For many patients, stereotactic radiosurgery (SRS) offers a minimally invasive, curative option when surgical techniques are not possible. To date, the literature supporting the efficacy and safety ...of SRS treatment techniques uses photon beams. However, with the number of proton therapy facilities exponentially growing and the favorable physical properties of proton beam radiation therapy, there is an opportunity to develop proton therapy techniques for SRS. The goal of this paper is to determine the ability of clinical proton treatment planning systems to model small field dosimetry accurately and to compare various planning metrics used to evaluate photon SRS to determine the optimum beam configurations and settings for proton SRS (PSRS) treatment plans. Once established, these plan settings were used to perform a planning comparison on a variety of different SRS cases and compare SRS metrics between the PSRS plans and HyperArc™ (VMAT) SRS plans.
The aim of this study was to identify factors associated with delayed cranial neuropathy following radiosurgery for vestibular schwannoma (VS or acoustic neuroma) and to determine how such factors ...may be manipulated to minimize the incidence of radiosurgical complications while maintaining high rates of tumor control.
From July 1988 to June 1998, 149 cases of VS were treated using linear accelerator radiosurgery at the University of Florida. In each of these cases, the patient's tumor and brainstem were contoured in 1-mm slices on the original radiosurgical targeting images. Resulting tumor and brainstem volumes were coupled with the original radiosurgery plans to generate dose-volume histograms. Various tumor dimensions were also measured to estimate the length of cranial nerve that would be irradiated. Patient follow-up data, including evidence of cranial neuropathy and radiographic tumor control, were obtained from a prospectively maintained, computerized database. The authors performed statistical analyses to compare the incidence of posttreatment cranial neuropathies or tumor growth between patient strata defined by risk factors of interest. One hundred thirty-nine of the 149 patients were included in the analysis of complications. The median duration of clinical follow up for this group was 36 months (range 18-94 months). The tumor control analysis included 133 patients. The median duration of radiological follow up in this group was 34 months (range 6-94 months). The overall 2-year actuarial incidences of facial and trigeminal neuropathies were 11.8% and 9.5%, respectively. In 41 patients treated before 1994, the incidences of facial and trigeminal neuropathies were both 29%, but in the 108 patients treated since January 1994, these rates declined to 5% and 2%, respectively. An evaluation of multiple risk factor models showed that maximum radiation dose to the brainstem, treatment era (pre-1994 compared with 1994 or later), and prior surgical resection were all simultaneously informative predictors of cranial neuropathy risk. The radiation dose prescribed to the tumor margin could be substituted for the maximum dose to the brainstem with a small loss in predictive strength. The pons-petrous tumor diameter was an additional statistically significant simultaneous predictor of trigeminal neuropathy risk, whereas the distance from the brainstem to the end of the tumor in the petrous bone was an additional marginally significant simultaneous predictor of facial neuropathy risk. The overall radiological tumor control rate was 93% (59% tumors regressed, 34% remained stable, and 7.5% enlarged), and the 5-year actuarial tumor control rate was 87% (95% confidence interval CI 76-98%). Analysis revealed that a radiation dose cutpoint of 10 Gy compared with more than 10 Gy prescribed to the tumor margin yielded the greatest relative difference in tumor growth risk (relative risk 2.4, 95% CI 0.6-9.3), although this difference was not statistically significant (p = 0.207).
Five points must be noted. 1) Radiosurgery is a safe, effective treatment for small VSs. 2) Reduction in the radiation dose has played the most important role in reducing the complications associated with VS radiosurgery. 3) The dose to the brainstem is a more informative predictor of postradiosurgical cranial neuropathy than the length of the nerve that is irradiated. 4) Prior resection increases the risk of late cranial neuropathies after radiosurgery. 5) A prescription dose of 12.5 Gy to the tumor margin resulted in the best combination of maximum tumor control and minimum complications in this series.
To investigate the risk of radiation-induced optic neuropathy according to total radiotherapy dose and fraction size, based on both retrospective and prospectively collected data.
Between October ...1964 and May 1989, 215 optic nerves in 131 patients received fractionated external-beam irradiation during the treatment of primary extracranial head and neck tumors. All patients had a minimum of 3 years of ophthalmologic follow-up (range, 3 to 21 years). The clinical end point was visual acuity of 20/100 or worse as a result of optic nerve injury.
Anterior ischemic optic neuropathy developed in five nerves (at mean and median times of 32 and 30 months, respectively, and a range of 2-4 years). Retrobulbar optic neuropathy developed in 12 nerves (at mean and median times of 47 and 28 months, respectively, and a range of 1-14 years). No injuries were observed in 106 optic nerves that received a total dose of < 59 Gy. Among nerves that received doses of > or = 60 Gy, the dose per fraction was more important than the total dose in producing optic neuropathy. The 15-year actuarial risk of optic neuropathy after doses of > or = 60 Gy was 11% when treatment was administered in fraction sizes of < 1.9 Gy, compared with 47% when given in fraction sizes of > or = 1.9 Gy. The data also suggest an increased risk of optic nerve injury with increasing age.
As there is no effective treatment of radiation-induced optic neuropathy, efforts should be directed at its prevention by minimizing the total dose, paying attention to the dose per fraction to the nerve, and using reduced-field techniques where appropriate to limit the volume of tissues that receive high-dose irradiation.
Between May, 1988 and August, 1993, 158 patients with arteriovenous malformations (AVMs) were treated radiosurgically at the University of Florida. A mean dose of 1560 cGy was directed to the ...periphery of the lesions, which had a mean volume of 9 cc (0.5 to 45.3 cc). One hundred thirty-nine of these individuals were treated with one isocenter. The mean follow-up interval was 33 months with clinical information available on 153 of these patients. Patients were followed until magnetic resonance (MR) studies suggested complete AVM thrombosis. An arteriogram was then performed, if possible, to verify occlusion status. If arteriography revealed any persistent nidus at 36 months posttreatment, the residual nidus was re-treated. Outcome categories of AVMs analyzed included the following possibilities: 1) angiographic cure; 2) angiographic failure; 3) re-treatment; 4) MR image suggested cure; 5) MR image suggested failure; 6) patient refused follow-up evaluation; 7) patient lost to follow-up study; or 8) patient deceased. The endpoints for success or failure of radiosurgery were as follows: angiographic occlusion (success), re-treatment (failure), and death due to AVM hemorrhage (failure). Fifty-six patients in this series reached one of the endpoints. Successful endpoints were seen in 91% of AVMs between 1 and 4 cc in volume, 100% of AVMs 4 to 10 cc in volume, and 79% of AVMs greater than 10 cc in volume. The more traditional measure of radiosurgical success, percentage of angiograms showing complete obliteration, was obtained in 81% of AVMs between 1 and 4 cc in volume, 89% of AVMs between 4 and 10 cc in volume, and 69% of AVMs greater than 10 cc in volume. A detailed analysis of the relationship of all outcome categories to size is presented.
Stereotactic radiosurgery (SRS) is a procedure that delivers a single large radiation dose to a well‐defined target. Here, we describe a frameless SRS technique suitable for intracranial targets in ...canines. Medical records of dogs diagnosed with a primary intracranial tumour by imaging or histopathology that underwent SRS were retrospectively reviewed. Frameless SRS was used successfully to treat tumours in 51 dogs with a variety of head sizes and shapes. Tumours diagnosed included 38 meningiomas, 4 pituitary tumours, 4 trigeminal nerve tumours, 3 gliomas, 1 histiocytic sarcoma and 1 choroid plexus tumour. Median survival time was 399 days for all tumours and for dogs with meningiomas; cause‐specific survival was 493 days for both cohorts. Acute grade III central nervous system toxicity (altered mentation) occurred in two dogs. Frameless SRS resulted in survival times comparable to conventional radiation therapy, but with fewer acute adverse effects and only a single anaesthetic episode required for therapy.
Objective
The objective of this pilot study was to describe the application and first preliminary data of a novel MRI and CT compatible patient‐specific facemask for stereotactic brain biopsy of ...intracranial lesions in dogs.
Methods
Five client‐owned dogs presenting for neurological deficits consistent with forebrain disease were included in the study. All dogs had MRI findings consistent with an intracranial lesion. Using images obtained from either MRI or CT, a virtual three‐dimensional model of each dog's face was generated. The contact surface of each dog's face was selected for facemask design and a target point for biopsy was chosen using specialised software and toolkits. A patient‐specific facemask with an attached biopsy port with premeasured and preselected trajectory was then fabricated by a 3D printer. The facemasks were sterilised and used intraoperatively to obtain biopsy samples. Biopsy samples were submitted for both cytological and histopathological evaluation.
Results
The diagnostic yield based on specific histological diagnosis was 80%. The one case in which a histological diagnosis could not be confirmed had a cytological interpretation consistent with meningioma. No major complications were observed during or immediately after brain biopsy and all dogs were discharged from the hospital within 72 hours postprocedure.
Clinical Significance
In conclusion, patient‐specific facemasks appear to be a safe and effective method of brain biopsy in dogs, with minimal complications observed.
Age-dependent human lens coloration may be explained by the binding of UV filters to crystallins. It has been proposed that glutathione may compete for reaction with UV filter degradation products ...and therefore protect crystallins from modification. To understand this process, UV filters were quantified together with oxidized and reduced glutathione in human lenses of varying age.
Lens tissues were homogenized in ethanol to extract the UV filters. Metabolites were quantified by HPLC and correlations between them in the nuclear and cortical regions of the lens were examined.
The concentrations of the UV filters 3-hydroxykynurenine, kynurenine, and 3-hydroxykynurenine glucoside decreased linearly with age, with slightly lower levels in the nucleus than the cortex. 4-(2-Amino-3-hydroxyphenyl)-4-oxobutanoic acid glucoside was found in higher levels in the nucleus than the cortex and decreased slowly in both regions with age. Glutathionyl-3-hydroxykynurenine glucoside was present in higher concentrations in the nucleus, barely detectable in young lenses, but increased significantly after age 50. Reduced glutathione levels were lower in the nucleus and decreased in both regions with age, yet oxidized glutathione increased in the nucleus but remained constant in the cortex.
Results are consistent with a predominantly nuclear origin for both 4-(2-amino-3-hydroxyphenyl)-4-oxobutanoic acid glucoside and glutathionyl-3-hydroxykynurenine glucoside. This is in accord with their proposed mechanism of formation, which involves an initial deamination of 3-hydroxykynurenine glucoside. This process is more pronounced in older lenses, possibly because of the barrier to diffusion. The barrier may also explain the increase in nuclear oxidized glutathione that is observed with age.
Though potentially beneficial, proton beam stereotactic radiosurgery has not been adopted widely secondary to the technical challenge of safely delivering multiple focused beams of proton radiation. ...In this study, we describe the design and characterization of a proton beam stereotactic radiosurgery system that can be adopted by existing passive scattering systems. This system utilizes a helmet-like device in which patient-specific brass apertures required for final beam collimation are positioned on a scaffold that is separate from the treatment gantry. The proton snout is then fitted with a generic aperture to focus the primary proton beam onto the patient specific apertures that are in the helmet-like device. The patient-specific apertures can all be placed at the start of the treatment, thus treatment with multiple beams can be accomplished without the delay of switching the apertures. In this report we describe a prototype design of this collimation system and dosimetric testing to verify efficacy. Subsequently, we describe a custom 3D printing of a prototype device and report on overall localization accuracy using Winston-Lutz tests. Our results show that it is possible to develop an add-on device for proton beam radiosurgery that is safe and efficient and capable of wide adoption on existing proton delivery systems.
Over the course of radiation therapy, a patient's anatomy may change substantially. The relatively recent addition of frequent in-room imaging to assist with patient localization has provided a ...database of images that may be used to recalculate dose distributions for adaptive radiotherapy purposes. The TomoTherapy Hi-Art II unit (Accuray Inc., Sunnyvale, CA, USA) uses a helical scanning geometry and a megavoltage (MV) beam to acquire volumetric patient images. This study evaluated the uncertainty of dose calculations performed on megavoltage CT (MVCT) images as a function of temporal Hounsfield Unit (HU) variations observed in the imaging system over three years on two machines. A baseline error between dose calculations performed on kVCT and MVCT images was established using a series of phantoms. This baseline error ranged from -1.4% to 0.6%. Materials of differing densities were imaged and MVCT numbers were measured periodically. The MVCT number of solid water varied from 5 to 103 HU and consistently increased prior to target replacement. Finally, the dosimetric uncertainty of the temporal HU variation was assessed using MVCT images of typical head and neck, lung and prostate cancer patients. Worst-case MVCT recalculation errors could approach 5%, 7% and 10% for the head and neck, lung and prostate images, respectively. However, if a tolerance of ±30 HU were maintained for the MVCT number of solid water, dosimetric errors were limited to ±2.5%, ±3% and ±4%, respectively.
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