The presentation of brain metastases in melanoma, non-small cell lung cancer, and breast cancer and potential implications for screening brain MRIs.

PURPOSE: This study assessed the presentation and institutional outcomes treating brain metastases (BM) of breast cancer (BC), non-small cell lung cancer (NSCLC), and melanoma origin. METHODS: Patients with brain metastases treated between 2014 and 2019 with primary melanoma, NSCLC, and BC were identified. Overall survival (OS) was calculated from dates of initial BM diagnosis using the Kaplan-Meier method. RESULTS: A total of 959 patients were identified including melanoma (31%), NSCLC (51%), and BC (18%). Patients with BC were younger at BM diagnosis (median age: 57) than NSCLC (65) and melanoma patients (62, p < 0.0001). Breast cancer patients were more likely to present with at least 5 BM (27%) than NSCLC (14%) and melanoma (13%), leptomeningeal disease (23%, 6%, and 6%, p = 0.0004) and receive whole brain radiation therapy (WBRT) (58%, 37%, and 22%, p < 0.0001). There were no differences in surgical resection (24%, 24%, and 29%, p = 0.166). Median OS was shorter for BC patients (9.9, 10.3, and 13.7 months, p = 0.0006). CONCLUSION: Breast cancer patients were more likely to be younger, present with advanced disease, require WBRT, and have poorer OS than NSCLC and melanoma patients. Further investigation is needed to determine which BC patients are at sufficient risk for brain MRI screening.

Management of brain metastases in breast cancer: a review of current practices and emerging treatments.

PURPOSE: Breast cancer brain metastases (BCBM) are becoming an increasingly common diagnosis due to improved systemic control and more routine surveillance imaging. Treatment continues to require a multidisciplinary approach managing systemic and intracranial disease burden. Although, improvements have been made in the diagnosis and management of BCBM, brain metastasis patients continue to pose a challenge for practitioners. METHODS: In this review, a group of medical oncologists, radiation oncologists, radiologists, breast surgeons, and neurosurgeons specializing in the treatment of breast cancer reviewed the available published literature and compiled a comprehensive review on the current state of BCBM. RESULTS: We discuss the pathogenesis, epidemiology, diagnosis, treatment options (including systemic, surgical, and radiotherapy treatment modalities), and treatment response evaluation for BCBM. Furthermore, we discuss the ongoing prospective trials enrolling BCBM patients and their biologic rationale. CONCLUSIONS: BCBM management is an increasing clinical concern. Multidisciplinary management combining the strengths of surgical, systemic, and radiation treatment modalities with prospective trials incorporating knowledge from the basic and translational sciences will ultimately lead to improved clinical outcomes for BCBM patients.

Breast leptomeningeal disease: a review of current practices and updates on management.

PURPOSE: Leptomeningeal disease (LMD) is an advanced metastatic disease presentation portending a poor prognosis with minimal treatment options. The advent and widespread use of new systemic therapies for metastatic breast cancer has improved systemic disease control and extended survival; however, as patients live longer, the rates of breast cancer LMD are increasing. METHODS: In this review, a group of medical oncologists, radiation oncologists, radiologists, breast surgeons, and neurosurgeons specializing in treatment of breast cancer reviewed the available published literature and compiled a comprehensive review on the current state of breast cancer LMD. RESULTS: We discuss the pathogenesis, epidemiology, diagnosis, treatment options (including systemic, intrathecal, surgical, and radiotherapy treatment modalities), and treatment response evaluation specific to breast cancer patients. Furthermore, we discuss the controversies within this unique clinical setting and identify potential clinical opportunities to improve upon the diagnosis, treatment, and treatment response evaluation in the management of breast LMD. CONCLUSIONS: We recognize the shortcomings in our current understanding of the disease and explore the future role of genomic/molecular disease characterization, technological innovations, and ongoing clinical trials attempting to improve the prognosis for this advanced disease state.

CDK 4/6 inhibitors and stereotactic radiation in the management of hormone receptor positive breast cancer brain metastases.

PURPOSE: Cyclin-dependent kinase (CDK) 4/6 inhibitors are becoming increasingly utilized in the setting of advanced, hormone receptor (HR+) positive breast cancer. Pre-clinical data suggests a potential synergy between radiation therapy (RT) and CDK4/6 inhibitors. We assessed clinical outcomes of patients treated at our institution with the use of CDK4/6 inhibitors and stereotactic radiation in the management of HR+ breast brain metastases. METHODS: A retrospective analysis of patients who received stereotactic radiotherapy for HR+ brain metastases within 6 months of CDK4/6 inhibitor administration was performed. The primary endpoint was neurotoxicity during or after stereotactic radiation. Secondary endpoints were local brain control, distant brain control, and overall survival (OS). RESULTS: A total of 42 lesions treated with stereotactic radiation in 15 patients were identified. Patients received either palbociclib (n = 10; 67%) or abemaciclib (n = 5; 33%). RT was delivered concurrently, before, or after CDK4/6 inhibitors in 18 (43%), 9 (21%), and 15 (36%) lesions, respectively. Median follow-up following stereotactic radiation was 9 months. Two lesions (5%) developed radionecrosis, both of which received four prior RT courses to the affected lesion prior to onset of radionecrosis and subsequently managed with steroids and bevacizumab. Six- and 12-month local control of treated lesions was 88% and 88%, while 6- and 12-month distant brain control was 61% and 39%, respectively. Median OS was 36.7 months from the date of brain metastases diagnosis. CONCLUSIONS: Stereotactic radiation to breast brain metastases was well tolerated alongside CDK4/6 inhibitors. Compared to historical data, brain metastases control rates are similar whereas survival appears prolonged.

Outcomes targeting the PD-1/PD-L1 axis in conjunction with stereotactic radiation for patients with non-small cell lung cancer brain metastases.

Anti-PD-1/PD-L1 therapies have demonstrated activity in patients with advanced stage non-small cell lung cancer (NSCLC). However, little is known about the safety and feasibility of patients receiving anti-PD-1/PD-L1 therapy and stereotactic radiation for the treatment of brain metastases. Data were analyzed retrospectively from NSCLC patients treated with stereotactic radiation either before, during or after anti-PD-1/PD-L1 therapy with nivolumab (anti-PD-1) or durvalumab (anti-PD-L1). Seventeen patients treated with stereotactic radiosurgery (SRS) or fractionated stereotactic radiation therapy (FSRT) to 49 brain metastases over 21 sessions were identified. Radiation was administered prior to, during and after anti-PD-1/PD-L1 therapy in 22 lesions (45%), 13 lesions (27%), and 14 lesions (29%), respectively. The 6 months Kaplan-Meier (KM) distant brain control rate was 48% following stereotactic radiation. Six and 12 month KM rates of OS from the date of stereotactic radiation and the date of cranial metastases diagnosis were 48/41% and 81/51%, respectively. The 6 month rate of distant brain control following stereotactic radiation for patients treated with stereotactic radiation during or prior to anti-PD-1/PD-L1 therapy was 57% compared to 0% among patients who received anti-PD-1/PD-L1 therapy before stereotactic radiation (p = 0.05). A Karnofsky Performance Status (KPS) of <90 was found to be predictive of worse OS following radiation treatment on both univariate and multivariate analyses (MVA, p = 0.01). In our series, stereotactic radiation to NSCLC brain metastases was well tolerated in patients who received anti-PD-1/PD-L1 therapy. Prospective evaluation to determine how these two modalities can be used synergistically to improve distant brain control and OS is warranted.

Multimodal Imaging of Head and Neck Squamous Cell Carcinoma.

BACKGROUND: The role of imaging in the staging, treatment planning, and ongoing surveillance of patients with head and neck squamous cell carcinoma (HNSCC) continues to evolve. Changes in patient demographics, treatment paradigms, and technology present opportunities and challenges for the management of HNSCC. METHODS: The general indications and usage of standard and multimodal cross-sectional imaging in the evaluation and management of HNSCC are reviewed, with an emphasis on incorporating them into treatment pathways. Emerging imaging technologies and methods with a potential near-term impact on HNSCC are discussed. RESULTS: In general, the complex, multidisciplinary approach to the treatment of advanced HNSCC requires multimodal imaging for adequate treatment planning and follow up. Early-stage disease can often be managed with clinical and endoscopic examinations and a single, cross-sectional imaging modality (eg, computed tomography, magnetic resonance imaging). CONCLUSIONS: Although generalized treatment pathways and guidelines do exist, the literature is rapidly advancing and new radiotracers and evaluation methods are expected to alter both imaging and treatment recommendations in the years to come.

Assessing Response of High-Grade Gliomas to Immune Checkpoint Inhibitors.

BACKGROUND: Immunotherapeutic agents, especially checkpoint inhibitors, have emerged as the mainstay of therapy for several solid and hematological malignancies. These therapies are under investigation for the treatment of high-grade gliomas and brain metastases. METHODS: This article reviews the unique challenges encountered when evaluating changes on magnetic resonance imaging (MRI) of glioblastomas seen in response to immunotherapy and checkpoint inhibitors and how to effectively incorporate MRI findings into the response assessment of high-grade gliomas to these emerging therapies. RESULTS: An increase in tumor size or the appearance of new lesions on MRI may represent either an immune-mediated inflammatory response or true tumor progression, which may precede the subsequent stabilization or response of high-grade gliomas to immunotherapy. These MRI findings should not result in the mandatory cessation of immunotherapy in patients with high-grade glioma. CONCLUSIONS: Although immunotherapy Response Assessment for Neuro-Oncology criteria have been developed to assist with response assessment of high-grade gliomas to immunotherapy and to provide guidance with treatment decisions, these criteria have not been validated in prospective clinical trials. In patients with brain tumors who are receiving immunotherapy, MRI findings suggestive of disease progression should be evaluated with caution to prevent premature discontinuation of potentially beneficial therapies. Close, clinical monitoring with appropriate short-term, follow-up imaging is often necessary, and histopathological analysis may be required in some cases to confirm disease progression before a decision on continuation of these novel therapies can accurately be made.

Rules-based Volumetric Segmentation of Multiparametric MRI for Response Assessment in Recurrent High-Grade Glioma.

We report domain knowledge-based rules for assigning voxels in brain multiparametric MRI (mpMRI) to distinct tissuetypes based on their appearance on Apparent Diffusion Coefficient of water (ADC) maps, T1-weighted unenhanced and contrast-enhanced, T2-weighted, and Fluid-Attenuated Inversion Recovery images. The development dataset comprised mpMRI of 18 participants with preoperative high-grade glioma (HGG), recurrent HGG (rHGG), and brain metastases. External validation was performed on mpMRI of 235 HGG participants in the BraTS 2020 training dataset. The treatment dataset comprised serial mpMRI of 32 participants (total 231 scan dates) in a clinical trial of immunoradiotherapy in rHGG (NCT02313272). Pixel intensity-based rules for segmenting contrast-enhancing tumor (CE), hemorrhage, Fluid, non-enhancing tumor (Edema1), and leukoaraiosis (Edema2) were identified on calibrated, co-registered mpMRI images in the development dataset. On validation, rule-based CE and High FLAIR (Edema1 + Edema2) volumes were significantly correlated with ground truth volumes of enhancing tumor (R = 0.85;p < 0.001) and peritumoral edema (R = 0.87;p < 0.001), respectively. In the treatment dataset, a model combining time-on-treatment and rule-based volumes of CE and intratumoral Fluid was 82.5% accurate for predicting progression within 30 days of the scan date. An explainable decision tree applied to brain mpMRI yields validated, consistent, intratumoral tissuetype volumes suitable for quantitative response assessment in clinical trials of rHGG.

Bacillus Cereus bacteremia complicated by brain abscess in a severely immunocompromised patient: Addressing importance of early recognition and challenges in diagnosis.

Bacillus cereus (B. cereus) is a known cause of a food poisoning in the general population. However, it can cause life-threatening sepsis and shock in severely immunocompromised patients with hematologic malignancies, which frequently lead to central nervous system (CNS) infections associated with high mortality and morbidity. In this case report, we describe a patient with a newly diagnosed acute myeloid leukemia that underwent induction chemotherapy and developed B. cereus infection that was associated with septic shock and brain abscesses. Definitive diagnosis of multiple brain abscesses was not manifested with routine microbiological investigation but required the use of 16S ribosomal (rRNA) gene polymerase chain reaction (PCR) sequencing of the resected brain lesion. The patient was eventually treated with 8-week course of intravenous vancomycin and high-dose ciprofloxacin which led to a full recovery. This report highlights the significant risk posed by B. cereus infection in neutropenic patients, the use of 16S rRNA PCR sequencing test for definitive diagnosis and use of combination therapy for successful treatment of B. Cereus CNS infection.

Spontaneous Spinal Subdural Hematoma Secondary to Hemophilia A and Zanubrutinib.

Spontaneous spinal subdural hematomas (SSH) are rare occurrences that can occur most commonly secondary to vascular malformations or coagulopathies. Only a small fraction of spontaneous SSHs are caused by acquired coagulation disorders such as leukemia, hemophilia, and thrombocytopenia. This case report describes a patient with a history of Guillain-Barré syndrome (GBS), hemophilia A, and mantle cell lymphoma, on zanubrutinib therapy, a Bruton tyrosine kinase inhibitor associated with a risk of spontaneous hemorrhage. This patient developed a spontaneous spinal subdural hematoma, most likely due to the zanubrutinib therapy and exacerbated due to hemophilia. Treatment was delayed due to the patient's history of GBS that confounded the clinical diagnosis. This case is the first report of a spontaneous SSH in a patient on zanubrutinib, highlighting the need for a high index of suspicion for CNS hemorrhage in patients on Bruton's tyrosine kinase (BTK) inhibitor therapy.

Molecular determinants of outcomes in meningiomas.

Meningiomas are the most common intracranial primary tumor in adults. Surgery is the predominant therapeutic modality for symptomatic meningiomas. Although the majority of meningiomas are benign, there exists a subset of meningiomas that are clinically aggressive. Recent advances in genetics and epigenetics have uncovered molecular alterations that drive tumor meningioma biology with prognostic and therapeutic implications. In this review, we will discuss the advances on molecular determinants of therapeutic response in meningiomas to date and discuss findings of targeted therapies in meningiomas.

Surgical and anatomic factors predict development of leptomeningeal disease in patients with melanoma brain metastases.

BACKGROUND: Leptomeningeal disease (LMD) is a devastating complication of systemic malignancy, of which there is an unclear etiology. The aim of this study is to determine if surgical or anatomic factors can predict LMD in patients with metastatic melanoma. METHODS: A retrospective chart review was performed of 1162 patients treated at single institution for melanoma brain metastases (MBM). Patients with fewer than 3 months follow-up or lacking appropriate imaging were excluded. Demographic information, surgical, and anatomic data were collected. RESULTS: Eight hundred and twenty-seven patients were included in the final review. On multivariate analysis for the entire cohort, female gender, dural-based and intraventricular metastasis, and tumor bordering CSF spaces were associated with increased risk of LMD. Surgical resection was not significant for risk of LMD. On multivariate analysis of patients who have undergone surgical resection of a metastatic tumor, dural-based and intraventricular metastasis, ventricular entry during surgery, and metastasis in the infratentorial space were associated with increased risk of LMD. On multivariate analysis of patients who did not undergo surgery, chemotherapy after initial diagnosis and metastasis bordering CSF spaces were associated with increased risk of LMD. CONCLUSION: In a single-institution cohort of MBM, we found that surgical resection alone did not result in an increased risk of LMD. Anatomical factors such as dural-based and intraventricular metastasis were significant for developing LMD, as well as entry into a CSF space during surgical resection. These data suggest a strong correlation between anatomic location and tumor cell seeding in relation to the development of LMD.

Resorption and remodeling of hydroxyapatite-poly-L-lactic acid composite anterior cruciate ligament interference screws.

PURPOSE: The purpose of this study was to evaluate the progression of hydroxyapatite-poly-L-lactic acid (HA-PLLA) interference screw resorption and remodeling in patients after anterior cruciate ligament (ACL) reconstruction. METHODS: Sixty-five patients undergoing ACL reconstruction with patellar tendon autograft or allograft fixed at both the femur and tibia with HA-PLLA screws were evaluated. We evaluated 10 patients each at 2, 3, and 4 years postoperatively, whereas 35 patients were evaluated at 5 years postoperatively. In all patients a physical examination was performed and functional outcome scores and computed tomography (CT) analysis were obtained at follow-up. RESULTS: Screw tract densities determined by CT at 5 years postoperatively were higher than muscle and were similar to the surrounding bone. At 4 years, 80% to 90% of screws were completely resorbed. At 5-year follow-up, 29% of patients showed complete ossification of the screw tract in the femur versus 34% in the tibia. There was no tunnel widening or sclerosis noted. Subjective and objective clinical results remained high throughout the study period. CONCLUSIONS: The HA-PLLA interference screws are slowly resorbed over time, and the majority are completely resorbed between 3 and 4 years after ACL reconstruction with patellar tendon autograft or allograft. Osteoconductivity and remodeling were confirmed by CT scans, and no tunnel widening, sclerosis, cysts, or inflammatory changes were noted. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Hypofractionated stereotactic re-irradiation with pembrolizumab and bevacizumab in patients with recurrent high-grade gliomas: results from a phase I study.

BACKGROUND: Radiotherapy may synergize with programmed cell death 1 (PD1)/PD1 ligand (PD-L1) blockade. The purpose of this study was to determine the recommended phase II dose, safety/tolerability, and preliminary efficacy of combining pembrolizumab, an anti-PD1 monoclonal antibody, with hypofractionated stereotactic irradiation (HFSRT) and bevacizumab in patients with recurrent high-grade gliomas (HGGs). METHODS: Eligible subjects with recurrent glioblastoma or anaplastic astrocytoma were treated with pembrolizumab (100 or 200 mg based on dose level Q3W) concurrently with HFSRT (30 Gy in 5 fractions) and bevacizumab 10 mg/kg Q2W. RESULTS: Thirty-two patients were enrolled (bevacizumab-naïve, n = 24; bevacizumab-resistant, n = 8). The most common treatment-related adverse events (TRAEs) were proteinuria (40.6%), fatigue (25%), increased alanine aminotransferase (25%), and hypertension (25%). TRAEs leading to discontinuation occurred in 1 patient who experienced a grade 3 elevation of aspartate aminotransferase. In the bevacizumab-naïve cohort, 20 patients (83%) had a complete response or partial response. The median overall survival (OS) and progression-free survival (PFS) were 13.45 months (95% CI: 9.46-18.46) and 7.92 months (95% CI: 6.31-12.45), respectively. In the bevacizumab-resistant cohort, PR was achieved in 5 patients (62%). Median OS was 9.3 months (95% CI: 8.97-18.86) with a median PFS of 6.54 months (95% CI: 5.95-18.86). The majority of patients (n = 20/26; 77%) had tumor-cell/tumor-microenvironment PD-L1 expression <1%. CONCLUSIONS: The combination of HFSRT with pembrolizumab and bevacizumab in patients with recurrent HGG is generally safe and well tolerated. These findings merit further investigation of HFSRT with immunotherapy in HGGs.

Nivolumab and Stereotactic Radiosurgery for Patients With Breast Cancer Brain Metastases: A Nonrandomized, Open-Label Phase 1b Study.

PURPOSE: We hypothesize treatment with nivolumab and stereotactic radiosurgery (SRS) will be feasible and well tolerated, and may improve intracranial tumor control rates compared with SRS alone. METHODS AND MATERIALS: The study was designed as a prospective, single-arm, nonrandomized, open-label, phase 1b trial of nivolumab and SRS among patients with metastatic breast cancer brain metastases. Key eligibility criteria included patients with breast cancer brain metastases of all subtypes, age ≥18, Eastern Cooperative Oncology Group Performance Status ≤2 with ≤10 brain metastases. Treatment was initiated with a dose of nivolumab (480 mg intravenously) that was repeated every 4 weeks. The initial dose of nivolumab was followed 1 week later by SRS. This study is closed to accrual and is registered with ClinicalTrials.gov, NCT03807765. RESULTS: Between February 2019 and July 2020, a total of 12 patients were treated to 17 lesions. No dose limiting toxicities were noted in our patient population. The most common neurologic adverse events included grade 1 to 2 headaches and dizziness occurring in 5 (42%) of patients. Median intracranial control was 6.2 months (95% confidence interval, 3-14 months) with 6- and 12-month control rates of 55% and 22%, respectively. A total of 4 patients had systemic progression during the study. Median time to systemic progression free survival has not been reached with 6- and-12 month rates of 63% and 51%, respectively. CONCLUSIONS: Nivolumab and SRS is a safe and feasible treatment option in breast cancer brain metastases. Preliminary data reveals activity in certain breast cancer patients to study therapy.

Tumor Volume Dynamics as an Early Biomarker for Patient-Specific Evolution of Resistance and Progression in Recurrent High-Grade Glioma.

Recurrent high-grade glioma (HGG) remains incurable with inevitable evolution of resistance and high inter-patient heterogeneity in time to progression (TTP). Here, we evaluate if early tumor volume response dynamics can calibrate a mathematical model to predict patient-specific resistance to develop opportunities for treatment adaptation for patients with a high risk of progression. A total of 95 T1-weighted contrast-enhanced (T1post) MRIs from 14 patients treated in a phase I clinical trial with hypo-fractionated stereotactic radiation (HFSRT; 6 Gy × 5) plus pembrolizumab (100 or 200 mg, every 3 weeks) and bevacizumab (10 mg/kg, every 2 weeks; NCT02313272) were delineated to derive longitudinal tumor volumes. We developed, calibrated, and validated a mathematical model that simulates and forecasts tumor volume dynamics with rate of resistance evolution as the single patient-specific parameter. Model prediction performance is evaluated based on how early progression is predicted and the number of false-negative predictions. The model with one patient-specific parameter describing the rate of evolution of resistance to therapy fits untrained data ( R 2 = 0.70 ). In a leave-one-out study, for the nine patients that had T1post tumor volumes ≥1 cm3, the model was able to predict progression on average two imaging cycles early, with a median of 9.3 (range: 3-39.3) weeks early (median progression-free survival was 27.4 weeks). Our results demonstrate that early tumor volume dynamics measured on T1post MRI has the potential to predict progression following the protocol therapy in select patients with recurrent HGG. Future work will include testing on an independent patient dataset and evaluation of the developed framework on T2/FLAIR-derived data.

Leptomeningeal disease in melanoma patients: An update to treatment, challenges, and future directions.

In February 2018, the Melanoma Research Foundation and the Moffitt Cancer Center hosted the Second Summit on Melanoma Central Nervous System Metastases in Tampa, Florida. The meeting included investigators from multiple academic centers and disciplines. A consensus summary of the progress and challenges in melanoma parenchymal brain metastases was published (Eroglu et al., Pigment Cell & Melanoma Research, 2019, 32, 458). Here, we will describe the current state of basic, translational, clinical research, and therapeutic management, for melanoma patients with leptomeningeal disease. We also outline key challenges and barriers to be overcome to make progress in this deadly disease.

Deep neural network to locate and segment brain tumors outperformed the expert technicians who created the training data.

Purpose: Deep learning (DL) algorithms have shown promising results for brain tumor segmentation in MRI. However, validation is required prior to routine clinical use. We report the first randomized and blinded comparison of DL and trained technician segmentations. Approach: We compiled a multi-institutional database of 741 pretreatment MRI exams. Each contained a postcontrast T1-weighted exam, a T2-weighted fluid-attenuated inversion recovery exam, and at least one technician-derived tumor segmentation. The database included 729 unique patients (470 males and 259 females). Of these exams, 641 were used for training the DL system, and 100 were reserved for testing. We developed a platform to enable qualitative, blinded, controlled assessment of lesion segmentations made by technicians and the DL method. On this platform, 20 neuroradiologists performed 400 side-by-side comparisons of segmentations on 100 test cases. They scored each segmentation between 0 (poor) and 10 (perfect). Agreement between segmentations from technicians and the DL method was also evaluated quantitatively using the Dice coefficient, which produces values between 0 (no overlap) and 1 (perfect overlap). Results: The neuroradiologists gave technician and DL segmentations mean scores of 6.97 and 7.31, respectively ( p < 0.00007 ). The DL method achieved a mean Dice coefficient of 0.87 on the test cases. Conclusions: This was the first objective comparison of automated and human segmentation using a blinded controlled assessment study. Our DL system learned to outperform its "human teachers" and produced output that was better, on average, than its training data.

Percutaneous Vertebroplasty: A History of Procedure, Technology, Culture, Specialty, and Economics.

Percutaneous vertebroplasty (VP) progressed from a virtually unknown procedure to one performed on hundreds of thousands of patients annually. The development of VP provides a historically exciting case study into a rapidly adopted procedure. VP was the synthesis of information gained from spinal biopsy developments, the inception of biomaterials used in medicine, and the unique health care climate in France during the 1980s. It was designed as a revolutionary technique to treat vertebral body fractures with minimal side effects and was rapidly adopted and marketed in the United States. The impact of percutaneous vertebroplasty on spine surgery was profound.