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  • 1
    Article
    Article
    Development of high-throughput ATR-FTIR technology for rapid triage of brain cancer
    2019
    ISSN: 2041-1723 
    Details
    Language: English
    In: Nature communications, 2019-10-08, Vol.10 (1), p.4501-9
    Description: Non-specific symptoms, as well as the lack of a cost-effective test to triage patients in primary care, has resulted in increased time-to-diagnosis and a poor prognosis for brain cancer patients. A rapid, cost-effective, triage test could significantly improve this patient pathway. A blood test using attenuated total reflection (ATR)-Fourier transform infrared (FTIR) spectroscopy for the detection of brain cancer, alongside machine learning technology, is advancing towards clinical translation. However, whilst the methodology is simple and does not require extensive sample preparation, the throughput of such an approach is limited. Here we describe the development of instrumentation for the analysis of serum that is able to differentiate cancer and control patients at a sensitivity and specificity of 93.2% and 92.8%. Furthermore, preliminary data from the first prospective clinical validation study of its kind are presented, demonstrating how this innovative technology can triage patients and allow rapid access to imaging.
    Subject(s): Adult ; Aged ; Biopsy ; Blood Chemical Analysis - economics ; Blood Chemical Analysis - methods ; Brain ; Brain - diagnostic imaging ; Brain - pathology ; Brain cancer ; Brain Neoplasms - blood ; Brain Neoplasms - diagnosis ; Brain Neoplasms - pathology ; Cancer ; Cost-Benefit Analysis ; Female ; Follow-Up Studies ; Fourier transforms ; Head and neck cancer ; Health care ; Humans ; Infrared reflection ; Infrared spectroscopy ; Instrumentation ; Laboratory techniques and procedures ; Learning algorithms ; Machine learning ; Male ; Middle Aged ; Multidisciplinary Sciences ; Neuroimaging ; Prospective Studies ; Retrospective Studies ; Sample preparation ; Science & Technology ; Science & Technology - Other Topics ; Sensitivity and Specificity ; Spectroscopy, Fourier Transform Infrared - economics ; Stability ; Technology ; Time Factors ; Translational research ; Triage - economics ; Triage - methods ; Young Adult
    ISSN: 2041-1723
    E-ISSN: 2041-1723
    DOI: 10.1038/s41467-019-12527-5
    Source: Nature Open Access
    Source: Web of Science - Science Citation Index Expanded - 2019〈img src="http://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /〉
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
    URL: https://www.ncbi.nlm.nih.gov/pubmed/31594931$$D View this record in MEDLINE/PubMed
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  • 2
    Article
    Article
    EANO guidelines for the diagnosis and treatment of meningiomas
    2016
    ISSN: 1470-2045  ISSN: 1474-5488 
    Details
    Language: English
    In: The lancet oncology, 2016, Vol.17 (9), p.e383-e391
    Description: Summary Although meningiomas are the most common intracranial tumours, the level of evidence to provide recommendations for the diagnosis and treatment of meningiomas is low compared with other tumours such as high-grade gliomas. The meningioma task force of the European Association of Neuro-Oncology (EANO) assessed the scientific literature and composed a framework of the best possible evidence-based recommendations for health professionals. The provisional diagnosis of meningioma is mainly made by MRI. Definitive diagnosis, including histological classification, grading, and molecular profiling, requires a surgical procedure to obtain tumour tissue. Therefore, in many elderly patients, observation is the best therapeutic option. If therapy is deemed necessary, the standard treatment is gross total surgical resection including the involved dura. As an alternative, radiosurgery can be done for small tumours, or fractionated radiotherapy in large or previously treated tumours. Treatment concepts combining surgery and radiosurgery or fractionated radiotherapy, which enable treatment of the complete tumour volume with low morbidity, are being developed. Pharmacotherapy for meningiomas has remained largely experimental. However, antiangiogenic drugs, peptide receptor radionuclide therapy, and targeted agents are promising candidates for future pharmacological approaches to treat refractory meningiomas across all WHO grades.
    Subject(s): Cancer and Oncology ; Cancer och onkologi ; Care and treatment ; Classification ; Clinical Medicine ; Clinical trials ; Diagnosis ; Diagnostic imaging ; Drug development ; Drug therapy ; Edema ; Europe ; Geriatrics ; Gliomas ; Health aspects ; Hematology, Oncology and Palliative Medicine ; Humans ; Klinisk medicin ; Magnetic resonance imaging ; Medical and Health Sciences ; Medical diagnosis ; Medical imaging ; Medical personnel ; Medical prognosis ; Medicin och hälsovetenskap ; Meningeal Neoplasms - diagnosis ; Meningeal Neoplasms - therapy ; Meningioma ; Meningioma - diagnosis ; Meningioma - therapy ; Morbidity ; Mutation ; NMR ; Nuclear magnetic resonance ; Oncology ; Practice Guidelines as Topic - standards ; Radiation therapy ; Radiosurgery ; Surgery ; Surgical outcomes ; Task forces ; Tumors
    ISSN: 1470-2045
    ISSN: 1474-5488
    E-ISSN: 1474-5488
    DOI: 10.1016/S1470-2045(16)30321-7
    Source: Alma/SFX Local Collection
    URL: https://www.ncbi.nlm.nih.gov/pubmed/27599143$$D View this record in MEDLINE/PubMed
    URL: http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-125967$$DView record from Swedish Publication Index
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  • 3
    Article
    Article
    ‘Meningiomics’—an integration of data on the patient, tumour, extent of resection and molecular pathology to optimise the management and follow-up for meningiomas
    2019
    ISSN: 0001-6268 
    Details
    Language: English
    In: Acta neurochirurgica, 2019-10-28, Vol.161 (12), p.2551-2552
    Subject(s): Clinical Neurology ; Editorial (by Invitation) - Tumor - Meningioma ; Follow-Up Studies ; Humans ; Interventional Radiology ; Life Sciences & Biomedicine ; Medicine ; Medicine & Public Health ; Meningeal Neoplasms ; Meningioma ; Minimally Invasive Surgery ; Neurology ; Neuroradiology ; Neurosciences & Neurology ; Neurosurgery ; Pathology, Molecular ; Science & Technology ; Surgery ; Surgical Orthopedics ; Tumor – Meningioma ; Tumors
    ISSN: 0001-6268
    E-ISSN: 0942-0940
    DOI: 10.1007/s00701-019-04102-0
    Source: Web of Science - Science Citation Index Expanded - 2019〈img src="http://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /〉
    Source: Alma/SFX Local Collection
    URL: https://www.ncbi.nlm.nih.gov/pubmed/31656984$$D View this record in MEDLINE/PubMed
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  • 4
    Article
    Article
    Incidental intracranial meningiomas: a systematic review and meta-analysis of prognostic factors and outcomes
    2019
    ISSN: 0167-594X 
    Details
    Language: English
    In: Journal of neuro-oncology, 2019-01-17, Vol.142 (2), p.211-221
    Description: Background Incidental discovery accounts for 30% of newly-diagnosed intracranial meningiomas. There is no consensus on their optimal management. This review aimed to evaluate the outcomes of different management strategies for these tumors. Methods Using established systematic review methods, six databases were scanned up to September 2017. Pooled event proportions were estimated using a random effects model. Meta-regression of prognostic factors was performed using individual patient data. Results Twenty studies (2130 patients) were included. Initial management strategies at diagnosis were: surgery (27.3%), stereotactic radiosurgery (22.0%) and active monitoring (50.7%) with a weighted mean follow-up of 49.5 months (SD = 29.3). The definition of meningioma growth and monitoring regimens varied widely impeding relevant meta-analysis. The pooled risk of symptom development in patients actively monitored was 8.1% (95% CI 2.7–16.1). Associated factors were peritumoral edema (OR 8.72 [95% CI 0.35–14.90]) and meningioma diameter ≥ 3 cm (OR 34.90 [95% CI 5.17–160.40]). The pooled proportion of intervention after a duration of active monitoring was 24.8% (95% CI 7.5–48.0). Weighted mean time-to-intervention was 24.8 months (SD = 18.2). The pooled risks of morbidity following surgery and radiosurgery, accounting for cross-over, were 11.8% (95% CI 3.7–23.5) and 32.0% (95% CI 10.6–70.5) respectively. The pooled proportion of operated meningioma being WHO grade I was 94.0% (95% CI 88.2–97.9). Conclusion The management of incidental meningioma varies widely. Most patients who clinically or radiologically progressed did so within 5 years of diagnosis. Intervention at diagnosis may lead to unnecessary overtreatment. Prospective data is needed to develop a risk calculator to better inform management strategies.
    Subject(s): Analysis ; Asymptomatic ; Clinical Neurology ; Diagnosis ; Edema ; Incidental ; Life Sciences & Biomedicine ; Management ; Medical research ; Medicine ; Medicine & Public Health ; Medicine, Experimental ; Meningioma ; Meta-analysis ; Morbidity ; Neurology ; Neurosciences & Neurology ; Oncology ; Radiosurgery ; Science & Technology ; Strategic planning (Business) ; Surgery ; Systematic review ; Topic Review ; Tumors
    ISSN: 0167-594X
    E-ISSN: 1573-7373
    DOI: 10.1007/s11060-019-03104-3
    Source: Web of Science - Science Citation Index Expanded - 2019〈img src="http://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /〉
    Source: Alma/SFX Local Collection
    URL: https://www.ncbi.nlm.nih.gov/pubmed/30656531$$D View this record in MEDLINE/PubMed
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  • 5
    Article
    Article
    Intraoperative imaging technology to maximise extent of resection for glioma
    2017
    ISSN: 1465-1858 
    Details
    Language: English
    In: Cochrane database of systematic reviews, 2017-09-04, Vol.2017 (9)
    Description: This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To establish the overall effectiveness and safety of intraoperative imaging in resection of glial tumours.
    Subject(s): Medicine General & Introductory Medical Sciences
    ISSN: 1465-1858
    E-ISSN: 1465-1858
    E-ISSN: 1469-493X
    DOI: 10.1002/14651858.CD012788
    Source: Alma/SFX Local Collection
    Source: Cochrane Library
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  • 6
    Article
    Article
    Brain tumour differentiation: rapid stratified serum diagnostics via attenuated total reflection Fourier-transform infrared spectroscopy
    2016
    ISSN: 0167-594X 
    Details
    Language: English
    In: Journal of neuro-oncology, 2016-02-13, Vol.127 (3), p.463-472
    Description: The ability to diagnose cancer rapidly with high sensitivity and specificity is essential to exploit advances in new treatments to lead significant reductions in mortality and morbidity. Current cancer diagnostic tests observing tissue architecture and specific protein expression for specific cancers suffer from inter-observer variability, poor detection rates and occur when the patient is symptomatic. A new method for the detection of cancer using 1 μl of human serum, attenuated total reflection—Fourier transform infrared spectroscopy and pattern recognition algorithms is reported using a 433 patient dataset (3897 spectra). To the best of our knowledge, we present the largest study on serum mid-infrared spectroscopy for cancer research. We achieve optimum sensitivities and specificities using a Radial Basis Function Support Vector Machine of between 80.0 and 100 % for all strata and identify the major spectral features, hence biochemical components, responsible for the discrimination within each stratum. We assess feature fed-SVM analysis for our cancer versus non-cancer model and achieve 91.5 and 83.0 % sensitivity and specificity respectively. We demonstrate the use of infrared light to provide a spectral signature from human serum to detect, for the first time, cancer versus non-cancer, metastatic cancer versus organ confined, brain cancer severity and the organ of origin of metastatic disease from the same sample enabling stratified diagnostics depending upon the clinical question asked.
    Subject(s): Adolescent ; Adult ; Aged ; Aged, 80 and over ; Algorithms ; Analysis ; ATR-FTIR ; Biomarkers, Tumor - blood ; Brain Neoplasms - blood ; Brain Neoplasms - diagnosis ; Brain tumors ; Cancer ; Case-Control Studies ; Cell Differentiation ; Diagnosis ; Diagnostics ; Early Detection of Cancer ; Female ; Follow-Up Studies ; Glioma ; Gliomas ; Health aspects ; Humans ; Infrared spectroscopy ; Laboratory Investigation ; Male ; Medicine ; Medicine & Public Health ; Metastasis ; Middle Aged ; Mortality ; Neoplasm Grading ; Neurology ; Oncology ; Prognosis ; Rapid ; Serum ; Spectroscopy ; Spectroscopy, Fourier Transform Infrared - methods ; Support Vector Machine ; Young Adult
    ISSN: 0167-594X
    E-ISSN: 1573-7373
    DOI: 10.1007/s11060-016-2060-x
    Source: Alma/SFX Local Collection
    URL: https://www.ncbi.nlm.nih.gov/pubmed/26874961$$D View this record in MEDLINE/PubMed
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  • 7
    Article
    Article
    Surgical management and long-term outcome of intracranial subependymoma
    2018
    ISSN: 0001-6268 
    Details
    Language: English
    In: Acta neurochirurgica, 2018-06-18, Vol.160 (9), p.1793-1799
    Description: Background Intracranial subependymomas account for 0.2–0.7% of central nervous system tumours and are classified as World Health Organization (WHO) grade 1 tumours. They are typically located within the ventricular system and are detected incidentally or with symptoms of hydrocephalus. Due to paucity of studies exploring this tumour type, the objective was to determine the medium- to long-term outcome of intracranial subependymoma treated by surgical resection. Methods Retrospective case note review of adults with intracranial WHO grade 1 subependymoma diagnosed between 1990 and 2015 at the Walton Centre NHS Foundation Trust was undertaken. Tumour location, extent of resection (defined as gross total resection (GTR), sub-total resection (STR) or biopsy) and the WHO performance status at presentation and through follow-up were recorded. Results Thirteen patients (7 males; 6 females) with a mean age of 47.6 years (range 33–58 years) and a median follow-up of 46 months (range 25–220 months) were studied. Eight patients had symptomatic tumours (headache, visual disturbance); five had incidental finding. Tumours were most commonly located in the fourth ventricle ( n  = 8). The performance status scores at diagnosis were 0 ( n  = 8) and 1 ( n  = 5). The early post-operative performance status scores at 6 months were 0 ( n  = 5) and 1 ( n  = 8) and at last follow-up were 0 ( n  = 11) and 1 ( n  = 2). There was no evidence of tumour re-growth following GTR or STR. The commonest complication was hydrocephalus ( n  = 3). Conclusion Subependymoma are indolent tumours. No patients exhibited a worsening of performance status at medium- to long-term follow-up and there were no tumour recurrence suggesting a shorter follow-up time may be sufficient. Surgical resection is indicated for symptomatic tumours or those without a clear imaging diagnosis. Incidental intraventricular subependymoma can be managed conservatively through MRI surveillance.
    Subject(s): Adult ; Adults ; Biopsy ; Brain Neoplasms - surgery ; Central nervous system ; Cerebral Ventricles - surgery ; Diagnosis ; Female ; Females ; Glioma, Subependymal - surgery ; Headache ; Humans ; Hydrocephalus ; Hydrocephalus - epidemiology ; Hydrocephalus - etiology ; Interventional Radiology ; Intracranial subependymoma ; Magnetic resonance imaging ; Male ; Males ; Medicine ; Medicine & Public Health ; Middle Aged ; Minimally Invasive Surgery ; Neurology ; Neuroradiology ; Neurosurgery ; Neurosurgical Procedures - adverse effects ; Postoperative Complications - epidemiology ; Review - Brain Tumors ; Review Article - Brain Tumors ; Surgery ; Surgical Orthopedics ; Surgical outcome ; Tumors ; Ventricle ; Ventricles (cerebral) ; WHO performance status
    ISSN: 0001-6268
    E-ISSN: 0942-0940
    DOI: 10.1007/s00701-018-3570-4
    Source: Alma/SFX Local Collection
    URL: https://www.ncbi.nlm.nih.gov/pubmed/29915887$$D View this record in MEDLINE/PubMed
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  • 8
    Article
    Article
    Ketogenic diets as an adjuvant therapy for glioblastoma (KEATING): a randomized, mixed methods, feasibility study
    2020
    ISSN: 0167-594X 
    Details
    Language: English
    In: Journal of neuro-oncology, 2020-02-08, Vol.147 (1), p.213-227
    Description: Purpose We conducted a feasibility study to investigate the use of ketogenic diets (KDs) as an adjuvant therapy for patients with glioblastoma (GBM), investigating (i) trial feasibility; (ii) potential impacts of the trial on patients’ quality of life and health; (iii) patients’ perspectives of their decision-making when invited to participate in the trial and (iv) recommending improvements to optimize future phase III trials. Methods A single-center, prospective, randomized, pilot study (KEATING), with an embedded qualitative design. Twelve newly diagnosed patients with GBM were randomized 1:1 to modified ketogenic diet (MKD) or medium chain triglyceride ketogenic diet (MCTKD). Primary outcome was retention at three months. Semi-structured interviews were conducted with a purposive sample of patients and caregivers (n = 15). Descriptive statistics were used for quantitative outcomes and qualitative data were analyzed thematically aided by NVivo. Results KEATING achieved recruitment targets, but the recruitment rate was low (28.6%). Retention was poor; only four of 12 patients completed the three-month diet (MCTKD n = 3; MKD n = 1). Participants’ decisions were intuitive and emotional; caregivers supported diet implementation and influenced the patients’ decision to participate. Those who declined made a deliberative and considered decision factoring diet burden and quality of life. A three-month diet was undesirable to patients who declined and withdrew. Conclusion Recruitment to a KD trial for patients with GBM is possible. A six-week intervention period is proposed for a phase III trial. The role of caregivers should not be underestimated. Future trials should optimize and adequately support the decision-making of patients.
    Subject(s): Caregivers ; Clinical Study ; Clinical trials ; Decision making ; Diet ; Feasibility ; Feasibility studies ; Glioblastoma ; High fat diet ; Ketogenesis ; Ketogenic diet ; Low carbohydrate diet ; Medicine ; Medicine & Public Health ; Mixed-method ; Neurology ; Oncology ; Pilot ; Quality of life ; Recruitment
    ISSN: 0167-594X
    E-ISSN: 1573-7373
    DOI: 10.1007/s11060-020-03417-8
    Source: Alma/SFX Local Collection
    URL: https://www.ncbi.nlm.nih.gov/pubmed/32036576$$D View this record in MEDLINE/PubMed
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  • 9
    Article
    Article
    T-Cell Densities in Brain Metastases Are Associated with Patient Survival Times and Diffusion Tensor MRI Changes
    2018
    ISSN: 0008-5472 
    Details
    Language: English
    In: Cancer research (Chicago, Ill.), 2018-02-01, Vol.78 (3), p.610-616
    Description: Brain metastases are common and are usually detected by MRI. Diffusion tensor imaging (DTI) is a derivative MRI technique that can detect disruption of white matter tracts in the brain. We have matched preoperative DTI with image-guided sampling of the brain-tumor interface in 26 patients during resection of a brain metastasis and assessed mean diffusivity and fractional anisotropy (FA). The tissue samples were analyzed for vascularity, inflammatory cell infiltration, growth pattern, and tumor expression of proteins associated with growth or local invasion such as Ki67, S100A4, and MMP2, 9, and 13. A lower FA in the peritumoral region indicated more white matter tract disruption and independently predicted longer overall survival times (HR for death = 0.21; 95% confidence interval, 0.06-0.82; = 0.024). Of all the biological markers studied, only increased density of CD3 lymphocytes in the same region correlated with decreased FA (Mann-Whitney = 0.037) as well as confounding completely the effect of FA on multivariate survival analyses. We conclude that the T-cell response to brain metastases is not a surrogate of local tumor invasion, primary cancer type, or aggressive phenotype and is associated with patient survival time regardless of these biological factors. Furthermore, it can be assayed by DTI, potentially offering a quick, noninvasive, clinically available method to detect an active immune microenvironment and, in principle, to measure susceptibility to immunotherapy. These findings show that white matter tract integrity is degraded in areas where T-cell infiltration is highest, providing a noninvasive method to identify immunologically active microenvironments in secondary brain tumors. .
    Subject(s): Adult ; Aged ; Biomarkers ; Brain cancer ; Brain Neoplasms - mortality ; Brain Neoplasms - secondary ; Brain Neoplasms - surgery ; Brain tumors ; Cancer ; CD3 antigen ; Cell survival ; Confidence intervals ; Diffusion ; Diffusion Magnetic Resonance Imaging - methods ; Female ; Follow-Up Studies ; Gelatinase A ; Humans ; Immunotherapy ; Infiltration ; Inflammation ; Integrity ; Lymphocytes ; Lymphocytes T ; Magnetic resonance imaging ; Male ; Metastases ; Metastasis ; Microenvironments ; Middle Aged ; Neoplasms - mortality ; Neoplasms - pathology ; Neoplasms - surgery ; Neuroimaging ; Phenotypes ; Prognosis ; Prospective Studies ; Proteins ; S100A4 protein ; Substantia alba ; Survival ; Survival Rate ; T-Lymphocytes - pathology ; Tumors ; Young Adult
    ISSN: 0008-5472
    E-ISSN: 1538-7445
    DOI: 10.1158/0008-5472.CAN-17-1720
    Source: HighWire Press (Free Journals)
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    URL: https://www.ncbi.nlm.nih.gov/pubmed/29212855$$D View this record in MEDLINE/PubMed
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  • 10
    Article
    Article
    Surgical management of posterior fossa metastases
    2016
    ISSN: 0167-594X 
    Details
    Language: English
    In: Journal of neuro-oncology, 2016-09-12, Vol.130 (3), p.535-542
    Description: The diagnosis of brain metastases is associated with a poor prognosis reflecting uncontrolled primary disease that has spread to the relative sanctuary of the central nervous system. 20 % of brain metastases occur in the posterior fossa and are associated with significant morbidity. The risk of acute hydrocephalus and potential for sudden death means these metastases are often dealt with as emergency cases. This approach means a full pre-operative assessment and staging of underlying disease may be neglected and a proportion of patients undergo comparatively high risk surgery with little or no survival benefit. This study aimed to assess outcomes in patients to identify factors that may assist in case selection. We report a retrospective case series of 92 consecutive patients operated for posterior fossa metastases between 2007 and 2012. Routine demographic data was collected plus data on performance status, primary cancer site, details of surgery, adjuvant treatment and survival. The only independent positive prognostic factors identified on multivariate analysis were good performance status (if Karnofsky performance score 〉70, hazard ratio (HR) for death 0.36, 95 % confidence interval (CI) 0.18–0.69), adjuvant whole brain radiotherapy (HR 0.37, 95 % CI 0.21–0.65) and adjuvant chemotherapy where there was extracranial disease and non-synchronous presentation (HR 0.51, 95 % CI 0.31–0.82). Patients presenting with posterior fossa metastases may not be investigated as thoroughly as those with supratentorial tumours. Staging and assessment is essential however, and in the meantime emergencies related to tumour mass effect should be managed with steroids and cerebrospinal fluid diversion as required.
    Subject(s): Adjuvant treatment ; Adult ; Age Factors ; Aged ; Analysis ; Asylum, Right of ; Brain metastasis ; Cancer ; Cerebellar metastasis ; Clinical Study ; Female ; Humans ; Infratentorial Neoplasms - secondary ; Infratentorial Neoplasms - surgery ; Karnofsky Performance Status ; Male ; Medicine ; Medicine & Public Health ; Metastasis ; Middle Aged ; Neurology ; Neurosurgery ; Neurosurgical Procedures - methods ; Oncology ; Posterior fossa metastasis ; Proportional Hazards Models ; Retrospective Studies
    ISSN: 0167-594X
    E-ISSN: 1573-7373
    DOI: 10.1007/s11060-016-2254-2
    Source: Alma/SFX Local Collection
    URL: https://www.ncbi.nlm.nih.gov/pubmed/27619980$$D View this record in MEDLINE/PubMed
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