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The American Association of Physicists in Medicine (AAPM) formed Task Group 178 (TG-178) to perform the following tasks: review in-phantom and in-air calibration protocols for gamma stereotactic radiosurgery (GSR), suggest a dose rate calibration protocol that can be successfully utilized with all gamma stereotactic radiosurgery (GSR) devices, and update quality assurance (QA) protocols in TG-42 (AAPM Report 54, 1995) for static GSR devices. The TG-178 report recommends a GSR dose rate calibration formalism and provides tabulated data to implement it for ionization chambers commonly used in GSR dosimetry. The report also describes routine mechanical, dosimetric, and safety checks for GSR devices, and provides treatment process quality assurance recommendations. Sample worksheets, checklists, and practical suggestions regarding some QA procedures are given in appendices. The overall goal of the report is to make recommendations that help standardize GSR physics practices and promote the safe implementation of GSR technologies.

Introduction We report results from a prospective phase I/II trial for patients with centrally located, early-stage NSCLC receiving stereotactic body radiation therapy. Methods Eligible patients were medically inoperable with biopsy-proven NSCLC within 2 cm of the proximal bronchial tree or 5 mm of the mediastinal pleura or parietal pericardium. Phase I had four dose levels using 5 fractions: 9, 10, 11, and 12 Gy per fraction. The primary phase II objective was to determine if the maximum tolerated dose in phase I achieved local control greater than 80% at 2 years. Results Seventy-four patients were enrolled; 23 to phase I and 51 to phase II. Two phase I patients treated with 10 Gy × 5 fractions developed unrelated acute grade 3 lung toxicities which resolved. The phase II dose level selected was 11 Gy × 5 fractions. The median follow-up for living phase II patients was 27 months (range, 9 to 58 months). Two-year local control using 11 Gy × 5 fractions was 85% (95% confidence interval [CI]: 62%–95%). Two-year overall survival was 43% (95% CI: 28%–57%). Three patients (6%, 95% CI: 1%–17%) experienced acute grade 3 and 4 cardiac or pulmonary toxicities. Of the 41 patients evaluable for late cardiac and pulmonary toxicity, 11 (27%, 95% CI: 14%–43%) developed grade 3, 5 (12%, 95% CI: 4%–26%) developed grade 4, and 1 (4%, 95% CI: 0%–13%) died of grade 5 toxicity. Conclusion Stereotactic body radiation therapy for central NSCLC using 11 Gy × 5 fractions is tolerable and has excellent local control, but is associated severe late toxicity in some patients.

Objective: To identify potentially actionable dosimetric predictors of local control (LC) for non-small cell lung cancer (NSCLC) brain metastases treated with single-fraction stereotactic radiosurgery (SRS). Methods and materials: Patients with NSCLC brain metastases treated with single-fraction SRS were identified. Eligible patients had at least 1 follow-up magnetic resonance imaging scan and were without prior metastasectomy or SRS to the same lesion. LC and overall survival (OS) were estimated using the Kaplan-Meier method. The Cox proportional hazards model was used for univariate (UVA) and multivariate analysis (MVA). Receiver operating characteristic (ROC) analysis was used to identify optimal cut points for dose-volume histogram metrics relative to LC. Results: A total of 612 NSCLC brain metastasis were identified in 299 patients with single-fraction SRS between 1999 and 2014. Median follow-up was 10 months. Median OS from time of SRS was 11 months. Overall LC was 75% and 66% at 1 and 2 years, respectively. On UVA, increasing dose by any measure was associated with improved LC. On MVA, volume receiving at least 32 Gy (V32; hazard ratio [HR], 0.069; P

BACKGROUND AND IMPORTANCE: Gamma Knife radiosurgery is an established technique for non-urgent treatment of various intracranial pathologies. Intra-procedural dislodgement of the stereotactic frame is an uncommon occurrence that could lead to abortion of ongoing treatment and necessitate more invasive treatment strategies. CLINICAL PRESENTATION: In this case report we describe a novel method for resumption of Gamma Knife treatment after an unplanned intra-procedural interruption. The case example involves a radiosurgical treatment of a Spetzler-Martin Grade I arteriovenous malformation. CONCLUSION: Our technique involves integration of scans and coordinate systems from two imaging sessions using the composite isodose line to resolve translational differences, thereby limiting delivery of remaining shots to the untreated region of the lesion. MRI follow-up at 13 months showed a reduction in the nidus size with no evidence of any radiation injury to the surrounding brain parenchyma. We believe this technique will allow care teams to effectively salvage interrupted gamma knife procedures and reduce progression to more invasive treatment options.

Purpose Accurate noninvasive diagnosis is vital for effective treatment planning. Presently, standard anatomical magnetic resonance imaging (MRI) is incapable of differentiating recurring tumor from delayed radiation injury, as both lesions are hyperintense in both postcontrast T1- and T2-weighted images. Further studies are therefore necessary to identify an MRI paradigm that can differentially diagnose these pathologies. Mouse glioma and radiation injury models provide a powerful platform for this purpose. Methods and Materials Two MRI contrasts that are widely used in the clinic were chosen for application to a glioma/radiation-injury model: diffusion weighted imaging, from which the apparent diffusion coefficient (ADC) is obtained, and magnetization transfer contrast, from which the magnetization transfer ratio (MTR) is obtained. These metrics were evaluated longitudinally, first in each lesion type alone–glioma versus irradiation – and then in a combined irradiated glioma model. Results MTR was found to be consistently decreased in all lesions compared to nonlesion brain tissue (contralateral hemisphere), with limited specificity between lesion types. In contrast, ADC, though less sensitive to the presence of pathology, was increased in radiation injury and decreased in tumors. In the irradiated glioma model, ADC also increased immediately after irradiation, but decreased as the tumor regrew. Conclusions ADC is a better metric than MTR for differentiating glioma from radiation injury. However, MTR was more sensitive to both tumor and radiation injury than ADC, suggesting a possible role in detecting lesions that do not enhance strongly on T1-weighted images.

Purpose: To quantify the effectiveness of anti-VEGF antibodies (bevacizumab and B20-4.1.1) as mitigators of radiation-induced, central nervous system (brain) necrosis in a mouse model. Experimental Design: Cohorts of mice were irradiated with single-fraction 50- or 60-Gy doses of radiation targeted to the left hemisphere (brain) using the Leksell Perfexion Gamma Knife. The onset and progression of radiation necrosis were monitored longitudinally by in vivo, small-animal MRI, beginning 4 weeks after irradiation. MRI-derived necrotic volumes for antibody (Ab)-treated and untreated mice were compared. MRI results were supported by correlative histology. Results: Hematoxylin and eosin–stained sections of brains from irradiated, non–Ab-treated mice confirmed profound tissue damage, including regions of fibrinoid vascular necrosis, vascular telangiectasia, hemorrhage, loss of neurons, and edema. Treatment with the murine anti-VEGF antibody B20-4.1.1 mitigated radiation-induced changes in an extraordinary, highly statistically significant manner. The development of radiation necrosis in mice under treatment with bevacizumab (a humanized anti-VEGF antibody) was intermediate between that for B20-4.1.1–treated and non–Ab-treated animals. MRI findings were validated by histologic assessment, which confirmed that anti-VEGF antibody treatment dramatically reduced late-onset necrosis in irradiated brain. Conclusions: The single-hemispheric irradiation mouse model, with longitudinal MRI monitoring, provides a powerful platform for studying the onset and progression of radiation necrosis and for developing and testing new therapies. The observation that anti-VEGF antibodies are effective mitigants of necrosis in our mouse model will enable a wide variety of studies aimed at dose optimization and timing and mechanism of action with direct relevance to ongoing clinical trials of bevacizumab as a treatment for radiation necrosis. Clin Cancer Res; 20(10); 2695–702. ©2014 AACR.

BACKGROUND This study tested the hypothesis that time of day of treatment with stereotactic radiosurgery (SRS) has an effect on local control (LC) and overall survival (OS) in a large cohort of patients with non–small cell lung cancer (NSCLC) brain metastases. METHODS At Washington University in St. Louis, 437 patients with NSCLC were treated with SRS for NSCLC brain metastases. Receiver operating characteristics analysis was used to identify an optimal cut-point for OS relative to time of day. Kaplan-Meier log-rank statistics, and Cox regression univariate and multivariate analysis were employed to isolate any independent effect of treatment time on OS and LC. Matched-pair analysis was performed to isolate any independent effect of time on OS and LC of day while controlling for confounding variables. RESULTS Receiver operating characteristics analysis identified a cut-point of 11:41 AM as providing the highest predictive value for OS. On univariate analysis, late SRS was associated with decreased OS, as was age, Karnofsky performance status, risk-stratification schemes, extracranial disease status, and overall burden of brain metastases. On univariate analysis for LC, late SRS was associated with decreased LC, as was burden of brain metastases. On multivariate analysis, only Graded Prognostic Assessment remained predictive of OS, and total number of targets and total tumor volume remained predictive of LC. Matched-pair analysis demonstrated no significant effect of time of day on LC or OS. CONCLUSIONS Although earlier treatment appears to be associated with improved LC and OS, treatment time fails to remain significant when accounting for confounding variables. Cancer 2013;119:3563–3569.. © 2013 American Cancer Society.

An anthropomorphic head phantom, constructed from a water‐equivalent plastic shell with only a spherical target, was modified to include a nonspherical target (pituitary) and an adjacent organ at risk (OAR) (optic chiasm), within 2 mm, simulating the anatomy encountered when treating acromegaly. The target and OAR spatial proximity provided a more realistic treatment planning and dose delivery exercise. A separate dosimetry insert contained two TLD for absolute dosimetry and radiochromic film, in the sagittal and coronal planes, for relative dosimetry. The prescription was 25 Gy to 90% of the GTV, with ≤10% of the OAR volume receiving ≥8Gy for the phantom trial. The modified phantom was used to test the rigor of the treatment planning process and phantom reproducibility using a Gamma Knife, CyberKnife, and linear accelerator (linac)‐based radiosurgery system. Delivery reproducibility was tested by repeating each irradiation three times. TLD results from three irradiations on a CyberKnife and Gamma Knife agreed with the calculated target dose to within ± 4% with a maximum coefficient of variation of ±2.1%. Gamma analysis in the coronal and sagittal film planes showed an average passing rate of 99.4% and 99.5% using ±5%/3mm criteria, respectively. Results from the linac irradiation were within ±6.2% for TLD with a coefficient of variation of ±0.1%. Distance to agreement was calculated to be 1.2 mm and 1.3 mm along the inferior and superior edges of the target in the sagittal film plane, and 1.2 mm for both superior and inferior edges in the coronal film plane. A modified, anatomically realistic SRS phantom was developed that provided a realistic clinical planning and delivery challenge that can be used to credential institutions wanting to participate in NCI‐funded clinical trials. PACS number: 87.55 ‐v

One of the most important aspects of quality assurance (QA) in radiation therapy is redundancy of patient treatment dose calculation. This work is focused on the patient‐specific time and 3D dose treatment plan verification for stereotactic radiosurgery using Leksell Gamma Knife Perfexion (LGK PFX). The virtual model of LGK PFX was developed in MATLAB, based on the physical dimensions provided by the manufacturer. The ring‐specific linear attenuation coefficients (LAC) and output factors (OFs) reported by the manufacturer were replaced by the measurement‐based collimator size‐specific OFs and a single LAC=0.0065 mm−1. Calculation depths for each LGK PFX shot were obtained by ray‐tracing technique, and the dose calculation formalism was similar to the one used by GammaPlan treatment planning software versions 8 and 9. The architecture of the QA process was based on the in‐house online database search of the LGK PFX database search for plan‐specific information. A series of QA phantom plans was examined to verify geometric and dosimetric accuracy of the software. The accuracy of the QA process was further evaluated through evaluation of a series of patient plans. The shot time/focus point dose verification for each shot took less than 1 sec/shot with full 3D isodose verification taking about 30 sec/shot on a desktop PC. GammaPlan database access time took less than 0.05 sec. The geometric accuracy (location of the point of maximum dose) of the phantom and patient plan was dependent on the resolution of the original dose matrix and was of the order of 1 dose element. Dosimetric accuracy of the independently calculated phantom and patient point (focus) doses was within 3.5% from the GammaPlan, with the mean=2.3% and SD=1.1%. The process for independent pretreatment patient‐specific Gamma Knife Perfexion time and dose verification was created and validated. PACS numbers: 87.53.Bn; 87.55.‐x; 87.56.Bg

Purpose To identify risk factors for the development of chest wall (CW) pain after thoracic stereotactic body radiotherapy (SBRT). Methods and materials A registry of patients with lung lesions treated with lung SBRT was explored to identify patients treated with 54Gy in three fractions or 50Gy in five fractions. One hundred and forty-six lesions in 140 patients were identified; complete electronic treatment plans were available on 86 CWs. The CW was contoured as a 3cm outward expansion from the involved lung. Univariate and multivariate analyses were used to correlate patient, tumor, and dosimetric factors to the development of CW toxicity. Results CW pain occurred in 22 patients (15.7%). The Kaplan–Meier estimated risk of CW pain at 2years was 20.1% (95% C.I., 13.2–28.8%). On univariate analysis of patient factors, elevated BMI ( p =0.026) and connective tissue disease ( p =0.036) correlated with CW pain. The percent of CW receiving 30, 35, or 40Gy was most predictive of CW pain on multivariate analysis using logistic regression, while V40 alone was predictive using Cox regression. A V30 threshold of 0.7% and V40 threshold of 0.19% was correlated with a 15% risk of CW pain. Conclusions We have described patient and dosimetric parameters that correlate with CW pain after lung SBRT. The risk of CW pain may be mitigated by attempting to reduce the relative proportion of CW receiving 30–40Gy during treatment planning.

Object Large cerebral arteriovenous malformations (AVMs) are often not amenable to direct resection or stereotactic radiosurgery (SRS) treatment. An alternative treatment strategy is staged endovascular embolization followed by SRS (Embo/SRS). The object of this study was to examine the experience at Washington University in St. Louis with Embo/SRS for large AVMs and review the results in earlier case series. Methods Twenty-one cases involving patients with large AVMs treated with Embo/SRS between 1994 and 2006 were retrospectively evaluated. The AVM size (before and after embolization), procedural complications, radiological outcome, and neurological outcome were examined. Radiological success was defined as AVM obliteration as demonstrated by catheter angiography, CT angiography, or MR angiography. Radiological failure was defined as residual AVM as demonstrated by catheter angiography, CT angiography, or MR angiography performed at least 3 years after SRS. Results The maximum diameter of all AVMs in this series was > 3 cm (mean 4.2 cm); 12 (57%) were Spetzler-Martin Grade IV or V. Clinical follow-up was available in 20 of 21 cases; radiological follow-up was available in 19 of 21 cases (mean duration of follow-up 3.6 years). Forty-three embolization procedures were performed; 8 embolization-related complications occurred, leading to transient neurological deficits in 5 patients (24%), minor permanent neurological deficits in 3 patients (14%), and major permanent neurological deficits in none (0%). Twenty-one SRS procedures were performed; 1 radiation-induced complication occurred (5%), leading to a permanent minor neurological deficit. Of the 20 patients with clinical follow-up, none experienced cerebral hemorrhage. In the 19 patients with radiological follow-up, AVM obliteration was confirmed by catheter angiography in 13, MR angiography in 2, and CT angiography in 1. Residual nidus was found in 3 patients. In patients with follow-up catheter angiography, the AVM obliteration rate was 81% (13 of 16 cases). Conclusions Staged endovascular embolization followed by SRS provides an effective means of treating large AVMs not amenable to standard surgical or SRS treatment. The outcomes and complication rates reported in this series compare favorably to the results of other reported therapeutic strategies for this very challenging patient population.

Background Patients with limited intracranial metastatic disease traditionally have been treated with surgery followed by WBRT. However, there is growing concern for the debilitating cognitive effects after WBRT in long-term survivors. We present a series of patients treated with surgery followed by SRS, while reserving WBRT as a salvage therapy for disease progression. Methods Medical records from 15 patients with 1 to 2 cerebral metastases who underwent both resection and SRS were reviewed. Outcome measures included overall survival, survival by RPA class, EOR, local tumor control, progression of intracranial disease, need for WBRT salvage therapy, and COD. Results Fifteen patients with cerebral metastases were treated with the combined surgery-SRS paradigm. Eight of the 15 patients (53.3%) were designated RPA class 1, with 6 of 15 (40.0%) in class 2 and 1 of 15 (6.7%) in class 3. Gross total resection was achieved in 12 cases (80.0%). Overall median survival was 20.0 months, with values of 22.0 and 13.0 months for RPA classes 1 and 2, respectively. Local recurrence occurred in 16.7% of those patients with GTR. Six patients (40.0%) went on to receive WBRT at a median of 8.0 months from initial presentation. Twelve patients (80.0%) had died at the completion of the study, and the COD was CNS progression in 33.3%. Conclusions Surgical resection combined with SRS is an effective treatment for selected patients with limited cerebral metastatic disease. Survival using this combined treatment was equivalent to or greater than that reported by other studies using surgery + WBRT or SRS + WBRT.

Treating shallow tumors with a homogeneous dose while simultaneously minimizing the dose to distal critical organs remains a challenge in radiotherapy. One promising approach is modulated electron radiotherapy (MERT). Due to the scattering properties of electron beams, the commercially provided secondary and tertiary photon collimation systems are not conducive for electron beam delivery when standard source-to-surface distances are used. Also, commercial treatment planning systems may not accurately model electron-beam dose distributions when collimated without the standard applicators. However, by using the photon multileaf collimators (MLCs) to create segments to modulate electron beams, the quality of superficial tumor dose distributions may improve substantially. The purpose of this study is to develop and evaluate calculations for the narrow segments needed to modulate megavoltage electron beams using photon beam multileaf collimators. Modulated electron radiotherapy (MERT) will be performed with a conventional linear accelerator equipped with a 120 leaf MLC for 6-20 MeV electron beam energies. To provide a sharp penumbra, segments were delivered with short SSDs (70-85 cm). Segment widths (SW) ranging from 1 to 10 cm were configured for delivery and planning, using BEAMnrc Monte Carlo (MC) code, and the DOSXYZnrc MC dose calculations. Calculations were performed with voxel size of 0.2 x 0.2 x 0.1 cm3. Dosimetry validation was performed using radiographic film and micro- or parallel-plate chambers. Calculated and measured data were compared using technical computing software. Beam sharpness (penumbra) degraded with decreasing incident beam energy and field size (FS), and increasing SSD. A 70 cm SSD was found to be optimal. The PDD decreased significantly with decreasing FS. The comparisons demonstrated excellent agreement for calculations and measurements within 3%, 1 mm. This study shows that accurate calculations for MERT as delivered with existing photon MLC are feasible and allows the opportunity to take advantage of the dynamic leaf motion capabilities and control systems, to provide conformal dose distributions.

Purpose: Absorbed dose calibration for gamma stereotactic radiosurgery is challenging due to the unique geometric conditions, dosimetry characteristics, and nonstandard field size of these devices. Members of the American Association of Physicists in Medicine (AAPM) Task Group 178 on Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance have participated in a round-robin exchange of calibrated measurement instrumentation and phantoms exploring two approved and two proposed calibration protocols or formalisms on ten gamma radiosurgery units. The objectives of this study were to benchmark and compare new formalisms to existing calibration methods, while maintaining traceability to U.S. primary dosimetry calibration laboratory standards. Methods: Nine institutions made measurements using ten gamma stereotactic radiosurgery units in three different 160 mm diameter spherical phantoms [acrylonitrile butadiene styrene (ABS) plastic, Solid Water, and liquid water] and in air using a positioning jig. Two calibrated miniature ionization chambers and one calibrated electrometer were circulated for all measurements. Reference dose-rates at the phantom center were determined using the well-established AAPM TG-21 or TG-51 dose calibration protocols and using two proposed dose calibration protocols/formalisms: an in-air protocol and a formalism proposed by the International Atomic Energy Agency (IAEA) working group for small and nonstandard radiation fields. Each institution’s results weremore » normalized to the dose-rate determined at that institution using the TG-21 protocol in the ABS phantom. Results: Percentages of dose-rates within 1.5% of the reference dose-rate (TG-21 + ABS phantom) for the eight chamber-protocol-phantom combinations were the following: 88% for TG-21, 70% for TG-51, 93% for the new IAEA nonstandard-field formalism, and 65% for the new in-air protocol. Averages and standard deviations for dose-rates over all measurements relative to the TG-21 + ABS dose-rate were 0.999 ± 0.009 (TG-21), 0.991 ± 0.013 (TG-51), 1.000 ± 0.009 (IAEA), and 1.009 ± 0.012 (in-air). There were no statistically significant differences (i.e., p > 0.05) between the two ionization chambers for the TG-21 protocol applied to all dosimetry phantoms. The mean results using the TG-51 protocol were notably lower than those for the other dosimetry protocols, with a standard deviation 2–3 times larger. The in-air protocol was not statistically different from TG-21 for the A16 chamber in the liquid water or ABS phantoms (p = 0.300 and p = 0.135) but was statistically different from TG-21 for the PTW chamber in all phantoms (p = 0.006 for Solid Water, 0.014 for liquid water, and 0.020 for ABS). Results of IAEA formalism were statistically different from TG-21 results only for the combination of the A16 chamber with the liquid water phantom (p = 0.017). In the latter case, dose-rates measured with the two protocols differed by only 0.4%. For other phantom-ionization-chamber combinations, the new IAEA formalism was not statistically different from TG-21. Conclusions: Although further investigation is needed to validate the new protocols for other ionization chambers, these results can serve as a reference to quantitatively compare different calibration protocols and ionization chambers if a particular method is chosen by a professional society to serve as a standardized calibration protocol.« less

Recently, radiation induced necrosis in the brain has been treated using bevacizumab, an anti-VEGF antibody. We validated the VEGF specificity by comparing the therapeutic efficacy of anti-VEGF with non-specific isotype control antibody. Additionally, we found that VEGF over-expression and RN developed simultaneously, which precludes preventative anti-VEGF treatment.

As complexity for treating patients increases, so does the risk of error. Some publications have suggested that record and verify (R&V) systems may contribute in propagating errors. Direct data transfer has the potential to eliminate most, but not all, errors. And although the dosimetric consequences may be obvious in some cases, a detailed study does not exist. In this effort, we examined potential errors in terms of scenarios, pathways of occurrence, and dosimetry. Our goal was to prioritize error prevention according to likelihood of event and dosimetric impact. For conventional photon treatments, we investigated errors of incorrect source‐to‐surface distance (SSD), energy, omitted wedge (physical, dynamic, or universal) or compensating filter, incorrect wedge or compensating filter orientation, improper rotational rate for arc therapy, and geometrical misses due to incorrect gantry, collimator or table angle, reversed field settings, and setup errors. For electron beam therapy, errors investigated included incorrect energy, incorrect SSD, along with geometric misses. For special procedures we examined errors for total body irradiation (TBI, incorrect field size, dose rate, treatment distance) and LINAC radiosurgery (incorrect collimation setting, incorrect rotational parameters). Likelihood of error was determined and subsequently rated according to our history of detecting such errors. Dosimetric evaluation was conducted by using dosimetric data, treatment plans, or measurements. We found geometric misses to have the highest error probability. They most often occurred due to improper setup via coordinate shift errors or incorrect field shaping. The dosimetric impact is unique for each case and depends on the proportion of fields in error and volume mistreated. These errors were short‐lived due to rapid detection via port films. The most significant dosimetric error was related to a reversed wedge direction. This may occur due to incorrect collimator angle or wedge orientation. For parallel‐opposed 60° wedge fields, this error could be as high as 80% to a point off‐axis. Other examples of dosimetric impact included the following: SSD, ~2%/cm for photons or electrons; photon energy (6 MV vs. 18 MV), on average 16% depending on depth, electron energy, ~0.5cm of depth coverage per MeV (mega‐electron volt). Of these examples, incorrect distances were most likely but rapidly detected by in vivo dosimetry. Errors were categorized by occurrence rate, methods and timing of detection, longevity, and dosimetric impact. Solutions were devised according to these criteria. To date, no one has studied the dosimetric impact of global errors in radiation oncology. Although there is heightened awareness that with increased use of ancillary devices and automation, there must be a parallel increase in quality check systems and processes, errors do and will continue to occur. This study has helped us identify and prioritize potential errors in our clinic according to frequency and dosimetric impact. For example, to reduce the use of an incorrect wedge direction, our clinic employs off‐axis in vivo dosimetry. To avoid a treatment distance setup error, we use both vertical table settings and optical distance indicator (ODI) values to properly set up fields. As R&V systems become more automated, more accurate and efficient data transfer will occur. This will require further analysis. Finally, we have begun examining potential intensity‐modulated radiation therapy (IMRT) errors according to the same criteria. PACS numbers: 87.53.Xd, 87.53.St

Seventy-three patients were evaluated for the changes in pain relief, numbness and paresthesias after Gamma Knife radiosurgery to a maximum dose of 76–87 Gy for trigeminal neuralgia. Patients experienced pain relief as follows: 59% attained complete pain relief without prior surgery (33% with prior surgery); 25% achieved ≧50% pain reduction (28% with prior surgery); 11% of surgery patients obtained minor pain relief, and 16% of patients without surgery had no relief (28% with prior surgery). Level of pain decreased rapidly within 6 weeks after radiosurgery. Numbness/paresthesias developed slowly over the first 12–15 months. Bothersome levels were experienced by 15% of the patients without prior surgery (22% with prior surgery). Comparison of the occurrence of numbness/paresthesias, with respect to prior surgery, was not statistically significant. Only 2% of all patients had persistently bothersome side effects. In conclusion, radiosurgery is an effective treatment of trigeminal neuralgia, especially for those patients not having prior surgery.

The purpose of this study is to develop a simple independent dose calculation method to verify treatment plans for Leksell Gamma Knife radiosurgery. Our approach uses the total integral dose within the skull as an end point for comparison. The total integral dose is computed using a spreadsheet and is compared to that obtained from Leksell GammaPlan®. It is calculated as the sum of the integral doses of 201 beams, each passing through a cylindrical volume. The average length of the cylinders is estimated from the Skull-Scaler measurement data taken before treatment. Correction factors are applied to the length of the cylinder depending on the location of a shot in the skull. The radius of the cylinder corresponds to the collimator aperture of the helmet, with a correction factor for the beam penumbra and scattering. We have tested our simple spreadsheet program using treatment plans of 40 patients treated with Gamma Knife® in our center. These patients differ in geometry, size, lesion locations, collimator helmet, and treatment complexities. Results show that differences between our calculations and treatment planning results are typically within ± 3 % , with a maximum difference of ± 3.8 % . We demonstrate that our spreadsheet program is a convenient and effective independent method to verify treatment planning irradiation times prior to implementation of Gamma Knife radiosurgery.

The role of 3-dimensional treatment planning in the management of rectal cancer is not well defined. This report reviews technical guidelines for simulation, defining target volumes, and suggested beam configurations. Outcome from pilot clinical trials, with emphasis on the impact of volume and dose on tumor response and treatment morbidity is discussed.

Gamma Knife radiosurgery (GKS) is a primary treatment modality for small, surgically-challenging meningiomas of the skull base in carefully selected patients. Despite the overall low incidence of complications from this procedure, rare instances of hemorrhagic events following GKS have been reported. In fact, only a single, probable case of acute hemorrhage after GKS for a meningioma exists in the literature.The authors present the case of a 59-year-old female treated with GKS to a clival meningioma who suffered an acute intra- and peritumoral hemorrhage within three hours after the procedure. The patient also had an ST-elevation myocardial infarction associated with the hemorrhage. At the time of her GKS she was taking aspirin and clopidogrel for treatment of coronary artery disease with multiple cardiac stents. Cerebral catheter angiography failed to reveal a source for the hemorrhage.Acute hemorrhage following GKS to a meningioma is a rare, but potentially serious, complication and consideration should be given to counseling patients of this risk prior to treatment. We hypothesize that acute change to the structural integrity of the vascular endothelium after GKS may have precipitated cerebrovascular dysfunction resulting in hemorrhage. While the administration of anti-platelet therapy may have been a contributing factor to his event, it appears that the low incidence of acute tumoral bleeding after GKS does not justify routinely discontinuing anti-platelet and/or anti-coagulation in patients with severe associated medical co-morbidities.

To evaluate local control rates and predictors of individual tumor local control for brain metastases from non-small cell lung cancer (NSCLC) treated with stereotactic radiosurgery (SRS).Between June 1998 and May 2011, 401 brain metastases in 228 patients were treated with Gamma Knife single-fraction SRS. Local failure was defined as an increase in lesion size after SRS. Local control was estimated using the Kaplan-Meier method. The Cox proportional hazards model was used for univariate and multivariate analysis. Receiver operating characteristic analysis was used to identify an optimal cutpoint for conformality index relative to local control. A P value.05 was considered statistically significant.Median age was 60 years (range, 27-84 years). There were 66 cerebellar metastases (16%) and 335 supratentorial metastases (84%). The median prescription dose was 20 Gy (range, 14-24 Gy). Median overall survival from time of SRS was 12.1 months. The estimated local control at 12 months was 74%. On multivariate analysis, cerebellar location (hazard ratio [HR] 1.94, P=.009), larger tumor volume (HR 1.09, P.001), and lower conformality (HR 0.700, P=.044) were significant independent predictors of local failure. Conformality index cutpoints of 1.4-1.9 were predictive of local control, whereas a cutpoint of 1.75 was the most predictive (P=.001). The adjusted Kaplan-Meier 1-year local control for conformality index ≥ 1.75 was 84% versus 69% for conformality index1.75, controlling for tumor volume and location. The 1-year adjusted local control for cerebellar lesions was 60%, compared with 77% for supratentorial lesions, controlling for tumor volume and conformality index.Cerebellar tumor location, lower conformality index, and larger tumor volume were significant independent predictors of local failure after SRS for brain metastases from NSCLC. These results warrant further investigation in a prospective setting.

The photon energy spectrum emanating from a Leksell Gamma Knife, Model 23004B, was measured between 0.250 and 3.5 MeV with the sources exposed. Measurements were made using a 2x2 inch NaI detector enclosed in a lead-shielded apparatus having a 1/4 inch diameter measurement aperture, which reduced the amount of radiation received by the crystal. All measurements were made one meter above the floor within a quadrant toward one side of the Gamma Knife couch. The measured spectra displayed the expected 60Co doublet of photon peaks at energies of 1.17 and 1.33 MeV. These peaks appeared in spectra beginning at approximately 50 degrees, as one proceeds from a point directly lateral to the source enclosure (0 degrees) toward the foot of the couch (90 degrees). The average photon energy of the spectrum shifts to lower values as the doublet decreases in magnitude with increasing angle until almost vanishing at an angle equal to 90 degrees. Inserting a 16 cm diameter plastic sphere phantom, provided with the Gamma Knife, into the radiation beams increases the low energy photon emissions appearing in the spectrum, especially for measurements at the foot of the couch. Implications for the design of shielding a treatment room containing the Gamma Knife, Model B, and estimation of the radiation exposure to personnel during an emergency procedure in the treatment room with the sources exposed are discussed.

Objective: A custom-designed anthropomorphic head phantom, containing computed tomography (CT)and magnetic resonance (MR) viewable targets, was used in the assessment of stereotactic localization accuracyMaterials and Methods: The Brown-Roberts-Wells (BRW) or Leksell stereotactic ring was rigidly fixed to the phantom. CT and MR images were then obtained according to radiosurgery protocols with the corresponding localizer frame attached. Plastic spheres and rods appeared at various locations within the phantom, when filled with aqueous solution, and their images served as targets to compute stereotactic target coordinates using software compatible with each frame. Coordinates derived using CT and MR were compared with mechanical measurements obtained using the BRW or Leksell stereotactic arc systemsResults: For the BRW stereotactic system, the average vector distance to agreement of image-derived coordinates with the mechanical measurements was 1.41 ± 0.90 mm (CT) and 1.37 ± 0.38 mm (MR). Similar results w...

With the introduction of new treatment devices, such as a multileaf collimator (MLC) and dynamic wedge (DW), therapists have an increased responsibility to ensure correct treatment. Simultaneously, three-dimensional treatment planning (3DTP) has led to an increased number of portals and table movements. To counteract this challenge and maintain efficiency, a comprehensive record and verify (RV) system is mandatory. We evaluated a commercial system (Varis) for reliability, ease of use, efficiency, and integration with our planning systems.Some key elements of the Varis system are: integration of MLC and DW; auto setup for MLC, jaw, collimator, gantry, and limited table parameters; direct download of simulation beam data; and a regimented field scheduling system that prescribes all beam data for particular fractions. Evaluation of the system was driven by treatment time analysis, error rates, and an increased workload. These issues were governed by how we disseminated duties and how the system accommodated or changed our processes.Most data entry is performed by our dosimetry staff. Data can be downloaded from the simulator, but more patients now move from CT simulation and/or 3DTP to the treatment machine. Varis does not link to these systems. The physics staff confirms all entries to correct data entry errors. The workload for dosimetrists increased by an average of 8 minutes/patient entry; physics time increased by 7 minutes/patient entry; the weekly electronic chart check takes approximately 3 minutes/patient. Therapists who used Varis efficiently showed a slight decrease in treatment times, attributed to MLC integration and auto-setup. Some therapists experienced a decrease in efficiency, because of unfamiliarity and excess intervention. On a positive note, notable events have decreased by a factor of 10 since full initiation. Unfortunately, the remaining errors are often the result of a therapist relying on incorrect electronic information.The Varis RV system has had an impact on our clinic's process and efficiency. Checking of all beam data and related field scheduling have helped reduce errors and misconceptions. We feel a dual-energy machine can be operated with two experienced therapists and an up-to-date RV system more accurately and efficiently than with three therapists working without an integrated RV. We anticipate future Varis releases will further promote efficiency and accuracy.

Purpose: The purpose of this project was to devise a practical fabrication process for passive scatter proton beam compensation filters (CF) that is competitive in time, cost and effort using 3D printing. Methods: DICOM compensator filter files for a proton beam were generated by our Eclipse (Varian, Inc.) treatment planning system. The compensator thickness specifications were extracted with in-house software written in Matlab (MathWorks, Inc.) code and written to a text file which could be read by the Rhinoceros 5, computer-aided design (CAD) package (Robert McNeel and Associates), which subsequently generated a smoothed model in a STereoLithographic also known as a Standard Tesselation Language file (STL). The model in the STL file was subsequently refined using Netfabb software and then converted to printing instructions using Cura. version 15.02.1. for our 3D printer. The Airwolf3D, model HD2x, fused filament fabrication (FFF) 3D printer (Airwolf3D.com) was used for our fabrication system with a print speed of 150mm per second. It can print in over 22 different plastic filament materials in a build volume of 11” x 8” x 12”. We choose ABS plastic to print the 3D model of the imprint for our CFs. Results: Prints of the CF could be performed at a print speed of 70mm per second. The time to print the 3D topology for the CF for the 14 cm diameter snout of our Mevion 250 proton accelerator was less than 3 hours. The printed model is intended to subsequently be used as a mold to imprint a molten wax cylindrical to form the compensation after cooling. The whole process should be performed for a typical 3 beam treatment plan within a day. Conclusion: Use of 3D printing is practical and can be used to print a 3D model of a CF within a few hours.

Purpose: The purpose of this multi-institutional study was to compare two new gamma stereotactic radiosurgery (GSRS) dosimetry protocols to existing calibration methods. The ultimate goal was to guide AAPM Task Group 178 in recommending a standard GSRS dosimetry protocol. Methods: Nine centers (ten GSRS units) participated in the study. Each institution made eight sets of dose rate measurements: six with two different ionization chambers in three different 160mm-diameter spherical phantoms (ABS plastic, Solid Water and liquid water), and two using the same ionization chambers with a custom in-air positioning jig. Absolute dose rates were calculated using a newly proposed formalism by the IAEA working group for small and non-standard radiation fields and with a new air-kerma based protocol. The new IAEA protocol requires an in-water ionization chamber calibration and uses previously reported Monte-Carlo generated factors to account for the material composition of the phantom, the type of ionization chamber, and the unique GSRS beam configuration. Results obtained with the new dose calibration protocols were compared to dose rates determined by the AAPM TG-21 and TG-51 protocols, with TG-21 considered as the standard. Results: Averaged over all institutions, ionization chambers and phantoms, the mean dose rate determined with the new IAEA protocol relative to that determined with TG-21 in the ABS phantom was 1.000 with a standard deviation of 0.008. For TG-51, the average ratio was 0.991 with a standard deviation of 0.013, and for the new in-air formalism it was 1.008 with a standard deviation of 0.012. Conclusion: Average results with both of the new protocols agreed with TG-21 to within one standard deviation. TG-51, which does not take into account the unique GSRS beam configuration or phantom material, was not expected to perform as well as the new protocols. The new IAEA protocol showed remarkably good agreement with TG-21. Conflict of Interests: Paula Petti, Josef Novotny, Gennady Neyman and Steve Goetsch are consultants for Elekta Instrument A/B; Elekta Instrument AB, PTW Freiburg GmbH, Standard Imaging, Inc., and The Phantom Laboratory, Inc. loaned equipment for use in these experiments; The University of Wisconsin Accredited Dosimetry Calibration Laboratory provided calibration services.

PURPOSE In a health care environment strongly concerned with cost containment, cost-benefit studies of new technology must include analyses of loco-regional tumor control, morbidity, impact on quality of life, and financial considerations. METHODS AND MATERIALS This nonrandomized study analyzes 124 patients treated with three-dimensional conformal radiation therapy (3D CRT) and 153 with standard irradiation (SRT) between January 1992 and December 1995, for histologically proven adenocarcinoma of prostate, clinical Stage T1 or T2. Mean follow-up is 1.4 years. Three-dimensional CRT consisted of six or seven coplanar oblique and lateral and, in some patients, AP fields designed to treat the prostate with a 1 to 1.7 cm margin. SRT consisted of 120 degrees bilateral arc rotation. Total doses to prostate were 67 to 70 Gy when pelvic lymph nodes were irradiated or 68.4 to 73.8 Gy when prostatic volume only was treated; dose per fraction was 1.8 Gy. Patients were interviewed weekly for severity of 12 acute intestinal and urinary pelvic irradiation side effects (0 to 4+ grading). Time and effort for 3D RTP and daily treatment with 3D CRT and SRT were recorded. Dose-volume histograms (DVHs) were calculated for gross tumor volume, planning target volume, bladder, and rectum. Actual reimbursement to the hospital and university was determined for 41 3D CRT, 43 SRT, and 40 radical prostatectomy patients treated during the same period. RESULTS Average treatment planning times (in minutes) were: 101 for 3D conformal therapy simulation, 66 for contouring of target volume and sensitive structures, 55 for virtual simulation, 39 for plan preparation and documentation, 65 for physical simulation, and 20 for approval of treatment plan. Daily mean treatment times were 19 min for 3D CRT with Cerrobend blocking, 16 with multileaf collimation, and 10 with bilateral arc rotation. Dosimetric analysis (DVHs) showed a reduction of 50% in volume of bladder or rectum receiving doses higher than 65 Gy. Acute side effects included dysuria, moderate difficulty in urinating, and nocturia in 25-39% of both SRT and CRT patients; loose stools or diarrhea in 5-12% of 3D CRT and 16-22% of SRT patients; moderate proctitis in 3% of 3D CRT and 12% of SRT patients (p = 0.01). Chemical disease-free survival (prostate-specific antigen < or =2 ng/ml) at 3 years was 90% with 3D CRT and 80% with SRT (p = 0.01). Average initial treatment reimbursements were $13,823 (3D CRT), $10,864 (SRT), and $12,250 (radical prostatectomy). Average total treatment reimbursement and projected cost of management of initial therapy failures per patients were $15,173, $16,264, and $16,405, respectively. CONCLUSIONS Three-dimensional CRT irradiated less bladder and rectum volume than SRT; CRT initial reimbursement was 28% higher than SRT and 12% higher than radical prostatectomy. Because of projected better local tumor control, average total cost of treating a patient with 3D CRT or radical prostatectomy is equivalent to cost of SRT. Treatment morbidity was lower with 3D CRT. Our findings reflect an overall benefit with 3D CRT as a new promising technology in treatment of localized prostate cancer. Dose-escalation studies may enhance its efficacy and cost benefit.

Ionizing radiation (IR) results in apoptosis in a number of actively proliferating or immature cell types. The effect of IR on rat dorsal root ganglion (DRG) neurons was examined in dissociated cell cultures. After exposure to IR, embryonic DRG neurons, established in cell culture for six days, underwent cell death in a manner that was dose-dependent, requiring a minimum of 8 to 16 Gy. Twenty-five per cent cell loss occurred in embryonic day 15 (E-15) neurons, grown in cell culture for 6 days (“immature”), and then treated with 24 Gy IR. In contrast, only 2% cell loss occurred in E-15 neurons maintained in culture for 21 days ("mature") and then treated with 24 Gy IR. Staining with a fluorescent DNA-binding dye demonstrated clumping of the nuclear chromatin typical of apoptosis. Initiation of the apoptosis occurred within 24 h after exposure to IR. Apoptosis was prevented by inhibition of protein synthesis with cycloheximide. Apoptosis induced by IR occurred more frequently in immature than in mature neurons. Immature DRG neurons have a lower concentration of intracellular calcium ([Ca2+]i) than mature neurons. Elevation of [Ca2+]i by exposure to a high extracellular potassium ion concentration (35 μM) depolarizes the cell membrane with a resultant influx of calcium ions. The activation of programmed cell death after nerve growth factor (NGF) withdrawal is inversely correlated with [Ca2+]i in immature DRG neurons. When treated with high extracellular potassium, these immature neurons were resistant to IR exposure in a manner similar to that observed in mature neurons. These data suggest that [Ca2+]i modulates the apoptotic response of neurons after exposure to IR in a similar manner to that proposed by the “Ca2+ setpoint hypothesis” for control of NGF withdrawal-induced apoptosis.

This study tested the hypothesis that time of day of treatment with stereotactic radiosurgery (SRS) has an effect on local control (LC) and overall survival (OS) in a large cohort of patients with non-small cell lung cancer (NSCLC) brain metastases.At Washington University in St. Louis, 437 patients with NSCLC were treated with SRS for NSCLC brain metastases. Receiver operating characteristics analysis was used to identify an optimal cut-point for OS relative to time of day. Kaplan-Meier log-rank statistics, and Cox regression univariate and multivariate analysis were employed to isolate any independent effect of treatment time on OS and LC. Matched-pair analysis was performed to isolate any independent effect of time on OS and LC of day while controlling for confounding variables.Receiver operating characteristics analysis identified a cut-point of 11:41 AM as providing the highest predictive value for OS. On univariate analysis, late SRS was associated with decreased OS, as was age, Karnofsky performance status, risk-stratification schemes, extracranial disease status, and overall burden of brain metastases. On univariate analysis for LC, late SRS was associated with decreased LC, as was burden of brain metastases. On multivariate analysis, only Graded Prognostic Assessment remained predictive of OS, and total number of targets and total tumor volume remained predictive of LC. Matched-pair analysis demonstrated no significant effect of time of day on LC or OS.Although earlier treatment appears to be associated with improved LC and OS, treatment time fails to remain significant when accounting for confounding variables.

Preliminary clinical results are presented for 209 patients with cancer who had treatment planned on our three-dimensional radiation treatment planning (3-D RTP) system and were treated with external beam conformal radiation therapy. Average times (min) for CT volumetric simulation were: 74 without or 84 with contrast material; 36 for contouring of tumor/target volume and 44 for normal anatomy; 78 for treatment planning; 53 for plan evaluation/optimization; and 58 for verification simulation. Average time of daily treatment sessions with 3-D conformal therapy or standard techniques was comparable for brain, head and neck, thoracic, and hepatobiliary tumors (11.8–14 min and 11.5–12.1, respectively). For prostate cancer patients treated with 3-D conformal technique and Cerrobend blocks, mean treatment time was 19 min; with multileaf collimation it was 14 min and with bilateral arc rotation, 9.8 min. Acute toxicity was comparable to or lower than with standard techniques. Sophisticated 3-D RTP and conformal irradiation can be performed in a significant number of patients at a reasonable cost. Further efforts, including dose-escalation studies, are necessary to develop more versatile and efficient 3-D RTP systems and to enhance the cost benefit of this technology in treatment of patients with cancer.

The stereotactic radiosurgery system used at the Mallinckrodt Institute of Radiology is patterned after that developed at the Joint Center for Radiation Therapy (Brigham & Women’s Hospital, Boston, MA) and uses the Brown–Roberts–Wells computed tomography(CT) stereotactic system. The patient’s head is attached to a stand that rotates with the treatment couch. The irradiation is conducted using a set of converging arcs of irradiation. Because of mechanical limitations, no accelerator or treatment couch is capable of placing the center of the radiation beam at precisely the same point for all gantry and couch angles and a compromise must be made when locating the nominal isocenter. The stand settings are checked by placing a radiopaque QA sphere at the desired target location. The QA sphere is imaged using a series of eight films exposed at a set of couch and gantry angles that encompass the treatment angles. The distances between the QA sphere image and the center of the radiation field indicate if the correct coordinates were set on the stand and if the radiation beam converges to a sufficiently small region (

Purpose : Produce a collection of software tools (computer programs) that support three-dimensional (3D) radiation therapy planning. The tools are not a complete 3D planning system. Instead, they work with any 3D planning system that meets certain minimal specifications. The tools assist in deriving anatomic data from images, generating target volume contours, evaluating treatment plans, and verifying accurate treatment delivery. The tools are portable: they can run without source code changes in any computing environment that provides a library of functions and data definitions called the Foundation. The Foundation couples the portable tools to the (usually nonportable) file system and dose calculation associated with a particular 3D planning system. Methods and Materials : Tools were written at three different (geographically separated) institutions. Software developers from all three sites specified the Foundation. The programmers' interface to the Foundation is portable, but a Foundation implementation need not be portable. Each group implemented a Foundation adapted to the (different) 3D planning system used at their site. Results : All tools run at all three sites without source code changes. Each Foundation was implemented in a few person-months of programming effort. The program text and documentation for the tools have been placed in the public domain. Conclusions : It is practical and economical to produce portable radiotherapy treatment planning tools. Providers of 3D planning programs should offer Foundations for their systems, so they can be used with tools. Researchers considering new computer programs should write them as tools, so they can work with any 3D planning system.

Purpose: This article announces the availability of a convenient and useful software environment for the evaluation of three-dimensional (3D) radiotherapy treatment plans. Materials and Methods: Using standards such as American National Standards for Information Systems C and the X Window System allowed us to bring the computation and display of dose-volume histograms, dose statistics, tumor control probabilities, normal tissue complication probabilities, and a figure of merit together under one user interface. These plan evaluation tools are not stand alone, but must interact with a 3D radiation therapy planning system to obtain the required dose matrices and patient anatomical contours. Installation of the software involves a programmer who writes a software bridge between the radiation therapy planning system and the tools, thereby providing access to local data files. This design strategy confines portability issues to one area of the software. Results: Access to the other tools is through the Graphical Plan Evaluation Tool (GPET). GPET coordinates the use of each of the tools and provides graphical facilities for display of their results. Importantly, GPET assures that the displayed results of each tool have been computed with the same input specifications for all treatment plans being compared. For added convenience, the user can rearrange the resultant data to be reviewed in various ways on the video screen. The software design also allows incorporation of customized algorithms and input data for computing tumor control probability and normal tissue complication probabilities, since those currently available are controversial. Conclusion: The Graphical Plan Evaluation Tool unifies the simultaneous computation for several analytical tools and graphical display of their results. Within the constraints of the X Window System environment, this assemblage of software tools provides a portable, flexible, and convenient method for the quantitative evaluation of several radiotherapy treatment plans.

Purpose : Stereotactic radiosurgery is generally a single , high-dose radiation treatment for the brain requiring targeting accuracy on the order of a millimeter. From the initial implementation of radiosurgery, therefore, quality assurance is an ongoing process of paramount importance. In this paper, we outline the basic elements of a quality assurance program for our linear accelerator that has been in use at Washington University Medical Center over the past 2 years. Methods and Materials : Various devices and procedures have been developed to verify the accuracy and safety of the stereotactic radiosurgery regimen. Specifically, we present methods for assessing the attainment of spatially correct patient images, the reliability of the computerized treatment planning system, achieving physical safety for the patient, as well as the proper operation of the radiation treatment device. Results : Our procedures have allowed us to assure quality patient treatments and, additionally, has permitted monitoring our performance for continual improvement. For example, a plot of targeting accuracy with the number of patients shows an asymptotic approach to a value within 0.6 mm of that ideally expected. Conclusion : To maintain high-quality patient care, one must review critical aspects of the treatment regimen on a periodic basis. Providing for the appropriate level of staff training, periodic reviews of procedures and maintenance of forms are also very important.

Object The effectiveness of Gamma Knife stereotactic surgery to obliterate brain arteriovenous malformations (AVMs) may be diminished by the preoperative adjunctive use of endovascular liquid embolic agents. The purpose of the present investigation was to determine if commercially available liquid embolic agents reduce the radiation dose to the target because of attenuation of the 60Co beam. Methods The apparent linear attenuation coefficients for 120- to 140-keV radiographs in embolized regions were retrieved from CT scans for several patients with AVMs who had undergone embolization procedures with liquid embolic agents to reduce nidal volumes. Based on these coefficients and a virtual model of Gamma Knife surgery (GKS) with basic ray tracing, the authors obtained the path lengths and densities of the embolized regions. The attenuation of 60Co beams was then calculated for various sizes and positions of embolized AVM regions and for the number of beams used for treatment. Published experiments for several high-atomic-number materials were used to estimate the effective 60Co beam attenuation coefficients for the N-butyl cyanoacrylate (NBCA, suspended in ethiodized oil) and ethylene vinyl alcohol copolymer (EVOH, with suspended micronized tantalum powder, Onyx) used in the AVM embolizations. Dose reductions during GKS were calculated for a theoretical model based on the CT-documented apparent linear attenuation coefficients and for the 60Co energy attenuation coefficient. Dose measurements were obtained in a phantom study with EVOH for comparison with the estimates generated from the two attenuation coefficients. Results Based on CT (keV) apparent attenuation coefficients, the authors' theoretical model predicted that the cumulative effect of either of the embolic agents decreased the number of kilovoltage photons in an embolized nidus by −8% to −15% because of the increased atomic number and density of NBCA and Onyx. However, in using the effective attenuation coefficient for the 60Co energies as is used in GKS, the authors' theoretical model yielded only a 0.2% dose reduction per beam and a < 0.01%–0.2% dose reduction in total. These theoretical results were validated by measurements in a head phantom containing Onyx. Conclusions Dose reduction due to attenuation of the 60Co beam by the AVM embolization material was negligible for both NBCA and EVOH because of the high-energy 60Co beam.

Large cerebral arteriovenous malformations (AVMs) are often not amenable to direct resection or stereotactic radiosurgery (SRS) treatment. An alternative treatment strategy is staged endovascular embolization followed by SRS (Embo/SRS). The object of this study was to examine the experience at Washington University in St. Louis with Embo/SRS for large AVMs and review the results in earlier case series.Twenty-one cases involving patients with large AVMs treated with Embo/SRS between 1994 and 2006 were retrospectively evaluated. The AVM size (before and after embolization), procedural complications, radiological outcome, and neurological outcome were examined. Radiological success was defined as AVM obliteration as demonstrated by catheter angiography, CT angiography, or MR angiography. Radiological failure was defined as residual AVM as demonstrated by catheter angiography, CT angiography, or MR angiography performed at least 3 years after SRS.The maximum diameter of all AVMs in this series was3 cm (mean 4.2 cm); 12 (57%) were Spetzler-Martin Grade IV or V. Clinical follow-up was available in 20 of 21 cases; radiological follow-up was available in 19 of 21 cases (mean duration of follow-up 3.6 years). Forty-three embolization procedures were performed; 8 embolization-related complications occurred, leading to transient neurological deficits in 5 patients (24%), minor permanent neurological deficits in 3 patients (14%), and major permanent neurological deficits in none (0%). Twenty-one SRS procedures were performed; 1 radiation-induced complication occurred (5%), leading to a permanent minor neurological deficit. Of the 20 patients with clinical follow-up, none experienced cerebral hemorrhage. In the 19 patients with radiological follow-up, AVM obliteration was confirmed by catheter angiography in 13, MR angiography in 2, and CT angiography in 1. Residual nidus was found in 3 patients. In patients with follow-up catheter angiography, the AVM obliteration rate was 81% (13 of 16 cases).Staged endovascular embolization followed by SRS provides an effective means of treating large AVMs not amenable to standard surgical or SRS treatment. The outcomes and complication rates reported in this series compare favorably to the results of other reported therapeutic strategies for this very challenging patient population.

Presently, in any centers around the world, radiation can be wielded like a surgical instrument, or loco-regional chemotherapy agent in modern, precisely focused intracranial treatment techniques called stereotactic radiosurgery (SRS), fractionated radiosurgery (fSRS) and stereotactic radiotherapy (SRT). This chapter presents a practical overview of the rationale, methodology, equipment, and personnel required to successfully perform cranial stereotactic radiosurgery, fractionated radiosurgery and stereotactic radiotherapy

Purpose : Selecting the optimal radiation treatment plan from a set of competing plans involves making trade-offs among the doses delivered to the target volumes and normal tissues by the competing plans. Evaluation of 3-dimensional radiation treatment plans is difficult because it requires the review of vast amount of graphical and numerical data. We have developed an objective plan-ranking model based on the concepts of decision analysis. Methods and Materials : Our model ranks a set of tentative radiation treatment plans from best to worst. A figure of merit is computed for each plan based on probabilities of possible clinical complications such as non-eradication of the tumor and radiation induced damage to the nearby healthy normal tissues, and weights which indicate their clinical relevance. This figure of merit is used to rank the plans. Key issues addressed by the model include the incorporation of individual treatment preferences of the radiation oncologist and clinical features of the patient. Results : A methodology has been established for eliciting the treatment preferences of radiation oncologists. Results of this elicitation, and examples of several plan evaluations are presented. An interactive computer-based tool has been developed as one of a set of tools to assist in the evaluation of 3-dimensional radiation treatment plans. Conclusion : The paper presents a decision-analytic model incorporating radiation oncologists' treatment preferences and an interactive computer-based tool for objectively ranking competing radiation treatment plans. The tool can be used by radiation oncologists for the evaluation of competing plans, or as part of a system which tries to automatically generate optimal treatment plans using mathematical or symbolic techniques.

Purpose : Real-time 3-dimensional dose calculation will allow display of isodose contours and other metrics for a planner to assess plan effectiveness during plan development, facilitating optimization. Methods and Materials : Parallel processing provides an effective means to calculate 3-dimensional dose distribution in real-time while plan parameters are being chosen and adjusted. An array of 20 transputers and a high performance graphics workstation have demonstrated the feasibility of real-time 3-dimensional beam parameter specification, dose calculation, and dose-distribution presentation for evaluation. A mesh connected set of processors using surface processors to generate and terminate rays, and ray processors to calculate ray attenuation and dose distribution has been developed to efficiently utilize large numbers of processors and provide good load sharing, even for small beams that intersect only a small part of the volume. Results : Our feasibility study has calculated dose distribution by the Effective Path Length method in about one second per beam for a treatment volume of 56,400 voxels. We expect to reduce the total time for computation, communication, and display, with even larger volumes, to less than one second. The number of processors can easily be increased for larger treatment volumes or more accurate and computation-intensive dose-calculation algorithms. Transputers provide an elegant and economical method for harnessing up to hundreds of powerful general-purpose processors for computational tasks including dose calculation and isodose contour generation. The same distributed-memory parallel-processing configuration is also suitable for calculation of isodose contours and dose-volume histograms for plan evaluation, automatic calculation of apertures and filters as beam parameters are manipulated, and more accurate dose calculation algorithms that incorporate the effects of scatter. Conclusion : Parallel processors can efficiently provide real-time calculation of the information necessary to evaluate treatment plans as they are developed allowing the planner to optimize the plan based on dose distribution and its effects on tumor control and complications.

Purpose: To compare the efficacy of three lung stereotactic body radiotherapy (SBRT) regimens in a large institutional cohort. Methods:Between2004and2009,130patientsunderwentdefinitivelungcancerSBRTtoasinglelesionattheMallinckrodt Institute of Radiology. We delivered 18 Gy � 3 fractions for peripheral tumors (n = 111) and either 9 Gy � 5 fractions (n =8 ) or 10 Gy� 5 fractions (n = 11) for tumors that were central or near critical structures. Univariate and multivariate analysis of prognostic factors was performed using the Cox proportional hazard model. Results: Median follow-up was 11, 16, and 13 months for the 9 Gy � 5, 10 Gy � 5, and 18 Gy � 3 groups, respectively. Local control statistics for Years 1 and 2 were, respectively, 75% and 50% for 9 Gy � 5, 100% and 100% for 10 Gy � 5, and 99% and 91% for 18 Gy � 3. Median overall survival was 14 months, not reached, and 34 months for the 9 Gy � 5, 10 Gy � 5, and 18 Gy � 3 treatments, respectively. No difference in local control or overall survival was found between the 10 Gy � 5 and 18 Gy � 3 groups on log–rank test, but both groups had improved local control and overall survival compared with 9 Gy � 5. Treatment with 9 Gy � 5 was the only independent prognostic factor for reduced local control on multivariate analysis, and increasing age, increasing tumor volume, and poor performance status predicted independently for reduced overall survival. Conclusion: Treatment regimens of 10 Gy � 5 and 18 Gy � 3 seem to be efficacious for lung cancer SBRT and provide superior local control and overall survival compared with 9 Gy � 5. 2011 Elsevier Inc. Lung, Cancer, NSCLC, SBRT, Stereotactic.

Background Stereotactic body radiation therapy (SBRT) represents a substantial paradigm shift in the treatment of patients with medically inoperable Stage I/II non–small-cell lung cancer. We reviewed our experience using either three- or five-fraction SBRT for peripheral or central tumors, respectively. Methods and Materials A total of 91 patients signed an institutional review board–approved consent form, were treated with SBRT, and have had ≥6 months of follow-up. Patients were referred for SBRT because of underlying comorbidities (poor performance status in 31 or poor lung function in 52) or refusal of surgery (8 patients). Of the cancers, 83 were peripheral and eight were central. Peripheral cancers received a mean dose of 18 Gy × three fractions. Cancers within 2 cm of the bronchus, esophagus, or brachial plexus were treated with 9 Gy × five fractions. Results The median follow-up duration for these patients was 18 months (range, 6–42 months). TNM staging was as follows: 58 patients with T1N0M0, 22 with T2N0M0, 2 with T3N0M0 (chest wall), and 6 with T1N0M1 cancers. The median tumor diameter was 2 cm (range, 1–5 cm). The median forced expiratory volume in 1 s was 46% (range, 17–133%) and the median carbon monoxide diffusing capacity (DLCO) was 49% (range, 15–144%). Two-year local tumor control was achieved in 86% of patients. The predominant pattern of failure was the development of distant metastasis or second lung cancer. The development of distant metastasis was the only significant prognostic factor for overall survival on multivariate analysis. Conclusions Local tumor control was shown to be high using SBRT for non–small-cell lung cancer. Overall survival is highly coerrelated with the development of distant metastasis.

The role of three-dimensional (3-D) treatment planning for postoperative radiation therapy was evaluated for rectal carcinoma as part of an NCI contract awarded to four institutions. It was found that the most important contribution of 3-D planning for this site was the ability to plan and localize target and normal tissues at all levels of the treatment volume, rather than using the traditional method of planning with only a single central transverse slice and simulation films. There was also a slight additional improvement when there were no constraints on the types of plans (i.e., when noncoplanar beams were used). Inhomogeneity considerations were not important at this site under the conditions of planning, i.e., with energies greater than 4 MV and multiple fields. Higher beam energies (15-25 MV) were preferred by a small margin over lower energies (down to 4 MV). The beam's eye view and dose-volume histograms were found quite useful as planning tools, but it was clear that work should continue on better 3-D displays and improved means of translating such plans to the treatment area.

Three-dimensional treatment planning has been used by four cooperating centers to prepare and analyze multiple treatment plans on two cervix cancer patients. One patient had biopsy-proven and CT-demonstrable metastasis to the para-aortic nodes, while the other was at high risk for metastatic involvement of para-aortic nodes. Volume dose distributions were analyzed, and an attempt was made to define the role of 3-D treatment planning to the para-aortic region, where moderate to high doses (50–66 Gy) are required to sterilize microscopic and gross metastasis. Plans were prepared using the 3-D capabilities for tailoring fields to the target volumes, but using standard field arrangements (3-D standard), and with full utilization of the 3-D capabilities (3-D unconstrained). In some but not all 3-D unconstrained plans, higher doses were delivered to the large nodal volume and to the volume containing gross nodal disease than in plans analyzed but not prepared with full 3-D capability (3-D standard). The small bowel was the major dose limiting organ. Its tolerance would have been exceeded in all plans which prescribed 66 Gy to the gross nodal mass, although some reduction in small bowel near-maximum dose was achieved in the 3-D unconstrained plans. All plans were able to limit doses to other normal organs to tolerance levels or less, with significant reductions seen in doses to spinal cord, kidneys, and large bowel in the 3-D unconstrained plans, as compared to the 3-D standard plans. A high probability of small bowel injury was detected in one of four 3-D standard plans prescribed to receive 50 Gy to the large para-aortic nodal volume; the small bowel dose was reduced to an acceptable level in the corresponding 3-D unconstrained plan. An optimum beam energy for treating this site was not identified, with plans using 4, 6, 10, 15, 18, and 25 MV photons all being equally acceptable. Attempts to deliver moderate or high doses (50–66 Gy) to this region should be made only after careful analysis of the plan with techniques similar to those employed in this study.

RTOG 95-02 assessed patient tolerance to hypoxic cell radiosensitizer, etanidazole (SR-2508), combined with radiosurgery. Patients had primary or metastatic brain tumors and previously localized or whole brain irradiation. The toxicity is reported in three groups of patients according to the tumor size. Etanidazole doses of 12g/m 2 combined with radiosurgery were well tolerated.

Purpose To develop a Gamma Knife-based mouse model of late time-to-onset, cerebral radiation necrosis (RN) with serial evaluation by magnetic resonance imaging (MRI) and histology. Methods and Materials Mice were irradiated with the Leksell Gamma Knife® (GK) PerfexionTM (Elekta AB; Stockholm, Sweden) with total single-hemispheric radiation doses (TRD) of 45- to 60-Gy, delivered in one to three fractions. RN was measured using T2-weighted MR images, while confirmation of tissue damage was assessed histologically by hematoxylin & eosin, trichrome, and PTAH staining. Results MRI measurements demonstrate that TRD is a more important determinant of both time-to-onset and progression of RN than fractionation. The development of RN is significantly slower in mice irradiated with 45-Gy than 50- or 60-Gy, where RN development is similar. Irradiated mouse brains demonstrate all of the pathologic features observed clinically in patients with confirmed RN. A semi-quantitative (0 to 3) histologic grading system, capturing both the extent and severity of injury, is described and illustrated. Tissue damage, as assessed by a histologic score, correlates well with total necrotic volume measured by MRI (correlation coefficient = 0.948, with p

Purpose: The purpose of this study was to develop and use a novel phantom to evaluate the accuracy and usefulness of the Leskell Gamma Plan convolution-based dose calculation algorithm compared with the current TMR10 algorithm. Methods: A novel phantom was designed to fit the Leskell Gamma Knife G Frame which could accommodate various materials in the form of one inch diameter, cylindrical plugs. The plugs were split axially to allow EBT2 film placement. Film measurements were made during two experiments. The first utilized plans generated on a homogeneous acrylic phantom setup using the TMR10 algorithm, with various materials inserted into the phantom during film irradiation to assess the effect on delivered dose due to unplanned heterogeneities upstream in the beam path. The second experiment utilized plans made on CT scans of different heterogeneous setups, with one plan using the TMR10 dose calculation algorithm and the second using the convolution-based algorithm. Materials used to introduce heterogeneities included air, LDPE, polystyrene, Delrin, Teflon, and aluminum. Results: The data shows that, as would be expected, having heterogeneities in the beam path does induce dose delivery error when using the TMR10 algorithm, with the largest errors being due to the heterogeneities with electron densities most different from that of water, i.e. air, Teflon, and aluminum. Additionally, the Convolution algorithm did account for the heterogeneous material and provided a more accurate predicted dose, in extreme cases up to a 7–12% improvement over the TMR10 algorithm. The convolution algorithm expected dose was accurate to within 3% in all cases. Conclusion: This study proves that the convolution algorithm is an improvement over the TMR10 algorithm when heterogeneities are present. More work is needed to determine what the heterogeneity size/volume limits are where this improvement exists, and in what clinical and/or research cases this would be relevant.