Repeat single-fraction stereotactic radiosurgery for recurrent vestibular schwannoma.

Background: Data are scarce on the efficacy of a second radiosurgery (SRS) treatment of vestibular schwannoma that has progressed following initial treatment with SRS. We sought to report the outcome of our repeat SRS series with long-term imaging follow-up. Materials and methods: We retrospectively analyzed 6 patients who met the following criteria: Repeat SRS at our institution between 1995 and 2018; solitary unilateral tumor; no evidence of neurofibromatosis; and magnetic resonance (MR) planning for both SRS treatments. All treatments were delivered with a linear accelerator-based system using head frame immobilization. The prescribed dose to the periphery of the tumor was 12.5 Gy in all initial and repeat SRS treatments, except for one repeat treatment to 10 Gy. Results: Follow-up with MR scan following the second SRS treatment was a median 8.4 years. The tumor control rate (lack of progression) following the second SRS treatment was 83% (5/6). Actuarial 10-year outcomes following repeat SRS were: tumor control, 80%; absolute survival, 80%; and cause-specific survival, 100%. Of the patients with at least minimal hearing retention before initial SRS, none had ipsilateral hearing preservation after initial radiation treatment. Improvement in any pretreatment cranial nerve deficits was not seen. The only permanent grade ≥ 3 toxicity from repeat SRS was a case of infraorbital nerve deficit. No patient developed a stroke, malignant transformation, induced second tumor, or facial nerve deficit. Conclusion: There was excellent overall survival, tumor control, and low morbidity in our series for recurrent vestibular schwannoma submitted to repeat single-fraction SRS, supporting additional studies of this treatment strategy.

The risk of malignancy anywhere in the body after linear accelerator (LINAC) stereotactic radiosurgery.

BACKGROUND: Despite the conformity of stereotactic radiosurgery (SRS) treatment, there are concerns about the risk of malignancy. OBJECTIVE: We compared the number of cancer cases observed after treatment in a group of SRS patients to the number of cancer cases that would be expected in an age- and gender-matched group. METHODS: We collected data from the University of Florida SRS database for patients treated for meningiomas, intracranial schwannomas, arteriovenous malformations (AVMs), trigeminal neuralgia, pituitary adenomas, cavernous angiomas, and metastases. We used the Florida Cancer Data System (FCDS) to determine the actual cancer rates for SRS-treated patients, and we compared these to the cancer rates in similar groups of non-SRS-treated patients based on rates available from the SEER (surveillance epidemiology and end results) database. RESULTS: A total of 2,369 patients were analyzed. Of these, 862 were patients with metastases who were analyzed only to ensure the sensitivity of using the FCDS to determine malignancy rates. The results for patients with more than 5 years of follow-up are reported. Without the metastases patients, a total of 627 patients had more than 5 years of follow-up data. Follow-up in patient-years was 1,711 for the meningioma patients, 1,851 for the schwannoma patients, 1,407 for the AVM patients and 338 for patients with a diagnosis of 'other'. The observed cancer rate in the meningioma patients was 3.96% compared to the expected rate of 10% (binomial 95% confidence interval, CI = 1.85-7.94). The observed cancer rate in the schwannoma patients was 4.93% compared to the expected rate of 12.5% (95% CI = 2.61-8.89). The observed cancer rate in the AVM patients was 3.64% compared to the expected rate of 4.43% (95% CI = 1.49-8.10). The observed cancer rate in patients treated for other diagnoses (e.g. pituitary adenoma or trigeminal neuralgia) was 0% compared to the expected rate of 6.36% (95% CI = 0-11.7). CONCLUSIONS: In a large population of SRS-treated patients, there was no increased risk of malignancy compared to the general population.

Intracranial arteriovenous malformation in a college football player and return-to-play considerations.

: The reported prevalence rates of arteriovenous malformations (AVMs) in the general population range from 0.001% to 0.50%. The following case describes the initial presentation of hemorrhage from an intracranial AVM in an 18-year-old college football player. It also discusses treatment of the AVM with stereotactic radiosurgery and successful return to football 17 months after radiosurgery (18.5 months after initial presentation). It is the first published description of return to contact sports after stereotactic radiosurgery for intracranial AVM.

Stereotactic Radiosurgery for Vestibular Schwannoma With Radiographic Brainstem Compression.

OBJECTIVE: The safety of single-treatment stereotactic radiosurgery (SRS) for vestibular schwannoma (VS) with radiographic evidence of brainstem compression but without motor deficit is controversial. Data on linear accelerator (linac)-based SRS in this setting are scarce. We address this with an outcomes report from an unselected series of patients with VS with radiographic brainstem compression treated with linac SRS. METHODS: We included 139 patients with unilateral VS (any size) with radiographic brainstem compression (all without serious brainstem neurological deficits). The SRS prescription dose was 12.5 Gy (single fraction) using 6MV linac-produced photon beams, delivered with a multiple arc technique. Inclusion criteria required at least 1 year of radiographic follow-up with magnetic resonance imaging. The primary endpoint was freedom from serious brainstem toxicity (≥grade 3 Common Terminology Criteria for Adverse Events v5); the secondary was freedom from enlargement (tumor progression or any requiring intervention). We assessed serious cranial nerve complications, excluding hearing loss, defined as Common Terminology Criteria for Adverse Events v5 grade 3 toxicity. RESULTS: Median magnetic resonance imaging follow-up time was 5 years, and median tumor size was 2.5 cm in greatest axial dimension and 5 ml in volume. The median brainstem D0.03 ml=12.6 Gy and median brainstem V10 Gy=0.4 ml. At 5 years, the actuarial freedom from serious brainstem toxicity was 100%, and freedom from tumor enlargement (requiring surgery and/or due to progression) was 90%. Severe facial nerve damage in patients without tumor enlargement was 0.9%. CONCLUSION: Linac-based SRS, as delivered in our series for VS with radiographic brainstem compression, is safe and effective.

Radiographic response of brain metastasis after linear accelerator radiosurgery.

BACKGROUND: Radiographic response of brain metastasis to stereotactic radiosurgery (SRS) over time has not been well characterized. Being able to predict SRS-induced changes in tumor size over time may allow improved counseling of patients and potentially earlier recognition of poor response to SRS. OBJECTIVE: To quantify the rate of change in size of metastatic brain tumors after treatment with a linear accelerator (LINAC) SRS. METHODS: We performed a retrospective analysis of patients with single metastatic brain tumors treated with LINAC SRS at the University of Florida between 1992 and 2009 who had at least one MRI after treatment. A total of 218 patients with 406 follow-up MRI scans were included in the study. Tumor area was calculated by measuring the largest tumor area on axial imaging and using the equation for area of an ellipse. Primary outcome was percent change in tumor size. The contribution of several factors including gender, primary tumor histology, synchronous or asynchronous presentation, prior treatment, primary tumor control, and SRS dose were examined using multivariate analysis. RESULTS: Mean patient age was 58.3 years (range 4-86), and 48.6% of patients were female. Sixty-three percent of patients had primary tumor control and 70.6% had asynchronous presentation of their brain metastases. SRS peripheral dose range was 1,000-2,250 cGy with a median of 1,750 cGy. The mean percent size change was -22.6% with a mean rate of change of -7.0% per month. The median percent change was -49.7% with a median rate of change of -8.8% per month. The median follow-up was 4.8 months (range 0.3-52.5). Female gender and melanoma histology were found to be significant predictors of an increase in tumor size. Lack of previous surgical resection was a significant predictor of a decrease in tumor size after SRS. Other factors tested with multivariate analysis, including age, synchronicity of presentation, dose, dose volume, Karnofsky performance score, and primary tumor control, were not significant in predicting tumor size change after SRS. CONCLUSION: In this study, brain metastases decreased in size by a median of 50% for a median follow-up of 4.8 months after SRS. The overall rate of decrease was 9% per month after treatment with SRS. Melanoma histology was a predictor of poor tumor control.

Reducing ventriculostomy-related infections to near zero: the eliminating ventriculostomy infection study.

Implementation of a standard protocol and use of antibiotic-coated ventricular catheters helped reduce EVD-related infections from 9.2% to almost zero at the University of Florida. This project demonstrated the success of creating a task force to identify areas of improvement, implement solutions, and monitor the outcomes.

Nucleus caudalis dorsal root entry zone lesions: a clinical-radiographic case report.

OBJECTIVE: The purpose of this paper is to report on a case of a successful dorsal root entry zone procedure done for the treatment of postherpetic neuralgia and to provide unique MRI documentation outlining the precise location of the surgical lesion. CLINICAL PRESENTATION: A 79-year-old female presented with postherpetic neuralgia in the left V1 distribution following a herpes zoster infection in that area 7 weeks earlier. She described the pain as constant, burning, aching, and throbbing, rating it as a 10 on a scale from 1 to 10. Prior to surgery, the patient was on large doses of narcotics, which were causing her to be severely somnolent. INTERVENTION OR TECHNIQUE: A dorsal root entry zone electrode with 2 mm of exposed tip was sequentially inserted into the dorsal root entry zone where 30-second, 80-degree lesions were made. The lesions were superficially continuous over the entire dorsal root entry zone from the upper cervical region to the obex. The postherpetic pain completely resolved immediately after surgery and the patient continued to have total pain relief 1 year later. An MRI performed 2 weeks after surgery clearly showed the location of the lesions. CONCLUSION: This unique clinical radiographic correlation shows that a nucleus caudalis dorsal root entry zone lesion, performed according to the described procedure, will be largely confined to the nucleus caudalis.

Linear accelerator radiosurgery for cavernous sinus meningiomas.

OBJECTIVE: In this paper, the authors review the results of a single-center experience using linear accelerator (LINAC) radiosurgery for the treatment of cavernous sinus meningiomas. METHODS: This is a retrospective analysis with a median follow-up of 50 months. All patients were treated on an outpatient basis. Fifty-five patients were treated and 6 patients were lost to follow-up. Changes in preradiosurgery cranial nerve deficits and symptoms as well as actuarial local tumor control were evaluated. RESULTS: The actuarial local tumor control was 100% at 5 years and 98% at 10 years. One patient had enlargement of tumor. Sixty-five percent had improvement in preradiosurgery cranial nerve deficits, 31% were unchanged and 1 patient (3.5%) was worse. Only 1 patient developed a new neurologic deficit. CONCLUSIONS: This is the largest LINAC radiosurgery experience for cavernous sinus meningiomas reported to date. Radiosurgery appears to offer greatly superior tumor control and much lower morbidity than surgical resection of cavernous sinus meningiomas.

Stereotactic radiosurgery and the linear accelerator: accelerating electrons in neurosurgery.

The search for efficacious, minimally invasive neurosurgical treatment has led to the development of the operating microscope, endovascular treatment, and endoscopic surgery. One of the most minimally invasive and exciting discoveries is the use of targeted, high-dose radiation for neurosurgical disorders. Radiosurgery is truly minimally invasive, delivering therapeutic energy to an accurately defined target without an incision, and has been used to treat a wide variety of pathological conditions, including benign and malignant brain tumors, vascular lesions such as arteriovenous malformations, and pain syndromes such as trigeminal neuralgia. Over the last 50 years, a tremendous amount of knowledge has been garnered, both about target volume and radiation delivery. This review covers the intense study of these concepts and the development of linear accelerators to deliver stereotactic radiosurgery. The fascinating history of stereotactic neurosurgery is reviewed, and a detailed account is given of the development of linear accelerators and their subsequent modification for radiosurgery.

Rapid fabrication of custom patient biopsy guides.

Image guided surgery is currently performed using frame-based as well as frameless approaches. In order to reduce the invasive nature of stereotactic guidance as well as to reduce the cost in both equipment and time required within the operating room we investigated the use of rapid prototyping (RP) technology. In our approach we fabricated custom patient specific face-masks and guides that can be applied to the patient during surgery. These guides provide a stereotactic reference for the accurate placement of surgical tools to a pre-planned target along a pre-planned trajectory. While the use of RP machines has previously been shown to be satisfactory for the accuracy standpoint, one of our design criteria, completing the entire built and introduction into the sterile field in less than 120 minutes, was unobtainable. Our primary problems were the fabrication time and the non-resistance of the built material to high-temperature sterilization. In the current study, we have investigated the use of subtractive rapid prototyping (SRP) machines to perform the same quality of surgical guidance while improving the fabrication time and allowing for choosing materials suitable for sterilization. Because SRP technology does not offer the same flexibility as RP in term of prototype shape and complexity, our software program was adapted to provide new guide designs suitable for SRP fabrication. The biopsy guide was subdivided for a more efficient built with the parts being uniquely assembled to form the final guide. The accuracy of the assembly was then assessed using a modified Brown-Roberts-Wells phantom base that allows measuring the position of a biopsy needle introduced into the guide and comparing it with the actual planned target. These tests showed that 1) SRP machines provide an average accuracy of 0.77 mm with a standard deviation of 0.05 mm (plus or minus one image pixel) and 2) SRP allows for fabrication and sterilization within three and a half hours after diagnostic image acquisition and we are confident that that further improvements can reduce this time to less than two hours. Further tests will determine the accuracy of the positioning of the face mask on the patient's head under an IRB-approved trial judged against actual frame-based and frameless systems.

The surgical treatment of trigeminal neuralgia: overview and experience at the University of Florida.

Trigeminal neuralgia, also called tic douloureux, is a commonly misdiagnosed disorder characterized by intense facial pain. It is a chronic pain disorder that affects the fifth cranial nerve, usually in the fifth to seventh decade of life. Medication is the first line of treatment but frequently fails over time. At that point, many patients seek surgical intervention. This study reviews 108 patients treated over a 1-year period at the University of Florida with one of two surgical procedures: radiofrequency lesioning and microvascular decompression. The short-term results of this experience are reviewed and discussed.

Long-term Outcomes After Radiosurgery for Temporal Bone Paragangliomas.

OBJECTIVES: To determine the long-term outcome after stereotactic radiosurgery (SRS) for temporal bone paragangliomas. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 11 patients with temporal bone paragangliomas (10 patients with a glomus jugulare tumor and 1 patient with a glomus tympanicum tumor) treated between January 1997 and July 2012 at the University of Florida with SRS to a median dose of 15 Gy in 1 fraction. Ten previously unirradiated patients received SRS as did 1 patient who received prior fractionated radiotherapy (FRT) and then received salvage SRS for a local recurrence. The major outcome endpoint was local control, meaning no further growth or shrinkage on follow-up computed tomography or magnetic resonance imaging scans. RESULTS: The median follow-up time was 5.3 years. Two patients developed a local recurrence after SRS, including the patient who received salvage SRS after prior FRT. The overall local control rates at 5 and 10 years were both 81%. The cause-specific survival rates at 5 and 10 years were both 88%. The distant metastasis-free survival rates at 5 and 10 years were both 100%. The overall survival rates at 5 and 10 years were both 78%. There were no severe complications. CONCLUSIONS: SRS for benign head and neck paragangliomas is a safe and efficacious treatment associated with minimal morbidity. SRS is suitable for patients with skull base tumors <3 cm when FRT is logistically unsuitable. Surgery is reserved for patients in good health whose risk of associated morbidity is low. Observation is a reasonable option for asymptomatic patients with a limited life expectancy.

A Distinct DNA Methylation Shift in a Subset of Glioma CpG Island Methylator Phenotypes during Tumor Recurrence.

Glioma diagnosis is based on histomorphology and grading; however, such classification does not have predictive clinical outcome after glioblastomas have developed. To date, no bona fide biomarkers that significantly translate into a survival benefit to glioblastoma patients have been identified. We previously reported that the IDH mutant G-CIMP-high subtype would be a predecessor to the G-CIMP-low subtype. Here, we performed a comprehensive DNA methylation longitudinal analysis of diffuse gliomas from 77 patients (200 tumors) to enlighten the epigenome-based malignant transformation of initially lower-grade gliomas. Intra-subtype heterogeneity among G-CIMP-high primary tumors allowed us to identify predictive biomarkers for assessing the risk of malignant recurrence at early stages of disease. G-CIMP-low recurrence appeared in 9.5% of all gliomas, and these resembled IDH-wild-type primary glioblastoma. G-CIMP-low recurrence can be characterized by distinct epigenetic changes at candidate functional tissue enhancers with AP-1/SOX binding elements, mesenchymal stem cell-like epigenomic phenotype, and genomic instability. Molecular abnormalities of longitudinal G-CIMP offer possibilities to defy glioblastoma progression.

Effect of treatment plan quality on outcomes after radiosurgery for vestibular schwannoma.

OBJECT: The goal in this study was to review the effects of treatment plan quality on outcomes after radiosurgery for vestibular schwannoma (VS). METHODS: Between July 1988 and August 2005, 390 patients were treated. The results of this experience have been published recently. In this study the authors looked at dosimetry variables: conformity of treatment plan and steepness of dose gradient, in the same group of patients. Over the duration of this study, dosimetry evolved from a single isocenter with marginal conformity to multiple isocenters with high conformity. Multivariate statistics were used to determine the effects of these variables on tumor control and on two types of complication, facial weakness and facial numbness. RESULTS: The 5-year actuarial tumor control was 91%. Dosimetry had no effect on tumor control. Eighteen patients (4.6%) reported new-onset facial weakness and 14 (3.6%) reported new-onset facial numbness. Since 1994, when peripheral treatment doses were lowered to 1250 cGy, only three (1%) of 298 patients have experienced facial weakness and two (0.7%) of 298 have experienced facial numbness. Statistical analysis confirms, as in the prior study, that treatment volume and treatment dose are significant predictors of both facial weakness and facial numbness. In this model, prior tumor growth was also significant. Dosimetry, however, is definitely not a significant predictor of either complication. CONCLUSIONS: Treatment dose appears to be much more important than treatment plan quality in the prevention of facial numbness or weakness after radiosurgery for VS.

Radiosurgery in patients with bilateral vestibular schwannomas.

BACKGROUND: Patients with bilateral vestibular schwannomas offer a unique opportunity to determine the effectiveness of radiosurgery. By using the untreated tumor as an internal control, one can determine whether radiosurgery was able to interrupt the natural history of the treated tumor. METHODS: From September 1998 to November 2004, 13 patients with neurofibromatosis type 2 had 14 tumors treated with radiosurgery at the University of Florida. A retrospective analysis was performed on these patients. Actuarial statistics were used to analyze local control in both the treated and untreated tumor. RESULTS: The average follow-up length was 38 months. One patient failed to send a follow-up MRI. Actuarial local control in the treated tumors was 100% at 1 year and 92% at 2 and 5 years. Only 1 of the treated tumors continued to grow. In the untreated tumors, actuarial local control was 100% at 1 year, 78% at 2 years and 21% at 5 years. None of the untreated tumors decreased in size. CONCLUSION: In all but 1 patient with follow-up data, radiosurgery successfully prevented or reversed tumor growth. Additionally, half of the untreated tumors continued to grow. This study shows that radiosurgery alters the natural history of vestibular schwannomas.

Optical tracking technology in stereotactic radiation therapy.

The last decade has seen the introduction of advanced technologies that have enabled much more precise application of therapeutic radiation. These relatively new technologies include multileaf collimators, 3-dimensional conformal radiotherapy planning, and intensity modulated radiotherapy in radiotherapy. Therapeutic dose distributions have become more conformal to volumes of disease, sometimes utilizing sharp dose gradients to deliver high doses to target volumes while sparing nearby radiosensitive structures. Thus, accurate patient positioning has become even more important, so that the treatment delivered to the patient matches the virtual treatment plan in the computer treatment planning system. Optical and image-guided radiation therapy systems offer the potential to improve the precision of patient treatment by providing a more robust fiducial system than is typically used in conventional radiotherapy. The ability to accurately position internal targets relative to the linac isocenter and to provide real-time patient tracking theoretically enables significant reductions in the amount of normal tissue irradiated. This report reviews the concepts, technology, and clinical applications of optical tracking systems currently in use for stereotactic radiation therapy. Applications of radiotherapy optical tracking technology to respiratory gating and the monitoring of implanted fiducial markers are also discussed.

Linear accelerator radiosurgery for vestibular schwannomas.

OBJECT: Radiosurgery has become a popular treatment for small vestibular schwannomas (VSs). The aim of this study was to review an extensive, single-institution experience with linear accelerator (LINAC) radiosurgery for VSs. METHODS: Between July 1988 and August 2005, 390 patients with VSs were treated with LINAC-based radiosurgery at the authors' institution. Patient and treatment variables were prospectively maintained in a computer database. Outcomes were tracked through periodic clinical examinations and annual scanning studies. Multivariate and actuarial statistics were used to analyze rates of local tumor control and complications, including facial and trigeminal neuropathies, after treatment. One- and 2-year actuarial control rates were both 98%, and the 5-year actuarial control rate was 90%. Only four patients (1%) required surgery for tumor growth. Seventeen patients (4.4%) reported facial weakness and 14 patients (3.6%) reported facial numbness after radiosurgery. The risk of these complications rose with increasing tumor volume or increasing radiosurgical dose to the tumor periphery. Since 1994, when doses were deliberately lowered to 1250 cGy, only two patients (0.7%) have experienced facial weakness and two (0.7%) have experienced facial numbness. CONCLUSIONS: Radiosurgery provides a safe and effective therapeutic alternative to surgery for small VSs.

An investigation of the potential of rapid prototyping technology for image guided surgery.

Image-guided surgery can be broken down into two broad categories: frame-based guidance and frameless guidance. In order to reduce both the invasive nature of stereotactic guidance and the cost in equipment and time, we have developed a new guidance technique based on rapid prototyping (RP) technology. This new system first builds a computer model of the patient anatomy and then fabricates a physical reference frame that provides a precise and unique fit to the patient anatomy. This frame incorporates a means of guiding the surgeon along a preplanned surgical trajectory. This process involves (1) obtaining a high-resolution CT or MR scan, (2) building a computer model of the region of interest, (3) developing a surgical plan and physical guide, (4) designing a frame with a unique fit to the patient's anatomy with a physical linkage to the surgical guide, and (5) fabricating the frame using an RP unit. Software was developed to support these processes. To test the accuracy of this process, we first scanned and reproduced a plastic phantom fabricated to validate the system's ability to build an accurate virtual model. A target on the phantom was then identified, a surgical approach planned, a surgical guide designed, and the accuracy and precision of guiding a probe to that target were determined. Steps 1 through 5 were also evaluated using a head phantom. The results show that the RP technology can replicate an object from CT scans with submillimeter resolution. The fabricated reference frames, when positioned on the surface of the phantom and used to guide a surgical probe, can position the probe tip with an accuracy of 1.7 mm at the probe tip. These results demonstrate that the RP technology can be used for the fabrication of customized positioning frames for use in image-guided surgery.

Linear accelerator surgery for meningiomas.

OBJECT: In this paper the authors review the results of a single-center experience in the use of linear accelerator (LINAC) surgery for radiosurgical treatment of meningiomas. METHODS: A retrospective analysis of all patients treated with LINAC surgery for meningiomas between May 1989 and December 2001 was performed. All patients participated in follow-up review for a minimum of 2 years, and no patients were excluded. Two hundred ten patients were treated during the study interval. The actuarial local control rate for benign tumors was 100% at both 1 and 2 years, and 96% at 5 years. The actuarial local control rate for atypical tumors was 100% at 1 year, 92% at 2 years, and 77% at 5 years; and that for malignant tumors was 100% at both 1 and 2 years, and only 19% at 5 years. Of the 210 patients 13 (6.2%) experienced temporary radiation-induced complications, and only five (2.3%) experienced permanent complications. In all patients with a permanent complication the histological characteristics of the meningioma were malignant. CONCLUSIONS: Linear accelerator surgery produced high local control rates and very low rates of permanent morbidity in patients harboring benign meningiomas.