Faculty Bibliography

Feasibility, safety, and utility of brain MRI for patients with non-MRI-conditioned cardiac implantable electrical devices (CIEDs) remains controversial. While a growing number of studies have shown safe employment in select patients under strict protocols, there is an increasing clinical need for further off-label investigations. To assess the feasibility and utility of brain MRI in neurological and neurosurgical patients with non-MRI-conditioned CIEDs using off-label protocol. We retrospectively evaluated 126 patients with non-MRI-conditioned CIEDs referred to our hospital between 2014 to 2018 for MRI under an IRB-approved protocol. A total of 126 off-label brain MRI scans were performed. The mean age was 67.5 ± 13.0. Seventy percent of scans were performed on female patients. Indications for MRI are neurosurgical (45.2%), neurological (51.6%), and others (3.2%). MRI utilization for tumor cases was highest for tumor cases (68.3%), but employment was valuable for vascular (12.7%), deep brain stimulators (3.2%), and other cases (15.9%). In the tumor category, (37.2%) of the scans were performed for initial diagnosis and pre-surgical planning, (47.7%) for post-intervention evaluation/surveillance, (15.1%) for stereotactic radiosurgery treatment (CyberKnife). No clinical complications were encountered. No functional device complications of the CIED were identified during and after the MRI in 96.9% of the studies. A 49.6% of the off-label brain MRI scans performed led to a clinically significant decision and/or intervention for the patients. A 42.9% of obtained MRI studies did not change the plan of care. A 7.9% of post-scan decision-making data was not available. We demonstrate that off-label brain MRI scans performed on select patients under a strict protocol is feasible, safe, and relevant. Almost 50% of scans provided critical information resulting in clinical intervention of the patients.

Background and purpose Recently published HyTEC report summarized lung toxicity data and proposed guidelines of mean lung dose (MLD) <8 Gy and normal lung receiving at least 20 Gy, V_20Gy<10-15% to avoid lung toxicity. Support for preferred use of a particular dosimetric parameter has been limited. We performed a detailed dose-volume analysis of data on radiation pneumonitis (RP) following lung stereotactic body radiation therapy (SBRT) to search for parameters showing the strongest correlation with RP. Materials and methods Two patient cohorts (primary and metastatic lung tumor patients) from previously reported studies were analyzed. Total number of patients was 96, and incidence of grade ≥2 RP was 13.5% (13/96). Fitting to the logistic function was performed to investigate correlation between incidence of RP and reported dosimetric and volumetric parameters. Another independent cohort was used to explore correlation between dosimetric parameters. Results Among normal lung parameters (MLD and reported V_x), only MLD consistently showed significant correlation with incidence of RP. Gross tumor volume (GTV), internal target volume, planning target volume (PTV), and minimum dose covering 95% of GTV or PTV did not show statistical significance. A significant correlation between reported V_x and MLD was observed in all cohorts. Conclusions In considering tumor- and target-specific (e.g., GTV, PTV) and normal lung-specific (e.g., MLD, V_x) metrics, MLD was the only parameter that consistently correlated with incidence of RP across both cohorts. Because SBRT planning constraints allow small normal lung volumes to receive high doses, utility of MLD is not obvious. The parallel structure of lung is one possible explanation, but correlation between dosimetric parameters obscures elucidation of the preferred or mechanistically based parameter to guide radiotherapy planning.

PURPOSE/OBJECTIVE:To assess the safety and efficacy of CyberKnife® radiotherapy (CKRT) for the treatment of olfactory groove meningiomas (OGMs). METHODS:A retrospective review was performed of 13 patients with OGM treated with CKRT from September 2005 to May 2018 at our institution. Nine patients were treated primarily with CKRT, 3 for residual disease following resection, and 1 for disease recurrence. RESULTS:. The median prescribed dose was 14.8 Gy for SRS, 27.3 Gy for HSRT, and 50.2 Gy for FSRT. The median maximal dose delivered was 32.27 Gy. Median post treatment follow-up was 48 months. Twelve of 13 patients yielded a 100% regional control rate with a median tumor volume reduction of 31.7%. Six of the 12 patients had reduced tumor volumes while the other 6 had no changes. The thirteenth patient had significant radiation-induced edema requiring surgical decompression. Twelve patients were alive and neurologically stable at the time of the review. One patient died from pneumonia unrelated to his CKRT treatment. CONCLUSIONS:CKRT appears to be safe and effective for the treatment of OGMs.

The National Cancer Institute's Radiation Research Program, in collaboration with the Radiosurgery Society, hosted a workshop called Understanding High-Dose, Ultra-High Dose Rate and Spatially Fractionated Radiotherapy on August 20 and 21, 2018 to bring together experts in experimental and clinical experience in these and related fields. Critically, the overall aims were to understand the biological underpinning of these emerging techniques and the technical/physical parameters that must be further defined to drive clinical practice through innovative biologically based clinical trials.

PURPOSE:Patients with larger (T1b, >4 cm) renal cell carcinoma (RCC) not suitable for surgery have few treatment options because thermal ablation is less effective in this setting. We hypothesize that SABR represents an effective, safe, and nephron-sparing alternative for large RCC. METHODS AND MATERIALS:Individual patient data from 9 institutions in Germany, Australia, USA, Canada, and Japan were pooled. Patients with T1a tumors, M1 disease, and/or upper tract urothelial carcinoma were excluded. Demographics, treatment, oncologic, and renal function outcomes were assessed using descriptive statistics. Kaplan-Meier estimates and univariable and multivariable Cox proportional hazards regression were generated for oncologic outcomes. RESULTS:Ninety-five patients were included. Median follow-up was 2.7 years. Median age was 76 years, median tumor diameter was 4.9 cm, and 81.1% had Eastern Cooperative Oncology Group performance status of 0 to 1 (or Karnofsky performance status ≥70%). In patients for whom operability details were reported, 77.6% were defined as inoperable as determined by the referring urologist. Mean baseline estimated glomerular filtration rate (eGFR) was 57.2 mL/min (mild-to-moderate dysfunction), with 30% of the cohort having moderate-to-severe dysfunction (eGFR <45mL/min). After SABR, eGFR decreased by 7.9 mL/min. Three patients (3.2%) required dialysis. Thirty-eight patients (40%) had a grade 1 to 2 toxicity. No grade 3 to 5 toxicities were reported. Cancer-specific survival, overall survival, and progression-free survival were 96.1%, 83.7%, and 81.0% at 2 years and 91.4%, 69.2%, 64.9% at 4 years, respectively. Local, distant, and any failure at 4 years were 2.9%, 11.1%, and 12.1% (cumulative incidence function with death as competing event). On multivariable analysis, increasing tumor size was associated with inferior cancer-specific survival (hazard ratio per 1 cm increase: 1.30; P < .001). CONCLUSIONS:SABR for larger RCC in this older, largely medically inoperable cohort, demonstrated efficacy and tolerability and had modest impact on renal function. SABR appears to be a viable treatment option in this patient population.

PURPOSE/OBJECTIVE:Therapeutic intervention at glioblastoma (GBM) progression, as defined by current assessment criteria, is arguably too late as second-line therapies fail to extend survival. Still, most GBM trials target recurrent disease. We propose integration of a novel imaging biomarker to more confidently and promptly define progression and propose a critical timepoint for earlier intervention to extend therapeutic exposure. METHODS:A retrospective review of 609 GBM patients between 2006 and 2019 yielded 135 meeting resection, clinical, and imaging inclusion criteria. We qualitatively and quantitatively analyzed 2000+ sequential brain MRIs (initial diagnosis to first progression) for development of T2 FLAIR signal intensity (SI) within the resection cavity (RC) compared to the ventricles (V) for quantitative inter-image normalization. PFS and OS were evaluated using Kaplan-Meier curves stratified by SI. Specificity and sensitivity were determined using a 2 × 2 table and pathology confirmation at progression. Multivariate analysis evaluated SI effect on the hazard rate for death after adjusting for established prognostic covariates. Recursive partitioning determined successive quantifiers and cutoffs associated with outcomes. Neurological deficits correlated with SI. RESULTS:Seventy-five percent of patients developed SI on average 3.4 months before RANO-assessed progression with 84% sensitivity. SI-positivity portended neurological decline and significantly poorer outcomes for PFS (median, 10 vs. 15 months) and OS (median, 20 vs. 29 months) compared to SI-negative. RC/V ratio ≥ 4 was the most significant prognostic indicator of death. CONCLUSION/CONCLUSIONS:Implications of these data are far-reaching, potentially shifting paradigms for glioma treatment response assessment, altering timepoints for salvage therapeutic intervention, and reshaping glioma clinical trial design.

OBJECTIVE:. compression or gating). METHODS:A PubMed search was performed for identifying literature regarding dose, volume, fractionation, and toxicity (grade 3 or higher) for SBRT treatments for tumors which move with respiration. From the identified papers logistic or probit dose-response models were fitted to the data using the maximum-likelihood technique and confidence intervals were based on the profile-likelihood method in the dose-volume histogram (DVH) Evaluator. RESULTS:Pooled logistic and probit models for grade 3 or higher toxicity for aorta, chest wall, duodenum, and small bowel suggest a significant difference when live motion tracking was used for targeting tumors with move with respiration which was on the average 10 times lower, in the high dose range. CONCLUSION/CONCLUSIONS:Live respiratory motion management appears to have a better toxicity outcome when treating targets which move with respiration with very steep peripheral dose gradients. This analysis is however limited by sparsity of rigorous data due to poor reporting in the literature.

CONTEXT/BACKGROUND:Stereotactic ablative radiotherapy (SABR) is an emerging treatment option for primary renal cell carcinoma (RCC). OBJECTIVE:To systematically review the literature on SABR for primary RCC and perform a meta-analysis evaluating local control (LC), toxicity, and renal function. EVIDENCE ACQUISITION/METHODS:statistic and Cochran's Q test were used to assess heterogeneity. EVIDENCE SYNTHESIS/RESULTS:=2%), respectively, and heterogeneity was minimal. Six patients with pre-existing renal dysfunction (2.9%) required dialysis. CONCLUSIONS:Renal SABR is locally effective and associated with low toxicity rates for primary RCC, despite treatment of larger tumors in older, mostly medically inoperable patients. PATIENT SUMMARY/RESULTS:Stereotactic ablative radiotherapy is a high-precision, noninvasive radiation treatment requiring few outpatient visits, and represents a safe and effective management option for primary renal cell carcinoma.

PURPOSE:Stereotactic ablative radiotherapy is an emerging treatment for renal cell carcinoma. Our study objective was to evaluate this therapy in patients with a solitary kidney, focusing on oncologic and renal function outcomes. MATERIALS AND METHODS:We pooled individual patient data from 9 IROCK (International Radiosurgery Oncology Consortium for Kidney) institutions in Germany, Australia, the United States of America, Canada and Japan. Median followup was 2.6 years. Baseline characteristics and outcomes were compared between the solitary and bilateral kidney cohorts. Predictors of renal function after stereotactic ablative radiotherapy were assessed by logistic regression modeling. RESULTS:A total of 81 patients with a solitary kidney underwent stereotactic ablative radiotherapy. Mean age was 67.3 years and 97.5% of patients had good performance status, including ECOG (Eastern Cooperative Oncology Group) 0-1 or KPS (Karnofsky Performance Status) 70% or greater. Median tumor diameter was 3.7 cm (IQR 2.5-4.3) and 37% of tumors were 4 cm or greater. The 138 patients in the bilateral cohort harbored larger tumors and were older (p <0.001) with a lower baseline estimated glomerular filtration rate (p = 0.024). After stereotactic ablative radiotherapy in the solitary kidney cohort the mean ± SD estimated glomerular filtration rate decrease was -5.8 ± 10.8 ml per minute (-9%). No patient with a solitary kidney required dialysis. After stereotactic ablative radiotherapy a tumor size of 4 cm or greater was associated with an estimated glomerular filtration rate decrease of 15 ml per minute or greater (OR 4.2, p = 0.029). At 2 years the rates of local control, and progression-free, cancer specific and overall survival in the solitary cohort were 98.0%, 77.5%, 98.2% and 81.5%, respectively. There was no significant difference in renal function or oncologic outcomes between the cohorts (p >0.05). CONCLUSIONS:In this analysis of the IROCK database stereotactic ablative radiotherapy in patients with a solitary kidney had an acceptable impact on renal function and achieved excellent oncologic outcomes, similar to those in patients with bilateral kidneys. Thus, stereotactic ablative radiotherapy represents a viable treatment option in patients with renal cell carcinoma in a solitary kidney.

INTRODUCTION/BACKGROUND:The aim of this paper was to systematically review the evidence linking Propionibacterium acnes (P. acnes) with the develop Tanycytic ependymoma (tcE) is a rare variant of ependymoma and management guidelines for patients with this disease are not established. EVIDENCE ACQUISITION/METHODS:We performed a systematic search on Pubmed complimented by hand-searching citation lists to identify patients with pathologically confirmed tcE. Signs and symptoms, radiological and specific pathological findings as well as reported treatment modalities and outcomes were recorded and analyzed. EVIDENCE SYNTHESIS/RESULTS:Fifty-one studies involving a total of 77 patients were identified and included in this review. Most cases of tcEs occurred in the spinal cord (50.6%), followed by lesions located in upper intracranial sites (36.4%) and only a few at the cervicomedullary junction (3.9%). Female to male ratio was calculated as about 1:1.5, with a mean age at diagnosis of approximately 36.1±18 years. Complete resection of the tumor without further additional therapy was the treatment of choice in most cases (63.6%), radiotherapy was considered in 10 cases (13.0%). In 18 reported cases of tcE (23.4%), the treatment was not documented. Defined follow-up periods for patients with tcE were only documented in 44 cases (57.1%), the mean follow-up was 22.3 months. 36 cases (46.8%) had no recurrence of tumor after treatment (26 months mean follow-up). CONCLUSIONS:This comprehensive review on tcEs supports surgery as the initial treatment modality of choice. Radiotherapy can be considered when total gross resection cannot be achieved and allows for prolonged progression-free survival. Given the benign nature of this subtype of ependymoma, aggressive treatment such as chemotherapy is usually not indicated.