Awake craniotomy for high-grade gliomas - a prospective cohort study in a UK tertiary-centre.

BACKGROUND: Studies from the UK reporting on awake craniotomy (AC) include a heterogenous group of patients which limit the evaluation of the true impact of AC in high-grade glioma (HGG) patients. This study aims to report solely the experience and outcomes of AC for HGG surgery from our centre. METHODS: A prospective review of all patients who underwent AC for HGG from 2013 to 2019 were performed. Data on patient characteristics including but not limited to demographics, pre- and post-operative Karnofsky performance status (KPS), tumour location and volume, type of surgery, extent of resection (EOR), tumour histopathology, intra- and post-operative complications, morbidity, mortality, disease recurrence, progression-free survival (PFS) and overall survival (OS) from the time of surgery were collected. RESULTS: Fifteen patients (6 males; 9 females; 17 surgeries) underwent AC for HGG (median age = 55 years). Two patients underwent repeat surgeries due to disease recurrence. Median pre- and post-operative KPS score was 90 (range:80-100) and 90 (range:60-100), respectively. The EOR ranges from 60 to 100 % with a minimum of 80 % achieved in 81.3 % cases. Post-operative complications include focal seizures (17.6 %), transient aphasia/dysphasia (17.6 %), permanent motor deficit (11.8 %), transient motor deficit (5.9 %) and transient sensory disturbance (5.9 %). There were no surgery-related mortality or post-operative infection. The median PFS and OS were 13 (95%CI 5-78) and 30 (95%CI 21-78) months, respectively. CONCLUSION: This is the first study in the UK to solely report outcomes of AC for HGG surgery. Our data demonstrates that AC for HGG in eloquent region is safe, feasible and provides comparable outcomes to those reported in the literature.

A 3D star shot to determine the gantry, collimator, and couch axes positions.

A linear accelerator has three independent axes that are nominally intersecting at the isocenter. Modern treatment techniques require the coincidence of these axes to lie within a 1-mm diameter sphere. A solution to verify this requirement is to wrap a film on a cylindrical surface, align the cylinder to the linac's isocenter and gantry axis, and take multiple exposures of slits, rotating either the gantry, collimator, or couch between exposures. The resulting exposure pattern is the 3D equivalent of the 2D star shot and encodes sufficient information to determine each axis' position in 3D. Moreover, this method uses a single sheet 8"x10" film, a standard film scanner, and a phantom that can be readily built in-house, making a practical solution to this 3D-measurement problem.

A quality assurance tool for daily checks of the gamma knife high definition motion management system.

PURPOSE: This note describes the performance of a quality assurance (QA) tool built for daily checks of the Gamma Knife's high definition motion management (HDMM) system. METHODS: The tool is a three-dimensional (3D)-printed platform with a raised corner in the center. A reflector post is placed at the corner and the HDMM tool is zeroed to this position. Gage blocks produce very accurate gaps between the post and corner and the HDMM system's readout is compared to the gage block thickness. The HDMM system and tool were tested for noise, stability, reproducibility, linearity, accuracy and overall setup times plus ease of use. RESULTS: The QA tool performed with accuracies better than 0.1 mm. The setup and use of this tool take less than two minutes making it a suitable tool for daily use. CONCLUSION: This QA tool is a cost-effective solution that provides a fast and easy confirmation of the HDMM accuracy, making it suitable for daily QA checks of the HDMM system.

Calibrating TrueBeam jaws by considering collimator walkout to improve the dose uniformity at abutting field junctions.

Jaw positions on a linear accelerator are calibrated to have accurate field size values over the range of jaw positions and to have excellent junctions when matching fields. It is sufficient to have field size accuracy on the order of a millimeter for most clinical applications but good junctions require submillimeter precision and accuracy in the jaw positioning. Presented is a method to measure collimator walkout with the MV imager and a mathematical model to determine an optimal origin for calibrating jaws on the TrueBeam accelerator. The calibration procedure uses the jaw position encoders which are sufficiently accurate and precise enough to achieve a homogeneous junction dose for abutting fields.

Prognostic factors for survival in adult patients with recurrent glioblastoma: a decision-tree-based model.

We assessed prognostic factors in relation to OS from progression in recurrent glioblastomas. Retrospective multicentric study enrolling 407 (training set) and 370 (external validation set) adult patients with a recurrent supratentorial glioblastoma treated by surgical resection and standard combined chemoradiotherapy as first-line treatment. Four complementary multivariate prognostic models were evaluated: Cox proportional hazards regression modeling, single-tree recursive partitioning, random survival forest, conditional random forest. Median overall survival from progression was 7.6 months (mean, 10.1; range, 0-86) and 8.0 months (mean, 8.5; range, 0-56) in the training and validation sets, respectively (p = 0.900). Using the Cox model in the training set, independent predictors of poorer overall survival from progression included increasing age at histopathological diagnosis (aHR, 1.47; 95% CI [1.03-2.08]; p = 0.032), RTOG-RPA V-VI classes (aHR, 1.38; 95% CI [1.11-1.73]; p = 0.004), decreasing KPS at progression (aHR, 3.46; 95% CI [2.10-5.72]; p < 0.001), while independent predictors of longer overall survival from progression included surgical resection (aHR, 0.57; 95% CI [0.44-0.73]; p < 0.001) and chemotherapy (aHR, 0.41; 95% CI [0.31-0.55]; p < 0.001). Single-tree recursive partitioning identified KPS at progression, surgical resection at progression, chemotherapy at progression, and RTOG-RPA class at histopathological diagnosis, as main survival predictors in the training set, yielding four risk categories highly predictive of overall survival from progression both in training (p < 0.0001) and validation (p < 0.0001) sets. Both random forest approaches identified KPS at progression as the most important survival predictor. Age, KPS at progression, RTOG-RPA classes, surgical resection at progression and chemotherapy at progression are prognostic for survival in recurrent glioblastomas and should inform the treatment decisions.

Evaluation of a national neurosurgical formative examination: the UK experience.

INTRODUCTION: Formative assessment is a key component in medical education and that it is a helpful process for all involved. Until recently there was no national formative examination for neurosurgical trainees. The Neurosurgery Annual in Training Examination (NAiTE) is an annual online, formative assessment that was introduced in 2014. In this paper, we seek to discuss how well NAiTE relates to established educational practice and principles and its fitness for purpose by discussing its rationale, structure and utility. METHODS: A national online examination was introduced in 2014. The NAiTE consists of 100 single best answer multiple choice questions. The examination and questions with were reviewed and the global results presented. The existing literature and educational theory are used to guide subjective assessment of the process. RESULTS: In 2016, 191 candidates participated in the NAiTE, of whom 154 were trainees working in UK neurosurgical units. The mean score for early stage UK trainees (years 1-3) was 52.4%, intermediate (years 4-5) 58.5% and senior (years 6-8) 65.4%. The NAiTE was found to be a reliable (Cronbach-Alpha of 0.89) and valid assessment of trainees with scores approximating those attained in the Intercollegiate Specialty Examination itself. DISCUSSION: Potential areas for improvement are highlighted, including reference to some that have already been implemented. CONCLUSION: Overall, the examination is a cheap, viable and reliable means of testing trainees and encouraging their onward development and learning as they work towards the Intercollegiate Specialty Examination.

The death of Henry II, King of France (1519-1559). From myth to medical and historical fact.

On 30 June 1559, Henry II, King of France, was mortally wounded in the head by a lance during a jousting match. Despite the best efforts of his physicians, Ambroise Paré and Andreas Vesalius, King Henry died 11 days later. This article, based on previously unpublished evidence, aims at examining the historical account of his death against modern medical practice to establish the probable cause of the king's death. We also discuss what treatments the doctors in the sixteenth century may have had to offer. Historical accounts of the joust provide details of the incident including the position of the visor of the king's helmet. Descriptions of the wood fragments removed from the right orbit by Italian observers and a new translation of the autopsy by Andreas Vesalius allow an accurate description of the actual injury. Our research counters previous theories and concludes that Henry II was the victim of craniofacial trauma involving the right eye and that he died from periorbital cellulitis caused by a retained foreign body in the wound, complicated by a left interhemispheric empyema preceded by a traumatic interhemispheric haematoma. It would appear that the royal court doctors advocated a wait-and-see strategy, with little actual input from Ambroise Paré or Andreas Vesalius, with a clearly regrettable outcome.

Pion effects in flattening filter-free radiation beams.

Flattening filter-free radiation beams have higher dose rates that significantly increase the ion recombination rate in an ion chamber's volume and lower the signal read by the chamber-electrometer pair. The ion collection efficiency correction (P(ion)) accounts for the loss of signal and subsequently changes dosimetric quantities when applied. We seek to characterize the changes to the percent depth dose, tissue maximum ratio, relative dose factor, absolute dose calibration, off-axis ratio, and the field width. We measured P(ion) with the two-voltage technique and represented P(ion) as a linear function of the signal strength. This linear fit allows us to correct measurement sets when we have only gathered the high voltage signal and to correct derived quantities. The changes to dosimetric quantities can be up to 1.5%. Charge recombination significantly affects percent depth dose, tissue maximum ratio, and off-axis ratio, but has minimal impact on the relative dose factor, absolute dose calibration, and field width.

Resection of olfactory groove meningioma - a review of complications and prognostic factors.

INTRODUCTION: High complication rates have been cited following olfactory groove meningioma (OGM) resection but data are lacking on attendant risk factors. We aimed to review the complications following OGM resection and identify prognostic factors. METHODS: A retrospective review was performed on 34 consecutive patients who underwent primary OGM resection at a single London institution between March 2008 and February 2013. Collected data included patient comorbidities, pre-operative corticosteroid use, tumour characteristics, imaging features, operative details, extent of resection, histology, use of elective post-operative ventilation, complications, recurrence and mortality. RESULTS: Complication rate was 39%. 58% of complications required intensive care or re-operation. Higher complication rates occurred with OGM > 40 mm diameter versus ≤ 40 mm (53 vs. 28%; p = 0.16); OGM with versus without severe perilesional oedema (59 vs. 19%; p = 0.26), more evident when corrected for tumour size; and patients receiving 1-2 days versus 3-5 days of pre-operative dexamethasone (75 vs. 19%; p = 0.016). Patients who were electively ventilated post-operatively versus those who were not had higher risk tumours but a lower complication rate (17 vs. 44%; p = 0.36) and a higher proportion making a good recovery (83 vs. 55%; p = 0.20). Complete versus incomplete resection had a higher complication rate (50 vs. 23%; p = 0.16) but no recurrence (0 vs. 25%; p = 0.07). CONCLUSION: Risk of morbidity with OGM resection is high. Higher complication risk is associated with larger tumours and greater perilesional oedema. Pre-operative dexamethasone for 3-5 days versus shorter periods may reduce the risk of complications. We describe a characteristic pattern of perilesional oedema termed 'sabre-tooth' sign, whose presence is associated with a higher complication rate and may represent an important radiological prognostic sign. Elective post-operative ventilation for patients with high-risk tumours may reduce the risk of complications.

Prevalence of recurrence and retreatment of ruptured intracranial aneurysms treated with endovascular coil occlusion.

OBJECT: Endovascular coiling is a common treatment for ruptured intracranial aneurysms. However, concerns have been raised over the durability of this treatment. The aim of this study was to establish the rate of recurrence and retreatment of coiled aneurysms treated in our unit. METHODS: We performed a retrospective analysis of 264 surviving patients with ruptured aneurysms treated by endovascular coiling between November 2003 and April 2007. Data was collected on patient age, location of aneurysm, angiogram results and any subsequent retreatment. RESULTS: Follow-up angiography performed at 6 months was available in 239 cases (91%) and revealed 158 (66%) aneurysms completely occluded, 51 (21%) had neck recurrence and 31 (13%) had significant recurrence. Thirty (12.6%) aneurysms required retreatment over a mean follow-up period of 46 (range 24-66) months. Younger age predisposed to a higher risk of recurrence and retreatment. Aneurysms of the anterior communicating and anterior cerebral arteries were less likely to recur or require retreatment (relative risk 0.42 and 0.29, respectively); aneurysms of the posterior communicating arteries were more likely to recur (relative risk 2.22). Aneurysms of the basilar and carotid arteries were more likely to undergo retreatment (relative risk 2.84 and 2.46, respectively). CONCLUSION: Long-term follow-up is required for ruptured aneurysms treated by coiling. Certain subgroups may require closer follow-up due to the increased risk of recurrence or retreatment, such as younger patients and those with aneurysms of the posterior communicating, basilar or carotid arteries.

Is referral to the neuro-oncology MDT safe?

INTRODUCTION: Since 2006, National Institute for Health and Clinical Excellence (NICE) guidelines advise referral of any suspected brain tumour to a dedicated neuro-oncology multidisciplinary team (MDT). We investigated two aspects of MDT safety: whether time to operation was delayed and whether brain abscesses were inappropriately referred to the MDT. MATERIAL(S) AND METHODS: We reviewed the notes of 220 consecutive patients referred to our neuro-oncology service before and after implementation of a pre-operative MDT meeting. RESULTS: Median time to operation was similar for patients referred before and after introduction of the MDT (8 days pre-MDT, 9 days post-MDT). There were four abscesses referred via the MDT with a significantly longer median time to operation than in the pre-MDT era (6 days vs. 1 day), although no patient came to any apparent harm as a consequence. No lesion imaged with MRI was misdiagnosed. DISCUSSION: Pre-operative MDT does not lengthen time to operation for patients with brain tumour. However, it may delay time to operation for abscesses inadvertently referred via the MDT route. We advocate the use of MRI to minimise the risk of misdiagnosis of cerebral abscesses.

Cerebral protothecosis mimicking high-grade glioma.

Prototheca wickerhamii is a common, indolent alga that seldom causes central nervous system infections in humans. We report the first UK case of cerebral protothecosis in an immunocompetent 56-year-old woman who presented with a 5-month history of intermittent fatigue followed by a 2-week history of symptoms, including right arm and leg weakness, a loss of fine motor coordination, worsening gait, right facial tingling, diplopia and a metallic oral taste. MRI scans revealed a multifocal abnormality suggestive of high-grade glioma. Given the clinical presentation, absence of immunodeficiency and characteristic MRI features, a diagnosis of high-grade glioma was deemed most likely by the multidisciplinary team. Surgical biopsy provided material for histopathological and microbiological diagnosis. She underwent a 2-year course of antimicrobials with surveillance MRI scans. The patient made a good functional recovery but still retains mild neurological sequelae.

Low grade cerebellar T-cell lymphoma: a novel response to treatment; a case report.

Low-grade primary T-cell lymphoma of the central nervous system is extremely rare. We present a case developing in a previously fit young woman presenting with symptoms of raised intracranial pressure and found on CT to have a cerebellar mass. Biopsy of this lesion revealed features of non-Hodgkin's lymphoma with histochemical analysis confirming T-cell phenotype and a Ki67 proliferation index of only 1%. Contrary to the prevailing view in the literature, the patient's clinical condition deteriorated following high-dose intravenous methotrexate and improved after a short course of whole-brain radiotherapy.

Measuring Workload with Paired Detectors.

Linear accelerator workloads for each available photon energy are important quantities to know for radiation safety considerations, and presented is a technique to measure the workload using paired detectors. The signals from the two detectors can give sufficient information to separate the signal contributions from 6 and 18 MV photon fields and, combined with a signal-per-monitor-unit calibration factor, yields the number of monitor units delivered for each energy. CR-39 NTD is a neutron detector chosen for its ability to discriminate between 6 MV and 18 MV radiation fields. TLD-100 is a detector responsive to both 6 MV and 18 MV fields. These appeared to be a good choice for a detector pair. This experiment had both failures and successes to report. The CR-39 NTD and TLD-100 were not a successful pairing. The CR-39 NTD signals saturated under this experiment's exposure conditions. The TLD-100 had a combination of detector noise and detector sensitivity that made extracting the 6 MV signal from the total signal impractical, unless the total exposure was overwhelmingly 6 MV. Nevertheless, the TLD-100 proved to be excellent for determining workloads when it was exposed to a single energy with 1% accuracy and 3% precision. The theory and data analysis showed the importance of understanding the noise contributions for the more general problem of pairing any two detector types. This experiment indicated the TLD-100 could be an excellent detector choice if paired with a suitable second detector.

Predictors of Epileptic Seizures and Ability to Work in Supratentorial Cavernous Angioma Located Within Eloquent Brain Areas.

BACKGROUND: The postoperative outcomes and the predictors of seizure control are poorly studied for supratentorial cavernous angiomas (CA) within or close to the eloquent brain area. OBJECTIVE: To assess the predictors of preoperative seizure control, postoperative seizure control, and postoperative ability to work, and the safety of the surgery. METHODS: Multicenter international retrospective cohort analysis of adult patients benefitting from a functional-based surgical resection with intraoperative functional brain mapping for a supratentorial CA within or close to eloquent brain areas. RESULTS: A total of 109 patients (66.1% women; mean age 38.4 ± 12.5 yr), were studied. Age >38 yr (odds ratio [OR], 7.33; 95% confidence interval [CI], 1.53-35.19; P = .013) and time to surgery > 12 mo (OR, 18.21; 95% CI, 1.11-296.55; P = .042) are independent predictors of uncontrolled seizures at the time of surgery. Focal deficit (OR, 10.25; 95% CI, 3.16-33.28; P < .001) is an independent predictor of inability to work at the time of surgery. History of epileptic seizures at the time of surgery (OR, 7.61; 95% CI, 1.67-85.42; P = .003) and partial resection of the CA and/or of the hemosiderin rim (OR, 12.02; 95% CI, 3.01-48.13; P < .001) are independent predictors of uncontrolled seizures postoperatively. Inability to work at the time of surgery (OR, 19.54; 95% CI, 1.90-425.48; P = .050), Karnofsky Performance Status ≤ 70 (OR, 51.20; 95% CI, 1.20-2175.37; P = .039), uncontrolled seizures postoperatively (OR, 105.33; 95% CI, 4.32-2566.27; P = .004), and worsening of cognitive functions postoperatively (OR, 13.71; 95% CI, 1.06-176.66; P = .045) are independent predictors of inability to work postoperatively. CONCLUSION: The functional-based resection using intraoperative functional brain mapping allows safe resection of CA and the peripheral hemosiderin rim located within or close to eloquent brain areas.

Vascular neurosurgery following the International Subarachnoid Aneurysm Trial: modern practice reflected by subspecialization.

OBJECT: In this paper the authors' goal was to report on and examine (in the context of a large hospital with good endovascular intervention provisions) the activities of a neurosurgeon with a dedicated vascular interest in the era after the International Subarachnoid Aneurysm Trial in the United Kingdom. They also aimed to establish therapeutic trends and outcomes. METHODS: The authors reviewed the multidisciplinary team activity of 1 neurosurgeon and 2 interventional radiologists during a period of 22 months (2005-2007). They reviewed 281 aneurysm interventions; the majority was used to treat subarachnoid hemorrhage. Data analysis showed a strong preference for endovascular treatment for acute rupture (86.6 vs 13.4%), with a progressively greater role for open microsurgery in the more elective context (57% endovascular vs 43% surgical). They also reviewed 66 interventions for arteriovenous malformations, of which only 6 were surgical. These data are compared against a sample year from 2001 to 2002 (pre-International Subarachnoid Aneurysm Trial), showing comparable rates of surgically treated aneurysms versus endovascularly treated aneurysms, but an increase overall in the number of patients requiring open surgery. RESULTS: The authors found that excellent outcomes for microsurgical clipping compared with endovascular therapy can be achieved within the current climate. These and previously published data strongly support a continuing role for vascular neurosurgery as a subspecialist interest in combination with a dedicated endovascular service and a multidisciplinary team. CONCLUSIONS: Despite a trend to prefer coiling for ruptured aneurysms, the authors have shown that there is still a vital role for open surgery in the management of the ruptured and unruptured aneurysm. They consider the remaining role for surgery for arteriovenous malformations within the modern era of endovascular therapy.

Solitary calvarial haemangioma presenting as metastatic renal cell carcinoma.

Renal cell carcinoma is the most common renal tumour in adult that often metastasises to the lung, liver or bone. Head and neck lesions are uncommon with no early warning signs and presents with overt metastases at primary presentation in 25%-30% of reported cases. The incidence of haemangiomas that suggest malignancy are similar to that of bone metastasis. Calvarial haemangiomas usually present as asymptomatic and discovered incidentally on imaging or postmortem examination. We report a case where an initial diagnosis of benign tumour of the skull was made based on clinical presentation and calvarial haemangioma on CT head but was confirmed as metastatic clear cell carcinoma of the kidney after histopathological results. Skull metastases are rare and present late in the course of the disease. It is unusual for metastatic lesion to be the primary presentation in a clinically silent renal cell carcinoma.

Intravenous delivery of oncolytic reovirus to brain tumor patients immunologically primes for subsequent checkpoint blockade.

Immune checkpoint inhibitors, including those targeting programmed cell death protein 1 (PD-1), are reshaping cancer therapeutic strategies. Evidence suggests, however, that tumor response and patient survival are determined by tumor programmed death ligand 1 (PD-L1) expression. We hypothesized that preconditioning of the tumor immune microenvironment using targeted, virus-mediated interferon (IFN) stimulation would up-regulate tumor PD-L1 protein expression and increase cytotoxic T cell infiltration, improving the efficacy of subsequent checkpoint blockade. Oncolytic viruses (OVs) represent a promising form of cancer immunotherapy. For brain tumors, almost all studies to date have used direct intralesional injection of OV, because of the largely untested belief that intravenous administration will not deliver virus to this site. We show, in a window-of-opportunity clinical study, that intravenous infusion of oncolytic human Orthoreovirus (referred to herein as reovirus) leads to infection of tumor cells subsequently resected as part of standard clinical care, both in high-grade glioma and in brain metastases, and increases cytotoxic T cell tumor infiltration relative to patients not treated with virus. We further show that reovirus up-regulates IFN-regulated gene expression, as well as the PD-1/PD-L1 axis in tumors, via an IFN-mediated mechanism. Finally, we show that addition of PD-1 blockade to reovirus enhances systemic therapy in a preclinical glioma model. These results support the development of combined systemic immunovirotherapy strategies for the treatment of both primary and secondary tumors in the brain.