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Background: Local treatment options for locally recurrent pancreatic adenocarcinoma (LR-PAC) are limited, with median survival time (MST) of 9-13 months (mos) following recurrence. MRI-guided stereotactic body radiation therapy (MRgSBRT) provides the ability to dose escalate while sparing normal tissue. Here we report on the early outcomes of MRgSBRT for LR-PAC., Methods: Patients with prior resection of pancreatic adenocarcinoma with local recurrence treated with MRgSBRT at a single tertiary referral center from 5-2021 to 2-2023 were identified from our prospective database. MRgSBRT was delivered to 40-50 Gy in 4-5 fractions with target and OAR delineation per institutional standards. Endpoints included local control per RECIST v1.1, distant failure, overall survival (OS), and acute and chronic toxicities per Common Terminology Criteria for Adverse Events, v5., Results: Fifteen patients with LR-PAC were identified with median follow-up of 10.6 mos (2.8-26.5 mos) from MRgSBRT. There were 8 females and 7 males, with a median age of 69 years (50-83). One patient underwent neoadjuvant radiation for 50.4 Gy in 28 fractions followed by resection, and one underwent adjuvant radiation for 45 Gy in 25 fractions prior to recurrence. MRgSBRT was delivered a median of 18.8 mos (3.5-52.8 mos) following resection. OS following recurrence at 6 and 12 mos were 87% and 51%, respectively, with a median survival time of 14.1 mos (3.2-27.4 mos). Three patients experienced local failure at 5.9, 7.8, and 16.6 months from MgSBRT with local control of 92.3% and 83.9% at 6 and 12 months. 10 patients experienced distant failure at a median of 2.9 mos (0.3-6.7 mos). Grade 1-2 acute GI toxicity was noted in 47% of patients, and chronic GI toxicity in 31% of patients. No grade > 3 toxicities were noted., Conclusions: This is the first report on toxicity and outcomes of MRgSBRT for LR-PAC in the literature. MRgSBRT is a safe, feasible treatment modality with the potential for improved local control in this vulnerable population. Future research is necessary to better identify which patients yield the most benefit from MRgSBRT, which should continue to be used with systemic therapy as tolerated., Trial Registration: Jefferson IRB#20976, approved 2/17/21., (© 2024. The Author(s).)

Meningeal melanocytomas are rare, benign tumours of the central nervous system arising from the melanocytes of the leptomeninges. First-line treatment consists of either gross or subtotal resection with or without radiotherapy. However, given the sensitive locations of these tumours, alternative treatment options such as definitive radiotherapy may be warranted in patients deemed high-risk or without accessible tumours. A 67-year-old male presenting with spastic gait, frequent falls, and vertical gaze palsy was diagnosed with a 2.4 cm primary meningeal melanocytoma arising from the interpeduncular fossa. Given the critical tumour position within the brainstem, definitive radiotherapy was recommended. He received fractionated stereotactic radiotherapy (FSRT) to a total dose of 54 Gy in 27 fractions, resulting in a gradual improvement in gait and ocular range of motion. Follow-up imaging over the next three years revealed largely stable disease and an increase in edema with mild upper extremity weakness that improved with steroids. He was followed for three years and expired four years after treatment due to pneumonia. For patients unable to receive surgical resection, definitive RT may provide local control with minimal morbidity.

Background: The utilization of stereotactic body radiation therapy (SBRT) is increasing for primary and secondary lung neoplasms. Despite encouraging results, SBRT is associated with an increased risk of osteoradionecrosis-induced rib fracture. We aimed to (1) evaluate potential clinical, demographic, and procedure-related risk factors for rib fractures and (2) describe the radiographic features of post-SBRT rib fractures., Methods: We retrospectively identified 106 patients who received SBRT between 2015 and 2018 for a primary or metastatic lung tumor with at least 12 months of follow up. Exclusion criteria were incomplete records, previous ipsilateral thoracic radiation, or relevant prior trauma. Computed tomography (CT) images were reviewed to identify and characterize rib fractures. Multivariate logistic regression modeling was employed to determine clinical, demographic, and procedural risk factors (e.g., age, sex, race, medical comorbidities, dosage, and tumor location)., Results: A total of 106 patients with 111 treated tumors met the inclusion criteria, 35 (32%) of whom developed at least one fractured rib (60 total fractured ribs). The highest number of fractured ribs per patient was five. Multivariate regression identified posterolateral tumor location as the only independent risk factor for rib fracture. On CT, fractures showed discontinuity between healing edges in 77% of affected patients., Conclusions: Nearly one third of patients receiving SBRT for lung tumors experienced rib fractures, 34% of whom experienced pain. Many patients developed multiple fractures. Post-SBRT fractures demonstrated a unique discontinuity between the healing edges of the rib, a distinct feature of post-SBRT rib fractures. The only independent predictor of rib fracture was tumor location along the posterolateral chest wall. Given its increasing frequency of use, describing the risk profile of SBRT is vital to ensure patient safety and adequately inform patient expectations., (© 2023. The Author(s).)

Background: Large variation regarding prescription and dose inhomogeneity exists in stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer. The aim of this modeling study was to identify which dose metric correlates best with local tumor control probability to make recommendations regarding SBRT prescription., Methods and Materials: We combined 2 retrospective databases of patients with non-small cell lung cancer, yielding 1500 SBRT treatments for analysis. Three dose parameters were converted to biologically effective doses (BEDs): (1) the (near-minimum) dose prescribed to the planning target volume (PTV) periphery (yielding BED min ); (2) the (near-maximum) dose absorbed by 1% of the PTV (yielding BED max ); and (3) the average between near-minimum and near-maximum doses (yielding BED ave ). These BED parameters were then correlated to the risk of local recurrence through Cox regression. Furthermore, BED-based prediction of local recurrence was attempted by logistic regression and fast and frugal trees. Models were compared using the Akaike information criterion., Results: There were 1500 treatments in 1434 patients; 117 tumors recurred locally. Actuarial local control rates at 12 and 36 months were 96.8% (95% confidence interval, 95.8%-97.8%) and 89.0% (87.0%-91.1%), respectively. In univariable Cox regression, BED ave was the best predictor of risk of local recurrence, and a model based on BED min had substantially less evidential support. In univariable logistic regression, the model based on BED ave also performed best. Multivariable classification using fast and frugal trees revealed BED max to be the most important predictor, followed by BED ave ., Conclusions: BED ave was generally better correlated with tumor control probability than either BED max or BED min . Because the average between near-minimum and near-maximum doses was highly correlated to the mean gross tumor volume dose, the latter may be used as a prescription target. More emphasis could be placed on achieving sufficiently high mean doses within the gross tumor volume rather than the PTV covering dose, a concept needing further validation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Early stage lung cancer is treated with stereotactic body radiation therapy (SBRT) in patients who are unable or unwilling to undergo surgical resection. Some patients' comorbidities are so severe that they are unable to even undergo a biopsy. A clinical diagnosis without biopsy before SBRT has been used, but there are limited data on its efficacy., Methods and Materials: Data on patients treated with SBRT for non-small cell lung cancer, with and without tissue confirmation, were collected from multiple institutions across Europe, Canada, and the United States. Patients with a minimum of 2 years of comprehensive follow up were selected for analysis. Treatment and patient characteristics were compared. Overall survival (OS), disease-free survival (DFS), cause-specific survival (CSS), and rates of local recurrence (LR), regional recurrence (RR), and distant metastasis (DM) were calculated and analyzed., Results: A total of 701 patients were identified, of which 67% had tissue confirmation of their tumors. The 3- and 5-year outcomes for OS, CSS, and DFS were 83.8%, 93.1%, 69%, and 60.6%, 86.7%, 45.5%, respectively. The rates for LR, RR, and DM at 3 and 5 years were 6.4%, 9.3%, 14.3%, and 10.5%, 14.3%, 19.7%, respectively. There were no statistically significant differences in survival outcomes or recurrences between the biopsy and no-biopsy cohorts., Conclusions: SBRT for clinically diagnosed lung cancers is efficacious in appropriately selected patients, with similar outcomes as those with a pathologic diagnosis. Thorough clinical and radiographic evaluations in a multidisciplinary setting are critical to the management of these patients., (Copyright © 2019 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: High-dose hypofractionated radiotherapy should theoretically result in a deviation from the typical linear-quadratic shape of the cell survival curve beyond a certain threshold dose, yet no evidence for this hypothesis has so far been found in clinical data of stereotactic body radiotherapy treatment (SBRT) for early-stage non-small cell lung cancer (NSCLC). A pragmatic explanation is a larger α/β ratio than the conventionally assumed 10 Gy. We here attempted an estimation of the α/β ratio for NSCLC treated with SBRT using individual patient data., Materials and Methods: We combined two large retrospective datasets, yielding 1294 SBRTs (≤10 fractions) of early stage NSCLC. Cox proportional hazards regression, a logistic tumor control probability model and a biologically motivated Bayesian cure rate model were used to estimate the α/β ratio based on the observed number of local recurrences and accounting for tumor size., Results: A total of 109 local progressions were observed after a median of 17.7 months (range 0.6-76.3 months). Cox regression, logistic regression of 3 year tumor control probability and the cure rate model yielded best-fit estimates of α/β = 12.8 Gy, 14.9 Gy and 12-16 Gy (depending on the prior for α/β), respectively, although with large uncertainties that did not rule out the conventional α/β = 10 Gy., Conclusions: Clinicians can continue to use the simple LQ formalism to compare different SBRT treatment schedules for NSCLC. While α/β = 10 Gy is not ruled out by our data, larger values in the range 12-16 Gy are more probable, consistent with recent meta-regression analyses., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background and Purpose: We conducted a phase I trial of alisertib, an oral aurora kinase inhibitor, with fractionated stereotactic re-irradiation therapy (FSRT) for patients with recurrent high grade glioma (HGG)., Materials and Methods: Adult patients with recurrent HGG were enrolled from Feb 2015 to Feb 2017. Patients were treated with concurrent FSRT and alisertib followed by maintenance alisertib. Concurrent alisertib dose was escalated from 20 mg to 50 mg twice daily (BID)., Results: 17 patients were enrolled. Median follow-up was 11 months. Median FSRT dose was 35 Gy. There were 6, 6, 3, and 2 patients enrolled in 20 mg, 30 mg, 40 mg, and 50 mg cohort, respectively. Only one DLT was observed. One patient in the 20 mg cohort had severe headache (Grade 3) resolved with steroids. There was no non-hematological grade 3 or higher toxicity. There were two Grade 4 late toxicities (one with grade 4 neutropenia and leukopenia, one with pulmonary embolism). One patient developed radiation necrosis (Grade 3). Sixteen patients finished concurrent treatment and received maintenance therapy (median cycles was 3, range 1-9). OS for all cohorts at 6 months was 88.2% with median survival time of 11.1 months. PFS at 6 months was 35.3% with median time to progression of 4.9 months. The trial stopped early due to closure of alisertib program with only 2 of 3 planned patients enrolled in the 50 mg cohort., Conclusion: Re-irradiation with FSRT combined with alisertib is safe and well tolerated for HGG with doses up to 40 mg BID. Although no DLT observed in the 50 mg cohort, this cohort was not fully enrolled and MTD was not reached. Clinical outcomes appear comparable to historical results. (NCT02186509)., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: To investigate if a local dose-effect (LDE) relationship for perfusion loss improves the NTCP model fit for SBRT induced radiation pneumonitis (RP) compared to conventional LDEs., Methods and Materials: Multi-institutional data of 1015 patients treated with SBRT were analyzed. Dose distributions were converted to NTD with α/β = 3 Gy. The Lyman-Kutcher-Burman NTCP model was fitted to the incidence grade ≥2 RP by maximum likelihood estimation with mean lung dose (MLD), equivalent uniform doses (EUD) using three LDE functions (power-law (EUD power ), logistic with 2 free parameters (EUD log-free ) and logistic with fixed parameters describing local perfusion loss (EUD Perfusion )) and volume above a threshold dose (V x ). Models were compared with the Akaike weights (Aw) derived from the Akaike information criteria (AIC)., Results: The median time to grade ≥2 RP was 4.2 months and plateaued after 17 months at 5.4%. A strong dose-effect relationship for RP incidence was observed. The EUD Perfusion based NTCP model had the lowest AIC. The Aw were 0.53, 0.19, 0.11, 0.11, 0.05 for the EUD Perfusion , V x , MLD, EUD log-free and EUD power LDEs respectively., Conclusion: A LDE for perfusion loss provided modest improvement in NTCP model fit for SBRT induced radiation pneumonitis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: Stereotactic body radiation therapy has been associated with increased toxicity when delivered to patients with early-stage non-small cell lung cancer with a tumor within 2 cm of the proximal bronchial tree (PBT). We investigated noncancer deaths for these patients as related to gross tumor volume (GTV) proximity to the PBT, compared with peripheral tumors., Methods and Materials: We included 765 patients with early-stage non-small cell lung cancer who were treated with stereotactic body radiation therapy to a median of 3 × 18 Gy. Central tumors were treated with a risk-adapted (less-intense) schedule (mostly 8 fractions) in 55% of the patients in the first-centimeter group and 27% of the patients in the second-centimeter group. An average anatomy with contouring of PBT and organs at risk (OARs) was deformed onto each patient to obtain the distance of the GTV to the PBT and doses to OARs. Log-rank, 1-way analysis of variance, and Cox regressions were performed to assess differences in the first-centimeter, second centimeter, and peripheral groups and associations with noncancer deaths., Results: The median overall survival was 42.7 months, the median noncancer death occurred in 57.3 months, and the median follow-up was 34.8 months. Noncancer death in the first-centimeter group (31 patients) was significantly different from noncancer death in the other groups, with a hazard ratio of 3.175 (P < .001). Noncancer death in the second-centimeter group (71 patients) was not different from noncancer death in the peripheral group (P = .53). Doses to OARs were higher in the first- and second-centimeter groups than in the peripheral group for all OARs. High dose to the PBT was associated with noncancer death (D1%; hazard ratio, 1.006 Gy -1 ; P = .003)., Conclusions: Patients with a GTV in the first centimeter surrounding the PBT died more often from causes other than cancer compared with other patients. Noncancer death in patients with a GTV in the second centimeter, who partly received a risk-adapted schedule, was comparable to that in patients with a peripheral tumor., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: European data suggest that 8-fraction stereotactic body radiation therapy (SBRT) regimens may be similar in efficacy with less toxicity than ≤5-fraction SBRT for central lung lesions. However, under current Centers for Medicare and Medicaid Services guidelines, SBRT in the United States (US) is reimbursed for only ≤5 fractions, whereas there are no such restrictions for reimbursement in Canada. We hypothesize that US-specific SBRT reimbursement policies influence the use of ≥5-fraction SBRT in US academic centers in comparison with comparable Canadian centers., Methods and Materials: A 15-question electronic survey was distributed to radiation oncologists at National Cancer Institute-designated cancer centers in the US and the 10 highest research-funded cancer centers in Canada. Fisher exact test or exact logistic regression if applicable was used, where P<.05 was considered statistically different from neutral., Results: Of the 143 radiation oncologists from 60 US cancer centers and 6 Canadian cancer centers who completed the survey (17.6% response rate), 125 routinely prescribe SBRT. Fifty percent of US physicians versus 0% of Canadian physicians indicated that there are instances when they would like to prescribe >5-fraction SBRT but prescribe ≤5 fractions because of insurance reimbursement (P=.076 and P=.001, respectively). Seventy percent (P=.006) of US radiation oncologists versus 0% (P=.001) of Canadian radiation oncologists report that SBRT clinical investigation is constrained by the insurance reimbursement. The most common reported deterrent to prescribing >5-fraction SBRT in the US was insurance reimbursement (49.5%)., Conclusions: US radiation oncologists are more likely than those in Canada to report that SBRT clinical investigation and >5-fraction SBRT use may be negatively influenced by health insurance reimbursement; this perception was not held by physicians in Canada. Health care environment may significantly affect radiation therapy decision making and practice patterns., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: We performed a phase 1 study to determine the maximum tolerable dose and safety of ipilimumab with stereotactic radiosurgery (SRS) or whole brain radiation therapy (WBRT) in patients with brain metastases from melanoma., Methods and Materials: Based on the intracranial disease burden, patients underwent WBRT (arm A) or SRS (arm B). The ipilimumab starting dose was 3 mg/kg every 3 weeks, starting on day 3 of WBRT or 2 days after SRS. The ipilimumab dose was escalated to 10 mg/kg using a 2-stage, 3+3 design. The primary endpoint was to determine the maximum tolerable dose of ipilimumab combined with radiation therapy. The secondary endpoints were overall survival, intracranial and extracranial control, progression-free survival, and toxicity. The ClinicalTrials.gov registration number is NCT01703507., Results: The characteristics of the 16 patients enrolled between 2011 and 2014 were mean age, 60 years; median number of brain metastases, 2 (range 1->10); and number with EC disease, 13 (81%). Treatment included WBRT (n=5), SRS (n=11), and ipilimumab 3 mg/kg (n=7) or 10 mg/kg (n=9). The median follow-up was 8 months (arm A) and 10.5 months (arm B). A total of 21 grade 1 to 2 neurotoxic effects occurred, with no dose-limiting toxicities. One patient experienced grade 3 neurotoxicity before ipilimumab administration. Ten additional grade 3 toxicities were reported, with gastrointestinal toxicities (n=5; 31%) the most common. No patient developed grade 4 or 5 toxicity. The median progression-free survival and overall survival in arm A was 2.5 months and 8 months and in arm B was 2.1 months and not reached, respectively., Conclusions: Concurrent ipilimumab 10 mg/kg with SRS is safe. The WBRT arm was closed early because of slow accrual but demonstrated safety with ipilimumab 3 mg/kg. No patient experienced dose-limiting toxicity. Larger studies, including those with combination checkpoint inhibitor therapy and SRS, are warranted., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To determine the safety and efficacy of lung stereotactic body radiation therapy (SBRT) in octo- and nonagenarians and to compare their outcomes with those of younger patients., Methods and Materials: Patients with primary lung cancer treated with SBRT were identified from a multi-institutional (5 institutions) database of 1083 cases. Details of patient factors, treatment specifics, toxicity, and clinical outcomes were extracted from the database. All events were calculated from the end of radiation therapy. Estimates of local recurrence, regional recurrence, and distant metastases were calculated using the competing risk method. Cause-specific survival (CSS) and overall survival (OS) were calculated using the Kaplan-Meier method. Outcomes were compared for those aged <70, 70 to 79, and ≥80 years. Univariable and multivariable analyses were performed to determine associations with CSS and OS in patients aged ≥80 years., Results: The median (range) follow-up was 1.7 (1-10) years, and median age was 75 (41-94) years. There were 305 patients aged <70 years (28%), 448 aged 70 to 79 years (41%), and 330 aged ≥80 years (30%). There was no difference in 2-year local recurrence (4.2% vs 5.4% vs 3.7%, respectively, P=.7), regional recurrence (10.4% vs 7.8% vs 5.3%, P=.1), distant metastases (12.2% vs 7.7% vs 9.5%, P=.2), or CSS (90.6% vs 90.3% vs 90.4%, P=.6). Those aged ≥80 years had significantly lower 2-year OS (73.6% vs 67.2% vs 63.3%, P<.01). The grade 3+ pneumonitis rate was 1.3% versus 1.6% versus 1.5% (P=1.0) in patients aged <70, 70 to 79, and ≥80 years, respectively. The 90-day mortality rates for patients aged <70, 70 to 79, and ≥80 years were 1.3%, 2.5%, and 2.4% (P=.01), respectively. In patients aged ≥80 years OS was associated with T category (hazard ratio 1.7; P<.01)., Conclusion: Stereotactic body radiation therapy is a safe treatment modality in elderly patients (aged ≥80 years). Despite larger tumor volumes, the tumor control outcomes were comparable to those in younger patients treated with SBRT. All patients with early-stage lung cancer, regardless of age, should be considered for treatment with SBRT., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: The study was aimed to compare online 6 degree-of-freedom image registrations of TrueBeam cone-beam computed tomography and BrainLab ExacTrac X-ray imaging systems for intracranial radiosurgery., Methods: Phantom and patient studies were performed on a Varian TrueBeam STx linear accelerator (version 2.5), which is integrated with a BrainLab ExacTrac imaging system (version 6.1.1). The phantom study was based on a Rando head phantom and was designed to evaluate isocenter location dependence of the image registrations. Ten isocenters at various locations representing clinical treatment sites were selected in the phantom. Cone-beam computed tomography and ExacTrac X-ray images were taken when the phantom was located at each isocenter. The patient study included 34 patients. Cone-beam computed tomography and ExacTrac X-ray images were taken at each patient's treatment position. The 6 degree-of-freedom image registrations were performed on cone-beam computed tomography and ExacTrac, and residual errors calculated from cone-beam computed tomography and ExacTrac were compared., Results: In the phantom study, the average residual error differences (absolute values) between cone-beam computed tomography and ExacTrac image registrations were 0.17 ± 0.11 mm, 0.36 ± 0.20 mm, and 0.25 ± 0.11 mm in the vertical, longitudinal, and lateral directions, respectively. The average residual error differences in the rotation, roll, and pitch were 0.34° ± 0.08°, 0.13° ± 0.09°, and 0.12° ± 0.10°, respectively. In the patient study, the average residual error differences in the vertical, longitudinal, and lateral directions were 0.20 ± 0.16 mm, 0.30 ± 0.18 mm, 0.21 ± 0.18 mm, respectively. The average residual error differences in the rotation, roll, and pitch were 0.40°± 0.16°, 0.17° ± 0.13°, and 0.20° ± 0.14°, respectively. Overall, the average residual error differences were <0.4 mm in the translational directions and <0.5° in the rotational directions. ExacTrac X-ray image registration is comparable to TrueBeam cone-beam computed tomography image registration in intracranial treatments.

Background and Purpose: To investigate potential associations between dose to heart (sub)structures and non-cancer death, in early stage non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiation therapy (SBRT)., Methods: 803 patients with early stage NSCLC received SBRT with predominant schedules of 3×18Gy (59%) or 4×12Gy (19%). All patients were registered to an average anatomy, their planned dose deformed accordingly, and dosimetric parameters for heart substructures were obtained. Multivariate Cox regression and a sensitivity analysis were used to identify doses to heart substructures or heart region with a significant association with non-cancer death respectively., Results: Median follow-up was 34.8months. Two year Kaplan-Meier overall survival rate was 67%. Of the deceased patients, 26.8% died of cancer. Multivariate analysis showed that the maximum dose on the left atrium (median 6.5Gy EQD2, range=0.009-197, HR=1.005, p-value=0.035), and the dose to 90% of the superior vena cava (median 0.59Gy EQD2, range=0.003-70, HR=1.025, p-value=0.008) were significantly associated with non-cancer death. Sensitivity analysis identified the upper region of the heart (atria+vessels) to be significantly associated with non-cancer death., Conclusions: Doses to mainly the upper region of the heart were significantly associated with non-cancer death. Consequently, dose sparing in particular of the upper region of the heart could potentially improve outcome, and should be further studied., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: The objective of this study was to determine the predictors and patterns of regional recurrence (RR) following stereotactic body radiotherapy (SBRT) for primary lung cancers., Material and Methods: Details of patient factors, treatment, and outcome factors were extracted from a multi-institutional (5) database. All events were calculated from the end of radiotherapy. Estimates of local recurrence, RR, and distant metastases (DM) were calculated using the competing risk method. Cause-specific and overall survival were calculated using the Kaplan-Meier method. Details of locations and number of simultaneous RRs were categorized by lymph node anatomic station., Results: A total of 734 patients were analyzed. The median follow-up was 3.0 years in surviving patients. Four hundred seventy-six (65%) patients had pathologic proof of disease. There were 64 patients with RR. The 2-year local recurrence, RR, and distant metastases rates were 5.6%, 9.0%, and 14.6% respectively. The 2-year cause-specific and overall survival were 89.9% and 63.7%, respectively. There were 136 simultaneous sites of RR. There were 21 recurrences in stations 4R (15.4%), 9 (6.6%) in 4L, 30 (22%) in 7, 19 (13.9%) in 10R, and 14 (10.3%) in 10L. The most common stations for isolated recurrence (n = 19) were station 7 (n = 5; 26.3%) and station 10R (n = 6; 31.6%). The most common RR levels were stations 4 and 7 for right and left upper lobe, stations 5, 7, and 10 for left lower lobe tumors, and stations 7 and 10 for right lower lobe tumors., Conclusion: Stations 4, 7, and 10 were the most common stations for RR. These patterns of recurrence may guide nodal staging procedures prior to SBRT., (Copyright © 2016 Elsevier Inc. All rights reserved.)

An automatic brain-metastases planning (ABMP) software has been installed in our institution. It is dedicated for treating multiple brain metastases with radiosurgery on linear accelerators (linacs) using a single-setup isocenter with noncoplanar dynamic conformal arcs. This study is to validate the calculated absolute dose and dose distribution of ABMP. Three types of measurements were performed to validate the planning software: 1, dual micro ion chambers were used with an acrylic phantom to measure the absolute dose; 2, a 3D cylindrical phantom with dual diode array was used to evaluate 2D dose distribution and point dose for smaller targets; and 3, a 3D pseudo-in vivo patient-specific phantom filled with polymer gels was used to evaluate the accuracy of 3D dose distribution and radia-tion delivery. Micro chamber measurement of two targets (volumes of 1.2 cc and 0.9 cc, respectively) showed that the percentage differences of the absolute dose at both targets were less than 1%. Averaged GI passing rate of five different plans measured with the diode array phantom was above 98%, using criteria of 3% dose difference, 1 mm distance to agreement (DTA), and 10% low-dose threshold. 3D gel phantom measurement results demonstrated a 3D displacement of nine targets of 0.7 ± 0.4 mm (range 0.2 ~ 1.1 mm). The averaged two-dimensional (2D) GI passing rate for several region of interests (ROI) on axial slices that encompass each one of the nine targets was above 98% (5% dose difference, 2 mm DTA, and 10% low-dose threshold). Measured D95, the minimum dose that covers 95% of the target volume, of the nine targets was 0.7% less than the calculated D95. Three different types of dosimetric verification methods were used and proved the dose calculation of the new automatic brain metastases planning (ABMP) software was clinical acceptable. The 3D pseudo-in vivo patient-specific gel phantom test also served as an end-to-end test for validating not only the dose calculation, but the treatment delivery accuracy as well., (© 2016 The Authors.)

Purpose: Fibrotic changes after stereotactic body radiation therapy (SBRT) for stage I non-small cell lung cancer (NSCLC) are difficult to distinguish from local recurrences (LR), hampering proper patient selection for salvage therapy. This study validates previously reported high-risk computed tomography (CT) features (HRFs) for detection of LR in an independent patient cohort., Methods and Materials: From a multicenter database, 13 patients with biopsy-proven LR were matched 1:2 to 26 non-LR control patients based on dose, planning target volume (PTV), follow-up time, and lung lobe. Tested HRFs were enlarging opacity, sequential enlarging opacity, enlarging opacity after 12 months, bulging margin, linear margin disappearance, loss of air bronchogram, and craniocaudal growth. Additionally, 2 new features were analyzed: the occurrence of new unilateral pleural effusion, and growth based on relative volume, assessed by manual delineation., Results: All HRFs were significantly associated with LR except for loss of air bronchogram. The best performing HRFs were bulging margin, linear margin disappearance, and craniocaudal growth. Receiver operating characteristic analysis of the number of HRFs to detect LR had an area under the curve (AUC) of 0.97 (95% confidence interval [CI] 0.9-1.0), which was identical to the performance described in the original report. The best compromise (closest to 100% sensitivity and specificity) was found at ≥4 HRFs, with a sensitivity of 92% and a specificity of 85%. A model consisting of only 2 HRFs, bulging margin and craniocaudal growth, resulted in a sensitivity of 85% and a specificity of 100%, with an AUC of 0.96 (95% CI 0.9-1.0) (HRFs ≥2). Pleural effusion and relative growth did not significantly improve the model., Conclusion: We successfully validated CT-based HRFs for detection of LR after SBRT for early-stage NSCLC. As an alternative to number of HRFs, we propose a simplified model with the combination of the 2 best HRFs: bulging margin and craniocaudal growth, although validation is warranted., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: Stereotactic body radiotherapy (SBRT) is the guideline-recommended treatment for medically inoperable patients with peripheral stage I non-small cell lung cancer (NSCLC). This study analyzed whether short-term (<6 months) death can be predicted reliably to select a subgroup of patients who will not have a benefit from SBRT., Methods: A total of 779 patients with early-stage NSCLC who had been treated with cone beam computed tomography-guided SBRT in five institutes and for whom information on overall survival during the first 6 months after treatment was available were included in this analysis. The probability of dying within 6 months after treatment was defined as the end point "early death" and modeled by multivariate logistic regression. Model fitting was performed using the least absolute shrinkage and selection operator method, and model test performance was estimated using double 10-fold cross validation. The variables age, sex, Eastern Cooperative Oncology Group performance status, operability, forced expiratory volume in 1 second, and Charlson comorbidity index were considered for model building., Results: Eastern Cooperative Oncology Group performance status and (to a lesser extent) operability were the most important predictors of early death, whereas the Charlson comorbidity index was associated only with the overall survival time. On the basis of the best expected test performance (area under the curve = 0.699), the risk for early death would be 8.8% (range 8.2%-13.7%) and 4.1% (3.0%-4.3%) for the 10% of patients with the highest and lowest risk, respectively. Overall, predictive performance was too low for clinical application., Conclusions: SBRT should be offered to all patients irrespective of their comorbidities, unless the performance status of the patients and the comorbidities prevent accurate SBRT planning and delivery., (Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Panobinostat is an oral HDAC inhibitor with radiosensitizing activity. We investigated the safety, tolerability and preliminary efficacy of panobinostat combined with fractionated stereotactic re-irradiation therapy (FSRT) for recurrent high grade gliomas. Patients with recurrent high grade gliomas were enrolled in a 3 + 3 dose escalation study to determine dose limiting toxicities (DLTs), maximum tolerated dose (MTD), safety, tolerability, and preliminary efficacy. FSRT was prescribed to 30-35 Gy delivered in 10 fractions. Panobinostat was administrated concurrently with radiotherapy. Of 12 evaluable patients, 8 had recurrent GBM, and 4 had recurrent anaplastic astrocytoma. There were three grade 3 or higher toxicities in each the 10 and 30 mg cohorts. In the 30 mg cohort, there was one DLT; grade 4 neutropenia. One patient developed late grade 3 radionecrosis. The median follow up was 18.8 months. The PFS6 was 67, 33, and 83 % for 10, 20, and 30 mg cohorts, respectively. The median OS was 7.8, 6.1 and 16.1 months for the 10, 20 and 30 mg cohorts, respectively. Panobinostat administrated with FSRT is well tolerated at 30 mg. A phase II trial is warranted to assess the efficacy of panobinostat plus FSRT for recurrent glioma.

Background and Purpose: Recent advances in multileaf collimator field shaping technology and inverse planning software have resulted in highly conformal LINAC based stereotactic radiosurgery (SRS) plans with minimal dose to critical structures. This modeling study compares Gamma Knife (GK) and LINAC SRS for vestibular schwannoma (VS)., Materials and Methods: 76 treatment plans from nineteen patients with VS were planned using GK forward planning and volumetric arc therapy (VMAT) inverse planning software. VMAT plans were generated with 1 coplanar, 3 and 5 non-coplanar arcs. Dose to normal structures and beam-on time (dose rate 600MU/min) were compared using Kruskal-Wallis and Dunn's post hoc test., Results: Median tumor volume was 1.2cm(3) (range 0.1-4.8cm(3)). A peripheral tumor dose of 12Gy was prescribed. Tumor coverage was >99.8%. VMAT plans had lower target D2% and mean dose, as well as decreased beam-on time, compared to GK plans (p<0.0001). Paddick conformity index in VMAT 5 arc plans was superior to that of GK plans for targets >0.5cm(3) (p=0.002). Similar dose to cochlea, normal brain tissue and brainstem was observed., Conclusion: VMAT should be considered as a safe, alternative modality to GK for VS SRS treatment, especially for tumors larger than 0.5cm(3)., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Radiation Therapy Oncology Group (RTOG) 9508 showed a survival advantage for patients with 1 but not 2 or 3 brain metastasis (BM) treated with whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) versus WBRT alone. An improved prognostic index, the graded prognostic assessment (GPA) has been developed. Our hypothesis was that if the data from RTOG 9508 were poststratified by the GPA, the conclusions may vary., Methods and Materials: In this analysis, 252 of the 331 patients were evaluable by GPA. Of those, 211 had lung cancer. Breast cancer patients were excluded because the components of the breast GPA are not in the RTOG database. Multiple Cox regression was used to compare survival between treatment groups, adjusting for GPA. Treatment comparisons within subgroups were performed with the log-rank test. A free online tool (brainmetgpa.com) simplified GPA use., Results: The fundamental conclusions of the primary analysis were confirmed in that there was no survival benefit overall for patients with 1 to 3 metastases; however, there was a benefit for the subset of patients with GPA 3.5 to 4.0 (median survival time [MST] for WBRT + SRS vs WBRT alone was 21.0 versus 10.3 months, P=.05) regardless of the number of metastases. Among patients with GPA 3.5 to 4.0 treated with WBRT and SRS, the MST for patients with 1 versus 2 to 3 metastases was 21 and 14.1 months, respectively., Conclusions: This secondary analysis of predominantly lung cancer patients, consistent with the original analysis, shows no survival advantage for the group overall when treated with WBRT and SRS; however, in patients with high GPA (3.5-4), there is a survival advantage regardless of whether they have 1, 2, or 3 BM. This benefit did not extend to patients with lower GPA. Prospective validation of this survival benefit for patients with multiple BM and high GPA when treated with WBRT and SRS is warranted., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose/objective(s): Angiogenic blockade with irradiation may enhance the therapeutic ratio of radiation therapy (RT) through vascular normalization. We sought to determine the safety and toxicity profile of continuous daily-dosed sunitinib when combined with hypofractionated stereotactic RT (fSRT) for recurrent high-grade gliomas (rHGG)., Methods and Materials: Eligible patients had malignant high-grade glioma that recurred or progressed after primary surgery and RT. All patients received a minimum of a 10-day course of fSRT, had World Health Organization performance status of 0 to 1, and a life expectancy of >3 months. During fSRT, sunitinib was administered at 37.5 mg daily. The primary endpoint was acute toxicity, and response was assessed via serial magnetic resonance imaging., Results: Eleven patients with rHGG were enrolled. The fSRT doses delivered ranged from 30 to 42 Gy in 2.5- to 3.75-Gy fractions. The median follow-up time was 40 months. Common acute toxicities included hematologic disorders, fatigue, hypertension, and elevated liver transaminases. Sunitinib and fSRT were well tolerated. One grade 4 mucositis toxicity occurred, and no grade 4 or 5 hypertensive events or intracerebral hemorrhages occurred. One patient had a nearly complete response, and 4 patients had stable disease for >9 months. Two patients (18%) remain alive and progression-free >3 years from enrollment. The 6-month progression-free survival was 45%., Conclusions: Sunitinib at a daily dose of 37.5 mg given concurrently with hypofractionated stereotactic reirradiation for rHGG yields acceptable toxicities and an encouraging 6-month progression-free survival., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: To examine potential dose-response relationships with various non-small-cell lung cancer (NSCLC) SBRT fractionation regimens delivered with online CT-based image guidance., Methods: 505 tumors in 483 patients with clinical stage T1-T2N0 NSCLC were treated with SBRT using on-line cone-beam-CT-based image guidance at 5 institutions (1998-2010). Median maximum tumor dimension was 2.6 cm (range 0.9-8.5 cm). Dose fractionation prescription was according to each institution's protocol with the most common schedules of 18-20 GyX3, 12 GyX4, 12 GyX5, 12.5 GyX3, 7.5 GyX8 (median = 54 Gy, 3 fractions). Median prescription (Rx) BED10 = 132 Gy (50.4-180). Median values (Gy) of 3D planned doses for BED10 were GTV(min) = 164.1, GTV(mean) = 188.4, GTV(max) = 205.9, PTV(min) = 113.9, PTV D99 = 123.9, PTV(mean) = 164.7, PTV D1 = 197.3, PTV(max) = 210.7. Mean follow-up = 1.6 years., Results: 26 cases (5%) had local recurrence (LR) for a 2-year rate of 6% and 3-year rate of 9%. All BED10 GTV&PTV endpoints were associated with LR as continuous variables on univariate analysis (p<0.05). Rx and PTV(mean) dose appeared to have the highest correlation with LR with area under ROC curve of 0.69 and 0.65 respectively and optimal cut points of 105 and 125 Gy, respectively. 2-year LR was 4% for PTV(mean)>125 vs 17% for <125 Gy (p<0.01) with sensitivity = 84% and specificity = 57% for predicting LR. 2-year LR for Rx BED10>105 was 4% vs 15% for <105 Gy (p<0.01). Longer treatment duration (⩾ 11 elapsed days) demonstrated a 2-year LR of 14% vs 4% for ⩽ 10 days (p<0.01). GTV size was associated with LR on univariate analysis as a continuous variable (p = 0.02) with 2-year LR = 3% for <2.7 cm vs 9% for ⩾ 2.7 cm (p = 0.03). BED10 (p = 0.01) and elapsed days during RT (p = 0.05) were independent predictors on multivariate analysis as continuous variables., Conclusions: There is a substantial dose-response relationship for local control of NSCLC following image-guided SBRT with optimal PTV(mean) BED10>125 Gy. Shorter treatment duration was also associated with better local control in this dataset., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Fractionated stereotactic radiotherapy (FSRT) is a noninvasive treatment for acoustic neuromas (ANs). Initial reports from our institution demonstrated that the reduction of treatment dose to 46.8 Gy resulted in improved preservation of functional hearing status., Objective: We now report the tumor control (TC), symptomatic outcome, and hearing preservation (HP) rate in patients treated with reduced-dose FSRT., Methods: We analyzed all patients with AN treated from 2002 to 2011. All patients received 46.8 Gy in 1.8-Gy fractions. Follow-up audiogram and magnetic resonance imaging were performed in ≤ 1-year intervals. TC and HP were calculated by the Kaplan-Meier method. Analysis of HP, defined as Gardner-Robertson value ≤ 2, was determined by audiometric data. Non-hearing-related symptoms were defined by Common Terminology Criteria for Adverse Events version 4., Results: In total, 154 patients were analyzed. At a median follow-up of 35 months (range, 4-108), TC was achieved in 96% of patients (n = 148/154) and at 3 and 5 years was 99% and 93%. Eighty-seven patients had serviceable hearing at the time of FSRT and evaluable audiometric follow-up. Overall HP was 67% and at 3 and 5 years was 66% and 54%. Pure tone average decreased by a median of 13 dB in all patients. Nineteen percent (n = 31) of patients experienced symptom improvement, and 8% (n = 13) had worsening of symptoms. Cranial nerve dysfunction occurred in 3.8% of patients (n = 6)., Conclusion: Reduced-dose FSRT to 46.8 Gy for AN achieves excellent functional HP rates and limited toxicity without compromising long-term TC. Based on these promising outcomes, further attempts at dose deescalation may be warranted.

Background: A phase 3 Radiation Therapy Oncology Group (RTOG) study subset analysis demonstrated improved overall survival (OS) with the addition of stereotactic radiosurgery (SRS) to whole brain radiation therapy (WBRT) in non-small cell lung cancer (NSCLC) patients with 1 to 3 brain metastases. Because temozolomide (TMZ) and erlotinib (ETN) cross the blood-brain barrier and have documented activity in NSCLC, a phase 3 study was designed to test whether these drugs would improve the OS associated with WBRT + SRS., Methods and Materials: NSCLC patients with 1 to 3 brain metastases were randomized to receive WBRT (2.5 Gy × 15 to 37.5 Gy) and SRS alone, versus WBRT + SRS + TMZ (75 mg/m(2)/day × 21 days) or ETN (150 mg/day). ETN (150 mg/day) or TMZ (150-200 mg/m(2)/day × 5 days/month) could be continued for as long as 6 months after WBRT + SRS. The primary endpoint was OS., Results: After 126 patients were enrolled, the study closed because of accrual limitations. The median survival times (MST) for WBRT + SRS, WBRT + SRS + TMZ, and WBRT + SRS + ETN were qualitatively different (13.4, 6.3, and 6.1 months, respectively), although the differences were not statistically significant. Time to central nervous system progression and performance status at 6 months were better in the WBRT + SRS arm. Grade 3 to 5 toxicity was 11%, 41%, and 49% in arms 1, 2, and 3, respectively (P<.001)., Conclusion: The addition of TMZ or ETN to WBRT + SRS in NSCLC patients with 1 to 3 brain metastases did not improve survival and possibly had a deleterious effect. Because the analysis is underpowered, these data suggest but do not prove that increased toxicity was the cause of inferior survival in the drug arms., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the influence of tumor size, prescription dose, and dose to the lungs on posttreatment pulmonary function test (PFT) changes after stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC)., Methods and Materials: The analysis is based on 191 patients treated at 5 international institutions: inclusion criteria were availability of pre- and post-SBRT PFTs and dose-volume histograms of the lung and planning target volume (PTV); patients treated with more than 1 SBRT course were excluded. Correlation between early (1-6 months, median 3 months) and late (7-24 months, median 12 months) PFT changes and tumor size, planning target volume (PTV) dose, and lung doses was assessed using linear regression analysis, receiver operating characteristics analysis, and Lyman's normal tissue complication probability model. The PTV doses were converted to biologically effective doses and lung doses to 2 Gy equivalent doses before correlation analyses., Results: Up to 6 months after SBRT, forced expiratory volume in 1 second and carbon monoxide diffusion capacity changed by -1.4% (95% confidence interval [CI], -3.4% to 0) and -7.6% (95% CI, -10.2% to -3.4%) compared with pretreatment values, respectively. A modest decrease in PFTs was observed 7-24 months after SBRT, with changes of -8.1% (95% CI, -13.3% to -5.3%) and -12.4% (95% CI, -15.5% to -6.9%), respectively. Using linear regression analysis, receiver operating characteristic analysis, and normal tissue complication probability modeling, all evaluated parameters of tumor size, PTV dose, mean lung dose, and absolute and relative volumes of the lung exposed to minimum doses of 5-70 Gy were not correlated with early and late PFT changes. Subgroup analysis based on pre-SBRT PFTs (greater or equal and less than median) did not identify any dose-effect relationship., Conclusions: This study failed to demonstrate a significant dose-effect relationship for changes of pulmonary function after SBRT for early-stage non-small cell lung cancer., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Skull base meningiomas commonly present with cranial neuropathies. Fractionated stereotactic radiation therapy (FSRT) has been used to treat these tumors with excellent local control, but rates of improvement in cranial neuropathies have not been well defined. We review the experience at Thomas Jefferson University using FSRT in the management of these patients with a focus on symptom outcomes., Methods: We identified 225 cases of skull base meningiomas treated with FSRT at Thomas Jefferson University from 1994 through 2009. The target volume was the enhancing tumor, treated to a standard prescription dose of 54 Gy. Symptoms at the time of RT were classified based on the cranial nerve affected. Logistic regression was performed to determine predictors of symptom improvement after FSRT., Results: The median follow-up time was 4.4 years. In 92% of cases, patients were symptomatic at the time of RT; the most common were impaired visual field/acuity (58%) or extraocular movements (34%). After FSRT, durable improvement of at least one symptom occurred in 57% of cases, including 40% of visual acuity/visual field deficits, and 40% of diplopia/ptosis deficits. Of all symptomatic patients, 27% experienced improvement of at least one symptom within 2 months of the end of RT., Conclusions: FSRT is very effective in achieving improvement of cranial neuropathies from skull base meningiomas, particularly visual symptoms. Over half of treated patients experience a durable improvement of at least one symptom, frequently within 2 months from the end of RT.

Purpose: Hypofractionated stereotactic body radiation therapy (SBRT) has emerged as an effective treatment option for early-stage non-small cell lung cancer (NSCLC). Using data collected by the Elekta Lung Research Group, we generated a tumor control probability (TCP) model that predicts 2-year local control after SBRT as a function of biologically effective dose (BED) and tumor size., Methods and Materials: We formulated our TCP model as follows: TCP = e([BED10 - c ∗ L - TCD50]/k) ÷ (1 + e([BED10 - c ∗ L - TCD50]/k)), where BED10 is the biologically effective SBRT dose, c is a constant, L is the maximal tumor diameter, and TCD50 and k are parameters that define the shape of the TCP curve. Least-squares optimization with a bootstrap resampling approach was used to identify the values of c, TCD50, and k that provided the best fit with observed actuarial 2-year local control rates., Results: Data from 504 NSCLC tumors treated with a variety of SBRT schedules were available. The mean follow-up time was 18.4 months, and 26 local recurrences were observed. The optimal values for c, TCD50, and k were 10 Gy/cm, 0 Gy, and 31 Gy, respectively. Thus, size-adjusted BED (sBED) may be defined as BED minus 10 times the tumor diameter (in centimeters). Our TCP model indicates that sBED values of 44 Gy, 69 Gy, and 93 Gy provide 80%, 90%, and 95% chances of tumor control at 2 years, respectively. When patients were grouped by sBED, the model accurately characterized the relationship between sBED and actuarial 2-year local control (r=0.847, P=.008)., Conclusion: We have developed a TCP model that predicts 2-year local control rate after hypofractionated SBRT for early-stage NSCLC as a function of biologically effective dose and tumor diameter. Further testing of this model with additional datasets is warranted., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: We report lung stereotactic-body radiotherapy (SBRT) outcomes for a large pooled cohort treated using daily online cone-beam computed tomography., Methods: Five hundred and five stage I-IIB (T1-3N0M0) non-small-cell lung cancer (NSCLC) cases underwent SBRT using cone-beam computed tomography image guidance at five international institutions from 1998 to 2010. Median age was 74 years (range, 42-92) whereas median forced expiratory volume in 1 second/diffusing lung capacity for carbon monoxide were 1.4 liter (65%) and 10.8 ml/min/mmHg (53%). Of the 505 cases, 64% were biopsy proven and 87% medically inoperable. Staging was: IA 63%, IB 33%, IIA 2%, and recurrent 1%. Median max tumor dimension was 2.6 cm (range, 0.9-8.5). Median heterogeneously calculated volumetric prescription dose (PD) was 54 Gy (range, 20-64 Gy) in three fractions (range, 1-15) over 8 days (range, 1-27). Median biologically equivalent PD biological equivalent doses (BED10) was 132 Gy (range, 60-180)., Results: With a median follow-up of 1.6 years (range, 0.1-7.3), the 2-year Kaplan-Meier local control (LC), regional control, and distant metastasis (DM) rates were 94%, 89%, and 20%, respectively, whereas cause-specific and overall survival were 87% and 60% (78% operable, 58% inoperable, p = 0.01), respectively. Stage, gross-tumor volume size (≥ 2.7 cm) and PD(BED10) predicted local relapse (LR) and DM. LR was 15% for BED10 less than 105 Gy versus 4% for BED10 of 105 Gy or more (p < 0.001); DM was 31% versus 18% for BED10 less than 105 versus 105 Gy or more (p = 0.01). On multivariate analysis, PD(BED10) and elapsed days during radiotherapy predicted LR; gross-tumor volume size predicted DM. Grade 2 or higher pneumonitis, rib fracture, myositis, and dermatitis were 7%, 3%, 1%, and 2%, respectively., Conclusions: In the largest early-stage NSCLC SBRT data set to date, a high rate of local control was achieved, which was correlated with a PD(BED10) of 105 Gy or more. Failures were primarily distant, severe toxicities were rare, and overall survival was encouraging in operable patients.

Background: Data on radiotherapy for trigeminal schwannomas (TSs) and comparison of stereotactic radiosurgery (SRS) with fractionated stereotactic radiotherapy (FSRT) are limited., Objective: We present a large retrospective review of our institutional experience treating TSs with SRS and FSRT. We also describe a flare phenomenon experienced by some patients., Methods: The records of 23 consecutive TSs patients treated with radiotherapy between 1996 and 2011 were reviewed. We investigated radiographic response, tumor control, and toxicity., Results: Ten patients underwent SRS and 13 underwent FSRT, with median clinical follow-up of 32 months (range, 3-120 months). Tumor control at 5 and 10 years was 94% overall. Symptom control at 5 years was achieved in 48% of all patients, with nonsignificant improvement in more patients in the FSRT group than those in the SRS group (56% vs 40%, P = .37). Acute toxicity was higher in the FSRT group (38.5 vs 0%, P < .01), although lesions treated with FSRT were larger (mean, 9.5 mL vs 4.8 mL, P < .01). A symptomatic flare phenomenon occurred in 2 patients (8.7% overall) during FSRT, involving transient cystic formation and dramatic size increase. One lesion regressed in size and 1 remained stable on follow-up., Conclusion: Tumor control rates for TSs are excellent with SRS and FSRT with minimal toxicity. This represents the first documented report of a flare phenomenon after FSRT for TS treatment. Flare risk after FSRT in previously resected large lesions should be discussed with patients before treatment, and prophylactic oral steroids may be considered.

Introduction: To evaluate the influence of pretreatment pulmonary function (PF) on survival, early and late pulmonary toxicity after stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer., Methods: Four hundred eighty-three patients with 505 tumors of early-stage non-small cell lung cancer cT1-3 cN0 were treated with image-guided SBRT at five international institutions (1998-2010). Sixty-four percent of the tumors were biopsy-proven and 18F-fluorodeoxyglucose-positron emission tomography was performed for staging in 84%. Image-guided SBRT was performed with a median of three fractions to a median total dose of 54 Gy. Pretreatment PF was available for 423 patients, and 617 posttreatment PF tests from 270 patients were available., Results: A large variability of pretreatment PF was observed: the 90% range of forced expiratory volume in 1 second and diffusing capacity for carbon monoxide was 29 to 109% and 5.5 to 19.1 ml/min/mmHg, respectively. PF was significantly correlated with overall survival but not cause-specific survival: diffusing capacity for carbon monoxide of 11.2 ml/min/mmHg differentiated between 3-year overall survival of 66% and 42%. Radiation-induced pneumonitis grade ≥II occurred in 7% of patients and was not increased in patients with lower PF. A significant and progressive change of PF was observed after SBRT: PF decreased by 3.6% and 6.8% on average within 6 and 6 to 24 months after SBRT, respectively. Changes of PF after SBRT were significantly correlated with pretreatment PF: PF improved for worst pretreatment PF and the largest loss was observed for best pretreatment PF., Conclusions: Image-guided SBRT is safe in terms of acute and chronic pulmonary toxicity even for patients with severe pulmonary comorbidities. SBRT should be considered as a curative treatment option for inoperable patients with pretreatment PF as reported in this study.

Purpose: We reviewed the treatment for patients with spine metastases who initially received conventional external beam radiation (EBRT) and were reirradiated with 1-5 fractions of stereotactic body radiotherapy (SBRT) who did or did not subsequently develop radiation myelopathy (RM)., Methods and Materials: Spinal cord dose-volume histograms (DVHs) for 5 RM patients (5 spinal segments) and 14 no-RM patients (16 spine segments) were based on thecal sac contours at retreatment. Dose to a point within the thecal sac that receives the maximum dose (P(max)), and doses to 0.1-, 1.0-, and 2.0-cc volumes within the thecal sac were reviewed. The biologically effective doses (BED) using α/β = 2 Gy for late spinal cord toxicity were calculated and normalized to a 2-Gy equivalent dose (nBED = Gy(2/2))., Results: The initial conventional radiotherapy nBED ranged from ~30 to 50 Gy(2/2) (median ~40 Gy(2/2)). The SBRT reirradiation thecal sac mean P(max) nBED in the no-RM group was 20.0 Gy(2/2) (95% confidence interval [CI], 10.8-29.2), which was significantly lower than the corresponding 67.4 Gy(2/2) (95% CI, 51.0-83.9) in the RM group. The mean total P(max) nBED in the no-RM group was 62.3 Gy(2/2) (95% CI, 50.3-74.3), which was significantly lower than the corresponding 105.8 Gy(2/2) (95% CI, 84.3-127.4) in the RM group. The fraction of the total P(max) nBED accounted for by the SBRT P(max) nBED for the RM patients ranged from 0.54 to 0.78 and that for the no-RM patients ranged from 0.04 to 0.53., Conclusions: SBRT given at least 5 months after conventional palliative radiotherapy with a reirradiation thecal sac P(max) nBED of 20-25 Gy(2/2) appears to be safe provided the total P(max) nBED does not exceed approximately 70 Gy(2/2), and the SBRT thecal sac P(max) nBED comprises no more than approximately 50% of the total nBED., (Copyright © 2012 Elsevier Inc. All rights reserved.)

To determine the safety, tolerability, and report on secondary efficacy endpoints of motexafin gadolinium (MGd) in combination with whole-brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) for patients with ≤ 6 brain metastases. We conducted an international study of WBRT (37.5 Gy in 15 fractions) and SRS (15-21 Gy) with the addition of MGd (5 mg/kg preceding each fraction beginning week 2). The primary endpoint was to evaluate the rate of irreversible grade 3 or any grade ≥ 4 neurotoxicity and establish feasibility in preparation for a phase III trial. Sixty-five patients were enrolled from 14 institutions, of which 45 (69%) received SRS with MGd as intended and were available for evaluation. Grade ≥ 3 neurotoxicity attributable to radiation therapy within 3 months of SRS was seen in 2 patients (4.4%), including generalized weakness and radionecrosis requiring surgical management. Immediately following the course of MGd plus WBRT, new brain metastases were detected in 11 patients (24.4%) at the time of the SRS treatment planning MRI. The actuarial incidence of neurologic progression at 6 months and 1 year was 17 and 20%, respectively. The median investigator-determined neurologic progression free survival and overall survival times were 8 (95% CI: 5-14) and 9 months (95% CI: 6-not reached), respectively. We observed a low rate of neurotoxicity, demonstrating that the addition of MGd does not increase the incidence or severity of neurologic complications from WBRT with SRS boost.

Purpose: Salvage options for recurrent high-grade gliomas (HGGs) are limited by cumulative toxicity and limited efficacy despite advances in chemotherapeutic and radiotherapeutic techniques. Previous studies have reported encouraging survival results and favorable toxicity with fractionated stereotactic radiotherapy, and small studies have shown similar benefit using a shortened course of hypofractionated stereotactic radiation therapy (H-SRT). We sought to determine the efficacy and toxicity profile of H-SRT alone or in addition to repeat craniotomy or concomitant chemotherapy., Patients and Methods: Between 1994 and 2008, 147 patients with recurrent HGG were treated with H-SRT (median dose, 35 Gy in 3.5-Gy fractions). Cox regression models were used to analyze survival outcomes. Variables included age, surgery before H-SRT, time to first recurrence, reirradiation dose, inclusion of chemotherapy with H-SRT, and gross tumor volume (GTV)., Results: Younger age (P = .001), smaller GTV (P = .025), and shorter time between diagnosis and recurrence (P = .034) were associated with improvement in survival from H-SRT. Doses of radiation > or = 35 Gy approached significance (P = .07). There was no significant benefit of surgical resection or chemotherapy in this population when analysis was controlled for other prognostic factors., Conclusion: H-SRT was well tolerated and resulted in a median survival time of 11 months after H-SRT, independent of re-operation or concomitant chemotherapy. Patients who experienced recurrence within 6 months after initial treatment had an excellent response and should not be disqualified from H-SRT. This is the largest series to examine the efficacy and tolerability of H-SRT in recurrent HGG.

Purpose: To describe our initial experience of fractionated stereotactic radiotherapy dose reduction comparing two dose cohorts with examination of tumor control rates and serviceable hearing preservation rates., Methods and Materials: After institutional review board approval, we initiated a retrospective chart review to study the hearing outcomes and tumor control rates. All data were entered into a JMP, version 7.01, statistical spreadsheet for analysis., Results: A total of 89 patients with serviceable hearing had complete serial audiometric data available for analysis. The higher dose cohort included 43 patients treated to 50.4 Gy with a median follow-up (latest audiogram) of 53 weeks and the lower dose cohort included 46 patients treated to 46.8 Gy with a median follow-up of 65 weeks. The tumor control rate was 100% in both cohorts, and the pure tone average was significantly improved in the low-dose cohort (33 dB vs. 40 dB, p = 0.023, chi-square). When the patient data were analyzed at comparable follow-up points, the actuarial hearing preservation rate was significantly longer for the low-dose cohort than for the high-dose cohort (165 weeks vs. 79 weeks, p = .0318, log-rank). Multivariate analysis revealed the dose cohort (p = 0.0282) and pretreatment Gardner-Robertson class (p = 0.0215) to be highly significant variables affecting the hearing outcome., Conclusion: A lower total dose at 46.8 Gy was associated with a 100% local control tumor rate and a greater hearing preservation rate. An additional dose reduction is justified to achieve the optimal dose that will yield the greatest hearing preservation rate without compromising tumor control for these patients.

Fractionated stereotactic radiotherapy (SRT) requires accurate and reproducible immobilization of the patient's head. This randomized study compared the efficacy of two commonly used forms of immobilization used for SRT. Two routinely used methods of immobilization, which differ in their approach to reproduce the head position from day to day, are the Gill-Thomas-Cosman (GTC) frame and the BrainLab thermoplastic mask. The GTC frame fixates on the patient's upper dentition and thus is in direct mechanical contact with the cranium. The BrainLab mask is a two-part masking system custom fitted to the front and back of the patient's head. After patients signed an IRB-approved informed consent form, eligible patients were randomized to either GTC frame or mask for their course of SRT. Patients were treated as per standard procedure; however, prior to each treatment a set of digital kilovolt images (ExacTrac, BrainLabAB, Germany) was taken. These images were fused with reference digitally reconstructed radiographs obtained from treatment planning CT to yield lateral, longitudinal, and vertical deviations of isocenter and head rotations about respective axes. The primary end point of the study was to compare the two systems with respect to mean and standard deviations using the distance to isocenter measure. A total of 84 patients were enrolled (69 patients evaluable with detailed positioning data). A mixed-effect linear regression and two-tiled t test were used to compare the distance measure for both the systems. There was a statistically significant (p < 0.001) difference between mean distances for these systems, suggesting that the GTC frame was more accurate. The mean 3D displacement and standard deviations were 3.17+1.95 mm for mask and 2.00+1.04 mm for frame. Both immobilization techniques were highly effective, but the GTC frame was more accurate. To optimize the accuracy of SRT, daily kilovolt image guidance is recommended with either immobilization system.

Objective: To review outcomes after fractionated stereotactic radiotherapy (FSR) and stereotactic radiosurgery (SRS) for nonacoustic cranial nerve schwannomas., Methods: We reviewed medical records of 39 patients who received FSR or SRS for nonacoustic cranial nerve schwannomas at our institution during the period from 1996 to 2007., Results: Tumors involved Cranial Nerves V (n = 19), III (n = 2), VI (n = 3), VII (n = 5), IX (n = 2), X (n = 5), and XII (n = 2) and the cavernous sinus (n = 1). Irradiation was performed after partial resection, biopsy, or no previous surgery in 16, 2, and 21 patients, respectively. Twenty-four patients received FSR, delivered in 1.8- to 2.0-Gy fractions to a median dose of 50.4 Gy (range, 45.0-54.0 Gy). Fifteen patients received SRS to a median dose of 12.0 Gy (range, 12-15 Gy). Mild acute toxicity occurred in 23% of the patients. The 2-year actuarial tumor control rate after FSR and SRS was 95%. The median follow-up period was 24 months. Changes in cranial nerve deficits after stereotactic irradiation were analyzed for patients with follow-up periods greater than 12 months (n = 26); cranial nerve deficits improved in 50%, were stable in 46%, and worsened in 4% of the patients. No significant difference was observed for FSR compared with SRS with regard to local control or to improvement of cranial nerve-related symptoms (P = 0.17)., Conclusion: SRS and FSR are both well-tolerated treatments for nonacoustic cranial nerve schwannomas, providing excellent tumor control and a high likelihood of symptomatic improvement.

Purpose: Long-term brain metastases survivors are at risk for neurologic morbidity after whole-brain radiotherapy (WBRT). Retrospective radiosurgery (RS) reports found no survival difference when compared with WBRT. Before RS alone was evaluated with delayed WBRT in a phase III trial, the feasibility of RS alone was tested prospectively., Patients and Methods: Patients with renal cell carcinoma, melanoma, or sarcoma; one to three brain metastases; and performance status of 0 to 2 were enrolled. Exclusion criteria were leptomeningeal disease; metastases in medulla, pons, or midbrain; or liver metastases. On the basis of tumor size, patients received 24, 18, or 15 Gy RS. At recurrence, management was discretionary. The primary end point was 3- and 6-month intracranial progression., Results: Between July 1998 and August 2003, 36 patients were accrued; 31 were eligible. Median follow-up was 32.7 months and the median survival was 8.3 months (95% CI, 7.4 to 12.2). Three- and 6-month intracranial failure with RS alone was 25.8% and 48.3%. Failure within and outside the RS volume, when in-field and distant intracranial failures were scored independently, was 19.3% and 16.2% (3 months) and 32.2% and 32.2% (6 months), respectively. Approximately 38% of patients experienced death attributable to neurologic cause. There were three grade 3 toxicities related to RS., Conclusion: Intracranial failure rates without WBRT were 25.8% and 48.3% at 3 and 6 months, respectively. Delaying WBRT may be appropriate for some subgroups of patients with radioresistant tumors, but routine avoidance of WBRT should be approached judiciously.

Purpose: Conventional treatment of glioblastoma multiforme (GBM) cures less than 5% of patients. We investigated the effect of stereotactic radiosurgery (SRS) added to conventional external beam radiation therapy (EBRT) with carmustine (BCNU) on the survival of patients with GBM., Methods and Materials: A total of 203 patients with supratentorial GBM (tumor < or =40 mm) were randomly assigned either to postoperative SRS followed by EBRT (60 Gy) plus BCNU (80 mg/m(2) Days 1-3 every 8 weeks for six cycles) or to EBRT with BCNU alone. The dose of radiosurgery was tumor size-dependent and ranged from 15 Gy for largest to 24 Gy for smallest tumors. RT and BCNU were identical in both arms., Results: At a median follow-up time of 61 months, the median survival in the radiosurgery group was 13.5 months (95% confidence interval, 11.0-14.8) as compared with 13.6 months (95% confidence interval, 11.2-15.2, p = 0.5711) for the standard treatment group. There were also no significant differences in 2- and 3-year survival rates and in patterns of failure between the two arms. Quality of life deterioration and cognitive decline at the end of therapy, compared with baseline, were comparable and there was no difference in quality-adjusted survival between the arms., Conclusions: Stereotactic radiosurgery followed by EBRT and BCNU does not improve the outcome in patients with GBM nor does it change the general quality of life or cognitive functioning.

Background: Brain metastases occur in up to 40% of all patients with systemic cancer. We aimed to assess whether stereotactic radiosurgery provided any therapeutic benefit in a randomised multi-institutional trial directed by the Radiation Therapy Oncology Group (RTOG)., Methods: Patients with one to three newly diagnosed brain metastases were randomly allocated either whole brain radiation therapy (WBRT) or WBRT followed by stereotactic radiosurgery boost. Patients were stratified by number of metastases and status of extracranial disease. Primary outcome was survival; secondary outcomes were tumour response and local rates, overall intracranial recurrence rates, cause of death, and performance measurements., Findings: From January, 1996, to June, 2001, we enrolled 333 patients from 55 participating RTOG institutions--167 were assigned WBRT and stereotactic radiosurgery and 164 were allocated WBRT alone. Univariate analysis showed that there was a survival advantage in the WBRT and stereotactic radiosurgery group for patients with a single brain metastasis (median survival time 6.5 vs 4.9 months, p=0.0393). Patients in the stereotactic surgery group were more likely to have a stable or improved Karnofsky Performance Status (KPS) score at 6 months' follow-up than were patients allocated WBRT alone (43% vs 27%, respectively; p=0.03). By multivariate analysis, survival improved in patients with an RPA class 1 (p<0.0001) or a favourable histological status (p=0.0121)., Interpretation: WBRT and stereotactic boost treatment improved functional autonomy (KPS) for all patients and survival for patients with a single unresectable brain metastasis. WBRT and stereotactic radiosurgery should, therefore, be standard treatment for patients with a single unresectable brain metastasis and considered for patients with two or three brain metastases.

Background: Stereotactic radiosurgery (SRS) and, more recently, fractionated stereotactic radiotherapy (SRT) have been recognized as noninvasive alternatives to surgery for the treatment of acoustic schwannomas. We review our experience of acoustic tumor treatments at one institution using a gamma knife for SRS and the first commercial world installation of a dedicated linac for SRT., Methods: Patients were treated with SRS on the gamma knife or SRT on the linac from October 1994 through August 2000. Gamma knife technique involved a fixed-frame multiple shot/high conformality single treatment, whereas linac technique involved daily conventional fraction treatments involving a relocatable frame, fewer isocenters, and high conformality established by noncoplanar arc beam shaping and differential beam weighting., Results: Sixty-nine patients were treated on the gamma knife, and 56 patients were treated on the linac, with 1 NF-2 patient common to both units. Three patients were lost to follow-up, and in the remaining 122 patients, mean follow-up was 119 +/- 67 weeks for SRS patients and 115 +/- 96 weeks for SRT patients. Tumor control rates were high (> or =97%) for sporadic tumors in both groups but lower for NF-2 tumors in the SRT group. Cranial nerve morbidities were comparably low in both groups, with the exception of functional hearing preservation, which was 2.5-fold higher in patients who received conventional fraction SRT., Conclusion: SRS and SRT represent comparable noninvasive treatments for acoustic schwannomas in both sporadic and NF-2 patient groups. At 1-year follow-up, a significantly higher rate of serviceable hearing preservation was achieved in SRT sporadic tumor patients and may therefore be preferable to alternatives including surgery, SRS, or possibly observation in patients with serviceable hearing.

Purpose: This study was initiated to evaluate the advantages of using three-dimensional time-of-flight magnetic resonance angiography (3D TOF MRA), as an adjuvant to conventional stereotactic angiography, in obtaining three-dimensional information about an arteriovenous malformation (AVM) nidus and in optimizing radiosurgical treatment plans., Methods and Materials: Following angiography, contrast-enhanced MRI and MRA studies were obtained in 22 consecutive patients undergoing Gamma Knife radiosurgery for AVM. A treatment plan was designed, based on the angiograms and modified as necessary, using the information provided by MRA. The quantitative analysis involved calculation of the ratio of the treated volume to the MRA nidus volume (the tissue volume ratio [TVR]) for the initial and final treatment plans., Results: In 12 cases (55%), the initial treatment plans were modified after including the MRA information in the treatment planning process. The mean TVR for the angiogram-based plans was 1.63 (range 1.17-2.17). The mean coverage of the MRA nidus by the angiogram-based plans was 93% (range 73-99%). The mean MRA nidus volume was 2.4 cc (range 0. 6-5.3 cc). The MRA-based modifications resulted in increased conformity with the mean TVR of 1.46 (range 1.20-1.74). These modifications were caused by MRA revealing irregular nidi and/or vascular components superimposed on the angiographic projections of the nidi. In a number of cases, the information from MRA was essential in defining the nidus when the projections of the angiographic outlines showed different superior and/or inferior extent of the nidus. In two cases, MRA revealed irregular nidi, correlating well with the angiograms and showed that the angiographically acceptable plans undertreated 27% of the MRA nidus in one case and 18% of the nidus in the other case. In the remaining 10 cases (45%), both MRI and MRA failed to detect the nidus due to surgical clip artifacts and the presence of embolizing glue., Conclusions: The 3D TOF MRA provided information on irregular AVM shape, which was not visualized by angiography alone, and it was superior to MRI for defining the AVM nidus. However, when imaging artifacts obscured the AVM nidus on MRI and MRA, angiography permitted detection of AVM. Utilizing MRA as a complementary imaging modality to angiography increased accuracy of the AVM radiosurgery and allowed for optimal dose planning.

Purpose: Despite increased utilization of fractionated stereotactic radiation therapy (SRT) or stereotactic radiosurgery (SRS), the incidence and nature of immediate side effects (ISE) associated with these treatment techniques are not well defined. We report immediate side effects from a series of 78 patients., Materials and Methods: Intracranial lesions in 78 adult patients were treated with SRT or SRS, using a dedicated linear accelerator. Those lesions included 13 gliomas, 2 ependymomas, 19 metastatic tumors, 15 meningiomas, 12 acoustic neuromas, 4 pituitary adenomas, 1 optic neuroma, 1 chondrosarcoma, and 11 arteriovenous malformations (AVM). SRT was used in 51 and SRS in 27 patients. Mean target volume was 9.0 cc. Eleven patients received prior external-beam radiation therapy within 2 months before SRT/SRS. Any side effects occurring during and up to 2 weeks after the course of radiation were defined as ISE and were graded as mild, moderate, or severe. The incidence of ISE and the significance of their association with several treatment and pretreatment variables were analyzed., Results: Overall, 28 (35%) of 78 patients experienced one or more ISE. Most of the ISE (87%) were mild, and consisted of nausea (in 5), dizziness/vertigo (in 5), seizures (in 6), and new persistent headaches (in 17). Two episodes of worsening neurological deficit and 2 of orbital pain were graded as moderate. Two patients experienced severe ISE, requiring hospitalization (1 seizure and 1 worsening neurological deficit). ISE in 6 cases prompted computerized tomography of the brain, which revealed increased perilesional edema in 3 cases. The incidence of ISE by diagnosis was as follows: 46% (6 of 13) for gliomas, 50% (6 of 12) for acoustic neuromas, 36% (4 of 11) for AVM, 33% (5 of 15) for meningiomas, and 21% (4 of 19) for metastases. A higher incidence of dizziness/vertigo (4 of 12 = 33%) was seen among acoustic neuroma patients than among other patients (p< 0.01). There was no significant association of dizziness/vertigo with either a higher average and maximum brainstem dose (p = 0.74 and 0.09, respectively) or with 2-Gy equivalents of the average and maximum brainstem doses (p = 0.28 and 0.09, respectively). Higher RT dose to the margin and higher maximum RT dose were associated with a higher incidence of ISE (p = 0.05 and 0.01, respectively). However, when RT dose to the margin was converted to a 2-Gy dose-equivalent, it lost its significance as predictor of ISE (p = 0.51). Recent conventional external-beam radiation therapy, target volume, number of isocenters, collimator size, dose inhomogeneity, prescription isodose, pretreatment edema, dose of prior radiation, fraction size (2.0-7.0 Gy with SRT and 13.0-21.0 Gy with SRS), fractionation schedule, and dose to brainstem were not significantly associated with ISE. ISE occurred in 26% (8) of 31 patients taking corticosteroids prior to SRT/SRS and in 20 (42%) of 47 patients not taking them (p = 0.15)., Conclusion: ISE occur in one third of patients treated with SRT and SRS and are usually mild or moderate and self-limited. Dizziness/vertigo are common and unique for patients with acoustic neuromas and are not associated with higher brainstem doses. We are unable to detect a relationship between ISE and higher margin or maximum RT doses. No specific conclusion can be drawn with regard to the effect of corticosteroids, used prior to SRS/SRT, on the occurrence of ISE.

Purpose: A phase I dose escalation of hypofractionated stereotactic radiotherapy (H-SRT) in recurrent or persistent malignant gliomas as a means of increasing the biologically effective dose and decreasing the high rate of reoperation due to toxicity associated with single-fraction stereotactic radiosurgery (SRS) and brachytherapy., Materials and Methods: From November 1994 to September 1996, 25 lesions in 20 patients with clinical and/or imaging evidence of malignant glioma persistence or recurrence received salvage H-SRT. Nineteen patients at the time of initial diagnosis had glioblastoma multiforme (GBM) and one patient had an anaplastic astrocytoma. All of these patients with tumor persistence or recurrence had received initial fractionated radiation therapy (RT) with a mean and median dose of 60 Gy (44.0-72.0 Gy). The median time from completion of initial RT to H-SRT was 3.1 months (0.7-45.5 months). Salvage H-SRT was delivered using daily 3.0-3.5 Gy fractions (fxs). Three different total dose levels were sequentially evaluated: 24.0 Gy/3.0 Gy fxs (five lesions), 30.0 Gy/3.0 Gy fxs (10 lesions), and 35.0 Gy/3.5 Gy fxs (nine lesions). Median treated tumor volume measured 12.66 cc (0.89-47.5 cc). The median ratio of prescription volume to tumor volume was 2.8 (1.4-5.0). Toxicity was judged by RTOG criteria. Response was determined by clinical neurologic improvement, a decrease in steroid dose without clinical deterioration, and/or radiologic imaging., Results: No grade 3 toxicities were observed and no reoperation due to toxicity was required. At the time of analysis, 13 of 20 patients had died. The median survival time from the completion of H-SRT is 10.5 months with a 1-year survival rate of 20%. Neurological improvement was found in 45% of patients. Decreased steroid requirements occurred in 60% of patients. Minor imaging response was noted in 22% of patients. Using Fisher's exact test, response of any kind correlated strongly to total dose (p = 0.0056). None of six lesions treated with 21 Gy or 24 Gy responded, whereas there was a 79% response rate among the 19 lesions treated with 30 or 35 Gy. Tumor volumes < or =20 cc were associated with a higher likelihood of response (p = 0.053)., Conclusions: H-SRT used in this cohort of previously irradiated patients with malignant glioma was not associated with the need for reoperation due to toxicity or grade 3 toxicity. This low toxicity profile and encouraging H-SRT dose-related response outcome justifies further evaluation and dose escalation.

Objective: We describe our initial experience with fractionated stereotactic radiotherapy (SRT) for the treatment of 19 patients with secretory and nonsecretory pituitary macroadenomas. The primary endpoints of local control and the documentation of any MRI T2-weighted changes in contiguous brain tissues are discussed., Methods: Between 1/95 and 1/97, 19 patients were planned with the X-Knife 3-D planning system (Radionics, Burlington, Mass., USA) and received a median dose of 46 Gy in daily 2.0-Gy fractions. Treatments were delivered stereotactically with a dedicated 600SR linear accelerator (Varian Corporation, Palo Alto, Calif., USA). Immobilization was achieved with the Gill-Thomas-Cosman relocatable frame. The mean tumor size was 2.24 cm. The mean prescription isodose was 87%. The mean age was 53 years (10 male, 9 female). The mean follow-up time was 10 months (range 1-24 months). The mean optic chiasm and brain stem doses were calculated at 38 and 13 Gy, respectively. All patients were evaluated with pre- and postgadolinum-enhanced MRI scans and Humphrey visual field tests., Results: In the posttreatment period, local control (absence of tumor progression) has been achieved in all of the patients. The treatment was well tolerated in all patients. No acute complications, no visual changes and no T2-weighted MRI or proton density changes were documented in any of the 19 patients., Conclusion: These preliminary results suggest that SRT compares favorably with conventional radiotherapy in achieving local control. The doses to the brainstem and the temporal lobes are significantly decreased and at early follow-up no white matter changes are seen on MRI after SRT. The true frequency of grade 1-4 changes are likely underestimated as similar changes often occur in association with tumor edema or after surgery. Given the uncertain neurocognitive significance of the white matter changes associated with treating these benign tumors by conventional radiotherapy, we are currently treating all pituitary adenomas with fractionated SRT to reduce the potential sequelae.

A stereotactic radiosurgery and radiotherapy (SRS/SRT) system on a dedicated Varian Clinac-600SR linear accelerator with Brown-Roberts-Wells and Gill-Thomas-Cosman relocatable frames along with the Radionics (RSA) planning system is evaluated. The Clinac-600SR has a single 6-MV beam with the same beam characteristics as that of the mother unit, the Clinac-600C. The primary collimator is a fixed cone projecting to a 10-cm diameter at isocenter. The secondary collimator is a heavily shielded cylindrical collimator attached to the face plate of the primary collimator. The tertiary collimation consists of the actual treatment cones. The cone sizes vary from 12.5 to 40.0 mm diameter. The mechanical stability of the entire system was verified. The variations in isocenter position with table, gantry, and collimator rotation were found to be < 0.5 mm with a compounded accuracy of < or = 1.0 mm. The radiation leakage under the cones was < 1% measured at a depth of 5 cm in a phantom. The beam profiles of all cones in the x and y directions were within +/- 0.5 mm and match with the physical size of the cone. The dosimetric data such as tissue maximum ratio, off-axis ratio, and cone factor were taken using film, diamond detector, and ion chambers. The mechanical and dosimetric characteristics including dose linearity of this unit are presented and found to be suitable for SRS/SRT. The difficulty in absolute dose measurement for small cone is discussed.

Twenty-seven acoustic tumors in 26 patients were treated with multiple fractionated linear-accelerator-based stereotactic radiotherapy (SRT). All patients with intact pretreatment facial nerve function with either small or large tumor volumes have thus far experienced no treatment-related facial neuropathy, including 9 patients with a mean follow-up of 22.4 +/- 1.6 months. The incidence of evaluable trigeminal neuropathy was 13%, and in 5 of 7 patients with serviceable pretreatment hearing, audiometry was unchanged in the immediate posttreatment period. Longer follow-up will be necessary to evaluate hearing preservation after SRT. Tumor response with central necrosis was seen in all assessable patients. SRT can be performed for cerebellopontine angle tumors with accuracy and reproducibility. It achieves a biological response similar to single fraction radiosurgery and may lower the incidence of facial and trigeminal neuropathies.