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Purpose To perform a propensity-score matched analysis comparing stereotactic body radiation therapy (SBRT) boost and high-dose-rate (HDR) boost for localized prostate cancer. Methods and Materials A single-institution retrospective chart review was conducted of men treated with pelvic external beam radiation therapy (EBRT) and SBRT boost (21 Gy and 19 Gy in 2 fractions) to the prostate for prostate cancer. A cohort treated at the same institution with HDR brachytherapy boost (19 Gy in 2 fractions) was compared. Propensity-score (PS) matching and multivariable Cox regression were used for analysis. Outcomes were biochemical recurrence freedom (BCRF) and metastasis freedom (MF). Results One hundred thirty-one men were treated with SBRT boost and 101 with HDR boost with median follow-up of 73.4 and 186.0 months, respectively. In addition, 68.8% of men had high-risk and 26.0% had unfavorable-intermediate disease, and 94.3% received androgen deprivation therapy. Five- and 10-year unadjusted BCRF was 88.8% and 85.3% for SBRT and 91.8% and 74.6% for HDR boost (log-rank P = .3), and 5- and 10-year unadjusted MF was 91.7% and 84.3% for SBRT and 95.8% and 82.0% for HDR (log-rank P = .8). After adjusting for covariates, there was no statistically significant difference in BCRF (hazard ratio [HR] 0.81; 95% confidence interval [CI], 0.37-1.79; P = .6) or MF (HR 1.07; 95% CI, 0.44-2.57; P = .9) between SBRT and HDR boost. Similarly, after PS matching, there was no statistically significant difference between SBRT and HDR (BCRF: HR 0.66, 0.27-1.62, P = .4; MF: HR 0.84, 0.31-2.26, P = .7). Grade 3+ genitourinary and gastrointestinal toxicity in the SBRT cohort were 4.6% and 1.5%, and 3.0% and 0.0% in the HDR cohorts (P = .4, Fisher exact test). Conclusions SBRT boost plus pelvic EBRT for prostate cancer resulted in similar BCRF and MF to HDR boost in this single institution, PS matched retrospective analysis. Toxicity was modest. Prospective evaluation of SBRT boost for the treatment of unfavorable-intermediate and high-risk prostate cancer is warranted.

As the COVID-19 pandemic spreads around the globe, access to radiation therapy remains critical for cancer patients. The priority for all radiation oncology departments is to protect the staff and to maintain operations in providing access to those patients requiring radiation therapy services. Patients with tumors of the aerodigestive tract and pelvis amongst others often experience toxicity during treatment, and there is a baseline risk that adverse effects may require hospital-based management. Routine care during weekly visits is important to guide patients through treatment and to mitigate against the need for hospitalization. Nevertheless, hospitalizations occur and there is a risk of nosocomial SARS-CoV-2 spread. During the COVID-19 pandemic, typical resources used to help manage patients, such as dental services, interventional radiology, rehabilitation and others are limited or not at all available. Recognizing the need to provide access to treatment and the anticipated toxicity of such treatment, we have developed and implemented guidelines for clinical care management with the hope of avoiding added risk to our patients. If successful, these concepts may be integrated into our care directives in non-pandemic times., Efforts to avoid hospitalization during cancer treatment represent typical clinical care. Nevertheless, a small percentage of patients succumb to such needs. During the COVID-19 pandemic where hospital resources are limited and risk of nosocomial infection significant, we have outlined critical clinical care guidelines that may help avoid hospitalizations during cancer treatment.

Purpose To identify clinical and imaging variables associated with symptomatic recurrence of osteoid osteomas (OOs) treated with computerized tomography (CT)–guided radiofrequency (RF) ablation. Materials and Methods Seventy-one patients treated with the use of CT-guided RF ablation for OO at a single institution from July 2005 to May 2018 were included in this retrospective cohort analysis. Clinical data, including patient age, sex, race, and clinical outcomes, were collected from institutional electronic health records and telephone follow-up. Imaging variables regarding tumor characteristics were gathered from imaging reports and a blinded review of preprocedural images by an experienced musculoskeletal radiologist. Logistic regression, Cox proportional hazards, and Kaplan-Meier analyses were used to identify variables that are significantly associated with symptomatic recurrence, which was defined as pain occurring > 2 weeks after RF ablation. Results Ten patients (14.1%) experienced symptomatic recurrence at a median of 21.5 months after RF ablation. Univariable logistic regression classified young age (≤ 13 years), female sex, maximum tumor length, and “eccentricity index” (EI) ≥ 3 as predictive variables significantly associated with symptomatic recurrence. Multivariable logistic regression identified female sex and EI ≥ 3 to be significant predictors for symptomatic recurrence. A multivariable proportional hazards Cox regression of time to recurrence revealed EI ≥ 3 to be the only significant predictor of symptomatic recurrence. Conclusions Female patients with OOs with an EI ≥ 3 have a greater risk of symptomatic recurrence following RF ablation. The EI is a useful tool to identify OOs with elongated 3-dimensional morphology, which may warrant more extensive ablation.

Purpose/Objective(s) Indications for postoperative radiotherapy after meningioma resection are controversial. DNA methylation profiling identifies meningiomas at risk for recurrence, but logistic and technical barriers have encumbered clinical translation of this approach. The aim of this study was to optimize and validate a clinically-tractable targeted gene expression biomarker to predict meningioma outcomes and responses to postoperative radiotherapy. Materials/Methods Targeted gene expression and Illumina 850k DNA methylation profiling were performed on a discovery cohort of 173 meningiomas (median follow-up 7.8 years) and an external validation cohort of 331 meningiomas (median follow-up 5.8 years) from patients treated with surgery (n = 504) and postoperative radiotherapy (n = 73) at independent, international institutions (70% WHO grade 1, 24% WHO grade 2, 6% WHO grade 3). RNA sequencing was performed on the discovery cohort, and 125 genes were selected for targeted gene expression profiling based on associations with meningioma recurrence. Regularized Cox regression was used to develop continuous gene expression risk score for local freedom from recurrence (LFFR). The model (34 meningioma genes and 7 housekeeping genes) and risk quartiles (low, low-intermediate, high-intermediate, and high) were locked and validated on the external cohort. Multivariate regressions (MVR) incorporating WHO grade, DNA methylation grouping, extent of resection, primary versus recurrent presentation, and postoperative radiotherapy were used to assess the risk score across clinical contexts. Results The gene expression risk score (concordance-index 0.78 ± 0.03) outperformed DNA methylation grouping (0.71 ± 0.03) and WHO grade (0.65 ± 0.03) in stratifying meningioma LFFR in the validation cohort (n = 331). The risk score classified 43% of WHO grade 1 meningiomas as high-intermediate (n = 82) or high risk (n = 34), with 5-year LFFR and overall survival (OS) of 83% and 89% for high-intermediate risk WHO grade 1 meningiomas, and 41% and 73% for high risk WHO grade 1 meningiomas, respectively. Low risk WHO grade 1 meningiomas (n = 50) had 5-year LFFR and OS of 92% and 88%, respectively. High and high-intermediate risk scores were independently prognostic for LFFR (HR 2.9, 95% CI 1.2-4.4) and OS (HR 2.7, 95% CI 1.3-5.6) on MVR. An interaction term between postoperative radiotherapy and risk score was predictive for LFFR (P = 0.046) and OS (P = 0.001) on MVR in the validation cohort, suggesting meningiomas with higher risk scores derived greater benefit from postoperative radiotherapy. Conclusion Here we use targeted gene expression profiling to develop a risk score predicting meningioma outcomes and responses to postoperative radiotherapy. This cost-effective assay outperforms DNA methylation grouping and WHO grade in discriminating meningioma outcomes, and may be useful for guiding clinical trial design.

Purpose/Objective(s) In contrast to benign Schwann cell derived tumors such as neurofibromas and schwannomas, malignant peripheral nerve sheath tumors (MPNSTs) metastasize, and have poor outcomes. MPNSTs are associated with loss of NF1, a tumor suppressor that inhibits Ras signaling, and loss of Polycomb Repressive Complex 2 (PRC2) which resulting in epigenetic dysregulation. Translationally, MPNSTs are resistant to Ras/MEK inhibition with selumetinib and radiation therapy yet the mechanisms underlying how PRC2 loss cooperates with Ras misactivation to drive transformation and treatment resistance remains unclear. Here, we performed DNA methylation profiling and RNA-sequencing of Schwann cell tumors and cell lines as well as investigated in vitro responses to radiotherapy and selumetinib. Materials/Methods We identified 119 Schwann cell tumor resection specimens with sufficient tissue for DNA methylation profiling (66 schwannoma, 13 neurofibroma, 40 MPNSTs) and RNA-sequencing (23 schwannoma, 9 neurofibroma, 9 MPNSTs). To study cell signaling and treatment responses, we utilized primary human cell lines generated from NF1 intact peripheral nerve, NF1 mutant neurofibromas, and MPNSTs (n = 6). We assessed Ras signal transduction by immunoblot/immunoprecipitation for downstream effectors and performed cell viability assays following selumetinib or radiotherapy. Results Principal component analysis (PCA) of DNA methylation and RNA-sequencing data demonstrated a gradient of epigenetic signatures across Schwann cell tumors, with schwannomas comprising a distinct cluster from neurofibromas and MPNST. Moreover, differential DNA methylation and RNA-sequencing analyses both revealed enrichment for PRC2 target genes and repression of Schwann cell differentiation genes in MPNSTs. RNA-sequencing of MPNST versus neurofibroma cell lines demonstrated a PRC2 mediated signature enriched for cell differentiation genes and negative feedback regulators of Ras signaling, suggesting PRC2 dysregulation mediates de-differentiation and increased Ras pathway output in MPNSTs. In contrast to neurofibroma cells, MPNST cells were deficient in PRC2 and NF1 while exhibiting increased basal active Ras-GTP levels insensitive to serum starvation. PRC2 deficient MPNST cell lines were more resistant to selumetinib and radiation therapy when compared to NF1 deficient neurofibroma cells. Conclusion PRC2 loss causes epigenetic dysregulation that may mediate Schwann cell de-differentiation programs and altered Ras signaling in MPNSTs compared to neurofibromas. Translationally, these epigenetic changes may contribute to increased resistance to targeted therapy and radiation. The mechanisms underlying transformation and treatment resistance upon PRC2 loss are under further investigation.

Purpose/objective(s) Management of progressive brain tumors following high dose radiotherapy is controversial. In select cases, surgical resection can provide rapid relief of regional mass effect and edema, and highly focal adjuvant re-irradiation can be administered in the form of brachytherapy. Permanent low-dose rate cesium-131 brachytherapy may offer dosimetric and radiobiologic advantages over other isotopes. The purpose of this study was to examine the safety and efficacy of intracranial cesium-131 brachytherapy after surgical resection in a heavily pre-treated patient cohort. Materials/methods A retrospective chart review was conducted of all patients treated with intraoperative intracranial cesium-131 brachytherapy from an institutional database. Treatment consisted of maximal safe resection followed by implantation of suture-stranded cesium-131 seeds, maintaining approximately 10mm spacing between seeds, with a planned target dose of 80 Gy to 5mm depth. Local failure was defined as recurrence in or contacting the resection cavity after salvage resection and brachytherapy. Regional failure was defined as recurrence within 10mm of the resection cavity. Recurrence was defined as a new lesion or growth of ≥25% in any axial dimension on interval MRI. Toxicity was collected based on CTCAE 4.0. Results A total of 35 patients with a median imaging follow up of 17.0 months (interquartile range [IQR] 9.7-25.9) underwent 41 consecutive cesium-131 implants between 2016 and 2020. 20 patients (59%; N = 22 implants) were treated for recurrent brain metastasis, 12 patients (34%; N = 16 implants) were treated for recurrent atypical (N = 8) or anaplastic meningioma (N = 4), and 3 patients (9%) were treated for recurrent glioma (N = 2) or hemangiopericytoma (N = 1). A majority of lesions had received prior surgery (N = 28, 66.7%, range 0-3 prior surgeries) and 34 patients had received prior high dose radiation. 34 of 41 (82.9%) tumors had received prior radiosurgery, and 12 (29.2%) had undergone prior external beam radiation (range 50-60 Gy). 17 of 41 lesions (41.5%) had radiologic evidence of adverse radiation/treatment effect (ARE) prior to salvage therapy. Median tumor size was 3.0cm (IQR 2.3-3.7). Overall actuarial local/loco-regional control at 1-year was 91.6%/84.7% (89.8%/88.9% for metastases and 100%/82.5% for meningiomas). Crude loco-regional control was 86.3% for metastases, 75% for meningiomas, and 66.7% for other lesions. Symptomatic ARE following treatment was observed in 9.8% (N = 4) resection cavities. The surgical complication rate was 14.6% (N = 6 total, N = 3 [7.3%] grade 3-5) including 1 peri-operative death. Conclusion Cesium-131 brachytherapy in this heavily pre-treated cohort resulted in good local control and an acceptable rate of symptomatic adverse radiation effect and toxicity and may be a reasonable treatment option for this select population. Author disclosure W.C. Chen: None. M. Lafreniere: None. C. Phuong: None. M. Lometti: None. O. Morin: None. B.P. Ziemer: None. H. Vasudevan: Research Grant; Children's Tumor Foundation. Patent/License Fees/Copyright; Genentech, Eli Lilly. S. Hervey-Jumper: None. P.V. Theodosopoulos: None. S. Magill: None. S.E. Fogh: Independent Contractor; Accuray. J.L. Nakamura: None. L. Boreta: None. P.K. Sneed: None. M.W. McDermott: Chair; Miami Baptist. D. Raleigh: None. S.E. Braunstein: Advisory Board; Radiation Oncology Questions, LLC.

Purpose/Objective(s) Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive neoplasms arising either sporadically or in patients with neurofibromatosis type 1 (NF1). To elucidate markers of prognosis and treatment response, we retrospectively identified MPNST tumor resection specimens at a single institution and performed histopathologic evaluation, immunohistochemistry (IHC), DNA methylation profiling, and whole exome sequencing (WES). Materials/Methods We identified a total of 54 consecutive patients treated at one institution between 1990 and 2019 with tumors meeting diagnostic criteria for MPNST and had sufficient tissue available for comprehensive histopathological evaluation (n = 54), DNA methylation profiling (n = 45) and whole exome sequencing (n = 35, n = 15 with paired normal). Overall survival (OS), metastasis free survival (MFS), and locoregional failure free rate (LFFR), were estimated using the Kaplan-Meier method. Log-rank test, Cox Proportional Hazards regression, and hierarchical clustering were performed in R. Results The median follow up was 22 months with no significant differences in LFFR, MFS, or OS between NF1 associated (n = 32) and sporadic MPNSTs (n = 22). Radiotherapy significantly improved LFFR (P = 0.05) but not OS. With regard to histopathologic and IHC analyses, increasing tumor grade using a two-tiered system (P = 0.01) and Ki-67 index (P = 0.01) were associated with worse OS. Unsupervised hierarchical clustering of DNA methylation profiles identified two groups with significant differences in chromosome instability and tumor purity but not clinical outcome. Recurrently identified copy number variants (CNVs) included chromosome 22q loss, 11q loss, 10 loss, 9p loss, 8q gain, and 1q loss. Chromosome 9p loss (P = 0.02) and 8q gain (P = 0.04) were significantly associated with worse OS. On WES analysis, recurrently mutated genes included NF1, EED, SUZ12, TP53, and CDKNA2A. Of these alterations, only CKND2A loss (on Chr9p) was associated with worse OS (P = 0.01). With regard to treatment response, MPNSTs exhibiting NF1 and H3K27 trimethylation loss demonstrated greater LFFR benefit from radiation therapy (P = 0.004) compared to NF1 and H3K27 trimethylation intact tumors (P = 0.83) with clinical NF1 diagnosis as the only significantly different baseline parameter between these two subgroups. Conclusion MPNSTs are a common cause of death in adult patients with NF1. Radiotherapy improves LFFR in all patients, and integrated IHC and genomic analysis further identifies putative prognostic and predictive markers, including the identification of a patient subset in whom the benefit of radiotherapy is most pronounced. Taken together, these data support radiation therapy in management of MPNSTs and suggest molecular characterization may be important for counseling patients with MPNST or potentially informing clinical trial design. Prospective and multi-institutional analyses are needed to validate these findings.

Purpose/objective(s) Premature discontinuation of radiation therapy (RT) is a significant challenge portending inferior outcomes, particularly with curative intent RT. This study measures the impact of the COVID-19 pandemic compared to prior treatment terminations (TTs) from a multi-institutional health system in the New York Metropolitan area. Materials/methods TT data was collected from the internal quality assurance records of a multicenter radiation oncology department for the September 2019-February 2020 pre-pandemic interval (BP) and the March 2020-August 2020 post-pandemic interval (AP). We measured aggregate and monthly CT simulations (CT sims), TTs, and terminations with zero fractions of radiation given (0Fx), the latter stratified by palliative vs. curative intent (0Fx-P vs. 0Fx-C). AP TTs attributed to COVID-19 anxiety were also obtained. The data were analyzed as aggregate ratios with monthly weighting of TTs/CT sims, 0Fx/CT sims, and 0Fx/TTs. Ratio statistics were employed and 95% confidence intervals generated. 0Fx-P and 0Fx-C were tested for association with BP and AP by chi-square analysis. Results For BP and AP respectively: TTs/CT sims were 8.1% (95% CI 5.2%-11.0%) and 11.2% (95% CI 9.2%-13.3%); 0Fx/CT sims were 1.4% (95% CI 0.16%-2.70%) and 2.5% (95% CI 1.49%-3.6%); 0Fx/TTs were 15.8% (95% CI 6.35%-25.21%) and 22% (95% CI 16.0%-27.9%). The association of 0Fx-P and 0Fx-C with BP and AP yielded chi-square = 0.43, P = 0.51. TTs attributed to COVID-19 anxiety comprised 3.9% of TTs in AP. Conclusion The endpoints for TTs in the BP and AP periods in our study cohort were suggestive of a COVID impact on patients discontinuing radiation therapy, but without statistical significance. Given the subtleties of TT dynamics and uncertainties such as the count of COVID-19 anxiety-related terminations, along with a relatively small sample size, it is reasonable to infer that this review was underpowered. Moreover, direct statistical attribution of TTs to COVID understates knock-on effects, e.g., the case of a 0Fx TT that would have occurred regardless of COVID but under the stress of the pandemic exacerbates the harm of the waste of resources. At the patient care level, understanding how COVID affects TT patterns may enable interventions that facilitate completion of care as intended by the treating physician. At the health system level, such understanding may elucidate a plausible mechanism of COVID's cascading downstream influence on oncologic outcomes. Nevertheless, it will require a multi-institutional cohort to quantitatively discern the impact of the pandemic on TT dynamics.

Purpose/Objective(s) We previously reported our experience using innovative and automated chatbots (“Health Chats”) in head and neck cancer patients during radiation treatment (RT). We created a breast cancer (BC) Health Chat. The aims of this pilot study are to 1) assess the usability of the Health Chats, 2) engage patients by providing frequent individualized education, and 3) identify areas of unmet needs specific to BC patients via collection of patient-reported outcomes (PROs). Materials/Methods Between January 2020 and December 2020, adults with BC aged ≥ 18 years who were English literate and were scheduled for RT at one of four academic hospitals were screened. Participants were sent chats 2 days before on-treatment visits during the duration of RT, then weekly for 4 weeks post-treatment, and monthly for an additional 3 months (“long-term follow-up”). Health Chats used PRO-CTCAE questions customized for BC patients. Clinicians were notified if any “red flag” symptoms were reported (PRO-CTCAE ≥ 3 or pain score ≥8). At the end of each chat, patients received customized educational material specific to symptoms reported. Results 20 breast cancer patients were enrolled, and 16 patients completed at least one chat. These 16 patients completed a median of 9 chats, out of a maximum of 10-12 chats. 11 patients continued to chat during the immediate post-treatment phase, and 10 patients continued to chat during long-term follow-up. Patient engagement with Chats is high, with 6 patients providing written feedback about the details of their symptoms, and 3 patients using unscheduled chats to contact the care team. The average System Usability Scale score (n = 9) was 82.77. A total of 811 pain or PRO-CTCAE scores were collected. There were 2 counts of pain scores ≥ 8, and no reports of grade 3+ skin toxicity or breast swelling. 5 out of 11 patients reported that their pain continued to worsen after finishing their last RT treatment, and 10 out of 11 patients reported that their breast pain, swelling, or skin toxicities peaked 2 weeks after RT. Patients reported severe and prolonged fatigue or insomnia: there were 4 counts of grade 3 fatigue and 3 counts of grade 4 fatigue, and 2 counts of grade 3 insomnia and 1 count of grade 4 insomnia. 4 out of 10 patients reported continued fatigue or insomnia during long-term follow-up. Of the 5 patients who screened positive for depression or anxiety using PHQ2 or GAD2 questionnaire, 3 patients continued to report persistent symptoms during long-term follow-up. Conclusion To our knowledge, this is the first study using chatbots to collect PROs for BC patients receiving RT. Our results show that BC patients are highly engaged and satisfied with Health Chats. As expected, patients report that pain and skin toxicities peak 2 weeks after RT. We also identify unexpectedly high rates of severe fatigue, insomnia, and persistent anxiety and depression. These toxicities are difficult to observe by clinicians and may represent unmet patient needs that should be addressed by future interventions.

To report the early experience using an automated chatbot (Chats)for patient-reported outcomes (PRO) and symptom self-managementinhead and neck cancer (HNC) patients undergoing radiation treatment (RT).Patients aged ≥ 18 yearsdiagnosed with HNC who were scheduled to begin RT were given the option to use Chats from June 2018 to June 2019. Enrolled patients received chat notifications two days before weekly on-treatment visitsand every 1-4 weeks after RT for an additional 4 months. After the first in-person follow-up visit, participants completed an electronic usability and satisfaction questionnaire.Of 95 patients who agreed to participate, 84 were eligible for analysis.Participantswere significantly younger than patients who declined participation (mean age 61.3 vs 68.3 years;p-value 0.001). Patient engagement with Chats was highest at 67% during the first month and declined over time (p-value = 0.004). Concordance between PRO and clinician-reported outcomes (CRO) was fair, ranging from 0.10 to 0.43 (Cohen κ statistics). The most commonly under-reported symptoms were salivary duct inflammation (53%), xerostomia (41%), and mucositis (37%). 89% (39 of 44) of patients who completed surveys found Chats easy to use, and 61% reported that Chats helped with symptom self-management and reduced the need to call the care team.These early results suggest that an interactive chatbot is feasible and provides support for HNC patients during and after RT. Chats identified discordance between PRO and CRO. Further study is required to measure benefits of Chats in a larger population.

Purpose/Objective(s) Unchecked growth of brainstem metastases (BSM) can lead to acute morbidity and death. Stereotactic radiosurgery (SRS) remains the only local therapy for BSM, but the safety and efficacy of this approach are not fully understood, partly because BSM patients are excluded from many clinical trials. The aim of this study was to perform a systematic review and comparative meta-analysis of studies of SRS for BSM in the context of prospective trials of SRS or molecular/targeted therapy for non-brainstem brain metastases (BM). Materials/Methods A comprehensive search of the PubMed and Embase databases was performed on 12/6/19 following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines to identify relevant studies of SRS for BSM, and prospective trials of SRS or molecular/targeted therapy for BM. Outcomes included 1-year local control (LC), objective response rate (ORR, defined as partial or complete response), 1-year overall survival (OS), neurologic death rate, and CTCAE 4.0 grade 3-5 adverse events. Pooled binomial proportions were estimated using a random effects model. Study heterogeneity was assessed using I2 and τ using the maximum likelihood method and the Wald test. Results A total of 32 retrospective studies with a study level median follow up of 8.5 months (interquartile range [IQR] 5.7-11.0) were identified comprising 1446 patients undergoing SRS for 1590 B.M.. Median BSM volume was 0.40cm3 (study level IQR 0.20-1.05cm3), and SRS treatments were delivered using fixed-frame radiosurgery (73.8%, median dose 16 Gy, range 6-30 Gy, median isodose 50%), linear accelerator (17.2%, median dose 13.7 Gy, range 11.1-39.0 Gy in 1-13 fractions, median isodose 85%), or robotic-arm radiosurgery (9%, median 17.5 Gy, range 16-24 in 1-5 fractions, median isodose 80%). Pooled 1-year LC was 86% (95% CI 83-88%, I2 = 38%), 1-year OS was 33% (30-37%, I2 = 35%), and the rate of grade 3-5 toxicity was 2.4% (1.5-3.7%, I2 = 33%). On univariate meta-regression, melanoma histology (coefficient 4.26, QM = 4.15, P = 0.042) and prior or concurrent WBRT (coefficient 1.62, QM = 3.98, P = 0.046) were associated with higher grade 3-5 toxicity from SRS for BSM. Deaths from BSM progression after SRS were rare (2.7%), and the neurologic death rate in BSM patients (24%, 19-31%, I2 = 62%) was not statistically different from the neurologic death rate in BM patients who were treated on prospective SRS trials (21%, 13-32%, I2 = 90%, N = 6 trials, Q = 0.36, P = 0.55). The pooled rate of ORR of 59% (47-71%, I2 = 88%) for SRS of BSM compared favorably to the wide range of intracranial ORR reported for molecular therapies (17-56%). Conclusion SRS for BSM is safe and effective, and the potential for acute morbidity or death from growth of untreated BSM is significant. The data here suggest SRS for BSM should be considered upon or prior to clinical trial enrollment of molecular/targeted therapy for BM. Author Disclosure W.C. Chen: None. U. Baal: None. J.D. Baal: None. J. Pai: None. H. Vasudevan: Research Grant; Children's Tumor Foundation. Patent/License Fees/Copyright; Genentech, Eli Lilly. L. Boreta: None. S.E. Braunstein: Advisory Board; Radiation Oncology Questions, LLC.D. Raleigh: None.

Purpose To evaluate the efficacy and safety of percutaneous ablation of adrenal metastases through a meta-analysis of various image-guided percutaneous ablation techniques. Materials and Methods A comprehensive literature search of PubMed and Embase databases was performed for studies evaluating the efficacy and/or safety of image-guided percutaneous ablation of adrenal metastases. A total of 37 studies published between 2009 and 2020 were analyzed, comprising a sample size of 959 patients. Proportion estimates of overall survival, local control, and toxicity were analyzed in a pooled meta-analysis. The pooled prevalence of adverse events after ablation was calculated based on common terminology criteria for adverse events (CTCAE) grading. Results Of the 959 included patients, 320 (33.3%) underwent radiofrequency ablation, 72 (7.5%) microwave ablation, 95 (9.9%) cryoablation, and 46 (4.8%) ethanol injections for treatment of adrenal metastases. The remaining 426 (44.4%) patients were from studies involving a mixture of the 4 listed percutaneous ablation techniques. The pooled 1-year local control rate was 80% (95% confidence interval [CI], 76%–83%). The pooled 1-year overall survival rate was 77% (95% CI, 70%–83%). The overall rate of severe adverse events after ablation (CTCAE grade 3 or higher) was 16.1%. The overall rate of low-grade adverse events after ablation (CTCAE grade 2 or lower) was 32.6%. Approximately 21.9% (n = 203) of patients experienced intraprocedural hypertensive crises, the majority of which were reversed with antihypertensive medications. Conclusions This study demonstrates that image-guided percutaneous ablation can be effective in achieving acceptable short- to mid-term local tumor control and overall survival with a moderate safety profile.

Background Cortical networks undergo large-scale switching between states of increased or decreased activity in normal sleep and cognition as well as in pathological conditions such as epilepsy. We previously found that focal hippocampal seizures in rats induce increased neuronal firing and cerebral blood flow in subcortical structures including the lateral septal area, along with frontal cortical slow oscillations resembling slow wave sleep. In addition, stimulation of the lateral septum in the absence of a seizure resulted in cortical deactivation with slow oscillations. Hypothesis We hypothesized that lateral septal activation might cause neocortical deactivation indirectly, possibly through impaired subcortical arousal. But how does subcortical stimulation cause slow wave activity in frontal cortex? How do arousal neurotransmitter levels (e.g. acetylcholine) change in cortex during the excitation of inhibitory projection nuclei? Methods and results In the current study, we used simultaneous electrophysiology and enzyme-based amperometry in a rat model, and found a decrease in choline, along with slow wave activity in orbital frontal cortex during lateral septal stimulation in the absence of seizures. In contrast, the choline signal and local field potential in frontal cortex had no significant changes when stimulating the hippocampus, but showed increased choline and decreased slow wave activity with an arousal stimulus produced by toe pinch. Conclusions These findings indicate that the activation of subcortical inhibitory structures (such as lateral septum) can depress subcortical cholinergic arousal. This mechanism may play an important role in large-scale transitions of cortical activity in focal seizures, as well as in normal cortical function.

Driving is an important part of everyday life for most adults, and restrictions on driving can place a significant burden on individuals diagnosed with epilepsy. Although sensorimotor deficits during seizures may impair driving, decreased level of consciousness often has a more global effect on patients' ability to respond appropriately to the environment. Better understanding of the mechanisms underlying alteration of consciousness in epilepsy is important for decision-making by people with epilepsy, their physicians, and regulators in regard to the question of fitness to drive. Retrospective cohort and cross-sectional studies based on surveys or crash records can provide valuable information about driving in epilepsy. However, prospective objective testing of ictal driving ability during different types of seizures is needed to more fully understand the role of impaired consciousness and other deficits in disrupting driving. Driving simulators adapted for use in the epilepsy video-EEG monitoring unit may be well suited to provide both ictal and interictal data in patients with epilepsy. Objective information about impaired driving in specific types of epilepsy and seizures can provide better informed recommendations regarding fitness to drive, potentially improving the quality of life of people living with epilepsy.

Intracranial EEG (icEEG) provides a critical road map for epilepsy surgery but it has become increasingly difficult to interpret as technology has allowed the number of icEEG channels to grow. Borrowing methods from neuroimaging, we aimed to simplify data analysis and increase consistency between reviewers by using 3D surface projections of intracranial EEG poweR (3D-SPIER). We analyzed 139 seizures from 48 intractable epilepsy patients (28 temporal and 20 extratemporal) who had icEEG recordings, epilepsy surgery, and at least one year of post-surgical follow-up. We coregistered and plotted icEEG β frequency band signal power over time onto MRI-based surface renderings for each patient, to create color 3D-SPIER movies. Two independent reviewers interpreted the icEEG data using visual analysis vs. 3D-SPIER, blinded to any clinical information. Overall agreement rates between 3D-SPIER and icEEG visual analysis or surgery were about 90% for side of seizure onset, 80% for lobe, and just under 80% for sublobar localization. These agreement rates were improved when flexible thresholds or frequency ranges were allowed for 3D-SPIER, especially for sublobar localization. Interestingly, agreement was better for patients with good surgical outcome than for patients with poor outcome. Localization using 3D-SPIER was measurably faster and considered qualitatively easier to interpret than visual analysis. These findings suggest that 3D-SPIER could be an improved diagnostic method for presurgical seizure localization in patients with intractable epilepsy and may also be useful for mapping normal brain function.

Purpose We report a case of lung carcinoma developing in the location of a migrated prostate brachytherapy seed. Methods and Materials A 57-year-old male nonsmoker was originally diagnosed with prostate adenocarcinoma Group IIB in October 1999. Treatment was completed at an outside local hospital and consisted of hormone suppression, pelvic external beam radiation, and transperineal interstitial permanent prostate brachytherapy with loose iodine-125 seeds. Results The treatment was unremarkable for any complications, and immediate postimplant evaluation did not reveal any loose seeds. The patient remained clinically without evidence of disease and was asymptomatic until an isolated episode of hematuria in December 2009. Radiographic evaluation noted an incidental right lower lobe lung mass with a 4-mm hyperdensity slightly off-center. Biopsy confirmed Stage IB limited-stage small-cell lung cancer, and he underwent thoracic radiation with concurrent systemic chemotherapy. The mass remained mildly avid on a positron emission tomographic scan after treatment, and he underwent surgical evaluation with final pathology demonstrating no residual tumor but a metal rod-like implant consistent with a migrated radioactive brachytherapy seed. Conclusions To our knowledge, this is the first case of a long-term adverse sequela seen in the location of a migrated brachytherapy seed. Although reported incidence of pulmonary seed emboli remains low with little measurable consequence on pulmonary function, we must appreciate that a theoretical risk for secondary malignancy remains not only locally within the periprostatic region but also at any site of seed migration.

Background Pathologic diagnosis and therapeutic interventions on the small bowel have been difficult and challenging for gastroenterologists. In the last few years, significant advances have been made in this direction. New diagnostic and therapeutic modalities for visualizing the small bowel have been introduced. Furthermore, increased indications for small-bowel imaging and therapeutics have been recognized. However, the currently available methods have limitations, and development of newer, rapid, minimally invasive, safe, and readily available techniques is needed. Objective Our purpose was to evaluate the safety and efficacy of a novel method of spiral enteroscopy using a specialized overtube (Endo-Ease Discovery SB) with a pediatric colonoscope (PCF-140L). Design Case series. Setting Two international tertiary referral centers. Patients Twenty-seven adult patients with obscure GI bleeding were enrolled in this study. Intervention Spiral enteroscopy with the Endo-Ease Discovery SB overtube and a pediatric colonoscope. Main Outcome Measurements Depth of insertion, time of procedure, and complications. Results Average depth of insertion was 176 cm (range 80-340 cm) from ligament of Treitz, and average time of procedure was 36.5 minutes (range 90-65 minutes). Eleven patients had minor complications, which included minimal mucosal trauma and sore throat. Limitations Small number of patients with a case series study design. Conclusions Preliminary data suggest that use of Endo-Ease Discovery SB overtube for enteroscopy is a safe and effective technique for visualization of the small bowel.