Repeat stereotactic radiosurgery for progressive vestibular schwannomas after primary gamma knife radiosurgery.

PURPOSE: Limited data provides guidance on the management of vestibular schwannomas (VSs) that have progressed despite primary Gamma Knife radiosurgery (GKRS). The present article reports our long-term experience after repeat GKRS for VS with sustained progression after solely primary GKRS management. METHODS: A retrospective review of 1997 patients managed between 1987 and 2023 was conducted. Eighteen patients had sustained tumor progression after primary GKRS and underwent repeat GKRS. The median repeat GKRS margin dose was 11 Gy (IQR: 11-12), the median tumor volume was 2.0 cc (IQR: 1.3-6.3), and the median cochlear dose in patients with preserved hearing was 3.9 Gy (IQR: 3-4.1). The median time between initial and repeat GKRS was 65 months (IQR: 38-118). RESULTS: The median follow-up was 70 months (IQR: 23-101). After repeat GKRS, two patients had further tumor progression at 4 and 21 months and required partial resection of their tumors. The 10-year actuarial tumor control rate after repeat GKRS was 88%. Facial nerve function was preserved in 13 patients who had House-Brackmann grade 1 or 2 function at the time of repeat GKRS. Two patients with serviceable hearing preservation (Gardner-Robertson grade 1 or 2) at repeat GKRS retained that function afterwards. In patients with tinnitus, vestibular dysfunction, and trigeminal neuropathy, symptoms remained stable or improved for 16/16 patients, 12/15 patients, and 10/12 patients, respectively. One patient developed facial twitching in the absence of tumor growth 21 months after repeat GKRS. CONCLUSIONS: Repeat GKRS effectively controlled tumor growth and preserved cranial nerve outcomes in most patients whose VS had sustained progression after initial primary radiosurgery.

Stereotactic radiosurgery for patients with spinal metastases from prostate cancer.

PURPOSE: Spinal metastases may result in intractable pain, neurological deficit, and vertebral body collapse. There are only a few studies describing outcomes following spine stereotactic radiosurgery (SRS) specifically for prostate cancer metastases. METHODS: A prospectively collected database of patients with prostate cancer spinal metastases treated at the University of Pittsburgh Medical Center from 2003 to 2023 was analyzed. The primary outcome was local control (LC). Secondary outcomes were overall survival (OS), pain resolution, and adverse radiation effects (AREs). RESULTS: Thirty-seven patients and 51 lesions were identified. Fifteen lesions (29%) were previously resected and 34 lesions (67%) were previously irradiated. The median tumor volume was 37.0 cc (range: 2.9-263.3). A majority of lesions (71%) were treated in a single fraction (median 20 Gy, range: 14-22.5); multi-fractionated treatment consisted of 21-30 Gy in 2-5 fractions. Median follow-up was 12 months (range: 1-146). The 6-month, 1-year, and 2-year LC rates were 97%, 91%, and 91%, respectively. No tested prognostic factors were associated with LC, including hormone sensitivity. The 6-month, 1-year, and 2-year OS rates were 71%, 56%, and 32%; age > 70 years (p = 0.048) and tumor volume > 30 cc (p = 0.03) were associated with inferior rates of OS. Complete or partial pain response was observed in 58% of patients. There were 8 instances (16%) of AREs, 2 of which were vertebral compression fractures (4%). CONCLUSION: Radiosurgery as a primary or adjuvant treatment modality for prostate cancer spinal metastases confers durable LC and moderate pain relief with minimal toxicity. Further studies are warranted to optimize management in this patient population.

The role of spine stereotactic radiosurgery for patients with breast cancer metastases.

PURPOSE: Breast cancer that metastasizes to the spine is associated with low quality of life and poor survival. Radiosurgery has an increasing role in this patient population. This single-institution (2003-2023) study analyzes clinical outcomes and prognostic factors for patients who underwent spinal stereotactic radiosurgery (SSRS) for metastatic breast cancer. METHODS: Ninety patients (155 unique breast cancer spinal metastases) were treated with SSRS. The median age was 57 years (range: 35-88), and the median KPS was 80 (range: 40-100). Forty-two (27%) lesions were managed surgically prior to radiosurgery. At SSRS, 75 (48%) lesions impinged or compressed the spinal cord per the epidural spinal cord scale (ESCC). Seventy-nine (51%) lesions were categorized as potentially unstable or unstable by the Spinal Instability Neoplastic Score (SINS). RESULTS: The median follow-up was 15 months (range: 1-183). The median single-session tumor volume was 25.4 cc (range: 2-197), and the median single-fraction prescription dose was 17 Gy (range: 12-25). Seven (5%) lesions locally progressed. The 1-, 2-, and 5-year local control rates were 98%, 97%, and 92%, respectively. The median overall survival (OS) for the cohort was 32 months (range: 2-183). The 1-, 2-, and 5-year OS rates were 72%, 53%, and 30%, respectively. On univariate analysis, KPS ≥ 80 (p = 0.009, HR: 0.51, 95% CI: 0.31-0.84) was associated with improved OS. Patient-reported pain improved (68%), remained stable (29%), or worsened (3%) following radiosurgery. Fifteen (10%) radiation-induced toxicities were reported. CONCLUSIONS: Spinal radiosurgery is a safe and highly effective long-term treatment modality for metastases to the spine that originate from breast cancer.

Is Halcyon feasible for single thoracic or lumbar vertebral segment SBRT?

PURPOSE: Halcyon linear accelerators employ intensity-modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) techniques. The Halcyon offers translational, but not rotational, couch correction, which only allows a 3 degrees of freedom (3-DOF) correction. In contrast, the TrueBeam (TB) linear accelerator offers full 6-DOF corrections. This study aims to evaluate the difference in treatment plan quality for single thoracic or lumbar vertebral segment SBRT between the Halcyon and TB linear accelerators. In addition, this study will also investigate the effect of patient rotational setup errors on the final plan quality. METHODS: We analyzed 20 patients with a single-level spine metastasis located between the T7 and L5 vertebrae near the spinal canal. The median planning target volume was 52.0 cm3 (17.9-138.7 cm3 ). The median tumor diameter in the axial plane was 4.6 cm (range 1.7-6.8 cm), in the sagittal plane was 3.3 cm (range 2-5 cm). The prescription doses were either 12-16 Gy in 1 fraction or 18-24 Gy in 3 fractions. All patients were treated on the TB linear accelerator with a 2.5 mm Multi-Leaf Collimator (MLC) leaf width. Treatment plans were retrospectively created for the Halcyon, which has a 5 mm effective MLC leaf width. The 20 patients had a total of 50 treatments. Analysis of the 50 cone beam computed tomography (CBCT) scans showed average rotational setup errors of 0.6°, 1.2°, and 0.8° in pitch, yaw, and roll, respectively. Rotational error in roll was not considered in this study, as the original TB plans used a coplanar volumetric modulated arc therapy (VMAT) technique, and each 1° of roll will contribute an error of 1/360. If a plan has 3 arcs, the contribution from errors in roll will be < 0.1%. To simulate different patient setup errors, for each patient, 12 CT image datasets were generated in Velocity AI with different rotational combinations at a pitch and yaw of 1°, 2°, and 3°, respectively. We recalculated both the TB and Halcyon plans on these rotated images.  The dosimetric plan quality was evaluated based on the percent tumor coverage, the Conformity Index (CI), Gradient Index (GI), Homogeneity index (HI), the maximum dose to the cord/cauda, and the volume of the cord/cauda receiving 8, 10, and 12 Gy (V8Gy, V10Gy and V12Gy). Paired t-tests were performed between the original and rotated plans with a significance level of 0.05. RESULTS: The Eclipse based VMAT plans on Halcyon achieved a similar target coverage (92.3 ± 3.0% vs. 92.4 ± 3.3%, p = 0.82) and CI (1.0 ± 0.1 vs. 1.1 ± 0.2, p = 0.12) compared to the TB plans. The Gradient index of Halcyon is higher (3.96 ±0.8) than TB (3.85 ±0.7), but not statistically significant. The maximum dose to the spinal cord/cauda was comparable (11.1 ± 2.8 Gy vs. 11.4 ± 3.6 Gy, p = 0.39), as were the V8Gy, V10Gy and V12Gy to the cord/cauda. The dosimetric influence of patient rotational setup error was statistically insignificant for rotations of up to 1° pitch/yaw (with similar target coverage, CI, max cord/cauda dose and V8Gy, V10Gy, V12Gy for cord/cauda). The total number of monitor units (MUs) for Halcyon (4998 ± 1688) was comparable to that of TB (5463 ± 2155) (p = 0.09). CONCLUSIONS: The Halcyon VMAT plans for a single thoracic or lumbar spine metastasis were dosimetrically comparable to the TB plans. Patient rotation within 1° in the pitch and yaw directions, if corrected by translation, resulted in insignificant dosimetric effects. The Halcyon linear accelerator is an acceptable alternative to TB for the treatment of single thoracic or lumbar spinal level metastasis, but users need to be cautious about the patient rotational setup error.  It is advisable to select patients appropriately, including only those with the thoracic or lumbar spine involvement and keeping at least 2 mm separation between the target and the cord/cauda. More margin is needed if the distance between the isocenter and cord/cauda is larger. It is advisable to place the planning isocenter close to the spinal canal to further mitigate the rotational error. SUMMARY: We simulated various scenarios of patient setup errors with different rotational combinations of pitch and yaw with 1°, 2°, and 3°, respectively. Rotation was corrected with translation only to mimic the Halcyon treatment scenario. Using the Halcyon for treating a tumor in a single thoracic or lumbar vertebral segment is feasible, but caution should be noted in patients requiring rotational corrections of > 1° in the absence of 6-DOF correction capabilities.

Optimizing stereotactic radiosurgery in patients with recurrent or residual craniopharyngiomas.

PURPOSE: Stereotactic radiosurgery (SRS) is an important management strategy for residual and recurrent craniopharyngiomas. The current study evaluated the factors which affected tumor control and complications in craniopharyngioma SRS. METHODS: This study includes 53 consecutive patients who underwent single-session SRS for recurrent or residual craniopharyngiomas. The median age was 41 years with 28 male and 25 females. The median tumor volume was 0.63 cm3 and median margin dose was 12 Gy (range 9-25 Gy). RESULTS: The overall 3-, 5-, and 10-year survival rates were 97.8%, 92.7% and 88.5%. The overall 3-, 5-, and 10-year tumor control rates were 81.0%, 72.1%, and 53.4%. In univariate analysis, ≥ 3 mm distance from optic structures (p = 0.002), only solid or cystic tumor type (p = 0.037), and ≥ 12 Gy to ≥ 85% of the tumor (p < 0.001) were significantly associated with improved tumor control. In multivariate analysis, only solid or cystic tumor type, (p = 0.034), and ≥ 85% of the tumor receiving ≥ 12 Gy (p = 0.004) were significantly associated with better tumor control. When ≥ 85% of the tumor received ≥ 12 Gy the tumor control rates at 3-, 5-, and 10-year were 100%, 93.3%, and 93.3%. Higher conformity index was not associated with better tumor control. CONCLUSIONS: The tumor control rates after recurrent or residual craniopharyngiomas SRS were improved by ensuring that at least 85% of the tumor received ≥ 12 Gy even when the distance between the tumor and the optic system is < 3 mm. This concept refutes the conformity theory that a high conformity index is a critical feature of effective SRS.

Useful hearing preservation is improved in vestibular schwannoma patients who undergo stereotactic radiosurgery before further hearing deterioration ensues.

INTRODUCTION: The present study evaluates whether hearing deterioration during observation reduces serviceable hearing preservation rates after stereotactic radiosurgery (SRS) in vestibular schwannoma (VS) patients with useful hearing. METHODS: We retrospectively analyzed 1447 VS patients who underwent SRS between 1992 and 2017. We identified 100 VS patients who had Grade I Gardner- Robertson (GR) hearing at initial diagnosis but were observed without surgery or SRS. We compared hearing after SRS in 67 patients who retained GR Grade I hearing from initial diagnosis to SRS (the hearing maintenance or HM group) to 33 patients whose hearing worsened from GR grade I to grade II (the hearing deterioration or HD group). We also investigated whether a decline in pure tone average (PTA) or speech discrimination score (SDS) before SRS affected hearing preservation after SRS. RESULTS: The serviceable hearing (GR I and II) preservation in HM patients was 80%s, 63%, and 51% at 3, 5, and 10 years, respectively. The serviceable hearing preservation in HD patients was 40%, 33%, and 20% at 3, 5, and 10 years, respectively. In multivariate analysis, younger age (< 55 years, p = 0.045) and HM during observation (p = 0.001) improved serviceable hearing preservation rates. Patients whose PTA increased ≥ 15 dB (p = 0.024) or whose SDS declined ≥ 10% (p = 0.019) had reduced serviceable hearing preservation rates. CONCLUSIONS: Hearing deterioration during observation before SRS reduced long term hearing preservation rate in VS patients with GR grade I hearing at initial diagnosis. SRS before hearing deterioration was recommended for hearing preservation.

Independently validated sex-specific nomograms for predicting survival in patients with newly diagnosed glioblastoma: NRG Oncology RTOG 0525 and 0825.

BACKGROUND/PURPOSE: Glioblastoma (GBM) is the most common primary malignant brain tumor. Sex has been shown to be an important prognostic factor for GBM. The purpose of this study was to develop and independently validate sex-specific nomograms for estimation of individualized GBM survival probabilities using data from 2 independent NRG Oncology clinical trials. METHODS: This analysis included information on 752 (NRG/RTOG 0525) and 599 (NRG/RTOG 0825) patients with newly diagnosed GBM. The Cox proportional hazard models by sex were developed using NRG/RTOG 0525 and significant variables were identified using a backward selection procedure. The final selected models by sex were then independently validated using NRG/RTOG 0825. RESULTS: Final nomograms were built by sex. Age at diagnosis, KPS, MGMT promoter methylation and location of tumor were common significant predictors of survival for both sexes. For both sexes, tumors in the frontal lobes had significantly better survival than tumors of multiple sites. Extent of resection, and use of corticosteroids were significant predictors of survival for males. CONCLUSIONS: A sex specific nomogram that assesses individualized survival probabilities (6-, 12- and 24-months) for patients with GBM could be more useful than estimation of overall survival as there are factors that differ between males and females. A user friendly online application can be found here- https://npatilshinyappcalculator.shinyapps.io/SexDifferencesInGBM/ .

TCR Retrogenic Mice as a Model To Map Self-Tolerance Mechanisms to the Cancer Mucosa Antigen GUCY2C.

Characterizing self-tolerance mechanisms and their failure is critical to understand immune homeostasis, cancer immunity, and autoimmunity. However, examination of self-tolerance mechanisms has relied primarily on transgenic mice expressing TCRs targeting well-characterized, but nonphysiologic, model Ags, such as OVA and hemagglutinin. Identifying TCRs directed against bona fide self-antigens is made difficult by the extraordinary diversity of TCRs and the low prevalence of Ag-specific clones (<10-100 naive cells per organism), limiting dissection of tolerance mechanisms restricting immunity to self-proteins. In this study, we isolated and characterized TCRs recognizing the intestinal epithelial cell receptor and colorectal cancer Ag GUCY2C to establish a model to study self-antigen-specific tolerance mechanisms. GUCY2C-specific CD4+ effector T cells were isolated from immunized, nontolerant Gucy2c -/- mice. Next-generation sequencing identified GUCY2C-specific TCRs, which were engineered into CD4+ T cells in vitro to confirm TCR recognition of GUCY2C. Further, the generation of "retrogenic" mice by reconstitution with TCR-transduced hematopoietic stem cells resulted in normal CD4+ T cell development, responsiveness to immunization, and GUCY2C-induced tolerance in recipient mice, recapitulating observations in conventional models. This retrogenic model can be employed to define self-tolerance mechanisms restricting T and B cell responses to GUCY2C to optimize colorectal cancer immunotherapy without autoimmunity.

Long term results of primary radiosurgery for vestibular schwannomas.

BACKGROUND: Stereotactic radiosurgery (SRS) has become a primary option for management for both newly diagnosed vestibular schwannomas (VS), as well as VS that enlarge after initial observation. METHODS: A retrospective review of our prospectively maintained data base found 871 patients who underwent Gamma knife® SRS as their initial (primary) management between 1987 and 2008. Follow-up ranged from 1-25 years (median = 5.2 years) Median tumor volume was 0.9 cc (0.02-36) and median margin dose was 13 Gy (12-25). RESULTS: Progression free survival (PFS) after SRS was 97% at 3 years, 95% at 5 years, and 94% at 10 years. Freedom from delayed surgical resection was found in 98.7% of patients. Smaller tumor volume was significantly associated with improved PFS. There were 326 patients with serviceable hearing (Gardner-Robertson 1 or 2) at the time of SRS with audiological follow-up of ≥ 1 year. Serviceable hearing preservation rates after SRS were 89.8% at 1 year, 76.9% at 3 years, 68.4% at 5 years, 62.5% at 7 years, and 51.4% at 10 years. Factors associated with improved serviceable hearing preservation included younger age, Gardner-Robertson grade 1 at SRS, and absence of subjective complaints of dysequilibrium or vertigo (vestibulopathy). Fifty-one patients (5.8%) developed trigeminal neuropathy. Fourteen (1.6%) developed a transient House-Brackmann grade 2 or 3 facial neuropathy. CONCLUSIONS: In this report with extended follow-up, primary SRS achieved tumor growth control in 94% of patients. Optimization of long- term cranial nerve outcomes remains an important achievement of this management strategy for VS.

Cranial nerve outcomes after primary stereotactic radiosurgery for symptomatic skull base meningiomas.

OBJECTIVE: To evaluate cranial nerve (CN) outcomes after primary stereotactic radiosurgery (SRS) for petroclival, cavernous sinus, and cerebellopontine angle meningiomas. METHODS: From our prospectively maintained database of 2022 meningioma patients who underwent Leksell stereotactic radiosurgery (SRS) during a 30-year interval, we found 98 patients with petroclival, 242 with cavernous sinus, and 55 patients with cerebellopontine angle meningiomas. Primary radiosurgery was performed in 245 patients. Patients included in this report had at least one CN deficit at the time of initial presentation and a minimum of 12 month follow up. Median age at the time of SRS was 58 years. Median follow up was 58 months (range 12-300 months), Median tumor volume treated with SRS was 5.9 cm3 (range 0.5-37.5 cm3), and median margin dose was 13 Gy (range 9-20Gy). RESULTS: Tumor control was achieved in 229 patients (93.5%) at a median follow up of 58 months. Progression free survival rate (PFS) after SRS was 98.7% at 1 year, 96.4% at 3 years, 93.7% at 5 years, and 86.4% at 10 years Overall, 114 of the 245 patients (46.5%) reported improvement of CN function. Patients with CP angle meningiomas demonstrated lower rates of CN improvement compared to petroclival and cavernous sinus meningioma patients. Deterioration of CN function after SRS developed in 24 patients (10%). The rate of deterioration was 2.8% at 1 year, 5.2% at 3 years, and 8% at 10 years. CONCLUSION: Primary SRS provides effective tumor control and favorable rate of improvement of preexisting CN deficit.

A Case of Symptomatic Granular Cell Tumor of the Pituitary Treated with Stereotactic Radiosurgery.

BACKGROUND: Granular cell tumors (GCT) of the pituitary are rare. Surgery is considered the primary management option. However, complete resection is often difficult, and surgery is associated with high rates of postoperative complications. AIMS: To report a unique case of pituitary GCT treated with stereotactic radiosurgery (SRS). CASE DESCRIPTION: We report a case of a 40-year-old female with endocrine dysfunction who underwent stereotactic biopsy and then SRS for the management of a suprasellar granular cell tumor. Over the ensuing 10 years, tumor regression was observed. Thirteen years after SRS, the patient remained asymptomatic; however, follow-up MRI demonstrated tumor progression. Fifteen years after SRS, the patient required endoscopic endonasal surgery after developing a new optic neuropathy. Her images demonstrated further tumor growth beyond the targeted area. CONCLUSION: SRS resulted in long-term tumor control without additional endocrine dysfunction, but the onset of new optic neuropathy associated with delayed tumor growth prompted surgical decompression.

Estimating the Risks of Adverse Radiation Effects After Gamma Knife Radiosurgery for Arteriovenous Malformations.

BACKGROUND AND PURPOSE: We evaluated risk factors associated with the development of adverse radiation effects (ARE) after stereotactic radiosurgery (SRS) for cerebral arteriovenous malformations (AVMs). METHODS: We evaluated 755 patients with AVM who underwent a single Gamma Knife SRS procedure with at least a 2-year minimum follow-up. Eighty-seven patients (12%) underwent previous resection and 128 (17%) had previous embolization. The median target volume was 3.6 mL (range, 0.1-26.3 mL). The median margin dose was 20 Gy (range, 13-27 Gy). RESULTS: Fifty-five patients (7%) developed symptomatic ARE at a median follow-up of 75 months. The cumulative rates of symptomatic ARE were 3.2%, 5.8%, 6.7%, and 7.5% at 1, 2, 3, and 5 years, respectively. Factors associated with a higher rate of developing symptomatic ARE included larger AVM volume, higher margin dose, larger 12-Gy volume, higher Spetzler-Martin grade, and higher radiosurgery-based score. The rates of developing symptomatic ARE were higher in the brain stem (22%) or thalamus (16%), compared with AVMs located in other brain locations (4%-8%). Nineteen patients (3%) sustained irreversible new neurological deficits related to ARE, and 1 patient died. The rates of irreversible symptomatic ARE were 0.8%, 1.9%, 2.1%, and 2.8% at 1, 2, 3, and 5 years, respectively. The 5-year cumulative rates of irreversible symptomatic ARE were 9.1% in thalamus, 12.1% in brain stem, and 1.4% in other locations. CONCLUSIONS: The knowledge of ARE risk rates after AVM radiosurgery can assist informed consent for patients with AVM, their families, and healthcare providers.

Stereotactic radiosurgery for essential tremor: Retrospective analysis of a 19-year experience.

BACKGROUND: Essential Tremor (ET) is a common movement disorder that can be disabling. Initial treatment is in the form of medical therapies. Patients with medically refractory ET seek surgical intervention which include radiofrequency thalamotomy, deep brain stimulation, and radiosurgical thalamotomy. Radiosurgical thalamotomy is a minimally invasive surgical option which is especially valuable for elderly and high surgical risk patients. OBJECTIVE: The purpose of this study was to retrospectively analyze the outcomes of stereotactic radiosurgery for patients suffering from medically refractory essential tremor. METHODS: During a 19-year period (1996-2015), 73 patients underwent gamma knife thalamotomy for intractable essential tremor. A median central dose of 140 Gy (range, 130-150) was delivered to the nucleus ventralis intermedius through a single 4-mm isocenter. We used the Fahn-Tolosa-Marin clinical tremor rating scale to score tremor, handwriting, drawing, and ability to drink fluids. The median time to last follow-up was 28 months (range, 6-152). RESULTS: After gamma knife thalamotomy, 93.2% improved in tremor. Forty-four patients (60.3%) experienced tremor arrest or barely perceptible tremor. Eighteen patients (24.7%) noted tremor arrest and complete restoration of motor function. Tremor improvement was sustained at last follow-up in 96% of patients who experience tremor relief. Mean tremor score improved from 3.19 before to 1.27 after gamma knife thalamotomy (P < 0.0001). Mean handwriting score improved from 2.97 to 1.25 (P < 0.0001). Mean drawing score improved from 3.16 to 1.26 (P < 0.0001). Mean drinking score improved from 3.14 to 1.56 (P < 0.0001). Imaging follow-up showed three types of lesions: enhancing lesion, streaking along internal capsule on fluid-attenuated inversion recovery, and significant reactive changes. Three patients (4%) experienced temporary adverse radiation effects. CONCLUSION: Radiosurgery is a safe and valuable treatment option for medically refractory essential tremor, especially for the elderly or those with high surgical risk for DBS or radiofrequency thalamotomy. © 2017 International Parkinson and Movement Disorder Society.

Glioblastoma multiforme (GBM) in the elderly: initial treatment strategy and overall survival.

The EORTC trial which solidified the role of external beam radiotherapy (EBRT) plus temozolomide (TMZ) in the management of GBM excluded patients over age 70. Randomized studies of elderly patients showed that hypofractionated EBRT (HFRT) alone or TMZ alone was at least equivalent to conventionally fractionated EBRT (CFRT) alone. We sought to investigate the practice patterns and survival in elderly patients with GBM. We identified patients age 65-90 in the National Cancer Data Base (NCDB) with histologically confirmed GBM from 1998 to 2012 and known chemotherapy and radiotherapy status. We analyzed factors predicting treatment with EBRT alone vs. EBRT plus concurrent single-agent chemotherapy (CRT) using multivariable logistic regression. Similarly, within the EBRT alone cohort we compared CFRT (54-65 Gy at 1.7-2.1 Gy/fraction) to HFRT (34-60 Gy at 2.5-5 Gy/fraction). Multivariable Cox proportional hazards model (MVA) with propensity score adjustment was used to compare survival. A total of 38,862 patients were included. Initial treatments for 1998 versus 2012 were: EBRT alone = 50 versus 10%; CRT = 6 versus 50%; chemo alone = 1.6% (70% single-agent) versus 3.2% (94% single-agent). Among EBRT alone patients, use of HFRT (compared to CFRT) increased from 13 to 41%. Numerous factors predictive for utilization of CRT over EBRT alone and for HFRT over CFRT were identified. Median survival and 1-year overall survival were higher in the CRT versus EBRT alone group at 8.6 months vs. 5.1 months and 36.0 versus 15.7% (p < 0.0005 by log-rank, multivariable HR 0.65 [95% CI = 0.61-0.68, p < 0.0005], multivariable HR with propensity adjustment 0.66 [95% CI = 0.63-0.70, p < 0.0005]). For elderly GBM patients in the United States, CRT is the most common initial treatment and appears to offer a survival advantage over EBRT alone. Adoption of hypofractionation has increased over time but continues to be low.

Stereotactic Radiosurgery for Intractable Tremor-Dominant Parkinson Disease: A Retrospective Analysis.

OBJECTIVE: The purpose of this study was to retrospectively analyze the outcomes of stereotactic radiosurgery for patients suffering from medically refractory Parkinson disease (PD) tremor. METHODS: We retrospectively studied the outcomes of 33 patients who were treated with gamma knife thalamotomy (GKT) over a 19-year period. Twelve patients were ≥80 years. A median dose of 140 Gy (range, 130-150 Gy) was delivered to the nucleus ventralis intermedius through a single 4-mm isocenter. We used the Fahn-Tolosa-Marin clinical tremor rating scale to score tremor, handwriting, drawing, and ability to drink fluids. The median time to the last follow-up was 23 months (range, 9-144 months). RESULTS: After GKT, 31 patients (93.9%) experienced improvement in tremor. Twenty-three patients (70.0%) had complete or nearly complete tremor arrest. Nine patients (27.2%) noted tremor arrest and resolution of impairment in writing, drawing, and ability to drink fluids. One patient (3%) improved in bradykinesia, 3 patients (9%) improved in rigidity, and 3 patients (9%) decreased their dosage of dopa after GKT. Tremor relief was fully maintained in the last follow-up for 96.8% of responding patients. Two patients (6%) experienced temporary adverse radiation effects. CONCLUSIONS: GKT is a safe and effective treatment for medically refractory PD tremor, especially for the elderly or those not suitable for deep brain stimulation or thermal thalamotomy.

Stereotactic Radiosurgery as Initial Surgical Management for Elderly Patients with Trigeminal Neuralgia.

BACKGROUND: Management of older patients with medically refractory trigeminal neuralgia (TN) is yet a matter of debate. OBJECTIVE: We sought to determine the benefit of stereotactic radiosurgery (SRS) as the sole surgical management in older patients (≥70 years). METHODS: One hundred and twenty-seven patients (≥70 years) with typical TN underwent SRS as initial surgical management. The median maximum dose for the first procedure was 80 Gy. Repeat SRS was performed in 46 patients who developed recurrent pain. RESULTS: After the first SRS, the initial pain control was achieved in 91% of patients. Complete pain relief (Barrow Neurological Institute [BNI] score I) developed in 75 patients (59%) and was maintained in 59, 39, and 22% of patients at 1, 3, and 5 years. Following repeat SRS, the rate of complete pain relief was 79, 55, and 41% at 1, 3, and 5 years. The chance of BNI I preservation was greater after repeat SRS compared to initial SRS (hazards ratio: 2.02, p < 0.0001). The incidence of trigeminal sensory loss was 17% after initial SRS but increased to 39% after repeat SRS. CONCLUSIONS: SRS alone was used effectively in older TN patients to achieve pain control. Recurrent pain responded to retreatment but was associated with an increased risk of sensory dysfunction.

Stereotactic radiosurgery for intradural spine tumors using cone-beam CT image guidance.

OBJECTIVE Cone-beam CT (CBCT) image guidance technology has been widely adopted for spine radiosurgery delivery. There is relatively little experience with spine radiosurgery for intradural tumors using CBCT image guidance. This study prospectively evaluated a series of intradural spine tumors treated with radiosurgery. Patient setup accuracy for spine radiosurgery delivery using CBCT image guidance for intradural spine tumors was determined. METHODS Eighty-two patients with intradural tumors were treated and prospectively evaluated. The positioning deviations of the spine radiosurgery treatments in patients were recorded. Radiosurgery was delivered using a linear accelerator with a beam modulator and CBCT image guidance combined with a robotic couch that allows positioning correction in 3 translational and 3 rotational directions. To measure patient movement, 3 quality assurance CBCTs were performed and recorded in 30 patients: before, halfway, and after the radiosurgery treatment. The positioning data and fused images of planning CT and CBCT from the treatments were analyzed to determine intrafraction patient movements. From each of 3 CBCTs, 3 translational and 3 rotational coordinates were obtained. RESULTS The radiosurgery procedure was successfully completed for all patients. Lesion locations included cervical (22), thoracic (17), lumbar (38), and sacral (5). Tumor histologies included schwannoma (27), neurofibromas (18), meningioma (16), hemangioblastoma (8), and ependymoma (5). The mean prescription dose was 17 Gy (range 12-27 Gy) delivered in 1-3 fractions. At the halfway point of the radiation, the translational variations and standard deviations were 0.4 ± 0.5, 0.5 ± 0.8, and 0.4 ± 0.5 mm in the lateral (x), longitudinal (y), and anteroposterior (z) directions, respectively. Similarly, the variations immediately after treatment were 0.5 ± 0.4, 0.5 ± 0.6, and 0.6 ± 0.5 mm along x, y, and z directions, respectively. The mean rotational angles were 0.3° ± 0.4°, 0.3° ± 0.4°, and 0.3° ± 0.4° along yaw, roll, and pitch, respectively, at the halfway point and 0.5° ± 0.5°, 0.4° ± 0.5°, and 0.2° ± 0.3° immediately after treatment. CONCLUSIONS Radiosurgery offers an alternative treatment option for intradural spine tumors in patients who may not be optimal candidates for open surgery. CBCT image guidance for patient setup for spine radiosurgery is accurate and successful in patients with intradural tumors.

Histopathological examination of spine tumors after treatment with radiosurgery.

OBJECTIVE Increased survival time after diagnosis of neoplastic disease has resulted in a gradual increase in spine tumor incidence. Radiosurgery is frequently a viable alternative to operative management in a population with severe medical comorbidities. The authors sought to assess the histopathological consequences of radiosurgery in the subset of patients progressing to operative intervention. METHODS Eighteen patients who underwent radiosurgery for spine tumors between 2008 and 2014 subsequently progressed to surgical treatment. A histopathological examination of these cases was performed. Indications for surgery included symptomatic compression fractures, radiographic instability, and symptoms of cord or cauda equina compression. Biopsy samples were obtained from the tumor within the radiosurgical zone in all cases and were permanently fixated. Viable tumor samples were stained for Ki 67. RESULTS Fifteen patients had metastatic lesions and 3 patients had neurofibromas. The mean patient age was 57 years. The operative indication was symptomatic compression in 10 cases (67%). The most frequent metastatic lesions were breast cancer (4 cases), renal cell carcinoma (3), prostate cancer (2), and endometrial cancer (2). In 9 (60%) of the 15 metastatic cases, histological examination of the lesions showed minimal evidence of inflammation. Viable tumor at the margins of the radiosurgery was seen in 9 (60%) of the metastatic cases. Necrosis in the tumor bed was frequent, as was fibrotic bone marrow. Vascular ectasia was seen in 2 of 15 metastatic cases, but sclerosis with ectasia was frequent. No evidence of malignant conversion was seen in the periphery of the lesions in the 3 neurofibroma cases. In 1 case of neurofibroma, the lesion demonstrated some small areas of remnant tumor in the radiosurgical target zone. CONCLUSIONS This case series demonstrates important histopathological characteristics of spinal lesions treated by SRS. Regions with the highest exposure to radiation appear to be densely necrotic and show little evidence of tumor growth, whereas peripheral regions distant from the radiation dosage are more likely to demonstrate viable tumor in malignant and benign neoplasms. Physiological tissue appears to be similarly affected. With additional investigation, a more homogenized field of hypofractionated radiation exposure may allow for tumor obliteration with relative preservation of critical anatomical structures.

Gamma Knife radiosurgery for meningiomas arising from the tentorium: a 22-year experience.

In order to evaluate long term clinical and imaging outcomes, the authors retrospectively reviewed our 22-year experience using stereotactic radiosurgery (SRS) for tentorial meningiomas. Thirty-nine patients with tentorial meningiomas underwent SRS using various Gamma Knife technologies between 1988 and 2010. The most common presenting symptoms were headache, dizziness or disequilibrium, and ataxia. The median tumor volume was 4.6 cm(3) (range 0.5-36.6 cm(3)) and the median radiation dose to the tumor margin was 14 Gy (range 8.9-18 Gy). The median follow-up period was 41 months (range 6-183 months). At the last imaging follow-up, tumor volumes decreased in 22 patients (57 %), remained stable in 13 patients (33 %), and increased in 4 patients (10 %). The progression-free survival after SRS was 97 % at 1 year, and 92 % at 5 years. At the last clinical follow-up, 35 patients (90 %) showed no change in symptoms, 1 patient (2 %) showed improvement of their neurologic symptom, and 3 patients (8 %) demonstrated worsening symptoms. The rate of symptom worsening after SRS was 5 % at 1 year, and 10 % at 5 years. Asymptomatic peritumoral edema after SRS occurred in 2 patients (5 %). Symptomatic adverse radiation effect developed in 2 patients (5 %). SRS for tentorial meningiomas provided long-term effective tumor control and a low risk of radiation related complications.

Gamma Knife radiosurgery of olfactory groove meningiomas provides a method to preserve subjective olfactory function.

Anosmia is a common outcome after resection of olfactory groove meningioma(s) (OGM) and for some patients represents a significant disability. To evaluate long term tumor control rates and preservation of subjective olfaction after Gamma Knife (GK) stereotactic radiosurgery (SRS) of OGM. We performed a retrospective chart review and telephone assessments of 41 patients who underwent GK SRS between 1987 and 2008. Clinical outcomes were stratified by full, partial or no subjective olfaction, whereas tumor control was assessed by changes in volume greater or lesser than 25%. The median clinical and imaging follow-up were 76 and 65 months, respectively. Prior to SRS, 19 (46%) patients had surgical resections and two (5%) had received fractionated radiation therapy. Twenty four patients (59%) reported a normal sense of smell, 12 (29%) reported a reduced sense of smell and five (12%) had complete anosmia. The median tumor volume was 8.5 cm(3) (range 0.6-56.1), the mean radiation dose at the tumor margin was 13 Gy (range 10-20) and the median estimated dose to the olfactory nerve was 5.1 Gy (range 1.1-18.1). At follow-up, 27 patients (66%) reported intact olfaction (three (7%) described return to a normal sense of smell), nine (22%) described partial anosmia, and five (12%) had complete anosmia. No patient reported deterioration in olfaction after SRS. Thirteen patients (32%) showed significant tumor regression, 26 (63%) had no further growth and two (5%) had progressed. The progression free tumor control rates were 97% at 1 year and 95% at 2, 10 and 20 years. Symptomatic adverse radiation effects occurred in three (7%) patients. Stereotactic radiosurgery provided both long term tumor control and preservation of olfaction.