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      Resection and permanent intracranial brachytherapy using modular, biocompatible cesium-131 implants: results in 20 recurrent, previously irradiated meningiomas

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          Abstract

          OBJECTIVE

          Effective treatments for recurrent, previously irradiated intracranial meningiomas are limited, and resection alone is not usually curative. Thus, the authors studied the combination of maximum safe resection and adjuvant radiation using permanent intracranial brachytherapy (R+BT) in patients with recurrent, previously irradiated aggressive meningiomas.

          METHODS

          Patients with recurrent, previously irradiated meningiomas were treated between June 2013 and October 2016 in a prospective single-arm trial of R+BT. Cesium-131 (Cs-131) radiation sources were embedded in modular collagen carriers positioned in the operative bed on completion of resection. The Cox proportional hazards model with this treatment as a predictive term was used to model its effect on time to local tumor progression.

          RESULTS

          Nineteen patients (median age 64.5 years, range 50–78 years) with 20 recurrent, previously irradiated tumors were treated. The WHO grade at R+BT was I in 4 (20%), II in 14 (70%), and III in 2 (10%) cases. The median number of prior same-site radiation courses and same-site surgeries were 1 (range 1–3) and 2 (range 1–4), respectively; the median preoperative tumor volume was 11.3 cm 3 (range 0.9–92.0 cm 3). The median radiation dose from BT was 63 Gy (range 54–80 Gy). At a median radiographic follow-up of 15.4 months (range 0.03–47.5 months), local failure (within 1.5 cm of the implant bed) occurred in 2 cases (10%). The median treatment-site time to progression after R+BT has not been reached; that after the most recent prior therapy was 18.3 months (range 3.9–321.9 months; HR 0.17, p = 0.02, log-rank test). The median overall survival after R+BT was 26 months, with 9 patient deaths (47% of patients). Treatment was well tolerated; 2 patients required surgery for complications, and 2 experienced radiation necrosis, which was managed medically.

          CONCLUSIONS

          R+BT utilizing Cs-131 sources in modular carriers represents a potentially safe and effective treatment option for recurrent, previously irradiated aggressive meningiomas.

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          Most cited references 32

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          Dose to normal tissues outside the radiation therapy patient's treated volume: a review of different radiation therapy techniques.

           Jason J Purdy (2008)
          Radiation therapy treatment planning and delivery capabilities have changed dramatically since the introduction of three-dimensional treatment planning and are continuing to change relatively rapidly in response to the implementation of new advanced technologies. Three-dimensional conformal radiation therapy (3DCRT) is now firmly in place as the standard of practice in clinics around the world. Medical accelerator manufacturers have employed advanced computer technology to produce treatment planning/delivery systems capable of precise shaping of dose distributions via computer-controlled multileaf collimator (MLC) systems, by which the beam fluence is varied optimally to achieve the desired dose distribution. This mode of conformal therapy is referred to as intensity modulated radiation therapy (IMRT), and is capable of generating dose distributions (including concave isodose volumes) that closely conform the prescription dose to the target volume and/or avoid specific sensitive normal structures. The increasing use of IMRT has focused attention on the need to better account for the intra- and inter-fraction spatial uncertainties in the dose delivery process. This has helped spur the development of treatment machines with integrated planar and volumetric advanced imaging capabilities, providing a new treatment modality referred to as image-guided IMRT (IG-IMRT), or simply image-guided radiation therapy (IGRT). In addition, there is a growing interest in replacing x rays with protons because of the physical characteristics of the depth dose curve, which peaks at the end of particle range, and eventually with even heavier charged particles to take advantage of the greater density of energy deposition close to the Bragg peak and hence larger relative biological effectiveness (RBE). Three-dimensional CRT, IMRT and proton beam therapy all provide improved target coverage and lower doses to surrounding normal tissues as compared to the previously used two-dimensional radiation therapy techniques. However, this is achieved at the expense of a greater volume of normal tissue in the irradiated volume receiving some dose and a higher whole body dose (or peripheral dose) to distant normal tissues. The higher whole body dose is a result of the increased x-ray leakage radiation to the patient due to the longer beam-on times associated with IMRT, and also from neutron leakage radiation associated with high energy x-ray beams (>10 MV) and proton beams. Dose distributions for the various CRT techniques and the current status of available data for normal tissues, and whole body dose are reviewed.
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            Patterns in neurosurgical adverse events: intracranial neoplasm surgery.

            Neurosurgery is a high-risk specialty currently undertaking the pursuit of systematic approaches to measuring and improving outcomes. As part of a project to devise evidence-based safety interventions for specialty surgery, the authors sought to review current evidence in cranial tumor resection concerning the frequency of adverse events in practice, their patterns, and current methods of reducing the occurrence of these events. This review represents part of a series of papers written to consolidate information about these events and preventive measures as part of an ongoing effort to ascertain the utility of devising system-wide policies and safety tools to improve neurosurgical practice. The authors performed a PubMed search using search terms "intracranial neoplasm," "cerebral tumor," "cerebral meningioma," "glioma," and "complications" or "adverse events." Only papers that specifically discussed the relevant complication rates were included. Papers were chosen to maximize the range of rates of occurrence for the reported adverse events. Review of the tumor neurosurgery literature showed that documented overall complication rates ranged from 9% to 40%, with overall mortality rates of 1.5%-16%. There was a wide range of types of adverse events overall. Deep venous thromboembolism (DVT) was the most common adverse event, with a reported incidence of 3%-26%. The presence of new or worsened neurological deficit was the second most common adverse event found in this review, with reported rates ranging from 0% for the series of meningioma cases with the lowest reported rate to 20% as the highest reported rate for treatment of eloquent glioma. Benign tumor recurrence was found to be a commonly reported adverse event following surgery for intracranial neoplasms. Rates varied depending on tumor type, tumor location, patient demographics, surgical technique, the surgeon's level of experience, degree of specialization, and changes in technology, but these effects remain unmeasured. The incidence on our review ranged from 2% for convexity meningiomas to 36% for basal meningiomas. Other relatively common complications were dural closure-related complications (1%-24%), postoperative peritumoral edema (2%-10%), early postoperative seizure (1%-12%), medical complications (6%-7%), wound infection (0%-4%), surgery-related hematoma (1%-2%), and wrong-site surgery. Strategies to minimize risk of these events were evaluated. Prophylactic techniques for DVT have been widely demonstrated and confirmed, but adherence remains unstudied. The use of image guidance, intraoperative functional mapping, and real-time intraoperative MRI guidance can allow surgeons to maximize resection while preserving neurological function. Whether the extent of resection significantly correlates with improved overall outcomes remains controversial. A significant proportion of adverse events in intracranial neoplasm surgery may be avoidable by use of practices to encourage use of standardized protocols for DVT, seizure, and infection prophylaxis; intraoperative navigation among other steps; improved teamwork and communication; and concentrated volume and specialization. Systematic efforts to bundle such strategies may significantly improve patient outcomes.
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              Intracranial meningiomas of atypical (WHO grade II) histology.

              Atypical (WHO grade II) meningiomas occupy an intermediate risk group between benign (WHO grade I) and anaplastic (WHO grade III) meningiomas. Although grade II meningiomas have traditionally been recognized in only about 5% of cases, after changes in diagnostic criteria with the current 2007 WHO standards, they now comprise approximately 20-35% of all meningiomas. Given the magnitude of this change, much work is now needed to solidify the adoption of these standards, to render inter-observer and inter-institutional comparisons more uniform, and to more carefully define the incidence of grade II histology. However, it is clear that they carry a several-fold increased risk of recurrence, as well as an increased rate of mortality. We will discuss the definition, diagnosis, and treatment of patients with atypical meningioma; review the current phase II cooperative trials; and draw attention to some questions timely for pre-clinical and clinical research.
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                Author and article information

                Journal
                Journal of Neurosurgery
                Journal of Neurosurgery Publishing Group (JNSPG)
                0022-3085
                1933-0693
                December 2019
                December 2019
                : 131
                : 6
                : 1819-1828
                Affiliations
                [1 ]Departments of 1Radiation Oncology,
                [2 ]3Neurology, Barrow Neurological Institute, and
                [3 ]2Neurosurgery, and
                [4 ]4St. Joseph’s Hospital and Medical Center, Phoenix, Arizona; and
                [5 ]5Lovelace Medical Center, Albuquerque, New Mexico
                Article
                10.3171/2018.7.JNS18656
                30579269
                © 2019

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