas and 10 other histologies, with 100 patients having brain metastases. Sixty tumors were post-operative, while 298 were intact. The median dose for primary tumors was 25 Gy in 5 fractions. Median doses to metastases were 20 Gy in 1 fraction, 27 Gy in 3 fractions, and 25 Gy in 5 fractions. Median interfraction CBCT shifts were submillimeter. Median patient follow-up was 6.28 months. 91% of patients with metastases maintained local control. Our early clinical experience has demonstrated limited toxicity profiles and high patient tolerance, which suggests that mask-based Gamma Knife SRS provides a safe alternative option for frameless SRS. Patients with large target volumes where fractionation is preferred or with small target volumes in non-eloquent areas can be considered for this approach. Response rates are encouraging, and continued follow-up is necessary to investigate long-term control and survival.
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http://dx.doi.org/10.1016/j.jocn.2020.11.033DOI Listing
January 2021

Stereotactic radiosurgery with versus without prior Onyx embolization for brain arteriovenous malformations.

J Neurosurg 2020 Dec 11:1-9. Epub 2020 Dec 11.

14Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania.

Objective: Investigations of the combined effects of neoadjuvant Onyx embolization and stereotactic radiosurgery (SRS) on brain arteriovenous malformations (AVMs) have not accounted for initial angioarchitectural features prior to neuroendovascular intervention. The aim of this retrospective, multicenter matched cohort study is to compare the outcomes of SRS with versus without upfront Onyx embolization for AVMs using de novo characteristics of the preembolized nidus.

Methods: The International Radiosurgery Research Foundation AVM databases from 1987 to 2018 were retrospectively reviewed. Patients were categorized based on AVM treatment approach into Onyx embolization (OE) and SRS (OE+SRS) or SRS alone (SRS-only) cohorts and then propensity score matched in a 1:1 ratio. The primary outcome was AVM obliteration. Secondary outcomes were post-SRS hemorrhage, all-cause mortality, radiological and symptomatic radiation-induced changes (RICs), and cyst formation. Comparisons were analyzed using crude rates and cumulative probabilities adjusted for competing risk of death.

Results: The matched OE+SRS and SRS-only cohorts each comprised 53 patients. Crude rates (37.7% vs 47.2% for the OE+SRS vs SRS-only cohorts, respectively; OR 0.679, p = 0.327) and cumulative probabilities at 3, 4, 5, and 6 years (33.7%, 44.1%, 57.5%, and 65.7% for the OE+SRS cohort vs 34.8%, 45.5%, 59.0%, and 67.1% for the SRS-only cohort, respectively; subhazard ratio 0.961, p = 0.896) of AVM obliteration were similar between the matched cohorts. The secondary outcomes of the matched cohorts were also similar. Asymptomatic and symptomatic embolization-related complication rates in the matched OE+SRS cohort were 18.9% and 9.4%, respectively.

Conclusions: Pre-SRS AVM embolization with Onyx does not appear to negatively influence outcomes after SRS. These analyses, based on de novo nidal characteristics, thereby refute previous studies that found detrimental effects of Onyx embolization on SRS-induced AVM obliteration. However, given the risks incurred by nidal embolization using Onyx, this neoadjuvant intervention should be used judiciously in multimodal treatment strategies involving SRS for appropriately selected large-volume or angioarchitecturally high-risk AVMs.
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http://dx.doi.org/10.3171/2020.7.JNS201731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192588PMC
December 2020

Quantitation and predictors of short-term mortality following extrapleural pneumonectomy, pleurectomy/decortication, and nonoperative management for malignant pleural mesothelioma.

J Thorac Dis 2020 Nov;12(11):6476-6493

Department of Radiation Oncology, New York Proton Center, New York, NY, USA.

Background: For malignant pleural mesothelioma (MPM), the benefit of resection, as well as the optimal surgical technique, remain controversial. In efforts to better refine patient selection, this retrospective observational cohort study queried the National Cancer Database in an effort to quantify and evaluate predictors of 30- and 90-day mortality between extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D), as well as nonoperative management.

Methods: After applying selection criteria, cumulative incidences of mortality by treatment paradigm were graphed for the unadjusted and propensity-matched populations, as well as for six age-based intervals (≤60, 61-65, 66-70, 71-75, 76-80, and ≥81 years). The interaction between age and hazard ratio (HR) for mortality between treatment paradigms was also graphed. Cox multivariable analysis ascertained factors independently associated with 30- and 90-day mortality.

Results: Of 10,723 patients, 2,125 (19.8%) received resection (n=438 EPP, n=1,687 P/D) and 8,598 (80.2%) underwent nonoperative management. The unadjusted 30/90-day mortality for EPP, P/D, and all operated cases was 3.0%/8.0%, 5.4%/14.1%, and 4.9%/12.8%, respectively. There were no short-term mortality differences between EPP and P/D following propensity-matching, within each age interval, or between age subgroups on interaction testing (P>0.05 for all). Nonoperative patients had a crude 30- and 90-day mortality of 9.9% and 24.6%, respectively. Several variables were identified as predictors of short-term mortality, notably patient age (HR 1.022, P<0.001), Charlson-Deyo comorbidity index (HR 1.882, P<0.001), receipt of treatment at high-volume centers (HR 0.834, P=0.032) and induction chemotherapy (HR 1.735, P=0.025), among others. The patient (yearly) incremental increase in age conferred 2.0% (30 day) and 2.2% (90 day) increased risk of mortality (P<0.001).

Conclusions: Quantitative estimates of age-associated 30- and 90-day mortality of EPP and P/D should be considered when potentially operable patients are counseled regarding the risks and benefits of resection.
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http://dx.doi.org/10.21037/jtd-20-1779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711390PMC
November 2020

Epidemiology of bone metastases.

Bone 2020 Dec 1:115783. Epub 2020 Dec 1.

Department of Radiation Oncology, Penn State Cancer Institute, Hershey, PA, USA; Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA. Electronic address: https://twitter.com/NicholasZaorsky.

Background: This study evaluated the incidence of de novo bone metastasis across all primary cancer sites and their impact on survival by primary cancer site, age, race, and sex.

Questions/purposes: Our objectives were (I) characterize the epidemiology of de novo bone metastasis with respect to patient demographics, (II) characterize the incidence by primary site, age, and sex (2010-2015), and (III) compare survival of de novo metastatic cancer patients with and without bone metastasis.

Methods: This is a retrospective, population-based study using nationally representative data from the Surveillance, Epidemiology, and End Results program, 2010-2015. Incidence rates by year of diagnosis, annual percentage changes, Kaplan-Meier, univariate and multiple Cox regression models are included in the analysis.

Results: Of patients with cancer in the SEER database, 5.1% were diagnosed with metastasis to bone, equaling ~18.8 per 100,000 bone metastasis diagnoses in the US per year (2010-2015). For adults >25, lung cancer is the most common primary site (2015 rate: 8.7 per 100,000) with de novo bone metastases, then prostate and breast primaries (2015 rates: 3.19 and 2.38 per 100,000, respectively). For patients <20 years old, endocrine cancers and soft tissue sarcomas are the most common primaries. Incidence is increasing for prostate (Annual Percentage Change (APC) = 4.6%, P < 0.001) and stomach (APC = 5.0%, P = 0.001) cancers. The presence of de novo bone metastasis was associated with a limited reduction in overall survival (HR = 1.02, 95%, CI = [1.01-1.03], p < 0.001) when compared to patients with other non-bone metastases.

Conclusion: The presence of bone metastasis versus metastasis to other sites has disease site-specific impact on survival. The incidence of de novo bone metastasis varies by age, sex, and primary disease site.
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http://dx.doi.org/10.1016/j.bone.2020.115783DOI Listing
December 2020

Estimating the Number of Patients Eligible for Carbon Ion Radiotherapy in the United States.

Int J Part Ther 2020 5;7(2):31-41. Epub 2020 Nov 5.

Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL, USA.

Purpose: Carbon ion radiotherapy (CIRT) is an emerging radiotherapy modality with potential advantages over conventional photon-based therapy, including exhibiting a Bragg peak and greater relative biological effectiveness, leading to a higher degree of cell kill. Currently, 13 centers are treating with CIRT, although there are no centers in the United States. We aimed to estimate the number of patients eligible for a CIRT center in the United States.

Materials And Methods: Using the National Cancer Database, we analyzed the incidence of cancers frequently treated with CIRT internationally (glioblastoma, hepatocellular carcinoma, cholangiocarcinoma, locally advanced pancreatic cancer, non-small cell lung cancer, localized prostate cancer, soft tissue sarcomas, and specific head and neck cancers) diagnosed in the United States in 2015. The percentage and number of patients likely benefiting from CIRT was estimated with inclusion criteria from clinical trials and retrospective studies, and that ratio was applied to 2019 cancer statistics. An adaption correction rate was applied to estimate the potential number of patients treated with CIRT. Given the high dependency on prostate and lung cancers and the uncertain adoption of CIRT in those diseases, the data were then reanalyzed excluding those diagnoses.

Results: Of the 1 127 455 new cases of cancer diagnosed in the United States in 2015, there were 213 073 patients (18.9%) eligible for treatment with CIRT based on inclusion criteria. When applying this rate and the adaption correction rate to the 2019 incidence data, an estimated 89 946 patients (42.2% of those fitting inclusion criteria) are eligible for CIRT. Excluding prostate and lung cancers, there were an estimated 8922 patients (10% of those eligible for CIRT) eligible for CIRT. The number of patients eligible for CIRT is estimated to increase by 25% to 27.7% by 2025.

Conclusion: Our analysis suggests a need for CIRT in the United States in 2019, with the number of patients possibly eligible to receive CIRT expected to increase during the coming 5 to 10 years.
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http://dx.doi.org/10.14338/IJPT-19-00079.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707324PMC
November 2020

Trends in Cancer Incidence in US Adolescents and Young Adults, 1973-2015.

JAMA Netw Open 2020 12 1;3(12):e2027738. Epub 2020 Dec 1.

Department of Radiation Oncology, Penn State Cancer Institute, Hershey, Pennsylvania.

Importance: Previous studies have demonstrated that adolescents and young adults (AYAs) with cancer are a distinct cancer population; however, research on long-term epidemiological trends and characteristics of cancers in AYAs is lacking.

Objective: To characterize the epidemiology of cancer in AYAs aged 15 to 39 years with respect to (1) patient demographic characteristics, (2) frequencies of cancer types, and (3) cancer incidence trends over time.

Design, Setting, And Participants: This retrospective, serial cross-sectional, population-based study used registry data from the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 1973, to December 31, 2015 (SEER 9 and SEER 18). The study population was from geographically distinct US regions, chosen to represent the racial and ethnic heterogeneity of the country. Initial analyses were performed from January 1 to August 31, 2019.

Main Outcomes And Measures: Incidence rates and descriptive epidemiological statistics for patients aged 15 to 39 years with invasive cancer.

Results: A total of 497 452 AYAs diagnosed from 1973 to 2015 were included in this study, with 293 848 (59.1%) female and 397 295 (79.9%) White participants. As AYAs aged, an increase in the relative incidence of carcinomas and decrease in the relative incidence of leukemias, lymphomas, germ cell and trophoblastic neoplasms, and neoplasms of the central nervous system occurred. Among the female AYAs, 72 564 (24.7%) were diagnosed with breast carcinoma; 48 865 (16.6%), thyroid carcinoma; and 33 828 (11.5%), cervix and uterus carcinoma. Among the male AYAs, 37 597 (18.5%) were diagnosed with testicular cancer; 20 850 (10.2%), melanoma; and 19 532 (9.6%), non-Hodgkin lymphoma. The rate of cancer in AYAs increased by 29.6% from 1973 to 2015, with a mean annual percentage change (APC) per 100 000 persons of 0.537 (95% CI, 0.426-0.648; P < .001). Kidney carcinoma increased at the greatest rate for both male (APC, 3.572; 95% CI, 3.049-4.097; P < .001) and female (APC, 3.632; 95% CI, 3.105-4.162; P < .001) AYAs.

Conclusions And Relevance: In this cross-sectional, US population-based study, cancer in AYAs was shown to have a unique epidemiological pattern and is a growing health concern, with many cancer subtypes having increased in incidence from 1973 to 2015. Continued research on AYA cancers is important to understanding and addressing the distinct health concerns of this population.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.27738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709088PMC
December 2020

Safety and Survival Rates Associated With Ablative Stereotactic Radiotherapy for Patients With Oligometastatic Cancer: A Systematic Review and Meta-analysis.

JAMA Oncol 2021 Jan;7(1):92-106

Department of Public Health Sciences, Penn State University, Hershey, Pennsylvania.

Importance: The oligometastatic paradigm postulates that patients with a limited number of metastases can be treated with ablative local therapy to each site of disease with curative intent. Stereotactic ablative radiotherapy (SABR) is a radiation technique that has become widely used in this setting. However, prospective data are limited and are mainly from single institutional studies.

Objective: To conduct a meta-analysis to characterize the safety and clinical benefit of SABR in oligometastatic cancer.

Data Sources: A comprehensive search was conducted in PubMed/MEDLINE, Embase, Cochrane Database of Systematic Reviews, and Cumulative Index to Nursing and Allied Health Literature on December 23, 2019, that included prospective clinical trials and review articles that were published within the past 15 years.

Study Selection: Inclusion criteria were single-arm or multiarm prospective trials including patients with oligometastatic cancer (ie, ≤5 sites of extracranial disease), and SABR was administered in less than or equal to 8 fractions with greater than or equal to 5 Gy/fraction.

Data Extraction And Synthesis: The Population, Intervention, Control, Outcomes and Study Design; Preferred Reporting Items for Systematic Reviews and Meta-analyses; and Meta-analysis of Observational Studies in Epidemiology methods were used to identify eligible studies. Study eligibility and data extraction were reviewed by 3 authors independently. Random-effects meta-analyses using the Knapp-Hartung correction, arcsine transformation, and restricted maximum likelihood method were conducted.

Main Outcomes And Measures: Safety (acute and late grade 3-5 toxic effects) and clinical benefit (1-year local control, 1-year overall survival, and 1-year progression-free survival).

Results: Twenty-one studies comprising 943 patients and 1290 oligometastases were included. Median age was 63.8 years (interquartile range, 59.6-66.1 years) and median follow-up was 16.9 months (interquartile range, 13.7-24.5 months). The most common primary sites were prostate (22.9%), colorectal (16.6%), breast (13.1%), and lung (12.8%). The estimate for acute grade 3 to 5 toxic effect rates under the random-effects models was 1.2% (95% CI, 0%-3.8%; I2 = 50%; 95% CI, 3%-74%; and τ = 0.20%; 95% CI, 0.00%-1.43%), and the estimate for late grade 3 to 5 toxic effects was 1.7% (95% CI, 0.2%-4.6%; I2 = 54%; 95% CI, 11%-76%; and τ = 0.25%; 0.01%-1.00%). The random-effects estimate for 1-year local control was 94.7% (95% CI, 88.6%-98.6%; I2 = 90%; 95% CI, 86%-94%; and τ = 0.81%; 95% CI, 0.36%-2.38%]). The estimate for 1-year overall survival was 85.4% (95% CI, 77.1%-92.0%; I2 = 82%; 95% CI, 71%-88%; and τ = 0.72%; 95% CI, 0.30%-2.09%) and 51.4% (95% CI, 42.7%-60.1%; I2 = 58%; 95% CI, 17%-78%; and τ = 0.20%; 95% CI, 0.02%-1.21%) for 1-year progression-free survival.

Conclusions And Relevance: In this meta-analysis, SABR appears to be relatively safe in patients with oligometastatic cancer with clinically acceptable rates of acute and late grade 3 to 5 toxic effects less than 13% and with clinically acceptable rates of 1-year local control overall survival, and progression-free survival. These findings are hypothesis generating and require validation by ongoing and planned prospective clinical trials.
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http://dx.doi.org/10.1001/jamaoncol.2020.6146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689573PMC
January 2021

Engineering Three-Dimensional Tumor Models to Study Glioma Cancer Stem Cells and Tumor Microenvironment.

Front Cell Neurosci 2020 16;14:558381. Epub 2020 Oct 16.

Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL, United States.

Glioblastoma (GBM) is the most common and devastating primary brain tumor, leading to a uniform fatality after diagnosis. A major difficulty in eradicating GBM is the presence of microscopic residual infiltrating disease remaining after multimodality treatment. Glioma cancer stem cells (CSCs) have been pinpointed as the treatment-resistant tumor component that seeds ultimate tumor progression. Despite the key role of CSCs, the ideal preclinical model to study the genetic and epigenetic landmarks driving their malignant behavior while simulating an accurate interaction with the tumor microenvironment (TME) is still missing. The introduction of three-dimensional (3D) tumor platforms, such as organoids and 3D bioprinting, has allowed for a better representation of the pathophysiologic interactions between glioma CSCs and the TME. Thus, these technologies have enabled a more detailed study of glioma biology, tumor angiogenesis, treatment resistance, and even performing high-throughput screening assays of drug susceptibility. First, we will review the foundation of glioma biology and biomechanics of the TME, and then the most up-to-date insights about the applicability of these new tools in malignant glioma research.
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http://dx.doi.org/10.3389/fncel.2020.558381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596188PMC
October 2020

Convexity Meningiomas in Patients with Neurofibromatosis Type 2: Long-Term Outcomes After Gamma Knife Radiosurgery.

World Neurosurg 2021 Feb 3;146:e678-e684. Epub 2020 Nov 3.

Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia, USA. Electronic address:

Background: Convexity meningiomas are common tumors requiring treatment in patients with neurofibromatosis type 2 (NF2). Although different therapeutic options are described for sporadic convexity meningioma, much less is known about these lesions in patients with NF2 despite their distinct biology and need for multiple treatments. We analyzed the value of Gamma Knife radiosurgery (GKRS) as definitive treatment for convexity meningiomas in patients with NF2.

Methods: This international multicenter retrospective study was approved by the International Radiosurgery Research Foundation. Patients with NF2 with at least 1 convexity meningioma and 6-month follow-up after primary GKRS were included.

Results: Inclusion criteria were met by 18 patients with NF2. A total of 120 convexity meningiomas (median treatment volume, 0.66 cm [range, 0.10-21.20 cm]) were analyzed. Median follow-up after initial GKRS was 15.6 years (range, 0.6-25.5 years). Median age at GKRS was 32.5 years (range, 16-53 years). Median number of meningiomas per patient was 13 (range, 1-27), and median number of convexity lesions receiving GKRS per patient was 3.5 (range, 1-27). One case of tumor progression was reported 24 years after GKRS, leading to actuarial progression-free survival rates of 100% at 2, 5, and 10 years. No malignant transformation or death due to meningioma or radiosurgery was recorded.

Conclusions: GKRS is safe and effective as definitive treatment of small to medium-sized convexity meningiomas in patients with NF2. Despite concerns about the particular mutational burden of these tumors, no malignant transformation manifested after treatment. GKRS represents a minimally invasive option that offers long-term tumor control to this specific group of patients.
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http://dx.doi.org/10.1016/j.wneu.2020.10.153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988886PMC
February 2021

Stereotactic Radiosurgery With Versus Without Embolization for Brain Arteriovenous Malformations.

Neurosurgery 2021 01;88(2):313-321

Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania.

Background: Prior comparisons of brain arteriovenous malformations (AVMs) treated using stereotactic radiosurgery (SRS) with or without embolization were inherently flawed, due to differences in the pretreatment nidus volumes.

Objective: To compare the outcomes of embolization and SRS, vs SRS alone for AVMs using pre-embolization malformation features.

Methods: We retrospectively reviewed International Radiosurgery Research Foundation AVM databases from 1987 to 2018. Patients were categorized into the embolization and SRS (E + SRS) or SRS alone (SRS-only) cohorts. The 2 cohorts were matched in a 1:1 ratio using propensity scores. Primary outcome was defined as AVM obliteration. Secondary outcomes were post-SRS hemorrhage, all-cause mortality, radiologic and symptomatic radiation-induced changes (RIC), and cyst formation.

Results: The matched cohorts each comprised 101 patients. Crude AVM obliteration rates were similar between the matched E + SRS vs SRS-only cohorts (48.5% vs 54.5%; odds ratio = 0.788, P = .399). Cumulative probabilities of obliteration at 3, 4, 5, and 6 yr were also similar between the E + SRS (33.0%, 46.4%, 56.2%, and 60.8%, respectively) and SRS-only (32.9%, 46.2%, 56.0%, and 60.6%, respectively) cohorts (subhazard ratio (SHR) = 1.005, P = .981). Cumulative probabilities of radiologic RIC at 3, 4, 5, and 6 yr were lower in the E + SRS (25.0%, 25.7%, 26.7%, and 26.7%, respectively) vs SRS-only (45.3%, 46.2%, 47.8%, and 47.8%, respectively) cohort (SHR = 0.478, P = .004). Symptomatic and asymptomatic embolization-related complication rates were 8.3% and 18.6%, respectively. Rates of post-SRS hemorrhage, all-cause mortality, symptomatic RIC, and cyst formation were similar between the matched cohorts.

Conclusion: This study refutes the prevalent notion that AVM embolization negatively affects the likelihood of obliteration after SRS.
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http://dx.doi.org/10.1093/neuros/nyaa418DOI Listing
January 2021

Multiple meningiomas: does quantity matter? a population-based survival analysis with underlined age and sex differences.

J Neurooncol 2020 Sep 28;149(3):413-420. Epub 2020 Sep 28.

Department of Neurologic Surgery, Mayo Clinic, Jacksonville, FL, USA.

Introduction: Intracranial meningiomas rarely present with multiple lesions. To the best of our knowledge, current literature regarding meningiomatosis (MM) is mostly comprised of small case series and individual reports. Hence, survival outcome data are limited. The Objective of this study is to explore the influence of sex, age, and number of lesions on overall survival (OS) in patients with MM.

Methods: We obtained demographic and clinical data from the surveillance, epidemiology, and end results program (SEER) on adult patients diagnosed with meningiomas from 1975 to 2017. Univariable and multivariable analyses were conducted to assess whether number of lesions, age, and sex had a significant influence on OS.

Results: 99,918 cases were included. Results showed that MM patients had a significantly decreased OS when compared to patients with a single lesion (median OS of 94 and 180 months, respectively; p < 0.001). Further analysis showed a progressive decrease on OS for every additional lesion; 2 (HR 1.659 [CI 95% 1.612-1.708], p < 0.001), 3 (HR 1.877 [CI 95% 1.773-1.988], p < 0.001), and ≥ 4 (HR 2.116 [CI 95% 1.886-2.373], p < 0.001). When assessing for sex differences, female patients had increased OS (HR 0.778 [CI 95% 0.743-0.815], p < 0.001) and decreased risk of developing MM (HR 0.809 [CI 95% 0.784-0.835], p < 0.001).

Conclusion: Increasing number of meningiomas has a significant negative impact on OS, with a progressive decrease on survival for every additional lesion. Furthermore, female patients had increased OS and decreased risk to develop MM.
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http://dx.doi.org/10.1007/s11060-020-03620-7DOI Listing
September 2020

Intraventricular choroid plexus tumors: clinical characteristics and impact of current management on survival.

J Neurooncol 2020 Sep 8;149(2):283-292. Epub 2020 Sep 8.

Department of Radiation Oncology, Mayo Clinic, 4500 San Pablo Road South, Jacksonville, FL, 32224, USA.

Introduction: Choroid plexus tumors (CPTs) represent one of the most common intraventricular tumors. Although most are benign, they often reach considerable sizes before clinical manifestation, challenging their surgical management. We aim to describe the clinical characteristics and the impact of current management on the survival of patients harboring intraventricular CPT.

Methods: The National Cancer Database (NCDB) was queried to identify biopsy-proven intraventricular CPT patients (2004-2015). Demographic and patterns of care were described, the log-rank method was used to independently analyze survival according to age, WHO grade and extent of resection (EOR). Multivariate analysis was performed to investigate the impact of prognostic factors on overall survival (OS).

Results: A total of 439 CPT patients with known WHO grade were included. WHO grade I tumors were more frequent in adults, while WHO grade III tumors were more common in pediatric population. Most CPTs were benign, with a median tumor size of 3-4 cm. Mean tumor size in pediatric population was greater than in adult population (4.39 cm vs. 2.7 cm; p < 0.01). Frequency was similar between males and females (51.7% vs. 48.3%; p > 0.0.5). Five- and ten-year OS among all patients was 87% and 84%, respectively. EOR was not associated with survival for any WHO grade. On multivariable analysis, only patient age (p = 0.022), WHO grade (p = 0.003) and medical comorbidity scores (p = 0.002) were independently associated with OS after diagnosis.

Conclusion: Patients with CPTs present at different stages of life, with sizable tumor burden and distinct WHO grade prevalence. Considering their favorable survival, efforts to improve tumor control should be meticulously weighed against the long-term risk associated with surgery, radiation, and chemotherapy.
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http://dx.doi.org/10.1007/s11060-020-03603-8DOI Listing
September 2020

Embolization of Brain Arteriovenous Malformations With Versus Without Onyx Before Stereotactic Radiosurgery.

Neurosurgery 2021 01;88(2):366-374

Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania.

Background: Embolization of brain arteriovenous malformations (AVMs) using ethylene-vinyl alcohol copolymer (Onyx) embolization may influence the treatment effects of stereotactic radiosurgery (SRS) differently than other embolysates.

Objective: To compare the outcomes of pre-SRS AVM embolization with vs without Onyx through a multicenter, retrospective matched cohort study.

Methods: We retrospectively reviewed International Radiosurgery Research Foundation AVM databases from 1987 to 2018. Embolized AVMs treated with SRS were selected and categorized based on embolysate usage into Onyx embolization (OE + SRS) or non-Onyx embolization (NOE + SRS) cohorts. The 2 cohorts were matched in a 1:1 ratio using de novo AVM features for comparative analysis of outcomes.

Results: The matched cohorts each comprised 45 patients. Crude AVM obliteration rates were similar between the matched OE + SRS vs NOE + SRS cohorts (47% vs 51%; odds ratio [OR] = 0.837, P = .673). Cumulative probabilities of obliteration were also similar between the OE + SRS vs NOE + SRS cohorts (subhazard ratio = 0.992, P = .980). Rates of post-SRS hemorrhage, all-cause mortality, radiation-induced changes, cyst formation, and embolization-associated complications were similar between the matched cohorts. Sensitivity analysis for AVMs in the OE + SRS cohort embolized with Onyx alone revealed a higher rate of asymptomatic embolization-associated complications in this subgroup compared to the NOE + SRS cohort (36% vs 15%; OR = 3.297, P = .034), but the symptomatic complication rates were similar.

Conclusion: Nidal embolization using Onyx does not appear to differentially impact the outcomes of AVM SRS compared with non-Onyx embolysates. The embolic agent selected for pre-SRS AVM embolization should reflect both the experience of the neurointerventionalist and target of endovascular intervention.
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http://dx.doi.org/10.1093/neuros/nyaa370DOI Listing
January 2021

Multidisciplinary patient-centered management of brain metastases and future directions.

Neurooncol Adv 2020 Jan-Dec;2(1):vdaa034. Epub 2020 Mar 16.

Department of Radiation Oncology, Centre Hospitalier de l' Université de Montreal, Montreal, Quebec, Canada.

The incidence of brain metastasis is increasing as improvements in systemic therapy lead to increased survival. This provides new and challenging clinical decisions for patients who are trying to balance the risk of recurrence or progression with treatment-related side effects, and it requires appropriate management strategies from multidisciplinary teams. Improvements in prognostic assessment and systemic therapy with increasing activity in the brain allow for individualized care to better guide the use of local therapies and/or systemic therapy. Here, we review the current landscape of brain-directed therapy for the treatment of brain metastasis in the context of recent improved systemic treatment options. We also discuss emerging treatment strategies including targeted therapies for patients with actionable mutations, immunotherapy, modern whole-brain radiation therapy, radiosurgery, surgery, and clinical trials.
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http://dx.doi.org/10.1093/noajnl/vdaa034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415255PMC
March 2020

Toxicity in combination immune checkpoint inhibitor and radiation therapy: A systematic review and meta-analysis.

Radiother Oncol 2020 10 24;151:141-148. Epub 2020 Jul 24.

Department of Radiation Oncology, Penn State Cancer Institute, Hershey, PA, USA; Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA. Electronic address:

Background And Purpose: Immune checkpoint inhibitor with radiation therapy (ICI + RT) is under investigation for improved patient outcome, so we performed a systematic review/meta-analysis of toxicities for ICI + RT compared to immune checkpoint inhibitor (ICI) therapy alone.

Materials And Methods: A PRISMA-compliant systematic review of studies in MEDLINE (PubMed) and in the National Comprehensive Cancer Network guidelines was conducted, with primary outcome grade 3 + toxicity. Criteria for ICI alone were: phase III/IV trials that compared immunotherapy to placebo, chemotherapy, or alternative immunotherapy; and for ICI + RT: prospective/retrospective studies with an arm treated with ICI + RT. Meta-analysis was performed by random effects models using the DerSimonian and Laird method. The I statistic and Cochran's Q test were used to assess heterogeneity, while funnel plots and Egger's test assessed publication bias.

Results: This meta-analysis included 51 studies (n = 15,398), with 35 ICI alone (n = 13,956) and 16 ICI + RT studies (n = 1,442). Our models showed comparable grade 3-4 toxicities in ICI + RT (16.3%; 95% CI, 11.1-22.3%) and ICI alone (22.3%; 95% CI, 18.1-26.9%). Stratification by timing of radiation and irradiated site showed no significant differences, but anti-CTLA-4 therapy and melanoma showed increased toxicity. The grade 5 toxicities were 1.1% and 1.9% for ICI alone and ICI + RT respectively. There was significant heterogeneity, but not publication bias.

Conclusions: The random effects model showed comparable grade 3-4 toxicity in using ICI + RT compared to ICI alone in CNS melanoma metastases, NSCLC, and prostate cancer. ICI + RT is safe for future clinical trials in these cancers.
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http://dx.doi.org/10.1016/j.radonc.2020.07.035DOI Listing
October 2020

Effect of Anatomic Segment Involvement on Stereotactic Radiosurgery for Facial Nerve Schwannomas: An International Multicenter Cohort Study.

Neurosurgery 2020 12;88(1):E91-E98

Department of Neurosurgery, University of Virginia Medical Center, Charlottesville, Virginia.

Background: Facial nerve schwannomas are rare, challenging tumors to manage due to their nerve of origin. Functional outcomes after stereotactic radiosurgery (SRS) are incompletely defined.

Objective: To analyze the effect of facial nerve segment involvement on functional outcome for these tumors.

Methods: Patients who underwent single-session SRS for facial nerve schwannomas with at least 3 mo follow-up at 11 participating centers were included. Preoperative and treatment variables were recorded. Outcome measures included radiological tumor response and neurological function.

Results: A total of 63 patients (34 females) were included in the present study. In total, 75% had preoperative facial weakness. Mean tumor volume and margin dose were 2.0 ± 2.4 cm3 and 12.2 ± 0.54 Gy, respectively. Mean radiological follow-up was 45.5 ± 38.9 mo. Progression-free survival at 2, 5, and 10 yr was 98.1%, 87.2%, and 87.2%, respectively. The cumulative proportion of patients with regressing tumors at 2, 5, and 10 yr was 43.1%, 63.6%, and 63.6%, respectively. The number of involved facial nerve segments significantly predicted tumor progression (P = .04). Facial nerve function was stable or improved in 57 patients (90%). Patients with involvement of the labyrinthine segment of the facial nerve were significantly more likely to have an improvement in facial nerve function after SRS (P = .03). Hearing worsened in at least 6% of patients. Otherwise, adverse radiation effects included facial twitching (3 patients), facial numbness (2 patients), and dizziness (2 patients).

Conclusion: SRS for facial nerve schwannomas is effective and spares facial nerve function in most patients. Some patients may have functional improvement after treatment, particularly if the labyrinthine segment is involved.
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http://dx.doi.org/10.1093/neuros/nyaa313DOI Listing
December 2020

Proton and carbon ion therapy for skull base chordomas.

Neuro Oncol 2020 09;22(9):1241-1242

Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.

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http://dx.doi.org/10.1093/neuonc/noaa169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523445PMC
September 2020