Efficacy of stereotactic radiosurgery for radiation-induced meningiomas.

PURPOSE: Stereotactic radiosurgery is an established treatment option for sporadic meningiomas, though limited data exists for radiation-induced lesions. METHODS: Patients treated with cobalt-60 radiosurgery between October 2005 and December 2018 in an institutional registry were reviewed. Single fraction treatments were prescribed to the 50% isodose line. Lesions were deemed to be radiation-induced according to standard criteria previously established by Cahan et al. RESULTS: A total of 37 patients with 72 lesions were analysed. Median follow up per patient was 44 months (range, 1.4-150.7 months). Median age at initial radiotherapy was 5 years (4 months-48 years), and at radiosurgery was 38 years. Of the 72 lesions, 62 were grade 1 (n = 4) or radiologically-diagnosed (n = 58), six were grade 2 and four were grade 3. Median lesion volume was 2.13 cc (0.04-13.8 cc), while the median radiosurgery margin dose was 13 Gy. Local control, on a per lesion basis, was 88.6% at 5 years (95% confidence interval [CI] 72.3-95.6). For grade 1 or radiologically-diagnosed lesions, local control was 96.6% at 5 years (95% CI 77.9-99.5), whereas those with grade 2 or higher lesions had a local control of 40% at 5 years (95% CI 5.2-75.3, p = 0.005). Radiologic oedema developed in 17 lesions (23.6%) and was symptomatic in 12 patients (16.7%). Doses above 12 Gy were not associated with local control probability (p = 0.292). CONCLUSION: Radiosurgery is an effective treatment option for grade 1 or radiologically-diagnosed radiation-induced meningiomas, with 12 Gy appearing to be a sufficient dose.

COMP report: CPQR technical quality control guidelines for Gamma Knife radiosurgery.

The Canadian Organization of Medical Physicists (COMP), in close partnership with the Canadian Partnership for Quality Radiotherapy (CPQR), has developed a series of Technical Quality Control (TQC) guidelines for radiation treatment equipment. These guidelines outline the performance objectives that equipment should meet in order to ensure an acceptable level of radiation treatment quality. The TQC guidelines have been rigorously reviewed and field tested in a variety of Canadian radiation treatment facilities. The development process enables rapid review and update to keep the guidelines current with changes in technology (the most updated version of this guideline can be found on the CPQR website). This particular TQC details recommended quality control testing for Gamma Knife radiosurgery.

Cancer nanotechnology: enhanced therapeutic response using peptide-modified gold nanoparticles.

The applications of nanoparticles (NPs) for improved therapeutics are at the forefront of cancer nanotechnology. Gold nanoparticles (GNPs) have been extensively used due to their ability to act as both an anticancer drug carrier in chemotherapy and as a dose enhancer in radiotherapy. GNPs used in the studies were predominantly localized in the cell cytoplasm. However, the therapeutic response can be further enhanced if NPs can be effectively targeted into the nucleus. Here, we present an effective strategy for designing a GNP-peptide complex for nuclear targeting. Two peptides were conjugated onto a NP: One peptide enhanced the uptake while the other peptide enhanced the nuclear delivery. The nuclear targeted cells displayed a four-fold increase in the therapeutic response when treated with radiation as compared to untargeted ones. There was a modest increase in the DNA damage for radiated cells with nuclear targeted GNPs. This research will establish a more successful NP-based platform for combining more than one treatment modality, such as chemotherapy and radiotherapy, and creates a more aggressive approach in eradicating cancer.

Effect of Cobalt-60 Treatment Dose Rate on Arteriovenous Malformation Obliteration After Stereotactic Radiosurgery With Gamma Knife.

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) marginal dose is associated with successful obliteration of cerebral arteriovenous malformations (AVM). SRS dose rate-how old the cobalt-60 sources are-is known to influence outcomes for some neurological conditions and benign tumors. The objective of this study was to determine the association between cobalt-60 treatment dose rate and cerebral AVM obliteration in patients treated with SRS. METHODS: We performed a retrospective cohort study of 361 patients undergoing 411 AVM-directed SRS treatments between 2005 and 2019 at a single institution. Lesion characteristics, SRS details, obliteration dates, and post-treatment toxicities were recorded. Univariate and multivariate regression analyses of AVM outcomes regarding SRS dose rate (range 1.3-3.7 Gy, mean = 2.4 Gy, median = 2.5 Gy) were performed. RESULTS: At 10 years post-SRS, 68% of AVMs were obliterated on follow-up imaging. Dose rates >2.9 Gy/min were found to be significantly associated with AVM obliteration compared with those <2.1 Gy/min ( P = .034). AVM size, biologically effective dose, and SRS marginal dose were also associated with obliteration, with obliteration more likely for smaller lesions, higher biologically effective dose, and higher marginal dose. Higher dose rates were not associated with the development of post-SRS radiological or symptomatic edema, although larger AVM volume was associated with both types of edema. CONCLUSION: Patients with cerebral AVMs treated with higher SRS dose rates (from newer cobalt-60 sources) experience higher incidences of obliteration without a significant change in the risk of post-treatment edema.

Dosimetric evaluation of adult and paediatric brain tumours planned using mask-based cobalt-60 fractionated stereotactic radiotherapy compared to linear accelerator-based volumetric modulated arc therapy.

INTRODUCTION: We conducted a study to evaluate the dosimetric feasibility of mask-based cobalt-60 fractionated stereotactic radiotherapy (mcfSRT) with the Leksell Gamma Knife® Icon™ device. METHODS: Eleven patients with intracranial tumours were selected for this dosimetry study. These patients, previously treated with volumetric arc therapy (VMAT), were re-planned using mcfSRT. Target volume coverage, conformity/gradient indices, doses to organs at risk and treatment times were compared between the mcfSRT and VMAT plans. Two-sided paired Wilcoxon signed-rank test was used to compare differences between the two plans. RESULTS: The V95 for PTV was similar between fractionated mcfSRT and VMAT (P = 0.47). The conformity index and gradient indices were 0.9 and 3.3, respectively, for mcfSRT compared to 0.7 and 4.2, respectively, for VMAT (P < 0.001 and 0.004, respectively). The radiation exposure to normal brain was lower for mcfSRT across V10, V25 and V50 compared with VMAT (P = 0.007, <0.001 and <0.001, respectively). The median D0.1cc for optic nerve and chiasm as well as the median D50 to the hippocampi were lower for mcfSRT compared to VMAT. Median beam-on time for mcfSRT was 9.7 min per fraction, compared to 0.9 min for VMAT (P = 0.002). CONCLUSION: mcfSRT plans achieve equivalent target volume coverage, improved conformity and gradient indices, and reduced radiation doses to organs at risk as compared with VMAT plans. These results suggest superior dosimetric parameters for mcfSRT plans and can form the basis for future prospective studies.

Simple and effective immobilization for radiation treatment of choroidal melanoma.

At our institution, patients diagnosed with choroidal melanoma requiring external beam radiation therapy are treated with two 6 MV volumetric-modulated arcs delivering 50 Gy over 5 daily fractions. The patient is immobilized using an Orfit head and neck mask and is directed to look at a light emitting diode (LED) during CT simulation and treatment to minimize eye movement. Patient positioning is checked with cone beam computed tomography (CBCT) daily. Translational and rotational displacements greater than 1 mm or 1° off the planned isocenter position are corrected using a Hexapod couch. The aim of this study is to verify that the mask system provides adequate immobilization and to verify our 2-mm planning target volume (PTV) margins are sufficient. Residual displacements provided by pretreatment verification and post-treatment CBCT data sets were used to assess the impact of patient mobility during treatment on the reconstructed delivered dose to the target and organs at risk. The PTV margin calculated using van Herk's method1 was used to assess patient motion plus other factors that affect treatment position, such as kV-MV isocenter coincidence. Patient position variations were small and were shown to not cause significant dose variations between the planned and reconstructed dose to the target and organs at risk. The PTV margin analysis showed patient translational motion alone required a PTV margin of 1 mm. Given other factors that affect treatment delivery accuracy, a 2-mm PTV margin was shown to be sufficient for treatment of 95% of our patients with 100% of dose delivered to the GTV. The mask immobilization with LED focus is robust and we showed a 2-mm PTV margin is adequate with this technique.

Importance of Cobalt-60 Dose Rate and Biologically Effective Dose on Local Control for Intracranial Meningiomas Treated With Stereotactic Radiosurgery.

BACKGROUND: Radiosurgery dose rate and biologically effective dose (BED) are associated with outcomes after stereotactic radiosurgery (SRS) for functional neurosurgical conditions and some benign tumors. It is not known if these factors affect the efficacy of SRS for meningioma. OBJECTIVE: To determine the association between cobalt-60 dose rate and BED on outcomes in patients with meningioma treated with SRS. METHODS: A single-institution cohort of 336 patients treated between 2005 and 2018 with cobalt-based SRS for 414 separate meningioma lesions was assembled. BED was calculated using an SRS-specific monoexponential model accounting for treatment time per lesion, assuming α/ß = 2.47 Gy. Cumulative incidences of local failure (LF) were reported after considering the competing risk of death, on a per-lesion basis. Multivariable analysis of LF was performed using a proportional hazards model. RESULTS: The most common SRS dose was 12 Gy (n = 227); 140 lesions received 14 Gy. Five-year LF was 15.6% (95% confidence interval 10.4-21.9) and 4.3% (1.4-9.8) in patients who had a dose rate of <2.95 and ≥2.95 Gy/min, respectively (P = .0375). Among 354 grade I or unresected lesions treated with SRS, BED >50 Gy2.47 was associated with a lower incidence of LF (P = .0030). Each 1 Gy/min increase in dose rate was associated with an adjusted hazard ratio of 0.53 (95% confidence interval, 0.29-0.97, P = .041) for LF. Prescription dose >12 Gy was not associated with a lower incidence of LF. CONCLUSION: Patients with meningiomas treated with lower dose rates experienced a higher incidence of LF than those treated with higher dose rates.

Digital Subtraction Myelography is Associated with Less Radiation Dose than CT-based Techniques.

PURPOSE: Both CT myelogram (CTM) and digital-subtraction myelogram (DSM) can be used to evaluate patients for possible cerebrospinal fluid (CSF) leaks. DSM is a relatively new technique. No data exists on the radiation dose associated with this procedure, and how it compares with CTM. MATERIALS AND METHODS: All patients who underwent DSM for spontaneous intracranial hypotension (SIH) refractory to blood patching from Dec 2016 - Sept 2019 were retrospectively assessed. DSM dose factors were then recorded (cumulative fluoroscopy time, total kerma area product (KAP, mGy.cm2), cumulative air kerma (mGy), as well as CTM dose factors (included CTDIvol (mGy) and dose-length product (DLP, mGy.cm). These indices were then used to calculate the effective dose for both procedures using standardized conversion factors. RESULTS: 61 DSMs were performed in 42 patients, 33 of which also underwent CTM. The median effective dose was 6.6 mSv per DSM study (range: 1.2 - 17.7). On a per-patient basis (i.e. those patients who underwent more than one DSM (as the initial one was negative), the median total effective dose was 13 mSv for their total DSM imaging (range: 2.6 -31.7). For the CTM, the median effective dose was 19.7 mSv (range: 3.2 - 82.4 mSv). CONCLUSION: The radiation dose with DSM appears to be significantly lower than that of CTM (p = 0.0005), when looking at CTM doses both from our institution and in the published literature.

Impact of EGFR mutation on outcomes following SRS for brain metastases in non-small cell lung cancer.

INTRODUCTION: Patients with EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC) are at particularly high risk of developing brain metastases (BrM). In addition to EGFR targeting tyrosine kinase inhibitors (TKI), radiosurgery (SRS) has an important role in the management of EGFRm BrM. However, data specific to the response and toxicity of EGFRm BrM to SRS are sparse. We evaluated the incidence of local failure (LF) and toxicity of EGFRm and EGFR-wild-type (EGFRwt) BrM treated with SRS. METHODS: We analyzed a prospective registry of BrM patients treated at our centre between 2008 and 2017 and identified EGFRm and EGFRwt NSCLC patients treated with SRS ±â€¯systemic therapy for BrM. Incidences of local failure (LF) and radionecrosis (RN) were determined, and Cox regression was performed for univariate and multivariate analyses (MVAs). RESULTS: We analyzed data from 218 patients (615 lesions - 225 EGFRm and 390 EGFRwt). Median imaging follow-up per patient was 14.5 months (0.5-96.3). Prior to or concomitant with SRS, 62 % of EGFRm patients received TKI and 93 % received TKI post SRS. The 24-month incidence of LF was 6% and 16 % for EGFRm BrM and EGFRwt, respectively (0.43(0.19-0.95); p = 0.037). The 24-month incidence of RN was 4% and 6% for EGFRm and EGFRwt BrM, respectively (0.8(0.32-1.98) p = 0.63). On MVA, BrM size and prescription dose (PD) significantly correlated with a higher risk of LF and BrM size correlated with a higher risk of RN. CONCLUSION: We observed excellent rates of response and toxicity following SRS in EGFRm compared to EGFRwt NSCLC, suggesting that EGFRm BrM have a favourable risk benefit ratio compared to EGFRwt NSCLC.

Radiation Dose Rate, Biologically Effective Dose, and Tumor Characteristics on Local Control and Toxicity After Radiosurgery for Acoustic Neuromas.

OBJECTIVE: To evaluate the relationships between calibration dose rate, calculated biologically effective dose (BED), and clinical factors and tumor control after stereotactic radiosurgery (SRS) for acoustic neuroma. METHODS: We performed a retrospective study of all patients with acoustic neuromas treated with frame-based cobalt-60 SRS at a single institution between 2005 and 2019. The calibration dose rate and cobalt-60 half-life were used to calculate the nominal dose rate during treatment. An SRS-specific monoexponential model accounting for treatment time per lesion was used to estimate BED. RESULTS: The study included 607 patients with 612 acoustic neuromas. Median follow-up was 5.0 years. There was no association between dose rate or BED with local failure (LF), radiologic edema, or symptomatic edema. Cystic tumors (adjusted hazard ratio 0.26, P = 0.028) were associated with lower LF, while use of SRS as salvage treatment for growing tumors (adjusted hazard ratio 4.9, P < 0.0001) was associated with higher LF. LF occurred more frequently in larger-diameter tumors, while radiologic or symptomatic edema occurred more frequently in larger-volume tumors. CONCLUSIONS: Radiosurgery dose rate and BED were not associated with tumor control or radiologic or symptomatic edema. Salvage SRS and larger tumors were associated with a higher LF rate, while cystic tumors were associated with a lower LF rate. Patients with larger tumors should be counseled appropriately about potential side effects and when to seek follow-up care.

Clinicopathologic and Treatment Features of Long-Term Surviving Brain Metastasis Patients.

BACKGROUND: The purpose of our study was to characterize clinical features among brain metastasis (BM) patients who were long term survivors (LTS). METHODS: We reviewed a registry of BM patients referred to our multidisciplinary BM clinic between 2006 and 2014 and identified 97 who lived ≥ 3 years following BM diagnosis. The clinical and treatment characteristics were obtained from a prospectively maintained database, and additional information was obtained through review of electronic medical records and radiologic images. Survival analyses were performed using the Kaplan-Meier method. RESULTS: Median follow up for LTS was 67 months (range 36-181). Median age was 54 years, 65% had single BM, 39% had stable extracranial disease at the time of BM treatment, and brain was the first site of metastasis in 76%. Targetable mutations were present in 39% of patients and 66% received treatment with targeted-, hormonal-, or immuno-therapy. Brain surgery at the time of diagnosis was performed in 40% and stereotactic radiosurgery (SRS) or whole brain radiotherapy (alone or combination) in 52% and 56%, respectively. Following initial BM treatment, 5-year intracranial disease-free survival was 39%, and the cumulative incidence of symptomatic radio-necrosis was 16%. Five and ten-year overall survival was 72% and 26%, respectively. CONCLUSION: Most LTS were younger than 60 years old and had a single BM. Many received treatment with surgery or targeted, immune, or hormonal therapy.

Verification of source and collimator configuration for Gamma Knife Perfexion using panoramic imaging.

PURPOSE: The new model of stereotactic radiosurgery system, Gamma Knife Perfexion, allows automatic selection of built-in collimation, eliminating the need for the time consuming manual collimator installation required with previous models. However, the configuration of sources and collimators inside the system does not permit easy access for the verification of the selected collimation. While the conventional method of exposing a film at the isocenter is useful for obtaining composite dose information, it is difficult to interpret the data in terms of the integrity of each individual source and corresponding collimation. The primary aim of this study was to develop a method of verifying the geometric configuration of the sources and collimator modules of the Gamma Knife Perfexion. In addition, the method was extended to make dose measurements and verify the accuracy of dose distributions calculated by the mathematical formalism used in the treatment planning system, Leksell Gamma Plan. METHODS: A panoramic view of all of 192 cobalt sources was simultaneously acquired by exposing a radiochromic film wrapped around the surface of a cylindrical phantom. The center of the phantom was mounted at the isocenter with its axis aligned along the longitudinal axis of the couch. The sizes and shapes of the source images projected on the phantom surface were compared to those calculated based on the manufacturer's design specifications. The measured dose at various points on the film was also compared to calculations using the algorithm of the planning system. RESULTS: The panoramic images allowed clear identification of each of the 192 sources, verifying source integrity and selected collimator sizes. Dose on the film surface is due to the primary beam as well as phantom scatter and leakage contributions. Therefore, the dose at a point away from the isocenter cannot be determined simply based on the proportionality of collimator output factors; the use of a dose computation algorithm is required. Scatter and leakage dose contributions from neighboring sources were calculated and found to be 6.3% (ranging from 4.5% to 7.4%), 16.7% (12.5%-19.3%), and 66.6% (38%-78%) for the 4, 8, and 16 mm collimators, respectively, at the centers of the source images. The measured average dose on films with 16 mm collimators agrees with the dose model of the treatment planning system to within 1.0%. The average doses on the film were 24.0, 60.8, and 186.2 cGy for 4, 8, and 16 mm diameter collimators, respectively, when the machine was set to deliver a reference dose of 100 Gy to the center of an 80 mm radius spherical dosimetry phantom. CONCLUSIONS: A method of simultaneously capturing and analyzing the panoramic images of 192 cobalt sources has been developed to verify the source and collimator configuration of GK systems. The method was extended to verify the dose calculation model of the treatment planning system by comparing the measured doses on the panoramic film images and the corresponding calculated doses. The method presented can play a significant role in comprehensive commissioning and routine quality assurance testing of the Gamma Knife systems.

Assessment and management of radiotherapy beam intersections with the treatment couch.

The impact of the treatment couch on a radiotherapy plan is rarely fully assessed during the treatment planning process. Incorporating a couch model into the treatment planning system (TPS) enables the planner to avoid or dosimetrically evaluate beam-couch intersections. In this work, we demonstrate how existing TPS tools can be used to establish this capability and assess the accuracy and effectiveness of the system through dose measurements and planning studies. Such capabilities may be particularly relevant for the planning of arc therapies.Treatment couch top models were introduced into a TPS by fusing their CT image sets with the patient CT dataset. Regions of interest characterizing couch elements were then imported and assigned appropriate densities in the TPS. Measurements in phantom agreed with TPS calculations to within 2% dose and 1 degrees gantry rotation. To clinically validate the model, a retrospective study was performed on patient plans that posed difficulties in beam-couch intersection during setup. Beam-couch intersection caused up to a 3% reduction in PTV coverage, defined by the 95% of the prescribed dose, and up to a 1% reduction in mean CTV coverage. Dose compensation strategies for IMRT treatments with beams passing through couch elements were investigated using a four-field IMRT plan with three beams passing through couch elements. In this study, ignoring couch effects resulted in point dose reductions of 8 +/- 3%.A methodology for incorporating detailed couch characteristics into a TPS has been established and explored. The method can be used to predict beam-couch intersections during planning, potentially eliminating the need for pretreatment appointments. Alternatively, if a beam-couch intersection problem arises, the impact of the couch can be assessed on a case-by-case basis and a clinical decision made based on full dosimetric information.

Neurological Death is Common in Patients With EGFR Mutant Non-Small Cell Lung Cancer Diagnosed With Brain Metastases.

PURPOSE: Brain metastases (BrM) are common in patients with epidermal growth factor receptor (EGFRm) mutant non-small cell lung cancer (NSCLC). We sought to determine the rate of neurologic death (ND) in this population. METHODS AND MATERIALS: We analyzed data from 198 patients who received a diagnosis of BrM from EGFRm NSCLC between 2004 and 2016, comparing patients whose initial treatment for BrM was stereotactic radiosurgery with or without tyrosine kinase inhibitors (TKI), whole brain radiation therapy (WBRT) with or without TKI, or TKI alone. The incidence of ND was determined using a competing risks analysis. Univariate and multivariate analyses were used to identify clinical variables associated with this outcome. RESULTS: The percentage of patients who initially received stereotactic radiosurgery, whole brain radiation therapy, or TKI alone was 22%, 61%, and 17%, respectively. Median overall survival in these subgroups was 31.1, 14.6, and 24.6 months, respectively (P = .0016). The 5-year incidence of ND among all patients was 40% and did not significantly vary according to treatment group. In a multivariable model, only leptomeningeal disease at any point in a patient's disease course significantly correlated with ND (hazard ratio 4.75, P <.001). CONCLUSIONS: Among our cohort of patients with BrM from EGFRm NSCLC, the incidence of ND was significantly higher than suggested by previous reports. BrM should be considered a driver of mortality in many patients with EGFRm NSCLC, and treatments providing better control of BrM, lower neurocognitive side effects, and maintenance of quality of life are needed.

Dosimetric comparison of IMRT vs. 3D conformal radiotherapy in the treatment of cancer of the cervical esophagus.

BACKGROUND AND PURPOSE: Radiotherapy planning for cervical esophageal cancer is challenging. We compared IMRT and 3D conformal radiotherapy (CRT) with respect to conformality of target coverage and normal tissue sparing. MATERIALS AND METHODS: We selected five patients with cervical esophagus cancer, who represented the heterogeneity of clinical cases, treated to radical dose and planned with Pinnacle v6.2. Target doses for CRT plans were 50, 60, and 70Gy (single-phase IMRT 56, 63, and 70). We compared PTV coverage by the 95% isodose (PTV(95)), conformality ratio (CR), conformation number (CN), and maximum or mean doses (D(max), D(mean)) to normal structures. RESULTS: Median PTV(95) for IMRT plans for PTV70, PTV63, and PTV56 were 97%, 99%, and 98% (CRT 91%, 98%, and 85%). IMRT plans demonstrated lower D(max) to the spinal cord and brainstem (42 and 36Gy) compared to CRT (46 and 39Gy). Median left parotid D(mean) was 35Gy (IMRT) vs. 53Gy (CRT). Median right parotid D(mean) was 35Gy (IMRT) vs. 36Gy (CRT). The median CR50/56Gy was 1.4 (CRT) vs. 1.2 (IMRT), CR70Gy 1.7 (CRT) vs. 1.1 (IMRT). CN50/56 and CN70 values were 0.80 and 0.85 (IMRT) vs. 0.56 and 0.5 (CRT). CONCLUSIONS: IMRT provides superior target volume coverage and conformality, with decreased dose to normal structures.

Limitation of conventional two dimensional radiation therapy planning in nasopharyngeal carcinoma.

PURPOSE: To assess the adequacy of coverage of gross tumor volume (GTV) with traditional two dimensional (2D) radiation therapy (RT) planning in patients with nasopharyngeal cancer (NPC). MATERIALS AND METHODS: The study comprised 94 of 179 patients treated with definitive RT between 1993 and 1997. The inclusion requirement was the availability of a digitally archived pretreatment magnetic resonance imaging. The digital images were used to record the precise location of the GTV in the sagittal plane. As a separate procedure, sagittal dose distributions for each treatment phase were created by digitizing the simulation field parameters into treatment planning software without knowledge of the GTV. The location of the GTV and dose distribution in the sagittal plane were superimposed on each other and GTV coverage by the 50, 90 and 95% isodose lines determined for each phase of treatment. RESULTS: The 1997 tumour node metastasis (TNM) stage distribution was: 7 (8%) stage I, 16 (16%) stage II, 30 (32%) stage III and 41 (44%) stage IV. Median follow-up was 4.4 years. Median primary dose was 66 Gy. The actuarial 5-year overall survival, disease free survival and local relapse free rates were 88, 54 and 66%, respectively. The GTV was covered by the 50, 90 and 95% isodose lines for all phases of the multiphase plan in only 53, 20 and 9% of patients, respectively. The GTV was more likely to be undercovered in the latter phases of the plan particularly in those patients with advanced T category. CONCLUSION: 2D RT planning has significant limitations in achieving adequate GTV coverage in NPC. We strongly recommend 3D planning using either conformal techniques of dose delivery or intensity modulated radiation therapy for the treatment of these patients.

Pretreatment predictors of adverse radiation effects after radiosurgery for arteriovenous malformation.

PURPOSE: To identify vascular and dosimetric predictors of symptomatic T2 signal change and adverse radiation effects after radiosurgery for arteriovenous malformation, in order to define and validate preexisting risk models. METHODS AND MATERIALS: A total of 125 patients with arteriovenous malformations (AVM) were treated at our institution between 2005 and 2009. Eighty-five patients have at least 12 months of clinical and radiological follow-up. Any new-onset headaches, new or worsening seizures, or neurological deficit were considered adverse events. Follow-up magnetic resonance images were assessed for new onset T2 signal change and the volume calculated. Pretreatment characteristics and dosimetric variables were analyzed to identify predictors of adverse radiation effects. RESULTS: There were 19 children and 66 adults in the study cohort, with a mean age of 34 (range 6-74). Twenty-three (27%) patients suffered adverse radiation effects (ARE), 9 patients with permanent neurological deficit (10.6%). Of these, 5 developed fixed visual field deficits. Target volume and 12 Gy volume were the most significant predictors of adverse radiation effects on univariate analysis (p < 0.001). Location and cortical eloquence were not significantly associated with the development of adverse events (p = 0.12). No additional vascular parameters were identified as predictive of ARE. There was a significant target volume threshold of 4 cm(3), above which the rate of ARE increased dramatically. Multivariate analysis target volume and the absence of prior hemorrhage are the only significant predictors of ARE. The volume of T2 signal change correlates to ARE, but only target volume is predictive of a higher volume of T2 signal change. CONCLUSIONS: Target volume and the absence of prior hemorrhage is the most accurate predictor of adverse radiation effects and complications after radiosurgery for AVMs. A high percentage of permanent visual field defects in this series suggest the optic radiation is a critical radiosensitive structure.

Predicting nonauditory adverse radiation effects following radiosurgery for vestibular schwannoma: a volume and dosimetric analysis.

PURPOSE: To define clinical and dosimetric predictors of nonauditory adverse radiation effects after radiosurgery for vestibular schwannoma treated with a 12 Gy prescription dose. METHODS: We retrospectively reviewed our experience of vestibular schwannoma patients treated between September 2005 and December 2009. Two hundred patients were treated at a 12 Gy prescription dose; 80 had complete clinical and radiological follow-up for at least 24 months (median, 28.5 months). All treatment plans were reviewed for target volume and dosimetry characteristics; gradient index; homogeneity index, defined as the maximum dose in the treatment volume divided by the prescription dose; conformity index; brainstem; and trigeminal nerve dose. All adverse radiation effects (ARE) were recorded. Because the intent of our study was to focus on the nonauditory adverse effects, hearing outcome was not evaluated in this study. RESULTS: Twenty-seven (33.8%) patients developed ARE, 5 (6%) developed hydrocephalus, 10 (12.5%) reported new ataxia, 17 (21%) developed trigeminal dysfunction, 3 (3.75%) had facial weakness, and 1 patient developed hemifacial spasm. The development of edema within the pons was significantly associated with ARE (p = 0.001). On multivariate analysis, only target volume is a significant predictor of ARE (p = 0.001). There is a target volume threshold of 5 cm3, above which ARE are more likely. The treatment plan dosimetric characteristics are not associated with ARE, although the maximum dose to the 5th nerve is a significant predictor of trigeminal dysfunction, with a threshold of 9 Gy. The overall 2-year tumor control rate was 96%. CONCLUSIONS: Target volume is the most important predictor of adverse radiation effects, and we identified the significant treatment volume threshold to be 5 cm3. We also established through our series that the maximum tolerable dose to the 5th nerve is 9 Gy.

Gold nanoparticles as radiation sensitizers in cancer therapy.

Among other nanoparticle systems, gold nanoparticles have been explored as radiosensitizers. While most of the research in this area has focused on either gold nanoparticles with diameters of less than 2 nm or particles with micrometer dimensions, it has been shown that nanoparticles 50 nm in diameter have the highest cellular uptake. We present the results of in vitro studies that focus on the radiosensitization properties of nanoparticles in the size range from 14-74 nm. Radiosensitization was dependent on the number of gold nanoparticles internalized within the cells. Gold nanoparticles 50-nm in diameter showed the highest radiosensitization enhancement factor (REF) (1.43 at 220 kVp) compared to gold nanoparticles of 14 and 74 nm (1.20 and 1.26, respectively). Using 50-nm gold nanoparticles, the REF for lower- (105 kVp) and higher- (6 MVp) energy photons was 1.66 and 1.17, respectively. DNA double-strand breaks were quantified using radiation-induced foci of gamma-H2AX and 53BP1, and a modest increase in the number of foci per nucleus was observed in irradiated cell populations with internalized gold nanoparticles. The outcome of this research will enable the optimization of gold nanoparticle-based sensitizers for use in therapy.