Histopathological correlation of brain tumor recurrence vs. radiation effect post-radiosurgery as detected by MRI contrast clearance analysis: a validation study.

PURPOSE: The differentiation between adverse radiation effects (ARE) and tumor recurrence or progression (TRP) is a major decision-making point in the follow-up of patients with brain tumors. The advent of immunotherapy, targeted therapy and radiosurgery has made this distinction difficult to achieve in several clinical situations. Contrast clearance analysis (CCA) is a useful technique that can inform clinical decisions but has so far only been histologically validated in the context of high-grade gliomas. METHODS: This is a series of 7 patients, treated between 2018 and 2023, for various brain pathologies including brain metastasis, atypical meningioma, and high-grade glioma. MRI with contrast clearance analysis was used to inform clinical decisions and patients underwent surgical resection as indicated. The histopathology findings were compared with the CCA findings in all cases. RESULTS: All seven patients had been treated with gamma knife radiosurgery and were followed up with periodic MR imaging. All patients underwent CCA when the necessity to distinguish tumor recurrence from radiation necrosis arose, and subsequently underwent surgery as indicated. Concordance of CCA findings with histological findings was found in all cases (100%). CONCLUSIONS: Based on prior studies on GBM and the surgical findings in our series, delayed contrast extravasation MRI findings correlate well with histopathology across a wide spectrum of brain tumor pathologies. CCA can provide a quick diagnosis and have a direct impact on patients' treatment and outcomes.

Bevacizumab and gamma knife radiosurgery for first-recurrence glioblastoma.

INTRODUCTION: Glioblastoma (GBM) is the most common central nervous system malignancy in adults. Despite decades of developments in surgical management, radiation treatment, chemotherapy, and tumor treating field therapy, GBM remains an ultimately fatal disease. There is currently no definitive standard of care for patients with recurrent glioblastoma (rGBM) following failure of initial management. OBJECTIVE: In this retrospective cohort study, we set out to examine the relative effects of bevacizumab and Gamma Knife radiosurgery on progression-free survival (PFS) and overall survival (OS) in patients with GBM at first-recurrence. METHODS: We conducted a retrospective review of all patients with rGBM who underwent treatment with bevacizumab and/or Gamma Knife radiosurgery at Roswell Park Comprehensive Cancer Center between 2012 and 2022. Mean PFS and OS were determined for each of our three treatment groups: Bevacizumab Only, Bevacizumab Plus Gamma Knife, and Gamma Knife Only. RESULTS: Patients in the combined treatment group demonstrated longer post-recurrence median PFS (7.7 months) and median OS (11.5 months) compared to glioblastoma patients previously reported in the literature, and showed improvements in total PFS (p=0.015), total OS (p=0.0050), post-recurrence PFS (p=0.018), and post-recurrence OS (p=0.0082) compared to patients who received either bevacizumab or Gamma Knife as monotherapy. CONCLUSION: This study demonstrates that the combined use of bevacizumab with concurrent stereotactic radiosurgery can have improve survival in patients with rGBM.

Preradiosurgical Embolization of Arteriovenous Malformations Reduces Target Volume - The Main Determinant for Complete Obliteration.

BACKGROUND: Embolization and stereotactic radiosurgery (SRS) have increasingly been used to treat complex arteriovenous malformations (AVMs). We studied outcomes of AVM patients treated through a multidisciplinary approach, examined the effect of embolization on SRS success, and analyzed predictors of treatment failure. METHODS: We retrospectively reviewed a prospectively maintained database of patients with AVMs treated with Gamma Knife (Leksell) SRS over an 11-year period. Patients with incomplete medical records and follow-up <2 years were excluded. Demographics, clinical presentation, previous rupture history, angiographic nidus size, Spetzler-Martin (S-M) grade, adjunctive endovascular embolization and microsurgical resection, radiologic evidence of obliteration and hemorrhage, and clinical outcomes (modified Rankin Scale [mRS] scores) were recorded. Radiosurgery-related details including nidus volume and number of sessions and radiosurgery-, embolization-, and resection-associated complications were also recorded. RESULTS: Eighty-three patients (mean age, 41.0 ± 21.3 years) were included. Mean reduction in AVM nidus target volume with endovascular embolization was 66.0 ± 19.7%. S-M grade reduction was achieved in 51.6% cases. Total obliteration after SRS was achieved in 56 AVMs (67.5%) after 2 years, and in 38 (86.4%) after 4 years. Two (2.4%) patients had rehemorrhage after SRS. Overall complication rate was 3.6%. Median angiographic follow-up was 55.5 months. Favorable outcomes (mRS = 0-2) were seen in 77.1%. SRS target volume was an independent predictor of treatment failure regardless of pre-SRS embolization. CONCLUSIONS: High AVM obliteration rates were achieved with judicious use of radiosurgery alone or with embolization. Embolization reduced target nidus volume by an average of 66%. SRS target volume was an independent predictor of treatment failure.

Incidence trends and survival analysis of atypical meningiomas: a population-based study from 2004 to 2018.

PURPOSE: Atypical meningiomas have histologic and clinical features that fall between those for benign and malignant meningiomas. The incidence of atypical meningiomas has not been well studied with respect to changes in the World Health Organization (WHO) classification scheme over time. METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database was queried to obtain data from 2004 to 2018 for patients with all meningiomas, including atypical. Age-adjusted incidence rates were generated and annual percent change (APC) in the incidence rates was calculated with joinpoint regression. Survival was analyzed using the Kaplan-Meier method and Cox proportional hazards models. RESULTS: A total of 4476 patients diagnosed with meningioma were identified from the SEER 18 registries. The incidence of atypical meningioma increased at an APC of 5.6% [95% confidence interval [CI], 3.4-7.8]; significantly faster than all meningiomas, which rose at an APC of 2.5% (95%CI 1.8-3.1;p = 0.008). For atypical meningiomas, the 1, 3, 5, and 10-year survival rates were 91.9%, 81.3%, 68.8%, and 34.3%, respectively. Male sex, older age (≥ 60 years), and large tumor size (> 5 cm) were independent risk factors for an unfavorable prognosis. CONCLUSIONS: The incidence of atypical meningioma was observed to be increasing relative to all meningiomas. It is important to diligently monitor atypical meningioma incidence and mortality rates over time to see whether observed uptrends persist. Continued effort toward improving outcomes in patients with atypical meningiomas is warranted, especially in light of an apparent rise in incidence.

[68Ga]Ga-DOTA-TATE uptake in subacute stroke following craniotomy for meningioma: a diagnostic tool for stroke?

Gallium 68 (68Ga) 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid labelled octreotate ([68Ga]Ga-DOTA-TATE) positron emission tomography (PET) is an established imaging technique for identifying tumours of neuroendocrine origin and meningiomas; the radiotracer binds to somatostatin receptor type 2 (SSTR2), which is richly expressed by these malignancies. Here, we present a rare case hinting at novel ischaemic stroke detection by [68Ga]Ga-DOTA-TATE PET scan. The scan was performed 14 days post resection of an atypical meningioma with the intention to assess the extent of residual tumour for radiosurgical treatment of the operative cavity. Surprisingly, the [68Ga]Ga-DOTA-TATE PET-avid region corresponded to an area of perioperative subacute ischaemic stroke detected by MRI. This case corroborates the two previously reported cases of incidental detection of ischaemic stroke during routine [68Ga]Ga-DOTA-TATE PET imaging, collectively suggesting the need for caution when interpreting the imaging findings. A possible underlying mechanism for [68Ga]Ga-DOTA-TATE uptake in stroke is increased SSTR2 expression by macrophages recruited into infarcted tissue.

Radiosurgery, reirradiation, and brachytherapy.

Radiosurgery and brachytherapy are potentially useful treatment techniques that are sparingly applied in pediatric oncology. They are often used in the setting of reirradiation for recurrent or metastatic tumors. Reirradiation in children with recurrent tumors is complicated by the tolerance of critical organs and the potential risks for overall long-term dose-dependent complications. We review the current literature available in support of reirradiation and the use of radiosurgery and brachytherapy in pediatric patients.

Lateral Temporal Approach for Image-Guided Stereotactic Biopsy of Pineal Region Tumors.

BACKGROUND: Biopsy of pineal region neoplasms is frequently accomplished by way of endoscopic transventricular access or using an image-guided, computer-assisted stereotactic approach. METHODS: We evaluated a nonorthogonal lateral temporal approach for stereotactic biopsy of pineal region tumors as a variation of previously described stereotactic methods. Magnetic resonance imaging-guided frameless stereotaxy was used to plan and perform biopsies of pineal region tumors using a nonorthogonal trajectory extending from the superior or middle temporal gyri through the temporal stem, anterior to the atrium of the lateral ventricle, and posterior to the corticospinal tract. RESULTS: All patients had an uncomplicated postoperative course and remained at neurologic baseline. No parenchymal or ventricular hemorrhage was present on postoperative scans. A tissue diagnosis was obtained in all patients. CONCLUSIONS: This method appears to be a safe alternative to stereotactic biopsy using other trajectories and provides adequate tissue for definitive diagnosis.

Do brain mets grow while you wait? A volumetric natural history assessment of brain metastases from time of diagnosis to gamma knife treatment.

Brain metastasis (BM) is a common neurologic complication of cancers such as lung, breast, and melanoma. Recently, there has been a shift in treatment of BM from whole brain radiation therapy to stereotactic radiosurgery (SRS) and the success is dependent on tumor volume. While most metastases grow over time, data on growth rate is lacking. Therefore, we document volume changes of metastases before treatment. We retrospectively reviewed MRI imaging records of 82 patients with a total of 294 BMs, treated in our cancer center by one neurosurgeon and one radiation oncologist with Gamma Knife SRS over a three-year period. We measured tumor volume at the time of diagnosis and compared with tumor volume on the day of treatment. Volumes were compared using the Wilcoxon signed-rank test. Lung, melanoma and breast made up the majority of metastases diagnosed. More than 75% of tumors grew and these changes in volume and percent changes in volume were statistically significant. Thirty percent of tumors doubled in size before treatment. Patients with the largest mean pretreatment tumor size were urgently treated within 6 days, yet still demonstrated the largest change in volume. This study is one of the first to document volume changes of brain metastases from the time of diagnosis to SRS treatment. Our results indicate that brain metastases can grow rapidly and it is imperative that we streamline patient management processes to minimize delays in treating patients with SRS, since outcomes are dependent on tumor size.

The case for radiosurgery for brainstem metastases.

PURPOSE: To challenge the prevalent pessimism regarding the outcome of patients with metastases in the brainstem resulting in the use of whole brain radiation for palliation rather than stereotactic radiosurgery for definitive control and preservation of quality of life. We present our single institution review of the efficacy and safety of treating brainstem metastases aggressively with GKRS. METHODS: Forty-one patients with 45 total lesions treated with GKRS were included. Mean age was 58.7 years, ranging from 22 to 82. Tumor volumes were objectively calculated, treatment effects assessed on imaging and clinical data collected and correlated to the radiosurgical response. RESULTS: Mean survival after diagnosis of BSM was 11.6 months, ranging from 1.4 to 58.8 months. Margin dose ranged from 12 to 20 Gy. At first follow up, 11 (27%) patients had complete resolution of the treated lesion. At the second follow up 15 (37%) and third follow up 19 (46%) patients had a complete response. On average, there was a 64% decrease in tumor size at first follow up after treatment. 25 (61%) patients received WBRT in addition to radiosurgery; 16 (39%) received radiosurgery alone. There was no difference in overall survival between the two groups (p = 0.1324). ARE was seen in one patient who received  16 Gy to the margin of a 2.06 cm3 pontine tumor, but without correlative symptoms. One patient was treated with Bevacizumab® for progressive, but asymptomatic, edema following treatment that was not controlled by corticosteroids. CONCLUSIONS: Location in brainstem should not be a deterrent to the use of radiosurgery for these patients. The addition or exclusion of WBRT should be based on the clinical progression of the patient and within the limits of this study does not seem to impact overall survival. With improved survival as a result of better systemic therapy, these patients can benefit from better preservation of cognitive function by this strategy.

Intracranial stereotactic radiosurgery.

Stereotactic radiosurgery (SRS) is the use of a single high dose of radiation, stereotactically directed to an intracranial region of interest, in order to create a lesion or obliterate a preexisting one. This technology has evolved over the years into the use of multiple radiation sources oriented at a variety of angles, thus permitting the creation of various treatment target shapes. This allows for non-open surgical treatment of intracranial pathologies, which significantly decreases the risk of morbidity. The destruction of pathological tissue following radiosurgery is a stepwise process that involves a number of different stages, beginning with the necrotic stage, followed by the resorption stage, and concluding with the glial scar formation stage. There are currently a number of different delivery methods of SRS, including linear accelerators, Gamma Knife units, and charged particle methods (Bragg-peak and plateau-beam). Various intracranial lesions exhibit different responses to radiosurgery; however, most lesions of appropriate size tend to respond favorably. Radiosurgery is used today in the treatment of brain metastases, meningiomas, vestibular schwannomas, sellar and suprasellar lesions, and arteriovenous malformations. SRS is widely used to treat functional conditions, such as trigeminal neuralgia and intractable tremor. The treatment of intracranial lesions with radiosurgery can result in undesirable effects on the adjacent normal brain, resulting in adverse radiation effects. The distinction between tumor progression and adverse radiation effects can be challenging but is aided by various imaging modalities. Treatment options for this condition include observation, corticosteroids, pentoxifylline and vitamin E, bevacizumab, laser-interstitial thermal therapy, and surgical resection.

Radiofrequency Ablation and Radiation Therapy Improve Local Control in Spinal Metastases Compared to Radiofrequency Ablation Alone.

PURPOSE:: The spinal column is the most common location for osseous metastases and is associated with pain and decreased quality of life. This study evaluated combined radiofrequency ablation (RFA) with radiation therapy (RT) compared to RFA alone for improving pain and local control. METHODS:: This was a single-institution retrospective review of patients who underwent RFA of spinal metastases between 2016 and 2017, with or without RT to the same vertebral level. Pain was measured with visual analog scale at initial presentation and at 3 and 12 weeks of follow-up. Local failure (LF), distant failure, and overall survival (OS) were compared and Kaplan-Meier statistics were calculated. RESULTS:: Twenty-six patients with 28 spinal metastases were treated with RFA. Ten patients with 11 metastases were treated with RFA + RT. More patients with lung primaries were treated with RFA alone and more patients with breast primaries were treated with combination RFA+RT. There was no significant difference in pain scores between groups ( P = .96). At a median follow-up of 8.2 months, LF was noted in 8 of 17 metastases treated with RFA alone compared to 1 of 11 metastases treated with RFA+RT ( P = .049). There was a significant benefit in time to LF favoring RFA+RT ( P = .02) and a significant benefit in OS ( P = .0045). CONCLUSION:: This study demonstrates a benefit in local control with RFA+RT versus RFA alone. Palliation of pain was effective using both regimens. This study was limited by a nearly unequal distribution of primary tumor histologies between groups. Literature regarding combined treatment of RFA and RT for spinal metastases is scarce and prospective protocols are warranted.

Quality assurance tests for the Gamma Knife® Icon™ image guidance system.

INTRODUCTION: The Gamma Knife® Icon™ comes with an image guidance system for tracking patient motion and correcting for inter- and intrafractional shifts, mainly used with frameless thermoplastic immobilization. The system consists of a cone-beam CT (CBCT) and a couch-mounted infrared camera (IFMM). We report our quality assurance program for Icon's image guidance system. METHODS: The manufacturer-provided tool is used for daily checks of CBCT positional precision. Catphan® phantom is used for monthly checks of CBCT image qualities (uniformity, contrast to noise ratio (CNR), and spatial resolution) for the two acquisition presets (low-dose and high-quality presets). On a semi-annual schedule, we use a frame tool to check the agreement of CBCT-based and Frame-based stereotactic space coordinates by comparing the locations of five attached ball bearings in CT-sim scans (Frame-based coordinates determination) and in Icon's CBCT scans. On an annual basis, the accuracy of IFMM, image registration, and delivery-after-shift are tested using a translational stage. A weighted CT dose index is measured annually with a pencil chamber in CTDI head phantom. RESULTS: The CBCT precision check: 0.12 ± 0.04 mm (maximum deviations average). CBCT image quality: spatial resolution range: [6,7] lp/cm (low), and [7,8] lp/cm (high); uniformity: 12.82 ± 0.69% (low), and 13.01 ± 0.69% (high); CNR: 1.07 ± 0.08 (low), and 1.69 ± 0.10 (high). Agreement of CBCT-based with Frame-based stereotactic coordinates range: [0.33, 0.66] mm. Accuracy of IFMM: 0.00 ± 0.12 mm (average) with 0.27 mm (max.); image registration: 0.03 ± 0.06 mm (average) with 0.23 mm (max.); and delivery-after-shift: 0.24 ± 0.09 mm (average) with 0.42 mm (max.). CTDIw : 2.3 mGy (low), and 5.7 mGy (high). CONCLUSIONS: The manufacturer-required QA checks together with additional user-defined checks are an important combination for a robust quality assurance program ensuring the safe use of Gamma Knife® Icon™'s image guidance and motion management features.

An Evaluation of the ICON® Mask Fixation: Curing Characteristics of the Thermoplastic Fixation and Implications for Patient Workflow.

BACKGROUND: Thermoplastic mask immobilization is used to perform hypo-fractionated treatments with the Gamma Knife ICON®. MATERIALS AND METHODS: We evaluated the curing characteristics of the ICON® Nanor mask using force sensing resistors coupled with a data logging tool designed by us. RESULTS: For patients being treated with masks made the same day as the treatment, often in the same sitting with no removal and replacement of the patient from the treatment cradle, based on the curves 80% of the force of fixation is reached at 30 minutes. CONCLUSIONS: Allowing for curing over 10-15 minutes and the subsequent localizing and delivery Cone beam CT (CBCT)s as well as the plan evaluation this is a reasonable time to start of therapy. For more exacting targets that are still requiring hypo-fractionation a cure period of 15 hours or greater will ensure that maximum rigidity of fixation is achieved.

Impact of the Number of Metastatic Tumors Treated by Stereotactic Radiosurgery on the Dose to Normal Brain: Implications for Brain Protection.

PURPOSE/OBJECTIVES: The purpose of this study was to evaluate the effect of the number of brain lesions for which stereotactic radiosurgery (SRS) was performed on the dose volume relationships in normal brain. MATERIALS AND METHODS: Brain tissue was segmented using the patient's pre-SRS MRI. For each plan, the following data points were recorded: total brain volume, number of lesions treated, volume of brain receiving 8 Gy (V8), V10, V12, and V15. RESULTS: A total of 225 Gamma Knife® treatments were included in this retrospective analysis. The number of lesions treated ranged from 1 to 29. The isodose for prescription ranged from 40 to 95% (mean 55%). The mean prescription dose to tumor edge was 18 Gy. The mean coverage, selectivity, conformity, and gradient index were 97.5%, 0.63, 0.56, and 3.5, respectively. The mean V12 was 9.5 cm3 (ranging from 0.5 to 59.29). There was no correlation between the number of lesions and brain V8, V12, V10, or V15. There was a direct and statistically significant relationship between the brain volume treated (V8, V10, V12, and V15) and total volume of tumors treated (p < 0.001). In our study, the integral dose to the brain exceeded 3 J when the total tumor volume exceeded 25 cm3. CONCLUSIONS: The number of metastatic brain lesions treated bears no significant relationship to total brain tissue volume treated when using SRS. The fact that the integral dose to the brain exceeded 3 J when the total tumor volume exceeded 25 cm3 is useful for establishing guidelines. Although standard practice has favored using whole brain radiation therapy in patients with more than 4 lesions, a significant amount of normal brain tissue may be spared by treating these patients with SRS. SRS should be carefully considered in patients with multiple brain lesions, with the emphasis on total brain volume involved rather than the number of lesions to be treated.

Evaluation of stability of stereotactic space defined by cone-beam CT for the Leksell Gamma Knife Icon.

The Gamma Knife Icon comes with an integrated cone-beam CT (CBCT) for image-guided stereotactic treatment deliveries. The CBCT can be used for defining the Leksell stereotactic space using imaging without the need for the traditional invasive frame system, and this allows also for frameless thermoplastic mask stereotactic treatments (single or fractionated) with the Gamma Knife unit. In this study, we used an in-house built marker tool to evaluate the stability of the CBCT-based stereotactic space and its agreement with the standard frame-based stereotactic space. We imaged the tool with a CT indicator box using our CT-simulator at the beginning, middle, and end of the study period (6 weeks) for determining the frame-based stereotactic space. The tool was also scanned with the Icon's CBCT on a daily basis throughout the study period, and the CBCT images were used for determining the CBCT-based stereotactic space. The coordinates of each marker were determined in each CT and CBCT scan using the Leksell GammaPlan treatment planning software. The magnitudes of vector difference between the means of each marker in frame-based and CBCT-based stereotactic space ranged from 0.21 to 0.33 mm, indicating good agreement of CBCT-based and frame-based stereotactic space definition. Scanning 4-month later showed good prolonged stability of the CBCT-based stereotactic space definition.

Comparison of Onsite Versus Online Chart Reviews as Part of the American College of Radiation Oncology Accreditation Program.

PURPOSE: Accreditation based on peer review of professional standards of care is essential in ensuring quality and safety in administration of radiation therapy. Traditionally, medical chart reviews have been performed by a physical onsite visit. The American College of Radiation Oncology Accreditation Program has remodeled its process whereby electronic charts are reviewed remotely. METHODS: Twenty-eight radiation oncology practices undergoing accreditation had three charts per practice undergo both onsite and online review. Onsite review was performed by a single reviewer for each practice. Online review consisted of one or more disease site-specific reviewers for each practice. Onsite and online reviews were blinded and scored on a 100-point scale on the basis of 20 categories. A score of less than 75 was failing, and a score of 75 to 79 was marginal. Any failed charts underwent rereview by a disease site team leader. RESULTS: Eighty-four charts underwent both onsite and online review. The mean scores were 86.0 and 86.9 points for charts reviewed onsite and online, respectively. Comparison of onsite and online reviews revealed no statistical difference in chart scores ( P = .43). Of charts reviewed, 21% had a marginal (n = 8) or failing (n = 10) score. There was no difference in failing charts ( P = .48) or combined marginal and failing charts ( P = .13) comparing onsite and online reviews. CONCLUSION: The American College of Radiation Oncology accreditation process of online chart review results in comparable review scores and rate of failing scores compared with traditional on-site review. However, the modern online process holds less potential for bias by using multiple reviewers per practice and allows for greater oversight via disease site team leader rereview.

Clinical outcomes in patients with brain metastases from breast cancer treated with single-session radiosurgery or whole brain radiotherapy.

OBJECTIVE Gamma Knife radiosurgery (GKRS) is used to treat brain metastases from breast cancer (BMB) as the sole treatment or in conjunction with tumor resection and/or whole brain radiotherapy (WBRT). This study evaluates outcomes in BMB based on treatment techniques and tumor biological features. METHODS The authors reviewed all patients treated with BMB between 2004 and 2014. Patients were identified from a prospectively collected radiosurgery database and institutional tumor registry; 214 patients were identified. Data were collected from aforementioned sources and supplemented with chart review where needed. Independent radiological review was performed for all available brain imaging in those treated with GKRS. Survival analyses are reported using Kaplan-Meier estimates. RESULTS During the 10-year study period, 214 patients with BMB were treated; 23% underwent GKRS alone, 46% underwent a combination of GKRS and WBRT, and 31% underwent WBRT alone. Median survival after diagnosis of BMB in those treated with GKRS alone was 21 months, and in those who received WBRT alone it was 3 months. In those treated with GKRS plus WBRT, no significant difference in median survival was observed between those receiving WBRT upfront or in a salvage setting following GKRS (19 months vs 14 months, p = 0.63). The median survival of patients with total metastatic tumor volume of ≤ 7 cm3 versus > 7 cm3 was 20 months vs 7 months (p < 0.001). Human epidermal growth factor receptor-2 (Her-2) positively impacted survival after diagnosis of BMB (19 months vs 12 months, p = 0.03). Estrogen receptor status did not influence survival after diagnosis of BMB. No difference was observed in survival after diagnosis of BMB based on receptor status in those who received WBRT alone. CONCLUSIONS In this single-institution series of BMB, the addition of WBRT to GKRS did not significantly influence survival, nor did the number of lesions treated with GKRS. Survival after the diagnosis of BMB was most strongly affected by Her-2 positivity and total metastatic tumor volume.