ORCID Profile
0000-0001-5528-8214
Current Organisation
Royal Brisbane and Women's Hospital
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Publisher: Elsevier BV
Date: 08-2023
Publisher: Cold Spring Harbor Laboratory
Date: 22-12-2020
DOI: 10.1101/2020.12.18.20248521
Abstract: While several key resources exist that interpret therapeutic significance of genomic alterations in cancer, many regional real-world issues limit access to drugs. There is a need for a pragmatic, evidence-based, context-adapted tool to guide clinical management based on molecular biomarkers. A compendium of approved and experimental therapies with associated biomarkers was built following a survey of drug regulatory databases, existing knowledge bases, and published literature. Each biomarker-disease-therapy triplet was then categorized using a tiering system reflective of key therapeutic considerations: approved and reimbursed standard-of-care therapies with respect to a jurisdiction (Tier 1), evidence of efficacy or approval in another jurisdiction (Tier 2), evidence of antitumour activity (Tier 3), and plausible biological rationale (Tier 4). Two resistance categories were defined: lack of efficacy (Tier R1), and lack of antitumor activity (Tier R2). Following comprehensive literature review and appraisal, we developed a curated knowledge base focused on drugs relevant and accessible in the Australian healthcare system (TOPOGRAPH: Therapy Oriented Precision Oncology Guidelines for Recommending Anticancer Pharmaceuticals). As of November 2020, TOPOGRAPH comprised 2810 biomarker-disease-therapy triplets in 989 expert-appraised entries, including 373 therapies, 199 predictive biomarkers, and 106 cancer types. In the 345 biomarker-linked therapies catalogued, 84 (24%) and 65 (19%) therapies in contexts of different cancer types have Tier 1 and 2 designations respectively, while 271 (79%) therapies were supported by preclinical studies, early clinical trials, retrospective studies, or case series (Tiers 3 and 4). A total of 119 of 373 (33%) therapies associated with biomarkers of resistance were also catalogued. A clinical algorithm was also developed to support therapeutic decision-making using predictive biomarkers. This resource is accessible online at topograph.info/ . TOPOGRAPH is intended to support oncologists with context-appropriate clinical decision-making– optimising selection and accessibility of the most appropriate targeted therapy for any given genomic biomarker. Our approach can be readily adapted to build jurisdiction-specific resources to standardise decision-making in precision oncology.
Publisher: Wiley
Date: 03-2000
DOI: 10.1002/(SICI)1520-6769(200003/04)26:2<123::AID-NRC7>3.0.CO;2-N
Publisher: Elsevier BV
Date: 2015
DOI: 10.1016/J.JOCN.2014.07.022
Abstract: Dysembryoplastic neuroepithelial tumour (DNET) is a benign tumour characterised by cortical location and presentation with drug resistant partial seizures in children. Recently the potential for malignant transformation has been reported, however progression without malignant transformation remains rare. We report a case of clinical and radiologic progression of a DNET in a girl 10 years after initial biopsy.
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.JOCN.2019.03.057
Abstract: Intraventricular abscess is a rare pathology. We present a case of primary intraventricular abscess in an immunocompetent 22 year old male. We review the literature and discuss our management of this case with aspiration via neuroendoscopy.
Publisher: Elsevier BV
Date: 09-2010
DOI: 10.1016/J.JOCN.2010.01.033
Abstract: A retrospective analysis of 301 patients was undertaken between 1993 and 2003 to evaluate the relationship of ethnicity with incidence, treatment and survival in patients undergoing surgery for high grade glioma (HGG) in New Zealand. There was no difference in age standardised incidence of HGG in Māori compared to non-Māori patients 4.2/100,000 person years (95% confidence interval [CI] 2.6-6.9) versus 4.1 (95% CI 3.6-4.6). Māori were more likely to have complete tumour resection (odds ratio 3.59 (95% CI 1.01-12.76)) but waited 1.32 (95% CI 0.98-1.79) times longer for radiotherapy. Median survival was 29 weeks with poorer survival in Māori compared to non-Māori (hazard ratio 1.55 [95% CI 0.95-2.55]). We concluded that the incidence of HGG in Māori is similar to non-Maori. However, Māori with HGG have higher rates of complete resection but wait longer for radiotherapy and may have poorer overall survival than non-Māori.
Publisher: Japan Neurosurgical Society
Date: 2013
DOI: 10.2176/NMC.53.266
Abstract: Rarely, midline or unilateral posterior fossa arachnoid cysts (ACs) exert local mass effect resulting in the symptoms and signs of cerebellar and brainstem dysfunction. These cysts are sometimes seen in conjunction with cerebellar tonsillar ectopia (TE), although the relationship between these two entities is unclear. Bilateral ACs in the posterior fossa are virtually unprecedented. We describe the case of a 33-year-old man with a history of multiple minor head injuries observed to harbour asymptomatic, bilateral cerebrospinal fluid-density collections over the cerebellar hemispheres. Six years later, he presented with headaches, limb paraesthesias, and drop attacks. Computed tomography, magnetic resonance imaging, and operative findings during burrhole drainage of the lesions showed bilateral posterior fossa ACs, with associated cerebellar TE of 11 mm. The cysts partially recurred, necessitating reopening of the burrholes, after which the patient's symptoms resolved entirely. We then discuss the challenges in diagnosing this unusual case, the relationship between AC and TE, and the role of minor head injury in the symptomatic progression of AC.
Publisher: Elsevier BV
Date: 03-2010
DOI: 10.1016/J.JOCN.2009.06.037
Abstract: Advances in transsphenoidal endoscopic surgery have allowed difficult clival tumours such as meningiomas causing effacement of the pons and basilar artery to be approached by this technique. We report a clival meningioma resected via a transsphenoidal endoscopic approach.
Publisher: Wiley
Date: 21-09-2021
DOI: 10.1002/HBM.25658
Abstract: Quadrantanopia caused by inadvertent severing of Meyer's Loop of the optic radiation is a well‐recognised complication of temporal lobectomy for conditions such as epilepsy. Dissection studies indicate that the anterior extent of Meyer's Loop varies considerably between in iduals. Quantifying this for in idual patients is thus an important step to improve the safety profile of temporal lobectomies. Previous attempts to delineate Meyer's Loop using diffusion MRI tractography have had difficulty estimating its full anterior extent, required manual ROI placement, and/or relied on advanced diffusion sequences that cannot be acquired routinely in most clinics. Here we present CONSULT: a pipeline that can delineate the optic radiation from raw DICOM data in a completely automated way via a combination of robust pre‐processing, segmentation, and alignment stages, plus simple improvements that bolster the efficiency and reliability of standard tractography. We tested CONSULT on 696 scans of predominantly healthy participants (539 unique brains), including both advanced acquisitions and simpler acquisitions that could be acquired in clinically acceptable timeframes. Delineations completed without error in 99.4% of the scans. The distance between Meyer's Loop and the temporal pole closely matched both averages and ranges reported in dissection studies for all tested sequences. Median scan‐rescan error of this distance was 1 mm. When tested on two participants with considerable pathology, delineations were successful and realistic. Through this, we demonstrate not only how to identify Meyer's Loop with clinically feasible sequences, but also that this can be achieved without fundamental changes to tractography algorithms or complex post‐processing methods.
Publisher: American Association for Cancer Research (AACR)
Date: 30-06-2014
DOI: 10.1158/0008-5472.CAN-14-0296
Abstract: Glioblastoma multiforme (GBM) is one of the most aggressive human brain malignancies. Even with optimal treatment, median survival is less than 6 months for patients with recurrent GBM. Immune-based therapies have the potential to improve patient outcome by supplementing standard treatment. Expression of human cytomegalovirus (CMV) antigens in GBM tissues provides the unique opportunity to target viral antigens for GBM therapy. Here, we report findings of a formal clinical assessment of safety and potential clinical efficacy of autologous CMV-specific T-cell therapy as a consolidative treatment for recurrent GBM. From a total of 19 patients with recurrent GBM, CMV-specific T cells were successfully expanded from 13 patients (68.4%), 11 of whom received up to four T-cell infusions. Combination therapy based on T-cell infusion and chemotherapy was well tolerated, and we detected only minor adverse events. The overall survival of these patients since first recurrence ranged from 133 to 2,428 days, with a median overall survival of 403 days. Most importantly, 4 of 10 patients that completed the treatment remained progression free during the study period. Furthermore, molecular profiling of CMV-specific T-cell therapy from these patients revealed distinct gene expression signatures, which correlated with their clinical response. Our study suggests that a combination therapy with autologous CMV-specific T cells and chemotherapy is a safe novel treatment option and may offer clinical benefit for patients with recurrent GBM. Cancer Res 74(13) 3466–76. ©2014 AACR.
Publisher: Georg Thieme Verlag KG
Date: 29-08-2012
Publisher: Elsevier BV
Date: 02-2010
DOI: 10.1016/J.JOCN.2009.05.020
Abstract: Primary spinal primitive neuroectodermal tumours are rare. We present a 45-year-old man with a peripheral primitive neuroectodermal tumour arising in the cervical spine. We believe this to be the first report of this type of tumour in the cervical spine.
Publisher: IEEE
Date: 08-2016
Publisher: Springer Science and Business Media LLC
Date: 27-03-2019
DOI: 10.1038/S41467-019-09111-2
Abstract: Myoglobin, encoded by MB , is a small cytoplasmic globular hemoprotein highly expressed in cardiac myocytes and oxidative skeletal myofibers. Myoglobin binds O 2, facilitates its intracellular transport and serves as a controller of nitric oxide and reactive oxygen species. Here, we identify a recurrent c.292C T (p.His98Tyr) substitution in MB in fourteen members of six European families suffering from an autosomal dominant progressive myopathy with highly characteristic sarcoplasmic inclusions in skeletal and cardiac muscle. Myoglobinopathy manifests in adulthood with proximal and axial weakness that progresses to involve distal muscles and causes respiratory and cardiac failure. Biochemical characterization reveals that the mutant myoglobin has altered O 2 binding, exhibits a faster heme dissociation rate and has a lower reduction potential compared to wild-type myoglobin. Preliminary studies show that mutant myoglobin may result in elevated superoxide levels at the cellular level. These data define a recognizable muscle disease associated with MB mutation.
Publisher: Wiley
Date: 30-04-2012
Abstract: Anterior cranial fossa (ACF) meningiomas are difficult to surgically manage. Endoscopic transnasal approaches have increasingly been used as a minimally invasive route and thus offer significant advantages. However, a paucity of literature describing the intraoperative challenges and postoperative outcomes of this technique still exists. Case series with chart review. The Royal Adelaide Hospital, Flinders Medical Centre, Wellington Hospital. Fifteen consecutive patients who underwent endoscopic resection of ACF meningiomas between 2004 and 2010 by the South Australian and Wellington Skull Base Units. Demographic and clinical information was compiled by reviewing patient charts and operation notes. Safety and efficacy of the procedure, role of a team approach, and areas for further improvement were analyzed. Of the patients, 87% were women. Tumor locations: 8 olfactory groove, 2 tuberculum sellae, 1 clinoidal, 1 jugum sphenoidale, 1 planum sphenoidale, 1 subfrontal, and 1 midline ACF floor. Commonest presenting symptom was visual change. Mean volume of tumor was 25.69 cm 3 , with a size area of 7.28 cm 2 . Five were revision cases. None had previous endonasal surgery. Average operating times decreased over time. Gross total removal was achieved in 14, with no deaths. Four patients had postoperative cerebrospinal fluid (CSF) leak. Rate of CSF leak decreased over time. Sixty percent of patients reported visual improvement. Two patients had radiological evidence of recurrence. ACF meningiomas can be safely removed endonasally, offering significant advantages over the traditional transcranial approach for suitable tumors. Early audit of this approach shows results achieved by this unit are comparable with the published literature.
No related grants have been discovered for Hamish Alexander.