Head and Neck Paragangliomas: Overview of Institutional Experience.

Head and neck paragangliomas (HNPGLs) are rare and have high rates of genetic mutations. We conducted a retrospective review of 187 patients with 296 PGLs diagnosed between 1974 and 2023. The mean age of diagnosis was 48.8 years (range 10 to 82) with 69.0% female and 26.5% patients with multiple PGLs. Among 119 patients undergoing genetic testing, 70 (58.8%) patients had mutations, with SDHB (30) and SDHD (26) being the most common. The rates of metastasis and recurrence were higher among patients with SDHB mutations or SDHD mutations associated with multiple PGLs. Metabolic evaluation showed elevated plasma dopamine levels were the most common derangements in HNPGL. MRI and CT were the most common anatomic imaging modalities and DOTATATE was the most common functional scan used in this cohort. Most patients (81.5%) received surgery as the primary definitive treatment, while 22.5% patients received radiation treatment, mostly as an adjuvant therapy or for surgically challenging or inoperable cases. Systemic treatment was rarely used in our cohort. Our single-center experience highlights the need for referral for genetic testing and metabolic evaluation and for a team-based approach to improve the clinical outcomes of patients with HNPGLs.

ACR benchmark testing of a novel high-speed ring-gantry linac kV-CBCT system.

A new generation cone-beam computed tomography (CBCT) system with new hardware design and advanced image reconstruction algorithms is available for radiation treatment simulation or adaptive radiotherapy (HyperSight CBCT imaging solution, Varian Medical Systems-a Siemens Healthineers company). This study assesses the CBCT image quality metrics using the criteria routinely used for diagnostic CT scanner accreditation as a first step towards the future use of HyperSight CBCT images for treatment planning and target/organ delineations. Image performance was evaluated using American College of Radiology (ACR) Program accreditation phantom tests for diagnostic computed tomography systems (CTs) and compared HyperSight images with a standard treatment planning diagnostic CT scanner (Siemens SOMATOM Edge) and with existing CBCT systems (Varian TrueBeam version 2.7 and Varian Halcyon version 2.0).  Image quality performance for all Varian HyperSight CBCT vendor-provided imaging protocols were assessed using ACR head and body ring CT phantoms, then compared to existing imaging modalities. Image quality analysis metrics included contrast-to-noise (CNR), spatial resolution, Hounsfield number (HU) accuracy, image scaling, and uniformity. All image quality assessments were made following the recommendations and passing criteria provided by the ACR. The Varian HyperSight CBCT imaging system demonstrated excellent image quality, with the majority of vendor-provided imaging protocols capable of passing all ACR CT accreditation standards. Nearly all (8/11) vendor-provided protocols passed ACR criteria using the ACR head phantom, with the Abdomen Large, Pelvis Large, and H&N vendor-provided protocols produced HU uniformity values slightly exceeding passing criteria but remained within the allowable minor deviation levels (5-7 HU maximum differences). Compared to other existing CT and CBCT imaging modalities, both HyperSight Head and Pelvis imaging protocols matched the performance of the SOMATOM CT scanner, and both the HyperSight and SOMATOM CT substantially surpassed the performance of the Halcyon 2.0 and TrueBeam version 2.7 systems. Varian HyperSight CBCT imaging system could pass almost all tests for all vendor-provided protocols using ACR accreditation criteria, with image quality similar to those produced by diagnostic CT scanners and significantly better than existing linac-based CBCT imaging systems.

A Prospective Phase I/II Clinical Trial of High-Dose Proton Therapy for Chordomas and Chondrosarcomas.

Purpose: The purpose of this study was to evaluate the feasibility and safety of dose-escalated proton beam therapy for treating chordomas and chondrosarcomas of the skull base and spine. Methods: A prospective cohort of 54 patients (42 with chordomas and 12 with chondrosarcomas) was enrolled between 2010 and 2018. The primary endpoints were feasibility and <20% rate of acute grade ≥3 toxicity, and secondary endpoints included cancer-specific outcomes and toxicities. Patients were followed with magnetic resonance imaging or computed tomography at 3-month intervals. Proton beam therapy was delivered with doses up to 79.2 Gy using protons only, combination protons/intensity modulated radiation therapy (IMRT), or IMRT only. Results: Feasibility endpoints were met, with only 2 out of 54 patient radiation therapy plans failing to meet dosimetric constraints with protons, and 4 out of 54 experiencing a delay or treatment break >5 days, none for toxicities related to treatment. There were no grade 4 acute toxicities and 1 grade 3 acute toxicity (sensory neuropathy). The only 2 grade 3 late toxicities recorded, osteoradionecrosis and intranasal carotid blowout (mild and not emergently treated), occurred in a single patient. We report overall survival as 83% at 5 years, with local failure-free survival and progression-free survival rates of 72% and 68%, respectively. Five patients developed distant disease, and among the 9/54 patients who died, 4 deaths were not attributed to treatment or recurrence. Conclusions: Our findings suggest that high-dose proton therapy alone or in combination with IMRT is a safe and effective treatment option for chordomas and chondrosarcomas of the skull base and spine.

Repeated peripheral infusions of anti-EGFRvIII CAR T cells in combination with pembrolizumab show no efficacy in glioblastoma: a phase 1 trial.

We previously showed that chimeric antigen receptor (CAR) T-cell therapy targeting epidermal growth factor receptor variant III (EGFRvIII) produces upregulation of programmed death-ligand 1 (PD-L1) in the tumor microenvironment (TME). Here we conducted a phase 1 trial (NCT03726515) of CAR T-EGFRvIII cells administered concomitantly with the anti-PD1 (aPD1) monoclonal antibody pembrolizumab in patients with newly diagnosed, EGFRvIII+ glioblastoma (GBM) (n = 7). The primary outcome was safety, and no dose-limiting toxicity was observed. Secondary outcomes included median progression-free survival (5.2 months; 90% confidence interval (CI), 2.9-6.0 months) and median overall survival (11.8 months; 90% CI, 9.2-14.2 months). In exploratory analyses, comparison of the TME in tumors harvested before versus after CAR + aPD1 administration demonstrated substantial evolution of the infiltrating myeloid and T cells, with more exhausted, regulatory, and interferon (IFN)-stimulated T cells at relapse. Our study suggests that the combination of CAR T cells and PD-1 inhibition in GBM is safe and biologically active but, given the lack of efficacy, also indicates a need to consider alternative strategies.

International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors.

BACKGROUND: Sinonasal neoplasms, whether benign and malignant, pose a significant challenge to clinicians and represent a model area for multidisciplinary collaboration in order to optimize patient care. The International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors (ICSNT) aims to summarize the best available evidence and presents 48 thematic and histopathology-based topics spanning the field. METHODS: In accordance with prior International Consensus Statement on Allergy and Rhinology documents, ICSNT assigned each topic as an Evidence-Based Review with Recommendations, Evidence-Based Review, and Literature Review based on the level of evidence. An international group of multidisciplinary author teams were assembled for the topic reviews using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses format, and completed sections underwent a thorough and iterative consensus-building process. The final document underwent rigorous synthesis and review prior to publication. RESULTS: The ICSNT document consists of four major sections: general principles, benign neoplasms and lesions, malignant neoplasms, and quality of life and surveillance. It covers 48 conceptual and/or histopathology-based topics relevant to sinonasal neoplasms and masses. Topics with a high level of evidence provided specific recommendations, while other areas summarized the current state of evidence. A final section highlights research opportunities and future directions, contributing to advancing knowledge and community intervention. CONCLUSION: As an embodiment of the multidisciplinary and collaborative model of care in sinonasal neoplasms and masses, ICSNT was designed as a comprehensive, international, and multidisciplinary collaborative endeavor. Its primary objective is to summarize the existing evidence in the field of sinonasal neoplasms and masses.

One-year outcomes after stereotactic body radiotherapy for refractory ventricular tachycardia.

BACKGROUND: Cardiac stereotactic body radiotherapy (SBRT) has emerged as a promising noninvasive treatment for refractory ventricular tachycardia (VT). OBJECTIVE: The purpose of this study was to describe the safety and effectiveness of SBRT for VT in refractory to extensive ablation. METHODS: After maximal medical and ablation therapy, patients were enrolled in a prospective registry. Available electrophysiological and imaging data were integrated to generate a plan target volume. All SBRTs were planned with a single 25 Gy fraction using respiratory motion mitigation strategies. Clinical outcomes at 6 weeks, 6 months, and 12 months were analyzed and compared with the 6 months prior to treatment. VT burden (implantable cardioverter-defibrillator [ICD] shocks and antitachycardia pacing sequences) as well as clinical and safety outcomes were the main outcomes. RESULTS: Fifteen patients were enrolled and underwent planning. Fourteen (93%) underwent treatment, with 12 (80%) surviving to the end of the 6-week period and 10 (67%) surviving to 12 months. From 6 week to 12 months, there was recurrence of VT, which resulted in either appropriate antitachycardia pacing or ICD shocks in 33% (4 of 12). There were significant reductions in treated VT at 6 weeks to 6 months (98%) and at 12 months (99%) compared to the 6 months before treatment. There was a nonsignificant trend toward lower amiodarone dose at 12 months. Four deaths occurred after treatment, with no changes in ventricular function. CONCLUSION: For a select group of high-risk patients with VT refractory to standard therapy, SBRT is associated with a reduction in VT and appropriate ICD therapies over 1 year.

Hypofractionation in Glioblastoma: An Overview of Palliative, Definitive, and Exploratory Uses.

Glioblastoma (GBM) is the most common primary brain malignancy in adults, and its incidence is increasing worldwide. Its prognosis remains limited despite recent imaging and therapeutic advances. The current standard of care is maximal safe resection followed by conventionally fractionated radiotherapy with concurrent and adjuvant temozolomide (TMZ), with or without tumor-treating fields (TTF). However, hypofractionated radiotherapy (HFRT) has also been utilized for a variety of reasons. It is an established treatment option in the palliative setting, where shortened treatment duration can positively impact the overall quality of life for older patients or those with additional health or socioeconomic considerations. HFRT, and in particular stereotactic radiosurgery (SRS), has also been explored in both the pre- and post-operative setting for newly diagnosed and recurrent diseases. In this review, we summarize the ways in which HFRT has been utilized in the GBM patient population and its evolving role in the experimental space. We also provide commentary on scenarios in which HFRT may be indicated, as well as guidance on dose and fractionation regimens informed by our institutional experience.

The ASNR-MICCAI Brain Tumor Segmentation (BraTS) Challenge 2023: Intracranial Meningioma.

Meningiomas are the most common primary intracranial tumor in adults and can be associated with significant morbidity and mortality. Radiologists, neurosurgeons, neuro-oncologists, and radiation oncologists rely on multiparametric MRI (mpMRI) for diagnosis, treatment planning, and longitudinal treatment monitoring; yet automated, objective, and quantitative tools for non-invasive assessment of meningiomas on mpMRI are lacking. The BraTS meningioma 2023 challenge will provide a community standard and benchmark for state-of-the-art automated intracranial meningioma segmentation models based on the largest expert annotated multilabel meningioma mpMRI dataset to date. Challenge competitors will develop automated segmentation models to predict three distinct meningioma sub-regions on MRI including enhancing tumor, non-enhancing tumor core, and surrounding nonenhancing T2/FLAIR hyperintensity. Models will be evaluated on separate validation and held-out test datasets using standardized metrics utilized across the BraTS 2023 series of challenges including the Dice similarity coefficient and Hausdorff distance. The models developed during the course of this challenge will aid in incorporation of automated meningioma MRI segmentation into clinical practice, which will ultimately improve care of patients with meningioma.

Prognostication of overall survival in patients with brain metastases using diffusion tensor imaging and dynamic susceptibility contrast-enhanced MRI.

OBJECTIVES: To investigate the prognostic utility of DTI and DSC-PWI perfusion-derived parameters in brain metastases patients. METHODS: Retrospective analyses of DTI-derived parameters (MD, FA, CL, CP, and CS) and DSC-perfusion PWI-derived rCBVmax from 101 patients diagnosed with brain metastases prior to treatment were performed. Using semi-automated segmentation, DTI metrics and rCBVmax were quantified from enhancing areas of the dominant metastatic lesion. For each metric, patients were classified as short- and long-term survivors based on analysis of the best coefficient for each parameter and percentile to separate the groups. Kaplan-Meier analysis was used to compare mOS between these groups. Multivariate survival analysis was subsequently conducted. A correlative histopathologic analysis was performed in a subcohort (n = 10) with DTI metrics and rCBVmax on opposite ends of the spectrum. RESULTS: Significant differences in mOS were observed for MDmin (p < 0.05), FA (p < 0.01), CL (p < 0.05), and CP (p < 0.01) and trend toward significance for rCBVmax (p = 0.07) between the two risk groups, in the univariate analysis. On multivariate analysis, the best predictive survival model was comprised of MDmin (p = 0.05), rCBVmax (p < 0.05), RPA (p < 0.0001), and number of lesions (p = 0.07). On histopathology, metastatic tumors showed significant differences in the amount of stroma depending on the combination of DTI metrics and rCBVmax values. Patients with high stromal content demonstrated poorer mOS. CONCLUSION: Pretreatment DTI-derived parameters, notably MDmin and rCBVmax, are promising imaging markers for prognostication of OS in patients with brain metastases. Stromal cellularity may be a contributing factor to these differences. ADVANCES IN KNOWLEDGE: The correlation of DTI-derived metrics and perfusion MRI with patient outcomes has not been investigated in patients with treatment naïve brain metastasis. DTI and DSC-PWI can aid in therapeutic decision-making by providing additional clinical guidance.

Gamma Knife radiosurgery for trigeminal neuralgia provides greater pain relief at higher dose rates.

In Gamma Knife (GK) radiosurgery, dose rate decreases during the life cycle of its radiation source, extending treatment times. Prolonged treatments influence the amount of sublethal radiation injury that is repaired during exposure, and is associated with decreased biologically-equivalent dose (BED). We assessed the impact of treatment times on clinical outcomes following GK of the trigeminal nerve - a rare clinical model to isolate the effects of treatment times. This is a retrospective analysis of 192 patients with facial pain treated across three source exchanges. All patients were treated to 80 Gy with a single isocenter. Treatment time was analyzed in terms of patient anatomy-specific dose rate, as well as BED calculated from individual patient beam-on times. An outcome tool measuring pain in three distinct domains (pain intensity, interference with general and oro-facial activities of daily living), was administered before and after intervention. Multivariate linear regression was performed with dose rate/BED, brainstem dose, sex, age, diagnosis, and prior intervention as predictors. BED was an independent predictor of the degree of improvement in all three dimensions of pain severity. A decrease in dose rate by 1.5 Gy/min corresponded to 31.8% less improvement in the overall severity of pain. Post-radiosurgery incidence of facial numbness was increased for BEDs in the highest quartile. Treatment time is an independent predictor of pain outcomes, suggesting that prescription dose should be customized to ensure iso-effective treatments, while accounting for the possible increase in adverse effects at the highest BEDs.

Multi-institutional review of sinonasal and skull base chondrosarcoma: 20-year experience.

BACKGROUND: Chondrosarcomas of the sinonasal cavity and skull base are uncommon malignancies. We sought to provide long-term outcomes at two tertiary care centers. METHODS: Patients with chondrosarcoma treated between 2000 and 2021 were included. The primary outcomes were overall survival (OS) and disease-specific survival (DSS). RESULTS: Thirty-eight patients met inclusion criteria. Fourteen patients had sinonasal (36.8%), 7 petroclival (18.4%), and 17 other primary skull base lesions (44.7%). Twenty-eight patients (73.7%) underwent radiation with an average dose of 67.3 ± 15.1 Gy. Eighteen patients (47.4%) required revision surgery for recurrence. 1, 5, and 10-year OS were 97.3%, 93.1%, and 74.7%. DSS at 5- and 10-year survival was 95.7%. Adjuvant radiation was associated with improved OS (HR: 0.12; 95% CI: 0.02-0.75, p = 0.023). CONCLUSION: We present our experience over the last 20 years treating chondrosarcomas. Favorable survival outcomes can be achieved but recurrence requiring repeat resection is common.

Cerebral hemodynamic and metabolic dysregulation in the postradiation brain.

Technological advances in the delivery of radiation and other novel cancer therapies have significantly improved the 5-year survival rates over the last few decades. Although recent developments have helped to better manage the acute effects of radiation, the late effects such as impairment in cognition continue to remain of concern. Accruing data in the literature have implicated derangements in hemodynamic parameters and metabolic activity of the irradiated normal brain as predictive of cognitive impairment. Multiparametric imaging modalities have allowed us to precisely quantify functional and metabolic information, enhancing the anatomic and morphologic data provided by conventional MRI sequences, thereby contributing as noninvasive imaging-based biomarkers of radiation-induced brain injury. In this review, we have elaborated on the mechanisms of radiation-induced brain injury and discussed several novel imaging modalities, including MR spectroscopy, MR perfusion imaging, functional MR, SPECT, and PET that provide pathophysiological and functional insights into the postradiation brain, and its correlation with radiation dose as well as clinical neurocognitive outcomes. Additionally, we explored some innovative imaging modalities, such as quantitative blood oxygenation level-dependent imaging, susceptibility-based oxygenation measurement, and T2-based oxygenation measurement, that hold promise in delineating the potential mechanisms underlying deleterious neurocognitive changes seen in the postradiation setting. We aim that this comprehensive review of a range of imaging modalities will help elucidate the hemodynamic and metabolic injury mechanisms underlying cognitive impairment in the irradiated normal brain in order to optimize treatment regimens and improve the quality of life for these patients.

Correlation of LET With MRI Changes in Brain and Potential Implications for Normal Tissue Complication Probability for Patients With Meningioma Treated With Pencil Beam Scanning Proton Therapy.

PURPOSE: This study aimed to investigate the correlation between imaging changes in brain normal tissue and the spatial distribution of linear energy transfer (LET) for a cohort of patients with meningioma treated with scanned proton beams. Then, assuming imaging changes are induced by cell lethality, we studied the correlation between normal tissue complication probability and LET. METHODS AND MATERIALS: Magnetic resonance imaging T2/fluid attenuated inversion recovery acquired at different intervals after proton radiation were coregistered with the planning computed tomography (CT) images from 26 patients with meningioma with abnormalities after proton radiation therapy. For this purpose, the T2/fluid attenuated inversion recovery areas not on the original magnetic resonance images were contoured, and the LET values for each voxel in the patient geometry were calculated to investigate the correlation between the position of imaging changes and the LET at those positions. To separate the effect of the dose as the inductor of these changes, we compared the LET in these areas with a sample of voxels matching the dose distributions across the image change areas. Patients with a higher LET in image change areas were grouped to verify whether they shared common characteristics. RESULTS: Eleven of the patients showed higher dose-averaged LET (LETd) in imaging change regions than in the group of voxels with the same dose. This group of patients had significantly shallower targets for their treatment than the other 15 and used fewer beams and angles. CONCLUSIONS: This study points toward the possibility that areas with imaging change are more likely to occur in regions with high dose or in areas with lower dose but increased LETd. The effect of LETd on imaging changes seems to be more relevant when treating superficial lesions with few nonopposed beams. However, most patients did not show a spatial correlation between their image changes and the LETd values, limiting the cases for the possible role of high LET as a toxicity inductor.

Proton radiotherapy for glioma and glioblastoma.

Radiotherapy (RT) continues to be an important component of treatment of glioma, particularly high-grade glioma and glioblastoma multiforme (GBM). GBM is one of the most aggressive central nervous system (CNS) tumors, with high rates of recurrence and very low rates of long-term survival. However, outcomes in these patients are improving with modern genetic profiling and multimodal therapy, which leads to more consideration for the risk for toxicities associated with traditional photon-based RT. Proton therapy (PT) is an increasingly available method to reduce off-target irradiation in CNS tumors due to the intrinsic properties of heavy-particle irradiation. Here, we review currently available data examining the used of PT in glioma patients, including dose escalation for GBM, re-irradiation (reRT) of recurrent glioma, and the potential cognitive sparing effects of conventional dose PT. We discuss the incorporation of PT into the multimodal therapy of GBM patients, and how the aggressive nature of the disease poses a unique challenge to PT study design. We also describe how PT may provide the most feasible method for implementing high rate 'FLASH' RT and the implications for glioma patients. We conclude with a discussion of ongoing clinical trials, the necessity of continued research, and how we interpret and incorporate available data into our current practice.

Factors Associated with and Temporal Trends in the Use of Radiation Therapy for the Treatment of Pituitary Adenoma in the National Cancer Database.

Objective Radiation therapy represents an uncommon but important component of treatment plans for some pituitary adenomas (PAs). Although radiation therapy has been used to treat pituitary adenomas for over a century, general trends in the usage of radiation therapy for this purpose have not been reviewed. Additionally, there are few large studies evaluating how radiation therapy is used for the treatment of these benign tumors. Investigating these trends and identifying any variations in radiation therapy utilization would help to better inform treatment decisions and improve patient outcomes. Design Present study is a retrospective analysis of cases using the National Cancer Database. Setting The research was organized at a tertiary academic medical center. Participants Patients were diagnosed with pituitary adenoma between 2004 and 2014 within the National Cancer Database (NCDB). Methods Temporal trends in the usage of radiation therapy to treat pituitary adenoma were analyzed through a retrospective analysis of 77,142 pituitary adenoma cases from the NCDB between 2004 and 2014. Univariate and multivariate analyses were to examine the relationship between patient, tumor, and treatment factors, and the incorporation of radiation therapy into the treatment of pituitary adenomas. We adjusted for potential confounders such as age, sex, race, comorbidity score, facility type, and year of diagnosis. Results A total of 77,142 patients met inclusion criteria. Inclusion of radiation therapy in pituitary adenoma treatment was 8.0% in 2004 and steadily declined to a low of 3.1% in 2014. Overall, patients were less likely to receive radiation for their pituitary adenoma over time ( p < 0.001). Similarly, patients were found to be less likely to receive any type of treatment for PA over time ( p < 0.001). Multivariable evaluation found patients who were female, between 54 and 64 years of age, or treated at either a Comprehensive Community Cancer Program or an Integrated Network Cancer Program were more likely to receive radiation as part of their pituitary adenoma treatment ( p < 0.001, odds ratio [OR] = 2.01, confidence interval [CI]: 1.54-2.63; p < 0.001, OR = 1.84, CI: 1.38-2.44, respectively). Patients were less likely to receive radiation for their PA if they were African American ( p < 0.001, OR = 0.81, CI: 0.72-0.91). Logistic regression also identified a progressive increase in the likelihood of receiving radiation after a PA diagnosis with increasing tumor size starting with microscopic tumors, peaking at 4 to 5 cm ( p < 0.001; OR = 15.57; CI: 12.20-19.87). Conclusion In this sample of pituitary adenoma patients treated at NCDB institutions between 2004 and 2014, we found a steady decline in the incorporation of radiation therapy in treatment, as well as in the use of any type of intervention for PA treatment, suggesting a rise in noninterventional observation of PA.

A Probability-Based Investigation on the Setup Robustness of Pencil-beam Proton Radiation Therapy for Skull-Base Meningioma.

INTRODUCTION: The intracranial skull-base meningioma is in proximity to multiple critical organs and heterogeneous tissues. Steep dose gradients often result from avoiding critical organs in proton treatment plans. Dose uncertainties arising from setup errors under image-guided radiation therapy are worthy of evaluation. PATIENTS AND METHODS: Fourteen patients with skull-base meningioma were retrospectively identified and planned with proton pencil beam scanning (PBS) single-field uniform dose (SFUD) and multifield optimization (MFO) techniques. The setup uncertainties were assigned a probability model on the basis of prior published data. The impact on the dose distribution from nominal 1-mm and large, less probable setup errors, as well as the cumulative effect, was analyzed. The robustness of SFUD and MFO planning techniques in these scenarios was discussed. RESULTS: The target coverage was reduced and the plan dose hot spot increased by all setup uncertainty scenarios regardless of the planning techniques. For 1 mm nominal shifts, the deviations in clinical target volume (CTV) coverage D99% was -11 ± 52 cGy and -45 ± 147 cGy for SFUD and MFO plans. The setup uncertainties affected the organ at risk (OAR) dose both positively and negatively. The statistical average of the setup uncertainties had <100 cGy impact on the plan qualities for all patients. The cumulative deviations in CTV D95% were 1 ± 34 cGy and -7 ± 18 cGy for SFUD and MFO plans. CONCLUSION: It is important to understand the impact of setup uncertainties on skull-base meningioma, as the tumor target has complex shape and is in proximity to multiple critical organs. Our work evaluated the setup uncertainty based on its probability distribution and evaluated the dosimetric consequences. In general, the SFUD plans demonstrated more robustness than the MFO plans in target coverages and brainstem dose. The probability-weighted overall effect on the dose distribution is small compared to the dosimetric shift during single fraction.

Initial Evaluation of a Novel Cone-Beam CT-Based Semi-Automated Online Adaptive Radiotherapy System for Head and Neck Cancer Treatment - A Timing and Automation Quality Study.

Introduction A novel on-line adaptive radiotherapy (ART) system based on O-ring linear accelerator (LINAC) and cone-beam CT (CBCT) was evaluated for treatment and management of head & neck (H&N) cancer in an emulated environment accessed via remote desktop connection. In this on-line ART system, organs-at-risk (OARs) and target contours and radiotherapy (RT) plans are semi-automatically generated based on the patient CBCT, expediting a typically hours-long RT planning session to under half an hour. In this paper, we describe our initial experiences with the system and explore optimization strategies to expedite the process further. Methods We retroactively studied five patients with head and neck cancers, treated 16-35 fractions to 50-70 Gys. For each patient, on-line ART was simulated with one planning CT and three daily CBCT images taken beginning, middle, and end of treatment (tx). Key OAR (mandible, parotids, and spinal cord) and target (planning target volume (PTV) = clinical target volume (CTV) + 3 mm margin) contours were auto-generated and adjusted as needed by therapist/dosimetrist and attending physician, respectively. Duration of OAR contouring, target contouring, and plan review was recorded. Key OAR auto-contours were qualitatively rated from 1 (unacceptable) - 5 (perfect OAR delineation), and then quantitatively compared to human-adjusted "ground truth" contours via dice similarity coefficient (DSC) and 95-percentile Hausdorff distance (HD95%). Once contours were approved, adapted RT plans were auto-generated for physician review. Simulated doses to OARs and targets from the adapted plan were compared to that from the original (un-adapted) plan. Results Median on-line ART planning duration in the remote emulated environment was 19 min 34 sec (range: 13 min 10 sec - 31 min 20 sec). Automated key OAR quality was satisfactory overall (98% scored ≥3; 82% ≥4), though mandible was rated lower than others (p < 0.05). Most key OARs and all targets were within 2 mm margin of human-adjusted contours, but a few parotid and spinal cord contours deviated up to 5 mm. Anatomical changes over tx course further increased auto-contour error (p < 0.05, ΔHD95% = 0.77 mm comparing start and end of tx). Further optimizing auto-contoured OAR and target quality could reduce the on-line treatment planning duration by ~5 min and ~4.5 min, respectively. Dosimetrically, adapted plan spared OARs at a rate much greater than random chance compared to the original plan (χ2 = 22.3, p << 0.001), while maintaining similar therapeutic dose to treatment target CTV (χ2 = 1.14, p > 0.05). In addition, a general decrease in accumulated OAR dose was observed with adaptation. Unsupervised adapted plans where contours were auto-generated without human review still spared OAR at a greater rate than the original plans, suggesting benefits of adaptation can be maintained even with some leniency in contour accuracy. Conclusion Feasibility of a novel, semi-automated on-line ART system for various head and neck (H&N) cancer sites was demonstrated in terms of treatment duration, dosimetric benefits, and automated contour accuracy in a remote emulator environment. Adaptive planning duration was clinically viable at 19 min and 34 sec, but further improvements in automated contour accuracy and performance improvements of plan auto-generation may reduce adaptive planning duration by up to 10 minutes.

Multi-institutional retrospective review of stereotactic radiosurgery for brain metastasis in patients with small cell lung cancer without prior brain-directed radiotherapy.

Introduction: Patients with small cell lung cancer (SCLC) brain metastasis (BM) typically receive whole brain radiotherapy (WBRT) as data regarding upfront radiosurgery (SRS) in this setting are sparse. Methods: Patients receiving SRS for SCLC BM without prior brain radiation were identified at three U.S. institutions. Overall survival (OS), freedom from intracranial progression (FFIP), freedom from WBRT (FFWBRT), and freedom from neurologic death (FFND) were determined from time of SRS. Results: Thirty-three patients were included with a median of 2 BM (IQR 1-6). Median OS and FFIP were 6.7 and 5.8 months, respectively. Median FFIP for patients with ≤2 versus >2 BM was 7.1 versus 3.6 months, p=0.0303. Eight patients received salvage WBRT and the 6-month FFWBRT and FFND were 87.8%. and 90.1%, respectively. Conclusions: Most SCLC patients with BM who received upfront SRS avoided WBRT and neurologic death, suggesting that SRS may be an option in select patients.

Factors Associated With Facial Nerve Paresis Following Gamma Knife for Vestibular Schwannoma.

OBJECTIVE: Evaluate the incidence of and potential contributory factors to facial nerve paresis and other cranial neuropathies (CN) following stereotactic radiosurgery with Gamma Knife (GK) for primary treatment of vestibular schwannoma (VS). STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: Charts were reviewed for all adult patients receiving primary GK treatment for unilateral VS between 2005 and 2013. Patients with NF2 or previous surgery were excluded from analysis. INTERVENTION: GK radiosurgery. MAIN OUTCOME MEASURES: The incidence of new-onset facial nerve paresis after primary GK treatment of VS was evaluated. Secondary endpoints included other cranial neuropathies. RESULTS: One hundred thirty-three patients with VS received primary GK therapy. Posttreatment CN developed in 33 patients (24.8%). Twelve patients (9.0%) experienced trigeminal paresthesia, 11 (8.3%) developed sudden sensorineural hearing loss (SSNHL) requiring steroids, and seven (5.3%) demonstrated facial paresis. The mean maximum cochlear dose was 15.49 Gy in patients with facial paresis compared with 12.42 Gy in subjects without facial paresis (p = 0.032). Subjects with facial paresis were more likely to have a lateral tumor without fundal fluid on magnetic resonance imaging (MRI) (71%) compared with subjects without facial paresis (43%). CONCLUSIONS: In the treatment of VS with primary GK, maximum cochlear dose was significantly associated with facial paresis. Laterally extending tumors without fundal fluid on MRI experienced higher rates of facial paresis. These factors should be considered during GK treatment planning for VS.