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Purpose: In patients with Wilms tumor with lung metastases, a cardiac-sparing intensity modulated radiation therapy (CS-IMRT) technique is increasingly being adopted for whole lung irradiation. However, the standard technique for flank and whole abdomen radiation remains 2-dimensional anterioposterior (AP), and overlap at the junction between the whole lung CS-IMRT and abdominal AP fields can result in overdose to normal organs. Here, we compared the dosimetry of patients who received whole lung irradiation and flank or abdominal radiation therapy with CS-IMRT with AP abdominal field (IMRT-AP) versus CS-IMRT with IMRT abdominal field (combined IMRT). Methods and Materials: We retrospectively reviewed the radiation plans of 2 patients with Wilms tumor who received CS-IMRT and flank or whole abdomen irradiation with a combined IMRT approach. Comparison IMRT-AP plans were generated with equivalent target coverage of 95% receiving the prescribed dose. Maximum doses to normal organs were compared at the junctional overlap. Results: Overlap at the junction between CS-IMRT and abdominal fields resulted in a significantly lower dose with combined IMRT plans compared with IMRT-AP plan. Differences in maximum doses (in cGy) to normal organs between combined IMRT versus IMRT-AP plans were most significant in the vertebral body (patient 1 = 1277 vs 2065; patient 2 = 1334 vs 2287), lungs (patient 1 = 1298 vs 2081; patient 2 = 1234 vs 1820), spinal cord (patient 1 = 1235 vs 1975; patient 2 = 1345 vs 2253), stomach (patient 1 = 1264 vs 1977; patient 2 = 1118 vs 2062), and liver (patient 1 = 1297 vs 1889; patient 2 = 1334 vs 2237). Conclusions: The combined IMRT approach for Wilms patients who require whole lung and abdomen irradiation can provide more uniform dose distribution in the junction area and significantly lower doses to normal organs at the junctional overlap.
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There is an urgent need to develop efficient and environmentally friendly technologies for separating Li+ from brines containing abundant Mg2+ to meet the growing demand for lithium resources. In this work, we prepared hybrid membranes by integrating hydrogen manganese oxide (HMO), a lithium-ion sieve, as a filler into anion-exchange membranes (AEMs), the quaternary ammonium-functionalized poly(2,6-dimethyl-1,4-phenylene oxide) (QPPO) and poly(m-terphenyl piperidinium) (m-PTP). Cations are transported by electrostatic attraction originating from anions and the concentration difference across membranes. Because of the effects of electrostatic repulsion of the fixed cationic groups and steric resistance in AEMs, Li+ with less charge and smaller radius will preferentially pass through the membrane. In addition, the presence of HMO provides an additional fast transport channel for Li+, resulting in an enhanced Li+/Mg2+ separation performance. The results show that 20%HMO@m-PTP exhibits high Li+ flux (0.48 mol/m2·h) and Li+/Mg2+ selectivity (ßLi+/Mg2+ = 14.1). Molecular dynamics simulations show that m-PTP has more free volume than QPPO, which is beneficial for rapid cation transport. Spectral analysis confirms the insertion and sieving of Li+ in HMO. This work illustrates the great potential of anion-exchange- and cation-concentration-driven hybrid membranes based on lithium-ion sieves for low-energy and efficient Li+ extraction processes.
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Objective.Treating multiple brain metastases in a single plan is a popular radiosurgery technique. However, targets positioned off-isocenter are subject to rotational uncertainties. This work introduces two new planning target volumes (PTVs) that address this increased uncertainty. The volume of normal tissue included in these PTVs when paired with optimized isocenters are evaluated and compared with conventional methods.Approach.Sets of 1000 random multi-target radiosurgery patients were simulated, each patient with a random number of spherical targets (2-10). Each target had a random volume (0.1-15 cc) and was randomly positioned between 5 and 50 mm or 100 mm from isocenter. Two new PTVs ('LensPTV' and 'SwipePTV') and conventional isotropic PTVs were created using isocenters derived from the center-of-centroids, the center-of-mass, or optimized per PTV type. The total volume of normal tissue in the PTVs for each patient was calculated and compared using 1 mm translations and 0.5°, 1.0°, and 2.0° rotations.Main results.Using the new PTVs and/or using optimized isocenters decreased the total volume of normal tissue in the PTVs per patient. The SwipePTV, in particular, provided the greatest decrease. Compared to the SwipePTV, the LensPTV and the conventional isotropic PTV included an extra 0.68 and 0.73 cc of normal tissue per patient (median), respectively, when using 50 mm max distance to isocenter and 1° max rotation angle. Under these conditions, 25% of patients had extra volume of normal tissue ≥ 0.96 and 1.04 cc. When using 100 mm max distance to isocenter and 2° max rotation angle, 25% of patients had extra volume of normal tissue ≥ 4.35 and 5.75 cc.Significance.PTVs like those presented here, especially when paired with optimized isocenters, can decrease the total volume of included normal tissue and reduce the risk of toxicity without compromising target coverage.
Subject(s)
Brain Neoplasms , Radiosurgery , Radiotherapy, Intensity-Modulated , Humans , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy Dosage , Radiosurgery/methods , Uncertainty , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/radiotherapy , Brain Neoplasms/pathology , Radiotherapy, Intensity-Modulated/methodsABSTRACT
BACKGROUND: It remains a clinical challenge to differentiate brain tumors from radiation-induced necrosis in the brain. Despite significant improvements, no single MRI method has been validated adequately in the clinical setting. METHODS: Multi-parametric MRI (mpMRI) was performed to differentiate 9L gliosarcoma from radiation necrosis in animal models. Five types of MRI methods probed complementary information on different scales i.e., T2 (relaxation), CEST based APT (probing mobile proteins/peptides) and rNOE (mobile macromolecules), qMT (macromolecules), diffusion based ADC (cell density) and SSIFT iAUC (cell size), and perfusion based DSC (blood volume and flow). RESULTS: For single MRI parameters, iAUC and ADC provide the best discrimination of radiation necrosis and brain tumor. For mpMRI, a combination of iAUC, ADC, and APT shows the best classification performance based on a two-step analysis with the Lasso and Ridge regressions. CONCLUSION: A general mpMRI approach is introduced to choosing candidate multiple MRI methods, identifying the most effective parameters from all the mpMRI parameters, and finding the appropriate combination of chosen parameters to maximize the classification performance to differentiate tumors from radiation necrosis.
Subject(s)
Brain Neoplasms , Multiparametric Magnetic Resonance Imaging , Radiation Injuries , Animals , Contrast Media , Rodentia , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/radiotherapy , Magnetic Resonance Imaging/methods , Necrosis/diagnostic imagingABSTRACT
Purpose: Our purpose was to develop a rodent model of brain radionecrosis using clinical linear accelerator based stereotactic radiosurgery. Methods and Materials: Single fraction maximum prescription points in the mouse's left hemisphere were irradiated using linear accelerator-based stereotactic radiosurgery with multiple arcs at 60 (n = 5), 100 (n = 5), and 140 (n = 5) Gy. Rats (n = 6) were similarly treated with 140 Gy. Gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) was used to track radiation injury in mice over weeks (100 and 140 Gy) or months (60 Gy). Target accuracy was measured by the distance from the prescription point to the center of the earliest Gd-MRI enhancement. Confirmation of necrosis via histology was performed at the subject endpoints. Results: Radiation injury as indicated by Gd-MRI was first identified at 2 weeks (140 Gy), 4 to 6 weeks (100 Gy), and 8 months (60 Gy). A volumetric time course showed rapid growth in the volume of Gd-MRI signal enhancement after the appearance of apparent necrosis. Histopathologic features were consistent with radionecrosis. Conclusions: The presented method uses a commonly available clinical linear accelerator to induce radiation necrosis in both mice and rats. The treatment is modeled after patient therapy for a more direct model of human tissue under a range of doses used in clinical neuro-ablation techniques. The short time to onset of apparent necrosis, accurate targeting of the prescription point, high incidence of necrosis, and similar pathologic features make this a suitable animal model for further research in radionecrosis.
ABSTRACT
Brain metastasis is a common characteristic of late-stage lung cancers. High doses of targeted radiotherapy can control tumor growth in the brain but can also result in radiotherapy-induced necrosis. Current methods are limited for distinguishing whether new parenchymal lesions following radiotherapy are recurrent tumors or radiotherapy-induced necrosis, but the clinical management of these two classes of lesions differs significantly. Here, we developed, validated, and evaluated a new MRI technique termed selective size imaging using filters via diffusion times (SSIFT) to differentiate brain tumors from radiotherapy necrosis in the brain. This approach generates a signal filter that leverages diffusion time dependence to establish a cell size-weighted map. Computer simulations in silico, cultured cancer cells in vitro, and animals with brain tumors in vivo were used to comprehensively validate the specificity of SSIFT for detecting typical large cancer cells and the ability to differentiate brain tumors from radiotherapy necrosis. SSIFT was also implemented in patients with metastatic brain cancer and radiotherapy necrosis. SSIFT showed high correlation with mean cell sizes in the relevant range of less than 20 µm. The specificity of SSIFT for brain tumors and reduced contrast in other brain etiologies allowed SSIFT to differentiate brain tumors from peritumoral edema and radiotherapy necrosis. In conclusion, this new, cell size-based MRI method provides a unique contrast to differentiate brain tumors from other pathologies in the brain. SIGNIFICANCE: This work introduces and provides preclinical validation of a new diffusion MRI method that exploits intrinsic differences in cell sizes to distinguish brain tumors and radiotherapy necrosis.
Subject(s)
Brain Neoplasms , Radiation Injuries , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/radiotherapy , Cell Size , Diagnosis, Differential , Humans , Magnetic Resonance Imaging/methods , Necrosis/diagnostic imaging , Neoplasm Recurrence, Local/diagnosis , Radiation Injuries/diagnostic imaging , Radiation Injuries/etiologyABSTRACT
PURPOSE: Effective treatment options for refractory depression are needed. Recent advancements permit both precise ablative radiation and functional neurologic connectome analysis using standard magnetic resonance imaging. We combined these innovations to perform stereotactic radiosurgical capsulotomy for the treatment of medically refractory major depressive disorder and study connectome response using a novel tractography-based approach. METHODS AND MATERIALS: Patients with medically refractory depression were enrolled on a prospective pilot single-arm observational trial from 2020 to 2021 at a single academic tertiary referral center. Bilateral ablation of the anterior limb of the internal capsule was accomplished by mask-based linear accelerator stereotactic radiosurgery. Beck's Depression Inventory measured efficacy. Montreal Cognitive Assessment evaluated cognition. RESULTS: Three patients were enrolled. Depression burden was improved by 88% at 12-month follow-up and by 55% at 18-month follow-up for patient 1 and 2, respectively. Patient 1 discontinued ketamine therapy, and patient 2 discontinued electroconvulsive therapy. Patient 3 reported global improvement in symptoms and function at 3 months. All 3 patients had reduction or resolution of suicidal ideation. No patient experienced cognitive decline or neurologic toxicity, and Montreal Cognitive Assessment score, as well as subjective patient-reported evaluations of concentration and attention, were superior after treatment. Tractography confirmed intended disruption of the cortico-striatal-thalamo-cortical loop with structural reorganization in the connectome. Connectome change was consistent between patients. Observed increases in caudate and putamen connectivity and decreases in thalamic connectivity may explain improved concentration, attention, and depression. The diversity and magnitude of connectome change may correlate with degree of clinical response. CONCLUSIONS: In 3 patients with refractory depression, radiosurgical capsulotomy significantly reduced the burden of depression. Functional connectome reorganization offers neurobiological evidence to support further investigations of the role of radiosurgery in depression.
Subject(s)
Depressive Disorder, Major , Depressive Disorder, Treatment-Resistant , Obsessive-Compulsive Disorder , Radiosurgery , Depressive Disorder, Major/diagnostic imaging , Depressive Disorder, Major/surgery , Depressive Disorder, Treatment-Resistant/diagnostic imaging , Depressive Disorder, Treatment-Resistant/surgery , Diffusion Tensor Imaging , Humans , Magnetic Resonance Imaging , Obsessive-Compulsive Disorder/pathology , Obsessive-Compulsive Disorder/psychology , Obsessive-Compulsive Disorder/surgery , Prospective Studies , Radiosurgery/methodsABSTRACT
PURPOSE: We sought to determine whether a more widely accessible, noninvasive, frameless approach to radiosurgical thalamotomy would improve objective measures of refractory essential or parkinsonian tremor without added toxicity compared with reports of frame-based radiosurgery. METHODS AND MATERIALS: We conducted a single-arm pilot observational prospective trial of adult patients with essential or parkinsonian tremor from 2013 to 2019 and report results at 1-year follow-up. Patients were treated with frameless unilateral radiosurgical ablation of the thalamic ventral intermediate nucleus to a maximum dose of 160 Gy. Treatment response was measured by the Fahn-Tolosa-Marin (FTM) tremor rating scale and the Quality of Life in Essential Tremor or Parkinson's Disease Questionnaire obtained before treatment and at 3, 6, 9, and 12 months. RESULTS: Thirty-three patients, including 23 with essential tremor and 10 with Parkinson's disease, were enrolled. Overall treatment response rate per FTM was 83% (15 of 18) at 6 months. There was a marked improvement in tremor, with an average total FTM reduction of 21% at 3 months (from 46 to 30 points; Pâ¯=â¯.003) and 41% at 6 months (from 46 to 24 points; Pâ¯=â¯.001). At 6 months, functional decline had regressed by 54% (from 15 to 7 points; Pâ¯=â¯.001). Quality of life improved by 57% (Pâ¯=â¯.001) at 6 months in patients with essential tremor, and patients with Parkinson's disease had unchanged quality of life. At 1-year follow-up, grade 2 neurologic adverse events were observed in 6% (2 of 33) of patients without any grade ≥ 3 events. CONCLUSION: Noninvasive, frameless radiosurgical thalamotomy may be a feasible treatment for patients with refractory tremor and demonstrates short-term safety at 1-year follow-up. This pilot study provides promising preliminary descriptions of efficacy, and definitive estimates of long-term safety and benefit require further study with longer follow-up.
Subject(s)
Radiosurgery , Thalamus , Tremor , Adult , Humans , Pilot Projects , Prospective Studies , Quality of Life , Radiosurgery/adverse effects , Radiosurgery/methods , Thalamus/surgery , Treatment Outcome , Tremor/radiotherapyABSTRACT
OBJECTIVE: Stereotactic radiosurgery (SRS) treats severe, medically refractory essential tremor and tremor-dominant Parkinson disease. However, the optimal target for SRS treatment within the thalamic ventral intermediate nucleus (VIM) is not clearly defined. This work evaluates the precision of the physician-selected VIM target, and determines the optimal SRS target within the VIM by correlation between early responders and nonresponders. METHODS: Early responders and nonresponders were assessed retrospectively by Elements Basal Ganglia Atlas autocontouring of the VIM on the pre-SRS-treatment 1-mm slice thickness T1-weighted MRI and correlating the center of the post-SRS-treatment lesion. Using pre- and posttreatment diffusion tensor imaging, the fiber tracking package in the Elements software generated tremor-related tracts from autosegmented motor cortex, thalamus, red nucleus, and dentate nucleus. Autocontouring of the VIM was successful for all patients. RESULTS: Among 23 patients, physician-directed SRS targets had a medial-lateral target range from +2.5 mm to -2.0 mm from the VIM center. Relative to the VIM center, the SRS isocenter target was 0.7-0.9 mm lateral for 6 early responders and 0.9-1.1 mm medial for 4 nonresponders (p = 0.019), and without differences in the other dimensions: 0.2 mm posterior and 0.6 mm superior. Dose-volume histogram analyses for the VIM had no significant differences between responders and nonresponders between 20 Gy and 140 Gy, mean or maximum dose, and dose to small volumes. Tractography data was obtained for 4 patients. CONCLUSIONS: For tremor control in early responders, the Elements Basal Ganglia Atlas autocontour for the VIM provides the optimal SRS target location that is 0.7-0.9 mm lateral to the VIM center.
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PURPOSE/OBJECTIVE: Linear accelerator (LINAC) based stereotactic radiosurgery (SRS) for arteriovenous malformations (AVMs) is delivered with cone or multileaf collimators (MLCs), and favorable dosimetry is associated with reduced radionecrosis in normal brain tissue. This study aims to determine whether cones or MLCs has better dosimetric characteristics, to predict differences in toxicity. METHODS: All patients treated for AVMs using LINAC SRS from 2003-2017 were examined retrospectively. Demographic data, volumes of normal tissue exposed to 12Gy (V12Gy[cc]) and 4Gy (V4Gy[cc]), maximal dose, and dose gradient were analyzed. Univariate and multivariate analyses were used to evaluate relationships between collimator type, dosimetric parameters, and toxicity. Propensity score matching was used to adjust for AVM size. RESULTS: Compared to MLC, cones were independently associated with reduced V12Gy[cc] after propensity score matching (p=0.008) and reduced neurotoxicity (p=0.016). Higher V12Gy[cc] (p=0.0008) and V4Gy[cc] (p=0.002) were associated with increased neurotoxicity. CONCLUSIONS: Treating AVMs with cone-based SRS over MLC-based SRS may improve dosimetry and reduce toxicities.
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Objective Local failure of incompletely resected vestibular schwannoma (VS) following salvage stereotactic radiosurgery (SRS) using standard doses of 12 to 13 Gy is common. We hypothesized that dose-escalated SRS, corrected for biologically effective dose, would have superior local control of high-grade VS progressing after subtotal or near-total resection compared with standard-dose SRS. Design Retrospective cohort study. Setting Tertiary academic referral center. Participants Adult patients treated with linear accelerator-based SRS for progressive VS following subtotal or near-total resection. Main Outcome Measures Dose-escalated SRS was defined by a biologically effective dose exceeding a single-fraction 13-Gy regimen. Study outcomes were local control and neurologic sequelae of SRS. Binary logistic regression was used to evaluate predictors of study outcomes. Results A total of 18 patients with progressive disease following subtotal (71%) and near-total (39%) resection of Koos grade IV disease (94%) were enrolled. Of the 18 patients, 7 were treated with dose-escalated SRS and 11 with standard-dose SRS. Over a median follow-up of 32 months after SRS, local control was 100% in the dose-escalated cohort and 91% in the standard-dose cohort ( p = 0.95). Neurologic sequelae occurred in 28% of patients, including 60% of dose-escalated cohort and 40% of the standard-dose cohort ( p = 0.12), although permanent neurologic sequelae were low at 6%. Conclusions Dose-escalated SRS has similar local control of recurrent VS following progression after subtotal or near-total resection and does not appear to have higher neurologic sequalae. Larger studies are needed.
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Objectives Hypofractionated stereotactic radiotherapy (HSRT) in two to five fractions may offer patients with large nonfunctioning pituitary adenomas (NFPAs) with chiasm involvement a safe and effective treatment over a single week. However, little has been reported regarding this novel approach. Design We compared the feasibility, outcomes, and toxicity of single-fraction stereotactic radiosurgery and HSRT. Setting This study was conducted at a tertiary academic referral center. Participants After approval by the institutional review board, we performed a retrospective cohort study of patients treated at our institution with stereotactic radiosurgery (SRS) and HSRT for NFPA. Selection for SRS or HSRT was based on clinicopathologic factors including tumor size and cavernous sinus invasion at the discretion of the treating physician. Main Outcome Measures Local control, endocrinopathy, and radiation-associated toxicity were evaluated by binary logistic regression and Cox's proportional hazards regression. Results A total of 45 patients with mean follow-up of 5 years were enrolled including 26 patients treated by HSRT with mean follow-up of 3 years and 19 patients treated by SRS with median follow-up of 6 years. Clinicopathologic characteristics were balanced between cohorts. Local failure at last follow-up was 5% in the SRS cohort and 8% in the HSRT cohort, and rates of post-SRS endocrinopathy were similar between each cohort. Late complications including radionecrosis, visual deficit, and secondary malignancy were minimal in either cohort. Conclusions HSRT is an appropriate treatment strategy for patients with NFPAs, particularly for optic pathway preservation in the setting of large tumors with chiasm involvement. Further studies are needed to optimize fractionated approaches and patient selection.
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BACKGROUND: Stereotactic radiosurgery (SRS) for cerebral arteriovenous malformations (AVMs) is well-established. Radiographic advantages exist for 3-dimensional rotational digital subtraction angiography (3DRA) over 2-dimensional digital subtraction angiography (2D DSA) in delineating AVM nidus structure for SRS treatment planning. However, currently there is limited to no data directly comparing 2D DSA versus 3DRA in terms of patient outcomes. OBJECTIVE: To investigate whether the use of 3DRA over 2D DSA in radiosurgical treatment planning for AVMs associates with improved clinical outcomes. METHODS: All AVM patients treated with SRS at our institution between the years 2000 and 2018 were identified. Primary outcomes were obliteration rates and time to obliteration (TTO); secondary outcomes included rates of post-SRS hemorrhage, salvage therapy, and symptomatic radionecrosis. A minimum of 12 mo of follow-up imaging/angiogram post-SRS was required, or alternatively evidence of obliteration on angiogram prior to 12 mo post-SRS. Single predictor and multivariable Cox regression and logistic regression models were constructed to test for association between radiographic, clinical, and treatment factors with outcomes. RESULTS: A total of 75 patients were included. Total 17 patients received 3DRA and 58 patients received 2D DSA, with a median follow-up of 3.29 yr. The 3DRA is significantly associated with improved TTO on single predictor (HR 2.87, 1.29-6.12; P = .0109) and multivariable analysis (HR 2.448, 1.076-5.750; P = .0330) and increased odds of achieving obliteration by 3 yr post-SRS on single predictor analysis (OR 6.044, 1.405-26.009; P = .0157). CONCLUSION: The 3DRA over 2D DSA in SRS treatment planning for AVMs may result in improved TTO and 3-yr obliteration rates. Further investigation and prospective study are warranted.
Subject(s)
Angiography, Digital Subtraction/methods , Arteriovenous Fistula/surgery , Imaging, Three-Dimensional/methods , Intracranial Arteriovenous Malformations/surgery , Radiosurgery/methods , Surgery, Computer-Assisted/methods , Adult , Female , Humans , Logistic Models , Male , Middle Aged , Retrospective Studies , Treatment OutcomeABSTRACT
Management of vestibular schwannoma (VS) includes stereotactic radiosurgery (SRS) in single or fractionated treatments. There is a paucity of literature on the three-dimensional (3D) volumetric kinetics and radiological changes following SRS and no consensus on appropriate post-SRS surveillance imaging timeline. This is a retrospective cohort study with institutional review board approval. A total of 55 patients met study criteria. We collected volumetric kinetic data in VS treated with SRS over time using a target volume contouring software. We also tracked radiographic phenomena such as pseudoprogression and necrosis. A secondary objective was to describe our overall treatment success rate and any failures. For all treatments groups, pseudoprogression most typically occurred within 12 months post-SRS, after which tumor volumes on average normalized and then decreased from pretreatment size at the last follow-up. Only two patients required salvage therapy post-SRS and were considered SRS treatment failures. Both patients were in the five-fraction cohort but with a lower biologically equivalent dose. Our study is first to collect 3D volumetric kinetics of VS following single and fractionated SRS in contrast to extrapolations from single and two-dimensional measurements. Our longitudinal data also show initial increases in volume in the first 12 months post-SRS followed by later declines, setting up interesting questions regarding the utility of early posttreatment surveillance imaging in the asymptomatic patient. Finally, we show low rates of treatment failure (3.6%) and show in our cohort that SRS dose de-escalation posed a risk of treatment failure.
ABSTRACT
Stereotactic radiosurgery (SRS) is used as a noninvasive treatment option for patients with trigeminal neuralgia (TN), but the effect of obesity on pain relief post SRS, if any, is unknown. The primary goal of our study was to evaluate the association between obesity and response to SRS in patients with TN. We conducted an IRB-approved retrospective review of patients treated with SRS for TN between 2010 and 2017. Barrow Neurologic Institute (BNI) Score was assigned pre-and post-SRS to quantify pain level. Thirty-two patients (65% female) between the ages of 24 and 96 were studied with a median follow-up time of 11 months. Patients with BMI >25 were significantly less likely to have improvement in their symptoms with SRS (p = 0.005). Elevated BMI may be associated with worsened response to SRS in the treatment of TN.
ABSTRACT
Radiation-associated malignancy and malignant transformation are risks associated with stereotactic radiosurgery (SRS); however, incidence is uncertain. The purpose of our study is to present the rate of radiation-associated malignancy and malignant transformation at our institution. After IRB approval, we undertook a retrospective cohort study evaluating patients treated with Gamma Knife® or linac-based SRS between 1990 and 2014 for benign CNS pathology with at least 5 years of clinical follow-up. Risk of transformation was calculated using the Kaplan-Meier method. A total of 273 patients met selection criteria. Median clinical follow-up after SRS was 11 years (range 5-27). Over 3,216 patient-years following SRS, we found zero cases of radiation-associated malignancy and two cases of radiation-associated malignant transformation for a crude rate of 0.73% or case rate of 0.62 per 1,000 patient-years. The Kaplan-Meier risk of malignant transformation at 5, 10, and 15 years was 0.4% (95% CI 0.05% 2.6%). These data support the continued use of SRS for benign intracranial pathology without significant concern for secondary malignancy.
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PURPOSE: Merkel cell carcinoma is highly sensitive to both radiation and immunotherapy. Moreover, concurrent radioimmunotherapy may capitalize on anti-tumor immune activity and improve Merkel cell treatment response, although an enhanced immune system may cross-react with native tissues and lead to significant sequelae. METHODS: Here we present a case study of a patient with metastatic Merkel cell carcinoma treated with radiotherapy concurrent with pembrolizumab. RESULTS: After radioimmunotherapy, the patient developed sensory neuropathy, visual hallucinations, and mixed motor neuron findings. Neurologic dysfunction progressed to profound gastrointestinal dysmotility necessitating parenteral nutrition and intubation with eventual expiration. CONCLUSION: This case represents a unique autoimmune paraneoplastic neurologic syndrome, likely specific to neuroendocrine tumors and motivated by concurrent radioimmunotherapy. Recognition of the potential role of radioimmunotherapy may provide an advantage in anticipating these severe sequelae.
Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Agents, Immunological/adverse effects , Autoimmune Diseases of the Nervous System/etiology , Carcinoma, Merkel Cell/secondary , Fingers , Lymphatic Metastasis/radiotherapy , Paraneoplastic Syndromes, Nervous System/etiology , Radioimmunotherapy/adverse effects , Radiotherapy, Intensity-Modulated , Skin Neoplasms/radiotherapy , Aged , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Autoimmune Diseases of the Nervous System/immunology , Axilla , Carboplatin/administration & dosage , Carcinoma, Merkel Cell/drug therapy , Carcinoma, Merkel Cell/radiotherapy , Combined Modality Therapy , Deglutition Disorders/etiology , Etoposide/administration & dosage , Fatal Outcome , Hallucinations/etiology , Humans , Lymphatic Metastasis/diagnostic imaging , Male , Neuralgia/drug therapy , Neuralgia/etiology , Palliative Care , Paraneoplastic Syndromes, Nervous System/immunology , Parenteral Nutrition, Total , Pneumonia, Aspiration/etiology , Positron Emission Tomography Computed Tomography , Radiotherapy, High-Energy , Radiotherapy, Intensity-Modulated/adverse effects , Skin Neoplasms/drug therapy , Skin Neoplasms/secondaryABSTRACT
OBJECTIVE: Accurate volume assessment is essential for the management of vestibular schwannoma after stereotactic radiosurgery (SRS). A cuboidal approximation for volume is the standard surveillance method; however, this may overestimate tumor volume. We sought to evaluate several volumetric models and their suitability for post-SRS surveillance. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. PATIENTS: We evaluated 54 patients with vestibular schwannoma before and after SRS. INTERVENTION(S): Gold-standard volumes were obtained by a radiation oncologist using contouring software. Volume was also calculated by cuboidal, ellipsoidal, and spherical formulae using tumor diameters obtained by a neuroradiologist. MAIN OUTCOME MEASURE(S): Percent error (PE) and absolute percent error (APE) were calculated. Paired t test evaluated bias, and the Bland-Altman method evaluated reproducibility. Linear regression evaluated predictors of model error. RESULTS: All models overestimated volume compared with the gold standard. The cuboidal model was not reproducible before SRS (pâ<â0.001), and no model was reproducible after SRS (cuboidal pâ<â0.001; ellipsoidal pâ=â0.02; spherical pâ=â0.02). Significant bias was present before SRS for the cuboidal model (pâ<â0.001), and post-SRS for all models [cuboidal (pâ<â0.001), ellipsoidal (pâ<â0.02), and spherical (pâ=â0.005)]. Model error was negatively associated with pretreatment volume for the cuboidal (PE pâ=â0.03; APE pâ=â0.03), ellipsoidal (PE pâ=â0.03; APE pâ=â0.04), and spherical (PE pâ=â0.02; APE pâ=â0.03) methods and lost linearity post-SRS. CONCLUSIONS: The standard cuboidal practice for following vestibular schwannoma tumor volume after SRS overestimates size. Ellipsoidal and spherical estimations have improved performance but also overestimate volume and lack reliability post-SRS. The development of other volumetric models or application of contouring software should be investigated.
Subject(s)
Neuroma, Acoustic , Radiosurgery , Humans , Neuroma, Acoustic/diagnostic imaging , Neuroma, Acoustic/radiotherapy , Neuroma, Acoustic/surgery , Reproducibility of Results , Retrospective Studies , Treatment Outcome , Tumor BurdenABSTRACT
OBJECTIVE: To analyze local control (LC) and toxicity rates between stereotactic radiosurgery (SRS) and intensity-modulated radiotherapy (IMRT) in relation to reported surgical rates in the treatment of paragangliomas (PG) in the upfront, adjuvant, and salvage settings, and to explore factors affecting tumor size reduction, toxicity rates, and symptom control. STUDY DESIGN: Retrospective cohort analysis. SETTING: Tertiary referral center. PATIENTS AND INTERVENTIONS: Thirty patients treated with either linear accelerator-based SRS or IMRT in the definitive, planned adjuvant, or unplanned salvage postsurgery settings. MAIN OUTCOME MEASURES: Local control, toxicities, symptom control, tumor size reduction, and factors affecting each. RESULTS: Median follow-up was 4.16 years. LC rates were 100%. Acute grade >3 toxicity rate was 6.7%, 86.7% of tumors had a reduction in volume, and 76.7% of patients had improvement in at least one tumor-induced symptom by last follow-up. Larger tumor size at presentation and longer time to last follow-up were significantly associated with greater tumor size reduction on multivariate analysis. CONCLUSIONS: SRS and IMRT are safe and effective treatment for PG with high efficacy and low morbidity rates in the upfront, planned adjuvant, and unplanned salvage settings.
Subject(s)
Head and Neck Neoplasms/radiotherapy , Paraganglioma/radiotherapy , Paraganglioma/therapy , Radiosurgery/methods , Radiotherapy, Intensity-Modulated/methods , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Paraganglioma/ultrastructure , Radiotherapy, Adjuvant/methods , Retrospective Studies , Salvage Therapy/methods , Treatment OutcomeABSTRACT
PURPOSE: Hypofractionated stereotactic radiotherapy (HSRT) for refractory Cushing's disease may offer a condensed treatment schedule for patients with large tumors abutting the optic chiasm unsuitable for stereotactic radiosurgery (SRS). To-date only four patients have been treated by HSRT in the published literature. We investigated the feasibility, toxicity, and efficacy of HSRT compared to SRS. METHODS: After approval, we retrospectively evaluated patients treated at our institution for refractory Cushing's disease with SRS or HSRT. Study outcomes included biochemical control, time to biochemical control, local control, and late complications. Binary logistic regression and Cox proportional hazards regression evaluated predictors of outcomes. RESULTS: Patients treated with SRS (n = 9) and HSRT (n = 9) were enrolled with median follow-up of 3.4 years. Clinicopathologic details were balanced between the cohorts. Local control was 100% in both cohorts. Time to biochemical control was 6.6. and 9.5 months in the SRS and HSRT cohorts, respectively (p = 0.6258). Two patients in each cohort required salvage bilateral adrenalectomy. Late complications including secondary malignancy, radionecrosis, cranial nerve neuropathy, and optic pathway injury were minimal for either cohort. CONCLUSIONS: HSRT is an appropriate treatment approach for refractory Cushing's disease, particularly for patients with large tumors abutting the optic apparatus. Prospective studies are needed to validate these findings and identify factors suggesting optimal fractionation approaches.