A self-monitoring wellbeing screening methodology for keyworkers, 'My Personal Wellbeing', using an integrative wellbeing model.

BACKGROUND: The detrimental impact of Covid-19 has led to an urgent need to support the wellbeing of UK National Health Service and care workers. This research develops an online diary to support the wellbeing of staff in public healthcare in real-time, allowing the exploration of population wellbeing and pro-active responses to issues identified. METHODS: The diary was co-produced by NHS and care stakeholders and university researchers. It was based on an integrative model monitoring mental health symptoms as well as wellbeing indicators. Diary users were encouraged to reflect on their experience confidentially, empowering them to monitor their wellbeing. The data collected was analysed using Mann-Whitney-Wilcoxon and Kruskal-Wallis statistical tests to determine any significant wellbeing trends and issues. RESULTS: A statistically significant decline in wellbeing (P < 2.2E-16), and a significant increase in symptoms (P = 1.2E-14) was observed. For example, indicators of post-traumatic stress, including, flashbacks, dissociation, and bodily symptoms (Kruskal-Wallis P = 0.00081, 0.0083, and 0.027, respectively) became significantly worse and users reported issues with sleeping (51%), levels of alertness (46%), and burnout (41%). CONCLUSIONS: The wellbeing diary indicated the value of providing ways to distinguish trends and wellbeing problems, thus, informing how staff wellbeing services can determine and respond to need with timely interventions. The results particularly emphasised the pressing need for interventions that help staff with burnout, self-compassion, and intrusive memories.

Long-term safety of gamma knife radiosurgery (SRS) for acromegaly.

PURPOSE: Acromegaly has high morbidity and mortality when growth hormone secretion remains uncontrolled. Stereotactic radiosurgery (SRS) may be used when pituitary surgery is not suitable or unsuccessful, but there are few very long-term safety data available, especially for significant adverse events such as stroke. METHODS: 118 patients with acromegaly were treated with SRS between 1985 and 2015, at the National Centre for Stereotactic Radiosurgery, Sheffield, UK. Data were gathered from case notes, hospital databases, and patient questionnaires. Stroke incidence in comparison to the normal population was quantified using the standardised incidence ratio (SIR), and visual complications assessed. RESULTS: 88% (104/118) had complete morbidity follow up data for analysis. The mean follow-up was 134 months, and median SRS dose was 30 Gy. 81% of tumours had cavernous sinus invasion. There was no excess stroke rate relative to that seen in two age- and sex-matched large population studies (SIR = 1.36, 95% CI 0.27-3.96; SIR = 0.52, 95% CI 0.06-1.89). In 68/104 patients who had MRI-guided SRS with no further radiation treatment (SRS or fractionated radiotherapy) there was no loss of visual acuity and 3% developed ophthalmoplegia. There was a positive correlation between > 1 radiation treatment and both ophthalmoplegia and worsening visual acuity. CONCLUSION: Stroke rate is not increased by SRS for acromegaly. Accurate MRI-based treatment planning and single SRS treatment allow the lowest complication rates. More than one radiation treatment (SRS or fractionated radiotherapy) was associated with increased visual complications.

The impact of unscheduled gaps and iso-centre sequencing on the biologically effective dose in Gamma Knife radiosurgery.

PURPOSE: Establish the impact of iso-centre sequencing and unscheduled gaps in Gamma Knife® (GK) radiosurgery on the biologically effective dose (BED). METHODS: A BED model was used to study BED values on the prescription iso-surface of patients treated with GK Perfexion™ (Vestibular Schwannoma). The effect of a 15 min gap, simulated at varying points in the treatment delivery, and adjustments to the sequencing of iso-centre delivery, based on average dose-rate, was quantified in terms of the impact on BED. RESULTS: Depending on the position of the gap and the average dose-rate profiles, the mean BED values were decreased by 0.1% to 9.9% of the value in the original plan. A heuristic approach to iso-centre sequencing showed variations in BED of up to 14.2%, relative to the mean BED of the original sequence. CONCLUSION: The treatment variables, like the iso-centre sequence and unscheduled gaps, should be considered during GK radiosurgery treatments.

Gamma Knife Stereotactic Radiosurgery for the treatment of chordomas and chondrosarcomas.

INTRODUCTION: Primary chordomas and chondrosarcomas of the skull base are difficult tumours to treat successfully. Despite advances in surgical techniques, a gross total resection is often impossible to achieve. In addition, some patients may be deemed unsuitable or not wish to undergo extensive surgery for these conditions. This study examines the role of Gamma Knife Stereotactic Radiosurgery (GKRS) in the treatment of these difficult cases. METHODS: All patients harbouring either a chordoma or chondrosarcoma treated at the National Centre for Stereotactic Radiosurgery, Royal Hallamshire Hospital, Sheffield, UK, between 1985 and 2018, were reviewed with regard to their clinical presentations, pre- and post-treatment imaging, GKRS prescriptions and outcomes. RESULTS: In total, 24 patients with a mean tumour volume of 13 cm3 in the chordoma group (n=15) and 12 cm3 in the chondrosarcoma group (n=9) underwent GKRS. The 5- and 10-year overall survival rates for the chordoma group were 67% and 53% respectively, while for the chondrosarcoma group, they were 78% at both time points. The tumour control rates at 5 and 10 years in the chordoma group were 67% and 49% and for the chondrosarcoma group 78% at both time points. Patients with tumour volumes of less than 7 cm3 before GKRS treatment demonstrated a statistically significant longer overall survival rate (p=0.03). CONCLUSIONS: GKRS offers a comparable option to proton beam therapy for the treatment of these tumours. Early intervention for tumour volumes of less than 7 cm3 gives the best long-term survival rates.

A Retrospective Analysis of the Role of Single-Session Gamma Knife Stereotactic Radiosurgery in Sporadic Vestibular Schwannomas with Tumor Volumes Greater Than 10 cm3: Is It Worth Stretching the Boundaries?

OBJECTIVE: To evaluate the role of single-session Gamma Knife stereotactic radiosurgery (GK-SRS) in the treatment of vestibular schwannomas (VSs) with volumes of greater 10 cm3. METHODS: A retrospective analysis was performed of 103 patients treated with single-session GK-SRS between 1993 and 2011 with a mean follow-up of 6.2 years ± 4.4 SD. Treatment, clinical and outcome details were recorded and assessed. RESULTS: Eighty-one (78.6%) patients achieved radiological control with slow progression in a further 5 (4.9%) patients, who did not require further treatment. Linear measurements did not correlate well with volume, which can predict outcome following treatment more precisely. 2.9% of patients developed a new facial paresis, 5.8% trigeminal numbness and 2.9% facial pain. In all, 26 (25.2%) patients who were tested preserved some level of hearing following treatment. CONCLUSIONS: The overall radiological control rate in this study was 78.6%, while tumor volumes less than 20 cm3 can be safely treated with single-stage GK-SRS with an expected control rate of 83.2% without unacceptable morbidity rates. GK-SRS can be utilized as a first-line treatment option in patients with large-volume VSs especially in whom surgery is unattractive.

Radiosurgery as primary management for acromegaly.

OBJECTIVE: Transsphenoidal surgery (TSS) remains the recommended primary treatment for acromegaly. Long-term outcome data are not available for patients treated with gamma knife radiosurgery (STRS) as a primary treatment. DESIGN: Retrospective cohort study. DATA COLLECTION: notes review, laboratory results, general physician notes, patient questionnaire and death certification. PATIENTS: Twenty acromegaly patients underwent primary STRS at the National Centre for Radiosurgery, Sheffield, UK, between 1985 and 2015. MEASUREMENTS: Biochemical control (GH/IGF1), hypopituitarism, morbidity and mortality were all recorded. RESULTS: At 20 years of follow-up, control was seen in all on acromegaly-specific medication (n = 12) and 75% of those off medication (3/4). Time for 50% to achieve control on medication was 3 years, and 7.4 years off medication. Median marginal radiation dose was 27.5 Gy, and median follow-up was 166.5 months. 53% of patients developed new hypopituitarism at a median follow-up of 146 months, and the development of first onset of hypopituitarism occurred as late as 20 years after treatment. With MRI planning, no other complications were noted. Three patients underwent subsequent TSS due to poor biochemical control. During follow-up, 7 patients died at a median age of 65 years. There were no STRS-related deaths. CONCLUSION: This is the longest follow-up of patients who have undergone primary STRS for acromegaly. It shows low morbidity, but significant latency to biochemical control and new-onset hypopituitarism. This mandates very long-term follow-up for these patients. STRS has shown good long-term efficacy providing initial control can be afforded by optimal medical management. While TSS remains best practice, STRS offers an alternative for those in whom surgery is not an option.

Safety of radiosurgery applied to conditions with abnormal tumor suppressor genes.

OBJECTIVE: To assess the risk of radiosurgery inducing malignancy in neurofibromatosis-2 (NF2) and von Hippel-Lindau disease. METHODS: A retrospective cohort study of 118 NF2 and 19 von Hippel-Lindau disease patients, totalling 906 and 62 patient-years of follow-up data, respectively. RESULTS: Two cases of intracranial malignancy were identified, both of which occurred in NF2 patients. One of these was thought to have arisen before the radiosurgery; the other was a glioblastoma diagnosed 3 years after radiosurgery. CONCLUSION: Because gliomas may occur in as many as 4% of NF2 patients, this may not represent an increased risk. We continue to offer radiosurgery treatment to selected NF2 and von Hippel-Lindau disease patients and consider that the late risk of malignancy arising after irradiation must be put in the context of the condition being treated, the treatment options available to these individuals, and their life expectancy.

Gamma Knife treatment for cerebral arteriovenous malformations.

One of the earliest indications for Gamma Knife treatment, radiosurgery for cerebral arteriovenous malformations, has stood the test of time. While initially only the ideal cases (small, compact nidus in a non-eloquent site) were chosen, increasingly larger, more complex AVMs were treated. Combination treatment with embolisation and surgery enables most lesions to be treated with success and remarkably low complication rate. This paper is a brief overview of the experience gained in Sheffield.

Risk of malignancy after gamma knife stereotactic radiosurgery.

OBJECTIVE: To assess the risk of radiosurgery to cause malignant transformation in benign tumors or to induce new malignancies. METHODS: A retrospective cohort study comparing the Sheffield, England, radiosurgery patient database with national mortality and cancer registries. This data set comprises approximately 5000 patients and 30,000 patient-years of follow-up, with more than 1200 patients having a follow-up period longer than 10 years. RESULTS: In this material, a single new astrocytoma was diagnosed, whereas, based on national incidence figures, 2.47 cases would have been predicted. CONCLUSION: No increased risk of malignancy was detected in this series, supporting the safety of radiosurgery. Pragmatically, in advising patients, the risks of malignancy would seem small, particularly if such risks are considered in the context of the other risks faced by patients with intracranial pathologies requiring radiosurgical treatments.

Cerebral arteriovenous malformations: comparison of novel magnetic resonance angiographic techniques and conventional catheter angiography.

OBJECTIVE: To investigate the potential of novel magnetic resonance (MR) angiographic techniques for the assessment of cerebral arteriovenous malformations. METHODS: Forty patients who were about to undergo stereotactic radiosurgery were prospectively recruited. Three-dimensional, sliding-slab interleaved ky (SLINKY), time-of-flight acquisition was performed, as was a dynamic MR digital subtraction angiography (DSA) procedure in which single thick slices (6-10 cm) were obtained using a radiofrequency spoiled Fourier-acquired steady-state sequence (1 image/s). Sixty images were acquired, in two or three projections, during passage of a 6- to 10-ml bolus of gadolinium chelate. Subtraction and postprocessing were performed, and images were viewed in an inverted cine mode. SLINKY time-of-flight acquisition was repeated after the administration of gadolinium. Routine stereotactic conventional catheter angiography was performed after MR imaging. All images were assessed (in a blinded randomized manner) for Spetzler-Martin grading and determination of associated vascular pathological features. RESULTS: Forty-one arteriovenous malformations were assessed in 40 patients. Contrast-enhanced (CE) SLINKY MR angiography was the most consistent MR imaging technique, yielding a 95% correlation with the Spetzler-Martin classification defined by conventional catheter angiography; MR DSA exhibited 90% agreement, and SLINKY MR angiography exhibited 81% agreement. CE SLINKY MR angiography provided improved nidus delineation, compared with non-CE SLINKY MR angiography. Dynamic information from MR DSA significantly improved the observation of early-draining veins and associated aneurysms. CONCLUSION: CE SLINKY MR angiographic assessment of cerebral arteriovenous malformations offers significant advantages, compared with the use of non-CE SLINKY MR angiography, including improved nidus demonstration. MR DSA shows promise as a noninvasive method for dynamic angiography but is presently restricted by limitations in both temporal and spatial resolution.

Radiosurgery of isolated cerebral vessels following administration of paclitaxel in the rat.

OBJECT: Progressive obliteration occurs in arteriovenous malformations (AVMs) after radiosurgery; however, the risk of hemorrhage remains until the obliteration process is complete. The authors sought to enhance the radiation effect and reduce the risk of hemorrhage by facilitating faster vessel obliteration. To that end, a combination of a lower radiation dose with the addition of a radiosensitizing agent was compared with the effect of a higher radiation dose alone. METHODS: Using a method described by Mulvany and Halpern, isometric myography measurements were made on isolated rat middle cerebral artery specimens. The vessels were treated with 200 Gy, 80 Gy, 50 Gy, 25 Gy, 20 Gy, or 15 Gy by using Gamma Knife surgery. Taxol (paclitaxel 3 mg/kg/body weight) was administered intravenously to the animals. Survival times posttreatment were 24 hours, 6 weeks, 12 weeks, 12 months, or 18 months. After dissection, the middle cerebral arteries were mounted on a small-vessel myograph, and contraction and relaxation studies were performed. In a second series of experiments these results were validated in human fibroblast culture. When the cultures were 75 to 80% colonized, the samples were treated in vitro with 60Co gamma radiation in similar doses with or without paclitaxel. CONCLUSIONS: Constriction responses were generally decreased in the paclitaxel-treated vessels. Differences were significant at 6 weeks (p < 0.05) and at 1 year (p < 0.05). After 1 year, in the paclitaxel-treated groups vascular reactivity was completely abolished in vessels receiving 50 Gy. In comparison, it took 6 months longer (18 months) for this reaction to be abolished in vessels without paclitaxel treatment. In tissue cultures Giemsa staining and immunohistochemical reactions for p53, Ki-67, CD-34, and SMA antigens revealed marked fibroblast hypertrophy in all of the paclitaxel-treated groups. Paclitaxel-treated vessels demonstrated decreased reactivity at significantly earlier stages than vessels that had not been treated. It would appear that paclitaxel causes acceleration in the time course of the late biological effect of gamma radiation. This beneficial effect could be used in Gamma Knife surgery in patients with AVMs, thus reducing the risk of posttreatment hemorrhage.

Automated gamma knife radiosurgery treatment planning with image registration, data-mining, and Nelder-Mead simplex optimization.

Gamma knife treatments are usually planned manually, requiring much expertise and time. We describe a new, fully automatic method of treatment planning. The treatment volume to be planned is first compared with a database of past treatments to find volumes closely matching in size and shape. The treatment parameters of the closest matches are used as starting points for the new treatment plan. Further optimization is performed with the Nelder-Mead simplex method: the coordinates and weight of the isocenters are allowed to vary until a maximally conformal plan specific to the new treatment volume is found. The method was tested on a randomly selected set of 10 acoustic neuromas and 10 meningiomas. Typically, matching a new volume took under 30 seconds. The time for simplex optimization, on a 3 GHz Xeon processor, ranged from under a minute for small volumes (<1000 cubic mm, 2-3 isocenters), to several tens of hours for large volumes (>30,000 cubic mm, >20 isocenters). In 8/10 acoustic neuromas and 8/10 meningiomas, the automatic method found plans with conformation number equal or better than that of the manual plan. In 4/10 acoustic neuromas and 5/10 meningiomas, both overtreatment and undertreatment ratios were equal or better in automated plans. In conclusion, data-mining of past treatments can be used to derive starting parameters for treatment planning. These parameters can then be computer optimized to give good plans automatically.

Radiosurgical planning of meningiomas: compromises with conformity.

The radiosurgical planning of meningiomas frequently necessitates compromises between irradiating tumour and risking damage to adjacent structures. In selected cases, we resolved this by excluding part of the tumour from the prescription isodose volume. Most of these compromises or 'suboptimal' plans achieved growth control. Growth control could not be related to conformity indices or to various measures of the radiation dose received by the meningioma. Examining recurrences, 75% arose from dura outside the original treatment field. These findings are discussed in terms of dose prescription protocols and the use of conformity indices in planning. The importance of the dural origin of meningiomas is well established in surgical practice, as reflected by Simpson's grades, but may be equally significant in radiosurgical practice.

Experimental stereotactic gamma knife radiosurgery. Vascular contractility studies of the rat middle cerebral artery after chronic survival.

In vitro isometric small vessel myograph experiments and pathological investigations were performed on rat middle cerebral arteries. Thirty-four animals provided 68 normal vessels, six further rats had the endothelial layer mechanically removed from their 12 arteries. Eighteen animals received gamma knife irradiation to the middle cerebral arteries. Fifteen of these received 50 Gray, and three 25 Gray dose to the 50% isodose and the contralateral vessels offered 20 Gray and 15 Gray irradiated specimens. Survival times varied from 12 weeks to 18 months. In the acute stage, abolition of potassium-induced relaxation occurred as early as 24 h after irradiation whilst in one year this reaction seemed to recover and remained active to 18 months. The contraction response to prostaglandin F2 alpha was diminished at six weeks in the 50 Gray-irradiated vessels. However, from one year further reduction was seen and by 18 months this response was totally abolished. We demonstrated reduction of contractile capability of the irradiated normal vessels while the vessels remained patent. When using low irradiation dose there were no pathological changes even at 18 months, but marked physiological changes could be demonstrated. Different vessel wall functions appear to have different radiosensitivity, time course and capability for regeneration.

Stereotactic radiosurgery for type 2 neurofibromatosis acoustic neuromas: patient selection and tumour size.

Acoustic neuromas which are secondary to type 2 neurofibromatosis (NF2) respond less well to radiosurgery than unilateral sporadic disease. To refine the selection of these patients, a regression analysis was performed examining the response to radiosurgery of 114 NF2 tumours. The major determinant of outcome was tumour volume (p < 0.001). Calculating sensitivity and specificity values for different tumour volume limits gives a sensitivity value of 0.96 for a volume limit of 10 cm(3). This suggests that the size constraints that apply to the radiosurgical management of NF2 acoustic neuromas differ and are more restricted than those which are accepted for acoustic neuromas in general.

Rotational movements of the automatic positioning system under load and their significance for patient treatments.

OBJECT: During routine quality assurance (QA) testing of the gamma knife Automatic Positioning System (APS), it was noticed that slight pressure applied to the handle of the QA test tool produced visible rotation of the APS assembly. The authors describe the tests performed to quantify these movements. METHODS: A stereotactic frame was positioned in the slides of the APS and known loads applied using a spring balance to the upper corner of the frame. Movement at the corner of the frame (y = 200) was measured using a dial gauge. The typical load applied to the APS by a patient with a medium-sized head was determined in a treatment simulation. Projecting the measured data, a plot showing the resultant error in the position of a target point was constructed. Error values increased with distance from the frame, up to a maximum of 0.3 mm (at the superior limit of treatment range). Increased loads could be applied to the system during patient movements, and these would result in larger displacements. Two volunteers enlisted to simulate patient movements and the deflections were recorded. It was estimated that maximum errors in the target positioning of 0.45 mm might take place during these movements. CONCLUSIONS: The use of the APS has some additional and unexpected associated errors. The authors believe, however, that because the errors are smaller than those of target localization and manual trunnion treatments, its clinical use is still justified. The manufacturer is investigating the cause of the movements and possible solutions.

The commissioning and quality assurance of the Automatic Positioning System on the Leksell gamma knife.

OBJECT: The authors describe a series of commissioning checks that were developed following the installation of the Automatic Positioning System (APS) on the model C gamma knife. METHODS: System reliability was checked by performing a series of test treatments using the APS. A phantom was designed to enable the exposure of small pieces of Gaf Chromic film at 40 different predefined x, y, and z coordinates. The phantom consisted of a base plate with a series of film holders to facilitate the exposures using a 4-mm field, the center of which was marked. A spreadsheet calculation was performed to verify the conversion from Leksell coordinates to the APS coordinates when the treatment angle (gamma angle) is other than 90 degrees. A number of APS plans were prepared and the coordinate transformation verified. Precision measurements were performed to verify the correct positioning of the high bars when attached to the frame. The Gaf Chromic films were exposed, and the APS plans were used when confined to positions within the high bar range. A test tool to verify accurate location of the high bars on the frame was also designed. CONCLUSIONS: The performance of APS was verified independently of the manufacturer by using specially designed tools, phantoms, and spread sheets. At all points tested, the positional accuracy was found to be within specification. Conversion to APS coordinates was verified as correct.

The clinical application of plugging patterns for the Leksell gamma knife.

OBJECT: In this report the authors explore the use of standardized plugging templates in formulating stereotactic radiosurgery dose plans for the Leksell gamma knife. METHODS: Unplugged gamma knife dose plans previously used in the treatment of patients with trigeminal neuralgia (TN) and vestibular schwannoma (VS) were studied. Standardized plugging templates were then superimposed on these plans, and their effects on the conformity index of tumors and the transposition of the radiation field from the brainstem to the cerebrospinal fluid spaces for the trigeminal cases were examined. CONCLUSIONS: The standardized plugging templates significantly increased the conformity indices in cases of VS plans and for TN. Plugging significantly reduced the brainstem exposure to radiation while at the same time not altering the length of the trigeminal nerve being treated. Standardized plugging templates may therefore be a useful tool in optimizing dose plans.